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The University of Alabama at Birmingham is a public university in Birmingham in the U.S. state of Alabama. Developed from an academic extension center established in 1936, the institution became an autonomous institution in 1969 and is today one of three institutions in the University of Alabama System. In the fall of 2013, 18,568 students from more than 110 countries were enrolled at UAB pursuing studies in 140 programs of study in 12 academic divisions leading to bachelor's, master's, doctoral, and professional degrees in the social and behavioral science, the liberal arts, business, education, engineering, and health-related fields such as medicine, dentistry, optometry, nursing, and public health.The UAB Health System, one of the largest academic medical centers in the United States, is affiliated with the university. UAB Hospital sponsors residency programs in medical specialties, including internal medicine, neurology, surgery, radiology, and anesthesiology. UAB Hospital is the only ACS verified Level I trauma center in Alabama, as rated by the American College of Surgeons Trauma Program.UAB is the state's largest employer, with more than 18,000 faculty and staff and over 53,000 jobs at the university and in the health system. An estimated 10 percent of the jobs in the Birmingham-Hoover Metropolitan Area and 1 in 33 jobs in the state of Alabama are directly or indirectly related to UAB. The university's overall annual economic impact was estimated to be $4.6 billion in 2010. Wikipedia.

Korf B.R.,University of Alabama at Birmingham
Discovery Medicine | Year: 2013

Although some have wondered whether the sequencing of the human genome has led to major advances in medicine, in fact there are multiple examples where genomics has been integrated into medical practice. In the area of prevention, genomic approaches are now used for non-invasive prenatal testing of fetal DNA in the maternal circulation, for expanded preconceptional screening for carrier status, for autosomal recessive disorders, and for assessment of risk of common disease. In the area of diagnosis, major advances have been made in cytogenomics and in use of whole exome or whole genome sequencing. In therapeutics, pharmacogenetic testing is now feasible, tumor genome sequencing is being used to guide cancer therapy, and genomic discoveries are enabling development of new targeted therapies. Ultimately it is possible that genome sequencing may be done for all individuals on a routine basis, though there remain significant technical, ethical, and medical systems challenges to be overcome. It is likely that integration of genomics into medical practice will occur gradually over a long period of time, but the process is now well underway. © Discovery Medicine.

Sivley M.D.,University of Alabama at Birmingham
Optometry and Vision Science | Year: 2013

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by accumulation of Gb-3 (globotriaosylceramide) in cellular lysosomes of tissues throughout the body. With advancing age, lysosomal Gb-3 accumulates in blood vessel walls, nerve cells, smooth muscle, and vital organs. Premature death commonly results from renal failure, heart attack, and stroke when the diagnosis is delayed or overlooked. One of the earliest and most distinctive physical features of FD is a whorl-like keratopathy. This finding is easily identifiable during a routine eye examination with a slit lamp, making eye care practitioners uniquely postured to identify patients and families with this incurable genetic disorder. Much of the pain, suffering, and adverse impact of FD can be avoided if an alert eye care expert sees the patient at an early age, identifies the condition, and makes the appropriate referral. The importance of obtaining a thorough medical history, ancestral health history, and review of systems to correlate ocular and systemic manifestations is emphasized. This report reviews the multisystem involvement of FD and describes the clinical characteristics and expected chronological appearance of ophthalmic and systemic manifestations. The discoveries of late-onset variants, increased prevalence, and modified inheritance pattern of FD are discussed. The profound therapeutic effects of recombinant enzyme replacement therapy (ERT) on multiple organ systems are detailed and demonstrated in a Fabry proband. Improved quality and quantity of life after initiation of ERT underscore the importance of early recognition and correlation of FD symptoms and clinical signs. Treatment strategies and the effectiveness of new adjunctive chaperone therapy are addressed. Copyright © 2013 American Academy of Optometry.

Cervical cancer is the leading cause of cancer death among women in Ghana. Despite the availability of cervical cancer screening in healthcare facilities throughout the country, less than 4 % of Ghanaian women seek preventive cervical cancer screenings regularly. There is a lack of culturally relevant cervical cancer education material available in Ghana. The aims of this study were to assess the social cultural factors that influence cervical cancer screening behaviors and the health communication preferences of Ghanaian women. A focus group guide based on the constructs of the PEN-3 model was used to conduct six focus groups that were stratified by educational attainment. Thirty-four women participated in the study. The qualitative data revealed that most participants were not aware of cervical cancer or cervical cancer screening. However, many of the participants were willing to seek screening if they knew more about it. The most common sources of health information were television, radio, friends, and family. And the participants preferred inspirational cervical-cancer-screening messages that would be delivered by a doctor and a cancer survivor. © 2014 Springer Science+Business Media New York.

Wang H.E.,University of Alabama at Birmingham | Yealy D.M.,University of Pittsburgh
Annals of Emergency Medicine | Year: 2012

Study objective: As a recommended strategy for optimally managing critical illness, regionalization of care involves matching the needs of the target population with available hospital resources. The national supply and characteristics of hospitals providing specialized critical care services is currently unknown. We seek to characterize the current distribution of specialized care centers in the United States. Methods: Using public data linked with the American Hospital Association directory and US Census, we identified US general acute hospitals providing specialized care for ST-segment elevation myocardial infarction (STEMI) (<40 annual primary percutaneous coronary interventions reported in Medicare Hospital Compare), stroke (The Joint Commission certified stroke centers), trauma (American College of Surgeons or state-designated, adult or pediatric, level I or II), and pediatric critical care (presence of a pediatric ICU) services. We determined the characteristics and state-level distribution and density of specialized care centers (centers per state and centers per state population). Results: Among 4,931 acute care hospitals in the United States, 1,325 (26.9%) provided one of the 4 defined specialized care services, including 574 STEMI, 763 stroke, 508 trauma, and 457 pediatric critical care centers. Approximately half of the 1,325 hospitals provided 2 or more specialized services, and one fifth provided 3 or 4 specialized services. There was variation in the number of each type of specialized care center in each state: STEMI median 7 interquartile range (IQR 2 to 14), stroke 8 (IQR 3 to 17), trauma 6 (IQR 3 to 11), pediatric specialized care 6 (IQR 3 to 11). Similarly, there was variation in the number of each type of specialized care center per population: STEMI median 1 center per 585,135 persons (IQR 418,729 to 696,143), stroke 1 center per 412,188 persons (IQR 321,604 to 572,387), trauma 1 center per 610,589 persons (IQR 406,192 to 917,588), and pediatric critical care 1 center per 665,282 persons (IQR 441,525 to 942,254). The national distribution patterns differed for each type of specialized care center. Conclusion: The distribution of specialized care centers varies across the United States. These observations highlight unanswered questions about the regional organization of specialized care in the United States. © 2012 American College of Emergency Physicians.

Fowler K.B.,University of Alabama at Birmingham
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America | Year: 2013

The association between congenital cytomegalovirus (CMV) infection and sensorineural hearing loss (SNHL) was first described almost 50 years ago. Studies over the intervening decades have further described the relationship between congenital CMV infection and SNHL in children. However, congenital CMV infection remains a leading cause of SNHL in children in the United States and the world today. As more CMV infections are identified, it is important to recognize that infants who are born to seroimmune mothers are not completely protected from SNHL, although their hearing loss is often milder than that seen in CMV-infected infants following primary maternal infections. Late-onset and progressive hearing losses occur following congenital CMV infection, and CMV-infected infants should be evaluated regularly to provide for early detection of hearing loss and appropriate intervention. Fluctuating hearing loss that is not explained by concurrent middle ear infections is another characteristic of CMV-related hearing loss in children. Challenges still remain in predicting which children with congenital CMV infection will develop hearing loss and, among those who do develop loss, whether or not the loss will continue to deteriorate.

Chalela J.A.,Medical University of South Carolina | Lopez J.I.,University of Alabama at Birmingham
Nutrition in Clinical Practice | Year: 2013

Hunger strikes are not infrequent occurrences in military and civilian prisons. Although practicing clinicians are familiar with the management of patients who have limited oral intake, managing hunger strikers is unfamiliar to most. The psychological, physiological, and social events that surround hunger strikes are very complex and need to be understood by those caring for hunger strike patients. To provide adequate medical care to hunger strike patients, clinicians most understand the physiological events that ensue after prolonged starvation. Careful vigilance for development of refeeding syndrome is of key importance. A multidisciplinary approach to hunger strikes is of utmost importance, and involvement of a multidisciplinary clinical team as well as prison officials is essential. © 2012 American Society for Parenteral and Enteral Nutrition.

Parker-Autry C.Y.,University of Alabama at Birmingham
International urogynecology journal | Year: 2012

Vitamin D is a micronutrient vital in calcium homeostasis and musculoskeletal function. Vitamin D insufficiency is a common variant of vitamin D deficiency that shows clinical signs of rickets and osteomalacia. The clinical significance of vitamin D insufficiency is being explored in several medical conditions. However, the most robust work suggests a role in musculoskeletal disease. The pelvic floor is a unique part of the body and the function of which is dependent on interrelationships between muscle, nerve, connective tissue, and bone. Pelvic floor disorders result when these relationships are disrupted. This paper reviews current knowledge regarding vitamin D nutritional status, the importance of vitamin D in muscle function, and how insufficient or deficient vitamin D levels may play a role in the function of the female pelvic floor.

There is no standard of care for older patients with newly diagnosed acute myeloid leukemia (AML) unfit for intensive therapy, and prognosis with currently recommended low-intensity therapies (decitabine, azacitidine, and low-dose cytarabine [LDAC]) remains poor. One promising strategy is to combine low-intensity treatments with novel agents. Gemtuzumab ozogamicin, tipifarnib, and barasertib have been investigated in phase 2/3 or 3 trials combined with LDAC, and phase 3 trials are currently investigating sapacitabine plus decitabine, and volasertib plus LDAC in AML. This review discusses current treatment recommendations and the development of combination therapies for older patients unfit for intensive therapy. © 2014 The Authors.

Dhossche D.M.,University of Mississippi Medical Center | Ross C.A.,The Colin A Ross Institute For Psychological Trauma | Stoppelbein L.,University of Alabama at Birmingham
Acta Psychiatrica Scandinavica | Year: 2012

Objective: Catatonia is considered a unique syndrome of motor signs, at times life-threatening when aggravated by autonomic dysfunction and fever, but eminently treatable with specific medical treatments, if recognized early. Catatonia commonly occurs in children and adolescents with a wide range of associated disorders. The role of deprivation, abuse, or trauma in the development of pediatric catatonia is examined. Method: Reports considering deprivation, abuse, or trauma as precipitants of catatonia in pediatric cases are culled from the classic writings on catatonia and from a selective review of modern contributions. Results: Kahlbaum gave trauma a central role in catatonia in many young adult cases. Kanner described children with psychogenic catalepsy. Anaclitic depression, a condition found by Spitz in deprived institutionalized children, strongly resembles stuporous catatonia. Leonhard considered lack of communication with the mother or substitute mother as an important risk factor for childhood catatonia. Children including those with autism who experience emotional and physical trauma sometimes develop catatonia. The clinical descriptions of children with classic catatonic syndromes and those of contemporary refugee children with a syndrome labeled Pervasive Refusal Syndrome are similar. Conclusion: The literature supports the view that deprivation, abuse, and trauma can precipitate catatonia in children and adolescents. © 2011 John Wiley & Sons A/S.

Allon M.,University of Alabama at Birmingham
Clinical Journal of the American Society of Nephrology | Year: 2015

Arteriovenous grafts (AVGs) are prone to frequent thrombosis that is superimposed on underlying hemodynamically significant stenosis, most commonly at the graft-vein anastomosis. There has been great interest in detecting AVG stenosis in a timely fashion and performing preemptive angioplasty, in the belief that this will prevent AVG thrombosis. Three surveillance methods (static dialysis venous pressure, flow monitoring, and duplex ultrasound) can detect AVG stenosis. Whereas observational studies have reported that surveillance with preemptive angioplasty substantially reduces AVG thrombosis, randomized clinical trials have failed to confirm such a benefit. There is a high frequency of early AVG restenosis after angioplasty caused by aggressive neointimal hyperplasia resulting from vascular injury. Stent grafts prevent AVG restenosis better than balloon angioplasty, but they do not prevent AVG thrombosis. Several pharmacologic interventions to prevent AVG failure have been evaluated in randomized clinical trials. Anticoagulation or aspirin plus clopidogrel do not prevent AVG thrombosis, but increase hemorrhagic events. Treatment of hyperhomocysteinemia does not prevent AVG thrombosis. Dipyridamole plus aspirin modestly decreases AVG stenosis or thrombosis. Fish oil substantially decreases the frequency of AVG stenosis and thrombosis. In patients who have exhausted all options for vascular access in the upper extremities, thigh AVGs are a superior option to tunneled internal jugular vein central vein catheters (CVCs). An immediate-use AVG is a reasonable option in patients with recurrent CVC dysfunction or infection. Tunneled femoral CVCs have much worse survival than internal jugular CVCs. © 2015 by the American Society of Nephrology.

Landier W.,University of Alabama at Birmingham
Cancer | Year: 2016

Ototoxicity is a well-established toxicity associated with a subgroup of antineoplastic therapies that includes platinum chemotherapy, radiation or surgery involving the ear and auditory nerve, and supportive care agents such as aminoglycoside antibiotics and loop diuretics. The reported prevalence of ototoxicity in patients who have received potentially ototoxic therapy ranges from 4% to 90% depending on factors such as age of the patient population, agent(s) used, cumulative dose, and administration techniques. The impact of ototoxicity on subsequent health-related and psychosocial outcomes in these patients can be substantial, and the burden of morbidity related to ototoxic agents is particularly high in very young children. Considerable interindividual variability in the prevalence and severity of ototoxicity has been observed among patients receiving similar treatment, suggesting genetic susceptibility as a risk factor. The development and testing of otoprotective agents is ongoing; however, to the author's knowledge, no US Food and Drug Administration-approved otoprotectants are currently available. Prospective monitoring for ototoxicity allows for comparison of auditory outcomes across clinical trials, as well as for early detection, potential alterations in therapy, and auditory intervention and rehabilitation to ameliorate the adverse consequences of hearing loss. © 2016 American Cancer Society.

McKeown J.L.,University of Alabama at Birmingham
Anesthesiology Clinics | Year: 2015

Adequate treatment of pain is of utmost importance in making uncomplicated the perioperative course for geriatric surgical patients. Effective analgesia reduces morbidity, improves patient and family satisfaction, and is a natural expectation of high-quality care. Pain treatment in older adults is more complicated than in younger counterparts, and great consideration must be given to age-related changes in physiology and pharmacokinetics. Pain treatment must be individualized based on each patient's profile. Side effects must be minimized and organ toxicity avoided. When complications occur they may be more severe, and treatment must be prompt. Alternative plans for analgesia must be readily enacted. © 2015 Elsevier Inc..

Schmalbach C.E.,University of Alabama at Birmingham | Bradford C.R.,University of Michigan
Laryngoscope | Year: 2015

Objectives/Hypothesis: Sentinel lymph node biopsy (SLNB) is considered one of the most important melanoma advancements to date. Since its inception in 1992, a plethora of data and associated controversies has emerged leading to the question: Is SLNB considered the standard of care for head and neck (HN) cutaneous melanoma?Study Design: English literature (1990-2014) review.Methods: The PubMed database search was conducted using key terms "melanoma" and "sentinel node." This review included both dedicated HN SLNB studies and larger prospective SLNB studies, in which HN patients were included among the cohort. Bibliography cross-referencing was conducted to ensure a comprehensive search.Results: SLNB is safe and accurate in the HN region. Review of large prospective SLNB trials identified the pathologic status of the SLN as the most important prognostic factor for recurrence and survival. Early lymphadenectomy following a positive SLNB imparts a survival benefit.Conclusions: Our review of the current literature suggests that SLNB is the standard of care for selected cases of HN cutaneous melanoma. It is now incorporated into the American Joint Committee on Cancer staging system, the National Comprehensive Cancer Network practice guidelines, and numerous national and international consensus statements. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Yamada T.,University of Alabama at Birmingham
Circulation Journal | Year: 2013

Transthoracic epicardial catheter ablation is a useful supplemental or even preferred strategy to eliminate cardiac arrhythmias in the electrophysiology laboratory. The indication for this technique has extended to a diverse range of cardiac arrhythmias, including scar-related ventricular tachycardia (VT), idiopathic VTs, accessory pathways, atrial tachycardias, inappropriate sinus tachycardia, and atrial fibrillation, as the epicardial substrates of these tachyarrhythmias have become increasingly recognized. When endocardial ablation and epicardial ablation through the cardiac veins are unsuccessful, transthoracic epicardial ablation should be the next option. Intrapericardial access is usually obtained through a subxiphoidal pericardial puncture. This approach might not be possible in patients with pericardial adhesions caused by prior cardiac surgery or pericarditis. In such cases, a hybrid procedure involving surgical access with a subxiphoid pericardial window and limited anterior or lateral thoracotomy might be a feasible and safe method of performing epicardial catheter ablation in the electrophysiology laboratory. Potential complications associated with this technique include bleeding and collateral damage to the coronary artery and phrenic nerve. Although the risk of these complications is low, electrophysiologists who attempt epicardial catheter ablation should know the complications associated with this technique, how to minimize their occurrence, and how to rapidly recognize and treat the complications that they encounter. This review discusses the indications, techniques, and complications of transthoracic epicardial catheter ablation.

Graven L.J.,Florida State University | Grant J.,University of Alabama at Birmingham
Journal of Cardiovascular Nursing | Year: 2013

Background: Approximately 50% of individuals living with heart failure (HF) experience depressive symptoms. Social support has been found to have a positive influence on depressive symptoms in individuals with HF. Objective: The purposes of this review were to (1) examine recent literature regarding the impact of social support on depressive symptoms in individuals with HF, (2) synthesize findings across those studies, (3) assess potential areas of future research regarding social support, and (4) identify implications for nursing practice. Methods: An integrative review of current empirical literature was conducted through a search of the CINAHL and PsycARTICLES computerized databases for the period of January 2000 to December 2010. The key words used for the search were heart failure, social support, coping, depressive symptoms, and depression. Results: Fifteen studies matched inclusion criteria. Eleven of these studies found social support to prevent or reduce depressive symptoms. Emotional and tangible support as coping resources or strategies, the perceived availability of or satisfaction with support, and assistance with problem solving positively influenced depressive symptoms. Perceived emotional and tangible support and the presence and availability of social networks lessened depression in patients with HF. Findings from 4 studies on the impact of social support were not statistically significant. Different definitions of social support and a variety of measurement instruments used made it difficult to generalize study findings. Conclusions: Social support seems to positively impact and influence the psychological well-being of those with HF. Additional research is needed to identify specific characteristics of support that is effective in influencing depressive symptoms in this population. Furthermore, more research is needed regarding how factors such as ethnicity influence depressive symptoms and depression. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Muzny C.A.,University of Alabama at Birmingham
Sexually transmitted diseases | Year: 2012

The random amplified polymorphic DNA technique was used to delineate the genetic relatedness of Trichomonas vaginalis isolates among 3 pairs of mutually infected women who have sex with women in sexual partnerships. One of the 3 pairs of women shared a T. vaginalis isolate with the same random amplified polymorphic DNA banding patterns. Shared use of washcloths to cleanse the vaginal area after receptive oral sex was the most likely method of T. vaginalis transmission among this pair of women.

Bellis S.L.,University of Alabama at Birmingham
Biomaterials | Year: 2011

Despite many years of in vitro research confirming the effectiveness of RGD in promoting cell attachment to a wide variety of biomaterials, animal studies evaluating tissue responses to implanted RGD-functionalized substrates have yielded more variable results. The goals of this report are to present some of the reasons why cell culture studies may not always reliably predict in vivo responses, and more importantly, to highlight potential applications that may benefit from the use of RGD peptides. © 2011 Elsevier Ltd.

Weech-Maldonado R.,University of Alabama at Birmingham
Medical care | Year: 2012

Cultural competency has been espoused as an organizational strategy to reduce health disparities in care. To examine the relationship between hospital cultural competency and inpatient experiences with care. The first model predicted Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) scores from hospital random effects, plus fixed effects for hospital cultural competency, individual race/ethnicity/language, and case-mix variables. The second model tested if the association between a hospital's cultural competency and HCAHPS scores differed for minority and non-Hispanic white patients. The National CAHPS Benchmarking Database's (NCBD) HCAHPS Surveys and the Cultural Competency Assessment Tool of Hospitals Surveys for California hospitals were merged, resulting in 66 hospitals and 19,583 HCAHPS respondents in 2006. Dependent variables include 10 HCAHPS measures: 6 composites (communication with doctors, communication with nurses, staff responsiveness, pain control, communication about medications, and discharge information), 2 individual items (cleanliness and quietness of patient rooms), and 2 global items (overall hospital rating, and whether patient would recommend hospital). Hospitals with greater cultural competency have better HCAHPS scores for doctor communication, hospital rating, and hospital recommendation. Furthermore, HCAHPS scores for minorities were higher at hospitals with greater cultural competency on 4 other dimensions: nurse communication, staff responsiveness, quiet room, and pain control. Greater hospital cultural competency may improve overall patient experiences, but may particularly benefit minorities in their interactions with nurses and hospital staff. Such effort may not only serve longstanding goals of reducing racial/ethnic disparities in inpatient experience, but may also contribute to general quality improvement.

Although there is general agreement that most forms of common disease develop as a consequence of a combination of factors, including genetic, environmental and behavioural contributors, the actual mechanistic basis of how these factors initiate or promote diabetes, cancer, neurodegenerative and cardiovascular diseases in some individuals but not in others with seemingly identical risk factor profiles, is not clearly understood. In this respect, consideration of the potential role for mitochondrial genetics, damage and function in influencing common disease susceptibility seems merited, given that the prehistoric challenges were the original factors that moulded cellular function, and these were based upon the mitochondrial-nuclear relationships that were established during evolutionary history. These interactions were probably refined during prehistoric environmental selection events that, at present, are largely absent. Contemporary risk factors such as diet, sedentary lifestyle and increased longevity, which influence our susceptibility to a variety of chronic diseases were not part of the dynamics that defined the processes of mitochondrial-nuclear interaction, and thus cell function. Consequently, the prehistoric challenges that contributed to cell functionality and evolution should be considered when interpreting and designing experimental data and strategies. Although several molecular epidemiological studies have generally supported this notion, studies that probe beyond these associations are required. Such investigation will mark the initial steps for mechanistically addressing the provocative concept that contemporary human disease susceptibility is the result of prehistoric selection events for mitochondrial-nuclear function, which increased the probability for survival and reproductive success during evolution. © 2013 Biochemical Society.

Calhoun D.A.,University of Alabama at Birmingham
Current Hypertension Reports | Year: 2010

Obstructive sleep apnea (OSA) and hypertension commonly coexist. Observational studies indicate that untreated OSA is associated with an increased risk of prevalent hypertension, whereas prospective studies of normotensive cohorts suggest that OSA may increase the risk of incident hypertension. Randomized evaluations of continuous positive airway pressure (CPAP) indicate an overall modest effect on blood pressure. However, these studies do indicate a wide variation in the blood pressure effects of CPAP, with some patients, on an individual basis, manifesting a large antihypertensive benefit. OSA is particularly common in patients with resistant hypertension. The reason for this high prevalence of OSA is not fully explained, but data from our laboratory suggest that it may be related to the high occurrence of hyperaldosteronism in patients with resistant hypertension. We hypothesize that aldosterone excess worsens OSA by promoting accumulation of fluid in the neck, which then contributes to increased upper airway resistance. © Springer Science+Business Media, LLC 2010.

Yuen H.K.,University of Alabama at Birmingham
Spinal Cord | Year: 2013

Study design:one group pre- and post-test design.Objectives:The primary aim was to examine both the short- and long-term effects of an oral home telecare program on improving gingival health among adults with tetraplegia.Methods:Eight adults with tetraplegia participated. The oral home telecare program consisted of individualized oral hygiene training in the use of assistive devices (powered toothbrush and adapted flosser and/or oral irrigator) using personal computer-based videoconferencing between each participant and an occupational therapist. Training was conducted on an average of five 15-30 min sessions across 3 months. During these training sessions, supervised practice of oral hygiene, and provision of immediate corrective feedback and positive reinforcement in the use of adaptive oral hygiene devices was emphasized. Gingival health assessment using the Löe-Silness gingival index (LSGI) was conducted at baseline, 6 and 12 months.Results:From baseline to 6 months, participants showed statistically significant differences (that is, improvement with less gingival inflammation) in their LSGI scores (z=2.18, P=.03). From baseline to 12 months, participants also showed a statistically significant difference (that is, improvement, z=2.03; P=0.04) in their LSGI scores.Conclusion:This study indicates that preventive oral home telecare with repeated oral hygiene training in the use of adaptive devices improved gingival health at 6 and 12 months among adults with tetraplegia. © 2013 International Spinal Cord Society All rights reserved.

Owsley C.,University of Alabama at Birmingham
Vision Research | Year: 2013

Older adults commonly report difficulties in visual tasks of everyday living that involve visual clutter, secondary task demands, and time sensitive responses. These difficulties often cannot be attributed to visual sensory impairment. Techniques for measuring visual processing speed under divided attention conditions and among visual distractors have been developed and have established construct validity in that those older adults performing poorly in these tests are more likely to exhibit daily visual task performance problems. Research suggests that computer-based training exercises can increase visual processing speed in older adults and that these gains transfer to enhancement of health and functioning and a slowing in functional and health decline as people grow older. © 2012 Elsevier Ltd.

Vance D.E.,University of Alabama at Birmingham
Medical Science Monitor | Year: 2010

HIV cognitive impairments are a common occurrence. Although some of the etiologies of such cognitive impairments are understood, some of the causes are not always straightforward because adults with HIV represent a very heterogenous population. Unfortunately, many of the studies that investigate cognition in this population rely on convenience samples of HIV-positive adults who may lack cognitive stimulation due to poor education or unemployment, both of which can promote negative neuroplasticity. By the same token, other adults with HIV may be cognitively stimulated by their work, educational pursuits, and intellectual interests which may promote positive neuroplasticity which may be protective against cognitive impairments. Implications for how this impacts research as well as prevention and intervention of cognitive impairments are posited. © Med Sci Monit, 2010.

Zhang H.-G.,University of Louisville | Grizzle W.E.,University of Alabama at Birmingham
American Journal of Pathology | Year: 2014

Normal and diseased cells release bilayered membrane-bound nanovesicles into interstitial spaces and into bodily fluids. A subgroup of such microvesicles is called exosomes and is described in blood as 30 to 100 nm in diameter and as spherical to cup-shaped nanoparticles with specific surface molecular characteristics (eg, expression of the tetraspanins CD9, CD81, and CD63). Extracellular microvesicles provide local signals (eg, autocrine and paracrine) and distant endocrine signals to cells via the transfer of their contents, which include signal proteins, lipids, miRNAs, and functional mRNAs. Exosomes and related microvesicles also aid cells in exporting less-needed molecules and potentially harmful molecules, including drugs; in the case of neoplasia, the export of chemotherapeutic drugs may facilitate cellular chemoresistance. Cancers have adapted the exosome and related microvesicles as a pathway by which neoplastic cells communicate with each other (autocrine) and with nonneoplastic cells (paracrine and endocrine); via this pathway, cancer suppresses the immune system and establishes a fertile local and distant environment to support neoplastic growth, invasion, and metastases. Because exosomes mirror and bind to the cells from which they arise, they can be used for delivery of drugs, vaccines, and gene therapy, as biomarkers and targets. We review how exosomes and related extracellular microvesicles facilitate the progression and metastases of cancers and describe how these microvesicles may affect clinical care. © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Weinmann A.S.,University of Washington | Weinmann A.S.,University of Alabama at Birmingham
Advances in Immunology | Year: 2014

The development of specialized helper T cells has garnered much attention because of their critical role in coordinating the immune response to invading pathogens. Recent research emphasizing novel functions for specialized helper T cells in a variety of infectious disease settings, as well as autoimmune states, has reshaped our view on the capabilities of helper T cells. Notably, one previously underappreciated aspect of the lifespan of helper T cells is that they often retain the capacity to respond to changes in the environment by altering the composition of helper T cell lineage-specifying transcription factors they express, which, in turn, changes their phenotype. This emerging realization is changing our views on the stability versus flexibility of specialized helper T cell subtypes. Now, there is a new concerted effort to define the mechanistic events that contribute to the potential for flexibility in specialized helper T cell gene expression programs in the different environmental circumstances that allow for the re-expression of helper T cell lineage-specifying transcription factors. In addition, we are also now beginning to appreciate that "helper T cell" lineage-specifying transcription factors are expressed in diverse types of innate and adaptive immune cells and this may allow them to play roles in coordinating aspects of the immune response. Our current challenges include defining the conserved mechanisms that are utilized by these lineage-specifying transcription factors to coordinate gene expression programs in different settings as well as the mechanistic events that contribute to the differential downstream consequences that these factors mediate in unique cellular environments. In this review, we will explore our evolving views on these topics, often times using the Th1-lineage-specifying transcription factor T-bet as an example. © 2014 Elsevier Inc.

Agarwal A.,University of Alabama at Birmingham
Transactions of the American Clinical and Climatological Association | Year: 2013

Tissue injury may result as a consequence of a physical, chemical, or biological insult. Such injury recruits an adaptive response to restore homeostasis and protect against further injury. One of the most prompt protective and adaptive responses by all tissues is the robust activation of the highly inducible, anti-inflammatory, anti-oxidant, and anti-apoptotic protein, heme oxygenase-1 (HO-1). HO-1, a microsomal enzyme, catalyzes the breakdown of pro-oxidant heme, which is released from heme proteins to equimolar quantities of iron, carbon monoxide, and biliverdin. Biliverdin is converted to bilirubin by biliverdin reductase. The beneficial effects of HO-1 expression are not merely due to heme degradation but are also attributed to the cytoprotective properties of the byproducts of the reaction. Manipulation of this enzymatic system in a myriad of disease models has provided substantial evidence to support its role as a cytoprotective enzyme and is therefore an emerging therapeutic molecule.

Rostand S.G.,University of Alabama at Birmingham
Clinical Journal of the American Society of Nephrology | Year: 2010

Vitamin D deficiency has increasingly been recognized in the general population and especially in African Americans whose deep skin pigmentation makes vitamin D photosynthesis inefficient. Over the last decade there has been increasing interest in the role that vitamin D deficiency may play in BP modulation because many epidemiologic studies have shown an inverse association between serum vitamin D concentration and BP. There is a high prevalence of vitamin D deficiency in African Americans who also have an increased susceptibility to develop hypertension and its consequences. This paper will review the circumstances leading to vitamin D deficiency in the African American population and will also discuss how vitamin D deficiency can affect the renin-angiotensin system, free radical production, inflammatory processes, and carbohydrate tolerance that in turn influence vascular endothelial function and vascular structure producing increased vascular resistance. It will speculate that the presence of vitamin D deficiency throughout life from its earliest phases may adversely affect the microvasculature in African Americans, thereby playing a major role in the genesis and maintenance of hypertension. Copyright © 2010 by the American Society of Nephrology.

Fields D.A.,The University of Oklahoma Health Sciences Center | Allison D.B.,University of Alabama at Birmingham
Obesity | Year: 2012

The objective of this study was to determine the accuracy, precision, bias, and reliability of percent fat (%fat) determined by air-displacement plethysmography (ADP) with the pediatric option against the four-compartment model in 31 children (4.1 1.2 years, 103.3 10.2 cm, 17.5 3.4 kg). %Fat was determined by (BOD POD Body Composition System; COSMED USA, Concord, CA) with the pediatric option. Total body water (TBW) was determined by isotope dilution (2H2 O; 0.2 g/kg) while bone mineral was determined by dual-energy X-ray absorptiometry (DXA) (Lunar iDXA v13.31; GE, Fairfield, CT and analyzed using enCore 2010 software). The four-compartment model by Lohman was used as the criterion measure of %fat. The regression for %fat by ADP vs. %fat by the four-compartment model did not deviate from the line of identity where: y = 0.849(x) 4.291. ADP explained 75.2% of the variance in %fat by the four-compartment model while the standard error of the estimate (SEE) was 2.09 %fat. The Bland-Altman analysis showed %fat by ADP did not exhibit any bias across the range of fatness (r = 0.04; P = 0.81). The reliability of ADP was assessed by the coefficient of variation (CV), within-subject SD, and Cronbach's α. The CV was 3.5%, within-subject SD was 0.9%, and Cronbach's α was 0.95. In conclusion, ADP with the pediatric option is accurate, precise, reliable, and without bias in estimating %fat in children 2-6 years old. © 2011 The Obesity Society.

Zhi D.,University of Alabama at Birmingham | Chen R.,Baylor College of Medicine
PLoS ONE | Year: 2012

Recently, whole-genome sequencing, especially exome sequencing, has successfully led to the identification of causal mutations for rare monogenic Mendelian diseases. However, it is unclear whether this approach can be generalized and effectively applied to other Mendelian diseases with high locus heterogeneity. Moreover, the current exome sequencing approach has limitations such as false positive and false negative rates of mutation detection due to sequencing errors and other artifacts, but the impact of these limitations on experimental design has not been systematically analyzed. To address these questions, we present a statistical modeling framework to calculate the power, the probability of identifying truly disease-causing genes, under various inheritance models and experimental conditions, providing guidance for both proper experimental design and data analysis. Based on our model, we found that the exome sequencing approach is well-powered for mutation detection in recessive, but not dominant, Mendelian diseases with high locus heterogeneity. A disease gene responsible for as low as 5% of the disease population can be readily identified by sequencing just 200 unrelated patients. Based on these results, for identifying rare Mendelian disease genes, we propose that a viable approach is to combine, sequence, and analyze patients with the same disease together, leveraging the statistical framework presented in this work. © 2012 Zhi, Chen.

Uddin N.,University of Alabama at Birmingham
Proceedings of the IEEE | Year: 2012

The primary objective of this paper is to present and discuss geotechnical issues and challenges for the design and stability of massive energy storage caverns in hard rock formations. In general, the challenges which confront the construction of massive underground caverns are a combination of the geological, hydrological, geochemical, geothermal, and geotechnical. The identification and remediation of the geotechnical challenges will be qualitatively discussed here and this discussion will be anchored with a particular practical example. © 2006 IEEE.

Pappas P.G.,University of Alabama at Birmingham
American Journal of the Medical Sciences | Year: 2010

Opportunistic fungi are a constantly evolving group of pathogens that plague a growing group of vulnerable patients. These include hospitalized patients, especially those in the intensive care unit; stem cell and solid organ transplant recipients; patients treated with immunosuppressant medications; those with advanced human immunodeficiency virus or other acquired immunodeficiency conditions; and patients with organ failure syndromes. Rapid diagnosis of invasive fungal infection is essential to optimize outcomes. Several newer nonculture-based diagnostics, including the Aspergillus galactomannan enzyme-linked immunosorbent assay, the β-D-glucan assay and the multiplex polymerase chain reaction-based assays, may emerge as important tools facilitating early intervention with effective antifungal therapy. Newer azoles, including posaconazole, isavuconazole and ravuconazole, will potentially provide more effective therapeutic options in the future, diminishing the role for amphotericin B. © 2010 Lippincott Williams & Wilkins.

Walters B.C.,University of Alabama at Birmingham
PM and R | Year: 2010

The application of electrical current to injured tissue is known to promote healing. The use of this modality in healing the injured spinal cord to promote neurologic recovery has been introduced as a potential treatment for patients who previously had minimal hope of recovery. In in vitro and in vivo experiments, neural regeneration has been seen to occur, especially when an oscillating field is used. With this modality, an electrical current is applied in which the polarity changes direction on a periodic basis, preventing the "die-back" phenomenon of severed neural pathways. This mechanism of recovery has been demonstrated in several species in which sacrifice has been undertaken and spinal cords examined. In a study of humans, a small number of patients participated in a single phase Ia trial in which the safety of an implantable device was demonstrated, with indications of probable benefit, consistent with laboratory and animal studies. In addition, a number of additional patients were treated, and their results were examined along with the original cohort and were compared with historical control subjects. The device used in this mode of treatment has not been approved for use in the general spinal cord-injured population, pending further study. A larger multi-institutional trial needs to be done to further demonstrate efficacy and effectiveness, and outcomes will need to be agreed upon by spinal cord injury researchers, patients, and regulators before widespread use will be permitted. Unfortunately, some subtle changes experienced and valued by patients are not recognized as important or desirable by regulators or by all researchers. © 2010 by the American Academy of Physical Medicine and Rehabilitation.

Morrow D.R.,University of Alabama at Birmingham
Climatic Change | Year: 2015

Disagreements about morally appropriate mitigation policies arise in part from implicit disagreements about the nature and moral significance of needs. One key question is what, if anything, distinguishes “needs” from “mere wants.” One approach, prominent in economics and implemented in existing integrated assessment models of climate change, rejects a hard distinction between needs and wants. An alternative approach, prominent in the philosophical literature on needs, identifies needs with the requirements for autonomous agency, which is the capacity to set and pursue one’s own goals. A second key question is in what sense, if any, the satisfaction of needs should take precedence over the satisfaction of wants. Those who reject the distinction between wants and needs can say only that some desires should be weighted more heavily than others. Those who endorse the distinction can say that, given certain ethical assumptions, it is wrong to frustrate one person’s needs in order to satisfy others’ mere wants. Thus, rejecting the distinction between wants and needs tends to justify less aggressive mitigation policies, in which satisfying the so-called “wants” of present generations compensates for frustrating the so-called “needs” of future generations. Endorsing the distinction between wants and needs, along with certain ethical assumptions, tends to justify more aggressive mitigation policies. Both positions are intellectually defensible; understanding them helps illuminate disagreements over mitigation policy. © 2014, Springer Science+Business Media Dordrecht.

Belov G.A.,University of Maryland University College | Sztul E.,University of Alabama at Birmingham
Journal of virology | Year: 2014

Viruses are obligatory intracellular parasites and utilize host elements to support key viral processes, including penetration of the plasma membrane, initiation of infection, replication, and suppression of the host's antiviral defenses. In this review, we focus on picornaviruses, a family of positive-strand RNA viruses, and discuss the mechanisms by which these viruses hijack the cellular machinery to form and operate membranous replication complexes. Studies aimed at revealing factors required for the establishment of viral replication structures identified several cellular-membrane-remodeling proteins and led to the development of models in which the virus used a preexisting cellular-membrane-shaping pathway "as is" for generating its replication organelles. However, as more data accumulate, this view is being increasingly questioned, and it is becoming clearer that viruses may utilize cellular factors in ways that are distinct from the normal functions of these proteins in uninfected cells. In addition, the proteincentric view is being supplemented by important new studies showing a previously unappreciated deep remodeling of lipid homeostasis, including extreme changes to phospholipid biosynthesis and cholesterol trafficking. The data on viral modifications of lipid biosynthetic pathways are still rudimentary, but it appears once again that the viruses may rewire existing pathways to generate novel functions. Despite remarkable progress, our understanding of how a handful of viral proteins can completely overrun the multilayered, complex mechanisms that control the membrane organization of a eukaryotic cell remains very limited. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Winstead C.J.,University of Alabama at Birmingham
Immunology Letters | Year: 2014

The basic functions of the immune system are protection from pathogens and maintenance of tolerance to self. The maintenance of commensal microbiota at mucosal surfaces adds a layer of complexity to these basic functions. Recent reports suggest follicular helper T cells (Tfh), a CD4+ T cell subset specialized to provide help to B cells undergoing isotype switching and affinity maturation in germinal centers (GC), interact with the microbiota and are essential to maintenance of mucosal barriers. Complicating the issue is ongoing controversy in the field regarding origin of the Tfh subset and its distinction from other effector CD4 T cell phenotypes (Th1/Th17/Treg). This review focuses on the differentiation, phenotypic plasticity, and function of CD4 T cells, with an emphasis on commensal-specific GC responses in the gut. © 2014 Elsevier B.V..

Iyer R.R.,Teva Branded Pharmaceutical Products R and D Inc | Pluciennik A.,Thomas Jefferson University | Napierala M.,University of Alabama at Birmingham | Napierala M.,Polish Academy of Sciences | Wells R.D.,Texas A&M University
Annual Review of Biochemistry | Year: 2015

DNA mismatch repair is a conserved antimutagenic pathway that maintains genomic stability through rectification of DNA replication errors and attenuation of chromosomal rearrangements. Paradoxically, mutagenic action of mismatch repair has been implicated as a cause of triplet repeat expansions that cause neurological diseases such as Huntington disease and myotonic dystrophy. This mutagenic process requires the mismatch recognition factor MutSβ and the MutLα (and/or possibly MutLγ) endonuclease, and is thought to be triggered by the transient formation of unusual DNA structures within the expanded triplet repeat element. This review summarizes the current knowledge of DNA mismatch repair involvement in triplet repeat expansion, which encompasses in vitro biochemical findings, cellular studies, and various in vivo transgenic animal model experiments. We present current mechanistic hypotheses regarding mismatch repair protein function in mediating triplet repeat expansions and discuss potential therapeutic approaches targeting the mismatch repair pathway. Copyright © 2015 by Annual Reviews. All rights reserved.

Jarome T.J.,University of Alabama at Birmingham | Jarome T.J.,University of Wisconsin - Milwaukee | Helmstetter F.J.,University of Wisconsin - Milwaukee
Frontiers in Molecular Neuroscience | Year: 2014

Long-term memory (LTM) formation requires transient changes in the activity of intracellular signaling cascades that are thought to regulate new gene transcription and de novo protein synthesis in the brain. Consistent with this, protein synthesis inhibitors impair LTM for a variety of behavioral tasks when infused into the brain around the time of training or following memory retrieval, suggesting that protein synthesis is a critical step in LTM storage in the brain. However, evidence suggests that protein degradation mediated by the ubiquitin-proteasome system (UPS) may also be a critical regulator of LTM formation and stability following retrieval. This requirement for increased protein degradation has been shown in the same brain regions in which protein synthesis is required for LTM storage. Additionally, increases in the phosphorylation of proteins involved in translational control parallel increases in protein polyubiquitination and the increased demand for protein degradation is regulated by intracellular signaling molecules thought to regulate protein synthesis during LTM formation. In some cases inhibiting proteasome activity can rescue memory impairments that result from pharmacological blockade of protein synthesis, suggesting that protein degradation may control the requirement for protein synthesis during the memory storage process. Results such as these suggest that protein degradation and synthesis are both critical for LTM formation and may interact to properly "consolidate" and store memories in the brain. Here, we review the evidence implicating protein synthesis and degradation in LTM storage and highlight the areas of overlap between these two opposing processes. We also discuss evidence suggesting these two processes may interact to properly form and store memories. LTM storage likely requires a coordinated regulation between protein degradation and synthesis at multiple sites in the mammalian brain. © 2014 Jarome and Helmstetter.

Mannon R.B.,University of Alabama at Birmingham
Kidney International | Year: 2010

Late failure of a kidney transplant continues to be a major problem after transplantation, in spite of more potent immunosuppressive strategies and the focus of clinical management shifting toward prolonging long-term graft survival. It is now recognized that graft failure occurs because of two major complications: death with a functioning graft and intrinsic allograft failure. Recent studies of late kidney graft loss have indicated a complexity of findings, including etiologies that are both immune and non-immune. These studies suggest that late graft failure is not an inevitable fact and that further investigation into the etiology of transplant graft failure may lead to a new understanding of the biology that will provide novel therapeutic strategies and biomarkers. In this review, we will focus on late allograft failure due to intrinsic injury to the transplant. The role of immune monitoring will be discussed in the context of monitoring for ongoing injury or for identifying late injury. A variety of methodologies have been used, including genomics, proteomics, and metabolomics, not only for monitoring allograft injury but also for identifying markers of graft failure that are more sensitive than serum creatinine. The available studies, as they relate to late or chronic graft injury, will also be reviewed. © 2010 International Society of Nephrology.

Johnson V.A.,University of Alabama at Birmingham
Topics in HIV medicine : a publication of the International AIDS Society, USA | Year: 2010

This December 2010 version of the International AIDS Society-USA (IAS-USA) drug resistance mutations list updates the figures last published in December 2009 (Johnson VA et al, Top HIV Med, 2009;17:138-145). This update includes 9 new mutations- E138G and E138K for etravirine (Haddad M et al, CROI, 2010; Abstract 574, and Vingerhoets J et al, Antivir Ther, 2010;15 [Suppl 2]:A125); E92Q for raltegravir (Geretti AM et al, Antivir Ther, 2010;15 [Suppl 2]:A62; Cooper et al, N Engl J Med, 2008;359:355-365; and Malet I et al, Antimicrob Agents Chemother, 2008;52:1351-1358); and M36L, M36V, H69R, L89I, L89M, and L89V for tipranavir/ritonavir. In addition, the tipranavir/ritonavir N83D mutation designation was changed to boldface to indicate its recognition as a major mutation rather than a minor mutation. The mutations I13V, K20M/R, E35G, and L90M were removed from the tipranavir/ritonavir bar, reflecting new understanding. For etravirine, L100I*, K101P*, and Y181C*/I*/V* are denoted with asterisks (instead of bolded) to reflect that these individual mutations each have the greatest impact (ie, highest weighting scores) on reduced phenotypic susceptibility and impaired clinical response when compared with other etravirine mutations (Haddad M et al, CROI, 2010; Abstract 574). In addition, user notes d, n, r, w, and z were revised.

Guyette N.,University of Alabama at Birmingham
Investigative ophthalmology & visual science | Year: 2013

Low tear volume limits the use of nonstimulated (NS) microcapillary tear collection in aqueous-deficient (AD) patients. Adding a small amount of "washout" fluid to the eye prior to tear collection is a potentially viable alternative method for abundant proteins, but is relatively untested for low-abundance biomarkers. This study determined the feasibility of the washout (WO) method as an NS alternative for low-abundance biomarkers. NS and WO biomarker profiles were compared between AD patients and non-AD controls to determine if the two methods identify the same intergroup differences. Matching NS and WO tears were collected from 48 patients by micropipette, the WO sample after instillation of 10 μL saline. Tear cytokine levels were measured by 27-Plex Bio-Rad assay. Bland-Altman analyses for each biomarker determined the agreement between tear sample types. Patients were grouped as AD or non-AD based on Schirmer score to determine if NS profile between-group differences were preserved in WO tears. Bland-Altman plots showed good biomarker level agreement between NS and WO tears for most cytokines. Five biomarkers, among those most often cited as differing in AD dry eye, differed significantly between non-AD and AD groups in both tear types. Additional biomarker differences were seen in NS tears only. The WO tear collection method is a viable alternative to NS tears for many low-abundance biomarkers and is able to replicate major NS tear differences between dry eye groups. More subtle intergroup differences are lost in WO samples because of reduced statistical power.

Thompson S.R.,University of Alabama at Birmingham
Trends in Microbiology | Year: 2012

In eukaryotes, mRNAs are primarily translated through a cap-dependent mechanism whereby initiation factors recruit the 40S ribosomal subunit to a cap structure at the 5' end of the mRNA. However, some viral and cellular messages initiate protein synthesis without a cap. They use a structured RNA element termed an internal ribosome entry site (IRES) to recruit the 40S ribosomal subunit. IRESs were discovered over 20 years ago, but only recently have studies using a model IRES from dicistroviruses expanded our understanding of how a 3D RNA structure can capture and manipulate the ribosome to initiate translation. © 2012 Elsevier Ltd.

Alexandrov A.V.,University of Alabama at Birmingham
Journal of Internal Medicine | Year: 2010

Alexandrov AV (University of Alabama Hospital, Birmingham, AL, USA). Current and future recanalization strategies for acute ischemic stroke (Review). J Intern Med 2010; 267: 209-219. In a quest for stroke treatment, reperfusion proved to be the first key to the puzzle. Systemic tissue plasminogen activator (tPA), the first and currently the only approved treatment, is also the fastest way to initiate thrombolyis for acute ischemic stroke. tPA works by induction of mostly partial recanalization since stroke patients often have large thrombus burden. Thus, early augmentation of fibrinolysis and multi-modal approach to improve recanalization are desirable. This review focuses on the following strategies available to clinicians now or being tested in clinical trials: (a) faster initiation of tPA infusion; (b) sonothrombolysis; (c) intra-arterial revascularization, bridging intravenous and intra-arterial thrombolysis, mechanical thrombectomy and aspiration; and (d) novel experimental approaches. Despite these technological advances, no single strategy was yet proven to be a 'silver bullet' solution to reverse acute ischemic stroke. Better outcomes are expected with faster treatment leading to early, at times just partial flow improvement rather than achieving complete recanalization with lengthy procedures. Arterial re-occlusion can occur with any of these approaches, and it remains a challenge since it leads to poor outcomes and no clinical trial data are available yet to determine safe strategies to prevent or reverse re-occlusion. © 2010 Blackwell Publishing Ltd.

Kushi L.H.,Kaiser Permanente | Doyle C.,American Physical Society | McCullough M.,Nutritional Epidemiology | Rock C.L.,University of California at San Diego | And 6 more authors.
CA Cancer Journal for Clinicians | Year: 2012

The American Cancer Society (ACS) publishes Nutrition and Physical Activity Guidelines to serve as a foundation for its communication, policy, and community strategies and, ultimately, to affect dietary and physical activity patterns among Americans. These Guidelines, published approximately every 5 years, are developed by a national panel of experts in cancer research, prevention, epidemiology, public health, and policy, and they reflect the most current scientific evidence related to dietary and activity patterns and cancer risk. The ACS Guidelines focus on recommendations for individual choices regarding diet and physical activity patterns, but those choices occur within a community context that either facilitates or creates barriers to healthy behaviors. Therefore, this committee presents recommendations for community action to accompany the 4 recommendations for individual choices to reduce cancer risk. These recommendations for community action recognize that a supportive social and physical environment is indispensable if individuals at all levels of society are to have genuine opportunities to choose healthy behaviors. The ACS Guidelines are consistent with guidelines from the American Heart Association and the American Diabetes Association for the prevention of coronary heart disease and diabetes, as well as for general health promotion, as defined by the 2010 Dietary Guidelines for Americans and the 2008 Physical Activity Guidelines for Americans. Copyright © 2012 American Cancer Society, Inc.

Mitchell T.S.,Iowa State University | Warner D.A.,University of Alabama at Birmingham | Janzen F.J.,Iowa State University
Ecology | Year: 2013

Identifying the relative contributions of genetic, maternal, and environmental factors to phenotypic variation is critical for evaluating the evolutionary potential of fitnessrelated traits. We employed a novel two-step cross-fostering experiment to quantify the relative contributions of clutch (i.e., maternal identity) and maternally chosen nest sites to phenotypic variation during three early life stages (incubation, hibernation, dispersal) of the painted turtle (Chrysemys picta). By translocating eggs between nests in the field, we demonstrated that both clutch and nest site contribute to phenotypic variation at hatching. Because hatchling C. picta hibernate inside nests, we performed a second cross-foster to decouple the effects of the incubation nest with that of the hibernation nest. Incubation nest explained little variation in phenotypes at spring emergence, but winter nest site was important. We found no evidence that mothers select nest sites specific to reaction norms of their own offspring, suggesting that females may select nest sites with microhabitats that broadly meet similar requirements across the population. After hibernation, we released hatchlings to assess performance and phenotypic selection during dispersal. Hibernation nest site influenced physiological performance during dispersal, and we detected nonlinear selection on hatchling carapace length. Our experiment demonstrates that nest-site choice has substantial effects on phenotypic variation and fitness across multiple early life stages. © 2013 by the Ecological Society of America.

Sachs C.B.,University of Alabama at Birmingham
Inquiry | Year: 2012

McDowell's contributions to epistemology and philosophy of mind turn centrally on his defense of the Aristotelian concept of a "rational animal". I argue here that a clarification of how McDowell uses this concept can make more explicit his distance from Davidson regarding the nature of the minds of non-rational animals. Close examination of his responses to Davidson and to Dennett shows that McDowell is implicitly committed to avoiding the following "false trichotomy": that animals are not bearers of semantic content at all, that they are bearers of content in the same sense we are, and that they are bearer of "as if" content. Avoiding the false trichotomy requires that we understand non-rational animals as having concepts but not as making judgments. Furthermore, we need to supplement McDowell's distinction between the logical spaces of reasons and of the realm of law with what Finkelstein calls "the logical space of animate life". Though McDowell has taken some recent steps to embrace a view like this, I urge a more demanding conception than what McDowell has thus far suggested. © 2012 Copyright Taylor and Francis Group, LLC.

Visscher K.M.,University of Alabama at Birmingham | Weissman D.H.,University of Michigan
BMC Medicine | Year: 2011

During the past two decades, the advent of functional magnetic resonance imaging (fMRI) has fundamentally changed our understanding of brain-behavior relationships. However, the data from any one study add only incrementally to the big picture. This fact raises important questions about the dominant practice of performing studies in isolation. To what extent are the findings from any single study reproducible? Are researchers who lack the resources to conduct a fMRI study being needlessly excluded? Is pre-existing fMRI data being used effectively to train new students in the field? Here, we will argue that greater sharing and synthesis of raw fMRI data among researchers would make the answers to all of these questions more favorable to scientific discovery than they are today and that such sharing is an important next step for advancing the field of cognitive neuroscience. © 2011 Visscher and Weissman; licensee BioMed Central Ltd.

Elewski B.,University of Alabama at Birmingham
Seminars in cutaneous medicine and surgery | Year: 2013

Currently approved options for the treatment of onychomycosis include systemic therapy (the antifungal agents fluconazole, itraconazole, and terbinafine), topical agents (ciclopirox, which has been available since 1996, efinaconazole, currently pending approval), and laser systems. Phase III studies on another topical, tavaborole, have been completed and this medication also shows promise. Mechanical modalities are sometimes used but are seldom necessary. Recurrence of infection is common; the risk for recurrence may be reduced by adherence to preventive measures, especially avoiding (if possible) or promptly treating tinea pedis infections.

Abraham W.T.,Ohio State University | Stevenson L.W.,Brigham and Womens Hospital | Bourge R.C.,University of Alabama at Birmingham | Lindenfeld J.A.,Vanderbilt University | And 2 more authors.
The Lancet | Year: 2016

Background In the CHAMPION trial, significant reductions in admissions to hospital for heart failure were seen after 6 months of pulmonary artery pressure guided management compared with usual care. We examine the extended efficacy of this strategy over 18 months of randomised follow-up and the clinical effect of open access to pressure information for an additional 13 months in patients formerly in the control group. Methods The CHAMPION trial was a prospective, parallel, single-blinded, multicentre study that enrolled participants with New York Heart Association (NYHA) Class III heart failure symptoms and a previous admission to hospital. Patients were randomly assigned (1:1) by centre in block sizes of four by a secure validated computerised randomisation system to either the treatment group, in which daily uploaded pulmonary artery pressures were used to guide medical therapy, or to the control group, in which daily uploaded pressures were not made available to investigators. Patients in the control group received all standard medical, device, and disease management strategies available. Patients then remained masked in their randomised study group until the last patient enrolled completed at least 6 months of study follow-up (randomised access period) for an average of 18 months. During the randomised access period, patients in the treatment group were managed with pulmonary artery pressure and patients in the control group had usual care only. At the conclusion of randomised access, investigators had access to pulmonary artery pressure for all patients (open access period) averaging 13 months of follow-up. The primary outcome was the rate of hospital admissions between the treatment group and control group in both the randomised access and open access periods. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00531661. Findings Between Sept 6, 2007, and Oct 7, 2009, 550 patients were randomly assigned to either the treatment group (n=270) or to the control group (n=280). 347 patients (177 in the former treatment group and 170 in the former control group) completed the randomised access period in August, 2010, and transitioned to the open access period which ended April 30, 2012. Over the randomised access period, rates of admissions to hospital for heart failure were reduced in the treatment group by 33% (hazard ratio [HR] 0·67 [95% CI 0·55-0·80]; p<0·0001) compared with the control group. After pulmonary artery pressure information became available to guide therapy during open access (mean 13 months), rates of admissions to hospital for heart failure in the former control group were reduced by 48% (HR 0·52 [95% CI 0·40-0·69]; p<0·0001) compared with rates of admissions in the control group during randomised access. Eight (1%) device-related or system related complications and seven (1%) procedure-related adverse events were reported. Interpretation Management of NYHA Class III heart failure based on home transmission of pulmonary artery pressure with an implanted pressure sensor has significant long-term benefit in lowering hospital admission rates for heart failure. Funding St Jude Medical Inc. © 2016 Elsevier Ltd.

Background: The objective of this study was to investigate whether the levels of glucose or certain amino acids could regulate the expression of a cell cycle repressor protein p27(Kip1), thereby dictating the risk of cancer in either obesity or caloric/dietary restriction. Previously, we identified and reported four different upstream molecular signaling pathways of p27 expression in human breast cancer cells. We called these four pathways as pathway #1, #2, #3 and #4. We found that 4-hydroxytamoxifen - but not tamoxifen - up-regulated the expression of p27 using pathway #1 which consisted mainly of receptor tyrosine kinases and mTORC1. We now investigate, using 4-hydroxytamoxifen as a reference anti-cancer agents, whether (a) the moderate increase in the concentration of D-(+)-glucose could down-regulate and, conversely, (b) the deficiency of D-(+)-glucose or certain L-amino acids could up-regulate the expression of p27 in these cells using pathway #2 which consists mainly of AMPK and mTORC1.Results: Using human MDA-MB-231 breast cancer cells in vitro, these hypotheses were tested experimentally by performing p27-luciferase reporter transfection assays and western immunoblot analyses. The results obtained are consistent with these hypotheses. Furthermore, the results indicated that, although 4-hydroxytamoxifen used primarily pathway #1 to down-regulate the phosphorylation of 4E-BP1 and up-regulate the expression of p27, it also secondarily down-regulated the phosphorylation of S6K1. In contrast, the deficiency of D-(+)-glucose or L-leucine used primarily pathway #2 to down-regulate the phosphorylation of S6K1, but they also secondarily down-regulated the phosphorylation of 4E-BP1 and up-regulated the expression of p27. Finally, deficiency of D-(+)-glucose or L-leucine - but not 4-hydroxytamoxifen - up-regulated the expression of mitochondrial ATP5A and SIRT3.Conclusions: (a) 4-Hydroxitamoxifen used primarily pathway #1 to up-regulate the expression of p27. (b) Moderate increase in the concentration of D-(+)-glucose used primarily pathway #2 to down-regulate the expression of p27. © Deficiency of D-(+)-glucose or L-leucine also used primarily pathway #2 to up-regulate the expression of p27. (d) Deficiency of D-(+)-glucose or L-leucine - but not 4-hydroxytamoxifen - up-regulated the expression of mitochondrial ATP5A in the Complex V of respiratory oxidation-phosphorylation chain and mitochondrial SIRT3. The SIRT3 is one of the seven mammalian anti-aging as well as anti-metabolic sirtuins. © 2011 Eto; licensee BioMed Central Ltd.

Gallego C.J.,University of Alabama at Birmingham
The Journal of craniofacial surgery | Year: 2010

Orofacial clefting is a common condition found in 1 per 700 to 1 per 1000 births. Although most cases are isolated, a subset is caused by a specific genetic mutation. Specific gene tests have been used for recognizable syndromes such as velocardiofacial syndrome or van der Woude syndrome, where the cleft is associated with other anomalies. However, many cleft lip and palate patients have other anomalies but do not fit in to a recognizable syndrome. For these patients, chromosome analysis has been a first-line genetic test; however, in the past few years, a new form of genetic testing has become available for these patients: array comparative genome hybridization (aCGH). We present a 7-month-old male infant with cleft palate, developmental delay, and a family history of velopharyngeal insufficiency in whom aCGH array was used to identify a small deletion on the short (p) arm of chromosome 7. This defect, which was also found in the mother, was undetected by chromosome analysis. In summary, this case demonstrates that aCGH is a new diagnostic tool that is useful in the evaluation of select cases of orofacial clefting. Array comparative genome hybridization should be considered when the suspicion for a genetic etiology of the clefting remains strong despite a normal cytogenetic analysis.

Stegall M.D.,Mayo Medical School | Gaston R.S.,University of Alabama at Birmingham | Cosio F.G.,Mayo Medical School | Matas A.,University of Minnesota
Journal of the American Society of Nephrology | Year: 2015

A common lament is that long-term kidney transplant outcomes remain the same despite improvements in early graft survival. To be fair, progress has been made - in both our understanding of chronic injury and modestly, graft survival. However, we are still a long way from actually solving this important and difficult problem. In this review, we outline recent data supporting the existence of several causes of renal allograft loss, the incidences of which peak at different time points after transplantation. On the basis of this broadened concept of chronic renal allograft injury, we examine the challenges of clinical trial design in longterm studies, including the use of surrogate end points and biomarkers. Finally, we suggest a path forward that, ultimately, may improve long-term renal allograft survival. Copyright © 2015 by the American Society of Nephrology.

Hanaway M.J.,University of Alabama at Birmingham | Woodle E.S.,University of Cincinnati | Mulgaonkar S.,St. Barnabas Health System | Peddi V.R.,California Pacific Medical Center | And 4 more authors.
New England Journal of Medicine | Year: 2011

BACKGROUND: There are few comparisons of antibody induction therapy allowing early glucocorticoid withdrawal in renal-transplant recipients. The purpose of the present study was to compare induction therapy involving alemtuzumab with the most commonly used induction regimens in patient populations at either high immunologic risk or low immunologic risk. METHODS: In this prospective study, we randomly assigned patients to receive alemtuzumab or conventional induction therapy (basiliximab or rabbit antithymocyte globulin). Patients were stratified according to acute rejection risk, with a high risk defined by a repeat transplant, a peak or current value of panel-reactive antibodies of 20% or more, or black race. The 139 high-risk patients received alemtuzumab (one dose of 30 mg, in 70 patients) or rabbit antithymocyte globulin (a total of 6 mg per kilogram of body weight given over 4 days, in 69 patients). The 335 low-risk patients received alemtuzumab (one dose of 30 mg, in 164 patients) or basiliximab (a total of 40 mg over 4 days, in 171 patients). All patients received tacrolimus and mycophenolate mofetil and underwent a 5-day glucocorticoid taper in a regimen of early steroid withdrawal. The primary end point was biopsy-confirmed acute rejection at 6 months and 12 months. Patients were followed for 3 years for safety and efficacy end points. RESULTS: The rate of biopsy-confirmed acute rejection was significantly lower in the alemtuzumab group than in the conventional-therapy group at both 6 months (3% vs. 15%, P<0.001) and 12 months (5% vs. 17%, P<0.001). At 3 years, the rate of biopsyconfirmed acute rejection in low-risk patients was lower with alemtuzumab than with basiliximab (10% vs. 22%, P = 0.003), but among high-risk patients, no significant difference was seen between alemtuzumab and rabbit antithymocyte globulin (18% vs. 15%, P = 0.63). Adverse-event rates were similar among all four treatment groups. CONCLUSIONS: By the first year after transplantation, biopsy-confirmed acute rejection was less frequent with alemtuzumab than with conventional therapy. The apparent superiority of alemtuzumab with respect to early biopsy-confirmed acute rejection was restricted to patients at low risk for transplant rejection; among high-risk patients, alemtuzumab and rabbit antithymocyte globulin had similar efficacy. (Funded by Astellas Pharma Global Development; INTAC ClinicalTrials.gov number, NCT00113269.). Copyright © 2011 Massachusetts Medical Society.

Bell D.S.H.,University of Alabama at Birmingham
Southern Medical Journal | Year: 2010

Chronic metformin use results in vitamin B12 deficiency in 30% of patients. Exhaustion of vitamin B12 stores usually occurs after twelve to fifteen years of absolute vitamin B12 deficiency. Metformin has been available in the United States for approximately fifteen years. Vitamin B12 deficiency, which may present without anemia and as a peripheral neuropathy, is often misdiagnosed as diabetic neuropathy, although the clinical findings are usually different. Failure to diagnose the cause of the neuropathy will result in progression of central and/or peripheral neuronal damage which can be arrested but not reversed with vitamin B12 replacement. To my knowledge, this is the first report of metformin-induced vitamin B12 deficiency causing neuropathy. Copyright © 2010 by The Southern Medical Association.

Stewart L.T.,University of Alabama at Birmingham
Journal of Neurophysiology | Year: 2015

Current theories on the pathogenesis of autism spectrum disorders (ASD) maintain that the associated cognitive and behavioral symptoms are caused by aberrant synaptic transmission affecting specific brain circuits. Transgenic mouse models have implicated the involvement of cell adhesion proteins in synaptic dysfunction and ASD pathogenesis. Recently, Aoto et al. (Cell 154: 75–88, 2013) has shown that alternatively spliced neurexin proteins affect the efficacy of AMPA receptormediated excitatory currents in both cultured neuronal networks and acute hippocampal slices constituting a potential ASD-related electrophysiological phenotype. © 2015 the American Physiological Society.

To determine the therapeutic efficacy and immunomodulatory effect of an anti-human death receptor 5 (DR5) antibody, TRA-8, in eliminating macrophage subsets in a mouse model of type II collagen-induced arthritis (CIA). A human/mouse-chimeric DR5-transgenic mouse, under the regulation of a mouse 3-kb promoter and a loxP-flanked STOP cassette, was generated and crossed with an ubiquitous Cre (Ubc.Cre) mouse and a lysozyme M-Cre (LysM.Cre)-transgenic mouse to achieve inducible or macrophage-specific expression. Chicken type II collagen was used to induce CIA in mice, which were then treated with an anti-human DR5 antibody, TRA-8. Clinical scores, histopathologic severity, macrophage apoptosis and depletion, and T cell subset development were evaluated. In human/mouse DR5-transgenic Ubc.Cre mice with CIA, transgenic DR5 was most highly expressed on CD11b+ macrophages, with lower expression on CD4+ T cells. In human/mouse DR5-transgenic LysM.Cre mice, transgenic DR5 was restrictively expressed on macrophages. Both in vivo near-infrared imaging of caspase activity and TUNEL staining demonstrated that TRA-8 rapidly induced apoptosis of macrophages in inflamed synovium. Depletion of pathogenic macrophages by TRA-8 led to significantly reduced clinical scores for arthritis; decreased macrophage infiltration, synovial hyperplasia, osteoclast formation, joint destruction, cathepsin activity, and inflammatory cytokine expression in joints; reduced numbers of Th17 cells; and an increased number of Treg cells in draining lymph nodes. The anti-human DR5 antibody TRA-8 was efficacious in reducing the severity of arthritis via targeted depletion of macrophages and immunomodulation. Our data provide preclinical evidence that TRA-8 is a potential novel biologic agent for rheumatoid arthritis therapy. Copyright © 2012 by the American College of Rheumatology.

Morris J.J.,University of Alabama at Birmingham | Morris J.J.,Michigan State University
Trends in Genetics | Year: 2015

Black Queen (BQ) functions are biological processes that yield neither purely private nor purely public products. This partitioning of benefits, also called 'leakiness', can produce negative frequency dependence of fitness in microbial communities, allowing coexistence between function-performing helpers and function-requiring beneficiaries. The ubiquity of leakiness favors a 'race to the bottom' as members of a community lose the ability to perform functions whose products are available from the environment. Rather than being social altruists, helpers are merely those populations that lost this race and got stuck in their role as function performers. Here I discuss many such BQ functions and the microbial communities that evolve around them. I also compile evidence from laboratory evolution experiments as well as phylogenetic reconstructions that show that organisms gain greater fitness increases from gene/function loss events than is commonly expected. Finally, I consider possible consequences of long-term BQ-stabilized coexistence, including sympatric speciation and the evolution of true mutualisms. © 2015 Elsevier Ltd.

Singh J.A.,University of Alabama at Birmingham
Journal of managed care pharmacy : JMCP | Year: 2012

In 2011, the Agency for Health Care Research and Quality (AHRQ) published a systematic review on the comparative effectiveness of disease-modifying anti-rheumatic drugs (DMARDs) used to treat adults with rheumatoid arthritis (RA). The publication was an update to a 2007 report. A total of 258 published articles were used in the AHRQ review to compare the effectiveness of corticosteroids, and oral and biologic DMARDs in the treatment of RA. Head-to-head studies and prospective cohort trials were used to compare one drug to another in determining efficacy and effectiveness. AHRQ compiled this report in an attempt to summarize and integrate the available data for clinicians to make evidence based practice decisions for their patients since there is limited consensus among the medical community regarding the comparative effectiveness of drugs used to treat RA. The report reveals there is still much research to be done concerning the side effects of these agents and their influence in different patient subgroups. To: (a) utilize review findings to make diagnostic and treatment management decisions in clinical practice, (b) inform clinicians on the findings from the updated AHRQ's 2011 comparative effectiveness review on drug therapy for RA in adults, and (c) identify shortcomings in the current research and future directions revealed by the report. Rheumatoid arthritis is a major public health burden. The 2011 updated AHRQ report includes several new medications approved by the FDA since 2007. The review includes 31 head-to-head randomized clinical trials (RCTs), 1 head-to-head nonrandomized controlled trial, 44 placebo controlled trials, 28 meta-analyses or systematic reviews, and 107 observational studies. Most of the studies used for the comparative analysis are of fair quality with an insufficient to moderate strength of evidence assigned to the findings (Table 1). A mixed treatment comparisons (MTC)meta-analysis from the AHRQ report found that the biologic etanercept has a higher probability of improvement in disease activity compared with other biologic DMARDs, but the MTC findings have a low strength of evidence and caution is recommended in the interpretation of this weak evidence. For patients with early RA, limited evidence precludes conclusions about the superiority of one combination therapy versus another. The data are also inconclusive for comparisons of therapeutic similarity among oral DMARDs including the limitation created by differences inmethotrexate (MTX) dosing across trials. Extensive clinical experience over the years support the preferred use of MTX in most patients versus other oral DMARDs as well as its use in multidrug regimens, whereas there is little data on the use of oral DMARDs in combination with biologic agents. The review does not support a specific biologic DMARD over another due to the lack of head-to-head trials comparing these agents using validated RA outcome measures. The data show that the majority of biologics have approximately the same efficacy except for anakinra, which was found to be less effective. The biologic and oral DMARDs are similar in overall tolerability, but several studies suggest that adverse events are more common with biologic DMARDs versus oral DMARDs. Based on limited evidence, the oral DMARDs do not appear to have an increased risk of severe adverse events including cardiovascular events and cancer. Although most studies also found no increased risk of cardiovascular events or cancer with the biologic DMARDs, cohort studies show an increased risk of heart failure with adalimumab, etanercept, and infliximab compared with oral DMARDs. The updated AHRQ review synthesizes the current literature on therapies used for the treatment of RA in adults. The investigators are also able to identify pertinent research gaps in the literature that can be addressed with future research.

Pappas P.G.,University of Alabama at Birmingham
Current Opinion in Infectious Diseases | Year: 2013

PURPOSE OF REVIEW: The recent outbreak of fungal meningitis related to contaminated methylprednisolone acetate injections represents an important cause of morbidity and continues to be a significant public health problem in the United States. RECENT FINDINGS: As of August 2013, there have been 749 cases and 63 deaths in 20 states associated with epidemic fungal meningitis, most of these because of Exserohilum rostratum. Clinical experience in managing these cases has grown dramatically in the last several months; most patients require at least 6 months of antifungal therapy for complicated disease. Most patients are treated with voriconazole, with or without liposomal amphotericin B, for central nervous system and paraspinal complications of the disease. For disease involving the sacroiliac and peripheral joints, voriconazole alone has been preferred. MRI spine imaging has identified several cases of asymptomatic disease, suggesting an aggressive diagnostic approach to exposed asymptomatic patients. Mortality remains low (<10%), but morbidity relating to persistent symptoms and treatment-associated toxicity is high. SUMMARY: The ongoing fungal meningitis epidemic demonstrates an important achievement for the public health community. Important questions remain relating to the diagnosis, management, and long-term outcomes of these patients. Important research questions pertaining to specific risks influencing disease manifestations remain unanswered. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Khashab M.A.,Johns Hopkins Medical Institutions | Varadarajulu S.,University of Alabama at Birmingham
Current Opinion in Gastroenterology | Year: 2012

PURPOSE OF REVIEW: Endoscopic ultrasonography (EUS) has taken on more of a therapeutic role in recent years. This review will focus on the therapeutic applications of EUS. RECENT FINDINGS: Multiple studies on the therapeutic applications of EUS have been published. EUS facilitates endoscopic drainage of pancreatic fluid collections (PFCs) including walled-off pancreatic necrosis, management of refractory gastrointestinal bleeding from gastric varix or vasculature by fine-needle injection and decompression of obstructive pancreatic or biliary ductal systems following failed access by standard endoscopic or radiological techniques. SUMMARY: The indications and role of therapeutic EUS have expanded rapidly in recent years. The procedures can be technically challenging, requiring expertise in both endosonography and endoscopic retrograde cholangiopancreatography. Refinement in echoendoscope design and dedicated accessories are required to further expand the applications of therapeutic EUS. Copyright © Lippincott Williams & Wilkins.

Cui X.,University of Alabama at Birmingham
Applied Immunohistochemistry and Molecular Morphology | Year: 2015

The commonly used Nottingham Grading System in breast cancer takes into consideration the presence of tubular formation, nuclear pleomorphism, and the mitotic index (MI), among which the latter has been shown to be the most powerful prognostic factor. In practice, histologic grading is highly subjective, with only moderate interobserver reproducibility. Phosphorylation of histone H3 has been demonstrated to be a specific event in the mitotic phase, and is negligible during interphase. In this study, we evaluated the efficacy of Phosphohistone H3 (PHH3) in the breast cancer grading of 97 consecutive biopsy specimens. PHH3 antibodies clearly revealed discrete, strong nuclear immunoreactivity in mitotically active cells even under low magnification. The PHH3 MI showed a significant correlation with that derived by hematoxylin and eosin (H&E) staining as well as the Ki-67 proliferation index. Further, the pairwise κ-value of the MI was significantly increased, and the pairwise agreement was also markedly improved by PHH3 immunostaining, although a significant proportion of breast cancer cases were upgraded by use of the PHH3 MI. Our data showed that PHH3 provided a more sensitive and accurate MI with less interobserver variability when compared with conventional H&E staining, thus emphasizing its potentially increased value in practice. Reconsideration of breast cancer grading with integration of PHH3 should be considered if it continues to demonstrate superiorly to traditional H&E staining. © 2015 Lippincott Williams & Wilkins, Inc.

Carvajal R.D.,Sloan Kettering Cancer Center | Spencer S.A.,University of Alabama at Birmingham | Lydiatt W.,University of Nebraska at Omaha
JNCCN Journal of the National Comprehensive Cancer Network | Year: 2012

Mucosal melanoma (MM) is an aggressive and clinically complex malignancy made more challenging by its relative rarity. Because of the rarity of MM as a whole, and because of the unique biology and clinical challenges of MM arising from each anatomic location, understanding of this disease and its optimal management remains limited. The impact of various treatment strategies on disease control and survival has been difficult to assess because of the small size of most reported series of MM arising from any one particular site, the retrospective nature of most series, and the lack of a uniform comprehensive staging system for this disease. This article summarizes the clinical, pathologic, and molecular features, and the diagnostic and therapeutic considerations for the management of MM, underscoring the similarities and differences from cutaneous melanoma. Furthermore, the distinct clinical features and management implications unique to melanoma arising from the mucosal surfaces of the head and neck, the anorectal region, and the female genital tract are highlighted. © JNCCN-Journal of the National Comprehensive Cancer Network.

Richman J.S.,University of Alabama at Birmingham
Methods in Enzymology | Year: 2011

The analysis of large and complex databases poses many challenges. Such databases arise in health-services, electronic medical records, insurance, and other commercial data sources where both the number of observations and variables can be enormous. The problems are particularly acute in genomics and proteomics where the number of variables is typically much higher than the number of observations. Extant methods seek to balance the demands of making efficient use of the data with the need to maintain the flexibility required to detect complex relationships and interactions. To overcome some limitations of current methods, a novel analytical tool, Multivariate Neighborhood Sample Entropy (MN-SampEn) is introduced. It is a generalization of Sample Entropy to multivariate data that inherits many of Sample Entropy's desirable properties. In principle, it selects significant covariates without reference to an underlying model and provides predictions similar to those of k-Nearest-Neighbor methods, with fewer covariates required. However, adaptation to multivariate data requires that several additional optimization issues be addressed. Several optimization strategies are discussed and tested on a set of MALDI mass spectra. With some optimization strategies, MN-SampEn identified a reduced set of covariates and exhibited lower predictive error rates than k-Nearest Neighbors. © 2011 Elsevier Inc.

Esposito M.,Free University of Colombia | Kawai R.,University of Alabama at Birmingham | Lindenberg K.,University of California at San Diego | Van Den Broeck C.,Hasselt University
Physical Review Letters | Year: 2010

We study the efficiency at maximum power, η*, of engines performing finite-time Carnot cycles between a hot and a cold reservoir at temperatures Th and Tc, respectively. For engines reaching Carnot efficiency ηC=1-Tc/Th in the reversible limit (long cycle time, zero dissipation), we find in the limit of low dissipation that η* is bounded from above by ηC/(2-ηC) and from below by ηC/2. These bounds are reached when the ratio of the dissipation during the cold and hot isothermal phases tend, respectively, to zero or infinity. For symmetric dissipation (ratio one) the Curzon-Ahlborn efficiency ηCA=1-√Tc/Th is recovered.

Bolger G.B.,University of Alabama at Birmingham
Cellular Signalling | Year: 2015

PDE4 family cAMP-selective cyclic nucleotide phosphodiesterases are important in the regulation of cAMP abundance in numerous systems, and thereby play an important role in the regulation of PKA and EPAC activity and the phosphorylation of CREB. We have used the yeast 2-hybrid system to demonstrate recently that long PDE4 isoforms form homodimers, consistent with data obtained recently by structural studies. The long PDE4 isoform PDE4D5 interacts selectively with β-arrestin2, implicated in the regulation of G-protein-coupled receptors and other cell signaling components, and also with the β-propeller protein RACK1. In the present study, we use 2-hybrid approaches to demonstrate that RACK1 and β-arrestin2 inhibit the dimerization of PDE4D5. We also show that serine-to-alanine mutations at PKA and ERK1/2 phosphorylation sites on PDE4D5 detectably ablate dimerization. Conversely, phospho-mimic serine-to-aspartate mutations at the MK2 and oxidative stress kinase sites ablate dimerization. Analysis of PDE4D5 that is locked into the dimeric configuration by the formation of a trans disulfide bond between Ser261 and Ser602 shows that RACK1 interacts strongly with both the monomeric and dimeric forms, but that β-arrestin2 interacts exclusively with the monomeric form. This is consistent with the concept that β-arrestin2 can preferentially recruit the monomeric, or "open," form of PDE4D5 to β2-adrenergic receptors, where it can regulate cAMP signaling. © 2015 Elsevier Inc.

Elewski B.E.,University of Alabama at Birmingham
Expert Review of Dermatology | Year: 2013

Onychomycosis is a common nail infection for which treatment options are limited, and no new treatment have been introduced for over 10 years. While patients might prefer a topical therapy, efficacy with ciclopirox and amorolfine lacquers has been disappointing especially in moderate to severe disease. Efinaconazole 10% solution is a new triazole antifungal, specifically developed for the topical treatment of onychomycosis. Its physicochemical properties, antifungal activity and formulation are all important aspects of the development program and are reviewed here. Efinaconazole 10% solution may provide the first viable alternative to oral therapy for onychomycosis. Mycologic cure rates are comparable to those seen with oral itraconazole, and greater than reported with ciclopirox lacquer. © 2013 Informa UK Ltd.

Morrow D.R.,University of Alabama at Birmingham
Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences | Year: 2014

Many commentators fear that climate engineering research might lead policy-makers to reduce mitigation efforts. Most of the literature on this so-called 'moral hazard' problem focuses on the prediction that climate engineering research would reduce mitigation efforts. This paper focuses on a related ethical question: Why would it be a bad thing if climate engineering research obstructed mitigation? If climate engineering promises to be effective enough, it might justify some reduction in mitigation. Climate policy portfolios involving sufficiently large or poorly planned reductions inmitigation, however, could lead to an outcome that would be worse than the portfolio that would be chosen in the absence of further climate engineering research. This paper applies three ethical perspectives to describe the kinds of portfolios that would be worse than that 'baseline portfolio'. The literature on climate engineering identifies various mechanisms that might cause policy-makers to choose these inferior portfolios, but it is difficult to know in advance whether the existence of these mechanisms means that climate engineering research really would lead to a worse outcome. In the light of that uncertainty, a precautionary approach suggests that researchers should take measures to reduce the risk of mitigation obstruction. Several such measures are suggested. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Higgins N.P.,University of Alabama at Birmingham
Current Opinion in Microbiology | Year: 2014

Most bacterial chromosomes and plasmids are covalently closed circular molecules that are maintained in a dynamic supercoiled state. Average supercoil density differs significantly between Escherichia coli and Salmonella. Two related questions are: What protein(s) create supercoil domain boundaries in a bacterial chromosome? and How is supercoil density regulated in different bacterial species? RNA polymerase plays pivotal roles in both of these topological phenomena. © 2014 Published by Elsevier Ltd.

Limdi N.A.,University of Alabama at Birmingham | Veenstra D.L.,University of Washington
Journal of Clinical Epidemiology | Year: 2010

In this review, we discuss the potential expectations, validity, predictive ability, and reality of pharmacogenetics in (1) titration of medication dose, (2) prediction of intended (efficacy) drug response, and (3) dose prediction of unintended (adverse) drug response. We expound on what these potential genetic predictors tell us and, more importantly, what they cannot tell us. Although pharmacogenetic markers have been hailed as promising tools, these proclamations are based mainly on associations rather than their evaluation as predictors. To put the expectations of the promise of pharmacogenetics in a realistic perspective, we review three examples. First, warfarin pharmacogenetics, wherein although the validity of the genetic variant dose is established and there is a validity of genetic variant-hemorrhage association, the clinical utility of testing is not clear. Second, the strong and clinically relevant HLA-Stevens-Johnson syndrome/toxic epidermal necrolysis association highlights the role of ethnicity. Third, the influence of CYP2D6 on tamoxifen efficacy, a model candidate with potential clinical utility but unclear validity. These examples highlight both the challenges and opportunities of pharmacogenomics. First, establishing a valid association between a genetic variation and drug response; second, doing so for a clinically meaningful outcome; and third, providing solid evidence or rationale for improvement in patient outcomes compared with current standard of care. © 2010 Elsevier Inc. All rights reserved.

Wood A.C.,University of Alabama at Birmingham | Neale M.C.,Virginia Commonwealth University
Journal of the American Academy of Child and Adolescent Psychiatry | Year: 2010

Objective: To describe the utility of twin studies for attention-deficit/ hyperactivity disorder (ADHD) research and demonstrate their potential for the identification of alternative phenotypes suitable for genomewide association, developmental risk assessment, treatment response, and intervention targets. Method: Brief descriptions of the classic twin study and genetic association study methods are provided, with illustrative findings from ADHD research. Biometrical genetics refers to the statistical modeling of data gathered from one or more group of known biological relation; it was apparently coined by Francis Galton in the 1860s and led to the "Biometrical School" at the University of London. Twin studies use genetic correlations between pairs of relatives, derived using this theoretical framework, to parse the individual differences in a trait into latent (unmeasured) genetic and environmental influences. This method enables the estimation of heritability, i.e., the percentage of variance due to genetic influences. It is usually implemented with a method called structural equation modeling, which is a statistical technique for fitting models to data, typically using maximum likelihood estimation. Genetic association studies aim to identify those genetic variants that account for the heritability estimated in twin studies. Measurements other than those used for the clinical diagnosis of the disorder are popular phenotype choices in current ADHD research. It is argued that twin studies have great potential to refine phenotypes relevant to ADHD. Results: Prior studies have consistently found that the majority of the variance in ADHD symptoms is due to genetic factors. To date, genomewide association studies of ADHD have not identified replicable associations that account for the heritable variation. Possibly, the application of genomewide association studies to these alternative phenotypic measurements will assist in identifying the pathways from genetic variants to ADHD. Conclusion: Power to detect associations should be improved by the study of highly heritable endophenotypes for ADHD and by reducing the number of phenotypes to be considered. Therefore, twin studies are an important research tool in the development of endophenotypes, defined as alternative, more highly heritable traits that act at earlier stages of the pathway from genes to behavior. Although genetic variation in liability to ADHD is likely polygenic, the proposed approach should help to identify improved alternative measurements for genetic association studies. © 2010 American Academy of Child and Adolescent Psychiatry.

Morgan D.E.,University of Alabama at Birmingham
Radiologic Clinics of North America | Year: 2012

Pancreatic surgery, until the Whipple era in the early 1900s, was once regarded as calamitous by most surgeons. With advances in surgical techniques, operative mortality has been greatly reduced, although morbidity remains a significant problem. Knowledge of the surgical options for treatment of pancreatic neoplastic and inflammatory disease is important for the practicing radiologist, to anticipate and identify complications commonly sought and well depicted with imaging. © 2012 Elsevier Inc.

Thannickal V.J.,University of Alabama at Birmingham
Biogerontology | Year: 2013

Our understanding of the biology of aging has advanced significantly in recent years. This has resulted in the recent formulation of the "hallmarks of aging" that include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease that results from the accumulation of scar tissue in the lungs of affected individuals. IPF is a disease of aging that most commonly affects human subjects older than 60 years of age. While progress has been made in elucidating key pathological processes in IPF, the relationship of these processes to those that occur during aging are not well defined. In this review, we explore existing and emerging paradigms in the pathogenesis of IPF in light of the recently defined hallmarks of aging. © 2013 Springer Science+Business Media Dordrecht.

Manicklal S.,University of Cape Town | Emery V.C.,University College London | Lazzarotto T.,University of Bologna | Boppana S.B.,University of Alabama at Birmingham | Gupta R.K.,University College London
Clinical Microbiology Reviews | Year: 2013

Human cytomegalovirus (CMV) is a leading cause of congenital infections worldwide. In the developed world, following the virtual elimination of circulating rubella, it is the commonest nongenetic cause of childhood hearing loss and an important cause of neurodevelopmental delay. The seroprevalence of CMV in adults and the incidence of congenital CMV infection are highest in developing countries (1 to 5% of births) and are most likely driven by nonprimary maternal infections. However, reliable estimates of prevalence and outcome from developing countries are not available. This is largely due to the dogma that maternal preexisting seroimmunity virtually eliminates the risk for sequelae. However, recent data demonstrating similar rates of sequelae, especially hearing loss, following primary and nonprimary maternal infection have underscored the importance of congenital CMV infection in resource-poor settings. Although a significant proportion of congenital CMV infections are attributable to maternal primary infection in well-resourced settings, the absence of specific interventions for seronegative mothers and uncertainty about fetal prognosis have discouraged routine maternal antibody screening. Despite these challenges, encouraging results from prototype vaccines have been reported, and the first randomized phase III trials of prenatal interventions and prolonged postnatal antiviral therapy are under way. Successful implementation of strategies to prevent or reduce the burden of congenital CMV infection will require heightened global awareness among clinicians and the general population. In this review, we highlight the global epidemiology of congenital CMV and the implications of growing knowledge in areas of prevention, diagnosis, prognosis, and management for both low (50 to 70%)- and high (>70%)-seroprevalence settings. © 2013, American Society for Microbiology. All Rights Reserved.

In this study, we have developed a SYBR Green I-based real-time multiplexed PCR assay for the detection of Vibrio parahaemolyticus in Gulf of Mexico water (gulf water), artificially seeded and natural oysters targeting three hemolysin genes, tlh, tdh and trh in a single reaction. Post-amplification melt-temperature analysis confirmed the amplification of all three targeted genes with high specificity. The detection sensitivity was 10 cfu (initial inoculum) in 1 ml of gulf water or oyster tissue homogenate, following 5 h enrichment. The results showed 58% of the oysters to be positive for tlh, indicating the presence of V. parahaemolyticus; of which 21% were positive for tdh; and 0.7% for trh, signifying the presence of pathogenic strains. The C(t) values showed that oyster tissue matrix had some level of inhibition, whereas the gulf water had negligible effect on PCR amplification. The assay was rapid (approximately 8 h), specific and sensitive, meeting the ISSC guidelines. Rapid detection using real-time multiplexed PCR will help reduce V. parahaemolyticus-related disease outbreaks, thereby increasing consumer confidence and economic success of the seafood industry.

Goodin B.R.,University of Alabama at Birmingham
Clinical Journal of Pain | Year: 2014

OBJECTIVES:: This study examined whether the administration of intranasal oxytocin was associated with pain sensitivity, endogenous pain inhibitory capacity, and negative mood states.METHODS:: A total of 30 pain-free, young adults each completed three laboratory sessions on consecutive days. The first session (baseline) assessed ischemic pain sensitivity, endogenous pain inhibition via conditioned pain modulation (CPM), and negative mood using the Profile of Mood States (POMS). CPM was tested on the dominant forearm and ipsilateral masseter muscle using algometry (test stimulus) and the cold pressor task (conditioning stimulus; non-dominant hand). For the second and third sessions, participants initially completed the State-Trait Anxiety Inventory (STAI) and then self-administered a single (40IU/1 mL) dose of intranasal oxytocin or placebo in a randomized counter-balanced order. Thirty minutes post-administration, participants again completed the STAI and repeated assessments of ischemic pain sensitivity and CPM followed by the POMS.RESULTS:: Findings demonstrated that ischemic pain sensitivity did not significantly differ across the three study sessions. CPM at the masseter, but not the forearm, was significantly greater following administration of oxytocin compared to placebo. Negative mood was also significantly lower following administration of oxytocin compared to placebo. Similarly, anxiety significantly decreased following administration of oxytocin but not placebo.DISCUSSION:: This study incorporated a placebo-controlled, double-blind, within-subjects crossover design with randomized administration of intranasal oxytocin and placebo. The data suggest that the administration of intranasal oxytocin may augment endogenous pain inhibitory capacity and reduce negative mood states including anxiety. © 2014 by Lippincott Williams & Wilkins

BACKGROUND:: Subthalamic nucleus (STN) deep brain stimulation is a successful intervention for medically refractory Parkinson disease, although its efficacy depends on optimal electrode placement. Even though the predominant effect is observed contralaterally, modest improvements in ipsilateral and midline symptoms are also observed.OBJECTIVE:: To elucidate the role of contact location of unilateral deep brain stimulation on contralateral, ipsilateral, and axial subscores of Parkinson disease motor symptoms.METHODS:: Eighty-six patients receiving first deep brain stimulation STN electrode placements were identified, yielding 73 patients with 3-month follow-up. Total preoperative and postoperative Unified Parkinson Disease Rating Scale Part III scores were obtained and divided into contralateral, ipsilateral, and midline subscores. Contact location was determined on immediate postoperative magnetic resonance imaging. A3-dimensional ordinary “kriging” algorithm generated spatial interpolations for total, ipsilateral, contralateral, and midline symptom categories. Interpolative reconstructions were performed in the axial planes (z = −0.5, −1.0, −1.5, −3.5, −4.5, −6.0) and a sagittal plane (x = 12.0). Interpolation error and significance were quantified by use of a cross-validation technique and quantile-quantile analysis.RESULTS:: There was an overall reduction in Unified Parkinson Disease Rating Scale Part III symptoms: total = 37.0 ± 24.11% (P < .05), ipsilateral = 15.9 ± 51.8%, contralateral = 56.2 ± 26.8% (P < .05), and midline = 26.5 ± 34.7%. Kriging interpolation was performed and cross-validated with quantile-quantile analysis with high correlation (R > 0.92) and demonstrated regions of efficacy for each symptom category. Contralateral symptoms demonstrated broad regions of efficacy across the peri-STN area. The ipsilateral and midline regions of efficacy were constrained and located along the dorsal STN and caudal zona incerta.CONCLUSION:: We provide evidence for a unique functional topographic window in which contralateral, ipsilateral, and midline structures may achieve the best efficacy. Although there are overlapping regions, laterality demonstrates distinct topographies. Surgical optimization should target the intersection of optimal regions for these symptom categories.ABBREVIATIONS:: AC, anterior commissureDBS, deep brain stimulationPC, posterior commissureROE, region of efficacySTN, subthalamic nucleusSW, Schaltenbrand-WahrenUPDRS, Unified Parkinson Disease Rating Scale Copyright © by the Congress of Neurological Surgeons

Patel D.M.,University of Alabama at Birmingham
Neurosurgery | Year: 2015

BACKGROUND:: Although numerous studies have focused on the efficacy of deep brain stimulation (DBS) for movement disorders, less is known about surgical adverse events, especially over longer time intervals.OBJECTIVE:: Here, we analyze adverse events in 510 consecutive cases from a tertiary movement disorders center at up to 10 years postoperatively.METHODS:: We conducted a retrospective review of adverse events from craniotomies between January 2003 and March 2013. The adverse events were categorized into 2 broad categories—immediate perioperative and time-dependent postoperative events.RESULTS:: Across all targets, perioperative mental status change occurred in 18 (3.5%) cases, and symptomatic intracranial hemorrhage occurred in 4 (0.78%) cases. The most common hardware-related event was skin erosion in 13 (2.5%) cases. The most frequent stimulation-related event was speech disturbance in 16 (3.1%) cases. There were no significant differences among surgical targets with respect to the incidence of these events. Time-dependent postoperative events leading to the revision of a given DBS electrode for any reason occurred in 4.7% ± 1.0%, 9.3% ± 1.4%, and 12.4% ± 1.5% of electrodes at 1, 4, and 7 years postoperatively, respectively. Staged bilateral DBS was associated with approximately twice the risk of repeat surgery for electrode replacement vs unilateral surgery (P = .020).CONCLUSION:: These data provide low incidences for adverse events in a large series of DBS surgeries for movement disorders at up to 10 years follow-up. Accurate estimates of adverse events will better inform patients and caregivers about the potential risks and benefits of surgery and provide normative data for process improvement.ABBREVIATIONS:: DBS, deep brain stimulationGPI, globus pallidus internaICH, intracranial hemorrhageIPG, implanted pulse generatorMER, microelectrode recordingPD, Parkinson diseaseSTN, subthalamic nucleusVIM, ventral intermediate thalamus Copyright © by the Congress of Neurological Surgeons

Hurst D.R.,University of Alabama at Birmingham | Welch D.R.,University of Kansas
FEBS Letters | Year: 2011

Expression of BRMS1 causes dramatic suppression of metastasis in multiple in vivo model systems. As we gain further insight into the biochemical mechanisms of BRMS1, we appreciate the importance of both molecular and cellular context for functional metastasis suppression. BRMS1 associates with large chromatin remodeling complexes including SIN3:HDAC which are powerful epigenetic regulators of gene expression. Additionally, BRMS1 inhibits the activity of NFκB, a well-known transcription factor that plays significant roles in tumor progression. Moreover, BRMS1 coordinately regulates the expression of metastasis-associated microRNA known as metastamir. How these biochemical mechanisms and biological pathways are linked, either directly or indirectly, and the influence of molecular and cellular context, are critical considerations for the discovery of novel therapeutic targets for the most deadly aspect of tumor progression-metastasis. © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Friedland B.A.,University of Alabama at Birmingham
Journal of Acquired Immune Deficiency Syndromes | Year: 2016

OBJECTIVE:: To evaluate the safety and pharmacokinetics (PK) of MIV-150 and zinc acetate in a carrageenan gel (PC-1005). Acceptability, adherence, and pharmacodynamics (PD) were also explored. DESIGN:: A 3-day open label safety run-in (n=5) preceded a placebo-controlled, double-blind trial in healthy, HIV-negative, abstinent women randomized (4:1) to vaginally apply 4 mL of PC-1005 or placebo once daily for 14d. METHODS:: Assessments included physical exams, safety labs, colposcopy, biopsies, cervicovaginal lavages (CVLs), and behavioral questionnaires. MIV-150 (plasma, CVL, tissue), zinc (plasma, CVL), and carrageenan (CVL) concentrations were determined with LCMS-MS, ICP-MS, and ELISA, respectively. CVL antiviral activity was measured using cell-based assays. Safety, acceptability and adherence were analyzed descriptively. PK parameters were calculated using non-compartmental techniques and actual sampling times. CVL antiviral EC50 values were calculated using a dose-response inhibition analysis. RESULTS:: Participants (n=20) ranged from 19-44 years old; 52% were Black or African American. Among those completing the trial (13/17, PC-1005; 3/3, placebo), 11/17 reported liking the gel overall; 7 recommended reducing the volume. Adverse events, which were primarily mild and/or unrelated, were comparable between groups. Low systemic MIV-150 levels were observed, without accumulation. Plasma zinc levels were unchanged from baseline. 7/7 CVLs collected 4h post-dose demonstrated antiviral (HIV, HPV) activity. High baseline CVL anti-HSV-2 activity precluded assessment of post-dose activity. CONCLUSION:: PC-1005 used vaginally for 14d was well-tolerated. Low systemic levels of MIV-150 were observed. Plasma zinc levels were unchanged. Post-dose CVLs had anti-HIV and anti-HPV activity. These data warrant further development of PC-1005 for HIV and STI prevention. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

Low antihypertensive medication adherence is common. During recent years, the impact of low medication adherence on increased morbidity and healthcare costs has become more recognized, leading to interventions aimed at improving adherence. We analyzed a 5% sample of Medicare beneficiaries initiating antihypertensive medication between 2007 and 2012 to assess whether reductions occurred in discontinuation and low adherence. Discontinuation was defined as having no days of antihypertensive medication supply for the final 90 days of the 365 days after initiation. Low adherence was defined as having a proportion of days covered <80% during the 365 days after initiation among beneficiaries who did not discontinue treatment. Between 2007 and 2012, 41 135 Medicare beneficiaries in the 5% sample initiated antihypertensive medication. Discontinuation was stable during the study period (21.0% in 2007 and 21.3% in 2012; P-trend=0.451). Low adherence decreased from 37.4% in 2007 to 31.7% in 2012 (P-trend<0.001). After multivariable adjustment, the relative risk of low adherence for beneficiaries initiating treatment in 2012 versus in 2007 was 0.88 (95% confidence interval, 0.83–0.92). Low adherence was more common among racial/ethnic minorities, beneficiaries with Medicaid buy-in (an indicator of low income), and those with polypharmacy, and was less common among females, beneficiaries initiating antihypertensive medication with multiple classes or a 90-day prescription fill, with dementia, a history of stroke, and those who reached the Medicare Part D coverage gap in the previous year. In conclusion, low adherence to antihypertensive medication has decreased among Medicare beneficiaries; however, rates of discontinuation and low adherence remain high. © 2016 American Heart Association, Inc

Jacobs B.A.,University of Texas at Dallas | Copes H.,University of Alabama at Birmingham
British Journal of Criminology | Year: 2015

Prior research suggests that serious predatory offenders are sufficiently committed to illicit conduct that they must neutralize good behaviour, rather than bad behaviour. Drawing from a sample of offenders who commit carjacking, we question that assumption. Specifically, our data reveal the manner in which such offenders neutralize bad conduct without meaningfully drifting. The notion of 'neutralization without drift' represents a theoretical refinement of neutralization theory and an extension of core conceptualization in the interpretation of criminal commitment. Through this concept, we attempt to make sense of how persistent predatory offenders who commit carjacking are able to embrace aggression, explain that it's not 'really them', neutralize bad rather than good conduct, yet retain their status as committed criminals. © 2014 The Author.

Turan J.M.,University of Alabama at Birmingham | Nyblade L.,Rti International
AIDS and Behavior | Year: 2013

The global community has set goals of virtual elimination of new child HIV infections and 50 percent reduction in HIV-related maternal mortality by the year 2015. Although much progress has been made in expanding prevention of mother-to-child transmission (PMTCT) services, there are serious challenges to these global goals, given low rates of utilization of PMTCT services in many settings. We reviewed the literature from low-income settings to examine how HIV-related stigma affects utilization of the series of steps that women must complete for successful PMTCT. We found that stigma negatively impacts service uptake and adherence at each step of this "PMTCT cascade". Modeling exercises indicate that these effects are cumulative and therefore significantly affect rates of infant HIV infection. Alongside making clinical services more available, effective, and accessible for pregnant women, there is also a need to integrate stigma-reduction components into PMTCT, maternal, neonatal, and child health services. © 2013 Springer Science+Business Media New York.

Goss A.M.,University of Alabama at Birmingham
Obesity (Silver Spring, Md.) | Year: 2013

Qualitative aspects of diet may affect body composition and propensity for weight gain or loss. We tested the hypothesis that consumption of a relatively low glycemic load (GL) diet would reduce total and visceral adipose tissue under both eucaloric and hypocaloric conditions. Participants were 69 healthy overweight men and women. Body composition was assessed by DXA and fat distribution by CT scan at baseline, after 8 weeks of a eucaloric diet intervention, and after 8 weeks of a hypocaloric (1000 kcal/day deficit) diet intervention. Participants were provided all food for both phases, and randomized to either a low GL diet (<45 points per 1000 kcal; n = 40) or high GL diet (>75 points per 1000 kcal, n = 29). After the eucaloric phase, participants who consumed the low GL diet had 11% less intra-abdominal fat (IAAT) than those who consumed the high GL diet (P < 0.05, adjusted for total fat mass and baseline IAAT). Participants lost an average of 5.8 kg during the hypocaloric phase, with no differences in the amount of weight loss with diet assignment (P = 0.39). Following weight loss, participants who consumed the low GL diet had 4.4% less total fat mass than those who consumed the high GL diet (P < 0.05, adjusted for lean mass and baseline fat mass). Consumption of a relatively low GL diet may affect energy partitioning, both inducing reduction in IAAT independent of weight change, and enhancing loss of fat relative to lean mass during weight loss. Copyright © 2012 The Obesity Society.

Neurodevelopmental disorders are a large family of conditions of genetic or environmental origin that are characterized by deficiencies in cognitive and behavioral functions. The therapeutic management of individuals with these disorders is typically complex and is limited to the treatment of specific symptoms that characterize each disorder. The neurodevelopmental disorder Rett syndrome (RTT) is the leading cause of severe intellectual disability in females. Mutations in the gene encoding the transcriptional regulator methyl-CpG-binding protein 2 (MECP2), located on the X chromosome, have been confirmed in more than 95% of individuals meeting diagnostic criteria for classical RTT. RTT is characterized by an uneventful early infancy followed by stagnation and regression of growth, motor, language, and social skills later in development. This review will discuss the genetics, pathology, and symptoms that distinguish RTT from other neurodevelopmental disorders associated with intellectual disability. Because great progress has been made in the basic and clinical science of RTT, the goal of this review is to provide a thorough assessment of current pharmacotherapeutic options to treat the symptoms associated with this disorder. Furthermore, we will highlight recent discoveries made with novel pharmacological interventions in experimental preclinical phases, and which have reversed pathological phenotypes in mouse and cell culture models of RTT and may result in clinical trials.

Beukelman T.,University of Alabama at Birmingham
F1000Prime Reports | Year: 2014

Systemic juvenile idiopathic arthritis (JIA) is an autoinflammatory condition that is distinct from other forms of childhood arthritis. Recently, biologic agents that specifically inhibit the cytokines interleukin (IL)-1 and IL-6 have demonstrated remarkable clinical effectiveness and confirmed the importance of these cytokines in the disease process. Future studies are likely to optimize the care of children with systemic arthritis and further elucidate the disease pathogenesis. © 2014 Faculty of 1000 Ltd.

Bell D.S.H.,University of Alabama at Birmingham
Diabetes, Obesity and Metabolism | Year: 2013

The majority of patients with type 2 diabetes mellitus (T2DM) do not achieve the glycaemic goals recommended by leading diabetes organizations using monotherapy alone, and often require multiple antihyperglycaemic agents to achieve glycaemic control. Fixed-dose combination (FDC) therapies offer a means to simplify complex treatment regimens, and have several advantages that help patients reach their glycaemic goals. In this review, four key benefits are identified and discussed in support of FDCs for treatment of patients with T2DM: (i) Greater efficacy compared with higher dose monotherapy, (ii) Reduced risk of adverse reactions relative to higher dose monotherapy, (iii) Lower overall costs and (iv) Improved medication concordance. Given these advantages, the place of fixed combination therapy in the course of treatment is discussed. Establishing a therapeutic strategy that incorporates fixed combination therapy (including combinations with insulin) will simplify the treatment of diabetes, ideally resulting in improved medication concordance, clinical outcomes and quality of life for patients with T2DM. © 2012 Blackwell Publishing Ltd.

Stepanikova I.,University of Alabama at Birmingham
Journal of Health and Social Behavior | Year: 2012

This study examined two types of potential sources of racial-ethnic disparities in medical care: implicit biases and time pressure. Eighty-one family physicians and general internists responded to a case vignette describing a patient with chest pain. Time pressure was manipulated experimentally. Under high time pressure, but not under low time pressure, implicit biases regarding blacks and Hispanics led to a less serious diagnosis. In addition, implicit biases regarding blacks led to a lower likelihood of a referral to specialist when physicians were under high time pressure. The results suggest that when physicians face stress, their implicit biases may shape medical decisions in ways that disadvantage minority patients. © American Sociological Association 2012.

Hook III E.W.,University of Alabama at Birmingham
American Journal of the Medical Sciences | Year: 2012

Emerging data suggest that males and females differ in important ways in terms of their biological risks for STD acquisition, the clinical manifestation of infection when present and their behavioral likelihood of both acquiring and transmitting STDs. Clinicians will benefit from being aware that women in particular who acquire STDs may not do so because they have had large numbers of sexual partners but may in fact be infected as a result of their sexual partners' behaviors. Thus, these data have implications both for routine screening in women and for men with and at risk for STDs. Copyright © by the Southern Society for Clinical Investigation.

Prevelige P.E.,University of Alabama at Birmingham | Fane B.A.,University of Arizona
Advances in Experimental Medicine and Biology | Year: 2012

For a machine to function, it must first be assembled. The morphogenesis of the simplest icosahedral virus would require only 60 copies of a single capsid protein to coalesce. If the capsid protein's structure could be entirely dedicated to this endeavor, the morphogenetic mechanism would be relatively uncomplicated. However, capsid proteins have had to evolve other functions, such as receptor recognition, immune system evasion, and the incorporation of other structure proteins, which can detract from efficient assembly. Moreover, evolution has mandated that viruses obtain additional proteins that allow them to adapt to their hosts or to more effectively compete in their respective niches. Consequently, genomes have increased in size, which has required capsids to do likewise. This, in turn, has lead to more complex icosahedral geometries. These challenges have driven the evolution of scaffolding proteins, which mediate, catalyze, and promote proper virus assembly. The mechanisms by which these proteins perform their functions are discussed in this review. © 2012 Springer Science+Business Media, LLC.

Luo M.,University of Alabama at Birmingham
Advances in Experimental Medicine and Biology | Year: 2012

As all the enveloped viruses, the entry of influenza viruses includes a number of steps in host cell infection. This chapter summarizes the current knowledge of the entry pathway and the role of the fusion protein of influenza virus, hemagglutinin, in this process. Hemagglutinin (HA) is a trimeric glycoprotein that is present in multiple copies in the membrane envelope of influenza virus. HA contains a fusion peptide, a receptor binding site, a metastable structural motif, and the transmembrane domain. The first step of influenza virus entry is the recognition of the host cell receptor molecule, terminal α-sialic acid, by HA. This multivalent attachment by multiple copies of trimetric HA triggers endocytosis of influenza virus that is contained in the endosome. The endosome-trapped virus traffics via a unidirectional pathway to near the nucleus. At this location, the interior pH of the endosome becomes acidic that induces a dramatic conformational change in HA to insert the fusion peptide into the host membrane, induce juxtaposition of the two membranes, and form a fusion pore that allows the release of the genome segments of influenza virus. HA plays a key role in the entire entry pathway. Inhibitors of virus entry are potentially effective antiviral drugs of influenza viruses. © 2012 Springer Science+Business Media, LLC.

Wang G.,University of Alabama at Birmingham | Wang G.,University of Nevada, Reno
Journal of Biological Chemistry | Year: 2010

The unique regulatory (R) domain differentiates the human CFTR channel from other ATP-binding cassette transporters and exerts multiple effects on channel function. However, the underlying mechanisms are unclear. Here, an intracellular high affinity (2.3 × 10-19 M) Fe3+ bridge is reported as a novel approach to regulating channel gating. It inhibited CFTR activity by primarily reducing an open probability and an opening rate, and inhibition was reversed by EDTA and phenanthroline. His-950, His-954, Cys-832, His-775, and Asp-836 were found essential for inhibition and phosphorylated Ser-768 may enhance Fe3+ binding. More importantly, inhibition by Fe3+ was state-dependent. Sensitivity to Fe 3+ was reduced when the channel was locked in an open state by AMP-PNP. Similarly, a K978C mutation from cytoplasmic loop 3 (CL3), which promotes ATP-independent channel opening, greatly weakened inhibition by Fe 3+ no matter whether NBD2 was present or not. Therefore, although ATP binding-induced dimerization of NBD1-NBD2 is required for channel gating, regulation of CFTR activity by Fe3+ may involve an interaction between the R domain and CL3. These findings may support proximity of the R domain to the cytoplasmic loops. They also suggest that Fe3+ homeostasis may play a critical role in regulating pathophysiological CFTR activity because dysregulation of this protein causes cystic fibrosis, secretary diarrhea, and infertility. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.

Walters B.C.,University of Alabama at Birmingham
Neurosurgery | Year: 2013

Efforts on the part of neurosurgical specialty societies to remain involved and active in the development of practice recommendations are commendable and completely necessary. The development of practice policies for control of healthcare costs is not a new movement and has been gaining momentum over the last 20 years. In 1990, David Eddy described the (then) recent changes in the view and use of practice policies22. © 2013 by the Congress of Neurological Surgeons.

Whitley R.J.,University of Alabama at Birmingham
Clinics in Perinatology | Year: 2012

Parenteral therapy of viral infections of the newborn and infant began with vidarabine (adenine arabinoside) for the treatment of neonatal herpes simplex virus (HSV) infections in the early 1980s. Acyclovir has become the treatment of choice for neonatal HSV infections and a variety of other herpesvirus infections. Ganciclovir is beneficial for the treatment of congenital cytomegalovirus (CMV) infections involving the central nervous system (CNS). This article reviews the use of acyclovir and ganciclovir in the treatment of neonatal HSV and congenital CMV infections. A brief summary precedes a detailed discussion of available established and alternative therapeutics. © 2012 Elsevier Inc.

Brown A.T.,University of Alabama at Birmingham
Tennessee medicine : journal of the Tennessee Medical Association | Year: 2013

More than 22 million Americans are living with addiction, including nearly seven million who misuse prescription medications. However, most medical schools and residency programs provide little to no education addressing alcohol and drug addiction. Implementation of a new addiction medicine curriculum at a single internal medicine program provided an opportunity for knowledge assessment in a select population of health professionals. We hypothesized that knowledge of addiction medicine would not differ by training level or geographical location of medical school, but that knowledge would improve following a structured curriculum. Study participants included internal medicine and transitional year residents, as well as a group of medical students who were enrolled in a single internal medicine program at the time of the didactic series. A pre-test was administered prior to a four-week structured curriculum. The topics addressed included but were not limited to: 1) an overview of addiction, 2) opioids and chronic pain, 3) benzodiazepines and illicit stimulants, and 4) alcohol. A panel discussion was convened at the end of the fourth session. Following participation in the symposium, participants completed an online post-test. ANOVA was used to compare means. Paired t-tests were used to compare pre-test and post-test scores. 36 of 44 eligible medical students and residents completed the pre-test. Mean pre-test percentage scores were 64 percent for fourth year medical students and 62.5 percent for all residents. For residents, U.S. medical school trainees answered 65 percent of the pre-test questions correctly, versus 58.6 percent correct responses among their international medical graduate peers. No inter-group differences were statistically significant. Of the 36 participants, 20 completed both pre-tests and post-tests. The mean post-test score of 68.75 percent was higher than the mean pre-test score of 61.75 percent, p = 0.009. Knowledge of addiction medicine can be improved for medical students and residents in an academic medicine department. Significant improvements were observed following completion of eight hours of interactive didactics.

Morgan D.E.,University of Alabama at Birmingham
Abdominal Imaging | Year: 2014

Although conceived of in the 1970s, practical use of dual-energy CT in the clinical setting did not come to fruition until 2006, and since that time an ever expanding exploration of the technology has been underway. This article will discuss technical aspects of the two commercially available CT scanners, review the recent literature, and provide an organ-based description of abdominal dual-energy CT applications for the practicing radiologist. © 2013 Springer Science+Business Media New York.

Kang H.S.,Chung - Ang University | Moneyham L.,University of Alabama at Birmingham
Vaccine | Year: 2010

This study examined the relationships between attitudes toward and intention to receive the human papilloma virus (HPV) vaccination and intention to use condoms in a sample of female Korean college students. The data were collected in 2008 using a survey administered to a convenience sample of 1359 female Korean college students. Despite the availability of the HPV vaccine in South Korea, many college-age females are not being vaccinated. Attitudes towards the HPV vaccine appear to be an important contributing factor in vaccination, underscoring the need to make information widely available, to promote HPV vaccination, and to help women make informed decisions. © 2009 Elsevier Ltd. All rights reserved.

Ponce B.A.,University of Alabama at Birmingham
The Journal of bone and joint surgery. American volume | Year: 2013

Proximal humeral fractures that are treated with locked plate constructs remain susceptible to collapse into a varus position. The objectives of the present study were to examine how medial comminution affects fracture stability and to determine the effect of calcar fixation on osteosynthesis stability. Eleven matched pairs of cadaveric humeri were osteotomized to create standard three-part fractures involving the surgical neck and the greater tuberosity. Five matched pairs were randomly assigned to have the medial calcar region remain intact. Six matched pairs had removal of a 10-mm medially based wedge of bone to simulate medial comminution. All fractures were stabilized in a uniform fashion with a proximal humeral locking plate. The constructs were secured, and the superior portion of the humeral head was subjected to compressive loading to induce varus collapse. Load-to-failure and energy-to-failure values along with stiffness and displacement at the time of failure were determined. Medial comminution decreased the mean load to failure by 48% (523 N) (p = 0.015) and the mean energy to failure by 44% (2009 Nmm) (p = 0.013). The use of calcar screw fixation increased the mean load to failure by 31% (219 N) (p = 0.002) and the mean energy to failure by 44% (1279 Nmm) (p = 0.006). Medial comminution significantly decreased the stability of proximal humeral fracture fixation constructs. Calcar restoration with screw fixation significantly improved the stability of repaired fractures in cadaveric specimens. The data suggest that medial comminution is a predictor of poor stability of proximal humeral fractures and that stability may be improved through calcar restoration.

SNPs&GO is a method for the prediction of deleterious Single Amino acid Polymorphisms (SAPs) using protein functional annotation. In this work, we present the web server implementation of SNPs&GO (WS-SNPs&GO). The server is based on Support Vector Machines (SVM) and for a given protein, its input comprises: the sequence and/or its three-dimensional structure (when available), a set of target variations and its functional Gene Ontology (GO) terms. The output of the server provides, for each protein variation, the probabilities to be associated to human diseases. The server consists of two main components, including updated versions of the sequence-based SNPs&GO (recently scored as one of the best algorithms for predicting deleterious SAPs) and of the structure-based SNPs&GO(3d) programs. Sequence and structure based algorithms are extensively tested on a large set of annotated variations extracted from the SwissVar database. Selecting a balanced dataset with more than 38,000 SAPs, the sequence-based approach achieves 81% overall accuracy, 0.61 correlation coefficient and an Area Under the Curve (AUC) of the Receiver Operating Characteristic (ROC) curve of 0.88. For the subset of ~6,600 variations mapped on protein structures available at the Protein Data Bank (PDB), the structure-based method scores with 84% overall accuracy, 0.68 correlation coefficient, and 0.91 AUC. When tested on a new blind set of variations, the results of the server are 79% and 83% overall accuracy for the sequence-based and structure-based inputs, respectively. WS-SNPs&GO is a valuable tool that includes in a unique framework information derived from protein sequence, structure, evolutionary profile, and protein function. WS-SNPs&GO is freely available at http://snps.biofold.org/snps-and-go.

Capriotti E.,University of Alabama at Birmingham
BMC genomics | Year: 2013

In recent years the number of human genetic variants deposited into the publicly available databases has been increasing exponentially. The latest version of dbSNP, for example, contains ~50 million validated Single Nucleotide Variants (SNVs). SNVs make up most of human variation and are often the primary causes of disease. The non-synonymous SNVs (nsSNVs) result in single amino acid substitutions and may affect protein function, often causing disease. Although several methods for the detection of nsSNV effects have already been developed, the consistent increase in annotated data is offering the opportunity to improve prediction accuracy. Here we present a new approach for the detection of disease-associated nsSNVs (Meta-SNP) that integrates four existing methods: PANTHER, PhD-SNP, SIFT and SNAP. We first tested the accuracy of each method using a dataset of 35,766 disease-annotated mutations from 8,667 proteins extracted from the SwissVar database. The four methods reached overall accuracies of 64%-76% with a Matthew's correlation coefficient (MCC) of 0.38-0.53. We then used the outputs of these methods to develop a machine learning based approach that discriminates between disease-associated and polymorphic variants (Meta-SNP). In testing, the combined method reached 79% overall accuracy and 0.59 MCC, ~3% higher accuracy and ~0.05 higher correlation with respect to the best-performing method. Moreover, for the hardest-to-define subset of nsSNVs, i.e. variants for which half of the predictors disagreed with the other half, Meta-SNP attained 8% higher accuracy than the best predictor. Here we find that the Meta-SNP algorithm achieves better performance than the best single predictor. This result suggests that the methods used for the prediction of variant-disease associations are orthogonal, encoding different biologically relevant relationships. Careful combination of predictions from various resources is therefore a good strategy for the selection of high reliability predictions. Indeed, for the subset of nsSNVs where all predictors were in agreement (46% of all nsSNVs in the set), our method reached 87% overall accuracy and 0.73 MCC. Meta-SNP server is freely accessible at http://snps.biofold.org/meta-snp.

Ambrosy A.P.,Stanford University | Butler J.,Emory University | Ahmed A.,University of Alabama at Birmingham | Vaduganathan M.,Harvard University | And 3 more authors.
Journal of the American College of Cardiology | Year: 2014

Digoxin is the oldest cardiac drug still in contemporary use, yet its role in the management of patients with heart failure (HF) remains controversial. A purified cardiac glycoside derived from the foxglove plant, digoxin increases ejection fraction, augments cardiac output, and reduces pulmonary capillary wedge pressure without causing deleterious increases in heart rate or decreases in blood pressure. Moreover, it is also a neurohormonal modulator at low doses. In the pivotal DIG (Digitalis Investigation Group) trial, digoxin therapy was shown to reduce all-cause and HF-specific hospitalizations but had no effect on survival. With the discovery of neurohormonal blockers capable of reducing mortality in HF with reduced ejection fraction, the results of the DIG trial were viewed as neutral, and the use of digoxin declined precipitously. Although modern drug and device-based therapies have dramatically improved the survival of ambulatory patients with HF, outcomes for patients with worsening chronic HF, defined as deteriorating signs and symptoms on standard therapy often leading to unscheduled clinic or emergency department visits or hospitalization, have largely remained unchanged over the past 2 decades. The available data suggest that a therapeutic trial of digoxin may be appropriate in patients with worsening chronic heart failure who remain symptomatic. © 2014 by the American College of Cardiology Foundation.

Mannon P.J.,University of Alabama at Birmingham
Expert Opinion on Biological Therapy | Year: 2011

Introduction: Human mesenchymal stem cells (Prochymal brand of remestemcel-L) have been developed for experimental use in Crohn's disease and other conditions. Mesenchymal stems cells (MSCs) have been shown to inhibit inflammatory responses of innate and adaptive immune cells as well as have reparative effects on inflamed tissues. Promising preliminary therapeutic results of MSCs on gastrointestinal graft-versus-host disease have lead to Phase III trials for active Crohn's disease. Areas covered: This review examines the discovery and characterization of mesenchymal stem cells, their immune effects, their use in animal models of disease, the production and administration of remestemcel-L and the published results of trials of remestemcel-L and alternative MSCs in Crohn's disease. Expert opinion: The Prochymal brand of remestemcel-L represents the successful pharmaceutical development of mesenchymal stem cells for potential therapy in human disease. While preliminary results show promise of this therapy in terms of efficacy and safety, robust trials confirming efficacy results, explanation of the mechanism of response and estimates of effect compared to other biologics and immunosuppressants will be needed before this is an approved and widely accepted therapy. © 2011 Informa UK, Ltd.

Haft D.H.,J. Craig Venter Institute | Selengut J.D.,J. Craig Venter Institute | Richter R.A.,J. Craig Venter Institute | Harkins D.,J. Craig Venter Institute | And 3 more authors.
Nucleic Acids Research | Year: 2013

TIGRFAMs, available online at http://www.jcvi.org/tigrfams is a database of protein family definitions. Each entry features a seed alignment of trusted representative sequences, a hidden Markov model (HMM) built from that alignment, cutoff scores that let automated annotation pipelines decide which proteins are members, and annotations for transfer onto member proteins. Most TIGRFAMs models are designated equivalog, meaning they assign a specific name to proteins conserved in function from a common ancestral sequence. Models describing more functionally heterogeneous families are designated subfamily or domain, and assign less specific but more widely applicable annotations. The Genome Properties database, available at http://www.jcvi.org/genome-properties, specifies how computed evidence, including TIGRFAMs HMM results, should be used to judge whether an enzymatic pathway, a protein complex or another type of molecular subsystem is encoded in a genome. TIGRFAMs and Genome Properties content are developed in concert because subsystems reconstruction for large numbers of genomes guides selection of seed alignment sequences and cutoff values during protein family construction. Both databases specialize heavily in bacterial and archaeal subsystems. At present, 4284 models appear in TIGRFAMs, while 628 systems are described by Genome Properties. Content derives both from subsystem discovery work and from biocuration of the scientific literature. © The Author(s) 2012.

Louis P.J.,University of Alabama at Birmingham
Oral and Maxillofacial Surgery Clinics of North America | Year: 2010

With tooth loss, there is increased bone loss of the alveolus. In some cases alveolar bone loss can be severe. Severe bone loss may cause difficulty for patients wearing a conventional prosthesis or being restored with dental implants. Severe alveolar bone loss can result in malnutrition, poor self-esteem, multiple dental visits for failed prosthesis, and jaw fracture. In many cases, patients with loss of alveolar bone height or width may require reconstructive procedures. Vertical ridge augmentation remains a challenge in the reconstruction of the atrophic maxilla and mandible. The main problem arises from the need to expand the soft-tissue envelope and achieve the proper bony architecture. Techniques that have been developed to solve or circumvent this problem include onlay bone grafting with particulate bone graft, block bone graft, barrier techniques with permanent or resorbable membranes, distraction osteogenesis, vascularized ridge splitting techniques, sinus lifts, nerve repositioning techniques, short implants, and angled implants. All of these techniques have advantages and disadvantages. This article focuses on augmentation procedures using titanium mesh, which acts as a barrier and physical support of the soft tissue over the bone graft. © 2010.

Olia A.S.,Purdue University | Prevelige Jr P.E.,University of Alabama at Birmingham | Johnson J.E.,Scripps Research Institute | Cingolani G.,Thomas Jefferson University
Nature Structural and Molecular Biology | Year: 2011

DNA viruses such as bacteriophages and herpesviruses deliver their genome into and out of the capsid through large proteinaceous assemblies, known as portal proteins. Here, we report two snapshots of the dodecameric portal protein of bacteriophage P22. The 3.25-Å-resolution structure of the portal-protein core bound to 12 copies of gene product 4 (gp4) reveals a ~1.1-MDa assembly formed by 24 proteins. Unexpectedly, a lower-resolution structure of the full-length portal protein unveils the unique topology of the C-terminal domain, which forms a ~200-Å-long α-helical barrel. This domain inserts deeply into the virion and is highly conserved in the Podoviridae family. We propose that the barrel domain facilitates genome spooling onto the interior surface of the capsid during genome packaging and, in analogy to a rifle barrel, increases the accuracy of genome ejection into the host cell.

Pimenta E.,University of Queensland | Oparil S.,University of Alabama at Birmingham
Nature Reviews Nephrology | Year: 2010

The term prehypertension was coined in 1939 in the context of early studies that linked high blood pressure recorded during physical examination for life insurance purposes to subsequent morbidity and mortality. These studies demonstrated that individuals with blood pressure 120/80 mmHg, but 140/90 mmHgthe accepted value for the lower limit of the hypertensive rangehad an increased risk of hypertension, cardiovascular disease and early death from cardiovascular causes. The prehypertension classification of blood pressure was later used by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure to define a group of individuals at increased risk of cardiovascular events because of elevated blood pressure, an increased burden of other risk factors such as obesity, diabetes mellitus, dyslipidemia, and inflammatory markers, and evidence of organ damage for example, microalbuminuria, retinal arteriolar narrowing, increased carotid arterial intima-media thickness, left ventricular hypertrophy and coronary artery disease. Nonpharmacological treatment with lifestyle modifications such as weight loss, dietary modification and increased physical activity is recommended for all patients with prehypertension as these approaches effectively reduce risk of cardiovascular events. Pharmacological therapy is indicated for some patients with prehypertension who have specific comorbidities, including diabetes mellitus, chronic kidney disease and coronary artery disease. © 2010 Macmillan Publisher Limited. All rights reserved.

Compiani M.,University of Camerino | Capriotti E.,University of Alabama at Birmingham
Biochemistry | Year: 2013

A computational approach is essential whenever the complexity of the process under study is such that direct theoretical or experimental approaches are not viable. This is the case for protein folding, for which a significant amount of data are being collected. This paper reports on the essential role of in silico methods and the unprecedented interplay of computational and theoretical approaches, which is a defining point of the interdisciplinary investigations of the protein folding process. Besides giving an overview of the available computational methods and tools, we argue that computation plays not merely an ancillary role but has a more constructive function in that computational work may precede theory and experiments. More precisely, computation can provide the primary conceptual clues to inspire subsequent theoretical and experimental work even in a case where no preexisting evidence or theoretical frameworks are available. This is cogently manifested in the application of machine learning methods to come to grips with the folding dynamics. These close relationships suggested complementing the review of computational methods within the appropriate theoretical context to provide a self-contained outlook of the basic concepts that have converged into a unified description of folding and have grown in a synergic relationship with their computational counterpart. Finally, the advantages and limitations of current computational methodologies are discussed to show how the smart analysis of large amounts of data and the development of more effective algorithms can improve our understanding of protein folding. © 2013 American Chemical Society.

Alexander L.F.,University of Alabama at Birmingham
Radiologic Clinics of North America | Year: 2012

Understanding pancreatic development and the congenital anomalies and variants that result from alterations in normal development allows for better recognition of these anomalies at diagnostic imaging. This article reviews normal pancreatic embryology and anatomy, and the appearance of the more common developmental anomalies and ductal variants, with emphasis on computed tomography and magnetic resonance imaging. Common mimics of masses are also covered. © 2012 Elsevier Inc.

Introduction The association of genetic rodent models of obesity and cancer still remains a controversial issue. Although this controversy has largely been resolved in recent years for homozygous leptin receptor-deficient obese Zucker rats and homozygous long-lived Ames dwarf mice, it is still unresolved for homozygous leptin-deficient obese ob/ob mice. Objective The objective of the present study described below was to investigate whether the expression of the cell cycle repressor protein p27(Kip1) is (a) down-regulated in the tumor-free homozygous leptin receptor-deficient obese Zucker rats as well as tumor-free homozygous leptin-deficient obese ob/ob mice and (b) up-regulated in the tumor-free homozygous long-lived Ames dwarf mice. Methods To achieve this objective, we first performed western immunoblot analysis of the hepatic expression of p27. We then performed western immunoblot analysis and proteomic analysis of the hepatic expression of the proteins involved in the upstream molecular signaling pathways for the expression of p27. Lastly, we analyzed the serum levels of glucose, insulin, and branched-chain amino acids, all of which have been shown to regulate, causally and inversely, the expression of p27. Results/Conclusions The results indicated that the hepatic expression of p27 was down-regulated in the homozygous leptin receptor-deficient obese Zucker rats and up-regulated in the homozygous long-lived Ames dwarf mice as expected. We also found that the hepatic expression of p27 was down-regulated in the homozygous leptin-deficient obese ob/ob mice. This last observation was not completely consistent with all of the results of the published studies where homozygous leptin-deficient obese ob/ob mice were used. © 2013 Elsevier Inc.

Korf B.R.,University of Alabama at Birmingham | Rehm H.L.,HealthCare Partners
JAMA - Journal of the American Medical Association | Year: 2013

Advances in understanding the molecular basis of rare and common disorders, as well as in the technology of DNA analysis, are rapidly changing the landscape of molecular genetic and genomic testing. High-resolution molecular cytogenetic analysis can now detect deletions or duplications of DNA of a few hundred thousand nucleotides, well below the resolution of the light microscope. Diagnostic testing for "single-gene" disorders can be done by targeted analysis for specific mutations, by sequencing a specific gene to scan for mutations, or by analyzing multiple genes in which mutation may lead to a similar phenotype. The advent of massively parallel next-generation sequencing facilitates the analysis of multiple genes and now is being used to sequence the coding regions of the genome (the exome) for clinical testing. Exome sequencing requires bioinformatic analysis of the thousands of variants that are identified to find one that is contributing to the pathology; there is also a possibility of incidental identification of other medically significant variants, which may complicate genetic counseling. DNA testing can also be used to identify variants that influence drug metabolism or interaction of a drug with its cellular target, allowing customization of choice of drug and dosage. Exome and genome sequencing are being applied to identify specific gene changes in cancer cells to guide therapy, to identify inherited cancer risk, and to estimate prognosis. Genomic testing may be used to identify risk factors for common disorders, although the clinical utility of such testing is unclear. Genetic and genomic tests may raise new ethical, legal, and social issues, some of which may be addressed by existing genetic non-discrimination legislation, but which also must be addressed in the course of genetic counseling. The purpose of this article is to assist physicians in recognizing where new approaches to genetic and genomic testing may be applied clinically and in being aware of the principles of interpretation of test results. ©2013 American Medical Association. All rights reserved.

Gnann Jr. J.W.,University of Alabama at Birmingham
Clinical Obstetrics and Gynecology | Year: 2012

Widespread use of varicella vaccine in the United States has drastically changed the epidemiology of the disease. Although chickenpox is no longer a ubiquitous childhood infection, varicella-zoster virus continues to circulate in the community and nonimmune pregnant women remain at risk. Varicella can cause severe infection in pregnant women, often complicated by viral pneumonia. Maternal varicella occurring in the first half of pregnancy can cause the rare but devastating congenital varicella syndrome, whereas infection in the late stages of pregnancy may cause neonatal varicella. The best approach to avoiding the morbidity and mortality associated with chickenpox in pregnancy is to screen and vaccinate susceptible reproductive-age women. © 2012, Lippincott Williams & Wilkins.

Percy A.K.,University of Alabama at Birmingham
Science | Year: 2013

Rigorous testing of potential disease-modifying factors of Rett syndrome is needed to guide research findings toward clinical trials.

Kau C.H.,University of Alabama at Birmingham
Orthodontics : the art and practice of dentofacial enhancement | Year: 2011

To compare landmark vs surface-shape measurements in a sample of patients with cleft lips and palates following secondary alveolar bone grafting. The faces of 10 patients (4 males and 6 females) with an unilateral cleft lip and palate were captured using a 3D surface camera system before and 6 weeks after alveolar bone grafting. In each face, six coordinates were registered. The pre- and postoperative images were superimposed on areas that were not affected by the surgery. Using 3D modeling software landmarks, nasal symmetry, and surface-to-surface deviation, analysis was performed. All data were subjected to standard statistical analyses. Color map surface-to-surface comparison revealed a significant anteroposterior elevation in the nasal region of the cleft side after surgery. The ala, alar base, and paranasal areas are increased anteroposteriorly after secondary bone grafting. This surgery tends to diminish the asymmetry in nasal morphology typically seen in patients with unilateral cleft lip and palate. Overall, 3D surface-to-surface analysis allows for a better quantification of treatment changes.

Wolverton S.E.,Indiana University | Harper J.C.,University of Alabama at Birmingham
American Journal of Clinical Dermatology | Year: 2013

Isotretinoin is a remarkably effective drug for severe, recalcitrant acne vulgaris. Soon after the drug's release in the early 1980s, a number of important adverse effects were reported subsequently leading to a variety of medical and medicolegal controversies. Three of these controversies will be highlighted concerning the putative role of isotretinoin in (1) depression and suicide, (2) inflammatory bowel disease, and (3) iPledge and pregnancy prevention programs. It appears that a very small subset of patients receiving isotretinoin for acne are at risk for depression, which is very manageable provided there is adequate patient awareness of the possibility, maximum communication between the patient and physician, and cessation of therapy if clinically important depression occurs (after which the depression rapidly resolves in a week or less). Multiple controlled studies actually suggest a very favorable effect of isotretinoin on depression and anxiety common in the population requiring isotretinoin. With regard to inflammatory bowel disease, in just one study, only ulcerative colitis association with isotretinoin reached statistical significance. The actual incidence of this association is strikingly low. Finally, it is clear that even the most recent pregnancy prevention program (iPledge) is no more successful than prior programs; there will likely always be a small number of female patients becoming pregnant while receiving isotretinoin for acne vulgaris. © 2013 Springer International Publishing Switzerland (outside the USA).

Friedman G.K.,University of Alabama at Birmingham
Pediatric research | Year: 2012

Cancer stem cells (CSCs), also termed "cancer-initiating cells" or "cancer progenitor cells," which have the ability to self-renew, proliferate, and maintain the neoplastic clone, have recently been discovered in a wide variety of pediatric tumors. These CSCs are thought to be responsible for tumorigenesis and tumor maintenance, aggressiveness, and recurrence due to inherent resistance to current treatment modalities such as chemotherapy and radiation. Oncolytic virotherapy offers a novel, targeted approach for eradicating pediatric CSCs using mechanisms of cell killing that differ from conventional therapies. Moreover, oncolytic viruses have the ability to target specific features of CSCs such as cell-surface proteins, transcription factors, and the CSC microenvironment. Through genetic engineering, a wide variety of foreign genes may be expressed by oncolytic viruses to augment the oncolytic effect. We review the current data regarding the ability of several types of oncolytic viruses (herpes simplex virus-1, adenovirus, reovirus, Seneca Valley virus, vaccinia virus, Newcastle disease virus, myxoma virus, vesicular stomatitis virus) to target and kill both CSCs and tumor cells in pediatric tumors. We highlight advantages and limitations of each virus and potential ways in which next-generation engineered viruses may target resilient CSCs.

Weiser P.,University of Alabama at Birmingham
Pediatric Clinics of North America | Year: 2012

Musculoskeletal pain is one of the most common presenting symptoms at the pediatrician's office. Etiology ranges from benign conditions to serious ones requiring prompt attention. This article addresses entities that present as musculoskeletal pain but are not associated with arthritis. The most common nonarthritic conditions are benign limb pain of childhood (growing pains), hypermobility, overuse syndromes with or without skeletal abnormalities, malignancies, and pain amplification syndromes. The| initial decision process, diagnosis, and treatment options for each of these conditions are discussed. © 2012 Elsevier Inc.

Sontheimer H.,University of Alabama at Birmingham | Bridges R.J.,University of Montana
Expert Opinion on Investigational Drugs | Year: 2012

Recent research has identified an important role for a cystineglutamate antiporter (system Xc) in the biology of malignant brain tumors. This transporter is effectively inhibited by sulfasalazine, a drug widely used to treat a number of chronic inflammatory conditions such as Crohn's disease. Preclinical data show that sulfasalazine is an effective inhibitor of tumor growth and tumor-associated seizures. These studies suggest that the cystineglutamate antiporter is a valuable drug target for which tumor-specific drugs can be generated. In the meantime, sulfasalazine may be considered as adjuvant treatment for malignant gliomas. © 2012 Informa UK, Ltd.

Elson C.O.,University of Alabama at Birmingham
Gut microbes | Year: 2012

The interaction of the host with its abundant intestinal microbiota is complex and engages most of the cells in the intestinal mucosa. The inflammatory bowel diseases appear to be disorders of the host immune response to the microbiota. This is supported by data from induced gene mutations in mice and more recently by the identification of gene variants in humans that result in IBD or IBD susceptibility. These genetic studies have provided insights into the cells and molecular pathways involved in the host-microbiota dialog. This review discusses the innate, adaptive, and regulatory immune response to the microbiota in the context of the mouse and human genes that are involved in maintaining intestinal homeostasis and preventing inflammation. These data continue to support the hypothesis that inflammatory bowel disease results from a dysregulated adaptive immune response, particularly a CD4 T-cell response, to the microbiota. The microbiota itself is an active participant in these homeostatic processes. The microbiota composition is perturbed during inflammation, resulting in a dysbiosis that may induce or perpetuate inflammation. However, host genotype and the environment have a major impact on the shape of such dysbiosis, as well as upon which members of the microbiota stimulate pathogenic immune responses.

Zeng Y.,University of Alabama at Birmingham
Archive for Rational Mechanics and Analysis | Year: 2015

We study the equations describing the motion of a thermal non-equilibrium gas in three space dimensions. It is a hyperbolic system of six equations with a relaxation term. The dissipation mechanism induced by the relaxation is weak in the sense that the Shizuta-Kawashima criterion is violated. This implies that a perturbation of a constant equilibrium state consists of two parts: one decays in time while the other stays. In fact, the entropy wave grows weakly along the particle path as the process is irreversible. We study thermal properties related to the well-posedness of the nonlinear system. We also obtain a detailed pointwise estimate on the Green’s function for the Cauchy problem when the system is linearized around an equilibrium constant state. The Green’s function provides a complete picture of the wave pattern, with an exact and explicit leading term. Comparing with existing results for one dimensional flows, our results reveal a new feature of three dimensional flows: not only does the entropy wave not decay, but the velocity also contains a non-decaying part, strongly coupled with its decaying one. The new feature is supported by the second order approximation via the Chapman-Enskog expansions, which are the Navier-Stokes equations with vanished shear viscosity and heat conductivity. © 2015 Springer-Verlag Berlin Heidelberg

Neumeier W.H.,University of Alabama at Birmingham
Medicine and Science in Sports and Exercise | Year: 2016

Mental work may promote caloric intake, while exercise may offset positive energy balance by decreasing energy intake and increasing energy expenditure. PURPOSE: This study aimed to replicate previous findings that mental work increases caloric intake compared to a rest condition and assess whether exercise following mental work can offset this effect. METHODS: Thirty-eight male and female university students were randomly assigned to Mental Work + Rest (MW+R) or Mental Work + Exercise (MW+E). Participants also completed a Baseline Rest (BR) visit consisting of no mental work or exercise. Visit order was counterbalanced. During the MW+R or MW+E visit, participants completed a 20 minute mental task and either 15 minutes rest (MW+R) or 15 minutes interval exercise (MW+E). Each visit ended with an ad libitum pizza lunch. A two-way repeated measures ANOVA was used to compare eating behavior between groups. RESULTS: Participants in the MW+R condition consumed an average of 100 more kcal compared to BR (633.3 ± 72.9 and 533.9 ± 67.7, respectively, p = 0.02), and participants in MW+E consumed an average of 25 kcal less compared to BR (432.3 ± 69.2 and 456.5 ± 64.2, respectively, p > 0.05). When including the estimated energy expenditure of exercise in the MW+E conditions, participants were in negative energy balance by an average of 98.5 ± 41.5 kcal, resulting in a significant difference in energy balance between the two groups (p = 0.001). CONCLUSION: An acute bout of interval exercise following mental work resulted in significantly decreased food consumption compared to a non-exercise condition. These results suggest an acute bout of exercise may be employed to offset positive energy balance induced by mental tasks. © 2016 American College of Sports Medicine

Thomas H.N.,University of Alabama at Birmingham
Journal of Hypertension | Year: 2016

OBJECTIVES:: Hypertension is a risk factor for the development of cardiovascular and kidney disease, but treatment can substantially reduce risks. Many patients avoid antihypertensive medications because of fear of side-effects. Although associations between antihypertensives and sexual dysfunction in men have been documented, it remains unclear whether antihypertensives are associated with sexual dysfunction in women. We conducted a cross-sectional analysis of baseline data from women in the Systolic Blood Pressure Intervention Trial (SPRINT) to evaluate the relations among class of antihypertensive medication and the outcomes: sexual activity and sexual function. METHODS:: SPRINT enrolled individuals 50 and older with hypertension at high risk for cardiovascular disease. A subset of participants completed questionnaires regarding quality of life, including sexual function. Antihypertensive class was determined by medications taken at baseline. RESULTS:: Of 690 women in the quality of life subset of SPRINT, 183 (26.5%) were sexually active. There were no significant differences in sexual activity among women taking one or more antihypertensives and women not taking any. Women taking an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker had higher odds of sexual activity [odds ratio 1.66 (1.12–4.27), P?=?0.011]. Among sexually active women, the prevalence of sexual dysfunction was high (52.5%). No class of medication was associated with sexual dysfunction in the multivariable model. CONCLUSION:: Angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use was associated with higher odds of sexual activity. Although prevalence of sexual dysfunction was high, no single class of antihypertensive medication was associated with sexual dysfunction. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

Core G.B.,University of Alabama at Birmingham
Plastic and Reconstructive Surgery | Year: 2013

BACKGROUND: Effective lower eyelid blepharoplasty is possible in a virtually closed fashion without either an anterior subciliary skin incision or a transconjunctival incision, both of which put the patient at risk for lower lid retraction. METHODS: Over a 6-year period, the author performed lower lid rejuvenation with only a lateral incision in 89 consecutive cases in 86 women and three men ranging in age from 42 to 65 years. Patients with lower lid laxity, prior surgery, trauma, significant excess skin, or festoons were excluded. Grading the aged eyelid in stages 1 to 3, with 3 being advanced, this procedure is indicated for stage 1 and 2 patients, characterized by deep nasojugal grooves, herniated lower lid compartment fat, mild to moderate rhytides, and increased lower lid height. The technique uses a lateral incision with dissection under the orbicularis and anterior to the orbital septum with release of the orbitomalar ligament. Loupe magnification is used. The nasal orbicularis fibers are released and the fat compartments are released and sewn to the midface fat using 6-0 transcutaneous sutures. An orbicularis muscle lift is performed for support and a lateral retinacular suspension is performed if necessary. RESULTS: Follow-up ranged from 3 months to 6 years, and there have been no major complications. All patients have been satisfied with the results. CONCLUSIONS: Lateral incision-only lower lid blepharoplasty allows all necessary structures to be addressed for rejuvenation by recontouring in selected patients without anterior or posterior incisions into the central part of the lid. Copyright © 2013 by the American Society of Plastic Surgeons.

Travis L.B.,University of Rochester | Wahnefried W.D.,University of Alabama at Birmingham | Allan J.M.,Northumbria University | Wood M.E.,University of Vermont | Ng A.K.,Dana-Farber Cancer Institute
Nature Reviews Clinical Oncology | Year: 2013

Second and higher-order malignancies now comprise about 18% of all incident cancers in the USA, superseding first primary cancers of the breast, lung, and prostate. The occurrence of second malignant neoplasms (SMN) is influenced by a myriad of factors, including the late effects of cancer therapy, shared aetiological factors with the primary cancer (such as tobacco use, excessive alcohol intake, and obesity), genetic predisposition, environmental determinants, host effects, and combinations of factors, including gene-environment interactions. The influence of these factors on SMN in survivors of adult-onset cancer is reviewed here. We also discuss how modifiable behavioural and lifestyle factors may contribute to SMN, and how these factors can be managed. Cancer survivorship provides an opportune time for oncologists and other health-care providers to counsel patients with regard to health promotion, not only to reduce SMN risk, but to minimize co-morbidities. In particular, the importance of smoking cessation, weight control, physical activity, and other factors consonant with adoption of a healthy lifestyle should be consistently emphasized to cancer survivors. Clinicians can also play a critical role by endorsing genetic counselling for selected patients and making referrals to dieticians, exercise trainers, and others to assist with lifestyle change interventions. © 2013 Macmillan Publishers Limited. All rights reserved.

Abrams M.,University of Alabama at Birmingham
Behavioral and Brain Sciences | Year: 2014

Smaldino suggests that patterns that give rise to group-level cultural traits can also increase individual-level cultural diversity. I distinguish social roles and related social network structures and discuss ways in which each might maintain diversity. I suggest that cognitive analogs of "cohesion," a property of networks that helps maintenance of diversity, might mediate the effects of social roles on diversity.

Martineau M.,University of Munster | Parpura V.,University of Alabama at Birmingham | Parpura V.,University of Rijeka | Mothet J.-P.,Aix - Marseille University
Frontiers in Synaptic Neuroscience | Year: 2014

Accumulating evidence during the last decade established that D-serine is a key signaling molecule utilized by neurons and astroglia in the mammalian central nervous system. D-serine is increasingly appreciated as the main physiological endogenous coagonist for synaptic NMDA receptors at central excitatory synapses; it is mandatory for long-term changes in synaptic strength, memory, learning, and social interactions. Alterations in the extracellular levels of D-serine leading to disrupted cell-cell signaling are a trademark of many chronic or acute neurological (i.e., Alzheimer disease, epilepsy, stroke) and psychiatric (i.e., schizophrenia) disorders, and are associated with addictive behavior (i.e., cocaine addiction). Indeed, fine tuning of the extracellular levels of D-serine, achieved by various molecular machineries and signaling pathways, is necessary for maintenance of accurate NMDA receptor functions. Here, we review the experimental data supporting the notion that astroglia and neurons use different pathways to regulate levels of extracellular D-serine. © 2014 Martineau, Parpura and Mothet.

Young M.E.,University of Alabama at Birmingham
Critical Reviews in Biochemistry and Molecular Biology | Year: 2013

Circadian rhythms are an integral part of life. These rhythms are apparent in virtually all biological processes studies to date, ranging from the individual cell (e.g. DNA synthesis) to the whole organism (e.g. behaviors such as physical activity). Oscillations in metabolism have been characterized extensively in various organisms, including mammals. These metabolic rhythms often parallel behaviors such as sleep/wake and fasting/feeding cycles that occur on a daily basis. What has become increasingly clear over the past several decades is that many metabolic oscillations are driven by cell-autonomous circadian clocks, which orchestrate metabolic processes in a temporally appropriate manner. During the process of identifying the mechanisms by which clocks influence metabolism, molecular-based studies have revealed that metabolism should be considered an integral circadian clock component. The implications of such an interrelationship include the establishment of a vicious cycle during cardiometabolic disease states, wherein metabolism-induced perturbations in the circadian clock exacerbate metabolic dysfunction. The purpose of this review is therefore to highlight recent insights gained regarding links between cell-autonomous circadian clocks and metabolism and the implications of clock dysfunction in the pathogenesis of cardiometabolic diseases. © 2013 Informa Healthcare USA, Inc.

Duffield J.S.,University of Washington | Lupher M.,Promedior | Thannickal V.J.,University of Alabama at Birmingham | Wynn T.A.,National Institute of Allergy and Infectious Diseases
Annual Review of Pathology: Mechanisms of Disease | Year: 2013

Myofibroblasts accumulate in the spaces between organ structures and produce extracellular matrix (ECM) proteins, including collagen I. They are the primary "effector" cells in tissue remodeling and fibrosis. Previously, leukocyte progenitors termed fibrocytes and myofibroblasts generated from epithelial cells through epithelial-to-mesenchymal transition (EMT) were considered the primary sources of ECM-producing myofibroblasts in injured tissues. However, genetic fate mapping experiments suggest that mesenchyme-derived cells, known as resident fibroblasts, and pericytes are the primary precursors of scar-forming myofibroblasts, whereas epithelial cells, endothelial cells, and myeloid leukocytes contribute to fibrogenesis predominantly by producing key fibrogenic cytokines and by promoting cell-to-cell communication. Numerous cytokines derived from T cells, macrophages, and other myeloid cell populations are important drivers of myofibroblast differentiation. Monocyte-derived cell populations are key regulators of the fibrotic process: They act as a brake on the processes driving fibrogenesis, and they dismantle and degrade established fibrosis. We discuss the origins, modes of activation, and fate of myofibroblasts in various important fibrotic diseases and describe how manipulation of macrophage activation could help ameliorate fibrosis. © 2013 by Annual Reviews. All rights reserved.

Overton E.T.,University of Alabama at Birmingham
Topics in Antiviral Medicine | Year: 2014

Non-AIDS morbidity and mortality are increasingly common in the HIVinfected population. Chronic inflammation and immunosenescence result in early onset of conditions associated with aging, including atherosclerosis and frailty. Risk for non-AIDS-related morbidity is also related to the metabolic effects of antiretroviral therapy and the increased prevalence of traditional cardiovascular and other risk factors in the HIV-infected population. Risk reduction is centered on maintaining full viral suppression and aggressively implementing measures to reduce standard modifiable risk factors. This article summarizes a presentation by Edgar Turner overton, MD, at the IAS-USA continuing education program held in New York, New York, in October 2013. © 2014, IAS-USA. All rights reserved.

Bertocchio J.-P.,French Institute of Health and Medical Research | Warnock D.G.,University of Alabama at Birmingham | Jaisser F.,French Institute of Health and Medical Research
Kidney International | Year: 2011

Slowing the progression of chronic kidney diseases (CKDs) requires new and effective treatment approaches. Aldosterone classically acts on the distal nephron: it facilitates sodium reabsorption, potassium secretion, and participates in blood pressure control. Recently, new targets of aldosterone have been described including the heart and the vasculature, and other kidney cells such as mesangial cells, podocytes, and renal fibroblasts. The pathophysiological implications of increased mineralocorticoid receptor (MR) expression and activation (either dependent on aldosterone or direct ligand-independent activation) and its blockade have been illustrated with ex vivo in cell cultures and in vivo in experimental animal models of CKD, including diabetic and hypertensive nephropathies, and glomerulopathies. The beneficial effects of the MR antagonists are independent of the hypertensive effect of aldosterone, indicating that blocking the activation of the MR may have unique clinical importance. Several studies have reported efficacy and safety studies with spironolactone or eplerenone in patients with kidney diseases. In this review, we discuss the recent results reported in experimental and clinical research in this field, and emphasize the direct activation of the MR that can occur in pathological states associated with CKD, even in the absence of increased circulating levels of aldosterone. © 2011 International Society of Nephrology.

Swanson M.W.,University of Alabama at Birmingham
Optometry and Vision Science | Year: 2012

Purpose. Large population studies carried out in the United States, while addressing refractive error prevalence, have published little addressing the modes of refractive correction. As such, there are little data in the biomedical literature concerning the characteristics of the contact lens wearing population in the United States. The purpose of this project was to develop estimates of the demographic characteristics of a cross section of contact lens wearers in the United States based on those who wore contact lenses on the day of their National Health and Nutrition Examination Survey (NHANES) examination. Methods. The NHANES is a nationally representative sample of the U.S. population. As part of NHANES, the type of refractive correction used is collected during a mobile medical clinic examination along with demographic variables. Data files from the 2005-2006 and 2007-2008 NHANES were obtained from the National Center for Health Statistics. Demographic characteristics of the U.S. population using contacts during the medical clinic examination were derived. Associations between demographic variables and contact lens use were explored in age-stratified univariate and multivariate analyses taking into account the complex sampling frame. Results. In univariate analysis, age (p < 0.001) and the availability of health insurance (p = 0.007) have negative associations with contact lens use, while female gender (p < 0.001), higher socioeconomic status (p < 0.001), and higher educational attainment (p < 0.001) are associated with increased contact lens use. In multivariate analysis, age (p < 0.001), socioeconomic status (p < 0.001), the interaction of age with gender (p < 0.001), and the interaction of socioeconomic status with education (p = 0.002) are associated with contact lens use. Conclusions. Four demographic variables, age, socioeconomic status, age-gender interaction, and socioeconomic status-education interaction, defined those likely to be using contact lens on any given day in the United States. Together, these four variables identify almost 9 of 10 contact lens users. © 2012 American Academy of Optometry.

Ncube N.M.,University of Alabama at Birmingham
Ghana medical journal | Year: 2012

To assess the prevalence and predictors of sexual risk behaviours among HIV-positive individuals in clinical care in Kumasi, Ghana. Cross-sectional survey of 267 (43 males and 224 females) HIV-positive individuals attending Kumasi South Regional Hospital. An interviewer-administered questionnaire was used to asses demographic and health characteristics, HIV/AIDS knowledge, attitudes, and beliefs and sexual risk behaviours. Forty-four percent of the sample reported having sex after testing positive for HIV. Of the 175 participants with regular sex partners, 24% had HIV-positive partners. Majority (67%) had HIV-negative partners (serodiscordant couples) or partners of unknown status. More than half (51%) of the study population with regular sex partners reported that they had unprotected anal or vaginal sex. Participants who scored < 50% on the HIV/AIDS knowledge scale were 90% less likely to have used condoms during their last sexual intercourse. Disclosure of HIV status was associated with protective patterns of condom use (OR=2.2; 95% CI: 1.3-12.9). Participants on ARV were 80% less likely to have used condoms during the last sexual intercourse (OR=0.2; 95% CI: 0.04-0.6). The high rates of sexual risk behaviour among HIV-positive individuals in this sample place others at risk of HIV infection. It also places these HIV positive individuals at risk for infection with sexually transmitted infections and super-infection with other HIV strains. These findings highlight the need to integrate HIV prevention in routine medical care in Ghana.

Saag M.S.,University of Alabama at Birmingham
Topics in Antiviral Medicine | Year: 2012

Numerous investigational antiretroviral agents are in clinical development. Among them are festinavir (BMS986001), a thymidine analogue similar to stavudine with reduced potential for toxicity; GS-7340, a prodrug of tenofovir that achieves greater intracellular concentrations; MK-1439, a nonnucleoside analogue reverse transcriptase inhibitor (NNRTI) that retains activity against common NNRTI-associated resistance mutations; and albuvirtide, a longacting parenteral fusion inhibitor. Investigational integrase strand transfer inhibitors (InSTIs) include elvitegravir, recently approved by the US Food and Drug Administration (FDA) as part of a once-daily, singletablet formulation with cobicistat/tenofovir/emtricitabine; dolutegravir, which maintains some activity against raltegravir- and elvitegravir-resistant mutants; and S/GSK1265744, which also maintains some activity against resistance mutations in the integrase gene and is being developed as a long-lasting parenteral agent. Novel 2-(quinolin-3-yl)acetic acid derivatives (LEDGINs), agents that were originally thought to inhibit the interaction of integrase with its cofactor lens epithelium-derived growth factor p75 (LEDGF/ p75), are active against InSTI-resistant mutants and to have additive activity when combined with InSTIs. © 2012, IAS-USA.

Rautiainen S.,Karolinska Institutet | Levitan E.B.,University of Alabama at Birmingham | Mittleman M.A.,Beth Israel Deaconess Medical Center | Wolk A.,Karolinska Institutet
European Journal of Heart Failure | Year: 2015

Aims: Although numerous studies have investigated fruit and vegetable consumption in association with cardiovascular diseases (CVD) such as coronary heart disease and stroke, a limited number of studies have investigated the association with heart failure. The aim of this study was to assess the association between fruit and vegetable intake and the incidence of heart failure among women. Methods and results: In September 1997, a total of 34 319 women (aged 49-83 years) from the Swedish Mammography Cohort, free of cancer and CVD at baseline, completed a food-frequency questionnaire. Women were followed for incident heart failure (diagnosis as primary or secondary cause) through December 2011 using administrative health registries. Over 12.9 years of follow-up (442 348 person-years), we identified 3051 incident cases of heart failure. Total fruit and vegetable consumption was inversely associated with the rate of heart failure {the multivariable-adjusted rate ratio (RR) in the highest quintile compared with the lowest was 0.80 [95% confidence interval (CI) 0.70-0.90]}. Fruit (mutually adjusted for vegetables) were not significantly associated with rate of heart failure (RR 0.94; 95% CI 0.83-1.07), whereas vegetables showed an inverse association (RR 0.83; 95% CI 0.73-0.95). When investigating the shape of association, we found evidence of a non-linear association (P = 0.01), and the lowest rates of heart failure were observed among women consuming ≤5 servings/day of fruit and vegetables, without further decrease with increasing intake. Conclusions: In this population-based prospective cohort study of women, higher total consumption of fruit and vegetables was inversely associated with the incidence of heart failure. © 2014 The Authors European Journal of Heart Failure © 2014 European Society of Cardiology.

Singh J.A.,Birmingham Medical Center | Singh J.A.,University of Alabama at Birmingham | Singh J.A.,Rochester College
Arthritis Research and Therapy | Year: 2014

Introduction: The aim of this study was to examine the impact of gout on quality of life (QOL) and study differences by gender and race.Methods: Ten race- and sex-stratified nominal groups were conducted, oversampling for African-Americans and women with gout. Patients presented, discussed, combined and rank-ordered their concerns.Results: A total of 62 patients with mean age 65.1 years, 60% men, 64% African-American, participated in 10 nominal groups: African-American men (n = 23; 3 groups); African-American women (n = 18; 3 groups); Caucasian men (n = 15; 3 groups); and Caucasian women (n = 6; 1 group). The most frequently cited high-ranked concerns among the ten nominal groups were: (1) effect of gout flare on daily activities (n = 10 groups); (2) work disability (n = 8 groups); (3) severe pain (n = 8 groups); (4) joint swelling and tenderness (n = 6 groups); (5) food restrictions (n = 6 groups); (6) medication related issues (n = 6 groups); (7) dependency on family and others (n = 5 groups); (8) emotional Impact (n = 5 groups); (9) interference with sexual function (n = 4 groups); (10) difficulty with shoes (n = 4 groups); and (11) sleep disruption (n = 4 groups). Compared with men, women ranked the following concerns high more often: problems with shoes (n = 4 versus n = 0 groups); dependency (n = 3 versus n = 2 groups); and joint/limb deformity (n = 2 versus n = 0 group). Compared with Caucasians, African-Americans ranked the following concerns high more often: dietary restrictions (n = 6 versus n = 0 groups); severe pain (n = 6 versus n = 2 groups); gout bringing the day to a " halt" (n = 2 versus n = 0 group); effect on emotional health (n = 4 versus n = 1 groups); and the need for canes/crutches during flares (n = 2 versus n = 0 group).Conclusions: Gout has a significant impact on a patient's QOL. Important differences in the impact of gout by gender and race were noted. © 2014 Singh; licensee BioMed Central Ltd.

Janss L.,University of Aarhus | de los Campos G.,University of Alabama at Birmingham | Sheehan N.,University of Leicester | Sorensen D.,University of Aarhus
Genetics | Year: 2012

Unaccounted population stratification can lead to spurious associations in genome-wide association studies (GWAS) and in this context several methods have been proposed to deal with this problem. An alternative line of research uses whole-genome random regression (WGRR) models that fit all markers simultaneously. Important objectives in WGRR studies are to estimate the proportion of variance accounted for by the markers, the effect of individual markers, prediction of genetic values for complex traits, and prediction of genetic risk of diseases. Proposals to account for stratification in this context are unsatisfactory. Here we address this problem and describe a reparameterization of a WGRR model, based on an eigenvalue decomposition, for simultaneous inference of parameters and unobserved population structure. This allows estimation of genomic parameters with and without inclusion of markerderived eigenvectors that account for stratification. The method is illustrated with grain yield in wheat typed for 1279 genetic markers, and with height, HDL cholesterol and systolic blood pressure from the British 1958 cohort study typed for 1 million SNP genotypes. Both sets of data show signs of population structure but with different consequences on inferences. The method is compared to an advocated approach consisting of including eigenvectors as fixed-effect covariates in a WGRR model. We show that this approach, used in the context of WGRR models, is ill posed and illustrate the advantages of the proposed model. In summary, our method permits a unified approach to the study of population structure and inference of parameters, is computationally efficient, and is easy to implement. © 2012 by the Genetics Society of America.

Adams P.C.,University of Western Ontario | Barton J.C.,Southern Iron Disorders Center | Barton J.C.,University of Alabama at Birmingham
Blood | Year: 2010

Hemochromatosis is a common genetic disorder in which iron may progressively accumulate in the liver, heart, and other organs. The primary goal of therapy is iron depletion to normalize body iron stores and to prevent or decrease organ dysfunction. The primary therapy to normalize iron stores is phlebotomy. In this opinion article, we discuss the indications for and monitoring of phlebotomy therapy to achieve iron depletion, maintenance therapy, dietary and pharmacologic maneuvers that could reduce iron absorption, and the role of voluntary blood donation. © 2010 by The American Society of Hematology.

Dangleben N.L.,University of California at Berkeley | Skibola C.F.,University of Alabama at Birmingham | Smith M.T.,University of California at Berkeley
Environmental Health: A Global Access Science Source | Year: 2013

Exposure to arsenic (As) is a global public health problem because of its association with various cancers and numerous other pathological effects, and millions of people worldwide are exposed to As on a regular basis. Increasing lines of evidence indicate that As may adversely affect the immune system, but its specific effects on immune function are poorly understood. Therefore, we conducted a literature search of non-cancer immune-related effects associated with As exposure and summarized the known immunotoxicological effects of As in humans, animals and in vitro models. Overall, the data show that chronic exposure to As has the potential to impair vital immune responses which could lead to increased risk of infections and chronic diseases, including various cancers. Although animal and in vitro models provide some insight into potential mechanisms of the As-related immunotoxicity observed in human populations, further investigation, particularly in humans, is needed to better understand the relationship between As exposure and the development of disease. © 2013 Dangleben et al.; licensee BioMed Central Ltd.

Soletsky B.,Baylor College of Medicine | Feig D.I.,University of Alabama at Birmingham
Hypertension | Year: 2012

Epidemiologic studies, animal models, and preliminary clinical trials in children implicate uric acid in the development of essential hypertension. Controversy remains as to whether the observations indicate a general mechanism or a surrogate phenomenon. We sought to determine whether uric acid is a causative mediator of increased blood pressure (BP) and impaired vascular compliance. We report a randomized, double-blinded, placebo-controlled trial comparing 2 mechanisms of urate reduction with placebo in prehypertensive, obese, adolescents, aged 11 to 17 years. Subjects were randomized to the xanthine oxidase inhibitor, allopurinol, uricosuric, probenecid, or placebo. Subjects treated with urate-lowering therapy experienced a highly significant reduction in BP. In clinic systolic BP fell 10.2 mm Hg and diastolic BP fell 9.0 mm Hg in treated patients compared with a rise of 1.7 mm Hg and 1.6 mm Hg systolic and diastolic BP, respectively in patients on placebo. Urate-lowering therapy also resulted in significant reduction in systemic vascular resistance. These data indicate that, at least in adolescents with prehypertension, uric acid causes increased BP that can be mitigated by urate lowering therapy. © 2012 American Heart Association, Inc.

Bolus N.E.,University of Alabama at Birmingham
Journal of Nuclear Medicine Technology | Year: 2013

The purpose of this paper is to briefly explain report 160 of the National Council on Radiation Protection and Measurement and the significance of the report to medical imaging as a whole and nuclear medicine specifically. The implications of the findings of report 160 have had repercussions and will continue to affect all of ionizing radiation medical imaging. The nuclear medicine community should have an understanding of why and how report 160 is important. After reading this article, the nuclear medicine technologist will be familiar with the main focus of report 160, the significant change that has occurred since the 1980s in the ionizing radiation exposure of people in the United States, the primary background source of ionizing radiation in the United States, the primary medical exposure to ionizing radiation in the United States, trends in nuclear medicine procedures and patient exposure, and a comparison of population doses between 2006 and the early 1980s as outlined in report 160. © 2013 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Andukuri A.,University of Alabama at Birmingham
Tissue engineering. Part C, Methods | Year: 2013

Endothelial progenitor cell (EPC)-capturing techniques have led to revolutionary strategies that can improve the performance of cardiovascular implant devices and engineered tissues by enhancing re-endothelialization and angiogenesis. However, these strategies are limited by controversies regarding the phenotypic identities of EPCs as well as their inability to target and prevent the other afflictions associated with current therapies, namely, thrombosis and neointimal hyperplasia. Therefore, the goal of this study was to study the efficacy of a bioinspired multifunctional nanomatrix in recruiting and promoting the differentiation of EPCs toward an endothelial lineage. The bioinspired nanomatrix combines multiple components, including self-assembled peptide amphiphiles (PAs) that include cell adhesive ligands, nitric oxide (NO)-producing donors, and enzyme-mediated degradable sequences to achieve an endothelium-mimicking character. In this study, human peripheral blood mononuclear cells (PBMNCs) were isolated and cultured on the bioinspired multifunctional nanomatrix. Initial cell adhesion, lectin staining, acetylated low-density lipoprotein uptake, and expression of endothelial markers, including CD31, CD34, von Willebrand Factor, and VEGFR2, were analyzed. The results from this study indicate that the NO releasing bioinspired multifunctional nanomatrix promotes initial adhesion of EPCs when compared to control surfaces. The expression of endothelial markers is also increased on the bioinspired multifunctional nanomatrix, suggesting that it directs the differentiation of EPCs toward an endothelial phenotype. The bioinspired nanomatrix therefore provides a novel biomaterial-based platform for capturing as well as directing EPC behavior. Therefore, this study has the potential to positively impact the patency of cardiovascular devices such as stents and vascular grafts as well as enhanced angiogenesis for ischemic or engineered tissues.

Austin E.L.,University of Alabama at Birmingham
Women and Health | Year: 2013

Concerns regarding sexual orientation disclosure to health care providers have been suggested as a barrier to care which may account for documented differences in the health care utilization of lesbians relative to heterosexual women. This study explored the correlates of sexual orientation disclosure to health care providers among 934 lesbian women living in urban and non-urban areas of the South. Psychosocial resources, such as self-esteem, social support, and mastery, along with several lesbian-specific experiences (proportion of lesbian, gay, bisexual, or transgender friends, access to the lesbian, gay, bisexual, or transgender community, degree of being "out"), were all independently associated with greater likelihood of having disclosed to a health care provider. Internalized homophobia and lesbian-related stigma decreased the likelihood of disclosure. Lesbians living in non-urban areas were significantly less likely to have disclosed than women in urban areas, suggesting that disclosure may present a special concern for populations in non-urban areas. © 2013 Copyright Taylor and Francis Group, LLC.

Tita A.T.N.,University of Alabama at Birmingham
Obstetrics and Gynecology | Year: 2010

Objective: To compare outcomes among neonates delivered after documentation of fetal lung maturity before 39 weeks and those delivered at 39 or 40 weeks. Methods: This was a retrospective cohort study of women with singleton pregnancy delivered at 36 0/7 to 38 6/7 weeks after positive fetal lung maturity testing (based on amniotic fluid lecithin to sphingomyelin ratio) or at 39 0/7 to 40 6/7 weeks (without maturity testing) at our center from 1999 to 2008. Women with fetuses with major congenital anomalies, cord prolapse, nonreassuring antepartum testing, placental abruption, or oligohydramnios were excluded. A primary composite neonatal outcome included death, adverse respiratory outcomes, hypoglycemia, treated hyperbilirubinemia, generalized seizures, necrotizing enterocolitis, hypoxic ischemic encephalopathy, periventricular leukomalacia, and suspected or proven sepsis. Results: There were 459 neonates delivered at 36 to 38 weeks and 13,339 delivered at 39 to 40 weeks; mean birth weight was 3,107±548 g and 3,362±439 g, respectively. The risk of the composite adverse neonatal outcome was 6.1% for the 36- to 38-week group compared with 2.5% for the 39- to 40-week group (relative risk 2.4; confidence interval [CI] 1.7-3.5). After multivariable adjustment, early delivery remained significantly associated with an increased risk of the composite outcome (adjusted odds ratio [OR]1.7; CI 1.1-2.6) as well as several individual outcomes, including respiratory distress syndrome (adjusted OR 7.6; CI 2.2-26.6), treated hyperbilirubinemia (adjusted OR 11.2; CI 3.6-34), and hypoglycemia (adjusted OR 5.8; CI 2.4-14.3). Conclusion: Neonates delivered at 36 to 38 weeks after confirmed fetal lung maturity are at higher risk of adverse outcomes than those delivered at 39 to 40 weeks. © 2010 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins.

Hwang T.-C.,University of Missouri | Kirk K.L.,University of Alabama at Birmingham
Cold Spring Harbor Perspectives in Medicine | Year: 2013

Cystic fibrosis transmembrane conductance regulator (CFTR) is an ATP-gated anion channel with two remarkable distinctions. First, it is the only ATP-binding cassette (ABC) transporter that is known to be an ion channel-almost all others function as transport ATPases. Second, CFTR is the only ligand-gated channel that consumes its ligand (ATP) during the gating cycle-a consequence of its enzymatic activity as an ABC transporter. We discuss these special properties of CFTR in the context of its evolutionary history as an ABC transporter. Other topics include the mechanisms by which CFTR gating is regulated by phosphorylation of its unique regulatory domain and our current view of the CFTR permeation pathway (or pore). Understanding these basic operating principles of the CFTR channel is central to defining the mechanisms of action of prospective cystic fibrosis drugs and to the development of new, rational treatment strategies. © 2013 Cold Spring Harbor Laboratory Press; all rights reserved.

Hughey L.C.,University of Alabama at Birmingham
Dermatologic Therapy | Year: 2011

Approaching the hospitalized patient with skin disease can be daunting. This article focuses on a practical approach to the patient with targetoid lesions. The discussion focuses on differentiating erythema multiforme from Stevens-Johnson syndrome and toxic epidermal necrolysis. In addition, the article offers a concise review of the broader differential diagnosis of targetoid lesions including ecthyma gangrenosum, fixed drug eruption, erythemamultiforme-like drug reaction, vasculitis, acute hemorrhagic edema of infancy, erythema chronicum migrans, connective tissue diseases, and blistering diseases. © 2011 Wiley Periodicals, Inc.

Andringa K.K.,University of Alabama at Birmingham
Methods in enzymology | Year: 2010

The ability to detect and identify mitochondrial proteins that are sensitive to oxidative modification and inactivation by reactive species is important in understanding the molecular mechanisms responsible for mitochondrial dysfunction and tissue injury. In particular, cysteine residues play critical roles in maintaining the functional and structural integrity of numerous proteins in the mitochondrion and throughout the cell. To define changes in mitochondrial protein thiol status, proteomic approaches have been developed in which unmodified, reduced thiols (i.e., R-SH or thiolate species R-S(-)) are tagged with thiol-labeling reagents that can be visualized following gel electrophoresis and immunoblotting techniques. Herein, we describe the use of one thiol-labeling approach in combination with blue native gel electrophoresis (BN-PAGE) to detect reactive thiol groups within mitochondrial proteins including those of the oxidative phosphorylation (OxPhos) system. Labeling or "tagging" of protein thiol groups in combination with various gel electrophoresis and proteomics techniques is a valuable way to measure alterations in cellular or organelle thiol proteomes in response to drug treatment, disease state, or metabolic/oxidative stress. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Wang H.E.,University of Alabama at Birmingham
Prehospital emergency care : official journal of the National Association of EMS Physicians and the National Association of State EMS Directors | Year: 2013

Despite its long history and current prominence in U.S. communities, only limited data describe the national characteristics of emergency medical services (EMS) care in the United States. We sought to characterize out-of-hospital EMS care in the United States. We conducted an analysis of the 2010 National Emergency Medical Services Information System (NEMSIS) research data set, encompassing EMS emergency response data from 29 states. From these data, we estimated the national number and incidence of EMS responses. We also characterized EMS responses and the patients receiving care. There were 7,563,843 submitted EMS responses, corresponding to an estimated national incidence of 17.4 million EMS emergency responses per year (56 per 1,000 person-years). The EMS response incidence varied by U.S. Census region (South 137.4 per 1,000 population per year, Northeast 85.2, West 39.7, and Midwest 33.3). The use of lights and sirens varied across Census regions (Northeast 90.3%, South 76.7%, West 68.8%, and Midwest 67.5%). The percentage of responses resulting in patient contact varied across Census regions (range 78.4% to 95.7%). The EMS time intervals were similar between Census regions; response median 5 minutes (interquartile range [IQR] 3-9), scene 14 minutes (10-20), and transport 11 minutes (7-19). Underserved populations (the elderly, minorities, rural residents, and the uninsured) were large users of EMS resources. These data highlight the breadth and diversity of EMS demand and care in the United States.

Riley B.H.,University of Alabama at Birmingham
Journal of Child and Adolescent Psychiatric Nursing | Year: 2010

TOPIC: A greater number of gay males, lesbians, and bisexual females or males (GLB) are "coming out" during adolescence. Discussion includes nursing implications.PURPOSE: The purpose of this paper is to review the process of GLB disclosure, highlight the trend toward earlier outing, and discuss its implications for nursing practice. SOURCES: Sources include scholarly published literature, professional organization documents, and GLB advocacy publications. CONCLUSIONS: Nurses need to update their knowledge of coming-out issues, as well as nondisclosing sexual behavior, to assess youth and family needs and direct care appropriately. © 2010 Wiley Periodicals, Inc.

Askenazi D.,University of Alabama at Birmingham
Pediatric Nephrology | Year: 2012

Acute kidney injury (AKI) is a common event in several neonatal populations, and those neonates with AKI have poor outcomes. Serum creatinine (SCr)-based definitions of AKI are not ideal and are additionally limited in neonates whose SCr reflects the maternal creatinine level at birth and normally drops over the first weeks of life dependent on gestational age. Recent studies show that urine and serum biomarkers may provide a better basis than SCr on which to diagnose AKI. In this month's issue of Pediatric Nephrology, Sarafidis et al. show that urine neutrophil gelatinase-associated lipocalin (uNGAL), serum NGAL (sNGAL), and urine cystatin c (uCysC) are highest in those neonates with asphyxia who have elevated SCr. Furthermore, those with asphyxia without a concomitant rise in SCr levels have elevated levels of biomarkers compared to controls, suggesting a dose response. Once the SCr level returns to normal, the levels of novel AKI biomarkers continue to be elevated. While these findings strengthen the argument for the clinical use of these AKI biomarkers, further work is needed before they can be implemented in clinical practice. Large-scale observational multi-center studies are needed to test these biomarkers against hard clinical endpoints. In addition, randomized intervention trials which use biomarkers to define AKI need to be performed. © IPNA 2011.

Ovalle F.,University of Alabama at Birmingham
Diabetes Research and Clinical Practice | Year: 2010

A number of patients with diabetes require very high (>2Ukg-1day-1), or extremely high (>3Ukg-1day-1), insulin doses for the management of their hyperglycemia. Unfortunately, many of the physicians who treat these patients limit themselves to prescribing ever higher doses of insulin, without questioning why. Furthermore, when the insulin requirements get to be extreme, demanding an explanation, clinicians are frequently lost in a sea of literature where there is not a single paper dealing with this problem systematically.A systematic approach to the evaluation of these patients is necessary to facilitate an appropriate diagnosis, select the most reasonable therapy, and hopefully improve the long-term outcome of these patients. This manuscript intends to provide the clinician with a review of the literature pertinent for the differential diagnosis, work-up, and management of these patients.We will review the definitions of insulin sensitivity during normality, the various degrees or categories of insulin resistance, and the expected insulin requirements during each of these states. Subsequently, we propose a simple alphabetic mnemonic approach to help remember the differential diagnosis, and a clinical algorithm to help guide the work-up of these patients. Lastly, we briefly discuss general management considerations in these conditions. © 2010 Elsevier Ireland Ltd.

Volpicelli-Daley L.A.,University of Alabama at Birmingham | Luk K.C.,University of Pennsylvania | Lee V.M.-Y.,University of Pennsylvania
Nature Protocols | Year: 2014

This protocol describes a primary neuronal model of formation of α-synuclein (α-syn) aggregates that recapitulate features of the Lewy bodies and Lewy neurites found in Parkinson's disease brains and other synucleinopathies. This model allows investigation of aggregate formation, their impact on neuron function, and development of therapeutics. Addition of preformed fibrils (PFFs) synthesized from recombinant α-syn to neurons seeds the recruitment of endogenous α-syn into aggregates characterized by detergent insolubility and hyperphosphorylation. Aggregate formation follows a lag phase of 2-3 d, followed by formation in axons by days 4-7, spread to somatodendritic compartments by days 7-10 and neuron death ∼14 d after PFF addition. Here we provide methods and highlight the crucial steps for PFF formation, PFF addition to cultured hippocampal neurons and confirmation of aggregate formation. Neurons derived from various brain regions from nontransgenic and genetically engineered mice and rats can be used, allowing interrogation of the effect of specific genes on aggregate formation. © 2014 Nature America, Inc. All rights reserved.

Hauth J.C.,University of Alabama at Birmingham
Obstetrics and Gynecology | Year: 2010

Objective: To estimate whether maternally administered vitamins C and E lower the risk of spontaneous preterm birth. Methods: This is a secondary analysis of a randomized, double-masked, placebo-controlled trial in nulliparous women at low-risk administered 1,000 mg vitamin C and 400 international units vitamin E or placebo daily from 9 to 16 weeks of gestation until delivery. Outcomes include preterm birth attributable to premature rupture of membranes (PROM) and total spontaneous preterm births (spontaneous preterm birth attributable to PROM or spontaneous labor). Results: Of the 10,154 women randomized, outcome data were available for 9,968 (4,992 vitamin group and 4,976 placebo group). A total of 1,038 women (10.4%) delivered preterm, of whom 698 (7.0%) had spontaneous preterm birth. A spontaneous preterm birth occurred in 356 women (7.1%) assigned to daily vitamin C and E supplementation and in 342 (6.9%) assigned to placebo. There were 253 women (2.5%) who delivered after preterm PROM and 445 (4.5%) after a spontaneous preterm labor. In women supplemented with vitamins C and E, births attributed to preterm PROM were similar at less than 37 and 35 weeks of gestation, but births were less frequent before 32 weeks of gestation (0.3% compared with 0.6%, adjusted odds ratio 0.3-0.9). However, total spontaneous preterm births across gestation in women supplemented with vitamins C and E or a placebo were similar. Conclusion: Maternal supplementation with vitamins C and E beginning at 9 to 16 weeks of gestation in nulliparous women at low risk did not reduce spontaneous preterm births. © 2010 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams &Wilkins.

Siegers G.M.,University of Western Ontario | Lamb L.S.,University of Alabama at Birmingham
Molecular Therapy | Year: 2014

Exploration of cancer immunotherapy strategies that incorporate γδ T cells as primary mediators of antitumor immunity are just beginning to be explored and with a primary focus on the use of manufactured phosphoantigen-stimulated Vγ9Vδ2 T cells. Increasing evidence, however, supports a critical role for Vδ1+ γδ T cells, a minor subset in peripheral blood with distinct innate recognition properties that possess powerful tumoricidal activity. They are activated by a host of ligands including stress-induced self-antigens, glycolipids presented by CD1c/d, and potentially many others that currently remain unidentified. In contrast to Vγ9Vδ2 T cells, tumor-reactive Vδ1+ T cells are not as susceptible to activation-induced cell death and can persist in the circulation for many years, potentially offering durable immunity to some cancers. In addition, specific populations of Vδ1+ T cells can also exhibit immunosuppressive and regulatory properties, a function that can also be exploited for therapeutic purposes. This review explores the biology, function, manufacturing strategies, and potential therapeutic role of Vδ1+ T cells. We also discuss clinical experience with Vδ1+ T cells in the setting of cancer, as well as the potential of and barriers to the development of Vδ1+ T cell-based adoptive cell therapy strategies. © The American Society of Gene & Cell Therapy.

Wood J.M.,Queensland University of Technology | Owsley C.,University of Alabama at Birmingham
Gerontology | Year: 2014

The useful field of view test was developed to reflect the visual difficulties that older adults experience with everyday tasks. Importantly, the useful field of view test (UFOV) is one of the most extensively researched and promising predictor tests for a range of driving outcomes measures, including driving ability and crash risk as well as other everyday tasks. Currently available commercial versions of the test can be administered using personal computers; these measure the speed of visual processing for rapid detection and localization of targets under conditions of divided visual attention and in the presence and absence of visual clutter. The test is believed to assess higher-order cognitive abilities, but performance also relies on visual sensory function because in order for targets to be attended to, they must be visible. The format of the UFOV has been modified over the years; the original version estimated the spatial extent of useful field of view, while the latest version measures visual processing speed. While deficits in the useful field of view are associated with functional impairments in everyday activities in older adults, there is also emerging evidence from several research groups that improvements in visual processing speed can be achieved through training. These improvements have been shown to reduce crash risk, and can have a positive impact on health and functional well-being, with the potential to increase the mobility and hence the independence of older adults. © 2014 S. Karger AG, Basel.

Burdette A.M.,Florida State University | Needham B.L.,University of Alabama at Birmingham
Journal of Adolescent Health | Year: 2012

To investigate whether neighborhood conditions during adolescence are associated with body mass index (BMI) extending into young adulthood. Latent growth curve modeling was used to examine BMI over three waves (1996, 2001, and 2008) of the National Longitudinal Study of Adolescent Health (n = 9,115). Parental perceptions of neighborhood disorder and neighborhood structural disadvantage were positively associated with BMI at baseline. Although parental perceptions of disorder were not associated with the rate of change in BMI over time, neighborhood structural disadvantage was positively associated with the slope of BMI. Adolescents who lived in more disadvantaged neighborhoods not only had higher BMI at the beginning of the study, but they also gained weight at a faster rate than those who lived in more advantaged neighborhoods at the first wave of data collection. The data also revealed notable gender, racial, and ethnic subgroup variations in the relationship between neighborhood context and BMI. The neighborhood environment during the critical period of adolescence appears to have a long-term effect on BMI in adulthood. Policy interventions focusing on the neighborhood environment may have far-reaching effects on adult health.

Keri L.,University of Alabama at Birmingham
African health sciences | Year: 2010

OBJECTIVES: To assess current beliefs, knowledge and practices of Ugandan traditional birth attendants (TBAs) and their pregnant patients regarding referral of obstructed labors and fistula cases. METHODS: Six focus groups were held in rural areas surrounding Kampala, the capital city of Uganda. RESULTS: While TBAs, particularly those with previous training, appear willing to refer problematic pregnancies and labors, more serious problems exist that could lessen any positive effects of training. These problems include reported abuse by doctors and nurses, and seeing fistula as a disease caused by hospitals. CONCLUSIONS: Training of TBAs can be helpful to standardize knowledge about and encourage timely emergency obstetric referrals, as well as increase knowledge about the causes and preventions of obstetric fistula. However, for full efficacy, training must be accompanied by greater collaboration between biomedical and traditional health personnel, and increased infrastructure to prevent mistreatment of pregnant patients by medical staff.

Day J.J.,University of Alabama at Birmingham
Dialogues in Clinical Neuroscience | Year: 2014

Cellular processes that control transcription of genetic information are critical for cellular function, and are often implicated in psychiatric and neurological disease states. Among the most critical of these processes are epigenetic mechanisms, which serve to link the cellular environment with genomic material. Until recently our understanding of epigenetic mechanisms has been limited by the lack of tools that can selectively manipulate the epigenome with genetic, cellular, and temporal precision, which in turn diminishes the potential impact of epigenetic processes as therapeutic targets. This review highlights an emerging suite of tools that enable robust yet selective interrogation of the epigenome. In addition to allowing site-specific epigenetic editing, these tools can be paired with optogenetic approaches to provide temporal control over epigenetic processes, allowing unparalleled insight into the function of these mechanisms. This improved control promises to revolutionize our understanding of epigenetic modifications in human health and disease states. © 2014, AICH - Servier Research Group.

Muensterer O.J.,University of Alabama at Birmingham
Journal of Gastrointestinal Surgery | Year: 2010

Background: Pyloromyotomy by single-incision pediatric endosurgery (SIPES) is a new technique that leaves virtually no appreciable scar. So far, it has not been compared to conventional laparoscopic (CL) pyloromyotomy. This study compares the results of the first 15 SIPES pyloromyotomies of a surgeon to his last 15 CL cases. Methods: Data were collected on all SIPES pyloromyotomies. Age, gender, operative time, estimated blood loss, conversion/complication rate, and outcome in the SIPES patients were compared to the CL cohort. Results: There was no difference in age, weight, gender, blood loss, or hospital stay. A trend toward shorter operating time was found in the CL group (21.7 ± 9.9 versus 30.3 ± 15.8, p=0.08, 95%CI 20.9-39.7 min). Two mucosal perforations occurred in the SIPES cohort. Both cases were converted to conventional laparoscopy, the defect was repaired, and both patients had an uncomplicated postoperative course. There were no wound infections or conversions to open surgery. Parents were uniformly pleased with the cosmetic results of SIPES. Conclusion: SIPES pyloromyotomy may have a higher perforation rate than the CL approach. If recognized, a laparoscopic repair is feasible. Improved cosmesis must be carefully weighed against the potentially increased risks of SIPES versus conventional laparoscopic pyloromyotomy. © 2010 The Society for Surgery of the Alimentary Tract.

Wilson W.W.,Mississippi State University | Delucas L.J.,University of Alabama at Birmingham
Acta Crystallographica Section F:Structural Biology Communications | Year: 2014

This article begins by highlighting some of the ground-based studies emanating from NASA's Microgravity Protein Crystal Growth (PCG) program. This is followed by a more detailed discussion of the history of and the progress made in one of the NASA-funded PCG investigations involving the use of measured second virial coefficients (B values) as a diagnostic indicator of solution conditions conducive to protein crystallization. A second application of measured B values involves the determination of solution conditions that improve or maximize the solubility of aqueous and membrane proteins. These two important applications have led to several technological improvements that simplify the experimental expertise required, enable the measurement of membrane proteins and improve the diagnostic capability and measurement throughput. © 2014 International Union of Crystallography All rights reserved.

Tucholski J.,University of Alabama at Birmingham
Amino Acids | Year: 2010

Tissue transglutaminase (TG2) is a multifunctional member of the transglutaminase (TGase) family (E.C., which catalyzes in a calcium-dependent reaction the formation of covalent bonds between the γ-carboxamide groups of peptide-bound glutamine residues and various primary amines. Here, we investigated the role of TG2 in a response of the neuroblastoma SH-SY5Y cells to topoisomerase II inhibitor etoposide, known to trigger DNA-damage cell response. We found an early and transient (∼2 h)increase of the TG2 proteininSH-SY5Y cells treated with etoposide, along with the increase of phosphorylated and total levels of the p53 protein. Next, we showed that SH-SY5Y cells, which overexpress wild-type TG2 were significantly protected against etoposide-induced cell death. The TG2 protective effect was associated only with the transamidation active form of TG2, because overexpression the wild-type TG2, but not its transamidation inactive C277S form, resulted in a pronounced suppression of caspase-3 activity as well as p53 phosphorylation during the etoposide induced stress. In addition, exacerbation of cell death with a significant increase in caspase-3 and p53 activation was observed in SH/anti-TG2 cells, in which expression of the endogenous TG2 protein has been greatly reduced by the antisense cDNA construct. Though the cell signaling and molecular mechanisms of the TG2-driven suppression of the cell death machinery remain to be investigated, our findings strongly suggest that TG2 plays an active role in the response of neuroblastoma cells to DNA-damage-induced stress by exerting a strong protective effect, likely by the suppression of p53 activation and p53-driven cell signaling events. © Springer-Verlag 2010.

Human cytomegalovirus (HCMV) is the most common virus infection in the developing fetus. A fraction of infants infected in utero develop significant life-threatening and organ-threatening disease with over 90 % of infected infants exhibiting no clinical evidence of infection in the newborn period. However, about 10 % of all infected infants will develop long-term sequelae. Early studies stressed the importance of primary maternal HCMV infection during pregnancy as a critical determinant of intrauterine transmission and outcome. This concept serves as the foundation for the development of prophylactic vaccines and biologics such as HCMV immune globulins. More recently, studies in maternal populations with high HCMV seroprevalence have challenged the concept of protective maternal immunity. Findings from multiple studies suggest that preexisting maternal HCMV immunity provides at best, partial protection from disease in the infected offspring and similarly may have limited impact on intrauterine transmission. This brief review will provide some considerations about the apparent paradox of maternal HCMV immunity and congenital infection. © 2015, Springer-Verlag Berlin Heidelberg.

Wang J.,University of Alabama at Birmingham
Cold Spring Harbor perspectives in biology | Year: 2012

Wnts are evolutionarily conserved signaling ligands critical for animal development. Genetic engineering in the mouse has enabled investigators to acquire a detailed activation profile of the β-catenin-dependent canonical Wnt pathway during mouse development, and to manipulate Wnt pathway activities with great spatial and temporal precision. Together, these studies have not only revealed important functions of Wnt signaling at multiple stages of early mouse development, but also elucidated how the Wnt pathway interacts with other pathways to form signaling networks that confer the unique features of mammalian embryogenesis. Additionally, the planar cell polarity pathway has emerged as an essential β-catenin independent noncanonical Wnt pathway that coordinates cell polarity and regulates tissue morphogenesis in various mammalian developmental processes. Importantly, studies of Wnt signaling in mouse development have also revealed important pathogenic mechanisms of several congenital disorders in humans.

Fouad M.N.,University of Alabama at Birmingham
Cancer | Year: 2014

The Community Health Advisor (CHA) model has been widely used to recruit rural and low-income, mostly African American women into clinical and behavioral research studies. However, little is known about its effectiveness in promoting retention and adherence of such women in clinical trials. The Community-Based Retention Intervention Study evaluated the effectiveness of a community-based intervention strategy using the CHA model and the empowerment theory to improve the retention and adherence of minority and low-income women in clinical trials. The research strategy included the training and use of the volunteer CHAs as research partners. The target population included women participating in the University of Alabama at Birmingham clinical site of the Atypical Squamous Cells of Undetermined Significance-Low-Grade Squamous Intraepithelial Lesion (ASCUS-LSIL) Triage Study (ALTS), a multicenter, randomized clinical trial. Two communities in Jefferson County, Alabama, that were matched according to population demographics were identified and randomly assigned to either an intervention group or a control group. Thirty community volunteers were recruited to be CHAs and to implement the intervention with the ALTS trial participants. In total, 632 ALTS participants agreed to participate in the project, including 359 in the intervention group, which received CHA care, and 273 in the control group, which received standard care. Adherence rates for scheduled clinic visits were significantly higher in the intervention group (80%) compared with the control group (65%; P < .0001). The results indicate that volunteer CHAs can be trained to serve as research partners and can be effective in improving the retention and adherence of minority and low-income women in clinical trials. © 2014 American Cancer Society.

Vyazovkin S.,University of Alabama at Birmingham
Physical Chemistry Chemical Physics | Year: 2016

This review deals with the phenomenon of variable activation energy frequently observed when studying the kinetics in the liquid or solid phase. This phenomenon commonly manifests itself through nonlinear Arrhenius plots or dependencies of the activation energy on conversion computed by isoconversional methods. Variable activation energy signifies a multi-step process and has a meaning of a collective parameter linked to the activation energies of individual steps. It is demonstrated that by using appropriate models of the processes, the link can be established in algebraic form. This allows one to analyze experimentally observed dependencies of the activation energy in a quantitative fashion and, as a result, to obtain activation energies of individual steps, to evaluate and predict other important parameters of the process, and generally to gain deeper kinetic and mechanistic insights. This review provides multiple examples of such analysis as applied to the processes of crosslinking polymerization, crystallization and melting of polymers, gelation, and solid-solid morphological and glass transitions. The use of appropriate computational techniques is discussed as well. © the Owner Societies 2016.

Sami N.,University of Alabama at Birmingham
Dermatologic Therapy | Year: 2011

Autoimmune mucocutaneous blistering diseases (AMBD) are a rare group of dermatoses that can be potentially fatal. There are many subtypes and their clinical presentation can vary from being localized to general involvement. It is crucial that a diagnosis be made as early as possible and appropriate treatments are implemented. This article will discuss the diagnosis and available treatments of the major AMBDs. There are very few case-controlled studies regarding the treatments of these diseases. Most of the treatments used for these diseases are based on anecdotal reports. Hence, a synopsis of the conventional treatments and some brief recommendations will also be discussed. A brief discussion regarding "rescue" therapies that have been used for those patients with more recalcitrant cases of AMBD will also be presented. © 2011 Wiley Periodicals, Inc.

Escudier B.,Institute Gustave Roussy | Albiges L.,Institute Gustave Roussy | Sonpavde G.,University of Alabama at Birmingham
Drugs | Year: 2013

The armamentarium for the systemic therapy of advanced renal cell carcinoma (RCC) has undergone dramatic changes over the past 6 years. While high-dose interleukin (IL)-2 remains an option for highly selected good and intermediate risk patients with clear-cell histology because of durable complete responses in a small fraction of patients, cytokine-based therapy including interferon (IFN) has been supplanted by vascular-endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) inhibitors. Treatment decision is initially based on prognostication of the disease. As metastatic RCC (mRCC) is commonly an indolent disease, a period of observation should always been considered. For good and intermediate risk disease, pazopanib, sunitinib or the combination of bevacizumab plus IFN are considered. Notably, recent data suggest non-inferiority for the efficacy of pazopanib compared to sunitinib coupled with a better toxicity profile. A novel VEGF receptor inhibitor, tivozanib, is expected to be approved based on improvement in PFS when compared to sorafenib in the first-line setting. The use of temsirolimus for poor risk disease is supported by a phase III trial dedicated to this group of patients. The role of cytoreductive nephrectomy in the context of VEGF and mTOR inhibitors is being studied in randomized trials. Selected patients with solitary or oligometastatic disease may be eligible for metastatectomy. Following first-line VEGF inhibitors, second-line therapy with everolimus and axitinib have demonstrated benefits in progression-free survival (PFS). One phase III trial comparing sorafenib and temsirolimus in the post-sunitinib setting showed no difference in PFS, the primary endpoint, but did show a superior overall survival for sorafenib. Sorafenib, pazopanib and axitinib have all demonstrated clinical benefit following cytokines. Therapy following first-line mTOR inhibitors remains undefined, although VEGF inhibitors have demonstrated activity in this setting. Optimal sequencing of agents and individualized therapy based on biomarkers is undergoing investigation. Today, the choice of therapy is based on patient and physician decision, which is a function of comorbidities, toxicity profiles and costs. Clinical trials evaluating novel agents and combinations should be preferred when available since agents in the current therapeutic arsenal have not yielded cures despite extending median survival to greater than 2 years. One noteworthy new class of agents that has yielded durable responses is programmed death (PD)-1 inhibitors, which target a T-lymphocyte checkpoint and are heralding a resurgence of immunotherapy. Finally, optimal therapy for non-clear cell RCC remains to be delineated, although sunitinib, everolimus and other VEGFR-TKI or mTOR inhibitors have all demonstrated modest benefit. © 2013 Springer International Publishing Switzerland.

Mountz J.D.,University of Alabama at Birmingham
Discovery medicine | Year: 2011

Chemotaxis is essential for shaping immune responses and chemokine-receptor antagonists are now being evaluated as therapies for various inflammatory and autoimmune diseases. However, the dysregulation of chemotaxis in autoimmune disease may involve both promotion and inhibition of B-cell migration. This review focuses on the disparate mechanisms by which two inflammatory cytokines that have been associated with autoimmune disease, namely interferon-alpha (IFN-alpha) and interleukin-17 (IL-17), may regulate B-cell migratory responses. Chemotactic responses play a key role in orchestrating the cell-cell interactions in the germinal centers (GCs). This process involves active shuttling of the antigen-carrying B cells between the marginal zone and the GCs. We have shown that in autoimmune BXD2 mice, the migration of marginal zone precursor B cells is promoted by high levels of IFN-alpha produced by plasmacytoid dendritic cells in the marginal sinus that antagonize the activity of the S1P(1) chemokine receptor. In contrast, within the GCs, interleukin-17A (IL-17A) upregulates the expression of regulators of G protein signaling (RGS) in B cells to desensitize the G protein-coupled receptor (GPCR) signaling pathway of CXCL12 and CXCL13 chemokines. This promotes a prolonged stable interaction of B and T cells in the GC that induces high levels of activation-induced cytidine deaminase (AICDA) thereby enabling development of pathogenic autoantibody-producing B cells.

Introduction: Weight-management options include lifestyle modifications, bariatric surgery and, until recently, limited pharmacotherapy. Phentermine and topiramate extended-release (phentermine/topiramate ER) has recently been approved in the USA for chronic weight management in obese adults and overweight adults with weight-related co-morbidities in conjunction with a reduced-calorie diet and increased physical activity. Areas covered: This review describes the pharmacology and clinical trials data for phentermine/topiramate ER and its role in a complications-centric approach to medical care of the overweight and obese patient. Expert opinion: Phentermine/topiramate ER is an effective and safe weight-loss medication that can produce and sustain approximately 10% loss of body weight. This is a landmark development in the pharmacotherapy of obesity. By offering an effective medical option to complement lifestyle and surgical approaches, phentermine/topiramate ER enables a comprehensive medical model for obesity care. The overall approach to the overweight and obese patient should be to identify individuals who will benefit most from therapy based on cardiometabolic or mechanical complications, establish therapeutic targets and goals for ameliorating these complications and selecting the treatment modality and intensity for weight loss to achieve these goals. This complications-centric model emphasizes weight loss as a tool to ameliorate obesity-related complications and optimizes benefit/risk for achieving the best outcomes in overweight/obese patients. © 2013 Informa UK, Ltd.

Kharkar S.,University of Alabama at Birmingham | Knowlton R.,University of California at San Francisco
Epilepsy and Behavior | Year: 2015

Magnetoencephalography (MEG) is an important tool in the presurgical evaluation of patients with medically refractory epilepsy. The appropriate utilization and interpretation of MEG studies can increase the proportion of patients who may be able to further pursue surgical evaluation, refine surgical planning, and potentially increase the probability of seizure freedom after surgery. The aim of this paper is to provide the reader with a comprehensive but accessible guide to MEG, with particular emphasis on acquiring a working knowledge of MEG analysis, identifying patient groups that are most likely to benefit, and clarifying the limitations of this technology. © 2014 Elsevier Inc.

Oparil S.,University of Alabama at Birmingham
Nature reviews. Cardiology | Year: 2011

Provocative new studies have shown that tight blood pressure (BP) control (goal systolic BP <120 mmHg) in high-risk patients with diabetes mellitus confers no significant cardiovascular benefit other than stroke reduction, and that BP variability is important for the diagnosis and management of hypertension. the impact of these findings on future hypertension guidelines remains to be assessed.

Bell D.S.H.,University of Alabama at Birmingham
Southern Medical Journal | Year: 2010

Correction of hyperlipidemia with statins is often limited by the side-effect of statin-induced myalgias. Vitamin D deficiency is also associated with myalgias that resolve with correction of the vitamin D deficiency. Myalgias associated with statin therapy may also resolve with correction of vitamin D deficiency. This case report presents a case where cardioprotective lipid levels were achieved with a powerful statin only after correction of vitamin D deficiency. Copyright © 2010 by The Southern Medical Association.

Elewski B.E.,University of Alabama at Birmingham
Journal of drugs in dermatology : JDD | Year: 2013

Onychomycosis is a fungal infection of the nail unit, more common in toenails than in fingernails, and caused by a variety of fungi including dermatophytes, nondermatophyte molds, and Candida. There are 4 to 5 subtypes related to the method of fungal invasion of the nail unit, the most common being distal lateral subungual onychomycosis. Here the fungus enters the distal lateral part of the nail bed, the region of the hyponychium, often as an extension of tinea pedis. Hyperkeratosis occurs under the nail plate, resulting in detachment of the nail plate from the nail bed (onycholysis), with subungual thickening.

Hoffnagle J.A.,Picarro Inc. | Shealy D.L.,University of Alabama at Birmingham
Journal of the Optical Society of America A: Optics and Image Science, and Vision | Year: 2011

The k-function of Stavroudis describes a solution of the eikonal equation in a region of constant refractive index. Given the k-function describing the optical field in one region of space, and given a prescribed refractive or reflective boundary, we construct the k-function for the refracted or reflected field. This procedure, which Stavroudis calls refracting the k-function, can be repeated any number of times, and therefore extends the usefulness of the k-function formalism to multielement optical systems. As examples, we present an analytic solution for the k-function, wavefronts, and caustics generated by a biconvex thick lens illuminated by a plane wave propagating parallel to the symmetry axis, and numerical results for off-axis plane-wave illumination of a two-mirror telescope. © 2011 Optical Society of America.

Bowling M.R.,University of Alabama at Birmingham
Obstetrics and Gynecology | Year: 2010

Backgrond: Uterine rupture after endometrial ablation is rare and has not been reported previously in the English literature. Case: A 33-year-old multigravida at 26 5/7 weeks of gestation had undergone two endometrial ablation procedures. The first attempt 2 years before pregnancy was complicated by uterine perforation. She presented with severe abdominal pain. A cesarean delivery was performed for recurrent late fetal heart rate deceleration, and a complete spontaneous uterine rupture was discovered. Conclusion: Pregnancies that occur after endometrial ablation have a risk of morbidity. Physicians must counsel women on the importance of contraception or sterilization as a critical component of the procedure. © 2010 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins.

Collawn S.S.,University of Alabama at Birmingham
Annals of Plastic Surgery | Year: 2010

Skin tightening occurs with the use of fractional lasers, radiofrequency, and Smartlipo. The fractional lasers Fraxel (1550 nm; Solta Medical, Inc., Hayward, CA) and Affirm (1440 nm, 1320 nm) (Cynosure, Westford, MA) when used in combination tighten skin and lessen solar keratoses, and improve acne scars. With radiofrequency, further tightening occurs. Smartlipo (Cynosure, Westford, MA) (1064 nm or the newer MPX with combined 1064 nm and 1320 nm) results in skin tightening and has been very helpful in improving skin tightness and smoothness on the neck either singularly or in combination with the above procedures; and with the addition of the Affirm fractional CO2 laser (Cynosure, Westford, MA), further skin improvement and tightening occurs. Copyright © 2010 by Lippincott Williams & Wilkins.

Hameed O.,University of Alabama at Birmingham
American Journal of Surgical Pathology | Year: 2010

Invasive urothelial carcinoma is characterized by a number of histologic variants that can sometimes lead to diagnostic difficulty. In addition to those described by the World Health Organization, 2 additional variants have recently been described, invasive urothelial carcinoma with chordoid features and urothelial carcinoma with abundant myxoid stroma, both being characterized by the presence of a prominent myxoid stroma. This report describes a peculiar type of cystitis that closely mimicked myxoid urothelial carcinoma. A transurethral resection specimen from a 73-year-old woman with an earlier diagnosis of invasive urothelial carcinoma focally displayed rounded, epithelioid cells arranged in a corded manner and separated by myxoid stroma; this was originally misinterpreted as recurrent invasive carcinoma. A review of the case with immunohistochemical studies showed the component cells to be polyclonal B-lymphocytes, based upon which the diagnosis of malignancy was reversed. This peculiar form of cystitis, herein termed myxoid cystitis with "chordoid" lymphocytes, has not been described earlier and should be considered among the mimics of invasive urothelial carcinoma, especially those with a myxoid stroma. © 2010 by Lippincott Williams & Wilkins.

Zhou D.,University of Alabama at Birmingham
Nature genetics | Year: 2010

We show that knockdown of KLF1 in human and mouse adult erythroid progenitors markedly reduces BCL11A levels and increases human gamma-globin/beta-globin expression ratios. These results suggest that KLF1 controls globin gene switching by directly activating beta-globin and indirectly repressing gamma-globin gene expression. Controlled knockdown of KLF1 in adult erythroid progenitors may provide a method to activate fetal hemoglobin expression in individuals with beta-thalassemia or sickle cell disease.

Abd Elmageed Z.Y.,Tulane University Medical Center | Naura A.S.,Louisiana State University Health Sciences Center | Errami Y.,Louisiana State University Health Sciences Center | Zerfaoui M.,University of Alabama at Birmingham
Cellular Signalling | Year: 2012

Post-transcriptional modification of proteins is crucial for balancing protein structure and function in many biological processes. The addition of polymers of adenosine diphosphate (ADP)-ribose (PAR), which are synthesized by PAR polymerases (PARPs) from nicotinamide adenine dinucleotide (NAD), is one such distinctive post-translational modification. PARP-1, the best characterized of the 17-member PARP family, is considered a key isoform responsible for poly(ADP-ribosyl)ation of several nuclear proteins. ADP-ribose polymers add a highly negative charge to their target proteins, resulting in a modification of their activities and functions. PARPs not only participate in regulating cell survival and cell death programs, but are also involved in other biological functions with which novel members of the PARP family have been shown to be involved. Among such functions are transcription regulation, telomere cohesion and mitotic spindle formation during cell division, and intracellular energy metabolism. Recent work from our laboratory and others has highlighted the novel role of PARP-1 in regulating the intracellular trafficking of key cellular proteins such as p53 and nuclear factor-kappa B (NF-κB). Recent literature has revealed that ADP-ribosylation reactions may play important roles in cellular trafficking during inflammation, cell death, and DNA repair. This review will summarize recent findings and concepts linking the role of PARP enzymes and their poly-ADP-ribosylation activity in the regulation of intracellular transport processes. A special focus is placed on the proposed molecular mechanisms involved in such transport processes as the functional significance of PARylation of p53, NF-κB, and high-mobility group protein box 1. © 2011 Elsevier Inc.

Tollefsbol T.O.,University of Alabama at Birmingham
Methods in Molecular Biology | Year: 2011

Epigenetics refers to the collective heritable changes in phenotype that arise independent of genotype. Two broad areas of epigenetics are DNA methylation and histone modifications and numerous techniques have been invented to analyze epigenetic processes not only at the level of specific genes, but also to analyze epigenetic changes that occur in defined regions of the genome as well as genome-wide. Advances have also been made in techniques devised to assess the enzymes that mediate epigenetic processes. These methods that are currently driving the field of epigenetics will greatly facilitate continued expansion of this exponentially growing discipline of genetics. © 2011 Springer Science+Business Media, LLC.

Bowling C.B.,Birmingham Atlanta Geriatric Research | Muntner P.,University of Alabama at Birmingham
Journals of Gerontology - Series A Biological Sciences and Medical Sciences | Year: 2012

The National Kidney Foundation (NKF), Kidney Disease Outcomes Quality Initiative (KDOQI) Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification expanded the focus of chronic kidney disease (CKD) management from end-stage renal disease (ESRD) to the entire spectrum of kidney disease including early kidney damage through the stages of kidney disease to kidney failure. A consequence of these guidelines is that a large number of older adults are being identified as having CKD, many of whom will not progress to ESRD. Concerns have been raised that reduced estimated glomerular filtration rate (eGFR) among older adults may not represent "disease" and using age-specific cut-points for staging CKD has been proposed. This implies that among older adults, CKD, as currently defined, may be benign. Several recent studies have shown that among people greater than or equal to 80 years old, CKD is associated with an increased risk for concurrent complications of CKD (eg, anemia, acidosis) and adverse outcomes including mortality and cardiovascular disease (CVD). Further, among older adults, CKD is associated with problems not traditionally thought to be associated with kidney disease. These nondisease-specific outcomes include functional decline, cognitive impairment, and frailty. Future research studies are necessary to determine the impact of concurrent complications of CKD and nondisease-specific problems on mortality and functional decline, the longitudinal trajectories of CKD progression, and patient preferences among the oldest old with CKD. © The Author 2012. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved.

Michaelis L.C.,Medical College of Wisconsin | Erba H.P.,University of Alabama at Birmingham
Current Opinion in Hematology | Year: 2015

PURPOSE OF REVIEW: The treatment of acute myeloid leukemia (AML) in older persons remains a tremendous clinical challenge. AML in older patients is more often associated with biologically unfavorable features, and these patients are less likely to tolerate or accept intensive therapy. There have not been substantial improvements in outcome for this group of patients despite decades of research. In this review, we summarize the most substantial contributions in the past 2 years. RECENT FINDINGS: There have been three major research themes in the recently published literature for older patients with AML: methods to predict response to therapy, models to predict toxicity of therapy in older, less-fit patients, and investigation of novel agents for AML patients with either newly diagnosed or relapsed disease. An unexpected recent finding has been the observation that complete remission in this disease may not necessarily translate into an overall survival advantage, and conversely, survival benefit has been demonstrated without any improvement in complete remission. SUMMARY: Although anthracycline and cytarabine-based therapy remains the standard of care for older patients with AML, this option remains suboptimal for the vast majority of patients. We argue for a national research agenda that may help to accelerate progress for older people with AML. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Tolwani A.,University of Alabama at Birmingham
New England Journal of Medicine | Year: 2012

Acute limb ischemia due to a perioperative type B (distal) thoracic aortic dissection develops in a 90-kg, 20-year-old man with Marfan's syndrome who is admitted to the hospital for elective aortic-valve replacement. On postoperative day 1, he undergoes endovascular repair of the thoracic aorta. On postoperative day 4, his urine output decreases to 420 ml over a 24-hour period. He requires mechanical ventilation with a fraction of inspired oxygen (FIO2) of 0.70; his mean arterial pressure is 74 mm Hg with vasopressor support. He has had a positive fluid balance of 9.8 liters since admission. The serum creatinine level has increased from a baseline of 0.6 mg per deciliter (53.0 μmol per liter) to 4.4 mg per deciliter (389.0 μmol per liter). The bicarbonate level is 19 mmol per liter despite bicarbonate infusion, and the potassium level is 6.1 mmol per liter. The creatine kinase level has increased to 129,040 U per liter. An intensive care specialist evaluates the patient and recommends initiation of continuous renal-replacement therapy. Copyright © 2012 Massachusetts Medical Society.

Hilton D.J.,University of Alabama at Birmingham
Optics Express | Year: 2012

We develop a new characteristic matrix-based method to analyze cyclotron resonance experiments in high mobility two-dimensional electron gas samples where direct interference between primary and satellite reflections has previously limited the frequency resolution. This model is used to simulate experimental data taken using terahertz time-domain spectroscopy that show multiple pulses from the substrate with a separation of 15 ps that directly interfere in the time-domain. We determine a cyclotron dephasing lifetime of 15.1±0.5 ps at 1.5 K and 5.0±0.5 ps at 75 K. © 2012 Optical Society of America.

McGwin Jr. G.,University of Alabama at Birmingham
Archives of Otolaryngology - Head and Neck Surgery | Year: 2010

Objective: To compare use of phosphodiesterase type 5 inhibitors (PDE-5i) between participants with and without self-reported hearing impairment using logistic regression, with and without adjustment for potentially confounding sociodemographic, behavioral, and healthrelated characteristics. Design: Cross-sectional. Setting: United States. Patients: A population-based sample of 11 525 men 40 years or older (248 217 013 weighted men) in the United States, selected from the Medical Expenditure Panel Survey (2003-2006). Main Outcome Measure: Self-reported hearing impairment. Results: The overall prevalence of self-reported hearing impairment and PDE-5i use in each group was 17.9% and 2%, respectively. Men who reported hearing impairment were more likely to have also reported the use of any PDE-5i (odds ratio [OR], 2.23; 95% confidence interval [CI], 1.36-3.66). However, this association was limited to sildenafil (Viagra) (OR, 2.05; 95% CI, 1.23-3.43); no significant associations were observed for tadalafil (Cialis) or vardenafil (Levitra) (ORs, 1.40 [95% CI, 0.49-4.04] and 0.88 [95% CI, 0.35-2.22], respectively). Conclusions: Current warnings regarding the risk of hearing loss related to PDE-5i use seems to be justified. However, the cross-sectional nature of the current study provides only limited insight regarding this relationship, and thus additional research is warranted. ©2010 American Medical Association. All rights reserved.

Epstein M.,University of Miami | Calhoun D.A.,University of Alabama at Birmingham
Journal of Clinical Hypertension | Year: 2011

Key Points and Practical Recommendations: Mineralocorticoid receptor (MR) antagonists (aldosterone blockers) provide effective antihypertensive treatment, especially in low-renin and salt-sensitive forms of hypertension, including resistant hypertension. Newer, more selective MR antagonists (eg, eplerenone) have fewer of the progestational and antiandrogenic effects than spironolactone, enhancing tolerability and potentially improving adherence to therapy. MR antagonists provide an additional benefit in the treatment of heart failure when combined with angiotensin-converting enzyme inhibitors, digoxin, and loop diuretics. Other potassium-sparing diuretics (amiloride or triamterene) are generally prescribed for essential hypertension as a fixed-dose combination with hydrochlorothiazide. The dose range for spironolactone with resistant hypertension is between 25mg/d and 50mg/d, and eplerenone is an appropriate alternative if spironolactone is not tolerated because of sexual side effects. In general, the combined use of spironolactone and adequate doses of a thiazide diuretic or a thiazide-like agent such as chlorthalidone for the treatment of resistant hypertension maximizes efficacy and reduces the risk of spironolactone-induced hyperkalemia. © 2011 Wiley Periodicals, Inc.

Gutierrez O.M.,University of Alabama at Birmingham
Advances in Chronic Kidney Disease | Year: 2015

Nutrition plays an important role in CKD outcomes. One of the strongest factors that affects nutrition is socioeconomic status as evidenced by the large body of epidemiologic data showing that income and education are directly associated with diet quality. Apart from individual-level markers of socioeconomic status such as income and education, contextual factors such as availability of and transportation to food outlets that provide healthy food options and the density of fast-food restaurants within particular regions markedly affect the ability of individuals to comply with nutrition recommendations. This is particularly true for nutrition guidelines most specific to individuals with CKD such as the consumption of protein, saturated fat, sodium, and phosphorus, all of which have been shown to affect CKD health and are influenced by the availability of healthy food options within individual neighborhood food environments. Because of the strong association of contextual poverty with the diet quality, any serious attempt to improve the diet of CKD patients must include a discussion of the environmental barriers that each individual faces in trying to access healthy foods, and health care providers should take account of these barriers when tailoring specific recommendations. © 2015 National Kidney Foundation, Inc.

Kirklin J.K.,University of Alabama at Birmingham
Current Opinion in Organ Transplantation | Year: 2014

Purpose of review: Permanent long-term mechanical circulatory support (MCS) is currently reserved for patients who are transplant ineligible. In light of improved outcomes with current continuous flow devices, increased interest has focused on the potential extension of MCS therapy to ambulatory advanced heart failure patients and as an alternative to cardiac transplantation. Recent findings: Average 1-year and 2-year survival with heart transplantation is about 85 and 80%, and with MCS therapy, it is 85 and 70% (with censoring at transplant). Specific subsets of destination therapy patients enjoy survival out to 2 years, which is comparable with transplant survival. Risk factor analyses identify similar risk profiles for each therapy. Life satisfaction after each is highly dependent on the frequency and severity of adverse events, which are quite different for these interventions. Patients with long expected waiting times will likely be the initial group for triage off the transplant wait list to MCS therapy. Summary: MCS has progressively improved and may become a reasonable alternative to transplantation for highly selected patients with long expected waiting time. More routine extension of MCS therapy to the transplant population awaits further reduction of major adverse events, miniaturized devices, and less invasive implant techniques. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Williams M.S.,University of Alabama at Birmingham
Ghana medical journal | Year: 2012

The age-standardized mortality rate for cervical cancer in Ghana, West Africa is more than three times the global cervical cancer mortality rate (27.6/100,000 vs. 7.8/100,000 respectively). The Pap test and visual inspection with acetic acid are available at public and private hospitals in Ghana. Approximately, 2.7% of Ghanaian women obtain cervical cancer screenings regularly. Men in middle-income countries play a key role in cervical cancer prevention. Increasing spousal support for cervical cancer screening may increase screening rates in Ghana. Five focus groups were conducted with Ghanaian men (N = 29) to assess their cervical cancer and cervical cancer screening knowledge and beliefs. The qualitative data was analyzed via indexed coding. Targets for education interventions were identified including inaccurate knowledge about cervical cancer and stigmatizing beliefs about cervical cancer risk factors. Cultural taboos regarding women's health care behaviours were also identified. Several participants indicated that they would be willing to provide spousal support for cervical cancer screening if they knew more about the disease and the screening methods. Men play a significant role in the health behaviours of some Ghanaian women. Cervical cancer education interventions targeting Ghanaian men are needed to correct misconceptions and increase spousal support for cervical cancer screening.

Pappas P.G.,University of Alabama at Birmingham
Transactions of the American Clinical and Climatological Association | Year: 2013

Infections due to Cryptococcus species occur globally and in a wide variety of hosts, ranging from those who are severely immunosuppressed to those who have phenotypically "normal" immune systems. Approximately 1 million cases of cryptococcosis occur throughout the world, and is it estimated that there are 650,000 associated deaths annually. Most of these cases occur among patients with advanced HIV disease, but a growing number occur among solid organ transplant recipients and others receiving exogenous immunosuppression, patients with innate and acquired immunodeficiency, and otherwise immunologically normal hosts. Much of our recent knowledge is solely derived from clinical experience over the last 2 to 3 decades of cryptococcosis among HIV-infected patients. However, based on recent observations, it is clear that there are substantial differences in the epidemiology, clinical features, approaches to therapy, and outcome when comparing HIV-infected to non-HIV-infected individuals who have cryptococcosis. If one carefully examines cryptococcosis in the three largest subgroups of patients based on host immune status, specifically, those with HIV, solid organ transplant recipients, and those who are non-HIV, non-transplant (NHNT) infected persons, then one can observe very different risks for infection, varied clinical presentations, long-term complications, mortality, and approaches to therapy. This article focuses on cryptococcosis in the non-HIV-infected patient, including a brief review of ongoing events in the Pacific Northwest of the United States and Canada relative to the outbreak of Cryptococcus gattii infections among a largely immunologically normal population, and highlights some of the key insights and questions which have emerged as a result of these important new observations.

Huddle T.S.,University of Alabama at Birmingham
Bioethics | Year: 2013

Opponents of physician-assisted suicide (PAS) maintain that physician withdrawal-of-life-sustaining-treatment cannot be morally equated to voluntary active euthanasia. PAS opponents generally distinguish these two kinds of act by positing a possible moral distinction between killing and allowing-to-die, ceteris paribus. While that distinction continues to be widely accepted in the public discourse, it has been more controversial among philosophers. Some ethicist PAS advocates are so certain that the distinction is invalid that they describe PAS opponents who hold to the distinction as in the grip of 'moral fictions'. The author contends that such a diagnosis is too hasty. The possibility of a moral distinction between active euthanasia and allowing-to-die has not been closed off by the argumentative strategies employed by these PAS advocates, including the contrasting cases strategy and the assimilation of doing and allowing to a common sense notion of causation. The philosophical debate over the doing/allowing distinction remains inconclusive, but physicians and others who rely upon that distinction in thinking about the ethics of end-of-life care need not give up on it in response to these arguments. Copyright © 2013 John Wiley & Sons Ltd.

Johnston A.C.,University of Alabama at Birmingham | Warkentin M.,Mississippi State University
MIS Quarterly: Management Information Systems | Year: 2010

Information technology executives strive to align the actions of end users with the desired security posture of management and of the firm through persuasive communication. In many cases, some element of fear is incorporated within these communications. However, within the context of computer security and information assurance, it is not yet clear how these fear-inducing arguments, known as fear appeals, will ultimately impact the actions of end users. The purpose of this study is to investigate the influence of fear appeals on the compliance of end users with recommendations to enact specific individual computer security actions toward the mitigation of threats. An examination was performed that culminated in the development and testing of a conceptual model representing an infusion of technology adoption and fear appeal theories. Results of the study suggest that fear appeals do impact end user behavioral intentions to comply with recommended individual acts of security, but the impact is not uniform across all end users. It is determined in part by perceptions of self-efficacy, response efficacy, threat severity, and social influence. The findings of this research contribute to information systems security research, human-computer interaction, and organizational communication by revealing a new paradigm in which IT users form perceptions of the technology, not on the basis of performance gains, but on the basis of utility for threat mitigation.

Almeida J.S.,University of Alabama at Birmingham
Briefings in Bioinformatics | Year: 2014

Among alignment-free methods, Iterated Maps (IMs) are on a particular extreme: they are also scale free (order free). The use of IMs for sequence analysis is also distinct from other alignment-free methodologies in being rooted in statistical mechanics instead of computational linguistics. Both of these roots go back over two decades to the use of fractal geometry in the characterization of phase-space representations. The time series analysis origin of the field is betrayed by the title of the manuscript that started this alignment-free subdomain in 1990, 'Chaos Game Representation'. The clash between the analysis of sequences as continuous series and the better established use of Markovian approaches to discrete series was almost immediate, with a defining critique published in same journal 2 years later. The rest of that decade would go by before the scale-free nature of the IM space was uncovered. The ensuing decade saw this scalability generalized for non-genomic alphabets as well as an interest in its use for graphic representation of biological sequences. Finally, in the past couple of years, in step with the emergence of BigData and MapReduce as a new computational paradigm, there is a surprising third act in the IM story. Multiple reports have described gains in computational efficiency ofmultiple orders of magnitude over more conventional sequence analysis methodologies. The stage appears to be now set for a recasting of IMs with a central role in processing nextgen sequencing results. © The Author 2013. Published by Oxford University Press.

Korf B.R.,University of Alabama at Birmingham
Handbook of Clinical Neurology | Year: 2013

The " neurofibromatoses" are a set of distinct genetic disorders that have in common the occurrence of tumors of the nerve sheath. They include NF1, NF2, and schwannomatosis. All are dominantly inherited with a high rate of new mutation and variable expression. NF1 includes effects on multiple systems of the body. The major NF1-associated tumor is the neurofibroma. In addition, clinical manifestations include bone dysplasia, learning disabilities, and an increased risk of malignancy. NF2 includes schwannomas of multiple cranial and spinal nerves, especially the vestibular nerve, as well as other tumors such as meningiomas and ependymomas. The schwannomatosis phenotype is limited to multiple schwannomas, and usually presents with pain. The genes that underlie each of the disorders are known: NF1 for neurofibromatosis type 1, NF2 for neurofibromatosis type 2, and INI1/SMARCB1 for schwannomatosis. Genetic testing is possible to identify mutations. Insights into pathogenesis are beginning to suggest new treatment strategies, and therapeutic trials with several new forms of treatment are underway. © 2013 Elsevier B.V.

Taub E.,University of Alabama at Birmingham
Developmental Psychobiology | Year: 2012

There are striking similarities between the visual defect of amblyopia and the motor deficit of the extremities produced by such types of damage to the central nervous system (CNS) as stroke and traumatic brain injury, both after and before maturity. Part of the motor deficit of the extremities following CNS injury can be attributed to a learning phenomenon termed "learned nonuse" or if present from birth, "developmental disregard." The same mechanism is hypothesized to be involved in the development of amblyopia. Treatments that are efficacious in the remediation of these defects, Constraint-Induced Movement therapy and amblyopia training, also share a number of strong similarities. In addition, plastic brain changes are produced by CI therapy and are hypothesized to occur during amblyopia training. © 2010 Wiley Periodicals, Inc.

Zhou L.,University of Alabama at Birmingham | O'Rourke B.,Johns Hopkins University
American Journal of Physiology - Heart and Circulatory Physiology | Year: 2012

In the heart, mitochondria form a regular lattice and function as a coordinated, nonlinear network to continuously produce ATP to meet the high-energy demand of the cardiomyocytes. Cardiac mitochondria also exhibit properties of an excitable system: electrical or chemical signals can spread within or among cells in the syncytium. The detailed mechanisms by which signals pass among individual elements (mitochondria) across the network are still not completely understood, although emerging studies suggest that network excitability might be mediated by the local diffusion and autocatalytic release of messenger molecules such as reactive oxygen species and/or Ca 2+. In this short review, we have attempted to described recent advances in the field of cardiac mitochondrial network excitability. Specifically, we have focused on how mitochondria communicate with each other through the diffusion and regeneration of messenger molecules to initiate and propagate waves or oscillations, as revealed by computational models of mitochondrial network. © 2012 the American Physiological Society.

Ahmed M.M.,San Antonio Military Medical Center | Moore B.A.,Ochsner Medical Center | Schmalbach C.E.,University of Alabama at Birmingham
Otolaryngology - Head and Neck Surgery (United States) | Year: 2014

Objective. Sentinel lymph node biopsy (SLNB) is standard of care for melanoma, but its role in cutaneous squamous cell carcinoma (cSCC) has not been established. Study objectives include: (1) analyze the feasibility and reliability SLNB for head and neck (H&N) cSCC and (2) identify risk factors associated with a positive SLN. Data Sources. MEDLINE, PubMed, Cochrane, and ASCO databases searches conducted (1946-2013). Review Methods. Using the PRISM model, a comprehensive systematic review of H&N cSCC SLNB studies with associated recurrence rates was conducted. Dual-blinded data extraction identify primary outcomes (successful SLN harvest and false omission rate) and secondary outcomes (risk factors associated with a 1SLN). Results. Two hundred twenty-one articles were screened; 73 patients from 11 publications met inclusion criteria (3 case series; 8 prospective cohorts). Studies ranged from 1 to 15 patients (median 5). Median age was 74 years. Median follow-up was 21.5 months. Average tumor size was 3.09 cm. At least 1 SLN was identified in 100% of patients (median 2). Ten (13.5%) had a positive SLN; no additional metastatic nodes were identified in 9 patients receiving completion lymphadenectomy. Tumor diameter was not associated with SLN status (P = .09; 95% CI, -.27 to 3.02). Risk factors (tumor depth, perineural invasion, location, differentiation) were not consistently recorded. Three of 63 (4.76%) failed regionally following a negative SLNB. Conclusion. H&N cSCC SLNB is feasible and reliable for staging, with a false omission rate of 4.7% mirroring melanoma. Prospective studies documenting high risk features are required to further define its role. © 2013 American Academy of Otolaryngology - Head and Neck Surgery Foundation.

Greer H.O.,University of Alabama at Birmingham
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society | Year: 2010

The objective of this study was to evaluate the impact of a weekly tumor board conference on the management of patients with gynecologic malignancies. The medical records of consecutive patients referred to a multidisciplinary gynecologic oncology tumor board were reviewed. Patient demographics were abstracted from medical records and tumor board minutes. An evaluation was made whether the pathological or radiological findings were changed by the tumor board consultants. If a discrepancy existed, it was determined whether the change impacted clinical management. From January 2004 to December 2006, 741 patients presented at the tumor board were evaluable. Seventy-one percent of the patients were presented for pathology review and 29% for radiology review. The most common diagnoses were ovarian cancer (29%), endometrial cancer (26%), and cervical cancer (12%). Of the 526 pathology reviews, 27% had a change in diagnosis; this discrepancy altered clinical management 74% of the time (20% of all reviews). Of the 215 radiology presentations, 89% were reviewed to confirm recurrent or persistent disease; malignant disease was confirmed 74% of the time. Review of imaging studies resulted in a new diagnosis or upstaging 10% of the time. A multidisciplinary tumor board allows a wide range of gynecologic diagnoses and clinical scenarios to be discussed. Careful review of pathology results in a change in the clinical management of 20% of patients presented at the tumor board. The majority of radiology reviews are presented to confirm persistent or recurrent cancer before recommending further therapy.

Singh J.A.,University of Alabama at Birmingham
Rheumatology (Oxford, England) | Year: 2014

METHODS: We examined whether demographic (gender, age) and clinical characteristics [BMI, co-morbidity measured by the Deyo-Charlson index (a 5-point increase), anxiety and depression] predict the use of NSAIDs and narcotic pain medications 2 and 5 years after revision TKA. Multivariable logistic regression adjusted for these predictors as well as operative diagnosis, American Society of Anesthesiologists class and distance from the medical centre.RESULTS: A total of 1533 patients responded to the 2-year questionnaire and 881 responded to the 5-year questionnaire. NSAID use was reported by 13.4% (206/1533) of patients at 2 years and 16.7% (147/881) at 5 years. Narcotic medication use was reported by 5.4% (83/1533) of patients at 2 years and 5.9% (52/881) at 5 years. Significant predictors of the use of NSAIDs for index TKA pain at 2 and 5 years were age >60-70 years [odds ratio (OR) 0.62 (95% CI 0.39, 0.98) and 0.46 (0.25, 0.85)] compared with age ≤60 years and a higher Deyo-Charlson index [OR 0.51 (95% CI 0.28, 0.93)] per 5-point increase at 5-year after revision TKA. Significant predictors of narcotic pain medication use for index TKA pain were age >60-70 years [OR 0.41 (0.21, 0.78)] and >70-80 years [0.40 (95% CI 0.22, 0.73)] at 2 years and depression [OR 4.58 (95% CI 1.58, 13.18)] at 5 years.CONCLUSION: Younger age and depression were risk factors for the use of NSAIDs and narcotic pain medications for index TKA pain at 2- and 5-years after revision TKA.OBJECTIVE: Our objective was to study the use of pain medications for persistent knee pain and their predictors after revision total knee arthroplasty (TKA). © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Pekmezi D.,University of Alabama at Birmingham
Journal of physical activity & health | Year: 2013

Due to high rates of inactivity and related chronic illnesses among Latinas, the current study examined the feasibility and acceptability of using pedometers as an intervention tool in this underserved population. Data were taken from a larger randomized, controlled trial2 and focused on the subsample of participants (N = 43) who were randomly assigned to receive a physical activity intervention with pedometers and instructions to log pedometer use daily and mail completed logs back to the research center each month for 6 months. Retention (90.7% at 6 months) and adherence to the pedometer protocol (68.89% returned ≥ 5 of the 6 monthly pedometer logs) were high. Overall, participants reported increased physical activity at 6 months and credited pedometer use for helping them achieve these gains (75.7%). Participants who completed a high proportion (≥ 5/6) of pedometer logs reported significantly greater increases in physical activity and related process variables (stages of change, self-efficacy, behavioral processes of change, social support from friends) than those who were less adherent (completed < 5 pedometer logs). Pedometers constitute a low-cost, useful tool for encouraging self-monitoring of physical activity behavior in this at-risk group.

Gharibi Z.,University of Alabama at Birmingham
Transplantation | Year: 2016

BACKGROUND: Induction therapy in deceased donor kidney transplantation is costly, with wide discrepancy in utilization and a limited evidence base, particularly regarding cost-effectiveness. METHODS: We linked the United States Renal Data System data set to Medicare claims to estimate cumulative costs, graft survival, and incremental cost-effectiveness ratio (ICER – cost per additional year of graft survival) within 3 years of transplantation in 19 450 deceased donor kidney transplantation recipients with Medicare as primary payer from 2000 to 2008. We divided the study cohort into high-risk (age > 60 years, panel-reactive antibody > 20%, African American race, Kidney Donor Profile Index > 50%, cold ischemia time > 24 hours) and low-risk (not having any risk factors, comprising approximately 15% of the cohort). After the elimination of dominated options, we estimated expected ICER among induction categories: no-induction, alemtuzumab, rabbit antithymocyte globulin (r-ATG), and interleukin-2 receptor-antagonist. RESULTS: No-induction was the least effective and most costly option in both risk groups. Depletional antibodies (r-ATG and alemtuzumab) were more cost-effective across all willingness-to-pay thresholds in the low-risk group. For the high-risk group and its subcategories, the ICER was very sensitive to the graft survival; overall both depletional antibodies were more cost-effective, mainly for higher willingness to pay threshold (US $100 000 and US $150 000). Rabbit ATG appears to achieve excellent cost-effectiveness acceptability curves (80% of the recipients) in both risk groups at US $50 000 threshold (except age > 60 years). In addition, only r-ATG was associated with graft survival benefit over no-induction category (hazard ratio, 0.91; 95% confidence interval, 0.84-0.99) in a multivariable Cox regression analysis. CONCLUSIONS: Antibody-based induction appears to offer substantial advantages in both cost and outcome compared with no-induction. Overall, depletional induction (preferably r-ATG) appears to offer the greatest benefits. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

Beatty M.S.,University of Washington | Beatty M.S.,University of Alabama at Birmingham | Curiel D.T.,University of Washington
Advances in Cancer Research | Year: 2012

Cancer gene therapy approaches have benefited greatly from the utilization of molecular-based therapeutics. Of these, adenovirus-based interventions hold much promise as a platform for targeted therapeutic delivery to tumors. However, a barrier to this progression is the lack of native adenovirus receptor expression on a variety of cancer types. As such, any adenovirus-based cancer therapy must take into consideration retargeting the vector to nonnative cellular surface receptors. Predicated upon the knowledge gained in native adenovirus biology, several strategies to transductionally retarget adenovirus have emerged. Herein, we describe the biological hurdles as well as strategies utilized in adenovirus transductional targeting, covering the progress of both adapter-based and genetic manipulation-based targeting. Additionally, we discuss recent translation of these targeting strategies into a clinical setting. © 2012 Elsevier Inc.

Hughes S.O.,Baylor College of Medicine | Shewchuk R.M.,University of Alabama at Birmingham
International Journal of Behavioral Nutrition and Physical Activity | Year: 2012

Background: Associations between parent and child characteristics and how they influence the approach parents take toward children in the feeding environment have not been examined extensively, especially in low-income minority families who are at a higher risk for obesity. The primary aim of the study was to examine positive and negative parent emotions as potential mediators of the relationship between child temperament and parents' perceptions of strategy effectiveness and problems encountered in feeding children fruit and vegetables.Methods: Participants were low-income families (n = 639, 73% minority, children aged 3-5 years) participating in Head Start programs in two states. Parents completed the Children's Behavior Questionnaire (CBQ), Positive and Negative Affect Schedule (PANAS), and measures of strategy effectiveness (teachable moments, practical methods, restriction, and enhanced availability) and problems encountered (vegetable characteristics, child attributions for dislike, external influences, and parental demands) in feeding children fruit and vegetables.Results: Positive parent emotions partially mediated the relationship between child Effortful Control and strategy effectiveness and fully mediated the relationship between Surgency and strategy effectiveness. Although negative parent emotions were associated with increased perception of problems in feeding children fruit and vegetables, the relationship between Negative Affectivity and problems in feeding was partially mediated by negative parent emotions.Conclusions: Positive parent emotions facilitated perceived effectiveness of feeding strategies, with child Effortful Control and Surgency instrumental to this process. Understanding mechanisms in parent-child feeding is important when developing interventions designed to promote healthy child eating behaviors. © 2012 Hughes and Shewchuk; licensee BioMed Central Ltd.

Schroeder Jr. H.W.,University of Alabama at Birmingham | Dougherty C.J.,Biotest Pharmaceuticals Corporation
Infection | Year: 2012

An available supply of intravenous immunoglobulin (IVIG) is essential for individuals with primary humoral immunodeficiency. A shortage in 1997 prompted the Food and Drug Administration (FDA) to revise guidelines for the licensure, production, and distribution of new IVIG products, including the standardization of United States clinical trials regarding endpoints for safety, efficacy, and pharmacokinetics. The following review is intended to present current information and results of clinical trials in patients with primary immunodeficiency treated with IVIG products currently licensed or awaiting licensure in the United States. The data presented are compiled from published clinical trials and prescribing information generated by manufacturers. © Springer-Verlag 2012.

Howard J.H.,John Wayne Cancer Institute | Bland K.I.,University of Alabama at Birmingham
Current Opinion in Obstetrics and Gynecology | Year: 2012

PURPOSE OF REVIEW: Breast cancer is the most common malignancy in women in the United States and the second most common cause of cancer death in women. This review will focus on the current and clinically relevant recommendations for breast cancer diagnosis, staging, and treatment. RECENT FINDINGS: Screening for breast cancer is based on patient history, exam, mammography, and ultrasound. In select patient populations, MRI adds additional detection benefit. Once pathology is found, nipple-sparing mastectomy is felt to be an oncologically well tolerated procedure for both ductal carcinoma in situ and invasive tumors in properly selected patients. Prophylactic mastectomy rates are increasing despite no clear survival benefit. Sentinel lymph node biopsy continues to be the staging procedure of choice, but data are available that completion axillary dissection for a positive sentinel node may not affect outcomes. SUMMARY: Strategies for caring for breast cancer patients continue to evolve. Multiple variables including genetic predisposition, disease burden, tumor markers, receptor status, and patient preference are integral to the decision making for each individual patient. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Gundemir S.,University of Rochester | Colak G.,University of Rochester | Tucholski J.,University of Alabama at Birmingham | Johnson G.V.W.,University of Rochester
Biochimica et Biophysica Acta - Molecular Cell Research | Year: 2012

Transglutaminase 2 (TG2) is the most widely distributed member of the transglutaminase family with almost all cell types in the body expressing TG2 to varying extents. In addition to being widely expressed, TG2 is an extremely versatile protein exhibiting transamidating, protein disulphide isomerase and guanine and adenine nucleotide binding and hydrolyzing activities. TG2 can also act as a protein scaffold or linker. This unique protein also undergoes extreme conformational changes and exhibits localization diversity. Being mainly a cytosolic protein; it is also found in the nucleus, associated with the cell membrane (inner and outer side) and with the mitochondria, and also in the extracellular matrix. These different activities, conformations and localization need to be carefully considered while assessing the role of TG2 in physiological and pathological processes. For example, it is becoming evident that the role of TG2 in cell death processes is dependent upon the cell type, stimuli, subcellular localization and conformational state of the protein. In this review we discuss in depth the conformational and functional diversity of TG2 in the context of its role in numerous cellular processes. In particular, we have highlighted how differential localization, conformation and activities of TG2 may distinctly mediate cell death processes. © 2011 Elsevier B.V.

Sweetwyne M.T.,University of Pennsylvania | Murphy-Ullrich J.E.,University of Alabama at Birmingham
Matrix Biology | Year: 2012

Thrombospondin 1 (TSP1) plays major roles in both physiologic and pathologic tissue repair. TSP1 through its type 1 repeats is a known regulator of latent TGF-β activation and plays a role in wound healing and fibrosis. Binding of the TSP N-terminal domain to cell surface calreticulin in complex with LDL-receptor related protein 1 stimulates intermediate cell adhesion, cell migration, anoikis resistance, collagen expression and matrix deposition in an in vivo model of the foreign body response. There is also emerging evidence that TSP EGF-like repeats alter endothelial cell-cell interactions and stimulate epithelial migration through transactivation of EGF receptors. The mechanisms underlying these functions of TSP1 and the implications for physiologic and pathologic wound repair and fibrosis will be discussed. © 2012 International Society of Matrix Biology.

Archer E.,University of Alabama at Birmingham
Mayo Clinic Proceedings | Year: 2015

Over the past century, socioenvironmental evolution (eg, reduced pathogenic load, decreased physical activity, and improved nutrition) led to cumulative increments in maternal energy resources (ie, body mass and adiposity) and decrements in energy expenditure and metabolic control. These decrements reduced the competition between maternal and fetal energy demands and increased the availability of energy substrates to the intrauterine milieu. This perturbation of mother-conceptus energy partitioning stimulated fetal pancreatic β-cell and adipocyte hyperplasia, thereby inducing an enduring competitive dominance of adipocytes over other tissues in the acquisition and sequestering of nutrient energy via intensified insulin secretion and hyperplastic adiposity. At menarche, the competitive dominance of adipocytes was further amplified via hormone-induced adipocyte hyperplasia and weight-induced decrements in physical activity. These metabolic and behavioral effects were propagated progressively when obese, inactive, metabolically compromised women produced progressively larger, more inactive, metabolically compromised children. Consequently, the evolution of human energy metabolism was markedly altered. This phenotypic evolution was exacerbated by increments in the use of cesarean sections, which allowed both the larger fetuses and the metabolically compromised mothers who produced them to survive and reproduce. Thus, natural selection was iatrogenically rendered artificial selection, and the frequency of obese, inactive, metabolically compromised phenotypes increased in the global population. By the late 20th century, a metabolic tipping point was reached at which the postprandial insulin response was so intense, the relative number of adipocytes so large, and inactivity so pervasive that the competitive dominance of adipocytes in the sequestering of nutrient energy was inevitable and obesity was unavoidable. © 2015 Mayo Foundation for Medical Education and Research.

Barnum S.R.,University of Alabama at Birmingham
Journal of Innate Immunity | Year: 2015

Activation of complement leads to generation of the 3 anaphylatoxins C3a, C4a, and C5a. Although all 3 peptides are structurally similar, only C3a and C5a share a similar functional profile that includes the classic inflammatory activities and, more recently, developmental homing and regenerative properties among others. In contrast, the functional profile of C4a is questionable in most cases owing to contamination of C4a preparations with physiologically relevant levels of C3a and/or C5a. Combined with the absence of an identified C4a receptor and the inability of C4a to signal through the C3a and C5a receptors, it is clear that C4a should not be included in the family of complement anaphylatoxins. © 2015 S. Karger AG, Basel.

Whitley R.,University of Alabama at Birmingham
Advances in Experimental Medicine and Biology | Year: 2011

Neonatal herpes simplex virus (HSV) infection continues to cause significant morbidity and mortality despite advances in diagnosis and treatment. Prior to antiviral therapy, 85% of patients with disseminated HSV disease and 50% of patients with central nervous system disease died within 1 year. The advent of antiviral therapy has dramatically improved the prognosis of neonatal HSV with initially vidarabine and subsequently acyclovir increasing the survival rate of infected neonates and improving long-term developmental outcomes. More recently, polymerase chain reaction has allowed earlier identification of HSV infection and provided a quantitative guide to treatment. Current advances in the treatment of neonatal HSV infections are looking toward the role of prolonged oral suppression therapy in reducing the incidence of recurrent disease. Of concern, however, are increasing reports of acyclovir-resistant HSV isolates in patients following prolonged therapy. © 2011 Springer Science+Business Media, LLC.

Perez P.,Colegio de Mexico | De Los Campos G.,University of Alabama at Birmingham
Genetics | Year: 2014

Many modern genomic data analyses require implementing regressions where the number of parameters (p, e.g., the number of marker effects) exceeds sample size (n). Implementing these large-p-with-small-n regressions poses several statistical and computational challenges, some of which can be confronted using Bayesian methods. This approach allows integrating various parametric and nonparametric shrinkage and variable selection procedures in a unified and consistent manner. The BGLR R-package implements a large collection of Bayesian regression models, including parametric variable selection and shrinkage methods and semiparametric procedures (Bayesian reproducing kernel Hilbert spaces regressions, RKHS). The software was originally developed for genomic applications; however, the methods implemented are useful for many nongenomic applications as well. The response can be continuous (censored or not) or categorical (either binary or ordinal). The algorithm is based on a Gibbs sampler with scalar updates and the implementation takes advantage of efficient compiled C and Fortran routines. In this article we describe the methods implemented in BGLR, present examples of the use of the package, and discuss practical issues emerging in real-data analysis. © 2014 by the Genetics Society of America All rights reserved.

Tita A.T.N.,University of Alabama at Birmingham
Obstetrics and Gynecology | Year: 2011

Objective: Elective repeat cesarean delivery at 37 or 38 weeks compared with 39 completed weeks of gestation is associated with adverse neonatal outcomes. We assessed whether delivery before 39 weeks is justifiable on the basis of decreased adverse maternal outcomes. Methods: We conducted a cohort study of women with live singleton pregnancies delivered by prelabor elective repeat cesarean delivery from 1999 through 2002 at 19 U.S. academic centers. Gestational age was examined by completed weeks (eg, 37 completed weeks=37 0/7-37 6/7 weeks). Maternal outcomes included a primary composite of death, hysterectomy, uterine rupture or dehiscence, blood transfusion, uterine atony, thromboembolic complications, anesthetic complications, surgical injury or need for arterial ligation, intensive care unit admission, wound complications, or endometritis. Results: Of 13,258 elective repeat cesareans performed at 37 weeks of gestation or later, 11,255 (84.9%) were between 37 0/7 and 39 6/7 weeks (6.3% at 37, 29.5% at 38, and 49.1% at 39 completed weeks), and 15.1% were at 40 0/7 weeks or more. The primary outcome occurred in 7.43% at 37 weeks, 7.47% at 38 weeks and 6.56% at 39 weeks (P for trend test=.09). Delivery before 39 weeks was not associated with a decrease in the primary outcome when compared with delivery at 39 weeks (adjusted odds ratio 1.16; 95% confidence interval 1.00-1.34). Early delivery was associated with increased maternal hospitalization of 5 days or more [1.96 (1.54, 2.49)] but not with a composite of death or hysterectomy or with individual maternal morbidities. Conclusion: Elective repeat cesarean delivery at 37 or 38 weeks is not associated with decreased maternal morbidity. © 2011 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins.

Groysman V.,University of Alabama at Birmingham
Dermatologic Clinics | Year: 2010

Vulvodynia is a multifactorial chronic pain disorder that is distressing to the patient and exigent to the physician. Although the condition is common, it remains little understood, so patients remain undiagnosed and untreated or undertreated for many years. Although multiple therapies exist in the treatment of vulvodynia, few randomized controlled clinical trials have been performed. Thus, treatment should be individualized and tailored to a patient's diagnosis, symptoms, and psychosexual functioning. Patient education is also important and is facilitated by patient brochures providing assurance that vulvodynia is a real disease. © 2010.

Durant R.W.,University of Alabama at Birmingham
Journal of cultural diversity | Year: 2011

The objective of this study was to identify racial differences in willingness to participate in a population with previous exposure to clinical research. A survey instrument was administered to community-dwelling whites and African Americans who were voluntarily receiving a lay research and health education newsletter from a local Boston geriatric clinical research institution. The survey instrument assessed willingness to participate in 3 hypothetical clinical trials (diet trial for obesity, medication trial for hypertension [HTN], chemotherapy trial for cancer). Surveys were received from 473 whites and 279 African Americans (53% response rate) with mean age 74 (SD +/- 9). In multivariate models, race was not significantly related to willingness to participate in the multivariate models for any of the 3 trials. Previous trial participation was related to a higher odds of willingness to participate in the diet trial only (OR 1.8, 95% CI 1.2, 2.6). Lower levels of trust in one's primary care physician were associated with a lower odds of willingness to participate in clinical trials for the diet and HTN trials (OR 0.5, 95% CI 0.3, 0.8 and OR 0.6, 95% CI 0.3, 0.9, respectively). These findings suggest that, within populations previously exposed to clinical research, African Americans are no less willing to participate in clinical trials compared to whites.

Scott D.W.,University of Alabama at Birmingham
Journal of the American Heart Association | Year: 2013

Endothelial cell responses during inflammation are heterogeneous and key for selectivity in how leukocytes hone in on specific sites and why vascular diseases are highly bed specific. However, mechanisms for this specificity remain unclear. Here, we exposed human endothelial cells isolated from 5 systemic arterial beds from 1 donor (to overcome donor-to-donor genetic/epigenetic differences), the umbilical vein, and pulmonary microvasculature to TNF-α, LPS, and IL-1β and assessed acute (ERK1/2 and p65) and chronic (ICAM-1, VCAM-1 total and surface expression) signaling responses and assessed changes in surface N-glycans and monocyte adhesion. Significant diversity in responses was evident by disparate changes in ERK1/2 and p65 NF-κB phosphorylation, which varied up to 5-fold between different cells and in temporal and magnitude differences in ICAM-1 and VCAM-1 expression (maximal VCAM-1 induction typically being observed by 4 hours, whereas ICAM-1 expression was increased further at 24 hours relative to 4 hours). N-glycan profiles both basally and with stimulation were also bed specific, with hypoglycosylated N-glycans correlating with increased THP-1 monocyte adhesion. Differences in surface N-glycan expression tracked with dynamic up- or downregulation of α-mannosidase activity during inflammation. These results demonstrate a critical role for the vascular bed of origin in controlling endothelial responses and function to inflammatory stimuli and suggest that bed-specific expression of N-linked sugars may provide a signature for select leukocyte recruitment.

Wynn T.A.,University of Alabama at Birmingham
Progress in community health partnerships : research, education, and action | Year: 2011

African Americans bear an unequal burden of breast, cervical, and colorectal cancer. The Deep South Network for Cancer Control (DSN) is a community-academic partnership operating in Alabama and Mississippi that was funded by the National Cancer Institute (NCI) to address cancer disparities using community-based participatory research approaches. In addition to reporting on the plans of this work in progress, we describe the participatory process that local residents and the DSN used to identify needs and priorities, and elaborate on lessons learned from applying a participatory approach to the development of a community action plan. We conducted 24 community discussion groups involving health care professionals, government officials, faith-based leaders, and other stakeholders to identify cancer health disparity needs, community resources/assets, and county priorities to eliminate cancer health disparities. To develop a community action plan, four working groups explored the themes that emerged from the discussion groups, taking into consideration evidence-based strategies and promising community practices. The DSN formulated a community action plan focusing on (1) increasing physical activity by implementing a campaign for individual-level focused activity; (2) increasing the consumption of fruits and vegetables by implementing NCI's Body and Soul Program in local churches; (3) increasing cancer screening by raising awareness through individual, system, and provider agents of change; and (4) training community partners to become effective advocates. A community-academic partnership must involve trust, respect, and an appreciation of partners' strengths and differences. The DSN applied these guiding principles and learned pivotal lessons.

Harper J.C.,University of Alabama at Birmingham
Journal of Drugs in Dermatology | Year: 2010

Benzoyl peroxide (BPO) is a commonly used and highly effective topical treatment for acne that is available in concentrations from 2.5-10%. The compound is not associated with bacterial resistance, and published acne treatment guidelines recommend BPO in conjunction with the long-term use of both topical and systemic antibiotics. A number of combination products containing antibiotics, BPO and/or retinoids are available and useful for tailoring treatment to the needs of each patient over the course of what is often a chronic condition. Fixed combinations of BPO and antibiotics or retinoids address multiple pathogenetic factors by using agents with complementary, but different modes of action. These agents are convenient to use and may improve adherence to therapy by simplifying the regimen for the patient. However, BPO is associated with dose-dependent irritation and dryness. Therefore, formulations containing lower concentrations of BPO (2.5%) minimize irritation, which may improve tolerability and maximize treatment outcomes. Copyright © 2010 Journal of Drugs in Dermatology.

Piyathilake C.,University of Alabama at Birmingham
Investigative and Clinical Urology | Year: 2016

It is biologically plausible for dietary factors to influence bladder cancer risk considering that beneficial as well as harmful components of a diet are excreted through the urinary tract and in direct contact with the epithelium of the bladder. However, studies that investigated the association between dietary factors and bladder cancer (BC) risk have largely reported inconsistent results. The macronutrient intake and risk of BC could have yield inconsistent results across studies because of lack of details on the type, source and the quantities of different dietary fatty acids consumed. There is evidence to suggest that consumption of processed meat may increase BC risk. Dietary carbohydrate intake does not appear to be directly associated with BC risk. Even though a large number of studies have investigated the association between fruit/vegetable consumption/micronutrients in those and BC risk, they have yielded inconsistent results. Gender-specific subgroup analysis, details of how fruits and vegetables are consumed (raw vs. cooked), adequate control for smoking status/aggressiveness of the cancer and consideration of genetic make-up may clarify these inconsistent results. There is no strong evidence to suggest that supplementation with any common micronutrient is effective in reducing BC risk. These limitations in published research however do not totally eclipse the observation that a diet rich in fruits and vegetables and low in processed meat along with especially smoking cessation may convey some protective effects against BC risk. © The Korean Urological Association, 2016.

Vogtle L.K.,University of Alabama at Birmingham
Developmental Medicine and Child Neurology | Year: 2015

This commentary is on the original article by Gutknecht et al. on pages 1070-1075 of this issue. Developmental Medicine and Child Neurology. © 2015 Mac Keith Press.

Zeng Y.,University of Alabama at Birmingham
Archive for Rational Mechanics and Analysis | Year: 2010

We study gas flows with any finite number of thermal nonequilibrium modes. The equations describing such flows are a hyperbolic system with several relaxation equations. An important feature is entropy increase dictated by physics for any irreversible process. Under physical assumptions we obtain properties of thermodynamic variables relevant to stability. By the energy method we prove global existence and uniqueness for the Cauchy problem when the initial data are small perturbations of constant equilibrium states. We give a precise formulation of the fundamental solution for the linearized system, and use it to obtain large time behavior of solutions to the nonlinear system. In particular, we show that the entropy increases but stays bounded. The resulting asymptotic picture of nonequilibrium flows is in a pointwise sense both in space and in time. © Springer-Verlag (2009).

Chatham W.,University of Alabama at Birmingham
Current Opinion in Rheumatology | Year: 2010

PURPOSE OF REVIEW: Sarcoidosis commonly involves the lungs but also not uncommonly presents as uveitis, arthritis, myositis or neurologic disease. Recognition of the presenting features, organ complications, and immunopathogenesis is important for timely diagnosis and appropriate management. RECENT FINDINGS: Current studies support the disorder developing as a consequence of a CD4+ T-cell-mediated response to variable environmental or microbial triggers in the context of one or more determined susceptibility genes including BTNL2, with other genes such as CARD15/NOD2, governing disease severity. Magnetic resonance imaging (MRI) is useful in defining the presence and extent of central nervous system (CNS), osseous, and both skeletal and cardiac muscle disease. Corticosteroids remain the mainstay of therapy; patients with refractory disease may respond to other immunomodulating drugs, including anti-TNF-α antibodies but the optimal roles of traditional immunomodulating as well as newer biologic therapies in management are continuing to be defined. SUMMARY: Insights into triggering immune events and susceptibility genes should provide potential new strategies and targets for therapy. The judicious use of MRI in suspected cases can enhance earlier recognition of disease in the CNS, bone, and both skeletal and cardiac muscle to guide diagnostic procedures as well as appropriate treatment. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Jetton J.G.,University of Iowa | Askenazi D.J.,University of Alabama at Birmingham
Current Opinion in Pediatrics | Year: 2012

PURPOSE OF REVIEW: Acute kidney injury (AKI) is associated with increased risk of morbidity and mortality in critically ill children and adults. Neonates remain an understudied group, although previous evidence suggests that this association holds true for them as well. RECENT FINDINGS: Attention to the issue of neonatal AKI is increasing. New studies in very low-birthweight infants, infants with congenital heart disease who undergo cardiopulmonary bypass, those who receive extracorporeal membrane oxygenation and infants with perinatal depression continue to demonstrate that AKI is common in neonates and associated with increased risk of morbidity and mortality. Additional advances in the field of neonatal AKI include adaptation of modern, categorical AKI definitions, as well as further evaluation of novel urinary biomarkers (e.g., neutrophil gelatinase-associated lipocalin) in this patient group. SUMMARY: AKI is an independent risk factor for poor outcomes in critically ill neonates. Our ability to improve outcomes for these patients depends on heightened awareness of this issue both at the bedside as well as in research, commitment to using standardized AKI definitions in order to pool and compare data more effectively and improvement in our diagnostic methods with better AKI biomarkers so that we can identify AKI and intervene much earlier in the disease course. © 2012 Lippincott Williams & Wilkins, Inc.

Bhatt S.P.,Birmingham Medical Center | Dransfield M.T.,University of Alabama at Birmingham
Translational Research | Year: 2013

Chronic obstructive pulmonary disease (COPD) is an inflammatory disease of the lung associated with progressive airflow limitation and punctuated by episodes of acute exacerbation. There is growing recognition that the inflammatory state associated with COPD is not confined to the lungs but also involves the systemic circulation and can impact nonpulmonary organs. Epidemiologic and mechanistic studies indicate that COPD is associated with a high frequency of coronary artery disease, congestive heart failure and cardiac arrhythmias, independent of shared risk factors. Possible pathways include complex interrelationships between chronic low-grade systemic inflammation and oxidative stress as well as shared risk factors such as age, cigarette smoking, and environmental pollutants. In this review, we provide an overview of the epidemiologic data linking COPD with cardiovascular disease, comment on the interrelationships among COPD, inflammation, and cardiovascular disease, and highlight diagnostic and therapeutic challenges. © 2013 Mosby, Inc. All rights reserved.

Kiryluk K.,Columbia University | Novak J.,University of Alabama at Birmingham | Gharavi A.G.,Columbia University
Annual Review of Medicine | Year: 2013

Recent genome-wide association studies (GWAS) have identified multiple susceptibility loci for immunoglobulin A nephropathy (IgAN), the most common form of glomerulonephritis, implicating independent defects in adaptive immunity (three loci on chromosome 6p21 in the MHC region), innate immunity (8p23 DEFA locus, 17p23 TNFSF13 locus, 22q12 HORMAD2 locus), and the alternative complement pathway (1q32 CFH/CFHR locus). In geospatial analysis of 85 populations, a genetic risk score based on the replicated GWAS loci is highest in Asians, intermediate in Europeans, and lowest in Africans, capturing the known difference in prevalence among world populations. The genetic risk score also uncovered a previously unsuspected increased prevalence of IgAN-attributable kidney failure inNorthernEurope.The IgAN risk alleles have opposing effects on many immune-mediated diseases, suggesting that selection has contributed to variation in risk allele frequencies among different populations. Incorporating genetic, immunologic, and biochemical data, we present a multistep pathogenesis model that provides testable hypotheses for dissecting the mechanisms of disease. Copyright © 2013 by Annual Reviews.

Sharief S.,Rush University Medical Center | Jariwala S.,Montefiore Medical Center | Kumar J.,New York Medical College | Muntner P.,University of Alabama at Birmingham | Melamed M.L.,Yeshiva University
Journal of Allergy and Clinical Immunology | Year: 2011

Background: Previous research supports a possible link between low vitamin D levels and atopic disease. However, the association between low vitamin D levels and total and allergen-specific IgE levels has not been studied. Objective: We sought to test the association between serum 25-hydroxyvitamin D (25[OH]D) deficiency (<15 ng/mL) and insufficiency (15-29 ng/mL) and allergic sensitization measured by serum IgE levels in a US nationally representative sample of 3136 children and adolescents and 3454 adults in the National Health and Nutrition Examination Survey 2005-2006. Methods: The association of 25(OH)D deficiency with 17 different allergens was assessed after adjustment for potential confounders, including age; sex; race/ethnicity; obesity, low socioeconomic status; frequency of milk intake; daily hours spent watching television, playing videogames, or using a computer; serum cotinine levels; and vitamin D supplement use. Results: In children and adolescents allergic sensitization to 11 of 17 allergens was more common in those with 25(OH)D deficiency. Compared with sufficient vitamin D levels of greater than 30 ng/mL, after multivariate adjustment, 25(OH)D levels of less than 15 ng/mL were associated with peanut (odds ratio [OR], 2.39; 95% CI, 1.29-4.45), ragweed (OR, 1.83; 95% CI, 1.20-2.80), and oak (OR, 4.75; 95% CI, 1.53-4.94) allergies (P < .01 for all). Eight other allergens were associated with 25(OH)D deficiency, with P values of less than .05 but greater than .01. There were no consistent associations seen between 25(OH)D levels and allergic sensitization in adults. Conclusion: Vitamin D deficiency is associated with higher levels of IgE sensitization in children and adolescents. Further research is needed to confirm these findings. © 2011 American Academy of Allergy, Asthma & Immunology.

Kiryluk K.,Columbia University | Novak J.,University of Alabama at Birmingham
Journal of Clinical Investigation | Year: 2014

IgA nephropathy (IgAN) represents the leading cause of kidney failure among East Asian populations and the most frequent form of primary glomerulonephritis among Europeans. Patients with IgAN develop characteristic IgA1-containing immune complexes that deposit in the glomerular mesangium, producing progressive kidney injury. Recent studies define IgAN as an autoimmune trait of complex architecture with a strong genetic determination. This Review summarizes new insights into the role of the O-glycosylation pathway, anti-glycan immune response, mucosal immunity, antigen processing and presentation, and the alternative complement pathway in the pathogenesis of IgAN.

Simor T.,University of Alabama at Birmingham
Journal of magnetic resonance imaging : JMRI | Year: 2010

To demonstrate the advantages of signal intensity percent-infarct-mapping (SI-PIM) using the standard delayed enhancement (DE) acquisition in assessing viability following myocardial infarction (MI). SI-PIM quantifies MI density with a voxel-by-voxel resolution in clinically used DE images. In canines (n= 6), 96 hours after reperfused MI and administration of 0.2 mmol/kg Gd(DTPA), ex vivo DE images were acquired and SI-PIMs calculated. SI-PIM data were compared with data from DE images analyzed with several thresholding levels using SI(remote+2SD), SI(remote+6SD), SI full width half maximum (SI(FWHM)), and with triphenyl-tetrazolium-chloride (TTC) staining. SI-PIM was also compared to R1 percent infarct mapping (R1-PIM). Left ventricular infarct volumes (IV) in DE images, IV(SIremote+2SD) and IV(SIremote+6SD), overestimated (P < 0.05) TTC by medians of 13.21 mL [10.2; 15.2] and 6.2 mL [3.79; 8.23], respectively. SI(FWHM), SI-PIM, and R1-PIM, however, only nonsignificantly underestimated TTC, by medians of -0.10 mL [-0.12, -0.06], -0.86 mL [-1.04; 1.54], and -1.30 mL [-4.99; -0.29], respectively. The infarct-involved voxel volume (IIVV) of SI-PIM, 32.4 mL [21.2, 46.3] is higher (P < 0.01) than IIVVs of SI(FWHM) 8.3 mL [3.79, 19.0]. SI-PIM(FWHM), however, underestimates TTC (-5.74 mL [-11.89; -2.52] (P < 0.01)). Thus, SI-PIM outperforms SI(FWHM) because larger IIVVs are obtained, and thus PIs both in the rim and the core of the infarcted tissue are characterized, in contradistinction from DE-SI(FWHM), which shows mainly the infarct core. We have shown here, ex vivo, that SI-PIM has the same advantages as R1-PIM, but it is based on the scanning sequences of DE imaging, and thus it is obtainable within the same short scanning time as DE. This makes it a practical method for clinical studies.

Gutierrez O.M.,University of Alabama at Birmingham
Advances in Chronic Kidney Disease | Year: 2013

Sodium- and phosphorus-based food additives are among the most commonly consumed nutrients in the world. This is because both have diverse applications in processed food manufacturing, leading to their widespread use by the food industry. Since most foods are naturally low in salt, sodium additives almost completely account for the excessive consumption of sodium throughout the world. Similarly, phosphorus additives represent a major and "hidden" phosphorus load in modern diets. These factors pose a major barrier to successfully lowering sodium or phosphorus intake in patients with CKD. As such, any serious effort to reduce sodium or phosphorus consumption will require reductions in the use of these additives by the food industry. The current regulatory environment governing the use of food additives does not favor this goal, however, in large part because these additives have historically been classified as generally safe for public consumption. To overcome these barriers, coordinated efforts will be needed to demonstrate that high intake of these additives is not safe for public consumption and as such should be subject to greater regulatory scrutiny. © 2013 National Kidney Foundation, Inc.

Iozzo R.V.,Thomas Jefferson University | Sanderson R.D.,University of Alabama at Birmingham
Journal of Cellular and Molecular Medicine | Year: 2011

• Introduction • Perlecan: a pro-angiogenic proteoglycan • Endorepellin, a C-terminal fragment of perlecan with anti-angiogenic activity • Syndecans in cancer biology • Glypicans and the control of cancer growth • Role of heparanase and proteoglycan remodelling in cancer • Decorin and growth control • Genetic evidence for a role for decorin in carcinogenesis • Mechanism of decorin action: suppression of β-catenin and Myc levels • Lumican in cancer biology • Conclusions and perspectives Proteoglycans, key molecular effectors of cell surface and pericellular microenvironments, perform multiple functions in cancer and angiogenesis by virtue of their polyhedric nature and their ability to interact with both ligands and receptors that regulate neoplastic growth and neovascularization. Some proteoglycans such as perlecan, have pro- and anti-angiogenic activities, whereas other proteoglycans, such as syndecans and glypicans, can also directly affect cancer growth by modulating key signalling pathways. The bioactivity of these proteoglycans is further modulated by several classes of enzymes within the tumour microenvironment: (i) sheddases that cleave transmembrane or cell-associated syndecans and glypicans, (ii) various proteinases that cleave the protein core of pericellular proteoglycans and (iii) heparanases and endosulfatases which modify the structure and bioactivity of various heparan sulphate proteoglycans and their bound growth factors. In contrast, some of the small leucine-rich proteoglycans, such as decorin and lumican, act as tumour repressors by physically antagonizing receptor tyrosine kinases including the epidermal growth factor and the Met receptors or integrin receptors thereby evoking anti-survival and pro-apoptotic pathways. In this review we will critically assess the expanding repertoire of molecular interactions attributed to various proteoglycans and will discuss novel proteoglycan functions modulating cancer progression, invasion and metastasis and how these factors regulate the tumour microenvironment. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Prevelige Jr. P.E.,University of Alabama at Birmingham
Journal of Molecular Biology | Year: 2011

The pressing need to develop antivirals active against resistant strains of HIV-1 has led to efforts to target steps in the virus life cycle other than reverse transcription and Gag proteolysis. Among those steps are entry, integration, and assembly and/or maturation. Advances in understanding the structural biology of both the immature and the mature forms of the HIV capsid have made it possible to design or discover small molecules and peptides that interfere with both assembly and maturation. Here, we review the current state of the art in assembly and maturation inhibitors. © 2011 Elsevier Ltd. All rights reserved.

Feldstein A.E.,Cleveland Clinic | Bailey S.M.,University of Alabama at Birmingham
Antioxidants and Redox Signaling | Year: 2011

Fatty liver disease (FLD), associated with chronic alcohol consumption or obesity, is a serious medical problem. Strong evidence indicates that oxidative stress and dysregulation of redox-sensitive signaling pathways are central to the pathobiology of FLD. Herein, this Forum summarizes current knowledge regarding mechanisms of FLD from both clinical and experimental studies. Special emphasis is given to the role of redox biology disturbances in the initiation and progression of FLD from both chronic alcohol consumption and obesity. Focus areas in this Forum include discussions on the (i) multi-hit hypothesis; (ii) interaction of adipokines and redox signaling pathways; (iii) role of sub-cellular organelle systems (i.e., endoplasmic reticulum and mitochondria); and (iv) contribution of the innate immune system, in FLD. A state-of-the-art discussion is also included highlighting key lessons learned from experimental studies using rodent models of FLD. © Copyright 2011, Mary Ann Liebert, Inc.

Siegel H.J.,University of Alabama at Birmingham
Orthopedic Clinics of North America | Year: 2014

The management of complex wounds remains a challenge, and although there have been many promising advances, patients often undergo a morbid and lengthy process to obtain sufficient, satisfactory healing. Sarcoma patients are especially vulnerable to soft tissue wound-healing complications. These patients are often treated with neoadjuvant radiation and/or chemotherapy and have compromised local vascularity to healing tissue. The advent and refinement of wound vacuum-assisted closure technology have been shown to have a tremendous impact. This article reviews the benefits of some novel technologies currently undergoing investigation in orthopedic oncology that will likely have applications in wound management from other causes. © 2014 Elsevier Inc.

Dell'italia L.J.,University of Alabama at Birmingham
Circulation Research | Year: 2011

The title of the proposed series of reviews is Translational Success Stories. The definition of "translation" according to Webster is, "an act, process, or instance of translating as a rendering of one language into another." In the context of this inaugural review, it is the translation of Tigerstedt's and Bergman's discovery in 1898 of the vasoconstrictive effects of an extract of rabbit kidney to the treatment of heart failure. As recounted by Marks and Maxwell, their discovery was heavily influenced by the original experiments of the French physiologist Brown-Séquard, who was the author of the doctrine that "many organs dispense substances into the blood which are not ordinary waste products, but have specific functions." They were also influenced by Bright's original observation that linked kidney disease with hypertension with the observation that patients dying with contracted kidneys often exhibited a hard, full pulse and cardiac hypertrophy. However, from Tigerstedt's initial discovery, there was a long and arduous transformation of ideas and paradigms that eventually translated to clinical applications. Although the role of the renin-angiotensin system in the pathophysiology of hypertension and heart failure was suspected through the years, beneficial effects from its blockade were not realized until the early 1970s. Thus, this story starts with a short historical perspective that provides the reader some insight and appreciation into the long delay in translation. © 2011 American Heart Association, Inc.

Afaq F.,University of Alabama at Birmingham
Archives of Biochemistry and Biophysics | Year: 2011

The skin is the largest organ of the body that produces a flexible and self-repairing barrier and protects the body from most common potentially harmful physical, environmental, and biological insults. Solar ultraviolet (UV) radiation is one of the major environmental insults to the skin and causes multi-tiered cellular and molecular events eventually leading to skin cancer. The past decade has seen a surge in the incidence of skin cancer due to changes in life style patterns that have led to a significant increase in the amount of UV radiation that people receive. Reducing excessive exposure to UV radiation is desirable; nevertheless this approach is not easy to implement. Therefore, there is an urgent need to develop novel strategies to reduce the adverse biological effects of UV radiation on the skin. A wide variety of natural agents have been reported to possess substantial skin photoprotective effects. Numerous preclinical and clinical studies have elucidated that natural agents act by several cellular and molecular mechanisms to delay or prevent skin cancer. In this review article, we have summarized and discussed some of the selected natural agents for skin photoprotection. © 2010 Elsevier Inc. All rights reserved.

Matthews Q.L.,University of Alabama at Birmingham
Molecular Pharmaceutics | Year: 2011

Some viral vectors are potent inducers of cellular and humoral responses; therefore, viral vectors can be used to vaccinate against cancer or infectious diseases. This report will focus on adenovirus (Ad)-based vectors. Traditional viral-vector vaccination embodies the concept that the vector uses the host-cell machinery to express antigens that are encoded as transgenes within the viral vector. Several preclinical successes have used this approach in animal model systems. However, in some instances, these conventional Ad-based vaccines have yielded suboptimal clinical results. These suboptimal results are ascribed, in part, to preexisting Ad serotype 5 (Ad5) immunity. To address this issue, the "antigen capsid-incorporation" strategy has been developed to circumvent the drawbacks associated with conventional transgene expression of antigens by Ad vectors. This strategy embodies the incorporation of antigenic peptides within the capsid structure of viral vectors. Incorporating immunogenic peptides into the Ad capsid offers potential advantages. Importantly, vaccination by means of the antigen capsid-incorporated approach results in a strong humoral response, similar to the response generated by native Ad capsid proteins. This strategy also allows for the boosting of antigenic specific responses. This strategy may be the way forward for improved vaccine schemes, especially for those infections requiring a strong humoral antigenic response. © 2011 American Chemical Society.

Kau C.H.,University of Alabama at Birmingham
Facial Plastic Surgery Clinics of North America | Year: 2011

The author provides an overview of the new imaging technologies that allow the practitioner to accurately capture the patient's soft tissue facial morphology and underlying bones and teeth, including details of dental model integration. This article describes how a virtual patient is created and manipulated and the practical use of this technology. It takes the quantification of the 3D surface further by proposing a reference framework of landmarks of craniofacial structure that can be used for comparison of surgical change, growth, gender, and phenotype. © 2011 Elsevier Inc.

Gorbatyuk M.,University of Alabama at Birmingham | Gorbatyuk O.,University of Florida
Molecular Vision | Year: 2013

Recently published literature has provided evidence that the unfolded protein response (UPR) is involved in the development of retinal degeneration. The scope of these studies encompassed diabetic retinopathy, retinopathy of prematurity, glaucoma, retinal detachment, light-induced retinal degeneration, age-related macular degeneration, and inherited retinal degeneration. Subsequent studies investigating the role of individual UPR markers in retinal pathogenesis and examining the therapeutic potential of reprogramming the UPR as a method for modulating the rate of retinal degeneration have been initiated. Manipulation of UPR markers has been made possible by the use of knockout mice, pharmacological agents, and viral vector-mediated augmentation of gene expression. Future research will aim at identifying specific inhibitors and/or inducers of UPR regulatory markers as well as expand the list of UPR-related animal models. Additionally, adeno-associated virus-mediated gene delivery is a safe and effective method for modulating gene expression, and thus is a useful research tool for manipulating individual UPR markers in affected retinas and a promising delivery vector for gene therapy in retinal degenerative disorders. © 2013 Molecular Vision.