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Cincinnati, OH, United States

The University of Cincinnati is a comprehensive public research university in Cincinnati, in the U.S. state of Ohio, and a part of the University System of Ohio.Founded in 1819 as Cincinnati College, it is the oldest institution of higher education in Cincinnati and has an annual enrollment of over 40,000 students, making it the second largest university in Ohio and one of the 50 largest universities in the United States. In the 2010 survey by Times Higher Education , the university was ranked in the top 100 universities in North America and as one of the top 200 in the world. Beginning with the 2011 edition of US News and World Report Best Colleges rankings, the University of Cincinnati has been ranked as a Tier One university, ranking as the 129th best overall university and 63rd best public university in the 2015 rankings. This includes being the number 3 ranked university in the nation in the "Up-and-Coming" National Universities section of the 2014 edition. In 2011-2012 academic year the Leiden University ranking put the University of Cincinnati at the 93rd place globally and at the 63rd place in North America by the proportion of top-cited publications. In 2014, US News and World Report ranked UC in the Top-200 of universities worldwide.The university garners nearly $500 million per annum in research funding, ranking 22nd among public universities in the US. Numerous programs across the university are nationally ranked, including: aerospace engineering, anthropology, architecture, classics, composition, conducting, cooperative education, criminal justice, design, environmental science, law, medicine, music, musical theater, neurology, opera, otolaryngology, paleontology, pediatrics, and pharmacy.The school offers over 100 bachelor degrees, over 300 degree granting programs, and over 600 total programs of study, ranging from certificates to doctoral and first professional education. With an economic impact of over $3.5 billion per year, it is the largest single employer in Greater Cincinnati. After extensive renovations through the implementation of the 1989 Master Plan, the university has been recognized by campus planners and architects as one of the most distinguished campus settings in the world. Wikipedia.

Heppner K.M.,University of Cincinnati
Methods in enzymology | Year: 2012

The discovery of ghrelin as the endogenous ligand for the growth hormone secretagogue receptor (GHS-R) led to subsequent studies characterizing the endogenous action of this gastrointestinal hormone. Accordingly, exogenous administration of ghrelin was found to increase food intake and adiposity in a variety of species, including rodents, nonhuman primates, and humans. Later work supported these findings and confirmed that ghrelin acts through hypothalamic neurons to mediate its effects on energy metabolism. Ghrelin acts specifically through GHS-R to promote a positive energy balance as demonstrated by loss of ghrelin action after pharmacological blockade or genetic deletion of GHS-R. More recently, ghrelin was found to be a mediator of glucose metabolism and acts to inhibit insulin secretion from pancreatic β-cells. Together, the literature highlights a predominant role of ghrelin in regulating energy and glucose metabolism. Copyright © 2012 Elsevier Inc. All rights reserved.

Vaz C.,University of Cincinnati
International Journal of Modern Physics D | Year: 2014

Recently, it was argued [A. Almheiri et al., arXiv: 1207.3123, A. Almheiri et al., arXiv: 1304.6483], via a delicate thought experiment, that it is not consistent to simultaneously require that (a) Hawking radiation is pure, (b) effective field theory is valid outside a stretched horizon and (c) infalling observers encounter nothing unusual as they cross the horizon. These are the three fundamental assumptions underlying Black Hole Complementarity and the authors proposed that the most conservative resolution of the paradox is that (c) is false and the infalling observer burns up at the horizon (the horizon acts as a «firewall»). However, the firewall violates the equivalence principle and breaks the CPT invariance of quantum gravity. This led Hawking to propose recently that gravitational collapse may not end up producing event horizons, although he did not give a mechanism for how this may happen. Here we will support Hawking's conclusion in a quantum gravitational model of dust collapse. We will show that continued collapse to a singularity can only be achieved by combining two independent and entire solutions of the Wheeler-DeWitt equation. We interpret the paradox as simply forbidding such a combination. This leads naturally to a picture in which matter condenses on the apparent horizon during quantum collapse. © 2014 World Scientific Publishing Company.

Eckman M.H.,University of Cincinnati
Journal of Thrombosis and Thrombolysis | Year: 2016

Until recently, vitamin K antagonists, warfarin being the most commonly used agent in the United States, have been the only oral anticoagulant therapies available to prevent stroke in patients with atrial fibrillation (AF). In the last 5 years four new, non-vitamin K oral anticoagulants, the so-called NOACs or novel oral anticoagulants, have come to market and been approved by the Federal Drug Administration. Despite comparable if not superior efficacy in preventing AF-related stroke, and generally lower risks of major hemorrhage, particularly intracranial bleeding, the uptake of these agents has been slow. A number of barriers stand in the way of the more widespread use of these novel agents. Chief among them is concern about the lack of antidotes or reversal agents. Other concerns include the need for strict medication adherence, since missing even a single dose can lead to a non-anticoagulated state; out-of-pocket costs for patients; the lack of easily available laboratory tests to quantitatively assess the level of anticoagulant activity when these agents are being used; contraindications to use in patients with severe chronic kidney disease; and black-box warnings about the increased risk of thromboembolic events if these agents are discontinued prematurely. Fortunately, a number of reversal agents are in the pipeline. Three reversal agents, idarucizumab, andexanet alfa, and aripazine, have already progressed to human studies and show great promise as either antidotes for specific drugs or as universal reversal agents. The availability of these reversal agents will likely increase the clinical use of the non-vitamin K oral anticoagulants. In light of the many complex and nuanced issues surrounding the choice of an optimal anticoagulant for any AF patient, a patient-centered/shared decision-making approach will be useful. © 2015, Springer Science+Business Media New York.

Bernstein J.A.,University of Cincinnati
American Journal of Rhinology and Allergy | Year: 2013

Background: Hereditary angioedema (HAE), a rare autosomal dominant disorder, is characterized by repeated attacks of swelling of the skin, gastrointestinal tract, face, larynx, and other organs. In most cases it is caused by low levels of functional C1 esterase inhibitor (C1-INH), a serine protease inhibitor that plays important regulatory roles in the complement, contact, and fibrinolytic pathways. Methods: Lack of functional C1-INH results in excessive release of bradykinin, which triggers vasodilation, vascular permeability, and edema. Most attacks are mild and self-limiting, but untreated laryngeal attacks may cause rapid asphyxiation and death. Potential triggers of laryngeal attacks include trauma to or manipulation of the face, mouth, or upper airway. Therefore, before performing such a procedure in a patient with HAE, the otolaryngologist should consult with the patient, the physician managing the HAE, and the anesthesiologist and make appropriate preparations for prevention and/or treatment of an attack. Results: Current World Allergy Organization and European guidelines recommend the use of i.v. plasma-derived C1-INH replacement for short-term prophylaxis of angioedema attacks. Other effective options include danazol given for several days before and after the procedure and fresh-frozen plasma, but these may not be as effective as C1-INH and may be associated with a high rate of adverse events. Conclusion: Acute attacks, which may occur many hours after a procedure, may be treated with C1-INH; icatibant, a bradykinin B2-receptor antagonist; or ecallantide, a kallikrein inhibitor, all of which have been shown to reduce the duration and severity of HAE attacks. Copyright © 2013, OceanSide Publications, Inc.

Bernstein J.A.,University of Cincinnati
Expert Opinion on Pharmacotherapy | Year: 2013

Introduction: Allergic rhinitis (AR) can be challenging to treat. For many patients, current therapies (including multiple therapies) provide insufficient symptom relief. There is, therefore, a clear unmet medical need for a new and more effective AR treatment option. MP29-02 (Dymista) is a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate in an advanced delivery system. Areas covered: The goal of this article is to review all MP29-02 clinical data currently published with a view to establish its potential to fill the current unmet medical need in AR. Relevant articles and abstracts were reviewed from PUBMED and conference proceedings. Expert opinion: MP29-02 represents a breakthrough in AR management for the following reasons: i) MP29-02 has been extensively studied in comparison to first-line therapies in both seasonal AR (SAR) patients and in those with chronic rhinitis (i.e., perennial allergic rhinitis [PAR] and nonallergic (vasomotor) rhinitis) in one of the largest direct head-to-head clinical trial programmes in AR, to date. ii) With MP29-02, the efficacy of an intranasal corticosteroid (INS), the first-line choice for AR has been exceeded for the first time without safety repercussions. AR patients treated with MP29-02 experience significantly greater relief from their overall nasal and ocular symptoms compared to two first-line AR therapies, irrespective of season, symptom type, or disease severity. More patients treated with MP29-02 achieve a substantial reduction (i.e., 50% reduction) in their symptoms and also complete symptom relief and achieve these clinically relevant responses days faster than an INS or antihistamine. iii) Formulation of a topical medication is critical, and MP29-02's novel formulation and/or its device contribute to its clinical efficacy. © Informa UK, Ltd.

Toygar O.,University of Cincinnati
Retina | Year: 2016

PURPOSE:: To demonstrate the outcomes of pars plana vitrectomy in patients with custom flexible iris prosthesis (CFIP). METHODS:: The medical records of patients who underwent CFIP placement were retrospectively reviewed. Patients who underwent pars plana vitrectomy concurrent with or after placement of CFIP were identified. Preoperative, intraoperative, and postoperative parameters were analyzed. Surgeons were surveyed regarding the technical aspects of the vitreoretinal surgery. Outcome measures included: anatomic success, complications, surgeon-rated ease of visualization through CFIP during pars plana vitrectomy, and Snellen best-corrected visual acuity. RESULTS:: Twenty-four surgeries were performed in 20 eyes of 20 patients. Postoperative best-corrected visual acuity improved in 11 eyes (55%), remained unchanged in 5 eyes (25%), and declined in 4 eyes (20%) after a mean follow-up of 16.1 ± 16.\nths (range: 3–53 months). No intraoperative complications were noted. Short-term anatomical success was 100%. Postoperative complications occurred in five eyes (recurrent retinal detachment in three eyes, recurrent epiretinal membrane in 1 eye, and CFIP and intraocular lens subluxation in 1 eye). CONCLUSION:: Visualization for pars plana vitrectomy with the assistance of both direct and wide angle viewing systems through the 3.35 mm pseudopupil of a CFIP is viable in the surgical management of complex vitreoretinal diseases. © 2016 by Ophthalmic Communications Society, Inc.

Ho S.-M.,University of Cincinnati
Journal of Allergy and Clinical Immunology | Year: 2010

Asthma, a chronic inflammatory disorder of the airway, is influenced by interplay between genetic and environmental factors now known to be mediated by epigenetics. Aberrant DNA methylation, altered histone modifications, specific microRNA expression, and other chromatin alterations orchestrate a complex early-life reprogramming of immune T-cell response, dendritic cell function, macrophage activation, and a breach of airway epithelial barrier that dictates asthma risk and severity in later life. Adult-onset asthma is under analogous regulation. The sharp increase in asthma prevalence over the past 2 or 3 decades and the large variations among populations of similar racial/ethnic background but different environmental exposures favors a strong contribution of environmental factors. This review addresses the fundamental question of whether environmental influences on asthma risk, severity, and steroid resistance are partly due to differential epigenetic modulations. Current knowledge on the epigenetic effects of tobacco smoke, microbial allergens, oxidants, airborne particulate matter, diesel exhaust particles, polycyclic aromatic hydrocarbons, dietary methyl donors and other nutritional factors, and dust mites is discussed. Exciting findings have been generated by rapid technological advances and well-designed experimental and population studies. The discovery and validation of epigenetic biomarkers linked to exposure, asthma, or both might lead to better epigenotyping of risk, prognosis, treatment prediction, and development of novel therapies. © 2010 American Academy of Allergy, Asthma & Immunology.

Fichtenbaum C.J.,University of Cincinnati
Current HIV/AIDS Reports | Year: 2010

Atherosclerosis is a complex inflammatory process that has been identified as an important problem in persons with HIV infection. Epidemiologic studies have linked certain antiretroviral medications (some nucleoside reverse transcriptase inhibitors and protease inhibitors) with a higher risk of coronary heart disease (CHD). Conversely, nonnucleoside reverse transcriptase inhibitors, entry inhibitors, and integrase inhibitors appear neutral. HIV infection is a chronic inflammatory process associated with endothelial dysfunction, atherogenic dyslipidemia, and a higher risk for CHD. Initiation of antiretroviral therapy in the short term appears to lower CHD risk, regardless of the specific agents used. However, adequately powered randomized trials of antiretroviral therapy with CHD as a primary end point are lacking. Thus, the evidence of whether antiretroviral therapy increases or decreases CHD risk in persons with HIV is perplexing. This article reviews the current controversy of the role of HIV and antiretroviral therapy in the development of cardiovascular disease. © Springer Science+Business Media, LLC 2010.

Guse D.M.,University of Cincinnati | Moran S.L.,Mayo Medical School
Annals of Plastic Surgery | Year: 2013

PURPOSE: Peripheral neuromas within the upper extremity result in significant disability. Treatment options vary, and established protocols have yet to be determined. We performed a long-term outcome comparison examining different treatment options for peripheral upper extremity neuromas to determine which method provided superior results using a validated upper extremity outcome measurement system. METHODS: A retrospective chart review was performed for all patients undergoing surgical intervention from 1980 to 2005 for a symptomatic neuroma of the hand or forearm. Patients' charts were reviewed for medical history, etiology of neuroma, and treatment outcomes. Patients were surveyed using the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire and pain evaluation questionnaires. RESULTS: We identified 127 eligible patients who had their index procedure performed at our institution. Fifty-six patients completed the questionnaires. In all cases, verification of a neuroma was made on pathologic and surgical examination. Follow-up averaged 240 months from the time of surgery. Mean age at the time of surgery was 40 years (range, 19-72 years). Of all the patients, 11 were treated with muscle or bone transposition, 17 with simple excision, and 28 with nerve repair and neurolysis. Mean DASH score at the final follow-up was 19.75 (range, 0-78.3). Patients who underwent neuroma excision with nerve repair had significantly lower postoperative DASH scores, averaging 11.42, compared with either muscle or bone transposition or simple excision (mean DASH score, 22.4 and 32.0, respectively, P = 0.01). The number of neuroma procedures (P = 0.04), preoperative pain severity (P = 0.03), and postoperative pain severity (P = 0.04) all affected the final DASH score. Fifteen patients (27%) required more than 1 surgery. Simple neuroma excision resulting in the highest incidence of reoperations (47%). CONCLUSIONS: Treatment of upper extremity neuromas remains a complicated problem. Within this study, nerve repair yielded improved DASH scores compared with nerve transposition or the use of simple resection. Resection alone was associated with an unacceptable recurrence rate and should be discouraged as treatment for upper extremity neuromas. Prior surgical procedures, neuroma size, and the severity of preoperative pain may all adversely impact the success of surgical intervention. © 2013 by Lippincott Williams & Wilkins.

Yassine M.H.,University of Cincinnati | Suidan M.T.,American University of Beirut | Venosa A.D.,U.S. Environmental Protection Agency
Water Research | Year: 2013

A novel mechanistic model is presented that describes the aerobic biodegradation kinetics of soybean biodiesel and petroleum diesel in batch experiments. The model was built on the assumptions that biodegradation takes place in the aqueous phase according to Monod kinetics, and that the substrate dissolution kinetics at the oil/water interface is intrinsically fast compared to biodegradation kinetics. Further, due to the very low aqueous solubility of these compounds, the change in the substrate aqueous-phase concentration over time was assumed to approaches zero, and that substrate aqueous concentration remains close to the saturation level while the non-aqueous phase liquid (NAPL) is still significant. No former knowledge of the saturation substrate concentration (Ssat) and the Monod half-saturation constant (Ks) was required, as the term Ssat/(Ks + Ssat) in the Monod equation remained constant during this phase. The n-alkanes C10-C24 of petroleum diesel were all utilized at a relatively constant actual specific utilization rate of 0.01-0.02 mg-alkane/mg-biomass-hr, while the fatty acid methyl esters (FAMEs) of biodiesel were utilized at actual specific rates significantly higher with increasing carbon chain length and lower with increasing number of double bonds. The results were found to be in agreement with kinetic, genetic, and metabolic evidence reported in the literature pertaining to microbial decay rates, uptake mechanisms, and the metabolic pathway by which these compounds are assimilated into microorganisms. The presented model can be applied, without major modifications, to estimate meaningful kinetic parameters from batch experiments, as well as near source zone field application. We suggest the estimated actual microbial specific utilization rate (kC) of such materials to be a better measure of the degradation rate when compared to the maximum specific utilization rate (k), which might be orders of magnitude higher than kC and might never be observed in reality. © 2012 Elsevier Ltd.

Acute kidney injury (AKI) is a common and serious condition, the diagnosis of which currently depends on functional markers such as serum creatinine measurements. Unfortunately, creatinine is a delayed and unreliable indicator of AKI. The lack of early biomarkers of structural kidney injury (akin to troponin in acute myocardial injury) has hampered our ability to translate promising experimental therapies to human AKI. Fortunately, understanding the early stress response of the kidney to acute injuries has revealed a number of potential biomarkers. The discovery, translation and validation of neutrophil gelatinase-associated lipocalin (NGAL), possibly the most promising novel AKI biomarker, is reviewed. NGAL is emerging as an excellent stand-alone troponin-like structural biomarker in the plasma and urine for the early diagnosis of AKI, and for the prediction of clinical outcomes such as dialysis requirement and mortality in several common clinical scenarios. The approach of using NGAL as a trigger to initiate and monitor therapies for AKI, and as a safety biomarker when using potentially nephrotoxic agents, is also promising. In addition, it is hoped that the use of sensitive and specific biomarkers such as NGAL as endpoints in clinical trials will result in a reduction in required sample sizes, and hence the cost incurred. Furthermore, predictive biomarkers like NGAL may play a critical role in expediting the drug development process. However, given the complexity of AKI, additional biomarkers (perhaps a panel of plasma and urinary biomarkers) may eventually need to be developed and validated for optimal progress to occur. © 2010 Asian Pacific Society of Nephrology.

Dawodu A.,University of Cincinnati
Paediatrics and international child health | Year: 2012

Vitamin D deficiency in mothers and infants is a global health disorder despite recognition that it is preventable. Recent data support the theory that vitamin D deficiency in adults and children may increase the risk of infections and auto-immune diseases. In most cases, vitamin D deficiency is caused by sunlight deprivation and inadequate corrective vitamin D intake. There is a strong mother/infant vitamin D relationship that affects vitamin D status both in utero and in infancy. Recognition that vitamin D deficiency is a worldwide mother/infant health problem is a basis on which to modify public health strategies to reduce the burden of disease and improve maternal and child vitamin D nutrition. This review provides an update on vitamin D function and the global scope and implications of vitamin D deficiency as it relates to pregnancy and infancy. It also addresses a combined strategy to prevent vitamin D deficiency during pregnancy, lactation and infancy.

Privitera M.,University of Cincinnati
Neurology: Clinical Practice | Year: 2013

Generic substitution of antiepileptic drugs remains a controversial area without a clear consensus to guide clinicians. The US Food and Drug Administration (FDA) requires rigorous testing of generic products and states that all approved products are interchangeable. FDA studies involve single doses in normal subjects so may not represent the performance of generic products in people with epilepsy. Physician surveys, case reports, and retrospective pharmacy database analyses suggest that antiepileptic drug generic substitution is associated with more health problems and high switchback rates, but these studies have insufficient detail on seizure control and blood levels. Several ongoing prospective randomized trials with rigorous pharmacokinetic methods aim to provide more data for decision-making. © 2013 American Academy of Neurology.

Ravyn D.,CME Inc | Ravyn V.,University of Colorado at Denver | Lowney R.,CME Inc | Nasrallah H.A.,University of Cincinnati
Schizophrenia Research | Year: 2013

Although a number of first- and second-generation antipsychotics are available, achieving optimal therapeutic response for patients with schizophrenia can be challenging. The presence of polymorphic alleles for cytochrome P (CYP) 450 may result in lack of expression, altered levels of expression, or altered function of CYP450 enzymes. CYP2D6*2, and CYP3A4*2013 Elsevier B.V.

Bernstein J.A.,University of Cincinnati
Allergy and Asthma Proceedings | Year: 2011

Hereditary Angioedema (HAE) is a multisystem, autosomal dominant disease that affects ∼1:10,000 to 1:50,000 individuals in the United States. The disease has several clinical characteristics that distinguish it from other forms of angioedema. Recurrent swelling attacks involve the abdomen, face, extremities, genitalia, oropharynx, or larynx without urticaria. The swelling attacks are typically unilateral, nonpitting, nonpruritic, and, although uncomfortable, are often painless. Other forms of isolated angioedema such as acquired angioedema and angiotensin-converting enzyme-induced angioedema have similar characteristics of HAE. Therefore, evaluation of patients with recurrent angioedema should be directed at excluding these different forms of angioedema before a diagnosis of idiopathic angioedema is made. The objective of this article is to provide an overview of the differential diagnosis of angioedema that reflects the angioedema guidelines that are currently in development. Copyright © 2011, OceanSide Publications, Inc.

In recent years there has been growing recognition that Field-Configuring Events (FCEs) play an important role in connecting stakeholders, conferring authority to certain members, and shaping the organizing visions surrounding emerging technologies. While much of this work has examined the features of FCEs, the implications and outcomes of FCEs, and the coalescence of FCEs, this study contributes to our understanding of fields that are not converging, rather different stakeholders are actively creating and summoning new FCEs to assert authority. This case also examines the relationship between definitions and organizing visions, as the discursive and social contexts in which these boundaries are being contested. This study follows the emerging interorganizational augmented reality (AR) community, as a group that unites under the term AR but has been continually negotiating its meaning for decades. Through extensive participant observation at numerous global conferences and in-depth interviews, this study shows how various definitions originated and evolved, how new emerging artifacts have challenged definitions, how specific groups have coalesced around definitions, and the various ways that they are organizing at and across FCEs to contest these definitions. These findings of how discourse flows across FCEs contribute to our empirical understanding of the tactics that various actors engage in to draw symbolic, social, and material boundaries around a field, as well as how these debates and commitments ultimately shape the participants in the community and subsequent work that comes out of the community. © 2016 Elsevier Ltd.

Denson L.A.,University of Cincinnati
Inflammatory Bowel Diseases | Year: 2013

Recent translational studies have provided new insights into the pathogenesis of pediatric-onset inflammatory bowel disease. Registry studies have identified distinct clinical phenotypes with increasing age of onset; this has led to a revision of the clinical phenotyping system, now termed the Paris classification system. It is recognized that there are infantile (age, <1 years), very early onset (VEO) (age, 1-10 years), and early onset (age, 10-17 years) forms of disease. Rare genetic mutations affecting antimicrobial and anti-inflammatory pathways have been discovered in infantile and VEO forms, although genetic pathways identified in early onset disease have been similar to adult-onset inflammatory bowel disease. An increasing incidence in the infantile and VEO forms has suggested an important environmental influence. This is likely ultimately expressed through alterations in the enteric flora (dysbiosis) and dysregulated immune responses to the flora, which are recognized as a critical trigger for mucosal inflammation. These data should ultimately guide new pathogenic models of disease, which will inform both therapy in individual patients and disease prevention in their at-risk family members. Copyright © 2013 Crohn's & Colitis Foundation of America, Inc.

Widdice L.E.,University of Cincinnati
Adolescent Medicine: State of the Art Reviews | Year: 2012

Human papillomaviruses (HPV) are a family of viruses that infect the epithelium of many parts of the body. Persistent infection with high-risk HPV is necessary but insufficient to cause cervical cancer. High-risk HPV types are increasingly recognized as a risk factor for cancers other than cervical cancer. A large proportion of vulvar, vaginal, anal, penile, and oropharyngeal cancers are associated with HPV. Low-risk HPV types cause genital warts. Recent advancement in the prevention of HPV infection, genital warts, and HPV-associated precancers and cancers include vaccination. Until the full potential of vaccination can be attained, cervical cancer screening remains an important component of prevention. Copyright © 2012 American Academy of Pediatrics. All rights reserved.

Vesper C.,Central European University | Richardson M.J.,University of Cincinnati
Experimental Brain Research | Year: 2014

How is coordination achieved in asymmetric joint actions where co-actors have unequal access to task information? Pairs of participants performed a non-verbal tapping task with the goal of synchronizing taps to different targets. We tested whether 'Leaders' knowing the target locations would support 'Followers' without this information. Experiment 1 showed that Leaders tapped with higher amplitude that also scaled with specific target distance, thereby emphasizing differences between correct targets and possible alternatives. This strategic communication only occurred when Leaders' movements were fully visible, but not when they were partially occluded. Full visual information between co-actors also resulted in higher and more stable behavioral coordination than partial vision. Experiment 2 showed that Leaders' amplitude adaptation facilitated target prediction by independent Observers. We conclude that fully understanding joint action coordination requires both representational (i.e., strategic adaptation) and dynamical systems (i.e., behavioral coupling) accounts. © 2014 Springer-Verlag.

Chen W.,University of Dayton | Abeysinghe D.C.,University of Cincinnati | Nelson R.L.,Air Force Research Lab | Zhan Q.,University of Dayton
Nano Letters | Year: 2010

A spiral plasmonic lens can focus circular polarization of a given handedness while simultaneously defocus the circular polarization of the opposite chirality, which may be used as a miniature circular polarization analyzer. In this letter, we experimentally investigated the plasmonic focusing properties of the spiral lens using a collection mode near-field scanning optical microscope. A single Archimedes' spiral slot with a single turn was etched through gold thin film as a spiral plasmonic lens. The plasmonic field at the focus of a spiral lens strongly depends on the spin of the incident photon. Circular polarization extinction ratio better than 50 is obtainable with a device size as small as only 4 times of surface plasmon wavelength. © 2010 American Chemical Society.

Fan G.-C.,University of Cincinnati
Progress in Molecular Biology and Translational Science | Year: 2012

Stress response is well appreciated to induce the expression of heat shock proteins (Hsps) in the cell. Numerous studies have demonstrated that Hsps function as molecular chaperones in the stabilization of intracellular proteins, repairing damaged proteins, and assisting in protein translocation. Various kinds of stem cells (embryonic stem cells, adult stem cells, or induced pluripotent stem cells) have to maintain their stemness and, under certain circumstances, undergo stress. Therefore, Hsps should have an important influence on stem cells. Actually, numerous studies have indicated that some Hsps physically interact with a number of transcription factors as well as intrinsic and extrinsic signaling pathways. Importantly, alterations in Hsp expression have been demonstrated to affect stem cell behavior including self-renewal, differentiation, sensitivity to environmental stress, and aging. This chapter summarizes recent findings related to (1) the roles of Hsps in maintenance of stem cell dormancy, proliferation, and differentiation; (2) the expression signature of Hsps in embryonic/adult stem cells and differentiated stem cells; (3) the protective roles of Hsps in transplanted stem cells; and (4) the possible roles of Hsps in stem cell aging. © 2012 Elsevier Inc.

Ingraffea A.,University of Cincinnati
Facial Plastic Surgery Clinics of North America | Year: 2013

The incidence of cutaneous malignant melanoma continues to increase worldwide. It is the deadliest form of skin malignancy. This article focuses on the epidemiology, diagnosis, prevention, and new staging criteria of melanoma. The author delves into standards of treatment and highlights new strategies, including but not limited to noninvasive imaging techniques and immunotherapy. © 2013 Elsevier Inc.

Krueger D.A.,University of Cincinnati
Current Treatment Options in Neurology | Year: 2013

Opinion statement: Historically, before the advent of modern imaging and genetic testing, Tuberous Sclerosis Complex (TSC) was more of a diagnostic challenge and less of a treatment challenge. This is because the natural history of TSC was poorly understood and TSC-specific treatments were non-existent. In the current era, diagnosis is more straightforward but management is much more complex. Disease manifestations vary by age, severity, and organ system. Management issues in the first few months of life, including neurologic manifestations, are very different than late childhood, adolescence, and adulthood. With increasing numbers of TSC diagnoses being made prenatally or shortly after birth, the opportunity for interventions that may improve long-term developmental and epilepsy outcomes now may precede the onset of neurological clinical symptoms. Familiarity and anticipation of these neurologic complications and rapid response to their emergence is crucial. Periodic imaging surveillance for development of subependymal giant cell astrocytoma (SEGA), preferably by magnetic resonance imaging (MRI) every 1-3 years, is now standard of care. Early SEGA detection provides opportunity to initiate pharmacologic treatment with everolimus if appropriate, thereby negating the need for invasive surgery. Routine electroencephalography (EEG) in asymptomatic infants for the first year or two of life is becoming increasingly accepted, with treatment initiation of vigabatrin dependent on concerning EEG findings instead of waiting until onset of clinical seizures, the traditional approach. Effective SEGA treatment and optimal seizure control remain principal during the first few decades of life for the clinical neurologist involved in the management of TSC. However, during the same period and extending through adulthood, assessment of TSC-associated neuropsychiatric disorder (TAND) is also key to the best clinical outcome and quality of life for affected individuals and their surrounding family and caregivers. © 2013 Springer Science+Business Media New York.

Background: Guidelines for the management and treatment of complicated intra-abdominal infections have been generated by a joint effort of the Surgical Infection Society and the Infectious Diseases Society of America. Continued review is needed of the process of these guideline development efforts, the evidence collected, and the recommendations developed by this collaboration. Methods: The literature employed in the development of these guidelines and the process for the development of the recommendations was reviewed. Results: The process for the development of the guidelines required providing answers to questions surrounding the type of evidence, the quality of that evidence, and whether the data used were generated from clinical trials with investigators blinded to the randomization scheme. The recommendations most commonly follow randomized comparative trials, with observational reports and expert opinions assuming a lesser role. Sources of bias and conflict of interest considerations also must be important in guideline development, with full disclosure from participants. Conclusions: Standards for the evaluation of data and recommendations in the guidelines for complicated intra-abdominal infection provided a rigorous evaluation of available clinical information. This process serves as a model for the development of additional guidelines for patient care. © 2010 Mary Ann Liebert, Inc.

Arnold L.,University of Cincinnati
The American journal of managed care | Year: 2010

OBJECTIVE: To review the efficacy and safety of pregabalin, an alpha(2)-delta (alpha(2)-delta) ligand, for the management of fibromyalgia (FM). METHODS: Review of 2 pivotal phase 3 trials that evaluated the efficacy and safety of pregabalin for the management of FM. RESULTS: FM is a chronic condition that is characterized by widespread musculoskeletal pain and has a greater prevalence in women than in men. In a 14-week, randomized, double-blind trial, pregabalin at all 3 doses (300, 450, and 600 mg daily) resulted in significantly greater improvements in pain and function relative to placebo. Parallel with these improvements, greater proportions of patients in the pregabalin groups reported improvement in global disease status compared with placebo. In a second study designed to evaluate the durability of response, patients were randomized to up to 6 months of treatment with pregabalin or placebo after a 6-week, open-label, dose-optimization treatment phase. Based on predefined criteria for loss of therapeutic response, patients treated with pregabalin were observed to maintain a therapeutic response for a significantly longer duration than patients treated with placebo. Pregabalin was tolerated by most patients in both trials; the incidence of the most commonly reported adverse events (dizziness, somnolence, weight gain, headache, dry mouth) appeared to be dose-related. CONCLUSION: Pregabalin has been demonstrated to be efficacious and well-tolerated for the management of FM.

Gerring J.P.,Johns Hopkins University | Wade S.,University of Cincinnati
Journal of Neurotrauma | Year: 2012

This article builds upon Traumatic Brain Injury Common Data Elements (TBI CDE) version 1.0 and the pediatric CDE Initiative by emphasizing the essential role of psychosocial risk and protective factors in pediatric TBI research. The goals are to provide a compelling rationale for including psychosocial risk and protective factors in addition to socioeconomic status (SES), age, and sex in the study design and analyses of pediatric TBI research and to describe recommendations for core common data elements in this domain. Risk and protective factor research is based on the ecological theory of child development in which children develop through a series of interactions with their immediate and more distant environments. Home, school, religious, and social influences are conceptualized as risk and/or protective factors. Child development and TBI researchers have interpreted risk and protective variables as main effects or as interactions and have used cumulative risk indices and moderation models to describe the relationship among these variables and outcomes that have to do with development and with recovery from TBI. It is likely that the number, type, and interaction among risk and protective factors each contribute unique variance to study outcomes. Longitudinal designs in TBI research will be essential to understanding the reciprocal relationships between risk/protective factors and the recovery/outcome made by the child. The search for effective interventions to hasten TBI recovery mandates the need to target modifiable risks and to promote protective factors in the child's environment. © 2012, Mary Ann Liebert, Inc.

Brzyski J.R.,University of Cincinnati
American Journal of Botany | Year: 2010

• Premise of the study: Microsatellite markers were developed in Spiraea virginiana, a federally threatened native shrub found along stream banks, to identify clonal genotypes and measure population genetic variability. • Methods and Results: Eleven primer sets were developed using a non-radioactive protocol. These revealed a moderate level of genetic variation, as indicated by the number of alleles per locus (range = 1 - 4) and an average observed heterozygosity of 0.595. Select loci also amplified successfully in the related species Spiraea japonica. • Conclusion: Development of the markers described here is critical for the genetic identification of clonal plants as a first step in demographic analyses, and is necessary for the future conservation of this rare species. Amplification of the markers in S. japonica suggests their potential utility in research regarding this species. © 2010 Botanical Society of America.

Miller J.H.,University of Cincinnati
Proceedings. Biological sciences / The Royal Society | Year: 2013

Bone accumulations faithfully record historical ecological data on animal communities, and owing to millennial-scale bone survival on high-latitude landscapes, have exceptional potential for extending records on arctic ecosystems. For the Porcupine Caribou Herd, maintaining access to calving grounds on the Arctic National Wildlife Refuge (ANWR, Alaska) is a central management concern. However, variability in calving ground geography over the 30+ years of monitoring suggests establishing the impacts of climate change and potential petroleum development on future calving success could benefit from extended temporal perspectives. Using accumulations of female antlers (shed within days of calving) and neonatal skeletons, we test if caribou calving grounds develop measureable and characteristic bone accumulations and if skeletal data may be helpful in establishing a fuller, historically integrated understanding of landscape and habitat needs. Bone surveys of an important ANWR calving area reveal abundant shed antlers (reaching 10(3) km(-2)) and high proportional abundance of newborn skeletal individuals (up to 60% neonate). Openly vegetated riparian terraces, which compose less than 10 per cent of ANWR calving grounds, yield significantly higher antler concentrations than more abundant habitats traditionally viewed as primary calving terrain. Differences between habitats appear robust to potential differences in bone visibility. The distribution of antler weathering stages mirrors known multi-decadal calving histories and highlights portions of the antler accumulation that probably significantly extends records of calving activity. Death assemblages offer historically integrated ecological data valuable for the management and conservation of faunas across polar latitudes.

Bernstein D.I.,University of Cincinnati
Journal of Asthma | Year: 2012

Background and aims. Traffic related air pollutants from diesel engine exhaust are found in fine and ultrafine particulates. The Cincinnati Childrens Allergy and Air Pollution Birth Cohort Study was initiated to determine if early exposure to these pollutants increased risk for development of early atopic sensitization and allergic respiratory disease phenotypes in children. Materials and methods. Over 700 infants born to at least one atopic parent were recruited to participate in a birth cohort study. Participants received annual medical evaluations and skin testing to two foods and 15 aeroallergens from ages 1-4 and again at age seven. Indoor home assessments were conducted at age one. Outdoor traffic related air pollutant exposure was estimated using proximity and land use regression (LUR) modeling. Clinical outcomes were based upon case definitions for wheezing at ages one and three and allergic rhinitis at age three. Results. At age 1 exposure to stop and go traffic was associated with wheezing during infancy and recurrent wheezing was twice more likely among African-American infants. Exposure to high levels of elemental carbon attributable to traffic (ECAT) estimated with a LUR model predicted recurrent wheezing at age 1 as well as multiple wheezing phenotypes at age 3. Exposure to high levels of endotoxin combined with multiple dogs during the first year reduced risk for recurrent wheezing during the first year of life. Early sensitization to tree pollen aeroallergens in foods (egg white, milk) in infancy increased likelihood of allergic rhinitis during age 3. Conclusion. High exposure to traffic related air pollutants represent independent risk factors for wheezing during infancy and early childhood. Further studies are needed to explore long-term effects of traffic exposure on development of asthma in childhood. Scientific significance. Reduction and mitigation of exposure to traffic related air pollutants could reduce risk of respiratory illnesses during childhood. © 2012 Informa Healthcare USA, Inc.

Hinders D.,University of Cincinnati
American Journal of Hospice and Palliative Medicine | Year: 2012

The number of elderly persons is expected to increase to 55 million by 2020, with the minority population increasing to 12.9 million, yet fewer than 30% of Americans have advance directives in place. Cultural values, religious beliefs, and family support systems are a few of the factors that influence or hinder the completion of advance directives. Health care provider perspectives regarding advance directives vary greatly with health care settings. Many primary care providers are reluctant to initiate conversations regarding advance directives for multiple reasons. Nurse practitioners cover more than 600 million office visits per year in the United States and are in a key position to educate, advocate, and assist in the completion of advance directives. © The Author(s) 2012.

Buschbeck E.K.,University of Cincinnati
Journal of Experimental Biology | Year: 2014

Stemmata, the eyes of holometabolous insect larvae, have gained little attention, even though they exhibit remarkably different optical solutions, ranging from compound eyes with upright images, to sophisticated single-chamber eyes with inverted images. Such optical differences raise the question of how major transitions may have occurred. Stemmata evolved from compound eye ancestry, and optical differences are apparent even in some of the simplest systems that share strong cellular homology with adult ommatidia. The transition to sophisticated single-chamber eyes occurred many times independently, and in at least two different ways: through the fusion of many ommatidia [as in the sawfly (Hymenoptera)], and through the expansion of single ommatidia [as in tiger beetles (Coleoptera), antlions (Neuroptera) and dobsonflies (Megaloptera)]. Although ommatidia-like units frequently have multiple photoreceptor layers (tiers), sophisticated image-forming stemmata tend to only have one photoreceptor tier, presumably a consequence of the lens only being able to efficiently focus light on to one photoreceptor layer. An interesting exception is found in some diving beetles [Dytiscidae (Coleoptera)], in which two retinas receive sharp images from a bifocal lens. Taken together, stemmata represent a great model system to study an impressive set of optical solutions that evolved from a relatively simple ancestral organization. © 2014, The Company of Biologists Ltd. All rights reserved.

Filippi M.-D.,University of Cincinnati
Advances in Immunology | Year: 2015

The neutrophil transmigration across the blood endothelial cell barrier represents the prerequisite step of innate inflammation. Neutrophil recruitment to inflamed tissues occurs in a well-defined stepwise manner, which includes elements of neutrophil rolling, firm adhesion, and crawling onto the endothelial cell surface before transmigrating across the endothelial barrier. This latter step known as diapedesis can occur at the endothelial cell junction (paracellular) or directly through the endothelial cell body (transcellular). The extravasation cascade is controlled by series of engagement of various adhesive modules, which result in activation of bidirectional signals to neutrophils and endothelial cells for adequate cellular response. This review will focus on recent advances in our understanding of mechanism of leukocyte crawling and diapedesis, with an emphasis on leukocyte-endothelial interactions and the signaling pathways they transduce to determine the mode of diapedesis, junctional or nonjunctional. I will also discuss emerging evidence highlighting key differences in the two modes of diapedesis and why it is clinically important to understand specificity in the regulation of diapedesis. © 2015 Elsevier Inc.

BACKGROUND: Although studies have identified an increased likelihood of marijuana and tobacco co-use among African Americans as compared to other racial groups, few studies have specifically examined the prevalence and substance use characteristics of co-users among African Americans in a national survey. METHODS: The current secondary analysis examined the prevalence rates and substance use characteristics (e.g., marijuana dependence) of 2024 African American past month marijuana and tobacco users and co-users participating in the 2013 National Survey on Drug Use and Health. RESULTS: Findings revealed that 18.5%, 53.8% and 27.7% of African Americans smoked marijuana only, tobacco only and marijuana and tobacco in the past 30days, respectively. Relative to participants who smoked marijuana only, African Americans who smoked marijuana and tobacco were more likely to be marijuana dependent in the past year and report more days of marijuana use in the past month. Further, relative to participants who smoked tobacco only, African Americans who smoked marijuana and tobacco were less likely to be dependent on nicotine, reported fewer days of cigarette use in the past month, and began smoking cigarettes, cigars and marijuana at a younger age, but were more likely to be marijuana dependent in the past year and reported more days of cigar use in the past month. CONCLUSIONS: Marijuana and tobacco co-use is a significant public health problem, especially among African Americans. Additional research on effective prevention and treatment interventions for African Americans who smoke marijuana and tobacco is warranted. © 2015 Elsevier Ltd. All rights reserved.

Mickiewicz B.,University of Calgary | Vogel H.J.,University of Calgary | Wong H.R.,University of Cincinnati | Winston B.W.,University of Calgary
American Journal of Respiratory and Critical Care Medicine | Year: 2013

Rationale: Septic shock is a significant cause of morbidity and mortality in the pediatric population. Early recognition of septic shock and appropriate treatment increase survival rate; thus, developing new diagnostic tools may improve patients' outcomes. Objectives: Todetermine whether a metabolomics approach could be useful in the diagnosis and prognosis of septic shock in pediatric intensive care unit (PICUs). Methods: Serum samples were collected from 60 patients with septic shock, 40 PICU patients with systemic inflammatory response syndrome (not suspected of having an infection), and 40 healthy children. Proton nuclear magnetic resonance spectroscopy spectra were analyzed and quantified using targeted profiling methodology. Measurements and Main Results: Multivariate statistical analysis was applied to detect specific patterns in metabolic profiles and to highlight differences between patient samples. Supervised analysis afforded good predictive models and managed to separate patient populations. Some of the metabolite concentrations identified in serum samples changed markedly, indicating their influence on the separation between patient groups. These metabolites represent a composite biopattern of the pediatric metabolic response to septic shock and might be considered as the basis for a biomarker panel for the diagnosis of septic shock and its mortality in PICU. Conclusions: Our results indicate that nuclear magnetic resonance metabolite profiling might serve as a promising approach for the diagnosis and prediction of mortality in septic shock in a pediatric population and that quantitative metabolomics methods can be applied in the clinical evaluations of pediatric septic shock. Copyright © 2013 by the American Thoracic Society.

Ghosh C.,Nokia Inc. | Roy S.,University of Washington | Rao M.B.,University of Cincinnati
IEEE Journal on Selected Areas in Communications | Year: 2012

The potential of successful cognitive radio networks operating in TV White Spaces (and other future bands re-allocated for unlicensed operation) has led to significant upsurge of interest in their design optimization-particularly those that are cross-layer in nature, involving both MAC protocols as well as physical layer aspects such as channel sensing. Typically, these seek to optimize a network-level metric (notably, aggregate throughput) of secondary (cognitive) network subject to interference constraints on the primary. In turn, this requires suitable sensing by cognitive users to detect availability of primary channels (currently unused by the protected incumbents) for opportunistic usage. To date, most studies have used largely hypothetical assumptions regarding channel idleness and resulting spectrum availability due to primary user dynamics. For example, idleness of channels over any spectrum are typically assumed to be an independent and identically distributed Bernoulli sequence. In contrast, nearly all real-time measurements suggest that channel idleness is frequency dependent, i.e., the probability that a channel is idle depends on the channel location. Cognitive radio research thus increasingly needs more realistic and validated models for channel idleness as the foundation of credible cross-layer analysis; this is the primary contribution of our work. We use two sets of real-time measurements conducted in disparate geographic locations over four distinct time intervals to show that channel idleness is appropriately modeled as independent but non-identical (i.n.i.d.) Bernoulli variables characterized by p-i, the probability of idleness for the i-th channel. We validate that Beta distribution can be used for modeling the variations in channel idleness probabilities; the Beta distribution parameters are estimated from the data to produce the best model fit. Based on the validated i.n.i.d. model, we build a predictive model by computing the availability probability of k channels, i.e, P Nidle = k, where N idle denotes the number of idle channels over the spectrum of N channels. However, the combinatorial complexity inherent in the computation of P N idle = k suggests the need for efficient approximations. We accomplish this by classifying idleness of channels based on the magnitude of p-i, and propose a novel Poisson-normal approximation for computing PN idle = k. For validation, the distribution obtained from our technique is compared with the exact distribution and normal approximation using the approximation error criterion. © 2012 IEEE.

Dariotis J.K.,Center for Adolescent Health | Dariotis J.K.,University of Cincinnati | Johnson M.W.,Johns Hopkins University
Experimental and Clinical Psychopharmacology | Year: 2015

Youth under 25 show substantial sexual and substance use risk behaviors. One factor associated with risk behaviors is delay discounting, the devaluation of delayed outcomes. This study determined if delay discounting for sexual outcomes is related to sexual risk and substance use among 18-24 year olds. Females (70) and males (56) completed the Sexual Discounting Task, which assessed their likelihood of having unprotected immediate sex versus waiting for sex with a condom, at various delays, with 4 hypothetical sexual partners selected from photographs: the person they most wanted to have sex with, least wanted to have sex with, judged most likely to have a sexually transmitted infection (STI), and judged least likely to have an STI. They also completed instruments assessing HIV knowledge, sexual behaviors, substance use, risk attitudes, inhibition, impulsivity, and sensation-seeking. Condom use likelihood generally decreased with increasing delay. Preference for immediate, unprotected sex was greater for partners whom participants most (vs. least) wanted to have sex with and judged least (vs. most) likely to have an STI. Preference for immediate, unprotected sex in the "most want to have sex with" and "least likely to have an STI" conditions was related to greater lifetime risky sexual partners, lifetime number of unique substances used, disregard of social approval/danger, disinhibition, and sensation/excitement-seeking. Males showed greater likelihood of unprotected sex than females when condom use was undelayed, but delay similarly affected condom use between sexes. Delay discounting should be considered in strategies to minimize youth risk behavior. © 2014 American Psychological Association.

Citrome L.,New York Medical College | Nasrallah H.A.,University of Cincinnati
Expert Opinion on Pharmacotherapy | Year: 2012

Introduction: The product label is commonly used as an authoritative source for drug information, especially for new medications that have a limited published evidence base. Key elements of the product label are descriptions of safety and tolerability. Areas covered: The package inserts of oral atypical antipsychotics approved by the US Food and Drug Administration are reviewed with regard to product safety and tolerability. Expert opinion: Product labels of oral second-generation antipsychotics provide an opportunity to indirectly compare the safety and tolerability profiles of each agent. Some warnings and precautions are found across the entire class; other warnings and precautions may be worded somewhat differently from agent to agent and some may be unique to a particular medication. Guidance is provided in the product label regarding use in specific populations, drugdrug interactions and other issues relating to dosing. Common adverse reactions are tabulated but the reader is left to calculate the risk differences from placebo and number needed to harm. The latter can be helpful in appraising potential differences in discontinuation rates because of adverse reactions, the proportion gaining at least 7% in body weight from baseline in short-term studies, the proportion experiencing somnolence and the proportion experiencing akathisia. The product label, although limited in terms of being product-specific, is often the most authoritative and accessible source of information about new agents in the marketplace. However, clinicians will need to mind the gap between the efficacy and preliminary safety and tolerability data provided by registration trials and the real-world effectiveness of medications when used in the clinic. © 2012 Informa UK, Ltd.

Stephen D.G.,Wyss Institute for Biologically Inspired Engineering | Van Orden G.,University of Cincinnati
Topics in Cognitive Science | Year: 2012

The commentators expressed concerns regarding the relevance and value of non-computational non-symbolic explanations of cognitive performance. But what counts as an "explanation" depends on the pre-theoretical assumptions behind the scenes of empirical science regarding the kinds of variables and relationships that are sought out in the first place, and some of the present disagreements stem from incommensurate assumptions. Traditional cognitive science presumes cognition to be a decomposable system of components interacting according to computational rules to generate cognitive performances (i.e., component-dominant dynamics). We assign primacy to interaction-dominant dynamics among components. Though either choice can be a good guess before the fact, the primacy of interactions is now supported by much recent empirical work in cognitive science. Consequently, in the main, the commentators have failed so far to address the growing evidence corroborating the theory-driven predictions of complexity science. © 2011 Cognitive Science Society, Inc.

Cost N.G.,University of Cincinnati
Minerva Urologica e Nefrologica | Year: 2013

Testicular germ cell tumors (T-GCTs) are the most common solid tumor in adolescent and young adult men. Due to the success of multidisciplinary management, the prognosis of all stages of T-GCT is quite good. The development of complimentary therapeutic strategies including modern cytotoxic chemotherapy regimens, appropriate utilization of radiotherapy, and timely surgical resection has made T-GCTs the model of a "curative" malignancy. Herein we review the background, epidemiology, and genetics of the disease, as well as an approach to its diagnosis and staging, including rationale for managing T-GCT in its various stages. In summary, while some areas in T-GCT care are debated, the vast majority of patients should be approached in a standardized manner which ensures optimal oncologic outcomes and minimal therapeutic morbidity.

Pecina C.A.,University of Cincinnati
Seminars in Neurology | Year: 2012

Tick paralysis is a rare, but readily treatable condition that if missed can lead to significant morbidity and death. The classic clinical presentation of tick paralysis is the development of an unsteady, ataxic type gait followed by an acute symmetric ascending flaccid paralysis. Symptoms generally begin within 2 to 6 days of tick attachment. If the tick continues to feed, the weakness ascends to the upper extremities over a matter of hours, followed by cranial nerve involvement. Due to the similarity in its presentation, tick paralysis is often misdiagnosed as Guillain-Barré's syndrome, particularly the Miller Fisher's subtype, given its cranial nerve involvement. However, the weakness seen in tick paralysis progresses more quickly than what is generally seen in Guillain-Barré's syndrome and the protein concentration is not elevated in the cerebrospinal fluid. The mainstay of treatment for tick paralysis is tick removal. The time to full neurologic recovery after tick removal is estimated to be around 1.5 days with initial improvement generally within hours. Copyright © 2012 by Thieme Medical Publishers, Inc.

Tan J.,University of Cincinnati
Current allergy and asthma reports | Year: 2014

Occupational asthma is a form of asthma that is often under-diagnosed and under-reported. Unrecognized occupational asthma can lead to progression of disease and increased morbidity. The medical history is a critical element for establishing a diagnosis of OA. The history should include a detailed assessment of the workplace environment, the work process, changes in symptoms in and away from the workplace, and a review of relevant material safety data sheets that may provide clues regarding exposure(s) and the potential cause(s). Objective testing including spirometry pre- and post-bronchodilators, peak expiratory flow rate monitoring in and out of the workplace, provocation testing (i.e., methacholine challenge) to assess for airway hyperresponsiveness, and, if feasible, specific provocation by experienced personnel in a controlled setting to a suspected inciting agent are necessary for confirming a diagnosis. Skin or serologic testing for specific IgE to aeroallergens to assess the worker's atopic status is useful especially when considering certain forms of OA where atopy is a risk factor. Specialized laboratory testing may be useful for specific OA causes. It is important to correctly make the diagnosis of OA as the impact on the worker's future employment and earning power can be significantly affected.

Roth E.M.,University of Cincinnati
Expert Opinion on Pharmacotherapy | Year: 2015

Introduction: ω-3 carboxylic acids (ω3 CA), also called ω3 free fatty acids (ω3 FFA), with the trade name Epanova™ is a new formulation of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) approved for the treatment of severe hypertriglyceridemia. The FFA form of EPA and DHA is associated with higher bioavailability than other forms of ω3 fatty acids, potentially resulting in efficacy at lower doses and less dependence on meal relationship.Areas covered: The efficacy and safety of ω3 CA from clinical trials as well as PK and PD data will be reviewed. The mechanism of action of ω3 fatty acids in the lowering of triglycerides (TG) will be discussed and comparison is made with ω3 ethyl ester compounds.Expert opinion: ω3 CA are a unique form of ω3 fatty acids that appear safe and effective in lowering serum TG and offer the possibility of better patient compliance due to lower-dose efficacy and the ability to take with or without food. ω3 CA lowered TG by 26 and 31% for the 2 and 4 g/day doses, respectively, and Apo CIII was also lowered 11 and 14%, respectively, as well. © 2015 Informa UK, Ltd.

Sun S.,University of Cincinnati
Health Services and Outcomes Research Methodology | Year: 2011

Cohen's κ is the most important and most widely accepted measure of inter-rater reliability when the outcome of interest is measured on a nominal scale. The estimates of Cohen's κ usually vary from one study to another due to differences in study settings, test properties, rater characteristics and subject characteristics. This study proposes a formal statistical framework for meta-analysis of Cohen's κ to describe the typical inter-rater reliability estimate across multiple studies, to quantify between-study variation and to evaluate the contribution of moderators to heterogeneity. To demonstrate the application of the proposed statistical framework, a meta-analysis of Cohen's κ is conducted for pressure ulcer classification systems. Implications and directions for future research are discussed. © 2011 Springer Science+Business Media, LLC.

Objective: This case report describes a new complication associated with a baclofen pump in which its fractured intrathecal catheter migrated into the patient's ventricular system. A thecal model was developed to evaluate catheter buoyancy in artificial cerebrospinal fluid (CSF). The literature was reviewed to identify possible mechanical and physiologic causes of catheter migration. Clinical Presentation: A 16-year-old boy with cerebral palsy presented with cervical pain, nausea, and vomiting. He was known to have a nonfunctioning baclofen pump with a 1-piece intrathecal catheter. Imaging studies showed mild ventriculomegaly and a fractured segment of the intrathecal catheter that extended from the cervical subarachnoid space into the third and fourth ventricles. Intervention: The patient had complete symptom resolution after undergoing urgent surgical removal of the catheter segment. Manufacturer analysis of the retrieved catheter revealed a crushed, jagged proximal end. In an experimental thecal sac model, catheter segments in lengths of 0.5 to 89 cm were denser than the artificial CSF and, therefore, did not float in the thecal sac. This finding negates the role of buoyancy in migration. Review of the literature advocates for caudocranial CSF flow patterns as a plausible mechanism for migration. Conclusion: This complication alerts surgeons to the migration risk of loose intrathecal catheter segments into the ventricular system. CSF flow patterns and mechanical processes, but not material properties of the catheter, are likely causes. Copyright © 2010 by the Congress of Neurological Surgeons.

Welsh B.C.,Northeastern University | Braga A.A.,Rutgers University | Sullivan C.J.,University of Cincinnati
Justice Quarterly | Year: 2014

It was not so long ago that scholarly writings pointed to the vast chasm that existed between criminal justice and public health approaches to understanding and controlling interpersonal violence. Other scholarship of the day examined how criminal justice and criminology could benefit from adopting elements of the public health approach. For sure, there still exist many differences in how the two disciplines approach the violence problem, but over the years there have been some promising developments at the intersection of public health and criminology. This paper surveys the evolving link between public health and criminology, with a special focus on serious youth violence. It is concerned with both research and practice and how these efforts-across primary, secondary, and tertiary prevention strategies-are contributing to improved public health-criminology collaborations or public health-influenced programs that have a discernable impact on youth violence. © 2012 © 2012 Academy of Criminal Justice Sciences.

Steiner B.,University of Nebraska - Lincoln | Wooldredge J.,University of Cincinnati
Criminal Justice and Behavior | Year: 2014

This study involved a comparison of the influences on inmate misconduct among female and male inmates. Data were collected from over 5,500 inmates housed in 46 facilities in Ohio and Kentucky (570 women and 5,059 men), and the relative effects of these inmates' background characteristics and confinement experiences were examined for sex-specific samples. The magnitudes of effects were then compared across the two groups. Findings revealed that background characteristics (e.g., age) and confinement experiences (e.g., involvement in education/vocational program) influence women's and men's odds of misconduct. Equality of coefficient tests revealed only three differences in the magnitude of these effects across the analyses of the sex-specific samples, suggesting there are far more similarities than differences in the predictors of misconduct among men versus women. © 2013 International Association for Correctional and Forensic Psychology.

Butler D.L.,University of Cincinnati
Nature protocols | Year: 2010

Tendon and ligament injuries are significant contributors to musculoskeletal injuries. Unfortunately, traditional methods of repair are not uniformly successful and can require revision surgery. Our research is focused on identifying appropriate animal injury models and using tissue-engineered constructs (TECs) from bone-marrow-derived mesenchymal stem cells and collagen scaffolds. Critical to this effort has been the development of functional tissue engineering (FTE). We first determine the in vivo mechanical environment acting on the tissue and then precondition the TECs in culture with aspects of these mechanical signals to improve repair outcome significantly. We describe here a detailed protocol for conducting several complete iterations around our FTE 'road map.' The in vitro portion, from bone marrow harvest to TEC collection, takes 54 d. The in vivo portion, from TEC implantation to limb harvest, takes 84 d. One complete loop around the tissue engineering road map, as presented here, takes 138 d to complete.

Thomas R.D.,Miami University Ohio | Silbert N.H.,University of Cincinnati
Psychonomic Bulletin and Review | Year: 2014

We offer a minor technical correction to the published proof of part (ii) of the main theorem in Silbert and Thomas (Psychonomic Bulletin & Review, 20, 1-20, 2013) that somewhat limits the scope of the equivalence observed in that work. Specifically, in order for a mean shift integrality with decisional separability to be mimicked by a perceptually separable but nondecisionally separable configuration, one needs to assume stimulus invariance. This holds when all of the covariance matrices in the stimulus configuration are equal to each other. We note that part (i) of the theorem is unaffected by this modification; an empirical finding of perceptual separability and the failure of decisional separability can be mimicked by a perceptually nonseparable, decisionally separable configuration without restricting the covariance matrices to be equal. We also note that stimulus invariance is often assumed in simple designs (e.g., Macmillan & Ornstein in Journal of the Acoustical Society of America, 97, 1261-1285, 1998), due to the implausibility of different perceptual correlations being present within stimuli perched very closely in perceptual space. © 2013 Psychonomic Society, Inc.

Mangelson J.J.,University of Cincinnati
Instructional course lectures | Year: 2014

Dorsal fracture-dislocations of the proximal interphalangeal joint are challenging injuries to treat and are associated with many complications. The determination of stability is crucial to appropriate management. Stable injuries can usually be treated nonsurgically, whereas unstable injuries typically require surgical stabilization. Many surgical techniques have been used, including extension block pinning, volar plate arthroplasty, open reduction and internal fixation, external fixation, and hemihamate autografting. Because stiffness and flexion contracture are frequent complications, every effort should be made to initiate early motion while maintaining concentric reduction. Other complications include redislocation, chronic swelling, swan neck and coronal plane deformities, and pin tract infections. Assessing injury characteristics, including chronicity, the percentage of articular surface fractured, and the degree of comminution, and understanding complications will help in determining the most appropriate treatment. Chronic dislocations and those injuries in which painful arthritis develops can be successfully treated with salvage procedures, including arthroplasty and arthrodesis.

Steiner B.,University of Nebraska at Omaha | Wooldredge J.,University of Cincinnati
Justice Quarterly | Year: 2014

Studies have revealed systematic measurement errors in self-report data on crime and deviance resulting from poor recall and/or underreporting by certain groups of respondents. Official crime data have also been criticized, but for different reasons (e.g. gross underestimations of less serious offenses). Very similar observations have been made in studies of inmate crime (misconduct committed by prison inmates). Despite these criticisms, official data on inmate misconduct continue to be the most frequently used data in related studies. This study compared self-report and official data on inmate assaults, property thefts, and drug offenses for samples of inmates from 46 correctional institutions for adults in Ohio and Kentucky. Findings revealed that officially recorded misconduct underestimates the total volume of inmate crime. Analyses designed to uncover sources of the divergence between self-reported misconduct and officially recorded misconduct revealed far more consistencies than differences in the magnitude of inmate and facility effects on the different types of offenses. A few important differences did emerge in the magnitude of effects such as amount of time served (at the individual level) and facility population size (at the aggregate level). © 2012 Academy of Criminal Justice Sciences.

Javaheri S.,University of Cincinnati | Brown L.K.,University of New Mexico | Randerath W.J.,Witten/Herdecke University
Chest | Year: 2014

The beginning of the 21st century witnessed the advent of new positive airway pressure (PAP) technologies for the treatment of central and complex (mixtures of obstructive and central) sleep apnea syndromes. Adaptive servoventilation (ASV) devices applied noninvasively via mask that act to maintain a stable level of ventilation regardless of mechanism are now widely available. These PAP devices function by continually measuring either minute ventilation or airfl ow to calculate a target ventilation to be applied as needed. The apparatus changes inspiratory PAP on an ongoing basis to maintain the chosen parameter near the target level, eff ectively controlling hypopneas of any mechanism. In addition, by applying pressure support levels anticyclic to the patient's own respiratory pattern and a backup rate, this technology is able to suppress central sleep apnea, including that of Hunter-Cheyne-Stokes breathing. Moreover, ASV units have become available that incorporate autotitration of expiratory PAP to fully automate the treatment of all varieties of sleep-disordered breathing. Although extremely eff ective in many patients when used properly, these are complex devices that demand from the clinician a high degree of expertise in understanding how they work and how to determine the proper settings for any given patient. In part one of this series we detail the underlying technology, whereas in part two we will describe the application of ASV in the clinical setting. ©2014 American college of chest physicians.

Silberstein E.B.,University of Cincinnati
Seminars in Nuclear Medicine | Year: 2011

The available data upon which to act in caring for patients with functioning thyroid cancer and thyroglobulin elevation/negative iodine scintigraphy (TENIS) are imperfect, almost never coming from randomized, blinded studies. When the serum thyroglobulin exceeds 2-10 ng/mL, one should use the latest imaging equipment available to find metastatic disease, especially in areas in which it is potentially resectable, ie, neck, bone, and occasionally brain, and collaborate with an experienced surgeon in removing such metastases. If one cannot locate operable metastases and/or tumor location remains elusive, empiric high-dose 131I therapy, preceded by dosimetry, should be considered. There are no randomized studies to prove that this treatment prolongs life, although there is definite evidence of cell killing, because the serum thyroglobulin level frequently diminishes after radioiodine therapy. In selected cases External beam radiotherapy will be helpful when the tumor has been located but cannot be fully removed, for example, with invasion of the trachea, spine, or muscles. There are several tyrosine kinase inhibitors that have shown some effectiveness against the TENIS syndrome, but these should ideally be used in the context of a clinical trial. Tyrosine kinase inhibitor drugs should be preferred to conventional chemotherapy at this time; data on lenalidominde have only appeared in abstract form. The return of NIS function, to permit functioning thyroid cancer with the TENIS syndrome to again concentrate therapeutic amounts of 131I, remains an elusive goal, with few drugs showing real promise. Gene therapy to restore the function of the NIS gene and enhance cellular immunomodulatory and tumor suppressive activity has not yet succeeded clinically. Physicians caring for patients with the TENIS syndrome are urged to enter them into clinical therapeutic studies whenever possible. © 2011 Elsevier Inc. All rights reserved.

Wooldredge J.,University of Cincinnati
Violence and victims | Year: 2013

Violent victimization in prison may enhance inmates' cynicism toward legal authority and the risk of subsequent criminality. Both micro- and macro-level effects on the prevalence and incidence of inmate-on-inmate physical assault during a 6-month period were examined for random samples of inmates (n1 = 5,640) from all state prisons in Ohio and Kentucky (n2 = 46). Findings revealed that nonprovoked assaults were more common among inmates with lifestyles that might have increased their vulnerability to victimization (less time spent in structured activities, committed violent acts themselves, etc.), and in prisons with larger populations and officers who practice lax rule enforcement. A supplementary analysis of violent offending also revealed that inmate offenders and victims may look less like each other compared to offenders and victims in the general population. Policies focused on increasing inmates' involvement in structured prison activities, enhancing professionalism among officers, and lowering prison populations may be most effective for minimizing the risk of violent victimization.

Kalamaras C.M.,University of Cyprus | Dionysiou D.D.,University of Cincinnati | Efstathiou A.M.,University of Cyprus
ACS Catalysis | Year: 2012

A series of y wt % Pt/CexZr1-xO2 catalysts (y = 0.1, 0.5, and 1.0; x = 0.3, 0.5, and 0.7) were synthesized and characterized to investigate the effect of CeO2 doping with Zr 4+ and of Pt particle size (Pt/Ce0.5Zr0.5O 2) on important mechanistic and kinetic aspects of the water-gas shift (WGS) reaction. These included the concentration (μmol·g -1 or θ (surface coverage based on Pts)) and chemical structure of active reaction intermediates present in the "carbon path" and "hydrogen path" of the WGS reaction in the 200-300 °C range and the prevailing mechanism among "redox" and "associative formate" largely considered in the literature. Toward this goal, steady-state isotopic transient kinetic analysis coupled with in situ DRIFTS and mass spectrometry experiments were performed for the first time using D2O and 13CO isotopic gases. A novel transient isotopic experiment allowed quantification of the initial transient rate of reaction of adsorbed formate (HCOO-) with water and that of adsorbed CO with water under steady-state WGS reaction conditions. On the basis of these results, it was concluded that formate should not be considered as an important intermediate. It was found that on Pt/CexZr1-xO 2 catalysts, the WGS reaction mechanism switches from "redox" to a combination of "redox" and "associative formate with -OH group regeneration" mechanisms by increasing the reaction temperature from 200 to 300 °C. The superior WGS activity exhibited by Pt/CexZr1-xO2 (x = 0.3, 0.5, and 0.7) catalysts in comparison with Pt/CeO2 was explained by the fact that the site reactivity of Pt across the metal-support interface was increased as a consequence of the introduction of Zr4+ into the ceria lattice. The concentration of active reaction intermediates was found to strongly depend on reaction temperature, support composition (Ce/Zr ratio), and Pt particle size, parameters that all determine the shape of the light-off CO-conversion curve. © 2012 American Chemical Society.

Henson B.,University of Cincinnati
Violence and Victims | Year: 2010

Over the past two decades, rates of violence in the workplace have grown signifi cantly. Such growth has been more prevalent in some fi elds than others, however. Research shows that rates of violence against healthcare workers are continuously among the highest of any career fi eld. Within the healthcare fi eld, the overwhelming majority of victims of workplace violence are hospital employees, with those working in emergency departments (EDs) experiencing the lion's share of violent victimization. Though this fact is well-known by medical researchers and practitioners, it has received relatively little attention from criminal justice researchers or practitioners. Unfortunately, this oversight has severely limited the use of effective crime prevention techniques in hospital EDs. The goal of this analysis is to utilize techniques of situational crime prevention to develop an effective and easily applicable crime prevention strategy for hospital EDs. © 2010 Springer Publishing Company.

OBJECTIVE: To determine whether modestly severe obesity modifies glucose homeostasis, levels of cardiometabolic markers, and HDL function in African Americans (AAs) and white Americans (WAs) with prediabetes. RESEARCH DESIGN AND METHODS: We studied 145 subjects with prediabetes (N = 61 WAs, N = 84 AAs, mean age 46.5 ± 11.2 years, mean BMI 37.8 ± 6.3 kg/m2). We measured fasting levels of lipids, lipoproteins, and an inflammatory marker (C-reactive protein [CRP]); HDL functionality (i.e., levels of paraoxonase 1 [PON1]); and levels of oxidized LDL, adiponectin, and interleukin-6 (IL-6). We measured serum levels of glucose, insulin, and C-peptide during an oral glucose tolerance test. Values for insulin sensitivity index (Si), glucose effectiveness index (Sg), glucose effectiveness at zero insulin (GEZI), and acute insulin response to glucose (AIRg) were derived using a frequently sampled intravenous glucose tolerance test (using MINMOD software). RESULTS: Mean levels of fasting and incremental serum glucose, insulin, and C-peptide tended to be higher in WAs versus AAs. The mean Si was not different in WAs versus AAs (2.6 ± 2.3 vs. 2.9± 3.0 3 10-4 3min-1 [μU/mL]-1). Mean values for AIRg and disposition index as well as Sg and GEZI were lower in WAs than AAs.WAs had higher serumtriglyceride levels than AAs (116.1±55.5 vs. 82.7±44.2 mg/dL, P = 0.0002). Mean levels of apolipoprotein (apo) A1, HDL cholesterol, PON1, oxidized LDL, CRP, adiponectin, and IL-6 were not significantly different in obese AAs versus WAs with prediabetes. CONCLUSIONS: Modestly severe obesity attenuated the ethnic differences in Si, but not in Sg and triglyceride levels in WAs and AAs with prediabetes. Despite the lower Si and PON1 values, AAs preserved paradoxical relationships between the Si and HDL/apoA1/triglyceride ratios. We conclude that modestly severe obesity has differential effects on the pathogenic mechanisms underlying glucose homeostasis and atherogenesis in obese AAs and WAs with prediabetes. © 2015 by the American Diabetes Association.

Liu R.,University of Cincinnati
Circulation Research | Year: 2016

RATIONALE:: Mitogen-activated protein kinase (MAPK) signaling regulates the growth response of the adult myocardium in response to increased cardiac workload or pathologic insults. The dual-specificity phosphatases (DUSPs) are critical effectors that dephosphorylate the MAPKs to control the basal tone, amplitude and duration of MAPK signaling. OBJECTIVE:: To examine the dual-specificity phosphatase 8 (DUSP8) as a regulator of MAPK signaling in the heart and its impact on ventricular and cardiac myocyte growth dynamics. METHODS AND RESULTS:: Dusp8 gene-deleted mice as well as transgenic mice with inducible expression of DUSP8 in the heart were used here to investigate how this MAPK-phosphatase might regulate intracellular signaling and cardiac growth dynamics in vivo. Dusp8 gene-deleted mice were mildly hypercontractile at baseline with a cardiac phenotype of concentric ventricular remodeling, which protected them from progressing towards heart failure in two surgery-induced disease models. Cardiac-specific overexpression of DUSP8 produced spontaneous eccentric remodeling and ventricular dilation with heart failure. At the cellular level, adult cardiac myocytes from Dusp8 gene-deleted mice were thicker and shorter, while DUSP8 overexpression promoted cardiac myocyte lengthening with a loss of thickness. Mechanistically, activation of extracellular signal-regulated kinases 1/2 (ERK1/2) were selectively increased in Dusp8 gene-deleted hearts at baseline as well as following acute pathologic stress stimulation, while p38 MAPK and c-Jun N-terminal kinases were unaffected. CONCLUSIONS:: These results indicate that DUSP8 controls basal and acute stress-induced ERK1/2 signaling in adult cardiac myocytes that then alters the length-width growth dynamics of individual cardiac myocytes, which further alters contractility, ventricular remodeling and disease susceptibility. © 2016 American Heart Association, Inc.

Bernstein J.A.,University of Cincinnati
American Journal of Rhinology and Allergy | Year: 2013

Background: Allergic rhinitis (AR) is estimated to affect 20-25% of the United States population and thus accounts for a significant portion of our annual total health care expenditure, especially when one includes all of the concomitant disorders associated with rhinitis such as asthma and sinusitis. Given the prevalence of chronic rhinitis, the significant comorbidities associated with this condition, its overall health burden, and dissatisfaction by allergy sufferers with treatment outcomes, it is essential that the allergist and otolaryngologist develop a consensus approach for the evaluation, diagnosis, and treatment of chronic rhinitis subtypes. Methods: This study was designed to achieve this end point. Investigators have taken several clinical, physiological, and mechanistic approaches toward better characterizing rhinitis subtypes. An accurate diagnosis directed at differentiating AR, nonallergic rhinitis, and mixed rhinitis is essential to ensure that treatment(s) prescribed will lead to more favorable clinical outcomes. Results: An accurate history taking into account age of symptom onset, family history, quantification of inciting allergic and/or nonallergic triggers, and seasonality followed by aeroallergen skin testing to assess atopic status has been shown to be the most useful approach for clearly differentiating rhinitis subtypes. Conclusion: Other cellular, cytokine, genetic, and physiological markers have thus far been proven to be less useful. Ultimately, treatment response to medications will be most effective when they are individualized to the patient's diagnosis. Copyright © 2013, OceanSide Publications, Inc.

Sherman K.E.,University of Cincinnati
Topics in Antiviral Medicine | Year: 2011

Identification and treatment of advanced hepatitis C virus (HCV) infection is often challenging. Accurate fibrosis staging can be performed only by liver biopsy. For patients with advanced fibrosis (Metavir score, F3 or F4), progression to decompensated liver disease occurs at a rate of approximately 5% per year and progression to hepatocellular carcinoma occurs at a rate of 1% to 2% per year. Liver decompensation primarily results from altered hepatic blood flow caused by liver scarring and is characterized by ascites and its complications (hepatorenal syndrome, hepatic hydrothorax, and spontaneous bacterial peritonitis), hepatic encephalopathy, bleeding varices, and coagulopathy. Patients with advanced fibrosis need to be regularly monitored for evidence of decompensated disease, and complications need to be aggressively managed. © 2011, IAS-USA.

Baye T.M.,University of Cincinnati | Wilke R.A.,Vanderbilt University
Pharmacogenomics Journal | Year: 2010

There is great interest in characterizing the genetic architecture underlying drug response. For many drugs, gene-based dosing models explain a considerable amount of the overall variation in treatment outcome. As such, prescription drug labels are increasingly being modified to contain pharmacogenetic information. Genetic data must, however, be interpreted within the context of relevant clinical covariates. Even the most predictive models improve with the addition of data related to biogeographical ancestry. The current review explores analytical strategies that leverage population structure to more fully characterize genetic determinants of outcome in large clinical practice-based cohorts. The success of this approach will depend upon several key factors: (1) the availability of outcome data from groups of admixed individuals (that is, populations recombined over multiple generations), (2) a measurable difference in treatment outcome (that is, efficacy and toxicity end points), and (3) a measurable difference in allele frequency between the ancestral populations. © 2010 Macmillan Publishers Limited. All rights reserved.

Chester T.L.,University of Cincinnati
Journal of Chromatography A | Year: 2012

Recent improvement efforts in chromatography have provided great improvements in the rate of plate production, but less attention has been spent on optimizing the kinds of problems that are most often encountered in industry. When factors are not independent in their effects on the responses of a chromatographic separation, all adjustable factors must be considered in concert in seeking the best or optimum condition that solves the problem. This requires careful attention to specifying the goals, the adjustable factors, and the constraints required to make sure the outcome can actually be implemented. Strategies for optimizing assay and screening methods in the context of industrial needs are presented. Expanding the factor space of the system being investigated can lead to better outcomes. The prospect of adding column-outlet pressure control and expanding the mobile phase composition to include condensed gases or supercritical fluids is explored. Reversed-phase liquid chromatography, hydrophilic interaction chromatography, electrostatic repulsion hydrophilic interaction chromatography, and supercritical fluid chromatography are contiguous with regard to mobile phase characteristics. Adjustment of selectivity through instrument-controlled factors can benefit method development. Opportunities obtained by blending modifiers, varying temperature and pressure with compressible mobile phases, and controlling pH are discussed in the context of optimizing methods. © 2012 Elsevier B.V.

Aly Hassan A.,U.S. Environmental Protection Agency | Sorial G.A.,University of Cincinnati
Chemosphere | Year: 2011

One of the main challenges that face successful biofiltration is the erratic loading pattern and long starvation periods. However, such patterns are common in practical applications. In order to provide long-term stable operation of a biofilter under these conditions, a cyclic adsorption/desorption beds system with flow switching was installed prior to a biofilter. Different square waves of a mixture containing n-hexane and benzene at a 2:1 ratio were applied to the cyclic adsorption/desorption beds and then fed to a biofilter. The performance of this integrated system was compared to a biofilter unit receiving the same feed of both VOCs. The cyclic adsorption/desorption beds unit successfully achieved its goal of stabilizing erratic loading even with very sharp peaks at the influent concentration equalizing influent concentrations ranging from 10-470. ppmv for n-hexane to 30-1410. ppmv for benzene. The study included different peak concentrations with durations ranging from 6 to 20. min. The cyclic beds buffered the fluctuating influent load and the followed biofilter had all the time a continuous stable flow. Another advantage achieved by the cyclic adsorption/desorption beds was the uninterrupted feed to the biofilter even during the starvation where there was no influent in the feed. The results of the integrated system with regard to removal efficiency and kinetics are comparable to published results with continuous feed studies at the same loading rates. The removal efficiency for benzene had a minimum of 85% while for n-hexane ranged from 50% to 77% according to the loading rate. The control unit showed very erratic performance highlighting the benefit of the utilization of the cyclic adsorption/desorption beds. The biofilter was more adaptable to concentration changes in benzene than n-hexane. © 2010 Elsevier Ltd.

Sherman A.C.,Emory University | Sherman K.E.,University of Cincinnati
Current HIV/AIDS Reports | Year: 2015

This article describes the importance of extrahepatic systemic manifestations of chronic hepatitis C virus (HCV) infection. While most HCV literature focuses on liver injury and fibrosis progression, a spectrum of systemic disease processes, collectively called C hepatitis-associated systemic manifestations (CHASMs), are present in a high proportion of infected persons. These include thyroid disease (Hashimoto’s thyroiditis, Graves disease, and thyroid cancer), cardiovascular disease (atherosclerosis, carotid artery disease, and coronary artery disease), renal disease (MPGN and glomerulosclerosis), eye disease (Mooren’s ulcers and sicca syndrome), skin disease (PCT, vasculitis, and lichen planus), lymphomas (NHL and splenic T-cell), and diabetes. Mechanistic understanding of how HCV leads to CHASM processes could lead to development of new interventions. The role of early HCV treatment and cure may result in preventive strategies for a variety of complex disease states. Key Points • Systemic extrahepatic complications of HCV comprise a spectrum of disease states in many organs and systems. • Effective treatment of HCV may reduce or eliminate some but not all of these systemic complications. • Further research into early treatment intervention as a prevention strategy for systemic disease is warranted. © 2015, Springer Science+Business Media New York.

Devarajan P.,University of Cincinnati
Biomarkers in Medicine | Year: 2010

Acute kidney injury (AKI) is a common and serious condition, the diagnosis of which depends on serum creatinine measurements. Unfortunately, creatinine is a delayed and unreliable indicator of AKI. The lack of early biomarkers has crippled our ability to translate promising experimental therapies to human AKI. Fortunately, understanding the early stress response of the kidney to acute injuries has revealed a number of potential biomarkers. The discovery, translation and validation of neutrophil gelatinase-associated lipocalin, arguably the most promising novel AKI biomarker, are reviewed in this article. Neutrophil gelatinase-associated lipocalin is emerging as an excellent standalone troponin-like biomarker in the plasma and urine for the prediction of AKI, monitoring clinical trials in AKI and for the prognosis of AKI in several common clinical scenarios. © 2010 Future Medicine Ltd.

Feng Q.,Hubei University | Algeo T.J.,Hubei University | Algeo T.J.,University of Cincinnati
Earth-Science Reviews | Year: 2014

The ~. 90% biodiversity loss among marine invertebrate species during the end-Permian mass extinction, the most severe Phanerozoic biocrisis, has been attributed to widespread oceanic anoxia ("superanoxia"). Recent studies of the lithofacies, inorganic geochemistry, and biomarkers of Permian-Triassic boundary (PTB) sections have yielded an inferred pattern of oceanic redox changes that is complex and sometimes inconsistent. In this contribution, we review the ecology of radiolarians, an important microzooplankton group during the Permo-Triassic transition, and consider its implications for contemporaneous changes in paleoceanographic conditions. Our analysis shows that (1) Late Permian radiolarian faunas were cosmopolitan with different orders having specific depth preferences, i.e., albaillellarians favoring deeper waters and spherical forms (entactinarians and spumellarians) shallower waters; (2) deep-water taxa declined earlier than shallow-water taxa; (3) many Paleozoic-type taxa survived into the Early Triassic but went extinct during a second crisis in the Dienerian ("dead clade walking"), followed by the appearance or expansion of Mesozoic-type taxa during the Olenekian; and (4) the survival of Paleozoic-type taxa during the Early Triassic was greater at higher paleolatitudes than in the tropics. These observations are consistent with a first-order redox control on radiolarian faunal distributions, specifically a shallowing and poleward expansion of the oceanic oxygen-minimum zone during the PTB crisis. The consequent adaptation of some deepwater taxa to shallower environments resulted in Early Triassic radiolarian faunas in continental basins becoming more similar to those in pelagic settings. Enhanced survival of Paleozoic-type taxa in high-latitude regions indicates that the main stressor on Permo-Triassic radiolarian communities was reduced oceanic oxygen levels (stronger in the tropics) rather than climatic warming (stronger at the poles). © 2014 Elsevier B.V.

Branson R.D.,University of Cincinnati
Respiratory Care | Year: 2013

Postoperative pulmonary complications (PPCs) are common and expensive. Costs, morbidity, and mortality are higher with PPCs than with cardiac or thromboembolic complications. Preventing and treating PPCs is a major focus of respiratory therapists, using a wide variety of techniques and devices, including incentive spirometry, CPAP, positive expiratory pressure, intrapulmonary percussive ventilation, and chest physical therapy. The scientific evidence for these techniques is lacking. CPAP has some evidence of benefit in high risk patients with hypoxemia. Incentive spirometry is used frequently, but the evidence suggests that incentive spirometry alone has no impact on PPC. Chest physical therapy, which includes mechanical clapping and postural drainage, appears to worsen atelectasis secondary to pain and splinting. As with many past respiratory therapy techniques, the profession needs to take a hard look at these techniques and work to provide only practices based on good evidence. The idea of a PPC bundle has merit and should be studied in larger, multicenter trials. Additionally, intraoperative ventilation may play a key role in the development of PPCs and should receive greater attention. © 2013 Daedalus Enterprises.

Roth T.,University of Cincinnati
Sleep medicine reviews | Year: 2014

Pregabalin is approved for the treatment of a variety of clinical conditions and its analgesic, anxiolytic and anticonvulsant properties are well documented. Pregabalin's effects on sleep, however, are less well known. This review summarizes the published data on the effects of pregabalin on sleep disturbance associated with neuropathic pain, fibromyalgia, restless legs syndrome, partial onset seizures and general anxiety disorder. The data demonstrate that pregabalin has a positive benefit on sleep disturbance associated with several different clinical conditions. Polysomnographic data reveal that pregabalin primarily affects sleep maintenance. The evidence indicates that pregabalin has a direct effect on sleep that is distinct from its analgesic, anxiolytic and anticonvulsant effects. Copyright © 2013 Elsevier Ltd. All rights reserved.

Choubey D.,University of Cincinnati | Moudgil K.D.,University of Maryland Baltimore County
Journal of Interferon and Cytokine Research | Year: 2011

Several lines of evidence strongly implicate type I interferons (IFN-α and β) and IFN-signaling in the pathogenesis of certain autoimmune inflammatory diseases. Accordingly, genome-wide association studies have identified polymorphisms in the type I IFN-signaling pathways. Other studies also indicate that a feed-forward loop of type I IFN production, which involves sensing of cytoplasmic nucleic acids by sensors, contributes to the development of immunopathology. In addition, a mutually positive regulatory feedback loop between type I IFNs and estrogen receptor-α may contribute to a gender bias, thus resulting in an increased production of type I IFNs and associated immunopathology in women. Increased levels of type I IFNs have numerous immunomodulatory functions for both the innate and adaptive immune responses. Given that the IFN-β also has some anti-inflammatory roles, identifying molecular links among certain genotypes, cytokine profiles, and associated phenotypes in patients with autoimmune inflammatory diseases is likely to improve our understanding of autoimmunity-associated pathogenesis and suboptimal outcomes following standard therapies. © 2011, Mary Ann Liebert, Inc.

Hershey A.D.,University of Cincinnati
Current Opinion in Neurology | Year: 2010

PURPOSE OF REVIEW: This review will focus on some of the recent findings in pediatric headache including headache characteristics, epidemiology, comorbid associations and treatment updates. RECENT FINDINGS: Pediatric headache remains a frequent health problem for children and their families, yet there remain many gaps in our knowledge. This review will broadly address some of the recent findings and highlight the gaps in our understanding and treatment of pediatric headache. There will be a focus on pediatric migraine as this has been the best characterized and studied. SUMMARY: Our understanding of pediatric headache is improving with increased recognition of the characteristics and associated symptomology. This should further guide the individualized treatment approaches for improved outcome and reduction of progression into adulthood. © 2010 Lippincott Williams & Wilkins.

Moudgil K.D.,University of Maryland Baltimore County | Choubey D.,University of Cincinnati
Journal of Interferon and Cytokine Research | Year: 2011

Cytokines play a pivotal role in the pathogenesis of autoimmune diseases. The precise triggers for the breakdown of self-tolerance and the subsequent events leading to the induction of pathogenic autoimmune responses remain to be defined for most of the naturally occurring autoimmune diseases. Studies conducted in experimental models of human autoimmune diseases and observations in patients have revealed a general scheme in which proinflammatory cytokines contribute to the initiation and propagation of autoimmune inflammation, whereas anti-inflammatory cytokines facilitate the regression of inflammation and recovery from acute phase of the disease. This idea is embodied in the T helper (Th) 1/Th2 paradigm, which over the past two decades has had a major influence on our thinking about the role of cytokines in autoimmunity. Interestingly, over the past decade, the interleukin (IL)-17/IL-23 axis has rapidly emerged as the new paradigm that has compelled us to critically re-examine the cytokine-driven immune events in the pathogenesis and treatment of autoimmunity. In this 2-volume special issue of the journal, leading experts have presented their research findings and viewpoints on the role of cytokines in the context of specific autoimmune diseases. © 2011, Mary Ann Liebert, Inc.

Karsten C.M.,University of Lubeck | Kohl J.,University of Lubeck | Kohl J.,University of Cincinnati
Immunobiology | Year: 2012

Immunoglobulin G (IgG)-mediated activation of complement and IgG Fc receptors (FcγRs) are important defense mechanisms of the innate immune system to ward off infections. However, the same mechanisms can drive severe and harmful inflammation, when IgG antibodies react with self-antigens in solution or tissues, as described for several autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, and immune vasculitis. More specifically, IgG immune complexes (ICs) can activate all three pathways of the complement system resulting in the generation of C3 and C5 cleavage products that can activate a panel of different complement receptors on innate and adaptive immune cells. Importantly, complement and FcγRs are often co-expressed on inflammatory immune cells such as neutrophils, monocytes, macrophages or dendritic cells and act in concert to mediate the inflammatory response in autoimmune diseases. In this context, the cross-talk between the receptor for the anaphylatoxin C5a, i.e. C5ar1 (CD88) and FcγRs is of major importance. Recent data suggest a model of bidirectional regulation, in which CD88 acts upstream of FcγRs and sets the threshold for FcγR-dependent effector responses by regulating the ratio between activating and inhibitory FcγRs. Vice versa, FcγR ligation can either amplify or block C5aR-mediated effector functions, depending on whether IgG IC aggregate activating or inhibitory FcγRs. Further, complement and FcγRs cooperate on B cells and on follicular dendritic cells to regulate the development of autoreactive B cells, their differentiation into plasma cells and, eventually, the production of autoantibodies. Here, we will give an update on recent findings regarding this complex regulatory network between complement and FcγRs, which may also regulate the inflammatory response in allergy, cancer and infection. © 2012 Elsevier GmbH.

Perez-Gil J.,Complutense University of Madrid | Weaver T.E.,University of Cincinnati
Physiology | Year: 2010

Pulmonary surfactant is an essential lipid-protein complex that stabilizes the respiratory units (alveoli) involved in gas exchange. Quantitative or qualitative derangements in surfactant are associated with severe respiratory pathologies. The integrated regulation of surfactant synthesis, secretion, and metabolism is critical for air breathing and, ultimately, survival. The goal of this review is to summarize our current understanding and highlight important knowledge gaps in surfactant homeostatic mechanisms. © 2010 Int. Union Physiol. Sci./Am. Physiol. Soc.

Ehrlich S.,University of Cincinnati
Fertility and Sterility | Year: 2015

Changing demographic trends and projections of the survival and fertility rates of each generation have been a topic of great interest to not only demographers and epidemiologists but also to evolutionary biologists and reproductive endocrinologists. Compelling evolutionary theories suggest that there is an inverse association between fertility and longevity. Multiple historic, demographic, and current studies have since been conducted to test this theory, but the results have been inconclusive. The average number of children born to each woman has been declining progressively in developed countries during recent decades. This is in part due to changes in the behavior of couples but also to environmental factors. While improved accessibility to assisted reproductive technology can relieve some of the burden of infertility on these couples and lessen the problem of low total fertility rates in many developed countries, it is not enough to overcome the overall decrease in total fertility rates that we have witnessed in recent decades. This article critically reviews some important studies and provides an overview of this ongoing debate, while highlighting the relevance of trying to understand the possible mechanisms that may link fertility and infertility to longevity. © 2015 American Society for Reproductive Medicine.

Marano R.J.,Ear science Institute Australia | Marano R.J.,University of Western Australia | Ben-Jonathan N.,University of Cincinnati
Molecular Endocrinology | Year: 2014

Prolactin (PRL) is an important hormone with many diverse functions. Although it is predominantly produced by lactrotrophs of the pituitary there are a number of other organs, cells, and tissues in which PRL is expressed and secreted. The impact of this extrapituitary PRL (ePRL) on localized metabolism and cellular functions is gaining widespread attention. In 1996, a comprehensive review on ePRL was published. However, since this time, there have been a number of advancements in ePRL research. This includes a greater understanding of the components of the control elements located within the superdistal promoter of the ePRL gene. Furthermore, several new sites of ePRL have been discovered, each under unique control by a range of transcription factors and elements. The functional role of ePRL at each of the expression sites also varies widely leading to gender and site bias. This review aims to provide an update to the research conducted on ePRL since the 1996 review. The focus is on new data concerning the sites of ePRL expression, its regulation, and its function within the organs in which it is expressed. © 2014 by the Endocrine Society.

Stein E.A.,University of Cincinnati | Raal F.J.,University of Witwatersrand
Best Practice and Research: Clinical Endocrinology and Metabolism | Year: 2014

Low density lipoprotein cholesterol (LDL-C) is one of the most validated targets in clinical medicine. Large randomized, outcome trials have demonstrated a clear relationship between reducing LDL-C and cardiovascular disease (CVD) risk, which has been maintained to LDL-C levels of <1.8 mmol/L. To assess the benefit of even lower LDL-C it is important to recognize that CVD risk reduction is related to absolute reduction in LDL-C, not to percent change. Furthermore measurement of LDL-C is also critical as recent studies show the Friedewald calculation significantly underestimates true LDL-C values <1.8 mmol/L, distorting the relationship with CVD risk reduction. Discussion of potential harm from low, or lower, LDL-C has centered on cancer, hemorrhagic stroke, and violent death, but there is little evidence from outcome trials to show a relationship with low LDL-C. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors which will reduce LDL-C well below 1.3 mmol/L, will likely provide the clearest answer to both the question of efficacy and safety of low LDL-C within the next few years. © 2013 Elsevier Ltd. All rights reserved.

Garcia-Borron J.C.,University of Murcia | Abdel-Malek Z.,University of Cincinnati | Jimenez-Cervantes C.,University of Murcia
Pigment Cell and Melanoma Research | Year: 2014

The melanocortin 1 receptor (MC1R) is a G protein-coupled receptor crucial for the regulation of melanocyte proliferation and function. Upon binding melanocortins, MC1R activates several signaling cascades, notably the cAMP pathway leading to synthesis of photoprotective eumelanin. Polymorphisms in the MC1R gene are a major source of normal variation of human hair color and skin pigmentation, response to ultraviolet radiation (UVR), and skin cancer susceptibility. The identification of a surprisingly high number of MC1R natural variants strongly associated with pigmentary phenotypes and increased skin cancer risk has prompted research on the functional properties of the wild-type receptor and frequent mutant alleles. We summarize current knowledge on MC1R structural and functional properties, as well as on its intracellular trafficking and signaling. We also review the current knowledge about the function of MC1R as a skin cancer, particularly melanoma, susceptibility gene and how it modulates the response of melanocytes to UVR. © 2014 John Wiley & Sons A/S.

Arasada R.R.,Ohio State University | Amann J.M.,Ohio State University | Rahman M.A.,Ohio State University | Huppert S.S.,University of Cincinnati | Carbone D.P.,Ohio State University
Cancer Research | Year: 2014

Mutations in the epidermal growth factor receptor (EGFR) are the most common actionable genetic abnormalities yet discovered in lung cancer. However, targeting these mutations with kinase inhibitors is not curative in advanced disease and has yet to demonstrate an impact on potentially curable, early-stage disease, with some data suggesting adverse outcomes. Here, we report that treatment of EGFR-mutated lung cancer cell lines with erlotinib, while showing robust cell death, enriches the ALDH+ stem-like cells through EGFR-dependent activation of Notch3. In addition, we demonstrate that erlotinib treatment increases the clonogenicity of lung cancer cells in a sphere-forming assay, suggesting increased stem-like cell potential. We demonstrate that inhibition of EGFR kinase activity leads to activation of Notch transcriptional targets in a γ secretase inhibitor-sensitive manner and causes Notch activation, leading to an increase in ALDH high+ cells. We also find a kinase-dependent physical association between the Notch3 and EGFR receptors and tyrosine phosphorylation of Notch3. This could explain the worsened survival observed in some studies of erlotinib treatment at early-stage disease, and suggests that specific dual targeting might overcome this adverse effect. © 2014 American Association for Cancer Research.

Maslove D.M.,Li Ka Shing Knowledge Institute | Maslove D.M.,University of Toronto | Wong H.R.,Foundation Medicine | Wong H.R.,University of Cincinnati
Trends in Molecular Medicine | Year: 2014

Sepsis is a complex inflammatory response to infection. Microarray-based gene expression studies of sepsis have illuminated the complex pathogen recognition and inflammatory signaling pathways that characterize sepsis. More recently, gene expression profiling has been used to identify diagnostic and prognostic gene signatures, as well as novel therapeutic targets. Studies in pediatric cohorts suggest that transcriptionally distinct subclasses might account for some of the heterogeneity seen in sepsis. Time series analyses have pointed to rapid and dynamic shifts in transcription patterns associated with various phases of sepsis. These findings highlight current challenges in sepsis knowledge translation, including the need to adapt complex and time-consuming whole-genome methods for use in the intensive care unit environment, where rapid diagnosis and treatment are essential. © 2014 Elsevier Ltd.

Baughman R.P.,University of Cincinnati
Panminerva Medica | Year: 2013

The treatment of pulmonary sarcoidosis is based on several factors. These include changes in pulmonary physiology, presence of extra-pulmonary disease, and symptoms. Several immunosuppressive agents have been studied and recommendations regarding the utility of these different agents have evolved. While glucocorticoids remain the most commonly used agent, other drugs have been used as steroid sparing and for those patients who progress despite routine treatment. Non immunosuppressive agents also play a role in the therapy of pulmonary sarcoidosis patients. These include treatments for pulmonary hypertension, infection, and fatigue.

Yamamoto B.K.,University of Toledo | Moszczynska A.,University of Toledo | Gudelsky G.A.,University of Cincinnati
Annals of the New York Academy of Sciences | Year: 2010

The drugs of abuse, methamphetamine and MDMA, produce long-term decreases in markers of biogenic amine neurotransmission. These decreases have been traditionally linked to nerve terminals and are evident in a variety of species, including rodents, nonhuman primates, and humans. Recent studies indicate that the damage produced by these drugs may be more widespread than originally believed. Changes indicative of damage to cell bodies of biogenic and nonbiogenic amine-containing neurons in several brain areas and endothelial cells that make up the blood-brain barrier have been reported. The processes that mediate this damage involve not only oxidative stress but also include excitotoxic mechanisms, neuroinflammation, the ubiquitin proteasome system, as well as mitochondrial and neurotrophic factor dysfunction. These mechanisms also underlie the toxicity associated with chronic stress and human immunodeficiency virus (HIV) infection, both of which have been shown to augment the toxicity to methamphetamine. Overall, multiple mechanisms are involved and interact to promote neurotoxicity to methamphetamine and MDMA. Moreover, the high coincidence of substituted amphetamine abuse by humans with HIV andor chronic stress exposure suggests a potential enhanced vulnerability of these individuals to the neurotoxic actions of the amphetamines. © 2010 New York Academy of Sciences.

Huthwaite P.,Imperial College London | Simonetti F.,University of Cincinnati
Wave Motion | Year: 2013

Quantifying wall thickness in the presence of corrosion damage allows the residual life of plate-like structures to be determined. Guided wave tomography is a solution which allows an area to be imaged with data from an array of ultrasonic transducers around the defect, using tomographic methods to establish wall thickness. We exploit the dispersive nature of Lamb waves travelling through the wall to convert the thickness variation into wave velocity variations, providing a mechanism to determine thickness from a velocity reconstruction. HARBUT (the Hybrid Algorithm for Robust Breast Ultrasound Tomography) has been developed to give high-resolution, accurate and robust reconstructions of ultrasonic velocity through the breast; in this paper we extend the method to generate thickness maps for guided wave tomography. By iterating HARBUT we show that we can improve the accuracy of reconstructions of the small, high contrast defects expected from corrosion, allowing estimates of thicknesses within 1mm for a 10mm plate from both simulated and experimental data. © 2013 Elsevier B.V.

Childress A.,Center for Psychiatry and Behavioral Medicine Inc | Sallee F.R.,University of Cincinnati
Expert Review of Neurotherapeutics | Year: 2013

More than 50 years ago, methylphenidate immediate-release (MPH-IR) was found to be effective in relieving symptoms of attention-deficit/hyperactivity disorder. Although the exact mechanism of the action is unknown, the efficacy of MPH is thought to be mediated by blocking the reuptake of norepinephrine and dopamine into the presynaptic neuron and increasing the release of these neurotransmitters into the extraneuronal space. Because of its short duration of effect, MPH-IR had to be dosed multiple times daily. In recent years, several methyphenidate extended-release (MPH-ER) formulations have been developed. Methylphenidate hydrochloride for extended-release oral suspension (MEROS or QuillivantTM XR) is the first long-acting MPH-ER oral suspension developed to treat attention-deficit/hyperactivity disorder. It offers advantages when compared with other MPH-ER preparations for patients who cannot or prefer not to swallow or manipulate capsules or wear a transdermal patch, while maintaining comparable efficacy and duration of effect. The pharmacokinetic, efficacy and safety profiles of this controlled substance are reviewed. © 2013 Informa UK Ltd.

Grigoryan K.V.,University of Cincinnati | Javedan H.,Brigham and Womens Hospital | Rudolph J.L.,Brigham and Womens Hospital | Rudolph J.L.,Geriatric Research
Journal of Orthopaedic Trauma | Year: 2014

Objectives: Hip fractures are common, morbid, and costly health events that threaten independence and function of older patients. The purpose of this systematic review and meta-analysis was to determine if orthogeriatric collaboration models improve outcomes. Data Sources: Articles in English and Spanish languages were searched in the electronic databases including MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, and the Cochrane Registry from 1992 to 2012. Study Selection: Studies were included if they described an inpatient multidisciplinary approach to hip fracture management involving an orthopaedic surgeon and a geriatrician. Studies were grouped into 3 following categories: routine geriatric consultation, geriatric ward with orthopaedic consultation, and shared care. After independent review of 1480 citations by 2 authors, 18 studies (9094 patients) were identified as meeting the inclusion criteria. Data Extraction: In-hospital mortality, length of stay, and long-term mortality outcomes were collected. Data Synthesis: A random effects model meta-analysis determined whether orthogeriatric collaboration was associated with improved outcomes. The overall meta-analysis found that orthogeriatric collaboration was associated with a significant reduction of in-hospital mortality [relative risk 0.60; 95% confidence interval (95% CI), 0.43-0.84) and long-term mortality (relative risk 0.83; 95% CI, 0.74-0.94). Length of stay (standardized mean difference -0.25; 95% CI, -0.44 to -0.05) was significantly reduced, particularly in the shared care model (standardized mean difference -0.61; 95% CI, -0.95 to -0.28), but heterogeneity limited this interpretation. Other variables such as time to surgery, delirium, and functional status were measured infrequently. Conclusions: This meta-analysis supports orthogeriatric collaboration to improve mortality after hip repair. Further study is needed to determine the best model of orthogeriatric collaboration and if these partnerships improve functional outcomes. Copyright © 2013 by Lippincott Williams & Wilkins.

Roy D.,University of California at San Diego | Roy D.,University of Cincinnati
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2011

We address correlated few-photon transport in one-dimensional waveguides coupled to a two-level system (TLS), such as an atom or a quantum dot. We derive exactly the single-photon and two-photon current (transmission) for linear and nonlinear (tight-binding sinusoidal) energy-momentum dispersion relations of photons in the waveguides and compare the results for the different dispersions. A large enhancement of the two-photon current for the sinusoidal dispersion has been seen at a certain transition energy of the TLS away from the single-photon resonances. © 2011 American Physical Society.

Nielsen J.T.,University of Aarhus | Eghbalnia H.R.,University of Cincinnati | Nielsen N.C.,University of Aarhus
Progress in Nuclear Magnetic Resonance Spectroscopy | Year: 2012

The exquisite sensitivity of chemical shifts as reporters of structural information, and the ability to measure them routinely and accurately, gives great import to formulations that elucidate the structure-chemical-shift relationship. Here we present a new and highly accurate, precise, and robust formulation for the prediction of NMR chemical shifts from protein structures. Our approach, shAIC (shift prediction guided by Akaikes Information Criterion), capitalizes on mathematical ideas and an information-theoretic principle, to represent the functional form of the relationship between structure and chemical shift as a parsimonious sum of smooth analytical potentials which optimally takes into account short-, medium-, and long-range parameters in a nuclei-specific manner to capture potential chemical shift perturbations caused by distant nuclei. shAIC outperforms the state-of-the-art methods that use analytical formulations. Moreover, for structures derived by NMR or structures with novel folds, shAIC delivers better overall results; even when it is compared to sophisticated machine learning approaches. shAIC provides for a computationally lightweight implementation that is unimpeded by molecular size, making it an ideal for use as a force field. © 2011 Elsevier B.V. All rights reserved.

Alemzadeh R.,University of Illinois at Chicago | Kichler J.,University of Cincinnati
Metabolic Syndrome and Related Disorders | Year: 2012

Background: 25-Hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) have been shown to correlate with several markers of metabolic syndrome in adult populations. We evaluated the relationship between circulating intact parathyroid hormone (iPTH) and 25(OH)D and indices of metabolic syndrome in obese adolescents. Methods: Body mass index (BMI), body composition, 25(OH)D, iPTH, fasting lipids, glucose, high-sensitivity C-reactive protein (hsCRP), glycosylated hemoglobin (HbA1c), insulin, and the homeostatic model assessment for insulin resistance (HOMA-IR) were evaluated in 133 obese adolescents. Results: Vitamin D deficiency [25(OH)D <50nmol/L] was present in 45.1% of all patients, with higher prevalence in African-American (AA) and Hispanic (H) than Caucasian (C) subgroups (63.9% and 56.4% vs. 25.9%; P<0.001). iPTH and 25(OH)D were inversely correlated (r=-0.75; P<0.0001), with AA displaying a higher iPTH: 25(OH)D ratio than H and C subgroups (P<0.05). Whereas fat mass (FM) was negatively correlated with 25(OH)D (r=-0.30; p<0.001), it was positively correlated with iPTH levels (r=0.38; P<0.0001). Metabolic syndrome was identified in 57.9% of the cohort with higher iPTH, iPTH:25(OH)D ratio, but lower 25(OH)D than participants without metabolic syndrome (P<0.02). Whereas iPTH showed main effects for hsCRP (β=0.24, t=2.61, P<0.05) and triglycerides:high-density lipoprotein cholesterol (TG:HDL-C) (β=0.21, t=2.13, p<0.05), independent of serum 25(OH)D, it did not reveal a main effect for HOMA-IR. Conclusions: Metabolic syndrome is associated with a higher iPTH:25(OH)D ratio than those without metabolic syndrome, implying greater risk of cardiovascular morbidities among AA subjects than other ethnic groups. Furthermore, the serum iPTH level is a predictor of chronic inflammation and dyslipidemia, independent of 25(OH)D. © Copyright 2012, Mary Ann Liebert, Inc.

Branson R.D.,University of Cincinnati
Respiratory Care | Year: 2012

Weaning comprises 40 percent of the duration of mechanical ventilation. Protocols to reduce weaning time and to identify candidates at the earliest possible moment have been introduced to reduce complications and costs. Increased demand for mechanical ventilation, an increase in the number of patients requiring prolonged ventilation, and resource/staffing issues have created an environment where automated weaning may play a role. A number of closed loop techniques have been introduced since the early 1990s, with increasing sophistication. Preliminary research has demonstrated mixed results. Current systems continue to be evaluated in different patient populations and environments. Automated weaning is part of the ICU armamentarium, and identification of the patient populations most likely to benefit needs to be further defined. © 2012 Daedalus Enterprises.

Li H.,University of Cincinnati
Oncogene | Year: 2015

Neurofibromatosis type 1 (NF1) patients are predisposed to neurofibromas but the driver(s) that contribute to neurofibroma formation are not fully understood. By cross comparison of microarray gene lists on human neurofibroma-initiating cells and developed neurofibroma Schwann cells (SCs) we identified RUNX1 overexpression in human neurofibroma initiation cells, suggesting RUNX1 might relate to neurofibroma formation. Immunostaining confirmed RUNX1 protein overexpression in human plexiform neurofibromas. Runx1 overexpression was confirmed in mouse Schwann cell progenitors (SCPs) and mouse neurofibromas at the messenger RNA and protein levels. Genetic inhibition of Runx1 expression by small hairpin RNA or pharmacological inhibition of Runx1 function by a Runx1/Cbfβ interaction inhibitor, Ro5-3335, decreased mouse neurofibroma sphere number in vitro. Targeted genetic deletion of Runx1 in SCs and SCPs delayed mouse neurofibroma formation in vivo. Mechanistically, loss of Nf1 increased embryonic day 12.5 Runx1+/Blbp+ progenitors that enable tumor formation. These results suggest that Runx1 has an important role in Nf1 neurofibroma initiation, and inhibition of RUNX1 function might provide a novel potential therapeutic treatment strategy for neurofibroma patients.Oncogene advance online publication, 15 June 2015; doi:10.1038/onc.2015.207. © 2015 Macmillan Publishers Limited

Nelson E.B.,University of Cincinnati
Current Psychiatry Reports | Year: 2012

Psychotic depression is an identified subtype of major depression that has many features of a distinct psychiatric disorder. Recent studies support previous findings that psychotic depression is associated with a less favorable course of illness. Moreover, the presence of a single psychotic symptom appears to predict decreased responsiveness to antidepressant monotherapy. Recent studies also support biological differences between psychotic and non-psychotic depression. Previous findings of greater HPA axis dysregulation are supported by evidence of diminished cortisol suppression with the mineralocorticoid antagonist fludrocortisone in psychotic depression. Moreover, a functional neuroimaging study demonstrated greater activation in parahippocampal and tempoparietal regions in psychotic depression during a memory task. In support of several previous treatment studies, a recent metaanalysis of studies that compared an antidepressantantipsychotic combination to antidepressants or antipsychotics alone found a therapeutic advantage with the combined treatment over monotherapy. A recent clinical trial suggests that mifepristone, a glucocorticoid antagonist, may be an effective adjunctive treatment for psychotic depression. © Springer Science+Business Media, LLC 2012.

Embi P.J.,Ohio State University | Leonard A.C.,University of Cincinnati
Journal of the American Medical Informatics Association | Year: 2012

Objective: Inadequate participant recruitment is a major problem facing clinical research. Recent studies have demonstrated that electronic health record (EHR)-based, point-of-care, clinical trial alerts (CTA) can improve participant recruitment to certain clinical research studies. Despite their promise, much remains to be learned about the use of CTAs. Our objective was to study whether repeated exposure to such alerts leads to declining user responsiveness and to characterize its extent if present to better inform future CTA deployments. Methods: During a 36-week study period, we systematically documented the response patterns of 178 physician users randomized to receive CTAs for an ongoing clinical trial. Data were collected on: (1) response rates to the CTA; and (2) referral rates per physician, per time unit. Variables of interest were offset by the log of the total number of alerts received by that physician during that time period, in a Poisson regression. Results: Response rates demonstrated a significant downward trend across time, with response rates decreasing by 2.7% for each advancing time period, significantly different from zero (flat) (p<0.0001). Even after 36 weeks, response rates remained in the 30%-40% range. Subgroup analyses revealed differences between community-based versus university-based physicians (p=0.0489). Discussion: CTA responsiveness declined gradually over prolonged exposure, although it remained reasonably high even after 36 weeks of exposure. There were also notable differences between community-based versus university-based users. Conclusions: These findings add to the limited literature on this form of EHR-based alert fatigue and should help inform future tailoring, deployment, and further study of CTAs.

Diab D.L.,University of Cincinnati | Watts N.B.,United Road Services
Endocrinology and Metabolism Clinics of North America | Year: 2013

Osteoporosis in the elderly is a serious problem that is increasing as the population ages. Diagnosis is established by measurement of bone mineral density or by the presence of a fragility fracture, especially a spine or hip fracture. Bone-active agents should be prescribed for older patients with osteoporosis to decrease fracture risk. Nonskeletal risk factors for fracture and psychosocial impairment must be identified and managed, and therapy must be individualized. © 2013 Elsevier Inc.

Pan B.S.,University of Cincinnati
Plastic and reconstructive surgery | Year: 2014

Conventional palatoplasty relies on extensive mucosal incisions and isolation of flaps on the palatine vessels to facilitate midline closure and velar reconstruction. This introduces substantial scarring, which has adverse effects on vascularity and growth. The authors have developed a minimally invasive palatoplasty technique that may have advantages over traditional techniques. The authors present their operative experience and outcomes when using the minimally invasive method paired with a novel cranial base maneuver for nasal mucosa closure. Based on cadaveric dissections, the authors developed a modified minimal-incision approach that permits anatomical reconstruction from a midline approach. From 2003 to 2010, a retrospective review was performed on 67 consecutive minimal-incision palatoplasties. Cases requiring relaxing incision and/or conversion to other palatoplasty techniques were compared with minimal incision alone. Minimally invasive palatoplasty alone was able to be performed in 78 percent (n=52) of all cases. Fistula rates were 7.6 percent (n=4) in the minimally invasive palatoplasty group and 20 percent (n=3) in the relaxing/conversion group (p=0.04). Of patients requiring relaxing incisions/conversion, a higher percentage were syndromic (73 percent; p=0.01). Eighty-nine percent of all Veau class I defects were able to be successfully closed with the minimally invasive palatoplasty approach (p=0.01). Minimal-incision palatoplasty paired with a cranial base maneuver for nasal mucosa elevation results in adequate soft-tissue mobility and length to arrive at a tension-free closure. Fistula and velopharyngeal insufficiency rates are comparable to that of other techniques, and theoretical advantages of this technique will be borne out by longer term follow-up. Therapeutic, III.

Denoyelles A.,University of Central Florida | Kyeong-Ju Seo K.,University of Cincinnati
Computers and Education | Year: 2012

A 3D multi-user virtual environment holds promise to support and enhance student online learning communities due to its ability to promote global synchronous interaction and collaboration, rich multisensory experience and expression, and elaborate design capabilities. Second Life®, a multi-user virtual environment intended for adult users 18 and older, is the most cited in educational literature, so it is important to explore how college-aged students are using it to form online learning communities. Previous research suggests that there is unbalanced participation between traditional college-aged men and women with regards to 3D multi-user video games, which closely resemble Second Life®. In this research study, we investigated in what manner women and men college students projected their virtual identities and engaged in interaction in Second Life®, and how this influenced their learning of course content. Analysis of multiple data sources revealed that conceptions of identity, beliefs of the nature of the virtual world, and technical skill were primary factors which affected group cohesion and learning within the community. Results from this study can provide insight into the class activities that can support all learners in accessing and contributing to the multi-user virtual environment learning community. © 2011 Elsevier Ltd. All rights reserved.

Privitera M.,University of Cincinnati
The American journal of managed care | Year: 2011

A series of conceptual reconsiderations and therapeutic advances in recent years has resulted in meaningful changes in the classification, diagnosis, and treatment of epilepsy. The first step in evaluation of the person with epilepsy is determining whether the seizures are partial or generalized in onset; this determination will guide further evaluation and is mandatory in choosing an antiepileptic drug (AED). With 12 new AEDs and 1 device approved for use in epilepsy by the US Food and Drug Administration since 1993, the choice of AED has become more complex and it is impossible to predict whether a patient will respond favorably to a drug based on clinical features or clinical laboratory results. AEDs have many different mechanisms of action, but there does not seem to be a strong base of evidence to demonstrate that AED choice should be based on mechanism of action. Yet, a new secondary analysis of data from clinical trials of the new AED lacosamide suggests that combining this AED with another AED that has minimal or no activity at the sodium channel may lead to better tolerability and efficacy. The new AEDs have been tested in randomized controlled trials and compared with placebo; however, there are few head-to-head trials assessing the efficacy of various AEDs, and none of them provide evidence of a clear first choice drug or first add-on drug. Adverse effect profiles of the new generation of AEDs generally show better overall tolerability, but the choice of AED must be individualized (often based on comorbidities) because the adverse effect profiles of the newer AEDs differ widely. One area where the new AEDs consistently outperform the older AEDs is pharmacokinetic profile. Three new AEDs have no hepatic metabolism or protein binding, and others have minimal drug-drug interactions. Ultimately, selection of an appropriate agent involves matching a patient to a medication, or combination of medications, with the best record of efficacy while avoiding issues of tolerability and unwanted drug interactions (specifically tied to the needs of a given patient). Despite major advances in AED development, approximately one-third of people with epilepsy will have incomplete control of seizures no matter which AED is used alone or in combination, emphasizing the need for more effective AEDs. Patients with medication-resistant epilepsy may be candidates for epilepsy surgery, a highly effective treatment that is underutilized in this population.

Turanovic J.J.,Arizona State University | Reisig M.D.,Arizona State University | Pratt T.C.,University of Cincinnati
Journal of Quantitative Criminology | Year: 2015

Objectives: The present study addresses whether unique or general processes lead to victimization across gendered pathways to crime. Specifically, the effects of low self-control and risky lifestyles—specified as various forms of offending and substance abuse—on violent victimization across developmental typologies for both men and women are examined. Methods: Using data from three waves of the National Longitudinal Study of Adolescent Health, a two-stage cluster analysis is used to identify taxonomic groups for males and females that represent different pathways to crime. Multivariate negative binomial regression models are estimated to assess whether both self-control and risky lifestyles (e.g., criminal offending) are significant predictors of general forms of violent victimization across each identified cluster. Results: Low self-control and risky lifestyles significantly predict violent victimization across each of the taxonomic groups identified in the data, suggesting that these causal processes are universal rather than unique to any particular gendered pathway. Conclusions: Although inferences cannot be made for types of victimization beyond those observed in the study (e.g., intimate partner violence and sexual assault), the findings lend credence to the notion that self-control and risky lifestyles are critical to the study of violent victimization among men and women following different gendered pathways. © 2014, Springer Science+Business Media New York.

Maurizi M.R.,U.S. National Cancer Institute | Stan G.,University of Cincinnati
Cell | Year: 2013

Protein degradation by the ClpXP protease requires collaboration among the six AAA+ domains of ClpX. Using single-molecule optical tweezers, Sen et al. show that ClpX uses a coordinated succession of power strokes to translocate polypeptides in ATP-tunable bursts before reloading with nucleotide. This strategy allows ClpX to kinetically capture transiently unfolded intermediates. © 2013 Elsevier Inc.

Clancy J.P.,University of Cincinnati | Jain M.,Northwestern University
American Journal of Respiratory and Critical Care Medicine | Year: 2012

Life expectancy in cystic fibrosis (CF) has improved substantially over the last 75 years, with a median predicted survival now approaching 40 years. This improvement has resulted largely from therapies treating end-organ manifestations. In an effort to develop drugs that would target the underlying defects in the CF transmembrane conductance regulator (CFTR), the Cystic Fibrosis Foundation embarkedon a bold initiative in which it established collaborations with biopharmaceutical companies to support early-stage efforts to discover new medicines for CF. This has led to the development and clinical trial testing of several novel drugs targeting specific CFTR mutations. One drug, ivacaftor, was recently approved by the US Food and Drug Administration for the approximately4%of patients with CF who have the G551D gating mutation. Drugs targeting F508del CFTR and premature termination codons, which would be applicable to 90% of patients with CF, are undergoing clinical trials. The impact of such drugson CFTR biomarkers, such as sweat chloride and nasal potential difference, suggests that they may reset the clinical trajectory of CF, but their effect on long-term outcomes will remain unknown formany years.Nevertheless, development of CFTR-targeted drugs represents an important milestone in CF, perhaps revolutionizing the care of these patients in a fundamental way. Copyright © 2012 by the American Thoracic Society.

Henske E.P.,Harvard University | McCormack F.X.,University of Cincinnati
Journal of Clinical Investigation | Year: 2012

Lymphangioleiomyomatosis (LAM) is a rare progressive lung disease of women. LAM is caused by mutations in the tuberous sclerosis genes, resulting in activation of the mTOR complex 1 signaling network. Over the past 11 years, there has been remarkable progress in the understanding of LAM and rapid translation of this knowledge to an effective therapy. LAM pathogenic mechanisms mirror those of many forms of human cancer, including mutation, metabolic reprogramming, inappropriate growth and survival, metastasis via blood and lymphatic circulation, infiltration/invasion, sex steroid sensitivity, and local and remote tissue destruction. However, the smooth muscle cell that metastasizes, infiltrates, and destroys the lung in LAM arises from an unknown source and has an innocent histological appearance, with little evidence of proliferation. Thus, LAM is as an elegant, monogenic model of neoplasia, defying categorization as either benign or malignant.

Jasiewicz J.,Adam Mickiewicz University | Stepinski T.F.,University of Cincinnati
IEEE Geoscience and Remote Sensing Letters | Year: 2013

Query-by-image-content (QBIC) tools are in demand in geospatial community because they enable exploration and mining of the rapidly increasing database of remotely sensed images. Accompanying the growth of the imagery database is the increase in the number of image-derived products, such as high-resolution large-spatial-extent maps of land cover/land use (LCLU). QBIC-like tools for exploration and mining of such products would significantly enhance their value. In this letter, we present a method for retrieval of alike scenes from a category-valued geospatial database of which an LCLU map is a particular example. Alikeness between the two scenes is tantamount to similarity between their spatial patterns of class labels. Our method works on the principle of query by example, its input is a reference scene, and its output is a similarity map indicating a degree of alikeness between a location on the map and the reference. The two core components of the method are as follows: scene signature - an encapsulation of the scene pattern by means of probability distribution of class labels and the sizes of the patches that they form, and scene similarity-a mutual-information-based function that assigns a level of similarity between any two scenes based on their signatures. The method is described in detail and applied to the National Land Cover Dataset 2006. Two examples of queries on this data set are presented and discussed. The applicability of the method to other data sets is discussed. © 2012 IEEE.

D'alessio D.,University of Cincinnati
Diabetes, Obesity and Metabolism | Year: 2011

Excessive production of glucose by the liver contributes to fasting and postprandial hyperglycaemia, hallmarks of type 2 diabetes. A central feature of this pathologic response is insufficient hepatic insulin action, due to a combination of insulin resistance and impaired β-cell function. However, a case can be made that glucagon also plays a role in dysregulated hepatic glucose production and abnormal glucose homeostasis. Plasma glucagon concentrations are inappropriately elevated in diabetic individuals, and α-cell suppression by hyperglycaemia is blunted. Experimental evidence suggests that this contributes to greater rates of hepatic glucose production in the fasting state and attenuated reduction after meals. Recent studies in animal models indicate that reduction of glucagon action can have profound effects to mitigate hyperglycaemia even in the face of severe hypoinsulinaemia. While there are no specific treatments for diabetic patients yet available that act specifically on the glucagon signalling pathway, newer agents including glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors reduce plasma glucagon and this is thought to contribute to their action to lower blood glucose. The α-cell and glucagon receptor remain tempting targets for novel diabetes treatments, but it is important to understand the magnitude of benefit new strategies would provide as preclinical models suggest that chronic interference with glucagon action could entail adverse effects as well. © 2011 Blackwell Publishing Ltd.

Bolhuis J.J.,University Utrecht | Brown G.R.,University of St. Andrews | Richardson R.C.,University of Cincinnati | Laland K.N.,University of St. Andrews
PLoS Biology | Year: 2011

Evolutionary Psychology (EP) views the human mind as organized into many modules, each underpinned by psychological adaptations designed to solve problems faced by our Pleistocene ancestors. We argue that the key tenets of the established EP paradigm require modification in the light of recent findings from a number of disciplines, including human genetics, evolutionary biology, cognitive neuroscience, developmental psychology, and paleoecology. For instance, many human genes have been subject to recent selective sweeps; humans play an active, constructive role in co-directing their own development and evolution; and experimental evidence often favours a general process, rather than a modular account, of cognition. A redefined EP could use the theoretical insights of modern evolutionary biology as a rich source of hypotheses concerning the human mind, and could exploit novel methods from a variety of adjacent research fields. © 2011 Bolhuis et al.

Shaw J.L.V.,Queens Medical Research Institute | Dey S.K.,University of Cincinnati | Critchley H.O.D.,Queens Medical Research Institute | Horne A.W.,Queens Medical Research Institute
Human Reproduction Update | Year: 2010

Background: An ectopic pregnancy is a pregnancy which occurs outside of the uterine cavity, and over 98% implant in the Fallopian tube. Tubal ectopic pregnancy remains the most common cause of maternal mortality in the first trimester of pregnancy. The epidemiological risk factors for tubal ectopic pregnancy are well established and include: tubal damage as a result of surgery or infection (particularly Chlamydia trachomatis), smoking and in vitro fertilization. This review appraises the data to date researching the aetiology of tubal ectopic pregnancy. methods: Scientific literature was searched for studies investigating the underlying aetiology of tubal ectopic pregnancy. results: Existing data addressing the underlying cause of tubal ectopic pregnancy are mostly descriptive. There are currently few good animal models of tubal ectopic pregnancy. There are limited data explaining the link between risk factors and tubal implantation. conclusions: Current evidence supports the hypothesis that tubal ectopic pregnancy is caused by a combination of retention of the embryo within the Fallopian tube due to impaired embryo-tubal transport and alterations in the tubal environment allowing early implantation to occur. Future studies are needed that address the functional consequences of infection and smoking on Fallopian tube physiology. A greater understanding of the aetiology of tubal ectopic pregnancy is critical for the development of improved preventative measures, the advancement of diagnostic screening methods and the development of novel treatments. © The Author 2010. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.

Goldstein S.L.,University of Cincinnati
Nephron - Clinical Practice | Year: 2014

While the field of acute kidney injury (AKI) research has undergone exponential growth over the past 15 years, the topic of renal recovery has only recently garnered much attention. Both lack of standardized renal recovery definitions and lack of systematic assessment of AKI survivors for chronic kidney disease development pose barriers to the complete understanding of the renal recovery epidemiology. In addition, evaluation of pediatric AKI renal recovery is further complicated by the potential AKI effects on renal development as well as a relatively greater renal reserve for younger children. The aims of this review are to review the current state of knowledge in pediatric AKI renal recovery. © 2014 S. Karger AG, Basel.

Liu Y.J.,University of Cincinnati
Engineering Analysis with Boundary Elements | Year: 2010

A new boundary meshfree method, to be called the boundary distributed source (BDS) method, is presented in this paper that is truly meshfree and easy to implement. The method is based on the same concept in the well-known method of fundamental solutions (MFS). However, in the BDS method the source points and collocation points coincide and both are placed on the boundary of the problem domain directly, unlike the traditional MFS that requires a fictitious boundary for placing the source points. To remove the singularities of the fundamental solutions, the concentrated point sources can be replaced by distributed sources over areas (for 2D problems) or volumes (for 3D problems) covering the source points. For Dirichlet boundary conditions, all the coefficients (either diagonal or off-diagonal) in the systems of equations can be determined analytically, leading to very simple implementation for this method. Methods to determine the diagonal coefficients for Neumann boundary conditions are discussed. Examples for 2D potential problems are presented to demonstrate the feasibility and accuracy of this new meshfree boundary-node method. © 2010 ElsevierLtd. All rights reserved.

Ayres N.,University of Cincinnati
Polymer Reviews | Year: 2011

Atom transfer radical polymerization (ATRP) has become an established synthetic methodology to prepare polymers of high molecular weights with narrow molecular weight distributions and living polymerization characteristics. This review is a conceptual overview of ATRP and the components of an ATRP system. Current approaches to reduce the transition metal concentration are then described including activators regenerated by electron transfer (ARGET) ATRP. Finally, a recent polymerization approach, single electron transfer living radical polymerization (SET-LRP), is described. © Taylor & Francis Group, LLC.

Langevin S.M.,University of Cincinnati | Kratzke R.A.,University of Minnesota | Kelsey K.T.,Brown University
Translational Research | Year: 2015

Lung cancer is the leading cause of cancer-related mortality in the United States. Epigenetic alterations, including DNA methylation, histone modifications, and noncoding RNA expression, have been reported widely in the literature to play a major role in the genesis of lung cancer. The goal of this review is to summarize the common epigenetic changes associated with lung cancer to give some clarity to its etiology, and to provide an overview of the potential translational applications of these changes, including applications for early detection, diagnosis, prognostication, and therapeutics. © 2015 Elsevier Inc.

Dasgupta R.,University of Cincinnati | Fishman S.J.,Harvard University
Seminars in Pediatric Surgery | Year: 2014

Mulliken and Glowacki, in 1982 created a classification system of vascular anomalies which divided vascular anomalies into tumors and malformations which provided the framework for great advances in the management of these patients. This classification system was recently expanded at the 2014 ISSVA workshop in Melbourne. This revision again provides much greater detail including newly named anomalies and identified genes to account for recent advances in knowledge and clinical associations. © 2014.

In A QUAL ITATIVE META-ANALYS I S , the researchers systematically reviewed qualitative and quantitative meta-analyses on reading research with PK-12 students published after the 2000 National Reading Panel (NRP) report. Eleven qualitative and 39 quantitative meta-analyses were reviewed examining reading research with typically developing hearing students, special education hearing students (including English Language Learners), and d/Deaf or hard of hearing (d/Dhh) students. Generally, the meta-analysis yielded findings similar to and corroborative of the NRP’s. Contradictory results (e.g., regarding the role of rhyme awareness in reading outcomes) most often resulted from differing definitions of interventions and their measurements. The analysis provided evidence of several instructional approaches that support reading development. On the basis of the qualitative similarity hypothesis (Paul, 2010, 2012; Paul & Lee, 2010; Paul & Wang, 2012; Paul, Wang, & Williams, 2013), the researchers argue that these instructional strategies also should effectively support d/Dhh children’s reading development. © 2014 Gallaudet University Press. All rights reserved.

Sherman K.E.,University of Cincinnati
Annals of the New York Academy of Sciences | Year: 2010

The hepatitis C virus (HCV) is a global public health problem, with chronic infection leading to development of cirrhosis, end-stage liver disease and hepatocellular carcinoma (HCC). Treatment of HCV is suboptimal with overall response rates of slightly greater than 50% when patients are treated with pegylated interferon alfa and ribavirin. Thymosin alpha 1 (Tα1; TA-1) is an immunomodulatory peptide with intrinsic activities that might improve treatment outcomes for HCV by incorporation of this agent in current treatment paradigms. An extensive body of literature supports a possible role for this agent in difficult to treat populations. However, clinical trials to date have failed to conclusively support the role of TA-1 in combination interferon-based therapies. Therefore, the promise of TA-1 adjunctive therapy for HCV remains, but the proof will require investment in large randomized clinical trials of appropriate patient populations. © 2010 New York Academy of Sciences.

Jandacek R.J.,University of Cincinnati
Physiology and Behavior | Year: 2012

The non-absorbable substitute for dietary triacylglycerol, olestra, has been marketed in the United States for fifteen years. Olestra is comprised of sucrose with six to eight of its hydroxyl groups forming ester links with long-chain fatty acids. Because olestra is not hydrolyzed by fat-splitting enzymes in the small intestine, it is not absorbed from the small intestine into blood and tissues, and therefore provides no energy that can be utilized by the body. The hedonic properties of olestra with a specific fatty acid composition are similar to those of a triacylglycerol with the same fatty acid composition. Its use by consumers has been restricted by federal regulation to the commercial preparation of savory snack food items, principally as a frying medium for potato chips. An important question about the substitution of olestra for absorbable fat in the diet is whether the consumer will sense that a smaller amount of energy has been ingested. If it is sensed, thereby providing no satiation, then consuming additional energy in later meals will compensate for the removal of absorbable energy from the diet. If it is not sensed at all, then there is no compensation, and the person reduces caloric intake. This review first summarizes studies with olestra that have focused on its effect on the physiology of appetite. In general these studies have demonstrated that olestra does not influence signals of satiation including cholecystokinin and stomach emptying. The review then discusses studies of food consumption in experimental animals in which olestra was substituted for fat in the diet. Rodents have been repeatedly observed to compensate completely for the substitution of olestra for normal fat by eating more total diet. Most studies of the effect of olestra on human satiation have found incomplete or no compensation through additional energy consumption when olestra was substituted for dietary fat. In two clinical studies, however, complete compensation was observed, suggesting that experimental conditions and individual variability influence the ability to sense the substitution of olestra for absorbable fat. There is no evidence that dietary olestra causes consumption of more energy than would have been consumed without olestra in the diet. The data from animals and humans strongly suggest that the rodent is not a satisfactory model for the human in the determination of the extent of compensation by substitution of olestra for dietary fat. © 2011 Elsevier Inc.

Bochner B.S.,Northwestern University | Zimmermann N.,Childrens Hospital Medical Center | Zimmermann N.,University of Cincinnati
Journal of Allergy and Clinical Immunology | Year: 2015

Virtually all cells and extracellular material are heavily decorated by various glycans, yet our understanding of the structure and function of these moieties lags behind the understanding of nucleic acids, lipids, and proteins. Recent years have seen a tremendous acceleration of knowledge in the field of glycobiology, revealing many intricacies and functional contributions that were previously poorly appreciated or even unrecognized. This review highlights several topics relevant to glycoimmunology in which mammalian and pathogen-derived glycans displayed on glycoproteins and other scaffolds are recognized by specific glycan-binding proteins (GBPs), leading to a variety of proinflammatory and anti-inflammatory cellular responses. The focus for this review is mainly on 2 families of GBPs, sialic acid-binding immunoglobulin-like lectins (siglecs) and selectins, that are involved in multiple steps of the immune response, including distinguishing pathogens from self, cell trafficking to sites of inflammation, fine-tuning of immune responses leading to activation or tolerance, and regulation of cell survival. Importantly for the clinician, accelerated rates of discovery in the field of glycoimmunology are being translated into innovative medical approaches that harness the interaction of glycans and GBPs to the benefit of the host and might soon lead to novel diagnostics and therapeutics. © 2014 American Academy of Allergy, Asthma & Immunology.

Woods S.C.,University of Cincinnati
Physiology and Behavior | Year: 2013

While a graduate student in the late 1960s I trained rats to lower their blood glucose in response to an arbitrary cue, a phenomenon called conditioned hypoglycemia. Over many years as my colleagues and I attempted to understand the underlying physiology of conditioned insulin secretion and conditioned hypoglycemia, it became clear that there were many implications that were highly important, including the entry of insulin into the brain, the existence of insulin receptors in certain brain areas, neural reflexes that project to insulin-secreting B-cells in the pancreas, the entrainment of those reflexes to improve the efficiency of meal-taking, and the possibility of adiposity signals from the body to the brain that influence behavior and metabolism. This article summarizes how we tackled each of these areas of research. © 2013.

Epplen K.T.,University of Cincinnati
American Journal of Health-System Pharmacy | Year: 2014

Purpose. This article discusses how to plan and implement an ambulatory care pharmacist service, how to integrate a hospital- or health-systembased service with the mission and operations of the institution, and how to help the institution meet its challenges related to quality improvement, continuity of care, and financial sustainability. CopyrightSummary. The steps in implementing an ambulatory care pharmacist service include (1) conducting a needs assessment, (2) aligning plans for the service with the mission and goals of the parent institution, (3) collaborating with patients and physicians, (4) standardizing the patient care process, (5) proposing the service, (6) attaining the necessary resources, (7) identifying stakeholders, (8) identifying applicable quality standards, (9) defining competency standards, (10) planning for service payment, and (11) monitoring outcomes. Ambulatory care pharmacists have current opportunities to become engaged with patient-centered medical homes, accountable care organizations, preventive and wellness programs, and continuity of care initiatives. Common barriers to the advancement of ambulatory care pharmacist services include lack of complete access to patient information, inadequate information technology, and lack of payment.Conclusion. Ambulatory care pharmacy practitioners must assertively promote appropriate medication use, provide patient-centered care, pursue integration with the patient care team, and seek appropriate recognition and compensation for the services they provide. © 2014, American Society of Health-System Pharmacists, Inc. All rights reserved.

Baccei M.L.,University of Cincinnati
Neuroscientist | Year: 2014

Spontaneous activity is known to be essential for the proper formation of sensory networks in the developing CNS. This activity can be produced by a variety of mechanisms including the presence of "pacemaker" neurons, which can be defined by their intrinsic ability to generate rhythmic bursts of action potential discharge. Recent work has identified pacemaker activity within lamina I of the neonatal rodent spinal cord that emerges from a complex interaction between voltage-dependent and voltage-independent ("leak") ionic conductances, including an important modulatory role for the inward-rectifying K+ (Kir) channels. The available evidence suggests that lamina I pacemakers are glutamatergic and project extensively throughout the dorsal-ventral axis of the spinal cord, although the identity of their postsynaptic targets has yet to be elucidated. A better understanding of this connectivity could yield valuable insight into the role of the lamina I pacemaker population in the maturation of spinal circuitry underlying nociceptive processing and/or sensorimotor integration. © The Author(s) 2014.

Wallace G.,University of Cincinnati
Topics in Stroke Rehabilitation | Year: 2010

This study sought to obtain authentic information about life participation after stroke and aphasia. An interview was conducted with 40 individuals from diverse backgrounds and living in 2 geographic locations who had aphasia of at least 9 months. Participants were interviewed using the Profile of Functional Activities and Life Participation (PFALP), a semistructured, conversational approach to obtain self-reported information about a person's life participation profile. Life participation profiles were unique for each participant. Overall, participants reported having difficulty with many activities for which they judged themselves to be moderately impaired and for which they reported low performance satisfaction. Interview data provided information about participation restrictions related to communication and other areas. Results highlight the need for personally relevant follow-up assessment of life participation among people with chronic aphasia to identify and guide viable interventions that extend beyond the traditional scope of care. © 2010 Thomas Land Publishers, Inc.

Gupta S.K.,Indiana University | Vitanza J.M.,Meritage Pharma | Collins M.H.,University of Cincinnati
Clinical Gastroenterology and Hepatology | Year: 2015

Background & Aims: No treatment has been approved by the U.S. Food and Drug Administration for eosinophilic esophagitis (EoE). We investigated the efficacy and safety of a new formulation of oral budesonide suspension (OBS), a corticosteroid, in a prospective, placebo-controlled, dose-ranging study. Methods: Subjects 2-18 years old with symptoms of EoE and peak eosinophil counts ≥20/high-power field at ≥2 levels of the esophagus were randomly assigned to groups given placebo or low-dose, medium-dose, or high-dose OBS for 12 weeks. Doses and volumes were adjusted on the basis of patients' age to cover the entire esophagus. The primary efficacy end point was compound response to therapy (peak eosinophil counts ≤6/high-power field at all levels of the esophagus and ≥50% reduction in EoE symptom score). Multiple safety parameters were evaluated. Results: Data from 71 subjects who completed all efficacy assessments were included in the primary efficacy analysis. At the end of 12 weeks, there were significantly greater percentages of responders in groups given medium-dose OBS (52.6%, P = .0092) and high-dose OBS (47.1%, P= .0174) than in the group given placebo (5.6%); there was no significant difference in percentages of responders between the low-dose OBS (11.8%) and placebo groups (P= .5282). The significant compound responses noted in the medium-dose and high-dose OBS groups were accounted for by the significant histologic responses; in contrast, all 4 groups (including the placebo group) had large symptom responses, and there was no significant difference in the percentage of subjects with a symptom response in either OBS group compared with the placebo group (P ≥ .1235). There were no unexpected safety concerns or signals. Conclusions: Peak eosinophil counts were significantly reduced throughout the esophagus in pediatric patients with EoE who were given medium-dose and high-dose OBS. There was a large symptom response to placebo that was similar to symptom responses in the OBS groups; symptom response did not distinguish OBS from placebo. ClinicalTrials.gov number, NCT00762073. © 2015 AGA Institute.

Espay A.J.,University of Cincinnati
CONTINUUM Lifelong Learning in Neurology | Year: 2013

PURPOSE OF REVIEW: Myoclonus remains a challenging movement phenotype to characterize, evaluate, and treat. A systematic assessment of the temporal sequence, phenomenology, and distribution of movements can assist in the rational approach to diagnosis and management. RECENT FINDINGS: Cortical forms of myoclonus are increasingly recognized as primarily cerebellar disorders. A syndrome of orthostatic myoclonus has been recognized by electrophysiology in patients with neurodegenerative disorders, mainly in Alzheimer disease, accounting for impairments in gait and balance previously mischaracterized as normal pressure hydrocephalus or orthostatic tremor. Tyrosine hydroxylase deficiency and Silver-Russell syndrome (uniparental disomy of chromosome 7) have been established as two novel causes of the myoclonus-dystonia syndrome. Mutations in the glycine receptor (GlyR) α1-subunit gene (GLRA1) explain the major expression of hyperekplexia, an inherited excessive startle disorder, butnewly identified mutations in GlyR β-subunit (GLRB) and glycine transporter 2 (GlyT2) genes (SLC6A5) account for "minor" forms of this disorder manifested as excessive startle and hypnic jerks. The entity previously known as palatal myoclonus has been reclassified as palatal tremor in recognition of its clinical and electromyographic features and no longer enters the differential diagnosis of myoclonic disorders. Increasing documentation of psychogenic features in patients previously characterized as having propriospinal myoclonus has cast doubts on the existence of this distinctive disorder. SUMMARY: Myoclonus can be a prominent manifestation of a wide range of disorders. Electrophysiologic testing aids in distinguishing myoclonus from other mimics and classifying them according to cortical, subcortical, or spinal origin, which assists the choice of treatment. Despite the lack of randomized clinical trials, levetiracetam appears most effective in patients with cortical myoclonus, whereas clonazepam remains the only first-line therapeutic option in subcortical and spinal myoclonus. Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

Riella M.C.,Catholic University of Parana | Roy-Chaudhury P.,University of Cincinnati
Nature Reviews Nephrology | Year: 2013

Despite all the progress achieved since Scribner first introduced the arteriovenous (AV) shunt in 1960 and Cimino and Brescia introduced the native AV fistula in 1962, we have continued to face a conundrum in vascular access for dialysis, in that dialysis vascular access is at the same time both the 'lifeline' and the 'Achilles' heel' of haemodialysis. Indeed, findings from a multitude of published articles in this area, unfortunately mainly observational studies, reflect both our frustration and our limited knowledge in this area. Despite improved understanding of the pathophysiology of stenosis and thrombosis of the vascular access, we have unfortunately not been very successful in translating these advances into either improved therapies or a superior process of care. As a result, we continue to face an epidemic of arteriovenous fistula (AVF) maturation failure, a proliferation of relatively ineffective interventions such as angioplasty and stent placement, an extremely high incidence of catheter use, and more doubts rather than guidance with regard to the role (or lack thereof) of surveillance. An important reason for these problems is the lack of focused translational research and robust randomized prospective studies in this area. In this Review, we will address some of these critical issues, with a special emphasis on identifying the best process of care pathways that could reduce morbidity and mortality. We also discuss the potential use of novel therapies to reduce dialysis vascular access dysfunction. © 2013 Macmillan Publishers Limited. All rights reserved.

Coldiron B.,University of Cincinnati | Ratnarathorn M.,Procedural
JAMA Dermatology | Year: 2014

MAIN OUTCOMES AND MEASURES: The scope of independent billing to Medicare for procedures performed by mid-level providers.RESULTS: In 2012, nurse practitioners and physician assistants billed independently for more than 4 million procedures at our cutoff of 5000 paid claims per procedure. Most (54.8%) of these procedures were performed in the specialty area of dermatology.CONCLUSIONS AND RELEVANCE The findings of this study are relevant to safety and quality of care. Recently, the shortage of primary care clinicians has prompted discussion of widening the scope of practice for mid-level providers. Itwould be prudent to temper widening the scope of practice of mid-level providers by recognizing that mid-level providers are not solely limited to primary care, andmay involve procedures for which theymay not have formal training.IMPORTANCE: Mid-level providers (nurse practitioners and physician assistants) were originally envisioned to provide primary care services in underserved areas. This study details the current scope of independent procedural billing to Medicare of difficult, invasive, and surgical procedures by medical mid-level providers.OBJECTIVE: To understand the scope of independent billing to Medicare for procedures performed by mid-level providers in an outpatient office setting for a calendar year.DESIGN: Analyses of the 2012 Medicare Physician/Supplier Procedure Summary Master File, which reflects fee-for-service claims that were paid by Medicare, for Current Procedural Terminology procedures independently billed by mid-level providers.SETTING AND PARTICIPANTS: Outpatient office setting among health care providers. © 2014 American Medical Association.

Thakar C.V.,University of Cincinnati
Advances in Chronic Kidney Disease | Year: 2013

The incidence of acute kidney injury (AKI) is generally 5-7.5% in all acute care hospitalizations and accounts for up to 20% of admissions to intensive care units (ICUs). Of all of the cases of AKI during hospitalization, approximately 30-40% are observed in operative settings. AKI is a serious morbidity that is associated with greater length of hospital stay, high risk of hospital mortality, and increased risk of incident and progressive chronic kidney disease. The incidence of AKI is variable depending on the specific surgical setting under consideration. Much of our knowledge regarding the epidemiology of AKI is derived from studies related to cardiac or vascular surgery. With limited treatment options, prevention of AKI and amelioration of its severity remain important cornerstones of improving patient outcomes. The magnitude of the problem and the unique set of patient characteristics calls for a multidisciplinary approach for the perioperative management of renal complications. The purpose of the review presented here is to discuss the current knowledge regarding the epidemiology and risk factors, outcomes, diagnoses, and prevention and treatment of AKI during the perioperative period in cardiovascular and noncardiovascular surgical settings. © 2013.

Goldstein S.L.,University of Cincinnati
Current Opinion in Pediatrics | Year: 2011

PURPOSE OF REVIEW: Continuous renal replacement therapy (CRRT) is the most common dialysis modality provided to critically ill children with acute kidney injury (AKI). However, confusion still exists with respect to CRRT terminology and the optimal use of this modality across the entire pediatric disease and age spectrum. RECENT FINDINGS: Data from both single-center and multicenter pediatric studies demonstrate that CRRT can be provided effectively to all pediatric patients, from infants to young adult aged patients. Furthermore, these data demonstrate a consistent and independent association between the degree of patient fluid accumulation at the initiation of a CRRT course and mortality in critically ill children with AKI. In addition, CRRT has been successfully utilized for rapid clearance of both exogenous and endogenous (e.g., ammonia) toxins without the concentration rebound that characterizes toxin removal by intermittent hemodialysis. SUMMARY: CRRT represents an essential dialytic modality for the pediatric nephrologist caring for critically ill children. Current data suggest that earlier initiation of CRRT to prevent excessive fluid accumulation may lead to improved survival in critically ill children, but prospective trials are required to test this hypothesis directly. © 2011 Lippincott Williams & Wilkins, Inc.

Northrup H.,University of Houston | Krueger D.A.,University of Cincinnati
Pediatric Neurology | Year: 2013

Background Tuberous sclerosis complex is highly variable in clinical presentation and findings. Disease manifestations continue to develop over the lifetime of an affected individual. Accurate diagnosis is fundamental to implementation of appropriate medical surveillance and treatment. Although significant advances have been made in the past 15 years in the understanding and treatment of tuberous sclerosis complex, current clinical diagnostic criteria have not been critically evaluated or updated since the last clinical consensus conference in 1998. Methods The 2012 International Tuberous Sclerosis Complex Consensus Group, comprising 79 specialists from 14 countries, was organized into 12 subcommittees, each led by a clinician with advanced expertise in tuberous sclerosis complex and the relevant medical subspecialty. Each subcommittee focused on a specific disease area with important diagnostic implications and was charged with reviewing prevalence and specificity of disease-associated clinical findings and their impact on suspecting and confirming the diagnosis of tuberous sclerosis complex. Results Clinical features of tuberous sclerosis complex continue to be a principal means of diagnosis. Key changes compared with 1998 criteria are the new inclusion of genetic testing results and reducing diagnostic classes from three (possible, probable, and definite) to two (possible, definite). Additional minor changes to specific criterion were made for additional clarification and simplification. Conclusions The 2012 International Tuberous Sclerosis Complex Diagnostic Criteria provide current, updated means using best available evidence to establish diagnosis of tuberous sclerosis complex in affected individuals.

Owen L.A.,University of Cincinnati | Dortch J.M.,University of Manchester
Quaternary Science Reviews | Year: 2014

Much effort has been made in recent years to define the timing and extent of Quaternary glaciation throughout the Himalayan-Tibetan orogen. These studies are challenging because of the logistical and political inaccessibility of the region, and the inherent problems associated with the application of numerical dating techniques. Nevertheless, the studies are providing abundant evidence for significant glacial advances throughout the last several glacial cycles and are beginning to accurately define the extent and timing of glaciation in selected regions. Studies are showing that Himalayan-Tibetan glaciers in arid regions during the last glacial cycle reached their maximum extent early in the cycle and that global Last Glacial Maximum glacier advances were significantly less extensive. However, along the more monsoonal-influenced Greater Himalaya, there is increasing evidence to suggest that glaciation was more extensive later in the last glacial cycle, but this has yet to be fully assessed. In addition, the new studies are showing that throughout most Himalayan-Tibetan regions, significant glacier advances occurred during the Lateglacial and early Holocene, with minor advances in some regions during the mid-Holocene. The still relatively poor chronological control in the Himalayan-Tibetan orogen, however, makes it difficult to construct correlations across the region, and with regions elsewhere in the world. This in turn makes it hard to assess the relative importance of the different climatic mechanisms that force glaciation across the Himalayan-Tibetan orogen, and to quantify paleoclimate change in this high altitude subtropical region. The Lateglacial and Holocene glacial records, however, are particularly well preserved in several Himalayan-Tibetan regions. Glacial successions such as these have the greatest potential to be examined in detail using newly developing numerical dating, and geomorphic and sedimentologic methods to derive high-resolution terrestrial records of glaciation that will help in paleoclimatic reconstruction for high altitude subtropical regions. © 2013 Elsevier Ltd.

Gibler W.B.,University of Cincinnati
Current Cardiology Reviews | Year: 2011

Chest pain is a common reason for presentation to the emergency department (ED). Absolute criteria for Acute Coronary Syndrome without ST elevation (NSTE-ACS) are lacking. An acute coronary syndrome (ACS) needs to be distinguished from a variety of other cardiac and non-cardiac diseases that may cause chest pain. For patients with confirmed ACS, several scoring methods can be applied in order to distinguish patients in the coronary care unit who may benefit most from therapies. The PURSUIT, TIMI, GRACE and FRISC risk scores are well validated with this respect. However, none of these risk scores has been used in the identification of an ACS in the emergency setting. The vast majority of patients with chest pain due to causes other than ACS were not evaluated in these trials. An evidence-based systematic stratification and policy for these patients does not currently exist. The more recently developed HEART score is specifically designed to stratify all chest pain patients in the ED. The HEART score was validated in a retrospective multicenter study and proved to be a strong predictor of event free survival on one hand and potentially life threatening cardiac events on the other hand. The HEART score facilitates risk stratification of chest pain patients in the ED. © 2011 Bentham Science Publishers Ltd.

Liu H.,Michigan State University | Reczek C.,University of Cincinnati | Brown D.,University of Texas at Austin
Journal of Health and Social Behavior | Year: 2013

A legacy of research finds that marriage is associated with good health. Yet same-sex cohabitors cannot marry in most states in the United States and therefore may not receive the health benefits associated with marriage. We use pooled data from the 1997 to 2009 National Health Interview Surveys to compare the self-rated health of same-sex cohabiting men (n = 1,659) and same-sex cohabiting women (n = 1,634) with that of their different-sex married, different-sex cohabiting, and unpartnered divorced, widowed, and never-married counterparts. Results from logistic regression models show that same-sex cohabitors report poorer health than their different-sex married counterparts at the same levels of socioeconomic status. Additionally, same-sex cohabitors report better health than their different-sex cohabiting and single counterparts, but these differences are fully explained by socioeconomic status. Without their socioeconomic advantages, same-sex cohabitors would report similar health to nonmarried groups. Analyses further reveal important racial-ethnic and gender variations. © American Sociological Association 2013.

Genomewide annotation of cytochrome P450 monooxygenases (P450s) in three white-rot species of the fungal order Polyporales, namely Bjerkandera adusta, Ganoderma sp. and Phlebia brevispora, revealed a large contingent of P450 genes (P450ome) in their genomes. A total of 199 P450 genes in B. adusta and 209 P450 genes each in Ganoderma sp. and P. brevispora were identified. These P450omes were classified into families and subfamilies as follows: B. adusta (39 families, 86 subfamilies), Ganoderma sp. (41 families, 105 subfamilies) and P. brevispora (42 families, 111 subfamilies). Of note, the B. adusta genome lacked the CYP505 family (P450foxy), a group of P450-CPR fusion proteins. The three polypore species revealed differential enrichment of individual P450 families in their genomes. The largest CYP families in the three genomes were CYP5144 (67 P450s), CYP5359 (46 P450s) and CYP5344 (43 P450s) in B. adusta, Ganoderma sp. and P. brevispora, respectively. Our analyses showed that tandem gene duplications led to expansions in certain P450 families. An estimated 33% (72 P450s), 28% (55 P450s) and 23% (49 P450s) of P450ome genes were duplicated in P. brevispora, B. adusta and Ganoderma sp., respectively. Family-wise comparative analysis revealed that 22 CYP families are common across the three Polypore species. Comparative P450ome analysis with Ganoderma lucidum revealed the presence of 143 orthologs and 56 paralogs in Ganoderma sp. Multiple P450s were found near the characteristic biosynthetic genes for secondary metabolites, namely polyketide synthase (PKS), non-ribosomal peptide synthetase (NRPS), terpene cyclase and terpene synthase in the three genomes, suggesting a likely role of these P450s in secondary metabolism in these Polyporales. Overall, the three species had a richer P450 diversity both in terms of the P450 genes and P450 subfamilies as compared to the model white-rot and brown-rot polypore species Phanerochaete chrysosporium and Postia placenta.

Shott S.R.,University of Cincinnati
Current Opinion in Otolaryngology and Head and Neck Surgery | Year: 2011

Purpose of Review: There is an increasing percentage of children with persistent obstructive sleep apnea (OSA) after removal of the tonsils and adenoids (T&A). Although sleep apnea has been an active area of research and treatment in the adult population, our awareness of this problem in children is still in its initial stages. In addition, therapies to successfully treat this residual OSA are still not fully established. It is important to develop evaluation and management protocols for these children. Recent Findings: This review will discuss risk factors associated with persistent OSA after T&A and techniques to evaluate the pediatric airway in order to identify the site, or sites, of obstruction. Various medical and surgical options are presented. Summary: Clinicians need to be aware of the potential for persistent sleep disordered breathing and OSA in children, despite previous T&A. Evaluation protocols and techniques will differ in children, due to limitations in their cooperation during the physical examination. Alternative methods, such as airway endoscopy and cine MRI, are presented. Medical and surgical options are presented. Outcomes data for pediatric populations are rare. Multilevel, single stage surgery has a higher risk for oropharyngeal stenosis in children compared with adults and conservative, multistage approaches may be more appropriate. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Nierkens S.,Radboud University Nijmegen | Nierkens S.,University Utrecht | Tel J.,Radboud University Nijmegen | Janssen E.,University of Cincinnati | Adema G.J.,Radboud University Nijmegen
Trends in Immunology | Year: 2013

Antigen cross-presentation describes the process through which dendritic cells (DCs) acquire exogenous antigens for presentation on MHC class I molecules. The ability to cross-present has been thought of as a feature of specialized DC subsets. Emerging data, however, suggest that the cross-presenting ability of each DC subset is tuned by and dependent on several factors, such as DC location and activation status, and the type of antigen and inflammatory signals. Thus, we argue that capacity of cross-presentation is not an exclusive trait of one or several distinct DC subtypes, but rather a common feature of the DC family in both mice and humans. Understanding DC subset activation and antigen-presentation pathways might yield improved tools and targets to exploit the unique cross-presenting capacity of DCs in immunotherapy. © 2013 Elsevier Ltd.

Yoon S.-O.,University of Cincinnati | Roux P.P.,University of Montreal
Current Biology | Year: 2013

The mechanism of action of the mTOR inhibitor rapamycin is poorly understood and why certain mTORC1 phosphorylation sites are rapamycin insensitive remains elusive. Site-specific analysis of mTORC1 substrates now suggests that the sequence composition of a phosphorylation site determines whether it is sensitive to rapamycin and starvation. © 2013 Elsevier Ltd.

Schmudde I.,University of Lubeck | Laumonnier Y.,University of Lubeck | Kohl J.,University of Lubeck | Kohl J.,University of Cincinnati
Seminars in Immunology | Year: 2013

Allergic asthma is a chronic disease of the airways in which maladaptive Th2 and Th17 immune responses drive airway hyperresponsiveness (AHR), eosinophilic and neutrophilic airway inflammation and mucus overproduction. Airway epithelial and pulmonary vascular endothelial cells in concert with different resident and monocyte-derived dendritic cells (DC) play critical roles in allergen sensing and consecutive activation of TH cells and their differentiation toward TH2 and TH17 effector or regulatory T cells (Treg). Further, myeloid-derived regulatory cells (MDRC) act on TH cells and either suppress or enhance their activation. The complement-derived anaphylatoxins (AT) C3a and C5a are generated during initial antigen encounter and regulate the development of maladaptive immunity at allergen sensitization. Here, we will review the complex role of ATs in activation and modulation of different DC populations, MDRCs and CD4+ TH cells. We will also discuss the potential impact of ATs on the regulation of the pulmonary stromal compartment as an important means to regulate DC functions. © 2013 Elsevier Ltd.

Barr J.,Stanford University | Kishman C.P.,University of Cincinnati | Jaeschke R.,McMaster University
Critical Care Medicine | Year: 2013

Objective: In 2006, the American College of Critical Care Medicine assembled a 20-member task force to revise the 2002 guidelines for sedation and analgesia in critically ill adults. This article describes the methodological approach used to develop the American College of Critical Care Medicine's 2013 ICU Pain, Agitation, and Delirium Clinical Practice Guidelines. Design: Review article. Setting: Multispecialty critical care units. Patients: Adult ICU patients. Interventions: The task force was divided into four subcommittees, focusing on pain, sedation, delirium, and related outcomes. Unique aspects of this approach included the use of: 1) the Grading of Recommendations Assessment, Development and Evaluation method to evaluate the literature; 2) a librarian to conduct literature searches and to create and maintain the pain, agitation, and delirium database; 3) creation of a single web-based database; 4) rigorous psychometric analyses of pain, sedation, and delirium assessment tools; 5) the use of anonymous electronic polling; and 6) creation of an ICU pain, agitation, and delirium care bundle. Results: The pain, agitation, and delirium database includes over 19,000 references. With the help of psychometric experts, members developed a scoring system and analyzed the psychometric properties of 6 behavioral pain scales, 10 sedation/agitation scales, and 5 delirium monitoring tools. A meta-analysis was performed to assess the overall impact of benzodiazepine versus nonbenzodiazepine sedation on ICU outcomes. The pain, agitation, and delirium guidelines include 54 evidence-based statements and recommendations. The quality of evidence and strength for each statement and recommendation was ranked. In the absence of sufficient evidence or group consensus, no recommendations were made. An ICU pain, agitation, and delirium care bundle was created to facilitate adoption of the pain, agitation, and delirium guidelines. It focuses on taking an integrated approach to assessing, treating, and preventing pain, agitation/sedation, and delirium in critically ill patients, and it links pain, agitation, and delirium management to spontaneous awakening trials, spontaneous breathing trials, and ICU early mobility and sleep hygiene programs in order to achieve synergistic benefits to ICU patient outcomes. Conclusions: The 2013 ICU pain, agitation, and delirium guidelines provide critical care providers with an evidence-based, integrated, and interdisciplinary approach to managing pain, agitation/sedation, and delirium. The methodological approach used to develop the guidelines ensures that they are rigorous, evidence-based, and transparent. Implementation of the ICU pain, agitation, and delirium care bundle is expected to have a significant beneficial impact on ICU outcomes and costs. © 2013 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins.

INTRODUCTION:: Pasireotide was recently shown to decrease leak rates after pancreatic resection, though the significant cost of the drug may be prohibitive. We conducted a cost-effectiveness analysis to determine whether prophylactic pasireotide possesses a reasonable cost profile by improving outcomes. METHODS:: A cost-effectiveness model was constructed to compare pasireotide administration after pancreatic resection versus usual care, populated by probabilities of clinical outcomes from a recent randomized trial and hospital costs (2013 US$) from a university pancreatic disease center. Sensitivity analyses were performed to identify the most influential clinical components of the model. RESULTS:: Without considering pasireotide cost, prophylactic use of the drug saved an average of $8,109 per patient. However, when the cost of pasireotide was included, per patient costs increased from $42,159 to $77,202. This was associated with a 56% reduction in pancreatic fistula/pancreatic leak/abscess (PF/PL/A) (21.9% to 9.2%). The resultant cost per PF/PL/A avoided was $301,628. Threshold analysis demonstrated that for this intervention to be cost neutral, either the purchase price of pasireotide ($43,172) must be reduced by 92.3% (to $3324) or drug reimbursement must be $39,848. Sensitivity analyses exploring variable perioperative mortality, rate of PF/PL/A, and readmission rates did not significantly alter model outcomes. CONCLUSIONS:: Our analyses demonstrate that when prophylactic pasireotide is administered, the cost per PF/PL/A avoided is approximately $300,000. Aggressive pricing negotiation, payer reimbursement for the drug, high-volume use, and consensus among the public, payers, and surgical community regarding the value of reducing morbidity will ultimately determine the utility of widespread pasireotide application in pancreatic resection. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Shen Y.,California Institute of Technology | Torchia M.L.G.,U.S. National Cancer Institute | Lawson G.W.,University of California at Los Angeles | Karp C.L.,University of Cincinnati | And 2 more authors.
Cell Host and Microbe | Year: 2012

Commensal bacteria impact host health and immunity through various mechanisms, including the production of immunomodulatory molecules. Bacteroides fragilis produces a capsular polysaccharide (PSA), which induces regulatory T cells and mucosal tolerance. However, unlike pathogens, which employ secretion systems, the mechanisms by which commensal bacteria deliver molecules to the host remain unknown. We reveal that Bacteroides fragilis releases PSA in outer membrane vesicles (OMVs) that induce immunomodulatory effects and prevent experimental colitis. Dendritic cells (DCs) sense OMV-associated PSA through TLR2, resulting in enhanced regulatory T cells and anti-inflammatory cytokine production. OMV-induced signaling in DCs requires growth arrest and DNA-damage-inducible protein (Gadd45α). DCs treated with PSA-containing OMVs prevent experimental colitis, whereas Gadd45α-/- DCs are unable to promote regulatory T cell responses or suppress proinflammatory cytokine production and host pathology. These findings demonstrate that OMV-mediated delivery of a commensal molecule prevents disease, uncovering a mechanism of interkingdom communication between the microbiota and mammals. © 2012 Elsevier Inc.

Zeltser L.M.,Columbia University | Seeley R.J.,University of Cincinnati | Tschop M.H.,TU Munich
Nature Neuroscience | Year: 2012

Maintaining energy balance is of paramount importance for metabolic health and survival. It is achieved through the coordinated regulation of neuronal circuits that control a wide range of physiological processes affecting energy intake and expenditure, such as feeding, metabolic rate, locomotor activity, arousal, growth and reproduction. Neuronal populations distributed throughout the CNS but highly enriched in the mediobasal hypothalamus, sense hormonal, nutrient and neuronal signals of systemic energy status and relay this information to secondary neurons that integrate the information and regulate distinct physiological parameters in a manner that promotes energy homeostasis. To achieve this, it is critical that neuronal circuits provide information about short-term changes in nutrient availability in the larger context of long-term energy status. For example, the same signals lead to different cellular and physiological responses if delivered under fasted versus fed conditions. Thus, there is a clear need to have mechanisms that rapidly and reversibly adjust responsiveness of hypothalamic circuits to acute changes in nutrient availability. © 2012 Nature America, Inc. All rights reserved.

Turanovic J.J.,Arizona State University | Pratt T.C.,University of Cincinnati
Journal of Pediatrics | Year: 2015

Objective To assess how prosocial attachments to school and family may diminish the effects of violent victimization during adolescence on adverse outcomes in adulthood. Study design Weanalyzed secondary data on 13 555 participants from waves 1 (1994-1995) and 3 (2001-2002) of the National Longitudinal Study of Adolescent Health, a nationally representative sample of US high school and middle school students. Adverse outcomes in adulthood included offending, alcohol problems, drug use, risky sexual behavior, violent victimization, depression, low self-esteem, suicidality, hospitalizations, sexually transmitted infections, extreme weight control, and obesity. Analyses were conducted separately for males and females. Results Our multivariate regression analyses demonstrated that adolescent victimization is a significant predictor of a host of problems in adulthood. Nevertheless, attachment to school and to family meaningfully reduced the effect of victimization on nearly every adult outcome we assessed. Conclusions Strong attachments to school and family in adolescence can reduce the long-term harms of violence on the lives of young persons. Incorporating this insight into regular clinical assessment could yield significant behavioral, health, and psychoemotional benefits for victims of violence. Copyright © 2015 Elsevier Inc. All rights reserved.

The t(8;21) rearrangement, which creates the AML1-ETO fusion protein, represents the most common chromosomal translocation in acute myeloid leukemia (AML). Clinical data suggest that CBL mutations are a frequent event in t(8;21) AML, but the role of CBL in AML1-ETO-induced leukemia has not been investigated. In this study, we demonstrate that CBL mutations collaborate with AML1-ETO to expand human CD34+ cells both in vitro and in a xenograft model. CBL depletion by shRNA also promotes the growth of AML1-ETO cells, demonstrating the inhibitory function of endogenous CBL in t(8;21) AML. Mechanistically, loss of CBL function confers hyper-responsiveness to thrombopoietin and enhances STAT5/AKT/ERK/Src signaling in AML1-ETO cells. Interestingly, we found the protein tyrosine phosphatase UBASH3B/Sts-1, which is known to inhibit CBL function, is upregulated by AML1-ETO through transcriptional and miR-9-mediated regulation. UBASH3B/Sts-1 depletion induces an aberrant pattern of CBL phosphorylation and impairs proliferation in AML1-ETO cells. The growth inhibition caused by UBASH3B/Sts-1 depletion can be rescued by ectopic expression of CBL mutants, suggesting that UBASH3B/Sts-1 supports the growth of AML1-ETO cells partly through modulation of CBL function. Our study reveals a role of CBL in restricting myeloid proliferation of human AML1-ETO-induced leukemia, and identifies UBASH3B/Sts-1 as a potential target for pharmaceutical intervention.Leukemia advance online publication, 1 December 2015; doi:10.1038/leu.2015.275. © 2015 Macmillan Publishers Limited

Heppner K.M.,Oregon Health And Science University | Perez-Tilve D.,University of Cincinnati
Frontiers in Neuroscience | Year: 2015

Glucagon-like peptide-1 (GLP-1) enhances meal-related insulin secretion, which lowers blood glucose excursions. In addition to its incretin action, GLP-1 acts on the GLP-1 receptor (GLP-1R) in the brain to suppress feeding. These combined actions of GLP-1R signaling cause improvements in glycemic control as well as weight loss in type II diabetes (T2DM) patients treated with GLP-1R agonists. This is a superior advantage of GLP-1R pharmaceuticals as many other drugs used to treat T2DM are weight neutral or actual cause weight gain. This review summarizes GLP-1R action on energy and glucose metabolism, the effectiveness of current GLP-1R agonists on weight loss in T2DM patients, as well as GLP-1R combination therapies. © 2015 Heppner and Perez-Tilve.

Franz D.N.,University of Cincinnati
Expert Review of Anticancer Therapy | Year: 2011

Tuberous sclerosis complex (TSC) is a devastating disease affecting virtually all organ systems of the body and is characterized by multiple hamartomas and neurodevelopmental disorders. The majority of patients with TSC have mutations in TSC1 or TSC2, resulting in constitutive activation of mTOR. Because the pathogenesis of the disease is mTOR hyperactivity, mTOR inhibitors have the potential to treat the underlying cause in TSC patients. Everolimus is the first mTOR inhibitor approved in the USA for the treatment of patients with subependymal giant-cell astrocytomas (SEGAs) associated with TSC. Evidence supports and ongoing studies are evaluating the role of mTOR inhibitors in the treatment of a wide spectrum of disease manifestations, including reduction in tumor volume (SEGAs, renal angiomyolipoma) and improvement in epilepsy, lung function and skin manifestations, including facial angiofibromas. In time, the use of mTOR inhibitors in patients with TSC will likely be very well established. © 2011 Expert Reviews Ltd.

McNamara R.K.,University of Cincinnati
Prostaglandins Leukotrienes and Essential Fatty Acids | Year: 2013

Animal studies have found that deficits in brain docosahexaenoic acid (DHA, 22:6n-3) accrual during perinatal development leads to transient and enduring abnormalities in brain development and function. Determining the relevance of this evidence to brain disorders in humans has been hampered by an inability to determine antimortem brain DHA levels and limitations associated with a postmortem approach. Accordingly, there is a need for alternate or complementary approaches to better understand the role of DHA in cortical function and pathology, and conventional magnetic resonance imaging (MRI) techniques may be ideally suited for this application. A major advantage of neuroimaging is that it permits prospective evaluation of the effects of manipulating DHA status on both clinical and neuroimaging variables. Emerging evidence from MRI studies suggest that greater DHA status is associated with cortical structural and functional integrity, and suggest that reduced DHA status and abnormalities in cortical function observed in psychiatric disorders may be interrelated phenomenon. Preliminary evidence from animal MRI studies support a critical role of DHA in normal brain development. Neuroimaging research in both human and animals therefore holds tremendous promise for developing a better understanding of the role of DHA status in cortical function, as well as for elucidating the impact of DHA deficiency on neuropathological processes implicated in the etiology and progression of neurodevelopmental and psychiatric disorders. © 2012 Elsevier Ltd.

Juvenile fibromyalgia (JFM) is a chronic musculoskeletal pain condition that is associated with reduced physical function. Recent research has demonstrated that cognitive-behavioral therapy (CBT) is effective in improving daily functioning among adolescents with JFM. However, it is not known whether these improvements were accompanied by increased physical activity levels. Our objective was to analyze secondary data from a randomized clinical trial of CBT to examine whether CBT was associated with improvement in objectively measured physical activity and whether actigraphy indices corresponded with self-reported functioning among adolescents with JFM. Participants were 114 adolescents (ages 11-18 years) recruited from pediatric rheumatology clinics that met criteria for JFM and were enrolled in a clinical trial. Subjects were randomly (1:1) assigned to receive either CBT or fibromyalgia education (FE). Participants wore a hip-mounted accelerometer for 1 week as part of their baseline and posttreatment assessments. The final sample included 68 subjects (94% female, mean age 15.2 years) for whom complete actigraphy data were obtained. Actigraphy measures were not found to correspond with self-reported improvements in functioning. While self-reported functioning improved in the CBT condition compared to FE, no significant changes were seen in either group for activity counts, sedentary, moderate, or vigorous activity. The CBT group had significantly lower peak and light activity at posttreatment. Actigraphy monitoring provides a unique source of information about patient outcomes. CBT intervention was not associated with increased physical activity in adolescents with JFM, indicating that combining CBT with interventions to increase physical activity may enhance treatment effects. Copyright © 2013 by the American College of Rheumatology.

Central sleep apnea is due to temporary failure in the pontomedullary inspiratory pacemaker generating breathing rhythm. There are many causes of central sleep apnea. The focus of this article is on three disorders: systolic heart failure, opioid-induced sleep apnea, and complex sleep apnea. © 2010 Elsevier Inc. All rights reserved.

Sallee F.,University of Cincinnati | Connor D.F.,University of Connecticut | Newcorn J.H.,Mount Sinai School of Medicine
Journal of Child and Adolescent Psychopharmacology | Year: 2013

Objective: Interest in the potential role for the α2- adrenoceptor agonists clonidine and guanfacine as treatments for attention-deficit/hyperactivity disorder (ADHD) has driven additional clinical studies as well as development of new formulations of these agents. This article reviews the published data that supported United States Food and Drug Administration approval and subsequent clinical use of α2- adrenoceptor agonists in the treatment of ADHD, and identifies promising directions for future research. Methods: Electronic searches were performed in PubMed through October 2012 using the base terms ADHD or attention deficit hyperactivity disorder and alpha agonists, as well as the following limits: humans, clinical trial, meta-analysis, practice guideline, randomized controlled trial, review, English. The electronic searches were complemented with reference lists from the articles retrieved by informal search of the literature, producing a qualitative review of published, pertinent drug-class preclinical and clinical data. Articles were selected for greater exposition based on hierarchy of evidence (e.g., randomized controlled trials), relevance, and quality of individual studies, as well as generalizability to clinical practice. Results: Results of clinical studies of immediate-release and extended-release formulations of α2-adrenoceptor agonists and basic science investigations of cognitive effects of these drugs are discussed. Studies of both clonidine and guanfacine extended-release formulations as monotherapy and adjunctive therapy with psychostimulants for the treatment of ADHD are also reviewed. Conclusions: Large, randomized, placebo-controlled clinical trials support the efficacy and safety of α2- adrenoceptor agonists as monotherapy and adjunctive therapy with psychostimulants for the symptomatic treatment of ADHD. Future research could reveal whether there are cognitive benefits associated with this drug class and thus further define the role of α2-adrenoceptor agonists in the treatment of ADHD. © Copyright 2013, Mary Ann Liebert, Inc. 2013.

Shulman J.I.,University of Cincinnati
Journal of Chemical Education | Year: 2013

In 2009, the Association of American Medical Colleges and the Howard Hughes Medical Institute released a report entitled Scientific Foundations for Future Physicians (SFFP). This report, produced in response to "concerns about the science content in the current premedical and medical education curricula", emphasizes competencies for premedical school students rather than mandating specific courses for admission to medical school. This commentary addresses the opportunities and challenges for the chemical education community presented by SFFP, some models that have been created or suggested for teaching chemistry in the premedical curriculum, and some issues that colleges and universities should keep in mind when considering their response to SFFP. © 2013 The American Chemical Society and Division of Chemical Education, Inc.

Martone M.,Cornell University | Zupan J.,University of Cincinnati
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

We investigate the implications of direct CP violation (CPV) on the determination of the unitarity triangle angle γ from B→DK decays. We show that γ can still be extracted even with the inclusion of direct CPV in charm if (i) at least one of the D decays has negligible CP violation; and (ii) data from a charm factory at threshold are used. If approximate expressions without direct CP violation in charm are used, this can result in a shift in γ that is O(rD/rB). It is modest for B→DK but can be O(1) for B→Dπ. We illustrate the size of the shift using an example of the Gronau-London-Wyler method. © 2013 American Physical Society.

Kemper C.,Kings College London | Kohl J.,University of Lubeck | Kohl J.,University of Cincinnati
Molecular Immunology | Year: 2013

Complement receptors are expressed on cells of the innate and the adaptive immune system. They play important roles in pathogen and danger sensing as they translate the information gathered by complement fluid phase sensors into cellular responses. Further, they control complement activation on viable and apoptotic host cells, clearance of immune complexes and mediate opsonophagocytosis. More recently, evidence has accumulated that complement receptors form a complex network with other innate receptors systems such as the Toll-like receptors, the Notch signaling system, IgG Fc receptors and C-type lectin receptors contributing to the benefit and burden of innate and adaptive immune responses in autoimmune and allergic diseases as well as in cancer and transplantation. Here, we will discuss recent developments and emerging concepts of complement receptor activation and regulation with a particular focus on the differentiation, maintenance and contraction of effector and regulatory T cells. © 2013 Elsevier Ltd.

Witt J.K.,Colorado State University | Riley M.A.,University of Cincinnati
Psychonomic Bulletin and Review | Year: 2014

Both the action-specific perception account and the ecological approach to perception–action emphasize the role of action in perception. However, the action-specific perception account demonstrates that different percepts are possible depending on the perceiver’s ability to act, even when the same optical information is available. These findings challenge one of the fundamental claims of the ecological approach— that perception is direct—by suggesting that perception is mediated by internal processes. Here, we sought to resolve this apparent discrepancy.We contend that perception is based on the controlled detection of the information available in a global array that includes higher-order patterns defined across interoceptive and exteroceptive stimulus arrays. These higher-order patterns specify the environment in relation to the perceiver, so direct sensitivity to them would be consistent with the ecological claims that perception of the environment is direct and animal-specific. In addition, the action-specific approach provides further evidence for the theory of affordances, by demonstrating that even seemingly abstract properties of the environment, such as distance and size, are ultimately perceived in terms of an agent’s action capabilities. © Psychonomic Society, Inc. 2014.

Tschop J.,University of Cincinnati
Endocrine, metabolic & immune disorders drug targets | Year: 2010

Sepsis, which is defined as a systemic inflammatory response syndrome that occurs during infection, is associated with several clinical conditions and high mortality rates. As sepsis progresses immune paralysis can become severe, leaving an already vulnerable patient ill equipped to eradicate primary or secondary infections. At present the predominant treatments for sepsis have not demonstrated convincing efficacy of decreased mortality. During sepsis, it has been observed that leptin levels initially increase but subsequently decline. A body of evidence has demonstrated that central or systemic leptin can beneficially regulate immune function. In this report expression of leptin and its receptor, signaling, and function on leukocytes will be reviewed. Furthermore, the effects mediated by central and systemic leptin during sepsis will be reviewed. Altogether, the ability of leptin to beneficially enhance inflammation and the host response during sepsis supports its use as a therapeutic agent, particularly during the latter phases of the syndrome.

Baker A.,Cornell University | Allmendinger R.W.,Cornell University | Owen L.A.,University of Cincinnati | Rech J.A.,Miami University Ohio
Nature Geoscience | Year: 2013

Earthquakes are accompanied by coseismic and post-seismic rebound: blocks of crust on either side of the fault spring back to their initial, undeformed configuration. This rebound is well documented by space geodetic data, such as the Global Positioning System. Thus, all earthquake-induced deformation of the crust is considered non-permanent and is modelled as an elastic or visco-elastic process. Here, however, we show that earthquakes larger than magnitude 7 in northern Chile caused the crust to deform permanently. We identify millimetre- to metre-scale tension cracks in the crust of the Atacama Desert and use cosmogenic nuclides to date the timing of crack formation. The cracks were formed by between 2,000 and 9,000 individual plate-boundary earthquakes that occurred in the past 0.8-1 million years. We show that up to 10% of the horizontal deformation generated during the earthquakes, recorded by Global Positioning System data and previously assumed to be recoverable, is permanent. Our data set provides a record of permanent strain in the shallow crust of the South American Plate. Although deformation of the deep crust may be predominantly elastic, we conclude that modelling of the earthquake cycle should also include a significant plastic component. © 2013 Macmillan Publishers Limited. All rights reserved.

An evidence-based practice project was completed to develop best practice recommendations for the treatment of aggression in children and adolescents with attention deficit hyperactivity disorder (ADHD). Ovid Medline, PsychInfo, the National Guidelines Clearinghouse, and the Cochrane Database of Systematic Reviews were searched with limits set for English language, years 1996 to January 2010. A search of the pediatric literature was conducted for synthesized evidence in the form of meta-analyses, systematic reviews, or practice guidelines related to the treatment of aggression in children and adolescents with attention deficit hyperactivity disorder. Data were extracted using the LEGEND system. Three evidence-based care recommendations for the management of aggression in children and adolescents with ADHD were developed with an associated grade for the body of evidence. First-line pharmacotherapy for aggressive behavior in children and adolescents with ADHD should be ADHD medications. Additional research is needed to evaluate the efficacy of psychiatric medications on signs of aggression within the context of ADHD. © 2010 Springer Science+Business Media, LLC.

Background: Worsening renal function (WRF) is an ominous complication in patients with acute heart failure syndrome (AHFS). Few data are available with regard to the clinical implications of transient versus persistent WRF in this setting. Methods and Results: We studied 467 patients with AHFS and creatinine measurements at baseline and on days 2, 5, 14, and 30. WRF (≥0.5 mg/dL increase in serum creatinine above baseline at any time point) was defined as persistent when serum creatinine remained ≥0.5 mg/dL above baseline throughout day 30, and transient when creatinine levels subsequently decreased to <0.5 mg/dL above baseline. WRF occurred in 115 patients, and was transient in 39 patients (33.9%). The 6-month mortality rates were 17.3%, 20.5%, and 46.1% in patients without WRF, transient WRF, and persistent WRF, respectively. In a multivariable Cox model, compared with patients with stable renal function, the adjusted hazard ratio for mortality was 0.8 (95% CI 0.4-1.7; P = .58) in patients with transient WRF and 3.2 (95% CI 2.1-5.0; P < .0001) in patients with persistent WRF. Conclusion: Transient WRF is frequent among patients with AHFS. Whereas persistent WRF portends increased mortality, transient WRF appears to be associated with a better outcome as compared with persistent renal failure. © 2010 Elsevier Inc. All rights reserved.

Widener M.J.,University of Cincinnati | Shannon J.,University of Georgia
Health and Place | Year: 2014

The food desert concept is used as a means for defining regions as having inadequate spatial and socioeconomic access to vendors selling nutritious foods. This primarily aggregate-level and static method for understanding the food environment is commonly used by researchers and policy makers seeking to improve health outcomes of those affected by reduced access. However, recent research findings have brought the association between living in a food desert and adverse health outcomes into question. In this viewpoint, we put forward the idea that the food desert concept, and food accessibility research more generally, should be expanded to include a temporal component, and note potential avenues for future research. © 2014 Elsevier Ltd.

Sibai B.M.,University of Cincinnati
American Journal of Obstetrics and Gynecology | Year: 2012

Postpartum hypertension can be related to persistence of gestational hypertension, preeclampsia, or preexisting chronic hypertension, or it could develop de novo postpartum secondary to other causes. There are limited data describing the etiology, differential diagnosis, and management of postpartum hypertension-preeclampsia. The differential diagnosis is extensive, and varies from benign (mild gestational or essential hypertension) to life-threatening such as severe preeclampsia-eclampsia, pheochromocytoma, and cerebrovascular accidents. Therefore, medical providers caring for postpartum women should be educated about continued monitoring of signs and symptoms and prompt management of these women in a timely fashion. Evaluation and management should be performed in a stepwise fashion and may require a multidisciplinary approach that considers predelivery risk factors, time of onset, associated signs/symptoms, and results of selective laboratory and imaging findings. The objective of this review is to increase awareness and to provide a stepwise approach toward the diagnosis and management of women with persistent and/or new-onset hypertension-preeclampsia postpartum period. © 2012 Mosby, Inc.

van Orden G.,University of Cincinnati
Medicina | Year: 2010

Will, purpose, and volition have long been viewed as either causes of behavior or of no direct consequence to behavior. In this essay, volition affects a flexible direct coupling of participant to task, modulating the degrees of freedom for kinematics in action, a point of view first introduced in theories of motor coordination. The consequence is an explanation consistent with present knowledge about involuntary and voluntary sources of control in human performance, and also the changes of the body expressed in aging and dynamical disease. Specifically, this view explains how tradeoffs between sources of overly regular versus overly random dynamics change the structure of variability in repeated measurements of voluntary performance.

Pestian J.,University of Cincinnati
Suicide and Life-Threatening Behavior | Year: 2010

This article is a transcript of a conversation that took place with Edwin Shneidman, PhD, on August 19, 2008. Recent advances in machine learning, particularly neurocognitive computing, have provided a fresh approach to the idea of using computers to analyze the language of the suicidal person. Here this notion and many others are discussed. © 2010 The American Association of Suicidology.

Blackard J.T.,University of Cincinnati
Antiviral Therapy | Year: 2012

The majority of acute HCV infections progress to chronicity, implying that the immune response is unable to clear virus in most instances. Reinfection with a second strain of HCV after clearance of an initial infection has been reported in several recent studies. Moreover, individuals with HCV infection may be at risk of HCV superinfection with a second strain of HCV even after the establishment of persistent infection and the development of an immunological response to the initial virus. In vivo and in vitro data regarding HCV reinfection and superinfection, including the clinical consequences of these phenomena and the impact they have on vaccines require consideration in future studies. ©2012 International Medical Press.

Denson L.A.,University of Cincinnati
Current Gastroenterology Reports | Year: 2012

Recent translational studies have provided new insights into pathogenesis, disease behavior, and treatment responses in pediatric Inflammatory Bowel Disease (IBD). Registry studies have identified distinct clinical phenotypes with increasing age of onset; this has led to a revision of the clinical phenotyping system, now termed the Paris classification system. It is recognized that there are infantile (age <2 years), very early onset (VEO, age 2-10), and early onset (EO, age 10-17) forms of disease. Rare genetic mutations affecting anti-microbial and anti-inflammatory pathways have been discovered in infantile and VEO forms, while genetic pathways identified in EO disease have been similar to adult-onset IBD. Genetic and serologic patterns measured soon after diagnosis have been shown to be associated with more aggressive stricturing behavior; these patterns may now be used clinically to help predict disease course. More recently, clinical and genetic models have been developed that, if validated, could be used to predict treatment responses. © Springer Science+Business Media, LLC 2012.

Martin G.V.,University of Cincinnati
Cephalalgia : an international journal of headache | Year: 2013

The aim of this article is to determine if lightning is associated with the frequency of headache in migraineurs. Participants fulfilling diagnostic criteria for International Headache Society-defined migraine were recruited from sites located in Ohio ( N = 23) and Missouri ( N = 67). They recorded headache activity in a daily diary for three to six months. A generalized estimating equations (GEE) logistic regression determined the odds ratio (OR) of headache on lightning days compared to non-lightning days. Other weather factors associated with thunderstorms were also added as covariates to the GEE model to see how they would attenuate the effect of lightning on headache. The mean age of the study population was 44 and 91% were female. The OR for headache was 1.31 (95% confidence limits (CL); 1.07, 1.66) during lighting days as compared to non-lightning days. The addition of thunderstorm-associated weather variables as covariates were only able to reduce the OR for headache on lightning days to 1.18 (95% CL; 1.02, 1.37). The probability of having a headache on lightning days was also further increased when the average current of lightning strikes for the day was more negative. This study suggests that lightning represents a trigger for headache in migraineurs that cannot be completely explained by other meteorological factors. It is unknown if lightning directly triggers headaches through electromagnetic waves or indirectly through production of bioaerosols (e.g. ozone), induction of fungal spores or other mechanisms. These results should be interpreted cautiously until replicated in a second dataset.

Arnold L.M.,University of Cincinnati
Psychiatric Clinics of North America | Year: 2010

Research in fibromyalgia has increased understanding of the possible genetic and environmental factors that could be involved in the etiology of fibromyalgia. There is now substantial evidence for augmentation of central pain processing in fibromyalgia. Because the clinical presentation of fibromyalgia is heterogeneous, treatment recommendations must be individualized for each patient. The rapid growth of trials in fibromyalgia in recent years has resulted in new evidence-based approaches to pharmacological and nonpharmacological treatment. © 2010 Elsevier Inc.

Hillman J.B.,University of Cincinnati
Discovery medicine | Year: 2011

The discovery of ghrelin and its role in human metabolism has promoted significant research and advances in the study of obesity and other weight-related disorders. Ghrelin is relevant to many disorders of metabolism and weight such as obesity, cachexia, Prader-Willi Syndrome (PWS), and Anorexia Nervosa (AN), and its role in the pathophysiology differs. The changes observed in ghrelin physiology in these disorders shed light on the overall role of ghrelin in human metabolism and growth. The purpose of this review is to summarize the existing literature on ghrelin and some disorders of metabolism and growth. The disorders that will be discussed include obesity, cachexia, PWS, and AN. Within each disorder we will review relevant ghrelin physiology, recent studies, and potential modes of intervention with ghrelin analogues.

Marketing pressures, regulatory policies, clinical guidelines, and consumer demand all affect health care providers' knowledge and use of health-related genetic tests that are sold and/or advertised to consumers. In addition, clinical guidelines, regulatory policies, and educational efforts are needed to promote the informed use of genetic tests that are sold and advertised to consumers and health care providers. A shift in culture regarding the regulation of genetic tests that are sold directly to consumers is suggested: by recent actions taken by the US Food and Drug Administration (FDA), including letters sent to direct-to-consumer (DTC) genetic testing companies stating that their tests meet the definition of medical devices; by public meetings held by the FDA to discuss laboratory developed tests; and by the convening of the Molecular and Clinical Genetics Panel to gather input on scientific issues concerning DTC genetic tests that make medical claims. This review provides a brief overview of DTC advertising and the regulation of pharmaceuticals and genetic tests in the United States. It highlights recent changes in the regulatory culture regarding genetic tests that are sold to consumers, and discusses the impact on health care providers of selling and advertising genetic tests directly to consumers. © 2011 BioMed Central Ltd.

McCullumsmith R.E.,University of Cincinnati
Molecular Psychiatry | Year: 2015

Excitatory amino-acid transporters (EAATs) bind and transport glutamate, limiting spillover from synapses due to their dense perisynaptic expression primarily on astroglia. Converging evidence suggests that abnormalities in the astroglial glutamate transporter localization and function may underlie a disease mechanism with pathological glutamate spillover as well as alterations in the kinetics of perisynaptic glutamate buffering and uptake contributing to dysfunction of thalamo-cortical circuits in schizophrenia. We explored this hypothesis by performing cell- and region-level studies of EAAT1 and EAAT2 expression in the mediodorsal nucleus of the thalamus in an elderly cohort of subjects with schizophrenia. We found decreased protein expression for the typically astroglial-localized glutamate transporters in the mediodorsal and ventral tier nuclei. We next used laser-capture microdissection and quantitative polymerase chain reaction to assess cell-level expression of the transporters and their splice variants. In the mediodorsal nucleus, we found lower expression of transporter transcripts in a population of cells enriched for astrocytes, and higher expression of transporter transcripts in a population of cells enriched for relay neurons. We confirmed expression of transporter protein in neurons in schizophrenia using dual-label immunofluorescence. Finally, the pattern of transporter mRNA and protein expression in rodents treated for 9 months with antipsychotic medication suggests that our findings are not due to the effects of antipsychotic treatment. We found a compensatory increase in transporter expression in neurons that might be secondary to a loss of transporter expression in astrocytes. These changes suggest a profound abnormality in astrocyte functions that support, nourish and maintain neuronal fidelity and synaptic activity.Molecular Psychiatry advance online publication, 29 September 2015; doi:10.1038/mp.2015.148. © 2015 Macmillan Publishers Limited

Owen L.A.,University of Cincinnati
Geological Society Special Publication | Year: 2010

The Himalayan-Tibetan orogen provides one of the best natural laboratories in which to examine the nature and dynamics of landscape development within continent-continent collision zones. Many new tectonic-climatic-geomorphological theories and models have emerged and/or have been greatly influenced as a consequence of the study of the region and the quest to understand its geomorphological development. These include models of the interactions between tectonics, climate and surfice processes, notably, the influence of climate on surface uplift by denudational unloading; the limiting of topography by glaciation (the glacial buzz-saw model); localized uplift at syntaxes by enhanced fluvial and glacial erosion that, in turn, weaken the lithosphere, enhancing surface uplift and exhumation (the tectonic aneurysm model); climate-driven out-of-sequence thrusting and crustal channel flow; glacial damming leading to differential erosion and uplift; paraglaciation; and the influence of extreme events such as earthquakes, landslides, and floods as major formative processes. The development of new technologies, including satellite remote sensing and global positioning systems, and analytical methods such as numerical dating is now allowing these theories and models to be tested and will inevitably lead to new paradigms. © 2010 The Geological Society of London.

Despa S.,University of California at Davis | Lingrel J.B.,University of Cincinnati | Bers D.M.,University of California at Davis
Cardiovascular Research | Year: 2012

Aims Na+/K+-ATPase (NKA) is essential in regulating [Na+]i, and thus cardiac myocyte Ca2+ and contractility via Na+/Ca2+ exchange. Different NKA-α subunit isoforms are present in the heart and may differ functionally, depending on specific membrane localization. In smooth muscle and astrocytes, NKA-α2 is located at the junctions with the endo(sarco)plasmic reticulum, where they could regulate local [Na+], and indirectly junctional cleft [Ca 2+]. Whether this model holds for cardiac myocytes is unclear. Methods and resultsThe ouabain-resistant NKA-α1 cannot be selectively blocked to assess its effect. To overcome this, we used mice in which NKA-α1 is ouabain sensitive and NKA-α2 is ouabain resistant (SWAP mice). We measured the effect of ouabain at low concentration on [Na +]i, Ca2+ transients, and the fractional sarcoplasmic reticulum (SR) Ca2+ release in cardiac myocytes from wild-type (WT; NKA-α2 inhibition) and SWAP mice (selective NKA-α1 block). At baseline, Na+ and Ca2+ regulations are similar in WT and SWAP mice. For equal levels of total NKA inhibition (∼25%), ouabain significantly increased Ca2+ transients (from ΔF/F0 1.5 ± 0.1 to 1.8 ± 0.1), and fractional SR Ca2+ release (from 24 ± 3 to 29 ± 3) in WT (NKA-α2 block) but not in SWAP myocytes (NKA-α1 block). This occurred despite a similar and modest increase in [Na+]i (∼2 mM) in both groups. The effect in WT mice was mediated specifically by NKA-α2 inhibition because at a similar concentration ouabain had no effect in transgenic mice where both NKA-α1 and NKA-α2 are ouabain resistant. ConclusionNKA-α2 has a more prominent role (vs. NKA-α1) in modulating cardiac myocyte SR Ca 2+ release. © 2012 The Author.

Gillespie G.L.,University of Cincinnati
Journal of trauma nursing : the official journal of the Society of Trauma Nurses | Year: 2013

Some emergency nurses are resilient following trauma patient care, while others report severe traumatic stress. The purpose of this study was to determine proactive coping behaviors used by emergency nurses to prevent traumatic stress. A cross-sectional research design was used with a national sample of emergency nurses. Participants completed a 5-component Web-based survey. Data analyses included 1-tailed partial correlations. The correlation of proactive coping score to traumatic stress was significant. Proactive coping strategies that focus on the planning and preparation to provide care for traumatically injured patients may be effective at preventing traumatic stress.

Almost all economic manganese ores are ultimately or directly derived from hydrothermal vents associated with intermediate volcanic rocks. This source is in contrast to deep-sea nodules, which likely have a larger component of sediment-derived manganese and whose volcanic sources are more mafic. Manganese deposits can be divided into sedimentary rock-hosted, volcanic rock-hosted and karst-hosted, in order of predominance. Two genetic types of sedimentary rock-hosted deposits can also be identified: those with Mn derived via upwelling from oxygen-minimum zones and those formed on the margins of euxinic basins. Most of the large tonnage deposits appear to form by the euxinic mechanism. Manganese ores, like those of Fe, show a strong concentration of deposits in the Paleoproterozoic and a lesser occurrence in the Neoproterozoic, but, unlike Fe, there is an additional strong peak in the Oligocene. Therefore, Mn is not controlled entirely by the level of oxygen in the Earths atmosphere. At each peak of Mn deposition, the associated ore deposits are concentrated in a few districts, suggesting a more local than global control on manganese metallogenesis. Age trends can, however, be discerned in some chemical properties of manganese deposits. Overall, there is a trend to progressive increases in chemical diversity from the Archean to the Recent, with a particularly steep increase in the Neoproterozoic-Early Cambrian, corresponding in time to the radiation of metazoans. Also beginning in the Cambrian is the development of upwelling-linked deposits. There is another sharp increase in chemical diversity at the Jurassic-Cretaceous boundary, which includes increased SiO2/Al2O3 ratios and corresponds to the radiation of diatoms. There is a conspicuous gap in sedimentary rock-hosted Mn deposits between 1800 and 800 Ma that may correspond to a monotonous, low-oxygen ocean, but one without sulfidic deep water. Alternatively, Mn may have been precipitated entirely in the deep ocean, beneath a sulfidic oxygen minimum layer. The positive Eu anomalies, which in iron formations are equated to vent-sourced metals, are not seen in most Mn deposits, although they are found in Mn-rich iron formations. By contrast, Fe deposits interbedded with major Mn ores lack the usual Eu signal. Therefore, mechanisms of transport between hydrothermal vents and the sites of deposition differed for Fe and for Mn deposits in the Archean-Paleoproterozoic. The dominant pattern in the time trend of Mn deposition is increasing chemical diversity, which reflects an increasing compartmentalization of the Earth's depositional environments. This compartmentalization was a response to, but also provided a spur to, the diversification of life forms. © 2010 Society of Economic Geologists, Inc.

Grossman A.W.,University of Cincinnati
Annals of neurology | Year: 2013

We review recent advances in the treatment and prevention of acute ischemic stroke, including the current state of endovascular therapy, in light of 5 randomized controlled trials published this past year. Although no benefit of endovascular therapy over intravenous (IV) recombinant tissue plasminogen activator (rt-PA) has been demonstrated, endovascular therapy is an appropriate treatment for acute ischemic stroke patients within the t-PA window who are ineligible for IV t-PA but have a large vascular occlusion. These trials reveal promises and current limitations of endovascular therapy, and comparison of reperfusion therapies remains an important area of research. One common theme is the strong association between a faster time to reperfusion, improved outcome, and reduced mortality. Primary and secondary stroke prevention trials emphasize the importance of aggressive management of medical risk factors as part of any preventative strategy. New oral anticoagulants, for example, offer cost-effective risk reduction in patients with atrial fibrillation, and may represent an opportunity for those with cryptogenic stroke. We highlight areas of unmet need and promising research in stroke, including the need to deliver proven therapies to more patients, and the need to recruit patients into clinical trials that better define the role of endovascular and other stroke therapies. Finally, improvement in strategies to recover speech, cognition, and motor function has the potential to benefit far more stroke patients than any acute stroke therapy, and represents the greatest opportunity for research in the coming century. Copyright © 2013 American Neurological Association.

Sweets T.M.,University of Tennessee at Chattanooga | Stern P.J.,University of Cincinnati
Journal of Bone and Joint Surgery - Series A | Year: 2011

Background: Pyrolytic carbon resurfacing arthroplasty of the proximal interphalangeal joint has been reported to provide favorable results. The purpose of this study was to evaluate the effectiveness of pyrolytic carbon joint replacement at an average follow-up of fifty-five months. Methods: A retrospective review of thirty-one arthroplasties of the proximal interphalangeal joint performed by a single surgeon in seventeen patients with interphalangeal joint osteoarthritis was conducted. Assessment included range of motion, patient satisfaction, and pain scores. Radiographs were evaluated for alignment, implant subsidence, and implant failure. The Michigan Hand Outcomes Questionnaire was administered at the time of the final follow-up. Results: The average follow-up period was fifty-five months (minimum, two years). No patient was lost to follow-up. The arc of motion of the interphalangeal joint decreased from 57° preoperatively to 31° (p < 0.05) at the time of the final followup. The average score for pain was 3 of 10 on a visual analog scale. Satisfaction averaged 3.4 points on a 5-point Likert scale, and twelve of seventeen patients stated that they would repeat the surgery. Data from the Michigan Hand Outcomes Questionnaire were compared for the involved and noninvolved hands of the fifteen patients who received implants unilaterally. Significant deficits were observed in the total outcome score, activities of daily living, function, and satisfaction for the operatively treated hand. Pain was also greater in the operatively treated hand. Complications included implant fracture (one joint), dislocation (five joints), squeaking (eleven), loosening (fifteen), and interphalangeal joint contracture (twenty). Six joints required a reoperation (an arthrodesis in four joints, a silicone arthroplasty in one, and excision of exostosis in one). Implant migration was severe for seven proximal phalanx implants and three distal phalanx implants, and one implant breached the phalangeal cortex. Conclusions: Interphalangeal joint motion decreased significantly at the final follow-up evaluation, following short-term gains in the initial postoperative period. Complications were numerous, and implant loosening with migration was a major problem. Arthroplasty of the proximal interphalangeal joint with a pyrolytic carbon implant has a high complication rate, poor outcomes, and variable patient satisfaction. On the basis of these findings, we no longer use this implant in our practice. Level of Evidence: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence. Copyright © 2011 by The Journal of Bone and Joint Surgery, Incorporated.

Diab D.L.,University of Cincinnati | Watts N.B.,Mercy Health Osteoporosis and Bone Health Services
Current Opinion in Endocrinology, Diabetes and Obesity | Year: 2013

There are numerous effective pharmacologic treatment options for postmenopausal osteoporosis. Bisphosphonate drug holidays continue to be an area of significant debate. ©2013 Wolters Kluwer Health Lippincott Williams & Wilkins.

Gamis A.S.,Childrens Mercy Hospitals and Clinics | Smith F.O.,University of Cincinnati
British Journal of Haematology | Year: 2012

Children with trisomy 21 have a unique predisposition to develop a megakaryoblastic proliferative disease of varying severity during their first 3 months of life. This disorder exists in no other children or adults without the presence of trisomy 21 and only occurs in the fetal or neonatal period of life. Its spontaneous resolution in most cases further delineates it from otherwise indistinguishable neonatal leukaemias. The identification that GATA1 mutations are the leukaemogenic source along with three recently reported prospective clinical trials now provide a clearer understanding of this haematopoietic disorder. These recent advances in this enigmatic disorder, now known as Transient Myeloproliferative Disorder, are reviewed here in order to bring clarity to the breadth of organ involvement, the range of severity, the risk factors for mortality, the therapeutic options for severe manifestations, the natural course of spontaneous resolution regardless of therapy, and the elucidation of the subsequent risk for myeloid leukaemia. © 2012 Blackwell Publishing Ltd.

Sandoval D.,University of Cincinnati
International Journal of Obesity | Year: 2011

Behavioral and pharmaceutical intervention to treat obesity and its comorbidities typically results in only a 5-10% weight loss. Thus, bariatric surgery is the most effective obesity treatment with some surgeries resulting in 30% sustained weight loss. Although this degree of weight loss has profound metabolic impact, these surgeries seem to have metabolic effects that are independent of weight loss. In support of this is the clinical literature showing rapid resolution of Type 2 diabetes mellitus (T2DM) that occurs before significant weight loss. To gain a complete understanding of the weight loss-independent effects of bariatric surgery, animal models have been developed. These are becoming more widely implemented and allow the use of pair-fed or weight-matched sham-operated controls in order to gain mechanistic insights into the mode of action of bariatric surgery. Increases in anorectic gut hormones, such as glucagon-like peptide-1 and peptide YY, or decreases in the orexigenic hormone ghrelin have been seen and are implicated as mediators of weight loss-independent actions of bariatric surgery. Changes in nutrient processing and sensing may also have a mechanistic role that is independent of, or that regulates, gut hormone responses to these surgeries. Ultimately, the hope is that understanding the mechanisms of bariatric surgeries will aid in the development of less invasive surgeries or pharmacological therapies that are more specifically, and perhaps individually, targeted at weight loss and/or resolution of T2DM. © 2011 Macmillan Publishers Limited All rights reserved.

Beck T.L.,University of Cincinnati
Journal of Statistical Physics | Year: 2011

In the quasichemical theory of molecular solutions, the hydration free energy is spatially partitioned in a three-step thermodynamic process: cavity formation, solute insertion into the cavity, and relaxation of the cavity constraint. In the alternative local molecular field theory that focuses on the relationship of fluid structure and forces, the interaction energies are directly partitioned into local and far-field components; a restructured local potential incorporates information from the far-field interactions at the mean-field level. Here the quasichemical and local molecular field theories are related via energetic partitioning of the potential distribution theorem free energy. The resulting theory leads to a free energy division in which the local contribution requires direct evaluation, but the far-field component can be accurately estimated at the Gaussian level. A numerical approach for computing hydration free energies is developed that employs interaction energy distributions from several sampling states. Classical model problems of nonpolar, polar, and ionic hydration are presented to illustrate the theory. Extensions of the theory for estimating free energies at the quantum level are also discussed. © 2011 Springer Science+Business Media, LLC.

Maume D.J.,University of Cincinnati
Journal of Health and Social Behavior | Year: 2013

Teens tend go to bed later, get less sleep, and report more daytime sleepiness. Medical research emphasizes biological determinants of teens' disrupted sleep (i.e., the timing of puberty and resultant drops in melatonin), rarely or inadequately considering youths' social ties as a determinant of sleep behaviors. Sociologists recognize how social ties affect health behaviors but have generally neglected sleep, especially among teens. Drawing on a sample of 974 teens from the Study of Early Child Care and Youth Development, this study controls for developmental and social relational factors to predict changes in youths' sleep patterns between 12 and 15 years of age. In general, social relational factors outperform developmental factors in determining youths' sleep patterns, particularly pointing to the importance of parental, peer, and school ties in promoting healthy sleep behaviors. The implications of these findings for further research are briefly discussed. © American Sociological Association 2013.

Mcleish A.C.,University of Cincinnati | Zvolensky M.J.,University of Vermont
Journal of Asthma | Year: 2010

The purpose of this review paper is to present and evaluate the empirical literature on the association between asthma and cigarette smoking. The authors conducted a literature search utilizing electronic search engines (i.e., PsycINFO and MEDLINE) to examine databases using the following key word algorithms: smoking OR nicotine OR tobacco AND asthma. Only articles that focused on active tobacco smoking and analyzed groups with asthma patients only were examined in the present review. Overall, empirical evidence suggests that (1) smoking is more prevalent among individuals with asthma than those without; (2) smoking is a risk candidate for the development of asthma; (3) smoking is associated with decreased asthma control and increased risk of mortality and asthma attacks and exacerbations; (4) smokers with and without asthma may have different risk factors for smoking onset as well as different smoking motives and outcome expectancies; and (5) smoking cessation is associated with improvements in lung functioning and asthma symptoms. Future work in this domain of study will lead to clinically relevant health care advances as well as the development of theoretically driven, methodologically diverse lines of research exploring asthma-smoking comorbidity issues. Copyright © 2010 Informa Healthcare USA, Inc.

Agabegi S.S.,University of Cincinnati | Fischgrund J.S.,27207 Lahser Rd
Spine Journal | Year: 2010

Background: Isthmic spondylolisthesis is common in pediatric and adult patients. Most cases are asymptomatic. When symptomatic, nonsurgical treatment is an appropriate first step. Surgical treatment of this condition varies depending on patient age, degree of slip, presence of neurologic findings, and degree of deformity. Purpose: To review the literature on the management of isthmic spondylolisthesis in pediatric and adult patients. Study Design: Review article. Methods: Literature review. Results and Conclusions: Achieving a solid fusion leads to improved functional outcomes and reduction in pain. A circumferential fusion is associated with a higher fusion rate and has become more common, especially with high-grade slips. The need for reduction is controversial and is mostly indicated for patients with significant lumbosacral kyphosis and sagittal imbalance. © 2010 Elsevier Inc. All rights reserved.

Beck T.L.,University of Cincinnati
Journal of Physical Chemistry B | Year: 2011

Monovalent ion hydration entropies are analyzed via energetic partitioning of the potential distribution theorem free energy. Extensive molecular dynamics simulations and free energy calculations are performed over a range of temperatures to determine the electrostatic and van der Waals components of the entropy. The far-field electrostatic contribution is negative and small in magnitude, and it does not vary significantly as a function of ion size, consistent with dielectric models. The local electrostatic contribution, however, varies widely as a function of ion size; the sign yields a direct indication of the kosmotropic (strongly hydrated) or chaotropic (weakly hydrated) nature of the ion hydration. The results provide a thermodynamic signature for specific ion effects in hydration and are consistent with experiments that suggest minimal perturbations of water structure outside the first hydration shell. The hydration entropies are also examined in relation to the corresponding entropies for the isoelectronic rare gas pairs; an inverse correlation is observed, as expected from thermodynamic hydration data. © 2011 American Chemical Society.

Molkentin J.D.,University of Cincinnati
Circulation Research | Year: 2013

Nine years ago, we published an article that suggested a specialized role for calcineurin-nuclear factor of activated T-cells (NFAT) signaling in regulating pathological cardiac hypertrophy preferentially over physiological growth and, in fact, the later response was associated with reduced calcineurin-NFAT activity. Since this time we and others have continued to uncover how this signaling effector pathway functions in the heart in regulating specific aspects of the growth response during disease and with exercise.

Rose S.R.,University of Cincinnati
Nature Reviews Endocrinology | Year: 2016

The cure rate for paediatric malignancies is increasing, and most patients who have cancer during childhood survive and enter adulthood. Surveillance for late endocrine effects after childhood cancer is required to ensure early diagnosis and treatment and to optimize physical, cognitive and psychosocial health. The degree of risk of endocrine deficiency is related to the child's sex and their age at the time the tumour is diagnosed, as well as to tumour location and characteristics and the therapies used (surgery, chemotherapy or radiation therapy). Potential endocrine problems can include growth hormone deficiency, hypothyroidism (primary or central), adrenocorticotropin deficiency, hyperprolactinaemia, precocious puberty, hypogonadism (primary or central), altered fertility and/or sexual function, low BMD, the metabolic syndrome and hypothalamic obesity. Optimal endocrine care for survivors of childhood cancer should be delivered in a multidisciplinary setting, providing continuity from acute cancer treatment to long-term follow-up of late endocrine effects throughout the lifespan. Endocrine therapies are important to improve long-term quality of life for survivors of childhood cancer. © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

Zalta A.H.,University of Cincinnati
Ophthalmic Surgery Lasers and Imaging | Year: 2012

■ BACKGROUND AND OBJECTIVE: To report the long-term incidence, timing, and experience of patch graft failure (PGF) after Ahmed Glaucoma Valve (AGV) (New World Medical, Inc., Rancho Cucamonga, CA) surgery in a large consecutive case series using donor dura mater and sclera sequentially as the allograft materials. ■ PATIENTS AND METHODS: The medical records of all AGV surgeries performed from June 1994 through December 2010 were retrospectively reviewed for cases of PGF. ■ RESULTS: Patch graft failure occurred in 44 (6.3%) of the initial 695 procedures using dura and in 65 (5.8%) of the subsequent 1,121 procedures using sclera (P = .64). The time interval after AGV surgery until the occurrence of PGF was significantly longer for dura (5.8 ± 3.8 years) than for sclera (2.7 ± 1.9 years) (P < .001). ■ CONCLUSION: After an average of 4 years, PGF occurred in 109 (6%) of 1,816 consecutive AGV surgeries using donor dura and sclera allografts. PGF may be the most frequent long-term complication after AGV surgery. Copyright © SLACK Incorporated.

Kaplan J.M.,Foundation Medicine | Wong H.R.,University of Cincinnati
Pediatric Critical Care Medicine | Year: 2011

Objectives: To frame the general process of biomarker discovery and development; and to describe a proposal for the development of a multibiomarker-based risk model for pediatric septic shock. Data Source: Narrative literature review and author-generated data. Data Selection: Biomarkers can be grouped into four broad classes, based on the intended function: diagnostic, monitoring, surrogate, and stratification. Data Extraction And Synthesis: Biomarker discovery and development requires a rigorous process, which is frequently not well followed in the critical care medicine literature. Very few biomarkers have successfully transitioned from the candidate stage to the true biomarker stage. There is great interest in developing diagnostic and stratification biomarkers for sepsis. Procalcitonin is currently the most promising diagnostic biomarker for sepsis. Recent evidence suggested that interleukin-8 can be used to stratify children with septic shock having a high likelihood of survival with standard care. Currently, there is a multi-institutional effort to develop a multibiomarker-based sepsis risk model intended to predict outcome and illness severity for individual children with septic shock. Conclusions: Biomarker discovery and development are an important portion of the pediatric critical care medicine translational research agenda. This effort will require collaboration across multiple institutions and investigators. Rigorous conduct of biomarker-focused research holds the promise of transforming our ability to care for individual patients and our ability to conduct clinical trials in a more effective manner. Copyright © 2011 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

Asghar F.A.,University of Cincinnati | Hilibrand A.S.,Thomas Jefferson University
Journal of the American Academy of Orthopaedic Surgeons | Year: 2012

The benefits of spinal surgery for relief of low back and leg pain in patients with degenerative spinal disorders have long been debated. The Spine Patient Outcomes Research Trial (SPORT) was designed to address the need for high-quality, prospectively collected data in support of such interventions. SPORT was intended to provide an evidential basis for spinal surgery in appropriate patients, as well as comparative and cost-effectiveness data. The trial studied the outcomes of the surgical and nonsurgical management of three conditions: intervertebral disk herniation, degenerative spondylolisthesis, and lumbar spinal stenosis. Both surgical and nonsurgical care of intervertebral disk herniation resulted in significant improvement in symptoms of low back and leg pain. Still, the treatment effect of surgery for intervertebral disk herniation was less than that seen in patients who underwent surgical versus nonsurgical treatment of degenerative spondylolisthesis and lumbar spinal stenosis. Across SPORT, more significant degrees of improvement with surgery were noted in chronic conditions of lumbar spinal stenosis and lumbar spinal stenosis with spondylolisthesis. In addition, no catastrophic progressions to neurologic deficit occurred as a result of watchful waiting.

Ghulmiyyah L.,American University of Beirut | Sibai B.,University of Cincinnati
Seminars in Perinatology | Year: 2012

Preeclampsia/eclampsia is one of the 3 leading causes of maternal morbidity and mortality worldwide. During the past 50 years, there has been a significant reduction in the rates of eclampsia, maternal mortality, and maternal morbidity in the developed countries. In contrast, the rates of eclampsia, maternal complications, and maternal mortality remain high in the developing countries. These differences are mainly due to universal access to prenatal care, access to timely care, and proper management of patients with preeclampsia-eclampsia in the developed countries. In contrast, most of maternal deaths and complications are due to lack of prenatal care, lack of access to hospital care, lack of resources, and inappropriate diagnosis and management of patients with preeclampsia-eclampsia in the developing countries. Preeclampsia/eclampsia is associated with substantial maternal complications, both acute and long-term. Clear protocols for early detection and management of hypertension in pregnancy at all levels of health care are required for better maternal as well as perinatal outcome. This is especially important in the developing countries. © 2012 Elsevier Inc.

Nguyen-Xuan H.,University of science | Liu G.R.,University of Cincinnati
Computers and Structures | Year: 2013

The edge-based smoothed finite element method (ES-FEM) was recently proposed to improve the performance of linearly triangular finite element models for mechanics problems. Such a good performance is attributed to the right amount softening induced by the edge-based smoothing operation. In this paper, we propose an improved formulation of the ES-FEM so that the bES-FEM can be further softened becoming volumetric locking free and hence works well also incompressible or nearly incompressible problems. The improved formulation uses the usual piecewise linear displacements but is supplemented with a cubic bubble function in triangular elements, which induces further softening to the bilinear form allowing the weakened weak (W2) procedure to search for a solution satisfying the divergence-free conditions. The smoothed strains are evaluated based on smoothing domains associated with edges of the adjacent elements as in the ES-FEM. The divergence-free condition of the bES-FEM is verified via detailed eigenvalue analyses. Several numerical examples are provided to show the effectiveness and reliability of the present method. We also show numerically that the present element is insensitive to mesh distortion and is superior to the bubble finite element (MINI element) in the incompressible limit. © 2013 Elsevier Ltd. All rights reserved.

Skipper R.A.,University of Cincinnati
Public Health Ethics | Year: 2012

This article draws on scientific explanations of obesity to motivate the creation of a system of paternalistic public health interventions into the obesity epidemic. Libertarian paternalists argue that paternalism is warranted in light of the cognitive limits of human decision-making abilities. There are further, specific biological limits on our capacity to choose and maintain a healthy diet. These biological facts strengthen the general motivation for libertarian paternalism. As a consequence, the creation of a system of paternalistic public health interventions into the obesity epidemic is warranted. © The Author 2012. Published by Oxford University Press.

Dey S.K.,University of Cincinnati
Journal of Clinical Investigation | Year: 2010

Human reproduction is relatively inefficient. Nearly 30% of pregnancies result in spontaneous losses, which are both a clinical problem and a psychological stress to the families involved. Furthermore, although the human population is growing rapidly and is predicted to reach 9 billion by 2050, 15% of couples worldwide are childless because of infertility. Many underlying causes of infertility have been overcome by assisted reproductive technologies such as in vitro fertilization, yet pregnancy success rates using such approaches remain disappointingly low. Since mechanistic approaches to study human reproductive processes are ethically restricted, future advances in fertility treatment and the development of new contraceptives rely predominantly on the study of the factors influencing reproduction in model systems. The articles in this Reproductive Biology Review series present updates on the current understanding of various reproductive processes in model systems and raise questions that need to be addressed if we are to improve human reproductive health.

Breech L.,University of Cincinnati
Seminars in Pediatric Surgery | Year: 2010

Children with anorectal malformations (ARMs) constitute a significant group within a pediatric surgery practice. In females, the most common ARM is an imperforate anus with a rectovestibular fistula, followed by an imperforate anus with a rectoperineal fistula and then cloacal anomalies. Some malformations, such as an imperforate anus with a rectovestibular fistula, may seem straightforward, treated with a posterior sagittal anorectoplasty; however, it is vital to recognize the association with gynecologic anomalies. Girls with the most complex anorectal defect, cloacal malformation, have significant associated urological and gynecologic anomalies, which should be recognized and treated. An opportunity to diagnose and treat such anomalies may be missed in the newborn period or at the definitive surgery, unless the pediatric surgeon is aware of this association. With the knowledge of the associated anomalies and long-term sequelae, surgeons can provide better care for girls and important counseling for parents. Important gynecologic issues to consider may be divided into several categories, such as infancy, puberty, sexual intimacy, and obstetrical concerns. Knowledge of reproductive-related issues in females with ARMs allows the pediatric surgeon and their gynecology colleagues to provide optimal surgical management throughout infancy, childhood, and into young adulthood. Appropriate counseling for patients and families about potential reproductive concerns that may develop many years after the definitive surgical repair allows preparation and planning to preserve future fertility. © 2010 Elsevier Inc.

The activity of protein phosphatase-1 (PP1) inhibitor-1 (I-1) is antithetically modulated by the cAMP-protein kinase A (PKA) and Ca(2+)-protein kinase C (PKC) signaling axes. β-adrenergic (β-AR) stimulation results in PKA-phosphorylation of I-1 at threonine 35 (Thr35) and depressed PP1 activity, while PKC phosphorylation at serine 67 (Ser67) and/or Thr75 increases PP1 activity. In heart failure, pThr35 is decreased while pSer67 and pThr75 are elevated. However, the role of Ser67/Thr75 phosphorylation in vivo and its effects on Ca(2+)-cycling are not known. Thus, our aim was to investigate the functional significance of Ser67 and Thr75 phosphorylation in intact hearts. We generated transgenic mice (TG) with cardiac-specific overexpression of constitutively phosphorylated I-1 at Ser67 and Thr75 (S67D/T75D) and evaluated cardiac function. The S67D/T75D cardiomyocytes exhibited significantly depressed Ca(2+)-kinetics and contractile parameters, compared with wild-type (WT) cells. The decreased Ca(2+)-cycling was associated with a 27 % increase in PP1 activity, no alterations in PP2 activity and impaired phosphorylation of myosin-binding protein-C (MyBPC). Upon aging, there was cardiac remodeling associated with increases in systolic and diastolic left ventricular internal diameter dimensions (at 16 months), compared with WTs. The results indicate that phosphorylation of I-1 at Ser67 and Thr75 is associated with increased PP1 activity and depressed cardiomyocyte Ca(2+)-cycling, which manifests in geometrical alterations over the long term. Thus, hyperphosphorylation of these sites in failing hearts may contribute to deteriorative remodeling.

Stalcup A.M.,University of Cincinnati
Annual Review of Analytical Chemistry | Year: 2010

The main goal of this review is to provide a brief overview of chiral separations to researchers who are versed in the area of analytical separations but unfamiliar with chiral separations. To researchers who are not familiar with this area, there is currently a bewildering array of commercially available chiral columns, chiral derivatizing reagents, and chiral selectors for approaches that span the range of analytical separation platforms (e.g., high-performance liquid chromatography, gas chromatography, supercritical-fluid chromatography, and capillary electrophoresis). This review begins with a brief discussion of chirality before examining the general strategies and commonalities among all of the chiral separation techniques. Rather than exhaustively listing all the chiral selectors and applications, this review highlights significant issues and differences between chiral and achiral separations, providing salient examples from specific classes of chiral selectors where appropriate. Copyright © 2010 by Annual Reviews. All rights reserved.

Defranco E.A.,University of Cincinnati | Defranco E.A.,Perinatal Institute | Lewis D.F.,University of South Alabama | Odibo A.O.,Washington University in St. Louis
American Journal of Obstetrics and Gynecology | Year: 2013

Objective: Our objective was to systematically review the current medical literature to assess the accuracy of the combination of fetal fibronectin (fFN) plus ultrasound assessment of cervical length (CL) as screening tools for preterm labor and prediction of preterm birth (PTB), and to compare this to the traditional clinical method of digital cervical examination. Study Design: We searched PubMed and Cochrane databases without date restriction using the key words "fibronectin" and "cervical length," limited to human studies published in English. In all, 85 studies were identified and supplemented by 1 additional study found through bibliographic search. Results: Nine studies reported the association between fFN positivity plus CL measurement with PTB in women presenting with symptomatic uterine contractions. We conducted an analytic review of the sensitivity, specificity, positive predictive value, and negative predictive value of fFN plus CL for PTB. Further metaanalysis was not performed due to study heterogeneity, especially with respect to the range of gestational ages and variations in cutoff values for the diagnosis of short cervix. Although the clinical diagnostic methodology of preterm labor diagnosis by documenting uterine contractions plus cervical change is currently standard practice, a newer approach combining fFN and CL screening results in a higher sensitivity and positive predictive value for PTB risk while maintaining high negative predictive value. Conclusion: We conclude that this combined screening approach yields useful information regarding short-term risks that can be used to guide acute management, and effectively identifies a population at low risk in whom expensive and potentially dangerous interventions could be avoided. © 2013 Mosby, Inc.

Itri J.N.,University of Cincinnati
Radiographics | Year: 2015

Patient-centered care (ie, care organized around the patient) is a model in which health care providers partner with patients and families to identify and satisfy patients’ needs and preferences. In this model, providers respect patients’ values and preferences, address their emotional and social needs, and involve them and their families in decision making. Radiologists have traditionally been characterized as “doctor-to-doctor” consultants who are distanced from patients and work within a culture that does not value patient centeredness. As medicine becomes more patient driven and the trajectory of health care is toward increasing patient self-reliance, radiologists must change the perception that they are merely consultants and become more active participants in patient care by embracing greater patient interaction. The traditional business model for radiology practices, which devalues interaction between patients and radiologists, must be transformed into a patient-centered model in which radiologists are reintegrated into direct patient care and imaging processes are reorganized around patients’ needs and preferences. Expanding radiology’s core assets to include direct patient care may be the most effective deterrent to the threat of commoditization. As the assault on the growth of Medicare spending continues, with medical imaging as a highly visible target, radiologists must adapt to the changing landscape by focusing on their most important consumer: the patient. This may yield substantial benefits in the form of improved quality and patient safety, reduced costs, higher-value care, improved patient outcomes, and greater patient and provider satisfaction. © RSNA, 2015.

Yamanaka O.,University of Cincinnati
Endocrine, metabolic & immune disorders drug targets | Year: 2010

The anterior segment of the eye ball, i. e., cornea and conjunctiva, serves as the barrier to the external stimuli. Cornea is transparent and is a "window"of the light sense, while conjunctiva covers the sclera, the main part of the eyeshell. Fibrosis/scarring in cornea potentially impairs vision by the reduction of its transparency and the alteration of the regular curvature. Fibrotic reaction in conjunctiva is also of a clinical importance because inflammatory fibrosis in this tissue affects the physiology of the cornea and also of a problem post-eye surgery. In this review we discuss on the topic that is quite critical in vision. Although various growth factors are considered to be involved in, focus was put on the roles of transforming growth factorβ (TGFβ).

Jobe A.H.,University of Cincinnati
Pediatrics and Neonatology | Year: 2010

The increased survival of very preterm infants is generally attributed to improved care strategies. This review develops the thesis that the features of abnormal pregnancies responsible for very preterm deliveries also provide an explanation of why very preterm infants often survive. A normal fetus born at 24 weeks is very unlikely to survive. However, pregnancies that result in deliveries at 24 weeks are generally highly abnormal, and may have been so for prolonged periods prior to the preterm deliveries. Inflammatory or vascular developmental abnormalities resulting in very preterm birth can alter fetal development in such a way that organ system maturation is induced. This is supported clinically by the relative lack of very preterm infants with respiratory distress syndrome. Interventions such as antenatal corticosteroid treatment and postnatal surfactant treatment for infants with respiratory distress syndrome and gentle ventilation strategies maximize fetal adaptations to the abnormal fetal environment and improve outcomes. © 2010 Taiwan Pediatric Association.

Van Aalst J.A.,University of Cincinnati
Journal of Craniofacial Surgery | Year: 2015

The history of cleft care in the Palestinian territories has largely been sporadic and dependent on foreign practitioners. This article discusses the recent history and the current status of cleft care in Palestine, including the quality of training among Palestinian cleft practitioners and limitations in operating room capacity. The discussion concludes with a future model of cleft care that focuses on carefully crafted programs to train surgeons (this is broadly applicable to other disciplines involved in cleft care), working in partnership with a designated National Cleft Organization, operationalized within a centrally located and accessible Cleft Center. © 2015 Mutaz B. Habal, MD.

Hui D.Y.,University of Cincinnati
Current Opinion in Lipidology | Year: 2016

PURPOSE OF REVIEW: Phospholipids are major constituents in the intestinal lumen after meal consumption. This article highlights current literature suggesting the contributory role of intestinal phospholipid metabolism toward cardiometabolic disease manifestation. RECENT FINDINGS: Group 1b phospholipase A2 (PLA2g1b) catalyzes phospholipid hydrolysis in the intestinal lumen. The digestive product lysophospholipid, particularly lysophosphatidylcholine (LPC), has a direct role in mediating chylomicron assembly and secretion. The LPC in the digestive tract is further catabolized into lysophosphatidic acid and choline via autotaxin-mediated and autotaxin-independent mechanisms. The LPC and lysophosphatidic acid absorbed through the digestive tract and transported to the plasma directly promote systemic inflammation and cell dysfunction, leading to increased risk of cardiovascular disease and obesity/diabetes. The choline moiety generated in the digestive tract can also be used by gut bacteria to generate trimethylamine, which is subsequently transported to the liver and oxidized into trimethylamine-N-oxide that also enhances atherosclerosis and cardiovascular abnormalities. SUMMARY: Products of phospholipid metabolism in the intestine through PLA2g1b and autotaxin-mediated pathways directly contribute to cardiometabolic diseases through multiple mechanisms. The implication of these studies is that therapeutic inhibition of PLA2g1b and autotaxin in the digestive tract may be a viable approach for cardiovascular and metabolic disease intervention. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

Huppert J.S.,University of Cincinnati
Dermatologic Therapy | Year: 2010

Acute genital ulcers are painful and distressing to women and perplexing to the providers who care for them. The differential diagnosis includes sexually and nonsexually transmitted infections, autoimmune conditions, drug reactions, and local manifestations of systemic illness. However, in many cases, no causative agent is identified, and lesions are classified as idiopathic aphthosis. In the setting of fever and acute onset of genital ulcers in girls and women, the term Lipschutz ulcers has been used to describe ulcers associated with an immunologic reaction to a distant source of infection or inflammation. The aims of this article are to review the differential diagnosis and pathogenesis of acute genital ulcers, to offer an evaluation and classification scheme, and to discuss treatment options for the dermatologist who cares for women and girls with vulvar ulcers. © 2010 Wiley Periodicals, Inc.

Geiger H.,University of Ulm | Geiger H.,University of Cincinnati | Denkinger M.,University of Ulm | Schirmbeck R.,University of Ulm
Current Opinion in Immunology | Year: 2014

Aging is organized in a hierarchy, in which aging of cells results in aged tissues, ultimately limiting lifespan. For organ systems that also in the adult depend on stem cells for tissue homeostasis like the hematopoietic system that forms immune cells, it is believed that aging of the stem cells strongly contributes to aging-associated dysfunction. In this review, we summarize current aspects on cellular and molecular mechanisms that are associated with aging of hematopoietic stem cells, the role of the stem cell niche for stem cell aging as well as novel and encouraging experimental approaches to attenuate aging of hematopoietic stem cells to target immunosenescence. © 2014 Elsevier Ltd.

Luttrell L.M.,Medical University of South Carolina | Luttrell L.M.,Research Service Of The Ralph hnson Veterans Affairs Medical Center | Miller W.E.,University of Cincinnati
Progress in Molecular Biology and Translational Science | Year: 2013

The discovery that, in addition to mediating G protein-coupled receptor (GPCR) desensitization and endocytosis, arrestins bind to diverse catalytically active nonreceptor proteins and act as ligand-regulated signaling scaffolds led to a paradigm shift in the study of GPCR signal transduction. Research over the past decade has solidified the concept that arrestins confer novel GPCR-signaling capacity by recruiting protein and lipid kinase, phosphatase, phosphodiesterase, and ubiquitin ligase activity into receptor-based multiprotein "signalsome" complexes. Signalsomes regulate downstream pathways controlled by Src family nonreceptor tyrosine kinases, mitogen-activated protein kinases, protein kinase B (AKT), glycogen synthase kinase 3, protein phosphatase 2A, nuclear factor-κB, and several others, imposing spatial and temporal control on their function. While many arrestin-bound kinases and phosphatases are involved in the control of cytoskeletal rearrangement, vesicle endocytosis, exocytosis, and cell migration, other signals reach into the nucleus, affecting cell proliferation, apoptosis, and survival. Indeed, the kinase/phosphatase network regulated by arrestins may be fully as diverse as that regulated by heterotrimeric G proteins. © 2013 Elsevier Inc.

Bernstein J.A.,University of Cincinnati
Allergy and Asthma Proceedings | Year: 2013

Angioedema (AE) is characterized by swelling of the mucosa or submucosa and/or the subcutaneous tissue of the skin. Hereditary AE (HAE) is an autosomal dominant genetic disorder caused by dysfunctional C1 esterase inhibitor, which affects an estimated 1:10,000 to 1:50,000 patients. A survey study that was conducted between 2007 and 2008 to assess the burden of illness of HAE patients revealed they had significant decreases in physical and mental health, impaired work productivity, and a significantly greater amount of depression compared with patients afflicted with other chronic diseases. The cost of treating HAE is quite significant ranging from s14,000 a year for mild disease to s96,000 for severe disease. Given the changing paradigm for evaluation and treatment with the advent of increased recognition and availability of novel prophylactic and on-demand therapeutic agents, updated survey studies of this nature to assess burden of illness, quality of life, and associated treatment costs should be conducted to provide a better understanding of the optimal management of HAE patients in the United States. Copyright © 2013, OceanSide Publications, Inc., U.S.A.

Novak K.J.,University of Missouri - Kansas City | Chamlin M.B.,University of Cincinnati
Crime and Delinquency | Year: 2012

Racial bias in traffic enforcement has become a popular line of inquiry, but examinations into explanations for the disparity have been scant. The current research integrates theoretical insights from the racial threat hypothesis with inferences drawn from the empirical analyses of the factors that stimulate officer suspicion. The most intriguing finding from this beat-level examination of the structural predictors of several traffic stop outcome measures concerns the conditional effect of the racial composition of the beat on search rates. The analyses reveal that the search rate increases in areas where the proportion of Black residents is higher; however, this finding is observed only for White motorists. This finding is interpreted as indicating that structural characteristics of an area can provide cues to officers regarding who belongs in that environment. As a result, social control increases among groups whose racial characteristics are inconsistent with the neighborhood racial composition. © SAGE Publications 2012.

Makarios M.D.,University of Cincinnati | Pratt T.C.,Arizona State University
Crime and Delinquency | Year: 2012

In response to rising rates of firearms violence that peaked in the mid-1990s, a wide range of policy interventions have been developed in an attempt to reduce violent crimes committed with firearms. Although some of these approaches appear to be effective at reducing gun violence, methodological variations make comparing effects across program evaluations difficult. Accordingly, in this article, the authors use meta-analytic techniques to determine what works in reducing gun violence. The results indicate that comprehensive community-based law enforcement initiatives have performed the best at reducing gun violence. © SAGE Publications 2012.

Wooldredge J.,University of Cincinnati
Justice Quarterly | Year: 2012

Racial disparities in court dispositions and sentences might reflect systemic biases toward minorities, but they might also stem from race group differences in legal or other extra-legal factors linked to a defendant's risk for future criminality. Analyses of over 5,000 felony defendants from an urban Ohio jurisdiction revealed that significant main effects of a defendant's race on release on one's own recognizance (ROR), bond amounts, and prison sentences were rendered nonsignificant when controlling for legal factors, such as offense severity. Analyses of interaction effects, on the other hand, revealed that African American males age 18-29 experienced lower odds of ROR, higher bond amounts, and higher odds of incarceration in prison relative to other demographic subgroups, even with the inclusion of rigorous controls for legally relevant criteria. The relevance of these findings for understanding disparate treatment at different stages of case processing is discussed. © 2012 Academy of Criminal Justice Sciences.

Sherman K.E.,University of Cincinnati | Thomas D.,Johns Hopkins Medical Institute | Chung R.T.,Harvard University
Hepatology | Year: 2014

In the United States, more than 1.1 million individuals are infected with the human immunodeficiency virus (HIV). These patients exhibit a high frequency of coinfections with other hepatotropic viruses and ongoing fibrosis, leading to cirrhosis and liver-related mortality. Etiologies of liver disease include viral hepatitis coinfections, drug-related hepatotoxicity, fatty liver disease, and direct and indirect effects from HIV infection, including increased bacterial translocation, immune activation, and presence of soluble proteins, that modulate the hepatic cytokine environment. New treatments for hepatitis C virus (HCV) using direct-acting agents appear viable, though issues related to intrinsic toxicities and drug-drug interactions remain. Recent research suggests that acute HCV infection, unrecognized hepatitis D infection, and hepatitis E may all represent emergent areas of concern. Antiretroviral agents, including those used in recent years, may represent risk factors for hepatic injury and portal hypertension. Key issues in the future include systematic implementation of liver disease management and new treatment in HIV-infected populations with concomitant injection drug use, alcohol use, and low socioeconomic status. © 2013 by the American Association for the Study of Liver Diseases.

Maglo K.N.,University of Cincinnati
Perspectives in Biology and Medicine | Year: 2012

This article addresses the philosophical and moral foundations of group-based and individualized therapy in connection with population care equality. The U. S. Food and Drug Administration (FDA) recently modified its public health policy by seeking to enhance the efficacy and equality of care through the approval of group-specific prescriptions and doses for some drugs. In the age of genomics, when individualization of care increasingly has become a major concern, investigating the relationship between population health, stratified medicine, and personalized therapy can improve our understanding of the ethical and biomedical implications of genomic medicine. I suggest that the need to optimize population health through population substructure-sensitive research and the need to individualize care through genetically targeted therapies are not necessarily incompatible. Accordingly, the article reconceptualizes a unified goal for modern scientific medicine in terms of individualized equal care. © 2012 by The Johns Hopkins University Press.

Munoz E.,University of Santiago de Chile | Bolech C.J.,University of Cincinnati | Kirchner S.,Max Planck Institute for the Physics of Complex Systems | Kirchner S.,Max Planck Institute for Chemical Physics of Solids
Physical Review Letters | Year: 2013

The nonlinear conductance of semiconductor heterostructures and single molecule devices exhibiting Kondo physics has recently attracted attention. We address the observed sample dependence of the measured steady state transport coefficients by considering additional electronic contributions in the effective low-energy model underlying these experiments that are absent in particle-hole symmetric setups. A novel version of the superperturbation theory of Hafermann et al. in terms of dual fermions is developed, which correctly captures the low-temperature behavior. We compare our results with the measured transport coefficients. © 2013 American Physical Society.

Brady C.F.,University of Cincinnati
The Journal of clinical psychiatry | Year: 2014

Patients with obsessive-compulsive disorder (OCD) often have comorbid psychiatric disorders, such as depression, bipolar disorder, psychotic disorders, and eating disorders, which present challenges to the treating physician. Symptoms of OCD may have an earlier onset and be more severe in patients with comorbid illnesses than in those with OCD alone. Both cognitive-behavioral therapy (using exposure and response/ritual prevention) and medication may be needed to treat patients with OCD and comorbid mood, psychotic, or eating disorders. © Copyright 2014 Physicians Postgraduate Press, Inc.

Diab D.L.,University of Cincinnati | Watts N.B.,Mercy Health Osteoporosis and Bone Health Services
Expert Opinion on Drug Safety | Year: 2014

Introduction: Denosumab is a fully human monoclonal antibody against the receptor activator of nuclear factor kappa-B ligand. It is an antiresorptive agent that reduces osteoclastogenesis. Areas covered: This drug evaluation reviews denosumab for use in osteoporosis. Denosumab has been shown to improve bone mineral density (BMD) and to reduce the incidence of new vertebral, hip and nonvertebral fractures in postmenopausal women. It prevents bone loss and reduces vertebral fracture risk in men with nonmetastatic prostate cancer who are receiving androgen deprivation therapy. It has also been shown to improve BMD in men with osteoporosis unrelated to androgen deprivation therapy. Safety concerns include infections, cancer, skin reactions, cardiovascular disease, hypocalcemia, osteonecrosis of the jaw and atypical femur fractures. Expert opinion: Although bisphosphonates are typically preferred as initial therapy for osteoporosis, denosumab could be used as initial therapy in select patients at high risk for fracture, including older patients who have difficulty with the dosing requirements of oral bisphosphonates, patients who are intolerant of or unresponsive to other therapies, and in those with impaired renal function. Additional data is needed to address issues regarding treatment duration and discontinuation, as well as to provide more information regarding denosumab's efficacy and safety. © Informa UK, Ltd.

Molano J.R.V.,University of Cincinnati
Seminars in Neurology | Year: 2013

Dementia with Lewy bodies (DLB) is a synucleinopathy that is clinically distinct from Alzheimer's disease, associated with cognitive decline, fluctuations in alertness and cognition, visual hallucinations, and parkinsonism. Other clinical symptoms that can occur with DLB include dysautonomia and sleep disorders such as rapid-eye-movement sleep behavior disorder (RBD). The pathological criteria of DLB are associated with the location of Lewy body pathology and the extent of Alzheimer's pathology seen. Treatment is symptomatic. The genetic basis of DLB is being explored, and future studies will investigate ways to identify those most at risk for DLB prior to the onset of cognitive symptoms. © Georg Thieme Verlag KG Stuttgart, New York.

Ma J.,University of Cincinnati
Protein and Cell | Year: 2011

Transcriptional activators are required to turn on the expression of genes in a eukaryotic cell. Activators bound to the enhancer can facilitate either the recruitment of RNA polymerase II to the promoter or its elongation. This article examines a few selected issues in understanding activator functions and activation mechanisms. © 2011 Higher Education Press and Springer-Verlag Berlin Heidelberg.

Mccullumsmith R.E.,University of Cincinnati | Hammond J.H.,University of Alabama at Birmingham | Shan D.,University of Alabama at Birmingham | Meador-Woodruff J.H.,University of Alabama at Birmingham
Neuropsychopharmacology | Year: 2014

We propose that postmortem tissue is an underutilized substrate that may be used to translate genetic and/or preclinical studies, particularly for neuropsychiatric illnesses with complex etiologies. Postmortem brain tissues from subjects with schizophrenia have been extensively studied, and thus serve as a useful vehicle for illustrating the challenges associated with this biological substrate. Schizophrenia is likely caused by a combination of genetic risk and environmental factors that combine to create a disease phenotype that is typically not apparent until late adolescence. The complexity of this illness creates challenges for hypothesis testing aimed at understanding the pathophysiology of the illness, as postmortem brain tissues collected from individuals with schizophrenia reflect neuroplastic changes from a lifetime of severe mental illness, as well as treatment with antipsychotic medications. While there are significant challenges with studying postmortem brain, such as the postmortem interval, it confers a translational element that is difficult to recapitulate in animal models. On the other hand, data derived from animal models typically provide specific mechanistic and behavioral measures that cannot be generated using human subjects. Convergence of these two approaches has led to important insights for understanding molecular deficits and their causes in this illness. In this review, we discuss the problem of schizophrenia, review the common challenges related to postmortem studies, discuss the application of biochemical approaches to this substrate, and present examples of postmortem schizophrenia studies that illustrate the role of the postmortem approach for generating important new leads for understanding the pathophysiology of severe mental illness. © 2014 American College of Neuropsychopharmacology.

Ravelli A.,University of Genoa | Grom A.A.,University of Cincinnati | Behrens E.M.,University of Pennsylvania | Cron R.Q.,University of Alabama at Birmingham
Genes and Immunity | Year: 2012

Macrophage activation syndrome (MAS) is a severe, frequently fatal complication of systemic juvenile idiopathic arthritis (sJIA) with features of hemophagocytosis leading to coagulopathy, pancytopenia, and liver and central nervous system dysfunction. MAS is overt in 10% of children with sJIA but occurs subclinically in another 30-40%. It is difficult to distinguish sJIA disease flare from MAS. Development of criteria for establishing MAS as part of sJIA are under way and will hopefully prove sensitive and specific. Mutations in cytolytic pathway genes are increasingly being recognized in children who develop MAS as part of sJIA. Identification of these mutations may someday assist in MAS diagnosis. Defects in cytolytic genes have provided murine models of MAS to study pathophysiology and treatment. Recently, the first mouse model of MAS not requiring infection but rather dependent on repeated stimulation through Toll-like receptors was reported. This provides a model of MAS that may more accurately reflect MAS pathology in the setting of autoinflammation or autoimmunity. This model confirms the importance of a balance between pro-and anti-inflammatory cytokines. There has been remarkable progress in the use of anti-pro-inflammatory cytokine therapy, particularly against interleukin-1, in the treatment of secondary forms of MAS, such as in sJIA. © 2012 Macmillan Publishers Limited All rights reserved.

Ko D.-G.,University of Cincinnati | Dennis A.R.,Indiana University Bloomington
Information Systems Research | Year: 2011

Although many organizations are implementing knowledge management systems (KMS), there is little empirical evidence about whether KMS use can improve individual performance, and how time and experience influence the value derived from KMS use. Using hierarchical linear modeling (HLM) statistical analysis, we examined the impact of using a codification-based KMS on the sales performance of 2,154 sales representatives in a pharmaceutical firm over a 24-month period. We found that KMS had significant positive impacts on individual performance and that these performance benefits grew over time. Moreover, experience moderated the relationship between KMS use and individual performance. Knowledge workers with more experience were able to more quickly absorb and apply the knowledge from the KMS than were those with less experience, who took longer to benefit from KMS use. However, over time experience played a diminishing role in leveraging performance gains from KMS use, and knowledge workers with less experience eventually derived similar performance benefits as those of their more experienced counterparts. © 2011 INFORMS.

Mersha T.B.,University of Cincinnati | Abebe T.,University of Northern Iowa
Human Genomics | Year: 2015

This review explores the limitations of self-reported race, ethnicity, and genetic ancestry in biomedical research. Various terminologies are used to classify human differences in genomic research including race, ethnicity, and ancestry. Although race and ethnicity are related, race refers to a person's physical appearance, such as skin color and eye color. Ethnicity, on the other hand, refers to communality in cultural heritage, language, social practice, traditions, and geopolitical factors. Genetic ancestry inferred using ancestry informative markers (AIMs) is based on genetic/genomic data. Phenotype-based race/ethnicity information and data computed using AIMs often disagree. For example, self-reporting African Americans can have drastically different levels of African or European ancestry. Genetic analysis of individual ancestry shows that some self-identified African Americans have up to 99% of European ancestry, whereas some self-identified European Americans have substantial admixture from African ancestry. Similarly, African ancestry in the Latino population varies between 3% in Mexican Americans to 16% in Puerto Ricans. The implication of this is that, in African American or Latino populations, self-reported ancestry may not be as accurate as direct assessment of individual genomic information in predicting treatment outcomes. To better understand human genetic variation in the context of health disparities, we suggest using "ancestry"(or biogeographical ancestry) to describe actual genetic variation, "race" to describe health disparity in societies characterized by racial categories, and "ethnicity" to describe traditions, lifestyle, diet, and values. We also suggest using ancestry informative markers for precise characterization of individuals' biological ancestry. Understanding the sources of human genetic variation and the causes of health disparities could lead to interventions that would improve the health of all individuals. © 2015 Mersha and Abebe; licensee BioMed Central.

A recent phase 1/2 study demonstrated that treatment with the mammalian target of rapamycin inhibitor everolimus reduced subependymal giant cell astrocytoma volume by 30% in 75% of the patients, all of whom were poor candidates for surgical resection. Of the enrolled patients, 4 had had previous surgery to remove subependymal giant cell astrocytoma, and the outcomes for these patients were retrospectively analyzed and are presented here. All 4 experienced over 50% initial reduction in the volume of their subependymal giant cell astrocytoma after 2 to 3 years of therapy with everolimus. Although the volume of 1 patient's subependymal giant cell astrocytoma returned to baseline volume 36 months after initiating everolimus, they have remained asymptomatic with no recurrent hydrocephalus. Further surgery has been avoided in all cases to date. This course of treatment offers a new and welcome option for these difficult-to-treat patients.

Bernstein J.A.,University of Cincinnati
Postgraduate medicine | Year: 2012

Hereditary angioedema (HAE) is a rare disorder generally caused by a deficit in the activity of C1-esterase inhibitor (C1-INH). Symptoms manifest as recurrent episodes of nonallergic, nonpruritic, and nonpitting edema. Attacks commonly occur on the extremities, trunk, genitalia, abdomen, or head and neck--the latter 2 locations are associated with the greatest morbidity and mortality. In the United States, there has been a considerable void in effective HAE treatments and emergency management guidelines. Clinical outcomes using agents such as fresh-frozen plasma, attenuated androgens (danazol), or plasmin inhibitors (aminocaproic acid) have not been ideal. Recent years have seen progress with US Food and Drug Administration (FDA) approval of several products for acute HAE treatment. Plasma concentrate of C1-INH has long been the treatment of choice in many parts of the world, and a pasteurized formula received FDA approval in October 2009 for treating attacks. Ecallantide, a plasma kallikrein inhibitor, and icatibant, a bradykinin receptor antagonist, were approved in December 2009 and August 2011, respectively, for treatment of acute attacks. A recombinant C1-INH product is in late development stages for treating acute attacks. These new treatments provide symptom relief within hours, dramatically shorten attack duration, and decrease mortality from airway compromise. For the first time, US physicians have rapid-acting and highly effective treatments for managing acute HAE attacks.

Neilson D.E.,University of Cincinnati
Current Opinion in Pediatrics | Year: 2010

Purpose of Review: Acute necrotizing encephalopathy (ANE) presents with fulminant encephalopathy and characteristic brain lesions following viral infection. The rarity and unpredictability of the disorder have significantly impaired its study. Growing recognition of ANE and the discovery of causative missense mutations in the nuclear pore gene RANBP2 give promising steps toward unraveling this disease. This review summarizes recent advances of clinical and scientific understanding of Ane. Recent Findings: Inflammatory factors participate in the pathogenesis of ANE, but the lack of difference between influenza and noninfluenza ANE focuses attention on the abnormal host response as causative. Early treatment with steroids provides the best outcome for patients who do not have brainstem lesions. Missense mutations in RANBP2 cause the majority of familial and recurrent ANE cases, but other single-gene causes of ANE are possible for familial, recurrent, and sporadic cases. Summary: Early recognition and systematic evaluation of ANE are necessary. Modeling ANE as a genetic disorder may provide the most immediate gains in the understanding and treatment of ANE and related disorders. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Beck T.L.,University of Cincinnati
Physical Chemistry Chemical Physics | Year: 2015

The recent development of real-space grid methods has led to more efficient, accurate, and adaptable approaches for large-scale electrostatics and density functional electronic structure modeling. With the incorporation of multiscale techniques, linear-scaling real-space solvers are possible for density functional problems if localized orbitals are used to represent the Kohn-Sham energy functional. These methods still suffer from high computational and storage overheads, however, due to extensive matrix operations related to the underlying wave function grid representation. In this paper, an alternative stochastic method is outlined that aims to solve directly for the one-electron density matrix in real space. In order to illustrate aspects of the method, model calculations are performed for simple one-dimensional problems that display some features of the more general problem, such as spatial nodes in the density matrix. This orbital-free approach may prove helpful considering a future involving increasingly parallel computing architectures. Its primary advantage is the near-locality of the random walks, allowing for simultaneous updates of the density matrix in different regions of space partitioned across the processors. In addition, it allows for testing and enforcement of the particle number and idempotency constraints through stabilization of a Feynman-Kac functional integral as opposed to the extensive matrix operations in traditional approaches. © 2015 the Owner Societies.

Kellum J.A.,University of Pittsburgh | Devarajan P.,University of Cincinnati
Biomarkers in Medicine | Year: 2014

Biomarkers for acute kidney injury have numerous potential roles to play both at the bedside and in the design and conduct of clinical trials. Given the heterogeneous nature of this disease and the difficulty, so far, in developing effective therapies, a strategy that deploys all of our available tools in the treatment and in study of treatments would seem prudent. In this review, we discuss how biomarkers will change the way we do we take care of patients with and do clinical trials in acute kidney injury and why, in fact, biomarkers are necessary. © 2014 Future Medicine Ltd.

Blomkalns A.L.,University of Cincinnati
Journal of the American Heart Association | Year: 2013

Recruitment of macrophage precursors to the adventitia plays a key role in the pathogenesis of abdominal aortic aneurysms (AAAs), but molecular mechanisms remain undefined. The innate immune signaling molecule CD14 was reported to be upregulated in adventitial macrophages in a murine model of AAA and in monocytes cocultured with aortic adventitial fibroblasts (AoAf) in vitro, concurrent with increased interleukin-6 (IL-6) expression. We hypothesized that CD14 plays a crucial role in adventitial macrophage precursor recruitment early during AAA formation. CD14(-/-) mice were resistant to AAA formation induced by 2 different AAA induction models: aortic elastase infusion and systemic angiotensin II (AngII) infusion. CD14 gene deletion led to reduced aortic macrophage infiltration and diminished elastin degradation. Adventitial monocyte binding to AngII-infused aorta in vitro was dependent on CD14, and incubation of human acute monocytic leukemia cell line-1 (THP-1) monocytes with IL-6 or conditioned medium from perivascular adipose tissue (PVAT) upregulated CD14 expression. Conditioned medium from AoAf and PVAT induced CD14-dependent monocyte chemotaxis, which was potentiated by IL-6. CD14 expression in aorta and plasma CD14 levels were increased in AAA patients compared with controls. These findings link CD14 innate immune signaling via a novel IL-6 amplification loop to adventitial macrophage precursor recruitment in the pathogenesis of AAA.

Cook D.M.,Oregon Health And Science University | Rose S.R.,University of Cincinnati
Pituitary | Year: 2012

Growth hormone (GH) is approved by the US Food and Drug Administration (FDA) for use in pediatric patients with disorders of growth failure or short stature and in adults with growth hormone deficiency (GHD) and HIV/AIDS wasting and cachexia. For pediatric patients, guidelines for the use of GH have been developed by several organizations that have identified specific criteria for initiating GH therapy for each FDA-approved indication. Guidelines for adults have also been developed and include recommendations for transition (adolescent) patients with GHD. These patients are often treated with GH as children but may require continued treatment as young adults to attain full skeletal mineralization and improve cardiovascular risk factors. Adult and pediatric guidelines are supported by efficacy and safety studies, which show that, when started at an early age, GH treatment can increase growth velocity and that GH is safe and well-tolerated. We summarize the guidelines that are available for all FDA-approved indications among pediatric and transition patients. Adherence to these guidelines will help to ensure that patients with disorders of growth failure or short stature receive the necessary therapy to increase linear growth and transition smoothly to healthy adulthood. © Springer Science+Business Media, LLC 2012.

Eckerle Mize D.L.,Vanderbilt University | Salehi M.,University of Cincinnati
Current Diabetes Reports | Year: 2013

Type 2 diabetes is a progressive disease characterized by the need for additional antidiabetic agents overtime to maintain a stable level of glycemic control. The discovery of the glucagon like peptide 1, 1 of the 2 major incretins, was pivotal to the development of novel therapies, which can be used in individuals with type 2 diabetes. Two classes of drugs, GLP-1 receptor agonists and dipeptidyl peptidase inhibitors, provide comparable or superior glycemic effects to previous antidiabetic agents without increasing side effects, such as weight gain and hypoglycemia. Therefore, they represent valuable additions to the current therapeutic options for type 2 diabetes. © 2013 Springer Science+Business Media New York.

Lopez-Candales A.,University of Cincinnati
Echocardiography | Year: 2015

Background Even though systolic eccentricity index has been traditionally categorized based on right ventricular (RV) pressure overload, which hemodynamic component is particularly responsible for modulating leftward ventricular septal bowing (LVSB) in chronic pulmonary arterial hypertension (PAH) is less well-known. Methods Therefore, currently used echocardiographic variables, as suggested by the American Society of Echocardiography, for evaluation of RV performance were evaluated in 60 patients to determine which of these commonly used parameters best determine an abnormal LVSB in chronic PAH patients. Results In a stepwise multiple regression analysis of the echocardiographic variables used in this study, elevated pulmonary artery systolic pressures was the best discriminatory variable to identify an abnormal LVSB at any level along the interventricular septum in chronic PAH patients followed by smaller left ventricular end-diastolic volumes and larger RV end-systolic areas. Conclusion Progressive RV failure in chronic PAH not only is associated with a decline in longitudinal base to apical motion of the annulus; but also with reduced inward displacement of the RV free wall. Additional reduction in RV systolic function also occurs as a result of progressive displacement of the interventricular septum toward the left ventricle. Therefore, as measures of LVSB along the interventricular septum not only are easily obtained and related to RV systolic performance in chronic PAH patients, routine use of these parameters might be helpful in monitoring decline of RV function as well as progression of end-stage PAH. © 2014, Wiley Periodicals, Inc.

Matter S.F.,University of Cincinnati | Roland J.,University of Alberta
Proceedings of the Royal Society B: Biological Sciences | Year: 2010

Spatial population theory predicts that synchrony in the dynamics of local populations should decrease as dispersal among populations decreases. Thus, it would be expected that the extinction of local populations and the attendant loss of immigrants to surrounding populations would reduce synchrony. We tested this hypothesis through a large-scale experiment, simulation of the experimental system and general models. Experimental removal of two adjacent subpopulations of the Rocky Mountain Apollo butterfly, Parnassius smintheus within a network consisting of 15 other local populations resulted in a decrease in immigration to surrounding populations that was proportional to their connectivity to the removal populations. These populations also showed a significant increase in synchrony during population removal. The spatial extent of the synchrony showed good agreement with the predicted loss of immigrants owing to the removals. Simulation of the Parnassius system showed a similar shortterm result and also indicated that permanent loss of populations produces structural changes increasing synchrony. General models indicate that an increase in synchrony following extinction occurs when populations undergoing extinction have different carrying capacities than surrounding populations. The result is not owing to biased migration per se, but rather is because of the number of immigrants relative to the carrying capacity. Synchrony following extinction should be most common for patchy populations, but can occur in any situation where carrying capacities differ. Overall, our results indicate that local extinction can create a positive feedback for extinction risk, increasing the probability of extinction for population networks by synchronizing their dynamics. © 2009 The Royal Society.

Gross J.B.,University of Cincinnati | Wilkens H.,University of Hamburg
Heredity | Year: 2013

The Mexican tetra, Astyanax mexicanus, comprises 29 populations of cave-adapted fish distributed across a vast karst region in northeastern Mexico. These populations have a complex evolutionary history, having descended from 'old' and 'young' ancestral surface-dwelling stocks that invaded the region ∼6.7 and ∼2.8 MYa, respectively. This study investigates a set of captive, pigmented Astyanax cavefish collected from the Micos cave locality in 1970, in which albinism appeared over the past two decades. We combined novel coloration analyses, coding sequence comparisons and mRNA expression level studies to investigate the origin of albinism in captive-bred Micos cavefish. We discovered that albino Micos cavefish harbor two copies of a loss-of-function ocular and cutaneous albinism type II (Oca2) allele previously identified in the geographically distant Pachón cave population. This result suggests that phylogenetically young Micos cavefish and phylogenetically old Pachón cave fish inherited this Oca2 allele from the ancestral surface-dwelling taxon. This likely resulted from the presence of the loss-of-function Oca2 haplotype in the 'young' ancestral surface-dwelling stock that colonized the Micos cave and also introgressed into the ancient Pachón cave population. The appearance of albinism in captive Micos cavefish, caused by the same loss-of-function allele present in Pachón cavefish, implies that geographically and phylogenetically distinct cave populations can evolve the same troglomorphic phenotype from standing genetic variation present in the ancestral taxon. © 2013 Macmillan Publishers Limited. All rights reserved.

Javaheri S.,University of Cincinnati | Dempsey J.A.,University of Wisconsin - Madison
Comprehensive Physiology | Year: 2013

Neurophysiologically, central apnea is due to a temporary failure in the pontomedullary pacemaker generating breathing rhythm. As a polysomnographic finding, central apneas occur in many pathophysiological conditions. Depending on the cause or mechanism, central apneas may not be clinically significant, for example, those that occur normally at sleep onset. In contrast, central apneas occur in a number of disorders and result in pathophysiological consequences. Central apneas occur commonly in high-altitude sojourn, disrupt sleep, and cause desaturation. Central sleep apnea also occurs in number of disorders across all age groups and both genders. Common causes of central sleep apnea in adults are congestive heart failure and chronic use of opioids to treat pain. Under such circumstances, diagnosis and treatment of central sleep apnea may improve quality of life, morbidity, and perhaps mortality. The mechanisms of central sleep apnea have been best studied in congestive heart failure and hypoxic conditions when there is increased CO2 sensitivity below eupnea resulting in lowering eupneic PCO2 below apneic threshold causing cessation of breathing until the PCO2 rises above the apneic threshold when breathing resumes. In many other disorders, the mechanism of central sleep apnea (CSA) remains to be investigated. © 2013 American Physiological Society.

Maglo K.N.,University of Cincinnati
Perspectives in Biology and Medicine | Year: 2010

This article addresses the question of whether race is a biological category and whether it is permissible to use it in biomedicine. I suggest that instrumentalism, a view that race is a problem-solving tool rather than a concept with an objective referent in nature, may be more consistent with the available scientific evidence. I argue that, to be morally permissible, the instrumentalist use of race in research and medicine requires stringent guidelines. I then provide four normative rules to guide race research in the biomedical sciences.The paper gathers evidence from philosophy of science, genomics, legal history, and normative ethics in order to ground the biomedical use of race in a converging ethical and epistemic framework. © 2010 by The Johns Hopkins University Press.

Rank M.A.,Mayo Medical School | Bernstein D.I.,University of Cincinnati
Journal of Allergy and Clinical Immunology: In Practice | Year: 2014

We present a 42-year-old woman who experienced a systemic reaction (SR) after a subcutaneous immunotherapy (SCIT) injection. Her physician must make a decision, along with the patient, on how to proceed. We consider the medical evidence pertinent to specific risk factors for SRs to SCIT, including asthma control, concomitant medications and new medical diagnoses, the influence of pollen season, adjustments for large local reactions, initial testing results, type of buildup protocol, and administration and dosing errors. We next discuss the potential risk-mitigating actions that the patient and provider should consider and the available evidence that supports various approaches, including cessation of SCIT, decreasing allergen dose or altering the timing of injections, initiating or changing the medical pretreatment regimen, and changing to sublingual immunotherapy, and also the role for anaphylaxis preparedness. Finally, we highlight the key knowledge gaps identified in this review and provide management recommendations for this 42-year-old woman. © 2013 American Academy of Allergy, Asthma & Immunology.

Kupfer D.J.,University of Pittsburgh | Wulsin L.,University of Cincinnati
Annual Review of Medicine | Year: 2013

Mental disorders represent a significant global burden whose effects are exacerbated by gaps in diagnosis and service provision. A substantial number of individuals seek services not through specialty psychiatric clinics but through primary care. Thus, the interface between psychiatry and the rest of medicine represents an appropriate area of focus in which to improve the detection and treatment of mental disorders. Development of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) can play a key role in this process. DSM-5 is expected to include specific revisions in diagnostic criteria, chapter organization, text structure, and classification approach that are designed to improve use of DSM by nonpsychiatrist physicians. Furthermore, revisions to DSM-5 will inform development of the primary care version of DSM-5. The goal is to publish a manual that enhances clinical utility in a manner that is concise and more amenable to use in primary care. Copyright © 2013 by Annual Reviews.

Lam C.K.,University of Cincinnati
Circulation research | Year: 2013

Ischemic heart disease is characterized by contractile dysfunction and increased cardiomyocyte death, induced by necrosis and apoptosis. Increased cell survival after an ischemic insult is critical and depends on several cellular pathways, which have not been fully elucidated. To test the hypothesis that the anti-apoptotic hematopoietic lineage substrate-1-associated protein X-1 (HAX-1), recently identified as regulator of cardiac Ca cycling, also may ameliorate cellular injury with an ischemic insult. We report that cardiac ischemia/reperfusion injury is associated with significant decreases in HAX-1 levels ex vivo and in vivo. Accordingly, overexpression of HAX-1 improved contractile recovery, coupled with reduced infarct size, plasma troponin I level, and apoptosis. The beneficial effects were associated with decreased endoplasmic reticulum (ER) stress response through specific inhibition of the inositol-requiring enzyme (IRE-1) signaling pathway, including its downstream effectors caspase-12 and the transcription factor C/EBP homologous protein. Conversely, HAX-1 heterozygous-deficient hearts exhibited increases in infarct size and IRE-1 activity. The inhibitory effects of HAX-1 were mediated by its binding to the N-terminal fragment of the heat shock protein 90 (Hsp90). Moreover, HAX-1 sequestered Hsp90 from IRE-1 to the phospholamban-sarcoplasmic/endoplasmic reticulum calcium ATPase complex. The HAX-1 regulation was further supported by loss of IRE-1 inhibition in presence of the Hsp90 inhibitor, 17-N-allylamino-17-demethoxygeldanamycin. Cardiac ischemia-reperfusion injury is associated with decreases in HAX-1 levels. Consequently, overexpression of HAX-1 promotes cardiomyocyte survival, mediated by its interaction with Hsp90 and specific inhibition of IRE-1 signaling at the ER/sarcoplasmic reticulum.

Abdel-Malek Z.A.,University of Cincinnati
Advances in Experimental Medicine and Biology | Year: 2010

Melanocortins, particularly α-melanocortin (α-melanocyte stimulating hormone, α-MSH), were first identified as the physiological regulators of pigmentation in many vertebrate species. Their role in regulating human pigmentation was unequivocally demonstrated in the 1990s, with the cloning of the human melanocortin 1 receptor (MC1R) gene from human melanocytes and the demonstration that functional MC1R is expressed by these cells. α-Melanocyte stimulating hormone is a tridecapeptide, with the core sequence His6-Phe7-Arg8-Trp9 shared with β- and γ-MSH and identified as essential for receptor activation and stimulation of pigmentation. The small size of α-MSH makes it an attractive molecule for drug design. There has been longstanding interest in the development of melanocortin analogs that target the MC1R expressed on normal melanocytes and melanoma cells. The aim has been to develop MC1R agonists that stimulate melanogenesis and confer photoprotection to human melanocytes and thus prevent skin cancer formation. Recent findings that the physiological α-MSH not only stimulates melanogenesis, but also reduces the extent of DNA damage caused by exposure to solar ultraviolet radiation have further rejuvenated the interest in developing synthetic MC1R agonists for skin cancer prevention. α-Melanocortin analogs have also been developed for imaging of melanoma tumors, localization of residual metastasis and specific delivery of radionuclides to eradicate melanoma tumors, sparing normal tissues. The main challenge is to develop specific MC1R agonists that will target melanocytes for skin cancer prevention, or for localization and treatment of metastatic melanoma. © 2010 Landes Bioscience and Springer Science+Business Media.

Herman W.H.,University of Michigan | Cohen R.M.,University of Cincinnati
Journal of Clinical Endocrinology and Metabolism | Year: 2012

Hemoglobin A1c (HbA1c) is widely used as an index of mean glycemia in diabetes, as a measure of risk for the development of diabetic complications,andas a measure of the quality of diabetes care. In 2010, the American Diabetes Association recommended that HbA1c tests, performed in a laboratory using a method certified by the National Glycohemoglobin Standardization Program, be used for the diagnosis of diabetes. Although HbA1c has a number of advantages compared to traditional glucose criteria, it has a number of disadvantages. Hemoglobinopathies, thalassemia syndromes, factors that impact red blood cell survival and red blood cell age, uremia, hyperbilirubinemia, and iron deficiency may alter HbA1c test results as a measure of average glycemia. Recently, racial and ethnic differences in the relationship between HbA1c and blood glucose have also been described. Although the reasons for racial and ethnic differences remain unknown, factors such as differences in red cell survival, extracellular-intracellular glucose balance, and nonglycemic genetic determinants of hemoglobin glycation are being explored as contributors. Until the reasons for these differences are more clearly defined, reliance on HbA1c as the sole, or even preferred, criterion for the diagnosis of diabetes creates the potential for systematic error and misclassification. HbA1c must be used thoughtfully and in combination with traditional glucose criteria when screening for and diagnosing diabetes. Copyright © 2012 by The Endocrine Society.