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Gewin L.,Veterans Affairs Hospital | Gewin L.,Vanderbilt Medical Center | Zent R.,Vanderbilt Medical Center | Zent R.,Veterans Affairs Hospital
Seminars in Nephrology | Year: 2012

Tubulointerstitial fibrosis mediates the development of end-stage renal disease from renal injuries of all etiologies and is considered an important predictor of renal survival. Transforming growth factor-β (TGF-β) is one of the most important growth factors that promotes tubulointerstitial fibrosis, but the mechanisms whereby this occurs are not well defined. This is because TGF-β has pleiotropic effects that depend on the target cell type. This review discusses how TGF-β signaling in each of the relevant cell types (eg, tubular epithelium, fibroblasts) may contribute to tubulointerstitial fibrosis progression and suggests ways in which future research can improve our understanding of TGF-β-mediated tubulointerstitial fibrosis. © 2012.


Kalantar-Zadeh K.,University of California Medical Center | Kalantar-Zadeh K.,University of California at Los Angeles | Ikizler T.A.,Vanderbilt Medical Center
Journal of Renal Nutrition | Year: 2013

In individuals with chronic kidney disease, surrogates of protein-energy wasting, including a relatively low serum albumin and fat or muscle wasting, are by far the strongest death risk factor compared with any other condition. There are data to indicate that hypoalbuminemia responds to nutritional interventions, which may save lives in the long run. Monitored, in-center provision of high-protein meals and/or oral nutritional supplements during hemodialysis is a feasible, inexpensive, and patient-friendly strategy despite concerns such as postprandial hypotension, aspiration risk, infection control and hygiene, dialysis staff burden, diabetes and phosphorus control, and financial constraints. Adjunct pharmacologic therapies can be added, including appetite stimulators (megesterol, ghrelin, and mirtazapine), anabolic hormones (testosterone and growth factors), antimyostatin agents, and antioxidative and anti-inflammatory agents (pentoxiphylline and cytokine modulators), to increase efficiency of intradialytic food and oral supplementation, although adequate evidence is still lacking. If more severe hypoalbuminemia (<3.0 g/dL) not amenable to oral interventions prevails, or if a patient is not capable of enteral interventions (e.g., because of swallowing problems), then parenteral interventions such as intradialytic parenteral nutrition can be considered. Given the fact that meals and supplements during hemodialysis would require only a small fraction of the funds currently used for dialysis patients this is also an economically feasible strategy. © 2013 National Kidney Foundation, Inc.


Penson D.,The Surgical Center | Krishnaswami S.,Institute for Medicine and Public Health | Jules A.,Vanderbilt Medical Center | McPheeters M.L.,Institute for Medicine and Public Health | McPheeters M.L.,Vanderbilt Medical Center
Pediatrics | Year: 2013

BACKGROUND AND OBJECTIVE: Controversy remains concerning the optimal treatment approach for cryptorchidism. The objective of this study was to assess effectiveness of hormone therapy or surgery for cryptorchidism. METHODS: We searched Medline and other databases from 1980 to February 2012. Two reviewers independently assessed studies against predetermined criteria. Two reviewers independently extracted data and assigned overall quality and strength of evidence ratings using predetermined criteria. RESULTS: Fourteen studies addressed effectiveness of hormonal treatments, and 26 studies addressed surgical intervention outcomes. Hormonal treatment is associated with testicular descent in some children, but rates generally do not exceed those seen with placebo by >10%. Surgical treatment is associated with success rates of testicular descent ranging from 33% to 100%, depending on surgery. Weighted success averages were 78.7% for 1-stage Fowler-Stephens (FS), 86% for 2-stage FS, and 96.4% for primary orchiopexy. Descent rates were similar among studies comparing laparoscopic and open surgeries. Reported harms of hormonal treatments were mild and transient. Adverse effects specifically associated with surgical repair were rare. CONCLUSIONS: The body of the reviewed literature comprises primarily fair- and poor-quality studies, limiting our ability to draw definitive conclusions. Hormonal treatment is marginally effective relative to placebo but is successful in some children and with minimal harms, suggesting that it may be an appropriate trial of care for some patients. Surgical options are effective, with high rates of testicular descent (moderate strength of evidence for FS procedures, high for primary orchiopexy). Comparable outcomes occur with laparoscopic and open approaches.


Landsperger J.S.,Vanderbilt Medical Center
Hospital practice (1995) | Year: 2011

Demands for critical care services are increasing, but the supply of qualified physicians is not. Moreover, there are mounting national expectations for continuous on-site, senior providers and for adherence to quality and safety practices. In teaching institutions, manpower shortages are exacerbated by shrinking trainee duty hours, and there is a growing desire to recoup the revenue lost when a non-credentialed provider delivers a service. Increasingly, hospitalists and acute-care nurse practitioners (ACNPs) are meeting these needs. This article describes the development of an ACNP service in a university hospital medical intensive care unit (ICU) designed to improve the range and quality of services and faculty staffing when the ICU expanded from 22 to 34 beds without adding physicians. Eight ACNPs were hired and, over 9 months, received didactic, procedural, simulation center, and supervised patient care training. Progressive workload and graded responsibility were used to transition to a 24-hour, in-house, resident-independent, attending-supervised service, which now admits just under half of all patients (3.4 ± 1.3 patients/day), cares for approximately one-fourth of the unit's critically ill patients (6.0 ± 1.4 patients/day), and responds to medical rapid response team calls daily (1.5 ± 1.7 calls/day). Over the first 5 months of operation, work output in all categories continued to increase, with ACNPs documenting an average of 11.1 ± 2.7 activities per day (all data mean ± standard deviation). Acute-care nurse practitioners also provide 40% of the daily resident core lectures and a monthly staff nurse conference. Insufficient data exist at this time, however, to report accurate billing or collection results. Specific areas discussed within this article include service structure, hiring and training, implementation, scheduling, supervision, problems encountered, productivity, monitoring, and future plans.


Dikalov S.I.,Vanderbilt Medical Center
American journal of physiology. Regulatory, integrative and comparative physiology | Year: 2012

Production of superoxide (O(2)(·-)) by NADPH oxidases contributes to the development of hypertension and atherosclerosis. Factors responsible for activation of NADPH oxidases are not well understood; interestingly, cardiovascular disease is associated with both altered NADPH oxidase activity and age-associated mitochondrial dysfunction. We hypothesized that mitochondrial dysfunction may contribute to activation of NADPH oxidase. The effect of mitochondrial inhibitors on phagocytic NADPH oxidase in human lymphoblasts and whole blood was measured at the basal state and upon PKC-dependent stimulation with PMA using extracellular 1-hydroxy-2,2,6,6-tetramethylpiperidin-4-yl-trimethylammonium or mitochondria-targeted 1-hydroxy-4-[2-triphenylphosphonio)-acetamido]-2,2,6,6-tetramethylpiperidine spin probes and electron spin resonance (ESR). Intracellular cytosolic calcium [Ca(2+)](i) was measured spectrofluorometrically using fura-2 AM. Incubation of lymphoblasts with the mitochondrial inhibitors rotenone, antimycin A, CCCP, or ruthenium red (an inhibitor of mitochondrial Ca(2+) uniporter) did not significantly change basal activity of NADPH oxidase. In contrast, preincubation with the mitochondrial inhibitors prior to PMA stimulation of lymphoblasts resulted in two- to three-fold increase of NADPH oxidase activity compared with stimulation with PMA alone. Most notably, the intracellular Ca(2+)-chelating agent BAPTA-AM abolished the effect of mitochondrial inhibitors on NADPH oxidase activity. Cytosolic Ca(2+) measurements with fura-2 AM showed that the mitochondrial inhibitors increased [Ca(2+)](i), while BAPTA-AM abolished the increase in [Ca(2+)](i). Furthermore, depletion of cellular Ca(2+) with thapsigargin attenuated CCCP- and antimycin A-mediated activation of NADPH oxidase in the presence of PMA by 42% and 31%, correspondingly. Our data suggest that mitochondria regulate PKC-dependent activation of phagocytic NADPH oxidase. In summary, increased mitochondrial O(2)(·-) and impaired buffering of cytosolic Ca(2+) by dysfunctional mitochondria result in enhanced NADPH oxidase activity, which may contribute to the development of cardiovascular diseases.


France D.J.,Vanderbilt Medical Center
Journal of Patient Safety | Year: 2016

OBJECTIVES: Rapid risk stratification and timely treatment are critical to favorable outcomes for patients with acute coronary syndrome (ACS). Our objective was to identify patient and system factors that influence time-dependent quality indicators (QIs) for patients with unstable angina/non–ST elevation myocardial infarction (NSTEMI) in the emergency department (ED). METHODS: A retrospective, cohort study was conducted during a 42-month period of all patients 24 years or older suspected of having ACS as defined by receiving an electrocardiogram and at least 1 cardiac biomarker test. Cox regression was used to model the effects of patient characteristics, ancillary service use, staffing provisions, equipment availability, and ED and hospital crowding on ACS QIs. RESULTS: Emergency department adherence rates to national standards for electrocardiogram readout time and biomarker turnaround time were 42% and 37%, respectively. Cox regression models revealed that chief complaints without chest pain and the timing of stress testing and medication administration were associated with the most significant delays. CONCLUSIONS: Patient and system factors both significantly influenced QI times in this cohort with unstable angina/NSTEMI. These results illustrate both the complexity of diagnosing patients with NSTEMI and the competing effects of clinical and system factors on patient flow through the ED. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved


Streubel P.N.,Vanderbilt Medical Center | Moustoukas M.J.,Vanderbilt Medical Center | Obremskey W.T.,Vanderbilt Medical Center
Journal of Orthopaedic Trauma | Year: 2013

Objectives: The aim of this study was analyze modes of mechanical failure in a consecutive cohort of Patients and establish possible risk factors. Design: This was a retrospective cohort study. Setting: The study was conducted at an academic level-1 trauma center. Patients: Twenty-nine patients (mean age 56 years, range 21-92; 45% males, 41% smokers, 17% diabetic, mean body mass index 26.9, range 20-56) with 30 OTA 31A3 fractures treated between 2003 and 2007 were included. Treatment: Operative fixation using 4.5-mm locking compression plate (LCP) proximal femur plate (Synthes, Paoli, PA). Main Outcome Measurements: Mechanical failure was defined as loss of alignment of at least 10° or shortening of at least 2 cm. Secondary outcomes included patient and fixation construct variables as possible predictors for mechanical failure. Result: At 20 months of follow-up, 11 failures (37%) occurred. Mean time to failure was 18 weeks (range 2-84). Cumulative failure rates were 10%, 20%, 27%, and 33% at 1, 2, 6, and 12 months, respectively. The most frequent failure mode was varus collapse with screw cut out (5 cases). There was no statistically significant difference between groups with regards to age, body mass index, diabetes, or smoking habit. The presence of a "kickstand screw" and medial cortical reduction were not significantly different in cases with and without failure. Proximal screw number and type were similar in both groups. Conclusions: A high rate of mechanical failure can be expected with proximal locking plate fixation of unstable proximal femur fractures. The use of a "kickstand" screw could not be established to reduce the risk for mechanical failure. Copyright © 2013 by Lippincott Williams & Wilkins.


Chinnadurai S.,Vanderbilt Medical Center | Goudy S.,Vanderbilt Medical Center
Current Opinion in Otolaryngology and Head and Neck Surgery | Year: 2012

Purpose of review: Improved recognition of velocardiofacial syndrome (VCFS) has led to increasing awareness of VCFS by otolaryngologists. Understanding the developmental biologic processes affected in VCFS patients will help improve treatment and outcomes. Advanced application of molecular labeling techniques has better outlined the role of T-Box transcription factor 1 (TBX1) as the primary genetic anomaly leading to VCFS. TBX1 plays multiple roles during branchial, cardiac, and craniofacial development and increased understanding of how these systems are affected by TBX1 mutations will improve patient outcomes. Furthermore, additional modifiers of TBX1 expression have been identified that may explain the variability of VCFS phenotypes. The phenotypic spectrum of VCFS may include cardiac anomalies, velopharyngeal insufficiency, aberrant calcium metabolism, and immune dysfunction. Recent interest has focused on the cognitive and neuropsychiatric manifestations of VCFS. Improved understanding of the biology of VCFS associated mutations has the potential to improve therapeutic outcomes. Recent findings: This article will discuss recent developmental biologic understanding of the role of TBX1 and genetic modifiers generating the phenotypic variability seen in VCFS patients. Special attention is given to advances in the realms of immunodeficiency, hypocalcemia, cardiac and arterial patterning anomalies, velopharyngeal insufficiency, as well as cognitive and psychiatric problems. Summary: Enhanced understanding of the multiple systems affected by TBX1 mutations will result in improved patient outcomes and improved family education. Future research will lead to improved detection of potential targets for gene therapy and change the way physicians counsel families and treat patients. © 2012 Lippincott Williams & Wilkins.


Asius Technologies, the only developer of music-enhancing personal audio devices that have been scientifically proven to preserve and protect hearing, has surpassed its goal on its ADEL™ Drum Bionic Earbuds crowdfunding campaign on Indiegogo. Boulder, CO, November 30, 2016 --( CEO Steven Lebischak states, “Many me-too audio devices vie for attention in the crowdfunding ecosystem – but with the support of, partners such as Vanderbilt Medical Center, Autodesk, and of course our forward thinking backers, we surpassed our funding goal. Next, we will be announcing a 'stretch' goal with even more benefits for more backers.” Unlike the earbuds used by millions of listeners with personal audio devices such as smartphones, and tablets, ADEL™ Drum Earbuds feature a patented bionic eardrum that functions as a “safety valve,” relieving the ear canal and ultimately the human eardrum from destructive pneumatic pressure that is compounded when a speaker seals the ear canal shut, and relentlessly pounds the eardrum. Lebsichak also adds: The personal audio/earbud space is full of overhyped performance claims. We are the only company who discovered the cause and invented a cure for Earbud Induced Hearing Loss that also improves audio quality by allowing the speaker and eardrum to work naturally for an open ear concert hall experience. The ADEL™ will protect you. That’s why top artists such as Beyoncé rely on ADEL. Independent tests have proven its efficacy and now customers in 28 countries will enjoy great music while preserving their hearing.” About Asius Technologies: Asius Technologies (www.AsiusTechnologies.com) develops audio technology that employs a patented second eardrum which absorbs the harmful pressures that cause hearing loss and degrade sound quality. Asius' products are enjoyed the world over by sound engineers, musicians, audiophiles, and anyone who wears ear devices for sustained periods in loud environments. Asius Technologies was founded by Stephen Ambrose, the “Father of Personal Audio,” who trail blazed the path for the Walkman, iPod, and virtual reality devices by inventing and then commercializing the in-ear monitor (IEM). Feeling responsible for the epidemic of hearing loss attributed to personal listening devices, Stephen is now dedicated to developing technology that not only enhances listening, but also preserves and even restores long lost hearing function. Boulder, CO, November 30, 2016 --( PR.com )-- Asius Technologies, the only developer of music-enhancing personal audio devices that have been scientifically proven to preserve and protect hearing, has surpassed its goal on its ADEL™ Drum Bionic Earbuds crowdfunding campaign on Indiegogo (https://igg.me/at/drum-earbuds).CEO Steven Lebischak states, “Many me-too audio devices vie for attention in the crowdfunding ecosystem – but with the support of, partners such as Vanderbilt Medical Center, Autodesk, and of course our forward thinking backers, we surpassed our funding goal. Next, we will be announcing a 'stretch' goal with even more benefits for more backers.”Unlike the earbuds used by millions of listeners with personal audio devices such as smartphones, and tablets, ADEL™ Drum Earbuds feature a patented bionic eardrum that functions as a “safety valve,” relieving the ear canal and ultimately the human eardrum from destructive pneumatic pressure that is compounded when a speaker seals the ear canal shut, and relentlessly pounds the eardrum.Lebsichak also adds: The personal audio/earbud space is full of overhyped performance claims. We are the only company who discovered the cause and invented a cure for Earbud Induced Hearing Loss that also improves audio quality by allowing the speaker and eardrum to work naturally for an open ear concert hall experience. The ADEL™ will protect you. That’s why top artists such as Beyoncé rely on ADEL. Independent tests have proven its efficacy and now customers in 28 countries will enjoy great music while preserving their hearing.”About Asius Technologies: Asius Technologies (www.AsiusTechnologies.com) develops audio technology that employs a patented second eardrum which absorbs the harmful pressures that cause hearing loss and degrade sound quality. Asius' products are enjoyed the world over by sound engineers, musicians, audiophiles, and anyone who wears ear devices for sustained periods in loud environments. Asius Technologies was founded by Stephen Ambrose, the “Father of Personal Audio,” who trail blazed the path for the Walkman, iPod, and virtual reality devices by inventing and then commercializing the in-ear monitor (IEM). Feeling responsible for the epidemic of hearing loss attributed to personal listening devices, Stephen is now dedicated to developing technology that not only enhances listening, but also preserves and even restores long lost hearing function. Click here to view the list of recent Press Releases from Asius Technologies


News Article | November 30, 2016
Site: www.24-7pressrelease.com

BOULDER, CO, November 30, 2016 /24-7PressRelease/ -- Asius Technologies, the only developer of music-enhancing personal audio devices that have been scientifically proven to preserve and protect hearing, has surpassed its goal on its ADEL Drum Bionic Earbuds crowdfunding campaign on Indiegogo (https://igg.me/at/drum-earbuds). CEO Steven Lebischak states, "Many me-too audio devices vie for attention in the crowdfunding ecosystem - but with the support of, partners such as Vanderbilt Medical Center, Autodesk, and of course our forward thinking backers, we surpassed our funding goal. Next, we will be announcing a "stretch" goal with even more benefits for more backers." Unlike the earbuds used by millions of listeners with personal audio devices such as smartphones, and tablets, ADEL Drum Earbuds feature a patented bionic eardrum that functions as a "safety valve," relieving the ear canal and ultimately the human eardrum from destructive pneumatic pressure that is compounded when a speaker seals the ear canal shut, and relentlessly pounds the eardrum. Lebsichak also adds: The personal audio/earbud space is full of overhyped performance claims. We are the only company who discovered the cause and invented a cure for Earbud Induced Hearing Loss that also improves audio quality by allowing the speaker and eardrum to work naturally for an open ear concert hall experience. The ADEL will protect you. That's why top artists such as Beyonce rely on ADEL. Independent tests have proven its efficacy and now customers in 28 countries will enjoy great music while preserving their hearing." Asius Technologies (www.AsiusTechnologies.com) develops audio technology that employs a patented second eardrum which absorbs the harmful pressures that cause hearing loss and degrade sound quality. Asius' products are enjoyed the world over by sound engineers, musicians, audiophiles, and anyone who wears ear devices for sustained periods in loud environments. Asius Technologies was founded by Stephen Ambrose, the "Father of Personal Audio," who trail blazed the path for the Walkman, iPod, and virtual reality devices by inventing and then commercializing the in-ear monitor (IEM). Feeling responsible for the epidemic of hearing loss attributed to personal listening devices, Stephen is now dedicated to developing technology that not only enhances listening, but also preserves and even restores long lost hearing function.

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