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Hemakumar M Reddy, Kyung-Ah Cho, Monkol Lek, Elicia Estrella, Elise Valkanas, Michael D Jones, Satomi Mitsuhashi, Basil T Darras, Anthony A Amato, Hart Gw Lidov, Catherine A Brownstein, David M Margulies, Timothy W Yu, Mustafa A Salih, Louis M Kunkel, Daniel G MacArthur, Peter B Kang
The current study characterizes a cohort of limb-girdle muscular dystrophy (LGMD) in the United States using whole-exome sequencing. Fifty-five families affected by LGMD were recruited using an institutionally approved protocol. Exome sequencing was performed on probands and selected parental samples. Pathogenic mutations and cosegregation patterns were confirmed by Sanger sequencing. Twenty-two families (40%) had novel and previously reported pathogenic mutations, primarily in LGMD genes, and also in genes for Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy, congenital myopathy, myofibrillar myopathy, inclusion body myopathy and Pompe disease...
October 6, 2016: Journal of Human Genetics
Grant P Redrow, Charles C Guo, Maurizio A Brausi, Jonathan A Coleman, Mario I Fernandez, Wassim Kassouf, Francis X Keeley, Vitaly Margulis, Jay D Raman, Morgan Roupret, Shahrokh F Shariat, Philippe E Spiess, George N Thalmann, Surena F Matin
PURPOSE: Carcinoma in situ of the urinary tract is a high-grade form of non-muscle invasive urothelial carcinoma, with poor understanding of this entity in the upper tract (UTCIS). Patient management remains challenging due to knowledge gaps regarding the definition, diagnosis, treatment options, and follow up of disease. We review the available literature for similarities and differences between bladder and upper tract CIS summarizing the best available data. MATERIALS AND METHODS: Thorough review of PubMed and MEDLINE databases was performed from January 1976 through September 2014...
September 21, 2016: Journal of Urology
Abigail Shatkin-Margolis, Maqdooda Merchant, Rebecca U Margulies, Olga Ramm
OBJECTIVES: Minimally invasive approaches to sacrocolpopexy have transformed it into a primary procedure for treatment of pelvic organ prolapse. Certain modifications are commonly used to facilitate the laparoscopic approach, but have not yet been widely studied. In this study, we investigated the efficacy and safety of titanium surgical tacks for the attachment of mesh to the anterior longitudinal ligament in laparoscopic sacrocolpopexy. METHODS: This retrospective cohort study involved all patients within 1 health care system who underwent laparoscopic sacrocolpopexy between January 2009 and December 2012...
September 21, 2016: Female Pelvic Medicine & Reconstructive Surgery
Livia S Eberlin, Katherine Margulis, Ivette Planell-Mendez, Richard N Zare, Robert Tibshirani, Teri A Longacre, Moe Jalali, Jeffrey A Norton, George A Poultsides
BACKGROUND: Surgical resection with microscopically negative margins remains the main curative option for pancreatic cancer; however, in practice intraoperative delineation of resection margins is challenging. Ambient mass spectrometry imaging has emerged as a powerful technique for chemical imaging and real-time diagnosis of tissue samples. We applied an approach combining desorption electrospray ionization mass spectrometry imaging (DESI-MSI) with the least absolute shrinkage and selection operator (Lasso) statistical method to diagnose pancreatic tissue sections and prospectively evaluate surgical resection margins from pancreatic cancer surgery...
August 2016: PLoS Medicine
Nirmish Singla, Ryan Hutchinson, Ahmed Haddad, Arthur Sagalowsky, Yair Lotan, Vitaly Margulis
INTRODUCTION: To compare renal function changes after radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC) based on the presence of preoperative hydronephrosis. MATERIALS AND METHODS: Clinicopathologic data of 208 patients with UTUC treated surgically from 1998 to 2013 were compiled. Patients with bilateral disease, less than 1 month follow up, missing hydronephrosis data, or who underwent nephron-sparing approaches were excluded...
August 2016: Canadian Journal of Urology
Leah Shelef, Shron Dotan, Dan Kaminsky, Ron Kedem, Alexander Margulis, Ayal Hassidim
One of the most common psychiatric diagnoses among adolescents is anxiety disorder. Many of the anxiety symptoms are expressed physiologically, and therefore can mimic other medical conditions. The aim of this study was to examine the association between anxiety disorders and other medical conditions sharing common symptoms with anxiety (MDSCSA: Irritable Bowel Syndrome, asthma, migraine and hyperhidrosis). The study was based on the national database of the candidates for military service in Israel. Data for the years 1998-2013 was retrieved to create the study dataset...
October 30, 2016: Psychiatry Research
Megan Y Harada, David M Hoang, Andrea A Zaw, Jason S Murry, Oksana Volod, Beatrice J Sun, Miriam Nuño, Russell Mason, Daniel R Margulies, Eric J Ley
OBJECTIVE: Recent studies reveal a high occurrence of overdiagnosis of heparin-induced thrombocytopenia in surgical patients with critical illness. The optimal criteria for diagnosis of heparin-induced thrombocytopenia remain unclear, contributing to unnecessary treatment. We reviewed patients who were admitted to surgical ICUs and were suspected of heparin-induced thrombocytopenia to identify how often patients were correctly treated. DESIGN: In this clinical prospective study, data were collected including age, sex, antiplatelet factor 4/heparin enzyme-linked immunosorbent assay, serotonin release assay, and Warkentin 4Ts scores...
August 4, 2016: Critical Care Medicine
Yaroslav G Gurskiy, David G Garbuz, Nataliya V Soshnikova, Aleksey N Krasnov, Alexei Deikin, Vladimir F Lazarev, Dmitry Sverchinskyi, Boris A Margulis, Olga G Zatsepina, Vadim L Karpov, Svetlana N Belzhelarskaya, Evgenia Feoktistova, Sofia G Georgieva, Michael B Evgen'ev
The production of major human heat shock protein Hsp70 (HSPA1A) in a eukaryotic expression system is needed for testing and possible medical applications. In this study, transgenic mice were produced containing wild-type human Hsp70 allele in the vector providing expression in the milk. The results indicated that human Hsp70 was readily expressed in the transgenic animals but did not apparently preserve its intact structure and, hence, it was not possible to purify the protein using conventional isolation techniques...
August 10, 2016: Cell Stress & Chaperones
Nirmish Singla, Ryan Hutchinson, Colleen Menegaz, Ahmed Q Haddad, Lai Jiang, Arthur I Sagalowsky, Jeffrey A Cadeddu, Yair Lotan, Vitaly Margulis
OBJECTIVE: To compare changes in renal function after radical nephrectomy for renal cell carcinoma (RCC) and radical nephroureterectomy for upper tract urothelial carcinoma (UTUC), and assess their effects on non-cancer-specific mortality (CSM). METHODS: Clinicopathologic data from 1114 patients with RCC or UTUC treated surgically from 1997 to 2013 were compiled. Patients who underwent nephron-sparing surgeries, had bilateral disease, received chemotherapy, or had <1 month of follow-up were excluded...
October 2016: Urology
Miao Liu, Nirmal Verma, Xiaoli Peng, Sarah Srodulski, Andrew Morris, Martin Chow, Louis B Hersh, Jing Chen, Haining Zhu, Mihai G Netea, Kenneth B Margulies, Sanda Despa, Florin Despa
Hypersecretion of amylin is common in individuals with prediabetes, causes amylin deposition and proteotoxicity in pancreatic islets, and contributes to the development of type 2 diabetes. Recent studies also identified amylin deposits in failing hearts from patients with obesity or type 2 diabetes and demonstrated that hyperamylinemia accelerates the development of heart dysfunction in rats expressing human amylin in pancreatic β-cells (HIP rats). To further determine the impact of hyperamylinemia on cardiac myocytes, we investigated human myocardium, compared diabetic HIP rats with diabetic rats expressing endogenous (nonamyloidogenic) rat amylin, studied normal mice injected with aggregated human amylin, and developed in vitro cell models...
September 2016: Diabetes
Ning Hou, Bo Ye, Xiang Li, Kenneth B Margulies, Haodong Xu, Xuejun Wang, Faqian Li
BACKGROUND: How canonical Wnt/β-catenin signals in adult hearts, especially in different diseased states, remains unclear. The proto-oncogene, c-Myc, is a Wnt target and an early response gene during cardiac stress. It is not clear whether c-Myc is activated or how it is regulated during heart failure. METHODS AND RESULTS: We investigated canonical Wnt/β-catenin signaling and how it regulated c-Myc expression in failing hearts of human ischemic heart disease, idiopathic dilated cardiomyopathy, and murine desmin-related cardiomyopathy...
June 2016: Circulation. Heart Failure
Francesco Soria, Marco Moschini, Andrea Haitel, Gregory J Wirth, Jose A Karam, Christopher G Wood, Morgan Rouprêt, Vitaly Margulis, Pierre I Karakiewicz, Alberto Briganti, Jay D Raman, Solene-Florence Kammerer-Jacquet, Romain Mathieu, Karim Bensalah, Yair Lotan, Mehmet Özsoy, Mesut Remzi, Kilian M Gust, Shahrokh F Shariat
PURPOSE: The aim of our study was to evaluate the expression pattern of HER2 overexpression in patients with upper tract urothelial carcinoma (UTUC) and to evaluate its association with clinical outcomes. METHODS: This multicenter retrospective study included 732 patients treated with radical nephroureterectomy for UTUC. HER2 expression was assessed using immunohistochemistry and scored according to the HercepTest: Scores of 0 or 1 were considered negative and 2 or 3 as positive...
June 7, 2016: World Journal of Urology
Rao S Mandalapu, Mesut Remzi, Theo M de Reijke, Vitaly Margulis, J Palou, A Kapoor, Ofer Yossepowitch, Jonathan Coleman, Olivier Traxer, J Kyle Anderson, James Catto, Jean de la Rosette, Timothy O'Brien, Anthony Zlotta, Surena F Matin
INTRODUCTION: The conservative management of upper tract urothelial carcinoma (UTUC) has historically been offered to patients with imperative indications. The recent International Consultation on Urologic Diseases (ICUD) publication on UTUC stratified treatment allocations based on high- and low-risk groups. This report updates the conservative management of the low-risk group. METHODS: The ICUD for low-risk UTUC working group performed a thorough review of the literature with an assessment of the level of evidence and grade of recommendation for a variety of published studies in this disease space...
May 27, 2016: World Journal of Urology
Jay D Raman, Joshua I Warrick, Carla Caruso, Zhaohai Yang, Lauren Shuman, Richard D Bruggeman, Shahrokh Shariat, Jose A Karam, Christopher Wood, Alon Z Weizer, Mesut Remzi, Andrea Haitel, Karim Bensalah, Nathalie Rioux-Leclerq, Christian Bolenz, Marco Roscigno, Laura-Maria Krabbe, Payal Kapur, Yair Lotan, Vitaly Margulis, David J DeGraff
OBJECTIVE: To determine the prognostic significance of Forkhead Box A1 (FOXA1) expression in patients with upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU). MATERIALS AND METHODS: A retrospective analysis of 566 patients undergoing RNU at seven academic medical centers was performed. Tissue microarrays were subjected to immunohistochemistry using a commercially available polyclonal FOXA1 antibody. Logistic regression determined the association of FOXA1 expression with pathologic features and survival outcomes...
August 2016: Urology
Mihai Dorin Vartolomei, Romain Mathieu, Vitaly Margulis, Jose A Karam, Morgan Rouprêt, Ilaria Lucca, Aurélie Mbeutcha, Christian Seitz, Pierre I Karakiewicz, Harun Fajkovic, Christopher G Wood, Alon Z Weizer, Jay D Raman, Nathalie Rioux-Leclercq, Andrea Haitel, Karim Bensalah, Michael Rink, Alberto Briganti, Evanguelos Xylinas, Shahrokh F Shariat
OBJECTIVE: Several retrospective studies with small cohorts reported neutrophil-to-lymphocyte ratio (NLR) as a prognostic marker in upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy (RNU). We aimed at validating the predictive and prognostic role of NLR in a large multi-institutional cohort. METHODS: Preoperative NLR was assessed in a multi-institutional cohort of 2477 patients with UTUC treated with RNU. Altered NLR was defined by a ratio >2...
May 21, 2016: World Journal of Urology
Ricardo L Favaretto, Atessa Bahadori, Romain Mathieu, Andrea Haitel, Bernhard Grubmüller, Vitaly Margulis, Jose A Karam, Morgan Rouprêt, Christian Seitz, Pierre I Karakiewicz, Isabela W Cunha, Stenio C Zequi, Christopher G Wood, Alon Z Weizer, Jay D Raman, Mesut Remzi, Nathalie Rioux-Leclercq, Solene Jacquet-Kammerer, Karim Bensalah, Yair Lotan, Alexander Bachmann, Michael Rink, Alberto Briganti, Shahrokh F Shariat
PURPOSE: To assess the role of E-cadherin as prognostic biomarker in upper tract urothelial carcinoma (UTUC) in a large multi-institutional cohort of patients. METHODS: Immunohistochemistry technique was used to evaluate E-cadherin expression in 678 patients with unilateral, sporadic UTUC treated with RNU. E-cadherin expression was considered decreased if 10 % or more cells had decreased expression (<90 %). RESULTS: Decreased E-cadherin expression was observed in 353 patients (52...
April 29, 2016: World Journal of Urology
Patrick Robison, Matthew A Caporizzo, Hossein Ahmadzadeh, Alexey I Bogush, Christina Yingxian Chen, Kenneth B Margulies, Vivek B Shenoy, Benjamin L Prosser
The microtubule (MT) cytoskeleton can transmit mechanical signals and resist compression in contracting cardiomyocytes. How MTs perform these roles remains unclear because of difficulties in observing MTs during the rapid contractile cycle. Here, we used high spatial and temporal resolution imaging to characterize MT behavior in beating mouse myocytes. MTs deformed under contractile load into sinusoidal buckles, a behavior dependent on posttranslational "detyrosination" of α-tubulin. Detyrosinated MTs associated with desmin at force-generating sarcomeres...
April 22, 2016: Science
Ryan Hutchinson, Ahmed Haddad, Arthur Sagalowsky, Vitaly Margulis
Upper tract urothelial carcinoma (UTUC) is an uncommon disease with a prognosis worse than that of primary urothelial carcinoma (UC) of the bladder. Although surgery remains the mainstay of UTUC therapy, there is increasing enthusiasm for combined-modality approaches in both adjuvant and neoadjuvant settings. Nephron-sparing surgical strategies, including partial ureterectomy and purely endoscopic tumor resection, are also increasingly used. Through the development of multi-institutional consortiums, novel treatment algorithms can now be used to evaluate patients more efficiently and thoroughly than in the past...
February 2016: Clinical Advances in Hematology & Oncology: H&O
Laura M Krabbe, Ryan C Hutchinson, Vitaly Margulis
Even though urothelial cancer may occur anywhere in the urinary tract, it is most commonly found in the urinary bladder. Due to its higher incidence, this disease is studied in the bladder much more frequently than in the upper urinary tract. The question that arises is, to what extent can concepts and treatment paradigms derived from lower tract disease be applied to urothelial carcinoma of the upper urinary tract? This review aims at providing an overview of established care concepts in urothelial carcinoma of the bladder and applicability of these findings to tumors of the upper urinary tract...
August 2016: Minerva Urologica e Nefrologica, the Italian Journal of Urology and Nephrology
Xuan Zhang, Erik R Abels, Jasmina S Redzic, Julia Margulis, Steve Finkbeiner, Xandra O Breakefield
In Huntington's disease (HD) the imperfect expanded CAG repeat in the first exon of the HTT gene leads to the generation of a polyglutamine (polyQ) protein, which has some neuronal toxicity, potentially mollified by formation of aggregates. Accumulated research, reviewed here, implicates both the polyQ protein and the expanded repeat RNA in causing toxicity leading to neurodegeneration in HD. Different theories have emerged as to how the neurodegeneration spreads throughout the brain, with one possibility being the transport of toxic protein and RNA in extracellular vesicles (EVs)...
April 2016: Cellular and Molecular Neurobiology
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