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https://www.readbyqxmd.com/read/29704482/new-hsf1-inducer-as-a-therapeutic-agent-in-a-rodent-model-of-parkinson-s-disease
#1
Irina V Ekimova, Daria V Plaksina, Yuri F Pastukhov, Ksenia V Lapshina, Vladimir F Lazarev, Elena R Mikhaylova, Sergey G Polonik, Bibhusita Pani, Boris A Margulis, Irina V Guzhova, Evgeny Nudler
Molecular chaperone HSP70 (HSPA1A) has therapeutic potential in conformational neurological diseases. Here we evaluate the neuroprotective function of the chaperone in a rat model of Parkinson's disease (PD). We show that the knock-down of HSP70 (HSPA1A) in dopaminergic neurons of the Substantia nigra causes an almost 2-fold increase in neuronal death and multiple motor disturbances in animals. Conversely, pharmacological activation of HSF1 transcription factor and enhanced expression of inducible HSP70 with the echinochrome derivative, U-133, reverses the process of neurodegeneration, as evidenced by а increase in the number of tyrosine hydroxylase-containing neurons, and prevents the motor disturbances that are typical of the clinical stage of the disease...
April 25, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29614076/a-deep-learning-classifier-identifies-patients-with-clinical-heart-failure-using-whole-slide-images-of-h-e-tissue
#2
Jeffrey J Nirschl, Andrew Janowczyk, Eliot G Peyster, Renee Frank, Kenneth B Margulies, Michael D Feldman, Anant Madabhushi
Over 26 million people worldwide suffer from heart failure annually. When the cause of heart failure cannot be identified, endomyocardial biopsy (EMB) represents the gold-standard for the evaluation of disease. However, manual EMB interpretation has high inter-rater variability. Deep convolutional neural networks (CNNs) have been successfully applied to detect cancer, diabetic retinopathy, and dermatologic lesions from images. In this study, we develop a CNN classifier to detect clinical heart failure from H&E stained whole-slide images from a total of 209 patients, 104 patients were used for training and the remaining 105 patients for independent testing...
2018: PloS One
https://www.readbyqxmd.com/read/29540468/genetic-reduction-in-left-ventricular-protein-kinase-c-%C3%AE-and-adverse-ventricular-remodeling-in-human-subjects
#3
Ray Hu, Michael P Morley, Jeffrey Brandimarto, Nathan R Tucker, Victoria A Parsons, Sihai D Zhao, Benjamin Meder, Hugo A Katus, Frank Rühle, Monika Stoll, Eric Villard, François Cambien, Honghuang Lin, Nicholas L Smith, Janine F Felix, Ramachandran S Vasan, Pim van der Harst, Christopher Newton-Cheh, Jin Li, Cecilia E Kim, Hakon Hakonarson, Sridhar Hannenhalli, Euan A Ashley, Christine S Moravec, W H Wilson Tang, Marjorie Maillet, Jeffery D Molkentin, Patrick T Ellinor, Kenneth B Margulies, Thomas P Cappola
BACKGROUND: Inhibition of PKC-α (protein kinase C-α) enhances contractility and cardioprotection in animal models, but effects in humans are unknown. Genotypes at rs9912468 strongly associate with PRKCA expression in the left ventricle, enabling genetic approaches to measure effects of reduced PKC-α in human populations. METHODS AND RESULTS: We analyzed the cis expression quantitative trait locus for PRKCA marked by rs9912468 using 313 left ventricular specimens from European Ancestry patients...
March 2018: Circulation. Genomic and precision medicine
https://www.readbyqxmd.com/read/29535082/expert-coaching-in-weight-loss-retrospective-analysis
#4
Stefanie Lynn Painter, Rezwan Ahmed, Robert F Kushner, James O Hill, Richard Lindquist, Scott Brunning, Amy Margulies
BACKGROUND: Providing coaches as part of a weight management program is a common practice to increase participant engagement and weight loss success. Understanding coach and participant interactions and how these interactions impact weight loss success needs to be further explored for coaching best practices. OBJECTIVE: The purpose of this study was to analyze the coach and participant interaction in a 6-month weight loss intervention administered by Retrofit, a personalized weight management and Web-based disease prevention solution...
March 13, 2018: Journal of Medical Internet Research
https://www.readbyqxmd.com/read/29500270/how-mhc-molecules-grab-citrullinated-peptides-to-foster-rheumatoid-arthritis
#5
David H Margulies
The molecular immunologist's dream is to elucidate a fundamental biochemical process that explains the basis of an affliction that affects millions of people, and that, precisely understood, might yield a rational approach to diagnosis, prevention, or therapy. In this issue of JBC, Ting et al. report proteomic, biochemical, and structural analyses that better explain how the antigen-presenting HLA-DR4 molecules bind citrullinated peptides to provoke rheumatoid arthritis (RA), a chronic autoimmune disease that affects 0...
March 2, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29482685/diagnosis-of-hypofibrinogenemia-after-dental-treatment-under-general-anesthesia
#6
Tracy Kim, Farhad Yeroshalmi, Keith S Margulis, Victor Badner, Kenneth Rivlin
Congenital hypofibrinogenemia is a rare coagulation disorder characterized by a deficiency in fibrinogen protein, which is critical to the normal coagulation process. This hematological disorder can go undiagnosed until an event leads to prolonged bleeding. The purposes of this report were to describe an incidental diagnosis of congenital hypofibrinogenemia after a dental procedure, discuss the importance of recognizing coagulopathies on the delivery of dental care, examine the multi-disciplinary clinical management of prolonged bleeding after a dental procedure, and evaluate the challenges health care practitioners may encounter when obtaining a thorough medical history...
January 1, 2018: Pediatric Dentistry
https://www.readbyqxmd.com/read/29457789/a-common-variant-alters-scn5a-mir-24-interaction-and-associates-with-heart-failure-mortality
#7
Xiaoming Zhang, Jin-Young Yoon, Michael Morley, Jared M McLendon, Kranti A Mapuskar, Rebecca Gutmann, Haider Mehdi, Heather L Bloom, Samuel C Dudley, Patrick T Ellinor, Alaa A Shalaby, Raul Weiss, W H Wilson Tang, Christine S Moravec, Madhurmeet Singh, Anne L Taylor, Clyde W Yancy, Arthur M Feldman, Dennis M McNamara, Kaikobad Irani, Douglas R Spitz, Patrick Breheny, Kenneth B Margulies, Barry London, Ryan L Boudreau
SCN5A encodes the voltage-gated Na+ channel NaV1.5 that is responsible for depolarization of the cardiac action potential and rapid intercellular conduction. Mutations disrupting the SCN5A coding sequence cause inherited arrhythmias and cardiomyopathy, and single-nucleotide polymorphisms (SNPs) linked to SCN5A splicing, localization, and function associate with heart failure-related sudden cardiac death. However, the clinical relevance of SNPs that modulate SCN5A expression levels remains understudied. We recently generated a transcriptome-wide map of microRNA (miR) binding sites in human heart, evaluated their overlap with common SNPs, and identified a synonymous SNP (rs1805126) adjacent to a miR-24 site within the SCN5A coding sequence...
March 1, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29427584/discordance-between-ureteroscopic-biopsy-and-final-pathology-for-upper-tract-urothelial-carcinoma
#8
Ezra J Margolin, Justin T Matulay, Gen Li, Xiaosong Meng, Brian Chao, Varun Vijay, Hayley Silver, Timothy N Clinton, Laura-Maria Krabbe, Solomon L Woldu, Nirmish Singla, Aditya Bagrodia, Vitaly Margulis, William C Huang, Marc A Bjurlin, Ojas Shah, Christopher B Anderson
PURPOSE: We evaluated the discordance between ureteroscopic biopsy and surgical pathology findings for grading and staging upper tract urothelial carcinoma. We also sought to establish preoperative predictors of aggressive tumors. MATERIALS AND METHODS: We retrospectively reviewed the records of 314 patients who underwent ureteroscopic biopsy followed by surgical management of upper tract urothelial carcinoma from 2000 to 2016 at a total of 3 institutions. Our primary outcomes were muscle invasive (pT2 or greater) disease at surgical pathology and upgrading of clinical low grade tumors to pathological high grade...
February 7, 2018: Journal of Urology
https://www.readbyqxmd.com/read/29352073/right-ventricular-myofilament-functional-differences-in-humans-with-systemic-sclerosis-associated-versus-idiopathic-pulmonary-arterial-hypertension
#9
Steven Hsu, Kristen M Kokkonen-Simon, Jonathan A Kirk, Todd M Kolb, Rachel L Damico, Stephen C Mathai, Monica Mukherjee, Ami A Shah, Fredrick M Wigley, Kenneth B Margulies, Paul M Hassoun, Marc K Halushka, Ryan J Tedford, David A Kass
Background -Patients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) have a far worse prognosis than those with idiopathic PAH (IPAH). In the intact heart, SSc-PAH exhibits depressed rest and reserve right ventricular (RV) contractility as compared to IPAH. We tested whether this disparity involves underlying differences in myofilament function. Methods -Cardiac myocytes were isolated from RV septal endomyocardial biopsies from patients with SSc-PAH, IPAH, or SSc with exertional dyspnea but no resting PAH (SSc-d); control RV septal tissue was obtained from non-diseased donor hearts (6-7/group)...
January 19, 2018: Circulation
https://www.readbyqxmd.com/read/29226251/tissue-based-biomarkers-in-prostate-cancer
#10
Timothy N Clinton, Aditya Bagrodia, Yair Lotan, Vitaly Margulis, Ganesh V Raj, Solomon L Woldu
Introduction: Prostate cancer is a heterogeneous disease. Existing risk stratification tools based on standard clinlicopathologic variables (prostate specific antigen [PSA], Gleason score, and tumor stage) provide a modest degree of predictive ability. Advances in high-throughput sequencing has led to the development of several novel tissue-based biomarkers that can improve prognostication in prostate cancer management. Areas Covered: The authors review commercially-available, tissue-based biomarker assays that improve upon existing risk-stratification tools in several areas of prostate cancer management, including the appropriateness of active surveillance and aiding in decision making regarding the use of adjuvant therapy...
2017: Expert Review of Precision Medicine and Drug Development
https://www.readbyqxmd.com/read/29174945/preoperative-predictors-of-nonorgan-confined-disease-in-upper-tract-urothelial-carcinoma-differ-between-china-and-the-united-states
#11
Nirmish Singla, Dong Fang, Xiaohong Su, Zhengqing Bao, Zhenpeng Cao, Haley Robyak, Gengyan Xiong, Lei Zhang, Solomon Woldu, Ryan Hutchinson, Arthur Sagalowsky, Yair Lotan, Xuesong Li, Liqun Zhou, Jay D Raman, Vitaly Margulis
OBJECTIVE: To compare preoperative predictors of nonorgan-confined (NOC) disease in patients with upper-tract urothelial carcinoma (UTUC) from the United States (US) and China. METHODS: Clinicopathologic data of patients with UTUC treated surgically at tertiary care facilities in the US or China from 1998 to 2015 were, retrospectively, compiled. Patient characteristics, preoperative imaging, cytology, ureteroscopic findings, and serum markers (neutrophil-to-lymphocyte ratio, estimated glomerular filtration rate, hemoglobin, and albumin) were evaluated...
March 2018: Urologic Oncology
https://www.readbyqxmd.com/read/29135571/validation-of-cancer-cases-using-primary-care-cancer-registry-and-hospitalization-data-in-the-united-kingdom
#12
Andrea V Margulis, Joan Fortuny, James A Kaye, Brian Calingaert, Maria Reynolds, Estel Plana, Lisa J McQuay, Willem Jan Atsma, Billy Franks, Stefan de Vogel, Susana Perez-Gutthann, Alejandro Arana
BACKGROUND: In the United Kingdom, hospital or cancer registry data can be linked to electronic medical records for a subset of general practices and years. METHODS: We used Clinical Practice Research Datalink data (2004-2012) from patients treated for overactive bladder. We electronically identified provisional cases of 10 common cancers in General Practitioner Online Database data and validated them by medical profile review. In practices with linkage to Hospital Episodes Statistics and National Cancer Data Repository (2004-2010), we validated provisional cancer cases against these data sources...
March 2018: Epidemiology
https://www.readbyqxmd.com/read/29133936/the-rho-gtpase-signalling-pathway-in-urothelial-carcinoma
#13
REVIEW
Solomon L Woldu, Ryan C Hutchinson, Laura-Maria Krabbe, Oner Sanli, Vitaly Margulis
Urothelial carcinoma remains a clinical challenge: non-muscle-invasive disease has a high rate of recurrence and risk of progression, and outcomes for patients with advanced disease are poor, owing to a lack of effective systemic therapies. The Rho GTPase family of enzymes was first identified >30 years ago and contains >20 members, which are divided into eight subfamilies: Cdc42, Rac, Rho, RhoUV, RhoBTB, RhoDF, RhoH, and Rnd. Rho GTPases are molecular on-off switches, which are increasingly being understood to have a critical role in a number of cellular processes, including cell migration, cell polarity, cell adhesion, cell cycle progression, and regulation of the cytoskeleton...
February 2018: Nature Reviews. Urology
https://www.readbyqxmd.com/read/29105239/different-shades-of-default-mode-disturbance-in-schizophrenia-subnodal-covariance-estimation-in-structure-and-function
#14
Jérémy Lefort-Besnard, Danielle S Bassett, Jonathan Smallwood, Daniel S Margulies, Birgit Derntl, Oliver Gruber, Andre Aleman, Renaud Jardri, Gaël Varoquaux, Bertrand Thirion, Simon B Eickhoff, Danilo Bzdok
Schizophrenia is a devastating mental disease with an apparent disruption in the highly associative default mode network (DMN). Interplay between this canonical network and others probably contributes to goal-directed behavior so its disturbance is a candidate neural fingerprint underlying schizophrenia psychopathology. Previous research has reported both hyperconnectivity and hypoconnectivity within the DMN, and both increased and decreased DMN coupling with the multimodal saliency network (SN) and dorsal attention network (DAN)...
February 2018: Human Brain Mapping
https://www.readbyqxmd.com/read/29079210/differences-at-presentation-and-treatment-of-testicular-cancer-in-hispanic-men-institutional-and-national-hospital-based-analyses
#15
Solomon L Woldu, Ahmet M Aydin, Ashwin V Rao, Ryan C Hutchinson, Nirmish Singla, Timothy N Clinton, Laura-Maria Krabbe, Niccolo M Passoni, Ganesh V Raj, David S Miller, James F Amatruda, Arthur I Sagalowsky, Yair Lotan, Yull Arriaga, Vitaly Margulis, Aditya Bagrodia
OBJECTIVE: To describe epidemiologic patterns, stage at presentation, histology, and treatment differences associated with Hispanic men diagnosed with testicular germ cell tumor (TGCT). Hispanics are the fastest growing demographic in the United States and reports suggest that the incidence of TGCT is rising most rapidly in this demographic, yet little is known about TGCTs in Hispanic patients. MATERIALS AND METHODS: We compared patient factors, tumor characteristics, treatment patterns, and outcomes of non-Hispanic white (NHW) vs Hispanic patients at our own institution in North Texas from 2010 to 2016...
February 2018: Urology
https://www.readbyqxmd.com/read/29058737/on-demand-electrically-controlled-drug-release-from-resorbable-nanocomposite-films
#16
Devleena Samanta, Rohan Mehrotra, Katy Margulis, Richard N Zare
Electroresponsive materials are promising carriers for developing drug delivery systems (DDSs) with excellent spatial, temporal, and dosage control over drug release. Current electroresponsive systems use high voltages (2-25 V), are not bioresorbable, or use materials with unknown long-term biocompatibility. We report here a nanocomposite film that is resorbable, electroresponsive at low voltages (<-2 V), and composed of entirely FDA-approved materials. Our DDS is based on poly(methyl methacrylate-co-methacrylic acid), commercially marketed as Eudragit S100 (EGT), which has pH-dependent aqueous solubility...
November 2, 2017: Nanoscale
https://www.readbyqxmd.com/read/29055387/the-colon-revisited-or-the-key-to-wellness-health-and-disease
#17
C A Gonzalez-Correa, E Mulett-Vásquez, D A Miranda, C H Gonzalez-Correa, P A Gómez-Buitrago
The hypothesis being advanced in this paper is that there is a new medical paradigm emerging from the biomedical research carried out in this century, mainly due to the explosion of the so called "omics" and associated techniques. The main idea is that there is a common pathway from wellbeing and health to chronic disease ("chronopathy") and even to death, which comprises following steps: 1) unhealthy diet, sedentary life style and permanent exposition to xenobiotics and all kinds of noxious stimuli;→2) intestinal dysbiosis;→3) alteration of the intestinal mucus layer (especially that of the colon);→4) disruption of the endothelial tight junctions;→5) metabolic endotoxemia+bacterial translocation;→6) inflammation;→7) exacerbation of the enteric nervous system (ENS) and consequent maladaptation and malfunctioning of the colon;→8) epigenetic manifestations;→9) "chronopathy" and premature death...
October 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29023576/overexpression-of-tissue-nonspecific-alkaline-phosphatase-tnap-in-endothelial-cells-accelerates-coronary-artery-disease-in-a-mouse-model-of-familial-hypercholesterolemia
#18
Filippo Romanelli, AnthonyMarco Corbo, Maryam Salehi, Manisha C Yadav, Soha Salman, David Petrosian, Omid J Rashidbaigi, Jesse Chait, Jes Kuruvilla, Maria Plummer, Ilian Radichev, Kenneth B Margulies, A Martin Gerdes, Anthony B Pinkerton, José Luis Millán, Alexei Y Savinov, Olga V Savinova
OBJECTIVE: Overexpression of tissue-nonspecific alkaline phosphatase (TNAP) in endothelium leads to arterial calcification in mice. The purpose of this study was to examine the effect of elevated endothelial TNAP on coronary atherosclerosis. In addition, we aimed to examine endogenous TNAP activity in human myocardium. APPROACH AND RESULTS: A vascular pattern of TNAP activity was observed in human non-failing, ischemic, and idiopathic dilated hearts (5 per group); no differences were noted between groups in this study...
2017: PloS One
https://www.readbyqxmd.com/read/28940605/adjuvant-chemotherapy-after-radical-nephroureterectomy-does-not-improve-survival-in-patients-with-upper-tract-urothelial-carcinoma-a-joint-study-by-the-european-association-of-urology-young-academic-urologists-and-the-upper-tract-urothelial-carcinoma-collaboration
#19
MULTICENTER STUDY
Andrea Necchi, Salvatore Lo Vullo, Luigi Mariani, Marco Moschini, Kees Hendricksen, Michael Rink, Roman Sosnowski, Jakub Dobruch, Jay D Raman, Christopher G Wood, Vitaly Margulis, Morgan Roupret, Alberto Briganti, Francesco Montorsi, Evanguelos Xylinas, Shahrokh F Shariat
OBJECTIVE: To analyse the outcomes of adjuvant chemotherapy vs observation in a multicentre cohort of patients with upper tract urothelial carcinoma (UTUC) in order to clarify whether such patients benefit from adjuvant chemotherapy after radical nephroureterectomy (RNU). PATIENTS AND METHODS: Data from 15 centres were collected for a total of 1544 patients, treated between 2000 and 2015. Criteria for patient selection included pT2-4N0/x stage, or lymph node-positive disease, and prior RNU...
February 2018: BJU International
https://www.readbyqxmd.com/read/28935185/impact-of-hospital-case-volume-on-testicular-cancer-outcomes-and-practice-patterns
#20
Solomon L Woldu, Justin T Matulay, Timothy N Clinton, Nirmish Singla, Laura-Maria Krabbe, Ryan C Hutchinson, Arthur Sagalowsky, Yair Lotan, Vitaly Margulis, Aditya Bagrodia
BACKGROUND: Given the rarity of testicular germ cell tumors (TGCTs) and the complex aspects of management, we evaluate the effect of hospital TGCT case volume on overall survival outcomes and practice patterns. MATERIALS AND METHODS: The National Cancer Database was queried for patients diagnosed with seminoma or nonseminomatous germ cell tumor (NSGCT). Hospitals were classified by case volume as high (99th percentile, ≥26.1 cases annually), high-intermediate (95-99th percentile, 14...
January 2018: Urologic Oncology
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