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Renaud Gaujoux, Elina Starosvetsky, Naama Maimon, Francesco Vallania, Haggai Bar-Yoseph, Sigal Pressman, Roni Weisshof, Idan Goren, Keren Rabinowitz, Matti Waterman, Henit Yanai, Iris Dotan, Edmond Sabo, Yehuda Chowers, Purvesh Khatri, Shai S Shen-Orr
OBJECTIVE: Although anti-tumour necrosis factor alpha (anti-TNFα) therapies represent a major breakthrough in IBD therapy, their cost-benefit ratio is hampered by an overall 30% non-response rate, adverse side effects and high costs. Thus, finding predictive biomarkers of non-response prior to commencing anti-TNFα therapy is of high value. DESIGN: We analysed publicly available whole-genome expression profiles of colon biopsies obtained from multiple cohorts of patients with IBD using a combined computational deconvolution-meta-analysis paradigm which allows to estimate immune cell contribution to the measured expression and capture differential regulatory programmes otherwise masked due to variation in cellular composition...
April 4, 2018: Gut
Corina Monagin, Blanca Paccha, Ning Liang, Sally Trufan, Huiqiong Zhou, De Wu, Bradley S Schneider, Aleksei Chmura, Jonathan Epstein, Peter Daszak, Changwen Ke, Peter M Rabinowitz
We report on a study conducted in Guangdong Province, China, to characterize behaviors and perceptions associated with transmission of pathogens with pandemic potential in highly exposed human populations at the animal-human interface. A risk factor/exposure survey was administered to individuals with high levels of exposure to wildlife. Serological testing was performed to evaluate prior infection with several wildlife viral pathogens. Follow up serology was performed on a subset of the cohort as well as close contacts of individuals...
2018: PloS One
Jay Menaker, Ronald P Rabinowitz, Ali Tabatabai, Ronald B Tesoriero, Katelyn Dolly, Christopher Cornachione, Edward Stene, Jessica Buchner, Joseph Kufera, Zachary N Kon, Kristopher B Deatrick, Daniel L Herr, James V O'Connor, Thomas M Scalea
The use of veno-venous extracorporeal membrane oxygenation (VV ECMO) in adults with respiratory failure has steadily increased during the past decade. Recent literature has demonstrated variable outcomes with the use of extended ECMO. The purpose of this study is to evaluate survival to hospital discharge in patients with extended ECMO runs compared with patients with short ECMO runs at a tertiary care ECMO referral center. We retrospectively reviewed all patients on VV ECMO for respiratory failure between August 2014 and February 2017...
March 28, 2018: ASAIO Journal: a Peer-reviewed Journal of the American Society for Artificial Internal Organs
Claudia Perez-Straziota, Ronald N Gaster, Yaron S Rabinowitz
PURPOSE: To comprehensively review the available published literature for cross-linking in the pediatric population. METHODS: Review of the literature published in English in PubMed. RESULTS: Two hundred ten publications were considered. One hundred fifteen were considered relevant to this review. CONCLUSIONS: Studies of cross-linking in pediatric patients are sparse, with relatively short follow-up times, and mostly on small groups of patients...
March 28, 2018: Cornea
Lauren E Latella, Robert J McAuley, Mitchell Rabinowitz
The current study compares health care professionals' beliefs about vaccination statements with the beliefs of a sample of individuals from the general population. Students and faculty within a medical school ( n = 58) and a sample from the general population in the United States ( n = 177) were surveyed regarding their beliefs about vaccinations. Participants evaluated statements about vaccinations (both supporting and opposing), and indicated whether they thought the general population would agree with them...
March 28, 2018: International Journal of Environmental Research and Public Health
Russell A Miller, Yuji Shi, Wenyun Lu, David A Pirman, Aditi Jatkar, Matthew Blatnik, Hong Wu, César Cárdenas, Min Wan, J Kevin Foskett, Junyoung O Park, Yiyi Zhang, William L Holland, Joshua D Rabinowitz, Morris J Birnbaum
Glucagon levels increase under homeostatic, fasting conditions, promoting the release of glucose from the liver by accelerating the breakdown of glycogen (also known as glycogenolysis). Glucagon also enhances gluconeogenic flux, including from an increase in the hepatic consumption of amino acids. In type 2 diabetes, dysregulated glucagon signaling contributes to the elevated hepatic glucose output and fasting hyperglycemia that occur in this condition. Yet, the mechanism by which glucagon stimulates gluconeogenesis remains incompletely understood...
March 26, 2018: Nature Medicine
Simon S Rabinowitz, Neha Ahuja, Jennifer Gottfried
An 11-year-old Caucasian boy, with a microdeletion in the 1q21.1-q21.2 region, had multiple medical conditions including gastroparesis documented initially at the age of 5. The patient had a history of poor feeding since infancy and had been treated for gastro-oesophageal reflux disease (GERD), constipation and multiple food allergies. As a consequence of the GERD and his concurrent immunoglobulin (IgG) subclass deficiency, the patient had multiple otolaryngologic (ENT) infections and required two sinus surgeries...
March 15, 2018: BMJ Case Reports
Donald M Hilty, Terry Rabinowitz, Robert M McCarron, David J Katzelnick, Trina Chang, Amy M Bauer, John Fortney
INTRODUCTION: In this era of patient-centered care, telepsychiatry (TP; video or synchronous) provides quality care with outcomes as good as in-person care, facilitates access to care, and leverages a wide range of treatments at a distance. METHOD: This conceptual review article explores TP as applied to newer models of care (e.g., collaborative, stepped, and integrated care). RESULTS: The field of psychosomatic medicine (PSM) has developed clinical care models, educates interdisciplinary team members, and provides leadership to clinical teams...
December 26, 2017: Psychosomatics
Miguel A Lanaspa, Ana Andres-Hernando, David J Orlicky, Christina Cicerchi, Cholsoon Jang, Nanxing Li, Tamara Milagres, Masanari Kuwabara, Michael F Wempe, Joshua D Rabinowitz, Richard J Johnson, Dean R Tolan
Increasing evidence suggests a role for excessive intake of fructose in the Western diet as a contributor to the current epidemics of metabolic syndrome and obesity. Hereditary fructose intolerance (HFI) is a difficult and potentially lethal orphan disease associated with impaired fructose metabolism. In HFI, the deficiency of a particular aldolase, aldolase B, results in the accumulation of intracellular phosphorylated fructose thus leading to phosphate sequestration and depletion, increased ATP turnover and a plethora of conditions leading to clinical manifestations including fatty liver, hyperuricemia, Fanconi syndrome and severe hypoglycemia...
March 13, 2018: Journal of Clinical Investigation
Ke-Chih Lin, Gonzalo Torga, Amy Wu, Joshua D Rabinowitz, Wesley J Murray, James C Sturm, Kenneth J Pienta, Robert Austin
We have improved our microfluidic cell culture device that generates an in vitro landscape of stress heterogeneity. We now can do continuous observations of different cancer cell lines and carry out downstream analysis of cell phenotype as a function of position on the stress landscape. We use this technology to probe adaption and evolution dynamics in prostate cancer cell metapopulations under a stress landscape of a chemotherapeutic drug (docetaxel). The utility of this approach is highlighted by analysis of heterogenous prostate cancer cell motility changes as a function of position in the stress landscape...
December 2017: Convergent Science Physical Oncology
Julianne Meisner, Manali V Vora, Mackenzie S Fuller, Amanda I Phipps, Peter M Rabinowitz
OBJECTIVE: Women in veterinary occupations are routinely exposed to potential reproductive hazards, yet research into their birth outcomes is limited. We conducted a population-based retrospective cohort study of the association between maternal veterinary occupation and adverse birth outcomes. METHODS: Using Washington State birth certificate, fetal death certificate and hospital discharge data from 1992 to 2014, we compared birth outcomes of mothers in veterinary professions (n=2662) with those in mothers in dental professions (n=10 653) and other employed mothers (n=8082)...
February 24, 2018: Occupational and Environmental Medicine
James Kirkpatrick, Razvan Pascanu, Neil Rabinowitz, Joel Veness, Guillaume Desjardins, Andrei A Rusu, Kieran Milan, John Quan, Tiago Ramalho, Agnieszka Grabska-Barwinska, Demis Hassabis, Claudia Clopath, Dharshan Kumaran, Raia Hadsell
No abstract text is available yet for this article.
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
Patrick A Gibney, Ariel Schieler, Jonathan C Chen, Jessie M Bacha-Hummel, Maxim Botstein, Matthew Volpe, Sanford J Silverman, Yifan Xu, Bryson D Bennett, Joshua D Rabinowitz, David Botstein
Toxicity resulting from accumulation of sugar-phosphate molecules is an evolutionarily conserved phenomenon, observed in multiple bacterial and eukaryotic systems, including a number of human diseases. However, the molecular mechanisms involved in sugar-phosphate toxicity remain unclear. Using the model eukaryote S. cerevisiae , we developed two systems to accumulate human disease-associated sugar-phosphate species. One system utilizes constitutive expression of galactose permease and galactose kinase to accumulate galactose-1-phosphate, while the other system utilizes constitutive expression of a mammalian ketohexokinase gene to accumulate fructose-1-phosphate...
February 14, 2018: Molecular Biology of the Cell
Myrto Denaxa, Guilherme Neves, Adam Rabinowitz, Sarah Kemlo, Petros Liodis, Juan Burrone, Vassilis Pachnis
Cortical networks are composed of excitatory projection neurons and inhibitory interneurons. Finding the right balance between the two is important for controlling overall cortical excitation and network dynamics. However, it is unclear how the correct number of cortical interneurons (CIs) is established in the mammalian forebrain. CIs are generated in excess from basal forebrain progenitors, and their final numbers are adjusted via an intrinsically determined program of apoptosis that takes place during an early postnatal window...
February 13, 2018: Cell Reports
Molly R Rabinowitz, Laura R Kair, Heather L Sipsma, Carrie A Phillipi, Ilse A Larson
BACKGROUND: Breastfeeding is fundamental to maternal and child health and is the most cost-effective intervention to reduce child mortality. Pasteurized human donor milk (HDM) is increasingly provided for term newborns requiring temporary supplementation. Few studies examine maternal perspectives on supplementation of term newborns. MATERIALS AND METHODS: We conducted semistructured in-person interviews with mothers of term newborns (n = 24) during postpartum hospitalization...
February 13, 2018: Breastfeeding Medicine: the Official Journal of the Academy of Breastfeeding Medicine
S E McKee, S Zhang, L Chen, J D Rabinowitz, T M Reyes
One carbon metabolism is regulated by the availability of nutrients known as methyl donors, and disruption of this pathway can affect multiple physiological systems. DNA methylation, critical for the regulation of gene expression, is linked to one carbon metabolism, and can be altered by perinatal diet. In the current study, dams (n=12/group) were fed HF or standard control (SC) diet through pregnancy and lactation, and male and female offspring were then fed either SC or methyl donor supplemented diet (MDS) between 3 and 6 weeks of age (n=20-26/group)...
February 9, 2018: Journal of Neurochemistry
Lior Drukker, Hen Y Sela, Orna Reichman, Ron Rabinowitz, Arnon Samueloff, Ori Shen
BACKGROUND: The sliding sign (the relative motion between the abdominal and uterine wall as assessed by ultrasonography) may help identify severe intra-abdominal adhesions before repeat cesarean delivery. METHODS: We conducted a prospective observational study of scheduled repeat cesarean deliveries. Using transabdominal ultrasonography, while the parturient breathed deeply, the ultrasonographer recorded a video clip in a sagittal plane lateral to the umbilicus...
March 2018: Obstetrics and Gynecology
Cholsoon Jang, Sheng Hui, Wenyun Lu, Alexis J Cowan, Raphael J Morscher, Gina Lee, Wei Liu, Gregory J Tesz, Morris J Birnbaum, Joshua D Rabinowitz
Excessive consumption of sweets is a risk factor for metabolic syndrome. A major chemical feature of sweets is fructose. Despite strong ties between fructose and disease, the metabolic fate of fructose in mammals remains incompletely understood. Here we use isotope tracing and mass spectrometry to track the fate of glucose and fructose carbons in vivo, finding that dietary fructose is cleared by the small intestine. Clearance requires the fructose-phosphorylating enzyme ketohexokinase. Low doses of fructose are ∼90% cleared by the intestine, with only trace fructose but extensive fructose-derived glucose, lactate, and glycerate found in the portal blood...
February 6, 2018: Cell Metabolism
Scott Quarrier, Ronald Rabinowitz
No abstract text is available yet for this article.
January 30, 2018: Urology
Raphael J Morscher, Gregory S Ducker, Sophia Hsin-Jung Li, Johannes A Mayer, Zemer Gitai, Wolfgang Sperl, Joshua D Rabinowitz
Folates enable the activation and transfer of one-carbon units for the biosynthesis of purines, thymidine and methionine. Antifolates are important immunosuppressive and anticancer agents. In proliferating lymphocytes and human cancers, mitochondrial folate enzymes are particularly strongly upregulated. This in part reflects the need for mitochondria to generate one-carbon units and export them to the cytosol for anabolic metabolism. The full range of uses of folate-bound one-carbon units in the mitochondrial compartment itself, however, has not been thoroughly explored...
February 1, 2018: Nature
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