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Paul I Costea, Falk Hildebrand, Manimozhiyan Arumugam, Fredrik Bäckhed, Martin J Blaser, Frederic D Bushman, Willem M de Vos, S Dusko Ehrlich, Claire M Fraser, Masahira Hattori, Curtis Huttenhower, Ian B Jeffery, Dan Knights, James D Lewis, Ruth E Ley, Howard Ochman, Paul W O'Toole, Christopher Quince, David A Relman, Fergus Shanahan, Shinichi Sunagawa, Jun Wang, George M Weinstock, Gary D Wu, Georg Zeller, Liping Zhao, Jeroen Raes, Rob Knight, Peer Bork
In the version of this Perspective originally published, the first and last name of co-author Manimozhiyan Arumugam were switched. This has now been corrected in all versions of the Perspective.
February 13, 2018: Nature Microbiology
R Zivadinov, D P Ramasamy, J Hagemeier, C Kolb, N Bergsland, F Schweser, M G Dwyer, B Weinstock-Guttman, D Hojnacki
BACKGROUND AND PURPOSE: Leptomeningeal contrast enhancement is found in patients with multiple sclerosis, though reported rates have varied. The use of 3D-fluid-attenuated inversion recovery pre- and postcontrast subtraction imaging may more accurately determine the frequency of leptomeningeal contrast enhancement. The purpose of this study was to investigate the frequency of leptomeningeal contrast enhancement using the pre- and postcontrast subtraction approach and to evaluate 3 different methods of assessing the presence of leptomeningeal contrast enhancement...
February 8, 2018: AJNR. American Journal of Neuroradiology
Jun Cheng, Fang Tao, Yanhong Liu, Scott A Venners, Yi-Hsiang Hsu, Shanqun Jiang, Justin Weinstock, Binyan Wang, Genfu Tang, Xiping Xu
OBJECTIVE: To confirm the association between baseline blood pressure (BP) levels and the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism in patients with essential hypertension. METHODS: A total of 347 patients were enrolled from the Dongzhi community in Anhui Province, China. The C677T polymorphism of the MTHFR gene was detected using high-throughput TaqMan allelic discrimination assay. Baseline BP was measured using a standardized mercury-gravity monometer...
February 13, 2018: Clinical and Experimental Hypertension: CHE
Khalid Aljabri, Ann Garlitski, Jonathan Weinstock, Christopher Madias
The rate of cardiac implantable electronic device (CIED) infection has increased disproportionately to the rate of implantation. Expanded indications for CIED implantation combined with a sicker patient population contribute to this increased rate. Device-related infections are most commonly due to perioperative contamination, and infection risk increases in conjunction with procedural complexity. Early pocket re-exploration and upgrade procedures confer a higher infectious risk. Confirmed CIED infection requires prompt removal of the CIED system combined with antimicrobial therapy...
March 2018: Cardiac Electrophysiology Clinics
Jonathan Weinstock
The wearable cardioverter defibrillator has been shown to be effective in terminating ventricular arrhythmias in patients at risk for sudden cardiac death. There are numerous scenarios in which implant of a permanent implantable cardioverter defibrillator is temporarily contraindicated or not advisable and a wearable cardioverter defibrillator may be beneficial. There are no prospective randomized studies published that provide conclusive guidance toward the use of the wearable cardioverter defibrillator, and thus, patient management needs to be individualized based on the available data...
March 2018: Cardiac Electrophysiology Clinics
Robert M Bowers, Nikos C Kyrpides, Ramunas Stepanauskas, Miranda Harmon-Smith, Devin Doud, T B K Reddy, Frederik Schulz, Jessica Jarett, Adam R Rivers, Emiley A Eloe-Fadrosh, Susannah G Tringe, Natalia N Ivanova, Alex Copeland, Alicia Clum, Eric D Becraft, Rex R Malmstrom, Bruce Birren, Mircea Podar, Peer Bork, George M Weinstock, George M Garrity, Jeremy A Dodsworth, Shibu Yooseph, Granger Sutton, Frank O Glöckner, Jack A Gilbert, William C Nelson, Steven J Hallam, Sean P Jungbluth, Thijs J G Ettema, Scott Tighe, Konstantinos T Konstantinidis, Wen-Tso Liu, Brett J Baker, Thomas Rattei, Jonathan A Eisen, Brian Hedlund, Katherine D McMahon, Noah Fierer, Rob Knight, Rob Finn, Guy Cochrane, Ilene Karsch-Mizrachi, Gene W Tyson, Christian Rinke, Alla Lapidus, Folker Meyer, Pelin Yilmaz, Donovan H Parks, A Murat Eren, Lynn Schriml, Jillian F Banfield, Philip Hugenholtz, Tanja Woyke
No abstract text is available yet for this article.
February 6, 2018: Nature Biotechnology
Lorraine E Levitt Katz, Fida Bacha, Samuel S Gidding, Ruth S Weinstock, Laure El Ghormli, Ingrid Libman, Kristen J Nadeau, Kristin Porter, Santica Marcovina
OBJECTIVES: Data regarding atherogenic dyslipidemia and the inflammation profile in youth with type 2 diabetes is limited and the effect of insulin therapy on these variables has not previously been studied in youth. We determined the impact of insulin therapy on lipid and inflammatory markers in youth with poorly controlled type 2 diabetes. STUDY DESIGN: In the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) multicenter trial, 285 participants failed to sustain glycemic control on randomized treatment (primary outcome, glycated hemoglobin A1c [HbA1c] at ≥8% for 6 months); 363 maintained glycemic control (never reached primary outcome)...
February 2, 2018: Journal of Pediatrics
Fiona M Shaw, Martin A Weinstock
Superficial basal cell carcinoma is a type of keratinocyte carcinoma that has increasing incidence and substantial morbidity. Jansen et al. report on a randomized trial with 5 years of follow-up that found imiquimod to be more effective than 5-fluorouracil or methyl aminolevulinate photodynamic therapy in preventing superficial basal cell carcinoma recurrence. However, the toxicity and cost of topical treatments, as well as patient preferences, need to be evaluated when making treatment decisions in clinical practice...
January 29, 2018: Journal of Investigative Dermatology
Mariangela Sociale, Anna-Lena Wulf, Bernadette Breiden, Kathrin Klee, Melanie Thielisch, Franka Eckardt, Julia Sellin, Margret H Bülow, Sinah Löbbert, Nadine Weinstock, André Voelzmann, Joachim Schultze, Konrad Sandhoff, Reinhard Bauer
Maintenance of metabolic homeostasis requires adaption of gene regulation to the cellular energy state via transcriptional regulators. Here, we identify a role of ceramide synthase (CerS) Schlank, a multiple transmembrane protein containing a catalytic lag1p motif and a homeodomain, which is poorly studied in CerSs, as a transcriptional regulator. ChIP experiments show that it binds promoter regions of lipases lipase3 and magro via its homeodomain. Mutation of nuclear localization site 2 (NLS2) within the homeodomain leads to loss of DNA binding and deregulated gene expression, and NLS2 mutants can no longer adjust the transcriptional response to changing lipid levels...
January 23, 2018: Cell Reports
Marlise R Luskin, Mark A Murakami, Scott R Manalis, David M Weinstock
Therapeutics that block kinases, transcriptional modifiers, immune checkpoints and other biological vulnerabilities are transforming cancer treatment. As a result, many patients achieve dramatic responses, including complete radiographical or pathological remission, yet retain minimal residual disease (MRD), which results in relapse. New functional approaches can characterize clonal heterogeneity and predict therapeutic sensitivity of MRD at a single-cell level. Preliminary evidence suggests that iterative detection, profiling and targeting of MRD would meaningfully improve outcomes and may even lead to cure...
January 29, 2018: Nature Reviews. Cancer
Shumita Roy, Allison Drake, Tom Fuchs, Michael G Dwyer, Robert Zivadinov, Benjamin P Chapman, Bianca Weinstock-Guttman, Ralph Hb Benedict
We previously reported that personality and cognition were stable over 3 years in patients with multiple sclerosis (MS). This study examined whether a longer duration would reveal evidence of emerging personality dysfunction. The NEO Five-Factor Inventory and Brief International Cognitive Assessment for MS was used to assess personality and cognition, respectively. Patients were classified as "Cog Stable" or "Cog Decline" based on cognitive deterioration over 5 years. Extraversion and Conscientiousness declined across pooled groups...
January 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
Brian D Piening, Wenyu Zhou, Kévin Contrepois, Hannes Röst, Gucci Jijuan Gu Urban, Tejaswini Mishra, Blake M Hanson, Eddy J Bautista, Shana Leopold, Christine Y Yeh, Daniel Spakowicz, Imon Banerjee, Cynthia Chen, Kimberly Kukurba, Dalia Perelman, Colleen Craig, Elizabeth Colbert, Denis Salins, Shannon Rego, Sunjae Lee, Cheng Zhang, Jessica Wheeler, M Reza Sailani, Liang Liang, Charles Abbott, Mark Gerstein, Adil Mardinoglu, Ulf Smith, Daniel L Rubin, Sharon Pitteri, Erica Sodergren, Tracey L McLaughlin, George M Weinstock, Michael P Snyder
Advances in omics technologies now allow an unprecedented level of phenotyping for human diseases, including obesity, in which individual responses to excess weight are heterogeneous and unpredictable. To aid the development of better understanding of these phenotypes, we performed a controlled longitudinal weight perturbation study combining multiple omics strategies (genomics, transcriptomics, multiple proteomics assays, metabolomics, and microbiomics) during periods of weight gain and loss in humans. Results demonstrated that: (1) weight gain is associated with the activation of strong inflammatory and hypertrophic cardiomyopathy signatures in blood; (2) although weight loss reverses some changes, a number of signatures persist, indicative of long-term physiologic changes; (3) we observed omics signatures associated with insulin resistance that may serve as novel diagnostics; (4) specific biomolecules were highly individualized and stable in response to perturbations, potentially representing stable personalized markers...
January 16, 2018: Cell Systems
Steven J Fliesler, Neal S Peachey, Josi Herron, Kelly M Hines, Nadav I Weinstock, Sriganesh Ramachandra Rao, Libin Xu
Smith-Lemli-Opitz Syndrome (SLOS) is a recessive human disease caused by defective cholesterol (CHOL) synthesis at the level of DHCR7 (7-dehydrocholesterol reductase), which normally catalyzes the conversion of 7-dehydrocholesterol (7DHC) to CHOL. Formation and abnormal accumulation of 7DHC and 7DHC-derived oxysterols occur in SLOS patients and in rats treated with the DHCR7 inhibitor AY9944. The rat SLOS model exhibits progressive and irreversible retinal dysfunction and degeneration, which is only partially ameliorated by dietary CHOL supplementation...
January 19, 2018: Scientific Reports
Thomas J Covey, Janet L Shucard, Ralph Hb Benedict, Bianca Weinstock-Guttman, David W Shucard
Background: Few studies of cognitive rehabilitation in multiple sclerosis (MS) have targeted working memory specifically. Objective: We examined the effects of n-back working memory training on cognitive performance and brain function in patients with MS. Methods: Patients with MS (n = 12) and healthy controls (HC; n = 12) underwent 20 sessions of n-back working memory training. Before and after training (pre- and posttest) cognitive event-related potential (ERP) measures were obtained during a 3-back task...
January 2018: Multiple Sclerosis Journal—Experimental, Translational and Clinical
Grazia Aleppo, Lori M Laffel, Andrew J Ahmann, Irl B Hirsch, Davida F Kruger, Anne Peters, Ruth S Weinstock, Dennis R Harris
After reviewing previously published methods, we developed a practical approach to adjusting insulin doses based on insulin sensitivity for adult patients with diabetes using rtCGM trend arrow data.
December 1, 2017: Journal of the Endocrine Society
Leonard B Weinstock, Jill B Brook, Trisha L Myers, Brent Goodman
A patient with severe postural orthostatic tachycardia syndrome (POTS) and mast cell activation syndrome (MCAS) received immunotherapy with low-dose naltrexone (LDN) and intravenous immunoglobulin (IVIg) and antibiotic therapy for small intestinal bacterial overgrowth (SIBO). A dramatic and sustained response was documented. The utility of IVIg in autoimmune neuromuscular diseases has been published, but clinical experience with POTS is relatively unknown and has not been reported in MCAS. As a short-acting mu-opioid antagonist, LDN paradoxically increases endorphins which then bind to regulatory T cells which regulate T-lymphocyte and B-lymphocyte production and this reduces cytokine and antibody production...
January 11, 2018: BMJ Case Reports
Noriaki Yoshida, David M Weinstock
No abstract text is available yet for this article.
January 11, 2018: Blood
Lisa Uebelacker, Steven C Dufour, Jacob G Dinerman, Samantha L Walsh, Casey Hearing, Lee T Gillette, Thilo Deckersbach, Andrew A Nierenberg, Lauren Weinstock, Louisa G Sylvia
BACKGROUND: Despite ongoing advances in the treatment of mood disorders, a substantial proportion of people diagnosed with major depression or bipolar disorder remain symptomatic over time. Yoga, which has been shown to reduce stress and depressive symptoms, as well as to improve overall quality of life, shows promise as an adjunctive treatment. However, dissemination of yoga for clinical populations remains challenging. The purpose of this pilot study was to test the feasibility and acceptability of an online yoga intervention for individuals with mood disorders...
January 2018: Journal of Psychiatric Practice
Robert Zivadinov, Jesper Hagemeier, Niels Bergsland, Eleonora Tavazzi, Bianca Weinstock-Guttman
BACKGROUND: Dimethyl fumarate (DMF) is an oral treatment for relapsing remitting multiple sclerosis (RRMS) with anti-inflammatory and possible neuroprotective properties. Its effect on white matter (WM) and gray matter (GM) pathology is still not fully understood. OBJECTIVE: To characterize the effect of DMF on normal appearing WM (NAWM) and thalamic pathology longitudinally. METHODS: In this observational, longitudinal, 24-month MRI study, 75 RRMS treated with DMF and 40 age- and sex- matched healthy individuals (HIs) were enrolled...
January 5, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
Dejan Jakimovski, Channa Kolb, Murali Ramanathan, Robert Zivadinov, Bianca Weinstock-Guttman
Despite that the availability of new therapeutic options has expanded the multiple sclerosis (MS) disease-modifying therapy arsenal, interferon β (IFN-β) remains an important therapy option in the current decision-making process. This review will summarize the present knowledge of IFN-β mechanism of action, the overall safety, and the short- and long-term efficacy of its use in relapsing remitting MS and clinically isolated syndromes. Data on secondary progressive MS is also provided, although no clear benefit was identified...
January 8, 2018: Cold Spring Harbor Perspectives in Medicine
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