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Liqing Wang, Suresh Kumar, Satinder Dahiya, Feng Wang, Jian Wu, Kheng Newick, Rongxiang Han, Arabinda Samanta, Ulf H Beier, Tatiana Akimova, Tricia R Bhatti, Benjamin Nicholson, Mathew P Kodrasov, Saket Agarwal, David E Sterner, Wei Gu, Joseph Weinstock, Tauseef R Butt, Steven M Albelda, Wayne W Hancock
Foxp3+ T-regulatory (Treg) cells are known to suppress protective host immune responses to a wide variety of solid tumors, but their therapeutic targeting is largely restricted to their transient depletion or "secondary" modulation, e.g. using anti-CTLA-4 monoclonal antibody. Our ongoing studies of the post-translational modifications that regulate Foxp3 demonstrated that the histone/protein acetyltransferase, Tip60, plays a dominant role in promoting acetylation, dimerization and function in Treg cells. We now show that the ubiquitin-specific protease, Usp7, controls Treg function largely by stabilizing the expression and promoting the multimerization of Tip60 and Foxp3...
October 15, 2016: EBioMedicine
Ruth S Weinstock, Ingrid Schütz-Fuhrmann, Crystal G Connor, Julia M Hermann, David M Maahs, Morten Schütt, Shivani Agarwal, Sabine E Hofer, Roy W Beck, Reinhard W Holl
AIMS: Compare characteristics, therapies and clinical outcomes in older adults with type 1 diabetes in the United States T1D Exchange (T1DX) and German/Austrian Diabetes Patienten Verlaufsdokumentation (DPV) registries. METHODS: Cross-sectional study of adults ≥60years old with type 1 diabetes seen in 2011-2012 in the T1DX (n=1283) and DPV (n=2014) registries. Wilcoxon rank-sum test was used for continuous variables and chi-square test for categorical variables...
October 4, 2016: Diabetes Research and Clinical Practice
Jeremiah Weinstock, Nancy M Petry
No abstract text is available yet for this article.
October 18, 2016: Annals of Internal Medicine
Joanne E Sordillo, Yanjiao Zhou, Michael J McGeachie, John Ziniti, Nancy Lange, Nancy Laranjo, Jessica R Savage, Vincent Carey, George O'Connor, Megan Sandel, Robert Strunk, Leonard Bacharier, Robert Zeiger, Scott T Weiss, George Weinstock, Diane R Gold, Augusto A Litonjua
BACKGROUND: The gut microbiome in infancy influences immune system maturation, and may have an important impact allergic disease risk. OBJECTIVE: To determine how prenatal and early life factors impact the gut microbiome in a relatively large, ethnically diverse study population of infants at 3-6 months of age, who were enrolled in VDAART, a clinical trial of vitamin D supplementation in pregnancy to prevent asthma and allergies in offspring. METHODS: We performed 16S rRNA gene sequencing on 333 infants' stool samples...
October 13, 2016: Journal of Allergy and Clinical Immunology
Carla J Rash, Maxine Stitzer, Jeremiah Weinstock
This article introduces the special issue on contingency management (CM), an efficacious intervention for the treatment of substance use disorders with low uptake in clinical settings that is not commensurate with evidence for efficacy. In this special issue of the Journal of Substance Abuse Treatment, we present 16 articles representing the latest research in efficacy, implementation, and technological advances related to CM. Combined, this collection of articles highlights the diverse populations, settings, and applications of CM in the treatment of substance use disorders...
September 28, 2016: Journal of Substance Abuse Treatment
Caron Jacobson, Nadja Kopp, Jacob V Layer, Robert A Redd, Sebastian Tschuri, Sarah Haebe, Diederik van Bodegom, Liat Bird, Amanda L Christie, Alexandra Christodoulou, Amy Saur, Trevor Tivey, Stefanie Zapf, Deepak Bararia, Ursula Zimber-Strobl, Scott J Rodig, Oliver Weigert, David M Weinstock
The BTK inhibitor ibrutinib induces responses in 70% of patients with relapsed and refractory mantle cell lymphoma. Intrinsic resistance can occur through activation of the non-classical NFκB pathway and acquired resistance may involve the BTK C481S mutation. Outcomes after ibrutinib failure are dismal, indicating an unmet medical need. We reasoned that newer HSP90 inhibitors could overcome ibrutinib resistance by targeting multiple oncogenic pathways in MCL. HSP90 inhibition induced the complete degradation of both BTK and IKKα in MCL lines and CD40-dependent B cells, with downstream loss of MAP kinase and non-classical NFκB signaling...
October 14, 2016: Blood
Elaine W Flagg, Elizabeth A Torrone, Hillard Weinstock
OBJECTIVES: To examine prevalence of low- and high-grade cervical lesions over time in a large cohort of US female adolescents and women. METHODS: We used health care claims data from 9 million privately insured female patients aged 15 to 39 years to estimate annual prevalence of cytologically detected cervical low-grade (LSIL) and high-grade squamous intraepithelial lesions (HSIL) and high-grade histologically detected cervical intraepithelial neoplasia grades 2 and 3 (CIN2+) during 2007 through 2014...
October 13, 2016: American Journal of Public Health
Mark M Stevens, Cecile L Maire, Nigel Chou, Mark A Murakami, David S Knoff, Yuki Kikuchi, Robert J Kimmerling, Huiyun Liu, Samer Haidar, Nicholas L Calistri, Nathan Cermak, Selim Olcum, Nicolas A Cordero, Ahmed Idbaih, Patrick Y Wen, David M Weinstock, Keith L Ligon, Scott R Manalis
Assays that can determine the response of tumor cells to cancer therapeutics could greatly aid the selection of drug regimens for individual patients. However, the utility of current functional assays is limited, and predictive genetic biomarkers are available for only a small fraction of cancer therapies. We found that the single-cell mass accumulation rate (MAR), profiled over many hours with a suspended microchannel resonator, accurately defined the drug sensitivity or resistance of glioblastoma and B-cell acute lymphocytic leukemia cells...
October 10, 2016: Nature Biotechnology
Helena Shifrin, Dorit Moradov, Corina Bejar, Donna Schorer-Apelbaum, Marta Weinstock
BACKGROUND: In search of safer treatments for inflammatory bowel disease in subjects not responding to, or showing adverse effects to TNF-α antagonists, we tested three novel indoline carbamates in the 2,4-dinitrobenzene sulfonic acid (DNBS) model of colitis in rats. The compounds have anti-inflammatory activity in other disease models in mice. METHODS: AN827 (3-(2-(methoxy carbonyl) ethyl) indolin-4-ylethyl methyl) carbamate (0.1 or 1mg/kg), AN680 (3-(2-(methoxy carbonyl) ethyl) indolin-6-ylethyl methyl) carbamate (1...
August 31, 2016: Pharmacological Reports: PR
Madhavi K Reddy, Thomas D Meyer, Natalie M Wittlin, Ivan W Miller, Lauren M Weinstock
BACKGROUND: According to data from epidemiological and clinical samples, there are elevated rates of posttraumatic stress disorder (PTSD) among patients with bipolar disorder (BD). However, little is known about the clinical correlates that may distinguish patients with BD and comorbid PTSD from those without comorbid PTSD. The present study sought to elucidate those differences and examine factors, such as psychosis, history of suicide attempts, and comorbid personality disorders, which may predict comorbid PTSD in patients with BD-I...
August 18, 2016: Comprehensive Psychiatry
Kachiu C Lee, Sue Peacock, Martin A Weinstock, Ge Alice Zhao, Stevan R Knezevich, David E Elder, Raymond L Barnhill, Michael W Piepkorn, Lisa M Reisch, Patricia A Carney, Tracy Onega, Jason P Lott, Joann G Elmore
BACKGROUND: The extent of variability in treatment suggestions for melanocytic lesions made by pathologists is unknown. OBJECTIVE: We investigated how often pathologists rendered suggestions, reasons for providing suggestions, and concordance with national guidelines. METHODS: We conducted a cross-sectional survey of pathologists. Data included physician characteristics, experience, and treatment recommendation practices. RESULTS: Of 301 pathologists, 207 (69%) from 10 states (California, Connecticut, Hawaii, Iowa, Kentucky, Louisiana, New Jersey, New Mexico, Utah, and Washington) enrolled...
September 28, 2016: Journal of the American Academy of Dermatology
Lloyd S Robinson, Justin Perry, Sai Lek, Aye Wollam, Erica Sodergren, George Weinstock, Warren G Lewis, Amanda L Lewis
Gardnerella vaginalis is a predominant species in bacterial vaginosis, a dysbiosis of the vagina that is associated with adverse health outcomes, including preterm birth. Here, we present the draft genome sequences of 15 Gardnerella vaginalis strains (now available through BEI Resources) isolated from women with and without bacterial vaginosis.
September 29, 2016: Genome Announcements
Jeremiah Weinstock, Nancy M Petry, Linda S Pescatello, Craig E Henderson
Heavy drinking by college students is exceedingly harmful to the individuals and to the overall college environment. Current interventions to reduce drinking and negative consequences are infrequently utilized. This randomized clinical trial examined an alternative approach that sought to increase exercise behavior, a substance free activity, in sedentary heavy drinking college students. Participants (N = 70) were randomized to an 8-week exercise intervention: (a) motivational interviewing plus weekly exercise contracting (MI + EC) or (b) motivational interviewing and weekly contingency management for exercise (MI + CM)...
September 26, 2016: Psychology of Addictive Behaviors: Journal of the Society of Psychologists in Addictive Behaviors
Jeremiah Weinstock, Margaret R Farney, Noel M Elrod, Craig E Henderson, Edward P Weiss
Substance use disorders (SUDs) are maladaptive patterns of substance use that are associated with psychiatric comorbidity, unhealthy lifestyle choices, and high rates of relapse. Exercise is associated with a wide range of acute and long-term benefits for both mental and physical health and is presently being investigated as a promising adjunctive treatment for SUD. Despite positive effects of regular physical activity on treatment outcomes and risk factors for relapse, low adherence and high attrition rates limit the benefits derived from exercise interventions...
September 9, 2016: Journal of Substance Abuse Treatment
Jahir Andres Miranda Acuña, Bianca Weinstock-Guttman
BACKGROUND: Natalizumab (NTZ) is an effective therapy for multiple sclerosis (MS). A common concern related to NTZ therapy is the risk of developing progressive multifocal leukoencephalopathy (PML). CLINICAL CASE: A patient that after seven years on NTZ therapy, testing on every 3 months repeated evaluations negative for anti-JCV status became positive (>3 units) 4 weeks after receiving influenza vaccine. Despite continuous therapy on NTZ for additional 2 years her anti-JCV index progressively declined to a level 0...
September 2016: Multiple Sclerosis and related Disorders
Julio Gallego-Delgado, Upal Basu-Roy, Maureen Ty, Matilde Alique, Cristina Fernandez-Arias, Alexandru Movila, Pollyanna Gomes, Ada Weinstock, Wenyue Xu, Innocent Edagha, Samuel C Wassmer, Thomas Walther, Marta Ruiz-Ortega, Ana Rodriguez
Cerebral malaria is characterized by cytoadhesion of Plasmodium falciparum-infected red blood cells (Pf-iRBCs) to endothelial cells in the brain, disruption of the blood-brain barrier, and cerebral microhemorrhages. No available antimalarial drugs specifically target the endothelial disruptions underlying this complication, which is responsible for the majority of malaria-associated deaths. Here, we have demonstrated that ruptured Pf-iRBCs induce activation of β-catenin, leading to disruption of inter-endothelial cell junctions in human brain microvascular endothelial cells (HBMECs)...
October 3, 2016: Journal of Clinical Investigation
M A Weinstock, J P Lott, Q Wang, L J Titus, T Onega, H D Nelson, L Pearson, M Piepkorn, J G Elmore, A N A Tosteson
BACKGROUND:  Melanoma incidence has increased in recent decades in the United States. Uncertainty remains regarding how much of this increase is attributable to greater melanoma screening activities, potential detection bias and overdiagnosis. OBJECTIVE: Use a cross-sectional ecological analysis to evaluate the relationship between skin biopsy and melanoma incidence rates over a more recent time period than prior reports. METHODS: Examination of the association of biopsy rates and melanoma incidence (invasive and in situ) in SEER-Medicare data (including 10 states) for 2002-2009...
September 17, 2016: British Journal of Dermatology
Nadav I Weinstock, Lawrence Wrabetz, M Laura Feltri, Daesung Shin
Krabbe disease (KD) is caused by mutations in the galactosylceramidase (GALC) gene, which encodes a lysosomal enzyme that degrades galactolipids, including galactosylceramide and galactosylsphingosine (psychosine). GALC deficiency results in progressive intracellular accumulation of psychosine, which is believed to be the main cause for the demyelinating neurodegeneration in KD pathology. Umbilical cord blood transplantation slows disease progression when performed presymptomatically but carries a significant risk of morbidity and mortality...
November 2016: Journal of Neuroscience Research
Nathan Cermak, Selim Olcum, Francisco Feijó Delgado, Steven C Wasserman, Kristofor R Payer, Mark A Murakami, Scott M Knudsen, Robert J Kimmerling, Mark M Stevens, Yuki Kikuchi, Arzu Sandikci, Masaaki Ogawa, Vincent Agache, François Baléras, David M Weinstock, Scott R Manalis
Methods to rapidly assess cell growth would be useful for many applications, including drug susceptibility testing, but current technologies have limited sensitivity or throughput. Here we present an approach to precisely and rapidly measure growth rates of many individual cells simultaneously. We flow cells in suspension through a microfluidic channel with 10-12 resonant mass sensors distributed along its length, weighing each cell repeatedly over the 4-20 min it spends in the channel. Because multiple cells traverse the channel at the same time, we obtain growth rates for >60 cells/h with a resolution of 0...
October 2016: Nature Biotechnology
Shreya Mukhopadhyay, Kelly Fellows, Richard W Browne, Prachi Khare, Sandhya Krishnan Radhakrishnan, Jesper Hagemeier, Bianca Weinstock-Guttman, Robert Zivadinov, Murali Ramanathan
PURPOSE: To investigate levels of oxysterols in healthy control (HC) and multiple sclerosis (MS) patients and their interdependence with demographic, clinical characteristics, and cholesterol biomarkers. METHODS: This study included 550 subjects (203 HC, 221 relapsing-remitting MS (RR-MS), 126 progressive MS (P-MS)). A complete lipid profile including total cholesterol (TC); high-density lipoprotein-cholesterol (HDL-C); low-density lipoprotein-cholesterol (LDL-C); apolipoproteins (Apo) A1, A2, B, and E; C-reactive protein (CRP); 24-hydroxycholesterol (HC); 25-HC; 27-HC; 7α-HC; and 7-ketocholesterol (KC) was obtained...
September 1, 2016: Multiple Sclerosis: Clinical and Laboratory Research
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