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Hua Lin, Jonathan Z Long, Alexander M Roche, Katrin J Svensson, Florence Dou, Mi Ra Chang, Timothy Strutzenberg, Claudia Ruiz, Michael D Cameron, Scott J Novick, Charles M Berdan, Sharon Louie, Daniel K Nomura, Bruce M Spiegelman, Patrick R Griffin, Theodore M Kamenecka
N-acyl amino acids directly bind mitochondria and function as endogenous uncouplers of UCP1-independent respiration. We found that administration of N-acyl amino acids to mice improves glucose homeostasis and increases energy expenditure indicating that this pathway might be useful for treating obesity and associated disorders. We report the full account of the synthesis and mitochondrial uncoupling bioactivity of lipidated N-acyl amino acids and their unnatural analogs. Unsaturated fatty acid chains of medium length and neutral amino acid head groups are required for optimal uncoupling activity on mammalian cells...
March 13, 2018: Journal of Medicinal Chemistry
Sirui Zhou, Ziv Gan-Or, Amirthagowri Ambalavanan, Dongbing Lai, Pingxing Xie, Cynthia V Bourassa, Stephanie Strong, Jay P Ross, Alexandre Dionne-Laporte, Dan Spiegelman, Nicolas Dupré, Tatiana M Foroud, Lan Xiong, Patrick A Dion, Guy A Rouleau
Intracranial Aneurysm (IA) is a common disease with a worldwide prevalence of 1-3%. In the French-Canadian (FC) population, where there is an important founder effect, the incidence of IA is higher and is frequently seen in families. In this study, we genotyped a cohort of 257 mostly familial FC IA patients and 1,992 FC controls using the Illumina NeuroX SNP-chip. The most strongly associated loci were tested in 34 Inuit IA families and in 32 FC IA patients and 106 FC controls that had been exome sequenced (WES)...
March 12, 2018: Scientific Reports
Brittany M Charlton, Andrea L Roberts, Margaret Rosario, Sabra L Katz-Wise, Jerel P Calzo, Donna Spiegelman, S Bryn Austin
OBJECTIVES: Young women who are sexual minorities (eg, bisexual and lesbian) are approximately twice as likely as those who are heterosexual to have a teen pregnancy. Therefore, we hypothesized that risk factors for teen pregnancy would vary across sexual orientation groups and that other potential risk factors exist that are unique to sexual minorities. METHODS: We used multivariable log-binomial models gathered from 7120 young women in the longitudinal cohort known as the Growing Up Today Study to examine the following potential teen pregnancy risk factors: childhood maltreatment, bullying victimization and perpetration, and gender nonconformity...
March 12, 2018: Pediatrics
Alexander Kintu, Enju Liu, Ellen Hertzmark, Donna Spiegelman, Rachel Margaret Zack, Aisa Muya, David Sando, Till Bärnighausen, Wafaie Fawzi
OBJECTIVE: To describe the incidence of and risk factors for overweight and obesity following antiretroviral therapy (ART) initiation. METHODS: We used Cox proportional hazards models to investigate risk factors for incident overweight and obesity in 79 074 individuals aged 15 years or older who initiated ART in Dar es Salaam, Tanzania. RESULTS: Twenty-five percent of the patients became overweight and 10% became obese. The incidence rate of obesity was 3...
January 2018: Journal of the International Association of Providers of AIDS Care
Jaber Lyahyai, Bouchra Oulad Amar Bencheikh, Siham C Elalaoui, Maria Mansouri, Lamia Boualla, Alexandre DIonne-Laporte, Dan Spiegelman, Patrick A Dion, Patrick Cossette, Guy A Rouleau, Abdelaziz Sefiani
BACKGROUND: Epilepsy regroups a common and diverse set of chronic neurological disorders that are characterized by spontaneous, unprovoked, and recurrent epileptic seizures. Epilepsies have a highly heterogeneous background with a strong genetic contribution and various mode of inheritance. X-linked epilepsy usually manifests as part of a syndrome or epileptic encephalopathy. The variability of clinical manifestations of X-linked epilepsy may be attributed to several factors including the causal genetic mutation, making diagnosis, genetic counseling and treatment decisions difficult...
February 27, 2018: BMC Pediatrics
Sumona Chaudhury, Ellen Hertzmark, Aisa Muya, David Sando, Nzovu Ulenga, Lameck Machumi, Donna Spiegelman, Wafaie W Fawzi
INTRODUCTION: Global scale up of anti-retroviral therapy (ART) has led to expansion of HIV treatment and prevention across sub-Saharan Africa. However, age and gender-specific disparities persist leading to failures in fulfillment of Sustainability Development Goals, including SDG3 (achieving healthy lives and wellbeing for all, at all ages) and SDG5 (gender equality). We assessed ART initiation and adherence, loss to follow-up, all-cause death and early death, according to SDG3 and SDG5 indicators among a cohort of HIV-infected children and adolescents enrolled in care in Dar-es-Salaam, Tanzania METHODS: SDG3 indicators included young (<5 years) and older paediatric children (5 to <10 years), early adolescent (10 to <15 years) and late adolescent (15 to <20 years) age group divisions and the SDG5 indicator was gender...
February 2018: Journal of the International AIDS Society
Xiaomei Liao, Xin Zhou, Molin Wang, Jaime E Hart, Francine Laden, Donna Spiegelman
Environmental epidemiologists are often interested in estimating the effect of functions of time-varying exposure histories, such as the 12-month moving average, in relation to chronic disease incidence or mortality. The individual exposure measurements that comprise such an exposure history are usually mis-measured, at least moderately, and, often, more substantially. To obtain unbiased estimates of Cox model hazard ratios for these complex mis-measured exposure functions, an extended risk set regression calibration method for Cox models is developed and applied to a study of long-term exposure to the fine particulate matter (PM2...
February 2018: Journal of the Royal Statistical Society. Series C, Applied Statistics
Hugues Aschard, Donna Spiegelman, Vincent Laville, Pete Kraft, Molin Wang
The identification of gene-environment interactions in relation to risk of human diseases has been challenging. One difficulty has been that measurement error in the exposure can lead to massive reductions in the power of the test, as well as in bias toward the null in the interaction effect estimates. Leveraging previous work on linear discriminant analysis, we develop a new test of interaction between genetic variants and a continuous exposure that mitigates these detrimental impacts of exposure measurement error in ExG testing by reversing the role of exposure and the diseases status in the fitted model, thus transforming the analysis to standard linear regression...
February 8, 2018: Genetic Epidemiology
Viswanathan Mohan, Rajagopal Gayathri, Lindsay M Jaacks, Nagarajan Lakshmipriya, Ranjit Mohan Anjana, Donna Spiegelman, Raman Ganesh Jeevan, Kandappa K Balasubramaniam, Shanmugam Shobana, Mathialagan Jayanthan, Viswanathan Gopinath, Selvakumar Divya, Vasudevan Kavitha, Parthasarathy Vijayalakshmi, Mookambika Ramya Bai R, Ranjit Unnikrishnan, Vasudevan Sudha, Kamala Krishnaswamy, Jordi Salas-Salvadó, Walter C Willett
Background: There is increasing evidence that nut consumption decreases the risk of cardiovascular disease. However, there are few data on the health effects of cashew nuts among adults with type 2 diabetes (T2DM). Objective: The study aimed to investigate the effects of cashew nut supplementation on glycemia, body weight, blood pressure, and lipid profile in Asian Indians with T2DM. Methods: In a parallel-arm, randomized controlled trial, 300 adults with T2DM [mean ± SD age: 51 ± 9...
January 1, 2018: Journal of Nutrition
Molly J Horstman, Andrew Spiegelman, Aanand D Naik, Barbara W Trautner
Background: Overuse of urine testing is a driver of inappropriate antimicrobial use. Limiting wasteful testing is important for patient safety. We examined the national prevalence and patterns of urine testing during adult inpatient admission in the United States. Methods: We performed a retrospective cohort study using a national dataset of inpatient admissions from 263 hospitals in the United States from 2009 to 2014. We included all adult inpatient admissions, excluding those related to pregnancy, urology procedures, and with lengths of stay >30 days...
October 1, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Tae Won Kim, Thomas Havighurst, KyungMann Kim, Mark Albertini, Yaohui G Xu, Vladimir S Spiegelman
Melanoma is one of the deadliest forms of skin cancer. Although BRAF inhibitors significantly enhance survival of metastatic melanoma patients, most patients relapse after less than a year of treatment. We previously reported that mRNA binding protein Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) is overexpressed in metastatic melanoma and that expression of IGF2BP1 confers resistance to chemotherapeutic agents. Here we demonstrate that IGF2BP1 plays an important role in the sensitivity of melanoma to targeted therapy...
January 25, 2018: Molecular Carcinogenesis
Ashley M Poenitzsch Strong, Scott M Berry, David J Beebe, Jian-Liang Li, Vladimir S Spiegelman
MicroRNAs (miRNAs), small 22-25 nucleotide non-coding RNAs, play important roles in cellular and tumor biology. However, characterizing miRNA function remains challenging due to an abundance of predicted targets and an experimental bottleneck in identifying biologically relevant direct targets. Here we developed a novel technique (miFAST) to identify direct miRNA target genes. Using miFAST, we confirmed several previously reported miR-340 target genes and identified five additional novel direct miR-340 targets in melanoma cells...
January 19, 2018: Molecular Carcinogenesis
Benedict H W Wong, Sarah B Peskoe, Donna Spiegelman
The partial population attributable risk (pPAR) is used to quantify the population-level impact of preventive interventions in a multifactorial disease setting. In this paper, we consider the effect of nondifferential risk factor misclassification on the direction and magnitude of bias of pPAR estimands and related quantities. We found that the bias in the uncorrected pPAR depends nonlinearly and nonmonotonically on the sensitivities, specificities, relative risks, and joint prevalence of the exposure of interest and background risk factors, as well as the associations between these factors...
January 15, 2018: Statistics in Medicine
Naomi Kaplan Damary, Micha Mandel, Sarena Wiesner, Yoram Yekutieli, Yaron Shor, Clifford Spiegelman
Randomly acquired characteristics (RACs), also known as accidental marks, are random markings on a shoe sole, such as scratches or holes, that are used by forensic experts to compare a suspect's shoe with a print found at the crime scene. This article investigates the relationships among three features of a RAC: its location, shape type and orientation. If these features, as well as the RACs, are independent of each other, a simple probabilistic calculation could be used to evaluate the rarity of a RAC and hence the evidential value of the shoe and print comparison, whereas a correlation among the features would complicate the analysis...
December 11, 2017: Forensic Science International
Melin J Khandekar, Alexander S Banks, Dina Laznik-Bogoslavski, James P White, Jang Hyun Choi, Lawrence Kazak, James C Lo, Paul Cohen, Kwok-Kin Wong, Theodore M Kamenecka, Patrick R Griffin, Bruce M Spiegelman
The peroxisome-proliferator receptor-γ (PPARγ) is expressed in multiple cancer types. Recently, our group has shown that PPARγ is phosphorylated on serine 273 (S273), which selectively modulates the transcriptional program controlled by this protein. PPARγ ligands, including thiazolidinediones (TZDs), block S273 phosphorylation. This activity is chemically separable from the canonical activation of the receptor by agonist ligands and, importantly, these noncanonical agonist ligands do not cause some of the known side effects of TZDs...
January 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
Hui Jing, Xiaoyu Zhang, Stephanie A Wisner, Xiao Chen, Nicole A Spiegelman, Maurine E Linder, Hening Lin
Ras proteins play vital roles in numerous biological processes and Ras mutations are found in many human tumors. Understanding how Ras proteins are regulated is important for elucidating cell signaling pathways and identifying new targets for treating human diseases. Here we report that one of the K-Ras splice variants, K-Ras4a, is subject to lysine fatty acylation, a previously under-studied protein post-translational modification. Sirtuin 2 (SIRT2), one of the mammalian nicotinamide adenine dinucleotide (NAD)-dependent lysine deacylases, catalyzes the removal of fatty acylation from K-Ras4a...
December 14, 2017: ELife
Emma G Thomas, Sarah B Peskoe, Donna Spiegelman
The first goal of the United Nations' 90-90-90 HIV/AIDS elimination strategy is to ensure that, by 2020, 90% of HIV-positive people know their HIV status. Estimating the prevalence of HIV among people eligible for screening allows assessment of the number of additional cases that might be diagnosed through continued screening efforts in this group. Here, we present methods for estimating prevalence when HIV status is verified by a gold standard only among those who test positive on an initial, imperfect screening test with known sensitivity and specificity...
March 30, 2018: Statistics in Medicine
Archana Shrestha, Prajjwal Pyakurel, Abha Shrestha, Rabin Gautam, Nisha Manandhar, Elizabeth Rhodes, Dipesh Tamrakar, Biraj Man Karmacharya, Vasanti Malik, Josiemer Mattei, Donna Spiegelman
Objective: Worksite interventions can serve as a potential platform for translating existing knowledge of diabetes prevention and facilitate healthy food choices. The study explored perceptions about healthy eating as well as potential facilitators and barriers to healthy eating among employees in a wire manufacturing factory in Nepal. Methods and materials: We conducted a cross-sectional exploratory qualitative study in a wire manufacturing industry in eastern Nepal...
2017: Heart Asia
Kseniia A Korchagina, Fernand Spiegelman, Jérôme Cuny
The successive hydrogenation of CO is supposed to be the main mechanism leading to the formation of complex oxygenated species in the interstellar medium, possibly mediated by ice layers or ice grains. In order to simulate the dynamical influence of a water environment on the first step of the hydrogenation process, we perform molecular dynamics simulations of the reactive collision of H with CO adsorbed on water clusters in the framework of the self-consistent-charge density functional based tight-binding approach (SCC-DFTB) to calculate potential energy surfaces...
December 14, 2017: Journal of Physical Chemistry. A
Archana Shrestha, Biraj Man Karmacharya, Polyna Khudyakov, Mary Beth Weber, Donna Spiegelman
OBJECTIVES: The translation of lifestyle intervention to improve glucose tolerance into the workplace has been rare. The objective of this meta-analysis is to summarize the evidence for the effectiveness of dietary interventions in worksite settings on lowering blood sugar levels. METHODS: We searched for studies in PubMed, Embase, Econlit, Ovid, Cochrane, Web of Science, and Cumulative Index to Nursing and Allied Health Literature. Search terms were as follows: (1) Exposure-based: nutrition/diet/dietary intervention/health promotion/primary prevention/health behavior/health education/food /program evaluation; (2) Outcome-based: diabetes/hyperglycemia/glucose/HbA1c/glycated hemoglobin; and (3) Setting-based: workplace/worksite/occupational/industry/job/employee...
January 25, 2018: Journal of Occupational Health
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