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https://www.readbyqxmd.com/read/28346484/a-neighborhood-wide-association-study-nwas-example-of-prostate-cancer-aggressiveness
#1
Shannon M Lynch, Nandita Mitra, Michelle Ross, Craig Newcomb, Karl Dailey, Tara Jackson, Charnita M Zeigler-Johnson, Harold Riethman, Charles C Branas, Timothy R Rebbeck
PURPOSE: Cancer results from complex interactions of multiple variables at the biologic, individual, and social levels. Compared to other levels, social effects that occur geospatially in neighborhoods are not as well-studied, and empiric methods to assess these effects are limited. We propose a novel Neighborhood-Wide Association Study(NWAS), analogous to genome-wide association studies(GWAS), that utilizes high-dimensional computing approaches from biology to comprehensively and empirically identify neighborhood factors associated with disease...
2017: PloS One
https://www.readbyqxmd.com/read/28343630/de-novo-truncating-mutations-in-the-last-and-penultimate-exons-of-ppm1d-cause-an-intellectual-disability-syndrome
#2
Sandra Jansen, Sinje Geuer, Rolph Pfundt, Rachel Brough, Priyanka Ghongane, Johanna C Herkert, Elysa J Marco, Marjolein H Willemsen, Tjitske Kleefstra, Mark Hannibal, Joseph T Shieh, Sally Ann Lynch, Frances Flinter, David R FitzPatrick, Alice Gardham, Birgitta Bernhard, Nicola Ragge, Ruth Newbury-Ecob, Raphael Bernier, Malin Kvarnung, E A Helena Magnusson, Marja W Wessels, Marjon A van Slegtenhorst, Kristin G Monaghan, Petra de Vries, Joris A Veltman, Christopher J Lord, Lisenka E L M Vissers, Bert B A de Vries
Intellectual disability (ID) is a highly heterogeneous disorder involving at least 600 genes, yet a genetic diagnosis remains elusive in ∼35%-40% of individuals with moderate to severe ID. Recent meta-analyses statistically analyzing de novo mutations in >7,000 individuals with neurodevelopmental disorders highlighted mutations in PPM1D as a possible cause of ID. PPM1D is a type 2C phosphatase that functions as a negative regulator of cellular stress-response pathways by mediating a feedback loop of p38-p53 signaling, thereby contributing to growth inhibition and suppression of stress-induced apoptosis...
March 18, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28342511/invited-commentary
#3
Thomas Lynch
No abstract text is available yet for this article.
April 2017: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/28341647/estimating-seven-coefficients-of-pairwise-relatedness-using-population-genomic-data
#4
Matthew S Ackerman, Parul Johri, Ken Spitze, Sen Xu, Thomas G Doak, Kimberly Young, Michael Lynch
Population structure can be described by genotypic correlation coefficients between groups of individuals, the most basic of which are the pair-wise relatedness coefficients between any two individuals. There are nine pair-wise relatedness coefficients in the most general model, and we show that these can be reduced to seven coefficients for biallelic loci. Although all nine coefficients can be estimated from pedigrees, six coefficients have been beyond empirical reach. We provide a numerical optimization procedure that estimates all seven reduced coefficients from population-genomic data...
March 24, 2017: Genetics
https://www.readbyqxmd.com/read/28337686/telephone-delivered-behavioral-skills-intervention-for-african-american-adults-with-type-2-diabetes-a-randomized-controlled-trial
#5
Leonard E Egede, Joni S Williams, Delia C Voronca, Mulugeta Gebregziabher, Cheryl P Lynch
BACKGROUND: Diabetes disproportionately affects African Americans and is associated with poorer outcomes. Self-management is important for glycemic control; however, evidence in African Americans is limited. OBJECTIVE: To assess the efficacy of a combined telephone-delivered education and behavioral skills intervention (TBSI) in reducing hemoglobin A1c (HbA1c) levels in African Americans with type 2 diabetes, using a factorial design. DESIGN: This is a four-year randomized clinical trial, using a 2 x 2 factorial design...
March 23, 2017: Journal of General Internal Medicine
https://www.readbyqxmd.com/read/28337602/depressive-symptoms-and-sleep-efficiency-sequentially-mediate-racial-differences-in-temporal-summation-of-mechanical-pain
#6
Hailey W Bulls, Mary K Lynch, Megan E Petrov, Ethan W Gossett, Michael A Owens, Sarah C Terry, Kate M Wesson-Sides, Burel R Goodin
BACKGROUND: Racial differences in endogenous pain facilitatory processes have been previously reported. Evidence suggests that psychological and behavioral factors, including depressive symptoms and sleep, can alter endogenous pain facilitatory processes. Whether depressive symptoms and sleep might help explain racial differences in endogenous pain facilitatory processes has yet to be determined. PURPOSE: This observational, microlongitudinal study examined whether depressive symptoms and sleep were sequential mediators of racial differences in endogenous pain facilitatory processes...
March 23, 2017: Annals of Behavioral Medicine: a Publication of the Society of Behavioral Medicine
https://www.readbyqxmd.com/read/28336914/inhibition-of-serum-and-glucocorticoid-regulated-kinase-1-as-novel-therapy-for-cardiac-arrhythmia-disorders
#7
Vassilios J Bezzerides, Aifeng Zhang, Ling Xiao, Bridget Simonson, Santosh A Khedkar, Shiro Baba, Filomena Ottaviano, Stacey Lynch, Katherine Hessler, Alan C Rigby, David Milan, Saumya Das, Anthony Rosenzweig
Alterations in sodium flux (INa) play an important role in the pathogenesis of cardiac arrhythmias and may also contribute to the development of cardiomyopathies. We have recently demonstrated a critical role for the regulation of the voltage-gated sodium channel NaV1.5 in the heart by the serum and glucocorticoid regulated kinase-1 (SGK1). Activation of SGK1 in the heart causes a marked increase in both the peak and late sodium currents leading to prolongation of the action potential duration and an increased propensity to arrhythmia...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28336808/potent-dual-bet-bromodomain-kinase-inhibitors-as-value-added-multi-targeted-chemical-probes-and-cancer-therapeutics
#8
Stuart W Ember, Que T Lambert, Norbert Berndt, Steven Gunawan, Muhammad Ayaz, Marilena Tauro, Jin-Yi Zhu, Paula J Cranfill, Patricia Greninger, Conor C Lynch, Cyril H Benes, Harshani R Lawrence, Gary W Reuther, Nicholas J Lawrence, Ernst Schonbrunn
Synergistic action of kinase and BET bromodomain inhibitors in cell killing has been reported for a variety of cancers. Using the chemical scaffold of the JAK2 inhibitor TG101348 we developed and characterized single agents which potently and simultaneously inhibit BRD4 and a specific set of oncogenic tyrosine kinases including JAK2, FLT3, RET, and ROS1. Lead compounds showed on-target inhibition in several blood cancer cell lines and were highly efficacious at inhibiting the growth of hematopoietic progenitor cells from myeloproliferative neoplasm (MPN) patients...
March 23, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28336345/dancing-for-parkinson-s-a-randomized-trial-of-irish-set-dancing-compared-to-usual-care
#9
Joanne Shanahan, Meg E Morris, Orfhlaith Ni Bhriain, Daniele Volpe, Tim Lynch, Amanda M Clifford
OBJECTIVE: This pilot trial examined the feasibility of a randomised controlled study design and explored the benefits of the set dancing intervention compared to usual care. DESIGN: Randomised controlled design, with participants randomised to Irish set dance classes or a usual care control group. SETTING: Community based PARTICIPANTS: Individuals with idiopathic PD INTERVENTIONS: The dance group attended a 1.5 hour dancing class each week for 10 weeks and undertook a home dance programme for 20 minutes three times per week...
March 21, 2017: Archives of Physical Medicine and Rehabilitation
https://www.readbyqxmd.com/read/28335725/surface-layer-proteins-from-virulent-clostridium-difficile-ribotypes-exhibit-signatures-of-positive-selection-with-consequences-for-innate-immune-response
#10
Mark Lynch, Thomas A Walsh, Izabela Marszalowska, Andrew E Webb, Micheál MacAogain, Thomas R Rogers, Henry Windle, Dermot Kelleher, Mary J O'Connell, Christine E Loscher
BACKGROUND: Clostridium difficile is a nosocomial pathogen prevalent in hospitals worldwide and increasingly common in the community. Sequence differences have been shown to be present in the Surface Layer Proteins (SLPs) from different C. difficile ribotypes (RT) however whether these differences influence severity of infection is still not clear. RESULTS: We used a molecular evolutionary approach to analyse SLPs from twenty-six C. difficile RTs representing different slpA sequences...
March 23, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28335350/shape-and-charge-of-gold-nanomaterials-influence-survivorship-oxidative-stress-and-moulting-of-daphnia-magna
#11
Fatima Nasser, Adam Davis, Eugenia Valsami-Jones, Iseult Lynch
Engineered nanomaterials (ENMs) are materials with at least one dimension between 1-100 nm. The small size of ENMs results in a large surface area to volume ratio, giving ENMs novel characteristics that are not traditionally exhibited by larger bulk materials. Coupled with large surface area is an enormous capacity for surface functionalization of ENMs, e.g., with different ligands or surface changes, leading to an almost infinite array of variability of ENMs. Here we explore the effects of various shaped (spheres, rods) and charged (negative, positive) gold ENMs on Daphnia magna (D...
November 25, 2016: Nanomaterials
https://www.readbyqxmd.com/read/28334938/clinical-and-genetic-characterization-of-leukoencephalopathies-in-adults
#12
David S Lynch, Anderson Rodrigues Brandão de Paiva, Wei Jia Zhang, Enrico Bugiardini, Fernando Freua, Leandro Tavares Lucato, Lucia Inês Macedo-Souza, Rahul Lakshmanan, Justin A Kinsella, Aine Merwick, Alexander M Rossor, Nin Bajaj, Brian Herron, Paul McMonagle, Patrick J Morrison, Deborah Hughes, Alan Pittman, Matilde Laurà, Mary M Reilly, Jason D Warren, Catherine J Mummery, Jonathan M Schott, Matthew Adams, Nick C Fox, Elaine Murphy, Indran Davagnanam, Fernando Kok, Jeremy Chataway, Henry Houlden
Leukodystrophies and genetic leukoencephalopathies are a rare group of disorders leading to progressive degeneration of cerebral white matter. They are associated with a spectrum of clinical phenotypes dominated by dementia, psychiatric changes, movement disorders and upper motor neuron signs. Mutations in at least 60 genes can lead to leukoencephalopathy with often overlapping clinical and radiological presentations. For these reasons, patients with genetic leukoencephalopathies often endure a long diagnostic odyssey before receiving a definitive diagnosis or may receive no diagnosis at all...
March 2, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334914/clinical-utility-of-a-self-administered-questionnaire-for-assessment-of-hereditary-gynecologic-cancer
#13
Kenta Masuda, Akira Hirasawa, Haruko Irie-Kunitomi, Tomoko Akahane, Arisa Ueki, Yusuke Kobayashi, Wataru Yamagami, Hiroyuki Nomura, Fumio Kataoka, Eiichiro Tominaga, Kouji Banno, Nobuyuki Susumu, Daisuke Aoki
Background: A patient's medical history and familial cancer history are important information for assessing the risk of hereditary cancer. We have generated a self-administered questionnaire for patients with gynecologic cancer. This pilot study analyzed the usefulness of this questionnaire and the rates of patients that meet the Society of Gynecologic Oncology criteria in ovarian cancer and endometrial cancer patients. Method: Ovarian or endometrial cancer patients were recruited for this study...
December 23, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28334867/the-silent-mutation-mlh1-c-543c-t-resulting-in-aberrant-splicing-can-cause-lynch-syndrome-a-case-report
#14
Tatsuro Yamaguchi, Tomokazu Wakatsuki, Mari Kikuchi, Shin-Ichiro Horiguchi, Kiwamu Akagi
The proband was a 67-year-old man with transverse and sigmoid colon cancer. Microsatellite instability analysis revealed a high frequency of microsatellite instability, and immunohistochemical staining showed the absence of both MLH1 and PMS2 proteins in the sigmoid colon cancer tissue specimens from the patient. DNA sequencing revealed a nucleotide substitution c.543C>T in MLH1, but this variant did not substitute an amino acid. The MLH1 c.543C>T variant was located 3 bases upstream from the end of exon 6 and created a new splice donor site 4 bases upstream from the end of exon 6...
March 1, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28333918/21-gene-recurrence-score-testing-among-medicare-beneficiaries-with-breast-cancer-in-2010-2013
#15
Julie A Lynch, Brygida Berse, Nicole Coomer, John Kautter
PURPOSE: We evaluated national patient-level utilization of the 21-gene recurrence score (21-gene RS) test among Medicare beneficiaries with breast cancer. We analyzed clinical, demographic, and regional factors that predict testing. METHODS: Using 2010-2013 Medicare claims, we conducted a retrospective study of breast cancer patients. The outcome variable was whether the patient underwent testing. Independent variables expected to predict testing were age, gender, race, Medicaid status, clinical characteristics, and hospital referral region (HRR)...
March 23, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28333842/review-article-sexuality-and-risk-reducing-salpingo-oophorectomy
#16
Paige E Tucker, Paul A Cohen
INTRODUCTION: Women with familial cancer syndromes such as hereditary breast and ovarian cancer syndrome (BRCA1 and BRCA2) and Lynch syndrome are at a significantly increased risk of developing ovarian cancer and are advised to undergo prophylactic removal of their ovaries and fallopian tubes at age 35 to 40 years, after childbearing is complete. METHODS: A comprehensive literature search of studies on risk-reducing salpingo-oophorectomy (RRSO), sexuality, and associated issues was conducted in MEDLINE databases...
March 23, 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28333301/preconception-maternal-lipoprotein-levels-in-relation-to-fecundability
#17
Sarah J Pugh, Enrique F Schisterman, Richard W Browne, Anne M Lynch, Sunni L Mumford, Neil J Perkins, Robert Silver, Lindsey Sjaarda, Joseph B Stanford, Jean Wactawski-Wende, Brian Wilcox, Katherine L Grantz
STUDY QUESTION: Are maternal preconception lipid levels associated with fecundability? SUMMARY ANSWER: Fecundability was reduced for all abnormal female lipid levels including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and total triglyceride levels. WHAT IS KNOWN ALREADY: Subfecundity affects 7-15% of the population and lipid disorders are hypothesized to play a role since cholesterol acts as a substrate for the synthesis of steroid hormones...
March 15, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28331811/proteomic-analysis-of-bronchoalveolar-lavage-fluid-balf-from-lung-cancer-patients-using-label-free-mass-spectrometry
#18
Abduladim Hmmier, Michael Emmet O'Brien, Vincent Lynch, Martin Clynes, Ross Morgan, Paul Dowling
BACKGROUND: Lung cancer is the leading cause of cancer-related mortality in both men and women throughout the world. The need to detect lung cancer at an early, potentially curable stage, is essential and may reduce mortality by 20%. The aim of this study was to identify distinct proteomic profiles in bronchoalveolar fluid (BALF) and plasma that are able to discriminate individuals with benign disease from those with non-small cell lung cancer (NSCLC). METHODS: Using label-free mass spectrometry analysis of BALF during discovery-phase analysis, a significant number of proteins were found to have different abundance levels when comparing control to adenocarcinoma (AD) or squamous cell lung carcinoma (SqCC)...
June 2017: BBA Clinical
https://www.readbyqxmd.com/read/28329411/tv-viewing-time-is-associated-with-increased-all-cause-mortality-in-brazilian-adults-independent-of-physical-activity
#19
Bruna Camilo Turi, Henrique Luiz Monteiro, Ítalo Ribeiro Lemes, Jamile Sanches Codogno, Kyle Robinson Lynch, Camila Angélica Asahi Mesquita, Rômulo Araújo Fernandes
The purpose of this study was to investigate the association between television (TV) viewing and all-cause mortality among Brazilian adults after six years of follow-up. This longitudinal study started in 2010 in the city of Bauru, SP, Brazil, and involved 970 adults aged ≥ 50 years. Mortality was reported by relatives and confirmed in medical records of the Brazilian National Health System. Physical activity (PA) and TV viewing were assessed by the Baecke questionnaire. Health status, sociodemographic and behavioural covariates were considered as potential confounders...
March 22, 2017: Scandinavian Journal of Medicine & Science in Sports
https://www.readbyqxmd.com/read/28328691/factors-associated-with-discharge-home-after-transfer-to-a-pediatric-emergency-department
#20
Erin R Peebles, Michael R Miller, Tim P Lynch, Janice A Tijssen
OBJECTIVES: The transfer of children from community emergency departments (EDs) to tertiary care pediatric EDs for investigations, interventions, or a second opinion is common. In order to improve health care system efficiency, we must have a better understanding of this population and identify areas for education and capacity building. METHODS: We conducted a retrospective chart review of all patients (aged 0-17 years) who were transferred from community ED to a pediatric ED from November 2013 to November 2014...
March 21, 2017: Pediatric Emergency Care
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