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Gerald J Pepe, Adina Maniu, Graham Aberdeen, Terrie J Lynch, Soon Ok Kim, Jerry Nadler, Eugene D Albrecht
We recently demonstrated that offspring delivered to baboons deprived of estrogen during the second half of gestation exhibited insulin resistance prior to onset of puberty. Because gonadal hormones have a profound effect on insulin action and secretion in adults, we determined whether insulin resistance is retained after initiation of gonadal secretion of testosterone and estradiol. Glucose tolerance tests were performed in postpubertal baboon offspring of untreated and letrozole-treated animals (serum estradiol reduced >95 %)...
October 21, 2016: Endocrine
Kathleen Falster, Emily Banks, Sanja Lujic, Michael Falster, John Lynch, Karen Zwi, Sandra Eades, Alastair H Leyland, Louisa Jorm
BACKGROUND: Australian Aboriginal children experience a disproportionate burden of social and health disadvantage. Avoidable hospitalizations present a potentially modifiable health gap that can be targeted and monitored using population data. This study quantifies inequalities in pediatric avoidable hospitalizations between Australian Aboriginal and non-Aboriginal children. METHODS: This statewide population-based cohort study included 1 121 440 children born in New South Wales, Australia, between 1 July 2000 and 31 December 2012, including 35 609 Aboriginal children...
October 21, 2016: BMC Pediatrics
Margaret L Salisbury, David A Lynch, Edwin J R van Beek, Ella A Kazerooni, Junfeng Guo, Meng Xia, Susan Murray, Kevin J Anstrom, Eric Yow, Fernando J Martinez, Eric A Hoffman, Kevin R Flaherty
RATIONALE: Adaptive Multiple Features Method (AMFM) lung texture analysis software recognizes high-resolution computed tomography (HRCT) patterns. OBJECTIVES: We evaluated AMFM and visual quantification of HRCT patterns and their relationship with disease progression in Idiopathic Pulmonary Fibrosis. METHODS: IPF patients in a clinical trial of prednisone, azathioprine, and N-acetylcysteine underwent HRCT at study start and finish. Proportion of lung occupied by ground glass, ground glass-reticular (GGR), honeycombing, emphysema, and normal were measured by AMFM and 3 radiologists, documenting baseline disease extent and post-baseline change...
October 21, 2016: American Journal of Respiratory and Critical Care Medicine
Tae Jun Kim, Eun Ran Kim, Sung Noh Hong, Young-Ho Kim, Jung Wook Huh, Yoon Ah Park, Yong Beom Cho, Seong Hyeon Yun, Hee Cheol Kim, Woo Yong Lee, Kiyoun Kim, Kyunga Kim, Dong Kyung Chang
BACKGROUND: The survival benefit of extensive colectomy is controversial in Lynch syndrome, and risk factors for metachronous colorectal cancer (CRC) after segmental colectomy are unclear. OBJECTIVE: The aim of this study was to investigate the survival outcome and risk of metachronous CRC after surgery in Lynch syndrome patients diagnosed with their first CRC. METHODS: Overall, 106 patients with Lynch syndrome who underwent surgery for CRC were included in the study...
October 20, 2016: Annals of Surgical Oncology
Nirav H Amin, Alex Volpi, T Sean Lynch, Ronak M Patel, Douglas L Cerynik, Mark S Schickendantz, Morgan H Jones
BACKGROUND: Anatomic reinsertion of the distal biceps is critical for restoring flexion and supination strength. Single- and double-incision surgical techniques have been reported, analyzing complications and outcomes measures. Which technique results in superior clinical outcomes and the lowest associated complications remains unclear. HYPOTHESIS: We hypothesized that rerupture rates would be similar between the 2 techniques, while nerve complications would be higher for the single-incision technique and heterotopic ossification would be more frequent with the double-incision technique...
October 2016: Orthopaedic Journal of Sports Medicine
H N Lynch, C T Loftus, J M Cohen, L E Kerper, E M Kennedy, J E Goodman
Research suggests that exposure to ambient particulate matter (PM) may be associated with lung cancer; however, no mode of action (MoA) for this has been established. We applied a weight-of-evidence (WoE) approach to evaluate recent evidence from four realms of research (controlled human exposure, epidemiology, animal, and in vitro) to determine whether the overall evidence supports one or more MoAs by which PM could cause lung cancer. We evaluated three general MoAs: DNA damage and repair; other genotoxic effects, including mutagenicity and clastogenicity; and gene expression, protein expression, and DNA methylation...
October 17, 2016: Regulatory Toxicology and Pharmacology: RTP
David A Siegel, Reda Wilson, Edward J Wilkinson, Julia W Gargano, Meg Watson, Brenda Y Hernandez, Marc T Goodman, Charles F Lynch, Elizabeth R Unger, Mona Saraiya
CONTEXT: -Knowing the subtype of vulvar cancer histology is important for estimating human papillomavirus-related cancer etiology. Surveillance of human papillomavirus-related vulvar cancers informs public health decisions related to vaccination against human papillomavirus. OBJECTIVE: -To assess the accuracy of registry classifications of vulvar cancer and determine the histologic classification of cases reported as not otherwise specified. DESIGN: -Pathology specimens were collected from Florida, Iowa, and Hawaii cancer registries...
October 20, 2016: Archives of Pathology & Laboratory Medicine
Nehal Eldeeb, Samia Halileh, Khalid A Alyafei, Rula Ghandour, Soha Dargham, Rita Giacaman, Madeeha Kamal, Sawsan Imseeh, Mona Korayem, Shiraz Nasr, Ziyad Mahfoud, Niveen Abu-Rmeileh, Mohamed H Mahmoud, Hassan Tawfik, Margaret A Lynch, Marcellina Mian
To compare the nature and determinants of child discipline in Qatar and Palestine among young adults through retrospective survey to develop legislation, policies and interventions for effective prevention of child maltreatment, and educational materials to promote positive discipline among parents and caregivers. Cross-sectional random household surveys were conducted in each country (Qataris N=697, Palestinians N=2064) using ISPCAN Child Abuse Screening Tool-Retrospective (ICAST-R) for young adults (18-24 years), to investigate child discipline methods into the maltreatment range...
October 16, 2016: Child Abuse & Neglect
Meabh O'Hare, Conor Fearon, Eoin C Kavanagh, Brian Murray, Timothy Lynch
No abstract text is available yet for this article.
October 18, 2016: Neurology
Takashi Takeda, Kouji Banno, Megumi Yanokura, Masataka Adachi, Moito Iijima, Haruko Kunitomi, Kanako Nakamura, Miho Iida, Yuya Nogami, Kiyoko Umene, Kenta Masuda, Yusuke Kobayashi, Wataru Yamagami, Akira Hirasawa, Eiichiro Tominaga, Nobuyuki Susumu, Daisuke Aoki
Germline mutation of DNA mismatch repair (MMR) genes is a cause of Lynch syndrome. Methylation of MutL homolog 1 (MLH1) and MutS homolog 2 (MSH2) has been detected in peripheral blood cells of patients with colorectal cancer. This methylation is referred to as epimutation. Methylation of these genes has not been studied in an unselected series of endometrial cancer cases. Therefore, we examined methylation of MLH1, MSH2, and MSH6 promoter regions of peripheral blood cells in 206 patients with endometrial cancer using a methylation-specific polymerase chain reaction (MSP)...
October 14, 2016: Genes
Julie Lynch, Scott L DuVall, Brygida Berse, Angela Whatley, Cathy St Pierre, Omobonike Oloruntoba, Christine M Hunt
We assessed implementation of precision medicine within the Veterans Health Administration. We analyzed the use of interleukin-28B (IL28B) pharmacogenetic test, which predicts interferon-α treatment response in patients with hepatitis C. Patients with favorable CC genotype exhibit a two-fold higher response than patients with less favorable genotypes (CT and TT). Linking IL28B tests to Veterans Health Administration clinical data, we analyzed test use, concordance with guidelines, subsequent interferon-α treatment, and site variations...
October 2016: Military Medicine
Tahnee L Kennedy, Kristy Swiderski, Kate T Murphy, Stefan M Gehrig, Claire L Curl, Chanchal Chandramouli, Mark A Febbraio, Lea M D Delbridge, René Koopman, Gordon S Lynch
Duchenne muscular dystrophy is a severe and progressive striated muscle wasting disorder that leads to premature death from respiratory and/or cardiac failure. We have previously shown that treatment of young dystrophic mdx and dystrophin/utrophin null (dko) mice with BGP-15, a coinducer of heat shock protein 72, ameliorated the dystrophic pathology. We therefore tested the hypothesis that later-stage BGP-15 treatment would similarly benefit older mdx and dko mice when the dystrophic pathology was already well established...
October 14, 2016: American Journal of Pathology
David S Lynch, Wei Jia Zhang, Rahul Lakshmanan, Justin A Kinsella, Günes Altiokka Uzun, Merih Karbay, Zeynep Tüfekçioglu, Hasmet Hanagasi, Georgina Burke, Nicola Foulds, Simon R Hammans, Anupam Bhattacharjee, Heather Wilson, Matthew Adams, Mark Walker, James A R Nicoll, Jeremy Chataway, Nick Fox, Indran Davagnanam, Rahul Phadke, Henry Houlden
Importance: Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a frequent cause of adult-onset leukodystrophy known to be caused by autosomal dominant mutations in the CSF1R (colony-stimulating factor 1) gene. The discovery that CSF1R mutations cause ALSP led to more accurate prognosis and genetic counseling for these patients in addition to increased interest in microglia as a target in neurodegeneration. However, it has been known since the discovery of the CSF1R gene that there are patients with typical clinical and radiologic evidence of ALSP who do not carry pathogenic CSF1R mutations...
October 17, 2016: JAMA Neurology
Bernadette M Lynch, Edward P Stern, Voon Ong, Mark Harber, Aine Burns, Christopher P Denton
The UK Scleroderma Study Group developed guidelines on the diagnosis and management of scleroderma renal crisis (SRC) based on best available evidence and clinical experience. SRC is characterised by the acute onset of severe hypertension and acute kidney injury. Current strategies to reduce the associated morbidity and mortality include identifying at risk patients to aid early diagnosis. ACE inhibitor therapy should be lifelong in all patients, regardless of whether they require renal replacement therapy...
September 2016: Clinical and Experimental Rheumatology
Carl S Rye, Nicola E A Chessum, Scott Lamont, Kurt G Pike, Paul Faulder, Julie Demeritt, Paul Kemmitt, Julie Tucker, Lorenzo Zani, Matthew D Cheeseman, Rosie Isaac, Louise Goodwin, Joanna Boros, Florence Raynaud, Angela Hayes, Alan T Henley, Emmanuel de Billy, Christopher J Lynch, Swee Y Sharp, Robert Te Poele, Lisa O' Fee, Kevin M Foote, Stephen Green, Paul Workman, Keith Jones
Heat shock factor 1 (HSF1) is a transcription factor that plays key roles in cancer, including providing a mechanism for cell survival under proteotoxic stress. Therefore, inhibition of the HSF1-stress pathway represents an exciting new opportunity in cancer treatment. We employed an unbiased phenotypic screen to discover inhibitors of the HSF1-stress pathway. Using this approach we identified an initial hit (1) based on a 4,6-pyrimidine scaffold (2.00 μM). Optimisation of cellular SAR led to an inhibitor with improved potency (25, 15 nM) in the HSF1 phenotypic assay...
August 1, 2016: MedChemComm
Raquel Castillo-Oyagüe, Carmen Perea, María-Jesús Suárez-García, Jaime Del Río, Christopher D Lynch, Arelis Preciado
OBJECTIVES: To validate the 'Quality of Life related to function, aesthetics, socialization, and thoughts about health-behavioural habits (QoLFAST-10)' questionnaire for assessing the whole concept of oral health-related quality of life (OHRQoL) of implant-supported fixed partial denture (FPD) wearers. METHODS: 107 patients were assigned to: Group 1 (HP; n=37): fixed-detachable hybrid prostheses (control); Group 2 (C-PD, n=35): cemented partial dentures; and Group 3 (S-PD, n=35): screwed partial dentures...
October 13, 2016: Journal of Dentistry
Katelyn M Mika, Vincent J Lynch
Variation in female reproductive traits, such as fertility, fecundity, and fecundability, is heritable in humans, but identifying and functionally characterizing genetic variants associated with these traits has been challenging. Here, we explore the functional significance and evolutionary history of a T/C polymorphism of SNP rs2071473, which we have previously shown is an eQTL for TAP2 and significantly associated with fecundability (time to pregnancy). We replicated the association between the rs2071473 genotype and TAP2 expression by using GTEx data and demonstrated that TAP2 is expressed by decidual stromal cells at the maternal-fetal interface...
September 24, 2016: American Journal of Human Genetics
Marcus M Dillon, Way Sung, Robert Sebra, Michael Lynch, Vaughn S Cooper
The vast diversity in nucleotide composition and architecture among bacterial genomes may be partly explained by inherent biases in the rates and spectra of spontaneous mutations. Bacterial genomes with multiple chromosomes are relatively unusual but some are relevant to human health, none more so than the causative agent of cholera, Vibrio cholerae Here, we present the genome-wide mutation spectra in wild-type and mismatch repair (MMR) defective backgrounds of two Vibrio species, the low-%GC squid symbiont V...
October 15, 2016: Molecular Biology and Evolution
E Stelloo, A M L Jansen, E M Osse, R A Nout, C L Creutzberg, D Ruano, D N Church, H Morreau, V T H B M Smit, T van Wezel, T Bosse
BACKGROUND: Mismatch repair (MMR)-deficiency analysis is increasingly recommended for all endometrial cancers, as it identifies Lynch syndrome-patients, and is emerging as a prognostic classifier to guide adjuvant treatment. The aim of this study was to define the optimal approach for MMR-deficiency testing and to clarify discrepancies between microsatellite instability (MSI) analysis and immunohistochemical (IHC) analysis of MMR protein expression. PATIENTS AND METHODS: 696 endometrial cancers were analyzed for MSI (pentaplex panel) and MMR protein expression (IHC)...
October 13, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Eitan Halper-Stromberg, Michael H Cho, Carla Wilson, Dipti Nevrekar, James D Crapo, George Washko, Raúl San José Estépar, David A Lynch, Edwin K Silverman, Sonia Leach, Peter J Castaldi
RATIONALE: Automated analysis of computed tomographic (CT) lung images for epidemiologic nand genetic association studies is increasingly common, but little is known about the utility of visual versus semi-automated emphysema and airway assessments for genetic association studies. OBJECTIVES: Assess the relative utility of visual versus semi-automated emphysema and airway assessments for genetic association studies. METHODS: A standardized inspection protocol was used to visually assess chest CTs for 1540 non-Hispanic white subjects within the COPDGene Study for the presence and severity of radiographic features representing airway wall thickness and emphysema...
October 14, 2016: Annals of the American Thoracic Society
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