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https://www.readbyqxmd.com/read/29912962/novel-genetic-associations-for-blood-pressure-identified-via-gene-alcohol-interaction-in-up-to-570k-individuals-across-multiple-ancestries
#1
Mary F Feitosa, Aldi T Kraja, Daniel I Chasman, Yun J Sung, Thomas W Winkler, Ioanna Ntalla, Xiuqing Guo, Nora Franceschini, Ching-Yu Cheng, Xueling Sim, Dina Vojinovic, Jonathan Marten, Solomon K Musani, Changwei Li, Amy R Bentley, Michael R Brown, Karen Schwander, Melissa A Richard, Raymond Noordam, Hugues Aschard, Traci M Bartz, Lawrence F Bielak, Rajkumar Dorajoo, Virginia Fisher, Fernando P Hartwig, Andrea R V R Horimoto, Kurt K Lohman, Alisa K Manning, Tuomo Rankinen, Albert V Smith, Salman M Tajuddin, Mary K Wojczynski, Maris Alver, Mathilde Boissel, Qiuyin Cai, Archie Campbell, Jin Fang Chai, Xu Chen, Jasmin Divers, Chuan Gao, Anuj Goel, Yanick Hagemeijer, Sarah E Harris, Meian He, Fang-Chi Hsu, Anne U Jackson, Mika Kähönen, Anuradhani Kasturiratne, Pirjo Komulainen, Brigitte Kühnel, Federica Laguzzi, Jian'an Luan, Nana Matoba, Ilja M Nolte, Sandosh Padmanabhan, Muhammad Riaz, Rico Rueedi, Antonietta Robino, M Abdullah Said, Robert A Scott, Tamar Sofer, Alena Stančáková, Fumihiko Takeuchi, Bamidele O Tayo, Peter J van der Most, Tibor V Varga, Veronique Vitart, Yajuan Wang, Erin B Ware, Helen R Warren, Stefan Weiss, Wanqing Wen, Lisa R Yanek, Weihua Zhang, Jing Hua Zhao, Saima Afaq, Najaf Amin, Marzyeh Amini, Dan E Arking, Tin Aung, Eric Boerwinkle, Ingrid Borecki, Ulrich Broeckel, Morris Brown, Marco Brumat, Gregory L Burke, Mickaël Canouil, Aravinda Chakravarti, Sabanayagam Charumathi, Yii-Der Ida Chen, John M Connell, Adolfo Correa, Lisa de Las Fuentes, Renée de Mutsert, H Janaka de Silva, Xuan Deng, Jingzhong Ding, Qing Duan, Charles B Eaton, Georg Ehret, Ruben N Eppinga, Evangelos Evangelou, Jessica D Faul, Stephan B Felix, Nita G Forouhi, Terrence Forrester, Oscar H Franco, Yechiel Friedlander, Ilaria Gandin, He Gao, Mohsen Ghanbari, Bruna Gigante, C Charles Gu, Dongfeng Gu, Saskia P Hagenaars, Göran Hallmans, Tamara B Harris, Jiang He, Sami Heikkinen, Chew-Kiat Heng, Makoto Hirata, Barbara V Howard, M Arfan Ikram, Ulrich John, Tomohiro Katsuya, Chiea Chuen Khor, Tuomas O Kilpeläinen, Woon-Puay Koh, José E Krieger, Stephen B Kritchevsky, Michiaki Kubo, Johanna Kuusisto, Timo A Lakka, Carl D Langefeld, Claudia Langenberg, Lenore J Launer, Benjamin Lehne, Cora E Lewis, Yize Li, Shiow Lin, Jianjun Liu, Jingmin Liu, Marie Loh, Tin Louie, Reedik Mägi, Colin A McKenzie, Thomas Meitinger, Andres Metspalu, Yuri Milaneschi, Lili Milani, Karen L Mohlke, Yukihide Momozawa, Mike A Nalls, Christopher P Nelson, Nona Sotoodehnia, Jill M Norris, Jeff R O'Connell, Nicholette D Palmer, Thomas Perls, Nancy L Pedersen, Annette Peters, Patricia A Peyser, Neil Poulter, Leslie J Raffel, Olli T Raitakari, Kathryn Roll, Lynda M Rose, Frits R Rosendaal, Jerome I Rotter, Carsten O Schmidt, Pamela J Schreiner, Nicole Schupf, William R Scott, Peter S Sever, Yuan Shi, Stephen Sidney, Mario Sims, Colleen M Sitlani, Jennifer A Smith, Harold Snieder, John M Starr, Konstantin Strauch, Heather M Stringham, Nicholas Y Q Tan, Hua Tang, Kent D Taylor, Yik Ying Teo, Yih Chung Tham, Stephen T Turner, André G Uitterlinden, Peter Vollenweider, Melanie Waldenberger, Lihua Wang, Ya Xing Wang, Wen Bin Wei, Christine Williams, Jie Yao, Caizheng Yu, Jian-Min Yuan, Wei Zhao, Alan B Zonderman, Diane M Becker, Michael Boehnke, Donald W Bowden, John C Chambers, Ian J Deary, Tõnu Esko, Martin Farrall, Paul W Franks, Barry I Freedman, Philippe Froguel, Paolo Gasparini, Christian Gieger, Jost Bruno Jonas, Yoichiro Kamatani, Norihiro Kato, Jaspal S Kooner, Zoltán Kutalik, Markku Laakso, Cathy C Laurie, Karin Leander, Terho Lehtimäki, Lifelines Cohort Study, Patrik K E Magnusson, Albertine J Oldehinkel, Brenda W J H Penninx, Ozren Polasek, David J Porteous, Rainer Rauramaa, Nilesh J Samani, James Scott, Xiao-Ou Shu, Pim van der Harst, Lynne E Wagenknecht, Nicholas J Wareham, Hugh Watkins, David R Weir, Ananda R Wickremasinghe, Tangchun Wu, Wei Zheng, Claude Bouchard, Kaare Christensen, Michele K Evans, Vilmundur Gudnason, Bernardo L Horta, Sharon L R Kardia, Yongmei Liu, Alexandre C Pereira, Bruce M Psaty, Paul M Ridker, Rob M van Dam, W James Gauderman, Xiaofeng Zhu, Dennis O Mook-Kanamori, Myriam Fornage, Charles N Rotimi, L Adrienne Cupples, Tanika N Kelly, Ervin R Fox, Caroline Hayward, Cornelia M van Duijn, E Shyong Tai, Tien Yin Wong, Charles Kooperberg, Walter Palmas, Kenneth Rice, Alanna C Morrison, Paul Elliott, Mark J Caulfield, Patricia B Munroe, Dabeeru C Rao, Michael A Province, Daniel Levy
Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions...
2018: PloS One
https://www.readbyqxmd.com/read/29908063/oligonucleotide-therapy-mitigates-disease-in-spinocerebellar-ataxia-type-3-mice
#2
Hayley S McLoughlin, Lauren R Moore, Ravi Chopra, Robert Komlo, Megan McKenzie, Kate G Blumenstein, Hien Zhao, Holly B Kordasiewicz, Vikram G Shakkottai, Henry L Paulson
OBJECTIVE: Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease, is the most common dominantly inherited ataxia. Despite advances in understanding this CAG repeat/polyglutamine expansion disease, there are still no therapies to alter its progressive fatal course. Here we investigate whether an antisense oligonucleotide (ASO) targeting the SCA3 disease gene, ATXN3, can prevent molecular, neuropathological, electrophysiological and behavioral features of the disease in a mouse model of SCA3...
June 16, 2018: Annals of Neurology
https://www.readbyqxmd.com/read/29907914/asylum-seekers-in-a-time-of-record-forced-global-displacement-the-role-of-physicians
#3
Katherine C McKenzie, Jon Bauer, P Preston Reynolds
In 2016, over 65 million individuals were displaced from their homes due to human rights abuses, and 262,000 people applied for asylum in the USA. Individuals who have experienced persecution are present in many primary and specialty clinics. A medical forensic evaluation can increase the likelihood of a successful asylum case. This paper reviews the legal framework for asylum and the contribution forensic evaluations can make to this vulnerable population. Physicians without asylum expertise can help these patients by recognizing their legal right to residential protection and referring them to lawyers and physicians with expert skills...
June 15, 2018: Journal of General Internal Medicine
https://www.readbyqxmd.com/read/29907525/tissue-restricted-adaptive-type-2-immunity-is-orchestrated-by-expression-of-the-costimulatory-molecule-ox40l-on-group-2-innate-lymphoid-cells
#4
Timotheus Y F Halim, Batika M J Rana, Jennifer A Walker, Bernhard Kerscher, Martin D Knolle, Helen E Jolin, Eva M Serrao, Liora Haim-Vilmovsky, Sarah A Teichmann, Hans-Reimer Rodewald, Marina Botto, Timothy J Vyse, Padraic G Fallon, Zhi Li, David R Withers, Andrew N J McKenzie
The local regulation of type 2 immunity relies on dialog between the epithelium and the innate and adaptive immune cells. Here we found that alarmin-induced expression of the co-stimulatory molecule OX40L on group 2 innate lymphoid cells (ILC2s) provided tissue-restricted T cell co-stimulation that was indispensable for Th2 and regulatory T (Treg) cell responses in the lung and adipose tissue. Interleukin (IL)-33 administration resulted in organ-specific surface expression of OX40L on ILC2s and the concomitant expansion of Th2 and Treg cells, which was abolished upon deletion of OX40L on ILC2s (Il7raCre/+ Tnfsf4fl/fl mice)...
May 31, 2018: Immunity
https://www.readbyqxmd.com/read/29907450/altered-maternal-and-placental-lipid-metabolism-and-fetal-fat-development-in-obesity-current-knowledge-and-advances-in-non-invasive-assessment
#5
Flavien Delhaes, Stephanie A Giza, Tianna Koreman, Genevieve Eastabrook, Charles A McKenzie, Samantha Bedell, Timothy R H Regnault, Barbra de Vrijer
Abnormal maternal lipid profiles, a hallmark of increased maternal adiposity, are associated with pregnancy complications such as preeclampsia and gestational diabetes, and offspring long-term metabolic health is impacted as the consequence of altered fetal growth, physiology and often iatrogenic prematurity. The metabolic changes associated with maternal obesity and/or the consumption of a high-fat diet effecting maternal lipid profiles and metabolism have also been documented to specifically affect placental function and may underlie changes in fetal development and life course disease risk...
May 26, 2018: Placenta
https://www.readbyqxmd.com/read/29905643/prevalence-of-burnout-in-bahamian-health-care-personnel
#6
Brandon McKenzie, Tonya Walker, Christine Chin
No abstract text is available yet for this article.
June 13, 2018: Journal of Occupational and Environmental Medicine
https://www.readbyqxmd.com/read/29904757/are-current-guidelines-for-sun-protection-optimal-for-health-exploring-the-evidence
#7
Robyn M Lucas, Rachel E Neale, Sasha Madronich, Richard L McKenzie
Exposure of the skin to ultraviolet (UV) radiation is the main risk factor for skin cancer, and a major source of vitamin D, in many regions of the world. Sun protection messages to minimize skin cancer risks but avoid vitamin D deficiency are challenging, partly because levels of UV radiation vary by location, season, time of day, and atmospheric conditions. The UV Index provides information on levels of UV radiation and is a cornerstone of sun protection guidelines. Current guidelines from the World Health Organization are that sun protection is required only when the UV Index is 3 or greater...
June 15, 2018: Photochemical & Photobiological Sciences
https://www.readbyqxmd.com/read/29896763/renal-in-patient-ward-nurse-experience-and-job-satisfaction-a-qualitative-study
#8
Aisha Tamika McKenzie, Gulen Addis
AIMS AND OBJECTIVES: The aim of this study was to examine the experience of registered nurses working in renal inpatients wards at an acute National Health Service (NHS) hospital Trust. Nurse perceptions of their experience particularly in relation to job satisfaction was analysed. BACKGROUND: Increased understanding of workplace organisation and culture can contribute to improved nurse work experience and better patient care. Worldwide many studies conducted on nurse experience and job satisfaction show that job satisfaction level varies across work settings so analysis of job satisfaction at a local level such as in a ward is important for producing useful analysis and recommendations...
June 13, 2018: Journal of Clinical Nursing
https://www.readbyqxmd.com/read/29895691/caspase-1-inhibition-prevents-glial-inflammasome-activation-and-pyroptosis-in-models-of-multiple-sclerosis
#9
Brienne A McKenzie, Manmeet K Mamik, Leina B Saito, Roobina Boghozian, Maria Chiara Monaco, Eugene O Major, Jian-Qiang Lu, William G Branton, Christopher Power
Multiple sclerosis (MS) is a progressive inflammatory demyelinating disease of the CNS of unknown cause that remains incurable. Inflammasome-associated caspases mediate the maturation and release of the proinflammatory cytokines IL-1β and IL-18 and activate the pore-forming protein gasdermin D (GSDMD). Inflammatory programmed cell death, pyroptosis, was recently shown to be mediated by GSDMD. Here, we report molecular evidence for GSDMD-mediated inflammasome activation and pyroptosis in both myeloid cells (macrophages/microglia) and, unexpectedly, in myelin-forming oligodendrocytes (ODCs) in the CNS of patients with MS and in the MS animal model, experimental autoimmune encephalomyelitis (EAE)...
June 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29892006/brain-cell-type-specific-gene-expression-and-co-expression-network-architectures
#10
Andrew T McKenzie, Minghui Wang, Mads E Hauberg, John F Fullard, Alexey Kozlenkov, Alexandra Keenan, Yasmin L Hurd, Stella Dracheva, Patrizia Casaccia, Panos Roussos, Bin Zhang
Elucidating brain cell type specific gene expression patterns is critical towards a better understanding of how cell-cell communications may influence brain functions and dysfunctions. We set out to compare and contrast five human and murine cell type-specific transcriptome-wide RNA expression data sets that were generated within the past several years. We defined three measures of brain cell type-relative expression including specificity, enrichment, and absolute expression and identified corresponding consensus brain cell "signatures," which were well conserved across data sets...
June 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29889261/sporadic-creutzfeldt-jakob-disease-in-a-woman-married-into-a-gerstmann-str%C3%A3-ussler-scheinker-family-an-investigation-of-prions-transmission-via-microchimerism
#11
Aušrine Areškeviciute, Linea Cecilie Melchior, Helle Broholm, Lars-Henrik Krarup, Suzanne Granhøj Lindquist, Peter Johansen, Neil McKenzie, Alison Green, Jørgen Erik Nielsen, Henning Laursen, Eva Løbner Lund
This is the first report of presumed sporadic Creutzfeldt-Jakob disease (sCJD) and Gerstmann-Sträussler-Scheinker disease (GSS) with the prion protein gene c.305C>T mutation (p.P102L) occurring in one family. The father and son were affected with GSS and the mother had a rapidly progressive form of CJD. Diagnosis of genetic, variant, and iatrogenic CJD was ruled out based on the mother's clinical history, genetic tests, and biochemical investigations, all of which supported the diagnosis of sCJD. However, given the low incidence of sCJD and GSS, their co-occurrence in one family is extraordinary and challenging...
June 7, 2018: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29887005/ranked-effects-of-heavy-metals-on-marine-bivalves-in-laboratory-mesocosms-a-meta-analysis
#12
McKenzie Mandich
Bivalves are commonly used as biomonitors for heavy metal pollution in marine environments because they accumulate heavy metal ions quickly, are sessile, abundant, and widely dispersed, and adult mortality from contamination is rare. However, the breadth of experiments used to measure the effect of heavy metal contamination can obscure general trends. It is unclear which heavy metals cause the most severe effects, how severity varies with exposure concentration and duration, and whether effects vary with level of biological organization...
June 2018: Marine Pollution Bulletin
https://www.readbyqxmd.com/read/29884728/an-empirical-approach-leveraging-tumorgrafts-to-dissect-the-tumor-microenvironment-in-renal-cell-carcinoma-identifies-missing-link-to-prognostic-inflammatory-factors
#13
Tao Wang, Rong Lu, Payal Kapur, Bijay S Jaiswal, Raquibul Hannan, Ze Zhang, Ivan Pedrosa, Jason J Luke, He Zhang, Leonard D Goldstein, Qurratulain Yousuf, Yi-Feng Gu, Tiffani McKenzie, Allison Joyce, Min S Kim, Xinlei Wang, Danni Luo, Oreoluwa Onabolu, Christina Stevens, Zhiqun Xie, Mingyi Chen, Alexander Filatenkov, Jose Torrealba, Xin Luo, Wenbin Guo, Jingxuan He, Eric Stawiski, Zora Modrusan, Steffen Durinck, Somasekar Seshagiri, James Brugarolas
By leveraging tumorgraft (PDX) RNA-Seq data, we developed an empirical approach, DisHet, to dissect the tumor microenvironment (eTME). We found that 65% of previously defined immune signature genes are not abundantly expressed in Renal Cell Carcinoma (RCC), and identified 610 novel immune/stromal transcripts. Using eTME, genomics, pathology and medical record data involving >1,000 patients, we established an inflamed pan-RCC subtype (IS) enriched for Tregs, NK cells, Th1 cells, neutrophils, macrophages, B cells, and CD8+ T cells...
June 8, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29883140/graphitization-of-glassy-carbon-after-compression-at-room-temperature
#14
T B Shiell, D G McCulloch, D R McKenzie, M R Field, B Haberl, R Boehler, B A Cook, C de Tomas, I Suarez-Martinez, N A Marks, J E Bradby
Glassy carbon is a technologically important material with isotropic properties that is nongraphitizing up to ∼3000 °C and displays complete or "superelastic" recovery from large compression. The pressure limit of these properties is not yet known. Here we use experiments and modeling to show permanent densification, and preferred orientation occurs in glassy carbon loaded to 45 GPa and above, where 45 GPa represents the limit to the superelastic and nongraphitizing properties of the material...
May 25, 2018: Physical Review Letters
https://www.readbyqxmd.com/read/29883103/fundamental-factors-impacting-the-stability-of-phosphonate-derivatized-ruthenium-polypyridyl-sensitizers-adsorbed-on-metal-oxide-surfaces
#15
McKenzie Raber, Matthew David Brady, Ludovic Troian-Gautier, John Dickenson, Seth L Marquard, Jacob Hyde, Santiago Lopez, Gerald J Meyer, Thomas J Meyer, Daniel P Harrison
A series of 18 ruthenium(II) polypyridyl complexes were synthesized and evaluated under electrochemically oxidative conditions, which generates the Ru(III) oxidation state and mimics the harsh conditions experienced during the kinetically-limited regime that can occur in dye-sensitized solar cells (DSSCs) and dye-sensitized photoelectrosynthesis cells (DSPECs), to further develop fundamental insights into the factors governing molecular sensitizer surface stability in aqueous 0.1 M HClO4 (aq). Both desorption and oxidatively induced ligand substitution were observed on planar fluorine doped tin oxide, FTO, electrodes, with a dependence on the E1/2 Ru(III/II) redox potential dictating the comparative ratios of the processes...
June 8, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29882869/mitochondrial-fatty-acid-oxidation-disorders-associated-with-short-chain-enoyl-coa-hydratase-echs1-deficiency
#16
REVIEW
Alice J Sharpe, Matthew McKenzie
Mitochondrial fatty acid β-oxidation (FAO) is the primary pathway for fatty acid metabolism in humans, performing a key role in liver, heart and skeletal muscle energy homeostasis. FAO is particularly important during times of fasting when glucose supply is limited, providing energy for many organs and tissues, including the heart, liver and brain. Deficiencies in FAO can cause life-threatening metabolic disorders in early childhood that present with liver dysfunction, hypoglycemia, dilated hypertrophic cardiomyopathy and Reye-like Syndrome...
May 23, 2018: Cells
https://www.readbyqxmd.com/read/29874559/synthesis-and-use-of-6-6-6-trifluoro-l-fucose-to-block-core-fucosylation-in-hybridoma-cell-lines
#17
Nicole C McKenzie, Nichollas E Scott, Alan John, Jonathan M White, Ethan D Goddard-Borger
Many monoclonal antibodies (mAbs) used in cancer immunotherapy mediate tumour cell lysis by recruiting natural killer (NK) cells; a phenomenon known as antibody-dependent cellular cytotoxicity (ADCC). Eliminating core-fucose from the N-glycans of a mAb enhances its capacity to induce ADCC. As such, inhibitors of fucosylation are highly desirable for the production of mAbs for research and therapeutic use. Herein, we describe a simple synthesis of 6,6,6-trifluoro-l-fucose (F3Fuc), a metabolic inhibitor of fucosylation, and demonstrate the utility of this molecule in the production of low-fucose mAbs from murine hybridoma cell lines...
May 23, 2018: Carbohydrate Research
https://www.readbyqxmd.com/read/29873653/two-photon-spectroscopy-and-microscopy-of-the-fluorescent-flavoprotein-ilov
#18
Rachael J Homans, Raja U Khan, Michael B Andrews, Annemette E Kjeldsen, Louise S Natrajan, Steven Marsden, Edward A McKenzie, John M Christie, Alex R Jones
LOV-domains are ubiquitous photosensory proteins that are commonly re-engineered to serve as powerful and versatile fluorescent proteins and optogenetic tools. The photoactive, flavin chromophore, however, is excited using short wavelengths of light in the blue and UV regions, which have limited penetration into biological samples and can cause photodamage. Here, we have used non-linear spectroscopy and microscopy of the fluorescent protein, iLOV, to reveal that functional variants of LOV can be activated to great effect by two non-resonant photons of lower energy, near infrared light, not only in solution but also in biological samples...
June 6, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29870417/venous-thromboembolism-prophylaxis-in-spine-surgery
#19
Christopher K Kepler, James McKenzie, Tyler Kreitz, Alexander Vaccaro
Venous thromboembolism (VTE) is a source of morbidity and mortality in patients undergoing orthopaedic surgery. A substantial body of literature supports the use of VTE prophylactic agents in patients undergoing lower extremity surgery. Treatment options include early mobilization, mechanical prophylaxis via pneumatic compression devices, pharmacologic agents, and venous filters. No consensus has been established regarding utilization or timing of VTE prophylaxis measures after spine surgery. The risk of VTE in patients undergoing spine surgery is not well characterized and varies substantially by the procedure and degree of neurologic compromise...
June 4, 2018: Journal of the American Academy of Orthopaedic Surgeons
https://www.readbyqxmd.com/read/29864205/correlates-of-private-secondary-schools-meeting-physical-education-guidelines
#20
David Kahan, Thomas L McKenzie
BACKGROUND: Although there are over 26,000 private schools in the United States, little is known about the relationship of their characteristics to mandated and recommended time allocations for physical education (PE). METHODS: Private secondary schools (N = 450; grades 6-12) in California completed a 15-item questionnaire related to school characteristics and PE policies and practices. Using correlational analysis and predictive modeling, we assessed the associations and influences of various factors relative to the schools meeting state (California) and national professional time targets for PE...
July 2018: Journal of School Health
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