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https://www.readbyqxmd.com/read/28811555/identification-of-novel-micrornas-in-the-sheep-heart-and-their-regulation-in-heart-failure
#1
Lee Lee Wong, Miriam T Rademaker, Eng Leng Saw, Kar Sheng Lew, Leigh J Ellmers, Christopher J Charles, Arthur Mark Richards, Peipei Wang
Study of microRNA (miRNAs) using sheep models is limited due to lack of miRNA information. We therefore investigated oar-miRNAs and their regulation in an ovine model of heart failure (HF). Left ventricular (LV) tissue was collected from normal (Cont), HF (LV pacing @ ~220bpm for 13-days) and HF-recovery sheep (HF-R, 26-days after pacing cessation). MiRNA expression was profiled using next-generation sequencing (NGS) and miRNA array, and validated by stem-loop qPCR. Detected sequences were mapped against the ovine genome (Oar v4...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808886/assessment-of-pharmacokinetic-interactions-between-obeticholic-acid-and-caffeine-midazolam-warfarin-dextromethorphan-omeprazole-rosuvastatin-and-digoxin-in-phase-1-studies-in-healthy-subjects
#2
Jeffrey E Edwards, Lise Eliot, Andrew Parkinson, Sharon Karan, Leigh MacConell
INTRODUCTION: Obeticholic acid (OCA), a potent and selective farnesoid X receptor agonist, is indicated for the treatment of primary biliary cholangitis (PBC). We investigated the potential drug-drug interaction effect of OCA on metabolic CYP450 enzymes and drug transporters. METHODS: Five phase 1 single-center, open-label, fixed-sequence, inpatient studies were conducted in healthy adult subjects to evaluate the effect of oral daily doses of 10 or 25 mg OCA on single-dose plasma pharmacokinetics of specific probe substrates for enzymes CYP1A2 (caffeine, R-warfarin), CYP3A (midazolam, R-warfarin), CYP2C9 (S-warfarin), CYP2D6 (dextromethorphan), CYP2C19 (omeprazole), and drug transporters, BCRP/OATP1B1/OATP1B3 (rosuvastatin), and P-gp (digoxin)...
August 14, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28806372/exploring-rural-disparities-in-medical-diagnoses-among-veterans-with-transgender-related-diagnoses-utilizing-veterans-health-administration-care
#3
Leigh A Bukowski, John Blosnich, Jillian C Shipherd, Michael R Kauth, George R Brown, Adam J Gordon
OBJECTIVES: Research shows transgender individuals experience pronounced health disparities compared with their nontransgender peers. Yet, there remains insufficient research about health differences within transgender populations. This study seeks to fill this gap by exploring how current urban/rural status is associated with lifetime diagnosis of mood disorder, alcohol dependence disorder, illicit drug abuse disorder, tobacco use, posttraumatic stress disorder, human immunodeficiency virus, and suicidal ideation or attempt among veterans with transgender-related diagnoses...
September 2017: Medical Care
https://www.readbyqxmd.com/read/28800689/evaluation-of-edar-vehicle-emissions-remote-sensing-technology
#4
Karl Ropkins, Timothy H DeFries, Francis Pope, David C Green, Jim Kemper, Sandeep Kishan, Gary W Fuller, Hu Li, Jim Sidebottom, Leigh R Crilley, Louisa Kramer, William J Bloss, J Stewart Hager
Despite much work in recent years, vehicle emissions remain a significant contributor in many areas where air quality standards are under threat. Policy-makers are actively exploring options for next generation vehicle emission control and local fleet management policies, and new monitoring technologies to aid these activities. Therefore, we report here on findings from two separate but complementary blind evaluation studies of one new-to-market real-world monitoring option, HEAT LLC's Emission Detection And Reporting system or EDAR, an above-road open path instrument that uses Differential Absorption LIDAR to provide a highly sensitive and selective measure of passing vehicle emissions...
August 7, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28794611/single-nucleotide-polymorphism-1623-a-g-rs180195-in-the-promoter-of-the-thyroglobulin-gene-is-associated-with-autoimmune-thyroid-disease-but-not-with-thyroid-ophthalmopathy
#5
Hooshang Lahooti, Senarath Edirimanne, John P Walsh, Leigh Delbridge, Emily J Hibbert, Jack R Wall
BACKGROUND: Our studies over recent years have focused on some new ideas concerning the pathogenesis for the orbital reaction that characterizes Graves' ophthalmopathy namely, that there are antigens expressed by thyroid tissue and orbital tissue where they are targeted by autoantibodies and/or sensitized T cells, leading to orbital inflammation. While this has been well studied for the thyroid stimulating hormone-receptor, the possible role of another major thyroid antigen, Thyroglobulin (TG), has been largely ignored...
2017: Clinical Ophthalmology
https://www.readbyqxmd.com/read/28777931/biallelic-mutations-in-mrps34-lead-to-instability-of-the-small-mitoribosomal-subunit-and-leigh-syndrome
#6
Nicole J Lake, Bryn D Webb, David A Stroud, Tara R Richman, Benedetta Ruzzenente, Alison G Compton, Hayley S Mountford, Juliette Pulman, Coralie Zangarelli, Marlene Rio, Nathalie Bodaert, Zahra Assouline, Mingma D Sherpa, Eric E Schadt, Sander M Houten, James Byrnes, Elizabeth M McCormick, Zarazuela Zolkipli-Cunningham, Katrina Haude, Zhancheng Zhang, Kyle Retterer, Renkui Bai, Sarah E Calvo, Vamsi K Mootha, John Christodoulou, Agnes Rötig, Aleksandra Filipovska, Ingrid Cristian, Marni J Falk, Metodi D Metodiev, David R Thorburn
The synthesis of all 13 mitochondrial DNA (mtDNA)-encoded protein subunits of the human oxidative phosphorylation (OXPHOS) system is carried out by mitochondrial ribosomes (mitoribosomes). Defects in the stability of mitoribosomal proteins or mitoribosome assembly impair mitochondrial protein translation, causing combined OXPHOS enzyme deficiency and clinical disease. Here we report four autosomal-recessive pathogenic mutations in the gene encoding the small mitoribosomal subunit protein, MRPS34, in six subjects from four unrelated families with Leigh syndrome and combined OXPHOS defects...
August 3, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28770322/metformin-for-diabetes-prevention-insights-gained-from-the-diabetes-prevention-program-diabetes-prevention-program-outcomes-study
#7
REVIEW
Vanita R Aroda, William C Knowler, Jill P Crandall, Leigh Perreault, Sharon L Edelstein, Susan L Jeffries, Mark E Molitch, Xavier Pi-Sunyer, Christine Darwin, Brandy M Heckman-Stoddard, Marinella Temprosa, Steven E Kahn, David M Nathan
The largest and longest clinical trial of metformin for the prevention of diabetes is the Diabetes Prevention Program/Diabetes Prevention Program Outcomes Study (DPP/DPPOS). In this review, we summarise data from the DPP/DPPOS, focusing on metformin for diabetes prevention, as well as its long-term glycaemic and cardiometabolic effects and safety in people at high-risk of developing diabetes. The DPP (1996-2001) was a RCT of 3234 adults who, at baseline, were at high-risk of developing diabetes. Participants were assigned to masked placebo (n = 1082) or metformin (n = 1073) 850 mg twice daily, or intensive lifestyle intervention (n = 1079)...
August 2, 2017: Diabetologia
https://www.readbyqxmd.com/read/28762738/enzyme-mediated-directional-transport-of-a-small-molecule-walker-with-chemically-identical-feet
#8
Christopher J Martin, Alan T L Lee, Ralph W Adams, David A Leigh
We describe a small-molecule "walker" that uses enzyme catalysis to discriminate between the relative positions of its "feet" on a track and thereby move with net directionality. The bipedal walker has identical carboxylic acid feet, and "steps" along an isotactic hydroxyl-group-derivatized polyether track by the formation/breakage of ester linkages. Lipase AS catalyzes the selective hydrolysis of the rear foot of macrocyclized walkers (an information ratchet mechanism), the rear foot producing an (R)-stereocenter at its point of attachment to the track...
August 15, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28753910/practical-use-of-metal-oxide-semiconductor-gas-sensors-for-measuring-nitrogen-dioxide-and-ozone-in-urban-environments
#9
Philip J D Peterson, Amrita Aujla, Kirsty H Grant, Alex G Brundle, Martin R Thompson, Josh Vande Hey, Roland J Leigh
The potential of inexpensive Metal Oxide Semiconductor (MOS) gas sensors to be used for urban air quality monitoring has been the topic of increasing interest in the last decade. This paper discusses some of the lessons of three years of experience working with such sensors on a novel instrument platform (Small Open General purpose Sensor (SOGS)) in the measurement of atmospheric nitrogen dioxide and ozone concentrations. Analytic methods for increasing long-term accuracy of measurements are discussed, which permit nitrogen dioxide measurements with 95% confidence intervals of 20...
July 19, 2017: Sensors
https://www.readbyqxmd.com/read/28753740/photopolymerized-micropatterns-with-high-feature-frequencies-overcome-chemorepulsive-borders-to-direct-neurite-growth
#10
Bradley W Tuft, Linjing Xu, Braden Leigh, Daniel Lee, C Allan Guymon, Marlan R Hansen
Developing and regenerating neurites respond to a variety of biophysical and biochemical cues in their microenvironment to reach target cells and establish appropriate synapses. Defining the hierarchal relationship of both types of cues to direct neurite growth carries broad significance for neural development, regeneration, and, in particular, engineering of neural prostheses that improve tissue integration with native neural networks. In this work, chemorepulsive biochemical borders are established on substrates with a range of surface microfeatures to determine the potential of physical cues to overcome conflicting biochemical cues...
July 28, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28752318/sex-differences-in-hippocampal-damage-cognitive-impairment-and-trophic-factor-expression-in-an-animal-model-of-an-alcohol-use-disorder
#11
Mark E Maynard, Emily A Barton, Caleb R Robinson, Jessica I Wooden, J Leigh Leasure
Compared to men, women disproportionally experience alcohol-related organ damage, including brain damage, and while men remain more likely to drink and to drink heavily, there is cause for concern because women are beginning to narrow the gender gap in alcohol use disorders. The hippocampus is a brain region that is particularly vulnerable to alcohol damage, due to cell loss and decreased neurogenesis. In the present study, we examined sex differences in hippocampal damage following binge alcohol. Consistent with our prior findings, we found a significant binge-induced decrement in dentate gyrus (DG) granule neurons in the female DG...
July 27, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28739512/modulation-of-mitochondrial-dysfunction-related-oxidative-stress-in-fibroblasts-of-patients-with-leigh-syndrome-by-inhibition-of-prooxidative-p66shc-pathway
#12
Aleksandra Wojtala, Agnieszka Karkucinska-Wieckowska, Vilma A Sardao, Joanna Szczepanowska, Pawel Kowalski, Maciej Pronicki, Jerzy Duszynski, Mariusz R Wieckowski
The mitochondrial respiratory chain, and in particular, complex I, is a major source of reactive oxygen species (ROS) in cells. Elevated levels of ROS are associated with an imbalance between the rate of ROS formation and the capacity of the antioxidant defense system. Increased ROS production may lead to oxidation of DNA, lipids and proteins and thus can affect fundamental cellular processes. The aim of this study was to investigate the magnitude of intracellular oxidative stress in fibroblasts of patients with Leigh syndrome with defined mutations in complex I...
July 21, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28730726/changes-in-the-extracellular-matrix-surrounding-human-chronic-wounds-revealed-by-2-photon-imaging
#13
Jessica E S Sutcliffe, Christopher Thrasivoulou, Thomas E Serena, Leigh Madden, Toby Richards, Anthony R J Phillips, David L Becker
Chronic wounds are a growing problem worldwide with no effective therapeutic treatments available. Our objective was to understand the composition of the dermal tissue surrounding venous leg ulcers and diabetic foot ulcers (DFU). We used novel 2-photon imaging techniques alongside classical histology to examine biopsies from the edges of two common types of chronic wound, venous leg ulcers and DFU. Compared to normal intact skin, we found that collagen levels are significantly reduced throughout the dermis of venous leg ulcer biopsies and DFU, with a reduction in both fibril thickness and abundance...
July 20, 2017: International Wound Journal
https://www.readbyqxmd.com/read/28727445/antibiotic-that-inhibits-the-atpase-activity-of-an-atp-binding-cassette-transporter-by-binding-to-a-remote-extracellular-site
#14
Leigh M Matano, Heidi G Morris, Anthony R Hesser, Sara E S Martin, Wonsik Lee, Tristan W Owens, Emaline Laney, Hidemasa Nakaminami, David Hooper, Timothy C Meredith, Suzanne Walker
Antibiotic-resistant strains of Staphylococcus aureus pose a major threat to human health and there is an ongoing need for new antibiotics to treat resistant infections. In a high throughput screen (HTS) of 230 000 small molecules designed to identify bioactive wall teichoic acid (WTA) inhibitors, we identified one hit, which was expanded through chemical synthesis into a small panel of potent compounds. We showed that these compounds target TarG, the transmembrane component of the two-component ATP-binding cassette (ABC) transporter TarGH, which exports WTA precursors to the cell surface for attachment to peptidoglycan...
July 28, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28726252/central-amygdala-relaxin-3-rxfp3-signalling-modulates-alcohol-seeking-in-rats
#15
Leigh C Walker, Hanna E Kastman, Elena Krstew, Andrew L Gundlach, Andrew J Lawrence
BACKGROUND AND PURPOSE: Alcohol use disorders are a leading cause of preventable deaths worldwide and stress is a major trigger of relapse. The neuropeptide relaxin-3 and its cognate receptor, relaxin family peptide receptor 3 (RXFP3), modulate stress-induced relapse to alcohol seeking in rats and while the bed nucleus of the stria terminalis has been implicated in this regard, the central nucleus of the amygdala (CeA) also receives a relaxin-3 innervation and CeA neurons densely express RXFP3 mRNA...
July 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28719997/the-benefit-of-evolving-multidisciplinary-care-in-als-a-diagnostic-cohort-survival-comparison
#16
Sarah Martin, Emma Trevor-Jones, Sabyha Khan, Keelan Shaw, Deepti Marchment, Anna Kulka, Catherine E Ellis, Rachel Burman, Martin R Turner, Liam Carroll, Leah Mursaleen, P Nigel Leigh, Christopher E Shaw, Neil Pearce, Daniel Stahl, Ammar Al-Chalabi
BACKGROUND: Care for people with amyotrophic lateral sclerosis (ALS) has altered at King's College Hospital over the last 20 years. The clinic has been a multidisciplinary, specialist, tertiary referral centre since 1995 with a large team with integrated palliative and respiratory care since 2006. We hypothesised that these changes would improve survival. METHODS: In this retrospective observational study, patients diagnosed with El Escorial definite, probable and possible ALS between 1995-1998 and 2008-2011 were followed up...
July 18, 2017: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
https://www.readbyqxmd.com/read/28702169/exome-sequencing-reveals-independent-sgcd-deletions-causing-limb-girdle-muscular-dystrophy-in-boston-terriers
#17
Melissa L Cox, Jacquelyn M Evans, Alexander G Davis, Ling T Guo, Jennifer R Levy, Alison N Starr-Moss, Elina Salmela, Marjo K Hytönen, Hannes Lohi, Kevin P Campbell, Leigh Anne Clark, G Diane Shelton
BACKGROUND: Limb-girdle muscular dystrophies (LGMDs) are a heterogeneous group of inherited autosomal myopathies that preferentially affect voluntary muscles of the shoulders and hips. LGMD has been clinically described in several breeds of dogs, but the responsible mutations are unknown. The clinical presentation in dogs is characterized by marked muscle weakness and atrophy in the shoulder and hips during puppyhood. METHODS: Following clinical evaluation, the identification of the dystrophic histological phenotype on muscle histology, and demonstration of the absence of sarcoglycan-sarcospan complex by immunostaining, whole exome sequencing was performed on five Boston terriers: one affected dog and its three family members and one unrelated affected dog...
2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28700459/the-microbiome-in-posttraumatic-stress-disorder-and-trauma-exposed-controls-an-exploratory-study
#18
Sian M J Hemmings, Stefanie Malan-Muller, Leigh L van den Heuvel, Brittany A Demmitt, Maggie A Stanislawski, David G Smith, Adam D Bohr, Christopher E Stamper, Embriette R Hyde, James T Morton, Clarisse A Marotz, Philip H Siebler, Maarten Braspenning, Wim Van Criekinge, Andrew J Hoisington, Lisa A Brenner, Teodor T Postolache, Matthew B McQueen, Kenneth S Krauter, Rob Knight, Soraya Seedat, Christopher A Lowry
OBJECTIVE: Inadequate immunoregulation and elevated inflammation may be risk factors for posttraumatic stress disorder (PTSD), and microbial inputs are important determinants of immunoregulation; however, the association between the gut microbiota and PTSD is unknown. This study investigated the gut microbiome in a South African sample of PTSD-affected individuals and trauma-exposed (TE) controls, to identify potential differences in microbial diversity or microbial community structure...
July 11, 2017: Psychosomatic Medicine
https://www.readbyqxmd.com/read/28697784/exome-sequencing-reveals-independent-sgcd-deletions-causing-limb-girdle-muscular-dystrophy-in-boston-terriers
#19
Melissa L Cox, Jacquelyn M Evans, Alexander G Davis, Ling T Guo, Jennifer R Levy, Alison N Starr-Moss, Elina Salmela, Marjo K Hytönen, Hannes Lohi, Kevin P Campbell, Leigh Anne Clark, G Diane Shelton
BACKGROUND: Limb-girdle muscular dystrophies (LGMDs) are a heterogeneous group of inherited autosomal myopathies that preferentially affect voluntary muscles of the shoulders and hips. LGMD has been clinically described in several breeds of dogs, but the responsible mutations are unknown. The clinical presentation in dogs is characterized by marked muscle weakness and atrophy in the shoulder and hips during puppyhood. METHODS: Following clinical evaluation, the identification of the dystrophic histological phenotype on muscle histology, and demonstration of the absence of sarcoglycan-sarcospan complex by immunostaining, whole exome sequencing was performed on five Boston terriers: one affected dog and its three family members and one unrelated affected dog...
July 11, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28685855/alcohol-exposure-during-pregnancy-altered-childhood-developmental-trajectories-in-a-rural-south-african-community
#20
Leigh-Anne Davies, Kate Cockcroft, Lynda Olinger, Matthew Chersich, Michael Urban, Candice M Chetty Makkan, Oliver H Turnbull, Leana Olivier, Denis Viljoen
AIM: This study examined the effects of prenatal alcohol exposure on childhood development trajectories in a rural South African community between 2003 and 2008. METHODS: We assessed 121 children at 7-12 months (year one) and 5-6 years (year five) using the Griffiths Mental Developmental Scales - Extended Revised, which measures sensorimotor, cognitive and social development, with lower scores indicating developmental delay. We also interviewed their mothers or caregivers...
July 7, 2017: Acta Paediatrica
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