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https://www.readbyqxmd.com/read/28935167/impact-of-lifetime-traumatic-experiences-on-suicidality-and-likelihood-of-conversion-in-a-cohort-of-individuals-at-clinical-high-risk-for-psychosis
#1
Margaux M Grivel, Wei Leong, Michael D Masucci, Rebecca A Altschuler, Leigh Y Arndt, Samantha L Redman, Lawrence H Yang, Gary Brucato, Ragy R Girgis
Recent research suggests that trauma history (TH) is a strong socio-environmental risk factor for the development of psychosis. While reported rates of childhood trauma are higher among individuals at clinical high-risk (CHR) for psychosis than in the general population, little research has explored the effects of trauma upon the severity of attenuated positive symptoms. We aimed to explore the specific relationships between TH and baseline symptom severity; likelihood of conversion to full-blown psychosis; suicidal ideation (SI); and suicidal behavior (SB) in a cohort of 200 help-seeking CHR individuals...
September 18, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28932113/cationic-lipid-based-nanoparticles-mediate-functional-delivery-of-acetate-to-tumor-cells-in-vivo-leading-to-significant-anticancer-effects
#2
Leigh P Brody, Meliz Sahuri-Arisoylu, James R Parkinson, Harry G Parkes, Po Wah So, Nabil Hajji, E Louise Thomas, Gary S Frost, Andrew D Miller, Jimmy D Bell
Metabolic reengineering using nanoparticle delivery represents an innovative therapeutic approach to normalizing the deregulation of cellular metabolism underlying many diseases, including cancer. Here, we demonstrated a unique and novel application to the treatment of malignancy using a short-chain fatty acid (SCFA)-encapsulated lipid-based delivery system - liposome-encapsulated acetate nanoparticles for cancer applications (LITA-CAN). We assessed chronic in vivo administration of our nanoparticle in three separate murine models of colorectal cancer...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28929430/new-drugs-in-the-pipeline-for-the-treatment-of-hiv-a-review
#3
REVIEW
Leigh Anne Hylton Gravatt, Crystal R Leibrand, Sulay Patel, MaryPeace McRae
PURPOSE OF REVIEW: The purpose of this paper is to review therapies with new mechanisms of action for the treatment of HIV that are at least in phase 2 clinical trials. RECENT FINDINGS: There are several new mechanisms of action being represented within clinical development, including histone deacetylase (HDAC) inhibitors, gene therapies, broadly neutralizing anti-HIV antibodies, immune modulation, and drugs with new mechanisms to block HIV entry. The new therapies are being developed for both as add-on therapy to existing combination antiretroviral therapy and as agents to be used during treatment interruption...
September 19, 2017: Current Infectious Disease Reports
https://www.readbyqxmd.com/read/28929126/nasopharyngeal-pneumococcal-density-is-associated-with-viral-activity-but-not-with-use-of-improved-stoves-among-young-andean-children
#4
Leigh M Howard, Roger Fan, Yuwei Zhu, Marie R Griffin, Kathryn M Edwards, Stella Hartinger, John V Williams, Jorge E Vidal, Keith P Klugman, Ana I Gil, Claudio F Lanata, Carlos G Grijalva
BACKGROUND: Indoor smoke exposure is common in developing countries and may influence nasopharyngeal (NP) pneumococcal colonization density and risk of acute respiratory illness. We compared colonization density among Andean children living in households previously enrolled in a randomized controlled trial of a home intervention package including improved stoves to reduce smoke, kitchen sinks, and water disinfection. METHODS: We enrolled 260 children aged <3 years and made weekly household visits to assess for acute respiratory illness (ARI) and collect nasal swabs for respiratory virus polymerase chain reaction (PCR) testing during ARI...
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28925066/beyond-the-androgen-receptor-ii-new-approaches-to-understanding-and-treating-metastatic-prostate-cancer-report-from-the-2017-coffey-holden-prostate-cancer-academy-meeting
#5
REVIEW
Andrea K Miyahira, Heather H Cheng, Wassim Abida, Leigh Ellis, Lauren C Harshman, Daniel E Spratt, Jonathan W Simons, Kenneth J Pienta, Howard R Soule
INTRODUCTION: The 2017 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, "Beyond the Androgen Receptor II: New Approaches to Understanding and Treating Metastatic Prostate Cancer," was held in Carlsbad, California from June 14-17, 2017. METHODS: The CHPCA is an annual scientific conference hosted by the Prostate Cancer Foundation (PCF) that is uniquely designed to produce extensive and constructive discussions on the most urgent and impactful topics concerning research into the biology and treatment of metastatic prostate cancer...
September 18, 2017: Prostate
https://www.readbyqxmd.com/read/28917132/a-novel-real-time-rt-pcr-assay-for-influenza-c-tested-in-peruvian-children
#6
Leigh M Howard, Monika Johnson, Ana I Gil, Andrew Pekosz, Marie R Griffin, Kathryn M Edwards, Claudio F Lanata, Carlos G Grijalva, John V Williams
BACKGROUND: Influenza C virus (ICV) is associated with acute respiratory illness. Yet ICV remains under recognized, with most previous studies using only culture to identify cases. OBJECTIVES: To develop a sensitive and specific real-time RT-PCR assay for ICV that allows for rapid and accurate detection in a clinical or research setting. STUDY DESIGN: Multiple ICV sequences obtained from GenBank were analyzed, including 141 hemagglutinin-esterase (HE), 106 matrix (M), and 97 nucleoprotein (NP) sequences...
September 1, 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/28902423/partitioning-k-space-for-cylindrical-three-dimensional-rapid-acquisition-with-relaxation-enhancement-imaging-in-the-mouse-brain
#7
T Leigh Spencer Noakes, R Mark Henkelman, Brian J Nieman
Three-dimensional rapid acquisition with relaxation enhancement (RARE) scans require the assignment of each phase encode step in two dimensions to an echo in the echo train. Although this assignment is frequently made across the entire Cartesian grid, collection of only the central cylinder of k-space by eliminating the corners in each phase encode dimension reduces the scan time by ~22% with negligible impact on image quality. The recipe for the assignment of echoes to grid points for such an acquisition is less straightforward than for the simple full Cartesian acquisition case, and has important implications for image quality...
September 13, 2017: NMR in Biomedicine
https://www.readbyqxmd.com/read/28899973/top2a-and-ezh2-provide-early-detection-of-an-aggressive-prostate-cancer-subgroup
#8
David P Labbé, Christopher J Sweeney, Myles Brown, Phillip Galbo, Spencer Rosario, Kristine M Wadosky, Sheng-Yu Ku, Martin Sjöström, Mohammed Alshalalfa, Nicholas Erho, Elai Davicioni, R Jeffrey Karnes, Edward M Schaeffer, Robert B Jenkins, Robert B Den, Ashley E Ross, Michaela Bowden, Ying Huang, Kathryn P Gray, Felix Y Feng, Daniel E Spratt, David W Goodrich, Kevin H Eng, Leigh Ellis
PURPOSE: Current clinical parameters do not stratify indolent from aggressive prostate cancer (PCa). Aggressive PCa, defined by the progression from localized disease to metastasis, is responsible for the majority of PCa-associated mortality. Recent gene expression profiling has proven successful in predicting the outcome of PCa patients, however they have yet to provide targeted therapy approaches that could inhibit a patient's progression to metastatic disease. EXPERIMENTAL DESIGN: We have interrogated a total of seven primary PCa cohorts (N = 1,900), two metastatic castration resistant PCa datasets (N = 293) and one prospective cohort (N = 1,385) to assess the impact of TOP2A and EZH2 expression on PCa cellular program and patient outcomes...
September 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28883086/characterizing-chilean-blue-whale-vocalizations-with-dtags-a-test-of-using-tag-accelerometers-for-caller-identification
#9
Mark R Saddler, Alessandro Bocconcelli, Leigh S Hickmott, Gustavo Chiang, Rafaela Landea-Briones, Paulina A Bahamonde, Gloria Howes, Paolo S Segre, Laela S Sayigh
Vocal behavior of blue whales (Balaenoptera musculus) in the Gulf of Corcovado, Chile, was analyzed using both audio and accelerometer data from digital acoustic recording tags (DTAGs). Over the course of three austral summers (2014, 2015, 2016), seventeen tags were deployed, yielding 124 hours of data. We report the occurrence of Southeast Pacific type 2 (SEP2) calls, which exhibit peak frequencies, durations, and timing consistent with previous recordings made using towed and moored hydrophones. We also describe tonal downswept (D) calls, which have not been previously described for this population...
September 7, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28862604/-high-resolution-respirometry-in-diagnostic-of-mitochondrial-disorders-caused-by-mitochondrial-complex-i-deficiency
#10
T D Krylova, P G Tsygankova, Yu S Itkis, N L Sheremet, T A Nevinitsyna, S V Mikhaylova, E Yu Zakharova
Complex I (CI) deficiency is one of the most common defects in the OXPHOS system; it represents more than 30% cases of mitochondrial diseases. The group is characterized by clinical and genetic heterogeneity and comprise several nosological forms. The most prevalent phenotypes for CI are LHON and Leigh syndrome. In this study we have analyzed skin fibroblasts from 11 patients with mutations in mtDNA, which cause LHON or Leigh-like phenotypes: m.11778 G>A (n=3), m.3460 A>G (n=2), m.3635 G>A (n=1), m...
July 2017: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/28859290/racial-differences-in-pam50-subtypes-in-the-carolina-breast-cancer-study
#11
Melissa A Troester, Xuezheng Sun, Emma H Allott, Joseph Geradts, Stephanie M Cohen, Chiu-Kit Tse, Erin L Kirk, Leigh B Thorne, Michelle Mathews, Yan Li, Zhiyuan Hu, Whitney R Robinson, Katherine A Hoadley, Olufunmilayo I Olopade, Katherine E Reeder-Hayes, H Shelton Earp, Andrew F Olshan, Lisa A Carey, Charles M Perou
Background: African American breast cancer patients have lower frequency of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-negative disease and higher subtype-specific mortality. Racial differences in molecular subtype within clinically defined subgroups are not well understood. Methods: Using data and biospecimens from the population-based Carolina Breast Cancer Study (CBCS) Phase 3 (2008-2013), we classified 980 invasive breast cancers using RNA expression-based PAM50 subtype and recurrence (ROR) score that reflects proliferation and tumor size...
February 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28851861/synthetic-lethality-between-androgen-receptor-signalling-and-the-parp-pathway-in-prostate-cancer
#12
Mohammad Asim, Firas Tarish, Heather I Zecchini, Kumar Sanjiv, Eleni Gelali, Charles E Massie, Ajoeb Baridi, Anne Y Warren, Wanfeng Zhao, Christoph Ogris, Leigh-Anne McDuffus, Patrice Mascalchi, Greg Shaw, Harveer Dev, Karan Wadhwa, Paul Wijnhoven, Josep V Forment, Scott R Lyons, Andy G Lynch, Cormac O'Neill, Vincent R Zecchini, Paul S Rennie, Aria Baniahmad, Simon Tavaré, Ian G Mills, Yaron Galanty, Nicola Crosetto, Niklas Schultz, David Neal, Thomas Helleday
Emerging data demonstrate homologous recombination (HR) defects in castration-resistant prostate cancers, rendering these tumours sensitive to PARP inhibition. Here we demonstrate a direct requirement for the androgen receptor (AR) to maintain HR gene expression and HR activity in prostate cancer. We show that PARP-mediated repair pathways are upregulated in prostate cancer following androgen-deprivation therapy (ADT). Furthermore, upregulation of PARP activity is essential for the survival of prostate cancer cells and we demonstrate a synthetic lethality between ADT and PARP inhibition in vivo...
August 29, 2017: Nature Communications
https://www.readbyqxmd.com/read/28841276/tuning-surface-and-topographical-features-to-investigate-competitive-guidance-of-spiral-ganglion-neurons
#13
Braden L Leigh, Kristy Truong, Reid Bartholomew, Mark Ramirez, Marlan R Hansen, C Allan Guymon
Cochlear Implants (CIs) suffer from limited tonal resolution due, in large part, to spatial separation between stimulating electrode arrays and primary neural receptors. In this work, a combination of physical and chemical micropatterns, formed on acrylate polymers, are used to direct the growth of primary spiral ganglion neurons (SGNs), the inner ear neurons. Utilizing the inherent temporal and spatial control of photopolymerization, physical microgrooves are fabricated using a photomask in a single step process...
September 20, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28811555/identification-of-novel-micrornas-in-the-sheep-heart-and-their-regulation-in-heart-failure
#14
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
#15
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
#16
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
#17
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...
December 31, 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
#18
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
#19
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
#20
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
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