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https://www.readbyqxmd.com/read/29168205/a-human-microdose-study-of-the-anti-malarial-gsk3191607-in-healthy-volunteers
#1
Malek Okour, Geo Derimanov, Rodger Barnett, Esther Fernandez, Santiago Ferrer, Stephanie Gresham, Mohammad Hossain, Francisco-Javier Gamo, Gavin Koh, Adrian Pereira, Katie Rolfe, Deborah Wong, Graeme Young, Harshad Rami, John Haselden
AIMS: GSK3191607, a novel inhibitor of the Plasmodium falciparum ATP4 (PfATP4) pathway, is being considered for development in humans. However, a key problem encountered during the preclinical evaluation of the compound was its inconsistent PK profile across preclinical species (mouse, rat and dog) which prevented reliable prediction of PK parameters in humans and precluded a well-founded assessment of the potential for clinical development of the compound. Therefore, an open label microdose (100 μg, 6 subjects) FTIH study was conducted in order to assess the human pharmacokinetics of GSK3191607 following IV administration of [14C]-GSK3191607...
November 22, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29167896/association-of-abnormal-renal-profiles-and-proliferative-diabetic-retinopathy-and-diabetic-macular-edema-in-an-asian-population-with-type-2-diabetes
#2
Yi-Ting Hsieh, Meng-Ju Tsai, Shih-Te Tu, Ming-Chia Hsieh
Importance: The comorbidity of chronic kidney disease and diabetic retinopathy (DR) is well known. However, to our knowledge, no cohort study has demonstrated the effect of chronic kidney disease on the development or progression of DR. Objective: To investigate the association of chronic kidney disease with the development of DR and diabetic macular edema (DME) in type 2 diabetes. Design, Setting, and Participants: This 8-year prospective cohort study that was conducted in 2 medical centers in Taiwan included 2135 patients with type 2 diabetes...
November 22, 2017: JAMA Ophthalmology
https://www.readbyqxmd.com/read/29167439/eroded-telomeres-are-rearranged-in-quiescent-fission-yeast-cells-through-duplications-of-subtelomeric-sequences
#3
Laetitia Maestroni, Julien Audry, Samah Matmati, Benoit Arcangioli, Vincent Géli, Stéphane Coulon
While the mechanisms of telomere maintenance has been investigated in dividing cells, little is known about the stability of telomeres in quiescent cells and how dysfunctional telomeres are processed in non-proliferating cells. Here we examine the stability of telomeres in quiescent cells using fission yeast. While wild type telomeres are stable in quiescence, we observe that eroded telomeres were highly rearranged during quiescence in telomerase minus cells. These rearrangements depend on homologous recombination (HR) and correspond to duplications of subtelomeric regions...
November 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/29167336/an-insight-into-the-role-of-e3-ubiquitin-ligase-c-cbl-escrt-machinery-and-host-cell-signaling-in-kaposi-s-sarcoma-associated-herpesvirus-kshv-entry-and-trafficking
#4
Binod Kumar, Arunava Roy, Mohanan Valiya Veettil, Bala Chandran
Kaposi's sarcoma-associated herpesvirus (KSHV) in vitro infection of dermal endothelial cell begins with its binding to host cell surface receptor molecules such as heparan sulfate (HS), integrins (α3β1, αVβ3 and αVβ5), xCT and EphA2 receptor tyrosine kinase (EphA2R). These initial events initiate dynamic host protein-protein interactions involving a multi-molecular complex of receptors, signal molecules (FAK, Src, PI3-K, RhoA-GTPase), adaptors (c-Cbl, CIB1, Crk, p130Cas and GEF-C3G), and actin/myosin II light chain that leads to virus entry via macropinocytosis...
November 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29167212/cardiovascular-disease-cancer-and-mortality-among-people-with-type-2-diabetes-and-alcoholic-or-nonalcoholic-fatty-liver-disease-hospital-admission
#5
Sarah H Wild, Jeremy J Walker, Joanne R Morling, David A McAllister, Helen M Colhoun, Bassam Farran, Stuart McGurnaghan, Rory McCrimmon, Stephanie H Read, Naveed Sattar, Christopher D Byrne
OBJECTIVE: To describe associations between alcoholic liver disease (ALD) or nonalcoholic fatty liver disease (NAFLD) hospital admission and cardiovascular disease (CVD), cancer, and mortality in people with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: We performed a retrospective cohort study by using linked population-based routine data from diabetes registry, hospital, cancer, and death records for people ages 40-89 years diagnosed with T2DM in Scotland between 2004 and 2013 who had one or more hospital admission records...
November 22, 2017: Diabetes Care
https://www.readbyqxmd.com/read/29167175/signaling-pathways-and-immune-evasion-mechanisms-in-classical-hodgkin-lymphoma
#6
W Robert Liu, Margaret A Shipp
Classical Hodgkin lymphoma (cHL) is an unusual B-cell derived malignancy in which rare malignant Hodgkin and Reed-Sternberg (HRS) cells are surrounded by an extensive but ineffective inflammatory/ immune cell infiltrate. This striking feature suggests that malignant HRS cells escape immunosurveillance and interact with immune cells in the cancer microenvironment for survival and growth. We previously found that cHLs have a genetic basis of immune evasion - near uniform copy number alterations (CNAs) of chromosome 9p24...
November 22, 2017: Blood
https://www.readbyqxmd.com/read/29167125/mesenchymal-stem-cells-reduce-hypoxia-induced-apoptosis-in-alveolar-epithelial-cells-by-modulating-hif-and-ros-hypoxic-signalings
#7
Olivier Bernard, Florence Jeny, Yurdagul Uzunhan, Elisabetta Dondi, Rahma Terfous, Rabab Label, Angela Sutton, Jérôme Larghero, Valérie Vanneaux, Hilario Nunes, Emilie Boncoeur, Carole Planès, Nicolas Dard
Distal lung diseases such as pulmonary fibrosis or acute lung injury are commonly associated with local alveolar hypoxia that may be deleterious through the stimulation of alveolar epithelial cell (AEC) apoptosis. In various murine models of alveolar injury, administration of allogenic human mesenchymal stem cells (hMSC) exerts an overall protective paracrine effect limiting lung inflammation and fibrosis. However, the precise mechanisms on lung cells themselves remain poorly understood. Here we investigated whether hMSC conditioned medium (hMSC-CM) would protect AECs from hypoxia-induced apoptosis and the mechanisms involved in this cytoprotective effect...
November 22, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29167072/induction-of-anaesthesia-with-remifentanil-after-bolus-midazolam-administration-in-landrace-large-white-swine
#8
Argyro Zacharioudaki, Pavlos Lelovas, Theodoros N Sergentanis, George Karlis, Axel K Hansen, Apostolos Papalois, Theodoros Xanthos
OBJECTIVE: To investigate an alternative combination for anaesthesia induction in swine. STUDY DESIGN: Randomized, 'blinded' experimental study. ANIMALS: Forty-five Landrace/Large White swine weighing 20.0±1.5 kg. METHODS: Pulse oximetry, heart rate (HR) and blood pressure were measured after premedication with ketamine, midazolam and atropine as well as after intubation following induction with a fixed dose of 0.2 mg kg(-1) midazolam combined with 1, 2, 3, 4 or 5 μg kg(-1) remifentanil (groups R1, R2, R3, R4 and R5, respectively)...
April 17, 2017: Veterinary Anaesthesia and Analgesia
https://www.readbyqxmd.com/read/29166672/increased-risk-of-dementia-following-herpes-zoster-ophthalmicus
#9
Ming-Chieh Tsai, Wan-Ling Cheng, Jau-Jiuan Sheu, Chung-Chien Huang, Ben-Chang Shia, Li-Ting Kao, Herng-Ching Lin
This retrospective cohort study aimed to examine the relationship between herpes zoster ophthalmicus (HZO) and the subsequent risk of dementia using a population-based database. We retrieved the study sample from the Taiwan Longitudinal Health Insurance Database 2005. The study group included 846 patients with HZO, and the comparison group included 2538 patients without HZO. Each patient was individually followed for a 5-year period to identify those patients who subsequently received a diagnosis of dementia...
2017: PloS One
https://www.readbyqxmd.com/read/29165320/effect-of-high-carbon-incorporation-in-co-substrates-on-the-epitaxy-of-hexagonal-boron-nitride-graphene-heterostructures
#10
Alireza Khanaki, Hao Tian, Zhongguang Xu, Renjing Zheng, Yanwei He, Zhenjun Cui, Jingchuan Yang, Jianlin Liu
We carried out a systematic study of hexagonal boron nitride/graphene (h-BN/G) heterostructure growth by introducing high incorporation of carbon (C) source on a heated cobalt (Co) foil substrate followed by boron and nitrogen sources in a molecular beam epitaxy system. With the increase of C incorporation in Co, three distinct regions of h-BN/G heterostructures were observed from region (1) where the C saturation is not attained at the growth temperature (900 °C) and G is grown only by precipitation during cooling process to form a "G network" underneath the h-BN film; to region (2) where the Co substrate is just saturated by C atoms at the growth temperature and a part of G growth occurs isothermally to form G islands and another part by precipitation, resulting in a non-uniform h-BN/G film; and to region (3) where a continuous layered G structure is formed at the growth temperature and precipitated C atoms add additional G layers to the system, leading to a uniform h-BN/G film...
November 22, 2017: Nanotechnology
https://www.readbyqxmd.com/read/29165118/age-at-first-birth-and-long-term-mortality-for-mothers-the-ohsaki-cohort-study
#11
Taichi Sakai, Yumi Sugawara, Ikue Watanabe, Takashi Watanabe, Yasutake Tomata, Naoki Nakaya, Ichiro Tsuji
BACKGROUND: Although maternal age at first birth has been rising in many developed countries, its long-term effects on the health of the mothers themselves are unclear. In this study, we investigated the relationship between maternal age at first birth and long-term mortality. METHODS: We conducted a cohort study of 20,624 parous Japanese women aged between 40 and 79 years in 1994 and followed up their survival for 14 years. Based on maternal age at first birth, the women were divided into four groups: ≤19 years, 20-24 years, 25-29 years, and ≥30 years...
April 4, 2017: Environmental Health and Preventive Medicine
https://www.readbyqxmd.com/read/29164595/frequency-of-leaving-the-house-and-mortality-from-age-70-to-95
#12
Jeremy M Jacobs, Aliza Hammerman-Rozenberg, Jochanan Stessman
OBJECTIVES: To determine the association between frequency of leaving the house and mortality. DESIGN: Prospective follow-up of an age-homogenous, representative, community-dwelling birth cohort (born 1920-21) from the Jerusalem Longitudinal Study (1990-2015). SETTING: Home. PARTICIPANTS: Individuals aged 70 (n = 593), 78 (n = 973), 85 (n = 1164), and 90 (n = 645), examined in 1990, 1998, 2005, and 2010, respectively...
November 22, 2017: Journal of the American Geriatrics Society
https://www.readbyqxmd.com/read/29163845/improved-medical-expenditure-and-survival-with-integration-of-traditional-chinese-medicine-treatment-in-patients-with-heart-failure-a-nationwide-population-based-cohort-study
#13
Ming-Yen Tsai, Wen-Long Hu, Jen-Huai Chiang, Yu-Chuen Huang, Shih-Yu Chen, Yu-Chiang Hung, Yung-Hsiang Chen
Background: No previous studies have evaluated the effects of traditional Chinese medicine (TCM) treatment on patients with heart failure (HF). Hence, in this study, we determined whether TCM treatment affects the healthcare burden and survival of HF patients. Methods: Samples were retrieved from the registry of catastrophic illness patients of the Taiwan National Health Insurance Research Database (NHIRD). Based on a frequency (1:1) matched case-control design, patients with HF between 2000 and 2010 were designated as cases (TCM users) and controls (non-TCM users)...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163831/muc1-overexpression-predicts-worse-survival-in-patients-with-non-small-cell-lung-cancer-evidence-from-an-updated-meta-analysis
#14
Xing Huang, Qi Sun, Chen Chen, Yi Zhang, Xin Kang, Jing-Yuan Zhang, Da-Wei Ma, Lei Xia, Lin Xu, Xin-Yu Xu, Bin-Hui Ren
Background: Previous studies on the prognostic role of MUC1 expression in non-small cell lung cancer (NSCLC) remain controversial. We conducted a meta-analysis to appraise the clinicopathological and prognostic effect of MUC1 in NSCLC patients. Materials and Methods: Searches of PubMed, EMBASE and CNKI (Chinese National Knowledge Infrastructure) were conducted and relevant studies were extracted. The pooled hazard ratio (HR) or odds ratio (OR) with 95% confidence intervals (CIs) were used to estimate effects...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29162544/immunostimulation-and-yellow-head-virus-yhv-disease-resistance-induced-by-a-lignin-based-pulping-by-product-in-black-tiger-shrimp-penaeus-monodon-linn
#15
Prapansak Srisapoome, Kaoru Hamano, Isao Tsutsui, Kenji Iiyama
Yellow head virus (YHV) is classified as one of the most serious pathogens causing a harmful disease in many penaeids, especially black tiger shrimp (Penaeus monodon), with high economic loss. To determine a potent and practical prophylactic strategy for controlling this disease, the toxicity of the by-product kraft lignin and its ability to control severe YHV infection were investigated in juvenile black tiger shrimp (15.9 ± 1.2 g body weight). The median lethal dosage at 96 h (96-hrs LD50) of lignin in shrimp was 297 mg/L...
November 18, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29162520/risk-of-unintentional-injuries-in-children-and-adolescents-with-adhd-and-the-impact-of-adhd-medications-a-systematic-review-and-meta-analysis
#16
REVIEW
Maite Ruiz-Goikoetxea, Samuele Cortese, Maite Aznarez-Sanado, Sara Magallón, Noelia Alvarez Zallo, Elkin O Luis, Pilar de Castro-Manglano, Cesar Soutullo, Gonzalo Arrondo
A systematic review with meta-analyses was performed to: 1) quantify the association between ADHD and risk of unintentional physical injuries in children/adolescents ("risk analysis"); 2) assess the effect of ADHD medications on this risk ("medication analysis"). We searched 114 databases through June 2017. For the risk analysis, studies reporting sex-controlled odds ratios (ORs) or hazard ratios (HRs) estimating the association between ADHD and injuries were combined. Pooled ORs (28 studies, 4,055,620 individuals without and 350,938 with ADHD) and HRs (4 studies, 901,891 individuals without and 20,363 with ADHD) were 1...
November 18, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/29162146/smoking-and-risk-of-breast-cancer-in-the-generations-study-cohort
#17
Michael E Jones, Minouk J Schoemaker, Lauren B Wright, Alan Ashworth, Anthony J Swerdlow
BACKGROUND: Plausible biological reasons exist regarding why smoking could affect breast cancer risk, but epidemiological evidence is inconsistent. METHODS: We used serial questionnaire information from the Generations Study cohort (United Kingdom) to estimate HRs for breast cancer in relation to smoking adjusted for potentially confounding factors, including alcohol intake. RESULTS: Among 102,927 women recruited 2003-2013, with an average of 7...
November 22, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29161705/maintained-folic-acid-supplementation-reduces-the-risk-of-mortality-in-continuous-ambulatory-peritoneal-dialysis-patients
#18
Rong Rong, Qian Zhou, Jianxiong Lin, Naya Huang, Wei Li, Yagui Qiu, Xueqing Yu, Haiping Mao
BACKGROUND: The association between folic acid (FA) supplementation and mortality in continuous ambulatory peritoneal dialysis (CAPD) patients is unclear. METHODS: FA exposure was calculated as a percentage of cumulative duration of drug usage to total follow-up duration (FA%). A total of 1,358 patients were classified by a cutoff value of FA%. The association of FA with mortality was evaluated using Cox proportional hazards models. RESULTS: The cutoff value of FA% for predicting mortality was <34% at a median follow-up of 40...
November 22, 2017: Blood Purification
https://www.readbyqxmd.com/read/29161426/family-history-of-gastric-mucosal-abnormality-and-the-risk-of-gastric-cancer-a-population-based-observational-study
#19
Huan Song, Isabella Guncha Ekheden, Alexander Ploner, Jan Ericsson, Olof Nyren, Weimin Ye
Background: An increased prevalence of gastric premalignant abnormalities was reported among relatives of gastric cancer (GC) patients, with rather unexplored clinical significance. Methods: In Swedish computerized pathology registers, we identified, as 'index' persons 232 681 patients who were born after 1931 and underwent endoscopic examination with stomach biopsy between 1979 and 2014. Through linkage with the Multi-Generation Register, we compiled a cohort consisting of 903 337 first-degree relatives of these biopsied patients...
November 17, 2017: International Journal of Epidemiology
https://www.readbyqxmd.com/read/29161239/the-impact-of-folate-intake-on-the-risk-of-head-and-neck-cancer-in-the-prostate-lung-colorectal-and-ovarian-cancer-screening-trial-plco-cohort
#20
Daisuke Kawakita, Yuan-Chin Amy Lee, Lisa H Gren, Saundra S Buys, Carlo La Vecchia, Mia Hashibe
BACKGROUND: Although low levels of folate leads to disturbances in DNA replication, DNA methylation and DNA repair, the association between dietary folate intake and head and neck cancer (HNC) risk remains unclear. METHODS: We evaluated the association between folate intake and HNC risk using prospective cohort data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial. This study included 101 700 participants and 186 cases with confirmed incident HNC...
November 21, 2017: British Journal of Cancer
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