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https://www.readbyqxmd.com/read/29346838/first-in-human-study-to-assess-safety-pharmacokinetics-and-pharmacodynamics-of-bms-962212-a-direct-reversible-small-molecule-factor-xia-inhibitor-in-non-japanese-and-japanese-healthy-subjects
#1
Vidya Perera, Joseph M Luettgen, Zhaoqing Wang, Charles E Frost, Cynthia Yones, Cesare Russo, John Lee, Yue Zhao, Frank P LaCreta, Xuewen Ma, Robert M Knabb, Dietmar Seiffert, Mary DeSouza, Pierre Mugnier, Brenda Cirincione, Takayo Ueno, Robert J A Frost
AIMS: To assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of BMS-962212, a first-in-class Factor XIa inhibitor, in Japanese and non-Japanese healthy subjects. METHODS: This was a randomized, placebo-controlled, double-blind, sequential, ascending dose study of 2 hour (Part A) and 5 day (Part B) intravenous (IV) infusions of BMS-962212. Part A used 4 doses (1.5, 4, 10, and 25 mg h-1 ) assigned to BMS-962212 or placebo in a 3:1 ratio per dose. Part B used 4 doses (1, 3, 9, and 20 mg h-1 ) enrolling Japanese (n = 4 active, n = 1 placebo) and non-Japanese subjects (n = 4 active, n = 1 placebo) per dose...
January 18, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29346762/transcriptome-and-dna-methylome-analysis-in-a-mouse-model-of-diet-induced-obesity-predicts-increased-risk-of-colorectal-cancer
#2
Ruifang Li, Sara A Grimm, Deepak Mav, Haiwei Gu, Danijel Djukovic, Ruchir Shah, B Alex Merrick, Daniel Raftery, Paul A Wade
Colorectal cancer (CRC) tends to occur at older age; however, CRC incidence rates have been rising sharply among young age groups. The increasing prevalence of obesity is recognized as a major risk, yet the mechanistic underpinnings remain poorly understood. Using a diet-induced obesity mouse model, we identified obesity-associated molecular changes in the colonic epithelium of young and aged mice, and we further investigated whether the changes were reversed after weight loss. Transcriptome analysis indicated that obesity-related colonic cellular metabolic switch favoring long-chain fatty acid oxidation happened in young mice, while obesity-associated downregulation of negative feedback regulators of pro-proliferative signaling pathways occurred in older mice...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346712/synergetic-effects-of-prenatal-and-postnatal-high-sucrose-intake-on-glucose-tolerance-and-hepatic-insulin-resistance-in-rat-offspring
#3
Pengjie Zhang, Di Zhu, Yueming Zhang, Lingjun Li, Xionghui Chen, Wenna Zhang, Ruixiu Shi, Jianying Tao, Bing Han, Zhice Xu
SCOPE: High sucrose intake during pregnancy is linked to type 2 diabetes mellitus and altered insulin resistance. METHODS AND RESULTS: This study attempted to ascertain whether prenatal high sucrose intake (20% sucrose) alleviates the detrimental effects of high postnatal sugar consumption in the offspring, and the molecular mechanisms were investigated using a rat model. High prenatal sucrose exposure increased the body weight of the offspring at 1 to 3 weeks of age...
January 18, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29346678/case-study-of-an-adaptation-and-implementation-of-a-diabetes-prevention-program-for-individuals-with-serious-mental-illness
#4
Maria M Quiñones, Judy Lombard-Newell, Daryl Sharp, Valerie Way, Wendi Cross
The Diabetes Prevention Program (DPP) is an evidence-based lifestyle intervention developed to decrease the risk for type 2 diabetes and promote weight loss in individuals at risk for diabetes. Individuals with serious mental illness have a greater risk for developing diabetes compared with the general population. In this article, the authors provide a detailed description of the adaptation process of the DPP for individuals with serious mental illness (DPP-SMI). The adaptation process was based on a cultural adaptation framework for modifying evidence-based interventions...
January 16, 2018: Translational Behavioral Medicine
https://www.readbyqxmd.com/read/29346599/magnetic-resonance-imaging-guided-laser-interstitial-thermal-therapy-for-the-treatment-of-hypothalamic-hamartomas-a-retrospective-review
#5
David S Xu, Tsinsue Chen, Randall J Hlubek, Ruth E Bristol, Kris A Smith, Francisco A Ponce, John F Kerrigan, Peter Nakaji
BACKGROUND: Hypothalamic hamartomas (HH) are rare lesions associated with treatment-resistant epilepsy. Open surgery results in modest seizure control (about 50%) but has a significant associated morbidity. Radiosurgery is limited to a subset of patients due to latent therapeutic effects. Magnetic resonance imaging-guided laser interstitial thermal therapy (LITT) offers a novel minimally invasive option. OBJECTIVE: To evaluate a single center's outcomes for the LITT treatment of HH...
January 13, 2018: Neurosurgery
https://www.readbyqxmd.com/read/29346582/it-s-not-just-what-you-do-it-s-also-the-way-that-you-do-it-patient-and-public-involvement-in-the-development-of-health-research
#6
Tracey J Devonport, Wendy Nicholls, Lynne H Johnston, Robin Gutteridge, Angela Watt
Purpose: This article presents a reflective account of Patient and Public Involvement (PPI) in the development of obesity and binge eating research. Method: We established Patient Advisory Groups (PAGs) at two English regional National Health Service (NHS) weight management services. PPI was evaluated as follows: (i) PAG members completed a Post Participation Evaluation Questionnaire, (ii) PAG meetings captured group discussion on PPI involvement, (iii) practitioner and researchers produced written reflections on PPI and (iv) sources one to three were consolidated during reflections that took place via e-mail and telephone correspondence between researchers and practitioners, culminating in a summary SKYPE meeting between one practitioner and one researcher involved in the PAGs...
January 16, 2018: International Journal for Quality in Health Care
https://www.readbyqxmd.com/read/29346581/melatonin-attenuates-lung-ischaemia-reperfusion-injury-via-inhibition-of-oxidative-stress-and-inflammation
#7
Ming-Liang Wang, Chun-Hua Wei, Wen-Dong Wang, Jia-Shun Wang, Jun Zhang, Jian-Jun Wang
OBJECTIVES: Lung ischaemia-reperfusion injury is a complex pathophysiological process due to the production of reactive oxygen species and the generation of inflammatory reaction. We investigated the protective effects and the corresponding mechanism of melatonin (MT), a potent free-radical scavenger, on lung injury induced by ischaemia-reperfusion in a mouse model. METHODS: Adult male C57BL/6J mice (n = 30) were randomly and equally allocated into 5 groups: sham controls, IR, IR + 10 mg/kg MT, IR + 20 mg/kg MT and IR + 30 mg/kg MT...
January 15, 2018: Interactive Cardiovascular and Thoracic Surgery
https://www.readbyqxmd.com/read/29346565/apigenin-induces-cell-shrinkage-in-candida-albicans-by-membrane-perturbation
#8
Heejeong Lee, Eun-Rhan Woo, Dong Gun Lee
Apigenin, a natural flavone, has been well characterized for its their anticarcinogenic property; however, its bioactivity against pathogenic fungi has not been investigated in detail. In the present study, we examined the antifungal activity and mode of action of apigenin. Apigenin inhibited the growth of fungal pathogens, which induced superficial infection and reduced biofilm mass. Three-dimensional flow cytometric analysis demonstrated that apigenin induced morphological changes, especially cell shrinkage, in Candida albicans...
January 16, 2018: FEMS Yeast Research
https://www.readbyqxmd.com/read/29346537/cerebral-mitochondrial-dysfunction-associated-with-deep-hypothermic-circulatory-arrest-in-neonatal-swine
#9
Constantine D Mavroudis, Michael Karlsson, Tiffany Ko, Marco Hefti, Javier I Gentile, Ryan W Morgan, Ross Plyler, Kobina G Mensah-Brown, Timothy W Boorady, Richard W Melchior, Tami M Rosenthal, Brandon C Shade, Kellie L Schiavo, Susan C Nicolson, Thomas L Spray, Robert M Sutton, Robert A Berg, Daniel J Licht, J William Gaynor, Todd J Kilbaugh
OBJECTIVES: Controversy remains regarding the use of deep hypothermic circulatory arrest (DHCA) in neonatal cardiac surgery. Alterations in cerebral mitochondrial bioenergetics are thought to contribute to ischaemia-reperfusion injury in DHCA. The purpose of this study was to compare cerebral mitochondrial bioenergetics for DHCA with deep hypothermic continuous perfusion using a neonatal swine model. METHODS: Twenty-four piglets (mean weight 3.8 kg) were placed on cardiopulmonary bypass (CPB): 10 underwent 40-min DHCA, following cooling to 18°C, 10 underwent 40 min DHCA and 10 remained at deep hypothermia for 40 min; animals were subsequently rewarmed to normothermia...
January 15, 2018: European Journal of Cardio-thoracic Surgery
https://www.readbyqxmd.com/read/29346507/activity-and-safety-of-afatinib-in-a-window-pre-operative-eortc-study-in-patients-with-squamous-cell-carcinoma-of-the-head-and-neck-scchn
#10
J P Machiels, P Bossi, J Menis, M Lia, C Fortpied, Y Liu, R Lhommel, M Lemort, S Schmitz, S Canevari, L De Cecco, M Guzzo, R Bianchi, P Quattrone, F Crippa, T Duprez, Y Lalami, M Quiriny, N de Saint Aubain, P M Clement, R Coropciuc, E Hauben, L F Licitra
Background: To investigate the activity and safety of afatinib in the pre-operative treatment of squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: This study was an open-label, randomized, multicenter, phase II window of opportunity trial. Treatment-naïve SCCHN patients selected for primary curative surgery were randomized (5:1 ratio) to receive afatinib during 14 days (day -15 until day -1) before surgery (day 0) or no treatment. Tumor biopsies, 2-[fluorine-18]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), and magnetic resonance imaging (MRI) were performed at diagnosis and just before surgery...
January 15, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29346484/association-of-dietary-inflammatory-potential-with-colorectal-cancer-risk-in-men-and-women
#11
Fred K Tabung, Li Liu, Weike Wang, Teresa T Fung, Kana Wu, Stephanie A Smith-Warner, Yin Cao, Frank B Hu, Shuji Ogino, Charles S Fuchs, Edward L Giovannucci
Importance: Inflammation is important in colorectal cancer development. Diet modulates inflammation and may thus be a crucial modifiable factor in colorectal cancer prevention. Objective: To examine whether proinflammatory diets are associated with increased colorectal cancer risk by using an empirical dietary inflammatory pattern (EDIP) score based on a weighted sum of 18 food groups that characterizes dietary inflammatory potential based on circulating levels of inflammation biomarkers...
January 18, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29346474/examining-non-participation-to-the-maternal-follow-up-within-the-danish-national-birth-cohort
#12
Mette Bliddal, Zeyan Liew, Anton Pottegård, Helene Kirkegaard, Jørn Olsen, Ellen A Nohr
A follow-up questionnaire on maternal health has been distributed within the Danish National Birth Cohort (established 1996-2002) 14 years after the index birth. Answers were obtained for 41,466 of 78,010 (53.2%) eligible mothers. To ensure the appropriate use of these data, the possibility of selection bias due to non-participation must be evaluated. We estimated four selected exposure-outcome associations (pre-pregnancy weight - depression; exercise - degenerative musculoskeletal conditions; smoking - heart disease; and alcohol consumption - breast cancer)...
January 16, 2018: American Journal of Epidemiology
https://www.readbyqxmd.com/read/29346448/a-cross-sectional-study-to-estimate-prevalence-of-periodontal-disease-in-a-population-of-dogs-canis-familiaris-in-commercial-breeding-facilities-in-indiana-and-illinois
#13
Judith L Stella, Amy E Bauer, Candace C Croney
The objectives of this cross-sectional study were: 1) to estimate the prevalence and characterize the severity of periodontal disease in a population of dogs housed in commercial breeding facilities; 2) to characterize PD preventive care utilized by facility owners; and 3) to assess inter-rater reliability of a visual scoring assessment tool. Adult dogs (N = 445) representing 42 breeds at 24 CB facilities in Indiana and Illinois were assessed. Periodontal disease was scored visually using the American Veterinary Dental Collage 0-IV scale...
2018: PloS One
https://www.readbyqxmd.com/read/29346447/pik3ca-is-required-for-mouse-uterine-gland-development-and-pregnancy
#14
Hye Jin Chang, Hee Sung Shin, Tae Hoon Kim, Jung-Yoon Yoo, Hanna E Teasley, Jean J Zhao, Un-Hwan Ha, Jae-Wook Jeong
The PI3K/AKT signaling pathway plays a critical role in the maintenance of equilibrium between cell survival and apoptosis. The Pik3ca gene is mutated in a range of human cancers. It has been found to be oncogenic, and mutations lead to constitutive activation of the PI3K/AKT pathway. The expression patterns of PIK3CA proteins in the uterus of mice during early pregnancy indicate that it may play a role in the regulation of glandular epithelial cells, which is required to support uterine receptivity. To further investigate the role of Pik3ca in uterine function, Pik3ca was conditionally ablated only in the PGR-positive cells (Pgrcre/+Pik3caf/f; Pik3cad/d)...
2018: PloS One
https://www.readbyqxmd.com/read/29346419/saxs-analysis-of-a-soluble-cytosolic-ngbr-construct-including-extracellular-and-transmembrane-domains
#15
Joshua Holcomb, Maysaa Doughan, Nicholas Spellmon, Brianne Lewis, Emerson Perry, Yingxue Zhang, Lindsey Nico, Junmei Wan, Srinivas Chakravarthy, Weifeng Shang, Qing Miao, Timothy Stemmler, Zhe Yang
The Nogo-B receptor (NgBR) is involved in oncogenic Ras signaling through directly binding to farnesylated Ras. It recruits farnesylated Ras to the non-lipid-raft membrane for interaction with downstream effectors. However, the cytosolic domain of NgBR itself is only partially folded. The lack of several conserved secondary structural elements makes this domain unlikely to form a complete farnesyl binding pocket. We find that inclusion of the extracellular and transmembrane domains that contain additional conserved residues to the cytosolic region results in a well folded protein with a similar size and shape to the E...
2018: PloS One
https://www.readbyqxmd.com/read/29346418/the-relationship-of-lung-function-with-ambient-temperature
#16
Joseph M Collaco, Lawrence J Appel, John McGready, Garry R Cutting
BACKGROUND: Lung function is complex trait with both genetic and environmental factors contributing to variation. It is unknown how geographic factors such as climate affect population respiratory health. OBJECTIVE: To determine whether ambient air temperature is associated with lung function (FEV1) in the general population. DESIGN/SETTING: Associations between spirometry data from two National Health and Nutrition Examination Survey (NHANES) periods representative of the U...
2018: PloS One
https://www.readbyqxmd.com/read/29346372/ceramides-in-tracheal-aspirates-of-preterm-infants-marker-for-bronchopulmonary-dysplasia
#17
Esther van Mastrigt, Salomé Zweekhorst, Bas Bol, Jeroen Tibboel, Joost van Rosmalen, Janneke N Samsom, André A Kroon, Johan C de Jongste, Irwin K M Reiss, Martin Post, Mariëlle W Pijnenburg
BACKGROUND: In an experimental mouse model we showed that ceramides play a role in the pathogenesis of bronchopulmonary dysplasia (BPD) and are a potential target for therapeutic intervention. We investigated whether ceramides are detectable in tracheal aspirates (TAs) of preterm infants and differ between infants with or without BPD. METHODS: Infants born ≤ 32 weeks of gestational age in need of mechanical ventilation in the first week of life were included. TAs were obtained directly after intubation and at day 1, 3, 5, 7, and 14...
2018: PloS One
https://www.readbyqxmd.com/read/29346357/type-of-cows-milk-consumption-and-relationship-to-health-predictors-in-new-zealand-preschool-children
#18
Hajar Mazahery, Carlos A Camargo, Carolyn Cairncross, Lisa A Houghton, Cameron C Grant, Jane Coad, Cathryn A Conlon, Pamela R von Hurst
AIMS: New Zealand dietary guidelines recommend children from two years of age consume low- or reduced-fat milk. We aimed to investigate the predictors of type of milk consumption in preschool children. METHODS: Data were drawn from a cross-sectional study which enrolled preschool children (2-<5 years, n=1,329) from throughout New Zealand. RESULTS: Cows' milk was consumed regularly by 88% of children. Of these, 26% consumed plain low- or reduced-fat milk, while 74% consumed full-fat milk...
January 19, 2018: New Zealand Medical Journal
https://www.readbyqxmd.com/read/29346340/disparities-in-preconception-health-indicators-%C3%A2-behavioral-risk-factor-surveillance-system-2013-2015-and-pregnancy-risk-assessment-monitoring-system-2013-2014
#19
Cheryl Robbins, Sheree L Boulet, Isabel Morgan, Denise V D'Angelo, Lauren B Zapata, Brian Morrow, Andrea Sharma, Charlan D Kroelinger
PROBLEM/CONDITION: Preconception health is a broad term that encompasses the overall health of nonpregnant women during their reproductive years (defined here as aged 18-44 years). Improvement of both birth outcomes and the woman's health occurs when preconception health is optimized. Improving preconception health before and between pregnancies is critical for reducing maternal and infant mortality and pregnancy-related complications. The National Preconception Health and Health Care Initiative's Surveillance and Research work group suggests ten prioritized indicators that states can use to monitor programs or activities for improving the preconception health status of women of reproductive age...
January 19, 2018: MMWR. Surveillance Summaries: Morbidity and Mortality Weekly Report. Surveillance Summaries
https://www.readbyqxmd.com/read/29346281/a-prototype-sensor-for-in-situ-sensing-of-fine-particulate-matter-and-volatile-organic-compounds
#20
Chee-Loon Ng, Fuu-Ming Kai, Ming-Hui Tee, Nicholas Tan, Harold F Hemond
Air pollution exposure causes seven million deaths per year, according to the World Health Organization. Possessing knowledge of air quality and sources of air pollution is crucial for managing air pollution and providing early warning so that a swift counteractive response can be carried out. An optical prototype sensor (AtmOptic) capable of scattering and absorbance measurements has been developed to target in situ sensing of fine particulate matter (PM2.5) and volatile organic compounds (VOCs). For particulate matter testing, a test chamber was constructed and the emission of PM2...
January 18, 2018: Sensors
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