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https://www.readbyqxmd.com/read/29052790/efficacy-and-safety-of-glecaprevir-pibrentasvir-in-hcv-infected-japanese-patients-with-prior-daa-experience-severe-renal-impairment-or-genotype-3-infection
#1
Hiromitsu Kumada, Tsunamasa Watanabe, Fumitaka Suzuki, Kenji Ikeda, Ken Sato, Hidenori Toyoda, Masanori Atsukawa, Akio Ido, Akinobu Takaki, Nobuyuki Enomoto, Koji Kato, Katia Alves, Margaret Burroughs, Rebecca Redman, David Pugatch, Tami J Pilot-Matias, Preethi Krishnan, Rajneet K Oberoi, Wangang Xie, Kazuaki Chayama
BACKGROUND: Once-daily, orally administered, co-formulated glecaprevir (NS3/4A protease inhibitor) and pibrentasvir (NS5A inhibitor) (G/P) demonstrated pangenotypic activity and high sustained virologic response (SVR) rates in studies outside Japan. Here we report safety and efficacy in a subset of Japanese patients with chronic HCV infection who received G/P 300/120 mg in a phase 3, open-label, multicenter study (CERTAIN-1). METHODS: This analysis focuses on three difficult-to-treat subgroups: HCV GT1/2-infected patients who failed to achieve SVR after treatment with a direct acting antiviral (DAA)-containing regimen; GT1/2-infected patients with severe renal impairment (estimated glomerular filtration rate < 30 mL/min/1...
October 20, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/29051544/estimating-prognosis-in-patients-with-acute-myocardial-infarction-using-personalized-computational-heart-models
#2
Hao Gao, Kenneth Mangion, David Carrick, Dirk Husmeier, Xiaoyu Luo, Colin Berry
Biomechanical computational models have potential prognostic utility in patients after an acute ST-segment-elevation myocardial infarction (STEMI). In a proof-of-concept study, we defined two groups (1) an acute STEMI group (n = 6, 83% male, age 54 ± 12 years) complicated by left ventricular (LV) systolic dysfunction; (2) an age- and sex- matched hyper-control group (n = 6, 83% male, age 46 ± 14 years), no prior history of cardiovascular disease and normal systolic blood pressure (SBP < 130 mmHg)...
October 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29051061/precise-laser-poration-to-control-drug-delivery-into-and-through-human-nail
#3
Simon Vanstone, Sarah F Cordery, James M Stone, Sergey N Gordeev, Richard H Guy
Drug treatment of diseases of the human nail remains a difficult challenge; topical therapy, in particular, is limited by very poor transport of active agents across the nail itself. The objective of this research was to examine the potential of controlled, and fibre-optic delivered, femtosecond laser light pulses to provide new pathways and opportunities for drug access to targets within and beneath the nail plate. Optical, confocal fluorescence and scanning electron microscopies demonstrated partial and complete laser poration of human nail samples, with the energy per pore and the exposure duration being the key modulating parameters that determined the extent of ablation achieved...
October 16, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29051047/ostomy-telehealth-for-cancer-survivors-design-of-the-ostomy-self-management-training-osmt-randomized-trial
#4
Virginia Sun, Elizabeth Ercolano, Ruth McCorkle, Maria Grant, Christopher S Wendel, Nancy J Tallman, Frank Passero, Sabreen Raza, Zuleyha Cidav, Michael Holcomb, Ronald S Weinstein, Mark C Hornbrook, Robert S Krouse
PURPOSE: An ostomy adversely affects health-related quality of life (HRQOL) in a diverse population of cancer survivors and their caregivers. Hit-or-miss ostomy care, nurse counseling, and community referral have been the primary modes of self-management education and support in the peri-operative setting. Few evidence-based, systematic ostomy self-management programs are available to ensure optimal post-operative care. This paper describes the study design of a telehealth-based Ostomy Self-management Training (OSMT) program for cancer survivors and their caregivers...
October 16, 2017: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/29050872/manf-promotes-differentiation-and-migration-of-neural-progenitor-cells-with-potential-neural-regenerative-effects-in-stroke
#5
Kuan-Yin Tseng, Jenni E Anttila, Konstantin Khodosevich, Raimo K Tuominen, Maria Lindahl, Andrii Domanskyi, Mikko Airavaara
Cerebral ischemia activates endogenous reparative processes, such as increased proliferation of neural stem cells (NSCs) in the subventricular zone (SVZ) and migration of neural progenitor cells (NPCs) toward the ischemic area. However, this reparative process is limited because most of the NPCs die shortly after injury or are unable to arrive at the infarct boundary. In this study, we demonstrate for the first time that endogenous mesencephalic astrocyte-derived neurotrophic factor (MANF) protects NSCs against oxygen-glucose-deprivation-induced injury and has a crucial role in regulating NPC migration...
September 21, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29050384/stimulating-thought-a-functional-mri-study-of-transcranial-direct-current-stimulation-in-schizophrenia
#6
Natasza D Orlov, Owen O'Daly, Derek K Tracy, Yusuf Daniju, John Hodsoll, Lorena Valdearenas, John Rothwell, Sukhi S Shergill
Individuals with schizophrenia typically suffer a range of cognitive deficits, including prominent deficits in working memory and executive function. These difficulties are strongly predictive of functional outcomes, but there is a paucity of effective therapeutic interventions targeting these deficits. Transcranial direct current stimulation is a novel neuromodulatory technique with emerging evidence of potential pro-cognitive effects; however, there is limited understanding of its mechanism. This was a double-blind randomized sham controlled pilot study of transcranial direct current stimulation on a working memory (n-back) and executive function (Stroop) task in 28 individuals with schizophrenia using functional magnetic resonance imaging...
September 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29050223/mir-23a-promotes-tgf-%C3%AE-1-induced-emt-and-tumor-metastasis-in-breast-cancer-cells-by-directly-targeting-cdh1-and-activating-wnt-%C3%AE-catenin-signaling
#7
Fei Ma, Wenjie Li, Chunxiao Liu, Wei Li, Haining Yu, Bo Lei, Yanlv Ren, Zhigao Li, Da Pang, Cheng Qian
TGF-β1-induced epithelial-mesenchymal transition (EMT) has been proved to be associated with metastasis of breast cancer cells. We attempted to detect a novel mechanism that microRNAs mediated the TGF-β1-induced EMT in the process of breast cancer metastasis. Here we reported that the expression of miR-23a was higher in breast cancer cells with high metastasis ability and patients with lymph node metastasis and the treatment of TGF-β1 significantly upregulated the expression of miR-23a in breast cancer cells...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29049890/dna-methylation-signatures-in-peripheral-blood-mononuclear-cells-from-a-lifestyle-intervention-for-women-at-midlife-a-pilot-rct
#8
Lisa M McEwen, Evan G Gatev, Meaghan J Jones, Julia L MacIsaac, Megan M McAllister, Rebecca E Goulding, Kenneth M Madden, Martin G Dawes, Michael S Kobor, Maureen C Ashe
OBJECTIVES: Physical activity confers many health benefits, but the underlying mechanisms require further exploration. In this pilot randomized controlled trial we tested the association between longitudinal measures of DNA methylation and changes in objective measures including physical activity, weight loss, and C-reactive protein levels in community-dwelling women aged 55 to 70 years. METHODS: We assessed DNA methylation from 20 healthy post-menopausal women (55-70 years of age), who did not have a mobility disability and allocated them to a group-based intervention, Everyday Activity Supports You (EASY), or a control group (monthly group-based health-related education sessions)...
October 19, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/29049835/the-photopic-negative-response-an-objective-measure-of-retinal-ganglion-cell-function-in-patients-with-leber-s-hereditary-optic-neuropathy
#9
Rustum Karanjia, Adriana Berezovsky, Paula Yuri Sacai, Nivea Nunes Cavascan, Henry Yuheng Liu, Samir Nazarali, Milton Nunes Moraes-Filho, Kirsten Anderson, Jeffrey Show Tran, Sung EunSong Watanabe, Milton Nunes Moraes, Federico Sadun, Anna Maria DeNegri, Piero Barboni, Carolina do Val Ferreira Ramos, Chiara La Morgia, Valerio Carelli, Rubens Belfort, Stuart Glenn Coupland, Solange Rios Salomao, Alfredo A Sadun
Purpose: The photopic negative response (PhNR) is a slow negative component of a flash photopic full-field ERG that has been shown to be specific for retinal ganglion cell (RGC) activity. Direct evaluation of RGC function is desirable in patients with Leber's hereditary optic neuropathy (LHON) in which the loss of central acuity can make it difficult to monitor patients with standard metrics. The purpose of this study was to evaluate the use of PhNR as an objective noninvasive clinical metric in LHON...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29046639/neonatal-colonic-inflammation-increases-spinal-transmission-and-cystathionine-%C3%AE-synthetase-expression-in-spinal-dorsal-horn-of-rats-with-visceral-hypersensitivity
#10
Liting Zhao, Ying Xiao, Rui-Xia Weng, Xuelian Liu, Ping-An Zhang, Chuang-Ying Hu, Shan P Yu, Guang-Yin Xu
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by chronic abdominal pain and alteration of bowel movements. The pathogenesis of visceral hypersensitivity in IBS patients remains largely unknown. Hydrogen sulfide (H2S) is reported to play an important role in development of visceral hyperalgesia. However, the role of H2S at spinal dorsal horn level remains elusive in visceral hypersensitivity. The aim of this study is designed to investigate how H2S takes part in visceral hypersensitivity of adult rats with neonatal colonic inflammation (NCI)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29046306/a-novel-yeast-based-therapeutic-vaccine-for-tuberculosis-gi-19007
#11
Thomas H King, Crystal A Shanley, Zhimin Guo, Donald Bellgrau, Timothy Rodell, Synthia Furney, Marcela Henao-Tamayo, Ian M Orme
As yet, very few vaccine candidates with activity in animals against Mycobacterium tuberculosis infection have been tested as therapeutic "post-exposure" vaccines. We recently described two pools of mycobacterial proteins with this activity and here we describe further studies in which four of these proteins (Rv1738, Rv2032, Rv3130, and Rv3841) were generated as a fusion polypeptide, and then delivered in a novel yeast-based platform ("Tarmogen®") which itself has immunostimulatory properties including activation of Toll-like receptors...
October 18, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/29045324/a-ball-skills-intervention-in-preschoolers-the-champ-randomized-controlled-trial
#12
Leah E Robinson, Sanne L C Veldman, Kara K Palmer, Anthony D Okely
PURPOSE: Fundamental motor skills (FMS) contribute to positive health trajectories. A high level of competence in ball skills (a subset of FMS) is a predictor for time spent in moderate- to vigorous-intensity physical activity during adolescence. This study examined the effects of a ball skills intervention on ball skill competence among preschool-aged boys and girls. METHODS: This is a two-armed randomized controlled trial. A total of 124 preschoolers (Mage ± SD = 48...
November 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/29044808/neuroprotective-effects-of-human-mesenchymal-stem-cells-hmsc-and-platelet-derived-growth-factor-pdgf-on-human-retinal-ganglion-cells-rgcs
#13
Andrew Osborne, Julie Sanderson, Keith R Martin
Optic neuropathies such as glaucoma occur when retinal ganglion cells (RGCs) in the eye are injured. Strong evidence suggests mesenchymal stem cells (MSCs) could be a potential therapy to protect RGCs, however little is known regarding their effect on the human retina. We therefore investigated if human MSCs (hMSCs), or platelet derived growth factor (PDGF) as produced by hMSC, could delay RGC death in a human retinal explant model of optic nerve injury. Our results showed hMSCs and the secreted growth factor PDGF-AB could substantially reduce human RGC loss and apoptosis following axotomy...
October 17, 2017: Stem Cells
https://www.readbyqxmd.com/read/29044596/angelicin-potentiates-trail-induced-apoptosis-in-renal-carcinoma-caki-cells-through-activation-of-caspase-3-and-down-regulation-of-c-flip-expression
#14
Kyoung-Jin Min, Hee Jung Um, Seung Un Seo, Seon Min Woo, Shin Kim, Jong-Wook Park, Hyun-Shik Lee, Sang Hyun Kim, Yung Hyun Choi, Tae-Jin Lee, Taeg Kyu Kwon
Preclinical Research & Development Angelicin is a furocoumarin derived from Psoralea corylifolia L. fruit that has anti-inflammatory and anti-tumor activity. In the present study, the effect of angelicin in enhancing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptotic cell death was studied in Caki (renal carcinoma) cells. Angelicin alone and TRAIL alone had no effect on apoptosis, but in combination these compounds markedly induced apoptosis in the cancer cell lines while not inducing apoptosis in normal cells...
October 16, 2017: Drug Development Research
https://www.readbyqxmd.com/read/29043101/protective-effect-of-rhus-verniciflua-stokes-extract-in-an-experimental-model-of-post-menopausal-osteoporosis
#15
Ji Heun Jeong, Jong Hoon An, Hui Yang, Do-Kyung Kim, Nam-Seob Lee, Young-Gil Jeong, Chun Soo Na, Dae Seung Na, Mi-Sook Dong, Seung Yun Han
Post-menopausal osteoporosis (PMO) is a major global human health concern. Owing to the need for therapeutic drugs without side effects, natural extracts containing various polyphenolic compounds that may exert estrogenic effects have been studied in depth. Rhus verniciflua Stokes (RVS), which has been used as a traditional herbal medicine for centuries in Korea, was recently revealed to exert estrogenic effects attributable to its bioactive ingredients sulfuretin and butein, which have strong estrogen receptor-binding affinities...
September 2017: Anatomy & Cell Biology
https://www.readbyqxmd.com/read/29042764/the-association-between-objectively-measured-physical-activity-and-morning-symptoms-in-copd
#16
Amanda R van Buul, Marise J Kasteleyn, Niels H Chavannes, Christian Taube
PURPOSE: The morning is the most bothersome period for COPD patients. Morning symptom severities in different Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages are not well studied. Furthermore, factors that are associated with morning symptoms, especially the associations with objectively measured physical activity, are also not well described. MATERIALS AND METHODS: The aim of this cross-sectional observational study was to assess morning symptom severity in GOLD A, B, C and D patients, according to the definitions of the GOLD 2015 statement...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/29042341/pain-self-management-for-veterans-development-and-pilot-test-of-a-stage-based-mobile-optimized-intervention
#17
Sara S Johnson, Deborah A Levesque, Lynne E Broderick, Dustin G Bailey, Robert D Kerns
BACKGROUND: Chronic pain is a significant public health burden affecting more Americans than cardiovascular disease, diabetes, and cancer combined. Veterans are disproportionately affected by chronic pain. Among previously deployed soldiers and veterans, the prevalence of chronic pain is estimated between 44% and 60%. OBJECTIVE: The objective of this research was to develop and pilot-test Health eRide: Your Journey to Managing Pain, a mobile pain self-management program for chronic musculoskeletal pain for veterans...
October 17, 2017: JMIR Medical Informatics
https://www.readbyqxmd.com/read/29042321/multimodal-imaging-approach-to-examine-biodistribution-kinetics-of-cabotegravir-gsk1265744-long-acting-parenteral-formulation-in-rat
#18
Beat M Jucker, Hasan Alsaid, Mary Rambo, Stephen C Lenhard, Bao Hoang, Fang Xie, M Reid Groseclose, Stephen Castellino, Valeriu Damian, Gary Bowers, Manish Gupta
Long-Acting Parenterals (LAPs) have been used in the clinic to provide sustained therapeutic drug levels at a target site, and thereby reducing the frequency of dosing required. In an effort to understand the factors associated with long-acting cabotegravir (GSK1265744 LAP) pharmacokinetic variability, the current study was designed to investigate the temporal relationship between intramuscular (IM) or subcutaneous (SC) drug depot morphology and distribution kinetics with plasma pharmacokinetics. Therefore, a multi-modal molecular imaging (MRI & MALDI IMS) approach was employed to examine the temporal GSK1265744 LAP biodistribution in rat following either IM or SC administration...
October 14, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29042285/regulating-the-regulators-epigenetic-transcriptional-and-post-translational-regulation-of-rgs-proteins
#19
REVIEW
Mohammed Alqinyah, Shelley B Hooks
Regulators of G protein signaling (RGS) are a family of proteins classically known to accelerate the intrinsic GTPase activity of G proteins, which results in accelerated inactivation of heterotrimeric G proteins and inhibition of G protein coupled receptor signaling. RGS proteins play major roles in essential cellular processes, and dysregulation of RGS protein expression is implicated in multiple diseases, including cancer, cardiovascular and neurodegenerative diseases. The expression of RGS proteins is highly dynamic and is regulated by epigenetic, transcriptional and post-translational mechanisms...
October 14, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29042269/the-comparison-of-acute-high-intensity-interval-exercise-vs-continuous-moderate-intensity-exercise-on-plasma-calprotectin-and-associated-inflammatory-mediators
#20
Brandon G Fico, Michael Whitehurst, Aaron L Slusher, James T Mock, Arun Maharaj, Katelyn M Dodge, Chun-Jung Huang
PURPOSE: Calprotectin promotes the release of inflammatory mediators (e.g., monocyte chemoattractant protein-1 [MCP-1] and myeloperoxidase [MPO]) during the innate immune response as a mechanism to augment leukocyte chemotaxis and phagocytosis. Although plasma calprotectin is elevated with traditional continuous moderate-intensity exercise (CME) as an indicator of the inflammatory response, high-intensity interval exercise (HIIE) has been shown to attenuate systemic inflammation while providing similar improvements in cardiovascular health...
October 14, 2017: Physiology & Behavior
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