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https://www.readbyqxmd.com/read/28220512/sofosbuvir-velpatasvir-voxilaprevir-with-or-without-ribavirin-in-daa-experienced-patients-with-genotype-1-hcv
#1
Eric Lawitz, Fred Poordad, Jennifer Wells, Robert H Hyland, Yin Yang, Hadas Dvory-Sobol, Luisa M Stamm, Diana M Brainard, John G McHutchison, Carmen Landaverde, Julio Gutierrez
: The optimal retreatment strategy for hepatitis C virus (HCV) genotype 1-infected patients who fail direct-acting antiviral (DAA)-based regimens remains unknown. In this phase 2, open-label study conducted at a single center in the United States, patients with HCV genotype 1 infection who previously failed to achieve sustained virologic response on a DAA-based regimen were randomized to receive treatment with a fixed-dose combination tablet of sofosbuvir-velpatasvir-voxilaprevir with or without ribavirin for 12 weeks...
February 21, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28220142/absence-of-an-n-linked-glycosylation-motif-in-the-glycoprotein-of-the-live-attenuated-argentine-hemorrhagic-fever-vaccine-candid-1-results-in-its-improper-processing-and-reduced-surface-expression
#2
John T Manning, Alexey V Seregin, Nadezhda E Yun, Takaaki Koma, Cheng Huang, José Barral, Juan C de la Torre, Slobodan Paessler
Junin virus (JUNV), a highly pathogenic New World arenavirus, is the causative agent of Argentine hemorrhagic fever (AHF). The live-attenuated Candid #1 (Can) strain currently serves as a vaccine for at-risk populations. We have previously shown that the Can glycoprotein (GPC) gene is the primary gene responsible for attenuation in a guinea pig model of AHF. However, the mechanisms through which the GPC contributes to the attenuation of the Can strain remain unknown. A more complete understanding of the mechanisms underlying the attenuation and immunogenicity of the Can strain will potentially allow for the rational design of additional safe and novel vaccines...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28220108/adaptations-in-basal-and-hypothalamic-pituitary-adrenal-activated-deoxycorticosterone-responses-following-ethanol-self-administration-in-cynomolgus-monkeys
#3
Vanessa A Jimenez, Patrizia Porcu, A Leslie Morrow, Kathleen A Grant
Acute ethanol activates the hypothalamic-pituitary-adrenal (HPA) axis, while long-term exposure results in a blunted neuroendocrine state, particularly with regards to the primary endpoint, cortisol, the primary glucocorticoid produced in the adrenal cortex. However, it is unknown if this dampened neuroendocrine status also influences other adrenocortical steroids. Plasma concentration of the mineralocorticoid and neuroactive steroid precursor deoxycorticosterone (DOC) is altered by pharmacological challenges of the HPA axis in cynomolgus monkeys...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28219917/isosorbide-dinitrate-with-or-without-hydralazine-does-not-reduce-wave-reflections-left-ventricular-hypertrophy-or-myocardial-fibrosis-in-patients-with-heart-failure-with-preserved-ejection-fraction
#4
Payman Zamani, Scott Akers, Haideliza Soto-Calderon, Melissa Beraun, Maheswara R Koppula, Swapna Varakantam, Deepa Rawat, Prithvi Shiva-Kumar, Philip G Haines, Jesse Chittams, Raymond R Townsend, Walter R Witschey, Patrick Segers, Julio A Chirinos
BACKGROUND: Wave reflections, which are increased in patients with heart failure with preserved ejection fraction, impair diastolic function and promote pathologic myocardial remodeling. Organic nitrates reduce wave reflections acutely, but whether this is sustained chronically or affected by hydralazine coadministration is unknown. METHODS AND RESULTS: We randomized 44 patients with heart failure with preserved ejection fraction in a double-blinded fashion to isosorbide dinitrate (ISDN; n=13), ISDN+hydralazine (ISDN+hydral; n=15), or placebo (n=16) for 6 months...
February 20, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28219643/identification-and-functional-analysis-of-variants-of-a-cancer-testis-antigen-lemd1-in-colorectal-cancer-stem-like-cells
#5
Rui Takeda, Yoshihiko Hirohashi, Min Shen, Liming Wang, Tadashi Ogawa, Aiko Murai, Eri Yamamoto, Terufumi Kubo, Munehide Nakatsugawa, Takayuki Kanaseki, Tomohide Tsukahara, Toshihiko Nishidate, Kenji Okita, Goro Kutomi, Noriyuki Sato, Ichiro Takemasa, Toshihiko Torigoe
Colorectal cancer (CRC) is one of the most common malignancy, and the prognosis is not still satisfactory due to treatment resistance, recurrence and distant metastasis. Cancer stem cells (CSCs)/cancer-initiating cells (CICs) is endowed with higher tumor-initiating ability, self-renewal ability and differentiation ability, and CSCs/CICs are resistant to treatments. Thus, CSCs/CICs are thought to be responsible for recurrence and distant metastasis, and eradication of CSCs/CICs is essential to cure CRCs. However, the molecular mechanisms of CSCs/CICs are remain unknown, and we aimed to elucidate molecular aspects of CR-CSCs/CICs in this study...
February 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28219020/anthropometrics-at-birth-and-risk-of-a-primary-central-nervous-system-tumour-a-systematic-review-and-meta-analysis
#6
REVIEW
Marios K Georgakis, Eleni I Kalogirou, Athanasios Liaskas, Maria A Karalexi, Paraskevi Papathoma, Kyriaki Ladopoulou, Maria Kantzanou, Georgios Tsivgoulis, Eleni Th Petridou
BACKGROUND: The aetiology of primary central nervous system (CNS) tumours remains largely unknown, but their childhood peak points to perinatal parameters as tentative risk factors. In this meta-analysis, we opted to quantitatively synthesise published evidence on the association between birth anthropometrics and risk of primary CNS tumour. METHODS: Eligible studies were identified via systematic literature review; random-effects meta-analyses were conducted for the effect of birth weight and size-for-gestational-age on childhood and adult primary CNS tumours; subgroup, sensitivity, meta-regression and dose-response by birth weight category analyses were also performed...
February 17, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28218967/representation-of-critical-natural-capital-in-china
#7
Yihe Lü, Liwei Zhang, Yuan Zeng, Bojie Fu, Charlotte Whitham, Shuguang Liu, Bingfang Wu
Traditional means of assessing representativeness of conservation value in protected areas depend on measures of structural biodiversity. The effectiveness of priority conservation areas at representing critical natural capital (CNC) (i.e., an essential and renewable subset of natural capital) remains largely unknown. We analyzed the representativeness of CNC-conservation priority areas in national nature reserves (i.e., nature reserves under jurisdiction of the central government with large spatial distribution across the provinces) in China with a new biophysical-based composite indicator approach...
February 20, 2017: Conservation Biology: the Journal of the Society for Conservation Biology
https://www.readbyqxmd.com/read/28218605/comparison-of-a-new-slender-6-french-sheath-with-a-standard-5-french-sheath-for-transradial-coronary-angiography-and-intervention-a-randomized-multicenter-trial-the-rap-and-beat-radial-artery-patency-and-bleeding-efficacy-adverse-event-trial
#8
Adel Aminian, Shigeru Saito, Akihiko Takahashi, Ivo Bernat, Robert Lee Jobe, Takashi Kajiya, Ian C Gilchrist, Yves Louvard, Ferdinand Kiemeneij, Niels Van Royen, Seiji Yamazaki, Takashi Matsukage, Sunil V Rao
AIMS: The 6 French(Fr) Glidesheath Slender (GSS6Fr, Terumo, Japan) is a recently developed thin-walled radial sheath with an outer diameter (OD) that is smaller than the OD of standard 6Fr sheaths. The effect of this introducer sheath on radial artery occlusion (RAO) is unknown. METHODS AND RESULTS: We conducted a randomized, multicenter, non-inferiority trial comparing the GSS6Fr against the standard 5Fr Glidesheath (GS5Fr, Terumo, Japan) in patients undergoing TR coronary angiography and/or intervention...
February 21, 2017: EuroIntervention
https://www.readbyqxmd.com/read/28218473/epigenetic-silencing-of-diacylglycerol-kinase-gamma-in-colorectal-cancer
#9
Masahiro Kai, Eiichiro Yamamoto, Akiko Sato, Hiro-O Yamano, Takeshi Niinuma, Hiroshi Kitajima, Taku Harada, Hironori Aoki, Reo Maruyama, Mutsumi Toyota, Tomo Hatahira, Hiroshi Nakase, Tamotsu Sugai, Toshiharu Yamashita, Minoru Toyota, Hiromu Suzuki
Diacylglycerol kinases (DGKs) are important regulators of cell signaling and have been implicated in human malignancies. Whether epigenetic alterations are involved in the dysregulation of DGKs in cancer is unknown, however. We therefore analyzed methylation of the promoter CpG islands of DGK genes in colorectal cancer (CRC) cell lines. We found that DGKG, which encodes DGKγ, was hypermethylated in all CRC cell lines tested (n = 9), but was not methylated in normal colonic tissue. Correspondingly, DGKG expression was suppressed in CRC cell lines but not in normal colonic tissue, and was restored in CRC cells by treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-dC)...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28217830/relationship-between-alcohol-metabolism-and-chemotherapy-induced-emetic-events-in-breast-cancer-patients
#10
Toshitaka Uomori, Yoshiya Horimoto, Kaoru Mogushi, Joe Matsuoka, Mitsue Saito
BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) can negatively affect quality of life and treatment compliance in breast cancer patients. Habitual alcohol consumption reportedly shows an inverse correlation with CINV, though the underlying mechanism is unknown. Acetaldehyde dehydrogenase 2 (ALDH2), one of the two ALDH isozymes, is reportedly the major factor among several genetic polymorphisms possibly affecting alcohol metabolism. More than 40% of Japanese have ALDH2 mutations, while almost all Westerners have the wild type...
February 20, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28217720/a-graph-partitioning-approach-to-simultaneous-angular-reconstitution
#11
Gabi Pragier, Ido Greenberg, Xiuyuan Cheng, Yoel Shkolnisky
One of the primary challenges in single particle reconstruction with cryo-electron microscopy is to find a three-dimensional model of a molecule using its noisy two-dimensional projection-images. As the imaging orientations of the projection-images are unknown, we suggest a common-lines-based method to simultaneously estimate the imaging orientations of all images that is independent of the distribution of the orientations. Since the relative orientation of each pair of images may only be estimated up to a two-way handedness ambiguity, we suggest an efficient procedure to consistently assign the same handedness to all relative orientations...
September 2016: IEEE Transactions on Computational Imaging
https://www.readbyqxmd.com/read/28216917/uterine-conserving-surgery-in-a-case-of-cervicovaginal-agenesis-with-unicornuate-uterus
#12
Vineet Mishra, Suwa Ram Saini, Sakshi Nanda, Sumesh Choudhary, Priyankur Roy, Tanvir Singh
The presence of cervicovaginal agenesis with unicornuate uterus is a very rare mullerian anomaly. Its true incidence is still unknown. The presence of functioning unicornuate uterus poses a great challenge for a gynecologist because a successful repair could restore normal menses and may preserve a patient's fertility. Hence, we report a case of 16-year-old unmarried female who presented with chief complaints of primary amenorrhea with cyclical lower abdominal pain. On clinical and radiological evaluation, she was diagnosed with complete cervicovaginal agenesis with right unicornuate uterus (hematometra and hematosalpinx)...
October 2016: Journal of Human Reproductive Sciences
https://www.readbyqxmd.com/read/28216198/relationship-between-intraoperative-hypotension-and-acute-kidney-injury-after-living-donor-liver-transplantation-a-retrospective-analysis
#13
Toshiyuki Mizota, Miho Hamada, Shino Matsukawa, Hideya Seo, Tomoharu Tanaka, Hajime Segawa
OBJECTIVE: Acute kidney injury (AKI) is common after liver transplantation (LT) and has a significant impact on outcomes. Although several risk factors for post-LT AKI have been identified, the effect of intraoperative hemodynamic status on post-LT AKI remains unknown. Therefore, the authors aimed to investigate the relationship between hemodynamic parameters during LT and postoperative AKI. DESIGN: A retrospective observational study. SETTING: University hospital...
December 2, 2016: Journal of Cardiothoracic and Vascular Anesthesia
https://www.readbyqxmd.com/read/28216147/differential-responses-of-human-fetal-brain-neural-stem-cells-to-zika-virus-infection
#14
Erica L McGrath, Shannan L Rossi, Junling Gao, Steven G Widen, Auston C Grant, Tiffany J Dunn, Sasha R Azar, Christopher M Roundy, Ying Xiong, Deborah J Prusak, Bradford D Loucas, Thomas G Wood, Yongjia Yu, Ildefonso Fernández-Salas, Scott C Weaver, Nikos Vasilakis, Ping Wu
Zika virus (ZIKV) infection causes microcephaly in a subset of infants born to infected pregnant mothers. It is unknown whether human individual differences contribute to differential susceptibility of ZIKV-related neuropathology. Here, we use an Asian-lineage ZIKV strain, isolated from the 2015 Mexican outbreak (Mex1-7), to infect primary human neural stem cells (hNSCs) originally derived from three individual fetal brains. All three strains of hNSCs exhibited similar rates of Mex1-7 infection and reduced proliferation...
February 9, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28215431/global-decrease-in-the-expression-of-signalling-pathways-genes-in-murine-uterus-during-preimplantation-pregnancy
#15
Katarzyna Buska, Anna Ewa Kedzierska, Anna Slawek, Anna Chelmonska-Soyta
Early preimplantation embryo-maternal communication is crucial for the establishment and development of pregnancy. Though the involvement of several candidate genes and proteins in this complex event has been described, the hierarchy of molecular networks governing this communication remains unknown. The primary objective of this study was to determine whether the presence of embryos in the uterine lumen stimulated or inhibited gene expression in the uterine tissue on day 3.5 post coitum. To answer this question, we investigated the gene expression of dedicated signal transduction pathways in the uterus of CD-1 mice during the preimplantation stage of pregnancy and compared this expression to mice with induced pseudopregnancy...
February 15, 2017: Reproductive Biology
https://www.readbyqxmd.com/read/28215427/method-of-hypertonic-saline-administration-effects-on-osmolality-in-traumatic-brain-injury-patients
#16
Kelly L Maguigan, Bradley M Dennis, Susan E Hamblin, Oscar D Guillamondegui
Hypertonic saline (HTS) is an effective therapy for reducing intracranial pressure (ICP). The ideal method of administration is unknown. The purpose of this study was to evaluate the method of HTS infusion and time to goal osmolality. A retrospective cohort analysis was conducted in severe TBI patients with ICP monitoring in place who received 2 doses of HTS. Patients were divided into bolus versus continuous infusion HTS cohorts. The primary outcome was median time to goal osmolality. Secondary outcomes included percentage of patients reaching goal osmolality, percent time at goal osmolality, mean cerebral perfusion pressure (CPP) and ICP, ICU length of stay, and mortality...
February 15, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28213791/tumor-associated-macrophage-infiltration-in-colorectal-cancer-liver-metastases-is-associated-with-better-outcome
#17
Michael J Cavnar, Simon Turcotte, Steven C Katz, Deborah Kuk, Mithat Gönen, Jinru Shia, Peter J Allen, Vinod P Balachandran, Michael I D'Angelica, T Peter Kingham, William R Jarnagin, Ronald P DeMatteo
BACKGROUND: Tumor-associated macrophages (TAMs) support growth in most human cancers, with the notable exception of colorectal adenocarcinoma, in which TAM infiltration of primary tumors is correlated with a better outcome. The importance of TAMs in colorectal liver metastases (CLM) is unknown. METHODS: Using a tissue microarray of CLM resected at their institution from 1998 to 2000, the authors quantified immune marker expression by immunohistochemistry (IHC) using Metamorph Image Analysis software...
February 17, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28213520/cholesterol-up-regulates-neuronal-g-protein-gated-inwardly-rectifying-potassium-girk-channel-activity-in-the-hippocampus
#18
Anna N Bukiya, Serdar Durdagi, Sergei Noskov, Avia Rosenhouse-Dantsker
Hypercholesterolemia is a well-known risk factor for the development of neurodegenerative disease. However, the underlying mechanisms are mostly unknown. In recent years, it has become increasingly evident that cholesterol-driven effects on physiology and pathophysiology derive from its ability to alter the function of a variety of membrane proteins including ion channels. Yet, the effect of cholesterol on G protein-gated inwardly rectifying potassium (GIRK) channels expressed in the brain is unknown. GIRK channels mediate the actions of inhibitory brain neurotransmitters...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28212984/hiv-1-vpr-disrupts-mitochondria-axonal-transport-and-accelerates-neuronal-aging
#19
Ying Wang, Maryline Santerre, Italo Tempera, Kayla Martin, Ruma Mukerjee, Bassel E Sawaya
Disruption of mitochondria axonal transport, essential for the maintenance of synaptic and neuronal integrity and function, has been identified in neurodegenerative diseases. Whether HIV-1 viral proteins affect mitochondria axonal transport is unknown, albeit HIV-associated neurocognitive disorders occur in around half of the patients living with HIV. Therefore, we sought to examine the effect of HIV-1 viral protein R (Vpr) on mitochondria axonal transport. Using mice primary neuronal cultures, we demonstrated that 4-day Vpr treatment reduced the ratio of moving mitochondria associated with (i) less energy (ATP) supply, (ii) reduction in Miro-1 and (iii) increase of α-synuclein which led to loss of microtubule stability as demonstrated by inconsecutive distribution of acetylated α-tubulin along the axons...
February 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28212505/long-term-validity-of-the-at-risk-mental-state-arms-for-predicting-psychotic-and-non-psychotic-mental-disorders
#20
P Fusar-Poli, G Rutigliano, D Stahl, C Davies, A De Micheli, V Ramella-Cravaro, I Bonoldi, P McGuire
BACKGROUND: The long-term clinical validity of the At Risk Mental State (ARMS) for the prediction of non-psychotic mental disorders is unknown. METHODS: Clinical register-based cohort study including all non-psychotic individuals assessed by the Outreach And Support in South London (OASIS) service (2002-2015). The primary outcome was risk of developing any mental disorder (psychotic or non-psychotic). Analyses included Cox proportional hazard models, Kaplan-Meier survival/failure function and C statistics...
December 6, 2016: European Psychiatry: the Journal of the Association of European Psychiatrists
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