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Silvia Beatriz Gorban de Lapertosa, Gustavo Frechtel, Elise Hardy, Leobardo Sauque-Reyna
AIMS: Socioeconomic changes in Latin American countries have led to an increased prevalence of type 2 diabetes (T2D). We examined the effects of exenatide twice daily (BID) or insulin lispro, each added to insulin glargine, in Latin American patients with T2D. METHODS: This was a subgroup analysis of patients from Argentina and Mexico in the 4B study (N=114). Patients with glycated hemoglobin (HbA1c) of 7.0-10.0% (53-86mmol/mol) after 12weeks of intensive basal insulin optimization were randomized to exenatide BID or thrice-daily insulin lispro added to insulin glargine and metformin...
October 8, 2016: Diabetes Research and Clinical Practice
Sawinee Aupanun, Patchara Phuektes, Saranya Poapolathep, Samak Sutjarit, Mario Giorgi, Amnart Poapolathep
Fusarenon X, a member of the type B trichothecene mycotoxin group, has been frequently observed, along with deoxynivalenol (DON) and nivalenol (NIV) as a contaminant in cereals. Our previous study demonstrated that a 14-day FX exposure caused apoptosis in the lymphoid tissues of mice, especially at 0.5 mg/kg bodyweight. However, the relationship between low concentrations of FX and apoptotic molecular machinery remains unclear. In the present study, we investigated the genetic regulatory mechanisms in the thymus and Peyer's patches of mice after 14 days oral administration of FX at 0...
October 20, 2016: Toxicon: Official Journal of the International Society on Toxinology
Pei-Jung Lin, Wei-Shi Yeh, Peter J Neumann
OBJECTIVES: The current US mandatory newborn screening panel does not include spinal muscular atrophy, the most common fatal genetic disease among children. We assessed population preferences for newborn screening for spinal muscular atrophy, and how test preferences varied depending on immediate treatment implications. METHODS: We conducted an online willingness-to-pay survey of US adults (n = 982). Respondents were asked to imagine being parents of a newborn...
September 15, 2016: Pediatric Neurology
K Reich, M Gooderham, L Green, A Bewley, Z Zhang, I Khanskaya, R M Day, J Goncalves, K Shah, V Piguet, J Soung
BACKGROUND: Apremilast, an oral, small-molecule phosphodiesterase 4 inhibitor, has demonstrated efficacy in patients with moderate to severe psoriasis. OBJECTIVE: Evaluate efficacy and safety of apremilast vs. placebo in biologic-naive patients with moderate to severe plaque psoriasis and safety of switching from etanercept to apremilast in a phase IIIb, randomized, double-blind, placebo-controlled study (NCT01690299). METHODS: 250 patients were randomized to placebo (n=84), apremilast 30 mg BID (n=83) or etanercept 50 mg QW (n=83) through Week 16; thereafter, all patients continued or switched to apremilast through Week 104...
October 21, 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
Viraj Suvarna
Stroke prevention in atrial fibrillation (AF) has reached an exciting phase with a plethora of newer, potentially more efficacious and safer agents being introduced for physicians to select from. Dabigatran belongs to a class of anticoagulants called direct thrombin inhibitors, while rivaroxaban, apixaban, and edoxaban are direct Factor Xa inhibitors. Purely from a therapeutic endpoint perspective-based on the action of anticoagulants in reducing cardioembolic stroke-in clinical trials, one should look at whether a new anticoagulant in patients with AF prevents ischemic stroke...
October 2016: Journal of the Association of Physicians of India
Zhi-Yong Xu, Ming-Xue Zheng, Yan Zhang, Xiao-Zhen Cui, Sha-Sha Yang, Rui-Li Liu, Shan Li, Rou Xi, Xin Gong, Rui Bai
The purpose of the present study was to investigate the dynamic changes in the main regulatory genes of the mitochondrial permeability transition pore in E. tenella host cells. Primary chick embryo cecum epithelial cell culture techniques, spectrophotometer technology, Hoechst-Annexin V-PI apoptosis staining and ELISA were used to detect the apoptosis rate and dynamic changes of Bcl-2, Bcl-xl, Bax, Bak, Bid, Bad, HK-II, and ATP content in E. tenella host cells at 4, 24, 48, 72, 96, and 120 h. The rates of early apoptosis, late apoptosis, and necrosis of group T0 were significantly lower (P < 0...
October 17, 2016: Experimental Parasitology
Zhen Cai, Chunge Wang, Peiwen Liu, Peng Shen, Yingying Han, Nawen Liu
BACKGROUND: Sorafenib is the only therapy shown to improve overall survival in advanced hepatocellular carcinoma (HCC). However, the clinical efficacy of sorafenib is limited. Combination therapy targeting multiple signaling pathways may improve outcomes. Ginkgo biloba extract (GBE) has exhibited antitumor activity in multiple human cancers. HYPOTHESIS/PURPOSE: This study was designed to evaluate the tolerability and effectiveness of GBE combined with sorafenib in patients with advanced HCC...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Robert F Gahl, Pallavi Dwivedi, Nico Tjandra
The most critical step in the initiation of apoptosis is the activation of the Bcl-2 family of proteins to oligomerize and permeabilize the outer-mitochondrial membrane (OMM). As this step results in the irreversible release of factors that enhance cellular degradation, it is the point of no return in programmed cell death and would be an ideal therapeutic target. However, the arrangement of the Bcl-2 proteins in the OMM during permeabilization still remains unknown. It is also unclear whether the Bcl-2 protein, Bid, directly participates in the formation of the oligomers in live cells, even though it is cleaved and translocates to the OMM at the initiation of apoptosis...
October 20, 2016: Cell Death & Disease
Qifang Long, Weipei Zhu, Jundong Zhou, Jinchang Wu, Weixian Lu, Cui Zheng, Dongmei Zhou, Ling Yu, Ru Yang
Ovarian cancer is one of the most lethal malignant gynecologic tumors with a high relapse rate worldwide. Cancer stem cells (CSC) have been identified in ovarian cancer and other malignant tumors as a small population of cells that are capable of self-renew and multi-differentiation. CD133 positive (CD133(+)) ovarian cancer stem cells have been reported to be more tumorigenic and more resistant to chemotherapeutic treatment. Thus, CD133 has emerged as one of the most promising therapeutic markers for ovarian cancer treatment...
October 18, 2016: Oncology Research
Joseph D Unsay, Katia Cosentino, Katharina Sporbeck, Ana J García-Sáez
Bcl-2 proteins are key regulators of the mitochondrial outer membrane (MOM) permeabilization that mediates apoptosis. During apoptosis, Bid is cleaved (cBid) and translocates to the MOM, where it activates Bax. Bax then oligomerizes and induces MOM permeabilization. However, little is known about how these proteins affect membrane organization aside from pore formation. In previous studies, we have shown that both cBid and Bax are able to remodel membranes and stabilize curvature. Here, we dissected the independent effects of Bax and cBid on supported lipid structures mimicking the mitochondrial composition by means of atomic force spectroscopy...
October 15, 2016: Biochimica et Biophysica Acta
Asim V Farooq, Joshua H Hou, Sarmad Jassim, Zeeshan Haq, Elmer Y Tu, Jose de la Cruz, Maria S Cortina
OBJECTIVES: To determine the rate of biofilm formation on bandage contact lenses worn by patients with the Boston type 1 keratoprosthesis (K-Pro) while on prophylactic topical vancomycin versus linezolid. METHODS: Patients wearing a bandage contact lens (BCL) with a K-Pro were eligible for enrollment. After irrigation of the ocular surface with 5% povidone-iodine solution, each patient was placed on either topical vancomycin 15 mg/mL or linezolid 0.2% BID for one month...
October 13, 2016: Eye & Contact Lens
Hae-Young Lee, Chan-Soon Park, Sang-Hoon Na, Kyung-Jin Kim, Chan Joo Lee, Sungha Park
A 47-year-old woman was admitted via emergency department due to dyspnea NYHA Fc II-III aggravated for 2 months after upper respiratory infection. Her height and body weight were 161 cm / 67 kg. Initial vital signs were 110/70 mmHg - 112 BPM - 24/min - 36.5°C. Chest PA showed cardiomegaly and pulmonary congestion (Figure 1). B-natriuretic peptide level was markedly increased (2002 pg/mL, normal range ≤ 100 pg/mL). The echocardiographic examination showed severely dilated LV cavity (61/72 mm) and severe LV systolic dysfunction (EF 28%) with normal left ventricular wall thickness (9/11 mm) (Figure 2)...
September 2016: Journal of Hypertension
Caroline M Swarbrick, Open Doors, Educate, Katie Davis, John Keady
The involvement of people living with dementia in research has traditionally been located in the realms of 'subject' or 'participant'. However, there has been an increase in demand for greater transparency by academic bidding teams (particularly within the UK) in demonstrating how people with a lived experience have been and will be involved in the research process. Located within the Economic and Social Research Council/National Institute for Health Research (ESRC/NIHR)-funded Neighbourhoods and Dementia Study (2014-2019), led by The University of Manchester (UK), this paper outlines the development of the CO-researcher INvolvement and Engagement in Dementia (COINED) Model, which was co-produced alongside three independent groups of people living with dementia: Open Doors, the Scottish Dementia Working Group and EDUCATE...
October 16, 2016: Dementia
Magdalene A Dohil
BACKGROUND: Actinic keratosis (AK) is a neoplastic keratosis and a precursor of squamous cell carcinoma (SCC). OBJECTIVE: We are presenting data on a novel formulation of 4% 5-Fluorouracil (5-FU) in an aqueous vehicle cream containing peanut oil (Tolak) with once daily application versus treatment with 5% 5-FU twice daily for 4 weeks. METHODS: 1) A dose ranging study of 4% 5-FU cream once or twice daily for 2 or 4 weeks and its vehicle, compared to 5% 5-FU cream twice daily for 4 weeks in 121 subjects...
October 1, 2016: Journal of Drugs in Dermatology: JDD
Niran J Amar, Tulin Shekar, Tracey A Varnell, Anish Mehta, George Philip
OBJECTIVES: Mometasone furoate (MF), delivered via dry-powder inhaler (DPI) QD in the evening (PM), is a treatment option for pediatric patients with asthma. We evaluated MF delivered via a metered-dose inhaler (MDI), in children ages 5-11 years with persistent asthma. METHODS: This was a 12-week double-blind, double-dummy, placebo-controlled trial. Pateints were randomized to the following treatments: MF-MDI 50 mcg BID, MF-MDI 100 mcg BID, MF-MDI 200 mcg BID, MF-DPI 100 mcg QD PM, and placebo...
October 14, 2016: Pediatric Pulmonology
Rishi G Vaswani, Victor S Gehling, Les A Dakin, Andrew Cook, Christopher G Nasveschuk, Martin Duplessis, Priyadarshini Iyer, Srividya Balasubramanian, Feng Zhao, Andrew C Good, Robert Campbell, Christina Lee, Nico Cantone, Richard T Cummings, Emmanuel Normant, Steven F Bellon, Brian K Albrecht, Jean-Christophe P Harmange, Patrick Trojer, James E Audia, Ying Zhang, Neil Justin, Shuyang Chen, Jon Wilson, Steve Gamblin
Polycomb repressive complex 2 (PRC2) has been shown to play a major role in transcriptional silencing in part by installing methylation marks on lysine 27 of histone 3. Dysregulation of PRC2 function correlates with certain malignancies and poor prognosis. EZH2 is the catalytic engine of the PRC2 complex and thus represents a key candidate oncology target for pharmacological intervention. Here we report the optimization of our indole based EZH2 inhibitor series that led to the identification of CPI-1205, a highly potent (biochemical IC50 = 0...
October 14, 2016: Journal of Medicinal Chemistry
Edward C Lauterbach
Dextromethorphan (DM) may have ketamine-like rapid-acting, treatment-resistant, and conventional antidepressant effects.(1,2) This reports our initial experience with DM in unipolar Major Depressive Disorder (MDD). A patient with treatment-resistant MDD (failing adequate trials of citalopram and vortioxetine) with loss of antidepressant response (to fluoxetine and bupropion) twice experienced a rapid-acting antidepressant effect within 48 hours of DM administration and lasting 7 days, sustained up to 20 days with daily administration, then gradually developing labile loss of antidepressant response over the ensuing 7 days...
August 15, 2016: Psychopharmacology Bulletin
Vincent Madelain, Jérémie Guedj, France Mentré, Thi Huyen Tram Nguyen, Frédéric Jacquot, Lisa Oestereich, Takumi Kadota, Koichi Yamada, Anne-Marie Taburet, Xavier de Lamballerie, Hervé Raoul
Favipiravir is a RNA polymerase inhibitor that showed a strong antiviral efficacy in vitro and in small animal models of several viruses responsible for hemorrhagic fever (HF) including Ebola virus. The aim of this work was to characterize the complex pharmacokinetics of favipiravir in non-human primates (NHP) in order to guide future efficacy studies of favipiravir in large animal models.Four different studies were conducted in 30 uninfected cynomolgus macaques of Chinese (n=17) or Mauritian (n=13) origin treated with intravenous favipiravir for 7 to 14 days with maintenance doses of 60 to 180 mg/kg BID...
October 10, 2016: Antimicrobial Agents and Chemotherapy
R Fleischmann, P J Mease, S Schwartzman, L-J Hwang, K Soma, C A Connell, L Takiya, E Bananis
Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This post hoc analysis investigated the effect of methotrexate (MTX) dose on the efficacy of tofacitinib in patients with RA. ORAL Scan (NCT00847613) was a 2-year, randomized, Phase 3 trial evaluating tofacitinib in MTX-inadequate responder (IR) patients with RA. Patients received tofacitinib 5 or 10 mg twice daily (BID), or placebo, with low (≤12.5 mg/week), moderate (>12.5 to <17.5 mg/week), or high (≥17...
October 12, 2016: Clinical Rheumatology
Tricia Adjei, Daniel Abásolo, David Santamarta
Hydrocephalus is a condition characterised by enlarged cerebral ventricles, which in turn affects intracranial pressure (ICP); however, the mechanisms regulating ICP are not fully understood. A nonlinear signal processing approach was applied to ICP signals measured during infusion studies from patients with two forms of hydrocephalus, in a bid to compare the differences. This is the first study of its kind. The two forms of hydrocephalus were idiopathic normal pressure hydrocephalus (iNPH) and secondary normal pressure hydrocephalus (SH)...
September 2016: Healthcare Technology Letters
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