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Maria Libera Ascierto, Tracee L McMiller, Alan E Berger, Ludmila Danilova, Robert A Anders, George J Netto, Haiying Xu, Theresa S Pritchard, Jinshui Fan, Chris Cheadle, Leslie Cope, Charles G Drake, Drew M Pardoll, Janis M Taube, Suzanne L Topalian
Pretreatment tumor PD-L1 expression has been shown to correlate with response to anti-PD-1/PD-L1 therapies. Yet, most patients with PD-L1(+) tumors do not respond to treatment. The current study was undertaken to investigate mechanisms underlying the failure of PD-1-targeted therapies in patients with advanced renal cell carcinoma (RCC) whose tumors express PD-L1. Formalin-fixed, paraffin-embedded pretreatment tumor biopsies expressing PD-L1 were derived from 13 RCC patients. RNA was isolated from PD-L1(+) regions and subjected to whole genome microarray and multiplex quantitative (q)RT-PCR gene expression analysis...
September 2, 2016: Cancer Immunology Research
C Alexander Valencia, Xinjian Wang, Jin Wang, Anna Peters, Julia R Simmons, Molly C Moran, Abhinav Mathur, Ammar Husami, Yaping Qian, Rachel Sheridan, Kevin E Bove, David Witte, Taosheng Huang, Alexander G Miethke
BACKGROUND & AIMS: The etiology of acute liver failure (ALF) remains elusive in almost half of affected children. We hypothesized that inherited mitochondrial and fatty acid oxidation disorders were occult etiological factors in patients with idiopathic ALF and impaired energy metabolism. METHODS: Twelve patients with elevated blood molar lactate/pyruvate ratio and indeterminate etiology were selected from a retrospective cohort of 74 subjects with ALF because their fixed and frozen liver samples were available for histological, ultrastructural, molecular and biochemical analysis...
2016: PloS One
Giovanni Landoni, Alberto Zangrillo, Vladimir V Lomivorotov, Valery Likhvantsev, Jun Ma, Francesco De Simone, Evgeny Fominskiy
Phosphocreatine (PCr) plays an important role in the energy metabolism of the heart and a decrease in its intracellular concentration results in alteration of myocardium energetics and work. We conducted a meta-analysis of all randomized and matched trials that compared PCr with placebo or standard treatment in patients with coronary artery disease or chronic heart failure or in those undergoing cardiac surgery. We systematically searched PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials and Google Scholar up to 1 November 2015, for pertinent trials...
October 2016: Interactive Cardiovascular and Thoracic Surgery
Silvia Polakova, Lucia Molnarova, Randy W Hyppa, Zsigmond Benko, Ivana Misova, Alexander Schleiffer, Gerald R Smith, Juraj Gregan
To identify new proteins required for faithful meiotic chromosome segregation, we screened a Schizosaccharomyces pombe deletion mutant library and found that deletion of the dbl2 gene led to missegregation of chromosomes during meiosis. Analyses of both live and fixed cells showed that dbl2Δ mutant cells frequently failed to segregate homologous chromosomes to opposite poles during meiosis I. Removing Rec12 (Spo11 homolog) to eliminate meiotic DNA double-strand breaks (DSBs) suppressed the segregation defect in dbl2Δ cells, indicating that Dbl2 acts after the initiation of meiotic recombination...
June 2016: PLoS Genetics
Maheshwar Lakkireddyl Shagun Aggarwal, Vijaykrishna Chilakamarri, Vasundhara S Chennuri, Madhulatha Karra
INTRODUCTION: Infantile Systemic Hyalinosis (ISH) is a rare and fatal genetic disorder with mutations in Capillary morphogenesis gene-2 CMG2 / Human anthrax toxin receptor gene-2 ANTXR2 resulting in spindle cell proliferation, altered collagen metabolism with extensive deposition of amorphous eosinophilic PAS positive hyaline material in the connective tissues of various organs. The common presenting features would be progressive stiffness of multiple joints, skin lesions, multiple episodes of protracted infections, prolonged diarrhoea and failure to thrive...
January 2016: Journal of Orthopaedic Case Reports
(no author information available yet)
In late 2015, the first-choice treatment for patients with chronic hepatitis C due to a genotype 1 virus (HCV-1) was the combination of ledipasvir (an NS5A protein inhibitor) + sofosbuvir (a nucleotide inhibitor of NS5B RNA polymerase), despite major uncertainties regarding its adverse effects. This combination is almost always virologically effective. Dasabuvir is a non-nucleoside inhibitor of the viral RNA polymerase NS5B. It is authorised in the EU for the treatment of patients with chronic hepatitis C due to HCV-1, usually combined with the fixed-dose combination (Viekirax) of ombitasvir (an HCV NS5A protein inhibitor) + paritaprevir (an HCV protease inhibitor) + ritonavir (to enhance paritaprevir bioavailability)...
May 2016: Prescrire International
Darrell Wiens, Alexandra DeWitt, Morgan Kosar, Celeste Underriner, Maren Finsand, Mikayla Freese
The vitamin folic acid (FA) is essential for DNA synthesis, repair and methylation, and for methionine synthesis. Although it is necessary for neural development, recent studies suggest a possible link between excess maternal supplemental FA intake and adverse interferences with single-carbon metabolism and neural development. Insufficient FA early in brain development can lead to failure of the neural tube closure, but the consequences of too much intake have not been fully investigated. Plasma FA concentrations can increase greatly with dietary supplementation...
2016: Cells, Tissues, Organs
Cher-Rin Chong, Benedetta Sallustio, John D Horowitz
Approaches to the pharmacotherapy of angina pectoris have previously centred on the concept that a transient imbalance between myocardial oxygen "demand" and supply within the myocardium can best be addressed by reducing demand (for example, with β-adrenoceptor antagonist) or by increasing availability of blood (via coronary vasomotor reactivity adjustment or coronary revascularization). However, this principle is potentially challenged by the emergence of cases of angina unsuitable for such therapies (for example because of concomitant severe systolic heart failure) and by the recognition that impaired myocardial energetics may precipitate angina in the absence of fixed or variable coronary obstruction (for example in hypertrophic cardiomyopathy)...
August 2016: Cardiovascular Drugs and Therapy
Marco Migliorati, Sara Drago, Fabio Gallo, Leonardo Amorfini, Domenico Dalessandri, Chiara Calzolari, Stefano Benedicenti, Armando Silvestrini-Biavati
INTRODUCTION: The aim of this randomized clinical trial was to compare torque recordings at insertion time and 1 week post-placement between immediately loaded orthodontic miniscrews and an unloaded control group. TRIAL DESIGN: This RCT was designed as parallel with an allocation ratio of 1:1. METHODS: Eligibility criteria to enroll patients were: needs of fixed orthodontic treatment, no systemic disease, absence of using drugs altering bone metabolism...
December 2016: European Journal of Orthodontics
Djillali Annane, Eric Bellissant, Pierre Edouard Bollaert, Josef Briegel, Didier Keh, Yizhak Kupfer
BACKGROUND: Sepsis occurs when an infection is complicated by organ failures as defined by a sequential organ failure assessment (SOFA) score of two or higher. Sepsis may be complicated by impaired corticosteroid metabolism. Giving corticosteroids may benefit patients. The original review was published in 2004 and was updated in 2010 and again in 2015. OBJECTIVES: To examine the effects of corticosteroids on death at one month in patients with sepsis, and to examine whether dose and duration of corticosteroids influence patient response to this treatment...
2015: Cochrane Database of Systematic Reviews
Heather A Vallier, Timothy A Moore, John J Como, Patricia A Wilczewski, Michael P Steinmetz, Karl G Wagner, Charles E Smith, Xiao-Feng Wang, Andrea J Dolenc
BACKGROUND: Our group developed a protocol, entitled Early Appropriate Care (EAC), to determine timing of definitive fracture fixation based on presence and severity of metabolic acidosis. We hypothesized that utilization of EAC would result in fewer complications than a historical cohort and that EAC patients with definitive fixation within 36 h would have fewer complications than those treated at a later time. METHODS: Three hundred thirty-five patients with mean age 39...
2015: Journal of Orthopaedic Surgery and Research
Elizabeth Osei, Susanne Fonville, Adrienne A M Zandbergen, Paul J A M Brouwers, Laus J M M Mulder, Hester F Lingsma, Diederik W J Dippel, Peter J Koudstaal, Heleen M den Hertog
BACKGROUND: Impaired glucose tolerance is present in one third of patients with a TIA or ischemic stroke and is associated with a two-fold risk of recurrent stroke. Metformin improves glucose tolerance, but often leads to side effects. The aim of this study is to explore the feasibility, safety, and effects on glucose metabolism of metformin and sitagliptin in patients with TIA or minor ischemic stroke and impaired glucose tolerance. We will also assess whether a slow increase in metformin dose and better support and information on this treatment will reduce the incidence of side effects in these patients...
2015: Trials
Wellington M Silva, Madeleine Berger, Chris Bass, Valdir Q Balbino, Marcelo H P Amaral, Mateus R Campos, Herbert A A Siqueira
The tomato leafminer, Tuta absoluta, is a major pest of tomato crops worldwide. This study surveyed the resistance of T. absoluta populations from four regions in Brazil to pyrethroid insecticides, the frequencies of L1014F, T929I and M918T Na channel mutations, and the role of detoxification metabolism in the resistance. Resistance ratios varied from 1- to 11-times among populations and insecticides, but control failure likelihood assays showed that all pyrethroids assessed exhibited no efficacy at all (and thus, 98-100% control failure likelihood) against all T...
July 2015: Pesticide Biochemistry and Physiology
Nicolai Preisler, Pascal Laforêt, Karen Lindhardt Madsen, Kira Philipsen Prahm, Gitte Hedermann, Christoffer Rasmus Vissing, Henrik Galbo, John Vissing
OBJECTIVE: Glycogen storage disease type IIIa (GSDIIIa) is classically regarded as a glycogenosis with fixed weakness, but we hypothesized that exercise intolerance in GSDIIIa is related to muscle energy failure and that oral fructose ingestion could improve exercise tolerance in this metabolic myopathy. METHODS: We challenged metabolism with cycle-ergometer exercise and measured substrate turnover and oxidation rates using stable isotope methodology and indirect calorimetry in 3 patients and 6 age-matched controls on 1 day, and examined the effect of fructose ingestion on exercise tolerance in the patients on another day...
April 28, 2015: Neurology
Keiichi Fujiwara, Shin Yasui, Yutaka Yonemitsu, Makoto Arai, Tatsuo Kanda, Masayuki Nakano, Shigeto Oda, Osamu Yokosuka
BACKGROUND: There has existed important differences in the definition of acute liver failure (ALF) between Japanese criteria and those of other countries. The novel diagnostic criteria for ALF in Japanese patients were established by the Intractable Hepato-Biliary Diseases Study Group of Japan, in order to correspond to those for ALF in Europe and the USA. We prospectively diagnosed our ALF patients based on this novel criteria, and discussed the etiology by a fixed point observation...
March 2015: Journal of Hepato-biliary-pancreatic Sciences
Archana Pandita, Bhupender Kumar, Siddharth Manvati, Samantha Vaishnavi, Shashank K Singh, Rameshwar N K Bamezai
Gemcitabine, an effective agent in treatment of cancer of pancreas, has undergone failures in many instances after multiple cycles of therapy due to emergence of drug resistance. Combination of dietary compounds with clinically validated drugs has emerged as an effective therapeutic approach to treat pancreatic tumors, refractory to gemcitabine therapy. In order to optimize a possible synergistic combination of Gemcitabine (GCB) with dietary molecules, Betuilnic acid (BA) and Thymoquinone (TQ), stand-alone IC50 dose of GCB, BA and TQ was calculated for pancreatic cancer cell lines...
2014: PloS One
Haqeel Jamil, John Gierula, Roo Byrom, Eleanor Joy, Mark Kearney, Klaus Witte
INTRODUCTION: Increased cardiac output during exercise is the result of greater stroke volume and an increase in heart rate. It is therefore assumed that a limitation to heart rate rise (HRR) in response to activity, chronotropic incompetence (CI), could contribute to the exercise intolerance that is characteristic of chronic heart failure (CHF). However, HRR is closely related to workload and subjects with impaired exercise capacity have a lower peak heart rate (PHR) and a lower HRR...
June 2014: Heart: Official Journal of the British Cardiac Society
Weerawat Manosuthi, Somnuek Sungkanuparph, Somsit Tansuphaswadikul, Wisit Prasithsirikul, Chatiya Athichathanabadi, Sirirat Likanonsakul, Achara Chaovavanich
BACKGROUND: Generic fixed-dose combination (FDC) antiretroviral therapy (ART) has been widely used in resource-limited settings. Treatment based on these combinations provide low pill burden and are less expensive. OBJECTIVE: The aim of this study was to determine the long-term effectiveness and metabolic complications of a generic FDC of stavudine (d4T)/lamivudine (3TC)/ nevirapine (NVP), among ART-naive HIV-infected patients. METHODS: A prospective study was conducted among patients who were initiated on d4T/3TC/NVP between November 2004 and March 2005...
February 2008: Current Therapeutic Research, Clinical and Experimental
Renato Samy Assad, Leonardo Augusto Miana, Miriam Helena Fonseca-Alaniz, Maria Cristina Donadio Abduch, Gustavo José Justo da Silva, Fernanda Santos de Oliveira, Luiz Felipe Pinho Moreira, José Eduardo Krieger
OBJECTIVE: Increased glucose 6-phosphate dehydrogenase activity has been demonstrated in heart failure. This study sought to assess myocardial glucose 6-phosphate dehydrogenase activity in retraining of the subpulmonary ventricle of adult goats. METHODS: Eighteen adult goats were divided into three groups: traditional (fixed banding), sham, and intermittent (adjustable banding, daily 12-hour systolic overload). Systolic overload (70% of systemic pressure) was maintained during a 4-week period...
October 2013: Revista Brasileira de Cirurgia Cardiovascular
Christian Manzardo, José M Gatell
Stribild® (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate) is a new single-tablet, fixed-dose formulation approved by both the US Food and Drug Administration and the European Medicine Agency as antiretroviral therapy. It is the first once-a-day therapy option containing an integrase inhibitor and cobicistat, a novel pharmacokinetic boosting agent without activity on HIV. Stribild® has demonstrated non-inferior virological efficacy and a similar recovery of CD4+ T-cells when compared to Atripla® (efavirenz/emtricitabine/tenofovir) and to ritonavir-boosted atazanavir plus emtricitabine/tenofovir in two large, phase III randomized clinical trials at 48, 96, and 144 weeks...
January 2014: AIDS Reviews
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