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https://www.readbyqxmd.com/read/28089763/comparison-of-multi-arm-multi-stage-design-and-adaptive-randomization-in-platform-clinical-trials
#1
REVIEW
Jianchang Lin, Veronica Bunn
Platforms trials are clinical trials that allow for concurrent evaluations of multiple treatments, thus allowing for more efficient and ethical studies compared to traditional two-arm trials. Conventional group-sequential multi-arm multi-stage (MAMS) designs use pre-specified stopping boundaries and treatment selection rules to determine if experimental treatments should be dropped. Flexible MAMS designs allow for interim modifications to the design plan without compromising error rates. Bayesian response adaptive randomization (BRAR) designs increase patient allocation to treatment arms that are performing well during the course of the trial...
January 12, 2017: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/28089135/phenotypic-continuum-between-autism-and-schizophrenia-evidence-from-the-movie-for-the-assessment-of-social-cognition-masc
#2
Gilles Martinez, Charlotte Alexandre, Célia Mam-Lam-Fook, Narjes Bendjemaa, Raphaël Gaillard, Patricia Garel, Isabel Dziobek, Isabelle Amado, Marie-Odile Krebs
Schizophrenic (SCZ) and autism (ASD) spectrum disorders share several features including social cognition impairments. In SCZ, the link between symptomatic dimensions and social cognition deficits remains unclear. The Movie for the Assessment of Social Cognition (MASC) test, available in several languages including English, investigates mental state attribution capabilities in complex interpersonal situations. After its translation into French, we used MASC to direct compare social cognition in 36 young participants with SCZ to 19 with ASD and 20 healthy controls (HC) matched for gender, age (18-25y...
January 11, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28087257/calcium-regulates-cell-death-in-cancer-roles-of-the-mitochondria-and-mitochondria-associated-membranes-mams
#3
REVIEW
Alberto Danese, Simone Patergnani, Massimo Bonora, Mariusz R Wieckowski, Maurizio Previati, Carlotta Giorgi, Paolo Pinton
Until 1972, the term 'apoptosis' was used to differentiate the programmed cell death that naturally occurs in organismal development from the acute tissue death referred to as necrosis. Many studies on cell death and programmed cell death have been published and most are, at least to some degree, related to cancer. Some key proteins and molecular pathways implicated in cell death have been analyzed, whereas others are still being actively researched; therefore, an increasing number of cellular compartments and organelles are being implicated in cell death and cancer...
January 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28067276/flip-flop-of-day-night-and-summer-winter-surface-urban-heat-island-intensity-in-india
#4
Hiteshri Shastri, Beas Barik, Subimal Ghosh, Chandra Venkataraman, Pankaj Sadavarte
The difference in land surface temperature (LST) between an urban region and its nearby non-urban region, known as surface urban heat island intensity (SUHII), is usually positive as reported in earlier studies. India has experienced unprecedented urbanization over recent decades with an urban population of 380 million. Here, we present the first study of the diurnal and seasonal characteristics of SUHII in India. We found negative SUHII over a majority of urban areas during daytime in pre-monsoon summer (MAM), contrary to the expected impacts of urbanization...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28065786/cisplatin-induced-necroptosis-in-tnf%C3%AE-dependent-and-independent-pathways
#5
Yanfang Xu, Hua-Bin Ma, Yu-Lu Fang, Zhi-Rong Zhang, Jing Shao, Mao Hong, Chao-Jun Huang, Jing Liu, Rui-Qing Chen
Cisplatin is a chemotherapeutic drug for treatment of many solid tumors. It has been shown to induce apoptosis and/or necrosis in different types of cancer cells. However, the underlying mechanisms remain elusive. In this study, we provide evidences that cisplatin induces necroptosis in receptor-interacting protein 3 (RIP3)-expressing cell lines, but not in cell lines lacking RIP3 protein expression. Deficiency of core components of necroptotic pathway, RIP1, RIP3, or mixed lineage kinase domain-like protein (MLKL) blocked cisplatin-induced cell death in L929 cells...
January 6, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28064001/endoplasmic-reticulum-mitochondria-calcium-signalling-in-hepatic-metabolic-diseases
#6
REVIEW
Jennifer Rieusset
The liver plays a central role in glucose homeostasis, and both metabolic inflexibility and insulin resistance predispose to the development of hepatic metabolic diseases. Mitochondria and endoplasmic reticulum (ER), which play a key role in the control of hepatic metabolism, also interact at contact points defined as mitochondria-associated membranes (MAM), in order to exchange metabolites and calcium (Ca(2+)) and regulate cellular homeostasis and signaling. Here, we overview the role of the liver in the control of glucose homeostasis, mainly focusing on the independent involvement of mitochondria, ER and Ca(2+) signaling in both healthy and pathological contexts...
January 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28060261/study-of-endoplasmic-reticulum-and-mitochondria-interactions-by-in-situ-proximity-ligation-assay-in-fixed-cells
#7
Emily Tubbs, Jennifer Rieusset
Structural interactions between the endoplasmic reticular (ER) and mitochondrial membranes, in domains known as mitochondria-associated membranes (MAM), are crucial hubs for cellular signaling and cell fate. Particularly, these inter-organelle contact sites allow the transfer of calcium from the ER to mitochondria through the voltage-dependent anion channel (VDAC)/glucose-regulated protein 75 (GRP75)/inositol 1,4,5-triphosphate receptor (IP3R) calcium channeling complex. While this subcellular compartment is under intense investigation in both physiological and pathological conditions, no simple and sensitive method exists to quantify the endogenous amount of ER-mitochondria contact in cells...
December 10, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28029332/mam-6e7-mam-3e7-mam-6g7-antirecombinant-human-trypsin-2
#8
(no author information available yet)
No abstract text is available yet for this article.
December 2016: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/28026026/mams-are-attractive-targets-for-bacterial-repurposing-of-the-host-cell-mam-functions-might-be-key-for-undermining-an-infected-cell
#9
Pedro Escoll, Monica Rolando, Carmen Buchrieser
Pathogenic bacteria frequently target the endoplasmic reticulum (ER) and mitochondria in order to exploit host functions. ER-mitochondria inter-organelle communication is topologically sub-compartmentalized at mitochondria-associated ER membranes (MAMs). MAMs are specific membranous microdomains with unique regulatory functions such as lipid synthesis and trafficking, calcium homeostasis, mitochondrial morphology, inflammasome activation, autophagosome formation, and apoptosis. These important cellular processes are all modulated by pathogens to subvert host functions and promote infection, thus it is tempting to assume that pathogenic bacteria target MAMs to subvert these different pathways in their hosts...
December 27, 2016: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28001323/prenatal-transplantation-of-epidermal-neural-crest-stem-cells-in-malformation-of-cortical-development-mouse-model
#10
Ameneh Omidi, Mohammad Akbari, Keywan Mortezaee, Ehsan Eqlimi, Cordian Beyer, Adib Zendedel, Iraj Ragerdi Kashani
Prenatal interventions may offer an immense opportunity in therapeutic protocols of malformations of cortical development (MCD). Epidermal neural crest stem cells (EPI-NCSCs) of the hair follicle bulge exhibit features of both embryonic and adult stem cells; these cells maintain their neurologic differentiation capability because of their neural crest origin. However, it is unknown if prenatal use of EPI-NCSCs could be beneficial in targeting methylazoxymethanol (MAM)-induced MCD, which further addressed in the present work...
December 21, 2016: Microscopy Research and Technique
https://www.readbyqxmd.com/read/28001250/nutritional-therapy-assessment-outpatient-mobility-monitoring-mam
#11
D F Ribas, R S Simões, R F Buzzini, G Kelman, W M Bernardo
No abstract text is available yet for this article.
December 2016: Revista da Associação Médica Brasileira
https://www.readbyqxmd.com/read/27996032/targeting-bacterial-adherence-inhibits-multidrug-resistant-pseudomonas-aeruginosa-infection-following-burn-injury
#12
Ryan M Huebinger, Daniel H Stones, Marcela de Souza Santos, Deborah L Carlson, Juquan Song, Diana Pereira Vaz, Emma Keen, Steven E Wolf, Kim Orth, Anne Marie Krachler
Classical antimicrobial drugs target proliferation and therefore place microbes under extreme selective pressure to evolve resistance. Alternative drugs that target bacterial virulence without impacting survival directly offer an attractive solution to this problem, but to date few such molecules have been discovered. We previously discovered a widespread group of bacterial adhesins, termed Multivalent Adhesion Molecules (MAMs) that are essential for initial binding of bacteria to host tissues and virulence...
December 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27995898/irbit-controls-apoptosis-by-interacting-with-the-bcl-2-homolog-bcl2l10-and-by-promoting-er-mitochondria-contact
#13
Benjamin Bonneau, Hideaki Ando, Katsuhiro Kawaai, Matsumi Hirose, Hiromi Takahashi-Iwanaga, Katsuhiko Mikoshiba
IRBIT is a molecule that interacts with the inositol 1,4,5-trisphosphate (IP3)-binding pocket of the IP3 receptor (IP3R), whereas the antiapoptotic protein, Bcl2l10, binds to another part of the IP3-binding domain. Here we show that Bcl2l10 and IRBIT interact and exert an additive inhibition of IP3R in the physiological state. Moreover, we found that these proteins associate in a complex in mitochondria-associated membranes (MAMs) and that their interplay is involved in apoptosis regulation. MAMs are a hotspot for Ca(2+) transfer between endoplasmic reticulum (ER) and mitochondria, and massive Ca(2+) release through IP3R in mitochondria induces cell death...
December 20, 2016: ELife
https://www.readbyqxmd.com/read/27991906/hepatic-stimulator-substance-inhibits-calcium-overflow-through-the-mitochondria-associated-membrane-compartment-during-nonalcoholic-steatohepatitis
#14
Fan Xiao, Jing Zhang, Can Zhang, Wei An
Nonalcoholic fatty liver disease is considered a disorder of the endoplasmic reticulum (ER) and mitochondria. Recent studies have shown that the ER and mitochondrial membranes overlap by 15-20%, a region referred to as the 'mitochondria-associated ER membrane' (MAM). Some proteins, including sarco/ER calcium ATPase (SERCA), are located in the MAM and have an important role in Ca(2+) signaling and homeostasis between the ER and the mitochondria. Our previous study showed that hepatic stimulator substance (HSS) inhibits the ER stress induced by reactive oxygen species, thus reducing mitochondrial damage...
December 19, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27979929/comparative-evaluation-of-drug-deposition-in-hair-samples-collected-from-different-anatomical-body-sites
#15
Manolis N Tzatzarakis, Athanasios K Alegakis, Matthaios P Kavvalakis, Elena Vakonaki, Polychronis D Stivaktakis, Katerina Kanaki, Alexander I Vardavas, Emmanouil G Barbounis, Aristidis M Tsatsakis
In this study, we focused on the validation of a method for the simultaneous detection and quantification of cannabinoids, cocaine and opiates in hair as well as on the distribution of the drugs deposition in hair collected from different anatomical body sites. The proposed analytical procedure was validated for various parameters such as selectivity, linearity, limit of quantification, precision, accuracy, matrix effect and recovery. Four hundred and eighty-one samples were collected during 2010-2015 from 231 drug abusers...
December 15, 2016: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/27965371/metabolic-signaling-functions-of-er-mitochondria-contact-sites-role-in-metabolic-diseases
#16
Emily Tubbs, Jennifer Rieusset
Beyond the maintenance of cellular homeostasis and the determination of cell fate, ER-mitochondria contact sites, defined as mitochondria-associated membranes (MAM), start to emerge as an important signaling hub that integrates nutrient and hormonal stimuli and adapts cellular metabolism. Here, we summarize the established structural and functional features of MAM, and mainly focus on the latest breakthroughs highlighting a crucial role of organelle crosstalk in the control of metabolic homeostasis. Lastly, we discuss recent studies that have revealed the importance of MAM in metabolic diseases, but also in other pathologies with disrupted metabolism, shedding light on potential common molecular mechanisms and leading hopefully to novel treatment strategies...
December 13, 2016: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/27939124/household-consumption-of-thiamin-fortified-fish-sauce-increases-erythrocyte-thiamin-concentrations-among-rural-cambodian-women-and-their-children-younger-than-5-years-of-age-a-randomized-controlled-efficacy-trial
#17
Kyly C Whitfield, Crystal D Karakochuk, Hou Kroeun, Ly Sokhoing, Benny B Chan, Mam Borath, Prak Sophonneary, Kirsten Moore, Jeffery K T Tong, Judy McLean, Aminuzzaman Talukder, Larry D Lynd, Eunice C Y Li-Chan, David D Kitts, Tim J Green
OBJECTIVES: To assess whether ad libitum consumption of thiamin-fortified fish sauce over 6 months yields higher erythrocyte thiamin diphosphate concentrations (eTDP) among women of childbearing age and their children aged 12-59 months compared with control sauce containing no thiamin. STUDY DESIGN: In this double-blind, randomized controlled efficacy trial, 276 nonpregnant, nonlactating women (18-45 years of age) and their families in Prey Veng, Cambodia, were randomized to receive 1 of 3 fish sauce formulations: low thiamin concentration (low, 2 g/L), high thiamin concentration (high, 8 g/L), or a control (no thiamin) fish sauce...
December 6, 2016: Journal of Pediatrics
https://www.readbyqxmd.com/read/27927860/prediction-of-outcome-from-adult-bacterial-meningitis-in-a-high-hiv-seroprevalence-resource-poor-setting-using-the-malawi-adult-meningitis-score-mams
#18
Emma C Wall, Mavuto Mukaka, Matthew Scarborough, Katherine Ma Ajdukiewicz, Katharine E Cartwright, Mulinda Nyirenda, Brigitte Denis, Theresa J Allain, Brian Faragher, David G Lalloo, Robert S Heyderman
: Acute bacterial meningitis (ABM) in adults residing in resource-poor countries is associated with mortality rates in excess of 50%. To improve outcome, interventional trials and standardised clinical algorithms are urgently required. To optimise these processes we developed and validated an outcome prediction tool to identify ABM patients at greatest risk of death. METHODS: We derived a nomogram using mortality predictors derived from a logistic regression model of a discovery database of adult Malawian ABM patients (n=523, 65% CSF culture positive)...
December 7, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/27924364/metabolic-characterization-of-1-5-fluoropentyl-1h-indol-3-yl-4-methyl-1-naphthalenyl-methanone-mam-2201-using-human-liver-microsomes-and-cdna-overexpressed-cytochrome-p450-enzymes
#19
Tae Yeon Kong, Ju-Hyun Kim, Won Gu Choi, Joo Young Lee, Hee Seung Kim, Jin Young Kim, Moon Kyo In, Hye Suk Lee
MAM-2201 is a synthetic cannabinoid that is increasingly found in recreational drug abusers and cases of severe intoxication. Thus, characterization of the metabolic pathways of MAM-2201 is necessary to predict individual pharmacokinetics and toxicity differences, and to avoid toxic drug-drug interactions. Collectively, 19 phase 1 metabolites of MAM-2201 were identified using liquid chromatography-Orbitrap mass spectrometry following human liver microsomal incubations in the presence of NADPH: 7 hydroxy-MAM-2201 (M1-M7), 4 dihydroxy-MAM-2201 (M8-M11), dihydrodiol-MAM-2201 (M12), N-(5-hydroxypentyl)-MAM-2201 (M13), hydroxy-M13 (M14), N-dealkyl-MAM-2201 (M15), 2 hydroxy-M15 (M16, M17), MAM-2201 N-pentanoic acid (M18), and hydroxy-M18 (M19)...
December 6, 2016: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/27911326/localization-and-processing-of%C3%A2-the%C3%A2-amyloid-%C3%AE-protein-precursor-in%C3%A2-mitochondria-associated-membranes
#20
Dolores Del Prete, Jan M Suski, Bénédicte Oulès, Delphine Debayle, Anne Sophie Gay, Sandra Lacas-Gervais, Renaud Bussiere, Charlotte Bauer, Paolo Pinton, Patrizia Paterlini-Bréchot, Mariusz R Wieckowski, Frédéric Checler, Mounia Chami
Alteration of mitochondria-associated membranes (MAMs) has been proposed to contribute to the pathogenesis of Alzheimer's disease (AD). We studied herein the subcellular distribution, the processing, and the protein interactome of the amyloid-β protein precursor (AβPP) and its proteolytic products in MAMs. We reveal that AβPP and its catabolites are present in MAMs in cellular models overexpressing wild type AβPP or AβPP harboring the double Swedish or London familial AD mutations, and in brains of transgenic mice model of AD...
2017: Journal of Alzheimer's Disease: JAD
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