A bayesian meta-analysis of multiple treatment comparisons of systemic regimens for advanced pancreatic cancer

© 2014 Chan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: For advanced pancreatic cancer, many regimens have been compared with gemcitabine (G) as the standard arm in randomized controlled trials. Few regimens have been directly compared with each other in randomized controlled trials and the relative efficacy and safety among them remains unclear

Effects of mobile learning in medical education: a counterfactual vvaluation

The aim of this research is to contribute to the general system education providing new insights and resources. This study performs a quasi-experimental study at University of Salamanca with 30 students to compare results between using an anatomic app for learning and the formal traditional method conducted by a teacher. The findings of the investigation suggest that the performance of learners using mobile apps is statistical better than the students using the traditional method. However, mobile devices should be considered as an additional tool to complement the teachers’ explanation and it is necessary to overcome different barriers and challenges to adopt these pedagogical methods at University

Relationship between Environmental Phthalate Exposure and the Intelligence of School-Age Children

BACKGROUND: Concern over phthalates has emerged because of their potential toxicity to humans. OBJECTIVE: We investigated the relationship between the urinary concentrations of phthalate metabolites and children`s intellectual functioning. METHODS: This study enrolled 667 children at nine elementary schools in five South Korean cities. A cross-sectional examination of urine phthalate concentrations was performed, and scores on neuro-psychological tests were obtained from both the children and their mothers. RESULTS: We measured mono-2-ethylhexyl phthalate (MEHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), both metabolites of di(2-ethylhexyl)phthalate (DEHP), and mono-n-butyl phthalate (MBP), a metabolite of dibutyl phthalate (DBP), in urine samples. The geometric mean (ln) concentrations of MEHP, MEOHP, and MBP were 21.3 mu g/L [geometric SD (GSD) = 2.2 mu g/L; range, 0.5-445.4], 18.0 mu g/L (GSD = 2.4; range, 0.07-291.1), and 48.9 mu g/L (GSD = 2.2; range, 2.1-1645.5), respectively. After adjusting for demographic and developmental covariates, the Full Scale IQ and Verbal IQ scores were negatively associated with DEHP metabolites but not with DBP metabolites. We also found a significant negative relationship between the urine concentrations of the metabolites of DEHP and DBP and children`s vocabulary subscores. After controlling for maternal IQ, a significant inverse relationship between DEHP metabolites and vocabulary subscale score remained. Among boys, we found a negative association between increasing MEHP phthalate concentrations and the sum of DEHP metabolite concentrations and Wechsler Intelligence Scale for Children vocabulary score; however, among girls, we found no significant association between these variables. CONCLUSION: Controlling for maternal IQ and other covariates, the results show an inverse relationship between phthalate metabolites and IQ scores; however, given the limitations in cross-sectional epidemiology, prospective studies are needed to fully explore these associations.This work was funded by the Eco-Technopia 21 project of Korea Institute of Environmental Science and Technology (091-081-059).Cho SC, 2010, J CHILD PSYCHOL PSYC, V51, P1050, DOI 10.1111/j.1469-7610.2010.02250.xKim BN, 2009, BIOL PSYCHIAT, V66, P958, DOI 10.1016/j.biopsych.2009.07.034Tanida T, 2009, TOXICOL LETT, V189, P40, DOI 10.1016/j.toxlet.2009.04.005Ghisari M, 2009, TOXICOL LETT, V189, P67, DOI 10.1016/j.toxlet.2009.05.004Barnett JH, 2009, AM J PSYCHIAT, V166, P909, DOI 10.1176/appi.ajp.2009.08081251Kim Y, 2009, NEUROTOXICOLOGY, V30, P564, DOI 10.1016/j.neuro.2009.03.012Engel SM, 2009, NEUROTOXICOLOGY, V30, P522, DOI 10.1016/j.neuro.2009.04.001Kamrin MA, 2009, J TOXICOL ENV HEAL B, V12, P157, DOI 10.1080/10937400902729226Brown JS, 2009, SCHIZOPHRENIA BULL, V35, P256, DOI 10.1093/schbul/sbm147Bellinger DC, 2008, NEUROTOXICOLOGY, V29, P828, DOI 10.1016/j.neuro.2008.04.005Wolff MS, 2008, ENVIRON HEALTH PERSP, V116, P1092, DOI 10.1289/ehp.11007van Neerven S, 2008, PROG NEUROBIOL, V85, P433, DOI 10.1016/j.pneurobio.2008.04.006Hatch EE, 2008, ENVIRON HEALTH-GLOB, V7, DOI 10.1186/1476-069X-7-27Zevalkink J, 2008, J GENET PSYCHOL, V169, P72Kolarik B, 2008, ENVIRON HEALTH PERSP, V116, P98, DOI 10.1289/ehp.10498SATHYANARAYANA S, 2008, CURR PROBL PEDIAT AD, V38, P34KHO YL, 2008, J ENV HLTH SCI, V34, P271Huang PC, 2007, HUM REPROD, V22, P2715, DOI 10.1093/humrep/dem205Janjua NR, 2007, ENVIRON SCI TECHNOL, V41, P5564, DOI 10.1021/es0628755Meeker JD, 2007, ENVIRON HEALTH PERSP, V115, P1029, DOI 10.1289/ehp.9852Fromme H, 2007, INT J HYG ENVIR HEAL, V210, P21, DOI 10.1016/j.ijheh.2006.09.005Xu Y, 2007, ARCH TOXICOL, V81, P57, DOI 10.1007/s00204-006-0143-8Pereira C, 2007, ACTA HISTOCHEM, V109, P29, DOI 10.1016/j.acthis.2006.09.008Hauser R, 2006, EPIDEMIOLOGY, V17, P682, DOI 10.1097/01.ede.0000235996.89953.d7Zhu DF, 2006, BRAIN, V129, P2923, DOI 10.1093/brain/awl215Andrade AJM, 2006, TOXICOLOGY, V227, P185, DOI 10.1016/j.tox.2006.07.022Lottrup G, 2006, INT J ANDROL, V29, P172, DOI 10.1111/j.1365-2605.2005.00642.xBreous E, 2005, MOL CELL ENDOCRINOL, V244, P75, DOI 10.1016/j.mce.2005.06.009Wenzel A, 2005, MOL CELL ENDOCRINOL, V244, P63, DOI 10.1016/j.mce.2005.02.008Kato K, 2005, ANAL CHEM, V77, P2985, DOI 10.1021/ac0481248Tanaka T, 2005, FOOD CHEM TOXICOL, V43, P581, DOI 10.1016/j.fct.2005.01.001Duty SM, 2005, HUM REPROD, V20, P604, DOI 10.1093/humrep/deh656Kota BP, 2005, PHARMACOL RES, V51, P85, DOI 10.1016/j.phrs.2004.07.012Hays T, 2005, CARCINOGENESIS, V26, P219, DOI 10.1093/carcin/bgh285Hauser R, 2004, ENVIRON HEALTH PERSP, V112, P1734, DOI 10.1289/ehp.7212Bornehag CG, 2004, ENVIRON HEALTH PERSP, V112, P1393, DOI 10.1289/ehp.7187Ishido M, 2004, J NEUROCHEM, V91, P69, DOI 10.1111/j.1471-4159.2004.02696.xMink PJ, 2004, EPIDEMIOLOGY, V15, P385, DOI 10.1097/01.ede.0000128402.86336.7eBellinger DC, 2004, EPIDEMIOLOGY, V15, P383, DOI 10.1097/01.ede.0000129525.15064.a4Shea KM, 2003, PEDIATRICS, V111, P1467Tanaka T, 2002, FOOD CHEM TOXICOL, V40, P1499, DOI 10.1016/S0278-6915(02)00073-XHoppin JA, 2002, ENVIRON HEALTH PERSP, V110, P515SATTLER JM, 2001, ASSESSMENT CHILDRENRice D, 2000, ENVIRON HEALTH PERSP, V108, P511Bellinger DC, 2000, NEUROTOXICOL TERATOL, V22, P133LIM YR, 2000, KOR J CLIN PSYCHOL, V19, P563Braissant O, 1998, ENDOCRINOLOGY, V139, P2748Peters JM, 1997, CARCINOGENESIS, V18, P2029Baldini IM, 1997, PROG NEURO-PSYCHOPH, V21, P925Roberts RA, 1997, FUND APPL TOXICOL, V38, P107PARK KS, 1996, DEV KEDI WISC INDIVIMONZANI F, 1993, CLIN INVESTIGATOR, V71, P367SILVERSTEIN AB, 1990, J CLIN PSYCHOL, V46, P333HINTON RH, 1986, ENVIRON HEALTH PERSP, V70, P195KIM MK, 1986, SEOUL J PSYCHIAT, V11, P194KAUFMAN AS, 1976, CONTEMP EDUC PSYCHOL, V1, P1801

Microguards and micromessengers of the genome

The regulation of gene expression is of fundamental importance to maintain organismal function and integrity and requires a multifaceted and highly ordered sequence of events. The cyclic nature of gene expression is known as ‘transcription dynamics’. Disruption or perturbation of these dynamics can result in significant fitness costs arising from genome instability, accelerated ageing and disease. We review recent research that supports the idea that an important new role for small RNAs, particularly microRNAs (miRNAs), is in protecting the genome against short-term transcriptional fluctuations, in a process we term ‘microguarding’. An additional emerging role for miRNAs is as ‘micromessengers’—through alteration of gene expression in target cells to which they are trafficked within microvesicles. We describe the scant but emerging evidence that miRNAs can be moved between different cells, individuals and even species, to exert biologically significant responses. With these two new roles, miRNAs have the potential to protect against deleterious gene expression variation from perturbation and to themselves perturb the expression of genes in target cells. These interactions between cells will frequently be subject to conflicts of interest when they occur between unrelated cells that lack a coincidence of fitness interests. Hence, there is the potential for miRNAs to represent both a means to resolve conflicts of interest, as well as instigate them. We conclude by exploring this conflict hypothesis, by describing some of the initial evidence consistent with it and proposing new ideas for future research into this exciting topic

Nanoparticulate TiO2-promoted PtRu/C catalyst for methanol oxidation: TiO2 nanoparticles promoted PtRu/C catalyst for MOR

To improve the electrocatalytic properties of PtRu/C in methanol electrooxidation, nanoparticulate TiO2-promoted PtRu/C catalysts were prepared by directly mixing TiO2 nanoparticles with PtRu/C. Using cyclic voltammetry, it was found that the addition of 10 wt% TiO2 nanoparticles can effectively improve the electrocatalytic activity and stability of the catalyst during methanol electro-oxidation. The value of the apparent activation energy (Ea) for TiO2-PtRu/C was lower than that for pure PtRu/C at a potential range from 0.45 to 0.60 V. A synergistic effect between PtRu and TiO2 nanoparticles is likely to facilitate the removal of CO-like intermediates from the surface of PtRu catalyst and reduce the poisoning of the PtRu catalysts during methanol electrooxidation. Therefore, we conclude that the direct introduction of TiO2 nanoparticles into PtRu/ C catalysts offers an improved facile method to enhance the electrocatalytic performance of PtRu/C catalyst in methanol electrooxidation.Web of Scienc

Spectroscopic evidence for an all-ferrous [4Fe–4S]0 cluster in the superreduced activator of 2-hydroxyglutaryl-CoA dehydratase from Acidaminococcus fermentans

The key enzyme of the fermentation of glutamate by Acidaminococcus fermentans, 2-hydroxyglutarylcoenzyme A dehydratase, catalyzes the reversible syn-elimination of water from (R)-2-hydroxyglutaryl-coenzyme A, resulting in (E)-glutaconylcoenzyme A. The dehydratase system consists of two oxygen-sensitive protein components, the activator (HgdC) and the actual dehydratase (HgdAB). Previous biochemical and spectroscopic studies revealed that the reduced [4Fe–4S]+ cluster containing activator transfers one electron to the dehydratase driven by ATP hydrolysis, which activates the enzyme. With a tenfold excess of titanium(III) citrate at pH 8.0 the activator can be further reduced, yielding about 50% of a superreduced [4Fe–4S]0 cluster in the all-ferrous state. This is inferred from the appearance of a new Mössbauer spectrum with parameters δ = 0.65 mm/s and ΔEQ = 1.51–2.19 mm/s at 140 K, which are typical of Fe(II)S4 sites. Parallel-mode electron paramagnetic resonance (EPR) spectroscopy performed at temperatures between 3 and 20 K showed two sharp signals at g = 16 and 12, indicating an integer-spin system. The X-band EPR spectra and magnetic Mössbauer spectra could be consistently simulated by adopting a total spin St = 4 for the all-ferrous cluster with weak zero-field splitting parameters D = −0.66 cm−1 and E/D = 0.17. The superreduced cluster has apparent spectroscopic similarities with the corresponding [4Fe–4S]0 cluster described for the nitrogenase Fe-protein, but in detail their properties differ. While the all-ferrous Fe-protein is capable of transferring electrons to the MoFe-protein for dinitrogen reduction, a similar physiological role is elusive for the superreduced activator. This finding supports our model that only one-electron transfer steps are involved in dehydratase catalysis. Nevertheless we discuss a common basic mechanism of the two diverse systems, which are so far the only described examples of the all-ferrous [4Fe–4S]0 cluster found in biology

Chronic multichannel neural recordings from soft regenerative microchannel electrodes during gait

Reliably interfacing a nerve with an electrode array is one of the approaches to restore motor and sensory functions after an injury to the peripheral nerve. Accomplishing this with current technologies is challenging as the electrode-neuron interface often degrades over time, and surrounding myoelectric signals contaminate the neuro-signals in awake, moving animals. The purpose of this study was to evaluate the potential of microchannel electrode implants to monitor over time and in freely moving animals, neural activity from regenerating nerves. We designed and fabricated implants with silicone rubber and elastic thin-film metallization. Each implant carries an eight-by-twelve matrix of parallel microchannels (of 120\u2009 7\u2009110\u2009\u3bcm2 cross-section and 4\u2009mm length) and gold thin-film electrodes embedded in the floor of ten of the microchannels. After sterilization, the soft, multi-lumen electrode implant is sutured between the stumps of the sciatic nerve. Over a period of three months and in four rats, the microchannel electrodes recorded spike activity from the regenerating sciatic nerve. Histology indicates mini-nerves formed of axons and supporting cells regenerate robustly in the implants. Analysis of the recorded spikes and gait kinematics over the ten-week period suggests firing patterns collected with the microchannel electrode implant can be associated with different phases of gait

Human disc cells in monolayer vs 3D culture: cell shape, division and matrix formation

BACKGROUND: The relationship between cell shape, proliferation, and extracellular matrix (ECM) production, important aspects of cell behavior, is examined in a little-studied cell type, the human annulus cell from the intervertebral disc, during monolayer vs three-dimensional (3D) culture. RESULTS: Three experimental studies showed that cells respond specifically to culture microenvironments by changes in cell shape, mitosis and ECM production: 1) Cell passages showed extensive immunohistochemical evidence of Type I and II collagens only in 3D culture. Chondroitin sulfate and keratan sulfate were abundant in both monolayer and 3D cultures. 2) Cells showed significantly greater proliferation in monolayer in the presence of platelet-derived growth factor compared to cells in 3D. 3) Cells on Matrigel™-coated monolayer substrates became rounded and formed nodular colonies, a finding absent during monolayer growth. CONCLUSIONS: The cell's in vivo interactions with the ECM can regulate shape, gene expression and other cell functions. The shape of the annulus cell changes markedly during life: the young, healthy disc contains spindle shaped cells and abundant collagen. With aging and degeneration, many cells assume a strikingly different appearance, become rounded and are surrounded by unusual accumulations of ECM products. In vitro manipulation of disc cells provides an experimental window for testing how disc cells from given individuals respond when they are grown in environments which direct cells to have either spindle- or rounded-shapes. In vitro assessment of the response of such cells to platelet-derived growth factor and to Matrigel™ showed a continued influence of cell shape even in the presence of a growth factor stimulus. These findings contribute new information to the important issue of the influence of cell shape on cell behavior

Distinct Functions of Period2 and Period3 in the Mouse Circadian System Revealed by In Vitro Analysis

The mammalian circadian system, which is composed of a master pacemaker in the suprachiasmatic nuclei (SCN) as well as other oscillators in the brain and peripheral tissues, controls daily rhythms of behavior and physiology. Lesions of the SCN abolish circadian rhythms of locomotor activity and transplants of fetal SCN tissue restore rhythmic behavior with the periodicity of the donor's genotype, suggesting that the SCN determines the period of the circadian behavioral rhythm. According to the model of timekeeping in the SCN, the Period (Per) genes are important elements of the transcriptional/translational feedback loops that generate the endogenous circadian rhythm. Previous studies have investigated the functions of the Per genes by examining locomotor activity in mice lacking functional PERIOD proteins. Variable behavioral phenotypes were observed depending on the line and genetic background of the mice. In the current study we assessed both wheel-running activity and Per1-promoter-driven luciferase expression (Per1-luc) in cultured SCN, pituitary, and lung explants from Per2−/− and Per3−/− mice congenic with the C57BL/6J strain. We found that the Per2−/− phenotype is enhanced in vitro compared to in vivo, such that the period of Per1-luc expression in Per2−/− SCN explants is 1.5 hours shorter than in Per2+/+ SCN, while the free-running period of wheel-running activity is only 11 minutes shorter in Per2−/− compared to Per2+/+ mice. In contrast, circadian rhythms in SCN explants from Per3−/− mice do not differ from Per3+/+ mice. Instead, the period and phase of Per1-luc expression are significantly altered in Per3−/− pituitary and lung explants compared to Per3+/+ mice. Taken together these data suggest that the function of each Per gene may differ between tissues. Per2 appears to be important for period determination in the SCN, while Per3 participates in timekeeping in the pituitary and lung