The association between histamine 2 receptor antagonist use and Clostridium difficile infection: a systematic review and meta-analysis.

Background Clostridium difficile infection (CDI) is a major health problem. Epidemiological evidence suggests that there is an association between acid suppression therapy and development of CDI. Purpose We sought to systematically review the literature that examined the association between histamine 2 receptor antagonists (H2RAs) and CDI. Data source We searched Medline, Current Contents, Embase, ISI Web of Science and Elsevier Scopus from 1990 to 2012 for all analytical studies that examined the association between H2RAs and CDI. Study selection Two authors independently reviewed the studies for eligibility. Data extraction Data about studies characteristics, adjusted effect estimates and quality were extracted. Data synthesis Thirty-five observations from 33 eligible studies that included 201834 participants were analyzed. Studies were performed in 6 countries and nine of them were multicenter. Most studies did not specify the type or duration of H2RAs therapy. The pooled effect estimate was 1.44, 95% CI (1.22–1.7), I2 = 70.5%. This association was consistent across different subgroups (by study design and country) and there was no evidence of publication bias. The pooled effect estimate for high quality studies was 1.39 (1.15–1.68), I2 = 72.3%. Meta-regression analysis of 10 study-level variables did not identify sources of heterogeneity. In a speculative analysis, the number needed to harm (NNH) with H2RAs at 14 days after hospital admission in patients receiving antibiotics or not was 58, 95% CI (37, 115) and 425, 95% CI (267, 848), respectively. For the general population, the NNH at 1 year was 4549, 95% CI (2860, 9097). Conclusion In this rigorous systematic review and meta-analysis, we observed an association between H2RAs and CDI. The absolute risk of CDI associated with H2RAs is highest in hospitalized patients receiving antibiotics

Galactic and Extragalactic Samples of Supernova Remnants: How They Are Identified and What They Tell Us

Supernova remnants (SNRs) arise from the interaction between the ejecta of a supernova (SN) explosion and the surrounding circumstellar and interstellar medium. Some SNRs, mostly nearby SNRs, can be studied in great detail. However, to understand SNRs as a whole, large samples of SNRs must be assembled and studied. Here, we describe the radio, optical, and X-ray techniques which have been used to identify and characterize almost 300 Galactic SNRs and more than 1200 extragalactic SNRs. We then discuss which types of SNRs are being found and which are not. We examine the degree to which the luminosity functions, surface-brightness distributions and multi-wavelength comparisons of the samples can be interpreted to determine the class properties of SNRs and describe efforts to establish the type of SN explosion associated with a SNR. We conclude that in order to better understand the class properties of SNRs, it is more important to study (and obtain additional data on) the SNRs in galaxies with extant samples at multiple wavelength bands than it is to obtain samples of SNRs in other galaxiesComment: Final 2016 draft of a chapter in "Handbook of Supernovae" edited by Athem W. Alsabti and Paul Murdin. Final version available at https://doi.org/10.1007/978-3-319-20794-0_90-

The four qualities of life: Ordering concepts and measures of the good life

The terms 'quality-of-life', 'wellbeing' and 'happiness' denote different meanings; sometimes they are used as an umbrella term for all of value, and the other times to denote special merits. This paper is about the specific meanings of the terms. It proposes a classification based on two bi-partitions; between life 'chances' and life 'results', and between 'outer' and 'inner' qualities. Together these dichotomies imply four qualities of life: 1) livability of the environment, 2) life-ability of the individual, 3) external utility of life and 4) inner appreciation of life. This fourfold matrix is applied in three ways: firstly to place related notions and alternative classifications, secondly to explore substantive meanings in various measures for quality of life and thirdly to find out whether quality-of-life can be measured comprehensively. This last question is answered in the negative. Current sum-scores make little sense. The most inclusive summary measure is still how long and happily people live

Non-minimal coupling of the Higgs boson to curvature in an inflationary universe

In the absence of new physics around 10^10 GeV, the electroweak vacuum is at best metastable. This represents a major challenge for high scale in ationary models as, during the early rapid expansion of the universe, it seems difficult to understand how the Higgs vacuum would not decay to the true lower vacuum of the theory with catas- trophic consequences if inflation took place at a scale above 10^10 GeV. In this paper we show that the non-minimal coupling of the Higgs boson to curvature could solve this problem by generating a direct coupling of the Higgs boson to the inflationary potential thereby stabilizing the electroweak vacuum. For specific values of the Higgs field initial condition and of its non-minimal coupling, inflation can drive the Higgs field to the electroweak vacuum quickly during inflation

Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

Chemical and Physical Environmental Conditions Underneath Mat- and Canopy-Forming Macroalgae, and Their Effects on Understorey Corals

Disturbed coral reefs are often dominated by dense mat- or canopy-forming assemblages of macroalgae. This study investigated how such dense macroalgal assemblages change the chemical and physical microenvironment for understorey corals, and how the altered environmental conditions affect the physiological performance of corals. Field measurements were conducted on macroalgal-dominated inshore reefs in the Great Barrier Reef in quadrats with macroalgal biomass ranging from 235 to 1029 g DW m−2 dry weight. Underneath mat-forming assemblages, the mean concentration of dissolved oxygen was reduced by 26% and irradiance by 96% compared with conditions above the mat, while concentrations of dissolved organic carbon and soluble reactive phosphorous increased by 26% and 267%, respectively. The difference was significant but less pronounced under canopy-forming assemblages. Dissolved oxygen declined and dissolved inorganic carbon and alkalinity increased with increasing algal biomass underneath mat-forming but not under canopy-forming assemblages. The responses of corals to conditions similar to those found underneath algal assemblages were investigated in an aquarium experiment. Coral nubbins of the species Acropora millepora showed reduced photosynthetic yields and increased RNA/DNA ratios when exposed to conditions simulating those underneath assemblages (pre-incubating seawater with macroalgae, and shading). The magnitude of these stress responses increased with increasing proportion of pre-incubated algal water. Our study shows that mat-forming and, to a lesser extent, canopy-forming macroalgal assemblages alter the physical and chemical microenvironment sufficiently to directly and detrimentally affect the metabolism of corals, potentially impeding reef recovery from algal to coral-dominated states after disturbance. Macroalgal dominance on coral reefs therefore simultaneously represents a consequence and cause of coral reef degradation

Extraction and sensitive detection of toxins A and B from the human pathogen Clostridium difficile in 40 seconds using microwave-accelerated metal-enhanced fluorescence.

Clostridium difficile is the primary cause of antibiotic associated diarrhea in humans and is a significant cause of morbidity and mortality. Thus the rapid and accurate identification of this pathogen in clinical samples, such as feces, is a key step in reducing the devastating impact of this disease. The bacterium produces two toxins, A and B, which are thought to be responsible for the majority of the pathology associated with the disease, although the relative contribution of each is currently a subject of debate. For this reason we have developed a rapid detection assay based on microwave-accelerated metal-enhanced fluorescence which is capable of detecting the presence of 10 bacteria in unprocessed human feces within 40 seconds. These promising results suggest that this prototype biosensor has the potential to be developed into a rapid, point of care, real time diagnostic assay for C. difficile

TDP-43 induces p53-mediated cell death of cortical progenitors and immature neurons

TAR DNA-binding protein 43 (TDP-43) is a key player in neurodegenerative diseases including frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Accumulation of TDP-43 is associated with neuronal death in the brain. How increased and disease-causing mutant forms of TDP-43 induce cell death remains unclear. Here we addressed the role of TDP-43 during neural development and show that reduced TDP-43 causes defects in neural stem/progenitor cell proliferation but not cell death. However, overexpression of wild type and TDP-43A315T proteins induce p53-dependent apoptosis of neural stem/progenitors and human induced pluripotent cell (iPS)-derived immature cortical neurons. We show that TDP-43 induces expression of the proapoptotic BH3-only genes Bbc3 and Bax, and that p53 inhibition rescues TDP-43 induced cell death of embryonic mouse, and human cortical neurons, including those derived from TDP-43G298S ALS patient iPS cells. Hence, an increase in wild type and mutant TDP-43 induces p53-dependent cell death in neural progenitors developing neurons and this can be rescued. These findings may have important implications for accumulated or mutant TDP-43 induced neurodegenerative diseases

Lung function, asthma symptoms, and quality of life for children in public housing in Boston: a case-series analysis

BACKGROUND: Children in urban public housing are at high risk for asthma, given elevated environmental and social exposures and suboptimal medical care. For a multifactorial disease like asthma, design of intervention studies can be influenced by the relative prevalence of key risk factors. To better understand risk factors for asthma morbidity in the context of an environmental intervention study, we conducted a detailed baseline evaluation of 78 children (aged 4–17 years) from three public housing developments in Boston. METHODS: Asthmatic children and their caregivers were recruited between April 2002 and January 2003. We conducted intake interviews that captured a detailed family and medical history, including questions regarding asthma symptom severity, access to health care, medication usage, and psychological stress. Quality of life was evaluated for both the child and caregiver with an asthma-specific scale. Pulmonary function was measured with a portable spirometer, and allergy testing for common indoor and outdoor allergens was conducted with skin testing using the prick puncture method. Exploratory linear and logistic regression models evaluating predictors of respiratory symptoms, quality of life, and pulmonary function were conducted using SAS. RESULTS: We found high rates of obesity (56%) and allergies to indoor contaminants such as cockroaches (59%) and dust mites (59%). Only 36% of children with persistent asthma reported being prescribed any daily controller medication, and most did not have an asthma action plan or a peak flow meter. One-time lung function measures were poorly correlated with respiratory symptoms or quality of life, which were significantly correlated with each other. In multivariate regression models, household size, body mass index, and environmental tobacco smoke exposure were positively associated with respiratory symptom severity (p < 0.10). Symptom severity was negatively associated with asthma-related quality of life for the child and the caregiver, with caregiver (but not child) quality of life significantly influenced by caregiver stress and whether the child was in the intensive care unit at birth. CONCLUSION: Given the elevated prevalence of multiple risk factors, coordinated improvements in the social environment, the built environment, and in medical management would likely yield the greatest health benefits in this high-risk population

Thioredoxin Glutathione Reductase as a Novel Drug Target: Evidence from Schistosoma japonicum

Background: Schistosomiasis remains a major public health concern affecting billions of people around the world. Currently, praziquantel is the only drug of choice for treatment of human schistosomiasis. The emergence of drug resistance to praziquantel in schistosomes makes the development of novel drugs an urgent task. Thioredoxin glutathione reductase (TGR) enzymes in Schistosoma mansoni and some other platyhelminths have been identified as alternative targets. The present study was designed to confirm the existense and the potential value of TGR as a target for development of novel antischistosomal agents in Schistosoma japonicum, a platyhelminth endemic in Asia. Methods and Findings: After cloning the S. japonicum TGR (SjTGR) gene, the recombinant SjTGR selenoprotein was purified and characterized in enzymatic assays as a multifunctional enzyme with thioredoxin reductase (TrxR), glutathione reductase (GR) and glutaredoxin (Grx) activities. Immunological and bioinformatic analyses confirmed that instead of having separate TrxR and GR proteins in mammalian, S. japonicum only encodes TGR, which performs the functions of both enzymes and plays a critical role in maintaining the redox balance in this parasite. These results were in good agreement with previous findings in Schistosoma mansoni and some other platyhelminths. Auranofin, a known inhibitor against TGR, caused fatal toxicity in S. japonicum adult worms in vitro and reduced worm and egg burdens in S. japonicum infected mice. Conclusions: Collectively, our study confirms that a multifunctional enzyme SjTGR selenoprotein, instead of separate Trx