Risk of Stillbirth in the Relation to Water Disinfection By-Products: A Population-Based Case-Control Study in Taiwan

Background: Few epidemiological studies that have assessed the relation between water disinfection by-products (DBPs) and the risk of stillbirth provide inconsistent results. The objective was to assess the relation between exposure to water disinfection by-products and the risk of stillbirth. Methods: We conducted a population-based case-control study of 3,289 cases of stillbirth and a random sample of 32,890 control subjects from 396,049 Taiwanese newborns in 2001–2003 using information from the Birth Registry and Waterworks Registry in Taiwan. We compared the risk of stillbirth in four disinfection by-product exposure categories based on the levels of total trihalomethanes (TTHMs) representing high (TTHMs 20+ mg/L), medium (TTHMs 10–19 mg/L), low exposure (TTHMs 5–9 mg/L), and 0–4 mg/L as the reference category. In addition, we conducted a meta-analysis of the results from the present and 5 previous studies focusing on stillbirth. Findings: In logistic regression analysis adjusting for gender, maternal age, plurality, conception of season and population density of the municipality where the mother lived during pregnancy, the odds ratio (OR) for stillbirth was 1.10 (95 % CI 1.00–1.21) for medium exposure and 1.06 (95 % 0.96–1.17) for high exposure compared to reference category. In the metaanalysis, the summary odds ratio for stillbirth (1.11, 95 % CI: 1.03, 1.19) was consistently elevated. Conclusions: The present study is consistent with the hypothesis that the risk of stillbirth is related to prenatal exposure t

Photon Reabsorption in Mixed CsPbCl3_{3}:CsPbI3_{3} Perovskite Nanocrystal Films for Light-Emitting Diodes

Cesium lead halide nanocrystals, CsPbX$_{3}$ (X = Cl, Br, I), exhibit photoluminescence quantum efficiencies approaching 100% without the core-shell structures usually used in conventional semiconductor nanocrystals. These high photoluminescence efficiencies make these crystals ideal candidates for light-emitting diodes (LEDs). However, because of the large surface area to volume ratio, halogen exchange between perovskite nanocrystals of different compositions occurs rapidly, which is one of the limiting factors for white-light applications requiring a mixture of different crystal compositions to achieve a broad emission spectrum. Here, we use mixtures of chloride and iodide CsPbX$_{3}$ (X = Cl, I) perovskite nanocrystals where anion exchange is significantly reduced. We investigate samples containing mixtures of perovskite nanocrystals with different compositions and study the resulting optical and electrical interactions. We report excitation transfer from CsPbCl$_{3}$ to CsPbI$_{3}$ in solution and within a poly(methyl methacrylate) matrix via photon reabsorption, which also occurs in electrically excited crystals in bulk heterojunction LEDs.N.J.L.K.D. thanks the Cambridge Commonwealth European and International Trust, Cambridge Australian Scholarships, and Charles K. Allen for financial support. M.T. thanks the Gates Cambridge Trust, EPSRC, and the Winton Programme for the Physics of Sustainability for financial support. J.R. thanks the Cambridge Commonwealth European and International Trust, EPSRC and the Winton Programme for the Physics of Sustainability for financial support. E.P.B. thanks the EPSRC Centre for Doctoral Training: New and Sustainable Photovoltaics. R.D.L. thanks the EPSRC for funding. S.M.M. acknowledges competitive research funding from King Abdullah University of Science and Technology (KAUST). F.W.R.R. gratefully thanks financial support from CNPq Grant No. 246050/2012-8. F.W.R.R. and C.D. acknowledge funding from the ERC under Grant No. 259619 PHOTO-EM. C.D. acknowledges financial support from the EU under Grant No. 312483 ESTEEM2. F.D. is thankful for the Herchel Smith fellowship. This work was supported by the EPSRC (Grant Nos. EP/M005143/1, EP/G060738/1, and EP/G037221/1)

A randomised controlled trial linking mental health inpatients to community smoking cessation supports: A study protocol

<p>Abstract</p> <p>Background</p> <p>Mental health inpatients smoke at higher rates than the general population and are disproportionately affected by tobacco dependence. Despite the advent of smoke free policies within mental health hospitals, limited systems are in place to support a cessation attempt post hospitalisation, and international evidence suggests that most smokers return to pre-admission smoking levels following discharge. This protocol describes a randomised controlled trial that will test the feasibility, acceptability and efficacy of linking inpatient smoking care with ongoing community cessation support for smokers with a mental illness.</p> <p>Methods/Design</p> <p>This study will be conducted as a randomised controlled trial. 200 smokers with an acute mental illness will be recruited from a large inpatient mental health facility. Participants will complete a baseline survey and will be randomised to either a multimodal smoking cessation intervention or provided with hospital smoking care only. Randomisation will be stratified by diagnosis (psychotic, non-psychotic). Intervention participants will be provided with a brief motivational interview in the inpatient setting and options of ongoing smoking cessation support post discharge: nicotine replacement therapy (NRT); referral to Quitline; smoking cessation groups; and fortnightly telephone support. Outcome data, including cigarettes smoked per day, quit attempts, and self-reported 7-day point prevalence abstinence (validated by exhaled carbon monoxide), will be collected via blind interview at one week, two months, four months and six months post discharge. Process information will also be collected, including the use of cessation supports and cost of the intervention.</p> <p>Discussion</p> <p>This study will provide comprehensive data on the potential of an integrated, multimodal smoking cessation intervention for persons with an acute mental illness, linking inpatient with community cessation support.</p> <p>Trial Registration</p> <p>Australian and New Zealand Clinical Trials Registry ANZTCN: <a href="http://www.anzctr.org.au/ACTRN12609000465257.aspx">ACTRN12609000465257</a></p

Limited clinical relevance of mitochondrial DNA mutation and gene expression analyses in ovarian cancer

<p>Abstract</p> <p>Background</p> <p>In recent years, numerous studies have investigated somatic mutations in mitochondrial DNA in various tumours. The observed high mutation rates might reflect mitochondrial deregulation; consequently, mutation analyses could be clinically relevant. The purpose of this study was to determine if mutations in the mitochondrial D-loop region and/or the level of mitochondrial gene expression could influence the clinical course of human ovarian carcinomas.</p> <p>Methods</p> <p>We sequenced a 1320-base-pair DNA fragment of the mitochondrial genome (position 16,000-750) in 54 cancer samples and in 44 corresponding germline control samples. In addition, six transcripts (<it>MT-ATP6, MT-CO1, MT-CYB, MT-ND1</it>, <it>MT-ND6</it>, and <it>MT-RNR1</it>) were quantified in 62 cancer tissues by real-time RT-PCR.</p> <p>Results</p> <p>Somatic mutations in the D-loop sequence were found in 57% of ovarian cancers. Univariate analysis showed no association between mitochondrial DNA mutation status or mitochondrial gene expression and any of the examined clinicopathologic parameters. A multivariate logistic regression model revealed that the expression of the mitochondrial gene <it>RNR1 </it>might be used as a predictor of tumour sensitivity to chemotherapy.</p> <p>Conclusion</p> <p>In contrast to many previously published papers, our study indicates rather limited clinical relevance of mitochondrial molecular analyses in ovarian carcinomas. These discrepancies in the clinical utility of mitochondrial molecular tests in ovarian cancer require additional large, well-designed validation studies.</p

Gastrointestinal decontamination in the acutely poisoned patient

ObjectiveTo define the role of gastrointestinal (GI) decontamination of the poisoned patient.Data sourcesA computer-based PubMed/MEDLINE search of the literature on GI decontamination in the poisoned patient with cross referencing of sources.Study selection and data extractionClinical, animal and in vitro studies were reviewed for clinical relevance to GI decontamination of the poisoned patient.Data synthesisThe literature suggests that previously, widely used, aggressive approaches including the use of ipecac syrup, gastric lavage, and cathartics are now rarely recommended. Whole bowel irrigation is still often recommended for slow-release drugs, metals, and patients who "pack" or "stuff" foreign bodies filled with drugs of abuse, but with little quality data to support it. Activated charcoal (AC), single or multiple doses, was also a previous mainstay of GI decontamination, but the utility of AC is now recognized to be limited and more time dependent than previously practiced. These recommendations have resulted in several treatment guidelines that are mostly based on retrospective analysis, animal studies or small case series, and rarely based on randomized clinical trials.ConclusionsThe current literature supports limited use of GI decontamination of the poisoned patient

Performance of mitochondrial DNA mutations detecting early stage cancer

<p>Abstract</p> <p>Background</p> <p>Mutations in the mitochondrial genome (mtgenome) have been associated with cancer and many other disorders. These mutations can be point mutations or deletions, or admixtures (heteroplasmy). The detection of mtDNA mutations in body fluids using resequencing microarrays, which are more sensitive than other sequencing methods, could provide a strategy to measure mutation loads in remote anatomical sites.</p> <p>Methods</p> <p>We determined the mtDNA mutation load in the entire mitochondrial genome of 26 individuals with different early stage cancers (lung, bladder, kidney) and 12 heavy smokers without cancer. MtDNA was sequenced from three matched specimens (blood, tumor and body fluid) from each cancer patient and two matched specimens (blood and sputum) from smokers without cancer. The inherited wildtype sequence in the blood was compared to the sequences present in the tumor and body fluid, detected using the Affymetrix Genechip^®Human Mitochondrial Resequencing Array 1.0 and supplemented by capillary sequencing for noncoding region.</p> <p>Results</p> <p>Using this high-throughput method, 75% of the tumors were found to contain mtDNA mutations, higher than in our previous studies, and 36% of the body fluids from these cancer patients contained mtDNA mutations. Most of the mutations detected were heteroplasmic. A statistically significantly higher heteroplasmy rate occurred in tumor specimens when compared to both body fluid of cancer patients and sputum of controls, and in patient blood compared to blood of controls. Only 2 of the 12 sputum specimens from heavy smokers without cancer (17%) contained mtDNA mutations. Although patient mutations were spread throughout the mtDNA genome in the lung, bladder and kidney series, a statistically significant elevation of tRNA and ND complex mutations was detected in tumors.</p> <p>Conclusion</p> <p>Our findings indicate comprehensive mtDNA resequencing can be a high-throughput tool for detecting mutations in clinical samples with potential applications for cancer detection, but it is unclear the biological relevance of these detected mitochondrial mutations. Whether the detection of tumor-specific mtDNA mutations in body fluidsy this method will be useful for diagnosis and monitoring applications requires further investigation.</p

Rule-Based Cell Systems Model of Aging using Feedback Loop Motifs Mediated by Stress Responses

Investigating the complex systems dynamics of the aging process requires integration of a broad range of cellular processes describing damage and functional decline co-existing with adaptive and protective regulatory mechanisms. We evolve an integrated generic cell network to represent the connectivity of key cellular mechanisms structured into positive and negative feedback loop motifs centrally important for aging. The conceptual network is casted into a fuzzy-logic, hybrid-intelligent framework based on interaction rules assembled from a priori knowledge. Based upon a classical homeostatic representation of cellular energy metabolism, we first demonstrate how positive-feedback loops accelerate damage and decline consistent with a vicious cycle. This model is iteratively extended towards an adaptive response model by incorporating protective negative-feedback loop circuits. Time-lapse simulations of the adaptive response model uncover how transcriptional and translational changes, mediated by stress sensors NF-κB and mTOR, counteract accumulating damage and dysfunction by modulating mitochondrial respiration, metabolic fluxes, biosynthesis, and autophagy, crucial for cellular survival. The model allows consideration of lifespan optimization scenarios with respect to fitness criteria using a sensitivity analysis. Our work establishes a novel extendable and scalable computational approach capable to connect tractable molecular mechanisms with cellular network dynamics underlying the emerging aging phenotype