Evaluation of the reproductive and developmental risks of caffeine

A risk analysis of in utero caffeine exposure is presented utilizing epidemiological studies and animal studies dealing with congenital malformation, pregnancy loss, and weight reduction. These effects are of interest to teratologists, because animal studies are useful in their evaluation. Many of the epidemiology studies did not evaluate the impact of the "pregnancy signal," which identifies healthy pregnancies and permits investigators to identify subjects with low pregnancy risks. The spontaneous abortion epidemiology studies were inconsistent and the majority did not consider the confounding introduced by not considering the pregnancy signal. The animal studies do not support the concept that caffeine is an abortafacient for the wide range of human caffeine exposures. Almost all the congenital malformation epidemiology studies were negative. Animal pharmacokinetic studies indicate that the teratogenic plasma level of caffeine has to reach or exceed 60 μg/ml, which is not attainable from ingesting large amounts of caffeine in foods and beverages. No epidemiological study described the "caffeine teratogenic syndrome." Six of the 17 recent epidemiology studies dealing with the risk of caffeine and fetal weight reduction were negative. Seven of the positive studies had growth reductions that were clinically insignificant and none of the studies cited the animal literature. Analysis of caffeine's reproductive toxicity considers reproducibility and plausibility of clinical, epidemiological, and animal data. Moderate or even high amounts of beverages and foods containing caffeine do not increase the risks of congenital malformations, miscarriage or growth retardation. Pharmacokinetic studies markedly improve the ability to perform the risk analyses.     

Methodology of assessment and reporting of safety in anti-malarial treatment efficacy studies of uncomplicated falciparum malaria in pregnancy: a systematic literature review

Background

Considering the uncertainty of safety of anti-malarial drugs in pregnancy, efficacy studies are one of the few sources of clinical safety data. Complete safety evaluation is not usually incorporated in efficacy studies due to financial and human resource constraints. This review reports the methods used for the assessment of safety of artemisinin-based and quinine-based treatments in efficacy studies in pregnancy.

Methods

Methodology of assessment and reporting of safety in efficacy studies of artemisinin-based and quinine-based treatment in pregnancy was reviewed using seven databases and two clinical trial registries. The protocol was registered to PROSPERO (CRD42017054808).

Results

Of 48 eligible efficacy studies the method of estimation of gestational age was reported in only 32 studies (67%, 32/48) and ultrasound was used in 18 studies (38%, 18/48). Seventeen studies (35%, 17/48) reported parity, 9 (19%, 9/48) reported gravidity and 13 (27%, 13/48) reported both. Thirty-eight studies (79%, 38/48) followed participants through to pregnancy outcome. Fetal loss was assessed in 34 studies (89%, 34/38), but the definition of miscarriage and stillbirth were defined only in 11 (32%, 11/34) and 7 (21%, 7/34) studies, respectively. Preterm birth was assessed in 26 studies (68%, 26/38) but was defined in 16 studies (62%, 16/26). Newborn weight was assessed in 30 studies (79%, 30/38) and length in 10 studies (26%, 10/38). Assessment of birth weight took gestational age into account in four studies (13%, 4/30). Congenital abnormalities were reported in 32 studies (84%, 32/38). Other common risk factors for adverse pregnancy outcomes were not well-reported.

Conclusion

Incomplete reporting and varied methodological assessment of pregnancy outcomes in anti-malarial drug efficacy studies limits comparison across studies. A standard list of minimal necessary parameters to assess and report the safety component of efficacy studies of anti-malarials in pregnancy is proposed.

     

Review of the mutagenicity/genotoxicity of butylated hydroxytoluene.

Butylated hydroxytoluene (BHT) is an effective, widely used, low cost antioxidant. A host of studies examining the potential of BHT to cause point mutations have been published. They include in vitro studies on various bacterial species and strains and on various types of mammalian cell lines as well as in vivo studies on Drosophila melanogaster, silk worms and also the mouse specific locus test (involving long-term exposure). Together these studies convincingly show the absence of a potential for BHT to cause point mutations. A great number of studies on many cell types and species have also been carried out to examine the potential of BHT to cause chromosome aberrations. In vitro studies have been published using plant cells and the WI-38, CHL, CHO, and V79 mammalian cell lines. In vivo studies have been carried out on somatic and/or germ cells of Drosophila melanogaster, rats and mice. Nearly all studies, especially those using validated test systems, indicate that BHT lacks clastogenic potential. In vitro studies on bacterial, yeast and various mammalian cell lines including DON, CHO, CHL cells and primary hepatocytes demonstrate the absence of interactions with or damage to DNA. Taking all the existing data into account, the weight of evidence suggests that BHT does not represent a relevant mutagenic/genotoxic risk to man.     

Smoking and Risk of Erectile Dysfunction: Systematic Review of Observational Studies with Meta-Analysis

Background

There are many recent observational studies on smoking and risk of erectile dysfunction (ED) and whether smoking increases the risk of ED is still inconclusive. The objective of this meta-analysis was to synthesize evidence from studies that evaluated the association between smoking and the risk of ED.

Methods

We searched PubMed, Embase, Web of Science, and Scopus in January 2013 to identify cohort and case-control studies that evaluated the association between smoking and ED. Study quality of included studies was assessed by the Newcastle-Ottawa scale. Random-effects meta-analyses were used to combine the results of included studies.

Results

Four prospective cohort studies and four case-control studies involving 28, 586 participants were included. Because of significant heterogeneity after including case-control studies in meta-analysis, the consistent results of prospective cohort studies were considered more accurate, Because of significant heterogeneity after including case-control studies in meta-analysis, the consistent results of prospective cohort studies were considered more accurate, Compared with non-smokers, the overall odd ratio of ED in prospective cohort studies was 1.51(95% CI: 1.34 to 1.71) for current smokers, and it was 1.29 (95% CI: 1.07 to 1.47) for former smokers. Evidence of publication bias was not found.

Conclusion

Evidence from epidemiological studies suggests that smoking, especially current smoking, may significantly increase the risk of ED     

Health effects of housing improvement: systematic review of intervention studies

ObjectiveTo review the evidence on the effects of interventions to improve housing on health.DesignSystematic review of experimental and non-experimental housing intervention studies that measured quantitative health outcomes.Results18 completed primary intervention studies were identified. 11 studies were prospective, of which six had control groups. Three of the seven retrospective studies used a control group. The interventions included rehousing, refurbishment, and energy efficiency measures. Many studies showed health gains after the intervention, but the small study populations and lack of controlling for confounders limit the generalisability of these findings.ConclusionsThe lack of evidence linking housing and health may be attributable to pragmatic difficulties with housing studies as well as the political climate in the United Kingdom. A holistic approach is needed that recognises the multifactorial and complex nature of poor housing and deprivation. Large scale studies that investigate the wider social context of housing interventions are required.

What is already known on this topic

Many epidemiological studies have described associations between poor housing and health

What this study adds

18 studies were reviewed that studied the health effects of housing improvementsMost studies found some health gainsSmall populations and lack of control for confounders limits the generalisability of the findingsMore large scale, controlled studies of housing interventions are needed to give qualitative and quantitative data     

Transcultural aspects of eating disorders: A critical literature review

A review of studies addressing anorexia nervosa and bulimia nervosa among Native Americans, African-Americans, Hispanics, Asians, Africans, and Middle Easterners yielded only 35 studies, of which 22 were qualitative case reports, three were clinical quantitative studies, and ten were non-clinical quantitative studies. The case studies reported symptoms similar to those of Caucasian patients, and eating disorders were reported in all SES classes. The clinical studies, all reported from Asian countries, described a number of cases for eating disorders quite different from one another. The non-clinical quantitative studies reported a number of cases consistent with the ranges previously reported for controlled samples of non-clinical Caucasian populations. We found few or no quantitative studies on eating disorders from Hispanic, Middle Eastern, African, or Asian countries other than Japan.     

Similarities of ordered gene lists

MOTIVATION: Many applications of microarray technology in clinical cancer studies aim at detecting molecular features for refined diagnosis. In this paper, we follow an opposite rationale: we try to identify common molecular features shared by phenotypically distinct types of cancer using a meta-analysis of several microarray studies. We present a novel algorithm to uncover that two lists of differentially expressed genes are similar, even if these similarities are not apparent to the eye. The method is based on the ordering in the lists. RESULTS: In a meta-analysis of five clinical microarray studies we were able to detect significant similarities in five of the ten possible comparisons of ordered gene lists. We included studies, where not a single gene can be significantly associated to outcome. The detection of significant similarities of gene lists from different microarray studies is a novel and promising approach. It has the potential to improve upon specialized cancer studies by exploring the power of several studies in one single analysis. Our method is complementary to previous methods in that it does not rely on strong effects of differential gene expression in a single study but on consistent ones across multiple studies.     

Recent adoption studies of IQ

Summary At least a half-dozen adoption studies of intelligence or related traits (such as socioeconomic status) have been reported in the past three or four years. They have yielded somewhat divergent findings, but the majority of the studies continue to provide evidence of a substantial genetic contribution to family resemblance in IQ. The recent studies have generally reported lower overall correlations among family members than were obtained in the classical adoption studies. The restricted IQ range in the samples of the recent studies may be responsible for this difference.     

Feasibility of future epidemiological studies on possible health effects of mobile phone base stations

The increasing deployment of mobile communication base stations led to an increasing demand for epidemiological studies on possible health effects of radio frequency emissions. The methodological challenges of such studies have been critically evaluated by a panel of scientists in the fields of radiofrequency engineering/dosimetry and epidemiology. Strengths and weaknesses of previous studies have been identified. Dosimetric concepts and crucial aspects in exposure assessment were evaluated in terms of epidemiological studies on different types of outcomes. We conclude that in principle base station epidemiological studies are feasible. However, the exposure contributions from all relevant radio frequency sources have to be taken into account. The applied exposure assessment method should be piloted and validated. Short to medium term effects on physiology or health related quality of life are best investigated by cohort studies. For long term effects, groups with a potential for high exposure need to first be identified; for immediate effect, human laboratory studies are the preferred approach.     

An effect of enzyme and ligand concentration on the state of aggregation of aspartate transcarbamylase of E. coli: I. The binding of CTP and ATP to the enzyme.

Detailed binding studies of the inhibitor, cytidine triphosphate (CTP), to native Escherichia coli aspartate transcarbamylase (EC 2.1.3.2) reveal significant changes in subunit interaction when enzyme concentration is altered. In contrast, similar binding studies of the activator, adenosine triphosphate (ATP), do not reveal such changes, but do indicate more complex subunit interactions than previously reported. Equilibrium dialysis studies of 4 degrees C are consistent with six binding sites for CTP and ATP per enzyme molecule of molecular weight 310 000, at all enzyme concentrations. CTP binding studies reveal a progressive change from apparent positive to negative cooperativity as the enzyme concentration is decreased. ATP binding studies reveal complex subunit interactions involving a mixture of apparent negative and positive cooperativity. Sucrose gradient studies indicate the presence of at least three enzymatically active polymeric forms of the enzyme. The preliminary sedimentation studies indicate possible ligand and enzyme concentration perturbations of a preexisting association equilibrium in the aspartate transcarbamylase system. The binding data are therefore interpreted in terms of an association model.     

Shoulder biomechanics of RC repair and Instability: A systematic review of cadaveric methodology

BackgroundNumerous biomechanical studies have addressed normal shoulder function and the factors that affect it. While these investigations include a mix of in-vivo clinical reports, ex-vivo cadaveric studies, and computer-based simulations, each has its own strengths and limitations. A robust methodology is essential in cadaveric work but does not always come easily. Precise quantitative measurements are difficult in in-vivo studies, and simulation studies require validation steps. This review focuses on ex-vivo cadaveric studies to emphasize the best research methodologies available to simulate physiologically and clinically relevant shoulder motion.MethodsA PubMed and Web of Science search was conducted in March 2017 (and updated in May 2018) to identify the cadaveric studies focused on the shoulder and its function. The key words for this search included rotator cuff (RC) injuries, RC surgery, and their synonyms. The protocol of the study was registered on PROSPERO and is accessible at CRD42017068873.ResultsThirty one studies consisting of 167 specimens with various biomechanical methods met our inclusion criteria. All studies were level V cadaveric studies. Cadaveric biomechanical models are widely used to study shoulder instability and RC repair. These models are commonly limited to the glenohumeral joint by a fixed scapula, passively and discretely move the humerus, and statically load the RC without regard for the integrity of the glenohumeral capsule.ConclusionAll studies captured in this review evaluated shoulder biomechanics. Recent studies in patients suggest that some assumptions made in this space may not fully characterize motion of the human shoulder. With reproducible scapular positioning, dynamic RC activation, and preservation of glenohumeral capsule integrity, cadaveric studies can facilitate proper validation for simulation models and broaden our understanding of the shoulder environment during motion in healthy and disease states.     

Association between Tooth Loss and Gastric Cancer: A Meta-Analysis of Observational Studies

Observational studies showed that tooth loss is associated with gastric cancer, but the findings are inconsistent. In this study, a meta-analysis was conducted to evaluate the relationship between tooth loss and gastric cancer. Relevant studies were screened in PubMed and Embase databases, and nine observational studies were considered eligible for the analysis. The combined relative risks for the highest versus the lowest categories of tooth loss were 1.86 (95% CI: 1.08–3.21) and 1.31 (95% CI: 1.12–1.53) in case control and cohort studies, respectively. However, unstable results were observed in the stratified and sensitivity analysis. The current evidence, based solely on four case-control studies and five cohort studies, suggested that tooth loss is a potential marker of gastric cancer. However, we can not concluded at this time that tooth loss may be a risk factor for gastric cancer due to significant heterogeneity among studies and mixed results between case-control studies and cohort studies. Additional large-scale and high-quality prospective studies are required to evaluate the association between tooth loss and risk of gastric cancer.     

The role of stress in the development and clinical course of inflammatory bowel disease: epidemiological evidence

BACKGROUND: It is unclear whether psychological stress contributes to the inflammatory process in the inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn's disease (CD). This review assesses the epidemiological evidence regarding a causal link between stress and gut inflammation in IBD. METHODS: A Medline search identified prospective studies of the effects of stress on subsequent disease activity and randomized controlled studies of the effects of psychological interventions on disease course in IBD. Controlled retrospective studies were included in the review of aspects of the stress-inflammatory relationship for which few prospective studies are available (e.g. the link between stress and disease onset). Studies were assessed qualitatively. RESULTS: Among 9 longitudinal studies of stress or depression and disease course, a significant stress-inflammation relationship has been found when UC and CD are studied independently (4 of 4 studies positive) but studies of mixed samples of CD and UC have mostly had negative results (1 of 5 studies positive). Evidence of a contribution of stress to disease onset is very weak. The results of 5 studies of psychological interventions in IBD have been negative or modestly supportive of benefit. Confidence in therapeutic benefits of psychological interventions results is limited by methodological weaknesses in these studies. DISCUSSION: There is consistent evidence for a contribution of psychological factors to IBD disease course, especially stress in UC and depressive symptoms in CD. More rigorous tests of psychological interventions in IBD are needed.     

Methodological issues in pooled analysis of biomarker studies

The number of epidemiological studies involving biological markers has dramatically increased in the last years. These studies are generally small sized and this feature has called attention to the need to summarize the individual results, while waiting for the completion of larger studies, designed to answer questions that have been raised by preliminary studies. We describe here some of the methodological issues related to pooling data of biomarker studies, taking advantage of the experience accumulated by conducting two pooled analyses, one of studies of metabolic gene polymorphisms and cancer, the other on cytogenetic damage. Topics that are considered are: data standardization, population selection and bias, statistical analysis, ethical issues.Pooled analysis seems to provide a relevant improvement over meta-analysis in molecular epidemiology studies, though more research on methodology is needed.     

The Impact of Study Size on Meta-analyses: Examination of Underpowered Studies in Cochrane Reviews

Background

Most meta-analyses include data from one or more small studies that, individually, do not have power to detect an intervention effect. The relative influence of adequately powered and underpowered studies in published meta-analyses has not previously been explored. We examine the distribution of power available in studies within meta-analyses published in Cochrane reviews, and investigate the impact of underpowered studies on meta-analysis results.

Methods and Findings

For 14,886 meta-analyses of binary outcomes from 1,991 Cochrane reviews, we calculated power per study within each meta-analysis. We defined adequate power as ≥50% power to detect a 30% relative risk reduction. In a subset of 1,107 meta-analyses including 5 or more studies with at least two adequately powered and at least one underpowered, results were compared with and without underpowered studies. In 10,492 (70%) of 14,886 meta-analyses, all included studies were underpowered; only 2,588 (17%) included at least two adequately powered studies. 34% of the meta-analyses themselves were adequately powered. The median of summary relative risks was 0.75 across all meta-analyses (inter-quartile range 0.55 to 0.89). In the subset examined, odds ratios in underpowered studies were 15% lower (95% CI 11% to 18%, P<0.0001) than in adequately powered studies, in meta-analyses of controlled pharmacological trials; and 12% lower (95% CI 7% to 17%, P<0.0001) in meta-analyses of controlled non-pharmacological trials. The standard error of the intervention effect increased by a median of 11% (inter-quartile range −1% to 35%) when underpowered studies were omitted; and between-study heterogeneity tended to decrease.

Conclusions

When at least two adequately powered studies are available in meta-analyses reported by Cochrane reviews, underpowered studies often contribute little information, and could be left out if a rapid review of the evidence is required. However, underpowered studies made up the entirety of the evidence in most Cochrane reviews.     

动物行为研究中被忽视的盲实验法

被广泛应用于临床医学、药理学和心理学等学科中的盲实验法,是一种为避免由于人为主观性而对实验观测结果产生偏差的实验设计方法.然而,该方法在动物行为研究领域一直不被重视.近年来有学者逐渐意识到这个问题,并通过文献综述和分析,发现大部分需要采用盲实验法的研究均忽略了此设计方法,使得其研究结果的效应量明显高于采用盲实验法的研究,说明实验中观测者的主观偏见对研究结果造成了影响.本文通过对盲实验法的介绍,强调了其在动物行为研究中的重要性,并对其在该研究领域中的应用进行了阐述和建议.     

Revealing the architecture of gene regulation: the promise of eQTL studies

Expression quantitative trait loci (eQTL) mapping studies have become a widely used tool for identifying genetic variants that affect gene regulation. In these studies, expression levels are viewed as quantitative traits, and gene expression phenotypes are mapped to particular genomic loci by combining studies of variation in gene expression patterns with genome-wide genotyping. Results from recent eQTL mapping studies have revealed substantial heritable variation in gene expression within and between populations. In many cases, genetic factors that influence gene expression levels can be mapped to proximal (putatively cis) eQTLs and, less often, to distal (putatively trans) eQTLs. Beyond providing great insight into the biology of gene regulation, a combination of eQTL studies with results from traditional linkage or association studies of human disease may help predict a specific regulatory role for polymorphic sites previously associated with disease.     

Extrapolating non-target risk of Bt crops from laboratory to field

The tiered approach to assessing ecological risk of insect-resistant transgenic crops assumes that lower tier laboratory studies, which expose surrogate non-target organisms to high doses of insecticidal proteins, can detect harmful effects that might be manifested in the field. To test this assumption, we performed meta-analyses comparing results for non-target invertebrates exposed to Bacillus thuringiensis (Bt) Cry proteins in laboratory studies with results derived from independent field studies examining effects on the abundance of non-target invertebrates. For Lepidopteran-active Cry proteins, laboratory studies correctly predicted the reduced field abundance of non-target Lepidoptera. However, laboratory studies incorporating tri-trophic interactions of Bt plants, herbivores and parasitoids were better correlated with the decreased field abundance of parasitoids than were direct-exposure assays. For predators, laboratory tri-trophic studies predicted reduced abundances that were not realized in field studies and thus overestimated ecological risk. Exposure to Coleopteran-active Cry proteins did not significantly reduce the laboratory survival or field abundance of any functional group examined. Our findings support the assumption that laboratory studies of transgenic insecticidal crops show effects that are either consistent with, or more conservative than, those found in field studies, with the important caveat that laboratory studies should explore all ecologically relevant routes of exposure.     

The matter of spatial and temporal scales: a review of reindeer and caribou response to human activity

Research on impacts of human activity and infrastructure development on reindeer and caribou (Rangifer tarandus) is reviewed in the context of spatial (m to many km) and temporal (min to decades) scales. Before the 1980s, most disturbance studies were behavioral studies of individual animals at local scales, reporting few and short-term (min to h) impacts within 0–2 km from human activity. Around the mid 1980s, focus shifted to regional-scale landscape studies, reporting that Rangifer reduced the use of areas within 5 km from infrastructure and human activity by 50–95% for weeks, months or even years and increased use of remaining undisturbed habitat far beyond those distances. The extent could vary with type of disturbance, sex, terrain, season, and sensitivity of herds. Of 85 studies reviewed, 83% of the regional studies concluded that the impacts of human activity were significant, while only 13% of the local studies did the same. Accurate assessment of impacts from human activity requires regional-scale studies, a pattern confirmed in a few long-term (decades) pre- and post-development studies. Such long-term studies are needed to improve understanding of both temporal and spatial patterns.