Parental risk factors and anorectal malformations: systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Anorectal malformations (ARM) are rare forms of congenital uro-rectal anomalies with largely unknown causes. Besides genetic factors, prenatal exposures of the parents to nicotine, alcohol, caffeine, illicit drugs, occupational hazards, overweight/obesity and diabetes mellitus are suspected as environmental risk factors.</p> <p>Methods</p> <p>Relevant studies published until August 2010 were identified through systematic search in PubMed, EMBASE, ISI Web of Knowledge and the Cochrane Library databases. Furthermore, related and cross-referencing publications were reviewed. Pooled odds ratios (95% confidence intervals) were determined to quantify associations of maternal and paternal smoking, maternal alcohol consumption, underweight (body mass index [BMI] < 18.5), overweight (BMI 25-29.9), obesity (BMI ≥30) and maternal diabetes mellitus with ARM using meta-analyses.</p> <p>Results</p> <p>22 studies that reported on the association between prenatal environmental risk factors and infants born with ARM were included in this review. These were conducted in the United States of America (n = 12), Spain (n = 2), Sweden (n = 2), the Netherlands (n = 2), Japan (n = 1), France (n = 1), Germany (n = 1) and Hungary (n = 1). However, only few of these studies reported on the same risk factors. Studies were heterogeneous with respect to case numbers, control types and adjustment for covariates. Consistently increased risks were observed for paternal smoking and maternal overweight, obesity and diabetes, but not for maternal smoking and alcohol consumption. In meta-analyses, pooled odds ratios (95% confidence intervals) for paternal smoking, maternal overweight, obesity, pre-gestational and gestational diabetes were 1.53 (1.04-2.26), 1.25 (1.07-1.47), 1.64 (1.35-2.00), 4.51 (2.55-7.97) and 1.81 (1.23-2.65), respectively.</p> <p>Conclusion</p> <p>Evidence on risk factors for ARM from epidemiological studies is still very limited. Nevertheless, the few available studies indicate paternal smoking and maternal overweight, obesity and diabetes to be associated with increased risks. Further, ideally large-scale multicentre and register-based studies are needed to clarify the role of key risk factors for the development of ARM.</p

Vitamin D status and epigenetic-based mortality risk score: strong independent and joint prediction of all-cause mortality in a population-based cohort study

Background: Vitamin D deficiency and insufficiency have been established to be strongly associated with increased overall mortality and deaths from specific aging-related diseases. Recently, an epigenetic “mortality risk score” (MS) based on whole blood DNA methylation at the 10 most prominent mortality-related cytosine-phosphate-guanine (CpG) sites has also been found to be highly related to all-cause mortality. This study aimed to explore whether vitamin D status, defined by serum 25-hydroxyvitamin D [25(OH)D] concentrations, is associated with the MS and to what extent both indicators are individually and jointly capable of predicting all-cause mortality in a general population sample of older adults. Results: The MS was derived from the blood DNA methylation profiles measured by Illumina Human Methylation 450K Beadchip, and serum 25(OH)D concentration was measured among 1467 participants aged 50–75 of the German ESTHER cohort study. There was no association between vitamin D status and the MS at baseline, but both metrics were prominently and independently associated with all-cause mortality during a median follow-up of 15.2 years. The combination of both indicators showed the potential to be a particularly strong prognostic index for all-cause mortality. Participants with vitamin D deficiency (&lt; 30 nmol/L) and high MS (&gt; 5 CpG sites with aberrant methylation) had almost sixfold mortality (hazard ratio 5.79, 95% CI 3.06–10.94) compared with participants with sufficient vitamin D (≥ 50 nmol/L) and a low MS (0–1 CpG site with aberrant methylation). Conclusions: This study suggests that vitamin D and the MS are strong independent predictors of all-cause mortality in older adults

Socioeconomic Differences and Lung Cancer Survival—Systematic Review and Meta-Analysis

Background: The impact of socioeconomic differences on cancer survival has been investigated for several cancer types showing lower cancer survival in patients from lower socioeconomic groups. However, little is known about the relation between the strength of association and the level of adjustment and level of aggregation of the socioeconomic status measure. Here, we conduct the first systematic review and meta-analysis on the association of individual and area-based measures of socioeconomic status with lung cancer survival.Methods: In accordance with PRISMA guidelines, we searched for studies on socioeconomic differences in lung cancer survival in four electronic databases. A study was included if it reported a measure of survival in relation to education, income, occupation, or composite measures (indices). If possible, meta-analyses were conducted for studies reporting on individual and area-based socioeconomic measures.Results: We included 94 studies in the review, of which 23 measured socioeconomic status on an individual level and 71 on an area-based level. Seventeen studies were eligible to be included in the meta-analyses. The meta-analyses revealed a poorer prognosis for patients with low individual income (pooled hazard ratio: 1.13, 95 % confidence interval: 1.08–1.19, reference: high income), but not for individual education. Group comparisons for hazard ratios of area-based studies indicated a poorer prognosis for lower socioeconomic groups, irrespective of the socioeconomic measure. In most studies, reported 1-, 3-, and 5-year survival rates across socioeconomic status groups showed decreasing rates with decreasing socioeconomic status for both individual and area-based measures. We cannot confirm a consistent relationship between level of aggregation and effect size, however, comparability across studies was hampered by heterogeneous reporting of socioeconomic status and survival measures. Only eight studies considered smoking status in the analysis.Conclusions: Our findings suggest a weak positive association between individual income and lung cancer survival. Studies reporting on socioeconomic differences in lung cancer survival should consider including smoking status of the patients in their analysis and to stratify by relevant prognostic factors to further explore the reasons for socioeconomic differences. A common definition for socioeconomic status measures is desirable to further enhance comparisons between nations and across different levels of aggregation

DNA methylation changes of whole blood cells in response to active smoking exposure in adults: a systematic review of DNA methylation studies

Details of CpG sites published in all active smoking EWASs included in the review. This table includes 5 sheets: 1) the general information of reported CpG sites in each included manuscript; 2) CpG sites reported ≥2 times; 3) characteristics of multiple reported (≥3 times) CpG sites; 4) the list of active smoking-related CpG sites (no duplicates); and 5) data of Fig. 2. (XLSX 284 kb

Smoking and γ-Glutamyltransferase: Opposite Interactions with Alcohol Consumption and Body Mass Index

BACKGROUND: Smoking has recently been suggested to synergistically interact with alcohol intake as a determinant of serum gamma-glutamyltransferase (γ-GT), an emergent powerful predictor of disease and mortality. This study investigated whether this also applies to higher smoking and alcohol exposure ranges and to body mass index (BMI), which likewise is strongly associated with γ-GT. METHODOLOGY/PRINCIPAL FINDINGS: Analyses were based on occupational health examinations of more than 15,000 German male workers aged 16-64 years, predominantly from the construction industry. Sociodemographics and other health-related information were collected during the exam. Joint associations of smoking and alcohol consumption or BMI with elevated or log-transformed γ-GT were examined by tabulation and multiple adjusted regression models. Cigarette smoking exerted no effect on γ-GT in teetotalers, but there was a statistically significant effect of smoking among participants with higher alcohol consumption intensity, odds of elevated γ-GT being increased by 24% and 27% per additional 10 cigarettes smoked per day in subjects drinking 61-90 and >90 gram alcohol per day, respectively (P for interaction = 0.039). The interaction was opposite for BMI, where no association was seen in obese subjects, whereas odds of elevated γ-GT were increased by 24% per 10 cigarettes below 25 kg/m(2) (P for interaction = 0.040). This novel interaction was replicable in an independent cohort. CONCLUSION: The evidence for opposite interactions of smoking with alcohol and BMI as determinants of serum γ-GT suggests that different physiological pathways are responsible for the associations between these factors

Quality of life and physical activity in long-term (≥5 years post-diagnosis) colorectal cancer survivors - systematic review

Background: Due to the increasing number of long-term (≥5 years post diagnosis) colorectal cancer survivors, long-term quality of life of these patients is highly relevant. Several studies have reported a positive association between physical activity and quality of life in colorectal cancer survivors, however, so far no systematic review has been published which focuses on long-term colorectal cancer survivors. Material and methods: A systematic review was conducted using the databases PubMed, Web of Science, PsychINFO, and CINAHL. Studies which investigated associations between physical activity and quality of life in long-term colorectal cancer survivors were included. Results and conclusion: Ten articles based on seven studies were identified. Long-term colorectal cancer survivors who were physically active reported better quality of life than long-term survivors who were not physically active. Both, moderate to vigorous physical activity and lower levels like light physical activity were associated with higher quality of life. Most studies assessed the association between physical activity and quality of life cross-sectionally but one prospective study which measured physical activity and quality of life at three different points in time also found associations between physical activity and quality of life. The association between physical activity and quality of life seemed to be stronger among women than among men. The findings of this systematic review support an association between physical activity and quality of life in long-term colorectal cancer survivors. However, the evidence is limited as most studies were based on cross-sectional and observational design

Efficient generation of neural stem cell-like cells from adult human bone marrow stromal cells

Clonogenic neural stem cells (NSCs) are self-renewing cells that maintain the capacity to differentiate into brain-specific cell types, and may also replace or repair diseased brain tissue. NSCs can be directly isolated from fetal or adult nervous tissue, or derived from embryonic stem cells. Here, we describe the efficient conversion of human adult bone marrow stromal cells (hMSC) into a neural stem cell-like population (hmNSC, for human marrow-derived NSC-like cells). These cells grow in neurosphere-like structures, express high levels of early neuroectodermal markers, such as the proneural genes NeuroD1, Neurog2, MSl1 as well as otx1 and nestin, but lose the characteristics of mesodermal stromal cells. In the presence of selected growth factors, hmNSCs can be differentiated into the three main neural phenotypes: astroglia, oligodendroglia and neurons. Clonal analysis demonstrates that individual hmNSCs are multipotent and retain the capacity to generate both glia and neurons. Our cell culture system provides a powerful tool for investigating the molecular mechanisms of neural differentiation in adult human NSCs. hmNSCs may therefore ultimately help to treat acute and chronic neurodegenerative diseases