Associations between chronotype,morbidity and mortality in the UK Biobank cohort

Later chronotype (i.e. evening preference) and later timing of sleep have been associated with greater morbidity, including higher rates of metabolic dysfunction and cardiovascular disease (CVD). However, no one has examined whether chronotype is associated with mortality risk to date. Our objective was to test the hypothesis that being an evening type is associated with increased mortality in a large cohort study, the UK Biobank. Our analysis included 433 268 adults aged 38–73 at the time of enrolment and an average 6.5-year follow-up. The primary exposure was chronotype, as assessed through a single self-reported question-defining participants as definite morning types, moderate morning types, moderate evening types or definite evening types. The primary outcomes were all-cause mortality and mortality due to CVD. Prevalent disease was also compared among the chronotype groups. Analyses were adjusted for age, sex, ethnicity, smoking, body mass index, sleep duration, socioeconomic status and comorbidities. Greater eveningness, particularly being a definite evening type, was significantly associated with a higher prevalence of all comorbidities. Comparing definite evening type to definite morning type, the associations were strongest for psychological disorders (OR 1.94, 95% CI 1.86–2.02, p = < 0.001), followed by diabetes (OR 1.30, 95% CI 1.24–1.36, p = < 0.001), neurological disorders (OR 1.25, 95% CI 1.20–1.30, p = < 0.001), gastrointestinal/abdominal disorders (OR 1.23, 95% CI 1.19–1.27, p = < 0.001) and respiratory disorders (OR 1.22, 95% CI 1.18–1.26, p = < 0.001). The total number of deaths was 10 534, out of which 2127 were due to CVD. Greater eveningness, based on chronotype as an ordinal variable, was associated with a small increased risk of all-cause mortality (HR 1.02, 95% CI 1.004–1.05, p = 0.017) and CVD mortality (HR 1.04, 95% CI 1.00–1.09, p = 0.06). Compared to definite morning types, definite evening types had significantly increased risk of all-cause mortality (HR 1.10, 95% CI 1.02–1.18, p = 0.012). This first report of increased mortality in evening types is consistent with previous reports of increased levels of cardiometabolic risk factors in this group. Mortality risk in evening types may be due to behavioural, psychological and physiological risk factors, many of which may be attributable to chronic misalignment between internal physiological timing and externally imposed timing of work and social activities. These findings suggest the need for researching possible interventions aimed at either modifying circadian rhythms in individuals or at allowing evening types greater working hour flexibility.     

Association between the OGG1 Ser326Cys and APEX1 Asp148Glu polymorphisms and lung cancer risk: a meta-analysis

The previous published data on the association between the 8-oxo-guanine glycosylase-1 (OGG1) and apurinic/apyrimidinic-endonuclease-1 (APEX1/APE1) polymorphisms and lung cancer risk remained controversial. Several polymorphisms in the OGG1 and APEX1 gene have been described, including the commonly occurring Ser326Cys in OGG1 and Asp148Glu in APEX1. This meta-analysis of literatures was performed to derive a more precise estimation of the relationship. A total of 37 studies were identified to the meta-analysis, including 9,203 cases and 10,994 controls for OGG1 Ser326Cys (from 25 studies) and 3,491 cases and 4,708 controls for APEX1 Asp148Glu (from 12 studies). When all the eligible studies were pooled into the meta-analysis of OGG1 Ser326Cys polymorphism, significantly increased lung cancer risk was observed in recessive model (OR?=?1.17, 95?% CI?=?1.03–1.33) and in additive model (OR?=?1.21, 95?% CI?=?1.03–1.42). In the stratified analysis, significantly increased risk of lung cancer was also observed on the population-based studies (recessive model: OR?=?1.26, 95?% CI?=?1.08–1.46, additive model: OR?=?1.42, 95?% CI?=?1.06–1.73) and non-smokers (dominant model: OR?=?1.20, 95?% CI?=?1.02–1.42, recessive model: OR?=?1.20, 95?% CI?=?1.02–1.40, additive model: OR?=?1.35, 95?% CI?=?1.08–1.68). Additionally, when one study was deleted in the sensitive analysis, the results of OGG1 Ser326Cys were changed in Asians (recessive model: OR?=?1.16, 95?% CI?=?1.06–1.27, additive model: OR?=?1.23, 95?% CI?=?1.09–1.38). When all the eligible studies were pooled into the meta-analysis of APEX1 Asp148Glu polymorphism, there was no evidence of significant association between lung cancer risk and APEX1 Asp148Glu polymorphism in any genetic model. In the stratified analysis, significantly decreased lung adenocarcinoma risk was observed in recessive model (OR?=?0.68, 95?% CI?=?0.48–0.97, P _h?=?0.475, I²?=?0.0?%). Additionally, when one study was deleted in the sensitive analysis, the results of APEX1 Asp148Glu were changed in Asians (recessive model: OR?=?1.21, 95?% CI?=?1.03–1.43) and smokers (dominant model: OR?=?1.62, 95?% CI?=?1.08–2.44, additive model: OR?=?1.37, 95?% CI?=?1.02–1.84). In summary, this meta-analysis indicates that OGG1 Ser326Cys show an increased lung cancer risk in Asians and non-smokers, APEX1 Asp148Glu polymorphism may be associated with decreased lung adenocarcinoma risk, and APEX1 Asp148Glu polymorphism show an increased lung cancer risk in Asians and smokers. However, a study with the larger sample size is needed to further evaluated gene-environment interaction on OGG1 Ser326Cys and APEX1 Asp148Glu polymorphisms and lung cancer risk.     

Prognostic significance of X-linked inhibitor of apoptosis protein in solid tumors: A systematic review and meta-analysis

X-linked inhibitor of apoptosis protein (XIAP) is aberrantly expressed in solid tumors. Considering conflicting data, we conducted this meta-analysis to investigate its prognostic role. Electronic databases were searched to collect studies about associations between XIAP expressions and survival outcomes. Hazard ratio (HR), odds ratio (OR), and 95% confidence interval (CI) were utilized as effect size estimates. A total of 3,794 patients from 21 published studies were included. The results revealed that high XIAP expressions correlated with age (OR = 2.02; 95% CI, 1.07–3.84), lymph node metastasis (OR = 1.69; 95% CI, 1.02–2.77), histological grade (OR = 2.04; 95% CI, 1.01–4.11), and tumor stage (OR = 2.18; 95% CI, 1.20–3.96). The combined HR revealed that high XIAP expressions associated with poor overall survival (OS) (HR = 1.60; 95% CI, 1.22–2.10). Our study suggested high XIAP expressions may be indicative of poor prognosis in solid tumors.     

miR-499 rs3746444 polymorphism is associated with cancer development among Asians and related to breast cancer susceptibility

To derive a more precise estimation of the relationship between miR-499 rs3746444 polymorphism (A>G) and cancer risk, a meta-analysis was performed. A total of 9 studies including 6,077 cases and 7,199 controls were involved in this meta-analysis. Overall, no significantly elevated cancer risk was associated with miR-499 G allele when all studies were pooled into the meta-analysis (AG vs. AA: OR?=?1.14, 95?% CI?=?0.98–1.32; GG vs. AA: OR?=?1.12, 95?% CI?=?0.95–1.33; dominant model: OR?=?1.13, 95?% CI?=?0.99–1.29; recessive model: OR?=?1.05, 95?% CI?=?0.83–1.33). In the subgroup analysis by ethnicity, significantly increased risk was only found for Asians (dominant model: OR?=?1.22, 95?% CI?=?1.02–1.46). When stratified by study design, no statistically significantly elevated risks were found in hospital-based studies or population-based studies. In the subgroup analysis by cancer type, significant cancer risk change was only found for breast cancer when miR-499 G allele was included (dominant model: OR?=?1.13, 95?% CI?=?1.01–1.26). In conclusion, this meta-analysis suggests that the miR-499 rs3746444 polymorphism (A>G) is a low-penetrant risk factor for cancer development among Asians and may contribute to breast cancer susceptibility.     

Combined effect of five single nucleotide polymorphisms related to IL23/Th17 pathway in the risk of psoriasis

Psoriasis is a common immune-mediated inflammatory skin disease with strong genetic components, in which the IL23/Th17 pathway has been implicated. To explore the effective role in psoriasis, we genotyped five single nucleotide polymorphisms in genes related to IL23/Th17 pathway in 14,929 Han Chinese samples. A Bonferroni-corrected significant single-variant association was identified between rs1512970 within IL21 (odds ratio (OR)?=?1.07, 95 % confidence interval (CI)?=?1.02–1.13, P?=?4.94?×?10^?03). We failed to validate rs744166 (OR?=?1.06, 95 % CI?=?1.01–1.11, P?=?1.52?×?10^?02) and other three SNPs (P?=?2.48?×?10^?01?～?1.27?×?10^?02) to meet the single-variant association significance threshold. However, we found that their combined effect substantially contributed to the risk of psoriasis in our sample (P?=?3.91?×?10^?07) and the highest score group conferred the largest risk effect size (OR?=?1.22, 95 % CI?=?1.11–1.34, P?=?1.85?×?10^?05). Our results implicate the ethnic heterogeneity in the susceptibility of psoriasis and suggest common variants with weak effect in IL23/Th17 pathway, which do not show significance in conventional single-variant association study, may contribute to the risk of psoriasis. This study sheds light on the important role of IL23/Th17 pathway in the susceptibility of psoriasis.     

Genetic association between IL-27 rs153109 polymorphism and cancer risk in Chinese population: a meta-analysis

IL-27 plays an important role in anti-cancer activity. The -964A/G polymorphism in IL-27 gene has been implicated in susceptibility to cancer, but the results were conflicting. The aim of this study was to assess the association between this polymorphism and cancer risk. Pubmed and Wanfang database were searched for all publications concerning IL-27 -964A/G polymorphism and cancer risk. Odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of association. Statistical analysis was performed using Stata 11.0 software. A total of eight case–control studies including 2044 cancer cases and 2197 controls were identified. Overall, significant association between IL-27 -964A/G polymorphism and cancer risk was observed (GG versus AA: OR?=?1.26, 95% CI?=?1.03–1.52; GG versus AG?+?AA: OR?=?1.20, 95% CI?=?1.00–1.44). In subgroup analysis based on cancer type, significant association was found in colorectal cancer (GG versus AA: OR?=?1.55, 95% CI?=?1.07–2.27; AG versus AA: OR?=?1.31, 95% CI?=?1.02–1.67). The current meta-analysis suggests that IL-27 -964A/G polymorphism might enhance cancer risk. However, large-scale and well-designed studies are still needed to confirm the result of our meta-analysis. The association of IL-27 polymorphism with colorectal cancer may provide insight for future therapies.     

Do Cadmium, Lead, and Aluminum in Drinking Water Increase the Risk of Hip Fractures? A NOREPOS Study

The aim of this study was to investigate relations between cadmium, lead, and aluminum in municipality drinking water and the incidence of hip fractures in the Norwegian population. A trace metals survey in 566 waterworks was linked geographically to hip fractures from hospitals throughout the country (1994–2000). In all those supplied from these waterworks, 5,438 men and 13,629 women aged 50–85 years suffered a hip fracture. Poisson regression models were fitted, adjusting for age, region of residence, urbanization, and type of water source as well as other possibly bone-related water quality factors. Effect modification by background variables and interactions between water quality factors were examined (correcting for false discovery rate). Men exposed to a relatively high concentration of cadmium (IRR?=?1.10; 95 % CI 1.01, 1.20) had an increased risk of fracture. The association between relatively high lead and hip fracture risk was significant in the oldest age group (66–85 years) for both men (IRR?=?1.11; 95 % CI 1.02, 1.21) and women (IRR?=?1.10; 95 % CI 1.04, 1.16). Effect modification by degree of urbanization on hip fracture risk in men was also found for all three metals: cadmium, lead, and aluminum. In summary, a relatively high concentration of cadmium, lead, and aluminum measured in drinking water increased the risk of hip fractures, but the associations depended on gender, age, and urbanization degree. This study could help in elucidating the complex effects on bone health by risk factors found in the environment.     

Two Novel Susceptibility SNPs for Ischemic Stroke Using Exome Sequencing in Chinese Han Population

Genome-wide association studies (GWAS) of ischemic stroke (IS) have been performed on several cohorts of Caucasian or African population and Japanese, resulting in somewhat inconsistent conclusion. We aimed to identify susceptibility loci for IS by exome sequencing in a Chinese Han population. Exome sequencing was used to screen susceptibility loci among 100 cases and 100 matched controls. Significant SNPs from the first stage were verified in up to 3,554 participants from three hospital-based case–control studies. In the initial exome sequencing analysis, rs10489177 in c1orf156 gene located on chromosome 1q24 (p?<?1?×?10^?8) and rs17118 in XYLB gene located on chromosome 3p21 (p?<?1?×?10^?6) were found to be significantly associated with IS. In the following validation stage, significantly increased odds ratios were observed in individuals with rs10489177 GG (OR?=?2.02, 95 % CI?=?1.35–3.03) or rs17118 AA genotype (OR?=?1.50, 95 % CI?=?1.17–1.91). The rs10489177 GG genotype was associated with significantly increased risk for IS in individuals without hypertension (OR?=?2.78, 95 % CI?=?1.59–4.86) and in individuals without diabetes (OR?=?1.93, 95 % CI?=?1.27–2.94). In contrast, the rs17118 AA genotype may significantly increase the risk for IS, particularly for individuals with hypertension (OR?=?1.73, 95 % CI?=?1.08–2.78) and for individuals without diabetes (OR?=?1.52, 95 % CI?=?1.17–1.98) or non-smoker (OR?=?1.59, 95 % CI?=?1.16–2.19). Collectively, our study identified two novel loci (rs17118 and rs10489177) which were associated with an increased risk for IS in Chinese Han populations. Further studies are needed to confirm these associations in other populations and elucidate the biological mechanisms underlying the observed associations.     

The Role of Genetic Risk Score in Predicting the Risk of Hypertension in the Korean population: Korean Genome and Epidemiology Study

Hypertension is regarded as a multifactorial disease with a modest contribution of genetic factors and strongly affected by environmental factors. Recent genome-wide association studies have identified specific loci associated with high blood pressure (BP) and hypertension. This study aimed to examine the association between the genetic risk score (GRS), a linear function of multiple single nucleotide polymorphisms (SNPs) associated with hypertension, and high BP and prevalent hypertension at baseline examination and to evaluate the efficacy of the GRS for predicting incident hypertension with longitudinal data in Korean subjects. Data for 8,556 participants, aged 40 to 69, in a community-based cohort study were analyzed. Unweighted GRS (cGRS) and weighted GRS (wGRS) were constructed from 4 SNPs related to high BP or hypertension in previous genome-wide association and its replication studies for the Korean middle-aged population. Cross-sectional analysis (n=8,556) revealed that cGRS was significantly associated with prevalent hypertension (odds ratio=1.15 per risk allele; 95%CI, 1.09-1.20). Additionally, the odds ratios (ORs) of prevalent hypertension for those who in medium and the highest tertile compared with those who in the lowest tertile of wGRS were 1.31 (95% CI, 1.15-1.50) and 1.59 (95%CI, 1.38-1.82), respectively. In a longitudinal analysis (n=5,632), participants in the highest tertile of wGRS had a 1.22-fold (OR=1.22, 95%CI, 1.02‒1.46) greater risk of incident hypertension relative to those in the lowest tertile, after adjusting for a number of confounding factors. However, wGRS topped with traditional risk factors had no significant effect on discrimination ability (c-statistics with and without wGRS were 0.811 and 0.810, P=0.1057). But, reclassification analysis showed that the addition of GRS to the model with conventional risk factors led to about 9% significant increment in category-free net reclassification improvement. GRSs based on 4 SNPs were independently associated with hypertension and may provide a statistically significant improvement over the existing model for prediction of incident hypertension.     

Apo A5 −1131T/C, FgB −455G/A, −148C/T, and CETP TaqIB gene polymorphisms and coronary artery disease in the Chinese population: a meta-analysis of 15,055 subjects

The Apolipoprotein A5 (APO A5) ?1131T/C, fibrinogen β (FgB) ?455G/A, ?148C/T, and cholesteryl ester transfer protein (CETP) TaqIB gene polymorphisms have been indicated to be associated with the coronary artery disease (CAD) risk, but the individual study results are still inconsistent. To explore the relationship between APO A5 ?1131T/C, FgB ?455G/A, ?148C/T, and CETP TaqIB gene polymorphisms and CAD in the Chinese population, the current meta-analysis involving 15,055 subjects from 40 individual studies was conducted. The pooled odds ratio (OR) for the association between APO A5 ?1131T/C, FgB ?455G/A, ?148C/T, and CETP TaqIB gene polymorphisms and CAD and its corresponding 95 % confidence interval (95 % CI) were evaluated by random or fixed effect model. A significant association between APO A5 ?1131T/C gene polymorphism and CAD in the Chinese population was found under an allelic (OR: 1.33, 95 % CI: 1.22–1.44, P < 0.00001), recessive (OR: 1.67, 95 % CI: 1.25–2.25, P = 0.0006), dominant (OR: 0.820, 95 % CI: 0.767–0.876, P = 1.0 × 10^?10), homozygous (OR: 2.36, 95 % CI: 1.55–3.58, P < 0.0001) and heterozygous genetic models (OR: 1.136, 95 % CI:1.075–1.200, P = 1.0 × 10^?10). A significant association between FgB ?455G/A gene polymorphism and CAD was also detected in the Chinese population under an allelic (OR: 1.50, 95 % CI: 1.25–1.81, P < 0.0001), dominant (OR: 0.864, 95 % CI: 0.819–0.912, P = 1.0 × 10^?10), homozygous (OR: 1.616, 95 % CI: 1.213–2.152, P = 0.001) and heterozygous genetic models (OR: 1.245, 95 % CI:1.138–1.361, P = 1.0 × 10^?10). No significant association was found between them under a recessive genetic model (OR: 1.124, 95 % CI: 0.844–1.497, P = 0.424). A significant association was also found between FgB ?148C/T gene polymorphism and CAD in the Chinese population under an allelic (OR: 1.34, 95 % CI: 1.06–1.71, P = 0.02), recessive (OR: 1. 65, 95 % CI: 1.02–2.69, P = 0.04), dominant (OR: 0.924, 95 % CI: 0.872–0.978, P = 0.007) and homozygous genetic models (OR: 0.968, 95 % CI: 0.942–0.995, P = 0.018). No significant association was found between them under a heterozygous genetic model (OR: 0.979, 95 % CI: 0.937–1.023, P = 0.342). In the whole Chinese population, no significant association between the CETP TaqIB gene polymorphism and CAD was found under an allelic (OR: 1.17, 95 % CI: 0.94–1.45, P = 0.15), dominant (OR: 1.46, 95 % CI: 0.80–2.67, P = 0.22) or recessive genetic models (OR: 0.68, 95 % CI: 0.32–1.44, P = 0.31). However, in the subgroup analysis stratified by ethnicity, there was a significant association between them under an allelic (OR: 1.27, 95 % CI: 1.07–1.52, P = 0.007) and dominant genetic model (OR: 2.04, 95 % CI: 1.49–2.79, P < 0.00001) in the Han subgroup. In the Chinese population, the APO A5 ?1131T/C and FgB ?455G/A, ?148C/T gene polymorphisms were implied to be associated with CAD susceptibility. The APO A5 ?1131C, FgB ?455A, and ?148T alleles might confer susceptibility to CAD. CETP TaqIB gene polymorphism was suggested to be associated with CAD susceptibility in the Chinese Han population. Carriers with B1 allele of CETP TaqIB gene might be predisposed to CAD in the Chinese Han population.     

The effect of solar-geomagnetic activity during and after admission on survival in patients with acute coronary syndromes

A number of studies have established the effects of solar-geomagnetic activity on the human cardio-vascular system. It is plausible that the heliophysical conditions existing during and after hospital admission may affect survival in patients with acute coronary syndromes (ACS). We analyzed data from 1,413 ACS patients who were admitted to the Hospital of Kaunas University of Medicine, Lithuania, and who survived for more than 4 days. We evaluated the associations between active-stormy geomagnetic activity (GMA), solar proton events (SPE), and solar flares (SF) that occurred 0–3 days before and after admission, and 2-year survival, based on Cox’s proportional-hazards model, controlling for clinical data. After adjustment for clinical variables, active-stormy GMA on the 2nd day after admission was associated with an increased (by 1.58 times) hazard ratio (HR) of cardiovascular death (HR?=?1.58, 95 % CI 1.07–2.32). For women, geomagnetic storm (GS) 2 days after SPE occurred 1 day after admission increased the HR by 3.91 times (HR?=?3.91, 95 % CI 1.31–11.7); active-stormy GMA during the 2nd–3rd day after admission increased the HR by over 2.5 times (HR?=?2.66, 95 % CI 1.40–5.03). In patients aged over 70 years, GS occurring 1 day before or 2 days after admission, increased the HR by 2.5 times, compared to quiet days; GS in conjunction with SF on the previous day, nearly tripled the HR (HR?=?3.08, 95 % CI 1.32–7.20). These findings suggest that the heliophysical conditions before or after the admission affect the hazard ratio of lethal outcome; adjusting for clinical variables, these effects were stronger for women and older patients.     

Maternal age and non‐chromosomal birth defects,Atlanta—1968–2000: Teenager or thirty‐something,who is at risk?

OBJECTIVE: This investigation explored the association between maternal age and non-chromosomal birth defects to assess any increased risk associated with maternal age. METHODS: Birth defect cases were ascertained by the Metropolitan Atlanta Congenital Defects Program (MACDP), denominator information was obtained using birth certificate data. Infants with any chromosomal diagnosis were excluded. Effect estimates were calculated using 5-year maternal age categories with 25-29 years as the referent. Multiple logistic regression was used to adjust for maternal race, parity, infant sex, and birth year. RESULTS: A total of 1,050,616 singleton infants, born after > or = 20 weeks gestation in the five counties of metropolitan Atlanta from 1968 through 2000 who did not have a chromosomal abnormality and whose mother was 14 to 40 years old, were included in the analyses, 32,816 of them were identified with birth defects by the MACDP. Young maternal age (14-19 years) was associated with anencephaly (OR = 1.81, 95% CI = 1.30-2.52), hydrocephaly without neural tube defect (OR = 1.56, 95% CI = 1.23-1.96), all ear defects (OR = 1.28, 95% CI = 1.10-1.49), cleft lip (OR = 1.88, 95% CI = 1.30-2.73), female genital defects (OR = 1.57, 95% CI = 1.12-2.19), hydronephrosis (OR = 1.42, 95% CI = 1.11-1.82), polydactyly (OR = 1.29, 95% CI = 1.09-1.52), omphalocele (OR = 2.08, 95% CI = 1.39-3.12), and gastroschisis (OR = 7.18, 95% CI = 4.39-11.75). Advanced maternal age (35-40 years) was associated with all heart defects (OR = 1.12, 95% CI = 1.03-1.22), tricuspid atresia (OR = 1.24, 95% CI = 1.02-1.50), right outflow tract defects (OR = 1.28, 95% CI = 1.10-1.49), hypospadias 2nd degree or higher (OR = 1.85, 95% CI = 1.33-2.58), male genital defects excluding hypospadias (OR = 1.25, 95% CI = 1.08-1.45) and craniosynostosis (OR = 1.65, 95% CI = 1.18-2.30). CONCLUSIONS: Young and advanced maternal ages are associated with different types of birth defects. Underlying causes for these associations are not clear.     

The social network around influenza vaccination in health care workers: a cross-sectional study

Background

Influenza vaccination coverage remains low among health care workers (HCWs) in many health facilities. This study describes the social network defined by HCWs’ conversations around an influenza vaccination campaign in order to describe the role played by vaccination behavior and other HCW characteristics in the configuration of the links among subjects.

Methods

This study used cross-sectional data from 235 HCWs interviewed after the 2010/2011 influenza vaccination campaign at the Hospital Clinic of Barcelona (HCB), Spain. The study asked: “Who did you talk to or share some activity with respect to the seasonal vaccination campaign?” Variables studied included sociodemographic characteristics and reported conversations among HCWs during the influenza campaign. Exponential random graph models (ERGM) were used to assess the role of shared characteristics (homophily) and individual characteristics in the social network around the influenza vaccination campaign.

Results

Links were more likely between HCWs who shared the same professional category (OR 3.13, 95% CI?=?2.61–3.75), sex (OR 1.34, 95% CI?=?1.09–1.62), age (OR 0.7, 95% CI?=?0.63–0.78 per decade of difference), and department (OR 11.35, 95% CI?=?8.17–15.64), but not between HCWs who shared the same vaccination behavior (OR 1.02, 95% CI?=?0.86–1.22). Older (OR 1.26, 95% CI?=?1.14–1.39 per extra decade of HCW) and vaccinated (OR 1.32, 95% CI?=?1.09–1.62) HCWs were more likely to be named.

Conclusions

This study finds that there is no homophily by vaccination status in whom HCWs speak to or interact with about a workplace vaccination promotion campaign. This result highlights the relevance of social network analysis in the planning of health promotion interventions.

     

A nested case-control study of lung cancer risk and ionizing radiation exposure at the portsmouth naval shipyard

Results have been inconsistent between studies of lung cancer risk and ionizing radiation exposures among workers at the Portsmouth Naval Shipyard (PNS). The purpose of this nested case-control study was to evaluate the relationship between lung cancer risk and external ionizing radiation exposure while adjusting for potential confounders that included gender, radiation monitoring status, smoking habit surrogates (socioeconomic status and birth cohort), welding fumes and asbestos. By incidence density sampling, we age-matched 3,291 controls selected from a cohort of 37,853 civilian workers employed at PNS between 1952 and 1992 with 1,097 lung cancer deaths from among the same cohort. Analyses using conditional logistic regression were conducted in various model forms: log-linear (main), linear excess relative risk (ERR), and categorical. Lung cancer risk was positively associated with occupational dose (OR = 1.02 at 10 mSv; 95% CI 0.99- 1.04) but flattened after the inclusion of work-related medical X-ray doses (OR = 1.00; 95% CI 0.98-1.03) in multivariate analyses. Similar risk estimates were observed in the linear ERR model at 10 mSv of cumulative exposure with a 15-year lag.     

Association of methylenetetrahydrofolate reductase gene 677C > T polymorphism and Down syndrome

The association between Down syndrome (DS) and maternal polymorphisms in genes encoding folic acid metabolizing enzymes remains a controversial issue. A meta-analysis was performed to evaluate the association of maternal MTHFR 677C > T polymorphism and the risk of having a child with DS. Case–control studies were screened from major literature databases. Twenty articles from 13 countries worldwide, with a total of 2,101 DS and 2,702 control mothers, attended the inclusion criteria. We found a 50 % increase for the association of maternal homozygous TT genotype and DS in both fixed (OR = 1.51; 95 % CI 1.22–1.87) and random effects models (OR 1.54; 95 % 1.15–2.05). Similarly, a significant pooled OR was found for the heterozygote CT, with an OR 1.26; 95 % CI 1.10–1.43 (fixed effects model) and OR 1.28; 95 % 1.08–1.51 (random effects model). As ultra-violet B solar radiation highly depends on latitude, and can promote, in less pigmented skin, intravascular folate photolysis, we stratified the analysis by latitude region, defining as Tropical (between 23.5^° S and 23.5^° N), Sub-Tropical (between 23.5^° and 40^° N and S), and Northern (≥40^o N). Significant association was only found for Sub-Tropical area, both using fixed and random effect models. In conclusion, MTHFR 677C > T polymorphism is a moderate risk factor for DS for some populations, and populations located in Sub-Tropical region seem to be at greater risk. Latitude, ethnicity, skin pigmentation, and red blood cell folate are important variables to be considered in future studies.     

The Impact of MMP-2 and Its Specific Inhibitor TIMP-2 Expression on the WHO Grade and Prognosis of Gliomas in Chinese Population: a Meta-Analysis

So far, the prognostic value of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of matrix metalloproteinase 2 (TIMP-2) expressions in patients with gliomas has been widely reported, especially in China. But, the results were inconsistent. Thus, we conducted a meta-analysis to determine the correlation of MMP-2 and TIMP-2 expressions with the prognosis of patients with gliomas. Identical search strategies were used to search relevant literature in electronic databases updated to May 1, 2015, and odds ratios (ORs) with 95 % confidence intervals (95 % CIs) were estimated. Funnel plots and Egger’s tests were conducted for the evaluation of publication bias, and heterogeneity and sensitivity were also analyzed. Finally, a total of 25 studies involving 1572 patients were included in the meta-analysis. Coincidentally, all these studies were conducted in Chinese population. It was found that MMP-2 expression was significantly associated with high-WHO grade gliomas (n?=?24, OR?=?6.54, CI?=?4.98–8.60; I ²?=?0 %, P?=?0.911) and poor overall survival (OS), while it did not correlate to age (n?=?2, OR?=?0.78, CI?=?0.35–1.74; I ²?=?0 %, P?=?0.621) and gender (n?=?2, OR?=?1.15, CI?=?0.51–2.62; I ²?=?0 %, P?=?0.995). Moreover, the results of the pooled analysis indicated that there was no association between TIMP-2 expression and the WHO grade of gliomas (n?=?7, OR?=?1.02, 95 % CI?=?0.68–1.54; I ²?=?71.4 %, P?=?0.002), but the ratio of MMP-2 and TIMP-2 (MMP-2/TIMP-2) rose with the increase of the WHO grade of gliomas. In conclusion, there was no correlation between TIMP-2 expression and the WHO grade of gliomas, while MMP-2 expression was potently associated with high-WHO grade of gliomas.     

MTHFR polymorphisms and ovarian cancer risk: a meta-analysis

The C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase (MTHFR) have been reported to alter the risk of ovarian cancer. However, the results are still inconclusive. For better understanding of the effect of these two polymorphisms on ovarian cancer risk, a meta-analysis was performed. An extensive search was performed to identify all case–control studies investigating such association. The strength of association between these two polymorphisms and ovarian cancer risk was assessed by odds ratio (OR) with the corresponding 95?% confidence interval (95?% CI). 3,496 cases and 3,631 controls for C677T polymorphism and 3,280 cases and 3,346 controls for A1298C polymorphism were included in this meta-analysis. The results suggested that there were no significant associations between C677T and A1298C polymorphisms and ovarian cancer risk in overall comparisons in all genetic models (For C677T: TT vs. CC: OR?=?0.94, 95?% CI?=?0.71–1.24, P?=?0.65; CT vs. CC: OR?=?1.03, 95?% CI?=?0.93–1.14, P?=?0.57; TT/CT vs. CC: OR?=?1.01, 95?% CI?=?0.88–1.16, P?=?0.87; TT vs. CC/CT: OR?=?0.93, 95?% CI?=?0.72–1.20, P?=?0.58. For A1298C: CC vs. AA: OR?=?1.05, 95?% CI?=?0.88–1.25, P?=?0.65; CA vs. AA: OR?=?0.98, 95?% CI?=?0.88–1.08, P?=?0.66; CC/CA vs. AA: OR?=?0.99, 95?% CI?=?0.90–1.09, P?=?0.85; CC vs. AA/CA: OR?=?1.06, 95?% CI?=?0.90–1.26, P?=?0.46). Subgroup analysis based on ethnicities and influence analysis did not perturb the results. In conclusion, the results of this meta-analysis indicate that the MTHFR C677T and A1298C polymorphisms are not associated with ovarian cancer risk, especially in Caucasians.     

Calcium-channel blockers and cognitive function in elderly people: results from the Canadian Study of Health and Aging

BACKGROUND: Concern has been raised about the potential for adverse cognitive effects associated with the use of calcium-channel blockers (CCBs) in older people. This study was undertaken to examine prospectively the association between the use of these and other antihypertensive drugs and cognitive function. METHODS: The authors examined data from the Canadian Study of Health and Aging (CSHA), a population-based, prospective 5-year investigation of the epidemiology of dementia and other health problems in Canadians 65 years of age and older. The risk of cognitive decline, as indicated by a decline in performance on the Modified Mini-Mental State (3MS) examination over the 5-year period, was assessed in relation to the use of antihypertensive and diuretic drugs by 205 subjects with a history of hypertension and no evidence of dementia at baseline. RESULTS: The proportion of subjects whose cognitive performance declined over the study period was significantly higher in the group using CCBs than in the group using other antihypertensive agents (75% v. 59%). The adjusted odds ratio (OR) for a significant decline in cognitive performance (defined as a decrease in 3MS score of 10 points or more) was 2.28 (95% confidence interval [CI] 1.12-4.66) for subjects using CCBs. The adjusted ORs (and 95% CIs) for cognitive decline in subjects using selected antihypertensive agents or diuretics relative to those exposed to beta-blockers were as follows: angiotensin-converting-enzyme inhibitor, OR 1.36 (95% CI 0.41-4.55); diuretic or other antihypertensive drug, OR 1.45 (95% CI 0.51-4.14); dihydropyridine CCB (nifedipine), OR 1.94 (95% CI 0.52-7.27) and non-dihydropyridine CCB (diltiazem or verapamil), OR 3.72 (95% CI 1.22-11.36). INTERPRETATION: Older people taking CCBs were significantly more likely than those using other agents to experience cognitive decline. These findings are consistent with the results of previous cross-sectional research and emphasize the need for further trials to examine the associations between CCB use, blood pressure and cognitive impairment in elderly patients.     

Cardiovascular risk factors and cognitive function in middle aged and elderly Lithuanian urban population: results from the HAPIEE study

Background

The purpose of this study was to examine associations between cardiovascular risk factors and cognitive ability in middle aged and elderly Lithuanian urban population.

Methods

Data from the survey performed in the framework of the HAPIEE (Health, Alcohol, Psychosocial Factors in Eastern Europe) study were presented. A random sample of 7,087 individuals aged 45–72 years was screened in 2006–2008.

Results

The scores of immediate recall and delayed verbal recall, cognitive speed and attention were significantly lower in men than in women; yet numerical ability scores were higher in men. Significant associations between lowered cognitive functions and previous stroke (in male OR?=?2.52; 95% CI?=?1.75-3.64; in female OR?=?2.45; 95% CI?=?1.75, 3.64) as well as ischemic heart disease history (among male OR?=?1.28; 95% CI?=?1.03-1.60) have been determined. Higher level of physical activity in leisure time (among female OR?=?1.32; 95% CI?=?1.03-1.69), poor self-rated health (among male OR?=?1.57; 95% CI?=?1.15-2.14) and poor quality of life (in male OR?=?1.67; 95% CI?=?1.07-2.61; in female OR?=?2.81; 95% CI?=?1.92-4.11) were related to lowered cognitive function.

Conclusions

The findings of the study suggest that associations between cardiovascular risk factors and lowered cognitive function among healthy middle-aged and elderly adults strongly depend on gender.