Awareness of vaccination status and its predictors among working people in Switzerland

BACKGROUND: Adult vaccination status may be difficult to obtain, often requiring providers to rely on individual patient recall. To determine vaccination status awareness and the sociodemographic predictors of awareness for tetanus, hepatitis A and B, tick born encephalitis (TBE) and influenza vaccination. METHODS: Multivariate analyses were used to evaluate a questionnaire survey of 10 321 employees (4070 women and 6251 men aged 15–72 years) of two companies in Switzerland. RESULTS: Among 10 321 respondents, 75.5% reported knowing their tetanus vaccination status, 64.1% hepatitis A, 61.1% hepatitis B, 64.3% TBE and 71.9% influenza. Between 1 in 4 and 1 in 3 employees were not aware of their vaccination status. Differences in awareness for the five vaccinations considered correlated with gender and language. These differences persisted in multivariate analyses. CONCLUSION: Women employees, German-speaking employees and employees who paid more attention to their diet were more often aware of their vaccination status. A more reliable and readily accessible data source for vaccination status is needed in order to capitalize on opportunities to update vaccinations among Swiss employees

Red wine: A drink to your heart

Mortality and morbidity are still high in cardiovascular disease (CVD). Myocardial ischemia reperfusion injury leading to myocardial infarction is one of the most frequent causes of the death in humans. Atherosclerosis and generation of reactive oxygen species through oxidative stress is the major risk factor for CVD. From the literature collection, it has been identified that moderate consumption of red wine helps in preventing CVD through several mechanisms, including increasing the high-density lipoprotein cholesterol plasma levels, decreasing platelet aggregation, by antioxidant effects, and by restoration of endothelial function. The aim of this review is to discuss the accumulating evidence that suggests that red wine possesses a diverse range of biological actions and may be beneficial in the prevention of CVD

Genome-Wide Association Study of Schizophrenia in Japanese Population

Schizophrenia is a devastating neuropsychiatric disorder with genetically complex traits. Genetic variants should explain a considerable portion of the risk for schizophrenia, and genome-wide association study (GWAS) is a potentially powerful tool for identifying the risk variants that underlie the disease. Here, we report the results of a three-stage analysis of three independent cohorts consisting of a total of 2,535 samples from Japanese and Chinese populations for searching schizophrenia susceptibility genes using a GWAS approach. Firstly, we examined 115,770 single nucleotide polymorphisms (SNPs) in 120 patient-parents trio samples from Japanese schizophrenia pedigrees. In stage II, we evaluated 1,632 SNPs (1,159 SNPs of p<0.01 and 473 SNPs of p<0.05 that located in previously reported linkage regions). The second sample consisted of 1,012 case-control samples of Japanese origin. The most significant p value was obtained for the SNP in the ELAVL2 [(embryonic lethal, abnormal vision, Drosophila)-like 2] gene located on 9p21.3 (p = 0.00087). In stage III, we scrutinized the ELAVL2 gene by genotyping gene-centric tagSNPs in the third sample set of 293 family samples (1,163 individuals) of Chinese descent and the SNP in the gene showed a nominal association with schizophrenia in Chinese population (p = 0.026). The current data in Asian population would be helpful for deciphering ethnic diversity of schizophrenia etiology

Knowledge synthesis of benefits and adverse effects of measles vaccination: the Lasbela balance sheet

<p>Abstract</p> <p>Background</p> <p>In preparation for a cluster-randomized controlled trial of a community intervention to increase the demand for measles vaccination in Lasbela district of Pakistan, a balance sheet summarized published evidence on benefits and possible adverse effects of measles vaccination.</p> <p>Methods</p> <p>The balance sheet listed: 1) major health conditions associated with measles; 2) the risk among the unvaccinated who contract measles; 3) the risk among the vaccinated; 4) the risk difference between vaccinated and unvaccinated; and 5) the likely net gain from vaccination for each condition.</p> <p>Results</p> <p>Two models revealed very different projections of net gain from measles vaccine. A Lasbela-specific combination of low period prevalence of measles among the unvaccinated, medium vaccination coverage and low vaccine efficacy rate, as revealed by the baseline survey, resulted in less-than-expected gains attributable to vaccination. Modelled on estimates where the vaccine had greater efficacy, the gains from vaccination would be more substantial.</p> <p>Conclusion</p> <p>Specific local conditions probably explain the low rates among the unvaccinated while the high vaccine failure rate is likely due to weaknesses in the vaccination delivery system. Community perception of these realities may have had some role in household decisions about whether to vaccinate, although the major discouraging factor was inadequate access. The balance sheet may be useful as a communication tool in other circumstances, applied to up-to-date local evidence.</p

Mutations in the nuclear localization sequence of the Aristaless related homeobox; sequestration of mutant ARX with IPO13 disrupts normal subcellular distribution of the transcription factor and retards cell division

The electronic version of this article is the complete one and can be found online at: http://www.pathogeneticsjournal.com/content/3/1/1Background: Aristaless related homeobox (ARX) is a paired-type homeobox gene. ARX function is frequently affected by naturally occurring mutations. Nonsense mutations, polyalanine tract expansions and missense mutations in ARX cause a range of intellectual disability and epilepsy phenotypes with or without additional features including hand dystonia, lissencephaly, autism or dysarthria. Severe malformation phenotypes, such as X-linked lissencephaly with ambiguous genitalia (XLAG), are frequently observed in individuals with protein truncating or missense mutations clustered in the highly conserved paired-type homeodomain. Results: We have identified two novel point mutations in the R379 residue of the ARX homeodomain; c.1135C>A, p.R379S in a patient with infantile spasms and intellectual disability and c.1136G>T, p.R379L in a patient with XLAG. We investigated these and other missense mutations (R332P, R332H, R332C, T333N: associated with XLAG and Proud syndrome) predicted to affect the nuclear localisation sequences (NLS) flanking either end of the ARX homeodomain. The NLS regions are required for correct nuclear import facilitated by Importin 13 (IPO13). We demonstrate that missense mutations in either the N- or C-terminal NLS regions of the homeodomain cause significant disruption to nuclear localisation of the ARX protein in vitro. Surprisingly, none of these mutations abolished the binding of ARX to IPO13. This was confirmed by co-immunoprecipitation and immmuno fluorescence studies. Instead, tagged and endogenous IPO13 remained bound to the mutant ARX proteins, even in the RanGTP rich nuclear environment. We also identify the microtubule protein TUBA1A as a novel interacting protein for ARX and show cells expressing mutant ARX protein accumulate in mitosis, indicating normal cell division may be disrupted. Conclusions: We show that the most likely, common pathogenic mechanism of the missense mutations in NLS regions of the ARX homeodomain is inadequate accumulation and distribution of the ARX transcription factor within the nucleus due to sequestration of ARX with IPO13.Cheryl Shoubridge, May Huey Tan, Tod Fullston, Desiree Cloosterman, David Coman, George McGillivray, Grazia M Mancini, Tjitske Kleefstra and Jozef Géc

The Framingham Heart Study 100K SNP genome-wide association study resource: overview of 17 phenotype working group reports

Background: The Framingham Heart Study (FHS), founded in 1948 to examine the epidemiology of cardiovascular disease, is among the most comprehensively characterized multi-generational studies in the world. Many collected phenotypes have substantial genetic contributors; yet most genetic determinants remain to be identified. Using single nucleotide polymorphisms (SNPs) from a 100K genome-wide scan, we examine the associations of common polymorphisms with phenotypic variation in this community-based cohort and provide a full-disclosure, web-based resource of results for future replication studies. Methods: Adult participants (n = 1345) of the largest 310 pedigrees in the FHS, many biologically related, were genotyped with the 100K Affymetrix GeneChip. These genotypes were used to assess their contribution to 987 phenotypes collected in FHS over 56 years of follow up, including: cardiovascular risk factors and biomarkers; subclinical and clinical cardiovascular disease; cancer and longevity traits; and traits in pulmonary, sleep, neurology, renal, and bone domains. We conducted genome-wide variance components linkage and population-based and family-based association tests. Results: The participants were white of European descent and from the FHS Original and Offspring Cohorts (examination 1 Offspring mean age 32 ± 9 years, 54% women). This overview summarizes the methods, selected findings and limitations of the results presented in the accompanying series of 17 manuscripts. The presented association results are based on 70,897 autosomal SNPs meeting the following criteria: minor allele frequency ≥ 10%, genotype call rate ≥ 80%, Hardy-Weinberg equilibrium p-value ≥ 0.001, and satisfying Mendelian consistency. Linkage analyses are based on 11,200 SNPs and short-tandem repeats. Results of phenotype-genotype linkages and associations for all autosomal SNPs are posted on the NCBI dbGaP website at http:// www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007. Conclusion: We have created a full-disclosure resource of results, posted on the dbGaP website, from a genome-wide association study in the FHS. Because we used three analytical approaches to examine the association and linkage of 987 phenotypes with thousands of SNPs, our results must be considered hypothesis-generating and need to be replicated. Results from the FHS 100K project with NCBI web posting provides a resource for investigators to identify high priority findings for replication.Molecular and Cellular Biolog

Convergent genetic and expression data implicate immunity in Alzheimer's disease

Background Late–onset Alzheimer's disease (AD) is heritable with 20 genes showing genome wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease we extended these genetic data in a pathway analysis. Methods The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (p = 3.27×10-12 after multiple testing correction for pathways), regulation of endocytosis (p = 1.31×10-11), cholesterol transport (p = 2.96 × 10-9) and proteasome-ubiquitin activity (p = 1.34×10-6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected p 0.002 – 0.05). Conclusions The immune response, regulation of endocytosis, cholesterol transport and protein ubiquitination represent prime targets for AD therapeutics