A systematic review investigating fatigue, psychological and cognitive impairment following TIA and minor stroke:protocol paper

Approximately 20,000 people have a transient ischemic attack (TIA) and 23,375 have a minor stroke in England each year. Fatigue, psychological and cognitive impairments are well documented post-stroke. Evidence suggests that TIA and minor stroke patients also experience these impairments; however, they are not routinely offered relevant treatment. This systematic review aims to: (1) establish the prevalence of fatigue, anxiety, depression, post-traumatic stress disorder (PTSD) and cognitive impairment following TIA and minor stroke and to investigate the temporal course of these impairments; (2) explore impact on quality of life (QoL), change in emotions and return to work; (3) identify where further research is required and to potentially inform an intervention study

Vitamin D receptor gene polymorphisms in multiple sclerosis patients in northwest Greece

<p>Abstract</p> <p>Background</p> <p>Polymorphisms of the vitamin D receptor (VDR) gene have been linked to both multiple sclerosis (MS) and osteoporosis. We examined the frequency of the Taq-I and Bsm-I polymorphisms of the vitamin D receptor (VDR) gene in 69 patients with MS and 81 age and sex-matched healthy individuals. Genotyping of Taq-I (rs731236) and Bsm-I (rs1544410) was performed using TaqMan^®SNP Genotyping Assay. All patients and controls had determination of body mass index (BMI), bone mineral density (BMD) and smoking history.</p> <p>Results</p> <p>The mean age of patients was 39 ± 10.5 years compared to 38.7 ± 10.7 years of the controls (p = 0.86), the BMI was 24.8 ± 4.2 kg/m²compared to 25.7 ± 4.8 kg/m²of the controls (p = 0.23), the BMD in the lumbar spine 0.981 ± 0.15 compared to 1.025 ± 013 of the controls (p = 0.06) and the total hip BMD was 0.875 ± 0.14 compared to 0.969 ± 0.12 of the controls (p < 0.001). There were no differences of the Taq-I (TT, CT, CC) and Bsm-I genotypes (GG, GA, AA) and allelic frequencies between MS and control individuals. Multivariate analysis also failed to show any association of the Taq-I and Bsm-I polymorphisms and MS or sex, BMI, BMD and smoking history.</p> <p>Conclusions</p> <p>This study suggests that the Taq-I and Bsm-I polymorphisms of the VDR gene are not associated with MS risk, BMI or BMD in the Greek population studied.</p

Characterizing Genetic Risk at Known Prostate Cancer Susceptibility Loci in African Americans

GWAS of prostate cancer have been remarkably successful in revealing common genetic variants and novel biological pathways that are linked with its etiology. A more complete understanding of inherited susceptibility to prostate cancer in the general population will come from continuing such discovery efforts and from testing known risk alleles in diverse racial and ethnic groups. In this large study of prostate cancer in African American men (3,425 prostate cancer cases and 3,290 controls), we tested 49 risk variants located in 28 genomic regions identified through GWAS in men of European and Asian descent, and we replicated associations (at p≤0.05) with roughly half of these markers. Through fine-mapping, we identified nearby markers in many regions that better define associations in African Americans. At 8q24, we found 9 variants (p≤6×10−4) that best capture risk of prostate cancer in African Americans, many of which are more common in men of African than European descent. The markers found to be associated with risk at each locus improved risk modeling in African Americans (per allele OR = 1.17) over the alleles reported in the original GWAS (OR = 1.08). In summary, in this detailed analysis of the prostate cancer risk loci reported from GWAS, we have validated and improved upon markers of risk in some regions that better define the association with prostate cancer in African Americans. Our findings with variants at 8q24 also reinforce the importance of this region as a major risk locus for prostate cancer in men of African ancestry

Serum cytokine and glucose levels as predictors of poststroke fatigue in acute ischemic stroke patients

Fatigue is a common but often overlooked symptom after stroke. This study investigated whether stroke type, infarct volume, and laterality, as well as the levels of various cytokines and other blood components in the acute phase of acute ischemic stroke (AIS), can predict the level of fatigue at 6, 12, and 18 months after its onset. In 45 patients with acute stroke, serum levels of C-reactive protein, hemoglobin, glucose, and 13 cytokines were measured within 72 h of stroke onset. The cytokine measurements were performed using BioPlex XMap technology (Luminex). The acute serum levels of interleukin (IL)-1β and glucose were positively correlated with the score on the Fatigue Severity Scale (FSS) at 6 months after the stroke (r = 0.37, p = 0.015, and r = 0.37, p = 0.017, respectively). The acute serum levels of IL-ra and IL-9 were negatively correlated with FSS score at 12 months after the stroke (r = −0.38, p = 0.013, and r = −0.36, p = 0.019, respectively). The FSS score at 12 months after stroke was significantly lower in patients with radiologically confirmed infarction than in those without such confirmation (p = 0.048). The FSS score at 18 months was not correlated with any of the measured variables. High acute serum levels of glucose and IL-1β, and low IL1-ra and IL-9 may predict fatigue after AIS, indicating that the development of poststroke fatigue can be accounted for by the proinflammatory response associated with AIS. These novel findings support a new cytokine theory of fatigue after stroke. However, more research is needed to validate the results of this study

Germline variation at 8q24 and prostate cancer risk in men of European ancestry

An Author Correction to this article was published on 17 January 2019.Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10 −15 ), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification. © 2018, The Author(s).Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10 −15 ), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification. © 2018, The Author(s).Peer reviewe

Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation.

Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa

Genome-wide association study identifies susceptibility loci for B-cell childhood acute lymphoblastic leukemia.

Genome-wide association studies (GWAS) have advanced our understanding of susceptibility to B-cell precursor acute lymphoblastic leukemia (BCP-ALL); however, much of the heritable risk remains unidentified. Here, we perform a GWAS and conduct a meta-analysis with two existing GWAS, totaling 2442 cases and 14,609 controls. We identify risk loci for BCP-ALL at 8q24.21 (rs28665337, P = 3.86 × 10-9, odds ratio (OR) = 1.34) and for ETV6-RUNX1 fusion-positive BCP-ALL at 2q22.3 (rs17481869, P = 3.20 × 10-8, OR = 2.14). Our findings provide further insights into genetic susceptibility to ALL and its biology

A physical map of Brassica oleracea shows complexity of chromosomal changes following recursive paleopolyploidizations

<p>Abstract</p> <p>Background</p> <p>Evolution of the Brassica species has been recursively affected by polyploidy events, and comparison to their relative, <it>Arabidopsis thaliana</it>, provides means to explore their genomic complexity.</p> <p>Results</p> <p>A genome-wide physical map of a rapid-cycling strain of <it>B. oleracea </it>was constructed by integrating high-information-content fingerprinting (HICF) of Bacterial Artificial Chromosome (BAC) clones with hybridization to sequence-tagged probes. Using 2907 contigs of two or more BACs, we performed several lines of comparative genomic analysis. Interspecific DNA synteny is much better preserved in euchromatin than heterochromatin, showing the qualitative difference in evolution of these respective genomic domains. About 67% of contigs can be aligned to the Arabidopsis genome, with 96.5% corresponding to euchromatic regions, and 3.5% (shown to contain repetitive sequences) to pericentromeric regions. Overgo probe hybridization data showed that contigs aligned to Arabidopsis euchromatin contain ~80% of low-copy-number genes, while genes with high copy number are much more frequently associated with pericentromeric regions. We identified 39 interchromosomal breakpoints during the diversification of <it>B. oleracea </it>and <it>Arabidopsis thaliana</it>, a relatively high level of genomic change since their divergence. Comparison of the <it>B. oleracea </it>physical map with Arabidopsis and other available eudicot genomes showed appreciable 'shadowing' produced by more ancient polyploidies, resulting in a web of relatedness among contigs which increased genomic complexity.</p> <p>Conclusions</p> <p>A high-resolution genetically-anchored physical map sheds light on Brassica genome organization and advances positional cloning of specific genes, and may help to validate genome sequence assembly and alignment to chromosomes.</p> <p>All the physical mapping data is freely shared at a WebFPC site (<url>http://lulu.pgml.uga.edu/fpc/WebAGCoL/brassica/WebFPC/</url>; Temporarily password-protected: account: pgml; password: 123qwe123.</p

Runs of homozygosity and testicular cancer risk

Background: Testicular germ cell tumour (TGCT) is highly heritable but > 50% of the genetic risk remains unexplained. Epidemiological observation of greater relative risk to brothers of men with TGCT compared to sons has long alluded to recessively acting TGCT genetic susceptibility factors, but to date none have been reported. Runs of homozygosity (RoH) are a signature indicating underlying recessively acting alleles and have been associated with increased risk of other cancer types. / Objective: To examine whether RoH are associated with TGCT risk. / Methods: We performed a genome‐wide RoH analysis using GWAS data from 3206 TGCT cases and 7422 controls uniformly genotyped using the OncoArray platform. / Results: Global measures of homozygosity were not significantly different between cases and controls, and the frequency of individual consensus RoH was not significantly different between cases and controls, after correction for multiple testing. RoH at three regions, 11p13‐11p14.3, 5q14.1‐5q22.3 and 13q14.11‐13q.14.13, were, however, nominally statistically significant at p < 0.01. Intriguingly, RoH200 at 11p13‐11p14.3 encompasses Wilms tumour 1 (WT1), a recognized cancer susceptibility gene with roles in sex determination and developmental transcriptional regulation, processes repeatedly implicated in TGCT aetiology. / Discussion and conclusion: Overall, our data do not support a major role in the risk of TGCT for recessively acting alleles acting through homozygosity, as measured by RoH in outbred populations of cases and controls

Fatigue after Stroke: Baseline Predictors and Influence on Survival. Analysis of Data from UK Patients Recruited in the International Stroke Trial

Little is known about the associations of post-stroke fatigue or its influence on survival. The vitality component of the Short Form 36 (SF-36) is a valid and reliable measure of post-stroke fatigue. We sought to identify associates of post-stroke fatigue and determine whether fatigue predicted survival.We used SF-36 vitality scores obtained by postal questionnaires from 1080 UK patients randomised in the International Stroke Trial, at a mean of 64 weeks after stroke onset. We used logistic regression to explore factors at randomisation which predicted SF-36 vitality at follow-up, and the relationship between SF-36 vitality and both SF-36 mental health and SF-36 emotional role function at follow-up. We used Cox proportional hazards to explore the influence of SF-36 vitality at follow-up on subsequent survival, using four different statistical models for handling missing data.Female sex, increasing age, lower mental health and lower emotional role function scores were associated with greater degrees of fatigue after stroke (i.e. lower vitality scores) but these factors explained <30% of the variance (R(2)) in fatigue. In two models, fatigue at follow-up was associated with shorter subsequent survival.Increasing age, female sex, emotional role function and mental health were associated with increased fatigue at a mean of 64 weeks after stroke onset, but explained less than 30% of the variance. Fatigue was associated with reduced subsequent long-term survival in 2/4 models. Further work is needed to identify the biological substrate of fatigue and to clarify its influence on survival