Background and hypothesis
Inflammation is implicated in the pathogenesis and outcome of ischaemic injury. Poststroke inflammation is associated with outcome but it remains unclear whether such ...inflammation precedes or results from ischaemic injury. We hypothesised that inflammatory markers are associated with an increased risk of recurrent vascular events soon after transient ischaemic attack and minor stroke.
Methods
This was a multicentre, prospective, nested case–control study. Plasma concentrations of C-reactive protein, interleukin-6, interleukin-1-receptor antagonist and fibrinogen, leucocyte counts, erythrocyte sedimentation rate and inflammatory gene allele frequencies were analysed in 711 patients with recent transient ischaemic attack or minor stroke. Cases were defined by the incidence of one or more recurrent vascular events during the three-month follow-up. Association of inflammatory markers with case-status was determined using conditional logistic regression.
Results
Plasma concentrations of C-reactive protein, interleukin-1-receptor antagonist and interleukin-6 were not associated with case-status. In secondary analyses, only erythrocyte sedimentation rate was significantly associated with case-status (odds ratio 1·39, 95% confidence interval 1·03–1·85; P=0·03), but this effect did not persist after adjustment for smoking and past history of transient ischaemic attack or stroke. Single nucleotide polymorphisms in four inflammatory genes (interleukin-6, fibrinogen, P-selectin and vascular cell adhesion molecule-1) were nominally associated with case-status.
Conclusions
Circulating inflammatory markers were not associated with recurrent vascular events. Nominally significant associations between genetic markers and case-status will require replication. These data provide little evidence for an inflammatory state predisposing to stroke and other vascular events in a susceptible population.
•Genetic variants that are related to epigenetic regulations and DNA repair may be associated with age-dependent variations of chronotype.•Postnatal seasons may program biological rhythms via ...epigenetic alterations and neural development.•Some polymorphisms contribute towards inter-individual variation in season of birth effect.•Previously reported genetic variants that were associated with chronotype could not fully explain the longitudinal change of chronotype.
Human chronotype, the temporal pattern of daily behaviors, is influenced by postnatal seasonal programming and ageing. The aim of this study was to investigate genetic variants that are associated with season of birth programming and longitudinal chronotype change. Longitudinal sleep timing and genotype data from 1449 participants were collected for up to 27 years. Gene-environment interaction analysis was performed for 445 candidate single nucleotide polymorphisms that have previously been associated with chronotype. Associations were tested using linear mixed model. We identified 67 suggestively significant genomic loci that have genotype-ageing interaction and 25 genomic loci that may have genotype-season of birth interaction in determining chronotype. We attempted to replicate the results using longitudinal data of the UK Biobank from approximately 30,000 participants. Biological functions of these genes suggest that epigenetic regulation of gene expression and neural development may have roles in these processes. The strongest associated gene for sleep trajectories was ALKBH5, which has functions of DNA repair and epigenetic regulation. A potential candidate gene for postnatal seasonal programming was SIRT1, which has previously been implicated in postnatal programming, ageing and longevity. Genetic diversity may explain the heterogeneity in ageing-related change of sleep timing and postnatal environmental programming of later-life chronotype.
Individuals with an 'evening' chronotype tend to sleep and wake later than people described to be 'morning' type if given a free choice. Since early awakening times, due to school and occupation, may ...be more challenging for those with evening chronotype, they are expected to be at greater risk of adverse health, occupational and educational outcomes. Our objectives are to investigate associations between chronotype and occupational, educational and health outcomes in a longitudinal cohort. We use sleep, sociodemographic and health data from The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age, 1982 through 2010. The relationship between employment and longitudinal midsleep trajectories were estimated using linear mixed models. Associations between employment status and Cornell Medical Index, Beck Depression Inventory scores, cortisol concentrations at different times of the day stratified by chronotype were estimated using regression. The relationship between chronotype, occupational success, education, and cognition were also examined using regression methods. In older adults, compared to non-employed participants, employed participants get up 0.45 hours earlier. Evening-type employed individuals had earlier midsleep time compared to their non-employed counterparts and had abnormal longitudinal trajectories with an increasing trend as they aged. Employed individuals with evening chronotype had a higher risk of depression than employed morning-types. Moreover, employed individuals with evening chronotype had a higher cortisol concentration at 14:00 h than non-employed individuals. In addition, memory score was lower in individuals with morning chronotype, however processing speed was higher in individuals with morning chronotype compared to evening. Morning-types had a higher age when they finished full time education. Relative to evening-types, those with morning chronotype were 6.5% more likely to be in a job classed as professional or intermediate. Our findings suggest that evening-types are at a disadvantage with regards to occupational, educational and health outcomes in older adults due to their vulnerability to circadian and sleep disruption.
Introduction
Kidney dysfunction is a highly significant disease, both in the United Kingdom and globally. Many previous studies have reported associations between human leukocyte antigens (HLA) and ...renal function; this systematic review attempts to identify, summarize and appraise all published studies of these associations.
Methods
A literature search was performed using Medline, Embase and Cochrane Central Register of Controlled Trials to identify papers whose keywords included each of the following concepts: HLA, renal failure and genetic association. A total of 245 papers were identified and assessed for eligibility; 35 of these were included in the final study.
Results
A total of 95 HLA types and 14 three‐locus haplotypes were reported to be associated with either increased or decreased renal function. A number of these findings were replicated by independent studies that reported 16 types were protective against renal dysfunction and 15 types were associated with reduced renal function. A total of 20 HLA types were associated with both increased risk of renal disease and decreased risk by independent studies.
Discussion
There is very little consensus on which HLA types have a protective or deleterious effect on renal function. Ethnicity may play a role, with HLA types possibly having different effects among different populations, and it is possible that the different primary diseases that lead to ESRD may have different HLA associations. Some of the studies may contain type I and type II errors caused by insufficient sample sizes, cohort selection and statistical methods. Although we have compiled a comprehensive list of published associations between renal function and HLA, in many cases, it is unclear which associations are reliable. Further studies are required to confirm or refute these findings.
An early symptom of Alzheimer's disease (AD) is a disturbance of the circadian rhythm that is associated with disrupted sleep/wake cycles.
To investigate if BMAL1, a key gene that drives the ...circadian cycle, is epigenetically regulated in brains in relation to longitudinal changes in cognition, sleep quality, and AD neuropathology.
Frontal cortex tissues were acquired from the Manchester Brain Bank (N = 96). DNA methylation at six CpG sites at the promoter of BMAL1, determined using bisulfite pyrosequencing, was tested for associations with Braak stage, CERAD score and Thal phase, longitudinal changes in cognition, sleep measurements and cross-section measures of depressive symptoms (BDI score).
Methylation across all the CpGs strongly correlated with each other. We found increased CpG2 methylation with higher Braak (t(92), p = 0.015) and CERAD (t(94), p = 0.044) stages. No significance was found between longitudinal fluid intelligence, processing speed and memory tests, but methylation at CpG1 (r = 0.20, p = 0.05) and CpG4 (r = 0.20, p = 0.05) positively correlated with vocabulary. CpG2 positively correlated with cross-sectional fluid intelligence (r = 0.20 p = 0.05) and vocabulary (r = 0.22 p = 0.03). Though longitudinal analysis revealed no significance between sleep duration, midsleep and efficiency for any of the CpG sites, CpG3 (B = 0.03, 95% CI, p = 0.03) and CpG5 (B = 0.04, 95% CI, p = 0.01) significantly correlated with night wake. CpG4 correlated with depressive symptoms (B = -0.27, 95% CI, p = 0.02).
Methylation of BMAL1 associated with tau pathology, changes in cognitive measures, a measure of sleep and depressive symptoms, suggesting an involvement of the circadian cycle.
Human leukocyte antigens (HLA) have been associated with renal function, but previous studies report contradictory findings. There has been a lack of research into how HLA affects renal function in ...Black, Asian and Minority Ethnic (BAME) people in the UK, despite BAME people being disproportionately affected by renal dysfunction. This study included >27 000 UK Biobank subjects of six ethnicities (>12 100 Irish, >5400 Indian, >4000 Black Caribbean, >3000 Black African, >1600 Pakistani, and >1400 Chinese) aged 39 to 73. Subjects' high‐resolution HLA genotypes were imputed using HLA*IMP:02 software. Regression analysis was used to compare 108 imputed HLA alleles with two measures of estimated glomerular filtration rate (eGFR): one based on serum creatinine; one based on serum cystatin. Secondary analysis compared CKD stage 2 subjects to healthy controls. Nine imputed HLA alleles were associated with eGFR (adjusted P < .05). Six associations were based on creatinine in Black African subjects: HLA‐B*53:01 (beta = −2.628, adjusted P = 4.69 × 10−4); C*04:01 (beta = −1.667, adjusted P = .0269); DPA1*02:01 (beta = −1.569, adjusted P = .0182); and DPA1*02:02 (beta = −1.716, adjusted P = .0251) were linked to decreased renal function, while DRB1*03:01 (beta = 3.200, adjusted P = 3.99 × 10−3) and DPA1*01:03 (beta = 2.276, adjusted P = 2.31 × 10−5) were linked to increased renal function. Two of these (HLA‐B*53:01 and C*04:01) are commonly inherited together. In Irish subjects, HLA‐DRB1*04:01 (beta = 1.075, adjusted P = .0138) was linked to increased eGFR (based on cystatin); in Indian subjects, HLA‐DRB1*03:01 (beta = −1.72, adjusted P = 4.78 × 10−3) and DQB1*02:01 (beta = −1.755, adjusted P = 2.26 × 10−3)were associated with decreased eGFR (based on cystatin). No associations were found in the other three ethnic groups. Nine HLA alleles appear to be associated with kidney function in BAME people in the UK. This could have applications for the diagnosis and treatment of renal disease and could help reduce health inequalities in the UK.
Streptococcus pneumoniae (pneumococcus) is responsible for over one million deaths per year, with young children, the elderly and immunocompromised individuals being most at risk. Approximately half ...of East African children have been reported to be asymptomatic carriers of pneumococcus with invasive infection occurring after the disruption of the respiratory membrane which is believed to be caused by the host immune response. Racial incidence of invasive pneumococcal disease (IPD) is higher in certain populations even after adjusting for environmental factors suggesting a genetic component to disease susceptibility. The nitric oxide synthase 2A (NOS2A) gene is responsible for the production of nitric oxide under pathological conditions including host defence against bacterial infection. Nitric oxide is a modulator of apoptotic and inflammatory cascades and endothelial permeability. We hypothesised that genetic variants within this gene may predispose to disease risk and survival.
A cohort of 299 children with IPD (221 meningitis, 41 pneumonia and 37 with bacteraemia) and 931 age matched controls from Malawi were used in this study. We investigated nine haplotype tagging single nucleotide polymorphisms within the NOS2A gene and compared the presence or absence of the minor alleles in cases and controls and survivors and non-survivors within the cases.
We observed no significant associations between cases and controls or with survival in either all IPD cases or in the separate analysis of meningitis cases. A near significant association was obtained for the comparison of rs8078340 in cases and controls (p-value, 0.078). However, results were unadjusted for multiple testing.
Our results suggest that polymorphic variation within the NOS2A gene does not influence invasive pneumococcal disease susceptibility or survival.
•There has been a rapid acceleration in healthcare related virtual reality research in the last five years.•Terminology around virtual reality technology is complex, varied and often can be ...confused.•The term ‘head mounted display’ has recently emerged in the definition of virtual reality.•We present an evidenced based definition for the term virtual reality to be used from the year 2022.
There has been significant advancement in virtual reality (VR) technology since its conception in 1960, and this evolution has particularly accelerated in recent years. Alongside this, we are seeing an expansion of research interest within which the definitions and nomenclature can be complex and lead to potential misunderstanding or confusion. We present a systematic review of definitions of the term VR as reported within the medical literature with the aim to establish the terminology used to define VR, the differences that exist through the literature, and if they have changed over time.
By reporting according to the PRISMA guidelines, we present a systematic review of VR definitions in the English language medical literature. The databases Medline, PubMed, Web of Science, and Scopus were searched using the search terms ‘virtual reality’, ‘definition’, ‘defined’, or ‘define’. Articles were included if they were peer-reviewed, within the medical literature, published between 22nd December 2001 and 22nd December 2021, and offered either an original or cited definition for the term VR. Following data extraction, quantitative analysis of terminology over time and term density maps have been created.
Eighty-eight studies were included offering 105 definitions of the term VR. Of these articles, 58 were published within the last 5 years. Common terms when defining VR included ‘computer’, ‘environment’, ‘user’, ‘interactive’ and ‘simulation’. In recent years, a novel term ‘head mounted display’ has emerged which was not previously featured in healthcare literature.
This systematic review highlights that the published literature in the field of VR is rapidly expanding. With the growth in technology we can see a complex network of terminology emerge with little homogeneity. Definitions of VR are numerable and high variability exists. We recommend the requirement for consensus in order to urgently unify terminology within the immersive technology field, and whilst waiting for agreement, an evidence-based definition for VR has been suggested.
A systematic review of the literature has been performed to better understand the terminology that academic authors have used to define what virtual reality technology is. This review concluded that a wide range of definitions have been used in the last 20 years. Throughout these definitions a large number of individual terms are being used with very little agreement on their appropriate use. With rapidly expanding technology and increasing complexity within the terminology, future research is at risk of misrepresentation until the academic community agree on the most appropriate terminology to be used when defining VR.
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