Promoting and maintaining health of people with sight loss: A scoping study

This study was undertaken in response to a request by the Thomas Pocklington Trust to identify and explore the following issues: • The needs and concerns regarding immediate risks to health and safety related to sight loss; • Additional risks arising from sight loss for those who are also managing a long term disease; • The difficulties in maintaining and promoting health; • Whether or not health promotion activities and policies sufficiently address perceived needs. Findings pertaining to these objectives have been generated from data collected in Leeds, UK, a city where innovative programming for sight loss has either been planned or is being incorporated into health planning and a review of the literature. Findings related to the last two issues indicate that gaps exist in service provision for maintaining health and emphasise the need for more explicitly targeted health promotion initiatives that could address current weaknesses. - A review of the literature; - Focus group discussions with a range of people who had experienced sight loss; - Interviews with professional practitioners engaged in service provision to this population; - An expert hearing with four professional practitioners, one of whom had sight loss, and two service users with sight loss. Most participants were from the West Yorkshire region and the services described in the study are largely located in Leeds. Evidence from the literature review suggests that people with visual impairment have increased risk of accidents within the home and that ensuing consequences include injuries incurred and decreased confidence. Rates of depression among people who are blind or partially sighted are far higher than in the wider population and the likelihood of depression increases with age, although psycho-social interventions and technological assistance can be successfully implemented to improve quality of life. Sight loss together with other long term health conditions exacerbates the impact of other health conditions and has particularly severe impact on the wellbeing of older people insofar as it may affect their mobility, which in turn increases their risk of falls and depression. The nature and level of support available to people is variable but it is clear that access both to the right information at the right time and to appropriate services is a critical issue. Focus group discussions, interviews and the expert hearing corroborated and extended the themes noted in the literature and discuss the differential impact of different risks to health and the difficulties of coping with these at different times in a person’s life. A simple typology was defined using two dimensions of experience (‘stage of life’ and ‘early/late onset of sight loss’) as a means of organizing findings and providing a means of making further distinctions in interpreting the data. Potentially, this scheme can allow health promotion initiatives to be targeted more effectively to stages at which people with sight loss are more likely to encounter specific difficulties in managing and maintaining their health. There was a clear consensus throughout the study that interventions to meet the needs of people with sight loss must be tailored to meet the specific needs of individuals: people with sight loss are not a homogeneous group and the way in which each person experiences the challenges of sight loss and of managing their health will inevitably vary from person to person. Recommendations generated by this study include: • The scope for more pro-active services and need for closer collaboration between service providers; • The need for provision and promotion of targeted information; • The need for greater awareness of the needs of people with visual impairments among generic service providers; and • Further research that explores the usefulness of the typology with a larger sample more representative of population demographics such as BME communities that are more likely to slip through the cracks of service provision

The geography of recent genetic ancestry across Europe

The recent genealogical history of human populations is a complex mosaic formed by individual migration, large-scale population movements, and other demographic events. Population genomics datasets can provide a window into this recent history, as rare traces of recent shared genetic ancestry are detectable due to long segments of shared genomic material. We make use of genomic data for 2,257 Europeans (the POPRES dataset) to conduct one of the first surveys of recent genealogical ancestry over the past three thousand years at a continental scale. We detected 1.9 million shared genomic segments, and used the lengths of these to infer the distribution of shared ancestors across time and geography. We find that a pair of modern Europeans living in neighboring populations share around 10-50 genetic common ancestors from the last 1500 years, and upwards of 500 genetic ancestors from the previous 1000 years. These numbers drop off exponentially with geographic distance, but since genetic ancestry is rare, individuals from opposite ends of Europe are still expected to share millions of common genealogical ancestors over the last 1000 years. There is substantial regional variation in the number of shared genetic ancestors: especially high numbers of common ancestors between many eastern populations likely date to the Slavic and/or Hunnic expansions, while much lower levels of common ancestry in the Italian and Iberian peninsulas may indicate weaker demographic effects of Germanic expansions into these areas and/or more stably structured populations. Recent shared ancestry in modern Europeans is ubiquitous, and clearly shows the impact of both small-scale migration and large historical events. Population genomic datasets have considerable power to uncover recent demographic history, and will allow a much fuller picture of the close genealogical kinship of individuals across the world.Comment: Full size figures available from http://www.eve.ucdavis.edu/~plralph/research.html; or html version at http://ralphlab.usc.edu/ibd/ibd-paper/ibd-writeup.xhtm

Enterovirus specific anti-peptide antibodies

Enterovirus 71 (EV-71) is the main causative agent of hand, foot, and mouth disease (HFMD) which is generally regarded as a mild childhood disease. In recent years, EV71 has emerged as a significant pathogen capable of causing high mortalities and severe neurological complications in large outbreaks in Asia. A formalin-inactivated EV71 whole virus vaccine has completed phase III trial in China but is currently unavailable clinically. The high cost of manufacturing and supply problems may limit practical implementations in developing countries. Synthetic peptides representing the native primary structure of the viral immunogen which is able to elicit neutralizing antibodies can be made readily and is cost effective. However, it is necessary to conjugate short synthetic peptides to carrier proteins to enhance their immunogenicity. This review describes the production of cross-neutralizing anti-peptide antibodies in response to immunization with synthetic peptides selected from in silico analysis, generation of B-cell epitopes of EV71 conjugated to a promiscuous T-cell epitope from Poliovirus, and evaluation of the neutralizing activities of the anti-peptide antibodies. Besides neutralizing EV71 in vitro, the neutralizing antibodies were cross-reactive against several Enteroviruses including CVA16, CVB4, CVB6, and ECHO13

Candidate gene analysis of spontaneous preterm delivery: New insights from re-analysis of a case-control study using case-parent triads and control-mother dyads

<p>Abstract</p> <p>Background</p> <p>Spontaneous preterm delivery (PTD) has a multifactorial etiology with evidence of a genetic contribution to its pathogenesis. A number of candidate gene case-control studies have been performed on spontaneous PTD, but the results have been inconsistent, and do not fully assess the role of how two genotypes can impact outcome. To elucidate this latter point we re-analyzed data from a previously published case-control candidate gene study, using a case-parent triad design and a hybrid design combining case-parent triads and control-mother dyads. These methods offer a robust approach to genetic association studies for PTD compared to traditional case-control designs.</p> <p>Methods</p> <p>The study participants were obtained from the Norwegian Mother and Child Cohort Study (MoBa). A total of 196 case triads and 211 control dyads were selected for the analysis. A case-parent triad design as well as a hybrid design was used to analyze 1,326 SNPs from 159 candidate genes. We compared our results to those from a previous case-control study on the same samples. Haplotypes were analyzed using a sliding window of three SNPs and a pathway analysis was performed to gain biological insight into the pathophysiology of preterm delivery.</p> <p>Results</p> <p>The most consistent significant fetal gene across all analyses was COL5A2. The functionally similar COL5A1 was significant when combining fetal and maternal genotypes. PON1 was significant with analytical approaches for single locus association of fetal genes alone, but was possibly confounded by maternal effects. Focal adhesion (hsa04510), Cell Communication (hsa01430) and ECM receptor interaction (hsa04512) were the most constant significant pathways.</p> <p>Conclusion</p> <p>This study suggests a fetal association of COL5A2 and a combined fetal-maternal association of COL5A1 with spontaneous PTD. In addition, the pathway analysis implied interactions of genes affecting cell communication and extracellular matrix.</p

Longitudinal Determinants of Consistent Condom Use by Partner Type Among Young Injection Drug Users: The Role of Personal and Partner Characteristics

We investigated the longitudinal influence of individual-, relationship- and social-level factors on condom use by partner type among young injections drug users (IDUs) enrolled in the Collaborative Injection Drug Users Study-III/Drug Users Intervention Trial (CIDUS-III/DUIT) from 2002 to 2004. Based on longitudinal analysis using generalized estimating equations (GEE), consistent condom use with main partners was more commonly reported among males and those with greater self-efficacy for condom use; main partner’s desire for pregnancy and needle sharing were negatively associated with consistent condom use. Among those with casual partners, having fewer sex partners was associated with consistent condom use. Positive attitudes toward condom use and partner norms supporting condom use were associated with greater consistent condom use with both partner types. These findings suggest that intervention strategies targeting individual- and partner-level factors may provide avenues for intervening upon sexual risks among young IDUs

Augmented Cardiac Hypertrophy in Response to Pressure Overload in Mice Lacking ELTD1

BACKGROUND: Epidermal growth factor (EGF), latrophilin and seven transmembrane domain-containing protein 1 (ELTD1) is developmentally upregulated in the heart. Little is known about the relationship between ELTD1 and cardiac diseases. Therefore, we aimed to clarify the role of ELTD1 in pressure overload-induced cardiac hypertrophy. METHODS AND RESULTS: C57BL/6J wild-type (WT) mice and ELTD1-knockout (KO) mice were subjected to left ventricular pressure overload by descending aortic banding (AB). KO mice exhibited more unfavorable cardiac remodeling than WT mice 28 days post AB; this remodeling was characterized by aggravated cardiomyocyte hypertrophy, thickening of the ventricular walls, dilated chambers, increased fibrosis, and blunted systolic and diastolic cardiac function. Analysis of signaling pathways revealed enhanced extracellular signal-regulated kinase (ERK) and the c-Jun amino-terminal kinase (JNK) phosphorylation in response to ELTD1 deletion. CONCLUSIONS: ELTD1 deficiency exacerbates cardiac hypertrophy and cardiac function induced by AB-induced pressure overload by promoting both cardiomyocyte hypertrophy and cardiac fibrosis. These effects are suggested to originate from the activation of the ERK and JNK pathways, suggesting that ELTD1 is a potential target for therapies that prevent the development of cardiac disease

A polygenic burden of rare disruptive mutations in schizophrenia.

Schizophrenia is a common disease with a complex aetiology, probably involving multiple and heterogeneous genetic factors. Here, by analysing the exome sequences of 2,536 schizophrenia cases and 2,543 controls, we demonstrate a polygenic burden primarily arising from rare (less than 1 in 10,000), disruptive mutations distributed across many genes. Particularly enriched gene sets include the voltage-gated calcium ion channel and the signalling complex formed by the activity-regulated cytoskeleton-associated scaffold protein (ARC) of the postsynaptic density, sets previously implicated by genome-wide association and copy-number variation studies. Similar to reports in autism, targets of the fragile X mental retardation protein (FMRP, product of FMR1) are enriched for case mutations. No individual gene-based test achieves significance after correction for multiple testing and we do not detect any alleles of moderately low frequency (approximately 0.5 to 1 per cent) and moderately large effect. Taken together, these data suggest that population-based exome sequencing can discover risk alleles and complements established gene-mapping paradigms in neuropsychiatric disease

Replication of CNTNAP2 association with nonword repetition and support for FOXP2 association with timed reading and motor activities in a dyslexia family sample

Two functionally related genes, FOXP2 and CNTNAP2, influence language abilities in families with rare syndromic and common nonsyndromic forms of impaired language, respectively. We investigated whether these genes are associated with component phenotypes of dyslexia and measures of sequential motor ability. Quantitative transmission disequilibrium testing (QTDT) and linear association modeling were used to evaluate associations with measures of phonological memory (nonword repetition, NWR), expressive language (sentence repetition), reading (real word reading efficiency, RWRE; word attack, WATT), and timed sequential motor activities (rapid alternating place of articulation, RAPA; finger succession in the dominant hand, FS-D) in 188 family trios with a child with dyslexia. Consistent with a prior study of language impairment, QTDT in dyslexia showed evidence of CNTNAP2 single nucleotide polymorphism (SNP) association with NWR. For FOXP2, we provide the first evidence for SNP association with component phenotypes of dyslexia, specifically NWR and RWRE but not WATT. In addition, FOXP2 SNP associations with both RAPA and FS-D were observed. Our results confirm the role of CNTNAP2 in NWR in a dyslexia sample and motivate new questions about the effects of FOXP2 in neurodevelopmental disorders