Social relationships and the risk of incident heart failure: results from a prospective population-based study of older men

Aims: Limited social relationships, particularly in older adults, have been implicated as a risk factor for cardiovascular disease. However, little is known about the associations between poor social relationships and heart failure incidence. Methods and results: Prospective study of socially representative men aged 60-79 years drawn from general practices in 24 British towns and followed up for a maximum of 18 years. A total of 3698 participants with no previous diagnosis of heart failure were included. Information on social relationships was based on a combination of marital status, living circumstances, and social contacts with friends and family. These provided information on contact frequency, contact satisfaction, and a social relationship score (low to high) combining frequency and satisfaction with contact. Heart failure included both incidents non-fatal heart failure and death from heart failure. Among 3698 participants, 330 developed heart failure. Men with low compared to high frequency of contact with family and friends had an increased risk of incident heart failure [hazard ratio (HR) 1.59, 95% confidence interval (CI) 1.15-2.18]; this remained statistically significant after adjustment for social class, behavioural, and biological risk factors. Low compared to high scores for satisfaction with contacts was associated with increased risk of heart failure (adjusted HR = 1.54; 95% CI 1.14-2.07). Lower social relationship scores (combining frequency and satisfaction with contact) were associated with greater risk of incident heart failure (adjusted HR = 1.38, 95% CI 1.02-1.87). Marital status and living alone were not significantly associated with heart failure. Conclusion: Weaker social relationships appear to increase the risk of developing heart failure in older age. Further research is needed to investigate pathways underlying these associations and to test whether interventions to strengthen social relationships can reduce the risk of heart failure

Implementation of a problem-solving training initiative to reduce self-harm in prisons: a qualitative perspective of prison staff, field researchers and prisoners at risk of self-harm.

BACKGROUND:Social problem-solving is one technique used to help reduce incidence of self-harm. Our study evaluated the feasibility and acceptability of the adaptation and implementation of a brief Problem-Solving Training (PST) intervention to reduce self-harm in prisons. METHODS:The process involved i) adaptation of the training materials using focus groups with prison staff and prisoners, ii) training frontline prison staff to use the skills, and iii) implementation of the skills with prisoners at risk of self-harm. Qualitative interviews were conducted with prison staff, prisoners and field researchers and were analysed using a thematic framework to produce a model of the barriers and facilitators to the process. RESULTS:We conducted 43 interviews across three prison sites. The interviews included 19 prison staff, 18 prisoners and six field researcher meetings. The adaptation to the training and intervention materials were well received. The findings identified the need to support training using a collaborative and flexible approach. Prisoner engagement was affected by their own personal circumstances and by a range of contextual issues relating to the prison environment. Implementation of the skills by prison staff were hindered by resource constraints, the prison environment and staff attitudes. CONCLUSIONS:We found that it was feasible to adapt an existing intervention and contextualise it within the prison environment. Although we could train large numbers of staff it was deemed unfeasible for staff to implement the problem-solving skills to prisoners at risk of self-harm. Prisoners who engaged with the intervention reported a range of benefits. Alternative implementation mechanisms to tackle the contextual barriers proposed by staff and prisoners included delivery of the intervention using an educational setting and/or use of a prisoner peer-led scheme

Social relationships and the risk of incident heart failure: results from a prospective population-based study of older men.

Aims: Limited social relationships, particularly in older adults, have been implicated as a risk factor for cardiovascular disease. However, little is known about the associations between poor social relationships and heart failure incidence. Methods and results: Prospective study of socially representative men aged 60-79 years drawn from general practices in 24 British towns and followed up for a maximum of 18 years. A total of 3698 participants with no previous diagnosis of heart failure were included. Information on social relationships was based on a combination of marital status, living circumstances, and social contacts with friends and family. These provided information on contact frequency, contact satisfaction, and a social relationship score (low to high) combining frequency and satisfaction with contact. Heart failure included both incidents non-fatal heart failure and death from heart failure. Among 3698 participants, 330 developed heart failure. Men with low compared to high frequency of contact with family and friends had an increased risk of incident heart failure [hazard ratio (HR) 1.59, 95% confidence interval (CI) 1.15-2.18]; this remained statistically significant after adjustment for social class, behavioural, and biological risk factors. Low compared to high scores for satisfaction with contacts was associated with increased risk of heart failure (adjusted HR = 1.54; 95% CI 1.14-2.07). Lower social relationship scores (combining frequency and satisfaction with contact) were associated with greater risk of incident heart failure (adjusted HR = 1.38, 95% CI 1.02-1.87). Marital status and living alone were not significantly associated with heart failure. Conclusion: Weaker social relationships appear to increase the risk of developing heart failure in older age. Further research is needed to investigate pathways underlying these associations and to test whether interventions to strengthen social relationships can reduce the risk of heart failure

Growing at the limit: Reef growth sensitivity to climate and oceanographic changes in the South Western Atlantic

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordWhilst the impacts of climatic and oceanographic change on lower latitude reefs are increasingly well documented, our understanding of how reef-building has fluctuated in higher latitude settings remains limited. Here, we explore the timing and longevity of reef-building through the mid- to late Holocene in the most southerly known reef (24°S) in the Western Atlantic. Reef core data show that reef growth was driven by a single coral species, Madracis decactis, and occurred over two phases since ~6000 calibrated (cal.) yr B.P.. These records further indicate that there was a clear growth hiatus from ~5500 to 2500 cal. yr B.P., and that there is no evidence of reef accretion on the Queimada Grande Reef (QGR) over the past 2000 yrs. It thus presently exists as a submerged senescent structure colonized largely by non-reef building organisms. Integration of these growth data with those from sites further north (18°S and 21°S) suggests that Intertropical Convergence Zone (ITCZ), South Westerlies Winds (SWW) and El Niño-Southern Oscillation (ENSO) variability and shifts during the Holocene drove changes in the position of the Brazil-Falklands/Malvinas Confluence (BFMC), and that this has had a strong regional influence on the timing and longevity of reef growth. Our results add new evidence to the idea that reef growth in marginal settings can rapidly turn-on or -off according to regional environmental changes, and thus are of relevance for predicting high latitude reef growth potential under climate change.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)razilian Research Council (CNPq

Diversification of importin-α isoforms in cellular trafficking and disease states.

The human genome encodes seven isoforms of importin α which are grouped into three subfamilies known as α1, α2 and α3. All isoforms share a fundamentally conserved architecture that consists of an N-terminal, autoinhibitory, importin-β-binding (IBB) domain and a C-terminal Arm (Armadillo)-core that associates with nuclear localization signal (NLS) cargoes. Despite striking similarity in amino acid sequence and 3D structure, importin-α isoforms display remarkable substrate specificity in vivo. In the present review, we look at key differences among importin-α isoforms and provide a comprehensive inventory of known viral and cellular cargoes that have been shown to associate preferentially with specific isoforms. We illustrate how the diversification of the adaptor importin α into seven isoforms expands the dynamic range and regulatory control of nucleocytoplasmic transport, offering unexpected opportunities for pharmacological intervention. The emerging view of importin α is that of a key signalling molecule, with isoforms that confer preferential nuclear entry and spatiotemporal specificity on viral and cellular cargoes directly linked to human diseases

High prevalence of methicillin resistant Staphylococcus aureus in the surgical units of Mulago hospital in Kampala, Uganda

<p>Abstract</p> <p>Background</p> <p>There is limited data on Methicillin resistant <it>Staphylococcus aureus </it>(MRSA) in Uganda where, as in most low income countries, the routine use of chromogenic agar for MRSA detection is not affordable. We aimed to determine MRSA prevalence among patients, healthcare workers (HCW) and the environment in the burns units at Mulago hospital, and compare the performance of CHROMagar with oxacillin for detection of MRSA.</p> <p>Results</p> <p>One hundred samples (from 25 patients; 36 HCW; and 39 from the environment, one sample per person/item) were cultured for the isolation of <it>Staphylococcus aureus</it>. Forty one <it>S. aureus </it>isolates were recovered from 13 patients, 13 HCW and 15 from the environment, all of which were oxacillin resistant and <it>mecA/femA/nuc</it>-positive. MRSA prevalence was 46% (41/89) among patients, HCW and the environment, and 100% (41/41) among the isolates. For CHROMagar, MRSA prevalence was 29% (26/89) among patients, HCW and the environment, and 63% (26/41) among the isolates. There was high prevalence of multidrug resistant isolates, which concomitantly possessed virulence and antimicrobial resistance determinants, notably biofilms, hemolysins, toxin and <it>ica </it>genes. One isolate positive for all determinants possessed the <it>bhp </it>homologue which encodes the biofilm associated protein (BAP), a rare finding in human isolates. SCC<it>mec </it>type I was the most common at 54% prevalence (22/41), followed by <it>SCCmec </it>type V (15%, 6/41) and <it>SCCmec </it>type IV (7%, 3/41). <it>SCCmec </it>types II and III were not detected and 10 isolates (24%) were non-typeable.</p> <p>Conclusions</p> <p>Hyper-virulent methicillin resistant <it>Staphylococcus aureus </it>is prevalent in the burns unit of Mulago hospital.</p

Wnt Signaling Is Required for Early Development of Zebrafish Swimbladder

10.1371/journal.pone.0018431PLoS ONE63

Defective Innate Cell Response and Lymph Node Infiltration Specify Yersinia pestis Infection

Since its recent emergence from the enteropathogen Yersinia pseudotuberculosis, Y. pestis, the plague agent, has acquired an intradermal (id) route of entry and an extreme virulence. To identify pathophysiological events associated with the Y. pestis high degree of pathogenicity, we compared disease progression and evolution in mice after id inoculation of the two Yersinia species. Mortality studies showed that the id portal was not in itself sufficient to provide Y. pseudotuberculosis with the high virulence power of its descendant. Surprisingly, Y. pseudotuberculosis multiplied even more efficiently than Y. pestis in the dermis, and generated comparable histological lesions. Likewise, Y. pseudotuberculosis translocated to the draining lymph node (DLN) and similar numbers of the two bacterial species were found at 24 h post infection (pi) in this organ. However, on day 2 pi, bacterial loads were higher in Y. pestis-infected than in Y. pseudotuberculosis-infected DLNs. Clustering and multiple correspondence analyses showed that the DLN pathologies induced by the two species were statistically significantly different and identified the most discriminating elementary lesions. Y. pseudotuberculosis infection was accompanied by abscess-type polymorphonuclear cell infiltrates containing the infection, while Y. pestis-infected DLNs exhibited an altered tissue density and a vascular congestion, and were typified by an invasion of the tissue by free floating bacteria. Therefore, Y. pestis exceptional virulence is not due to its recently acquired portal of entry into the host, but is associated with a distinct ability to massively infiltrate the DLN, without inducing in this organ an organized polymorphonuclear cell reaction. These results shed light on pathophysiological processes that draw the line between a virulent and a hypervirulent pathogen

Joint effects of known type 2 diabetes susceptibility loci in genome-wide association study of Singapore Chinese: The Singapore Chinese health study

Background: Genome-wide association studies (GWAS) have identified genetic factors in type 2 diabetes (T2D), mostly among individuals of European ancestry. We tested whether previously identified T2D-associated single nucleotide polymorphisms (SNPs) replicate and whether SNPs in regions near known T2D SNPs were associated with T2D within the Singapore Chinese Health Study. Methods: 2338 cases and 2339 T2D controls from the Singapore Chinese Health Study were genotyped for 507,509 SNPs. Imputation extended the genotyped SNPs to 7,514,461 with high estimated certainty (r2>0.8). Replication of known index SNP associations in T2D was attempted. Risk scores were computed as the sum of index risk alleles. SNPs in regions ±100 kb around each index were tested for associations with T2D in conditional fine-mapping analysis. Results: Of 69 index SNPs, 20 were genotyped directly and genotypes at 35 others were well imputed. Among the 55 SNPs with data, disease associations were replicated (at p<0.05) for 15 SNPs, while 32 more were directionally consistent with previous reports. Risk score was a significant predictor with a 2.03 fold higher risk CI (1.69-2.44) of T2D comparing the highest to lowest quintile of risk allele burden (p = 5.72×10-14). Two improved SNPs around index rs10923931 and 5 new candidate SNPs around indices rs10965250 and rs1111875 passed simple Bonferroni corrections for significance in conditional analysis. Nonetheless, only a small fraction (2.3% on the disease liability scale) of T2D burden in Singapore is explained by these SNPs. Conclusions: While diabetes risk in Singapore Chinese involves genetic variants, most disease risk remains unexplained. Further genetic work is ongoing in the Singapore Chinese population to identify unique common variants not already seen in earlier studies. However rapid increases in T2D risk have occurred in recent decades in this population, indicating that dynamic environmental influences and possibly gene by environment interactions complicate the genetic architecture of this disease. © 2014 Chen et al