Monitoring the level of government trust, risk perception and intention of the general public to adopt protective measures during the influenza A (H1N1) pandemic in the Netherlands

<p>Abstract</p> <p>Background</p> <p>During the course of an influenza pandemic, governments know relatively little about the possibly changing influence of government trust, risk perception, and receipt of information on the public's intention to adopt protective measures or on the acceptance of vaccination. This study aims to identify and describe possible changes in and factors associated with public's intentions during the 2009 influenza A (H1N1) pandemic in the Netherlands.</p> <p>Methods</p> <p>Sixteen cross-sectional telephone surveys were conducted (N = 8060) between April - November 2009. From these repeated measurements three consecutive periods were categorized based on crucial events during the influenza A (H1N1) pandemic. Time trends in government trust, risk perception, intention to adopt protective measures, and the acceptance of vaccination were analysed. Factors associated with an intention to adopt protective measures or vaccination were identified.</p> <p>Results</p> <p>Trust in the government was high, but decreased over time. During the course of the pandemic, perceived vulnerability and an intention to adopt protective measures increased. Trust and vulnerability were associated with an intention to adopt protective measures in general only during period one. Higher levels of intention to receive vaccination were associated with increased government trust, fear/worry, and perceived vulnerability. In periods two and three receipt of information was positively associated with an intention to adopt protective measures. Most respondents wanted to receive information about infection prevention from municipal health services, health care providers, and the media.</p> <p>Conclusions</p> <p>The Dutch response to the H1N1 virus was relatively muted. Higher levels of trust in the government, fear/worry, and perceived vulnerability were all positively related to an intention to accept vaccination. Only fear/worry was positively linked to an intention to adopt protective measures during the entire pandemic. Risk and crisis communication by the government should focus on building and maintaining trust by providing information about preventing infection in close collaboration with municipal health services, health care providers, and the media.</p

The role of facemasks and hand hygiene in the prevention of influenza transmission in households: results from a cluster randomised trial; Berlin, Germany, 2009-2011

Background: Previous controlled studies on the effect of non-pharmaceutical interventions (NPI) - namely the use of facemasks and intensified hand hygiene - in preventing household transmission of influenza have not produced definitive results. We aimed to investigate efficacy, acceptability, and tolerability of NPI in households with influenza index patients. Methods: We conducted a cluster randomized controlled trial during the pandemic season 2009/10 and the ensuing influenza season 2010/11. We included households with an influenza positive index case in the absence of further respiratory illness within the preceding 14 days. Study arms were wearing a facemask and practicing intensified hand hygiene (MH group), wearing facemasks only (M group) and none of the two (control group). Main outcome measure was laboratory confirmed influenza infection in a household contact. We used daily questionnaires to examine adherence and tolerability of the interventions. Results: We recruited 84 households (30 control, 26 M and 28 MH households) with 82, 69 and 67 household contacts, respectively. In 2009/10 all 41 index cases had a influenza A (H1N1) pdm09 infection, in 2010/11 24 had an A (H1N1) pdm09 and 20 had a B infection. The total secondary attack rate was 16% (35/218). In intention-totreat analysis there was no statistically significant effect of the M and MH interventions on secondary infections. When analysing only households where intervention was implemented within 36 h after symptom onset of the index case, secondary infection in the pooled M and MH groups was significantly lower compared to the control group (adjusted odds ratio 0.16, 95% CI, 0.03-0.92). In a per-protocol analysis odds ratios were significantly reduced among participants of the M group (adjusted odds ratio, 0.30, 95% CI, 0.10-0.94). With the exception of MH index cases in 2010/11 adherence was good for adults and children, contacts and index cases. Conclusions: Results suggest that household transmission of influenza can be reduced by the use of NPI, such as facemasks and intensified hand hygiene, when implemented early and used diligently. Concerns about acceptability and tolerability of the interventions should not be a reason against their recommendation

Metabolic Network for the Biosynthesis of Intra- and Extracellular alpha-Glucans Required for Virulence of Mycobacterium tuberculosis

Mycobacterium tuberculosis synthesizes intra- and extracellular alpha-glucans that were believed to originate from separate pathways. The extracellular glucose polymer is the main constituent of the mycobacterial capsule that is thought to be involved in immune evasion and virulence. However, the role of the alpha-glucan capsule in pathogenesis has remained enigmatic due to an incomplete understanding of alpha-glucan biosynthetic pathways preventing the generation of capsule-deficient mutants. Three separate and potentially redundant pathways had been implicated in alpha-glucan biosynthesis in mycobacteria: the GlgC-GlgA, the Rv3032 and the TreS-Pep2-GlgE pathways. We now show that alpha-glucan in mycobacteria is exclusively assembled intracellularly utilizing the building block alpha-maltose-1-phosphate as the substrate for the maltosyltransferase GlgE, with subsequent branching of the polymer by the branching enzyme GlgB. Some alpha-glucan is exported to form the alpha-glucan capsule. There is an unexpected convergence of the TreS-Pep2 and GlgC-GlgA pathways that both generate alpha-maltose-1-phosphate. While the TreS-Pep2 route from trehalose was already known, we have now established that GlgA forms this phosphosugar from ADP-glucose and glucose 1-phosphate 1000-fold more efficiently than its hitherto described glycogen synthase activity. The two routes are connected by the common precursor ADPglucose, allowing compensatory flux from one route to the other. Having elucidated this unexpected configuration of the metabolic pathways underlying alpha-glucan biosynthesis in mycobacteria, an M. tuberculosis double mutant devoid of alpha-glucan could be constructed, showing a direct link between the GlgE pathway, alpha-glucan biosynthesis and virulence in a mouse infection model

Conditional Ablation of Ezh2 in Murine Hearts Reveals Its Essential Roles in Endocardial Cushion Formation, Cardiomyocyte Proliferation and Survival

Ezh2 is a histone trimethyltransferase that silences genes mainly via catalyzing trimethylation of histone 3 lysine 27 (H3K27Me3). The role of Ezh2 as a regulator of gene silencing and cell proliferation in cancer development has been extensively investigated; however, its function in heart development during embryonic cardiogenesis has not been well studied. In the present study, we used a genetically modified mouse system in which Ezh2 was specifically ablated in the mouse heart. We identified a wide spectrum of cardiovascular malformations in the Ezh2 mutant mice, which collectively led to perinatal death. In the Ezh2 mutant heart, the endocardial cushions (ECs) were hypoplastic and the endothelial-to-mesenchymal transition (EMT) process was impaired. The hearts of Ezh2 mutant mice also exhibited decreased cardiomyocyte proliferation and increased apoptosis. We further identified that the Hey2 gene, which is important for cardiomyocyte proliferation and cardiac morphogenesis, is a downstream target of Ezh2. The regulation of Hey2 expression by Ezh2 may be independent of Notch signaling activity. Our work defines an indispensible role of the chromatin remodeling factor Ezh2 in normal cardiovascular development

Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

Peer reviewe

Common genetic variants contribute to risk of transposition of the great arteries

Rationale: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored. Objective: We sought to study the role of common single nucleotide polymorphisms (SNPs) in risk for D-TGA. Methods and Results: We conducted a genome-wide association study in an international set of 1,237 patients with D-TGA and identified a genome-wide significant susceptibility locus on chromosome 3p14.3, which was subsequently replicated in an independent case-control set (rs56219800, meta-analysis P=8.6x10-10, OR=0.69 per C allele). SNP-based heritability analysis showed that 25% of variance in susceptibility to D-TGA may be explained by common variants. A genome-wide polygenic risk score derived from the discovery set was significantly associated to D-TGA in the replication set (P=4x10-5). The genome-wide significant locus (3p14.3) co-localizes with a putative regulatory element that interacts with the promoter of WNT5A, which encodes the Wnt Family Member 5A protein known for its role in cardiac development in mice. We show that this element drives reporter gene activity in the developing heart of mice and zebrafish and is bound by the developmental transcription factor TBX20. We further demonstrate that TBX20 attenuates Wnt5a expression levels in the developing mouse heart. Conclusions: This work provides support for a polygenic architecture in D-TGA and identifies a susceptibility locus on chromosome 3p14.3 near WNT5A. Genomic and functional data support a causal role of WNT5A at the locus

Indirect Genetic Effects and Housing Conditions in Relation to Aggressive Behaviour in Pigs

Indirect Genetic Effects (IGEs), also known as associative effects, are the heritable effects that an individual has on the phenotype of its social partners. Selection for IGEs has been proposed as a method to reduce harmful behaviours, in particular aggression, in livestock and aquaculture. The mechanisms behind IGEs, however, have rarely been studied. The objective was therefore to assess aggression in pigs which were divergently selected for IGEs on growth (IGEg). In a one generation selection experiment, we studied 480 offspring of pigs (Sus scrofa) that were selected for relatively high or low IGEg and housed in homogeneous IGEg groups in either barren or enriched environments. Skin lesion scores, a proxy measure of aggression, and aggressive behaviours were recorded. The two distinct IGEg groups did not differ in number of skin lesions, or in amount of reciprocal fighting, both under stable social conditions and in confrontation with unfamiliar pigs in a 24 h regrouping test. Pigs selected for a positive effect on the growth of their group members, however, performed less non-reciprocal biting and showed considerably less aggression at reunion with familiar group members after they had been separated during a 24 h regrouping test. The enriched environment was associated with more skin lesions but less non-reciprocal biting under stable social conditions. Changes in aggression between pigs selected for IGEg were not influenced by G×E interactions with regard to the level of environmental enrichment. It is likely that selection on IGEg targets a behavioural strategy, rather than a single behavioural trait such as aggressiveness