Elevated plasma CXCL12 alpha is associated with a poorer prognosis in pulmonary arterial hypertension.

Recent work in preclinical models suggests that signalling via the pro-angiogenic and proinflammatory cytokine, CXCL12 (SDF-1), plays an important pathogenic role in pulmonary hypertension (PH). The objective of this study was to establish whether circulating concentrations of CXCL12α were elevated in patients with PAH and related to mortalit

Hepatitis B virus infection among HIV-infected pregnant women in Malawi and transmission to infants

The extent of HBV infection to infants of HBV/HIV-coinfected pregnant women in sub-Saharan Africa is unknown. The aim of this study was to assess prevalence of HBV infection among antiretroviral-naïve, HIV-infected pregnant women in Malawi and examine HBV transmission to their infants

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10-5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p < 1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Healthcare assistants and qualified carers, a trained, but untapped underutilised resource: a population-based study in Ireland of skillset, career satisfaction, wellbeing and change across all sectors and care settings.

INTRODUCTION: This report addresses aspects of the function, wellbeing and satisfaction of healthcare assistants and qualified carers in Ireland. The study on which it is based was undertaken under the auspices of the Irish Healthcare Assistants and Carers Ireland Social Association. It set out to elicit the views of carers about their background, training, skillset, work environments and conditions, career satisfaction and aspirations and is based on responses from almost 2,000 healthcare assistants and carers. It is the first study of its kind in Ireland. The report provides a historical perspectives on the evolution of the caring role in Ireland and internationally with the development of hospitals and healthcare. In parallel with this there have been changes in the perception of the role and those who carry it out, the training required and in the value placed on it by society. METHODS: This is a quantitative, cross-sectional population-based study of Healthcare Assistants and Qualified Carers in Ireland. The population for this study were all members of HCA and Carers Ireland, the national association and support network for Healthcare Assistants and Qualified Carers in Ireland. Participants were employed in different areas of care during the study period, which lasted two weeks to allow for work schedules and shift work and to obtain as many responses. All data collected was anonymous and was collected using two published and validated research instruments, The General Well-being Schedule (GWBS) and The Minnesota Career Satisfaction Survey (MCSS). The instruments were incorporated into an accessible Google form for online distribution. Descriptive and comparative statistics were carried out to analyse the data collected. RESULTS: Skills acquired in training appear to be closely aligned with those needed in practice. Three quarters of respondents reported training in activities of daily living (ADL); almost half reported training in dementia care; 20% reported both training and use in practice of skills relating to medication administration. It is of note, however that 16% of respondents did not have a full formal qualification in caring. In terms of general satisfaction with their chosen career 11% of respondents reported with a high degree of satisfaction, while 87% of respondents reported an average level of satisfaction. Of note, 6% reported a high degree of Intrinsic satisfaction (i.e. satisfaction with occupational condition) while 91% reported average satisfaction. Responses to the General Wellbeing Schedule (GWS) demonstrated more than half (54%) reported positive (41%) or low positive (13%) wellbeing; 13% reported marginal wellbeing while 31% appear to be experiencing significant stress or distress. CONCLUSION: This study aimed to provide real, precise information for policy makers, institutions and companies to inform policy, legislation and change from the perspective of the population it affects. The study did find that there is still much room for improvement for the development of the role, legislation, policy and skillset of healthcare assistants and qualified carers. Regarding general wellbeing, there still remains issues regarding stress problems, which the population suspect is from their occupation; this was found to be statistically significant. In relation to career satisfaction, a majority of the study population are in a grey area regarding how satisfied they are with their occupation. There still remains many opportunities to entice people into the occupation which have not been availed of yet; but accreditisied professionalisation of the role is required to ensure that Ireland stay in line with international guidelines and continue to protect and ensure patient safety, worker mental health and betterment of public health.University College Dublin, Centre for Support and Training in Analysis and Research (UCD CSTAR

Core competencies in applied infectious disease epidemiology: a framework for countries in Europe.

From Europe PMC via Jisc Publications RouterHistory: ppub 2023-02-01Publication status: PublishedIn 2009, the European Centre for Disease Prevention and Control (ECDC) developed a competency framework to support European Union countries and the European Commission in ensuring a competent public health workforce for Europe. The coronavirus disease (COVID-19) pandemic emphasised the importance of harmonised public health strategies and competencies across international boundaries, specifically for infectious diseases. This perspective presents the process to update the competency framework for applied infectious disease epidemiology, highlighting ECDC's efforts to support countries with using the framework. ECDC commissioned the Association of Schools of Public Health in the European Region (ASPHER) to update the framework through publication and dissemination of a technical report and a self-assessment tool linked to training resources. A mixed methods approach to gather input from experts in relevant specialities included qualitative interviews with 42 experts, workshops with ECDC Technical Advisory Group and an online survey of 212 public health professionals across Europe and beyond. Modifications resulted in 157 core competencies in 23 domains, each mapping to one of six subject areas of importance in applied infectious disease epidemiology. The framework serves as a basis to update the curriculum of the ECDC Fellowship programme with two alternative paths: intervention epidemiology or public health microbiology