Practitioner perspectives of domestic abuse and women over 45

Low reporting of domestic abuse among women 45 and older has resulted in the needs of those women becoming forgotten among service development. We interviewed 18 practitioners to explore their experiences of working with this client group. Descriptive thematic analysis identified two core themes: an uncertain future as a barrier to seeking support, and a lack in knowledge of domestic abuse and service provision. There is still a long way to go: (i) to break down social barriers for middle-aged and older women to seeking support; and (ii) to acknowledge domestic abuse among professionals and the public. The research draws on a practitioner voice alongside reflections on one of the UK’s first safe houses aimed at supporting women 45 and over

Timing the multiple cell death pathways initiated by Rose Bengal acetate photodynamic therapy

Rose Bengal acetate photodynamic therapy (RBAc–PDT) induced multiple cell death pathways in HeLa cells through ROS and ER stress. Indeed, apoptosis was the first preferred mechanism of death, and it was triggered by at least four different pathways, whose independent temporal activation ensures cell killing when one or several of the pathways are inactivated. Apoptosis occurred as early as 1 h after PDT through activation of intrinsic pathways, followed by activation of extrinsic, caspase-12-dependent and caspase-independent pathways, and by autophagy. The onset of the different apoptotic pathways and autophagy, that in our system had a pro-death role, was timed by determining the levels of caspases 9, 8, 3 and 12; Bcl-2 family; Hsp70; LC3B; GRP78 and phospho-eIF2α proteins. Interestingly, inhibition of one pathway, that is, caspase-9 (Z-LEHD-FMK), caspase-8 (Z-IETD-FMK), pan-caspases (Z-VAD-FMK), autophagy (3-MA) and necrosis (Nec-1), did not impair the activation of the others, suggesting that the independent onset of the different apoptotic pathways and autophagy did not occur in a subordinated manner. Altogether, our data indicate RBAc as a powerful photosensitiser that induces a prolonged cytotoxicity and time-related cell death onset by signals originating from or converging on almost all intracellular organelles. The fact that cancer cells can die through different mechanisms is a relevant clue in the choice and design of anticancer PDT

Does the pharmacy expenditure of patients always correspond with their morbidity burden? Exploring new approaches in the interpretation of pharmacy expenditure

<p>Abstract</p> <p>Background</p> <p>The computerisation of primary health care (PHC) records offers the opportunity to focus on pharmacy expenditure from the perspective of the morbidity of individuals. The objective of the present study was to analyse the behaviour of pharmacy expenditure within different morbidity groups. We paid special attention to the identification of individuals who had higher values of pharmacy expenditure than their morbidity would otherwise suggest (i.e. outliers).</p> <p>Methods</p> <p>Observational study consisting of 75,574 patients seen at PHC centres in Zaragoza, Spain, at least once in 2005. Demographic and disease variables were analysed (ACG^®8.1), together with a response variable that we termed 'total pharmacy expenditure per patient'. Outlier patients were identified based on boxplot methods, adjusted boxplot for asymmetric distributions, and by analysing standardised residuals of tobit regression models.</p> <p>Results</p> <p>The pharmacy expenditure of up to 7% of attendees in the studied PHC centres during one year exceeded expectations given their morbidity burden. This group of patients was responsible for up to 24% of the total annual pharmacy expenditure. There was a significantly higher number of outlier patients within the low-morbidity band which matched up with the higher variation coefficient observed in this group (3.2 vs. 2.0 and 1.3 in the moderate- and high-morbidity bands, respectively).</p> <p>Conclusions</p> <p>With appropriate validation, the methodologies of the present study could be incorporated in the routine monitoring of the prescribing profile of general practitioners. This could not only enable evaluation of their performance, but also target groups of outlier patients and foster analyses of the causes of unusually high pharmacy expenditures among them. This interpretation of pharmacy expenditure gives new clues for the efficiency in utilisation of healthcare resources, and could be complementary to management interventions focused on individuals with a high morbidity burden.</p

Human Cardiac-Derived Adherent Proliferating Cells Reduce Murine Acute Coxsackievirus B3-Induced Myocarditis

BACKGROUND: Under conventional heart failure therapy, inflammatory cardiomyopathy typically has a progressive course, indicating a need for alternative therapeutic strategies to improve long-term outcomes. We recently isolated and identified novel cardiac-derived cells from human cardiac biopsies: cardiac-derived adherent proliferating cells (CAPs). They have similarities with mesenchymal stromal cells, which are known for their anti-apoptotic and immunomodulatory properties. We explored whether CAPs application could be a novel strategy to improve acute Coxsackievirus B3 (CVB3)-induced myocarditis. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate the safety of our approach, we first analyzed the expression of the coxsackie- and adenovirus receptor (CAR) and the co-receptor CD55 on CAPs, which are both required for effective CVB3 infectivity. We could demonstrate that CAPs only minimally express both receptors, which translates to minimal CVB3 copy numbers, and without viral particle release after CVB3 infection. Co-culture of CAPs with CVB3-infected HL-1 cardiomyocytes resulted in a reduction of CVB3-induced HL-1 apoptosis and viral progeny release. In addition, CAPs reduced CD4 and CD8 T cell proliferation. All CAPs-mediated protective effects were nitric oxide- and interleukin-10-dependent and required interferon-γ. In an acute murine model of CVB3-induced myocarditis, application of CAPs led to a decrease of cardiac apoptosis, cardiac CVB3 viral load and improved left ventricular contractility parameters. This was associated with a decline in cardiac mononuclear cell activity, an increase in T regulatory cells and T cell apoptosis, and an increase in left ventricular interleukin-10 and interferon-γ mRNA expression. CONCLUSIONS: We conclude that CAPs are a unique type of cardiac-derived cells and promising tools to improve acute CVB3-induced myocarditis

A Genome-Wide Homozygosity Association Study Identifies Runs of Homozygosity Associated with Rheumatoid Arthritis in the Human Major Histocompatibility Complex

Rheumatoid arthritis (RA) is a chronic inflammatory disorder with a polygenic mode of inheritance. This study examined the hypothesis that runs of homozygosity (ROHs) play a recessive-acting role in the underlying RA genetic mechanism and identified RA-associated ROHs. Ours is the first genome-wide homozygosity association study for RA and characterized the ROH patterns associated with RA in the genomes of 2,000 RA patients and 3,000 normal controls of the Wellcome Trust Case Control Consortium. Genome scans consistently pinpointed two regions within the human major histocompatibility complex region containing RA-associated ROHs. The first region is from 32,451,664 bp to 32,846,093 bp (−log10(p)>22.6591). RA-susceptibility genes, such as HLA-DRB1, are contained in this region. The second region ranges from 32,933,485 bp to 33,585,118 bp (−log10(p)>8.3644) and contains other HLA-DPA1 and HLA-DPB1 genes. These two regions are physically close but are located in different blocks of linkage disequilibrium, and ∼40% of the RA patients' genomes carry these ROHs in the two regions. By analyzing homozygote intensities, an ROH that is anchored by the single nucleotide polymorphism rs2027852 and flanked by HLA-DRB6 and HLA-DRB1 was found associated with increased risk for RA. The presence of this risky ROH provides a 62% accuracy to predict RA disease status. An independent genomic dataset from 868 RA patients and 1,194 control subjects of the North American Rheumatoid Arthritis Consortium successfully validated the results obtained using the Wellcome Trust Case Control Consortium data. In conclusion, this genome-wide homozygosity association study provides an alternative to allelic association mapping for the identification of recessive variants responsible for RA. The identified RA-associated ROHs uncover recessive components and missing heritability associated with RA and other autoimmune diseases

Vitamin D in health and disease: Current perspectives

Despite the numerous reports of the association of vitamin D with a spectrum of development, disease treatment and health maintenance, vitamin D deficiency is common. Originating in part from the diet but with a key source resulting from transformation by exposure to sunshine, a great deal of the population suffers from vitamin D deficiency especially during winter months. It is linked to the treatment and pathogenesis and/or progression of several disorders including cancer, hypertension, multiple sclerosis, rheumatoid arthritis, osteoporosis, muscle weakness and diabetes. This widespread deficiency of Vitamin D merits consideration of widespread policies including increasing awareness among the public and healthcare professionals