679 research outputs found

    Australian University Nursing and Allied Health Students’ and Staff Physical Activity Promotion Preparedness and Knowledge: A Pre-Post Study Using an Educational Intervention

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    The promotion of physical activity (PA) by health professionals is a key strategy to increase PA levels in the population. In this study, we investigated PA promotion, preparedness, and knowledge among university nursing and allied health students and staff, as well as PA resource usage within curricula, before and after an educational intervention. Students and staff from 13 health disciplines at one Australian university were invited to complete an online survey, and a curriculum audits were conducted before and after PA teaching resources were promoted by academic PA champions (n = 14). A total of 299 students and 43 staff responded to the survey pre-intervention, and 363 and 32 responded to the post-intervention, respectively. PA promotion role perception (≥93%) and confidence to provide general PA advice (≥70%) were high throughout the study. Knowledge of PA guidelines was poor (3–10%). Students of physiotherapy, sport and exercise science, as well as more active students, were more likely to be aware of the PA guidelines (p < 0.05). Over 12 months, PA promotion preparedness and knowledge did not change significantly, nor was there a change in the amount of PA content delivered, despite a significant increase in the use of the teaching resources across a number of disciplines (p = 0.007). Future research should be carried out to investigate the implementation of the resources over time and to develop additional strategies for PA promotion and education scaffolded across curricula

    Genome-to-genome analysis highlights the effect of the human innate and adaptive immune systems on the hepatitis C virus

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    Outcomes of hepatitis C virus (HCV) infection and treatment depend on viral and host genetic factors. Here we use human genome-wide genotyping arrays and new whole-genome HCV viral sequencing technologies to perform a systematic genome-to-genome study of 542 individuals who were chronically infected with HCV, predominantly genotype 3. We show that both alleles of genes encoding human leukocyte antigen molecules and genes encoding components of the interferon lambda innate immune system drive viral polymorphism. Additionally, we show that IFNL4 genotypes determine HCV viral load through a mechanism dependent on a specific amino acid residue in the HCV NS5A protein. These findings highlight the interplay between the innate immune system and the viral genome in HCV control

    CB1 Expression Is Attenuated in Fallopian Tube and Decidua of Women with Ectopic Pregnancy

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    BACKGROUND: Embryo retention in the Fallopian tube (FT) is thought to lead to ectopic pregnancy (EP), a considerable cause of morbidity. In mice, genetic/pharmacological silencing of cannabinoid receptor Cnr1, encoding CB1, causes retention of embryos in the oviduct. The role of the endocannabinoids in tubal implantation in humans is not known. METHODS AND FINDINGS: Timed FT biopsies (n = 18) were collected from women undergoing gynecological procedures for benign conditions. Endometrial biopsies and whole blood were collected from women undergoing surgery for EP (n = 11); management of miscarriage (n = 6), and termination of pregnancy (n = 8). Using RT-PCR and immunohistochemistry, CB1 mRNA and protein expression levels/patterns were examined in FT and endometrial biopsies. The distribution of two polymorphisms of CNR1 was examined by TaqMan analysis of genomic DNA from the whole blood samples. In normal FT, CB1 mRNA was higher in luteal compared to follicular-phase (p<0.05). CB1 protein was located in smooth muscle of the wall and of endothelial vessels, and luminal epithelium of FT. In FT from women with EP, CB1 mRNA expression was low. CB1 mRNA expression was also significantly lower (p<0.05) in endometrium of women with EP compared to intrauterine pregnancies (IUP). Although of 1359G/A (rs1049353) polymorphisms of CNR1 gene suggests differential distribution of genotypes between the small, available cohorts of women with EP and those with IUP, results were not statistically significant. CONCLUSIONS: CB1 mRNA shows temporal variation in expression in human FT, likely regulated by progesterone. CB1 mRNA is expressed in low levels in both the FT and endometrium of women with EP. We propose that aberrant endocannabinoid-signaling in human FT leads to EP. Furthermore, our finding of reduced mRNA expression along with a possible association between polymorphism genotypes of the CNR1 gene and EP, suggests a possible genetic predisposition to EP that warrants replication in a larger sample pool

    Viral genome wide association study identifies novel hepatitis C virus polymorphisms associated with sofosbuvir treatment failure

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    Persistent hepatitis C virus (HCV) infection is a major cause of chronic liver disease, worldwide. With the development of direct-acting antivirals, treatment of chronically infected patients has become highly effective, although a subset of patients responds less well to therapy. Sofosbuvir is a common component of current de novo or salvage combination therapies, that targets the HCV NS5B polymerase. We use pre-treatment whole-genome sequences of HCV from 507 patients infected with HCV subtype 3a and treated with sofosbuvir containing regimens to detect viral polymorphisms associated with response to treatment. We find three common polymorphisms in non-targeted HCV NS2 and NS3 proteins are associated with reduced treatment response. These polymorphisms are enriched in post-treatment HCV sequences of patients unresponsive to treatment. They are also associated with lower reductions in viral load in the first week of therapy. Using in vitro short-term dose-response assays, these polymorphisms do not cause any reduction in sofosbuvir potency, suggesting an indirect mechanism of action in decreasing sofosbuvir efficacy. The identification of polymorphisms in NS2 and NS3 proteins associated with poor treatment outcomes emphasises the value of systematic genome-wide analyses of viruses in uncovering clinically relevant polymorphisms that impact treatment

    RANTES/CCL5 and Risk for Coronary Events: Results from the MONICA/KORA Augsburg Case-Cohort, Athero-Express and CARDIoGRAM Studies

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    BACKGROUND: The chemokine RANTES (regulated on activation, normal T-cell expressed and secreted)/CCL5 is involved in the pathogenesis of cardiovascular disease in mice, whereas less is known in humans. We hypothesised that its relevance for atherosclerosis should be reflected by associations between CCL5 gene variants, RANTES serum concentrations and protein levels in atherosclerotic plaques and risk for coronary events. METHODS AND FINDINGS: We conducted a case-cohort study within the population-based MONICA/KORA Augsburg studies. Baseline RANTES serum levels were measured in 363 individuals with incident coronary events and 1,908 non-cases (mean follow-up: 10.2±4.8 years). Cox proportional hazard models adjusting for age, sex, body mass index, metabolic factors and lifestyle factors revealed no significant association between RANTES and incident coronary events (HR [95% CI] for increasing RANTES tertiles 1.0, 1.03 [0.75-1.42] and 1.11 [0.81-1.54]). None of six CCL5 single nucleotide polymorphisms and no common haplotype showed significant associations with coronary events. Also in the CARDIoGRAM study (&gt;22,000 cases, &gt;60,000 controls), none of these CCL5 SNPs was significantly associated with coronary artery disease. In the prospective Athero-Express biobank study, RANTES plaque levels were measured in 606 atherosclerotic lesions from patients who underwent carotid endarterectomy. RANTES content in atherosclerotic plaques was positively associated with macrophage infiltration and inversely associated with plaque calcification. However, there was no significant association between RANTES content in plaques and risk for coronary events (mean follow-up 2.8±0.8 years). CONCLUSIONS: High RANTES plaque levels were associated with an unstable plaque phenotype. However, the absence of associations between (i) RANTES serum levels, (ii) CCL5 genotypes and (iii) RANTES content in carotid plaques and either coronary artery disease or incident coronary events in our cohorts suggests that RANTES may not be a novel coronary risk biomarker. However, the potential relevance of RANTES levels in platelet-poor plasma needs to be investigated in further studies

    RANTES/CCL5 and risk for coronary events: Results from the MONICA/KORA Augsburg case-cohort, Athero-express and CARDIoGRAM studies

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    Background: The chemokine RANTES (regulated on activation, normal T-cell expressed and secreted)/CCL5 is involved in the pathogenesis of cardiovascular disease in mice, whereas less is known in humans. We hypothesised that its relevance for atherosclerosis should be reflected by associations between CCL5 gene variants, RANTES serum concentrations and protein levels in atherosclerotic plaques and risk for coronary events. Methods and Findings: We conducted a case-cohort study within the population-based MONICA/KORA Augsburg studies. Baseline RANTES serum levels were measured in 363 individuals with incident coronary events and 1,908 non-cases (mean follow-up: 10.2±

    Implicit and explicit self-esteem discrepancies in people with psychogenic nonepileptic seizures

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    Abstract PURPOSE: Self-esteem (SE), or one's sense of competence and worth, is reduced in many mental and physical disorders. Low SE is associated with perceived stigma and disability and poor treatment outcomes. The present study examined implicit and explicit SE (automatic and deliberate views about the self) in people with epilepsy and people with psychogenic nonepileptic seizures (PNESs). Discrepancies between implicit SE and explicit SE have been found to correlate with psychological distress in disorders often associated with PNESs but are relatively unexplored in PNESs. We hypothesized that, compared with epilepsy, PNESs would be associated with lower self-reported SE and greater discrepancies between implicit SE and explicit SE. METHODS: Thirty adults with PNESs, 25 adults with epilepsy, and 31 controls without a history of seizures were asked to complete the Rosenberg Self-esteem Scale as a measure of explicit SE and an Implicit Relational Assessment Procedure as a measure of implicit SE. The State-Trait Anxiety Inventory and Patient Health Questionnaire-15 (a somatic symptom inventory) were also administered. RESULTS: We found significant group differences in explicit (p<0.001) but not implicit SE. Patients with PNESs reported lower SE than the other groups. No group differences were found in implicit SE. Implicit-explicit SE discrepancies were larger in the group with PNESs than in the other groups (p<0.001). Higher frequency of PNESs (but not epileptic seizures) was associated with lower explicit SE (rs=-.83, p<0.01) and greater SE discrepancies (i.e., lower explicit relative to implicit SE; rs=.65, p<0.01). These relationships remained significant when controlling for anxiety and somatization. CONCLUSION: Patients with PNESs had lower explicit SE than those with epilepsy or healthy controls. In keeping with our expectations, there were greater discrepancies between implicit SE and explicit SE among patients with PNESs than in the other groups. Our results, including the strong relationship between PNES frequency, anxiety, and explicit-implicit SE discrepancies, support the interpretation that PNESs serve to reduce cognitive dissonance, perhaps protecting patients' implicit SE
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