Sequestration of human cytomegalovirus by human renal and mammary epithelial cells

AbstractUrine and breast milk represent the main routes of human cytomegalovirus (HCMV) transmission but the contribution of renal and mammary epithelial cells to viral excretion remains unclear. We observed that kidney and mammary epithelial cells were permissive to HCMV infection and expressed immediate early, early and late antigens within 72h of infection. During the first 24h after infection, high titers of infectious virus were measured associated to the cells and in culture supernatants, independently of de novo synthesis of virus progeny. This phenomenon was not observed in HCMV-infected fibroblasts and suggested the sequestration and the release of HCMV by epithelial cells. This hypothesis was supported by confocal and electron microscopy analyses. The sequestration and progressive release of HCMV by kidney and mammary epithelial cells may play an important role in the excretion of the virus in urine and breast milk and may thereby contribute to HCMV transmission

The Patient Enablement Instrument-French version in a family practice setting: a reliability study

Background: Patient enablement can be defined as the extent to which a patient is capable of understanding and coping with his or her health issues. This concept is linked to a number of health outcomes such as self-management of chronic diseases and quality of life. The Patient Enablement Instrument (PEI) was designed to measure this concept after a medical consultation. The instrument, in its original form and its translations into several languages, has proven to be reliable and valid. The purpose of this study was to evaluate the reliability of the French version of the PEI (PEI-Fv) in a family practice setting. Methods: One hundred and ten participants were recruited in a family medicine clinic in the Saguenay region of Quebec (Canada). The PEI-Fv was completed twice, immediately after consultation with a physician (T1) and 2 weeks after the consultation (T2). The internal consistency of the tool was assessed with Cronbach's α and test-retest reliability by intraclass correlation coefficient. Results: The mean score for the PEI-Fv was 5.06 ± 3.97 (95% confidence interval [CI]: 4.30-5.81) at T1 and 4.63 ± 3.90 (95% CI: 3.82-5.44) at T2. Cronbach's α was high at T1 (α1 = 0.93; 95% CI: 0.91-0.95) and T2 (α2 = 0.93; 95% CI: 0.91-0.95). The intraclass correlation coefficient was 0.62 (95% CI: 0.48-0.74), indicating a moderate test-retest reliability. Conclusions: The internal consistency of the PEI-Fv is excellent. Test-retest reliability was moderate to good. Test-retest reliability should be examined in further studies at a less than 2-week interval to reduce maturation bias. This instrument can be used to measure enablement after consultation in a French-speaking family practice setting

In a New Land:Mobile Phones, Amplified Pressures and Reduced Capabilities

Framed within the theoretical lens of positive and negative security, this paper presents a study of newcomers to Sweden and the roles of mobile phones in the establishment of a new life. Using creative engagement methods through a series of workshops, two researchers engaged 70 adult participants enrolled into further education colleges in Sweden. Group narratives about mobile phone use were captured in creative outputs, researcher observations and notes and were analysed using thematic analysis. Key findings show that the mobile phone offers security for individuals and a safe space for newcomers to establish a new life in a new land as well as capitalising on other spaces of safety, such as maintaining old ties. This usage produces a series of threats and vulnerabilities beyond traditional technological security thinking related to mobile phone use. The paper concludes with recommendations for policies and support strategies for those working with newcomers

The impact of provider-initiated (opt-out) HIV testing and counseling of patients with sexually transmitted infection in Cape Town, South Africa: a controlled trial

<p>Abstract</p> <p>Background</p> <p>The effectiveness of provider-initiated HIV testing and counseling (PITC) for patients with sexually transmitted infection (STI) in resource-constrained settings are of particular concern for high HIV prevalence countries like South Africa. This study evaluated whether the PITC approach increased HIV testing amongst patients with a new episode of sexually transmitted infection, as compared to standard voluntary counseling and testing (VCT) at the primary care level in South Africa, a high prevalence and low resource setting.</p> <p>Methods</p> <p>The design was a pragmatic cluster-controlled trial with seven intervention and 14 control clinics in Cape Town. Nurses in intervention clinics integrated PITC into standard HIV care with few additional resources, whilst lay counselors continued with the VCT approach in control clinics. Routine data were collected for a six-month period following the intervention in 2007, on new STI patients who were offered and who accepted HIV testing. The main outcome measure was the proportion of new STI patients tested for HIV, with secondary outcomes being the proportions who were offered and who declined the HIV test.</p> <p>Results</p> <p>A significantly higher proportion of new STI patients in the intervention group tested for HIV as compared to the control group with (56.4% intervention versus 42.6% control, p = 0.037). This increase was achieved despite a significantly higher proportion intervention group declining testing when offered (26.7% intervention versus 13.5% control, p = 0.0086). Patients were more likely to be offered HIV testing in intervention clinics, where providers offered the HIV test to 76.8% of new STI patients versus 50.9% in the control group (p = 0.0029). There was significantly less variation in the main outcomes across the intervention clinics, suggesting that the intervention also facilitated more consistent performance.</p> <p>Conclusions</p> <p>PITC was successful in three ways: it increased the proportion of new STI patients tested for HIV; it increased the proportion of new STI patients offered HIV testing; and it delivered more consistent performance across clinics. Recommendations are made for increasing the impact and feasibility of PITC in high HIV prevalence and resource-constrained settings. These include more flexible use of clinical and lay staff, and combining PITC with VCT and other community-based approaches to HIV testing.</p> <p>Trial registration</p> <p>Controlled trial ISRCTN93692532</p

Human cytomegalovirus elicits fetal γδ T cell responses in utero

The fetus and infant are highly susceptible to viral infections. Several viruses, including human cytomegalovirus (CMV), cause more severe disease in early life compared with later life. It is generally accepted that this is a result of the immaturity of the immune system. γδ T cells are unconventional T cells that can react rapidly upon activation and show major histocompatibility complex–unrestricted activity. We show that upon CMV infection in utero, fetal γδ T cells expand and become differentiated. The expansion was restricted to Vγ9-negative γδ T cells, irrespective of their Vδ chain expression. Differentiated γδ T cells expressed high levels of IFN-γ, transcription factors T-bet and eomes, natural killer receptors, and cytotoxic mediators. CMV infection induced a striking enrichment of a public Vγ8Vδ1-TCR, containing the germline-encoded complementary-determining-region-3 (CDR3) δ1–CALGELGDDKLIF/CDR3γ8–CATWDTTGWFKIF. Public Vγ8Vδ1-TCR–expressing cell clones produced IFN-γ upon coincubation with CMV-infected target cells in a TCR/CD3-dependent manner and showed antiviral activity. Differentiated γδ T cells and public Vγ8Vδ1-TCR were detected as early as after 21 wk of gestation. Our results indicate that functional fetal γδ T cell responses can be generated during development in utero and suggest that this T cell subset could participate in antiviral defense in early life

Can, Want and Try: Parents' Viewpoints Regarding the Participation of Their Child with an Acquired Brain Injury

BACKGROUND: Acquired brain injury (ABI) is a leading cause of permanent disability, currently affecting 20,000 Australian children. Community participation is essential for childhood development and enjoyment, yet children with ABI can often experience barriers to participation. The factors which act as barriers and facilitators to community participation for children with an ABI are not well understood. AIM: To identify the viewpoints of parents of children with an ABI, regarding the barriers and facilitators most pertinent to community participation for their child. METHODS: Using Q-method, 41 parents of children with moderate/severe ABI sorted 37 statements regarding barriers and facilitators to community participation. Factor analysis identified three viewpoints. RESULTS: This study identified three distinct viewpoints, with the perceived ability to participate decreasing with a stepwise trend from parents who felt their child and family "can" participate in viewpoint one, to "want" in viewpoint two and "try" in viewpoint three. CONCLUSIONS: Findings indicated good participation outcomes for most children and families, however some families who were motivated to participate experienced significant barriers. The most significant facilitators included child motivation, supportive relationships from immediate family and friends, and supportive community attitudes. The lack of supportive relationships and attitudes was perceived as a fundamental barrier to community participation. SIGNIFICANCE: This research begins to address the paucity of information regarding those factors that impact upon the participation of children with an ABI in Australia. Findings have implications for therapists, service providers and community organisations

Evaluation of a toolkit to improve cardiovascular disease screening and treatment for people with type 2 diabetes: protocol for a cluster-randomized pragmatic trial

<p>Abstract</p> <p>Background</p> <p>The gap between the level of care recommended by evidence-based clinical practice guidelines and the actual care delivered to patients in practice has been well established. The Canadian Diabetes Association (CDA) created an implementation strategy to improve the implementation of its 2008 guidelines. This study will evaluate the impact of the strategy to improve cardiovascular disease (CVD) screening, prevention and treatment for people with diabetes.</p> <p>Design</p> <p>A pragmatic cluster-randomized trial will be conducted to evaluate the CDA's CVD Toolkit. All family physicians in Ontario, Canada were randomly allocated to receive the Toolkit, which includes several printed educational materials targeting CVD screening, prevention and treatment, either in spring 2009 (intervention arm) or in spring 2010 (control arm). Randomization occurred at the level of the practice. Forty family physicians from each arm will be recruited to participate, and the medical records for 20 of their diabetic patients at high risk for CVD will be retrospectively reviewed. Outcome measures will be assessed for each patient between July 2009 and March 2010. The primary outcome will be that the patient is receiving a statin. Secondary outcomes will include 1) the receipt of an angiotensin converting enzyme inhibitor or angiotensin receptor blocker, 2) various intermediate measures (A1c, blood pressure, LDL-cholesterol, total-/HDL-cholesterol ratio, body mass index and waist circumference), and 3) clinical inertia (the failure to change therapy in response to an abnormal A1c, blood pressure or cholesterol reading). The analysis will be carried out using multilevel hierarchical logistic regression models to account for the clustered nature of the data. The group assignment will be a physician-level variable. In addition, a process evaluation study with six focus groups of family physicians will assess the acceptability of the CDA's Toolkit and will explore factors contributing to any change or lack of change in behaviour, from the perspectives of family physicians.</p> <p>Discussion</p> <p>Printed educational materials for physicians have been shown to exert small-to-moderate changes in patient care. The CDA's CVD Toolkit is an example of a practice guideline implementation strategy that can be disseminated to a wide audience relatively inexpensively, and so demonstrating its effectiveness at improving diabetes care could have important consequences for guideline developers, policy makers and clinicians.</p> <p>Trial Registration</p> <p>The trial is registered with <url>http://www.clinicaltrials.gov</url>, ID # NCT01026688</p

Fever, hyperglycaemia and swallowing dysfunction management in acute stroke: A cluster randomised controlled trial of knowledge transfer

Background: Hyperglycaemia, fever, and swallowing dysfunction are poorly managed in the admission phase of acute stroke, and patient outcomes are compromised. Use of evidence-based guidelines could improve care but have not been effectively implemented. Our study aims to develop and trial an intervention based on multidisciplinary team-building to improve management of fever, hyperglycaemia, and swallowing dysfunction in patients following acute stroke. Methods and design: Metropolitan acute stroke units (ASUs) located in New South Wales, Australia will be stratified by service category (A or B) and, within strata, by baseline patient recruitment numbers (high or low) in this prospective, multicentre, single-blind, cluster randomised controlled trial (CRCT). ASUs then will be randomised independently to either intervention or control groups. ASUs allocated to the intervention group will receive: unit-based workshops to identify local barriers and enablers; a standardised core education program; evidence-based clinical treatment protocols; and ongoing engagement of local staff. Control group ASUs will receive only an abridged version of the National Clinical Guidelines for Acute Stroke Management. The following outcome measures will be collected at 90 days post-hospital admission: patient death, disability (modified Rankin Score); dependency (Barthel Index) and Health Status (SF-36). Additional measures include: performance of swallowing screening within 24 hours of admission; glycaemic control and temperature control. Discussion: This is a unique study of research transfer in acute stroke. Providing optimal inpatient care during the admission phase is essential if we are to combat the rising incidence of debilitating stroke. Our CRCT will also allow us to test interventions focussed on multidisciplinary ASU teams rather than individual disciplines, an imperative of modern hospital services

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types