Modulation of Early Host Innate Immune Response by an Avipox Vaccine Virus' Lateral Body Protein

The avian pathogen fowlpox virus (FWPV) has been successfully used as a vaccine vector in poultry and humans, but relatively little is known about its ability to modulate host antiviral immune responses in these hosts, which are replication-permissive and nonpermissive, respectively. FWPV is highly resistant to avian type I interferon (IFN) and able to completely block the host IFN-response. Microarray screening of host IFN-regulated gene expression in cells infected with 59 different, nonessential FWPV gene knockout mutants revealed that FPV184 confers immunomodulatory capacity. We report that the FPV184-knockout virus (FWPVΔ184) induces the cellular IFN response as early as 2 h postinfection. The wild-type, uninduced phenotype can be rescued by transient expression of FPV184 in FWPVΔ184-infected cells. Ectopic expression of FPV184 inhibited polyI:C activation of the chicken IFN-β promoter and IFN-α activation of the chicken Mx1 promoter. Confocal and correlative super-resolution light and electron microscopy demonstrated that FPV184 has a functional nuclear localisation signal domain and is packaged in the lateral bodies of the virions. Taken together, these results provide a paradigm for a late poxvirus structural protein packaged in the lateral bodies, capable of suppressing IFN induction early during the next round of infection

Having a Family Doctor is Associated with Some Better Patient-Reported Outcomes of Primary Care Consultations

Background: Hong Kong (HK) has pluralistic primary care that is provided by a variety of doctors. The aim of our study was to assess patient-reported outcomes of primary care consultations in HK and whether having a family doctor (FD) made any difference. Methods: We interviewed by telephone 3148 subjects from 5174 contacted households (response rate 60.8%) randomly selected from the general population of HK about the experience of their last primary care consultations in September 2007 and April 2008. We compared the patient-reported outcomes (PRO) and patient-centered process of care in those with a FD, those with other types of regular primary care doctors (ORD) and those without any regular primary care doctor (NRD). PRO included patient enablement, global improvement in health, overall satisfaction, and likelihood of recommending their doctors to family and friends. Patient-centered process of care indicators was explanations about the illness, and address of patient’s concerns. Results: One thousand one hundred fifty, 746, and 1157 reported to have FD, ORD, and NRD, respectively. Over 80% of those with FD consulted their usual primary care doctors in the last consultation compared with 27% of those with NRD. Compared with subjects having ORD or NRD, subjects with FD reported being more enabled after the consultation and were more likely to recommend their doctors to family and friends. Subjects with FD and ORD were more likely than those having NRD to report a global improvement in health and satisfaction. FD group was more likely than the other two groups to report receiving an explanation on the diagnosis, nature, and expected course of the illness, and having their concerns addressed. Patient enablement was associated with explanation of diagnosis, nature, and expected course of illness, and address of patient’s concerns. Conclusion: People with a regular FD were more likely to feel being enabled and to experience patient-centered care in consultations.published_or_final_versio

A qualitative study of patients' views on quality of primary care consultations in Hong Kong and comparison with the UK CARE Measure

<b>Background</b> Patients' priorities and views on quality care are well-documented in Western countries but there is a dearth of research in this area in the East. The aim of the present study was to explore Chinese patients' views on quality of primary care consultations in Hong Kong and to compare these with the items in the CARE measure (a process measure of consultation quality widely used in the UK) in order to assess the potential utility of the CARE measure in a Chinese population.<p></p> <b>Methods</b> Individual semi-structured interviews were conducted on 21 adult patients from 3 different primary care clinics (a public primary healthcare clinic, a University health centre, and a private family physician's clinic). Topics discussed included expectations, experiences, and views about quality of medical consultations. Interviews were typed verbatim, and a thematic approach was taken to identify key issues. These identified issues were then compared with the ten CARE measure items, using a CARE framework: Connecting (Care Measure items 1–3), Assessing (item 4), Responding (items 5,6), and Empowering (items 7–10).<p></p> <b>Results</b> Patients judged doctors in terms of both the process of the consultation and the perceived outcomes. Themes identified that related to the interpersonal process of the consultation fitted well under the CARE framework; Connecting and communicating (18/21 patients), Assessing holistically (10/21 patients), Responding (18/21 patients) and Empowering (19/21 patients). Patients from the public clinic, who were generally of lower socio-economic status, were least likely to expect holistic care or empowerment. Two-thirds of patients also judged doctors on whether they performed an adequate physical examination, and three-quarters on the later outcomes of consultation (in terms of relief or cure and/or side-effects of prescribed drugs).<p></p> <b>Conclusion</b> These findings suggest that Chinese patients in Hong Kong value engaged, empathic primary care doctors and judge the quality of consultations largely on these human skills and the attitudes and values that underpin them, as well as on the perceived outcomes of treatment. The match between themes relating to consultation process and the CARE Measure items suggests utility of this measure in this population, but further quantitative validation is required

On the behaviour of lung tissue under tension and compression

Lung injuries are common among those who suffer an impact or trauma. The relative severity of injuries up to physical tearing of tissue have been documented in clinical studies. However, the specific details of energy required to cause visible damage to the lung parenchyma are lacking. Furthermore, the limitations of lung tissue under simple mechanical loading are also not well documented. This study aimed to collect mechanical test data from freshly excised lung, obtained from both Sprague-Dawley rats and New Zealand White rabbits. Compression and tension tests were conducted at three different strain rates: 0.25, 2.5 and 25 min−1. This study aimed to characterise the quasi-static behaviour of the bulk tissue prior to extending to higher rates. A nonlinear viscoelastic analytical model was applied to the data to describe their behaviour. Results exhibited asymmetry in terms of differences between tension and compression. The rabbit tissue also appeared to exhibit stronger viscous behaviour than the rat tissue. As a narrow strain rate band is explored here, no conclusions are being drawn currently regarding the rate sensitivity of rat tissue. However, this study does highlight both the clear differences between the two tissue types and the important role that composition and microstructure can play in mechanical response

Increasing condom use in heterosexual men: development of a theory-based interactive digital intervention

Increasing condom use to prevent sexually transmitted infections is a key public health goal. Interventions are more likely to be effective if they are theory- and evidence-based. The Behaviour Change Wheel (BCW) provides a framework for intervention development. To provide an example of how the BCW was used to develop an intervention to increase condom use in heterosexual men (the MenSS website), the steps of the BCW intervention development process were followed, incorporating evidence from the research literature and views of experts and the target population. Capability (e.g. knowledge) and motivation (e.g. beliefs about pleasure) were identified as important targets of the intervention. We devised ways to address each intervention target, including selecting interactive features and behaviour change techniques. The BCW provides a useful framework for integrating sources of evidence to inform intervention content and deciding which influences on behaviour to target

Plasma cholesterol levels and brain development in preterm newborns.

BackgroundTo assess whether postnatal plasma cholesterol levels are associated with microstructural and macrostructural regional brain development in preterm newborns.MethodsSixty preterm newborns (born 24-32 weeks gestational age) were assessed using MRI studies soon after birth and again at term-equivalent age. Blood samples were obtained within 7 days of each MRI scan to analyze for plasma cholesterol and lathosterol (a marker of endogenous cholesterol synthesis) levels. Outcomes were assessed at 3 years using the Bayley Scales of Infant Development, Third Edition.ResultsEarly plasma lathosterol levels were associated with increased axial and radial diffusivities and increased volume of the subcortical white matter. Early plasma cholesterol levels were associated with increased volume of the cerebellum. Early plasma lathosterol levels were associated with a 2-point decrease in motor scores at 3 years.ConclusionsHigher early endogenous cholesterol synthesis is associated with worse microstructural measures and larger volumes in the subcortical white matter that may signify regional edema and worse motor outcomes. Higher early cholesterol is associated with improved cerebellar volumes. Further work is needed to better understand how the balance of cholesterol supply and endogenous synthesis impacts preterm brain development, especially if these may be modifiable factors to improve outcomes

Impact of socioeconomic deprivation on rate and cause of death in severe mental illness

Background: Socioeconomic status has important associations with disease-specific mortality in the general population. Although individuals with Severe Mental Illnesses (SMI) experience significant premature mortality, the relationship between socioeconomic status and mortality in this group remains under investigated.<p></p> Aims: To assess the impact of socioeconomic status on rate and cause of death in individuals with SMI (schizophrenia and bipolar disorder) relative to the local (Glasgow) and wider (Scottish) populations.<p></p> Methods: Cause and age of death during 2006-2010 inclusive for individuals with schizophrenia or bipolar disorder registered on the Glasgow Psychosis Clinical Information System (PsyCIS) were obtained by linkage to the Scottish General Register Office (GRO). Rate and cause of death by socioeconomic status, measured by Scottish Index of Multiple Deprivation (SIMD), were compared to the Glasgow and Scottish populations.<p></p> Results: Death rates were higher in people with SMI across all socioeconomic quintiles compared to the Glasgow and Scottish populations, and persisted when suicide was excluded. Differences were largest in the most deprived quintile (794.6 per 10,000 population vs. 274.7 and 252.4 for Glasgow and Scotland respectively). Cause of death varied by socioeconomic status. For those living in the most deprived quintile, higher drug-related deaths occurred in those with SMI compared to local Glasgow and wider Scottish population rates (12.3% vs. 5.9%, p = <0.001 and 5.1% p = 0.002 respectively). A lower proportion of deaths due to cancer in those with SMI living in the most deprived quintile were also observed, relative to the local Glasgow and wider Scottish populations (12.3% vs. 25.1% p = 0.013 and 26.3% p = <0.001). The proportion of suicides was significantly higher in those with SMI living in the more affluent quintiles relative to Glasgow and Scotland (54.6% vs. 5.8%, p = <0.001 and 5.5%, p = <0.001). Discussion and conclusions: Excess mortality in those with SMI occurred across all socioeconomic quintiles compared to the Glasgow and Scottish populations but was most marked in the most deprived quintiles when suicide was excluded as a cause of death. Further work assessing the impact of socioeconomic status on specific causes of premature mortality in SMI is needed

Increased HIV Incidence in Men Who Have Sex with Men Despite High Levels of ART-Induced Viral Suppression: Analysis of an Extensively Documented Epidemic

Background: There is interest in expanding ART to prevent HIV transmission, but in the group with the highest levels of ART use, men-who-have-sex-with-men (MSM), numbers of new infections diagnosed each year have not decreased as ART coverage has increased for reasons which remain unclear. Methods: We analysed data on the HIV-epidemic in MSM in the UK from a range of sources using an individual-based simulation model. Model runs using parameter sets found to result in good model fit were used to infer changes in HIV-incidence and risk behaviour. Results: HIV-incidence has increased (estimated mean incidence 0.30/100 person-years 1990–1997, 0.45/100 py 1998–2010), associated with a modest (26%) rise in condomless sex. We also explored counter-factual scenarios: had ART not been introduced, but the rise in condomless sex had still occurred, then incidence 2006–2010 was 68% higher; a policy of ART initiation in all diagnosed with HIV from 2001 resulted in 32% lower incidence; had levels of HIV testing been higher (68% tested/year instead of 25%) incidence was 25% lower; a combination of higher testing and ART at diagnosis resulted in 62% lower incidence; cessation of all condom use in 2000 resulted in a 424% increase in incidence. In 2010, we estimate that undiagnosed men, the majority in primary infection, accounted for 82% of new infections. Conclusion: A rise in HIV-incidence has occurred in MSM in the UK despite an only modest increase in levels of condomless sex and high coverage of ART. ART has almost certainly exerted a limiting effect on incidence. Much higher rates of HIV testing combined with initiation of ART at diagnosis would be likely to lead to substantial reductions in HIV incidence. Increased condom use should be promoted to avoid the erosion of the benefits of ART and to prevent other serious sexually transmitted infections

Accessibility and suitability of residential alcohol treatment for older adults: a mixed method study

Background Whilst alcohol misuse is decreasing amongst younger adults in many countries, it is increasing in older adults. Residential rehabilitation (rehab) is a vital component of the alcohol treatment system, particularly for those with relatively complex needs and entrenched alcohol problems. In this study, we sought to find out to what extent rehabs in England have upper age limits that exclude older adults, whether rehabs are responsive to older adults’ age-related needs and how older adults experience these services. Method This is a mixed method study. A search was carried out of Public Health England’s online directory of rehabs to identify upper age thresholds. Semi-structured qualitative interviews were carried out with 16 individuals who had attended one of five residential rehabs in England and Wales since their 50th birthday. A researcher with experience of a later life alcohol problem conducted the interviews. Results Of the 118 services listed on Public Health England’s online directory of rehabs, 75% stated that they had an upper age limit that would exclude older adults. Perceived differences in values, attitudes and behaviour between younger and older residents had an impact on older residents’ experience of rehab. Activities organised by the rehabs were often based on physical activity that some older adults found it difficult to take part in and this could create a sense of isolation. Some older adults felt unsafe in rehab and were bullied, intimidated and subjected to ageist language and attitudes. Conclusion This study identified direct and indirect age discrimination in rehabs contrary to the law. Further research is required to find out if age discrimination exists in rehabs in other countries. Rehabs should remove arbitrary age limits and ensure that they are responsive to the needs of older adults

Genetic variation in genes regulating skeletal muscle regeneration and tissue remodelling associated with weight loss in chronic obstructive pulmonary disease

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. COPD patients with cachexia or weight loss have increased risk of death independent of body mass index (BMI) and lung function. We tested the hypothesis genetic variation is associated with weight loss in COPD using a genome-wide association study approach. METHODS: Participants with COPD (N = 4308) from three studies (COPDGene, ECLIPSE, and SPIROMICS) were analysed. Discovery analyses were performed in COPDGene with replication in SPIROMICS and ECLIPSE. In COPDGene, weight loss was defined as self-reported unintentional weight loss > 5% in the past year or low BMI (BMI < 20 kg/m2). In ECLIPSE and SPIROMICS, weight loss was calculated using available longitudinal visits. Stratified analyses were performed among African American (AA) and Non-Hispanic White (NHW) participants with COPD. Single variant and gene-based analyses were performed adjusting for confounders. Fine mapping was performed using a Bayesian approach integrating genetic association results with linkage disequilibrium and functional annotation. Significant gene networks were identified by integrating genetic regions associated with weight loss with skeletal muscle protein–protein interaction (PPI) data. RESULTS: At the single variant level, only the rs35368512 variant, intergenic to GRXCR1 and LINC02383, was associated with weight loss (odds ratio = 3.6, 95% confidence interval = 2.3–5.6, P = 3.2 × 10−8) among AA COPD participants in COPDGene. At the gene level in COPDGene, EFNA2 and BAIAP2 were significantly associated with weight loss in AA and NHW COPD participants, respectively. The EFNA2 association replicated among AA from SPIROMICS (P = 0.0014), whereas the BAIAP2 association replicated in NHW from ECLIPSE (P = 0.025). The EFNA2 gene encodes the membrane-bound protein ephrin-A2 involved in the regulation of developmental processes and adult tissue homeostasis such as skeletal muscle. The BAIAP2 gene encodes the insulin-responsive protein of mass 53 kD (IRSp53), a negative regulator of myogenic differentiation. Integration of the gene-based findings participants with PPI data revealed networks of genes involved in pathways such as Rho and synapse signalling. CONCLUSIONS: The EFNA2 and BAIAP2 genes were significantly associated with weight loss in COPD participants. Collectively, the integrative network analyses indicated genetic variation associated with weight loss in COPD may influence skeletal muscle regeneration and tissue remodelling