Expression of Human CD4 and chemokine receptors in cotton rat cells confers permissiveness for productive HIV infection

<p>Abstract</p> <p>Background</p> <p>Current small animal models for studying HIV-1 infection are very limited, and this continues to be a major obstacle for studying HIV-1 infection and pathogenesis, as well as for the urgent development and evaluation of effective anti-HIV-1 therapies and vaccines. Previously, it was shown that HIV-1 can infect cotton rats as indicated by development of antibodies against all major proteins of the virus, the detection of viral cDNA in spleen and brain of challenged animals, the transmission of infectious virus, albeit with low efficiency, from animal to animal by blood, and an additional increase in the mortality in the infected groups.</p> <p>Results</p> <p>Using <it>in vitro </it>experiments, we now show that cotton rat cell lines engineered to express human receptor complexes for HIV-1 (hCD4 along with hCXCR4 or hCCR5) support virus entry, viral cDNA integration, and the production of infectious virus.</p> <p>Conclusion</p> <p>These results further suggest that the development of transgenic cotton rats expressing human HIV-1 receptors may prove to be useful small animal model for HIV infection.</p

Health on the Move (HOME) Study: Using a smartphone app to explore the health and wellbeing of migrants in the United Kingdom.

Background/Aim: We have a limited understanding of the broader determinants of health of international migrants and how these change over time since migration to the United Kingdom (UK). To address this knowledge gap, we aim to conduct a prospective cohort study with data acquisition via a smartphone application (app). In this pilot study, we aim to 1) determine the feasibility of the use of an app for data collection in international migrants, 2) optimise app engagement by quantifying the impact of specific design features on the completion rates of survey questionnaires and on study retention, 3) gather preliminary profile health status data, to begin to examine how risk factors for health are distributed among migrants. Methods: We will recruit 275 participants through a social media campaign and through third sector organisations that work with or support migrants in the UK. Following consent and registration, data will be collected via surveys. To optimise app engagement and study retention, we will quantify the impact of specific design features (i.e. the frequency of survey requests, the time of day for app notifications, the frequency of notifications, and the wording of notifications) via micro-randomised process evaluations. The primary outcome for this study is survey completion rates with numerator as the number of surveys completed and denominator as the total number of available surveys. Secondary outcomes are study retention rates and ratings of interest after app usage. Ethics and dissemination: We have obtained approval to use consented patient identifiable data from the University College London Ethics Committee. Improving engagement with the app and gathering preliminary health profile data will help us identify accessibility and usability issues and other barriers to app and study engagement prior to moving to a larger study

In what ways does the mandatory nature of Victoria's municipal public health planning framework impact on the planning process and outcomes?

BACKGROUND: Systems for planning are a critical component of the infrastructure for public health. Both in Australia and internationally there is growing interest in how planning processes might best be strengthened to improve health outcomes for communities. In Australia the delivery of public health varies across states, and mandated municipal public health planning is being introduced or considered in a number of jurisdictions. In 1988 the Victorian State government enacted legislation that made it mandatory for each local government to produce a Municipal Public Health Plan, offering us a 20-year experience to consider. RESULTS: In-depth interviews were undertaken with those involved in public health planning at the local government level, as part of a larger study on local public health infrastructure and capacity. From these interviews four significant themes emerge. Firstly, there is general agreement that the Victorian framework of mandatory public health planning has led to improvements in systems for planning. However, there is some debate about the degree of that improvement. Secondly, there is considerable variation in the way in which councils approach planning and the priority they attach to the process. Thirdly, there is concern that the focus is on producing a plan rather than on implementing the plan. Finally, some tension over priorities is evident. Those responsible for developing Municipal Public Health Plans express frustration over the difficulty of having issues they believe are important addressed through the MPHP process. CONCLUSION: There are criticisms of Victoria's system for public health planning at the local government level. Some of these issues may be specific to the arrangement in Victoria, others are problems encountered in public health planning generally. In Victoria where the delivery structure for public health is diverse, a system of mandatory planning has created a minimum standard. The implementation of the framework was slow and factors in the broader political environment had a significant impact. Work done in recent years to support the process appears to have led to improvements. There are lessons for other states as they embark upon mandated public health plans

Risk factors for squamous cell carcinoma of the oesophagus in women: a case–control study

Oesophageal cancer rates in women in the UK are more than 3 times higher than in most other European populations. A population-based matched case–control study of histologically confirmed squamous cell carcinoma of the oesophagus in women was carried out in 4 regions in England and Scotland. Interviews were carried out in hospital or at home and topics included: smoking; alcohol; tea and coffee consumption; medical and obstetric history; and diet. Response rates were 62% for cases and 65% for first-chosen controls. There were 159 case–control pairs. Significant results were found for: eating salads (odds ratio (OR) 0.42, 95% CI 0.20–0.92 in the highest quartile of consumption) and a light (as distinct from no) breakfast (OR 0.18, 95% CI 0.07 – 0.48) were protective; quantity of tea was a risk factor and there was a significant positive trend with temperature at which hot drinks were consumed (P = 0.03). Alcohol consumption was unrelated to risk, but there was a significant trend with years of smoking (P = 0.015). A protective effect of aspirin consumption was confined to the English centres (OR 0.08, 95% CI 0.01–0.56). Comparison with a parallel study of adenocarcinoma indicated a common protective effect of a healthy diet but otherwise distinct risk factors. © 2001 Cancer Research Campaign http://www.bjcancer.co

Evaluation of a pilot cooperative medical scheme in rural China: impact on gender patterns of health care utilization and prescription practices

<p>Abstract</p> <p>Background</p> <p>In 2003 the Chinese government introduced voluntary cooperative medical schemes (CMS), soon to be in place throughout rural China. Families who chose to enroll do so as a single unit and nothing is known about any differential effect of these new schemes on family members. This study evaluates the impact of one pilot CMS in Anhui Province on health care use by girls aged less than 5 years and women 65 years or older, and on the pattern and cost of prescriptions.</p> <p>Methods</p> <p>Health care records were extracted covering a 10 year period, before, during and after the pilot CMS in 4 townships, one with the intervention and 3 comparison townships without. The impact of the intervention on the age and gender distribution of patients presenting for health care and on the prescription of certain drugs was assessed by logistic regression. The cost of prescriptions before, during and after the intervention period was also assessed.</p> <p>Results</p> <p>203,058 registration and 643,588 prescription records were identified. During the intervention there was a reduced likelihood overall that a patient was female (OR = 0.92: 95%CI 0.87 - 0.97) at the intervention site. Girls aged < 5 years had an increased likelihood of health care (OR = 1.41: 95%CI 1.23 - 1.59) during the CMS, but women ≥ 65 years were relatively disadvantaged (OR = 0.84: 95%CI 0.75 - 0.95). The use of antibiotics and systemic steroids increased disproportionately at the intervention site for patients ≥ 5 years. Prescription costs at the township hospital also increased at the intervention site, particularly for older men.</p> <p>Conclusions</p> <p>This evaluation suggests that all family members did not benefit equally from the pilot CMS and that women ≥ 65 years may be disadvantaged by the newly available reimbursements of health care costs through the CMS. It points to the need, in future evaluations, to use individuals rather than families as the unit of analysis, in order to determine whether such health care inequalities are wide-spread and persistent or are reduced in the longer term. The results also support earlier concerns about the influence of new funding resources on prescription practices and the need for regulation of for-profit prescribing.</p

Impact of Indian Total Sanitation Campaign on latrine coverage and use: a cross-sectional study in Orissa three years following programme implementation.

BACKGROUND: Faced with a massive shortfall in meeting sanitation targets, some governments have implemented campaigns that use subsidies focused on latrine construction to overcome income constraints and rapidly expand coverage. In settings like rural India where open defecation is common, this may result in sub-optimal compliance (use), thereby continuing to leave the population exposed to human excreta. METHODS: We conducted a cross-sectional study to investigate latrine coverage and use among 20 villages (447 households, 1933 individuals) in Orissa, India where the Government of India's Total Sanitation Campaign had been implemented at least three years previously. We defined coverage as the proportion of households that had a latrine; for use we identified the proportion of households with at least one reported user and among those, the extent of reported use by each member of the household. RESULTS: Mean latrine coverage among the villages was 72% (compared to <10% in comparable villages in the same district where the Total Sanitation Campaign had not yet been implemented), though three of the villages had less than 50% coverage. Among these households with latrines, more than a third (39%) were not being used by any member of the household. Well over a third (37%) of the members of households with latrines reported never defecating in their latrines. Less than half (47%) of the members of such households reported using their latrines at all times for defecation. Combined with the 28% of households that did not have latrines, it appears that most defecation events in these communities are still practiced in the open. CONCLUSION: A large-scale campaign to implement sanitation has achieved substantial gains in latrine coverage in this population. Nevertheless, gaps in coverage and widespread continuation of open defecation will result in continued exposure to human excreta, reducing the potential for health gains

Mapping interactions with the chaperone network reveals factors that protect against tau aggregation.

A network of molecular chaperones is known to bind proteins ('clients') and balance their folding, function and turnover. However, it is often unclear which chaperones are critical for selective recognition of individual clients. It is also not clear why these key chaperones might fail in protein-aggregation diseases. Here, we utilized human microtubule-associated protein tau (MAPT or tau) as a model client to survey interactions between ~30 purified chaperones and ~20 disease-associated tau variants (~600 combinations). From this large-scale analysis, we identified human DnaJA2 as an unexpected, but potent, inhibitor of tau aggregation. DnaJA2 levels were correlated with tau pathology in human brains, supporting the idea that it is an important regulator of tau homeostasis. Of note, we found that some disease-associated tau variants were relatively immune to interactions with chaperones, suggesting a model in which avoiding physical recognition by chaperone networks may contribute to disease

Maternal education is associated with vaccination status of infants less than 6 months in Eastern Uganda: a cohort study

<p>Abstract</p> <p>Background</p> <p>Despite provision of free childhood vaccinations, less than half of all Ugandan infants are fully vaccinated. This study compares women with some secondary schooling to those with only primary schooling with regard to their infants' vaccination status.</p> <p>Methods</p> <p>A community-based prospective cohort study conducted between January 2006 and May 2008 in which 696 pregnant women were followed up to 24 weeks post partum. Information was collected on the mothers' education and vaccination status of the infants.</p> <p>Results</p> <p>At 24 weeks, the following vaccinations had been received: bacille Calmette-Guérin (BCG): 92%; polio-1: 91%; Diphteria-Pertussis-Tetanus-Hepatitis B-Haemophilus Influenza b (DPT-HB-Hib) 3 and polio-3: 63%. About 51% of the infants were fully vaccinated (i.e., had received all the scheduled vaccinations: BCG, polio 0, polio 1, DPT-HB-Hib1, polio 2, DPT-HB-Hib 2, polio 3 and DPT-HB-Hib 3). Only 46% of the infants whose mothers' had 5-7 years of primary education had been fully vaccinated compared to 65% of the infants whose mothers' had some secondary education. Infants whose mothers had some secondary education were less likely to miss the DPT-HB-Hib-2 vaccine (RR: 0.5, 95% CI: 0.3, 0.8), Polio-2 (RR: 0.4, 95%CI: 0.3, 0.7), polio-3 (RR: 0.5, 95%CI: 0.4, 0.7) and DPT-HB-Hib-3 (RR: 0.5, 95%CI: 0.4, 0.7). Other factors showing some association with a reduced risk of missed vaccinations were delivery at a health facility (RR = 0.8; 95%CI: 0.7, 1.0) and use of a mosquito net (RR: 0.8; 95%CI: 0.7, 1.0).</p> <p>Conclusion</p> <p>Infants whose mothers had a secondary education were at least 50% less likely to miss scheduled vaccinations compared to those whose mothers only had primary education. Strategies for childhood vaccinations should specifically target women with low formal education.</p

Presumptive treatment with sulphadoxine-pyrimethamine versus weekly chloroquine for malaria prophylaxis in children with sickle cell anaemia in Uganda: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Malaria carries high case fatality among children with sickle cell anaemia. In Uganda, chloroquine is used for prophylaxis in these children despite unacceptably high levels of resistance. Intermittent presumptive treatment with sulphadoxine-pyrimethamine (SP) has shown great potential for reducing prevalence of malaria and anaemia among pregnant women and infants.</p> <p>Objective</p> <p>To compare the efficacy of monthly SP presumptive treatment, versus weekly chloroquine for malaria prophylaxis in children attending the Sickle Cell Clinic, Mulago Hospital.</p> <p>Methods</p> <p>Two hundred and forty two children with sickle cell anaemia were randomized to presumptive treatment with SP or weekly chloroquine for malaria prophylaxis. Active detection of malaria was made at each weekly visit to the clinic over one month. The primary outcome measure was the proportion of children with one malaria episode at one month follow-up. The secondary outcome measures included malaria-related admissions and adverse effects of the drugs.</p> <p>Results</p> <p>Ninety-three percent (114/122) of the children in the chloroquine group and 94% (113/120) in the SP group completed one month follow up. SP reduced prevalence of malaria by 50% compared to chloroquine [OR = 0.50, (95% CI 0.26-0.97)]; p = 0.042. Six percent (7/122) of the children receiving weekly chloroquine had malaria related admissions compared to 2.5% (3/120) on presumptive treatment with SP. No serious drug effects were reported in both treatment groups</p> <p>Conclusion</p> <p>Presumptive treatment with SP was more efficacious than weekly chloroquine in reducing prevalence of malaria in children with sickle cell anaemia. Continued use of chloroquine for malaria chemoprophylaxis in children with sickle cell anaemia in Uganda does not seem to be justified.</p> <p>Clinical Trials Registration</p> <p>ClinicalTrials.gov Identifier: NCTOO124267</p