Estimating the public health impact of the effect of herpes simplex virus suppressive therapy on plasma HIV-1 viral load.

OBJECTIVE: Trials of herpes simplex virus (HSV) suppressive therapy among HSV-2/HIV-1-infected individuals have reported an impact on plasma HIV-1 viral loads (PVLs). Our aim was to estimate the population-level impact of suppressive therapy on female-to-male HIV-1 sexual transmission. DESIGN AND METHODS: By comparing prerandomization and postrandomization individual-level PVL data from the first two HSV suppressive therapy randomized controlled trials in sub-Saharan Africa, we estimated the effect of treatment on duration of asymptomatic infection and number of HIV-1 transmission events for each trial. RESULTS: Assuming that a reduction in PVL is accompanied by an increased duration of HIV-1 asymptomatic infection, 4-6 years of HSV suppressive therapy produce a 1-year increase in the duration of this stage. To avert one HIV-1 transmission requires 8.8 [95% confidence interval (CI), 5.9-14.9] and 11.4 (95% CI, 7.8-27.5) women to be treated from halfway through their HIV-1 asymptomatic period, using results from Burkina Faso and South African trials, respectively. Regardless of the timing of treatment initiation, 51.6 (95% CI, 30.4-137.0) and 66.5 (95% CI, 36.7-222.6) treatment-years are required to avert one HIV-1 infection. Distributions of set-point PVL values from sub-Saharan African populations suggest that unintended adverse consequences of therapy at the population level (i.e. increased HIV-1 transmission due to increased duration of infection) are unlikely to occur in these settings. CONCLUSION: HSV suppressive therapy may avert relatively few HIV-1 transmission events per person-year of treatment. Its use as a prevention intervention may be limited; however, further research into its effect on rate of CD4 cell count decline and the impact of higher dosing schedules is warranted

Genetic variation exists for telomeric array organization within and among the genomes of normal, immortalized, and transformed chicken systems

This study investigated telomeric array organization of diverse chicken genotypes utilizing in vivo and in vitro cells having phenotypes with different proliferation potencies. Our experimental objective was to characterize the extent and nature of array variation present to explore the hypothesis that mega-telomeres are a universal and fixed feature of chicken genotypes. Four different genotypes were studied including normal (UCD 001, USDA-ADOL Line 0), immortalized (DF-1), and transformed (DT40) cells. Both cytogenetic and molecular approaches were utilized to develop an integrated view of telomeric array organization. It was determined that significant variation exists within and among chicken genotypes for chromosome-specific telomeric array organization and total genomic-telomeric sequence content. Although there was variation for mega-telomere number and distribution, two mega-telomere loci were in common among chicken genetic lines (GGA 9 and GGA W). The DF-1 cell line was discovered to maintain a complex derivative karyotype involving chromosome fusions in the homozygous and heterozygous condition. Also, the DF-1 cell line was found to contain the greatest amount of telomeric sequence per genome (17%) as compared to UCD 001 (5%) and DT40 (1.2%). The chicken is an excellent model for studying unique and universal features of vertebrate telomere biology, and characterization of the telomere length variation among genotypes will be useful in the exploration of mechanisms controlling telomere length maintenance in different cell types having unique phenotypes

Priority sites for wildfowl conservation in Mexico

A set of priority sites for wildfowl conservation in Mexico was determined using contemporary count data (1991–2000) from the U.S. Fish & Wildlife Service mid-winter surveys. We used a complementarity approach implemented through linear integer programming that addresses particular conservation concerns for every species included in the analysis and large fluctuations in numbers through time. A set of 31 priority sites was identified, which held more than 69% of the mid-winter count total in Mexico during all surveyed years. Six sites were in the northern highlands, 12 in the central highlands, six on the Gulf of Mexico coast and seven on the upper Pacific coast. Twenty-two sites from the priority set have previously been identified as qualifying for designation as wetlands of international importance under the Ramsar Convention and 20 sites are classified as Important Areas for Bird Conservation in Mexico. The information presented here provides an accountable, spatially-explicit, numerical basis for ongoing conservation planning efforts in Mexico, which can be used to improve existing wildfowl conservation networks in the country and can also be useful for conservation planning exercises elsewhere

To what extent can the activities of the South Australian Health in All Policies initiative be linked to population health outcomes using a program theory-based evaluation?

BACKGROUND: This paper reports on a five-year study using a theory-based program logic evaluation, and supporting survey and interview data to examine the extent to which the activites of the South Australian Health in All Policies initiative can be linked to population health outcomes. METHODS: Mixed-methods data were collected between 2012 and 2016 in South Australia (144 semi-structured key informant interviews; two electronic surveys of public servants in 2013 (n = 435) and 2015 (n = 483); analysis of state government policy documents; and construction of a program logic model to shape assessment of the feasibility of attribution to population health outcomes). RESULTS: Multiple actions on social determinants of health in a range of state government sectors were reported and most could be linked through a program logic model to making some contribution to future population health outcomes. Context strongly influences implementation; not all initiatives will be successful and experimentation is vital. Successful initiatives included HiAP influencing the urban planning department to be more concerned with the health impacts of planning decisions, and encouraging the environment department to be concerned with the health impacts of its work. CONCLUSIONS: The theory-based program logic suggests that SA HiAP facilitated improved population health through working with multiple government departments. Public servants came to appreciate how their sectors impact on health. Program logic is a mechanism to evaluate complex public health interventions in a way that takes account of political and economic contexts. SA HiAP was mainly successful in avoiding lifestyle drift in strategy. The initiative encouraged a range of state government departments to tackle conditions of daily living. The broader underpinning factors dictating the distribution of power, money and resources were not addressed by HiAP. This reflects HiAP's use of a consensus model which was driven by (rather than drove) state priorities and sought 'win-win' strategies

A Single Nucleotide Change Affects Fur-Dependent Regulation of sodB in H. pylori

Helicobacter pylori is a significant human pathogen that has adapted to survive the many stresses found within the gastric environment. Superoxide Dismutase (SodB) is an important factor that helps H. pylori combat oxidative stress. sodB was previously shown to be repressed by the Ferric Uptake Regulator (Fur) in the absence of iron (apo-Fur regulation) [1]. Herein, we show that apo regulation is not fully conserved among all strains of H. pylori. apo-Fur dependent changes in sodB expression are not observed under iron deplete conditions in H. pylori strains G27, HPAG1, or J99. However, Fur regulation of pfr and amiE occurs as expected. Comparative analysis of the Fur coding sequence between G27 and 26695 revealed a single amino acid difference, which was not responsible for the altered sodB regulation. Comparison of the sodB promoters from G27 and 26695 also revealed a single nucleotide difference within the predicted Fur binding site. Alteration of this nucleotide in G27 to that of 26695 restored apo-Fur dependent sodB regulation, indicating that a single base difference is at least partially responsible for the difference in sodB regulation observed among these H. pylori strains. Fur binding studies revealed that alteration of this single nucleotide in G27 increased the affinity of Fur for the sodB promoter. Additionally, the single base change in G27 enabled the sodB promoter to bind to apo-Fur with affinities similar to the 26695 sodB promoter. Taken together these data indicate that this nucleotide residue is important for direct apo-Fur binding to the sodB promoter

Practicing physiotherapy in Danish private practice: an ethical perspective.

Despite an increasingly growth of professional guidelines, textbooks and research about ethics in health care, awareness about ethics in Danish physiotherapy private practice seen vague. This article explores how physiotherapists in Danish private practice, from an ethical perspective, perceive to practice physiotherapy. The empirical data consists of interviews with twenty-one physiotherapists. The interviews are analysed from a hermeneutic approach, inspired by Ricoeur's textual interpretation of distanciation. The analysis follows three phases: naïve reading, structural analysis and comprehensive analysis. Four main themes are constructed: Beneficence as the driving force; Disciplining the patient through the course of physiotherapy; Balancing between being a trustworthy professional and a businessperson; The dream of a code of practice. Private practice physiotherapy is embedded in a structural frame directed by both political and economical conditions that shape the conditions for practicing physiotherapy. It means that beneficence in practice is a balance between the patient, the physiotherapists themselves and the business. Beneficence towards the patient is expressed as an implicit demand. Physiotherapeutic practice is expressed as being an integration of professionalism and personality which implies that the physiotherapists also have to benefit themselves. Private practice seems to be driven by a paternalistic approach towards the patient, where disciplining the patient is a crucial element of practice, in order to optimise profit. Physiotherapists wish for a more beneficent practice in the future by aiming at bridging 'to be' and 'ought to be'

Investing in the future: lessons learnt from communicating the results of HSV/ HIV intervention trials in South Africa

<p>Abstract</p> <p>Background</p> <p>Communicating the results of randomised controlled trials may present challenges for researchers who have to work with communities and policy-makers to anticipate positive outcomes, while being aware that results may show no effect or harm.</p> <p>Methods</p> <p>We present a case study from the perspective of researchers in South Africa about the lessons learnt from communicating the results of four trials evaluating treatment for herpes simplex virus type 2 (HSV-2) as a new strategy for HIV prevention.</p> <p>Results</p> <p>We show that contextual factors such as misunderstandings and mistrust played an important role in defining the communications response. Use of different approaches in combination was found to be most effective in building understanding, credibility and trust in the research process. During the communication process, researchers acted beyond their traditional role of neutral observers and became agents of social change. This change in role is in keeping with a global trend towards increased communication of research results and presents both opportunities and challenges for the conduct of future research.</p> <p>Conclusions</p> <p>Despite disappointing trial results which showed no benefit of HSV-2 treatment for HIV prevention, important lessons were learnt about the value of the communication process in building trust between researchers, community members and policy-makers, and creating an enabling environment for future research partnerships.</p