Polymorphisms of CUL5 are Associated with CD4+ T Cell Loss in HIV-1 Infected Individuals

Human apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (Apobec3) antiretroviral factors cause hypermutation of proviral DNA leading to degradation or replication-incompetent HIV-1. However, HIV-1 viral infectivity factor (Vif) suppresses Apobec3 activity through the Cullin 5-Elongin B-Elongin C E3 ubiquitin ligase complex. We examined the effect of genetic polymorphisms in the CUL5 gene (encoding Cullin 5 protein) on AIDS disease progression in five HIV-1 longitudinal cohorts. A total of 12 single nucleotide polymorphisms (SNPs) spanning 93 kb in the CUL5 locus were genotyped and their haplotypes inferred. A phylogenetic network analysis revealed that CUL5 haplotypes were grouped into two clusters of evolutionarily related haplotypes. Cox survival analysis and mixed effects models were used to assess time to AIDS outcomes and CD4+ T cell trajectories, respectively. Relative to cluster I haplotypes, the collective cluster II haplotypes were associated with more rapid CD4+ T cell loss (relative hazards [RH] = 1.47 and p = 0.009), in a dose-dependent fashion. This effect was mainly attributable to a single cluster II haplotype (Hap10) (RH = 2.49 and p = 0.00001), possibly due to differential nuclear protein–binding efficiencies of a Hap10-specifying SNP as indicated by a gel shift assay. Consistent effects were observed for CD4+ T cell counts and HIV-1 viral load trajectories over time. The findings of both functional and genetic epidemiologic consequences of CUL5 polymorphism on CD4+ T cell and HIV-1 levels point to a role for Cullin 5 in HIV-1 pathogenesis and suggest interference with the Vif-Cullin 5 pathway as a possible anti-HIV-1 therapeutic strategy

Comparison of the cobas 4800 CT/NG test with culture for detecting neisseria gonorrhoeae in genital and nongenital specimens in a low-prevalence population in New Zealand

To assess the clinical utility of replacing microbial culture for Neisseria gonorrhoeae with a nucleic acid amplification test (NAAT), we compared N. gonorrhoeae culture with the cobas 4800 CT/NG test for 18,247 urogenital and 666 nongenital samples. For urogenital specimens, the sensitivity, specificity, and positive and negative predictive values of the cobas N. gonorrhoeae PCR were 98.7%, 100%, 95.6%, and 100%, respectively, and for nongenital specimens, the values were 100%, 99.8%, 92.9%, and 100%, respectively. In our test population, 37% (10,185) of patients tested over the study period were screened for C. trachomatis by PCR but were not screened for gonorrhea by culture. Of these, 43 were N. gonorrhoeae positive by PCR and therefore went undiagnosed. The cobas 4800 CT/NG test diagnosed 33% (n=30) more urogenital and 25% (n=3) more rectal gonorrhea infections than culture and, based on the above performance indicators, does not require supplementary testing for urogenital or rectal specimens. The ability to test noninvasive specimens (such as urine and self-taken vulvovaginal swabs) for N. gonorrhoeae will enable more patients to be screened for infection, thus offering significant positive public health benefits. Copyrigh

A theory-based approach to understanding condom errors and problems reported by men attending an STI clinic

The official published version can be accessed from the link below - Copyright @ 2008 Springer VerlagWe employed the information–motivation–behavioral skills (IMB) model to guide an investigation of correlates for correct condom use among 278 adult (18–35 years old) male clients attending a sexually transmitted infection (STI) clinic. An anonymous questionnaire aided by a CD-recording of the questions was administered. Linear Structural Relations Program was used to conduct path analyses of the hypothesized IMB model. Parameter estimates showed that while information did not directly affect behavioral skills, it did have a direct (negative) effect on condom use errors. Motivation had a significant direct (positive) effect on behavioral skills and a significant indirect (positive) effect on condom use errors through behavioral skills. Behavioral skills had a direct (negative) effect on condom use errors. Among men attending a public STI clinic, these findings suggest brief, clinic-based, safer sex programs for men who have sex with women should incorporate activities to convey correct condom use information, instill motivation to use condoms correctly, and directly enhance men’s behavioral skills for correct use of condoms

Percepção de autoeficácia, assertividade sexual e uso do preservativo em jovens colombianos

El uso correcto y consistente del condón en las relaciones sexuales es un procedimiento altamente eficaz para la prevención del VIH/SIDA, así como para otras infecciones de transmisión sexual (ITS). Algunos estudios reportan que las habilidades psicosociales y de interrelación favorecen el desarrollo de prácticas sexuales protegidas, como con el uso de preservativos. El objetivo del presente estudio fue determinar en qué medida la percepción de autoeficacia y la asertividad sexual predicen el uso del condón en las relaciones sexuales en un grupo de jóvenes. Se realizó un estudio descriptivo correlacional y predictivo con una muestra de 631 jóvenes con edades entre 19 y 26 años que reportaron haber tenido relaciones o ser activos sexualmente. Los resultados muestran que la percepción de autoeficacia y la asertividad sexual fueron fuertes predictores del uso del condón en las relaciones sexuales de las mujeres, mientras que para el caso de los hombres, solo la asertividad sexual predijo su uso.O uso correto e consistente do preservativo nas relações sexuais é um procedimento altamente eficaz para a prevenção do HIV/ Aids, bem como para outras infecções de transmissão sexual (ITS). Alguns estudos mostram que as habilidades psicossociais e de inter-relação favorecem o desenvolvimento de práticas sexuais protegidas, como com o uso do preservativo. O objetivo do presente estudo foi determinar em que medida a percepção de autoeficácia e a assertividade sexual predizem o uso do preservativo nas relações sexuais em um grupo de jovens. Realizou-se um estudo descritivo correlacional e preditivo com uma amostra de 631 jovens com idades entre 19 e 26 anos que relataram ter tido relações ou ser ativos sexualmente. Os resultados mostram que a percepção de autoeficácia e a assertividade sexual foram fortes indicadores do uso do preservativo nas relações sexuais das mulheres, enquanto para o caso dos homens, só a assertividade sexual predisse seu uso.The correct and consistent use of condoms during sexual intercourse is a highly effective procedure for the prevention of HIV / AIDS as well as other sexually transmitted infections (STIs). Some studies report that psychosocial skills and interaction promote the development of safe sexual relations by using condoms. The objective of this study was to determine to what extent the perception of self-efficacy and sexual assertiveness predicts condom use in sexual activity in a group of young people. The study was descriptive correlational and predictive.The sample consisted of 645 young people aged between 19 and 26 years who reported having had sex or being sexually active. Results showed that, unlike men, the perception of selfefficacy coupled with sexual assertiveness are strong predictors of condom use in women's sexual relations, whereas for men only sexual assertiveness predicts condom use in sexual relations

Correlates of psychological distress and major depressive disorder among African American men

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/88155/1/lincoln_taylor_watkins_chatters2011.pd

Arctic passages: liminality, Iñupiat Eskimo mothers and NW Alaska communities in transition

Background. While the primary goal of the NW Alaska Native maternal transport is safe deliveries for mothers from remote villages, little has been done to question the impact of transport on the mothers and communities involved. This study explores how presence of Iñupiat values influences the desire of indigenous women of differing eras and NW Alaska villages to participate in biomedical birth, largely made available by a tribal health-sponsored transport system. Objective. This paper portrays how important it is (and why) for Alaska Native families and women of different generations from various areas of Iñupiat villages of NW Alaska to get to the hospital to give birth. This research asks: How does a community’s presence of Iñupiat values influence women of different eras and locations to participate in a more biomedical mode of birth? Design. Theoretical frameworks of medical anthropology and maternal identity work are used to track the differences in regard to the maternal transport operation for Iñupiat mothers of the area. Presence of Iñupiat values in each of the communities is compared by birth era and location for each village. Content analysis is conducted to determine common themes in an inductive, recursive fashion. Results. A connection is shown between a community’s manifestation of Iñupiat cultural expression and mothers’ acceptance of maternal transport in this study. For this group of Iñupiat Eskimo mothers, there is interplay between community expression of Iñupiat values and desire and lengths gone to by women of different eras and locations. Conclusions. The more openly manifested the Iñupiat values of the community, the more likely alternative birthing practices sought, lessening the reliance on the existing transport policy. Conversely, the more openly western values are manifested in the village of origin, the less likely alternative measures are sought. For this study group, mothers from study villages with openly manifested western values are more likely to easily acquiesce to policy, and “make the best” of their prenatal travel

Socially-marketed rapid diagnostic tests and ACT in the private sector: ten years of experience in Cambodia.

Whilst some populations have recently experienced dramatic declines in malaria, the majority of those most at risk of Plasmodium falciparum malaria still lack access to effective treatment with artemisinin combination therapy (ACT) and others are already facing parasites resistant to artemisinins.In this context, there is a crucial need to improve both access to and targeting of ACT through greater availability of good quality ACT and parasitological diagnosis. This is an issue of increasing urgency notably in the private commercial sector, which, in many countries, plays an important role in the provision of malaria treatment. The Affordable Medicines Facility for malaria (AMFm) is a recent initiative that aims to increase the provision of affordable ACT in public, private and NGO sectors through a manufacturer-level subsidy. However, to date, there is little documented experience in the programmatic implementation of subsidized ACT in the private sector. Cambodia is in the unique position of having more than 10 years of experience not only in implementing subsidized ACT, but also rapid diagnostic tests (RDT) as part of a nationwide social marketing programme. The programme includes behaviour change communication and the training of private providers as well as the sale and distribution of Malarine, the recommended ACT, and Malacheck, the RDT. This paper describes and evaluates this experience by drawing on the results of household and provider surveys conducted since the start of the programme. The available evidence suggests that providers' and consumers' awareness of Malarine increased rapidly, but that of Malacheck much less so. In addition, improvements in ACT and RDT availability and uptake were relatively slow, particularly in more remote areas.The lack of standardization in the survey methods and the gaps in the data highlight the importance of establishing a clear system for monitoring and evaluation for similar initiatives. Despite these limitations, a number of important lessons can still be learnt. These include the importance of a comprehensive communications strategy and of a sustained and reliable supply of products, with attention to the geographical reach of both. Other important challenges relate to the difficulty in incentivising providers and consumers not only to choose the recommended drug, but to precede this with a confirmatory blood test and ensure that providers adhere to the test results and patients to the treatment regime. In Cambodia, this is particularly complicated due to problems inherent to the drug itself and the emergence of artemisinin resistance

The evolution of transmission mode

This article reviews research on the evolutionary mechanisms leading to different transmission modes. Such modes are often under genetic control of the host or the pathogen, and often in conflict with each other via trade-offs. Transmission modes may vary among pathogen strains and among host populations. Evolutionary changes in transmission mode have been inferred through experimental and phylogenetic studies, including changes in transmission associated with host-shifts and with evolution of the unusually complex life cycles of many parasites. Understanding the forces that determine the evolution of particular transmission modes presents a fascinating medley of problems for which there is a lack of good data and often a lack of conceptual understanding or appropriate methodologies. Our best information comes from studies that have been focused on the vertical vs. horizontal transmission dichotomy. With other kinds of transitions, theoretical approaches combining epidemiology and population genetics are providing guidelines for determining when and how rapidly new transmission modes may evolve, but these are still in need of empirical investigation and application to particular cases. Obtaining such knowledge is a matter of urgency in relation to extant disease threats

Developing core elements and checklist items for global hospital antimicrobial stewardship programmes:a consensus approach

International audienc

Design, implementation and evaluation of a national campaign to distribute nine million free LLINs to children under five years of age in Tanzania.

BACKGROUND\ud \ud After a national voucher scheme in 2004 provided pregnant women and infants with highly subsidized insecticide-treated nets (ITNs), use among children under five years (U5s) in mainland Tanzania increased from 16% in 2004 to 26.2% in 2007. In 2008, the Ministry of Health and Social Welfare planned a catch-up campaign to rapidly and equitably deliver a free long-lasting insecticidal net (LLIN) to every child under five years in Tanzania.\ud \ud METHODS\ud \ud The ITN Cell, a unit within the National Malaria Control Programme (NMCP), coordinated the campaign on behalf of the Ministry of Health and Social Welfare. Government contractors trained and facilitated local government officials to supervise village-level volunteers on a registration of all U5s and the distribution and issuing of LLINs. The registration results formed the basis for the LLIN order and delivery to village level. Caregivers brought their registration coupons to village issuing posts during a three-day period where they received LLINs for their U5s. Household surveys in five districts assessed ITN ownership and use immediately after the campaign.\ud \ud RESULTS\ud \ud Nine donors contributed to the national campaign that purchased and distributed 9.0 million LLINs at an average cost of $7.07 per LLIN, including all campaign-associated activities. The campaign covered all eight zones of mainland Tanzania, the first region being covered separately during an integrated measles immunization/malaria LLIN distribution in August 2008, and was implemented one zone at a time from March 2009 until May 2010. ITN ownership at household level increased from Tanzania's 2008 national average of 45.7% to 63.4%, with significant regional variations. ITN use among U5s increased from 28.8% to 64.1%, a 2.2-fold increase, with increases ranging from 22.1-38.3% percentage points in different regions.\ud \ud CONCLUSION\ud \ud A national-level LLIN distribution strategy that fully engaged local government authorities helped avoid additional burden on the healthcare system. Distribution costs per net were comparable to other public health interventions. Particularly among rural residents, ITN ownership and use increased significantly for the intended beneficiaries. The upcoming universal LLIN distribution and further behaviour change communication will further improve ITN ownership and use in 2010-2011