Sox2 Controls Periderm and Rugae Development to Inhibit Oral Adhesions.

In humans, ankyloglossia and cleft palate are common congenital craniofacial anomalies, and these are regulated by a complex gene regulatory network. Understanding the genetic underpinnings of ankyloglossia and cleft palate will be an important step toward rational treatment of these complex anomalies. We inactivated the Sry (sex-determining region Y)-box 2 (Sox2) gene in the developing oral epithelium, including the periderm, a transient structure that prevents abnormal oral adhesions during development. This resulted in ankyloglossia and cleft palate with 100% penetrance in embryos examined after embryonic day 14.5. In Sox2 conditional knockout embryos, the oral epithelium failed to differentiate, as demonstrated by the lack of keratin 6, a marker of the periderm. Further examination revealed that the adhesion of the tongue and mandible expressed the epithelial markers E-Cad and P63. The expanded epithelia are Sox9-, Pitx2-, and Tbx1-positive cells, which are markers of the dental epithelium; thus, the dental epithelium contributes to the development of oral adhesions. Furthermore, we found that Sox2 is required for palatal shelf extension, as well as for the formation of palatal rugae, which are signaling centers that regulate palatogenesis. In conclusion, the deletion of Sox2 in oral epithelium disrupts palatal shelf extension, palatal rugae formation, tooth development, and periderm formation. The periderm is required to inhibit oral adhesions and ankyloglossia, which is regulated by Sox2. In addition, oral adhesions occur through an expanded dental epithelial layer that inhibits epithelial invagination and incisor development. This process may contribute to dental anomalies due to ankyloglossia.

Age-Related Differences in Socio-demographic and Behavioral Determinants of HIV Testing and Counseling in HPTN 043/NIMH Project Accept.

Youth represent a large proportion of new HIV infections worldwide, yet their utilization of HIV testing and counseling (HTC) remains low. Using the post-intervention, cross-sectional, population-based household survey done in 2011 as part of HPTN 043/NIMH Project Accept, a cluster-randomized trial of community mobilization and mobile HTC in South Africa (Soweto and KwaZulu Natal), Zimbabwe, Tanzania and Thailand, we evaluated age-related differences among socio-demographic and behavioral determinants of HTC in study participants by study arm, site, and gender. A multivariate logistic regression model was developed using complete individual data from 13,755 participants with recent HIV testing (prior 12 months) as the outcome. Youth (18-24 years) was not predictive of recent HTC, except for high-risk youth with multiple concurrent partners, who were less likely (aOR 0.75; 95% CI 0.61-0.92) to have recently been tested than youth reporting a single partner. Importantly, the intervention was successful in reaching men with site specific success ranging from aOR 1.27 (95% CI 1.05-1.53) in South Africa to aOR 2.30 in Thailand (95% CI 1.85-2.84). Finally, across a diverse range of settings, higher education (aOR 1.67; 95% CI 1.42, 1.96), higher socio-economic status (aOR 1.21; 95% CI 1.08-1.36), and marriage (aOR 1.55; 95% CI 1.37-1.75) were all predictive of recent HTC, which did not significantly vary across study arm, site, gender or age category (18-24 vs. 25-32 years).

Discussing childbearing with HIV-infected women of reproductive age in clinical care: a comparison of Brazil and the US.

Despite long term access to highly active antiretroviral therapy in Brazil and the US, little is known about women's communication with their HIV provider regarding childbearing or the unmet need for reproductive counseling. We utilized identical survey questions to collect data from HIV-infected women of reproductive age in Rio de Janeiro (n = 180) and Baltimore (n = 181). We conducted univariate analyses to compare findings between samples of women and multivariate logistic regression to determine factors associated with childbearing desires, childbearing intentions, and provider communication among the combined sample of women (n = 361). Over one-third of women in Rio de Janeiro and nearly one-half of women in Baltimore reported the desire for future childbearing. Nevertheless, the majority of women in clinical care had not discussed future childbearing with their HIV provider. Even in countries with an advanced approach to HIV care, we found low and inadequate communication between providers and female patients about childbearing.

Developing WHO guidelines with pragmatic, structured, evidence-based processes: A case study.

Many guidelines, including those produced by the World Health Organisation (WHO), have failed to adhere to rigorous methodological standards. Operational examples of guideline development processes may provide important lessons learned to improve the rigour and quality of future guidelines. To this end, this paper describes the process of developing WHO guidelines on prevention and care interventions for adults and adolescents living with HIV. Using a pragmatic, structured, evidence-based approach, we created an organising committee, identified topics, conducted systematic reviews, identified experts and distributed evidence summaries. Subsequently, 55 global HIV experts drafted and anonymously submitted guideline statements at the beginning of a conference. During the conference, participants voted on statements using scales evaluating appropriateness of the statements, strength of recommendation and level of evidence. After review of voting results, open discussion, re-voting and refinement of statements, a draft version of the guidelines was completed. A post-conference writing team refined the guidelines based on pre-determined guideline writing principles and incorporated external comments into a final document. Successes and challenges of the guideline development process were identified and are used to highlight current issues and debates in developing guidelines with a focus on implications for future guideline development at WHO.

The HIV testing experiences of adolescents in Ndola, Zambia: do families and friends matter?

This study explored how adolescents involve their families, friends and sex partners when making decisions about seeking HIV voluntary counseling and testing (VCT) and disclosing their HIV-status. The study is based on 40 qualitative in-depth interviews with 16 to 19 year olds who knew their HIV status in Ndola, Zambia. The findings show that: a) almost half of the youth turned to family members for advice or approval prior to seeking VCT; b) a disapproving reaction from family members or friends often discouraged youth from attending VCTuntil they found someone supportive; c) informants often attended VCTalone or with a friend, but rarely with a family member; and d) disclosure was common to family and friends, infrequent to sex partners, and not linked to accessing care and support services. Family members need access to information on VCT so they can support young peoples' decisions to test for HIV and to disclose their HIV status. These results reinforce the need to provide confidential VCT services for adolescents and the need to develop and test innovative strategies to reach adolescents, their families and sex partners with VCT information and services.

The impact of HIV treatment on risk behaviour in developing countries: a systematic review.

In developing countries, access to antiretroviral therapy (ART) is improving as HIV treatment becomes a greater priority in the global fight against AIDS. While ART has clearly beneficial clinical effects, increased access to treatment may also affect sexual behaviour. To examine the strength of evidence for the impact of medical treatment for HIV-positive individuals on behavioural outcomes in developing countries, we conducted a comprehensive search of the peer-reviewed literature. Studies were included if they provided clinical treatment to HIV-positive individuals in a developing country, compared behavioural, psychological, social, care, or biological outcomes related to HIV-prevention using a pre/post or multi-arm study design, and were published between January 1990 and January 2006. Only three studies were identified that met the inclusion criteria. All were conducted in Africa, utilized before/after or multi-arm study designs, and relied on self-reported behaviour. In all three studies, a majority of HIV-infected individuals reported being sexually abstinent, and access to ART was not associated with an increase in HIV-related risky sexual behaviours. However, one cross-sectional study found that ART patients were more likely to report STD treatment. The available evidence indicates a significant reduction in risk behaviour associated with ART in developing countries. However, there are few existing studies and the rigor of these studies is weak. More studies are needed to build an evidence base on which to make programmatic and policy decisions.

Women's barriers to HIV-1 testing and disclosure: challenges for HIV-1 voluntary counselling and testing.

In view of the ever-increasing HIV/AIDS epidemic in sub-Saharan Africa, the expansion of HIV-1 voluntary counselling and testing (VCT) as an integral part of prevention strategies and medical research is both a reality and an urgent need. As the availability of HIV-1 VCT grows two limitations need to be addressed, namely: low rates of HIV-1 serostatus disclosure to sexual partners and negative outcomes of serostatus disclosure. Results from a study among men, women and couples at an HIV-1 VCT clinic in Dar es Salaam, Tanzania are presented. The individual, relational and environmental factors that influence the decision to test for HIV-1 and to share test results with partners are described. The most salient barriers to HIV-1 testing and serostatus disclosure described by women include fear of partners' reaction, decision-making and communication patterns between partners, and partners' attitudes towards HIV-1 testing. Perception of personal risk for HIV-1 is the major factor driving women to overcome barriers to HIV-1 testing. The implications of findings for the promotion of HIV-1 VCT programmes, the implementation of partner notification policies and the development of post-test support services are discussed.

Cost-effectiveness of a brief video-based HIV intervention for African American and Latino sexually transmitted disease clinic clients.

BACKGROUND AND OBJECTIVES: Decisions about the dissemination of HIV interventions need to be informed by evidence of their cost-effectiveness in reducing negative health outcomes. Having previously shown the effectiveness of a single-session video-based group intervention (VOICES/VOCES) in reducing incidence of sexually transmitted diseases (STD) among male African American and Latino clients attending an urban STD clinic, this study estimates its cost-effectiveness in terms of disease averted. METHODS: Cost-effectiveness was calculated using data on effectiveness from a randomized clinical trial of the VOICES/VOCES intervention along with updated data on the costs of intervention from four replication sites. STD incidence and self-reported behavioral data were used to make estimates of reduction in HIV incidence among study participants. RESULTS: The average annual cost to provide the intervention to 10 000 STD clinic clients was estimated to be US$447 005, with a cost per client of US$43.30. This expenditure would result in an average of 27.69 HIV infections averted, with an average savings from averted medical costs of US$5 544 408. The number of quality adjusted life years saved averaged 387.61, with a cost per HIV infection averted of US$21 486. CONCLUSIONS: This brief behavioral intervention was found to be feasible and cost-saving when targeted to male STD clinic clients at high risk of contracting and transmitting infections, indicating that this strategy should be considered for inclusion in HIV prevention programming.

Vietnam nursing: the experience lives on. Interview by Margaret Ann La Salle.

Through personal interviews and a review of the literature, this article examines the experiences of three nurses who served in the Vietnam conflict. Common themes emerging were the strength of the medical teams, the camaraderie, and the willingness of everyone to pitch in. Common coping strategies were turning to God for comfort and emotional support through peers.

Cost-effectiveness of voluntary HIV-1 counselling and testing in reducing sexual transmission of HIV-1 in Kenya and Tanzania.

BACKGROUND: Access to HIV-1 voluntary counselling and testing (VCT) is severely limited in less-developed countries. We undertook a multisite trial of HIV-1 VCT to assess its impact, cost, and cost-effectiveness in less-developed country settings. METHODS: The cost-effectiveness of HIV-1 VCT was estimated for a hypothetical cohort of 10000 people seeking VCT in urban east Africa. Outcomes were modelled based on results from a randomised controlled trial of HIV-1 VCT in Tanzania and Kenya. Our main outcome measures included programme cost, number of HIV-1 infections averted, cost per HIV-1 infection averted, and cost per disability-adjusted life-year (DALY) saved. We also modelled the impact of targeting VCT by HIV-1 prevalence of the client population, and the proportion of clients who receive VCT as a couple compared with as individuals. Sensitivity analysis was done on all model parameters. FINDINGS: HIV-1 VCT was estimated to avert 1104 HIV-1 infections in Kenya and 895 in Tanzania during the subsequent year. The cost per HIV-1 infection averted was US$249 and $346, respectively, and the cost per DALY saved was $12.77 and $17.78. The intervention was most cost-effective for HIV-1-infected people and those who received VCT as a couple. The cost-effectiveness of VCT was robust, with a range for the average cost per DALY saved of $5.16-27.36 in Kenya, and $6.58-45.03 in Tanzania. Analysis of targeting showed that increasing the proportion of couples to 70% reduces the cost per DALY saved to $10.71 in Kenya and $13.39 in Tanzania, and that targeting a population with HIV-1 prevalence of 45% decreased the cost per DALY saved to $8.36 in Kenya and $11.74 in Tanzania. INTERPRETATION: HIV-1 VCT is highly cost-effective in urban east African settings, but slightly less so than interventions such as improvement of sexually transmitted disease services and universal provision of nevirapine to pregnant women in high-prevalence settings. With the targeting of VCT to populations with high HIV-1 prevalence and couples the cost-effectiveness of VCT is improved significantly.

The intersections of HIV and violence: directions for future research and interventions.

The purpose of this paper is to review the available literature on the intersections between HIV and violence and present an agenda for future research to guide policy and programs. This paper aims to answer four questions: (1) How does forced sex affect women's risk for HIV infection? (2) How do violence and threats of violence affect women's ability to negotiate condom use? (3) Is the risk of violence greater for women living with HIV infection than for noninfected women? (4) What are the implications of the existing evidence for the direction of future research and interventions? Together this collection of 29 studies from the US and from sub-Saharan Africa provides evidence for several different links between the epidemics of HIV and violence. However, there are a number of methodological limitations that can be overcome with future studies. First, additional prospective studies are needed to describe the ways which violence victimization may increase women's risk for HIV and how being HIV positive affects violence risk. Future studies need to describe men's perspective on both HIV risk and violence in order to develop effective interventions targeting men and women. The definitions and tools for measurement of concepts such as physical violence, forced sex, HIV risk, and serostatus disclosure need to be harmonized in the future. Finally, combining qualitative and quantitative research methods will help to describe the context and scope of the problem. The service implications of these studies are significant. HIV counseling and testing programs offer a unique opportunity to identify and assist women at risk for violence and to identify women who may be at high risk for HIV as a result of their history of assault. In addition, violence prevention programs, in settings where such programs exist, also offer opportunities to counsel women about their risks for sexually transmitted diseases and HIV.

Foundations for effective strategies to control sexually transmitted infections: voices from rural Kenya.

Achieving maximal benefit from clinic-based, sexually transmitted infection (STI) control strategies requires that persons seek treatment at public clinics. Community-based, ethnographic research methods were used to examine patterns of health-seeking behavior for sexually transmitted infections in western Kenya. Illness narratives of sexually transmitted infections provided the basis for an analysis of sequential steps in health-seeking behavior, namely recognition, classification, overcoming stigma, identification of treatment options and selection of a course of therapy. A variety of terms were used to identify STI, including multiple terms referring to "women's disease". The stigma associated with STI, reflected in the terminology, was based on a set of beliefs on the causes, contagiousness and sequelae of STI, and resulted in delays in seeking treatment. Five commonly used treatment options were identified, with multiple sources of care often used concurrently. The desire for privacy, cost and belief in the efficacy of traditional medicines strongly influenced health-seeking behaviour. A belief that sexually transmitted infections must be transmitted in order to achieve cure was professed by several respondents and promoted by a traditional healer. Implications for STI control strategies are derived, including the development of educational messages and the design of clinics.

PIP: Data on health-seeking behavior were collected in Vihiga and Homa Bay Districts of western Kenya, as part of formative research for a sexually transmitted disease (STD) control and HIV/AIDS home care project with the main goal of securing information to guide project design and implementation. Community-based, ethnographic research methods were used from January 1995 to June 1996, including key informant interviews, focus group discussions, and in-depth interviews. Illness narratives of STDs provided the basis for an analysis of sequential steps in health-seeking behavior, namely recognizing, classifying, overcoming stigma, identifying treatment options, and selecting a course of therapy. A range of terms were used to identify STDs, including multiple terms referring to "women's disease." Stigma associated with STDs was based upon a set of beliefs of the causes, contagiousness, and sequelae of STDs, and resulted in treatment seeking delays. 5 commonly used treatment options were identified, with multiple sources of care often used concurrently. The desire for privacy, cost, and belief in the efficacy of traditional medicines strongly influenced health-seeking behavior. The belief that STDs must be transmitted in order to achieve cure was held by several respondents and promoted by a traditional healer. Implications for STD control strategies are considered, including the development of educational messages and clinic design.

HIV-1 subtype E incidence and sexually transmitted diseases in a cohort of military conscripts in northern Thailand.

OBJECTIVES: To determine the rate of and risk factors for HIV-1 seroconversion and describe sexually transmitted disease (STD) prevalence rates for young men in northern Thailand. METHODS: Data were collected from self-administered questionnaires and serologic testing at enrollment in a prospective study in 1991 and at follow-up after 6, 17, and 23 months on a cohort of 1115 men selected by lottery for military conscription. RESULTS: A total of 14 men seroconverted to HIV-1 envelope subtype E. The overall HIV-1 incidence rate was 1.1 (95% confidence interval [CI], 0.6-1.8) per 100 person-years (PY) of follow-up. However, the rate was 2.0/100 PY for conscripts from the upper northern subregion of Thailand compared with 0.5/100 PY from other regions (adjusted rate ratio [RR] = 2.69; 95% CI, 0.8-12.2). On multivariate analyses, the behavioral factors associated with HIV-1 seroconversion were frequency of sex with female sex workers (FSWs; p = .04), receptive anal sex (adjusted RR = 6.73; 95% CI, 1.8-21.7), and large amount of alcohol consumption (adjusted RR = 3.12; 95% CI, 1.0-10.9). Genital ulceration was the STD most strongly associated with seroconversion. The prevalence of serologic reactivity to syphilis, Haemophilus ducreyi, and herpes simplex virus type 2 increased with greater frequency of sex with FSWs and was generally higher for men from the upper north. CONCLUSION: Young men in northern Thailand are at high risk for HIV-1, primarily through sex with FSWs; and other STDs are highly associated with HIV-1 incidence. As HIV-1 infection extends into the general population, intervention programs are needed to address the problem of sexual transmission apart from commercial sex venues.

PIP: Findings are presented from a prospective study conducted to determine the rate of and risk factors for HIV-1 seroconversion, and to describe sexually transmitted diseases (STD) prevalence rates for young men in northern Thailand. Study findings are based upon data collected from self-administered questionnaires and serologic testing at enrollment in 1991 and at follow-up after 6, 17, and 23 months on a cohort of 1115 young men chosen by lottery for military conscription. Men in Thailand are generally eligible for conscription in the year of their 21st birthday. 6.9% of the men were HIV-1 seropositive at enrollment; 15.3% of men from the upper northern region compared with 2.5% of men from elsewhere. 14 subjects seroconverted to HIV-1 envelope subtype E over the course of the study. The overall HIV-1 incidence rate was 1.1/100 person-years (PY) of follow-up. However, the rate was 2.0/100 PY for conscripts from the upper northern subregion of Thailand compared with 0.5/100 PY from other regions. Multivariate analyses found frequent sex with female prostitutes, receptive anal sex, and high levels of alcohol consumption to be positively associated with HIV-1 seroconversion. Genital ulceration was the STD most strongly associated with seroconversion. The prevalence of serologic reactivity to syphilis, Haemophilus ducreyi, and herpes simplex virus type 2 increased with greater frequency of sex with female prostitutes, and was generally higher for men from the upper north.

Alcohol consumption, brothel attendance, and condom use: normative expectations among Thai military conscripts.

This article investigates the relationship between alcohol consumption and inconsistent condom use with brothel-based commercial sex workers among Thai military conscripts in Northern Thailand. Data from 10 focus groups indicate that alcohol consumption (1) is consciously used by men to reduce inhibitions that constrain their interpersonal interaction with women and with each other; (2) reduces inhibitions of individuals to sexual risk taking; (3) provides a socially acceptable excuse for nonuse of condoms; (4) is associated by conscripts with brothel attendance; and (5) is seen to enhance male sexual pleasure, in contrast to condoms, which are said to reduce pleasure. Understanding the culturally defined expectations that surround alcohol consumption and sexual behavior is critical for developing realistic interventions to reduce HIV transmission.

Depression and use of mental health services among HIV-infected men.

Depression is a serious, common, and treatable condition among HIV-infected persons. We examined the prevalence and predictors of depression and use of mental health services among 475 HIV-infected men without AIDS. Participants were drawn from three sites in San Francisco and Denver that did not provide ongoing medical care or mental health services. Depression was measured using the Center for Epidemiology Studies Depression scale (CES-D). Overall, 176 men (37.1%) were classified as depressed based on having a CES-D score above the standard cut-off of > or = 16. In logistic regression analysis, persons with HIV-related symptoms (OR = 3.4; 95% CI = 2.0.-5.6), low social support (OR = 2.5; 95% CI = 1.6-3.9), who were unemployed (OR = 1.9; 95% CI = 1.1-3.3), and with CD4 count < 200 cells (OR = 1.9; 95% CI = 1.1-3.3), were significantly more likely to be depressed. Only 40.3% of depressed men had seen a mental health clinician in the previous year and only 6.3% were taking an antidepressant. Among depressed men, in logistic regression analysis, men who were unemployed (OR = 2.4; 95% CI = 1.2-4.7) and those with health insurance (OR = 2.2; 95% CI = 1.1-4.5) were more likely to have received these services. Increased evaluation and treatment of HIV-infected persons for depression is needed.

HIV/AIDS knowledge among the U.S. population.

This analysis examines knowledge of HIV and AIDS among 71,370 persons interviewed in a national sample of the U.S. population. Factor analysis of 26 questions about HIV infection and AIDS identified four distinct dimensions of AIDS knowledge: 1) transmission mechanisms; 2) commonly known nontechnical information; 3) definitions of AIDS; and 4) technical information. Significant differences across racial, ethnic, socioeconomic, and demographic groups exist for each dimension of AIDS knowledge. In general, racial minorities and those with lower socioeconomic status are shown to have lower knowledge levels. Exposure to mass media about AIDS, and knowing a person with HIV or AIDS, are also strong predictors of increased knowledge. Multivariate analysis demonstrates 1) that socioeconomic status is a better predictor of knowledge of AIDS than race or ethnicity; and 2) exposure to AIDS mass media has the strongest effect on all dimensions of AIDS knowledge except for knowledge of technical issues about AIDS. Policy implications of these results are discussed.

AIDS awareness among a cohort of young Thai men: exposure to information, level of knowledge, and perception of risk.

Structured interviews and focus group discussions were conducted among 834 young Thai men drafted into military service by random lottery in northern Thailand. Level of AIDS risk, exposure to AIDS information, level of knowledge about AIDS, and perception of risk for acquiring HIV and AIDS were assessed at baseline and six months after induction into the Army in 1991. General fear of AIDS was high, yet personal perception of risk for acquiring HIV was low, even for those at enhanced behavioural risk of infection with HIV. Multivariate PATH analysis shows that exposure to information about AIDS significantly reduced risk taking from baseline to follow-up, but only by first affecting personal risk perception. Focus group discussions revealed that risk perception for acquiring AIDS was low due to never knowing a person with AIDS, because prostitutes had health certificates for STD, and since many believed that AIDS could be cured or prevented with folk medicines. Implications and recommendations for intervention programmes are discussed.