Publications

Advanced endoscopic resection techniques allow curative treatment of difficult colonic lesions and avoid the need for surgery in certain cases. If endoscopic resection is indicated, the choice of the most appropriate resection technique depends on lesion characteristics and endoscopist expertise.

INTRODUCTION

While the rate of vertically transmitted HIV infection has fallen in most regions of Brazil, there have been no similar decreases in northern and northeastern Brazil.

OBJECTIVE

The objective of this study was to evaluate the risk factors associated with vertical transmission in the state of Sergipe in northeastern Brazil.

METHODS

This was a retrospective cohort study. We recorded clinic and registry data for all HIV-infected pregnant women and exposed children diagnosed in Sergipe from 1990 to 2011.

RESULTS

We identified 538 deliveries and 561 HIV-exposed infants (23 sets of twins). One hundred one (18.9%) infants were HIV-infected. In the multivariate analysis, infant antiretroviral prophylaxis was a significant protective factor (adjusted odds ratio (aOR) 0.07, 95% confidence interval (CI) 0.01-0.41, p=0.003). Breastfeeding was marginally associated with an increased odds of perinatal transmission (aOR 4.52, 95% CI 0.78-26.17, p = 0.092). The attributable risk percentage for breastfeeding over the study period was 91.0%. Transmission decreased from 91 per 100 live births before 1997 to 2 per 100 in 2011 following the adoption of the prevention protocol.

CONCLUSION

Transmission declined over the study period. The screening of pregnant women and timely initiation of prophylaxis and therapy are issues that require further attention.

Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic expression of the metabolic syndrome, and its prevalence is increasing. The factors that influence the development of fatty liver and its progression to steatohepatitis and cirrhosis are not well understood. The pleiotropic hormone, GH, has been associated with an increased risk of NAFLD in humans and mice. GH is known to have diverse effects on lipid metabolism including decreasing body fat in vivo, presumably through stimulation of lipolysis via an undefined mechanism. Previously we described mice with hepatocyte-specific deletion of the GH signaling mediator, Janus kinase 2 (JAK2L). JAK2L animals have elevated serum GH, reduced body fat, high liver triglyceride content, and increased serum markers of hepatocyte injury (alanine transaminase and aspartate transaminase). We aimed to determine whether the elevation of GH in JAK2L mice contributed to fatty liver by promoting lipolysis directly in adipocytes. We generated mice with adipocyte-specific disruption of JAK2 (JAK2A) and found that GH resistance in adipocytes reduced lipolysis and increased body fat. JAK2A mice were then crossed to JAK2L mice, and the resultant JAK2L/A animals had increased body fat and decreased lipolysis, despite elevated circulating GH. Furthermore, the increased triglyceride content, serum alanine transaminase, and serum aspartate transaminase observed in JAK2L mice were nearly normalized with the additional disruption of JAK2 in adipocytes (JAK2L/A mice). Our results offer novel mechanistic insights into the long-recognized effects of GH on lipid flux and suggest that GH signaling may play an important regulatory role in the development of NAFLD.

Bas-Congo virus (BASV) is a novel rhabdovirus recently identified from a patient with acute hemorrhagic fever in the Bas-Congo province of the Democratic Republic of Congo (DRC). Here we show that the BASV glycoprotein (BASV-G) can be successfully used to pseudotype glycoprotein-deficient vesicular stomatitis virus (VSV), allowing studies of BASV-G-driven membrane fusion and viral entry into target cells without replication-competent virus. BASV-G displayed broad tissue and species tropism in vitro, and BASV-G-mediated membrane fusion was pH dependent. The conformational changes induced in BASV-G by acidification were fully reversible and did not lead to inactivation of the viral fusion protein. Our data combined with comparative sequence similarity analyses suggest that BASV-G shares structural and functional features with other rhabdovirus glycoproteins and falls into the group of class III viral fusion proteins. However, activation of BASV-G-driven fusion required a lower pH and higher temperatures than did VSV-G-mediated fusion. Moreover, in contrast to VSV-G, mature BASV-G in VSV pseudotypes consists of a mixture of high-mannose and complex glycans that enables it to bind to certain C-type lectins, thereby enhancing its attachment to target cells. Taken together, the results presented in this study will facilitate future investigations of BASV-G-mediated cell entry and its inhibition in the absence of an infectious cell culture assay for BASV and at lower biosafety levels. Moreover, serology testing based on BASV-G pseudotype neutralization can be used to uncover the prevalence and importance of BASV as a potential novel human pathogen in the DRC and throughout Central Africa.

A parallel-process latent growth curve model was used to model alcohol and marijuana use (vs. nonuse). Participation in team sports and gender were considered to be time-invariant covariates. The sample consisted of 8,179 youth from the National Survey of Parents and Youth. Data were collected over four yearly rounds. Analysis revealed that being part of a competitive sports team was related to a lower probability of marijuana initiation, but to increased rates of alcohol use over time. Males had significantly higher levels of marijuana initiation and decreases in rates of alcohol use over time; females had significantly greater rate of increase in alcohol use over time. Analysis suggests that youth involved in sports are less likely to use marijuana over time. This information may help to uncover other predictors of use over time and to inform policy making as well design as effective prevention.

Linkage to care is a critical corollary to expanded HIV testing, but many adolescents are not successfully linked to care, in part due to fragmented care systems. Through a collaboration of the National Institutes of Health (NIH), Centers for Disease Control and Prevention (CDC) and the Adolescent Trials Network (ATN), a linkage to care outreach worker was provided to ATN clinics. Factors related to linkage were explored to better understand how to improve retention rates and health outcomes for HIV-positive adolescents. We conducted 124 interviews with staff at 15 Adolescent Trials Network clinics to better understand linkage to care processes, barriers, and facilitators. Content analysis was conducted focusing on structural barriers to care and potential solutions, specifically at the macro-, meso-, and micro-levels. Macro-level barriers included navigating health insurance policies, transportation to appointments, and ease of collecting and sharing client-level contact information between testing agencies, local health departments and clinics; meso-level barriers included lack of youth friendliness within clinic space and staff, and duplication of linkage services; micro-level barriers included adolescents' readiness for care and adolescent developmental capacity. Staff initiated solutions included providing transportation for appointments and funding clinic visits and tests with a range of grants and clinic funds while waiting for insurance approval. However, such solutions were often ad hoc and partial, using micro-level solutions to address macro-level barriers. Comprehensive initiatives to improve linkage to care are needed to address barriers to HIV-care for adolescents, whose unique developmental needs make accessing care particularly challenging. Matching the level of structural solution to the level of structural barriers (i.e., macro-level with macro-level), such as creating policy to address needed youth healthcare entitlements versus covering uninsured patients with clinic funds is imperative to achieving the goal of increasing linkage to care rates for newly diagnosed adolescents.