Neurobiology of depression

Current treatments for depression are inadequate for many individuals, and progress in understanding the neurobiology of depression is slow. Several promising hypotheses of depression and antidepressant action have been formulated recently. These hypotheses are based largely on dysregulation of the hypothalamic-pituitary-adrenal axis and hippocampus and implicate corticotropin-releasing factor, glucocorticoids, brain-derived neurotrophic factor, and CREB. Recent work has looked beyond hippocampus to other brain areas that are also likely involved. For example, nucleus accumbens, amygdala, and certain hypothalamic nuclei are critical in regulating motivation, eating, sleeping, energy level, circadian rhythm, and responses to rewarding and aversive stimuli, which are all abnormal in depressed patients. A neurobiologic understanding of depression also requires identification of the genes that make individuals vulnerable or resistant to the syndrome. These advances will fundamentally improve the treatment and prevention of depression.     

Identifying Programmatic Gaps: Inequities in Harm Reduction Service Utilization among Male and Female Drug Users in Dar es Salaam,Tanzania

Introduction

Current estimates suggest an HIV prevalence of 42% among people who inject drugs (PWIDs) in Dar es Salaam, while HIV prevalence is estimated to be 8.8% among the general population in the city. To address the HIV epidemic in this population, the government of Tanzania began establishing HIV prevention, treatment and care services including outreach and medication assisted treatment (MAT) for PWIDs in 2010. We assessed gender inequities in utilization of outreach and MAT services and evaluated differences in HIV risk behaviors between female and male PWIDs.

Materials and Methods

Routine outreach data between December 2010 to mid-August 2012 and baseline data on clients enrolling in methadone from February 2011 to August 2012 were utilized. Binomial regression was used to estimate adjusted relative risk estimates comparing females to males.

Results

From December 2010 to August 2012, 8,578 contacts were made to drug users; among them 1,898 were injectors. A total of 453 injectors were eligible and referred to MAT, of which, 443 enrolled in treatment. However, regarding total outreach contacts, outreach to PWID, referral to MAT and enrollment in MAT, 8% or less of drug users accessing services were women. In contrast, weighted estimations from surveys suggest that 34% of PWIDs are female, and this approximation is similar to recent population size estimations. Overall, 43% of traditional outreach workers conducting outreach with drug users were female. Though reporting higher levels of condom usage, female PWID were more likely to report multiple sex partners, anal sex, commercial sex work and struggle under a higher burden of addiction, mental disorders and abuse.

Conclusions

Services have not been mobilized adequately to address the clear needs of females who inject drugs. A clear and urgent need exists for women-centered strategies that effectively engage female PWID into HIV prevention services.     

The SHAZ! Project: Results from a Pilot Randomized Trial of a Structural Intervention to Prevent HIV among Adolescent Women in Zimbabwe

Adolescent females in Zimbabwe are at high risk for HIV acquisition. Shaping the Health of Adolescents in Zimbabwe (SHAZ!) was a randomized controlled trial of a combined intervention package including life-skills and health education, vocational training, micro-grants and social supports compared to life-skills and health education alone. SHAZ! was originally envisioned as a larger effectiveness trial, however, the intervention was scaled back due to contextual and economic conditions in the country at the time. SHAZ! enrolled 315 participants randomly assigned to study arm within blocks of 50 participants (158 intervention and 157 control). The intervention arm participants showed statistically significant differences from the control arm participants for several outcomes during the two years of follow up including; reduced food insecurity [IOR = 0.83 vs. COR = 0.68, p-0.02], and having their own income [IOR = 2.05 vs. COR = 1.67, p = 0.02]. Additionally, within the Intervention arm there was a lower risk of transactional sex [IOR = 0.64, 95% CI (0.50, 0.83)], and a higher likelihood of using a condom with their current partner [IOR = 1.79, 95% CI (1.23, 2.62)] over time compared to baseline. There was also evidence of fewer unintended pregnancies among intervention participants [HR = 0.61, 95% CI (0.37, 1.01)], although this relationship achieved only marginal statistical significance. Several important challenges in this study included the coordination with vocational training programs, the political and economic instability of the area at the time of the study, and the difficulty in creating a true standard of care control arm. Overall the results of the SHAZ! study suggest important potential for HIV prevention intervention packages that include vocational training and micro-grants, and lessons for further economic livelihoods interventions with adolescent females. Further work is needed to refine the intervention model, and test the impact of the intervention at scale on biological outcomes.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02034214","term_id":"NCT02034214"}}NCT02034214     

A pre-operative planning for endoprosthetic human tracheal implantation: a decision support system based on robust design of experiments

Swallowing depends on physiological variables that have a decisive influence on the swallowing capacity and on the tracheal stress distribution. Prosthetic implantation modifies these values and the overall performance of the trachea. The objective of this work was to develop a decision support system based on experimental, numerical and statistical approaches, with clinical verification, to help the thoracic surgeon in deciding the position and appropriate dimensions of a Dumon prosthesis for a specific patient in an optimal time and with sufficient robustness. A code for mesh adaptation to any tracheal geometry was implemented and used to develop a robust experimental design, based on the Taguchi's method and the analysis of variance. This design was able to establish the main swallowing influencing factors. The equations to fit the stress and the vertical displacement distributions were obtained. The resulting fitted values were compared to those calculated directly by the finite element method (FEM). Finally, a checking and clinical validation of the statistical study were made, by studying two cases of real patients. The vertical displacements and principal stress distribution obtained for the specific tracheal model were in agreement with those calculated by FE simulations with a maximum absolute error of 1.2 mm and 0.17 MPa, respectively. It was concluded that the resulting decision support tool provides a fast, accurate and simple tool for the thoracic surgeon to predict the stress state of the trachea and the reduction in the ability to swallow after implantation. Thus, it will help them in taking decisions during pre-operative planning of tracheal interventions.