Rate and Predictors of Ineffective HIV Protection in African Men Who Have Sex with Men Taking Pre-Exposure Prophylaxis

AIDS and Behavior - We investigated the rate and predictors of ineffective HIV protection in men who have sex with men (MSM) taking pre-exposure prophylaxis (PrEP) in a prospective cohort study...     

Medical students¿ choices of specialty in the Gambia: the need for career counseling

ABSTRACT: BACKGROUND: Understanding preferences for specialties by medical students and the factors driving choices assists policy makers in ensuring optimal spread of personnel across disciplines. METHODS: This cross-sectional survey using self-administered structured questionnaires was conducted on consenting students of the first medical school in The Gambia, established in 1999. Data collection was in June/July 2011. Questions were on sociodemographic characteristics of students, their parents, factors related to career preferences and opinions about counselling services. Data were analysed using JMP 8.0 software. RESULTS: Respondents were 52.4% of 202 eligible students. Mean age was 24.1+5.0 years. Females constituted 54.7%. Muslims were 72.7% while Gambians formed 77.0%. Commonest specialties chosen by females were Obstetrics/Gynaecology, Paediatrics and Surgery in that order, while males preferred Internal Medicine, Surgery and Obstetrics/Gynaecology. Commonest factors influencing choices by females were 'focus on urgent care' (65.5%) and 'intellectual content of specialty' (56.9%). For males, these were 'intellectual content of specialty' (60.4%) and 'focus on urgent care' / 'individual's competence' (50.0% each). More females (30.0%) than males (23.0%) had ever received career counselling, but all students desired it. CONCLUSIONS: Significant gender differences exist in specialty choices and factors influencing these choices amongst these students. All want career counselling. Key words: medical students, specialties, choices, careers.     

Mycobacterium tuberculosis dysregulates MMP/TIMP balance to drive rapid cavitation and unrestrained bacterial proliferation

Active tuberculosis (TB) often presents with advanced pulmonary disease, including irreversible lung damage and cavities. Cavitary pathology contributes to antibiotic failure, transmission, morbidity and mortality. Matrix metalloproteinases (MMPs), in particular MMP‐1, are implicated in TB pathogenesis. We explored the mechanisms relating MMP/TIMP imbalance to cavity formation in a modified rabbit model of cavitary TB. Our model resulted in consistent progression of consolidation to human‐like cavities (100% by day 28), with resultant bacillary burdens (>10⁷ CFU/g) far greater than those found in matched granulomatous tissue (10⁵ CFU/g). Using a novel, breath‐hold computed tomography (CT) scanning and image analysis protocol, we showed that cavities developed rapidly from areas of densely consolidated tissue. Radiological change correlated with a decrease in functional lung tissue, as estimated by changes in lung density during controlled pulmonary expansion (R² = 0.6356, p < 0.0001). We demonstrated that the expression of interstitial collagenase (MMP‐1) was specifically greater in cavitary compared to granulomatous lesions (p < 0.01), and that TIMP‐3 significantly decreased at the cavity surface. Our findings demonstrated that an MMP‐1/TIMP imbalance is associated with the progression of consolidated regions to cavities containing very high bacterial burdens. Our model provided mechanistic insight, correlating with human disease at the pathological, microbiological and molecular levels. It also provided a strategy to investigate therapeutics in the context of complex TB pathology. We used these findings to predict a MMP/TIMP balance in active TB and confirmed this in human plasma, revealing the potential of MMP/TIMP levels as key components of a diagnostic matrix aimed at distinguishing active from latent TB (PPV = 92.9%, 95% CI 66.1–99.8%, NPV = 85.6%; 95% CI 77.0–91.9%). Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd     

Induction of human T-cell tolerance to porcine xenoantigens through mixed hematopoietic chimerism

Xenotransplantation from pigs could provide a potential solution to the severe shortage of allogeneic donor organs. Because xenogeneic tissues are subject to vigorous immune rejection, tolerance induction is likely to be essential to the success of clinical xenotransplantation. Here we explore the possibility of inducing human T-cell tolerance to porcine xenografts through mixed chimerism. We previously showed that NOD/SCID-Tg mice expressing porcine cytokine transgenes permit the induction of durable porcine hematopoietic chimerism. In this study we achieved human T-cell development in these mice by engrafting human fetal thymus/liver tissues. In porcine hematopoietic chimeras, human thymus grafts were populated with porcine class II(high) cells in addition to human cells, and human T cells were tolerant of the porcine hematopoietic donor as measured by mixed lymphocyte reaction assay and skin grafting. This study proves the principle that porcine chimerism induces tolerance of xenoreactive human T cells.     

Roflumilast,a Type 4 Phosphodiesterase Inhibitor,Shows Promising Adjunctive,Host-Directed Therapeutic Activity in a Mouse Model of Tuberculosis

With phosphodiesterase inhibitors (PDE-Is) showing significant promise in shortening tuberculosis treatment, we assessed the effect of roflumilast, an FDA-approved type 4 PDE-I, in both acute and chronic murine models of tuberculosis. Alone, roflumilast had no effect on lung bacillary burden and mortality. However, when roflumilast was used in combination with isoniazid, a reduction in lung bacillary burden was observed. These data suggest that roflumilast may be a good candidate for tuberculosis host-directed therapy (HDT).     

Empowering Malian women living with HIV regarding serostatus disclosure management: Short-term effects of a community-based intervention

Objective

The objective of this study was to assess the short-term effects of Gundo-So—a program aimed at empowering Malian women living with HIV (WLHIV) regarding serostatus disclosure management.

T cells from presensitized donors fail to cause graft-versus-host disease in a pig-to-mouse xenotransplantation model

BACKGROUND: The ability of T cells from pigs, the most suitable donors for clinical xenotransplantation, to induce graft-versus-host disease (GVHD) and to facilitate hematopoietic cell engraftment in highly disparate xenogeneic recipients remains unclear. In this article, the authors address these questions in a presensitized pig-to-mouse transplantation model using porcine cytokine-transgenic mice. METHODS: Swine donors were presensitized by mouse skin grafting and boosted by the injection of mouse cells after the skin graft was rejected. Porcine peripheral blood mononuclear cells (PBMC) and splenocytes were collected at various times after mouse skin grafting, and their potential to induce GVHD and to facilitate donor hematopoietic cell engraftment in conditioned murine recipients was evaluated. RESULTS: Presensitization of donor pigs resulted in marked enhancement of anti-mouse responses, as reflected in augmented anti-mouse mixed lymphocyte responses, cell-mediated cytotoxicity, and antibody production. However, injection of high numbers of PBMC and splenocytes (>1 x 10(8)) with bone marrow cells from the presensitized pigs failed to induce detectable GVHD or long-term chimerism in mice that were treated with depleting anti-T-cell and natural killer cell antibodies, cobra venom factor, medronate-liposomes, and 4 Gy of whole-body and 7 Gy of thymic irradiation. Histologic analysis revealed no mononuclear cell infiltration or GVHD-associated lesions in the liver, intestine, lungs, or skin of the mouse recipients. Furthermore, the recipient mice had no detectable T cells or anti-pig immunoglobulin G antibodies in the blood by 6 weeks after injection of porcine cells. CONCLUSION: These results demonstrate that porcine T-cell function is severely impaired in the xenogeneic murine microenvironment.