Liposomal amphotericin B for visceral leishmaniasis in human immunodeficiency virus-coinfected patients: 2-year treatment outcomes in Bihar, India

Reports on treatment outcomes of visceral leishmaniasis (VL)-human immunodeficiency virus (HIV) coinfection in India are lacking. To our knowledge, none have studied the efficacy of liposomal amphotericin B in VL-HIV coinfection. We report the 2-year treatment outcomes of VL-HIV-coinfected patients treated with liposomal amphotericin B followed by combination antiretroviral treatment (cART) in Bihar, India

Constitutive and inducible co-expression systems for non-viral osteoinductive gene therapy

Tissue regenerative gene therapy requires expression strategies that deliver therapeutic effective amounts of transgenes. As physiological expression patterns are more complex than high-level expression of a singular therapeutic gene, we aimed at constitutive or inducible co-expression of 2 transgenes simultaneously. Co-expression of human bone morphogenetic protein 2 and 7 (BMP2/7) from constitutively expressing and doxycycline inducible plasmids was evaluated in vitro in C2C12 cells with osteocalcin reporter gene assays and standard assays for osteogenic differentiation. The constitutive systems were additionally tested in an in vivo pilot for ectopic bone formation after repeated naked DNA injection to murine muscle tissue. Inductor controlled differentiation was demonstrated in vitro for inducible co-expression. Both co-expression systems, inducible and constitutive, achieved significantly better osteogenic differentiation than single factor expression. The potency of the constitutive co-expression systems was dependent on relative expression cassette topology. In vivo, ectopic bone formation was demonstrated in 6/13 animals (46 % bone formation efficacy) at days 14 and 28 in hind limb muscles as proven by in vivo μCT and histological evaluation. In vitro findings demonstrated that the devised single vector BMP2/7 co-expression strategy mediates superior osteoinduction, can be applied in an inductor controlled fashion and that its efficiency is dependent on expression cassette topology. In vivo results indicate that co-expression of BMP2/7 applied by non-viral naked DNA gene transfer effectively mediates bone formation without the application of biomaterials, cells or recombinant growth factors, offering a promising alternative to current treatment strategies with potential for clinical translation in the future

High mortality in tuberculosis patients despite HIV interventions in Swaziland.

SETTING: All health facilities providing tuberculosis (TB) care in Swaziland. OBJECTIVE: To describe the impact of human immunodeficiency virus (HIV) interventions on the trend of TB treatment outcomes during 2010-2013 in Swaziland; and to describe the evolution in TB case notification, the uptake of HIV testing, antiretroviral therapy (ART) and cotrimoxazole preventive therapy (CPT), and the proportion of TB-HIV co-infected patients with adverse treatment outcomes, including mortality, loss to follow-up and treatment failure. DESIGN: A retrospective descriptive study using aggregated national TB programme data. RESULTS: Between 2010 and 2013, TB case notifications in Swaziland decreased by 40%, HIV testing increased from 86% to 96%, CPT uptake increased from 93% to 99% and ART uptake among TB patients increased from 35% to 75%. The TB-HIV co-infection rate remained around 70% and the proportion of TB-HIV cases with adverse outcomes decreased from 36% to 30%. Mortality remained high, at 14-16%, over the study period, and anti-tuberculosis treatment failure rates were stable over time (<5%). CONCLUSION: Despite high CPT and ART uptake in TB-HIV patients, mortality remained high. Further studies are required to better define high-risk patient groups, understand the reasons for death and design appropriate interventions

Vascular endothelial growth factor and fibroblast growth Factor-2 incorporation in starch-based bone tissue-engineered constructs promote the In vivo expression of neovascularization mediators

The ideal bone tissue-engineered (TE) construct remains to be found, although daily discoveries significantly contribute to improvements in the field and certainly have valuable long-term outcomes. In this work, different TE elements, aiming at bone TE applications, were assembled and its effect on the expression of several vas- cularization/angiogenesis mediators analyzed. Starch/polycaprolactone (SPCL) scaffolds, obtained by two different methodologies, were combined with fibrin sealant (Baxter), human adipose-derived stem cells (hASCs), and growth factors (vascular endothelial growth factor [VEGF] or fibroblast growth factor-2 [FGF-2]), and implanted in vascular endothelial growth factor receptor-2 (VEGFR2)-luc transgenic mice. The expression of VEGFR2 along the implantation of the designed constructs was followed using a luminescence device (XenogenÒ) and after 2 weeks, the explants were retrieved to perform histological analysis and reverse transcriptase–polymerase chain reaction for vascularization (VEGF and VEGFR1) and inflammatory (tumor necrosis factor-alpha, interleukin-4, and interferon-gamma) markers. It was showed that SPCL scaffolds ob- tained by wet spinning and by fiber bonding constitute an adequate support for hASCs. The assembled TE constructs composed by fibrin sealant, hASCs, VEGF, and FGF-2 induce only a mild inflammatory reaction after 2 weeks of implantation. Additionally, the release of VEGF and FGF-2 from the constructs enhanced the ex- pression of VEGFR2 and other important mediators in neovascularization (VEGF and VEGFR1). These results indicate the potential of VEGF or FGF-2 within a bone TE construct composed by wet-spun SPCL, fibrin sealant, and hASCs in promoting the vascularization of newly formed tissue.The author Tircia C. Santos acknowledges the Marie Curie European Program for a short-term scholarship in the Alea Jacta EST project (MEST-CT-2004-008104). This work was developed under the scope of the European Network of Excellence EXPERTISSUES (NMP3-CT-2004-5000283)

Chitosan improves the biological performance of soy-based biomaterials

Soybean protein has been proposed for distinct applications within nutritional, pharmaceutical, and cosmetic industries among others. More recently, soy-based biomaterials have also demonstrated promising properties for biomedical applications.However, althoughmany reports within other fields exist, the inflammatory/immunogenic potential of those materials is still poorly understood and therefore can hardly be controlled. On the contrary, chitosan (Cht) has been well explored in the biomedical field, either by itself or combined with synthetic or other natural-based polymers. Therefore, the combination of chitosan with soybean protein is foreseen as a suitable approach to control the biological behavior of soy-based biomaterials. Under this context this work was designed to try to understand the influence of chitosan in the host response elicited by soy-based biomaterials. Soybean protein isolate powder (SI-P) and Cht powder (Cht-P) were injected as suspension into the intraperitoneal cavity of rats. SI-P induced the recruitment of higher numbers of leukocytes compared to the Cht-P during the entire observation period. In this sense, SI-P elicited a considerable reaction from the host comparing to the Cht-P, which elicited leukocyte recruitment similar to the negative control.After subcutaneous implantation of the soybean and denatured membranes, (SI-M and dSI-M) a severe host inflammatory reaction was observed. Conversely, Cht/soy-based membranes (Cht/soy-based membranes) showed the induction of a normal host response after subcutaneous implantation in rats, which allowed concluding that the addition of chitosan to the soy-based membranes improved their in vivo performance. Thus, the presented results assert the improvement of the host response, considering inflammatory cells recruitment, and overall inflammatory reaction,when chitosan is combined to soybean. Together with previous results that reported their promising physicochemical characteristics and their inability to activate human polymorphonuclear neutrophils in vitro, the herein presented conclusions reinforce the usefulness of theCht/ soy-based membranes and justify the pursue for a specific application within the biomedical field.The author Tircia C. Santos acknowledges the Marie Curie European Program for a short-term scholarship in the Alea Jacta EST project (MEST-CT-2004-008104). This work was developed under the scope of the European Network of Excellence EXPERTISSUES (NMP3-CT-2004-5000283)

Awareness and willingness to use HIV pre-exposure prophylaxis amongst gay and bisexual men in Scotland: implications for biomedical HIV prevention

Objectives:&lt;p&gt;&lt;/p&gt; To investigate the awareness of, and willingness to use, HIV Pre-Exposure Prophylaxis (PrEP), and willingness to take part in a PrEP study among gay and bisexual men in Scotland.&lt;p&gt;&lt;/p&gt; Methods:&lt;p&gt;&lt;/p&gt; Cross-sectional survey of 17 gay commercial venues in Glasgow and Edinburgh in May 2011 (N = 1515, 65.2% response rate); 1393 are included in the analyses.&lt;p&gt;&lt;/p&gt; Results:&lt;p&gt;&lt;/p&gt; Just under one-third of participants had heard of PrEP (n = 434; 31.2%), with awareness associated with being aged older than 35 years, talking to UAI partners about HIV, and with having had an HIV or STI test in the previous 12 months. Around half were willing to take part in a PrEP study (n = 695; 49.9%) or to take PrEP on a daily basis (n = 756; 54.3%). In multivariate analysis, willingness to take PrEP was associated with lower levels of education, regular gay scene attendance, ‘high-risk’ unprotected anal intercourse (UAI) and testing for HIV or STI in the previous 12 months. Reasons for not wanting to participate in a PrEP study or take PrEP included perceptions of low personal risk of HIV and concerns with using medication as an HIV prevention method.&lt;p&gt;&lt;/p&gt; Conclusions:&lt;p&gt;&lt;/p&gt; There is a willingness to engage in new forms of HIV prevention and research amongst a significant number of gay and bisexual men in Scotland. Future biomedical HIV interventions need to consider the links between sexual risk behaviour, testing, and potential PrEP use