Stigma impedes AIDS prevention

Thirty years since the first cases of AIDS were described, there is much to celebrate regarding progress in the treatment and prevention of the disease. Within the past year alone, several studies have revealed that antiretroviral drugs can prevent the sexual transmission of HIV. Yet worldwide, many people who are potentially exposed to the virus avoid finding out whether they carry it, or deny that they are at risk of contracting it. Unless people establish whether they are infected, they will not be able to be adopt the most appropriate preventive measures. As scientists and clinicians, our ability to overcome this denialism will determine whether we ultimately succeed in using combinations of all the preventive and therapeutic tools now available to slow, and eventually stop, the HIV/AIDS pandemic

Finding a way: long-term care homes to support dementia

An ageing demographic has increased the number of people with dementia. Although dementia is commonly associated with memory loss, other early symptoms include difficulty with wayfinding. Dementia alters visuo-spatial perception and the processes used to interpret the physical environment. The role of the design of the physical environment for people with dementia has gained increased recognition. Despite this, design for dementia is often overlooked, focusing on issues relating to physical impairment. This paper presents the results of a PhD study and aims to examine the role of the design of the physical environment in supporting wayfinding for people with dementia living in long-term care settings in Northern Ireland. Mixed methods combined the observation of wayfinding walks and conversational style interviews to elicit perspectives and experiences of residents with dementia. The findings aim to promote well-being for those with dementia living in long-term care settings

MTN-001: Randomized Pharmacokinetic Cross-Over Study Comparing Tenofovir Vaginal Gel and Oral Tablets in Vaginal Tissue and Other Compartments

Background: Oral and vaginal preparations of tenofovir as pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection have demonstrated variable efficacy in men and women prompting assessment of variation in drug concentration as an explanation. Knowledge of tenofovir concentration and its active form, tenofovir diphosphate, at the putative vaginal and rectal site of action and its relationship to concentrations at multiple other anatomic locations may provide key information for both interpreting PrEP study outcomes and planning future PrEP drug development. Objective: MTN-001 was designed to directly compare oral to vaginal steady-state tenofovir pharmacokinetics in blood, vaginal tissue, and vaginal and rectal fluid in a paired cross-over design. Methods and Findings: We enrolled 144 HIV-uninfected women at 4 US and 3 African clinical research sites in an open label, 3-period crossover study of three different daily tenofovir regimens, each for 6 weeks (oral 300 mg tenofovir disoproxil fumarate, vaginal 1% tenofovir gel [40 mg], or both). Serum concentrations after vaginal dosing were 56-fold lower than after oral dosing (p<0.001). Vaginal tissue tenofovir diphosphate was quantifiable in ≥90% of women with vaginal dosing and only 19% of women with oral dosing. Vaginal tissue tenofovir diphosphate was ≥130-fold higher with vaginal compared to oral dosing (p<0.001). Rectal fluid tenofovir concentrations in vaginal dosing periods were higher than concentrations measured in the oral only dosing period (p<0.03). Conclusions: Compared to oral dosing, vaginal dosing achieved much lower serum concentrations and much higher vaginal tissue concentrations. Even allowing for 100-fold concentration differences due to poor adherence or less frequent prescribed dosing, vaginal dosing of tenofovir should provide higher active site concentrations and theoretically greater PrEP efficacy than oral dosing; randomized topical dosing PrEP trials to the contrary indicates that factors beyond tenofovir's antiviral effect substantially influence PrEP efficacy. Trial Registration: ClinicalTrials.gov NCT00592124

Population-Level Benefits from Providing Effective HIV Prevention Means to Pregnant Women in High Prevalence Settings

Background:HIV prevalence among pregnant women in Southern Africa is extremely high. Epidemiological studies suggest that pregnancy increases the risk of HIV sexual acquisition and that HIV infections acquired during pregnancy carry higher risk of mother-to-child transmission (MTCT). We analyze the potential benefits from extending the availability of effective microbicide to pregnant women (in addition to non-pregnant women) in a wide-scale intervention.Methods and Findings:A transmission dynamic model was designed to assess the impact of microbicide use in high HIV prevalence settings and to estimate proportions of new HIV infections, infections acquired during pregnancy, and MTCT prevented over 10 years. Our analysis suggests that consistent use of microbicide with 70% efficacy by 60% of non-pregnant women may prevent approximately 40% and 15% of new infections in women and men respectively over 10 years, assuming no additional increase in HIV risk to either partner during pregnancy (RRHIV/preg = 1). It may also prevent 8-15% MTCT depending on the increase in MTCT risk when HIV is acquired during pregnancy compared to before pregnancy (RRMTCT/preg). Extending the microbicides use during pregnancy may improve the effectiveness of the intervention by 10% (RRHIV/preg = 1) to 25% (RRHIV/preg = 2) and reduce the number of HIV infections acquired during pregnancy by 40% to 70% in different scenarios. It may add between 6% (RRHIV/preg = 1, RRMTCT/preg = 1) and 25% (RRHIV/preg = 2, RRMTCT/preg = 4) to the reduction in the residual MTCT.Conclusion:Providing safe and effective microbicide to pregnant women in the context of wide-scale interventions would be desirable as it would increase the effectiveness of the intervention and significantly reduce the number of HIV infections acquired during pregnancy. The projected benefits from covering pregnant women by the HIV prevention programs is more substantial in communities in which the sexual risk during pregnancy is elevated. © 2013 Dimitrov et al

Bilateral testicular self-castration due to cannabis abuse: a case report

<p>Abstract</p> <p>Introduction</p> <p>The self-mutilating patient is an unusual psychiatric presentation in the emergency room. Nonetheless, serious underlying psychiatric pathology and drug abuse are important background risk factors. A careful stepwise approach in the emergency room is essential, although the prognosis, follow-up, and eventual rehabilitation can be problematic.</p> <p>We present a unique and original case of bilateral self-castration caused by cannabis abuse.</p> <p>Case Presentation</p> <p>We report a case of a 40-year-old Berber man, who was presented to our emergency room with externalization of both testes using his long fingernails, associated with hemodynamic shock. After stabilization of his state, our patient was admitted to the operating room where hemostasis was achieved.</p> <p>Conclusion</p> <p>The clinical characteristics of self-mutilation are manifold and there is a lack of agreement about its etiology. The complex behavior associated with drug abuse may be one cause of self-mutilation. Dysfunction of the inhibitory brain circuitry caused by substance abuse could explain why this cannabis-addicted patient lost control and self-mutilated. To the best of our knowledge, this is the first case report which presents an association between self-castration and cannabis abuse.</p

Rectal Transmission of Transmitted/Founder HIV-1 Is Efficiently Prevented by Topical 1% Tenofovir in BLT Humanized Mice

Rectal microbicides are being developed to prevent new HIV infections in both men and women. We focused our in vivo preclinical efficacy study on rectally-applied tenofovir. BLT humanized mice (n = 43) were rectally inoculated with either the primary isolate HIV-1(JRCSF) or the MSM-derived transmitted/founder (T/F) virus HIV-1(THRO) within 30 minutes following treatment with topical 1% tenofovir or vehicle. Under our experimental conditions, in the absence of drug treatment we observed 50% and 60% rectal transmission by HIV-1(JRCSF) and HIV-1(THRO), respectively. Topical tenofovir reduced rectal transmission to 8% (1/12; log rank p = 0.03) for HIV-1(JRCSF) and 0% (0/6; log rank p = 0.02) for HIV-1(THRO). This is the first demonstration that any human T/F HIV-1 rectally infects humanized mice and that transmission of the T/F virus can be efficiently blocked by rectally applied 1% tenofovir. These results obtained in BLT mice, along with recent ex vivo, Phase 1 trial and non-human primate reports, provide a critically important step forward in the development of tenofovir-based rectal microbicides

Suppression of Cellular Transformation by Poly (A) Binding Protein Interacting Protein 2 (Paip2)

Controlling translation is crucial for the homeostasis of a cell. Its deregulation can facilitate the development and progression of many diseases including cancer. Poly (A) binding protein interacting protein 2 (Paip2) inhibits efficient initiation of translation by impairing formation of the necessary closed loop of mRNA. The over production of Paip2 in the presence of a constitutively active form of hRasV12 can reduce colony formation in a semi-solid matrix and focus formation on a cell monolayer. The ability of Paip2 to bind to Pabp is required to suppress the transformed phenotype mediated by hRasV12. These observations indicate that Paip2 is able to function as a tumor suppressor

Analysis of vaginal microbicide film hydration kinetics by quantitative imaging refractometry

We have developed a quantitative imaging refractometry technique, based on holographic phase microscopy, as a tool for investigating microscopic structural changes in water-soluble polymeric materials. Here we apply the approach to analyze the structural degradation of vaginal topical microbicide films due to water uptake. We implemented transmission imaging of 1-mm diameter film samples loaded into a flow chamber with a 1.5×2 mm field of view. After water was flooded into the chamber, interference images were captured and analyzed to obtain high resolution maps of the local refractive index and subsequently the volume fraction and mass density of film material at each spatial location. Here, we compare the hydration dynamics of a panel of films with varying thicknesses and polymer compositions, demonstrating that quantitative imaging refractometry can be an effective tool for evaluating and characterizing the performance of candidate microbicide film designs for anti-HIV drug delivery. © 2014 Rinehart et al

Emergence of Carbapenem resistant Gram negative and vancomycin resistant Gram positive organisms in bacteremic isolates of febrile neutropenic patients: A descriptive study

<p>Abstract</p> <p>Background</p> <p>This study was conducted to evaluate drug resistance amongst bacteremic isolates of febrile neutropenic patients with particular emphasis on emergence of carbapenem resistant Gram negative bacteria and vancomycin resistant <it>Enterococcus </it>species.</p> <p>Methods</p> <p>A descriptive study was performed by reviewing the blood culture reports from febrile neutropenic patients during the two study periods i.e., 1999–00 and 2001–06. Blood cultures were performed using BACTEC 9240 automated system. Isolates were identified and antibiotic sensitivities were done using standard microbiological procedures.</p> <p>Results</p> <p>Seven twenty six febrile neutropenic patients were admitted during the study period. A total of 5840 blood cultures were received, off these 1048 (18%) were culture positive. Amongst these, 557 (53%) grew Gram positive bacteria, 442 (42%) grew Gram negative bacteria, 43 (4%) fungi and 6 (1%) anaerobes. Sixty (5.7%) out of 1048 positive blood cultures were polymicrobial. In the Gram negative bacteria, <it>Enterobacteriaceae </it>was the predominant group; <it>E. coli </it>was the most frequently isolated organism in both study periods. Amongst non- Enterobacteriaceae group, <it>Pseudomonas aeruginosa </it>was the commonest organism isolated during first study period followed by <it>Acinetobacter </it>spp. However, during the second period <it>Acinetobacter </it>species was the most frequent pathogen.</p> <p><it>Enterobacteriaceae </it>group showed higher statistically significant resistance in the second study period against ceftriaxone, quinolone and piperacillin/tazobactam, whilst no resistance observed against imipenem/meropenem. The susceptibility pattern of <it>Acinetobacter </it>species shifted from sensitive to highly resistant one with significant p values against ceftriaxone, quinolone, piperacillin/tazobactam and imipenem/meropenem. Amongst Gram positive bacteria, MRSA isolation rate remained static, vancomycin resistant <it>Enterococcus </it>species emerged in second study period while no <it>Staphylococcus </it>species resistant to vancomycin was noted.</p> <p>Conclusion</p> <p>This rising trend of highly resistant organisms stresses the increasing importance of continuous surveillance system and stewardship of antibiotics as strategies in the overall management of patients with febrile neutropenia.</p