Low Rates of Repeat HIV Testing Despite Increased Availability of Antiretroviral Therapy in Rural Tanzania: Findings from 2003–2010

Background

HIV counselling and testing (HCT) services can play an important role in HIV prevention by encouraging safe sexual behaviours and linking HIV-infected clients to antiretroviral therapy (ART). However, regular repeat testing by high-risk HIV-negative individuals is important for timely initiation of ART as part of the ‘treatment as prevention’ approach.

Aim

To investigate HCT use during a round of HIV serological surveillance in northwest Tanzania in 2010, and to explore rates of repeat testing between 2003 and 2010.

Methods

HCT services were provided during the fourth, fifth and sixth rounds of serological surveillance in 2003–2004 (Sero-4), 2006–2007 (Sero-5) and 2010 (Sero-6). HCT services have also been available at a government-run health centre and at other clinics in the study area since 2005. Questionnaires administered during sero-surveys collected information on socio-demographic characteristics, sexual behaviour and reported previous use of HCT services.

Results

The proportion of participants using HCT increased from 9.4% at Sero-4 to 16.6% at Sero-5 and 25.5% at Sero-6. Among participants attending all three sero-survey rounds (n = 2,010), the proportions using HCT twice or more were low, with 11.1% using the HCT service offered at sero-surveys twice or more, and 25.3% having tested twice or more if reported use of HCT outside of sero-surveys was taken into account. In multivariable analyses, individuals testing HIV-positive were less likely to repeat test than individuals testing HIV-negative (aOR 0.17, 95% CI 0.006–0.52).

Discussion/Conclusions

Although HCT service use increased over time, it was disappointing that the proportions ever testing and ever repeat-testing were not even larger, considering the increasing availability of HCT and ART in the study area. There was some evidence that HIV-negative people with higher risk sexual behaviours were most likely to repeat test, which was encouraging in terms of the potential to pick-up those at greatest risk of HIV-infection.     

Biomedical engineering continues to make the future

Biomedical engineering (BME) continues to make the future, not just respond to the present, by anticipating the needs of interface engineering and clinical medicine. In many respects, BME is the educational mode of the future, fostering collaboration among disciplines at its core by building on basic concepts in engineering and biology. We strive to educate where the needs, opportunities, and jobs are and will be in the future. The bridge between engineering, biology, and medicine is a growing link, and there is no sign that this interface will slow. With an aging population, dynamic changes in health care, as well as global economies and related themes upon us, we are only at the very beginning of the impact that BME will have on medicine and the quality of life. Those of us in BME are excited to be setting this agenda and welcome your participation. In part, this is why we have designed our BME major to cover both the depth and breadth, always a challenge, but one that we are committed to. The depth of the design projects, research experience, coursework, study abroad options, and internships all convenes to establish a solid foundation for our students as they embark on their career paths.     

Expanding ART for treatment and prevention of HIV in South Africa: estimated cost and cost-effectiveness 2011-2050

Background

Antiretroviral Treatment (ART) significantly reduces HIV transmission. We conducted a cost-effectiveness analysis of the impact of expanded ART in South Africa.

Methods

We model a best case scenario of 90% annual HIV testing coverage in adults 15–49 years old and four ART eligibility scenarios: CD4 count <200 cells/mm³ (current practice), CD4 count <350, CD4 count <500, all CD4 levels. 2011–2050 outcomes include deaths, disability adjusted life years (DALYs), HIV infections, cost, and cost per DALY averted. Service and ART costs reflect South African data and international generic prices. ART reduces transmission by 92%. We conducted sensitivity analyses.

Results

Expanding ART to CD4 count <350 cells/mm³ prevents an estimated 265,000 (17%) and 1.3 million (15%) new HIV infections over 5 and 40 years, respectively. Cumulative deaths decline 15%, from 12.5 to 10.6 million; DALYs by 14% from 109 to 93 million over 40 years. Costs drop $504 million over 5 years and $3.9 billion over 40 years with breakeven by 2013. Compared with the current scenario, expanding to <500 prevents an additional 585,000 and 3 million new HIV infections over 5 and 40 years, respectively. Expanding to all CD4 levels decreases HIV infections by 3.3 million (45%) and costs by $10 billion over 40 years, with breakeven by 2023. By 2050, using higher ART and monitoring costs, all CD4 levels saves $0.6 billion versus current; other ART scenarios cost $9–194 per DALY averted. If ART reduces transmission by 99%, savings from all CD4 levels reach $17.5 billion. Sensitivity analyses suggest that poor retention and predominant acute phase transmission reduce DALYs averted by 26% and savings by 7%.

Conclusion

Increasing the provision of ART to <350 cells/mm3 may significantly reduce costs while reducing the HIV burden. Feasibility including HIV testing and ART uptake, retention, and adherence should be evaluated.     

Studies on metacercarial excystment in Himasthla leptosoma (Trematoda: Echinostomatidae) and newly emerged metacercariae

Metacercarial cysts of Himasthla leptosoma were subjected to a solution containing bile salts, trypsin and l cysteine at 41°C. The treatment induced intense metacercarial activity and after 20 min metacercariae burst through the cyst walls and emerged. Electron microscopy demonstrated that organisms burst through a small area of cyst wall which was devoid of a layer of lamellae present elsewhere towards the innermost surface. The appearance of ruptured cyst walls indicated that they had been softened by the excystment medium. Newly emerged metacercariae possessed a reniform collar of 29 cephalic spines and these were sometimes withdrawn into pits, presumably by action of a muscle complex in the head region. Sensory papillae were distributed in a bilaterally symmetrical arrangement around the anterior sucker and none were visible on the surface of the ventral sucker. Tegumental spines were found only from a point some distance behind the head collar to the region of the ventral sucker. The most anterior spines were simple and peg-like and they quickly merged posteriorly into more complex palmate forms.     

Obatoclax induces Atg7-dependent autophagy independent of beclin-1 and BAX/BAK

Direct pharmacological targeting of the anti-apoptotic B-cell lymphoma-2 (BCL-2) family is an attractive therapeutic strategy for treating cancer. Obatoclax is a pan-BCL-2 family inhibitor currently in clinical development. Here we show that, although obatoclax can induce mitochondrial apoptosis dependent on BCL-2 associated x protein/BCL-2 antagonist killer (BAX/BAK) consistent with its on-target pharmacodynamics, simultaneous silencing of both BAX and BAK did not abolish acute toxicity or loss of clonogenicity. This is despite complete inhibition of apoptosis. Obatoclax dramatically reduced viability without inducing loss of plasma membrane integrity. This was associated with rapid processing of light chain-3 (LC3) and reduction of S6 kinase phosphorylation, consistent with autophagy. Dramatic ultrastructural vacuolation, not typical of autophagy, was also induced. Silencing of beclin-1 failed to prevent LC3 processing, whereas knockout of autophagy-related (Atg)7 abolished LC3 processing but failed to prevent obatoclax-induced loss of clonogenicity or ultrastructural changes. siRNA silencing of Atg7 in BAX/BAK knockout mouse embryonic fibroblasts did not prevent obatoclax-induced loss of viability. Cells selected for obatoclax resistance evaded apoptosis independent of changes in BCL-2 family expression and displayed reduced LC3 processing. In summary, obatoclax exhibits BAX- and BAK-dependent and -independent mechanisms of toxicity and activation of autophagy. Mechanisms other than autophagy and apoptosis are blocked in obatoclax resistant cells and contribute significantly to obatoclax''s anticancer efficacy.     

Comparison of computational modelling techniques for braided stent analysis

Abstract

Braided stents are associated with a number of complications in vivo. Accurate computational modelling of these devices is essential for the design and development of the next generation of these stents. In this study, two commonly utilised methods of computationally modelling filament interaction in braided stents are investigated: the join method and the weave method. Three different braided stent designs are experimentally tested and computationally modelled in both radial and v-block configurations. The results of the study indicate that while both methods are capable of capturing braided stent performance to some degree, the weave method is much more robust.     

The role of Azadinium spinosum (Dinophyceae) in the production of azaspiracid shellfish poisoning in mussels

Azaspiracids (AZAs) are a group of lipophilic polyether compounds first detected in Ireland which have been implicated in shellfish poisoning incidents around Europe. These toxins regularly effect shellfish mariculture operations including protracted closures of shellfish harvesting areas for human consumption. The armoured dinoflagellate Azadinium spinosum Elbrächter et Tillmann gen. et sp. nov. (Dinophyceae) has been described as the de novo azaspiracid toxin producer; nonetheless the link between this organism and AZA toxin accumulation in shellfish has not yet been established. In August 2009, shellfish samples of blue mussel (Mytilus edulis) from the Southwest of Ireland were analysed using liquid chromatography–tandem-mass spectrometry (LC–MS/MS) and were found to be above the regulatory limit (0.16 μg g⁻¹ AZA-equiv.) for AZAs. Water samples from this area were collected and one algal isolate was identified as A. spinosum and was shown to produce azaspiracid toxins. This is the first strain of A. spinosum isolated from Irish waters. The Irish A. spinosum is identical with the other two available A. spinosum strains from Scotland (3D9) and from Denmark (UTHE2) in its sequence of the D1–D2 regions of the LSU rDNA.A 24 h feeding trial of blue mussels (M. edulis) using an algal suspension of the Irish A. spinosum culture at different cell densities demonstrated that A. spinosum is filtered, consumed and digested directly by mussels. Also, LC–MS/MS analysis had shown that AZAs were accumulating in the shellfish hepatopancreas. The toxins AZA1 and -2 were detected in the shellfish together with the AZA analogues AZA3, AZA6, AZA17 and -19 suggesting that AZA1 and -2 are metabolised in the shellfish within the first 24 h after ingestion of the algae. The levels of AZA17 detected in the shellfish hepatopancreas (HP) were equivalent to the levels of AZA1 but in the remainder tissues the levels of AZA17 were four to five times higher than that of AZA1, only small quantities of AZA3 and -19 were present with negligible amounts of AZA6 detected after the 24 h period. This could have implications in the future monitoring of these toxins given that at present according to EU legislation only AZA1–AZA3 is regulated for. This is the first report of blue mussels’ (M. edulis) feeding on the azaspiracid producing algae A. spinosum from Irish waters.     

Draft Genome Sequence of the Yeast Kazachstania telluris CBS 16338 Isolated from Forest Soil in Ireland

Mycopathologia - Draft genomes of several Kazachstania species, a large group of ascomycetous budding yeasts, have been recently published. However, there is none yet available for pathogenic...     

From Single Cells to Tissues: Interactions between the Matrix and Human Breast Cells in Real Time

Background

Mammary gland morphogenesis involves ductal elongation, branching, and budding. All of these processes are mediated by stroma - epithelium interactions. Biomechanical factors, such as matrix stiffness, have been established as important factors in these interactions. For example, epithelial cells fail to form normal acinar structures in vitro in 3D gels that exceed the stiffness of a normal mammary gland. Additionally, heterogeneity in the spatial distribution of acini and ducts within individual collagen gels suggests that local organization of the matrix may guide morphogenesis. Here, we quantified the effects of both bulk material stiffness and local collagen fiber arrangement on epithelial morphogenesis.

Results

The formation of ducts and acini from single cells and the reorganization of the collagen fiber network were quantified using time-lapse confocal microscopy. MCF10A cells organized the surrounding collagen fibers during the first twelve hours after seeding. Collagen fiber density and alignment relative to the epithelial surface significantly increased within the first twelve hours and were a major influence in the shaping of the mammary epithelium. The addition of Matrigel to the collagen fiber network impaired cell-mediated reorganization of the matrix and increased the probability of spheroidal acini rather than branching ducts. The mechanical anisotropy created by regions of highly aligned collagen fibers facilitated elongation and branching, which was significantly correlated with fiber organization. In contrast, changes in bulk stiffness were not a strong predictor of this epithelial morphology.

Conclusions

Localized regions of collagen fiber alignment are required for ductal elongation and branching suggesting the importance of local mechanical anisotropy in mammary epithelial morphogenesis. Similar principles may govern the morphology of branching and budding in other tissues and organs.