A Model for the Roll-Out of Comprehensive Adult Male Circumcision Services in African Low-Income Settings of High HIV Incidence: The ANRS 12126 Bophelo Pele Project

Background

World Health Organization (WHO)/Joint United Nations Programme on AIDS (UNAIDS) has recommended adult male circumcision (AMC) for the prevention of heterosexually acquired HIV infection in men from communities where HIV is hyperendemic and AMC prevalence is low. The objective of this study was to investigate the feasibility of the roll-out of medicalized AMC according to UNAIDS/WHO operational guidelines in a targeted African setting.

Methods and Findings

The ANRS 12126 “Bophelo Pele” project was implemented in 2008 in the township of Orange Farm (South Africa). It became functional in 5 mo once local and ethical authorizations were obtained. Project activities involved community mobilization and outreach, as well as communication approaches aimed at both men and women incorporating broader HIV prevention strategies and promoting sexual health. Free medicalized AMC was offered to male residents aged 15 y and over at the project''s main center, which had been designed for low-income settings. Through the establishment of an innovative surgical organization, up to 150 AMCs under local anesthesia, with sterilized circumcision disposable kits and electrocautery, could be performed per day by three task-sharing teams of one medical circumciser and five nurses. Community support for the project was high. As of November 2009, 14,011 men had been circumcised, averaging 740 per month in the past 12 mo, and 27.5% of project participants agreed to be tested for HIV. The rate of adverse events, none of which resulted in permanent damage or death, was 1.8%. Most of the men surveyed (92%) rated the services provided positively. An estimated 39.1% of adult uncircumcised male residents have undergone surgery and uptake is steadily increasing.

Conclusion

This study demonstrates that a quality AMC roll-out adapted to African low-income settings is feasible and can be implemented quickly and safely according to international guidelines. The project can be a model for the scale-up of comprehensive AMC services, which could be tailored for other rural and urban communities of high HIV prevalence and low AMC rates in Eastern and Southern Africa. Please see later in the article for the Editors'' Summary     

Systems analysis of iron metabolism: the network of iron pools and fluxes

Background  

Every cell of the mammalian organism needs iron as trace element in numerous oxido-reductive processes as well as for transport and storage of oxygen. The very versatility of ionic iron makes it a toxic entity which can catalyze the production of radicals that damage vital membranous and macromolecular assemblies in the cell. The mammalian organism maintains therefore a complex regulatory network of iron uptake, excretion and intra-body distribution. Intracellular regulation in different cell types is intertwined with a global hormonal signalling structure. Iron deficiency as well as excess of iron are frequent and serious human disorders. They can affect every cell, but also the organism as a whole.     

Phenolic compounds in Hypericum species from the Trigynobrathys section

Phenolic compounds of thirteen Hypericum species growing in South Brazil were investigated aiming to evaluate the usefulness of their distribution as a taxonomic character. The HPLC analysis of the methanolic fractions displayed similar chemical profile and significant contents variation among the investigated taxa, being chlorogenic acid the main metabolite quantified in most of the species (ranging from traces to 16.65 mg% of extract), followed by hyperoside (between 0.27 and 11.48 mg%), quercitrin (0.09 and 13.34 mg%), guaijaverin (0.14 and 2.91 mg%) and isoquercitrin (0.14 and 6.97 mg%), whereas rutin and the xanthone mangiferin were not detected.     

1,2-diamino-ethane-substituted-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepines as TRPV1 antagonists with improved properties

Based upon a previously reported lead compound 1, a series of 1,2-diamino-ethane-substituted-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepines were synthesized and evaluated for improved physiochemical and pharmacokinetic properties while maintaining TRPV1 antagonist activity. Structure-activity relationship studies directed toward improving the aqueous solubility (pH 2 and fasted-state simulated intestinal fluid (SIF)) and rat pharmacokinetics led to the discovery of compound 13. Aqueous solubility of compound 13 (pH 2 ≥237 μg/mL and SIF=11 μg/mL) was significantly improved over compound 1 (pH 2=5 μg/mL and SIF=0.5 μg/mL). In addition, compound 13 afforded improved rat pharmacokinetics (CL=0.7 L/kg/h) compared to compound 1 (CL=3.1 L/kg/h). Compound 13 was orally bioavailable and afforded a significant reversal of carrageenan-induced thermal hyperalgesia at 5 and 30 mg/kg in rats.     

ApoA-I mimetic peptides promote pre-β HDL formation in vivo causing remodeling of HDL and triglyceride accumulation at higher dose

Reverse cholesterol transport promoted by HDL-apoA-I is an important mechanism of protection against atherosclerosis. We have previously identified apoA-I mimetic peptides by synthesizing analogs of the 22 amino acid apoA-I consensus sequence (apoA-I(cons)) containing non-natural aliphatic amino acids. Here we examined the effect of different aliphatic non-natural amino acids on the structure-activity relationship (SAR) of apoA-I mimetic peptides. These novel apoA-I mimetics, with long hydrocarbon chain (C(5-8)) amino acids incorporated in the amphipathic α helix of the apoA-I(cons), have the following properties: (i) they stimulate in vitro cholesterol efflux from macrophages via ABCA1; (ii) they associate with HDL and cause formation of pre-β HDL particles when incubated with human and mouse plasma; (iii) they associate with HDL and induce pre-β HDL formation in vivo, with a corresponding increase in ABCA1-dependent cholesterol efflux capacity ex vivo; (iv) at high dose they associate with VLDL and induce hypertriglyceridemia in mice. These results suggest our peptide design confers activities that are potentially anti-atherogenic. However a dosing regimen which maximizes their therapeutic properties while minimizing adverse effects needs to be established.     

High‐Performance Tandem Organic Solar Cells Using HSolar as the Interconnecting Layer

Tandem structure provides a practical way to realize high efficiency organic photovoltaic cells, it can be used to extend the wavelength coverage for light harvesting. The interconnecting layer (ICL) between subcells plays a critical role in the reproducibility and performance of tandem solar cells, yet the processability of the ICL has been a challenge. In this work the fabrication of highly reproducible and efficient tandem solar cells by employing a commercially available material, PEDOT:PSS HTL Solar (HSolar), as the hole transporting material used for the ICL is reported. Comparing with the conventional PEDOT:PSS Al 4083 (c‐PEDOT), HSolar offers a better wettability on the underlying nonfullerene photoactive layers, resulting in better charge extraction properties of the ICL. When FTAZ:IT‐M and PTB7‐Th:IEICO‐4F are used as the subcells, a power conversion efficiency (PCE) of 14.7% is achieved in the tandem solar cell. To validate the processability of these tandem solar cells, three other research groups have successfully fabricated tandem devices using the same recipe and the highest PCE obtained is 16.1%. With further development of donor polymers and device optimization, the device simulation results show that a PCE > 22% can be realized in tandem cells in the near future.     

Pollen sources used by species of Meliponini (Hymenoptera: Apidae) along the Rio Negro channel in Amazonas,Brazil

This work analyses the pollen stored by Meliponini bees whose nests were sampled along the Rio Negro channel, Amazonas, Brazil, during the final phase of the rainy season, which is also the time of pollen scarcity. From a total of 51 samples studied, 78 pollen types were identified, of which 39 were determined to species level. The pollen types were from 70 genera and 42 families. Based on the pollen records, a clustering analysis was performed, as well as the calculation of the trophic overlap index. The study demonstrates that the plants used by the bees do not depend on them for pollination in most cases; it rather suggests scarcity of pollen resources from the plants adapted to the pollination of Meliponini, and emphasises the ability of such bees to switch to new available resources. This work indicates a list of important plants for meliponiculture suitable for cultures near meliponaries.     

Mapping quantitative trait loci (QTL) in sheep. IV. Analysis of lactation persistency and extended lactation traits in sheep

Background

In sheep dairy production, total lactation performance, and length of lactation of lactation are of economic significance. A more persistent lactation has been associated with improved udder health. An extended lactation is defined by a longer period of milkability. This study is the first investigation to examine the presence of quantitative trait loci (QTL) for extended lactation and lactation persistency in sheep.

Methods

An (Awassi × Merino) × Merino single-sire backcross family with 172 ewes was used to map QTL for lactation persistency and extended lactation traits on a framework map of 189 loci across all autosomes. The Wood model was fitted to data from multiple lactations to estimate parameters of ovine lactation curves, and these estimates were used to derive measures of lactation persistency and extended lactation traits of milk, protein, fat, lactose, useful yield, and somatic cell score. These derived traits were subjected to QTL analyses using maximum likelihood estimation and regression analysis.

Results

Overall, one highly significant (LOD > 3.0), four significant (2.0 < LOD < 3.0) and five suggestive (1.7 < LOD < 2.0) QTL were detected across all traits in common by both mapping methods. One additional suggestive QTL was identified using maximum likelihood estimation, and four suggestive (0.01 < P < 0.05) and two significant (P < 0.01) QTL using the regression approach only. All detected QTL had effect sizes in the range of 0.48 to 0.64 SD, corresponding to QTL heritabilities of 3.1 to 8.9%. The comparison of the detected QTL with results in cattle showed conserved linkage regions. Most of the QTL identified for lactation persistency and extended lactation did not coincide. This suggests that persistency and extended lactation for the same as well as different milk yield and component traits are not controlled by the same genes.

Conclusion

This study identified ten novel QTL for lactation persistency and extended lactation in sheep, but results suggest that lactation persistency and extended lactation do not have a major gene in common. These results provide a basis for further validation in extended families and other breeds as well as targeting regions for genome-wide association mapping using high-density SNP arrays.     

Quality of Voluntary Medical Male Circumcision Services during Scale-Up: A Comparative Process Evaluation in Kenya,South Africa,Tanzania and Zimbabwe

Background

The rapid expansion of voluntary medical male circumcision (VMMC) has raised concerns whether health systems can deliver and sustain VMMC according to minimum quality criteria.

Methods and Findings

A comparative process evaluation was used to examine data from SYMMACS, the Systematic Monitoring of the Voluntary Medical Male Circumcision Scale-Up, among health facilities providing VMMC across two years of program scale-up. Site-level assessments examined the availability of guidelines, supplies and equipment, infection control, and continuity of care services. Direct observation of VMMC surgeries were used to assess care quality. Two sample tests of proportions and t-tests were used to examine differences in the percent of facilities meeting requisite preparedness standards and the mean number of directly-observed surgical tasks performed correctly. Results showed that safe, high quality VMMC can be implemented and sustained at-scale, although substantial variability was observed over time. In some settings, facility preparedness and VMMC service quality improved as the number of VMMC facilities increased. Yet, lapses in high performance and expansion of considerably deficient services were also observed. Surgical tasks had the highest quality scores, with lower performance levels in infection control, pre-operative examinations, and post-operative patient monitoring and counseling. The range of scale-up models used across countries additionally underscored the complexity of delivering high quality VMMC.

Conclusions

Greater efforts are needed to integrate VMMC scale-up and quality improvement processes in sub-Saharan African settings. Monitoring of service quality, not just adverse events reporting, will be essential in realizing the full health impact of VMMC for HIV prevention.