Couple-oriented prenatal HIV counseling for HIV primary prevention: an acceptability study

<p>Abstract</p> <p>Background</p> <p>A large proportion of the 2.5 million new adult HIV infections that occurred worldwide in 2007 were in stable couples. Feasible and acceptable strategies to improve HIV prevention in a conjugal context are scarce. In the preparatory phase of the ANRS 12127 Prenahtest multi-site HIV prevention trial, we assessed the acceptability of couple-oriented post-test HIV counseling (COC) and men's involvement within prenatal care services, among pregnant women, male partners and health care workers in Cameroon, Dominican Republic, Georgia and India.</p> <p>Methods</p> <p>Quantitative and qualitative research methods were used: direct observations of health services; in-depth interviews with women, men and health care workers; monitoring of the COC intervention and exit interviews with COC participants.</p> <p>Results</p> <p>In-depth interviews conducted with 92 key informants across the four sites indicated that men rarely participated in antenatal care (ANC) services, mainly because these are traditionally and programmatically a woman's domain. However men's involvement was reported to be acceptable and needed in order to improve ANC and HIV prevention services. COC was considered by the respondents to be a feasible and acceptable strategy to actively encourage men to participate in prenatal HIV counseling and testing and overall in reproductive health services.</p> <p>Conclusions</p> <p>One of the keys to men's involvement within prenatal HIV counseling and testing is the better understanding of couple relationships, attitudes and communication patterns between men and women, in terms of HIV and sexual and reproductive health; this conjugal context should be taken into account in the provision of quality prenatal HIV counseling, which aims at integrated PMTCT and primary prevention of HIV.</p

MiTF links Erk1/2 kinase and p21CIP1/WAF1 activation after UVC radiation in normal human melanocytes and melanoma cells

As a survival factor for melanocytes lineage cells, MiTF plays multiple roles in development and melanomagenesis. What role MiTF plays in the DNA damage response is currently unknown. In this report we observed that MiTF was phosphorylated at serine 73 after UVC radiation, which was followed by proteasome-mediated degradation. Unlike after c-Kit stimulation, inhibiting p90RSK-1 did not abolish the band shift of MiTF protein, nor did it abolish the UVC-mediated MiTF degradation, suggesting that phosphorylation on serine 73 by Erk1/2 is a key event after UVC. Furthermore, the MiTF-S73A mutant (Serine 73 changed to Alanine via site-directed mutagenesis) was unable to degrade and was continuously expressed after UVC exposure. Compared to A375 melanoma cells expressing wild-type MiTF (MiTF-WT), cells expressing MiTF-S73A mutant showed less p21WAF1/CIP1 accumulation and a delayed p21WAF1/CIP1 recovery after UVC. Consequently, cells expressing MiTF-WT showed a temporary G1 arrest after UVC, but cells expressing MiTF-S73A mutant or lack of MiTF expression did not. Finally, cell lines with high levels of MiTF expression showed higher resistance to UVC-induced cell death than those with low-level MiTF. These data suggest that MiTF mediates a survival signal linking Erk1/2 activation and p21WAF1/CIP1 regulation via phosphorylation on serine 73, which facilitates cell cycle arrest. In addition, our data also showed that exposure to different wavelengths of UV light elicited different signal pathways involving MiTF

Appropriate training and retention of community doctors in rural areas: a case study from Mali

Background While attraction of doctors to rural settings is increasing in Mali, there is concern for their retention. An orientation course for young practicing rural doctors was set up in 2003 by a professional association and a NGO. The underlying assumption was that rurally relevant training would strengthen doctors' competences and self-confidence, improve job satisfaction, and consequently contribute to retention. Methods Programme evaluation distinguished trainees' opinions, competences and behaviour. Data were collected through participant observation, group discussions, satisfaction questionnaires, a monitoring tool of learning progress, and follow up visits. Retention was assessed for all 65 trainees between 2003 and 2007. Results and discussion The programme consisted of four classroom modules – clinical skills, community health, practice management and communication skills – and a practicum supervised by an experienced rural doctor. Out of the 65 trained doctors between 2003 and 2007, 55 were still engaged in rural practice end of 2007, suggesting high retention for the Malian context. Participants viewed the training as crucial to face technical and social problems related to rural practice. Discussing professional experience with senior rural doctors contributed to socialisation to novel professional roles. Mechanisms underlying training effects on retention include increased self confidence, self esteem as rural doctor, and sense of belonging to a professional group sharing a common professional identity. Retention can however not be attributed solely to the training intervention, as rural doctors benefit from other incentives and support mechanisms (follow up visits, continuing training, mentoring...) affecting job satisfaction. Conclusion Training increasing self confidence and self esteem of rural practitioners may contribute to retention of skilled professionals in rural areas. While reorientations of curricula in training institutions are necessary, other types of professional support are needed. This experience suggests that professional associations dedicated to strengthening quality of care can contribute significantly to rural practitioners' morale

Identification of Sare0718 As an Alanine-Activating Adenylation Domain in Marine Actinomycete Salinispora arenicola CNS-205

BACKGROUND: Amino acid adenylation domains (A domains) are critical enzymes that dictate the identity of the amino acid building blocks to be incorporated during nonribosomal peptide (NRP) biosynthesis. NRPs represent a large group of valuable natural products that are widely applied in medicine, agriculture, and biochemical research. Salinispora arenicola CNS-205 is a representative strain of the first discovered obligate marine actinomycete genus, whose genome harbors a large number of cryptic secondary metabolite gene clusters. METHODOLOGY/PRINCIPAL FINDINGS: In order to investigate cryptic NRP-related metabolites in S. arenicola CNS-205, we cloned and identified the putative gene sare0718 annotated "amino acid adenylation domain". Firstly, the general features and possible functions of sare0718 were predicted by bioinformatics analysis, which suggested that Sare0718 is a soluble protein with an AMP-binding domain contained in the sequence and its cognate substrate is L-Val. Then, a GST-tagged fusion protein was expressed and purified to further explore the exact adenylation activity of Sare0718 in vitro. By a newly mentioned nonradioactive malachite green colorimetric assay, we found that L-Ala but not L-Val is the actual activated amino acid substrate and the basic kinetic parameters of Sare0718 for it are K(m) = 0.1164±0.0159 (mM), V(max) = 3.1484±0.1278 (µM/min), k(cat) = 12.5936±0.5112 (min(-1)). CONCLUSIONS/SIGNIFICANCE: By revealing the biochemical role of sare0718 gene, we identified an alanine-activating adenylation domain in marine actinomycete Salinispora arenicola CNS-205, which would provide useful information for next isolation and function elucidation of the whole cryptic nonribosomal peptide synthetase (NRPS)-related gene cluster covering Sare0718. And meanwhile, this work also enriched the biochemical data of A domain substrate specificity in newly discovered marine actinomycete NRPS system, which bioinformatics prediction will largely depend on

Malonylation of GAPDH is an inflammatory signal in macrophages.

Macrophages undergo metabolic changes during activation that are coupled to functional responses. The gram negative bacterial product lipopolysaccharide (LPS) is especially potent at driving metabolic reprogramming, enhancing glycolysis and altering the Krebs cycle. Here we describe a role for the citrate-derived metabolite malonyl-CoA in the effect of LPS in macrophages. Malonylation of a wide variety of proteins occurs in response to LPS. We focused on one of these, glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In resting macrophages, GAPDH binds to and suppresses translation of several inflammatory mRNAs, including that encoding TNFα. Upon LPS stimulation, GAPDH undergoes malonylation on lysine 213, leading to its dissociation from TNFα mRNA, promoting translation. We therefore identify for the first time malonylation as a signal, regulating GAPDH mRNA binding to promote inflammation

Access to myocardial revascularization procedures: Closing the gap with time?

BACKGROUND: Early access to revascularization procedures is known to be related to a more favorable outcome in myocardial infarction (MI) patients, but access to specialized care varies widely amongst the population. We aim to test if the early gap found in the revascularization rates, according to distance between patients' location and the closest specialized cardiology center (SCC), remains on a long term basis. METHODS: We conducted a population-based cohort study using data from the Quebec's hospital discharge register (MED-ECHO). The study population includes all patients 25 years and older living in the province of Quebec, who were hospitalized for a MI in 1999 with a follow up time of one year after the index hospitalization. The main variable is revascularization (percutaneous transluminal coronary angioplasty or a coronary artery bypass graft). The population is divided in four groups depending how close they are from a SCC (<32 km, 32–64 km, 64–105 km and ≥105 km). Revascularization rates are adjusted for age and sex. RESULTS: The study population includes 11,802 individuals, 66% are men. The one-year incidence rate of MI is 244 individuals per 100,000 inhabitants. At index hospitalization, a significant gap is found between patients living close (< 32 km) to a SCC and patients living farther (≥32 km). During the first year, a gap reduction can be observed but only for patients living at an intermediate distance from the specialized center (64–105 km). CONCLUSION: The gap observed in revascularization rates at the index hospitalization for MI is in favour of patients living closer (< 32 km) to a SCC. This gap remains unchanged over the first year after an MI except for patients living between 64 and 105 km, where a closing of the gap can be noticed

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

Application of X-ray micro-computed tomography on high-speed cavitating diesel fuel flows

The flow inside a purpose built enlarged single-orifice nozzle replica is quantified using time-averaged X-ray micro-computed tomography (micro-CT) and high-speed shadowgraphy. Results have been obtained at Reynolds and cavitation numbers similar to those of real-size injectors. Good agreement for the cavitation extent inside the orifice is found between the micro-CT and the corresponding temporal mean 2D cavitation image, as captured by the high-speed camera. However, the internal 3D structure of the developing cavitation cloud reveals a hollow vapour cloud ring formed at the hole entrance and extending only at the lower part of the hole due to the asymmetric flow entry. Moreover, the cavitation volume fraction exhibits a significant gradient along the orifice volume. The cavitation number and the needle valve lift seem to be the most influential operating parameters, while the Reynolds number seems to have only small effect for the range of values tested. Overall, the study demonstrates that use of micro-CT can be a reliable tool for cavitation in nozzle orifices operating under nominal steady-state conditions