Factors associated with HIV infection in married or cohabitating couples in Kenya: results from a nationally representative study

Background

In order to inform prevention programming, we analyzed HIV discordance and concordance within couples in the Kenya AIDS Indicator Survey (KAIS) 2007.

Methods

KAIS was a nationally representative population-based sero-survey that examined demographic and behavioral indicators and serologic testing for HIV, HSV-2, syphilis, and CD4 cell counts in 15,853 consenting adults aged 15–64 years. We analyzed interview and blood testing data at the sexual partnership level from married or cohabitating couples. Multivariable regression models were used to identify factors independently associated with HIV discordant and concordant status.

Results

Of 3256 couples identified in the survey, 2748 (84.4%) had interview and blood testing data. Overall, 3.8% of couples were concordantly infected with HIV, and in 5.8% one partner was infected, translating to 338,000 discordant couples in Kenya. In 83.6% of HIV-infected Kenyans living in married or cohabitating couples neither partner knew their HIV status. Factors independently associated with HIV-discordance included young age in women (AOR 1.5, 95% CI: 1.2–1.8; p<0.0001), increasing number of lifetime sexual partners in women (AOR 1.5, 95% CI: 1.3–1.8; p<0.0001), HSV-2 infection in either or both partners (AOR 4.1, 95% CI: 2.3–7.2; p<0.0001), and lack of male circumcision (AOR 1.6, 95% CI: 1.0–2.5; p = 0.032). Independent factors for HIV-concordance included HSV-2 infection in both partners (AOR 6.5, 95% CI: 2.3–18.7; p = 0.001) and lack of male circumcision (AOR 1.8, 95% CI: 1.0–3.3; p = 0.043).

Conclusions

Couple prevention interventions should begin early in relationships and include mutual knowledge of HIV status, reduction of outside sexual partners, and promotion of male circumcision among HIV-uninfected men. Mechanisms for effective prevention or suppression of HSV-2 infection are also needed.     

In situ assessment of erythrocyte membrane properties during cold storage

Membrane fluidity and overall protein secondary structure of human erythrocytes were studied in situ using Fourier transform infrared spectroscopy (FTIR). Erythrocyte membranes were found to have weakly cooperative phase transitions at 14 degrees C and at 34 degrees C, which were tentatively assigned to the melting of the inner membrane leaflet and the sphingolipid rich outer leaflet, respectively. Cholesterol depletion by methyl-beta-cyclodextrin (MbetaCD) resulted in a large increase in the cooperativity of these transitions, and led to the appearance of another phospholipid transition at 25 degrees C. Multiple, sharp membrane phase transitions were observed after 5 days cold storage (4 degrees C ), which indicated phase separation of the membrane lipids. Using fluorescence microscopy, it was determined that the lipid probe 1,1'-dioctadecyl-3,3,3',3-tetramethyl-indocarbocyanine perchlorate (dil-C18) remained homogeneously distributed in the erythrocyte membrane during cold storage, suggesting that lipid domains were below the resolution limit of the microscope. Using thin layer chromatography, changes in the membrane lipid composition were detected during cold storage. By contrast, assessment of the amide-II band with FTIR showed that the overall protein secondary structure of haemoglobin was stable during cold storage.     

Mapping of Bacterial Biofilm Local Mechanics by Magnetic Microparticle Actuation

Most bacteria live in the form of adherent communities forming three-dimensional material anchored to artificial or biological surfaces, with profound impact on many human activities. Biofilms are recognized as complex systems but their physical properties have been mainly studied from a macroscopic perspective. To determine biofilm local mechanical properties, reveal their potential heterogeneity, and investigate their relation to molecular traits, we have developed a seemingly new microrheology approach based on magnetic particle infiltration in growing biofilms. Using magnetic tweezers, we achieved what was, to our knowledge, the first three-dimensional mapping of the viscoelastic parameters on biofilms formed by the bacterium Escherichia coli. We demonstrate that its mechanical profile may exhibit elastic compliance values spread over three orders of magnitude in a given biofilm. We also prove that heterogeneity strongly depends on external conditions such as growth shear stress. Using strains genetically engineered to produce well-characterized cell surface adhesins, we show that the mechanical profile of biofilm is exquisitely sensitive to the expression of different surface appendages such as F pilus or curli. These results provide a quantitative view of local mechanical properties within intact biofilms and open up an additional avenue for elucidating the emergence and fate of the different microenvironments within these living materials.     

Loss of STOP Protein Impairs Peripheral Olfactory Neurogenesis

Background

STOP (Stable Tubulin-Only Polypeptide) null mice show behavioral deficits, impaired synaptic plasticity, decrease in synaptic vesicular pools and disturbances in dopaminergic transmission, and are considered a neurodevelopmental model of schizophrenia. Olfactory neurons highly express STOP protein and are continually generated throughout life. Experimentally-induced loss of olfactory neurons leads to epithelial regeneration within two months, providing a useful model to evaluate the role played by STOP protein in adult olfactory neurogenesis.

Methodology/Principal Findings

Immunocytochemistry and electron microscopy were used to study the structure of the glomerulus in the main olfactory bulb and neurogenesis in the neurosensorial epithelia. In STOP null mice, olfactory neurons showed presynaptic swellings with tubulovesicular profiles and autophagic-like structures. In olfactory and vomeronasal epithelia, there was an increase in neurons turnover, as shown by the increase in number of proliferating, apoptotic and immature cells with no changes in the number of mature neurons. Similar alterations in peripheral olfactory neurogenesis have been previously described in schizophrenia patients. In STOP null mice, regeneration of the olfactory epithelium did not modify these anomalies; moreover, regeneration resulted in abnormal organisation of olfactory terminals within the olfactory glomeruli in STOP null mice.

Conclusions/Significance

In conclusion, STOP protein seems to be involved in the establishment of synapses in the olfactory glomerulus. Our results indicate that the olfactory system of STOP null mice is a well-suited experimental model (1) for the study of the mechanism of action of STOP protein in synaptic function/plasticity and (2) for pathophysiological studies of the mechanisms of altered neuronal connections in schizophrenia.     

Chromium (VI) Can Activate and Impair Antioxidant Defense System

The changes in glutathione-dependent cycle enzymes and catalase activities under Cr(VI)-induced oxidative stress were investigated in two distinct cell lines: L-41−human epithelial-like cells and HLF−fetal human diploid lung fibroblasts, which differ in tissue origin, proliferation, and antioxidant enzymes activities. The chromium concentrations from 1 to 5 μM cause nontoxic effects and activate antioxidant enzymes to overcome oxidative stress. In spite of some differences in the endogenous antioxidant activities, both cell lines reveal the same range of toxic concentrations (20–30 μM). The irreversible inhibition of glutathione-dependent antioxidant enzymes develops under toxic concentrations and serves as a marker of toxicity. The endogenous antioxidant activity influences time-dependent expression of Cr(VI) toxicity and the dynamics of antioxidant enzymes activity under nontoxic conditions. The cell antioxidant defense system is an important marker of the cell adaptive capacity under nontoxic and toxic conditions.     

Percoll centrifugation eliminates mold contaminants from cell cultures

This work was supported by a grant and research associateship to N.A. from the Medical Research Council of Canada and the National Cancer Institute of Canada.     

Rescue of Mtp siRNA-induced hepatic steatosis by DGAT2 siRNA silencing

Microsomal triglyceride transfer protein (Mtp) inhibitors represent a novel therapeutic approach to lower circulating LDL cholesterol, although therapeutic development has been hindered by the observed increase in hepatic triglycerides and liver steatosis following treatment. Here, we used small interfering RNAs (siRNA) targeting Mtp to achieve target-specific silencing to study this phenomenon and to determine to what extent liver steatosis is induced by changes in Mtp expression. We observed that Mtp silencing led to a decrease in many genes involved in hepatic triglyceride synthesis. Given the role of diacylglycerol O-acyltransferase 2 (Dgat2) in regulating hepatic triglyceride synthesis, we then evaluated whether target-specific silencing of both Dgat2 and Mtp were sufficient to attenuate Mtp silencing-induced liver steatosis. We showed that the simultaneous inhibition of Dgat2 and Mtp led to a decrease in plasma cholesterol and a reduction in the accumulation of hepatic triglycerides caused by the inhibition of Mtp. Collectively, these findings provide a proof-of-principle for a triglyceride synthesis/Mtp inhibitor combination and represent a potentially novel approach for therapeutic development in which targeting multiple pathways can achieve the desired response.