HIV-1 molecular epidemiology evidence and transmission patterns in the Middle East and North Africa

The distribution of HIV-1 subtypes in a population tracks the spread and evolution of the epidemic. This study is a systematic review of all available evidence on HIV-1 molecular epidemiology and subtype distribution in the Middle East and North Africa. Sources of data included Medline and various institutional documents and databases. In several countries, a diverse distribution of HIV-1 subtypes was observed principally reflecting travel-related exogenous exposures. A trend for a dominant HIV-1 subtype was observed in a few other settings and was often linked to HIV transmission within specific high-risk groups such as subtype A and CRF35_AD among injecting drug users and subtype C among commercial sex networks. Multiple exogenous introductions of HIV-1 variants seemed common to all countries, as observed from the high diversity in subtypes, or the high genetic divergence among any specific subtype even if predominant. In several countries though, epidemic-type clustering of specific subtypes suggests established or nascent HIV epidemics among classic core risk groups for HIV infection. HIV prevention efforts in MENA must be prioritized for these high-risk groups.     

A non-toxic ligand for voxel-based MRI analysis of plaques in AD transgenic mice

Amyloid plaques are a characteristic feature in Alzheimer's disease (AD). A novel non-toxic contrast agent is presented, Gd-DTPA-K6Aβ1–30, which is homologous to Aβ, and allows plaque detection in vivo. μMRI was performed on AD model mice and controls prior to and following intracarotid injection with Gd-DTPA-K6Aβ1–30 in mannitol solution, to transiently open the blood–brain barrier. A gradient echo T2^*-weighted sequence was used to provide 100 μm isotropic resolution with imaging times of 115 min. The scans were examined with voxel-based analysis (VBA) using statistical parametric mapping, for un-biased quantitative comparison of ligand-injected mice and controls. The results indicate that: (1) Gd-DTPA-K6Aβ1–30 is an effective, non-toxic, ligand for plaque detection when combined with VBA (p ≤ 0.01–0.001), comparing pre and post-ligand injection scans. (2) Large plaques can be detected without the use of a contrast agent and this detection co-localizes with iron deposition. (3) Smaller, earlier plaques require contrast ligand for MRI visualization. Our ligand when combined with VBA may be useful for following therapeutic approaches targeting amyloid in transgenic mouse models.     

Is there a specific abnormality of sperm morphology in men with varicoceles?

With the use of a case-control design, we have studied seminal cytology in 53 infertile men with large left varicoceles to determine whether they had a specific morphologic pattern. An equal number of infertile controls without varicoceles were matched for characteristics such as left testicular size, serum follicle-stimulating hormone levels, and sperm concentration to ensure similar degrees of testicular dysfunction. No significant difference in the morphologic patterns was observed, especially in the hallmarks of the "stress pattern": increased percentages of spermatozoa with tapering heads (1.8 +/- 2.6:1.9 +/- 4.0) and immature forms (8.1 +/- 5.4:6.4 +/- 2.9) in the varicocele and control groups, respectively. Assessment of morphologic characteristics was associated with wide errors (approximately 20% to 80%) among technicians working in the same laboratory. There does not appear to be a characteristic morphologic stress pattern in infertile men with large left varicoceles.     

Knowledge of Kidney Donation Among Care Givers in Two Tertiary Hospitals in Southwest Nigeria

One of the major challenges of kidney transplantation is shortage of kidney donors. Care givers (CGs) are potential kidney donors, but the majority of them are unwilling to donate due to inadequate knowledge on kidney donation. This study evaluated the knowledge of kidney donation and its determinants among CGs in two tertiary hospitals in Southwest Nigeria. This was a cross‐sectional study that was carried out in the Kidney Care Centre (KCC), Ondo and Babcock University Teaching Hospital (BUTH), Ilishan‐Remo using a self‐administered pretested questionnaire that assessed knowledge of kidney donation and its determinants. Pvalue of <0.05 was taken as significant. A total of 244 respondents participated in the study. The majority were below 40 years, married, and female. The proportion of respondents with adequate knowledge of kidney donation was 63.4%. More respondents from BUTH compared to KCC had adequate knowledge of kidney donation (80% vs. 46.7%, P ≤ 0.001). Similarly, the mean knowledge score was higher in respondents from BUTH (P ≤ 0.001). Factors that determined knowledge of kidney donation were female gender (AOR: 3.43, 95% CI: 1.25–9.40, P = 0.02) and social class (AOR: 1.22, 95% CI: 0.50–2.95, P ≤ 0.001). There was positive correlation between knowledge of kidney donation among the respondents from both hospitals and their willingness to donate kidneys (r = 0.439, P ≤ 0.001). Knowledge of kidney donation was better among BUTH's respondents. Gender and social class were predictors of knowledge of kidney donation. Improving knowledge of kidney donation may improve willingness to donate among the public.     

Effect of Cadmium Stress on Non-enzymatic Antioxidant and Nitric Oxide Levels in Two Varieties of Maize (<Emphasis Type="Italic">Zea mays</Emphasis>)

Cadmium (Cd) is one of the most toxic heavy metals that inhibit physiological processes of plants. Hence, the present study sought to investigate the effect of cadmium-contaminated seeds from two varieties of maize (Zea mays) on non-enzymatic antioxidant and nitric oxide levels. Seeds of yellow and white maize were exposed to different concentrations of Cd (0, 1, 3 and 5 ppm) for two weeks. The results from this study revealed that both varieties of maize bio-accumulate Cd in leaves in a dose-dependent manner. In addition, Cd exposure caused a significant (p?<?0.05) decrease in total phenolic, GSH and nitric oxide (NO) levels at the highest concentration tested when compared with control. Therefore, the observed decrease in NO and endogenous antioxidant status by Cd treatment in maize plants could suggest some possible mechanism of action for Cd-induced oxidative stress and counteracting effect of the plants against Cd toxicity.     

Quantifying cardiac‐induced brain tissue expansion using DENSE

Brain tissue undergoes viscoelastic deformation and volumetric strain as it expands over the cardiac cycle due to blood volume changes within the underlying microvasculature. Volumetric strain measurements may therefore provide insights into small vessel function and tissue viscoelastic properties. Displacement encoding via stimulated echoes (DENSE) is an MRI technique that can quantify the submillimetre displacements associated with brain tissue motion. Despite previous studies reporting brain tissue displacements using DENSE and other MRI techniques, a complete picture of brain tissue volumetric strain over the cardiac cycle has not yet been obtained. To address this need we implemented 3D cine‐DENSE at 7 T and 3 T to investigate the feasibility of measuring cardiac‐induced volumetric strain as a marker for small vessel blood volume changes. Volumetric strain over the entire cardiac cycle was computed for the whole brain and for grey and white matter tissue separately in six healthy human subjects. Signal‐to‐noise ratio (SNR) measurements were used to determine the voxel‐wise volumetric strain noise. Mean peak whole brain volumetric strain at 7 T (mean ± SD) was (4.5 ± 1.0) × 10^?4 (corresponding to a volume expansion of 0.48 ± 0.1 mL), which is in agreement with literature values for cerebrospinal fluid that is displaced into the spinal canal to maintain a stable intracranial pressure. The peak volumetric strain ratio of grey to white matter was 4.4 ± 2.8, reflecting blood volume and tissue stiffness differences between these tissue types. The mean peak volumetric strains of grey and white matter tissue were found to be significantly different (p < 0.001). The mean SNR at 7 T and 3 T of the DENSE measurements was 22.0 ± 7.3 and 7.0 ± 2.8 respectively, which currently limits a voxel‐wise strain analysis at both field strengths. We demonstrate that tissue specific quantification of volumetric strain is feasible with DENSE. This metric holds potential for studying blood volume pulsations in the ageing brain in healthy and diseased states.     

Maternal and Fetal Outcomes After Introduction of Magnesium Sulphate for Treatment of Preeclampsia and Eclampsia in Selected Secondary Facilities: A Low-Cost Intervention

The aim of this study was to evaluate whether a new low-cost strategy for the introduction of magnesium sulphate (MgSO₄) for preeclampsia and eclampsia in low-resource areas will result in improved maternal and perinatal outcomes. Doctors and midwives from ten hospitals in Kano, Nigeria, were trained on the use of MgSO₄. The trained health workers later conducted step-down trainings at their health facilities. MgSO₄, treatment protocol, patella hammer, and calcium gluconate were then supplied to the hospitals. Data was collected through structured data forms. The data was analyzed using SPSS software. From February 2008 to January 2009, 1,045 patients with severe preeclampsia and eclampsia were treated. The case fatality rate for severe preeclampsia and eclampsia fell from 20.9 % (95 % CI 18.7–23.2) to 2.3 % (95 % CI 1.5–3.5). The perinatal mortality rate was 12.3 % as compared to 35.3 % in a center using diazepam. Introduction of MgSO₄ in low-resource settings led to improved maternal and fetal outcomes in patients presenting with severe pre-eclampsia and eclampsia. Training of health workers on updated evidence-based interventions and providing an enabling environment for their practice are important components to the attainment of the Millenium Development Goals (MDG) in developing countries.     

Performance of mutation pathogenicity prediction methods on missense variants

Single nucleotide polymorphisms (SNPs) are the most common form of genetic variation in humans. The number of SNPs identified in the human genome is growing rapidly, but attaining experimental knowledge about the possible disease association of variants is laborious and time-consuming. Several computational methods have been developed for the classification of SNPs according to their predicted pathogenicity. In this study, we have evaluated the performance of nine widely used pathogenicity prediction methods available on the Internet. The evaluated methods were MutPred, nsSNPAnalyzer, Panther, PhD-SNP, PolyPhen, PolyPhen2, SIFT, SNAP, and SNPs&GO. The methods were tested with a set of over 40,000 pathogenic and neutral variants. We also assessed whether the type of original or substituting amino acid residue, the structural class of the protein, or the structural environment of the amino acid substitution, had an effect on the prediction performance. The performances of the programs ranged from poor (MCC 0.19) to reasonably good (MCC 0.65), and the results from the programs correlated poorly. The overall best performing methods in this study were SNPs&GO and MutPred, with accuracies reaching 0.82 and 0.81, respectively.