High rates of clustering of strains causing tuberculosis in Harare, Zimbabwe: a molecular epidemiological study

We examined the pattern of tuberculosis (TB) transmission (i.e., reactivation versus recent transmission) and the impact of human immunodeficiency virus (HIV) infection in Harare, Zimbabwe. Consecutive adult smear-positive pulmonary TB patients presenting to an urban hospital in Harare were enrolled. A detailed epidemiological questionnaire was completed, and tests for HIV type 1 and CD4 cell counts were performed for each patient. Molecular fingerprinting of the genomic DNA recovered from cultures of sputum was performed by two molecular typing methods: spacer oligonucleotide typing (spoligotyping) and analysis of variable number of tandem DNA repeats (VNTRs). A cluster was defined as isolates from two or more patients that shared the same spoligotype pattern or the same VNTR pattern, or both. DNA suitable for typing was recovered from 224 patients. The prevalence of HIV infection was 79%. Of 187 patient isolates (78.6%) typed by both spoligotyping and analysis of VNTRs, 147 were identified as part of a cluster by both methods. By spoligotyping alone, 84.1% of patient isolates were grouped into 20 clusters. The cluster size was generally <8 patient isolates, although three large clusters comprised 68, 25, and 23 patient isolates. A total of 89.4% of the patient isolates grouped into 12 clusters defined by analysis of VNTRs, with 2 large clusters consisting of 127 and 13 patient isolates, respectively. Thirty-six percent of patient isolates with a shared spoligotype and 17% with a shared VNTR pattern were geographically linked within Harare, but they were not linked on the basis of the patient's home district. In a multivariate analysis, there were no independent predictors of clustering, including HIV infection status. Comparison with the International Spoligotype database (Pasteur Institute, Pointe a Pitre, Guadeloupe) demonstrated that our three largest spoligotype clusters are well recognized and ubiquitous in Africa. In this epidemiologically well characterized urban population with a high prevalence of HIV infection, we identified a very high level of strain clustering, indicating substantial ongoing recent TB transmission. Geographic linkage could be detected in a proportion of these clusters. A small group of actively circulating strains accounted for most of the cases of TB transmission.     

Glycosylated hemoglobin-defined prediabetes and cardiovascular risk markers in rural India: the Nallampatti noncommunicable disease study

The aim of this study is to assess the associations between glycosylated hemoglobin in the prediabetes range and cardiovascular risk markers in a rural South Indian population. Local Ethics Committee approval and informed consent was obtained from all participants. Inclusion criteria were participants, aged ≥20 and ≤85 years, from Nallampatti, a classical farming village from Tamil Nadu State, India. Those with known history of diabetes were excluded from this analysis. All participants were administered a detailed questionnaire, had anthropometric measurements including height, weight, and waist circumference. Bloods were drawn for random blood glucose, glycosylated hemoglobin, nonfasting lipid profile, cystatin C, uric acid, and hemoglobin. All participants had carotid intima thickness done by high-resolution B-mode carotid ultrasound. Progressive hyperglycemia across the glucose tolerance continuum based on glycosylated hemoglobin levels in a rural South Indian population seems to be associated with worsening cardiovascular risk markers. A cut-off value of ≥6% (42 mmol/mol) seems to herald a much more significant increase in such markers. Long-term follow-up of this cohort for incident cardiovascular disease will help to substantiate the associations between glycosylated hemoglobin levels within the prediabetes range and cardiovascular disease in an Indian population. Evidence-based race-specific criteria for diagnosis of prediabetes and diabetes are the need of the hour for risk stratification and appropriate management.     

Hierarchically self-assembled NiCo2O4 nanopins as a high-performance supercapacitor cathodic material: a morphology controlled study

In this study, 3D hierarchically self-assembled NiCo₂O₄ nanopins were synthesized by a morphology controlled hydrothermal method. Structure, morphology, and composition of the samples were investigated using FT-IR, XRD, EDS, and SEM methods. Electrochemical tests such as cyclic voltammetry (CV) and galvanostatic charge/discharge (GCD) studies were done in a three-electrode system with 1.0 M Na₂SO₄ solution as the electrolyte for the supercapacitive study of the samples on a carbon paste electrode for the first time. The results confirmed the high-performance supercapacitive behavior of the dense nanostructure and acceptable stability during the charge–discharge cycle. The specific capacitance for the dense self-organized nanopins was calculated using a galvanostatic charge/discharge experiment which gave 2168 F g⁻¹ at a current density of 5 A g⁻¹.

In this study, 3D hierarchically self-assembled NiCo₂O₄ nanopins were synthesized by a morphology controlled hydrothermal method.     

Emblica officinalis improves glycemic status and oxidative stress in STZ induced type 2 diabetic model rats

Objective:To evaluate the antidiabetic and antioxidant potential of Emblica officinalis(E.officinalis)fruit on normal and type 2 diabetic rats.Methods:Type 2 diabetes was induced into the male Long-Evans rats.The rats were divided into nine groups including control groups receiving water,type 2 diabetic controls,type 2 diabetic rats treated with glibenclamide(T2GT)and type 2diabetic rats treated with aqueous extract of fruit pulp of E.officinalis.They were fed orally for8 weeks with a single feeding.Blood was collected by cutting the tail tip on 0 and 28 days and by decapitation on 56 day.Packed red blood cells and serum were used for evaluating different biochemical parameters.Results:Four weeks administration of aqueous extract of E.officinalis improved oral glucose tolerance in type 2 rats and after 8 weeks it caused significant(P0.007)reduction in fasting serum glucose level compared to 0 day.Triglycerides decreased by 14%but there was no significant change in serum ALT,creatinine,cholesterol and insulin level in any group.Furthermore,reduced erythrocyte malondialdehyde level showed no significant change(P0.07)but reduced glutathione content was found to be increased significantly(P0.05).Conclusions:The aqueous extract of E.officinalis has a promising antidiabetic and antioxidant properties and may be considered for further clinical studies in drug development.     

Analysis of CYP2D6 genotype and response to tetrabenazine

Tetrabenazine is effective in the treatment of the chorea associated with Huntington disease and other hyperkinetic movement disorders. Following oral administration, tetrabenazine is hepatically transformed into 2 active metabolites that are CYP2D6 substrates. There are 4 CYP2D6 genotypes: poor metabolizers, intermediate metabolizers, extensive metabolizers, and ultrarapid metabolizers. CYP2D6 genotyping was performed on sequential subjects treated with tetrabenazine, but results were not known at the time of titration. Duration of titration to a stable dose, total daily dose, response rating scores, and adverse events were retrospectively collected and subsequently analyzed. Of 127 patients, the majority (n = 100) were categorized as extensive metabolizers, 14 as intermediate metabolizers, 11 as poor metabolizers, and 2 as ultrarapid metabolizers. Ultrarapid metabolizer patients needed a longer titration (8 vs 3.3, 4.4, and 3 weeks, respectively; P < .01) to achieve optimal benefit and required a higher average daily dose than the other patients, but this difference did not reach statistical significance. The treatment response was less robust in the intermediate metabolizer group when compared with the extensive metabolizer patients (P = .013), but there were no statistically significant differences between the various groups with regard to adverse effects. Our findings demonstrate that, aside from the need for a longer titration in the ultrarapid metabolizers, there are no distinguishing features of patients with various CYP2D6 genotypes, and therefore the current recommendation to systematically genotype all patients prescribed more than 50 mg/day of tetrabenazine should be reconsidered. © 2012 Movement Disorder Society     

A multi-institutional analysis of clinical outcomes and patterns of care of 1p/19q codeleted oligodendrogliomas treated with adjuvant or salvage radiation therapy

Journal of Neuro-Oncology - Practice patterns vary for adjuvant treatment of 1p/19q-codeleted oligodendroglioma patients. This study evaluates the outcomes of adjuvant (aRT) versus salvage...     

Living-related liver transplantation for Crigler-Najjar syndrome in Saudi Arabia

OBJECTIVE: To analyse the outcome of six children with Crigler-Najjar syndrome type I (CNS-I) and report the first three living-related liver transplants for this syndrome in Saudi Arabia and the Middle East. SETTINGS: To review the medical records of six children suffering from CNS-I, three of whom underwent living-related liver transplantation (LRLT) between 22 November 1998 and January 2001. MAIN RESULTS: Living-related liver transplantation was performed in three children with a pre-transplant unconjugated bilirubin level of 362, 381 and 502 micromol/L, respectively, despite daily phototherapy of >or= 12 h. Two of the transplanted children developed acute hepatocellular rejection, which was successfully treated with methylprednisolone pulse therapy. One tested cytomegalovirus positive (using the PP65 method), but showed no signs of clinical infection and was treated with ganciclovir. One patient had a biliary leak at the cut surface of the graft which was surgically repaired. Post-operative bilirubin levels returned to normal in all three transplanted children and no further phototherapy was required. One patient, who was not transplanted but received phototherapy, developed severe neurological damage prior to the start of our living-related liver transplant programme with a bilirubin level of 450 micromol/L, her sister is still awaiting transplantation. A 14-yr-old child with a bilirubin level of 420 micromol/L is presently undergoing phototherapy whilst awaiting orthotopic liver transplantation because of the lack of a suitable living-related donor. Six siblings of the six children in our series were reported dead by the families. CONCLUSION: Crigler-Najjar syndrome type I is a relatively common disease in Saudi Arabia for which LRLT is a curative treatment when performed at an early age before the development of kernicterus and neurological deficiency. In countries where there is a severe shortage of cadaveric organs, as is the case in Saudi Arabia, LRLT is the optimum treatment modality for this syndrome.