Current Zinc Intake and Risk of Diabetes and Coronary Artery Disease and Factors Associated with Insulin Resistance in Rural and Urban Populations of North India

Objective: To determine the association between current zinc intake and prevalence of coronary artery disease (CAD) and diabetes as well as factors associated with insulin resistance.

Design, Subjects and Methods: In this cross sectional survey, 3575 subjects, aged 25 to 64 years, including 1769 rural (894 men, 875 women) and 1806 urban (904 men, 902 women) subjects were studied. The survey methods included questionnaires for 7-day food intake record, physical examination, and electrocardiography using World Health Organization criteria.

Results: The prevalence of CAD, diabetes and glucose intolerance was significantly higher among subjects consuming lower intakes of dietary zinc. There was a higher prevalence of hypertension, hypertriglyceridemia and low high-density lipoprotein cholesterol levels which showed significant upward trend with lower zinc intakes. Serum lipoprotein (a) and 2-hour plasma insulin levels also were associated with low zinc intake. Multivariate logistic regression analysis after adjustment for age showed that zinc intake and CAD were inversely associated. Serum zinc (odds ratio:men 0.77, women 0.57), serum triglycerides (men 0.86, women 0.81), blood pressure (0.83 men, women 0.76), diabetes mellitus (men 0.90, women 0.85), central obesity (men 0.88, women 0.87), glucose intolerance (men 0.66, women 0.57) and low high-density lipoprotein cholesterol (men 0.72, women 0.70) were significant risk factors for CAD (explained by tertiles of zinc status) in urban subjects. These associations were not observed in rural subjects.

Conclusion: Lower consumption of dietary zinc and low serum zinc levels were associated with an increased prevalence of CAD and diabetes and several of their associated risk factors including hypertension, hypertriglyceridemia and other factors suggestive of mild insulin resistance in urban subjects.     

Automated GMP production and long-term experience in radiosynthesis of CB1 tracer [18F]FMPEP-d2

Here, we describe the development of an in-house-built device for the fully automated multistep synthesis of the cannabinoid CB₁ receptor imaging tracer (3R,5R)-5-(3-([¹⁸F]fluoromethoxy-d₂)phenyl)-3-(((R)-1-phenylethyl)amino)-1-(4-(trifluoromethyl)phenyl)pyrrolidin-2-one ([¹⁸F]FMPEP-d₂), following good manufacturing practices. The device is interfaced to a HPLC and a sterile filtration unit in a clean room hot cell. The synthesis involves the nucleophilic ¹⁸F-fluorination of an alkylating agent and its GC purification, the subsequent ¹⁸F-fluoroalkylation of a precursor molecule, the semipreparative HPLC purification of the ¹⁸F-fluoroalkylated product, and its formulation for injection. We have optimized the duration and temperature of the ¹⁸F-fluoroalkylation reaction and addressed the radiochemical stability of the formulated product. During the past 5 years (2013–2018), we have performed a total of 149 syntheses for clinical use with a 90% success rate. The activity yield of the formulated product has been 1.0 ± 0.4 GBq starting from 11 ± 2 GBq and the molar activity 600 ± 300 GBq/μmol at the end of synthesis.     

Increasing drug resistance in extensively drug-resistant tuberculosis, South Africa

We expanded second-line tuberculosis (TB) drug susceptibility testing for extensively drug-resistant Mycobacterium tuberculosis isolates from South Africa. Of 19 patients with extensively drug-resistant TB identified during February 2008-April 2009, 13 (68%) had isolates resistant to all 8 drugs tested. This resistance leaves no effective treatment with available drugs in South Africa.     

Copper-induced toxicity in aquatic macrophyte, Hydrilla verticillata: effect of pH

Copper uptake and toxicity were evaluated in Hydrilla verticillata. Its effect on lipid peroxidation, chlorophyll, protein, ascorbate, cysteine and sugars was studied at pH 6.8. Dose- and durationdependent uptake of Cu followed by a significant decrease in malondialdehyde and sugar content was found in plant tissue. Chlorophyll, ascorbic acid and protein contents were increased non-significantly up to 8, 16 and 32 þM Cu, respectively. Cysteine content was slightly increased at lower concentrations followed by a significant decline. At 80 þM Cu, plants of H. verticillata showed significant toxic effects after 168 h of exposure indicating the sensitivity of the plant to this level of Cu stress. The effect of low and high pH in combination with different concentrations of Cu was determined at 168 h of exposure. Low pH (4.5) enhanced Cu toxicity while at high pH (9.5) toxicity was considerably reduced.     

Workplace‐based assessments of junior doctors: do scores predict training difficulties?

Medical Education 2011: 45 : 1190–1198 Objectives Workplace‐based assessment (WPBA) is an increasingly important part of postgraduate medical training and its results may be used as evidence of professional competence. This study evaluates the ability of WPBA to distinguish UK Foundation Programme (FP) doctors with training difficulties and its effectiveness as a surrogate marker for deficiencies in professional competence. Methods We conducted a retrospective observational study using anonymised records for 1646 trainees in a single UK postgraduate deanery. Data for WPBAs conducted from August 2005 to April 2009 were extracted from the e‐portfolio database. These data included all scores submitted by trainees in FP years 1 and 2 on mini‐clinical evaluation exercise (mini‐CEX), case‐based discussion (CbD), direct observation of procedural skills (DOPS) and mini‐peer assessment tool (mini‐PAT) assessments. Records of trainees in difficulty, as identified by their educational supervisors, were tagged as index cases. Main outcome measures were odds ratios (ORs) for associations between mean WPBA scores and training difficulties. Further analyses by the reported aetiology of the training difficulty (health‐, conduct‐ or performance‐related) were performed. Results Of the 1646 trainees, 92 had been identified as being in difficulty. Mean CbD and mini‐CEX scores were lower for trainees in difficulty and an association was found between identified training difficulties and average scores on the mini‐CEX (OR = 0.54; p = 0.034) and CbD (OR = 0.39; p = 0.002). A receiver operator characteristic curve analysis of mean WPBA scores for diagnosing ‘in difficulty’ status yielded an area under the curve of 0.64, indicating weak predictive value. There was no statistical evidence that mean scores on DOPS and mini‐PAT assessments differed between the two groups. Conclusions Analysis of a large dataset of WPBA scores revealed significant associations between training difficulties and lower mean scores on both the mini‐CEX and CbD. Models show that using WPBA scores is, however, not a valid way of screening for trainees in difficulty. Workplace‐based assessments have value as formative assessments that prompt supervision, feedback and reflection. They should not be relied upon to certify competence and their use for such ends may reduce their effectiveness in training. Their results should be interpreted in the context of multiple other methods of assessment, with the aim of achieving a genuinely holistic and representative assessment of professional competence.     

Development of a System for Expressing Heterologous Genes in the Oral Spirochete Treponema denticola and Its Use in Expression of the Treponema pallidum flaA Gene

The present communication describes the construction of a new Escherichia coli-Treponema denticola shuttle vector based on the naturally occurring spirochete plasmid pTS1 and the expression of the heterologous T. pallidum flaA gene from the plasmid in T. denticola. This new shuttle vector system should prove useful in characterizing virulence factors from unculturable pathogenic spirochetes.     

A study of the mechanism of selenite-induced hypomethylated DNA and differentiation of Friend erythroleukemic cells

Sodium selenite is a good inducer of hemoglobin production inFriend erythroleukemic cells (FELC). At a concentration of 20µM 70-80% of the cells produce hemoglobin and the DNAis hypomethylated. What is the mechanism for sodium selenitealteration of the DNA methylation pattern? Experiments withmethionine adenosyltransferase (the enzyme that synthesizesadenosylmethionine) showed little effect of selenite on theactivity of this enzyme in vitro or in vivo. Therefore, FELCare able to synthesize S-adenosyhnethionine in the presenceof sodium selenite. When sodium selenite was added to an invitro assay for DNA methylase, the enzyme was non-competitivelyinhibited by 80% at 20 µM selenite with a K₁ of 6 µM.DNA methylase isolated from control and selenite-treated FELCwas purified through a DEAE-Sephacel column and no differencein activity was found. In the presence of selenite, DNA methylaseis very sensitive to selenite inhibition, but removal of theselenite restores activity. However, DNA synthesized by FELCgrown in the presence of selenite (no DNA methylase activity)was found to be hypomethylated. These results suggest that DNAmethylase activity is inhibited in FELC grown in the presenceof sodium selenite.