Hyperhomocysteinemia and Low Folate and Vitamin B12 Are Associated with Vascular Dysfunction and Impaired Nitric Oxide Sensitivity in Morbidly Obese Patients.

There is a high prevalence of hyperhomocysteinemia that has been linked to high cardiovascular risk in obese individuals and could be attributed to poor nutritional status of folate and vitamin B12. We sought to examine the association between blood homocysteine (Hcy) folate, and vitamin B12 levels and vascular dysfunction in morbidly obese adults using novel ex vivo flow-induced dilation (FID) measurements of isolated adipose tissue arterioles. Brachial artery flow-mediated dilation (FMD) was also measured. Subcutaneous and visceral adipose tissue biopsies were obtained from morbidly obese individuals and non-obese controls. Resistance arterioles were isolated in which FID, acetylcholine-induced dilation (AChID), and nitric oxide (NO) production were measured in the absence or presence of the NO synthase inhibitor, L-NAME, Hcy, or the superoxide dismutase mimetic, TEMPOL. Our results demonstrated that plasma Hcy concentrations were significantly higher, while folate, vitamin B12, and NO were significantly lower in obese subjects compared to controls. Hcy concentrations correlated positively with BMI, fat %, and insulin levels but not with folate or vitamin B12. Brachial and arteriolar vasodilation were lower in obese subjects, positively correlated with folate and vitamin B12, and inversely correlated with Hcy. Arteriolar NO measurements and sensitivity to L-NAME were lower in obese subjects compared to controls. Finally, Hcy incubation reduced arteriolar FID and NO sensitivity, an effect that was abolished by TEMPOL. In conclusion, these data suggest that high concentrations of plasma Hcy and low concentrations of folate and vitamin B12 could be independent predictors of vascular dysfunction in morbidly obese individuals

Association of the serum chemerin level with the development of diabetic retinopathy in patients with type 1 diabetes mellitus

Background: In patients with type 2 diabetes mellitus, the development of diabetic retinopathy (DR) correlates positively with elevated serum chemerin levels. This study was aimed at investigating the probable association between the serum chemerin level and the development of DR in patients with type 1 diabetes mellitus (T1DM). Methods: In this cross-sectional study, we included Egyptians and classified them into four groups: group 1, including healthy individuals; group 2, including patients with T1DM without DR; group 3, including patients with T1DM with non-proliferative DR (NPDR); and group 4, including patients with T1DM with proliferative DR (PDR). The assessment included best-corrected distance visual acuity assessment, slit-lamp biomicroscopy, funduscopy, fundus fluorescein angiography, and macular ocular coherence tomography. Fasting blood samples were obtained from all participants to measure serum chemerin, glycated hemoglobin (HbA1c), total cholesterol, triglyceride, and creatinine levels. Serum chemerin levels were compared among the groups, and their correlations with age, duration of diabetes, HbA1c, total cholesterol, triglyceride, and creatinine levels were analyzed. Results: We recruited 209 participants, including 46 healthy individuals in group 1, 52 patients (T1DM and no DR) in group 2, 61 patients (T1DM and NPDR) in group 3, and 50 patients (T1DM and PDR) in group 4, with comparable mean ages and sex ratios among groups. The diabetes duration, body mass index, HbA1c, total cholesterol, triglyceride, and serum chemerin levels differed significantly among the groups (all P < 0.001), whereas the creatinine level did not (P > 0.05). The serum chemerin level was significantly higher in group 4 than in groups 3 and 2, in group 3 than in group 2, and in groups 3 and 4 than in group 1 (all P < 0.001). However, it was comparable between groups 1 and 2 (P > 0.05). It correlated with the duration of T1DM and HbA1c, total cholesterol, triglyceride, and creatinine levels but not with age. Conclusions: Patients with T1DM with DR showed higher serum chemerin levels than those with T1DM without DR or healthy individuals. Serum chemerin levels were higher in those with PDR than in those with NPDR. Thus, serum chemerin levels are a potential biomarker of the development and severity of DR in patients with T1DM. Nevertheless, future diagnostic accuracy studies are required to confirm these potential applications

World scientists’ warnings into action, local to global

‘We have kicked the can down the road once again – but we are running out of road.’ – Rachel Kyte, Dean of Fletcher School at Tufts University. We, in our capacities as scientists, economists, governance and policy specialists, are shifting from warnings to guidance for action before there is no more ‘road.’ The science is clear and irrefutable; humanity is in advanced ecological overshoot. Our overexploitation of resources exceeds ecosystems’ capacity to provide them or to absorb our waste. Society has failed to meet clearly stated goals of the UN Framework Convention on Climate Change. Civilization faces an epochal crossroads, but with potentially much better, wiser outcomes if we act now. What are the concrete and transformative actions by which we can turn away from the abyss? In this paper we forcefully recommend priority actions and resource allocation to avert the worst of the climate and nature emergencies, two of the most pressing symptoms of overshoot, and lead society into a future of greater wellbeing and wisdom. Humanity has begun the social, economic, political and technological initiatives needed for this transformation. Now, massive upscaling and acceleration of these actions and collaborations are essential before irreversible tipping points are crossed in the coming decade. We still can overcome significant societal, political and economic barriers of our own making. Previously, we identified six core areas for urgent global action – energy, pollutants, nature, food systems, population stabilization and economic goals. Here we identify an indicative, systemic and time-limited framework for priority actions for policy, planning and management at multiple scales from household to global. We broadly follow the ‘Reduce-Remove-Repair’ approach to rapid action. To guide decision makers, planners, managers, and budgeters, we cite some of the many experiments, mechanisms and resources in order to facilitate rapid global adoption of effective solutions. Our biggest challenges are not technical, but social, economic, political and behavioral. To have hope of success, we must accelerate collaborative actions across scales, in different cultures and governance systems, while maintaining adequate social, economic and political stability. Effective and timely actions are still achievable on many, though not all fronts. Such change will mean the difference for billions of children and adults, hundreds of thousands of species, health of many ecosystems, and will determine our common future

Alternative Routes for a Proposed Nigerian Superhighway to Limit Damage to Rare Ecosystems and Wildlife

The Cross River State Government in Nigeria is proposing to construct a ‘‘Cross River Superhighway’’ that would bisect critical remaining areas of tropical rainforest in south eastern Nigeria. We offer and evaluate two alternative routes to the superhighway that would be less damaging to forests, protected areas, and biological diversity. The first alternative we identified avoids intact forests entirely while seeking to benefit agriculture and existing settlements. The second alternative also avoids intact forests while incorporating existing paved and unpaved roads to limit construction costs. As currently proposed, the superhighway would be 260 km long, would intersect 115 km of intact forests or protected areas, and would cost an estimated ～US$2.5 billion to construct. Alternative Routes 1 and 2 are only slightly longer (～290 and ～353 km, respectively) and have markedly lower estimated construction costs (～US$0.92 billion). Furthermore, the alternative routes would have negligible impacts on forests and protected areas and would be better aligned to benefit local communities and agriculture. We argue that alternative routings such as those we examined here could markedly reduce the economic and environmental costs, and potentially increase the socioeconomic benefits, for the proposed Cross River Superhighway

Utility of certain nucleophilic aromatic substitution reactions for the assay of pregabalin in capsules

<p>Abstract</p> <p>Background</p> <p>Pregabalin (PG) is an anticonvulsant, analgesic and anxiolytic drug. A survey of the literature reveals that all the reported spectrophotometric methods are either don't offer high sensitivity, need tedious extraction procedures, recommend the measurement of absorbance in the near UV region where interference most probably occurs and/or use non specific reagent that don't offer suitable linearity range.</p> <p>Results</p> <p>Two new sensitive and simple spectrophotometric methods were developed for determination of pregabalin (PG) in capsules. Method (I) is based on the reaction of PG with 1,2-naphthoquinone-4-sulphonate sodium (NQS), yielding an orange colored product that was measured at 473 nm. Method (II) is based on the reaction of the drug with 2,4-dinitrofluorobenzene (DNFB) producing a yellow product measured at 373 nm. The different experimental parameters affecting the development and stability of the reaction product in methods (I) and (II) were carefully studied and optimized. The absorbance-concentration plots were rectilinear over the concentration ranges of 2-25 and 0.5-8 μg mL^-1for methods (I) and (II) respectively. The lower detection limits (LOD) were 0.15 and 0.13 μg mL^-1and the lower quantitation limits (LOQ) were 0.46 and 0.4 μg mL^-1for methods (I) and (II) respectively.</p> <p>Conclusion</p> <p>The developed methods were successfully applied to the analysis of the drug in its commercial capsules. The mean percentage recoveries of PG in its capsule were 99.11 ± 0.98 and 100.11 ± 1.2 (n = 3). Statistical analysis of the results revealed good agreement with those given by the comparison method. Proposals of the reaction pathways were postulated.</p

Experience with tacrolimus in children with steroid-resistant nephrotic syndrome

Children with steroid-resistant nephrotic syndrome (SRNS) are at risk of developing renal failure. We report here the results of a single-center retrospective observational study of the remission rate in pediatric patients with SNRS receiving tacrolimus. Serial renal biopsies from children on tacrolimus therapy were evaluated for tubulointerstitial fibrosis and transforming growth factor-β immunostaining. Of the 16 children with SRNS, 15 went into complete remission after a median of 120 days of therapy. Nine children were able to stop steroids, while the others were on tapering doses. Forty-seven percent had relapses, most of which were steroid-responsive. Serial renal biopsies were obtained from seven children after a median treatment duration of 24 months; two of these children had increased tubulointerstitial fibrosis and four showed increased transforming growth factor-β tissue staining. Children with worsening histological findings were younger. There was no significant association between tacrolimus exposure and biopsy changes, although the average trough level was higher in those children with worsening histological findings. In conclusion, tacrolimus may be a safe and effective alternative agent for inducing remission in children with SRNS. However, caution needs to be taken when prescribing this agent due to its narrow therapeutic index. Serial renal biopsies are necessary to check for subclinical nephrotoxicity, especially in younger children and those with higher trough levels

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO