Bi(OTf)3-, TfOH-, and TMSOTf-Mediated, One-Pot Epoxide Rearrangement, Addition, and Intramolecular Silyl-Modified Sakurai (ISMS) Cascade toward Dihydropyrans: Comparison of Catalysts and Role of Bi(OTf)3

Catalytic quantities of bismuth(III) triflate efficiently initiate the rearrangement of epoxides to aldehydes, which subsequently react with (Z)-δ-hydroxyalkenylsilanes to afford 2,6-disubstituted 3,6-dihydro-2H-pyrans. Isolated yields of desired products using Bi(OTf)3 were compared with yields obtained when the reactions were run with TfOH and TMSOTf in the presence and absence of several additives. These studies, as well as NMR spectroscopic analyses, indicate an initial Lewis acid/base interaction between Bi(OTf)3 and substrates providing TfOH in situ

The effect of selective beta1-blockade on EMG signal characteristics during progressive endurance exercise

This study analysed the effect of selective b1- blockade on neuromuscular recruitment characteristics during progressive endurance exercise. Ten healthy subjects ingested a selective b1-blocker, acebutolol (200 mg b.d.), for 7 days (for one of two cycling trials), with a 10-day wash-out period between trials. On the last day of acebutolol ingestion subjects performed three successive 15-min rides at 30%, 50% and 70% of their peak power output and then cycled at increasing (15 W min-1) work rates to exhaustion. Force output, heart rate, submaximal V_O2, rate of perceived exertion (RPE), electromyographic (EMG) data and blood lactate were captured during the cycling activity. Peak work rate [270 (111) W vs 197 (75) W, CON vs BETA, P<0.01], time to exhaustion [49.7 (23.2) min vs 40.3 (23.7) min, CON vs BETA, P <0.05] and heart rate [mean, for the full ride 135.5 (38.3) beats min-1 vs 111.5 (30.0) beats min-1 CON vs BETA, P <0.05] were significantly lower for the group who ingested b1-blockade (BETA) compared to the control group (CON). Although not significant, submaximal V_O2 was reduced in BETA during the ride, while RPE was significantly higher during the ride for BETA (P <0.01). Mean integrated electromyography was higher in the BETA group although these differences were not significant. Mean power frequency values of the BETA group showed a significant (P <0.05) shift to the upper end of the spectrum in comparison to the control group. Lactate values [11.7 (3.5) mmol.l-1 vs 7.1 (4.1) mmol.l-1 CON vs BETA] were significantly lower (P <0.05) at exhaustion in BETA. Significant reductions in cycling performance were found when subjects ingested b1- blockers. This study has shown significant shifts to the upper end of the EMG frequency spectrum after b1- blocker ingestion, which could be caused by a change in neuromuscular recruitment strategy to compensate for the impaired submaximal exercise performance

NRP2 as an Emerging Angiogenic Player; Promoting Endothelial Cell Adhesion and Migration by Regulating Recycling of α5 Integrin.

Angiogenesis relies on the ability of endothelial cells (ECs) to migrate over the extracellular matrix via integrin receptors to respond to an angiogenic stimulus. Of the two neuropilin (NRP) orthologs to be identified, both have been reported to be expressed on normal blood and lymphatic ECs, and to play roles in the formation of blood and lymphatic vascular networks during angiogenesis. Whilst the role of NRP1 and its interactions with integrins during angiogenesis has been widely studied, the role of NRP2 in ECs is poorly understood. Here we demonstrate that NRP2 promotes Rac-1 mediated EC adhesion and migration over fibronectin (FN) matrices in a mechanistically distinct fashion to NRP1, showing no dependence on β3 integrin (ITGB3) expression, or VEGF stimulation. Furthermore, we highlight evidence of a regulatory crosstalk between NRP2 and α5 integrin (ITGA5) in ECs, with NRP2 depletion eliciting an upregulation of ITGA5 expression and disruptions in ITGA5 cellular organization. Finally, we propose a mechanism whereby NRP2 promotes ITGA5 recycling in ECs; NRP2 depleted ECs were found to exhibit reduced levels of total ITGA5 subunit recycling compared to wild-type (WT) ECs. Our findings expose NRP2 as a novel angiogenic player by promoting ITGA5-mediated EC adhesion and migration on FN

A Randomized Controlled Double Blind Trial of Ciclosporin versus Prednisolone in the Management of Leprosy Patients with New Type 1 Reaction, in Ethiopia.

BACKGROUND: Leprosy Type 1 (T1R) reactions are immune-mediated events leading to nerve damage and preventable disability affecting hands, feet and eyes. Type 1 Reactions are treated with oral corticosteroids. There is little evidence on alternative treatments for patients who do not respond to steroids or experience steroid adverse effects. We report the results of a randomized controlled trial testing the efficacy and adverse effect profile of ciclosporin and prednisolone (CnP) in comparison to prednisolone only (P) in patients with new T1R in Ethiopia. Ciclosporin is a potent immunosuppressant. Outcomes were measured using a clinical severity score, recurrence rate, adverse events and quality of life. RESULTS: Seventy three patients with new T1R were randomized to receive CnP or P for 20 weeks. Recovery rates in skin signs was similar in both groups (91% vs 88%). Improvements in nerve function both, new and old, sensory (66% vs 49%) and motor (75% vs 74%) loss were higher (but not significantly so) in the patients on CnP. Recurrences rates of T1R (85%) were high in both groups, and recurrences occurred significantly earlier (8 weeks) in patients CnP, who needed 10% more additional prednisolone. Serious major and minor adverse events rates were similar in patients in the two treatment arms of the study. Both groups had a significant improvement in their quality of life after the study, measured by the SF-36. CONCLUSIONS: This is the first double-blind RCT assessing ciclosporin, in the management of T1R in Africa. Ciclosporin could be a safe alternative second-line drug for patients with T1R who are not improving with prednisolone or are experiencing adverse events related to prednisolone. This study illustrates the difficulty in switching off leprosy inflammation. Better treatment agents for leprosy patients with reactions and nerve damage are needed

Changes in PPARδ Protein Content following Acute Aerobic Exercise in Human Vastus Lateralis Muscle.

PPARδ is a transcription factor which functions in the regulation of lipid and glucose metabolism, and may be implicated as a therapeutic target for several metabolic diseases. Exercise training has previously been shown to increase PPARδ protein content, but the response of PPARδ to acute exercise is not yet understood. PURPOSE: To explore changes in PPARδ protein content following an acute bout of aerobic exercise in untrained obese adults. METHODS: 8 men and 4 women participated in the study. Subjects’ mean age, weight, VO2MAX (Bruce treadmill GXT), and body composition (DEXA) were 44 yr, 93.2 kg, 28.2 mL/kg/min, and 40.5% body fat, respectively. Subjects were asked to refrain from exercise for 1 week prior to the experiment and to maintain normal dietary habits during the study. Muscle biopsies were obtained from the vastus lateralis 3 days prior to acute exercise and again 24 hours after exercise. Subjects were exercised on a motorized treadmill at 70% VO2MAX for a target duration of 400kcal energy expenditure during the exercise session. PPARδ protein content in biopsied tissue was determined by Western blot analysis. Data were analyzed by repeated measures ANOVA and expressed as means ± standard error. RESULTS: PPARδ content was enhanced 24 hours following acute exercise in previously untrained, obese adults (unexercised 1.54±0.38 vs. exercised 2.30±0.39 arbitrary units, P\u3c0.05). Gel mobility shift indicated no difference in activity of PPARδ (phosphorylated: total) following exercise (unexercised 0.36±0.03 vs. exercised 0.34±0.04). CONCLUSION: Our study shows that PPARδ expression is enhanced in untrained, obese adults following a single bout of aerobic exercise with no relative change in phosphorylation of PPARδ. These data indicate that acute exercise plays a role in the expression of PPARδ. Funding for this research was provided by HydroWorx International, Inc., the Sydney & J.L. Huffines Institute for Sports Medicine and Human Performance at Texas A&M University and The Texas Chapter of The American College of Sports Medicin

Macrolide antibiotics for non-cystic fibrosis bronchiectasis

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To determine the impact of macrolide antibiotics in the treatment of adults and children with non-cystic fibrosis bronchiectasis

Aquatic Treadmill Training Reduces Blood Pressure Reactivity to Acute Graded Exercise in Previously Sedentary Adults

Endurance exercise may reduce blood pressure and improve vasodilatory capacity thereby blunting the hypertensive response to stress. To test the efficacy of a novel model of low-impact endurance training, the aquatic-based treadmill (ATM), to improve blood pressure parameters, we recruited 60 sedentary adults and randomized to 12-weeks of either ATM (n = 36 [19 men, 17 women] , 41±2 yr, 173.58 ±1.58cm, 93.19 ±3.15kg) or land-based treadmill (LTM, n = 24 [11 men, 13 women], 42 ±2yr, 170.39 ±1.94cm, 88.14 ±3.6kg) training; 3sessions·wk-1, progressing to 500 kcal·session-1, 85% VO2max. The maximal Bruce treadmill test protocol was performed before and after training with blood pressures measured prior to, at the end of each stage, and for 5 minutes following exercise testing. Twelve subjects (5 ATM, 7 LTM) volunteered for biopsies of the vastus lateralis before and after training, and muscle samples were assessed for eNOS content. Blood pressure data were analyzed using group by training ANCOVA repeated across training, α = 0.05. Data obtained from muscle sample analysis were analyzed using group by training ANOVA repeated across training α = 0.05. Training reduced systolic blood pressure (9- 18.2mmHg), diastolic blood pressure (3.2-8.1 mmHg), mean arterial pressure (4.8-8.3mmHg), pulse pressure (7.5-15mmHg), and rate pressure product (1.8-3.9 bpm·mm Hg·103) during exercise stress and recovery in the ATM group, but not in the LTM group. Additionally, the ATM group, but not the LTM group, displayed a 31% increase in skeletal muscle eNOS content following training. Both groups improved VO2max (+3.6mL O2·kg-1·min-1), but resting blood pressure was not changed following training. These data support the use of ATM training as a novel therapeutic modality to combat hypertension

Power transformer dissolved gas analysis through Bayesian networks and hypothesis testing

Accurate diagnosis of power transformers is critical for the reliable and cost-effective operation of the power grid. Presently there are a range of methods and analytical models for transformer fault diagnosis based on dissolved gas analysis. However, these methods give conflicting results and they are not able to generate uncertainty information associated with the diagnostics outcome. In this situation it is not always clear which model is the most accurate. This paper presents a novel multiclass probabilistic diagnosis framework for dissolved gas analysis based on Bayesian networks and hypothesis testing. Bayesian network models embed expert knowledge, learn patterns from data and infer the uncertainty associated with the diagnostics outcome, and hypothesis testing aids in the data selection process. The effectiveness of the proposed framework is validated using the IEC TC 10 dataset and is shown to have a maximum diagnosis accuracy of 88.9%