Increasing skeletal muscle carnitine availability does not alter the adaptations to high-intensity interval training

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Accepted manuscript online: 27 March 2017Increasing skeletal muscle carnitine availability alters muscle metabolism during steady-state exercise in healthy humans. We investigated whether elevating muscle carnitine, and thereby the acetyl-group buffering capacity, altered the metabolic and physiological adaptations to 24 weeks of high-intensity interval training (HIIT) at 100% maximal exercise capacity (Wattmax ). Twenty-one healthy male volunteers (age 23±2 years; BMI 24.2±1.1 kg/m(2) ) performed 2x3 minute bouts of cycling exercise at 100% Wattmax , separated by five minutes rest. Fourteen volunteers repeated this protocol following 24 weeks of HIIT and twice-daily consumption of 80g carbohydrate (CON) or 3g L-carnitine+carbohydrate (CARN). Before HIIT, muscle phosphocreatine (PCr) degradation (P<0.0001), glycogenolysis (P<0.0005), PDC activation (P<0.05), and acetylcarnitine (P<0.005) were 2.3, 2.1, 1.5 and 1.5-fold greater, respectively, in exercise bout two compared to bout one, whilst lactate accumulation tended (P<0.07) to be 1.5-fold greater. Following HIIT, muscle free carnitine was 30% greater in CARN vs CON at rest and remained 40% elevated prior to the start of bout two (P<0.05). Following bout two, free carnitine content, PCr degradation, glycogenolysis, lactate accumulation, and PDC activation were all similar between CON and CARN, albeit markedly lower than before HIIT. VO2max , Wattmax and work-output were similarly increased in CON and CARN, by 9, 15 and 23% (P<0.001). In summary, increased reliance on non-mitochondrial ATP resynthesis during a second bout of intense exercise is accompanied by increased carnitine acetylation. Augmenting muscle carnitine during 24 weeks of HIIT did not alter this, nor enhance muscle metabolic adaptations or performance gains beyond those with HIIT alone. This article is protected by copyright. All rights reserved.This research was supported by a BBSRC PhD studentship award for CS

Dietary fat oxidation is elevated in middle-aged type 2 diabetes

This is the author accepted manuscript. The final version is available from the publisher via the link in this record.N/

Anomalous material-dependent transport of focused, laser-driven proton beams.

Intense lasers can accelerate protons in sufficient numbers and energy that the resulting beam can heat materials to exotic warm (10 s of eV temperature) states. Here we show with experimental data that a laser-driven proton beam focused onto a target heated it in a localized spot with size strongly dependent upon material and as small as 35 μm radius. Simulations indicate that cold stopping power values cannot model the intense proton beam transport in solid targets well enough to match the large differences observed. In the experiment a 74 J, 670 fs laser drove a focusing proton beam that transported through different thicknesses of solid Mylar, Al, Cu or Au, eventually heating a rear, thin, Au witness layer. The XUV emission seen from the rear of the Au indicated a clear dependence of proton beam transport upon atomic number, Z, of the transport layer: a larger and brighter emission spot was measured after proton transport through the lower Z foils even with equal mass density for supposed equivalent proton stopping range. Beam transport dynamics pertaining to the observed heated spot were investigated numerically with a particle-in-cell (PIC) code. In simulations protons moving through an Al transport layer result in higher Au temperature responsible for higher Au radiant emittance compared to a Cu transport case. The inferred finding that proton stopping varies with temperature in different materials, considerably changing the beam heating profile, can guide applications seeking to controllably heat targets with intense proton beams

Increasing skeletal muscle carnitine content in older individuals increases whole-body fat oxidation during moderate-intensity exercise

This is the final version. Available on open access from Wiley via the DOI in this recordData availability: The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.Intramyocellular lipid (IMCL) utilization is impaired in older individuals, and IMCL accumulation is associated with insulin resistance. We hypothesized that increasing muscle total carnitine content in older men would increase fat oxidation and IMCL utilization during exercise, and improve insulin sensitivity. Fourteen healthy older men (69 ± 1 year, BMI 26.5 ± 0.8 kg/m2 ) performed 1 h of cycling at 50% VO2 max and, on a separate occasion, underwent a 60 mU/m2 /min euglycaemic hyperinsulinaemic clamp before and after 25 weeks of daily ingestion of a 220 ml insulinogenic beverage (44.4 g carbohydrate, 13.8 g protein) containing 4.5 g placebo (n = 7) or L-carnitine L-tartrate (n = 7). During supplementation, participants performed twice-weekly cycling for 1 h at 50% VO2 max. Placebo ingestion had no effect on muscle carnitine content or total fat oxidation during exercise at 50% VO2 max. L-carnitine supplementation resulted in a 20% increase in muscle total carnitine content (20.1 ± 1.2 to 23.9 ± 1.7 mmol/kg/dm; p < 0.01) and a 20% increase in total fat oxidation (181.1 ± 15.0 to 220.4 ± 19.6 J/kg lbm/min; p < 0.01), predominantly due to increased IMCL utilization. These changes were associated with increased expression of genes involved in fat metabolism (ACAT1, DGKD & PLIN2; p < 0.05). There was no change in resting insulin-stimulated whole-body or skeletal muscle glucose disposal after supplementation. This is the first study to demonstrate that a carnitine-mediated increase in fat oxidation is achievable in older individuals. This warrants further investigation given reduced lipid turnover is associated with poor metabolic health in older adults.Dunhill Medical Trus

Dual-gated bilayer graphene hot electron bolometer

Detection of infrared light is central to diverse applications in security, medicine, astronomy, materials science, and biology. Often different materials and detection mechanisms are employed to optimize performance in different spectral ranges. Graphene is a unique material with strong, nearly frequency-independent light-matter interaction from far infrared to ultraviolet, with potential for broadband photonics applications. Moreover, graphene's small electron-phonon coupling suggests that hot-electron effects may be exploited at relatively high temperatures for fast and highly sensitive detectors in which light energy heats only the small-specific-heat electronic system. Here we demonstrate such a hot-electron bolometer using bilayer graphene that is dual-gated to create a tunable bandgap and electron-temperature-dependent conductivity. The measured large electron-phonon heat resistance is in good agreement with theoretical estimates in magnitude and temperature dependence, and enables our graphene bolometer operating at a temperature of 5 K to have a low noise equivalent power (33 fW/Hz1/2). We employ a pump-probe technique to directly measure the intrinsic speed of our device, >1 GHz at 10 K.Comment: 5 figure

Whom and Where Are We Not Vaccinating? Coverage after the Introduction of a New Conjugate Vaccine against Group A Meningococcus in Niger in 2010

MenAfriVac is a new conjugate vaccine against Neisseria meningitidis serogroup A developed for the African “meningitis belt”. In Niger, the first two phases of the MenAfriVac introduction campaign were conducted targeting 3,135,942 individuals aged 1 to 29 years in the regions of Tillabéri, Niamey, and Dosso, in September and December 2010. We evaluated the campaign and determined which sub-populations or areas had low levels of vaccination coverage in the regions of Tillabéri and Niamey. After Phase I, conducted in the Filingué district, we estimated coverage using a 30×15 cluster-sampling survey and nested lot quality assurance (LQA) analysis in the clustered samples to identify which subpopulations (defined by age 1–14/15–29 and sex) had unacceptable vaccination coverage (<70%). After Phase II, we used Clustered Lot Quality Assurance Sampling (CLQAS) to assess if any of eight districts in Niamey and Tillabéri had unacceptable vaccination coverage (<75%) and estimated overall coverage. Estimated vaccination coverage was 77.4% (95%CI: 84.6–70.2) as documented by vaccination cards and 85.5% (95% CI: 79.7–91.2) considering verbal history of vaccination for Phase I; 81.5% (95%CI: 86.1–77.0) by card and 93.4% (95% CI: 91.0–95.9) by verbal history for Phase II. Based on vaccination cards, in Filingué, we identified both the male and female adult (age 15–29) subpopulations as not reaching 70% coverage; and we identified three (one in Tillabéri and two in Niamey) out of eight districts as not reaching 75% coverage confirmed by card. Combined use of LQA and cluster sampling was useful to estimate vaccination coverage and to identify pockets with unacceptable levels of coverage (adult population and three districts). Although overall vaccination coverage was satisfactory, we recommend continuing vaccination in the areas or sub-populations with low coverage and reinforcing the social mobilization of the adult population

Utilization, retention and bio-efficacy studies of PermaNet® in selected villages in Buie and Fentalie districts of Ethiopia

<p>Abstract</p> <p>Background</p> <p>Malaria remains a major public health problem in Ethiopia. Pyrethroid-treated mosquito nets are one of the major tools available for the prevention and control of malaria transmission. PermaNet^®is a long-lasting insecticide-treated net (LLIN) recommended by WHO for malaria control.</p> <p>Objective</p> <p>The objective of the study was to assess utilization and retention of PermaNet^®nets distributed for malaria control in Buie and Fentalie districts and monitor the bio-efficacy of the nets using the WHO cone bioassay test procedures.</p> <p>Methods</p> <p>A cross sectional study was carried out by interviewing household heads or their representative in Buie and Fentalie districts. The two districts were selected based on a priori knowledge of variations on ethnic background and housing construction. Clusters of houses were chosen within each of the study villages for selection of households. 20 households that had received one or more PermaNet^®nets were chosen randomly from the clusters in each village. A total of eight used PermaNet^®nets were collected for the bio-efficacy test. The bio-efficacy of PermaNet^®nets was monitored according to the standard WHO procedures using a susceptible colony of <it>Anopheles arabiensis </it>to deltamethrin.</p> <p>Results</p> <p>A total of 119 household heads were interviewed during the study. The retention rate of nets that were distributed in 2005 and 2006 season was 72%. A total of 62.2% of the interviewees claimed children under five years of age slept under LLIN, while only 50.7% of the nets were observed to be hanged inside houses when used as a proxy indicator of usage of LLIN. For the bio-efficacy test the mean knock-down was 94% and 100%, while the mean mortality rate observed after 24 hr holding period was 72.2% and 67% for Buie and Fentalie districts respectively.</p> <p>Conclusion</p> <p>The study revealed a moderately high retention of PermaNet^®in the study villages and effectiveness of the nets when tested according to the standard WHO procedure.</p

Superconductivity above 30 K in alkali-metal-doped hydrocarbon

The recent discovery of superconductivity with a transition temperature (Tc) at 18 K in Kxpicene has extended the possibility of high-Tc superconductors in organic materials. Previous experience based on similar hydrocarbons, like alkali-metal doped phenanthrene, suggested that even higher transition temperatures might be achieved in alkali-metals or alkali-earth-metals doped such polycyclic-aromatic-hydrocarbons (PAHs), a large family of molecules composed of fused benzene rings. Here we report the discovery of high-Tc superconductivity at 33 K in K-doped 1,2:8,9-dibenzopentacene (C30H18). To our best knowledge, it is higher than any Tc reported previously for an organic superconductor under ambient pressure. This finding provides an indication that superconductivity at much higher temperature may be possible in such PAHs system and is worthy of further exploration

Characterization of human Sec16B: indications of specialized, non-redundant functions

The endoplasmic reticulum (ER) represents the entry point into the secretory pathway and from here newly synthesized proteins and lipids are delivered to the Golgi. The selective cargo export from the ER is mediated by COPII-assembly at specific sites of the ER, the so-called transitional ER (tER). The peripheral membrane protein Sec16, first identified in yeast, localizes to transitional ER and plays a key role in organization of these sites. Sec16 defines the tER and is thought to act as a scaffold for the COPII coat assembly. In humans two isoforms of Sec16 are present, the larger Sec16A and the smaller Sec16B. Nevertheless, the functional differences between the two isoforms are ill-defined. Here we describe characterization of the localization and dynamics of Sec16B relative to Sec16A, provide evidence that Sec16B is likely a minor or perhaps specialized form of Sec16, and that it is not functionally redundant with Sec16A

Modified Alvarado Scoring System as a diagnostic tool for Acute Appendicitis at Bugando Medical Centre, Mwanza, Tanzania

<p>Abstract</p> <p>Background</p> <p>Decision-making in patients with acute appendicitis poses a diagnostic challenge worldwide, despite much advancement in abdominal surgery. The Modified Alvarado Scoring System (MASS) has been reported to be a cheap and quick diagnostic tool in patients with acute appendicitis. However, differences in diagnostic accuracy have been observed if the scores were applied to various populations and clinical settings. The purpose of this study was to evaluate the diagnostic value of Modified Alvarado Scoring System in patients with acute appendicitis in our setting.</p> <p>Methods</p> <p>A cross-sectional study involving all patients suspected to have acute appendicitis at Bugando Medical Centre over a six-month period between November 2008 and April 2009 was conducted. All patients who met the inclusion criteria were consecutively enrolled in the study. They were evaluated on admission using the MASS to determine whether they had acute appendicitis or not. All patients underwent appendicectomy according to the hospital protocol. The decision to operate was the prerogative of the surgeon or surgical resident based on overall clinical judgment and not the MASS. The diagnosis was confirmed by histopathological examination. Data was collected using a pre-tested coded questionnaire and analyzed using SPSS statistical computer software.</p> <p>Results</p> <p>A total number of 127 patients were studied. Their ages ranged from eight to 76 years (mean 29.64 ± 12.97). There were 37 (29.1%) males and 90 (70.9%) females (M: F = 1:2.4). All patients in this study underwent appendicectomy. The perforation rate was 9.4%. Histopathological examination confirmed appendicitis in 85 patients (66.9%) and the remaining 42 patients had normal appendix giving a negative appendicectomy rate of 33.1% (26.8% for males and 38.3% for females). The sensitivity and specificity of MASS in this study were 94.1% (males 95.8% and females 88.3%) and 90.4% (males 92.9% and females 89.7%) respectively. The Positive Predictive Value and Negative Predictive Value were 95.2% (males 95.5% and females 90.6%) and 88.4% (males 89.3% and females 80.1%) respectively. The accuracy of MASS was 92.9% (males 91.5% and females 87.6%).</p> <p>Conclusion</p> <p>The study shows that use of MASS in patients suspected to have acute appendicitis provides a high degree of diagnostic accuracy and can be employed at Bugando Medical Centre to improve the diagnostic accuracy of acute appendicitis and subsequently reduces negative appendicectomy and complication rates. However, additional investigations may be required to confirm the diagnosis in case of atypical presentation.</p