Variable-frequency-train stimulation of skeletal muscle after spinal cord injury

Skeletal muscle, after spinal cord injury (SCI), becomes highly susceptible to fatigue. Variable-frequency trains (VFTs) enhance force in fatigued human skeletal muscle of able-bodied (AB) individuals. VFTs do this by taking advantage of the catch-like property of skeletal muscle. However, mechanisms responsible for fatigue in AB and SCI subjects may not be the same, and the efficacy of VFT stimulation after SCI is unknown. Accordingly, we tested the hypothesis that VFT stimulation would augment torque-time integral in SCI subjects. The quadriceps femoris muscle was stimulated with constant frequency trains (CFTs) (six 200 s square wave pulses separated by 70 ms) or VFTs (a train identical to the CFT, except that the first two pulses were separated by 5 ms) in SCI and AB subjects. After 180 contractions (50% duty cycle), isometric peak torque decreased 44, 56, and 67 percent, in the AB (n = 10), acute SCI (n = 10), and chronic SCI (n = 12) groups, respectively. In fatigued muscle, VFTs enhanced the torque-time integral by 18 percent in AB subjects and 6 percent in chronic SCI patients, and had no effect in acute SCI patients when compared to the corresponding CFT. The much faster rise times in SCI subjects (~80 ms vs. 120 ms in AB subjects) probably contributed to the inability of VFTs to enhance torque-time integrals in SCI patients. The results suggest that the use of VFT stimulation in patients with SCI may not be as efficacious as it is in AB persons

Impacting attitudes towards gambling: A prison gambling awareness and prevention program

Research indicates that approximately one third of prison inmates meet the criteria for problem or pathological gambling (Williams, Royston, & Hagen, 2005). However, despite this rate being among the highest of all gambling populations (Walters, 1997; Shaffer & Hall, 2001), there appears to be a lack of prison gambling awareness and prevention programs. This study sought to develop, implement, and evaluate one such program at the Lethbridge Correctional Facility in Alberta, Canada. Forty-nine inmates completed a six-session program over 18 months. Gambling screen results revealed a significant increase in cognitive error recognition, and attitudes towards gambling became significantly more negative. The program did not render any significant differences in math skill score, Canadian Problem Gambling Index (CPGI) score, or past-year South Oaks Gambling Screen (SOGS) score. Changes in the past-year frequency score approached significance. This study suggests that programs of this kind can be effective for inmate populations, particularly in changing attitudes towards gambling.Alberta Gaming Research InstituteYe

Associations of Mitochondrial Fatty Acid Oxidation with Body Fat in Premenopausal Women

Higher in vivo fatty acid (FA) oxidation rates have been reported in obese individuals compared to lean counterparts; however whether this reflects a shift in substrate-specific oxidative capacity at the level of the skeletal muscle mitochondria has not been examined. The purpose of this study was to test the hypothesis that in situ measures of skeletal muscle mitochondria FA oxidation would be positively associated with total body fat. Participants were 38 premenopausal women (BMI=26.5±4.3 kg/m2). Total and regional fat were assessed by dual-energy X-ray absorptiometry (DXA). Mitochondrial FA oxidation was assessed in permeabilized myofibers using high-resolution respirometry and a palmitoyl carnitine substrate. We found positive associations of total fat mass with State 3 (ADP-stimulated respiration) (r=0.379, p<0.05) and the respiratory control ratio (RCR, measure of mitochondrial coupling) (r=0.348, p<0.05). When participants were dichotomized by high or low body fat percent, participants with high total body fat displayed a higher RCR compared to those with low body fat (p<0.05). There were no associations between any measure of regional fat and mitochondrial FA oxidation independent of total fat mass. In conclusion, greater FA oxidation in obesity may reflect molecular processes that enhance FA oxidation capacity at the mitochondrial level

Impact of Age and Estimated Glomerular Filtration Rate on the Glycemic Efficacy and Safety of Canagliflozin: A Pooled Analysis of Clinical Studies.

AbstractObjectiveReduced efficacy has been reported in the elderly; it may be a consequence of an age-dependent decline in estimated glomerular filtration rate (eGFR) rather than ageing per se. We sought to determine the impact of these 2 parameters, as well as sex and baseline body mass index (BMI), on the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in people with type 2 diabetes.MethodsData were pooled from 6 randomized, double-blind, placebo-controlled studies (18 or 26 weeks; N=4053). Changes in glycated hemoglobin (A1C) and systolic blood pressure (BP) from baseline with canagliflozin 100 mg and 300 mg and placebo were evaluated in subgroups by sex, baseline BMI, baseline age and baseline eGFR. Safety was assessed by reports of adverse events.ResultsPlacebo-subtracted reductions in A1C with canagliflozin 100 mg and 300 mg were similar in men and women. A1C reductions with canagliflozin were seen across BMI subgroups and in participants aged <65 years and ≥65 years. Significantly greater placebo-subtracted reductions in A1C were seen with both canagliflozin doses in participants with higher baseline eGFR (≥90 mL/min/1.73 m2). Reductions in systolic BP were seen with canagliflozin across subgroups of sex, BMI, age and eGFR. A1C reductions with canagliflozin were similar for participants aged <65 or ≥65 years who had baseline eGFR ≥60 mL/min/1.73 m2 and were smaller in older than in younger participants with baseline eGFR 45 to <60 mL/min/1.73 m2. The overall incidence of adverse events was similar across treatment groups regardless of sex, baseline BMI, baseline age or baseline eGFR.ConclusionsCanagliflozin improved glycemic control, reduced BP and was generally well tolerated in people with type 2 diabetes across a range of ages, BMIs and renal functions

The effect of Mg location on Co-Mg-Ru/gamma-Al2O3 Fischer-Tropsch catalysts

The effectiveness of Mg as a promoter of Co-Ru/γ-Al(2)O(3) Fischer–Tropsch catalysts depends on how and when the Mg is added. When the Mg is impregnated into the support before the Co and Ru addition, some Mg is incorporated into the support in the form of Mg(x)Al(2)O(3+x) if the material is calcined at 550°C or 800°C after the impregnation, while the remainder is present as amorphous MgO/MgCO(3) phases. After subsequent Co-Ru impregnation Mg(x)Co(3−x)O(4) is formed which decomposes on reduction, leading to Co(0) particles intimately mixed with Mg, as shown by high-resolution transmission electron microscopy. The process of impregnating Co into an Mg-modified support results in dissolution of the amorphous Mg, and it is this Mg which is then incorporated into Mg(x)Co(3−x)O(4). Acid washing or higher temperature calcination after Mg impregnation can remove most of this amorphous Mg, resulting in lower values of x in Mg(x)Co(3−x)O(4). Catalytic testing of these materials reveals that Mg incorporation into the Co oxide phase is severely detrimental to the site-time yield, while Mg incorporation into the support may provide some enhancement of activity at high temperature

(Re)constructing Dimensions

Compactifying a higher-dimensional theory defined in R^{1,3+n} on an n-dimensional manifold {\cal M} results in a spectrum of four-dimensional (bosonic) fields with masses m^2_i = \lambda_i, where - \lambda_i are the eigenvalues of the Laplacian on the compact manifold. The question we address in this paper is the inverse: given the masses of the Kaluza-Klein fields in four dimensions, what can we say about the size and shape (i.e. the topology and the metric) of the compact manifold? We present some examples of isospectral manifolds (i.e., different manifolds which give rise to the same Kaluza-Klein mass spectrum). Some of these examples are Ricci-flat, complex and K\"{a}hler and so they are isospectral backgrounds for string theory. Utilizing results from finite spectral geometry, we also discuss the accuracy of reconstructing the properties of the compact manifold (e.g., its dimension, volume, and curvature etc) from measuring the masses of only a finite number of Kaluza-Klein modes.Comment: 23 pages, 3 figures, 2 references adde

Low plasma citrulline levels are associated with acute respiratory distress syndrome in patients with severe sepsis

INTRODUCTION: The role of nitric oxide synthase (NOS) in the pathophysiology of acute respiratory distress syndrome (ARDS) is not well understood. Inducible NOS is upregulated during physiologic stress; however, if NOS substrate is insufficient then NOS can uncouple and switch from NO generation to production of damaging peroxynitrites. We hypothesized that NOS substrate levels are low in patients with severe sepsis and that low levels of the NOS substrate citrulline would be associated with end organ damage including ARDS in severe sepsis. METHODS: Plasma citrulline, arginine and ornithine levels and nitrate/nitrite were measured at baseline in 135 patients with severe sepsis. ARDS was diagnosed by consensus definitions. RESULTS: Plasma citrulline levels were below normal in all patients (median 9.2 uM, IQR 5.2 - 14.4) and were significantly lower in ARDS compared to the no ARDS group (6.0 (3.3 - 10.4) vs. 10.1 (6.2 - 16.6), P = 0.002). The rate of ARDS was 50% in the lowest citrulline quartile compared to 15% in the highest citrulline quartile (P = 0.002). In multivariable analyses, citrulline levels were associated with ARDS even after adjustment for covariates including severity of illness. CONCLUSIONS: In severe sepsis, levels of the NOS substrate citrulline are low and are associated with ARDS. Low NOS substrate levels have been shown in other disease states to lead to NOS uncoupling and oxidative injury suggesting a potential mechanism for the association between low citrulline and ARDS. Further studies are needed to determine whether citrulline supplementation could prevent the development of ARDS in patients with severe sepsis and to determine its role in NOS coupling and function