Impaired musculoskeletal response to age and exercise in PPARβ(-/-) diabetic mice.

Fragility fractures are recognized complication of diabetes, but yet the underlying mechanisms remain poorly understood. This is particularly pronounced in type 2 diabetes in which the propensity to fall is increased but bone mass is not necessarily low. Thus, whether factors implicated in the development of insulin resistance and diabetes directly impact on the musculoskeletal system remains to be investigated. PPARβ(-/-) mice have reduced metabolic activity and are glucose intolerant. We examined changes in bone and muscle in PPARβ(-/-) mice and investigated both the mechanism behind those changes with age as well as their response to exercise. Compared with their wild type, PPARβ(-/-) mice had an accelerated and parallel decline in both muscle and bone strength with age. These changes were accompanied by increased myostatin expression, low bone formation, and increased resorption. In addition, mesenchymal cells from PPARβ(-/-) had a reduced proliferation capacity and appeared to differentiate into more of an adipogenic phenotype. Concomitantly we observed an increased expression of PPARγ, characteristic of adipocytes. The anabolic responses of muscle and bone to exercise were also diminished in PPARβ(-/-) mice. The periosteal bone formation response to direct bone compression was, however, maintained, indicating that PPARβ controls periosteal bone formation through muscle contraction and/or metabolism. Taken together, these data indicate that PPARβ deficiency leads to glucose intolerance, decreased muscle function, and reduced bone strength. On a molecular level, PPARβ appears to regulate myostatin and PPARγ expression in muscle and bone, thereby providing potential new targets to reverse bone fragility in patients with metabolic disturbances.

Fat oxidation kinetics during exercise in obese individuals

Introduction An impaired ability to oxidize fat may be a factor in the obesity's aetiology (3). Moreover, the exercise intensity (Fatmax) eliciting the maximal fat oxidation rate (MFO) was lower in obese (O) compared with lean (L) individuals (4). However, difference in fat oxidation rate (FOR) during exercise between O and L remains equivocal and little is known about FORs during high intensities (>60% ) in O compared with L. This study aimed to characterize fat oxidation kinetics over a large range of intensities in L and O. Methods 12 healthy L [body mass index (BMI): 22.8±0.4] and 16 healthy O men (BMI: 38.9±1.4) performed submaximal incremental test (Incr) to determine whole-body fat oxidation kinetics using indirect calorimetry. After a 15-min resting period (Rest) and 10-min warm-up at 20% of maximal power output (MPO, determined by a maximal incremental test), the power output was increased by 7.5% MPO every 6-min until respiratory exchange ratio reached 1.0. Venous lactate and glucose and plasma concentration of epinephrine (E), norepinephrine (NE), insulin and non-esterified fatty acid (NEFA) were assessed at each step. A mathematical model (SIN) (1), including three variables (dilatation, symmetry, translation), was used to characterize fat oxidation (normalized by fat-free mass) kinetics and to determine Fatmax and MFO. Results FOR at Rest and MFO were not significantly different between groups (p≥0.1). FORs were similar from 20-60% (p≥0.1) and significantly lower from 65-85% in O than in L (p≤0.04). Fatmax was significantly lower in O than in L (46.5±2.5 vs 56.7±1.9 % respectively; p=0.005). Fat oxidation kinetics was characterized by similar translation (p=0.2), significantly lower dilatation (p=0.001) and tended to a left-shift symmetry in O compared with L (p=0.09). Plasma E, insulin and NEFA were significantly higher in L compared to O (p≤0.04). There were no significant differences in glucose, lactate and plasma NE between groups (p≥0.2). Conclusion The study showed that O presented a lower Fatmax and a lower reliance on fat oxidation at high, but not at moderate, intensities. This may be linked to a: i) higher levels of insulin and lower E concentrations in O, which may induce blunted lipolysis; ii) higher percentage of type II and a lower percentage of type I fibres (5), and iii) decreased mitochondrial content (2), which may reduce FORs at high intensities and Fatmax. These findings may have implications for an appropriate exercise intensity prescription for optimize fat oxidation in O. References 1. Cheneviere et al. Med Sci Sports Exerc. 2009 2. Holloway et al. Am J Clin Nutr. 2009 3. Kelley et al. Am J Physiol. 1999 4. Perez-Martin et al. Diabetes Metab. 2001 5. Tanner et al. Am J Physiol Endocrinol Metab. 2002

Research priorities for nursing care of infants, children and adolescents: a West Australian Delphi study.

This paper describes a study that aimed to identify research priorities for the care of infants, children and adolescents at the sole tertiary referral hospital for children in Western Australia. The secondary aim was to stimulate nurses to explore clinical problems that would require further inquiry. Background. Planning for research is an essential stage of research development; involving clinicians in this exercise is likely to foster research partnerships that are pertinent to clinical practice. Nursing research priorities for the paediatric population have not previously been reported in Australia. Design. Delphi study. Method. Over 12 months in 2005-2006, a three-round questionnaire, using the Delphi technique, was sent to a randomly selected sample of registered nurses. This method was used to identify and prioritise nursing research topics relevant to the patient and the family. Content analysis was used to analyse Round I data and descriptive statistics for Round II and III data. Results. In Round I, 280 statements were identified and reduced to 37 research priorities. Analysis of data in subsequent rounds identified the top two priority research areas as (1) identification of strategies to reduce medication incidents (Mean = 6 center dot 47; SD 0 center dot 88) and (2) improvement in pain assessment and management (Mean = 6; SD 1 center dot 38). Additional comments indicated few nurses access the scientific literature or use research findings because of a lack of time or electronic access. Conclusions. Thirty-seven research priorities were identified. The identification of research priorities by nurses provided research direction for the health service and potentially other similar health institutions for children and adolescents in Australia and internationally. Relevance to clinical practice. The nurse participants showed concern about the safety of care and the well-being of children and their families. This study also enabled the identification of potential collaborative research and development of pain management improvement initiatives.

Differential DNA extraction of challenging simulated sexual assault samples: a Swiss collaborative study.

ABSTRACT: In sexual assault cases, autosomal DNA analysis of gynecological swabs is a challenge, as the presence of a large quantity of female material may prevent the detection of the male DNA. A solution to this problem is differential DNA extraction, but as there are different protocols, it was decided to test their efficiency on simulated casework samples. Four difficult samples were sent to the nine Swiss laboratories active in the forensic genetics. They used their routine protocols to separate the epithelial cell fraction, enriched with the non-sperm DNA, from the sperm fraction. DNA extracts were then sent to the organizing laboratory for analysis. Estimates of male to female DNA ratio without differential DNA extraction ranged from 1:38 to 1:339, depending on the semen used to prepare the samples. After differential DNA extraction, most of the ratios ranged from 1:12 to 9:1, allowing the detection of the male DNA. Compared to direct DNA extraction, cell separation resulted in losses of 94-98% of the male DNA. As expected, more male DNA was generally present in the sperm than in the epithelial cell fraction. However, for about 30% of the samples, the reverse trend was observed. The recovery of male and female DNA was highly variable depending on the laboratories. Experimental design similar to the one used in this study may help for local protocol testing and improvement.

RV contractility and exercise-induced pulmonary hypertension in chronic mountain sickness: a stress echocardiographic and tissue Doppler imaging study.

OBJECTIVES: The aim of this study was to evaluate right ventricular (RV) and left ventricular function and pulmonary circulation in chronic mountain sickness (CMS) patients with rest and stress echocardiography compared with healthy high-altitude (HA) dwellers. BACKGROUND: CMS or Monge's disease is defined by excessive erythrocytosis (hemoglobin >21 g/dl in males, 19 g/dl in females) and severe hypoxemia. In some cases, a moderate or severe increase in pulmonary pressure is present, suggesting a similar pathogenesis of pulmonary hypertension. METHODS: In La Paz (Bolivia, 3,600 m sea level), 46 CMS patients and 40 HA dwellers of similar age were evaluated at rest and during semisupine bicycle exercise. Pulmonary artery pressure (PAP), pulmonary vascular resistance, and cardiac function were estimated by Doppler echocardiography. RESULTS: Compared with HA dwellers, CMS patients showed RV dilation at rest (RV mid diameter: 36 ± 5 mm vs. 32 ± 4 mm, CMS vs. HA, p = 0.001) and reduced RV fractional area change both at rest (35 ± 9% vs. 43 ± 9%, p = 0.002) and during exercise (36 ± 9% vs. 43 ± 8%, CMS vs. HA, p = 0.005). The RV systolic longitudinal function (RV-S') decreased in CMS patients, whereas it increased in the control patients (p < 0.0001) at peak stress. The RV end-systolic pressure-area relationship, a load independent surrogate of RV contractility, was similar in CMS patients and HA dwellers with a significant increase in systolic PAP and pulmonary vascular resistance in CMS patients (systolic PAP: 50 ± 12 mm Hg vs. 38 ± 8 mm Hg, CMS vs. HA, p < 0.0001; pulmonary vascular resistance: 2.9 ± 1 mm Hg/min/l vs. 2.2 ± 1 mm Hg/min/l, p = 0.03). Both groups showed comparable systolic and diastolic left ventricular function both at rest and during stress. CONCLUSIONS: Comparable RV contractile reserve in CMS and HA suggests that the lower resting values of RV function in CMS may represent a physiological adaptation to chronic hypoxic conditions rather than impaired RV function. (Chronic Mountain Sickness, Systemic Vascular Function [CMS]; NCT01182792).

Exercise and nonspecific low back pain: a literature review.

We reviewed the literature to clarify the effects of exercise in preventing and treating nonspecific low back pain. We evaluated several characteristics of exercise programs including specificity, individual tailoring, supervision, motivation enhancement, volume, and intensity. The results show that exercise is effective in the primary and secondary prevention of low back pain. When used for curative treatment, exercise diminishes disability and pain severity while improving fitness and occupational status in patients who have subacute, recurrent, or chronic low back pain. Patients with acute low back pain are usually advised to continue their everyday activities to the greatest extent possible rather than to start an exercise program. Supervision is crucial to the efficacy of exercise programs. Whether general or specific exercises are preferable is unclear, and neither is there clear evidence that one-on-one sessions are superior to group sessions. Further studies are needed to determine which patient subsets respond to specific characteristics of exercise programs and which exercise volumes and intensities are optimal.

Long-term swimming exercise does not modulate the Akt-dependent endothelial nitric oxide synthase phosphorylation in healthy mice.

Molecular mechanisms by which exercise exerts cardiovascular benefits are poorly understood. Exercise-induced increase of endothelial NO synthase (eNOS) phosphorylation through the protein kinase Akt has been shown to be a key mechanism underlying the beneficial effect of exercise in coronary artery disease patients. We examined whether this protective pathway might also be activated in long-term-exercised healthy mice. C57BL/6 wild-type mice swam for 24 weeks. A group of sedentary animals were used as controls. Aortic levels of total protein kinase Akt (protein kinase B), phosphorylated Akt at ser473 (p-Akt), total eNOS, phosphorylated eNOS at Ser1177 (p-eNOS), and PECAM-1 (platelet endothelial cell adhesion molecule-1) were assessed by Western blotting. Protein expressions of Akt, p-Akt, eNOS, p-eNOS, and PECAM-1 were not modulated by 24 weeks of exercise. The Akt-dependent eNOS phosphorylation did not seem to be a primary molecular adaptation in response to long-term exercise in healthy mice.

Survey on batch-to-batch variation in spray paints: a collaborative study

This study represents the most extensive analysis of batch-to-batch variations in spray paint samples to date. The survey was performed as a collaborative project of the ENFSI (European Network of Forensic Science Institutes) Paint and Glass Working Group (EPG) and involved 11 laboratories. Several studies have already shown that paint samples of similar color but from different manufacturers can usually be differentiated using an appropriate analytical sequence. The discrimination of paints from the same manufacturer and color (batch-to-batch variations) is of great interest and these data are seldom found in the literature. This survey concerns the analysis of batches from different color groups (white, papaya (special shade of orange), red and black) with a wide range of analytical techniques and leads to the following conclusions. Colored batch samples are more likely to be differentiated since their pigment composition is more complex (pigment mixtures, added pigments) and therefore subject to variations. These variations may occur during the paint production but may also occur when checking the paint shade in quality control processes. For these samples, techniques aimed at color/pigment(s) characterization (optical microscopy, microspectrophotometry (MSP), Raman spectroscopy) provide better discrimination than techniques aimed at the organic (binder) or inorganic composition (fourier transform infrared spectroscopy (FTIR) or elemental analysis (SEM - scanning electron microscopy and XRF - X-ray fluorescence)). White samples contain mainly titanium dioxide as a pigment and the main differentiation is based on the binder composition (Csingle bondH stretches) detected either by FTIR or Raman. The inorganic composition (elemental analysis) also provides some discrimination. Black samples contain mainly carbon black as a pigment and are problematic with most of the spectroscopic techniques. In this case, pyrolysis-GC/MS represents the best technique to detect differences. Globally, Py-GC/MS may show a high potential of discrimination on all samples but the results are highly dependent on the specific instrumental conditions used. Finally, the discrimination of samples when data was interpreted visually as compared to statistically using principal component analysis (PCA) yielded very similar results. PCA increases sensitivity and could perform better on specific samples, but one first has to ensure that all non-informative variation (baseline deviation) is eliminated by applying correct pre-treatments. Statistical treatments can be used on a large data set and, when combined with an expert's opinion, will provide more objective criteria for decision making.

Application of the 2008 definitions for invasive fungal diseases to the trial comparing voriconazole versus amphotericin B for therapy of invasive aspergillosis: a collaborative study of the Mycoses Study Group (MSG 05) and the European Organization for Research and Treatment of Cancer Infectious Diseases Group.

BACKGROUND: Strict definition of invasive aspergillosis (IA) cases is required to allow precise conclusions about the efficacy of antifungal therapy. The Global Comparative Aspergillus Study (GCAS) compared voriconazole to amphotericin B (AmB) deoxycholate for the primary therapy of IA. Because predefined definitions used for this trial were substantially different from the consensus definitions proposed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group in 2008, we recategorized the 379 episodes of the GCAS according to the later definitions. METHODS: The objectives were to assess the impact of the current definitions on the classification of the episodes and to provide comparative efficacy for probable/proven and possible IA in patients treated with either voriconazole or AmB. In addition to original data, we integrated the results of baseline galactomannan serum levels obtained from 249 (65.7%) frozen samples. The original response assessment was accepted unchanged. RESULTS: Recategorization allowed 59 proven, 178 probable, and 106 possible IA cases to be identified. A higher favorable 12-week response rate was obtained with voriconazole (54.7%) than with AmB (29.9%) (P < .0001). Survival was higher for voriconazole for mycologically documented (probable/proven) IA (70.2%) than with AmB (54.9%) (P = .010). Higher response rates were obtained in possible IA treated with voriconazole vs AmB with the same magnitude of difference (26.2%; 95% confidence interval [CI], 7.2%-45.3%) as in mycologically documented episodes (24.3%; 95% CI, 11.9%-36.7%), suggesting that possible cases are true IA. CONCLUSIONS: Recategorization resulted in a better identification of the episodes and confirmed the higher efficacy of voriconazole over AmB deoxycholate in mycologically documented IA.

Effects of prior repeated-sprints with different recovery duration on oxygen uptake kinetics during subsequent heavy-exercise

Introduction: Prior repeated-sprints (6) has become an interesting method to resolve the debate surrounding the principal factors that limits the oxygen uptake (V'O2) kinetics at the onset of exercise [i.e., muscle O2 delivery (5) or metabolic inertia (3)]. The aim of this study was to compare the effects of two repeated-sprints sets of 6x6s separated by different recovery duration between the sprints on V'O2 and muscular de-oxygenation [HHb] kinetics during a subsequent heavy-intensity exercise. Methods: 10 male subjects performed a 6-min constant-load cycling test (T50) at intensity corresponding to half of the difference between V'O2max and the ventilatory threshold. Then, they performed two repeated-sprints sets of 6x6s all-out separated by different recovery duration between the sprints (S1:30s and S2:3min) followed, after 7-min-recovery, by the T50 (S1T50 and S2T50, respectively). V'O2, [HHb] of the vastus lateralis (VL) and surface electromyography activity [i.e., root-mean-square (RMS) and the median frequency of the power density spectrum (MDF)] from VL and vastus medialis (VM) were recorded throughout T50. Models using a bi-exponential function for the overall T50 and a mono-exponential for the first 90s of T50 were used to define V'O2 and [HHb] kinetics respectively. Results: V'O2 mean value was higher in S1 (2.9±0.3l.min-1) than in S2 (1.2±0.3l.min-1); (p<0.001). The peripheral blood flow was increased after sprints as attested by a higher basal heart rate (HRbaseline) (S1T50: +22%; S2T50: +17%; p≤0.008). Time delay [HHb] was shorter for S1T50 and S2T50 than for T50 (-22% for both; p≤0.007) whereas the mean response time of V'O2 was accelerated only after S1 (S1T50: 32.3±2.5s; S2T50: 34.4±2.6s; T50: 35.7±5.4s; p=0.031). There were no significant differences in RMS between the three conditions (p>0.05). MDF of VM was higher during the first 3-min in S1T50 than in T50 (+6%; p≤0.05). Conclusion: The study show that V'O2 kinetics was speeded by prior repeated-sprints with a short (30s) but not a long (3min) inter-sprints-recovery even though the [HHb] kinetics was accelerated and the peripheral blood flow was enhanced after both sprints. S1, inducing a greater PCr depletion (1) and change in the pattern of the fibres recruitment (increase in MDF) compared with S2, may decrease metabolic inertia (2), stimulate the oxidative phosphorylation activation (4) and accelerate V'O2 kinetics at the beginning of the subsequent high-intensity exercise.

Neuromuscular fatigue induced by whole-body vibration exercise

The aim of this study was to examine the magnitude and the origin of neuromuscular fatigue induced by half-squat static whole-body vibration (WBV) exercise, and to compare it to a non-WBV condition. Nine healthy volunteers completed two fatiguing protocols (WBV and non-WBV, randomly presented) consisting of five 1-min bouts of static half-squat exercise with a load corresponding to 50 % of their individual body mass. Neuromuscular fatigue of knee and ankle muscles was investigated before and immediately after each fatiguing protocol. The main outcomes were maximal voluntary contraction (MVC) torque, voluntary activation, and doublet peak torque. Knee extensor MVC torque decreased significantly (P < 0.01) and to the same extent after WBV (-23 %) and non-WBV (-25 %), while knee flexor, plantar flexor, and dorsiflexor MVC torque was not affected by the treatments. Voluntary activation of knee extensor and plantar flexor muscles was unaffected by the two fatiguing protocols. Doublet peak torque decreased significantly and to a similar extent following WBV and non-WBV exercise, for both knee extensors (-25 %; P < 0.01) and plantar flexors (-7 %; P < 0.05). WBV exercise with additional load did not accentuate fatigue and did not change its causative factors compared to non-WBV half-squat resistive exercise in recreationally active subjects.