Creatine and low-dose lithium supplementation separately alter energy expenditure, body mass, and adipose metabolism for the promotion of thermogenesis.

Nutraceutical approaches to promote adipose tissue thermogenesis may help to prevent obesity onset. Creatine is a critical regulator of adipose metabolic function and low-dose lithium supplementation has been shown to promote adipose thermogenesis. In the present study, we sought to directly compare the two supplements for their effects on adipose metabolism and thermogenesis. We show that both supplements increase daily energy expenditure (EE) and reduce body mass in male Sprague-Dawley rats. Lithium increased brown adipose tissue (BAT) mitochondrial and lipolytic proteins that are associated with thermogenesis, while creatine increased BAT UCP1 and mitochondrial respiration. The BAT thermogenic findings were not observed in females. White adipose tissue and skeletal muscle markers of thermogenesis were unaltered with the supplements. Together, the data show that low-dose lithium and creatine have diverging effects on markers of BAT thermogenesis and that each increase daily EE and lower body mass in a sex-dependent manner.

The ESCRT-0 subcomplex component Hrs/Hgs is a master regulator of myogenesis via modulation of signaling and degradation pathways.

BACKGROUND: Myogenesis is a highly regulated process ending with the formation of myotubes, the precursors of skeletal muscle fibers. Differentiation of myoblasts into myotubes is controlled by myogenic regulatory factors (MRFs) that act as terminal effectors of signaling cascades involved in the temporal and spatial regulation of muscle development. Such signaling cascades converge and are controlled at the level of intracellular trafficking, but the mechanisms by which myogenesis is regulated by the endosomal machinery and trafficking is largely unexplored. The Endosomal Sorting Complex Required for Transport (ESCRT) machinery composed of four complexes ESCRT-0 to ESCRT-III regulates the biogenesis and trafficking of endosomes as well as the associated signaling and degradation pathways. Here, we investigate its role in regulating myogenesis. RESULTS: We uncovered a new function of the ESCRT-0 hepatocyte growth factor-regulated tyrosine kinase substrate Hrs/Hgs component in the regulation of myogenesis. Hrs depletion strongly impairs the differentiation of murine and human myoblasts. In the C2C12 murine myogenic cell line, inhibition of differentiation was attributed to impaired MRF in the early steps of differentiation. This alteration is associated with an upregulation of the MEK/ERK signaling pathway and a downregulation of the Akt2 signaling both leading to the inhibition of differentiation. The myogenic repressors FOXO1 as well as GSK3ß were also found to be both activated when Hrs was absent. Inhibition of the MEK/ERK pathway or of GSK3ß by the U0126 or azakenpaullone compounds respectively significantly restores the impaired differentiation observed in Hrs-depleted cells. In addition, functional autophagy that is required for myogenesis was also found to be strongly inhibited. CONCLUSIONS: We show for the first time that Hrs/Hgs is a master regulator that modulates myogenesis at different levels through the control of trafficking, signaling, and degradation pathways.

Effects of High-Intensity Interval Running Versus Cycling on Sclerostin, and Markers of Bone Turnover and Oxidative Stress in Young Men.

This study compared sclerostin's response to impact versus no-impact high-intensity interval exercise in young men and examined the association between exercise-induced changes in sclerostin and markers of bone turnover and oxidative stress. Twenty healthy men (22.3 ± 2.3 years) performed two high-intensity interval exercise trials (crossover design); running on treadmill and cycling on cycle ergometer. Trials consisted of eight 1 min running or cycling intervals at ≥ 90% of maximal heart rate, separated by 1 min passive recovery intervals. Blood samples were collected at rest (pre-exercise), and 5 min, 1 h, 24 h, and 48 h following each trial. Serum levels of sclerostin, cross-linked telopeptide of type I collagen (CTXI), procollagen type I amino-terminal propeptide (PINP), thiobarbituric acid reactive substances (TBARS), and protein carbonyls (PC) were measured. There was no significant time or exercise mode effect for PINP and PC. A significant time effect was found for sclerostin, CTXI, and TBARS with no significant exercise mode effect and no significant time-by-mode interaction. Sclerostin increased from pre- to 5 min post-exercise (47%, p < 0.05) and returned to baseline within 1 h following the exercise. CTXI increased from pre- to 5 min post-exercise (28%, p < 0.05), then gradually returned to baseline by 48 h. TBARS did not increase significantly from pre- to 5 min post-exercise but significantly decreased from 5 min to 48 h post-exercise. There were no significant correlations between exercise-induced changes in sclerostin and any other marker. In young men, sclerostin's response to high-intensity interval exercise is independent of impact and is not related to changes in bone turnover and oxidative stress markers.

Ethno-Cultural Considerations in Cardiac Patients' Medication Adherence.

We aimed to develop an in-depth understanding about factors that influence cardiac medication adherence among South Asian, Chinese, and European White cardiac patients. Sixty-four patients were purposively sampled from an ongoing study cohort. Interviews were audio-recorded and transcribed for analyses. Physicians' culturally sensitive communication and patients' motivation to live a symptom-free and longer life enhanced adherence. European Whites were motivated to enhance personal well-being and enjoy family life. South Asians' medication adherence was influenced by the desire to fulfill the will of God and family responsibilities. The Chinese were motivated to avoid pain, illness, and death, and to obey a health care provider. The South Asians and Chinese wanted to ultimately reduce medication use. Previous positive experiences, family support, and establishing a routine also influenced medication adherence. Deterrents to adherence were essentially the reverse of the motivators/facilitators. This analysis represents an essential first step forward in developing ethno-culturally tailored interventions to optimize adherence.

Multistate outbreak of listeriosis caused by imported cheese and evidence of cross-contamination of other cheeses, USA, 2012.

Listeria monocytogenes is a foodborne pathogen that can cause bacteraemia, meningitis, and complications during pregnancy. In July 2012, molecular subtyping identified indistinguishable L. monocytogenes isolates from six patients and two samples of different cut and repackaged cheeses. A multistate outbreak investigation was initiated. Initial analyses identified an association between eating soft cheese and outbreak-related illness (odds ratio 17·3, 95% confidence interval 2·0-825·7) but no common brand. Cheese inventory data from locations where patients bought cheese and an additional location where repackaged cheese yielded the outbreak strain were compared to identify cheeses for microbiological sampling. Intact packages of imported ricotta salata yielded the outbreak strain. Fourteen jurisdictions reported 22 cases from March-October 2012, including four deaths and a fetal loss. Six patients ultimately reported eating ricotta salata; another reported eating cheese likely cut with equipment also used for contaminated ricotta salata, and nine more reported eating other cheeses that might also have been cross-contaminated. An FDA import alert and US and international recalls followed. Epidemiology-directed microbiological testing of suspect cheeses helped identify the outbreak source. Cross-contamination of cheese highlights the importance of using validated disinfectant protocols and routine cleaning and sanitizing after cutting each block or wheel.

Changes in mitochondrial perilipin 3 and perilipin 5 protein content in rat skeletal muscle following endurance training and acute stimulated contraction.

NEW FINDINGS: What is the central question of this study? The aim was to determine whether mitochondrial protein content of perilipin 3 (PLIN3) and perilipin 5 (PLIN5) is increased following endurance training and whether mitochondrial PLIN5 protein is increased to a greater extent in endurance-trained rats when compared with sedentary rats following acute contraction. What is the main finding and its importance? Mitochondrial PLIN3 but not PLIN5 protein was increased in endurance-trained compared with sedentary rats, suggesting a mitochondrial role for PLIN3 due to chronic exercise. Contrary to our hypothesis, acute mitochondrial PLIN5 protein was similar in both sedentary and endurance-trained rats. Endurance training results in an increased association between skeletal muscle lipid droplets and mitochondria. This association is likely to be important for the expected increase in intramuscular fatty acid oxidation that occurs with endurance training. The perilipin family of lipid droplet proteins, PLIN(2-5), are thought to play a role in skeletal muscle lipolysis. Recently, results from our laboratory demonstrated that skeletal muscle mitochondria contain PLIN3 and PLIN5 protein. Furthermore, 30 min of stimulated contraction induces an increased mitochondrial PLIN5 content. To determine whether mitochondrial content of PLIN3 and PLIN5 is altered with endurance training, Sprague-Dawley rats were randomized into sedentary or endurance-trained groups for 8 weeks of treadmill running followed by an acute (30 min) sciatic nerve stimulation to induce lipolysis. Mitochondrial PLIN3 protein was ∼1.5-fold higher in red gastrocnemius of endurance-trained rats compared with sedentary animals, with no change in mitochondrial PLIN5 protein. In addition, there was an increase in plantaris intramuscular lipid storage. Acute electrically stimulated contraction in red gastrocnemius from sedentary and endurance-trained rats resulted in a similar increase of mitochondrial PLIN5 between these two groups, with no net change in PLIN3 in either group. Plantaris intramuscular lipid content decreased to a similar extent in sedentary and endurance-trained rats. These results suggest that while total mitochondrial PLIN5 content is not altered by endurance training, PLIN5 does have an acute role in the mitochondrial fraction during muscle contraction. Conversely, mitochondrial PLIN3 does not change acutely with muscle contraction, but PLIN3 content was increased following endurance training, indicating a role in chronic adaptations of skeletal muscle.

[Tardive dyskinesia and second generation antipsychotics: a review of four cases]. / Dyskinésies tardives et neuroleptiques atypiques : revue de quatre cas cliniques et discussion.

We report four cases of tardive dyskinesia (TD) with second generation antipsychotics (SGA). All of those cases where women, three of them had affective psychosis. The presentation of TD where choreo athetosis in one case, respiratory dyskinesia in another and a tardive dystonia in a third. The fourth one had a very precocious form after just a few weeks of treatment. All of them, except one, had a major form of the disorder, with a major impact on their quality of live. We discuss the necessity to remain aware of this dangerous side effect and to keep it in mind while prescribing SGA for bipolar disorders.

Scaling of resistive guiding of laser-driven fast-electron currents in solid targets.

The resistive magnetic field plays a crucial role in determining the laser produced fast-electron transport in solid targets. The scaling of the resistive guiding is derived and benchmarked against two-dimensional collisional particle-in-cell simulations. We study the impact of the initial state of the material (Z dependence, conductor, or insulator) on global electron-transport patterns, and conclude that the initial state of a conductor or insulator is not important. Instead, global transport patterns depend on the material Z. The fast-electron transport seen in the simulations is consistent with the derived scaling rule. Previous experimental observations [e.g., R. B. Stephens et al., Phys. Rev. E 69, 066414 (2004) and Y. Sentoku et al., Phys. Rev. Lett. 107, 135005 (2011)] that show confinement or divergence in various regimes are also explained by our scaling. The presented scaling then becomes a useful tool to design compact radiation sources or fast ignitor experiments.

Understanding the influence of urban- or rural-living on cardiac patients' decisions about diet and physical activity: descriptive decision modeling.

BACKGROUND: It is challenging to assist people to attend to risk factors for coronary artery disease (CAD). There is potential for cultural elements associated with place of residence (i.e., urban- or rural-living) to have an effect on peoples' decision-making about managing CAD risk. AIM: To better understand patient's decision-making processes regarding having a heart-healthy diet and engaging in regular physical activity (major CAD risk factors), and the potential influence of urban- or rural-living. METHODS: Based on a previous series of qualitative interviews with 42 cardiac patients (21 urban-living, 21 rural-living), hierarchical decision-models regarding eating a heart-healthy diet and engaging in regular physical activity were developed, and a survey based on the decision-models generated. The models were then tested for 'fit' with another group of 42 cardiac patients, and were revised to make them more parsimonious. The final models were tested with a novel group of 647 CAD patients from Alberta, Canada (327 urban-living, 320 rural-living). The primary analysis was focused on determining the extent to which patients completing the survey fell in the correct behavioral group. Thereafter individual nodes were examined to determine decision-making constructs that were different between urban- and rural-living patients. RESULTS: When tested, the models had overall accuracy of 93.5% for diet and 97.5% for physical activity. The most salient model nodes that led to differing behavioral outcomes reflected these constructs: perception of control over health; time, effort, or competing priorities; receipt of appropriate information; and appeal of the activity. CONCLUSIONS: This information is potentially useful to assist healthcare providers to: (1) understand patients' decisions regarding their cardiac risk factor modification behavior, and (2) better direct conversations about risk factor modification and educational activities.

Skeletal effects of zoledronic acid in an animal model of chronic kidney disease.

UNLABELLED: Bisphosphonates reduce skeletal loss and fracture risk, but their use has been limited in patients with chronic kidney disease. This study shows skeletal benefits of zoledronic acid in an animal model of chronic kidney disease. INTRODUCTION: Bisphosphonates are routinely used to reduce fractures but limited data exists concerning their efficacy in non-dialysis chronic kidney disease. The goal of this study was to test the hypothesis that zoledronic acid produces similar skeletal effects in normal animals and those with kidney disease. METHODS: At 25 weeks of age, normal rats were treated with a single dose of saline vehicle or 100 µg/kg of zoledronic acid while animals with kidney disease (approximately 30% of normal kidney function) were treated with vehicle, low dose (20 µg/kg), or high dose (100 µg/kg) zoledronic acid, or calcium gluconate (3% in the drinking water). Skeletal properties were assessed 5 weeks later using micro-computed tomography, dynamic histomorphometry, and mechanical testing. RESULTS: Animals with kidney disease had significantly higher trabecular bone remodeling compared to normal animals. Zoledronic acid significantly suppressed remodeling in both normal and diseased animals yet the remodeling response to zoledronic acid was no different in normal and animals with kidney disease. Animals with kidney disease had significantly lower cortical bone biomechanical properties; these were partially normalized by treatment. CONCLUSIONS: Based on these results, we conclude that zoledronic acid produces similar amounts of remodeling suppression in animals with high turnover kidney disease as it does in normal animals, and has positive effects on select biomechanical properties that are similar in normal animals and those with chronic kidney disease.

Propagation of a laser-driven relativistic electron beam inside a solid dielectric.

Laser probe diagnostics: shadowgraphy, interferometry, and polarimetry were used for a comprehensive characterization of ionization wave dynamics inside a glass target induced by a laser-driven, relativistic electron beam. Experiments were done using the 50-TW Leopard laser at the University of Nevada, Reno. We show that for a laser flux of ∼2 × 10(18) W/cm2 a hemispherical ionization wave propagates at c/3 for 10 ps and has a smooth electron-density distribution. The maximum free-electron density inside the glass target is ∼2 × 10(19) cm-3, which corresponds to an ionization level of ∼0.1%. Magnetic fields and electric fields do not exceed ∼15 kG and ∼1 MV/cm, respectively. The electron temperature has a hot, ringlike structure with a maximum of ∼0.7 eV. The topology of the interference phase shift shows the signature of the "fountain effect", a narrow electron beam that fans out from the propagation axis and heads back to the target surface. Two-dimensional particle-in-cell (PIC) computer simulations demonstrate radial spreading of fast electrons by self-consistent electrostatic fields driven by laser. The very low ionization observed after the laser heating pulse suggests a fast recombination on the sub-ps time scale.

Tiotropium improves walking endurance in COPD.

The primary objective of this study was to evaluate the effects of a 3-week treatment with tiotropium on walking capacity in chronic obstructive pulmonary disease (COPD). After familiarisation with study procedures, 36 patients were randomised to receive tiotropium 18 µg once daily or a matching placebo in a double-blind, parallel-group study. Pre- (trough) and 2-h post-dose pulmonary function was measured. An endurance shuttle walk was then completed. The same procedures were repeated after 3 weeks of treatment. Ventilatory parameters were monitored during exercise. At 3 weeks, tiotropium significantly improved walking endurance time in comparison with placebo, with a mean±sd between-group difference of 128±141 s (p=0.017). At 3 weeks, trough values for forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC) were significantly improved with tiotropium in comparison with placebo. The post-dose response to tiotropium was statistically superior to placebo after the first dose and after 3 weeks of treatment for FEV(1), FVC and inspiratory capacity. Ventilation and tidal volume at the end of walking were significantly improved with tiotropium. 3 weeks of tiotropium resulted in a greater walking endurance in patients with COPD. Improvements in FEV(1), maximal ventilation and tidal volume may contribute to this enhanced exercise capacity.

O2 uptake kinetics, pyruvate dehydrogenase activity, and muscle deoxygenation in young and older adults during the transition to moderate-intensity exercise.

The adaptation of pulmonary O(2) uptake (Vo(2)(p)) kinetics is slowed in older compared with young adults during the transition to moderate-intensity exercise. In this study, we examined the relationship between Vo(2)(p) kinetics and mitochondrial pyruvate dehydrogenase (PDH) activity in young (n = 7) and older (n = 6) adults. Subjects performed cycle exercise to a work rate corresponding to approximately 90% of estimated lactate threshold. Phase 2 Vo(2)(p) kinetics were slower (P < 0.05) in older (tau = 40 +/- 17 s) compared with young (tau = 21 +/- 6 s) adults. Relative phosphocreatine (PCr) breakdown was greater (P < 0.05) at 30 s in older compared with young adults. Absolute PCr breakdown at 6 min was greater (P < 0.05) in older compared with young adults. In young adults, PDH activity increased (P < 0.05) from baseline to 30 s, with no further change observed at 6 min. In older adults, PDH activity during baseline exercise was similar to that seen in young adults. During the exercise transition, PDH activity did not increase (P > 0.05) at 30 s of exercise but was elevated (P < 0.05) after 6 min. The change in deoxyhemoglobin (HHb) was greater for a given Vo(2)(p) in older adults, and there was a similar time course of HHb accompanying the slower Vo(2)(p) kinetics in the older adults, suggesting a slower adaptation of bulk O(2) delivery in older adults. In conclusion, the slower adaptation of Vo(2)(p) in older adults is likely a result of both an increased metabolic inertia and lower O(2) availability.

[Does cerebral salt wasting syndrome exist?]. / Le syndrome de perte de sel d'origine cérébrale existe-t-il?

Increased natriuresis is a frequent situation after subarachnoid haemorrhage (SAH). It may be responsible for hyponatremia, which can be dangerous in case of severe hypo-osmolarity or hypovolemia. Inappropriate secretion of antidiuretic hormone or cerebral salt wasting syndrome (CSWS) have been incriminated for hyponatremia after SAH, but it remains difficult to distinguish between both syndromes. There are many explanations for increased natriuresis after SAH, depending on the level of blood pressure, the volemia, and the presence or not of natriuretic peptides. The cerebral insult and the treatments, which are done to fight against elevated intracranial pressure or vasospasm, can modify any of these parameters. So it appears that the word "cerebral" in CSWS is probably not a good term and it would be better to talk about appropriate or non-appropriate natriuretic response. Corticoïds or urea can be useful for controlling hypernatriuresis.

[Early diagnostic for vasospasm after aneurysmal subarachnoid haemorrhage]. / Comment faire le diagnostic précoce d'un vasospasme?

Vasospasm is the leading cause of sequelae or deaths after aneurysmal subarachnoid haemorrhage. Vasospasm occurs 2-10 days after haemorrhage and that justifies close monitoring during this period. Because clinical signs appear often to late to reverse ischaemia, paraclinic tools have been developed. Arteriography is the historical gold standard for diagnosis but no clear validated rules exist to measure vessel sections. Diagnosis of vasospasm is, thus, relatively subjective and only reflects one moment of arteries status. Transcranial doppler is a non-invasive and easily repeatable method but sensibility and specificity for vasospasm diagnosis are low compared to arteriography. However, day-to-day changes of arterial blood cells velocities can help to determine vasospasm risk and/or indicate time for arteriography. CT-scanner, PET-scan or IRM can help to evaluate ratio between perfusion and metabolism. Nevertheless, as arteriography, it is only a one-time measurement without control of treatment effects. Waiting for improvement of diagnosis techniques, arteriography stays the gold standard. To choose the right moment for invasive methods, intensivists need to use clinical and transcranial doppler data and start treatment as early as possible to be efficacious.

[Intracerebral monitoring of a patient with vasopasm]. / Monitorage intracérébral d'un patient ayant un vasospasme.

Delayed neurological deficit occurs among 30% of patients after aneurysmal subarachnoid haemorrhage, mainly related to cerebral vasospasm. The early detection of cerebral ischemia remains problematic. Conventional cerebral monitoring (as intracranial pressure and cerebral perfusion pressure) appears to be insufficient, because cerebral ischemia may occur without elevated intracranial pressure. Global cerebral monitoring as venous jugular oxygen saturation are useful for regional monitoring. Local monitoring as oxygen tissue partial pressure (PtiO2) and microdialysis are sensible for brain ischemia detection, but may also ignore episodes occurring in non-monitored brain area. For the detection of most episodes of brain ischemia, several monitoring system should be use performing a multimodal intracerebral monitoring. Brain microdialysis and oxygen tissue partial pressure are promising monitoring system.