Effects of aquatic exercise on appetitive responses in adolescents with obesity: An exploratory study.

Aquatic exercise has been suggested as a beneficial modality to improve weight loss, cardiorespiratory fitness and quality of life in adolescents with obesity; however, its impact on appetite control in youth remains unknown. The aim of this preliminary study was to examine the effect of an acute aquatic exercise session on energy intake (EI), appetite feelings and food reward in adolescents with obesity. Twelve adolescents with obesity (12-16 years, Tanner stage 3-5, 9 males) randomly completed two conditions: i) control (CON); ii) aquatic exercise session (AQUA). One hour before lunch, the adolescents stayed at rest outside the water in a quiet room for 45 min on CON while they performed a 45-min aquatic exercise session on AQUA. Ad libitum EI and macronutrients were assessed at lunch and dinner, subjective appetite feelings taken at regular intervals, and food reward measured before and after lunch. Paired T-test showed that EI was not different between CON and AQUA at lunch (1333 ± 484 kcal vs 1409 ± 593 kcal; p = 0.162) and dinner (528 ± 218 kcal vs 513 ± 204 kcal; p = 0.206). Total daily ad libitum EI was significantly higher on AQUA (1922 ± 649 kcal) compared with CON (1861 ± 685 kcal; p = 0.044) but accounting for the exercise-induced energy expenditure, relative energy intake did not differ (2263 ± 732 kcal vs 2117 ± 744 kcal, p = 0.304). None of the appetite feelings (hunger, fullness, prospective food consumption and desire to eat) and food reward dimensions were significantly different between conditions. These preliminary and exploratory results suggest that an acute aquatic-exercise session might not induce energy compensatory responses in adolescents with obesity.

Using machine learning to predict perfusionists' critical decision-making during cardiac surgery.

The cardiac surgery operating room is a high-risk and complex environment in which multiple experts work as a team to provide safe and excellent care to patients. During the cardiopulmonary bypass phase of cardiac surgery, critical decisions need to be made and the perfusionists play a crucial role in assessing available information and taking a certain course of action. In this paper, we report the findings of a simulation-based study using machine learning to build predictive models of perfusionists' decision-making during critical situations in the operating room (OR). Performing 30-fold cross-validation across 30 random seeds, our machine learning approach was able to achieve an accuracy of 78.2% (95% confidence interval: 77.8% to 78.6%) in predicting perfusionists' actions, having access to only 148 simulations. The findings from this study may inform future development of computerised clinical decision support tools to be embedded into the OR, improving patient safety and surgical outcomes.

Diet- but not exercise-induced iso-energetic deficit induces compensatory appetitive responses.

Although physical exercise and dietary restriction can be both used to induce energy deficits, they have been suggested to favor different compensatory appetitive responses. While dietary restriction might favor increased subsequent energy intake and appetite sensations, such compensatory responses have not been observed after a similar deficit by exercise. The present work provides a first overview of the actual evidences discussing the effects of iso-energetic deficits induced by exercise versus dietary restriction on subsequent energy intake, appetite sensations, and on the potentially involved hedonic and physiological mechanisms.

Satiety responsiveness but not food reward is modified in response to an acute bout of low versus high intensity exercise in healthy adults.

To compare the effect of iso-caloric low and high intensity exercises on Satiety Quotient and Food Reward in response to a fixed meal in healthy young adults. Anthropometric measurements, body composition (BIA), aerobic capacity (VO2 max) and food preferences were assessed in 19 healthy normal-weight young adults (21 ±â€¯0.5 years old, 10 men). They randomly completed 3 experimental sessions: i) control session without exercise (CON); ii) High Intensity exercise session (HIE); iii) Low intensity exercise session (LIE). Thirty minutes after exercise or rest, then received a fixed lunch. Food reward (Leeds Food Preference Questionnaire) was assessed before and after the meal. Appetite sensations were assessed at regular intervals, SQ was calculated from the lunch meal and self-reported food intake was collected for the rest of the day. Mean body weight was 66.7 ±â€¯9.2 kg, body mass index was 22.3 ±â€¯2.9 kg/m2 and FM% was 18.7 ±â€¯6.8%. Appetite feelings did not differ between conditions and were not affected by exercise. SQ for satiety was not different between conditions. SQ hunger on CON was significantly higher than on LIE and HIE (p ≤ 0.05) with no difference between exercise conditions. SQ for desire to eat was significantly higher on CON versus HIE (p ≤ 0.01) with no differences between CON and LIE and between exercise sessions. SQ PFC was significantly lower on HIE compared with CON (p = 0.02) with no differences between LIE and CON and between LIE and HIE. Food reward was not significantly different between the three condition as well as self-reported total food and macronutrient intake for the rest of the days. Acute exercise, depending on its intensity, might affect the satiating response to food intake in healthy adults, without altering food reward.

FLAIR2 improves LesionTOADS automatic segmentation of multiple sclerosis lesions in non-homogenized, multi-center, 2D clinical magnetic resonance images.

BACKGROUND: Accurate segmentation of MS lesions on MRI is difficult and, if performed manually, time consuming. Automatic segmentations rely strongly on the image contrast and signal-to-noise ratio. Literature examining segmentation tool performances in real-world multi-site data acquisition settings is scarce. OBJECTIVE: FLAIR2, a combination of T2-weighted and fluid attenuated inversion recovery (FLAIR) images, improves tissue contrast while suppressing CSF. We compared the use of FLAIR and FLAIR2 in LesionTOADS, OASIS and the lesion segmentation toolbox (LST) when applied to non-homogenized, multi-center 2D-imaging data. METHODS: Lesions were segmented on 47 MS patient data sets obtained from 34 sites using LesionTOADS, OASIS and LST, and compared to a semi-automatically generated reference. The performance of FLAIR and FLAIR2 was assessed using the relative lesion volume difference (LVD), Dice coefficient (DSC), sensitivity (SEN) and symmetric surface distance (SSD). Performance improvements related to lesion volumes (LVs) were evaluated for all tools. For comparison, LesionTOADS was also used to segment lesions from 3 T single-center MR data of 40 clinically isolated syndrome (CIS) patients. RESULTS: Compared to FLAIR, the use of FLAIR2 in LesionTOADS led to improvements of 31.6% (LVD), 14.0% (DSC), 25.1% (SEN), and 47.0% (SSD) in the multi-center study. DSC and SSD significantly improved for larger LVs, while LVD and SEN were enhanced independent of LV. OASIS showed little difference between FLAIR and FLAIR2, likely due to its inherent use of T2w and FLAIR. LST replicated the benefits of FLAIR2 only in part, indicating that further optimization, particularly at low LVs is needed. In the CIS study, LesionTOADS did not benefit from the use of FLAIR2 as the segmentation performance for both FLAIR and FLAIR2 was heterogeneous. CONCLUSIONS: In this real-world, multi-center experiment, FLAIR2 outperformed FLAIR in its ability to segment MS lesions with LesionTOADS. The computation of FLAIR2 enhanced lesion detection, at minimally increased computational time or cost, even retrospectively. Further work is needed to determine how LesionTOADS and other tools, such as LST, can optimally benefit from the improved FLAIR2 contrast.

Global transcriptome profiling of mild relapsing-remitting versus primary progressive multiple sclerosis.

BACKGROUND AND PURPOSE: Genetic research in multiple sclerosis (MS) mostly compares patients with MS with healthy controls, but does not differentiate between MS disease courses. We compared peripheral blood gene expression patterns between extremes of MS phenotypes, i.e. patients with mild relapsing-remitting MS (mRRMS) and primary progressive MS (PPMS). METHODS: We analyzed global gene expression profiles of peripheral blood samples of age- and gender-matched patients with mRRMS and PPMS. Detailed bioinformatic and gene set enrichment analysis, pathway and principle component analyses were used to identify differentially expressed genes and pathways. RESULTS: A total of 84 genes were significantly deregulated between the groups. Of those, 19 had been previously reported to be deregulated in patients with MS as compared with healthy controls, including major histocompatibility complex, interferon receptor 2 and interleukin 6 receptor. Detailed molecular pathway analysis revealed significant up-regulation of antigen processing and presentation, leukocyte transendothelial migration, nucleotide-binding oligomerization domain-like receptor signaling, chemokine signaling and down-regulation of RNA transport, spliceosome and aminoacyl-tRNA biosynthesis pathways in PPMS compared with mRRMS. CONCLUSION: Our analyses show significant differences between mRRMS and PPMS gene expression. Surprisingly, the differentially expressed genes were mostly involved in immunological and inflammatory pathways, suggesting that the difference in MS phenotypes is caused primarily by a difference in immune responses. It should be kept in mind that our analyses were in peripheral blood only, and that the observed differences in inflammatory pathways may be a substrate of the analysed tissue. Further research into gene expression differences between disease courses including analyses in central nervous system tissue is warranted.

Smoking does not influence disability accumulation in primary progressive multiple sclerosis.

BACKGROUND AND PURPOSE: The modifiable risk factor cigarette smoking has been associated with an increased risk of developing multiple sclerosis (MS) and with disease activity in relapsing-remitting MS. However, less is known about the effect of smoking on disease progression in progressive MS. Here the association between cigarette smoking and disability accumulation in primary progressive MS (PPMS) is investigated. METHODS: Kaplan-Meier survival analyses and Cox proportional hazard modelling were used to investigate the influence of cigarette smoking on the risk of reaching Expanded Disability Status Scale (EDSS) 4 and 6 as well as the time from EDSS 4 to 6 in patients with PPMS. RESULTS: In all, 416 patients with PPMS and available smoking history were identified. Median time to EDSS 4 was 4 years in ever-smokers and 5 years in never-smokers (P = 0.27), and it was 9 years to EDSS 6 in both ever-smokers and never-smokers (P = 0.48). Smokers were not at increased risk of faster progression to EDSS 4, 6 and from EDSS 4 to 6. Age at disease onset was the strongest risk factor for progression to EDSS 4, 6 and from EDSS 4 to 6. CONCLUSIONS: Our investigation of a large and well-characterized population based PPMS cohort suggests that cigarette smoking does not influence disability accumulation in PPMS. Our findings support the idea that PPMS is driven by different underlying pathomechanisms than relapsing-remitting MS.

Characterisation of osteoarthritis in a small animal model of type 2 diabetes mellitus.

OBJECTIVES: Our objective in this article is to test the hypothesis that type 2 diabetes mellitus (T2DM) is a factor in the onset and progression of osteoarthritis, and to characterise the quality of the articular cartilage in an appropriate rat model. METHODS: T2DM rats were obtained from the UC Davis group and compared with control Lewis rats. The diabetic rats were sacrificed at ages from six to 12 months, while control rats were sacrificed at six months only. Osteoarthritis severity was determined via histology in four knee quadrants using the OARSI scoring guide. Immunohistochemical staining was also performed as a secondary form of osteoarthritic analysis. RESULTS: T2DM rats had higher mean osteoarthritis scores than the control rats in each of the four areas that were analysed. However, only the results at the medial and lateral femur and medial tibia were significant. Cysts were also found in T2DM rats at the junction of the articular cartilage and subchondral bone. Immunohistochemical analysis does not show an increase in collagen II between control and T2DM rats. Mass comparisons also showed a significant relationship between mass and osteoarthritis score. CONCLUSIONS: T2DM was found to cause global degeneration in the UCD rat knee joints, suggesting that diabetes itself is a factor in the onset and progression of osteoarthritis. The immunohistochemistry stains showed little to no change in collagen II degeneration between T2DM and control rats. Overall, it seems that the animal model used is pertinent to future studies of T2DM in the development and progression of osteoarthritis. Cite this article: Bone Joint Res 2014;3:203-11.

Application and a proposed modification of the 2010 McDonald criteria for the diagnosis of multiple sclerosis in a Canadian cohort of patients with clinically isolated syndromes.

BACKGROUND: The 2005 and 2010 McDonald criteria utilize magnetic resonance imaging (MRI) to provide evidence of disease dissemination in space (DIS) and time (DIT) for the diagnosis of multiple sclerosis (MS) in patients who have clinically isolated syndromes (CIS). METHODS: Data from 109 CIS patients not satisfying the 2005 criteria at entry into a randomized controlled minocycline trial were analyzed to determine the proportion who would have been diagnosed with MS at screening based on 2010 criteria. The impact of including symptomatic, as well as asymptomatic, MRI lesions to confirm DIT was also explored. RESULTS: Thirty percent (33/109) of patients, retrospectively, met the 2010 criteria for a diagnosis of MS at baseline. When both symptomatic and asymptomatic lesions were used to confirm DIT, three additional patients met the 2010 criteria. There was a significant 10.1% increase in the proportion of patients who met the 2010 DIS criteria, compared with the 2005 DIS criteria; however, two patients satisfied the 2005 DIS but not 2010 DIS criteria. CONCLUSION: Using 2010 McDonald criteria, 30% of the CIS patients could be diagnosed with MS using a single MRI scan. Inclusion of symptomatic lesions in the DIT criteria further increases this proportion to 33%.

Is there spontaneous energy expenditure compensation in response to intensive exercise in obese youth?

BACKGROUND: Physical activity is mainly used in weight control strategies to favour energy expenditure. Some evidence suggests that exercise might not have the expected impact on energy balance, and may actually cause a decrease in the subsequent physical activity energy expenditure. OBJECTIVE: To question the impact of an acute exercise session of varying intensities on daily energy expenditure in lean and obese adolescents. METHODS: Data from three separate studies conducted in lean and obese 12-15 years old adolescents (study 1: 12 obese; study 2: 10 obese and nine lean; study 3: 15 obese) have been used. Daily energy expenditure (DEE) was assessed in studies 1 and 2 during an exercise condition with an exercise bout at 70%VO(2max) (EX) and a rest day (REST) (using Actiheart and Armbands, respectively). In study 3, DEE was assessed in calorimetric chambers during (i) a high intensity exercise condition (HIE - 75%VO(2max)) and (ji) a condition with a low intensity exercise (LIE - 40%VO(2max)) and (iii) a rest condition (REST). RESULTS: Morning energy expenditure was significantly higher during the exercise conditions whatever the intensity compared with rest. Afternoon energy expenditure was significantly lower following HIE compared to the rest condition in studies 2 and 3. Afternoon energy expenditure was not significantly different between LIE and REST in study 2. Total DEE was not significantly different between conditions in the three studies. CONCLUSION: Obese adolescents seem to show a compensatory response to an acute session of HIE (>70%VO(2max)) by decreasing their following physical activity energy expenditure. Although HIE favours body composition, physical fitness and metabolic profile improvements, this induced compensatory energy expenditure response has to be considered to optimize its effect on weight loss.

Potential impact of releases from a new molybdenum-99 production facility on regional measurements of airborne xenon isotopes.

The monitoring of the radioactive xenon isotopes (131m)Xe, (133)Xe, (133m)Xe, and (135)Xe is important for the detection of nuclear explosions. While backgrounds of the xenon isotopes are short-lived, they are constantly replenished from activities dominated by the fission-based production of (99)Mo used for medical procedures. At present, one of the most critical locations on earth for the monitoring of nuclear explosions is the Korean peninsula where the Democratic People's Republic of Korea (DPRK) has announced that it conducted three nuclear tests between 2006 and 2013. This paper explores the backgrounds that would be caused by the medium to large scale production of (99)Mo in the region of the Korean peninsula.

Corpus callosum volume and interhemispheric transfer in multiple sclerosis.

BACKGROUND: The corpus callosum (CC) is frequently compromised in patients with multiple sclerosis (MS). Structural and functional measurements of the CC may be useful to monitor the progression of the disease. The aim of this pilot study was to determine if bimanual tactile temporal thresholds correlates with CC volume. A tactile temporal threshold is the longest temporal interval that separates the onsets of two tactile stimuli when they are judged by the observer as simultaneous. Judgments to bimanual stimulations require interhemispheric transfer via the CC. METHODS: Thresholds were examined in MS patients and matched controls. Magnetic resonance (MR) images were acquired on a 3T MR system within 48 hours of clinical assessment and measurement of thresholds. RESULTS: Corpus callosum volume was assessed by using a semiautomatic livewire algorithm. The CC volume was smaller (by 21% on average, p < 0.01) and thresholds were higher (by 49% on average, p < 0.03) in MS patients when compared to controls. A significant correlation (r = -0.66, p = 0.01) between CC volume and thresholds emerged for the MS patients. CONCLUSION: Measuring treatment benefits of neuroprotective and repair therapies is a well recognized challenge in MS research. The overall findings of this study suggest that these measurements, which involve the transfer of information interhemispherically via the CC, may be promising outcome measures that warrant further scientific exploration to develop a model to measure recovery.

3T deep gray matter T2 hypointensity correlates with disability over time in stable relapsing-remitting multiple sclerosis: a 3-year pilot study.

Abnormally decreased deep gray matter (GM) signal intensity on T2-weighted MRI (T2 hypointensity) is associated with brain atrophy and disability progression in patients with multiple sclerosis (MS) and is believed to represent excessive iron deposition. We investigated the time course of deep GM T2 hypointensity and its relationship with disability at 3T in 8 stable relapsing-remitting (RR) MS patients treated with minocycline over 3years. MRI and disability measurements were compared at baseline, 6, 12, 24, and 36months. Grand mean deep GM T2 hypointensity was negatively correlated with EDSS over time (r=-0.94, P=0.02). This correlation was strongest in the head of caudate (r=-0.95, P=0.01) and putamen (r=-0.89, P=0.04). Additionally, baseline grand mean deep GM T2 hypointensity appears to predict third year EDSS (r=-0.72, P=0.04). These results suggest that iron associated deep GM injury correlates with patient disability in stable RRMS. Measurements of deep GM T2 hypointensity at high field MRI may prove to be useful in monitoring individuals with MS. Further studies are required to confirm these results in a large sample and to determine if T2 hypointensity changes in clinically active MS patients.

Intramyocellular lipid accumulation is associated with permanent relocation ex vivo and in vitro of fatty acid translocase (FAT)/CD36 in obese patients.

AIMS/HYPOTHESIS: Intramyocellular lipids (IMCL) accumulation is a classical feature of metabolic diseases. We hypothesised that IMCL accumulate mainly as a consequence of increased adiposity and independently of type 2 diabetes. To test this, we examined IMCL accumulation in two different models and four different populations of participants: muscle biopsies and primary human muscle cells derived from non-obese and obese participants with or without type 2 diabetes. The mechanism regulating IMCL accumulation was also studied. METHODS: Muscle biopsies were obtained from ten non-obese and seven obese participants without type 2 diabetes, and from eight non-obese and eight obese type 2 diabetic patients. Mitochondrial respiration, citrate synthase activity and both AMP-activated protein kinase and acetyl-CoA carboxylase phosphorylation were measured in muscle tissue. Lipid accumulation in muscle and primary myotubes was estimated by Oil Red O staining and fatty acid translocase (FAT)/CD36 localisation by immunofluorescence. RESULTS: Obesity and type 2 diabetes are independently characterised by skeletal muscle IMCL accumulation and permanent FAT/CD36 relocation. Mitochondrial function is not reduced in type 2 diabetes. IMCL accumulation was independent of type 2 diabetes in cultured myotubes and was correlated with obesity markers of the donor. In obese participants, membrane relocation of FAT/CD36 is a determinant of IMCL accumulation. CONCLUSIONS/INTERPRETATION: In skeletal muscle, mitochondrial function is normal in type 2 diabetes, while IMCL accumulation is dependent upon obesity or type 2 diabetes and is related to sarcolemmal FAT/CD36 relocation. In cultured myotubes, IMCL content and FAT/CD36 relocation are independent of type 2 diabetes, suggesting that distinct factors in obesity and type 2 diabetes contribute to permanent FAT/CD36 relocation ex vivo.

Glatiramer acetate in combination with minocycline in patients with relapsing--remitting multiple sclerosis: results of a Canadian, multicenter, double-blind, placebo-controlled trial.

Minocycline is proposed as an add-on therapy to improve the efficacy of glatiramer acetate in relapsing-remitting multiple sclerosis. The effect of minocycline plus glatiramer acetate was evaluated in this double-blind, placebo-controlled study by determining the total number of T1 gadolinium-enhanced lesions at months 8 and 9 in patients who were starting glatiramer acetate and had at least one T1 gadolinium-enhanced lesion on screening magnetic resonance imaging. Forty-four participants were randomized to either minocycline 100 mg twice daily or matching placebo for 9 months as add-on therapy. They were assessed at screening and months 1, 3, 6, 8 and 9. Forty participants completed the study. Compared with glatiramer acetate/placebo, glatiramer acetate/minocycline reduced the total number of T1 gadolinium-enhanced lesions by 63% (mean 1.47 versus 2.95; p = 0.08), the total number of new and enlarging T2 lesions by 65% (mean 1.84 versus 5.14; p = 0.06), and the total T2 disease burden (p = 0.10). A higher number of gadolinium-enhanced lesions were present in the glatiramer acetate/minocycline group at baseline; this was incorporated into the analysis of the primary endpoint but makes interpretation of the data more challenging. The risk of relapse tended to be lower in the combination group (0.19 versus 0.41; p = NS). Treatment was safe and well tolerated. We conclude that efficacy endpoints showed a consistent trend favoring combination treatment. As minocycline is a relatively safe oral therapy, further study of this combination is warranted in relapsing-remitting multiple sclerosis.

High dose oral steroids commonly used to treat relapses in Canadian MS clinics.

BACKGROUND: Glucocorticoid treatment improves the speed of functional recovery of acute multiple sclerosis (MS) relapses but has not been shown to provide any long-term functional benefit. There is currently no convincing evidence that the clinical benefit is influenced by the route of administration or the dosage of glucocorticoid, or the particular glucocorticoid prescribed. Recent studies support similarities in the bioequivalence and in the clinical effect of high dose oral corticosteroids for MS relapses. OBJECTIVE: This survey aimed to determine the relapse treatment preferences of clinicians in Canadian MS clinics. METHODS: Members of the Canadian Network of MS Clinics are linked by an email server. A one page survey was distributed to the group to determine and report use of corticosteroids to manage MS relapses amongst Canadian MS specialists. RESULTS: Fifty-one clinicians from 17 MS clinics were surveyed. 32 (63%) surveys were returned representing 16 clinics. Five doses are most commonly prescribed, usually without a taper. Three or four doses and the use of a corticosteroid taper, however, are not uncommon. Gastric cytoprotection and sedatives are often prescribed for use as needed. CONCLUSION: This survey illustrates that when Canadian clinicians with expertise in managing MS treat MS relapses they choose high dose corticosteroids, either oral or i.v. The results therefore represent Canadian practice as these clinicians provide direct patient care and influence care by community neurologists. Until evidence clearly identifies a superior practice all options should be available to clinicians and their patients.

Safety and immunogenicity of a new formulation of interferon beta-1a (Rebif New Formulation) in a Phase IIIb study in patients with relapsing multiple sclerosis: 96-week results.

BACKGROUND: A new formulation of subcutaneous (s.c.) interferon-beta-1a has been developed (Rebif New Formulation, RNF), produced without fetal bovine serum and without human serum albumin as an excipient, with the aim of improving injection tolerability, and reducing immunogenicity. OBJECTIVES: This article reports 96-week analyses of a Phase IIIb, open-label study of the safety and immunogenicity of RNF compared with historical (EVIDENCE study) and recent (REGARD study) data on the original formulation. METHODS: Patients with relapsing multiple sclerosis (McDonald criteria) and an Expanded Disability Status Scale score < 6.0 received RNF, 44 microg s.c. three times weekly. RESULTS: The proportion of neutralizing antibody-positive (NAb+) patients (serum NAb status >or=20 neutralizing units/mL) at week 96 (last observation carried forward; primary endpoint) was 17.4% (exact 95% confidence interval [CI]: 13.0-22.5), compared with 21.4% (95% CI: 17.2-26.2) in the EVIDENCE study, and 27.3% (95% CI: 22.8-32.1) in the REGARD study. The proportion of patients NAb+ at any time during the 96 weeks was 18.9% (95% CI: 14.4-24.2), compared with 27.1% (95% CI: 22.4-32.2) and 33.7% (95% CI: 28.9-38.7), respectively. Most pre-specified categories of adverse events were reported by patients in the RNF study at a similar or lower proportion than in the EVIDENCE and REGARD studies. Injection-site reactions were experienced by fewer patients than in the EVIDENCE and REGARD studies. CONCLUSIONS: RNF has improved overall immunogenicity and safety profiles compared with the original formulation.

Training-induced improvement in lipid oxidation in type 2 diabetes mellitus is related to alterations in muscle mitochondrial activity. Effect of endurance training in type 2 diabetes.

AIM: We investigated whether or not, in type 2 diabetic (T2D) patients, an individualized training effect on whole-body lipid oxidation would be associated with changes in muscle oxidative capacity. METHODS: Eleven T2D patients participated in the study. Whole-body lipid oxidation during exercise was assessed by indirect calorimetry during graded exercise. Blood samples for measuring blood glucose and free fatty acids during exercise, and muscle oxidative capacity measured from skeletal muscle biopsy (mitochondrial respiration and citrate synthase activity), were investigated in the patients before and after a 10-week individualized training program targeted at LIPOXmax, corresponding to the power at which the highest rate of lipids is oxidized (lipid oxidation at LIPOXmax). RESULTS: Training induced both a shift to a higher-power intensity of LIPOXmax (+9.1+/-4.2W; P<0.05) and an improvement of lipid oxidation at LIPOXmax (+51.27+/-17.93 mg min(-1); P<0.05). The improvement in lipid oxidation was correlated with training-induced improvement in mitochondrial respiration (r=0.78; P<0.01) and citrate synthase activity (r=0.63; P<0.05). CONCLUSION: This study shows that a moderate training protocol targeted at the LIPOXmax in T2D patients improves their ability to oxidize lipids during exercise, and that this improvement is associated with enhanced muscle oxidative capacity.

Ethics of placebo-controlled clinical trials in multiple sclerosis: a reassessment.

The increasing number of established effective therapies for relapsing multiple sclerosis (MS) and emerging consensus for early treatment raise practical concerns and ethical dilemmas for placebo-controlled clinical trials in this disease. An international group of clinicians, ethicists, statisticians, regulators, and representatives from the pharmaceutical industry convened to reconsider prior recommendations regarding the ethics of placebo-controlled trials in MS. The group concluded that placebo-controlled trials can still be done ethically, with restrictions. For patients with relapsing MS for which established effective therapies exist, placebo-controlled trials should only be offered with rigorous informed consent if the subjects refuse to use these treatments, have not responded to them, or if these treatments are not available to them for other reasons (e.g., economics). Suggestions are provided to protect subject autonomy and improve informed consent procedures. Recommendations are tighter than previously suggested for placebo-controlled trials in "resource-restricted" environments where established therapies may not be available. Guidance is also provided on the ethics of alternative trial designs and the balance between study subject burden and risk, scientific rationale and interpretability of trial outcomes.