Train your T cells: How skeletal muscles and T cells keep each other fit during aging.

Frailty and a failing immune system lead to significant morbidities in the final years of life and bring along a significant burden on healthcare systems. The good news is that regular exercise provides an effective countermeasure for losing muscle tissue when we age while supporting proper immune system functioning. For a long time, it was assumed that exercise-induced immune responses are predominantly mediated by myeloid cells, but it has become evident that they receive important help from T lymphocytes. Skeletal muscles and T cells interact, not only in muscle pathology but also during exercise. In this review article, we provide an overview of the most important aspects of T cell senescence and discuss how these are modulated by exercise. In addition, we describe how T cells are involved in muscle regeneration and growth. A better understanding of the complex interactions between myocytes and T cells throughout all stages of life provides important insights needed to design strategies that effectively combat the wave of age-related diseases the world is currently faced with.

Effects of breaking up sitting with light-intensity physical activity on cognition and mood in university students.

BACKGROUND: University students often exhibit high levels of sedentary behavior that is negatively associated with cognition and mood. On the other hand, light-intensity physical activity (LIPA) may improve cognitive performance and mood. Therefore, this study investigated the acute effect of LIPA breaks during prolonged sitting on attention, executive functioning, and mood. METHODS: A randomized crossover design was used in this study. In total, 21 healthy adults (15 women, age = 24 ± 3 years, BMI = 23 ± 2 kg/m2 ) completed three prolonged sitting conditions: (1) without a demanding cognitive task (SIT), (2) with a demanding cognitive task (COGN), and (3) with every 25 min sitting interrupted by a 5-minute walk (INTERRUPT). Attention, executive function (response inhibition, task shifting, and working memory updating), and mood were assessed before and after each condition. RESULTS: Linear mixed models analyses showed that prolonged sitting frequently interrupted by LIPA (INTERRUPT) or with cognitively demanding activities (COGN) significantly improved task shifting compared to SIT. However, INTERRUPT did not significantly improve task shifting compared with COGN. No significant acute effects on attention, response inhibition, working memory updating, or mood were found. CONCLUSIONS: Frequent LIPA breaks or cognitively demanding activities have a selective, acute positive impact on one aspect of cognitive performance compared to idle sitting. No evidence was found that LIPA breaks have an acute improvement in attention, executive function, and mood compared to sitting with cognitive loading. To further investigate the effect of PA on cognitive performance, it is necessary to consider cognitive loading and control for the cognitive activity during sitting in the experimental design.

Exercise-induced myocardial T1 increase and right ventricular dysfunction in recreational cyclists: a CMR study.

PURPOSE: Although cardiac troponin I (cTnI) increase following strenuous exercise has been observed, the development of exercise-induced myocardial edema remains unclear. Cardiac magnetic resonance (CMR) native T1/T2 mapping is sensitive to the pathological increase of myocardial water content. Therefore, we evaluated exercise-induced acute myocardial changes in recreational cyclists by incorporating biomarkers, echocardiography and CMR. METHODS: Nineteen male recreational participants (age: 48 ± 5 years) cycled the 'L'étape du tour de France" (EDT) 2021' (175 km, 3600 altimeters). One week before the race, a maximal graded cycling test was conducted to determine individual heart rate (HR) training zones. One day before and 3-6 h post-exercise 3 T CMR and echocardiography were performed to assess myocardial native T1/T2 relaxation times and cardiac function, and blood samples were collected. All participants were asked to cycle 2 h around their anaerobic gas exchange threshold (HR zone 4). RESULTS: Eighteen participants completed the EDT stage in 537 ± 58 min, including 154 ± 61 min of cycling time in HR zone 4. Post-race right ventricular (RV) dysfunction with reduced strain and increased volumes (p < 0.05) and borderline significant left ventricular global longitudinal strain reduction (p = 0.05) were observed. Post-exercise cTnI (0.75 ± 5.1 ng/l to 69.9 ± 41.6 ng/l; p < 0.001) and T1 relaxation times (1133 ± 48 ms to 1182 ± 46 ms, p < 0.001) increased significantly with no significant change in T2 (p = 0.474). cTnI release correlated with increase in T1 relaxation time (p = 0.002; r = 0.703), post-race RV dysfunction (p < 0.05; r = 0.562) and longer cycling in HR zone 4 (p < 0.05; r = 0.607). CONCLUSION: Strenuous exercise causes early post-race cTnI increase, increased T1 relaxation time and RV dysfunction in recreational cyclists, which showed interdependent correlation. The long-term clinical significance of these changes needs further investigation. TRIAL REGISTRATION NUMBERS AND DATE: NCT04940650 06/18/2021. NCT05138003 06/18/2021.

Oxidative stress and impaired oligodendrocyte precursor cell differentiation in neurological disorders.

Oligodendrocyte precursor cells (OPCs) account for 5% of the resident parenchymal central nervous system glial cells. OPCs are not only a back-up for the loss of oligodendrocytes that occurs due to brain injury or inflammation-induced demyelination (remyelination) but are also pivotal in plastic processes such as learning and memory (adaptive myelination). OPC differentiation into mature myelinating oligodendrocytes is controlled by a complex transcriptional network and depends on high metabolic and mitochondrial demand. Mounting evidence shows that OPC dysfunction, culminating in the lack of OPC differentiation, mediates the progression of neurodegenerative disorders such as multiple sclerosis, Alzheimer's disease and Parkinson's disease. Importantly, neurodegeneration is characterised by oxidative and carbonyl stress, which may primarily affect OPC plasticity due to the high metabolic demand and a limited antioxidant capacity associated with this cell type. The underlying mechanisms of how oxidative/carbonyl stress disrupt OPC differentiation remain enigmatic and a focus of current research efforts. This review proposes a role for oxidative/carbonyl stress in interfering with the transcriptional and metabolic changes required for OPC differentiation. In particular, oligodendrocyte (epi)genetics, cellular defence and repair responses, mitochondrial signalling and respiration, and lipid metabolism represent key mechanisms how oxidative/carbonyl stress may hamper OPC differentiation in neurodegenerative disorders. Understanding how oxidative/carbonyl stress impacts OPC function may pave the way for future OPC-targeted treatment strategies in neurodegenerative disorders.

Carnosine quenches the reactive carbonyl acrolein in the central nervous system and attenuates autoimmune neuroinflammation.

BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune disease driven by sustained inflammation in the central nervous system. One of the pathological hallmarks of MS is extensive free radical production. However, the subsequent generation, potential pathological role, and detoxification of different lipid peroxidation-derived reactive carbonyl species during neuroinflammation are unclear, as are the therapeutic benefits of carbonyl quenchers. Here, we investigated the reactive carbonyl acrolein and (the therapeutic effect of) acrolein quenching by carnosine during neuroinflammation. METHODS: The abundance and localization of acrolein was investigated in inflammatory lesions of MS patients and experimental autoimmune encephalomyelitis (EAE) mice. In addition, we analysed carnosine levels and acrolein quenching by endogenous and exogenous carnosine in EAE. Finally, the therapeutic effect of exogenous carnosine was assessed in vivo (EAE) and in vitro (primary mouse microglia, macrophages, astrocytes). RESULTS: Acrolein was substantially increased in inflammatory lesions of MS patients and EAE mice. Levels of the dipeptide carnosine (ß-alanyl-L-histidine), an endogenous carbonyl quencher particularly reactive towards acrolein, and the carnosine-acrolein adduct (carnosine-propanal) were ~ twofold lower within EAE spinal cord tissue. Oral carnosine treatment augmented spinal cord carnosine levels (up to > tenfold), increased carnosine-acrolein quenching, reduced acrolein-protein adduct formation, suppressed inflammatory activity, and alleviated clinical disease severity in EAE. In vivo and in vitro studies indicate that pro-inflammatory microglia/macrophages generate acrolein, which can be efficiently quenched by increasing carnosine availability, resulting in suppressed inflammatory activity. Other properties of carnosine (antioxidant, nitric oxide scavenging) may also contribute to the therapeutic effects. CONCLUSIONS: Our results identify carbonyl (particularly acrolein) quenching by carnosine as a therapeutic strategy to counter inflammation and macromolecular damage in MS.

Carnosine and skeletal muscle dysfunction in a rodent multiple sclerosis model.

Muscle weakness and fatigue are primary manifestations of multiple sclerosis (MS), a chronic disease of the central nervous system. Interventions that enhance muscle function may improve overall physical well-being of MS patients. Recently, we described that levels of carnosine, an endogenous muscle dipeptide involved in contractile function and fatigue-resistance, are reduced in muscle tissue from MS patients and a monophasic rodent MS model (experimental autoimmune encephalomyelitis, EAE). In the present study, we aimed to (1) confirm this finding in a chronic EAE model, along with the characterization of structural and functional muscle alterations, and (2) investigate the effect of carnosine supplementation to increase/restore muscle carnosine levels and improve muscle function in EAE. We performed muscle immunohistochemistry and ex vivo contractility measurements to examine muscle structure and function at different stages of EAE, and following nutritional intervention (oral carnosine: 3, 15 or 30 g/L in drinking water). Immunohistochemistry revealed progressively worsening muscle fiber atrophy and a switch towards a fast-twitch muscle phenotype during EAE. Using ex vivo muscle contractility experiments, we observed reductions in muscle strength and contraction speed, but no changes in muscle fatigability of EAE mice. However, carnosine levels were unaltered during all stages of EAE, and even though oral carnosine supplementation dose-dependently increased muscle carnosine levels up to + 94% after 56 days EAE, this did not improve muscle function of EAE mice. In conclusion, EAE mice display significant, yet time-dependent, muscular alterations, and carnosine intervention does not improve muscle function in EAE.

Lifestyle interventions to reduce sedentary behaviour in clinical populations: A systematic review and meta-analysis of different strategies and effects on cardiometabolic health.

Cardiometabolic comorbidities are highly prevalent in clinical populations, and have been associated (partly) with their sedentary lifestyle. Although lifestyle interventions targeting sedentary behaviour (SB) have been studied extensively in the general population, the effect of such strategies in clinical populations is not yet clear. Therefore, this systematic review and meta-analysis evaluated the effect of different lifestyle interventions on SB and cardiometabolic health in clinical populations. Randomised controlled trials were collected from five bibliographic databases (PubMed, Embase, Web of Science, The Cochrane Central Register of Controlled Trials, and Scopus). Studies were eligible for inclusion if they evaluated a lifestyle intervention to reduce objectively measured SB, in comparison with a control intervention among persons with a clinical condition. Data were pooled using a random-effects meta-analysis. In total, 7094 studies were identified. Eighteen studies met the inclusion criteria and were categorised in five population groups: overweight/obesity, type 2 diabetes mellitus, cardiovascular, neurological/cognitive and musculoskeletal diseases. Participants reduced their SB by 64 min/day (95%CI: [-91, -38] min/day; p < 0.001), with larger within-group differences of multicomponent behavioural interventions including motivational counselling, self-monitoring, social facilitation and technologies (-89 min/day; 95%CI: [-132, -46] min/day; p < 0.001). Blood glycated haemoglobin concentration (-0.17%; 95% CI: [-0.30, -0.04]%; p = 0.01), fat percentage (-0.66%; 95% CI: [-1.26, -0.06]%, p = 0.03) and waist circumference (-1.52 cm; 95%CI: [-2.84, -0.21] cm; p = 0.02) were significantly reduced in the intervention groups compared to control groups. Behavioural lifestyle interventions reduce SB among clinical populations and improve cardiometabolic risk markers such as waist circumference, fat percentage, and glycaemic control. Sedentary behaviour, Cardiometabolic health, Clinical populations.

Can consumer wearable activity tracker-based interventions improve physical activity and cardiometabolic health in patients with chronic diseases? A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: To date, it is unclear if consumer wearable activity trackers (CWATs), with or without behaviour multi-component strategies, effectively improve adherence to physical activity and health outcomes under free living conditions in populations with chronic diseases. Therefore, we systematically evaluated the efficacy of CWAT-based interventions to promote physical activity levels and cardiometabolic health in populations with chronic diseases. METHODS: Randomised controlled trials were collected from five bibliographic databases (PubMed, Embase, Web of Science, The Cochrane Central Register of Controlled Trials and CINAHL). Studies were eligible for inclusion if they evaluated a CWAT-based counselling intervention versus control intervention among patients with chronic respiratory diseases, type 2 diabetes mellitus, cardiovascular diseases, overweight/obesity, cognitive disorders, or sedentary older adults. Data were pooled using a random-effects model. RESULTS: After deduplication 8147 were identified of which 35 studies met inclusion criteria (chronic respiratory diseases: 7, type 2 diabetes mellitus: 12, cardiovascular diseases: 6, overweight/obesity: 3, cognitive disorders: 1, sedentary older adults: 6). Compared to control groups, CWAT-based interventions significantly increased physical activity by 2123 steps per day (95% confidence interval [CI], [1605-2641]; p < 0.001). In addition, CWAT-based interventions in these populations significantly decreased systolic blood pressure (- 3.79 mm Hg; 95% CI: [- 4.53, - 3.04] mm Hg; p < 0.001), waist circumference (- 0.99 cm; 95% CI: [- 1.48, - 0.50] cm; p < 0.001) and low-density lipoprotein cholesterol concentration (- 5.70 mg/dl; 95% CI: [- 9.24, - 2.15] mg/dl; p = 0.002). CONCLUSION: CWAT-based interventions increase physical activity and have beneficial effects on important health-related outcomes such as systolic blood pressure, waist circumference and LDL cholesterol concentration in patients with chronic diseases.

Cardiac function in adolescents with obesity: cardiometabolic risk factors and impact on physical fitness.

OBJECTIVE: To gain greater insights in the etiology and clinical consequences of altered cardiac function in obese adolescents. Therefore, we aimed to examine cardiac structure and function in obese adolescents, and to examine associations between altered cardiac function/structure and cardiometabolic disease risk factors or cardiopulmonary exercise capacity. METHODS: In 29 obese (BMI 31.6 ± 4.2 kg/m², age 13.4 ± 1.1 years) and 29 lean (BMI 19.5 ± 2.4 kg/m², age 14.0 ± 1.5 years) adolescents, fasted blood samples were collected to study hematology, biochemistry, liver function, glycemic control, lipid profile, and hormones, followed by a transthoracic echocardiography to assess cardiac structure/function, and a cardiopulmonary exercise test (CPET) to assess cardiopulmonary exercise parameters. Regression analyses were applied to examine relations between altered echocardiographic parameters and blood parameters or CPET parameters in the entire group. RESULTS: In obese adolescents, left ventricular septum thickness, left atrial diameter, mitral A-wave velocity, E/e' ratio were significantly elevated (p < 0.05), as opposed to lean controls, while mitral e'-wave velocity was significantly lowered (p < 0.01). Elevated homeostatic model assessment of insulin resistance and blood insulin, c-reactive protein, and uric acid concentrations (all significantly elevated in obese adolescents) were independent risk factors for an altered cardiac diastolic function (p < 0.01). An altered cardiac diastolic function was not related to exercise tolerance but to a delayed heart rate recovery (HRR; p < 0.01). CONCLUSIONS: In obese adolescents, an altered cardiac diastolic function was independently related to hyperinsulinemia and whole-body insulin resistance, and only revealed by a delayed HRR during CPET. This indicates that both hyperinsulinemia, whole-body insulin resistance, and delayed HRR could be regarded as clinically relevant outcome parameters.

Effects of an individual 12-week community-located "start-to-run" program on physical capacity, walking, fatigue, cognitive function, brain volumes, and structures in persons with multiple sclerosis.

BACKGROUND: Exercise therapy studies in persons with multiple sclerosis (pwMS) primarily focused on motor outcomes in mid disease stage, while cognitive function and neural correlates were only limitedly addressed. OBJECTIVES: This pragmatic randomized controlled study investigated the effects of a remotely supervised community-located "start-to-run" program on physical and cognitive function, fatigue, quality of life, brain volume, and connectivity. METHOD: In all, 42 pwMS were randomized to either experimental (EXP) or waiting list control (WLC) group. The EXP group received individualized training instructions during 12 weeks (3×/week), to be performed in their community aiming to participate in a running event. Measures were physical (VO2max, sit-to-stand test, Six-Minute Walk Test (6MWT), Multiple Sclerosis Walking Scale-12 (MSWS-12)) and cognitive function (Rao's Brief Repeatable Battery (BRB), Paced Auditory Serial Attention Test (PASAT)), fatigue (Fatigue Scale for Motor and Cognitive Function (FSMC)), quality of life (Multiple Sclerosis Impact Scale-29 (MSIS-29)), and imaging. Brain volumes and diffusion tensor imaging (DTI) were quantified using FSL-SIENA/FIRST and FSL-TBSS. RESULTS: In all, 35 pwMS completed the trial. Interaction effects in favor of the EXP group were found for VO2max, sit-to-stand test, MSWS-12, Spatial Recall Test, FSMC, MSIS-29, and pallidum volume. VO2max improved by 1.5 mL/kg/min, MSWS-12 by 4, FSMC by 11, and MSIS-29 by 14 points. The Spatial Recall Test improved by more than 10%. CONCLUSION: Community-located run training improved aerobic capacity, functional mobility, visuospatial memory, fatigue, and quality of life and pallidum volume in pwMS.

Adrenergically and non-adrenergically mediated human adipose tissue lipolysis during acute exercise and exercise training.

Obesity-related adipose tissue (AT) dysfunction, in particular subcutaneous AT (SCAT) lipolysis, is characterized by catecholamine resistance and impaired atrial natriuretic peptide (ANP) responsiveness. It remains unknown whether exercise training improves (non-)adrenergically mediated lipolysis in metabolically compromised conditions. We investigated the effects of local combined α-/ß-adrenoceptor blockade on abdominal SCAT lipolysis in lean insulin sensitive (IS) (n=10), obese IS (n=10), and obese insulin resistant (IR) (n=10) men. Obese men participated in a 12-week exercise training intervention to determine the effects on SCAT lipolysis. Abdominal SCAT extracellular glycerol concentration and blood flow (ATBF) were investigated using microdialysis, with/without locally combined α-/ß-adrenoceptor blockade at rest, during low-intensity endurance-type exercise and post-exercise recovery. In obese IR men, microdialysis was repeated after exercise intervention. The exercise-induced increase in SCAT extracellular glycerol was more pronounced in obese IS compared with lean IS men, possibly resulting from lower ATBF in obese IS men. The exercise-induced increase in extracellular glycerol was blunted in obese IR compared with obese IS men, despite comparable local ATBF. Abdominal SCAT extracellular glycerol was markedly reduced (remaining ~60% of exercise-induced SCAT extracellular glycerol) following the local α-/ß-adrenoceptor blockade in obese IS but not in IR men, suggesting reduced catecholamine-mediated lipolysis during exercise in obese IR men. Exercise training did not affect (non-)adrenergically mediated lipolysis in obese IR men. Our findings showed a major contribution of non-adrenergically-mediated lipolysis during exercise in male abdominal SCAT. Furthermore, catecholamine-mediated lipolysis may be blunted during exercise in obese IR men but could not be improved by exercise intervention, despite an improved metabolic profile and body composition.

Twelve Weeks of Medium-Intensity Exercise Therapy Affects the Lipoprotein Profile of Multiple Sclerosis Patients.

Multiple sclerosis (MS) is an inflammatory auto-immune disease of the central nervous system (CNS). Serum glucose alterations and impaired glucose tolerance (IGT) are reported in MS patients, and are commonly associated with the development of cardio-metabolic co-morbidities. We previously found that a subgroup of MS patients shows alterations in their lipoprotein profile that are similar to a pre-cardiovascular risk profile. In addition, we showed that a high-intensity exercise training has a positive effect on IGT in MS patients. In this study, we hypothesize that exercise training positively influences the lipoprotein profile of MS patients. To this end, we performed a pilot study and determined the lipoprotein profile before (controls, n = 40; MS patients, n = 41) and after (n = 41 MS only) 12 weeks of medium-intensity continuous training (MIT, n = 21, ~60% of VO2max) or high-intensity interval training (HIT, n = 20, ~100-200% of VO2max) using nuclear magnetic resonance spectroscopy (NMR). Twelve weeks of MIT reduced intermediate-density lipoprotein particle count ((nmol/L); -43.4%; p < 0.01), low-density lipoprotein cholesterol (LDL-c (mg/dL); -7.6%; p < 0.05) and VLDL size ((nm); -6.6%; p < 0.05), whereas HIT did not influence the lipoprotein profile. These results show that MIT partially normalizes lipoprotein alterations in MS patients. Future studies including larger patient and control groups should determine whether MIT can reverse other lipoprotein levels and function and if these alterations are related to MS disease progression and the development of co-morbidities.

Attenuated atrial natriuretic peptide-mediated lipolysis in subcutaneous adipocytes of obese type 2 diabetic men.

Catecholamines and atrial natriuretic peptide (ANP) are major regulators of adipocyte lipolysis. Although obesity is characterized by catecholamine resistance in subcutaneous adipose tissue (SCAT), data on ANP lipolytic response and sensitivity in different adipose tissue (AT) depots of metabolically distinct humans are scarce. Ex vivo catecholamine- and ANP-induced lipolysis was investigated in adipocytes derived from SCAT and visceral AT (VAT) depot of lean (n=13) and obese men, with (n=11) or without (n=18) type 2 diabetes (HbA1c < or ≥ 6.5%). Underlying molecular mechanisms were examined by looking at functional receptors in the NP signalling pathway at the mRNA and protein level. Maximal ANP- and catecholamine-induced lipolysis in SCAT was blunted in obese type 2 diabetics compared with age-matched lean men whereas non-diabetic obese subjects showed intermediate responses. This blunted ANP-mediated lipolytic response was accompanied by lower mRNA and protein expression of the type-A natriuretic peptide (NP) receptor and higher mRNA but reduced protein expression of the scavenging type-C receptor. Maximal ANP-induced lipolysis was lower in VAT compared with SCAT but not different between groups. Collectively, our data show that both ANP- and catecholamine-mediated lipolysis is attenuated in SCAT of obese men with type 2 diabetes, and might be partially explained by NP receptor defects. Therefore, improving maximal ANP responsiveness in adipose tissue might be a potential novel strategy to improve obesity-associated metabolic complications.

Cardiopulmonary fitness is related to disease severity in multiple sclerosis.

BACKGROUND: In persons with MS (pwMS), a lower cardiopulmonary fitness has been associated with a higher risk for secondary disorders, decreased functional capacity, symptom worsening and reduced health-related quality of life. OBJECTIVE: To investigate the association between disease severity and cardiopulmonary fitness. METHODS: Data from cardiopulmonary exercise tests, previously conducted in three different countries, were pooled. The association between disease severity (Expanded Disability Status Scale (EDSS)) and cardiopulmonary fitness (peak oxygen uptake (VO2peak)) was adjusted for age, sex and the country of origin. RESULTS: The combined sample comprised 116 ambulant pwMS having a mean (± SD) EDSS score of 2.7 ± 1.3. There was a significant correlation (r = -0.418, p < .01) between VO2peak and EDSS. A multiple regression model (R(2) = 0.520, p < .01) was constructed to describe VO2peak (mL∙kg(-1)∙min(-1)); VO2peak = 36.622 - 5.433 (Sex (1=men)) - 0.124 (Age) - 2.082 (EDSS) + 2.737 (Belgium) + 8.674 (Denmark). CONCLUSION: There was a significant association between disease severity and cardiopulmonary fitness. The close relation between cardiopulmonary fitness and chronic conditions associated with physical inactivity, suggest a progressive increase in risk of secondary health conditions in pwMS.

12 Weeks of Combined Endurance and Resistance Training Reduces Innate Markers of Inflammation in a Randomized Controlled Clinical Trial in Patients with Multiple Sclerosis.

Previously, we reported that patients with multiple sclerosis (MS) demonstrate improved muscle strength, exercise tolerance, and lean tissue mass following a combined endurance and resistance exercise program. However, the effect of exercise on the underlying disease pathogenesis remains elusive. Since recent evidence supports a crucial role of dendritic cells (DC) in the pathogenesis of MS, we investigated the effect of a 12-week combined exercise program in MS patients on the number and function of DC. We demonstrate an increased number of plasmacytoid DC (pDC) following the exercise program. These pDC display an activated phenotype, as evidenced by increased numbers of circulating CD62L(+) and CD80(+) pDC. Interestingly, the number of CD80(+) pDC positively correlates with the presence of IL-10-producing regulatory type 1 cells (Tr1), an important cell type for maintaining peripheral tolerance to self-antigens. In addition, decreased production of the inflammatory mediators, TNF-α and MMP-9, upon Toll-like receptor (TLR) stimulation was found at the end of the exercise program. Overall, our findings suggest that the 12-week exercise program reduces the secretion of inflammatory mediators upon TLR stimulation and promotes the immunoregulatory function of circulating pDC, suggestive for a favorable impact of exercise on the underlying immunopathogenesis of MS.

Magnitude of muscle wasting early after on-pump coronary artery bypass graft surgery and exploration of aetiology.

NEW FINDINGS: What is the central question of this study? It remains uncertain whether significant fat-free mass wasting occurs early after coronary artery bypass graft surgery, and the aetiology of this wasting in these particular conditions is unexplored. What is the main finding and its importance? Significant fat-free mass wasting is present after coronary artery bypass graft surgery, and this wasting effect is greater in younger patients and in patients with greater increments in blood cortisol-to-testosterone ratios after surgery. The magnitude and aetiology of muscle wasting early after coronary artery bypass graft (CABG) surgery remains unknown. In the present study, we assessed changes in fat-free mass early after CABG surgery and explored the possible aetiology (relationships with postsurgical changes in blood hormones, insulin resistance, subject characteristics and inflammation) for these changes. Fat-free mass was assessed before and 23 (range: 25) days after CABG surgery in 25 subjects. Blood testosterone, cortisol, insulin-like growth factor-1, growth hormone, sex hormone-binding globulin, glucose, insulin, C-peptide and C-reactive protein concentrations were determined, and free androgen index, cortisol-to-testosterone ratio and HOMA-IR index were all calculated before surgery, during the first 3 days after surgery and at reassessment of body composition. Relationships between changes in fat-free mass and changes in blood parameters after surgery or subject characteristics were studied. After surgery, free androgen index and blood sex hormone-binding globulin, testosterone and insulin-like growth factor-1 concentrations decreased significantly, while HOMA-IR index, cortisol-to-testosterone ratio, blood growth hormone, insulin and C-reactive protein concentrations increased significantly (P < 0.0025, observed α > 0.80). Whole-body fat-free mass decreased significantly [by -1.9 (range: 9.1) kg, P < 0.0025, observed α = 0.99] after surgery. According to regression analysis, greater absolute loss of fat-free mass was observed after CABG surgery in subjects who were younger, who experienced a greater increase in blood cortisol-to-testosterone ratio after surgery and/or who underwent earlier reassessment of body composition (P < 0.05). Significant decrements in fat-free mass were observed early after CABG surgery, especially in younger subjects and/or subjects with elevated blood cortisol-to-testosterone ratios after surgery. Interventions to preserve fat-free mass soon after CABG surgery are thus warranted.

Rapid Exercise-Induced Mobilization of Dendritic Cells Is Potentially Mediated by a Flt3L- and MMP-9-Dependent Process in Multiple Sclerosis.

In healthy individuals, one exercise bout induces a substantial increase in the number of circulating leukocytes, while their function is transiently suppressed. The effect of one exercise bout in multiple sclerosis (MS) is less studied. Since recent evidence suggests a role of dendritic cells (DC) in the pathogenesis of MS, we investigated the effect of one combined endurance/resistance exercise bout on the number and function of DC in MS patients and healthy controls. Our results show a rapid increase in the number of DC in response to physical exercise in both MS patients and controls. Further investigation revealed that in particular DC expressing the migratory molecules CCR5 and CD62L were increased upon acute physical activity. This may be mediated by Flt3L- and MMP-9-dependent mobilization of DC, as demonstrated by increased circulating levels of Flt3L and MMP-9 following one exercise bout. Circulating DC display reduced TLR responsiveness after acute exercise, as evidenced by a less pronounced upregulation of activation markers, HLA-DR and CD86, on plasmacytoid DC and conventional DC, respectively. Our results indicate mobilization of DC, which may be less prone to drive inflammatory processes, following exercise. This may present a negative feedback mechanism for exercise-induced tissue damage and inflammation.

Circulating dendritic cells of multiple sclerosis patients are proinflammatory and their frequency is correlated with MS-associated genetic risk factors.

BACKGROUND: The role of the adaptive immune system and more specifically T cells in the pathogenesis of multiple sclerosis (MS) has been studied extensively. Emerging evidence suggests that dendritic cells (DCs), which are innate immune cells, also contribute to MS. OBJECTIVES: This study aimed to characterize circulating DC populations in MS and to investigate the contribution of MS-associated genetic risk factors to DCs. METHODS: Ex vivo analysis of conventional (cDCs) and plasmacytoid DCs (pDCs) was carried out on peripheral blood of MS patients (n = 110) and age- and gender-matched healthy controls (n = 112). RESULTS: Circulating pDCs were significantly decreased in patients with chronic progressive MS compared to relapsing-remitting MS and healthy controls. While no differences in cDCs frequency were found between the different study groups, HLA-DRB1*1501(+) MS patients and patients not carrying the protective IL-7Rα haplotype 2 have reduced frequencies of circulating cDCs and pDCs, respectively. MS-derived DCs showed enhanced IL-12p70 production upon TLR ligation and had an increased expression of the migratory molecules CCR5 and CCR7 as well as an enhanced in vitro chemotaxis. CONCLUSION: DCs in MS are in a pro-inflammatory state, have a migratory phenotype and are affected by genetic risk factors, thereby contributing to pathogenic responses.

Intramedullary headless compression screw fixation of the middle phalanx: tips, tricks, and pitfalls.

This report emphasizes careful consideration of surgical technique for intramedullary screw fixation in middle phalanx fractures. Highlighting pitfalls, particularly with K-wire placement, it suggests the antegrade trans-articular approach as superior, urging further research for improved patient outcomes.

Risk factors related to cardiovascular diseases and the metabolic syndrome in multiple sclerosis - a systematic review.

Despite many epidemiological studies examining comorbidity in people with multiple sclerosis (pMS), there are conflicting opinions on whether pMS are at more or less risk of cardiovascular disease (CVD) and the metabolic syndrome compared with the general population. As pMS can now expect longer survival, this as an important question both at an individual and public health level. This study aimed to systematically review the literature linking MS to CVD risks and to the risk factors constituting the metabolic syndrome. This systematic review is based on a comprehensive literature search of six databases (Swemed+, Pubmed, Embase, Cochrane, PEDro and CINAHL). In total 34 studies were identified. Despite the high number of identified papers, only limited and inconsistent data exist on the risk factors of the metabolic syndrome and MS. Overall, the data suggest an increased CVD risk in pMS. From the existing studies it is not clear whether the increased risk of CVD is related to an increased risk of obesity or changes in body composition, hypertension, dyslipidemia or type II diabetes in pMS, indicating the need for future research in the field, if we are to advise pMS adequately in avoiding preventable comorbidity.