Automated, Point-of-Care mobile flow cytometry: Bringing the laboratory to the sample.

Background: Innate effector cells are very responsive to infectious and inflammatory cues found in damaged and inflamed tissues. Their activation is a potential target to assess the state of the immune system. Unfortunately, these cells are very susceptible for ex-vivo activation, hampering accurate interpretation of flow cytometry data. Whether a brief window exists before ex-vivo activation starts to occur is currently unknown. Aims: 1) This study extensively investigated ex-vivo activation of innate effector cells over time. 2) We tested the feasibility of applying a mobile, automated, flow cytometry laboratory for out-of-hospital Point-of-Care analyses to minimize ex-vivo activation bias. Methods: 1) Ex-vivo neutrophil, eosinophil and monocyte activation in a blood collection tube over time and the reactivity to a formyl-peptide was investigated in a healthy cohort. 2) To facilitate fast, out-of-hospital analysis, application of the mobile flow cytometry was tested by placing an automated flow cytometer into a van. The stability of the setup was assessed by repetitively measuring laser alignment and fluorescence verification beads. Findings: 1) Immediately after venipuncture activation marker expression on neutrophils, eosinophils and monocyte subsets started to change in a time-dependent manner. 2) The mobile flow cytometry laboratory travelled over 3000 km, performing measurements at 19 locations with a median single-person-set-up time of 14 min. The laser alignment and fluorescence were stable during all experiments. Conclusions: Accurate flow data of innate immune cells are only obtained when ex-vivo activation is kept to minimum. The use of a mobile, fast, automated, flow cytometry laboratory for out-of-hospital Point-of-Care analyses provides new investigational and diagnostic possibilities outside major hospital flow cytometry laboratories.

Exertional Heat Stroke and Rhabdomyolysis: A Medical Record Review and Patient Perspective on Management and Long-Term Symptoms.

INTRODUCTION: Exertional heat stroke (EHS) is a medical emergency, occurring when the body generates more heat than it can dissipate, and frequently associated with exertional rhabdomyolysis (ERM). In the present study we aimed to (I) identify clinical features and risk factors, (II) describe current prehospital management, (III) investigate long-term outcomes including the impact on mental health, and review the guidance received during restarting activities. We hope that our approach will improve individual and organizational heat illness preparedness, and improve follow-up care. METHODS: We performed a prospective online survey and retrospective medical record review among athletes and military personnel with an episode of EHS/ERM in the Netherlands between 2010 and 2020. We evaluated prehospital management, risk factors, clinical features and long-term outcomes at 6 and 12 months after the event, including mental health symptoms. Furthermore, we investigated what guidance participants received during follow-up, and assessed the patients' perspective on these outcomes. RESULTS: Sixty participants were included, 42 male (70%) and 18 female (30%), of which 47 presented with EHS (78%) and 13 with ERM (22%). Prehospital management was inconsistent and in the majority of participants not conducted according to available guidelines. Self-reported risk factors included not feeling well-acclimatized to environmental heat (55%) and peer pressure (28%). Self-reported long-term symptoms included muscle symptoms at rest (26%) or during exercise (28%), and neurological sequelae (11%). Validated questionnaires (CIS, HADS and SF-36) were indicative of severe fatigue (30%) or mood/anxiety disorders (11%). Moreover, 90% expressed a lack of follow-up care and that a more frequent and intensive follow-up would have been beneficial for their recovery process. CONCLUSION: Our findings indicate major inconsistencies in the management of patients with EHS/ERM, emphasizing the compelling need for implementing standardized protocols. Based on the results of long-term outcome measures, we recommend to counsel and evaluate every patient not only immediately after the event, but also in the long-term.

Effectiveness of an intervention to reduce sedentary behaviour as a personalised secondary prevention strategy for patients with coronary artery disease: main outcomes of the SIT LESS randomised clinical trial.

BACKGROUND: A high sedentary time is associated with increased mortality risk. Previous studies indicate that replacement of sedentary time with light- and moderate-to-vigorous physical activity attenuates the risk for adverse outcomes and improves cardiovascular risk factors. Patients with cardiovascular disease are more sedentary compared to the general population, while daily time spent sedentary remains high following contemporary cardiac rehabilitation programmes. This clinical trial investigated the effectiveness of a sedentary behaviour intervention as a personalised secondary prevention strategy (SIT LESS) on changes in sedentary time among patients with coronary artery disease participating in cardiac rehabilitation. METHODS: Patients were randomised to usual care (n = 104) or SIT LESS (n = 108). Both groups received a comprehensive 12-week centre-based cardiac rehabilitation programme with face-to-face consultations and supervised exercise sessions, whereas SIT LESS participants additionally received a 12-week, nurse-delivered, hybrid behaviour change intervention in combination with a pocket-worn activity tracker connected to a smartphone application to continuously monitor sedentary time. Primary outcome was the change in device-based sedentary time between pre- to post-rehabilitation. Changes in sedentary time characteristics (prevalence of prolonged sedentary bouts and proportion of patients with sedentary time ≥ 9.5 h/day); time spent in light-intensity and moderate-to-vigorous physical activity; step count; quality of life; competencies for self-management; and cardiovascular risk score were assessed as secondary outcomes. RESULTS: Patients (77% male) were 63 ± 10 years and primarily diagnosed with myocardial infarction (78%). Sedentary time decreased in SIT LESS (- 1.6 [- 2.1 to - 1.1] hours/day) and controls (- 1.2 [ ─1.7 to - 0.8]), but between group differences did not reach statistical significance (─0.4 [─1.0 to 0.3]) hours/day). The post-rehabilitation proportion of patients with a sedentary time above the upper limit of normal (≥ 9.5 h/day) was significantly lower in SIT LESS versus controls (48% versus 72%, baseline-adjusted odds-ratio 0.4 (0.2-0.8)). No differences were observed in the other predefined secondary outcomes. CONCLUSIONS: Among patients with coronary artery disease participating in cardiac rehabilitation, SIT LESS did not induce significantly greater reductions in sedentary time compared to controls, but delivery was feasible and a reduced odds of a sedentary time ≥ 9.5 h/day was observed. TRIAL REGISTRATION: Netherlands Trial Register: NL9263. Outcomes of the SIT LESS trial: changes in device-based sedentary time from pre-to post-cardiac rehabilitation (control group) and cardiac rehabilitation + SIT LESS (intervention group). SIT LESS reduced the odds of patients having a sedentary time >9.5 hours/day (upper limit of normal), although the absolute decrease in sedentary time did not significantly differ from controls. SIT LESS appears to be feasible, acceptable and potentially beneficial, but a larger cluster randomised trial is warranted to provide a more accurate estimate of its effects on sedentary time and clinical outcomes. CR: cardiac rehabilitation.

Neutrophil and Eosinophil Responses Remain Abnormal for Several Months in Primary Care Patients With COVID-19 Disease.

Introduction: Neutrophil and eosinophil activation and its relation to disease severity has been understudied in primary care patients with COVID-19. In this study, we investigated whether the neutrophil and eosinophil compartment were affected in primary care patients with COVID-19. Methods: COVID-19 patients, aged ≥ 40 years with cardiovascular comorbidity presenting to the general practitioner with substantial symptoms, partaking in the COVIDSat@Home study between January and April 2021, were included. Blood was drawn during and 3 to 6 months after active COVID-19 disease and analyzed by automated flow cytometry, before and after stimulation with a formyl-peptide (fNLF). Mature neutrophil and eosinophil markers at both time points were compared to healthy controls. A questionnaire was conducted on disease symptoms during and 3 to 6 months after COVID-19 disease. Results: The blood of 18 COVID-19 patients and 34 healthy controls was analyzed. During active COVID-19 disease, neutrophils showed reduced CD10 (p = 0.0360), increased CD11b (p = 0.0002) and decreased CD62L expression (p < 0.0001) compared to healthy controls. During active COVID-19 disease, fNLF stimulated neutrophils showed decreased CD10 levels (p < 0.0001). Three to six months after COVID-19 disease, unstimulated neutrophils showed lowered CD62L expression (p = 0.0003) and stimulated neutrophils had decreased CD10 expression (p = 0.0483) compared to healthy controls. Both (un)stimulated CD10 levels increased 3 to 6 months after active disease (p = 0.0120 and p < 0.0001, respectively) compared to during active disease. Eosinophil blood counts were reduced during active COVID-19 disease and increased 3 to 6 months after infection (p < 0.0001). During active COVID-19, eosinophils showed increased unstimulated CD11b (p = 0.0139) and decreased (un)stimulated CD62L expression (p = 0.0036 and p = 0.0156, respectively) compared to healthy controls. Three to six months after COVID-19 disease, (un)stimulated eosinophil CD62L expression was decreased (p = 0.0148 and p = 0.0063, respectively) and the percentage of CD11bbright cells was increased (p = 0.0083 and p = 0.0307, respectively) compared to healthy controls. Conclusion: Automated flow cytometry analysis reveals specific mature neutrophil and eosinophil activation patterns in primary care patients with COVID-19 disease, during and 3 to 6 months after active disease. This suggests that the neutrophil and eosinophil compartment are long-term affected by COVID-19 in primary care patients. This indicates that these compartments may be involved in the pathogenesis of long COVID.

Sedentary Behaviour Intervention as a Personalised Secondary Prevention Strategy (SIT LESS) for patients with coronary artery disease participating in cardiac rehabilitation: rationale and design of the SIT LESS randomised clinical trial.

Patients with coronary artery disease (CAD) are more sedentary compared with the general population, but contemporary cardiac rehabilitation (CR) programmes do not specifically target sedentary behaviour (SB). We developed a 12-week, hybrid (centre-based+home-based) Sedentary behaviour IntervenTion as a personaLisEd Secondary prevention Strategy (SIT LESS). The SIT LESS programme is tailored to the needs of patients with CAD, using evidence-based behavioural change methods and an activity tracker connected to an online dashboard to enable self-monitoring and remote coaching. Following the intervention mapping principles, we first identified determinants of SB from literature to adapt theory-based methods and practical applications to target SB and then evaluated the intervention in advisory board meetings with patients and nurse specialists. This resulted in four core components of SIT LESS: (1) patient education, (2) goal setting, (3) motivational interviewing with coping planning, and (4) (tele)monitoring using a pocket-worn activity tracker connected to a smartphone application and providing vibrotactile feedback after prolonged sedentary bouts. We hypothesise that adding SIT LESS to contemporary CR will reduce SB in patients with CAD to a greater extent compared with usual care. Therefore, 212 patients with CAD will be recruited from two Dutch hospitals and randomised to CR (control) or CR+SIT LESS (intervention). Patients will be assessed prior to, immediately after and 3 months after CR. The primary comparison relates to the pre-CR versus post-CR difference in SB (objectively assessed in min/day) between the control and intervention groups. Secondary outcomes include between-group differences in SB characteristics (eg, number of sedentary bouts); change in SB 3 months after CR; changes in light-intensity and moderate-to-vigorous-intensity physical activity; quality of life; and patients' competencies for self-management. Outcomes of the SIT LESS randomised clinical trial will provide novel insight into the effectiveness of a structured, hybrid and personalised behaviour change intervention to attenuate SB in patients with CAD participating in CR. Trial registration number NL9263.

Higher Levels of Physical Activity Are Associated with Greater Fruit and Vegetable intake in Older Adults.

OBJECTIVE: High levels of physical activity (PA) and optimal nutrition independently improve healthy aging, but few data are available about how PA may influence food preferences in older populations. Therefore, the aim of our study was to establish if there is an association between habitual PA and intake of nutrient-dense foods (i.e. fruits and vegetables). DESIGN: A cross-sectional survey was conducted. SETTING: The Netherlands. PARTICIPANTS: 2466 older adults (56% male, age 62±9 yr). MEASUREMENTS: PA was assessed using the short questionnaire to assess health (SQUASH) and participants were classified into quintiles of weekly PA (MET-h/wk). Total fruit and vegetable intake was assessed using a validated food frequency questionnaire (FFQ) and were corrected for energy intake (g/kcal/d) in the analyses. Multiple regression analyses were performed to determine the association between PA and fruit and vegetable intake, including covariates. RESULTS: Being in the higher quintiles of PA (Q3, Q4 and Q5) was positively associated with more daily fruit and vegetable consumption, even after correction for total energy intake (Q3; ß=0.089, P<0.001, Q4; ß=0.047, P=0.024, Q5; ß=0.098, P<0.001). CONCLUSIONS: Older adults who are moderately to highly physically active tend to consume more fruit and vegetable compared to less active peers, when corrected for total energy intake. Female gender, under- and overreporting dietary intake (Goldberg score), non-smoking, high level of education, less alcohol consumption and a lower body mass index positivity affected this relationship. Our data will help health-care professionals to accelerate their efforts to treat and prevent chronic diseases.

Relationship between intake and plasma concentrations of vitamin B12 and folate in 873 adults with a physically active lifestyle: a cross-sectional study.

BACKGROUND: Vitamin B12 and folate function as co-factors in pathways used during physical activity. Physical activity may therefore increase vitamin requirements, leading to a risk of deficient plasma concentrations. We aimed to investigate the relationship between intake and plasma concentrations of vitamin B12 and folate in physically active adults, as well as identify other determinants of vitamin B12 and folate plasma concentrations. METHODS: The study population consisted of 873 adults (528 men and 345 women), aged 19-78 years, who participated in a 4-day walking event. The relationship between intake and plasma concentrations of vitamin B12 and folate was assessed using correlation and linear regression analyses. In addition, potential other determinants (sex, age, body mass index, energy intake and physical activity) of vitamin plasma concentrations were investigated. RESULTS: Significant positive correlations were observed between intake and plasma concentrations of vitamin B12 [Pearson's correlation coefficient = 0.15; 95% confidence interval (CI) = 0.08-0.21] and folate (Pearson's correlation coefficient = 0.18; 95% CI = 0.12-0.25). In addition to vitamin intake, sex, age and energy intake were also determinants of both vitamin B12 and folate plasma concentrations in multivariable regression models. CONCLUSIONS: The results suggest a positive association between intake and plasma concentrations for both vitamin B12 and folate in physically active people. By contrast to our hypothesis, physical activity was not a determinant of vitamin B12 and folate plasma concentrations. However, sex, age and energy intake were found to be determinants. Thus, when studying the relationship between intake and plasma concentrations of vitamin B12 or folate, these factors should be taken into account.

The impact of feedback during formative testing on study behaviour and performance of (bio)medical students: a randomised controlled study.

BACKGROUND: A potential concern of formative testing using web-based applications ("apps") is provision of limited feedback. Adopting a randomised controlled trial in 463 first year (bio) medical students, we explored if providing immediate, detailed feedback during "app"-based formative testing can further improve study behaviour and study performance of (bio)medical students. METHODS: Students had access to a formative testing "app", which involved 7 formative test modules throughout the 4-week course. In a randomised order, subjects received the "app" with (n = 231, intervention) or without (n = 232, control) detailed feedback during the formative test modules. RESULTS: No differences in app-use was found between groups (P = 0.15), whereas the intervention group more frequently reviewed information compared to controls (P = 0.007). Exam scores differed between non-/moderate-/intensive- users of the "app" (P < 0.001). No differences in exam scores were found between intervention (6.6 ± 1.1) versus control (6.6 ± 1.1, P = 0.18). Time spent studying was significantly higher compared to previous courses in moderate- and intensive-users (P = 0.006 and < 0.001, respectively), but not in non-users (P = 0.55). Time spent studying did not differ between groups (P > 0.05). CONCLUSIONS: Providing detailed feedback did not further enhance the effect of a web-based application of formative testing on study behaviour or study performance in (bio)medical students, possibly because of a ceiling-effect.

Determinants of vitamin D status in physically active elderly in the Netherlands.

PURPOSE: Vitamin D deficiencies are common in elderly, which increases the risk for, e.g., bone fractures. Identification of determinants of vitamin D status may provide leads for specific deficiency prevention strategies. Although determinants of vitamin D status have been studied in various populations, this has not been examined in elderly that have a physically active lifestyle. METHODS: Vitamin D status of 450 physically active elderly who do not use vitamin D supplements was determined and information on possible determinants (demographic, dietary intake and physical activity) was collected around a prolonged four day walking event in July and analyzed in linear regression models. RESULTS: The average summertime serum 25(OH)D concentration was 88.8 ± 22.4 nmol/L. Only 2% of the participants had a 25(OH)D concentration below 50 nmol/L. Dietary intake of vitamin D was 4.0 ± 1.9 µg/day, and the participants spent 12.4 ± 8.6 h/week on outdoor activities. In the multivariate model, lower age (= - 0.48, 95% CI - 0.80 to - 0.16), lower BMI (= - 0.86, 95% CI - 1.62 to - 0.10), being a moderate to high drinker versus a non-drinker (= 7.97, 95% CI 0.43-15.51) and more outdoor physical activity (= 0.25, 95% CI 0.01-0.50) were significantly associated with higher 25(OH)D concentrations. CONCLUSIONS: In physically active elderly, vitamin D status was very high in summertime, with few deficiencies, suggesting that elderly with a physical active lifestyle might not necessarily need supplements during the summer period. Lower age, lower BMI, higher alcohol intake and more outdoor physical activity had a significant association with vitamin D status.

Insufficient Protein Intakes is Highly Prevalent among Physically Active Elderly.

OBJECTIVES: Sufficient protein intake and habitual physical activity are key factors in the prevention and treatment of sarcopenia. In the present study, we assessed habitual dietary protein intake and the contribution of animal proteins in male versus female physically active elderly and identified determinants of protein intake. DESIGN: a cross-sectional study. SETTING: the study was performed within the Nijmegen Exercise Study. PARTICIPANTS: physically active elderly ≥ 65 yrs. MEASUREMENTS: Physical activity was assessed using the SQUASH questionnaire and expressed in Metabolic Equivalent of Task hours per week (METhr/wk). Dietary protein intake was determined using a validated food frequency questionnaire (FFQ). Multivariate linear regression analysis was used to determine whether age, sex, educational level, smoking, alcohol intake and physical activity were associated with protein intake (g/kg/d). RESULTS: A total of 910 participants (70±4 yrs, 70% male) were included and reported a habitual physical activity level of 85.0±53.5 METhr/wk. Protein intake was 1.1±0.3 g/kg/d with 57% animal-based proteins for males, and 1.2±0.3 g/kg/d with 59% animalbased proteins for females (both P<0.05). In total, 16%, 42% and 67% of the male elderly and 10%, 34% and 56% of the female elderly did not meet the recommended protein intake of 0.8, 1.0 and 1.2 g/kg/d, respectively. Female sex (ß=0.055, P=0.036) and more physical activity (ß=0.001, P=0.001) were associated with a higher daily protein intake (g/kg/d). CONCLUSION: The majority of physically active elderly and in particular males (i.e. 67%) does not reach a protein intake of 1.2 g/kg/d, which may offset the health benefits of an active lifestyle on muscle synthesis and prevention of sarcopenia. Intervention studies are warranted to assess whether protein supplementation may enhance muscle mass and strength in physically active elderly.

Changes in iron metabolism during prolonged repeated walking exercise in middle-aged men and women.

PURPOSE: The aim of the present study was to assess the effect of prolonged and repeated exercise on iron metabolism in middle-aged adults and to compare differences between sexes. METHODS: 50 male (58.9 ± 9.9 year) and 48 female (50.9 ± 11.2 year) individuals were monitored on 4 consecutive days at which they walked on average 8 h and 44 min per day at a self-determined pace. Blood samples were collected 1 or 2 days prior to the start of the exercise (baseline) and every day immediately post-exercise. Samples were analysed for iron, ferritin, haemoglobin, and haptoglobin concentrations. RESULTS: Plasma iron decreased across days, while ferritin increased across days (both p < 0.001). Haptoglobin showed a decrease (p < 0.001) after the first day and increased over subsequent days (p < 0.001). Haemoglobin did not change after the first day, but increased during subsequent days (p < 0.05). At baseline, 8% of the participants had iron concentrations below minimum reference value (10 µmol/L), this increased to 43% at day 4. There was an interaction between sex and exercise days on iron (p = 0.028), ferritin (p < 0.001) and haemoglobin levels (p = 0.004), but not on haptoglobin levels. CONCLUSION: This study showed decreases in iron, increases in ferritin, a decrease followed by increases in haptoglobin and no change followed by increases in haemoglobin. This is most likely explained by (foot strike) haemolysis, inflammation, and sweat and urine losses. These processes resulted in iron levels below minimum reference value in a large number of our participants.

A systematic review and meta-analysis on the effects of exercise training versus hypocaloric diet: distinct effects on body weight and visceral adipose tissue.

Exercise training ('exercise') and hypocaloric diet ('diet') are frequently prescribed for weight loss in obesity. Whilst body weight changes are commonly used to evaluate lifestyle interventions, visceral adiposity (VAT) is a more relevant and stronger predictor for morbidity and mortality. A meta-analysis was performed to assess the effects of exercise or diet on VAT (quantified by radiographic imaging). Relevant databases were searched through May 2014. One hundred seventeen studies (n = 4,815) were included. We found that both exercise and diet cause VAT loss (P < 0.0001). When comparing diet versus training, diet caused a larger weight loss (P = 0.04). In contrast, a trend was observed towards a larger VAT decrease in exercise (P = 0.08). Changes in weight and VAT showed a strong correlation after diet (R(2) = 0.737, P < 0.001), and a modest correlation after exercise (R(2) = 0.451, P < 0.001). In the absence of weight loss, exercise is related to 6.1% decrease in VAT, whilst diet showed virtually no change (1.1%). In conclusion, both exercise and diet reduce VAT. Despite a larger effect of diet on total body weight loss, exercise tends to have superior effects in reducing VAT. Finally, total body weight loss does not necessarily reflect changes in VAT and may represent a poor marker when evaluating benefits of lifestyle-interventions.

Within-subject Variation of Thermoregulatory Responses during Repeated Exercise Bouts.

AIM: To assess the within-subject variation of thermoregulatory responses during 2 consecutive 15-km road races. Secondly, we explored whether gastrointestinal temperature (TGI) data from the first race could improve our previously established predictive model for finish TGI in the second race. METHODS: We measured TGI before and immediately after both races in 58 participants and determined correlation coefficients. Finish TGI in the second race was predicted using a linear regression analysis including age, BMI, pre-race fluid intake, TGI increase between baseline and the start of the race and finish TGI in the first race. RESULTS: Under cool conditions (WBGT 11-12°C), TGI was comparable between both races at baseline (37.6±0.4°C vs. 37.9±0.4°C; p=0.24) and finish (39.4±0.6°C vs. 39.4±0.6°C; p=0.83). Finish TGI correlated significantly between both races (r=0.50; p<0.001). The predictive model (p<0.001) could predict 32.2% of the finish TGI in the second race (vs. 17.1% without finish TGI in race 1). CONCLUSION: Our findings demonstrate that the use of previously obtained thermoregulatory responses results in higher predictability of finish core body temperatures in future races, enabling better risk assessment for those athletes that are most likely to benefit from preventive measures.

The effect of exercise training on cardiac remodelling in children and young adults with corrected tetralogy of Fallot or Fontan circulation: a randomized controlled trial.

BACKGROUND: Exercise can improve physical fitness in children and adults with congenital heart disease. We hypothesized that exercise training would not lead to adverse cardiac remodelling in this population. METHODS AND RESULTS: This multi-centre randomized controlled trial included children and young adults (10 to 25 years) with either corrected tetralogy of Fallot or Fontan circulation. The exercise-group was enrolled in a 12 week standardized aerobic dynamic exercise training program. The control-group continued their life-style and received care as usual. Both groups underwent cardiopulmonary exercise testing, cardiac magnetic resonance imaging (MRI), echocardiography and neurohormonal assessment, within 2 weeks before and 2 weeks after the intervention period. Fifty-six patients were randomized to the exercise-group and 37 to the control-group. We assessed changes between the pre- and the post-intervention period for the exercise group compared to the changes in the control-group. Peak load increased significantly in the exercise-group compared to the control-group (exercise-group 6.9 ± 11.8 W; control-group 0.8 ± 13.9 W; p=0.047). There were no adverse events linked to the study. Ventricular systolic parameters, cardiac dimensions and neurohormonal markers during follow-up did not change in patients allocated to the exercise-group and control-group. Although there were some isolated minor changes in inflow parameters, there was no consistent pattern of changes, indicating a lack of true change in the diastolic function. CONCLUSION: We demonstrated that no clinically relevant adverse cardiac remodelling occurred after 12 weeks of exercise training in patients with either corrected tetralogy of Fallot or Fontan circulation. CLINICAL TRIAL REGISTRATION: www.trialregister.nl, identification NTR2731.

Physical fitness can partly explain the metabolically healthy obese phenotype in women.

To investigate whether physical fitness and/or fat distribution and inflammation profile may explain why approximately 30% of the women with obesity are protected against obesity-related disorders.10 metabolically healthy obese women and 10 age- and weight-matched women with the metabolic syndrome were enrolled. Physical fitness (VO2max), daily physical activity levels (METs, steps per day), insulin sensitivity (clamp), body fat distribution (DXA scan) and, inflammation markers and adipokines were determined.The metabolically healthy obese women had a 17% higher VO2max (25.1±3.9 vs. 21.5±3.1 ml ∙ min-1 ∙ kg-1, p=0.04) and tended to take more steps per day (7 388±1 440 vs. 5 927±1 301, p=0.06) than women with the metabolic syndrome. Despite equivalent levels of fat mass, metabolically healthy obese women had significantly lower circulating TNF-α levels compared to women with the metabolic syndrome (3.55±3.83 vs. 0.43±0.97 ng/ml, p=0.03). No differences were seen in insulin sensitivity, adipokines, and inflammatory markers between both groups.Metabolically healthy obese women have a higher cardio-respiratory fitness and lower TNF-α levels, which may partly explain why these women are protected from the detrimental effects of obesity compared to obese women with the metabolic syndrome.

Systematic review of the effects of physical exercise training programmes in children and young adults with congenital heart disease.

BACKGROUND: Most patients with congenital heart disease (ConHD) do not perform regular physical exercise. Consensus reports have stated that exercise should be encouraged and regularly performed in these patients, but this is not common practise. We reviewed the literature on actual evidence for either negative or positive effects of physical exercise training programmes in children and young adults with ConHD. METHODS: Using the Medline database, we systematically searched for articles on physical exercise training programmes in ConHD. RESULTS: A total of 31 articles met all inclusion criteria; in total, 621 subjects (age range 4 to 45 years) were included. Most studies used training programmes with a duration of 12 weeks. On average, the number of training sessions was 3 times per week. In 12 studies, training intensity was set at a percentage of peak heart rate. Outcome measures reported were PeakVO2, activity levels and muscle strength. Twenty-three studies (72%) found a significant positive change in the main outcome measure after the physical exercise training period. None of the studies reported negative findings related to physical exercise training in ConHD. Cardiac effects have hardly been studied. CONCLUSION: In most studies, participation in a physical exercise training programme was safe and improved fitness in children and young adults with ConHD. We recommend that patients with ConHD participate in physical exercise training. Cardiac effects need to be studied more extensively.

The role of physical activity and physical fitness in postcancer fatigue: a randomized controlled trial.

PURPOSE: Patients suffering from postcancer fatigue have both an inferior physical activity and physical fitness compared to non-fatigued cancer survivors. The aims of this study were (1) to examine the effect of cognitive behavior therapy, an effective treatment for postcancer fatigue, on physical activity and physical fitness and (2) to examine whether the effect of cognitive behavior therapy on postcancer fatigue is mediated by physical activity and/or physical fitness. METHODS: Severely fatigued cancer survivors were randomly assigned to either the intervention (cognitive behavior therapy) or the waiting list condition. After assigning 23 patients in the intervention condition and 14 patients in the waiting list condition, they were assessed both at baseline and 6 months later. Physical activity was assessed via actigraphy and physical fitness was assessed by a maximal exercise test. A nonparametric bootstrap approach was used to test the statistical significance of the mediation effects. RESULTS: A significant increase in physical activity was observed in the intervention group from baseline to follow-up, whereas physical activity did not change from baseline to follow-up in the waiting list group. Physical fitness did not significantly change after cognitive behavior therapy or after 6 months of waiting for therapy. Fatigue decreased more significantly in the intervention group than in the waiting list group. The mediation hypotheses were rejected. CONCLUSIONS: Cognitive behavior therapy effectively reduced postcancer fatigue and increased physical activity but did not change physical fitness. The effect of cognitive behavior therapy on postcancer fatigue is not mediated by a change in physical activity or physical fitness.

Maximal exercise performance in patients with postcancer fatigue.

PURPOSE: The aim of this study is to examine whether physical fitness of severely fatigued and non-fatigued cancer survivors, as measured by maximal exercise performance, is different between both groups and, if so, whether this difference can be explained by differences in physical activity, self-efficacy regarding the exercise test, and/or social support. METHODS: Severely fatigued (n = 20) and sex- and age-matched non-fatigued (n = 20) disease-free cancer survivors, who completed treatment for a malignant, solid tumor at least 1 year earlier, participated in this case-control study. Maximal oxygen consumption was measured during an incremental cycling exercise test. Physical activity was assessed via actigraphy. Self-efficacy regarding the test and social support were assessed via questionnaires to study its relationship with physical fitness. RESULTS: Maximal oxygen consumption was significantly lower in fatigued compared to non-fatigued participants. Actual physical activity, self-efficacy regarding the test, and negative interactions of social support were significantly different between both groups. However, after inclusion of these three variables in linear regression analyses, the difference in physical fitness between fatigued and non-fatigued cancer survivors persisted. CONCLUSIONS: Maximal oxygen consumption, a measure for physical fitness, was reduced in severely fatigued compared to non-fatigued cancer survivors. The inferior maximal exercise performance cannot fully be explained by differences in physical activity, self-efficacy, or social support between both groups. Other currently still unknown factors, such as a disturbance in the cardiopulmonary circuit, may play a role.

Sex difference in fluid balance responses during prolonged exercise.

Maintaining a proper fluid balance is important during exercise as athletes are prone to develop dehydration during exercise. Although several factors may regulate the fluid balance, little is known about the role of sex during prolonged moderate-intensity exercise. Therefore, we compared body mass changes and fluid balance parameters in men vs women in a large heterogeneous group of participants during prolonged exercise. Ninety-eight volunteers walked 30-50 km at a self-selected pace. Exercise duration (8 h, 32 min) and intensity (69% HRmax) were comparable between groups. Men demonstrated a significantly larger change in body mass than women (-1.6% vs -0.9%, respectively, P < 0.001) and a higher incidence of dehydration (defined as ≥ 2% body mass loss) compared with women (34% vs 12%, respectively, odds ratio = 4.2, 95% CI = 1.1-16.7). Changes in blood sodium levels were significantly different between men (+1.5 mmol/L) and women (-0.4 mmol/L), while 27% of the men vs 0% of the women showed postexercise hypernatremia (sodium levels ≥ 145 mmol/L). Moreover, men demonstrated a significantly lower fluid intake (2.9 mL/kg/h) and higher fluid loss (5.0 mL/kg/h) compared with women (3.7 and 4.8 mL/kg/h, respectively). Taken together, our data suggest that men and women demonstrate different changes in fluid balance in response to a similar bout of exercise.