Maximal cardiopulmonary exercise testing in glioblastoma patients undergoing chemotherapy: assessment of feasibility, safety, and physical fitness status.

PURPOSE: Maximal cardiopulmonary exercise testing (max. CPET) provides the most accurate measurement of cardiorespiratory fitness. However, glioblastoma (GBM) patients often undergo less intensive tests, e.g., 6-min walk test or self-rating scales. This study aims to demonstrate feasibility and safety of max. CPET in GBM patients, concurrently evaluating their physical fitness status. METHODS: Newly diagnosed GBM patients undergoing adjuvant chemotherapy were offered participation in an exercise program. At baseline, max. CPET assessed cardiorespiratory fitness including peak oxygen consumption (VO2peak), peak workload, and physical work capacity (PWC) at 75% of age-adjusted maximal heart rate (HR). Criteria for peak workload were predefined based on threshold values in HR, respiratory quotient, respiratory equivalent, lactate, and rate of perceived effort. Data were compared to normative values. Adverse events were categorized according to standardized international criteria. Further, self-reported exercise data pre- and post-diagnosis were gathered. RESULTS: All 36 patients (median-aged 60; 21 men) met the predefined criteria for peak workload. Mean absolute VO2peak was 1750 ± 529 ml/min, peak workload averaged 130 ± 43 W, and mean PWC was 0.99 ± 0.38 W/kg BW, all clinically meaningful lower than age- and sex-predicted normative values (87%, 79%, 90%, resp.). Only once (3%) a minor, transient side effect occurred (post-test dizziness, no intervention needed). Self-reported exercise decreased from 15.8 MET-h/week pre-diagnosis to 7.2 MET-h/week post-diagnosis. CONCLUSION: Max. CPET in this well-defined population proved feasible and safe. GBM patients exhibit reduced cardiorespiratory fitness, indicating the need for tailored exercise to enhance health and quality of life. CPET could be essential in establishing precise exercise guidelines.

Conceptual development of an intensive exercise program for glioma patients (ActiNO): summary of clinical experience.

PURPOSE: Exercise proved to reduce cancer-related symptoms and prolong survival in some cancer types. However, brain tumor patients are often advised against strenuous exercise. Here, we summarize our experience with a submaximal exercise program for glioma patients: ActiNO (Active in Neuro-Oncology). METHODS: Glioma patients were invited to participate in the program. Since 2011, a sports scientist individualized two one-hour sessions per week adapted to the patients' symptoms. One session consisted of bicycle ergometry (average workload: 75% of maximum heart rate), the other of whole-body resistance training. Both sessions were further complimented by coordinative elements. Cardiorespiratory fitness was assessed using the "Physical Work Capacity" procedure. Patients were followed up regularly to assess adherence to the program and disease activity. RESULTS: Until December 2019, 45 glioma patients, median-aged 49 years (IQR 42-59), were included in the analysis. Most patients suffered from glioblastoma (58%), followed by diffuse lower-grade astrocytoma (29%). In overall 1828 training sessions, two minor epileptic events occurred (1 speech arrest; 1 focal seizure). During fitness assessment, all patients achieved at least 75% of their age-adjusted maximum heart rate. Peak workload averaged 172 W (95% CI 156-187). Median survival of participating glioblastoma patients was 24.1 months (95% CI 8.6-39.5). CONCLUSION: This supervised training program with submaximal exertion was feasible and safe in glioma regardless of WHO grading. Based on these experiences, we initiated a prospective multicenter study to objectify improvements in physical performance and quality of life in patients with glioblastoma.

Discovery of BAY-985, a Highly Selective TBK1/IKKε Inhibitor.

The serine/threonine kinase TBK1 (TANK-binding kinase 1) and its homologue IKKε are noncanonical members of the inhibitor of the nuclear factor κB (IκB) kinase family. These kinases play important roles in multiple cellular pathways and, in particular, in inflammation. Herein, we describe our investigations on a family of benzimidazoles and the identification of the potent and highly selective TBK1/IKKε inhibitor BAY-985. BAY-985 inhibits the cellular phosphorylation of interferon regulatory factor 3 and displays antiproliferative efficacy in the melanoma cell line SK-MEL-2 but showed only weak antitumor activity in the SK-MEL-2 human melanoma xenograft model.

Acute physical exercise improves shifting in adolescents at school: evidence for a dopaminergic contribution.

The executive function of shifting between mental sets demands cognitive flexibility. Based on evidence that physical exercise fostered cognition, we tested whether acute physical exercise can improve shifting in an unselected sample of adolescents. Genetic polymorphisms were analyzed to gain more insight into possibly contributing neurophysiological processes. We examined 297 students aged between 13 and 17 years in their schools. Physical exercise was manipulated by an intense incremental exercise condition using bicycle ergometers and a control condition which involved watching an infotainment cartoon while sitting calm. The order of conditions was counterbalanced between participants. Shifting was assessed by a switching task after both conditions. Acute intense physical exercise significantly improved shifting as indicated by reduced switch costs. Exercise-induced performance gains in switch costs were predicted by a single nucleotide polymorphism (SNP) targeting the Dopamine Transporter (DAT1/SLCA6A3) gene suggesting that the brain dopamine system contributed to the effect. The results demonstrate the potential of acute physical exercise to improve cognitive flexibility in adolescents. The field conditions of the present approach suggest applications in schools.

Recommendations for promoting physical activity for children and adolescents in Germany. A consensus statement.

Increasing physical activity and reduction of sedentary behaviour play important roles in health promotion and prevention of lifestyle-related diseases in children and adolescents. However, the question of how much physical activity is useful for which target group is still a matter of debate. International guidelines (World Health Organization; European Association for the Study of Obesity), which are mainly based on expert opinions, recommend 60 min of physical activity every day. Age- and sex-specific features and regional differences are not taken into account. Therefore, expert consensus recommendations for promoting physical activity of children and adolescents in Germany were developed with special respect to national data, but also with respect to aspects of specific target groups, e.g., children with a lower socio-economic status (SES) or with migration background. They propose 90 min/day of physical activity, or at least 12,000 steps daily. Additionally, lifestyle factors, especially restriction of media consumption, were integrated. The recommendations provide orientation for parents and caregivers, for institutions such as schools and kindergartens as well as for communities and stakeholders.

Exercise delays neutrophil apoptosis by a G-CSF-dependent mechanism.

The aim of the study was to determine whether exercise affects neutrophil apoptosis and to characterize the underlying mechanisms. Using annexin V labeling, neutrophil apoptosis was measured using flow cytometry after various bouts of exercise (marathon run, concentric/eccentric treadmill exercise, moderate/intensive resistance training) and in vitro conditions. Similarly, apoptosis-related markers as death receptors/ligands and mitochondrial membrane potential were detected. Furthermore, concentrations of intracellular free calcium and glutathione were measured using spectrofluorometry. After both marathon run and intensive laboratory exercise tests, neutrophil apoptosis was delayed. Furthermore, neutrophils mitochondrial membrane potential and death receptor/ligand expression were not affected by exercise. Apoptosis delay was accompanied under some exercise conditions by enhanced intracellular calcium transients and decreased glutathione levels. A delay of spontaneous apoptosis in vitro could be induced by incubation of neutrophils in postexercise serum. Heating of postexercise serum abolished the apoptosis delaying effect. In vitro stimulation of resting neutrophils with granulocyte-colony-stimulating factor (G-CSF) and C-reactive protein resulted in apoptosis delay too. Addition of anti-G-CSF antibody to postexercise serum was also effective in reversing its apoptosis-delaying effect. Exercise-induced mobilization of neutrophils is associated with a delay of apoptosis. This fundamental process seems to maintain exercise-induced neutrophilia and to contribute to the alerting and activation of the nonadaptive immune system known from other inflammatory conditions. An important extracellular trigger of apoptosis delay during exercise conditions seems to be G-CSF; intracellular processes may include calcium and redox signaling.

The effect of attentional focus on running economy.

In research on motor control, the detrimental effect of an internal focus of attention on movement execution of well-learned motor skills is a frequently replicated finding. This experimental study was designed to determine whether this effect is observed with physiological variables during endurance exercise. We examined whether the focus of attention can influence running economy (oxygen consumption at a set running speed). Trained runners had to focus their attention on three different aspects while running on a treadmill. For three consecutive 10-min periods, runners concentrated on the running movement, on their breathing, and on their surroundings. Results showed an increased running economy in the external focus condition. In line with research on motor control, endurance sport also shows that an external focus of attention is better than an internal focus in terms of the physiological performance measure of oxygen consumption.

Sports activities and endurance capacity of bone tumor patients after rotationplasty.

OBJECTIVES: To investigate the preferred types of sports activities of patients with rotationplasty and to measure their physiologic performance characteristics through treadmill ergometry. DESIGN: Cross-sectional, descriptive analysis and repeated measures of different velocities. SETTING: Biomechanics research laboratory. PARTICIPANTS: Patients (n=61) with rotationplasty after bone tumor surgery, 30 of whom participated in a functional trial (treadmill), and a control group (n=20). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Patients' participation in sports compared with that of the healthy population, treadmill performance at 2 or 3 different speeds, heart rate, lactate accumulation, oxygen consumption, ventilatory equivalent, efficiency, respiratory minute volume, and respiratory quotient. RESULTS: High activity in sports participation (85%) in most common sports (8 competitive, 17 sports club members, the remaining subjects were recreational athletes). At the same treadmill speed, lactate accumulation and all cardiorespiratory functions were higher in rotationplasty patients than in the control group. CONCLUSIONS: Patients can re-engage in a high level of physical activity after rotationplasty for bone tumor treatment. This physical activity is necessary if patients want to maintain or improve a desired level of sports activity.

Passive stability characteristics of ankle braces and tape in simulated barefoot and shoe conditions.

BACKGROUND: Ankle sprains are among the most common injuries in barefoot sport activities such as dance, gymnastics, or trampoline. At present, the use of external ankle devices for prevention of ligament injuries for barefoot activities remains unclear. HYPOTHESIS: External ankle devices have a significant loss of passive stability when used without a shoe in barefoot activities. STUDY DESIGN: Controlled laboratory study. METHODS: Twenty-five healthy subjects participated in the project (mean age, 26.2 +/- 3.3 years; mean body mass, 71.2 +/- 10.3 kg; mean height, 178 +/- 7 cm). Passive range of motion measurements were performed with 3 different ankle stabilizers (a stirrup brace, a lace-up brace, and tape), as well as 2 different shoe conditions (cutout shoe [simulated barefoot] and normal shoe). RESULTS: In the simulated barefoot condition, a significantly reduced stabilizing effect for inversion and eversion (19% and 29%, respectively) was found for the stirrup ankle brace. Small decreases were noted with the soft brace and tape, but these were not statistically significant. CONCLUSION: The passive stability characteristics of ankle braces depend to a great extent on being used in combination with a shoe. This is especially true for semirigid braces with stirrup design. Therefore, it is recommended that soft braces (like the one tested in the present investigation) be used in barefoot sports for restricting passive range of motion of the foot and ankle complex. CLINICAL RELEVANCE: This study provides useful information for clinicians to select or recommend an external ankle stabilizing device in barefoot sports to restrict passive range of motion of the foot-ankle complex most effectively.

[Physical activity and prevention of cardiovascular diseases]. / Körperliche Aktivität und Primärprävention kardiovaskulärer Erkrankungen.

Physical inactivity is one of the major risk factors for cardiovascular diseases. Regular physical activity, conversely, is effective in reducing all-cause mortality, cardiovascular morbidity and mortality. Older and recent meta-analyses confirm the reduction of all-cause mortality and cardiovascular mortality by regular physical activity. So far, there is a dose-effect relationship especially from low to moderate training intensity; the steepness of this curve is more curvilinear with a decrease at higher categories of activity intensity. Regular physical activity even at low level of intensity should be a part of daily life and of lifestyle. The risks and side effects of physical activity can be neglected, preparticipation examination before training is strongly recommended. Counseling healthy persons and patients at any age for physical activity, and training prescription should be an essential part of physicians' work in general practice.

[Physical activity, hypertension, and cardiac and circulatory system]. / Sport, Hypertonie und Herz-Kreislauf-Erkrankungen.

Because of its increasing incidence hypertension is--as one of the most important risk factor of diseases of the cardiac and circulatory system--a challenge for prevention and rehabilitation. Besides the established pharmacological therapy regular physical activity is one of the effective nonpharmacological therapies; particularly, there are also effects on other risk factors. Meta-analyses show a decreasing effect of physical activity both on the systolic and diastolic value. With a nonresponder rate of 25% the effects are similar to pharmacological therapy. Modulators can be found in the pathology of the disease itself, in the age, and in genetic polymorphisms. The mechanisms for blood pressure reduction might be the diuretic effect of physical activity, the reorganization of the vegetative reaction toward a sympathicolysis, the humeral modifications like changes in glucose metabolism and the improvement of endothelial function. Recommendations concerning the nature, the intensity and duration of physical activity refer more to consent statements than to evidence-based studies. Nevertheless, the following recommendations can be given. Endurance events with cyclic movements should be performed at a moderate intensity between 40% and 60% VO2(max). Though a duration of 60-90 min has the highest effect on blood pressure reduction, a duration of only 30 min per unit is favored to reach a higher compliance. No influence has yet been verified concerning the frequency of physical activity. Because of its effects on risk factors other than hypertension physical activity represents an all-embracing treatment concept. Therefore it is desirable to integrate physical activity in the treatment routine, especially in the therapy of patients with different risk factors.

Phase diagram and critical exponents of a dissipative Ising spin chain in a transverse magnetic field.

We consider a one-dimensional Ising model in a transverse magnetic field coupled to a dissipative heat bath. The phase diagram and the critical exponents are determined from extensive Monte Carlo simulations. It is shown that the character of the quantum phase transition is radically altered from the corresponding nondissipative model and the double well coupled to a dissipative heat bath with linear friction. Spatial couplings and the dissipative dynamics combine to form a new quantum criticality which is independent of dissipation strength.

The influence of external ankle braces on subjective and objective parameters of performance in a sports-related agility course.

With lateral ankle sprains being the most frequent sports-related injury, there is an evident demand for the preventive measures in active individuals with chronic ankle instability. Braces are commonly used for prevention and treatment of ankle injuries. Various investigations-mostly performed with healthy subjects-focused on this problem, yet they often compared only a few models or used only limited testing procedures. However, controversy exists whether braces affect sports performance. The purpose of the present study was to compare the effects of ten different ankle braces-one rigid, five semirigid, four soft models-in a comprehensive evaluation with multiple testing procedures in 34 subjects with self-reported chronic ankle instability. The multiple testing procedures evaluated objective performance-related parameters and subjective parameters related to comfort and stability. The subjects performed an agility course with maximal effort. The course included a vertical jump and a cutting maneuver, both on a force platform, a single leg hopping test on level and inclined plates, a combined straight and curve sprint and sidesteps. Three valid trials were measured and averaged for each brace and every subject. Subjective aspects were evaluated with a questionnaire about handling, perceived restrictions, support and comfort; it was completed after each brace was worn and tried. With regard to the objective parameters, no significant differences were found between the braces except for the rigid brace which showed decreased values for the vertical jump and longer times for the other tests compared to all other braces. The subjective evaluation of the braces revealed significant differences with respect to comfort and handling and therefore, permitted a distinction between semirigid and soft braces. Although significant differences between braces were found in subjective performance restriction, no significant differences were revealed in the objective evaluation. From that point of view, patients could choose a brace model according to their individual needs. A comfortable brace might have a positive influence on the athlete's state of mind although other aspects like the brace's stabilizing effect play an additional role and should also be taken into account for recommendation of braces.

Exercise-induced apoptosis of lymphocytes depends on training status.

PURPOSE: To investigate the effect of training status on lymphocyte apoptosis as well as the expression of cell death receptors and ligands after a marathon run, and to compare these data with the alterations after treadmill exercise tests. METHODS: Sixteen volunteers successfully finished the 2002 Münster marathon. Venous blood samples were drawn before and 0, 3, and 24 h after the race. After cell isolation, cell-based apoptosis markers annexin V, Fas receptor, and Fas ligand were measured by flow cytometry. The same parameters were investigated in a group of 10 subjects before, and 0 and 1 h after both an exhaustive (ExT) and a low-intensity (LoT) treadmill test. RESULTS: The percentage of apoptotic cells after the marathon changed in a biphasic manner. An early increase 3 h after the run was followed by a significant decrease 1 d later. Interestingly, the increase in apoptotic cells was not observed in highly trained athletes, whereas it was significantly more pronounced in badly trained athletes. ExT induced a lymphocyte apoptosis similar to the marathon, whereas no change in apoptosis was observed after the LoT. Both Fas receptor and ligand were increased after the marathon with different kinetics. Whereas the Fas receptor peaked at 1 h, Fas ligand was increased 3 h after the run. After the treadmill tests Fas receptor expression was enhanced in both groups, whereas Fas ligand increased only after the ExT. CONCLUSIONS: Endurance exercise like a marathon is able to induce apoptosis in lymphocytes. Thereby, apoptosis sensitivity seems to be related to training status in an inverse relationship. The increased expression levels of death receptors and ligands might indicate the high apoptosis inducing potential of this type of exercise.

Reduced plantar sensation causes a cautious walking pattern.

The aim of this study was to investigate the influence of reduced plantar sensation on gait patterns during walking in 20 healthy subjects (25.9 +/- years, 61.6 +/- 11.5 kg, 178 +/- 9.5 cm) with no history of sensory disorders. Force plate measurements, electromyography (EMG) measurements and a three-dimensional movement analysis were performed simultaneously during barefoot walking before and after reduction of plantar sensation using an ice immersion technique. The results show that reduced plantar sensation leads to significant changes in gait patterns that are present at the ankle, knee and hip joint and indicate a more cautious ground contact and push-off with modified EMG and motion patterns.

An explanation for a universality of transition temperatures in families of copper oxide superconductors.

A remarkable mystery of the copper oxide high-transition-temperature (T(c)) superconductors is the dependence of T(c) on the number of CuO2 layers, n, in the unit cell of a crystal. In a given family of these superconductors, T(c) rises with the number of layers, reaching a peak at n = 3, and then declines: the result is a bell-shaped curve. Despite the ubiquity of this phenomenon, it is still poorly understood and attention has instead been mainly focused on the properties of a single CuO2 plane. Here we show that the quantum tunnelling of Cooper pairs between the layers simply and naturally explains the experimental results, when combined with the recently quantified charge imbalance of the layers and the latest notion of a competing order nucleated by this charge imbalance that suppresses superconductivity. We calculate the bell-shaped curve and show that, if materials can be engineered so as to minimize the charge imbalance as n increases, T(c) can be raised further.

Characteristic plantar pressure distribution patterns during soccer-specific movements.

PURPOSE: To characterize in-shoe pressure measurements during different soccer-specific maneuvers on two playing surfaces to identify the main loading areas of the foot. METHODS: Twenty-one experienced male soccer players participated in the study (25.5 +/- 1.8 years, 78.7 +/- 5.4 kg, and 182.9 +/- 5.7 cm). The Pedar Mobile system was used to collect plantar pressure information inside the soccer shoe. Four soccer-specific movements were performed (normal run, cutting maneuver, sprint, and goal shot) on both a grass and a red cinder surface. RESULTS: Results showed characteristic pressure distribution patterns with specific loading areas of the foot that correspond to the evaluated movements. In addition, loading patterns with higher pressure values than those observed during normal run were found. In cutting, the medial part of the foot; in sprinting, the first and second ray; and in kicking, the lateral part of the foot are predominantly loaded. No global effect of the two surfaces on pressure parameters was found. CONCLUSION: The results of the present investigation suggest that the high load in soccer in combination with a high repetition may have an important influence in the development of overuse injuries.

Comprehensive testing of 10 different ankle braces. Evaluation of passive and rapidly induced stability in subjects with chronic ankle instability.

OBJECTIVE: The aim of the present investigation was to test the stability of 10 different ankle braces under passive and rapidly induced loading conditions in a population suffering from chronic ankle instability in order to provide objective information to choose or recommend an appropriate model for specific needs. In addition, the relationship between passive and rapidly induced testing of the stabilizing effect against inversion was evaluated to identify if passive support characteristics of braces are reflected under rapidly induced conditions. DESIGN: An experimental in vivo study with a repeated-measures design was used. BACKGROUND: Ankle braces are commonly used for treatment, rehabilitation, and prevention of ankle injuries. A variety of products exists but there is few information available to assist clinicians, physiotherapists and coaches as well as consumers in choosing a brace on a basis of objective information. Furthermore, there is a lack of studies that provide data for both passively and rapidly induced movement of the ankle joint when using different ankle braces. METHODS: Twenty-four subjects with chronic ankle instability participated in the project. Passive ankle range of motion measurements were performed in a custom-built fixture and simulated inversion sprains were elicited on a tilting platform. RESULTS: The tested braces restrict range of motion significantly compared to the no-brace condition for both the passively and rapidly induced inversion and marked differences between braces were revealed. A close relationship between passive and rapidly induced test results for inversion was found. CONCLUSIONS: Passive as well as rapidly induced stability tests provide a basis of objective information to describe the characteristics of different ankle braces. Combined results of passive and rapidly induced inversion as well as correlation between results demonstrate that passive support characteristics of braces are reflected under rapidly induced conditions but the amount of restriction is reduced. Therefore, caution should be taken when recommending braces for applications under dynamic circumstances only on the basis of passive support characteristics. RELEVANCE: A basis of information regarding the stability characteristics of different ankle braces under passive and rapidly induced conditions will help the clinician and consumer in choosing the most appropriate brace model for specific use. The results also provide more insights into factors that influence stability characteristics of ankle braces.