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Introduction: Peripheral neuropathies are a prevalent, heterogeneous group of diseases of the peripheral nervous system. Symptoms are often debilitating, difficult to treat, and usually become chronic. Not only do they diminish patients’ quality of life, but they can also affect medical therapy and lead to complications. To date, for most conditions there are no evidence-based causal treatment options available. Research has increased considerably since the last review in 2014 regarding the therapeutic potential of exercise interventions for patients with polyneuropathy. Objective: Our objective in this systematic review with meta-analysis was to analyze exercise interventions for neuropathic patients in order to update a systematic review from 2014 and to evaluate the potential benefits of exercise on neuropathies of different origin that can then be translated into practice. Methods: Two independent reviewers performed a systematic review with meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Inclusion criteria according to the PICOS approach were: neuropathic patients, exercise interventions only, an inactive or non-exercising control group, and solely randomized controlled trials with the following outcome parameters: neuropathic symptoms, balance parameters, functional mobility, gait, health-related quality of life, and HbA1c (glycated hemoglobin). Results: A total of 41 randomized, controlled trials met all inclusion criteria, 20 of which could be included in the quantitative analysis. Study quality varied from moderate to high. Current data further support the hypothesis that exercise is beneficial for neuropathic patients. This is best documented for patients with diabetic peripheral neuropathy (DPN) (27 studies) as well as for chemotherapy-induced peripheral neuropathy (CIPN) (nine studies), while there are only few studies (five) on all other causes of neuropathy. We found standardized mean differen

Introduction: Reduced testosterone levels due to androgen deprivation therapy (ADT) in prostate cancer patients cause common side effects, such as reduced muscle strength and bone density, increased fat mass, sexual dysfunction and fatigue. Short-term exercise during ADT has proven to be safe and effective in exhibiting a positive impact on body composition, sexual dysfunction and fatigue. However, there are only three randomized controlled trials that investigate one-year supervised impact exercise interventions, none of which examined follow-up effects after the intervention. Therefore, this study will conduct a one-year impact exercise intervention and assess follow-up effects up to one year later. Material and methods: The aim of the randomized, controlled Burgdorf study is to assess the effects of a supervised 12- month intensive multimodal exercise intervention in comparison to a moderate aerobic exercise intervention, on muscle strength in prostate cancer patients receiving ADT. Additionally, quality of life, fatigue, body composition, erectile dysfunction, bone pain, physical activity level, endurance capacity, body-mass-index, waist and hip circumference and prostate-specific antigen- and testosterone levels will be assessed up to one year later. Discussion: The Burgdorf study is the first study to conduct two different one-year supervised exercise interventions, and follow-up with patients for up to one year after the intervention. Results could provide important insights into the long-term effects of interventions on those parameters negatively affected by ADT, which could specify or newly establish care structures. Trial registration: German Clinical Trials Register, DRKS00009975. Registered 2016-02-09, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00009975

Purpose Reduced physical performance due to therapy-related dysfunctions in children diagnosed with cancer contributes to insufficient physical activity levels. It is therefore essential that relevant functions are restored. Whole-body vibration (WBV) training, a neuromuscular stimulating exercise intervention, could have the potential to target those functions adequately. Therefore, the aim of this study was to evaluate the feasibility of a combined supervised and home-based WBV intervention with children after inpatient oncological treatment. Methods Eight children aged 6-21 years were included after cessation of their inpatient oncological treatment. They performed a 12-week WBV training including one supervised and two home-based sessions per week according to a standardized training protocol. Feasibility, adherence and compliance to the vibration protocol were documented. Subjective benefits and satisfaction were assessed using a questionnaire. Results Study participants attended 84.03 +/- 13.09% of WBV sessions. No serious adverse events occurred. Some patients reported side effects partially resulting in modifications of the vibration protocol by therapists. Almost all children regarded the intervention as beneficial. Conclusion A combined supervised and home-based WBV intervention with children after inpatient oncological treatment is feasible and safe. The beneficial potential regarding relevant sensory and motor dysfunctions is now to be investigated.

Break-off of part of the down-going plate during continental collision occurs due to tensile stresses built-up between the deep and shallow slab, for which buoyancy is increased because of continental-crust subduction. Break-off governs the subsequent orogenic evolution but real-time observations are rare as it happens over geologically short times. Here we present a finite-frequency tomography, based on jointly inverted local and remote earthquakes, for the Hindu Kush in Afghanistan, where slab break-off is ongoing. We interpret our results as crustal subduction on top of a northwards-subducting Indian lithospheric slab, whose penetration depth increases along-strike while thinning and steepening. This implies that break-off is propagating laterally and that the highest lithospheric stretching rates occur during the final pinching-off. In the Hindu Kush crust, earthquakes and geodetic data show a transition from focused to distributed deformation, which we relate to a variable degree of crust-mantle coupling presumably associated with break-off at depth.

BACKGROUND: Data on changes in natural killer cell cytolytic activity (NKCA) in response to acute physical exercise are contradictory. OBJECTIVE: The aim of this systematic review, meta-analysis and meta-regression is to (1) examine the effect of acute physical exercise on NKCA, (2) shed more light on the moderating factors, and (3) test the assumption of NKCA suppression subsequent to performing sports. METHODS: Two comparisons of NKCA were performed: (1) pre- versus post-exercise and (2) pre-exercise versus recovery. Data were acquired through a systematic search of MEDLINE (via PubMed), Scopus, and SportDiscus. Studies were eligible for inclusion if the effect of acute physical exercise was assessed including a passive control group and reporting NKCA prior to and immediately after the trial, and during the first 2 h of recovery. To better explain between-study heterogeneity, a moderator analysis was conducted. RESULTS: Pooled estimate from 12 studies reporting 18 effect sizes show that NKCA is largely elevated by acute physical exercise (Hedges' g = 1.02, 95% CI 0.59-1.46, p < 0.01). Meta-regressions reveal that this effect is larger for endurance versus resistance exercise and increases with the intensity of exercise (both p < 0.01), whereas the blood material used in the assay (p = 0.71), and the quantitative change in NK-cell count (R2 = 0%, p = 0.55) do not play a significant role. Physical exercise does not affect the level of NKCA after the recovery period (g = 0.06, 95% CI - 0.37 to 0.50, p < 0.76). CONCLUSIONS: This work provides solid evidence for elevated NKCA through performing sports which returns to baseline during the first 1-2 h of recovery, but not below the pre-exercise values providing counterevidence to the assumption of temporarily reduced NKCA. Remarkably, the functional change in NKCA exists independently from the quantitative change in NK-cell count. PROSPERO registration number: CRD42020134257.

Exercise under fasting conditions induces a switch to lipid metabolism, eliciting beneficial metabolic effects. Knowledge of signaling responses underlying metabolic adjustments in such conditions may help to identify therapeutic strategies. Therefore, w

The combination of aging populations with the obesity pandemic results in an alarming rise in non-communicable diseases. Here, we show that the enigmatic adenosine A2B receptor (A2B) is abundantly expressed in skeletal muscle (SKM) as well as brown adipose tissue (BAT) and might be targeted to counteract age-related muscle atrophy (sarcopenia) as well as obesity. Mice with SKM-specific deletion of A2B exhibited sarcopenia, diminished muscle strength, and reduced energy expenditure (EE), whereas pharmacological A2B activation counteracted these processes. Adipose tissue-specific ablation of A2B exacerbated age-related processes and reduced BAT EE, whereas A2B stimulation ameliorated obesity. In humans, A2B expression correlated with EE in SKM, BAT activity, and abundance of thermogenic adipocytes in white fat. Moreover, A2B agonist treatment increased EE from human adipocytes, myocytes, and muscle explants. Mechanistically, A2B forms heterodimers required for adenosine signaling. Overall, adenosine/A2B signaling links muscle and BAT and has both anti-aging and anti–obesity potential.

CaTeNA – Climatic and Tectonic Natural Hazards in Central Asia – is an interdisciplinary, international project funded by the German Ministry of Education and Research to study natural hazards in Central Asia. Central Asia is one of the most tectonically active regions of the world and is influenced by both the west wind zone and monsoon. CaTeNA is examining the two most serious natural hazards arising from these conditions: Earthquakes and mass movements. The project goal is to better understand the underlying processes and triggering factors and to better estimate the resulting risks. For this purpose, CaTeNA localises tectonic faults and determines deformation rates and their changes. Focus is put on two of the most active fault systems, the Main Pamir Thrust and the Darvaz Fault crossing Tajikistan and Kyrgyzstan. We try to estimate recurrence intervals of large earthquakes and to understand their relationship to mass movements using paleo-seismology, geomorphology and remote sensing. The current deformation field is characterised and quantified using the methods of space geodesy and seismology. The results will be incorporated into the openly accessible Central Asian Tectonic Database developed within the project, making it accessible to the public, stakeholders and decision-makers. They form the basis for a more accurate estimation of the risk for earthquakes and landslides. Another important project goal is the development and implementation of a dynamic risk assessment for landslides, including high-resolution, model-based precipitation and snowmelt maps. This allows for improved estimation of the effects of geological hazards on inhabited areas and traffic infrastructure. Direct and efficient risk communication is achieved through interactive visualisation based on a dynamic multilingual web GIS platform. This is an essential step on the path to an early-warning system that takes into account the most important triggering factors. This data repository provi

Chemotherapy-induced peripheral neuropathy (CIPN) is a prevalent and clinically relevant side effect of chemotherapy. The symptoms diminish patients' quality of life and represent a decisive limiting factor for medical therapy. To date, effective treatment options are lacking. Specific exercise interventions have proven promising to target relevant symptoms. We conducted a prospective, four-armed, randomized, controlled trial, to evaluate the effects of sensorimotor training (SMT) and whole-body vibration training (WBV) on patients with CIPN. Participants (N=40) were randomized to either one of two intervention groups (SMT N=10 or WBV N=10) or oncological control group (N=10) and matched by gender and age with a healthy control (N=10). The intervention groups exercised twice a week for 6weeks. Primary endpoint was the reduction of CIPN-related symptoms (improve peripheral deep sensitivity, Achilles tendon reflex (ASR) and patellar tendon reflex (PSR), light-touch perception, sense of position, and lower leg strength). Secondary endpoints were nerve conduction velocity and amplitude, balance control, quality of life, and CIPN-related pain. Patients exercising improved sensory and associated motor symptoms. Significant intergroup differences were found for the tendon reflexes (ASR P=.017 and PSR P=.020), peripheral deep sensitivity (P=.010), and pain (P=.043). Furthermore, tendencies were found regarding the subjective improvement of symptoms (P=.075) and two subscales of the EORTC-QLQ-C30 questionnaire: pain (P=.054) and dyspnea (P=.054). The results for the SMT group were superior regarding the tendon reflexes, and a tendency regarding the subjective report of symptoms, while WBV was superior regarding pain. SMT and WBV behold a large potential to reduce CIPN-related symptoms and can be considered feasible and safe for patients with CIPN (compliance 97.5%, no adverse events).Registration: DRKS00013027

Background: Acute aerobic exercise leads to positive physiological adaptations within the central nervous system. These findings inspired research on potential cognitive benefits following acute aerobic exercise. The effects of acute aerobic exercise on subsequent cognitive performance, by far, have been the most researched for interference control, a subcomponent of executive function. The results of primary studies on the effects of acute aerobic exercise on subsequent interference control performance are inconsistent. Therefore, we used meta-analytic methods to pool available effect sizes, and to identify covariates that determine the magnitude of exercise-induced interference control benefits. Methods: Medline, PsycINFO, and SPORTDiscus were searched for eligible records. Hedges' g corrected standardized mean difference values (SMDs) were used for analyses. Random-effects weights were used to pool effect sizes. Moderator analyses were conducted using meta-regressions and subgroups analyses. Covariates that were here tested for moderation included parameters of the applied exercise regimen (exercise intensity and exercise duration), characteristics of examined participants (age and fitness), and methodological features of existing research (type of control group, familiarization with test procedure, type of test variable, delay between exercise cessation, and testing). Results: Fifty studies, with data from 2,366 participants, were included in qualitative and quantitative synthesis. A small, significant beneficial effect of acute aerobic exercise on time-dependent measures of interference control was revealed (k = 49, Hedges' g = −0.26, 95%CI: −34 to −0.18). Effect sizes from time-dependent measures of interference control varied widely and heterogeneity reached statistical significance (T2 = 0.0557, I2 = 28.8%). Moderator analyses revealed that higher exercise intensities (vigorous intensity and high-intensity interval training), also participants at younger or

While molecular signal transduction pathways are well described, less is known about selective protein degradation pathways and changes of the human skeletal muscle metabolome in response to resistance exercise (RE). We determined that maximal eccentric RE leads to a significant degree of z-disc streaming and myofibrillar damage associated with a significant degree of unfolding and degradation of filaminC (FlnC) proteins. FlnC proteins act by crosslinking actin filaments in the sarcomeric z-disc and further as molecular sensors of damage. Its degradation is coordinated via chaperone-assisted selective autophagy (CASA) by the cochaperone BAG3 which also controls increased FlnC expression. › In contrast to low intense RE, maximal eccentric RE induces a significant reduction of FlnC and BAG3 within 24 h after acute RE. In a chronic RE intervention (13 RE units; 3 times per week) a progressive but not constant training intensity was associated with a significant increase in FlnC levels over five weeks of RE. This was accompanied by a fast reduction of z-disc streaming and myofibrillar damage and attributes CASA-mediated FlnC incorporation into z-discs a potential role in mediating the “Repeated bout” effect. As it can be assumed that during frequent RE and in a growing muscle various metabolic pathways will be activated, we hypothesized that branches of the skeletal muscle metabolome will change acutely and also after several weeks of RE. › In a combined approach using liquid chromatography followed by detection through mass spectrometry we detected 589 metabolites within biopsy samples in which we also found a significant increase in type I and II myofiber diameter. Metabolites of the amino acid and nucleotide metabolism increased significantly after the first unaccustomed RE session while being reduced up to the 13th RE session. In contrast, metabolites of the lipid metabolism were significantly reduced up to the last training session indicating a reduction in skeleta