The effect of physical exercise interventions on insomnia: A systematic review and meta-analysis.

6-10 % of Europeans suffer from chronic insomnia. They have a higher risk to develop mental and cardiovascular diseases. Treatment of insomnia primarily recommended by the European guideline is cognitive behavioral therapy for insomnia (CBT-I). A quarter of patients treated with CBT-I do not respond sufficiently. The objective of this paper is to examine the influence of exercise interventions on insomnia by conducting a systematic review and meta-analysis. A database search was conducted, including randomized controlled trials (RCT) in which participants had received a diagnosis of insomnia or experienced symptoms thereof. Exercise interventions had to meet the definition of the World Health Organization (WHO), and their implementation was reported according to the FITT (Frequency, Intensity, Time and Type) principle. There was an inactive control and subjective or objective sleep parameters as outcomes. Nineteen studies were included. Results showed a significant improvement for objective (standardized mean difference, SMD = 0.37; confidence interval, CI = [0.17; 0.57]) as well as subjective (SMD = 0.90; CI = [0.61; 1.19]) sleep parameters. Meta-regression showed that the effect increased with intensity of intervention, mean age of participants and percentage of females, but showed high heterogeneity across studies. These results suggest great potential for treating insomnia. Conducting larger trials is advisable to provide precise recommendations.

COVID-19 in Female and Male Athletes: Symptoms, Clinical Findings, Outcome, and Prolonged Exercise Intolerance-A Prospective, Observational, Multicenter Cohort Study (CoSmo-S).

BACKGROUND: An infection with SARS-CoV-2 can lead to a variety of symptoms and complications, which can impair athletic activity. OBJECTIVE: We aimed to assess the clinical symptom patterns, diagnostic findings, and the extent of impairment in sport practice in a large cohort of athletes infected with SARS-CoV-2, both initially after infection and at follow-up. Additionally, we investigated whether baseline factors that may contribute to reduced exercise tolerance at follow-up can be identified. METHODS: In this prospective, observational, multicenter study, we recruited German COVID elite-athletes (cEAs, n = 444) and COVID non-elite athletes (cNEAs, n = 481) who tested positive for SARS-CoV-2 by PCR (polymerase chain reaction test). Athletes from the federal squad with no evidence of SARS-CoV-2 infection served as healthy controls (EAcon, n = 501). Questionnaires were used to assess load and duration of infectious symptoms, other complaints, exercise tolerance, and duration of training interruption at baseline and at follow-up 6 months after baseline. Diagnostic tests conducted at baseline included resting and exercise electrocardiogram (ECG), echocardiography, spirometry, and blood analyses. RESULTS: Most acute and infection-related symptoms and other complaints were more prevalent in cNEA than in cEAs. Compared to cEAs, EAcon had a low symptom load. In cNEAs, female athletes had a higher prevalence of complaints such as palpitations, dizziness, chest pain, myalgia, sleeping disturbances, mood swings, and concentration problems compared to male athletes (p < 0.05). Until follow-up, leading symptoms were drop in performance, concentration problems, and dyspnea on exertion. Female athletes had significantly higher prevalence for symptoms until follow-up compared to male. Pathological findings in ECG, echocardiography, and spirometry, attributed to SARS-CoV-2 infection, were rare in infected athletes. Most athletes reported a training interruption between 2 and 4 weeks (cNEAs: 52.9%, cEAs: 52.4%), while more cNEAs (27.1%) compared to cEAs (5.1%) had a training interruption lasting more than 4 weeks (p < 0.001). At follow-up, 13.8% of cNEAs and 9.9% of cEAs (p = 0.24) reported their current exercise tolerance to be under 70% compared to pre-infection state. A persistent loss of exercise tolerance at follow-up was associated with persistent complaints at baseline, female sex, a longer break in training, and age > 38 years. Periodical dichotomization of the data set showed a higher prevalence of infectious symptoms such as cough, sore throat, and coryza in the second phase of the pandemic, while a number of neuropsychiatric symptoms as well as dyspnea on exertion were less frequent in this period. CONCLUSIONS: Compared to recreational athletes, elite athletes seem to be at lower risk of being or remaining symptomatic after SARS-CoV-2 infection. It remains to be determined whether persistent complaints after SARS-CoV-2 infection without evidence of accompanying organ damage may have a negative impact on further health and career in athletes. Identifying risk factors for an extended recovery period such as female sex and ongoing neuropsychological symptoms could help to identify athletes, who may require a more cautious approach to rebuilding their training regimen. TRIAL REGISTRATION NUMBER: DRKS00023717; 06.15.2021-retrospectively registered.

Trends in the numbers of SARS-CoV-2 infections among students: a prospective cohort study comparing students in sports boarding schools with students in day schools during early COVID-19 pandemic.

Introduction: During the first months of the COVID pandemic it emerged that facilities where people gather or live together in cohorts, such as nursing homes or schools, were particularly at high risk for becoming hotspots of virus transmission. German political and health institutions responded with far-reaching interventions and preventive strategies to protect the population from infection with SARS-CoV-2. In this context, it remains unclear whether boarding schools for sports particularly pose a risk of infection to their residents. Methods: In a single-center prospective cohort study, numbers of SARS-CoV-2 infections of students in sports boarding schools (n = 11) vs. students attending regular day schools (n = 22) in the region Freiburg/Hochschwarzwald in Germany were investigated over a period from October 2020 to January 2021 via regular virus and antibody screening (German Clinical Trials Register; Study ID: DRKS00021909). In addition, individual and behavioral risk factors for infection were stratified via questionnaire, which provide an indication of cohort specific risk factors for infection and the success of the implementation of hygiene concepts, as well as other infection prevention strategies, within the respective facilities. Results: Regarding SARS-CoV-2 infection numbers, the screening detected no significant group difference between sports boarding schools vs. day schools. Discussion: The study results provide indications that sports boarding schools did not pose an increased risk of infection, assuming that the facilities prevent virus transmissions with appropriate preventive strategies and hygiene measures. In future pandemic scenarios larger-scale and multicenter studies are necessary to achieve more comprehensive epidemiological data in this field.

A Comparison of the Impact of COVID-19-Related Restrictions on Physical Activity Among Public Employees.

OBJECTIVES: This article compares the impact of COVID-19-related restrictions on the level of physical activity, performed by public servants, in April and November 2020. METHODS: The survey examined the amount (in minutes per week) and the energy expenditure (in metabolic equivalent of task in minutes per week [METmin/week]) of physical activity for both before and during contact restrictions in April and November 2020, respectively. RESULTS: Especially for sports activity difference was determined by the medians before (April/November: median [Mdn] = 180.0 min/wk) and during (April: Mdn = 130 minutes, November: Mdn = 60 min/wk) restrictions ( P < 0.05).Also for energy consumption (METmin/wk), the medians before and during the contact restrictions declined for both periods. CONCLUSIONS: Measures against the coronavirus have led to a reduction in activity levels among public employees, regardless of their work environment. The decrease in participation in sport activities seemed to be even more noticeable within the second restriction period.

Macrophages: From Simple Phagocyte to an Integrative Regulatory Cell for Inflammation and Tissue Regeneration-A Review of the Literature.

The understanding of macrophages and their pathophysiological role has dramatically changed within the last decades. Macrophages represent a very interesting cell type with regard to biomaterial-based tissue engineering and regeneration. In this context, macrophages play a crucial role in the biocompatibility and degradation of implanted biomaterials. Furthermore, a better understanding of the functionality of macrophages opens perspectives for potential guidance and modulation to turn inflammation into regeneration. Such knowledge may help to improve not only the biocompatibility of scaffold materials but also the integration, maturation, and preservation of scaffold-cell constructs or induce regeneration. Nowadays, macrophages are classified into two subpopulations, the classically activated macrophages (M1 macrophages) with pro-inflammatory properties and the alternatively activated macrophages (M2 macrophages) with anti-inflammatory properties. The present narrative review gives an overview of the different functions of macrophages and summarizes the recent state of knowledge regarding different types of macrophages and their functions, with special emphasis on tissue engineering and tissue regeneration.

[Influence of the contact restrictions against SARS-CoV-2 on physical activity among public sector employees.] / Einfluss der Kontaktbeschränkungen gegen SARS-CoV-2 auf die körperliche Aktivität von Beschäftigten des öffentlichen Dienstes.

Objective: Preliminary results from activity surveys conducted in spring 2020 suggest that athletic activity may have decreased within the contact restrictions against the spread of coronavirus. The coronavirus pandemic poses many challenges to the workforce in the healthcare system. Therefore, this study investigated whether the measures to limit the pandemic have an influence on the activity behavior of employees in the public sector. Method: A retrospective cross-sectional survey was conducted to collate the activity behavior among employees of three institutions in the public sector before and during the measures against the coronavirus in April 2020. An online version of the Freiburg Activity Questionnaire was used. Using Wilcoxon tests on connected samples with a significance level of p < 0.05, the activity behavior was examined for differences before compared to during the contact restrictions in min/week and MET-min./week. Results: A total of 1797 public sector employees in Freiburg (36.0% male, 63.9% female, and 0.1% diverse) participated in the survey. For sports activity, a relevant difference (p < 0.05) was measured in the medians (Mdn) of activities per week before (Mdn = 180 min) and during (Mdn = 120 min) the relevant contact restrictions. Similarly, for energy expenditure through exercise, the median value within the contact restrictions decreased from Mdn = 1022 MET-min/week to Mdn = 750 MET-min./week. Conclusion: Measures to limit the spread of the coronavirus have led to a reduction in activity levels among public sector employees. In particular, fewer employees engaged in sports. This could be related to the closure of fitness studios as these activities were particularly reduced. Decreased physical activity can lead to unfavorable individual risk profiles, which must be compensated for in the future.

In Vivo Comparison of Synthetic Macroporous Filamentous and Sponge-like Skin Substitute Matrices Reveals Morphometric Features of the Foreign Body Reaction According to 3D Biomaterial Designs.

Synthetic macroporous biomaterials are widely used in the field of skin tissue engineering to mimic membrane functions of the native dermis. Biomaterial designs can be subclassified with respect to their shape in fibrous designs, namely fibers, meshes or fleeces, respectively, and porous designs, such as sponges and foams. However, synthetic matrices often have limitations regarding unfavorable foreign body responses (FBRs). Severe FBRs can result in unfavorable disintegration and rejection of an implant, whereas mild FBRs can lead to an acceptable integration of a biomaterial. In this context, comparative in vivo studies of different three-dimensional (3D) matrix designs are rare. Especially, the differences regarding FBRs between synthetically derived filamentous fleeces and sponge-like constructs are unknown. In the present study, the FBRs on two 3D matrix designs were explored after 25 days of subcutaneous implantation in a porcine model. Cellular reactions were quantified histopathologically to investigate in which way the FBR is influenced by the biomaterial architecture. Our results show that FBR metrics (polymorph-nucleated cells and fibrotic reactions) were significantly affected according to the matrix designs. Our findings contribute to a better understanding of the 3D matrix tissue interactions and can be useful for future developments of synthetically derived skin substitute biomaterials.

First detection of primary cilia in injured human anterior cruciate ligament: A pilot study with pathophysiological reflections.

The anterior cruciate ligament (ACL) plays a significant role in knee stability, protects the joint under multiple loading conditions and shows complex biomechanics. Beside mechanical stability, the ACL seems to play a crucial role in proprioception, and it is well known, that ACL injuries can cause functional deficits due to decreased proprioception. However, the mechanism of proprioception is not completely understood yet. In this context, primary cilia (PC), which play a significant role in the signaling between the intra- and extracellular space, could be of interest. However, until today, primary cilia are not yet described in human ACL. In total, seven human ACL's underwent transmission electron microscopical examination. Three cadaveric ACL's and four freshly injured ACL's were examined. Single cells of each ACL were examined regarding the presence of axonemes or basal bodies, which represent components of a PC. In total, 276 cells of the cadaveric ACL's and 180 cells of the injured ACL's were examined. Basal bodies could be detected in three of the four specimens of the injured ACL's as well as in one of the three cadaveric ACL's, resulting in a mean positivity of 2.54% in the cadaveric group and 2.78% in the injured group. In case of PC-presence, only one PC per cell could be detected. No statistically significant difference regarding the frequency could be detected between both groups. In this pilot-study, we present for the first time an ultrastructural study of human ACLs with respect to the occurrence of PC and any structural and morphological features of these complex and dynamic cell organelles. PCs are present in almost all non-hematopoietic tissues of the human body. However, there are different reports on the number, incidence, orientation, and morphology of these cell organelles in the respective tissues. Compared to other tissues and ligaments of other species, we found a significantly lower rate of PC positive cells. This observation might represent a tissue-specific characteristic of ACL tissue. However, our observations need to be explored in more detail in further studies.

Case Report: Assessing COVID-19 Transmission in Professional Volleyball in Germany, September to December 2020: An Epidemiological Study.

Introduction: The SARS-CoV-2 pandemic poses extraordinary challenges in all fields of daily life. The WHO recommended social distancing guidelines and person-to-person contact was strongly discouraged to contain transmission. Team-based sports were questioned and widely debated. However, there is a lack of available evidence on the risk of in-game SARS-CoV-2 transmission. We aim to derive new insights regarding the risk of SARS-CoV2 infection during team sports and provide current opinion on how to behave during training and competition. Methods: We report on six competitive male volleyball players (national level) of the same team who were infected with COVID-19. The mode of transmission and potential virus spreading within the team was investigated. The entire course of infection was documented by detailed medical history of the players and RT-PCR tests confirmed suspected infections. Serological testing was performed to establish the antibody status of the team. Results: The investigation did not show strong evidence of viral transmission within the team during sporting activities. Only two players with PCR-proven infection hat detectable antibodies in two antibody assays. Conclusion: Private and social gatherings can spread infection into team sports. Clearly defined test strategies and strict adherence to standard COVID-19 hygiene guidelines during sports seasons cannot be overemphasized.

Structural Analysis of Mitochondrial Dynamics-From Cardiomyocytes to Osteoblasts: A Critical Review.

Mitochondria play a crucial role in cell physiology and pathophysiology. In this context, mitochondrial dynamics and, subsequently, mitochondrial ultrastructure have increasingly become hot topics in modern research, with a focus on mitochondrial fission and fusion. Thus, the dynamics of mitochondria in several diseases have been intensively investigated, especially with a view to developing new promising treatment options. However, the majority of recent studies are performed in highly energy-dependent tissues, such as cardiac, hepatic, and neuronal tissues. In contrast, publications on mitochondrial dynamics from the orthopedic or trauma fields are quite rare, even if there are common cellular mechanisms in cardiovascular and bone tissue, especially regarding bone infection. The present report summarizes the spectrum of mitochondrial alterations in the cardiovascular system and compares it to the state of knowledge in the musculoskeletal system. The present paper summarizes recent knowledge regarding mitochondrial dynamics and gives a short, but not exhaustive, overview of its regulation via fission and fusion. Furthermore, the article highlights hypoxia and its accompanying increased mitochondrial fission as a possible link between cardiac ischemia and inflammatory diseases of the bone, such as osteomyelitis. This opens new innovative perspectives not only for the understanding of cellular pathomechanisms in osteomyelitis but also for potential new treatment options.

COVID-19 in German Competitive Sports: Protocol for a Prospective Multicenter Cohort Study (CoSmo-S).

Objective: It is unclear whether and to what extent COVID-19 infection poses health risks and a chronic impairment of performance in athletes. Identification of individual health risk is an important decision-making basis for managing the pandemic risk of infection with SARS-CoV-2 in sports and return to play (RTP). Methods: This study aims 1) to analyze the longitudinal rate of seroprevalence of SARS-CoV-2 in German athletes, 2) to assess health-related consequences in athletes infected with SARS-CoV-2, and 3) to reveal effects of the COVID-19 pandemic in general and of a cleared SARS-CoV-2 infection on exercise performance. CoSmo-S is a prospective observational multicenter study establishing two cohorts: 1) athletes diagnosed positive for COVID-19 (cohort 1) and 2) federal squad athletes who perform their annual sports medical preparticipation screening (cohort 2). Comprehensive diagnostics including physical examination, laboratory blood analyses and blood biobanking, resting and exercise electrocardiogram (ECG), echocardiography, spirometry and exercise testing added by questionnaires are conducted at baseline and follow-up. Results and Conclusion: We expect that the results obtained, will allow us to formulate recommendations regarding RTP on a more evidence-based level.

Effects of Atrial Fibrillation on the Human Ventricle.

RATIONALE: Atrial fibrillation (AF) and heart failure often coexist, but their interaction is poorly understood. Clinical data indicate that the arrhythmic component of AF may contribute to left ventricular (LV) dysfunction. OBJECTIVE: This study investigates the effects and molecular mechanisms of AF on the human LV. METHODS AND RESULTS: Ventricular myocardium from patients with aortic stenosis and preserved LV function with sinus rhythm or rate-controlled AF was studied. LV myocardium from patients with sinus rhythm and patients with AF showed no differences in fibrosis. In functional studies, systolic Ca2+ transient amplitude of LV cardiomyocytes was reduced in patients with AF, while diastolic Ca2+ levels and Ca2+ transient kinetics were not statistically different. These results were confirmed in LV cardiomyocytes from nonfailing donors with sinus rhythm or AF. Moreover, normofrequent AF was simulated in vitro using arrhythmic or rhythmic pacing (both at 60 bpm). After 24 hours of AF-simulation, human LV cardiomyocytes from nonfailing donors showed an impaired Ca2+ transient amplitude. For a standardized investigation of AF-simulation, human iPSC-cardiomyocytes were tested. Seven days of AF-simulation caused reduced systolic Ca2+ transient amplitude and sarcoplasmic reticulum Ca2+ load likely because of an increased diastolic sarcoplasmic reticulum Ca2+ leak. Moreover, cytosolic Na+ concentration was elevated and action potential duration was prolonged after AF-simulation. We detected an increased late Na+ current as a potential trigger for the detrimentally altered Ca2+/Na+-interplay. Mechanistically, reactive oxygen species were higher in the LV of patients with AF. CaMKII (Ca2+/calmodulin-dependent protein kinase IIδc) was found to be more oxidized at Met281/282 in the LV of patients with AF leading to an increased CaMKII activity and consequent increased RyR2 phosphorylation. CaMKII inhibition and ROS scavenging ameliorated impaired systolic Ca2+ handling after AF-simulation. CONCLUSIONS: AF causes distinct functional and molecular remodeling of the human LV. This translational study provides the first mechanistic characterization and the potential negative impact of AF in the absence of tachycardia on the human ventricle.

Semiautomated quantification of the fibrous tissue response to complex three-dimensional filamentous scaffolds using digital image analysis.

Fibrosis represents a relevant response to the implantation of biomaterials, which occurs not only at the tissue-material interface (fibrotic encapsulation) but also within the void fraction of complex three-dimensional (3D) biomaterial constructions (fibrotic ingrowth). Usual evaluation of the biocompatibility mostly depicts fibrosis at the interface of the biomaterial using semiquantitative scores. Here, the relations between encapsulation and infiltrating fibrotic growth are poorly represented. Virtual pathology and digital image analysis provide new strategies to assess fibrosis in a more differentiated way. In this study, we adopted a method previously used to quantify fibrosis in visceral organs to the quantification of fibrosis to 3D biomaterials. In a proof-of-concept study, we transferred the "Collagen Proportionate Area" (CPA) analysis from hepatology to the field of biomaterials. As one task of an experimental animal study, we used CPA analysis to quantify the fibrotic ingrowth into a filamentous scaffold after subcutaneous implantation. We were able to demonstrate that the application of the CPA analysis is well suited as an additional fibrosis evaluation strategy for new biomaterial constructions. The CPA method can contribute to a better understanding of the fibrotic interactions between 3D scaffolds and the host tissue responses.

Physical activity is associated with less comorbidity, better treatment tolerance and improved response in patients with multiple myeloma undergoing stem cell transplantation.

OBJECTIVES: Multiple myeloma (MM) is the second most common hematological malignancy. Progression free survival (PFS) and overall survival (OS) have substantially improved, nonetheless MM usually remains incurable. Patients with active disease may be affected by numerous comorbidities, including fatigue, depression and osteolytic lesions, which influence their quality of life (QoL). Albeit, it is known that exercising is beneficial for patients' QoL, few clinical trials are available in patients with MM. We therefore aimed to compare comorbidities and clinical outcome in physically active and inactive patients with MM. MATERIAL AND METHODS: We defined physical activity according to WHO criteria (150 min of moderate activity and two sessions of resistance training/week). We matched 53 physically active patients with 53 controls (for age, gender, cytogenetics, disease stage, and therapy) and compared the cohorts for incidence of comorbidities/MM symptoms (osteolytic lesions, anemia, infections, fatigue, depression, Revised-Myeloma Comorbidity Index [R-MCI]) and clinical outcome (treatment tolerance, responses to therapy, PFS and OS) in a retrospective audit. All patients were newly diagnosed with MM and received autologous stem cell transplantations (ASCT) between 2001 and 2017. RESULTS: Physically active patients showed superior outcomes in R-MCI (p = 0.0005), fatigue (p = 0.0063), treatment tolerance (p = 0.0258) and hospital stays (p = 0.0072). Furthermore, they showed better treatment responses (p = 0.0366), especially complete remission (CR; p = 0.0018) as well as better OS and PFS. CONCLUSION: Physical activity in patients with MM undergoing ASCT seemed associated with better overall clinical outcome. Randomized clinical trials are required to understand the benefits and devise strategies for improving exercising among patients with MM.

Physiological and Pathophysiological Aspects of Primary Cilia-A Literature Review with View on Functional and Structural Relationships in Cartilage.

Cilia are cellular organelles that project from the cell. They occur in nearly all non-hematopoietic tissues and have different functions in different tissues. In mesenchymal tissues primary cilia play a crucial role in the adequate morphogenesis during embryological development. In mature articular cartilage, primary cilia fulfil chemo- and mechanosensitive functions to adapt the cellular mechanisms on extracellular changes and thus, maintain tissue homeostasis and morphometry. Ciliary abnormalities in osteoarthritic cartilage could represent pathophysiological relationships between ciliary dysfunction and tissue deformation. Nevertheless, the molecular and pathophysiological relationships of 'Primary Cilia' (PC) in the context of osteoarthritis is not yet fully understood. The present review focuses on the current knowledge about PC and provide a short but not exhaustive overview of their role in cartilage.