SARS-CoV-2 Test-to-Stay in Daycare.

BACKGROUND AND OBJECTIVES: Test-to-stay concepts apply serial testing of children in daycare after exposure to SARS-CoV-2 without use of quarantine. This study aims to assess the safety of a test-to-stay screening in daycare facilities. METHODS: 714 daycare facilities and approximately 50 000 children ≤6 years in Cologne, Germany participated in a SARS-CoV-2 Pool-polymerase chain reaction (PCR) screening from March 2021 to April 2022. The screening initially comprised post-exposure quarantine and was adapted to a test-to-stay approach during its course. To assess safety of the test-to-stay approach, we explored potential changes in frequencies of infections among children after the adaptation to the test-to-stay approach by applying regression discontinuity in time (RDiT) analyses. To this end, PCR-test data were linked with routinely collected data on reported infections in children and analyzed using ordinary least squares regressions. RESULTS: 219 885 Pool-PCRs and 352 305 Single-PCRs were performed. 6440 (2.93%) Pool-PCRs tested positive, and 17 208 infections in children were reported. We estimated that during a period of 30 weeks, the test-to-stay concept avoided between 7 and 20 days of quarantine per eligible daycare child. RDiT revealed a 26% reduction (Exp. Coef: 0.74, confidence interval 0.52-1.06) in infection frequency among children and indicated no significant increase attributable to the test-to-stay approach. This result was not sensitive to adjustments for 7-day incidence, season, SARS-CoV-2 variant, and socioeconomic status. CONCLUSIONS: Our analyses provide evidence that suggest safety of the test-to-stay approach compared with quarantine measures. This approach offers a promising option to avoid use of quarantine after exposure to respiratory pathogens in daycare settings.

Results of the Cologne Corona Surveillance (CoCoS) project- a cross-sectional study: survey data on risk factors of SARS-CoV-2 infection, and moderate-to-severe course in primarily immunized adults.

BACKGROUND: Amidst the COVID-19 pandemic, vaccination has been a crucial strategy for mitigating transmission and disease severity. However, vaccine-effectiveness may be influenced by various factors, including booster vaccination, as well as personal factors such as age, sex, BMI, smoking, and comorbidities. To investigate the potential effects of these factors on SARS-CoV-2 infection and disease severity, we analyzed data from the third round of the Cologne Corona Surveillance (CoCoS) project, a large cross-sectional survey. METHODS: The study was conducted mid-February to mid-March 2022 in Cologne, Germany. A random sample of 10,000 residents aged 18 years and older were invited to participate in an online survey. Information on participants' demographics (age, sex), SARS-CoV-2 infections, vaccination status, smoking, and preexisting medical conditions were collected. The outcomes of the study were: (1) the occurrence of SARS-CoV-2 infection despite vaccination (breakthrough infection) and (2) the occurrence of moderate-to-severe disease as a result of a breakthrough infection. Cox proportional-hazards regression was used to investigate possible associations between the presence/absence of booster vaccination, personal factors and the occurrence of SARS-CoV-2 infection. Associations with moderate-to-severe infection were analyzed using the Fine and Gray subdistribution hazard model. RESULTS: A sample of 2,991 residents responded to the questionnaire. A total of 2,623 primary immunized participants were included in the analysis of breakthrough infection and 2,618 in the analysis of SARS-CoV-2 infection severity after exclusions due to incomplete data. The multivariable results show that booster vaccination (HR = 0.613, 95%CI 0.415-0.823) and older age (HR = 0.974, 95%CI 0.966-0.981) were associated with a reduced hazard of breakthrough infection. Regarding the severity of breakthrough infection, older age was associated with a lower risk of moderate-to-severe breakthrough infection (HR = 0.962, 95%CI0.949-0.977). Female sex (HR = 2.570, 95%CI1.435-4.603), smoking (HR = 1.965, 95%CI1.147-3.367) and the presence of chronic lung disease (HR = 2.826, 95%CI1.465-5.450) were associated with an increased hazard of moderate-to-severe breakthrough infection. CONCLUSION: The results provide a first indication of which factors may be associated with SARS-CoV-2 breakthrough infection and moderate-to-severe course of infection despite vaccination. However, the retrospective nature of the study and risk of bias in the reporting of breakthrough infection severity limit the strength of the results. TRIAL REGISTRATION: DRKS.de, German Clinical Trials Register (DRKS), Identifier: DRKS00024046, Registered on 25 February 2021.

Impact of Systemic Sclerosis-Associated Interstitial Lung Disease With and Without Pulmonary Hypertension on Survival: A Large Cohort Study of the German Network for Systemic Sclerosis.

BACKGROUND: Pulmonary involvement is the leading cause of death in systemic sclerosis (SSc) and may manifest as interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), or in combination of both (ILD with pulmonary hypertension [ILD-PH]). The aim of this analysis was to determine prevalence, clinical characteristics, and survival of these different forms within the registry of the German Network for Systemic Sclerosis. RESEARCH QUESTION: Does SSc-associated ILD-PH or ILD without PH affect survival differently, and are there any risk factors that have an additional impact? STUDY DESIGN AND METHODS: Clinical data of 5,831 patients with SSc were collected in the German Network for Systemic Sclerosis registry. Kaplan-Meier estimates were used to compare overall survival in patients with SSc-associated ILD-PH and ILD without PH with patients without pulmonary involvement and those with PAH. The Cox proportional hazard model was used to analyze the influence of pulmonary involvement and other potential predictors on patient survival. RESULTS: Clinical data of 3,257 patients with a mean follow-up time of 3.45 ± 1.63 years have been included in our analysis. At baseline, ILD was present in 34.5%, whereas PH without ILD had a lower prevalence with 4.5%. At the end of follow-up, 47.6% of patients with SSc had ILD, 15.2% had ILD-PH, and 6.5% had PAH. ILD was more frequent in the diffuse cutaneous form (57.3%), whereas PAH did not differ significantly between SSc subtypes. Significant differences in baseline characteristics between PAH vs ILD-PH vs ILD without PH were found for age at diagnosis, sex, SSc subsets, antibody status, FVC, diffusing capacity of the lung for carbon monoxide, and therapy. Overall survival at 5 years was 96.4% for patients without pulmonary involvement and differed significantly between patients with ILD without PH, PAH, and being worst in patients with ILD-PH. Female sex (hazard ratio [HR], 0.3), higher BMI (HR, 0.9), and higher diffusing capacity of the lung for carbon monoxide values (HR, 0.98) were associated with a lower mortality risk. INTERPRETATION: ILD is the most prevalent pulmonary involvement in SSc, whereas the combination of ILD and PH is associated with the most detrimental survival.

[Movement as a Neuromodulator: How Physical Activity Influences the Physiology of Adolescent Depression]. / Bewegung als Neuromodulator: Wie körperliche Aktivität die Physiologie der adoleszenten Depression reguliert.

Movement as a Neuromodulator: How Physical Activity Influences the Physiology of Adolescent Depression Abstract: In the context of adolescent depression, physical activity is becoming increasingly recognized for its positive effects on neuropathology. Current scientific findings indicate that physical training affects the biological effects of depression during adolescence. Yet the pathophysiology of adolescent depression is not yet fully understood. Besides psychosocial and genetic influences, various neurobiological factors are being discussed. One explanation model describes a dysfunction of the hypothalamus-pituitary-adrenal axis (HPA axis) with a sustained elevation in cortisol concentration. Recent studies highlight neuroimmunological processes and a reduced concentration of growth factors as causative factors. These changes appear to lead to a dysregulation of the excitation and inhibition balance of the cerebral cortex as well as to cerebral morphological alterations. Regular physical training can potentially counteract the dysregulation of the HPA axis and normalize cortisol levels. The release of proinflammatory cytokines is inhibited, and the expression of growth factors involved in adult neurogenesis is stimulated. One should ensure the synergistic interaction of biological and psychosocial factors when designing the exercise schedule (endurance or strength training, group or individual sports, frequency, duration, and intensity). Addressing these open questions is essential when integrating physical activity into the guidelines for treating depressive disorders in children and adolescents.

Validation of the maximal cardiopulmonary exercise test in adolescents with major depressive disorder and comparison of cardiorespiratory fitness with sex- and age-related control values.

Endurance training has been shown to be effective in treating adolescents with major depressive disorder (MDD). To integrate endurance training into the therapeutic setting and the adolescents' daily lives, the current performance status of the adolescents should be accurately assessed. This study aims to examine adolescents with MDD concerning exhaustion criteria during a cardiopulmonary exercise test (CPET), as well as to compare the values obtained thereon with sex- and age-related control values. The study included a retrospective examination of exhaustion criteria ((i) oxygen consumption (V̇O2) plateau, (ii) peak respiratory exchange ratio (RERpeak) > 1.0, (iii) peak heart rate (HRpeak) ≥ 95% of the age-predicted maximal HR, and (iv) peak blood lactate concentration (BLCpeak) > 8.0 mmol⋅L-1) during a graded CPET on a cycle ergometer in adolescents with MDD (n = 57). Subsequently, maximal V̇O2, peak minute ventilation, V̇O2 at the first ventilatory threshold, and peak work rate of participants who met at least two of four criteria were compared with published control values using an independent-sample t-test. Thirty-three percent of the total population achieved a V̇O2 plateau and 75% a RERpeak > 1.0. The HR and BLC criteria were met by 19% and 22%, respectively. T-test results revealed significant differences between adolescents with MDD and control values for all outcomes. Adolescents with MDD achieved between 56% and 83% of control values.   Conclusions: The study shows that compared with control values, fewer adolescents with MDD achieve the exhaustion criteria on a CPET and adolescents with MDD have significantly lower cardiorespiratory fitness.   Clinical trial registration: No. U1111-1145-1854. What is Known: • It is already known that endurance training has a positive effect on depressive symptoms. What is New: • A relevant proportion of adolescents with major depressive disorder do not achieve their V̇O2max during a graded cardiopulmonary exercise test. • Adolescents with major depressive disorder have significantly lower cardiorespiratory fitness compared to sex- and age-related control values.

Interaction of panic and episodic breathlessness among patients with life-limiting diseases: a cross-sectional study.

BACKGROUND: Episodic breathlessness is often accompanied by panic. A vicious cycle of breathlessness-panic-breathlessness leads to emergencies with severe breathlessness and/or fear of dying. However, the interaction between episodic breathlessness and panic is poorly understood. Thus, the aim is a better understanding of the interaction between panic and episodic breathlessness to develop appropriate support for patients suffering from this symptom. METHODS: Patients suffering from episodic breathlessness due to life-limiting diseases answered questions on the characteristics of episodic breathlessness and panic-spectrum psychopathology, including underlying mechanisms. Using the Patient Health Questionnaire and the Structured Clinical Interview for DSM-IV Diagnoses (SCID), patients were screened for panic disorder. An open-ended question captured the patients' descriptions of panic during breathlessness episodes. RESULTS: Forty-six patients [52% women, mean age =66 years; standard deviation (SD) 7.3 years] provided information: 61% suffered from panic during the entire breathlessness episode, 39% experienced panic in every episode, and 25% were diagnosed with panic disorder. Exploratory data analysis was conducted. Patients with high scores in breathlessness catastrophizing thoughts experienced more panic in a breathlessness episode (P<0.001) and considered themselves more panic than low-scorers (P=0.024). There was a significant indirect effect of episodic breathlessness intensity on the panic experienced in an episode, and this effect was mediated by catastrophizing thoughts regarding breathlessness (b=0.164; 95% CI: 0.105, 0.222). Patients described in the open-ended question experiencing only panic or breathlessness, or a combination of both. Some patients managed to differentiate panic from episodic breathlessness, and used strategies to avoid panic in an episode. CONCLUSIONS: Research on treatment options for episodic breathlessness should not only focus on panic in breathlessness episodes, but also on underlying mechanisms such as catastrophizing thoughts, as they aggravate the burden.

Effects of inpatient energy management education and high-intensity interval training on health-related quality of life in persons with multiple sclerosis: A randomized controlled superiority trial with six-month follow-up.

BACKGROUND: Fatigue is one of the most frequent symptoms in persons with multiple sclerosis (pwMS) and impacts health-related quality of life (HRQoL). A multidisciplinary rehabilitation approach is recommended for the treatment of fatigue in pwMS. However, high-quality evidence exists only for unimodal interventions, such as physical therapies/exercise or energy/fatigue management programmes. The primary objective of the current study was to test the hypothesis that a combination of inpatient energy management education (IEME) and high-intensity interval training (HIIT) is superior to a combination of progressive muscle relaxation (PMR) and moderate continuous training (MCT) for improving HRQoL at 6-month follow-up in fatigued pwMS. METHODS: A randomized (1:1) controlled superiority trial with fatigued pwMS >18 years of age, with Expanded Disability Status Scale (EDSS) score ≤6.5, recruited at the Valens clinic, Switzerland. Participants in the experimental group performed IEME twice and HIIT 3 times per week and those in the usual care group performed PMR twice and MCT 3 times per week, during a 3-week inpatient rehabilitation stay. Primary outcome was HRQoL (Physical and Mental Component Scales of the Medical Outcome Study 36-item Short Form Health Survey (SF-36)), assessed at entry to the clinic (T0), after 3 weeks' rehabilitation (T1) and 4 (T2) and 6 (T3) months after T0. Secondary outcomes included SF-36 subscales, fatigue (Fatigue Scale for Motor and Cognitive Functions (FSMC)), mood (Hospital Anxiety and Depression Scale (HADS)), self-efficacy for performing energy conservation strategies (Self-Efficacy for Performing Energy Conservation Strategies Assessment (SEPECSA)), self-perceived competence in activities of daily living (Occupational Self Assessment (OSA)) and cardiorespiratory fitness (peak oxygen consumption (VÈ®2peak)). Data were analysed using a mixed model for repeated measures approach. RESULTS: A total of 106 pwMS (age (years): 49.75 (9.87), 66% female, EDSS: 4.64 (1.32)) were recruited. There were no significant group × time interaction effects in the primary and secondary outcomes. There were significant between-group differences in the pairwise comparisons of the group × time interaction in favour of the IEME + HIIT group at: (i) T1 in cardiorespiratory fitness (p = 0.011) and SEPECSA (p = 0.032); (ii) T2 in SF-36 mental health subscale (p = 0.022), HADS anxiety subscale (p = 0.014) and SEPECSA (p = 0.040); (iii) T3 in SF-36 physical functioning subscale (p = 0.012) and SEPECSA (p = 0.003). CONCLUSION: IEME + HIIT was not superior to PMR + MCT regarding the effects on HRQoL (SF-36 Physical and Mental Component Scales) at 6-month follow-up in pwMS. However, there were significant between-group differences in favour of IEME + HIIT in physical functioning and mental health (SF-36 subscales), anxiety (HADS), cardiorespiratory fitness (VÈ®2peak) and self-efficacy (SEPECSA) at different measurement time-points that need to be considered in clinical practice.

Results of the Cologne Corona Surveillance (CoCoS) study - a cross-sectional study: survey data on risk factors of SARS-CoV-2 infection in adults.

BACKGROUND: The personal, environmental, and behavioral risk factors that play an important role in the spread of SARS-CoV-2 are still largely unclear. At the same time, there is limited evidence on the effectiveness of specific countermeasures for SARS-CoV-2. As a first approach to these questions, we use data from the Cologne Corona Surveillance (CoCoS) study, a large cross-sectional study conducted in Cologne, Germany, in June 2021. METHODS: This study was conducted in Cologne, Germany. Six thousand randomly selected Cologne residents who were 18 years of age or older were invited to participate in this study. Participant information was obtained via an online survey. Previous SARS-CoV-2 infections were recorded using self-reports. Sociodemographic and environmental information such as age, sex, living situation were collected. Potential SARS-CoV-2 risk behaviors were captured (workplace situation, adherence to hygiene regulations, and regular use of public transportation). Adherence to hygiene regulations was surveyed by determining the compliance with the 'AHA'-rules (German acronym that stands for keeping a distance of 1.5 m from fellow citizens, hand disinfection, and wearing a face mask). Binary logistic regression analysis was used to identify risk factors for SARS-CoV-2 infection. RESULTS: A sample of 2,433 study participants provided information. Comparison of the sample with the general population showed representativeness for most sociodemographic characteristics with a preference for higher level of education in the study sample. Younger age, as well as living with minor children (under 18 years) in the same household were associated with a higher number of self-reported SARS-CoV-2 infections. Adherence to hygiene regulations was associated with fewer self-reported SARS-CoV-2 infections in adults. Gender, size of living space per person, workplace situation (work from home versus working with contact to colleagues/customers), and regular use of public transportation showed no significant association with self-reported SARS-CoV-2 infections in multivariable analysis. CONCLUSION: The presented results provide initial indications of which sociodemographic and behavioral factors may be associated with SARS-CoV-2 infection. However, the fact that these factors were recorded without exact dates and could have changed accordingly during the pandemic or after infection limits the strength of the results. TRIAL REGISTRATION: DRKS.de, German Clinical Trials Register (DRKS), Identifier: DRKS00024046, Registered on 25 February 2021.

Physical exercise is tied to emotion-related impulsivity: insights from correlational analyses in healthy humans.

Seminal work has found a negative association between physical exercise and impulsivity levels in humans. This paper aims to strengthen these findings by evaluating the association between the amount of self-reported physical exercise per week and emotion-related impulsivity whilst considering age and gender as covariates on a large-scale dataset.Participants completed an online self-report questionnaire about emotion-related impulsivity (i.e. Feelings Trigger Action) and exercise-related questions. After quality control, 773 participants were included in the analysis. Correlational analyses and a multiple regression model explaining the emotion-related impulsivity scores via the amount of exercise per week and demographic characteristics (i.e. age and gender) were performed.The number of hours spent exercising per week was significantly inversely correlated with the Feelings Trigger Action score (r = -.131, p < .001) and two out of its three subscales. The multiple linear regression model showed that hours of exercise per week and gender were significantly associated with the Feelings Trigger Action score (std. ß = -.122, p < .001), however, this model explained only 3.2% of the overall variance.This large-scale dataset confirms seminal work displaying an inverse association between emotion-related impulsivity and hours of exercise per week. Further studies are required to understand the mechanisms underlying the relationship between the two variables.HighlightsThis study (N = 773) confirms seminal work on the connection between exercise and impulsivity.When controlling for demographic variables, the amount of exercise per week was inversely correlated (small effect size) with emotion-related impulsivity levels.In the multiple-regression model, hours of exercise per week and gender were significantly associated with the Feelings Trigger Action score.

Autologous hematopoietic stem cell transplantation improves long-term survival-data from a national registry.

BACKGROUND: Current recommendations on the management of systemic sclerosis (SSc) suggest that autologous hematopoietic stem cell therapy (HSCT) can be a rescue therapy for patients with rapidly progressive SSc. OBJECTIVES: To assess the safety and efficacy of HSCT for patients with SSc and to compare these with non-HSCT patients in a control cohort with adjusted risk factors. METHODS: A retrospective analysis of data from the multicentric German network for systemic scleroderma (DNSS) with 5000 patients with SSc. Control groups consisted of all patients with diffuse cutaneous (dc)-SSc (group A) and an adjusted high-risk cohort of male patients with Scl70-positive dc-SSc (group B). RESULTS: Eighty SSc patients received an HSCT 4.1 ± 4.8 years after SSc diagnosis. Among them, 86.3% had dc-SSc, 43.5% were males, and 71.3% were positive for Scl70 antibodies. The control group A (n=1513) showed a significant underrepresentation of these risk factors for mortality. When the survival of the control group B (n=240) was compared with the HSCT group, a lower mortality of the latter was observed instead. Within 5 years after HSCT, we observed an improvement of the mRSS from 17.6 ± 11.5 to 11.0 ± 8.5 (p=0.001) and a stabilization of the DLCO. We did not see differences in transplant-related mortality between patients who received HSCT within 3 years after SSc diagnosis or later. CONCLUSION: Our analysis of real-life data show that the distribution of risk factors for mortality is critical when HSCT cohorts are compared with non-HSCT control groups.

Effect of sleep and fatigue on cardiovascular performance in young, healthy subjects.

Physical performance could be negatively affected by sleep deficiency and fatigue. The present study assesses the role of sleep quality, fatigue and motivation on cardiovascular performance (VO2peak, Wmax, and HRmax) in a sample of active young subjects. The current study is a cross-sectional design. Ninety-six university students (males 54.2%; 21.5 ± 2.9 yrs) completed an incremental exercise test on a bicycle ergometer. Sleep, fatigue, and motivation were assessed with the Pittsburgh Sleep Quality Index and two visual analogue scales, respectively. Differences in VO2peak, Wmax, HRmax, self-perceived fatigue and motivation were compared between good and bad sleepers and sleep duration >/<7.5 h, while regression analysis defined the predictors of VO2peak, Wmax, and HRmax. In the male sample, good and bad sleepers' differences were significant only for self-perceived fatigue (p = 0.04). The female sample showed no statistically significant differences between good and bad sleepers and different sleep durations. In the male sample, linear regression analysis showed a significant inverse correlation between Wmax and the PSQI score (-0.4, p = 0.004). The stepwise regression model indicated that sleep (ß = -0.3, p = 0.02) was a significant predictor of VO2peak in males accounting for 20% of the variance, whereas physical performance seems more affected by fatigue (ß = -0.4, p = 0.03) in females. In conclusion, chronic inadequate and self-reported sleep quality seems to be one of the factors compromising cardiovascular performance in males.

Results of the Cologne Corona surveillance (CoCoS) study - a prospective population-based cohort study: incidence data and potential underestimation of new SARS-CoV-2 adult infections by health authorities.

BACKGROUND: Current incidence estimates of SARS-CoV-2 in Germany rely to a large extent on case notifications. However, the large number of mild or asymptomatic infections is likely to result in underestimation. Population-based studies can provide valid estimates of the SARS-CoV-2 incidence and thus support health authorities to monitor the epidemiological situation and to initiate, maintain, strengthen or relax effective countermeasures. METHODS: This study was conducted in Cologne, Germany. Six-thousand randomly drawn Cologne residents, 18 years of age or older, were contacted by mail in March 2021. Study envelopes contained a kit for self-administered saliva sample and access details to a questionnaire on sociodemographic characteristics, previous positive SARS-CoV-2 RT-qPCR and completed COVID-19 vaccinations. Participants were again invited for a second round in June 2021, while those who declined participation were replaced by additional randomly drawn Cologne residents in order to reach a total of 6000 potential participants again. The saliva samples were sent to the laboratory by mail and tested for SARS-CoV-2 using RT-qPCR. The incidence estimates were adjusted for sensitivity and specificity of the test procedure and compared with the official numbers of new SARS-CoV-2 cases in the adult Cologne population. RESULTS: The first surveillance round in March 2021 (response rate: 34.08%, N = 2045) showed a SARS-CoV-2 seven-day incidence of 85 cases per 100,000 adult Cologne residents (95% CI: 9 to 319). In the same period, the officially registered cases were 125 per 100,000. The second surveillance round in June 2021 (response rate: 36.53%, N = 2192) showed a seven-day incidence of 27 per 100,000 adult Cologne residents (95% CI: 1 to 142), while the official figures for newly registered SARS-CoV-2 cases in the same period were 15 per 100,000. CONCLUSIONS: The incidence estimates do not indicate relevant underestimation of new SARS-CoV-2 infections based on case notification. Regular use of the surveillance method developed here may nevertheless complement the efforts of the health authorities to assess the epidemiological situation. TRIAL REGISTRATION: DRKS.de, German Clinical Trials Register (DRKS), Identifier: DRKS00024046 , Registered on 25 February 2021.

Exercise Interventions Combined With Dietary Supplements in Type 2 Diabetes Mellitus Patients-A Systematic Review of Relevant Health Outcomes.

Introduction: Physical training can improve several health variables in patients with type 2 diabetes mellitus (T2DM). A growing body of studies also finds a positive influence of dietary supplement (DS) intake. The aim of this review is to shed light on the possible effects of training interventions combined with DS intake in T2DM patients. Methods: A systematic search was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in the PubMed and BISp Surf databases. Inclusion criteria were defined using the Patient-Intervention-Comparison-Outcome (PICO) scheme. The Physiotherapy Evidence Database (PEDro) scale was used for quality assessment and risk of bias analysis. Results: Ten controlled interventional studies with a total number of 643 subjects met the inclusion criteria. These studies investigated the effects of (a) vitamin D (VD), (b) VD + whey protein, (c) polyphenol containing antioxidant capsules, (d) creatine, (e) L-arginine, (f) leucine-rich amino acids, and (g) broccoli sprouts powder. Eight studies investigated effects on one or more of the following health outcomes: body mass index, fat mass, insulin resistance, glycemic control, lipid profile, oxidative stress/antioxidative capacity and/or inflammatory markers/molecules. Five of the studies show clear superior effects of physical training combined with DS intake (supplements a, b, c, e) on some of these variables compared with training only. However, one study indicates that VD intake might attenuate the training effects on triglyceride levels. Another study found that training + VD + whey protein intake increased tumor necrosis factor-α levels in T2DM patients. The effects of training combined with DS intake on renal function (supplement d) or incretin metabolism (supplement a) were investigated in two further studies. These studies do not show any additional effects of DS intake. The quality of the majority of the studies was high. Conclusion: DS intake can potentially increase the benefits of physical training for specific health outcomes in T2DM patients. However, negative effects can also be observed. Possible cellular and molecular mechanisms behind potential synergistic or divergent effects of exercise training and DS use in T2DM should be explored in detail in future studies for the development of safe recommendations.

The diagnostic value of cytokines for the discrimination of vertebral osteomyelitis and degenerative diseases of the spine.

Vertebral osteomyelitis (VO) is a primary infection of the endplates of the vertebral bodies with secondary infection of the adjacent intervertebral discs. Diagnosis is often delayed due to unspecific symptoms and a lack of specific infection markers. In this prospective study, we determined the suitability of 27 cytokines for the discrimination of VO and degenerative diseases of the spine and compared its diagnostic potential in relation to the C-reactive protein (CRP), which is widely used as a non-specific inflammation marker in clinical diagnostics. The patients included in this study underwent surgical stabilization of the lumbar and/or thoracic spine with removal of 1 or more affected intervertebral discs, as therapy for VO (n = 16) or for erosive osteochondrosis (EO, control group, n = 20). We evaluated the cytokine and CRP concentrations before (pre-OP = -20-0d where 0 means the day of surgery) and after surgery (post-OP) on days 3-5, 6-11, 40-56, and 63-142. Compared to the control patients pre-OP, a significantly higher elevation of the 4 cytokines IL-6, IL-8, IL-12 (p70), and VEGF as well as CRP were found in the VO patients, showing an area under the curve > 0.80 pre-OP. No significant differences were observed between VO patients with high and low virulent bacteria with respect to all 5 elevated biomarkers. This is the first prospective study in which a broad spectrum of 27 cytokines was analysed via multiplex assay using sera from patients with and without VO. Our results show that, in addition to CRP, 4 different cytokines were significantly altered in VO but not control patients. The results implicate that these candidate cytokines may be used in a multiplex assay for discrimination between VO and degenerative diseases of the spine.

Only I Know Now, of Course, How to Deal With it, or Better to Deal With it: A Mixed Methods Phase II Study of a Cognitive and Behavioral Intervention for the Management of Episodic Breathlessness.

CONTEXT: Episodic breathlessness is characterized by increased breathlessness intensity, and it is burdensome for patients. A vicious cycle of breathlessness-anxiety/panic-breathlessness leads to emergencies that can rarely be alleviated by drugs. Non-pharmacological interventions seem to be beneficial: Can a brief cognitive and behavioral intervention help patients to better manage episodic breathlessness? OBJECTIVES: To evaluate the feasibility, safety, acceptability, and potential effects of a brief cognitive and behavioral intervention for the management of episodic breathlessness. METHODS: Between February 2019 and February 2020, 49 patients with life-limiting diseases suffering from episodic breathlessness were enrolled in the single-arm phase II study. The baseline assessment was followed by the one- to two-hour intervention. In weeks two, four, and six after the intervention, the outcomes (main outcome of potential effects: mastery of breathlessness) were assessed, and in week six, a qualitative interview, and the final assessment took place. A mixed-methods approach was used to evaluate mainly the feasibility, including interviewing informal carers. RESULTS: 46/49 patients (24 female; 36 with COPD; mean age: 66.0 years) participated in the baseline assessment, 38 attended the intervention, 32 completed the final assessment, and 22 were interviewed. Study procedures and the intervention were feasible and mainly well accepted and patients did not experience burdens caused by it (28/32). In the interviews, patients described a positive change in their competencies in managing episodic breathlessness and feelings of anxiety during the episode. Mastery of breathlessness improved after the intervention. CONCLUSION: The brief cognitive and behavioral intervention and the study procedures are feasible, safe, and well accepted. We can describe a change for better management of episodic breathlessness in patients after the intervention, still, this needs to be evaluated in a Phase III trial for inclusion in the management of episodic breathlessness.

Mobile PCR-based surveillance for SARS-CoV-2 to reduce visiting restrictions in nursing homes during the COVID-19 pandemic: a pilot study.

PURPOSE: Residents in nursing homes for the elderly (NH) are at high risk for death from COVID-19. We investigated whether repeated non-mandatory RT-PCR SARS-CoV-2 surveillance of NH staff and visitors reduces COVID-19 incidence rates in NH residents and allows to reduce visiting restrictions. METHODS: This pilot study at the beginning of the COVID-19 pandemic compared a surveillance approach of regular, twice-weekly voluntary PCR testing of health-care workers (HCW) and visitors in interventional NH (INH) with a setting without regular testing in control NH (CNH). Residents were not tested routinely within this study. Testing was performed in a mobile testing site with same-day result reporting. SARS-CoV-2 incidence among residents in both INH and CNH was the primary endpoint; secondary endpoints being SARS-CoV-2 infection among visitors and HCW in INH. RESULTS: Two INH and two CNH participated between October and December, 2020. At INH1, 787 tests of HCW and 350 tests of visitors were performed, accounting for 18.1% (n = 1930) of visits. At INH2, 78 tests of HCW and 372 tests of visitors were done, i.e., 30.5% (n = 1220) of visits. At the two INH 23 HCW and three visitors tested positive for SARS-CoV-2. COVID-19 outbreaks occurred among residents in INH1 (identified through study testing) and in CNH1. Utilization of voluntary testing was low. CONCLUSION: In a real-world setting without available rapid testing, voluntary RT-PCR SARS-CoV-2 testing of HCW and visitors does not prevent COVID-19 outbreaks in NH. Complete, non-selective testing for these groups should be instituted before visiting restrictions can be reduced. TRIAL REGISTRATION: The study has been registered at ClinicalTrials.gov with the identifier: NCT04933981.

Influence of motivational placebo-related factors on the effects of exercise treatment in depressive adolescents.

Recent meta-analyses reveal a moderate effect of physical activity (PA) in the treatment of adolescent depression. However, not only the underlying neurobiological mechanisms, also the influences of placebo-related motivational factors (beliefs and expectancies in sporting, enjoyment and prior sports experiences), are still unclear. Based on the data of our prior study "Mood Vibes", we hypothesized that placebo-inherent factors like positive prior sports experiences and motivational factors, (positive beliefs, expectancies, and enjoyment related to PA), would increase the effects of an add-on exercise-therapy in juvenile depression. From 64 included depressed adolescents, 41 underwent an intensive add-on PA-therapy. Motivational factors were assessed using sport-specific scales. The changes in depression scores under treatment were rated by self-rating scale (German "Childhood Depression Inventory", (DIKJ)). A mixed model for repeated measures (MMRM) was used to analyze the effects of the different motivational variates on DIKJ. While prior sports experiences had no impact, motivational factors showed a significant effect on PA-induced changes in DIKJ scores (p = 0.002). The demotivated participants improved less, whereas it was sufficient to be neutral towards sporting to benefit significantly more. Motivational placebo-related factors (beliefs, expectancies and enjoyment regarding PA) affected the outcomes of an exercise treatment in depressed adolescents. Yet, a neutral mindset was sufficient to profit more from PA. Prior sporting in the sense of positive conditioning and as a protective factor did not play a role. Knowledge about these influences could in a second step help to develop tailored therapies.

Differential effects of ergometer-cycling and Whole-Body-Vibration training on serological BDNF and IGF-1 in the treatment of adolescent depression - is there an impact of BDNFp.Val66Met variants?

BACKGROUND: Pathogenesis and treatment of adolescent depression may be influenced by growth-factors, including brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1). We investigated, if treatment response to two different add-on exercise-therapies in juvenile depression, differ in the changes of BDNF and IGF-1 serology. A subgroup analysis for genetic variations in BDNF p.Val66Met-variants was added. METHODS: Included subjects in the study (N = 64), aged 13 to 17 years, were diagnosed with major depression, controls received inpatient treatment as usual (TAU). Intervention groups performed as add-on to TAU two different forms of exercise-therapy: endurance ergometer cycling (EC) and muscle strengthening whole body vibration (WBV). We expected both exercise-forms to increase BDNF and IGF-1 serology and by this pathway to improve depression scores significantly stronger than the control group. RESULTS: None of the experimental groups showed significant changes in BDNF between measurement time points. However, after 6 weeks exercise, BDNF of both intervention groups were significantly higher compared to TAU,. The IGF-1 increase after 6 weeks intervention was significant for EC only. No correlations of BDNF and IGF-1 to depression scores were found. Group analysis in BDNF p.Val66Met variants showed a trend for better response in depression scores to exercise-treatment for the Val66Val group. LIMITATIONS: A small sample size, the non-randomized controls and the neglect of psychosocial factors have to be considered as limitations. CONCLUSIONS: Endurance and muscle strengthening trainings seem to influence serological BDNF and IGF-1 differentially. However, the changes in growth factors did not correlate to the decreases in depression scores. BDNF p.Val66Val variant seems to be more receptive for exercise treatment. Identifying biomarkers (growth factors, genetic variants) in adolescent depression could help to develop tailored treatment strategies.

Acute aerobic exercise to recover from mental exhaustion - a randomized controlled trial.

PURPOSE: Prolonged periods of intense cognitive activity lead to a state of mental exhaustion. While widespread strategies to recover from mental exhaustion (i.e., watching TV) are non-effective, aerobic exercise seems to be a promising approach. This can be explained by the acute and chronic aerobic exercise-induced benefits on the central nervous system. METHODS: This study investigated the potential of a single bout of moderate aerobic exercise (65-75% of each participants' individual V˙O2peak) to recover from experimentally induced mental exhaustion. A randomized controlled trial on healthy adults (N = 99) was conducted. They performed 60 min of a cognitively demanding test battery, in order to induce mental exhaustion. Subsequently, they were randomized to one of three treatments: 30 min of moderate aerobic exercise on a cycle ergometer, 30 min of a simple lower body stretching routine (= active control treatment) or watching a popular sitcom (= passive control treatment). Cognitive flexibility performance, mood, tiredness, restlessness, self-perceived cognitive capacity, and motivation were assessed before and after treatment. RESULTS: The empirical results showed that moderate aerobic exercise led to a better recovery for cognitive flexibility (mean difference divided by pooled standard deviation, Cohen's d= 0.737), mood (d= 0.405), tiredness (d= 0.480), self-perceived cognitive capacity (d= 0.214), and motivation (d= 0.524) compared to active control treatment. Moderate aerobic exercise was also more effective than passive control treatment (d= 0.102 - 0.286) with the exemption of tiredness (d= 0.015) and restlessness (d = -0.473). CONCLUSION: In conclusion, this study suggests that a single bout of acute aerobic exercise supports regeneration of cognitive flexibility performance and of subjective well-being. This holds true not just compared to artificial active control treatment but also compared to widespread leisure time activity, namely watching TV.

Immunological Effects of an Add-On Physical Exercise Therapy in Depressed Adolescents and Its Interplay with Depression Severity.

BACKGROUND: Pro-inflammatory cytokines (PICs) have gained attention in the pathophysiology and treatment of depressive disorders. At the same time, the therapeutic effect of physical activity seems to work via immunomodulatory pathways. The interventional study "Mood Vibes" analyzed the influence of exercise on depression severity (primary endpoint) in depressive adolescents; the influence of PICs on the clinical outcome was analyzed as a secondary endpoint. METHODS: Clinically diagnosed depressed adolescents (N = 64; 28.1% male; mean age = 15.9; mean BMI = 24.6) were included and participated either in Whole Body Vibration (WBV) (n = 21) or bicycle ergometer training (n = 20) in addition to treatment-as-usual (TAU). Patients in the control treatment group received TAU only (n = 23). The PICs (interleukin-6-IL-6 and tumor necrosis factor-α-TNF-α) were analyzed before intervention, after 6 weeks of training (t1), and 8 weeks post-intervention (t2). The effects of the treatment on depression severity were rated by self-rating "Depression Inventory for Children and Adolescents" (DIKJ). RESULTS: Basal IL-6 decreased in all groups from t0 to t1, but it increased again in WBV and controls at t2. TNF-α diminished in ergometer and controls from baseline to t1. PIC levels showed no correlation with depression severity at baseline. The influence on DIKJ scores over time was significant for IL-6 in the WBV group (p = 0.008). Sex had an impact on TNF-α (p < 0.001), with higher concentrations in male patients. Higher body mass index was associated with higher IL-6 concentrations over all measurement points (p < 0.001). CONCLUSIONS: The positive effects of an intensive add-on exercise therapy on adolescent depression seem to be partly influenced by immunomodulation. A small sample size and non-randomized controls are limitations of this study.