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Abstract Previous works have suggested a high prevalence of painkiller intake (PI) among sport students but also improved health literacy (HL) for sports-active students than for sports-inactive students. Since health-related content also forms part of the sport science curriculum, the study focuses on these seemingly paradoxical results. Music students who are also physically active through their instrumental practice, who act in an area with increased PI and who have no health-related teaching content in their curriculum composed the comparison group. Therefore, this study investigated the prevalence of PI and HL in cohorts of sport (n = 222; 54.5% female) and music students (n = 89; 67.4% female) using a cross-sectional online survey in Lower Saxony, Germany. The hypothesis tests were validated by calculating frequentist and Bayesian statistics. The results show that 50.9% of sport and 28.1% of music students exhibit PI concerning their study programs, often for prophylactical purposes and in the presence of low HL levels. The weak negative correlation between PI and HL was not statistically confirmed and requires further research with improved test power. Regarding the possible health consequences of an inconsiderate PI, target group-specific prevention is indicated to increase general health awareness and HL.

Abstract Background Childhood obesity is associated with various health outcomes. Restrictive measures to contain the spread of the Coronavirus Disease 2019 (COVID-19) pandemic, like lockdowns and school closures, affected children’s daily structure, physical activity, dietary habits, and sleep quality, possibly exacerbating risk factors for childhood obesity and higher body mass index (BMI) in children. Poor socioeconomic conditions may have led to relatively higher risk for elevated BMI levels following pandemic measures. In this study, the impact of measures related to the COVID-19 pandemic on the BMI of third graders was investigated regarding children’s socioeconomic background (SEB). Methods Data from 41,728 children (8.84 ± 0.56 years, 20,431 female) were collected in the context of a cohort study. Children were tested either before the pandemic (preCOVID: Sept2017–March2020, n = 26,314), or following the first (postLDI: Aug2020–Dec2020, n = 6657) or second lockdown in Germany (postLDII: Aug2021–Jan2022, n = 8757). SEB was based on the official school type classification of the state of Berlin. Outcome was BMI standard deviation scores (SDS). Results Significant effects of Time and SEB revealed elevated BMIs in postLDI (M = 0.23, p = 0.011) and postLDII (M = 0.22, p = 0.011) compared to preCOVID (M = 0.17) cohorts and higher BMIs for children with lower SEB (b = − 0.13, p

IntroductionHandball goalkeepers have to act under severe spatio-temporal pressure in both standardised (e.g., 7 m penalty) and non-standardised situations (e.g., backcourt throws) which require them to predict action outcome before ball flight is visible. So far, research on goalkeepers’ cue utilisation for anticipation of an opponent’s action has mainly focused on 7 m throw situations whereas little attention has been paid to the latter, more complex and far more frequently occurring backcourt throw situations.MethodsTo address this gap, we conducted semi-structured interviews with N = 6 expert handball goalkeepers and goalkeeper coaches [all of whom were (former) expert handball goalkeepers] on anticipation and cue utilisation when facing backcourt throws. The interviews were subsequently transcribed, coded and results were inductively as well as deductively categorised by means of a thematic analysis.ResultsResults reveal a variety of kinematic and contextual cues relevant for action anticipation that become available before the game and before or during the throw. Participants reported to use information from the offence (e.g., thrower’s jump; opposing team’s task distribution) and the defence (e.g., defensive players’ strategies, block position) for anticipation in backcourt throw situations. Additionally, we identified several factors that influence cue availability and utilisation.DiscussionOur findings provide a thorough basis to (a) guide future research that yields questions on kinematic and contextual cue integration and in-situ cue usage as well as (b) inform the development of training programs to foster goalkeepers’ anticipatory skill.

Background: The reduction of muscular hypertonia is important in the treatment of various diseases or rehabilitation. This study aims to test the efficacy of a 5 Hz mechanical muscle stimulation (tapotement massage) in comparison to a 5 Hz repetitive peripheral magnetic stimulation (rPMS) on the neuromuscular reflex response. Methods: In a randomized control trial, 15 healthy volunteers were administered with either 5 Hz rPMS, tapotement massage, or rPMS sham stimulation. The posterior tibial nerve was stimulated with rPMS and sham stimulation. The Achilles tendon was exposed to a mechanically applied high-amplitude 5 Hz repetitive tendon tapotement massage (rTTM). The tendon reflex (TR) was measured for the spinal response of the soleus muscle. Results: After rPMS, there was a reduction of the TR response (−9.8%, p ≤ 0.034) with no significant changes after sham stimulation. Likewise, TR decreased significantly (−17.4%, p ≤ 0.002) after Achilles tendon tapotement intervention. Conclusions: These findings support the hypothesis that both afferent 5 Hz sensory stimulations contributed to a modulation within the spinal and/or supraspinal circuits, which resulted in a reduction of the spinal reflex excitability. The effects could be beneficial for patients with muscle hypertonia and could improve the functional results of rehabilitation programs.

This study developed a cutting technique modification training program and investigated its effects on cutting performance and movement quality in adolescent American football players. For six weeks, an intervention group (IG) of 11 players participated in 25 min cutting technique modification training sessions integrated into team training twice a week, while a control group (CG) of 11 players continued their usual team training. Movement quality was assessed by evaluating 2D high-speed videos, obtained during preplanned 45° and 90° cutting tests, using the Cutting Movement Assessment Score (CMAS) qualitative screening tool. Cutting performance was assessed based on change of direction deficit (CODD). Significant interaction effects of time × group were found for CMAS in 45° and 90° cuttings (p < 0.001, ηp2 = 0.76, p < 0.001, ηp2 = 0.64, respectively), with large improvements in the IG (p < 0.001, g = −2.16, p < 0.001, g = −1.78, respectively) and deteriorations in the CG for 45° cuttings (p = 0.002, g = 1.15). However, no statistically significant differences in CODD were observed pre-to-post intervention. The cutting technique modification training was effective at improving movement quality without impairing cutting performance, and it can be used by practitioners working with adolescent athletes.

BackgroundAgility is acknowledged as a crucial factor of performance in various open skill sports in both adult and youth athletes. However, despite its significance for sports performance the development and the trainability of agility are under-researched within the pediatric literature. A systematic scoping review was considered most appropriate to provide researchers and practitioners with an overview of the current body of literature approaching agility in youth.ObjectivesThe objectives of this scoping review were to map the extent, range, and nature of existing evidence regarding trainability and “natural” development of agility and to summarize corresponding study results.MethodsThe scoping review protocol was pre-registered at Open Science Framework. Systematic searches were conducted using the databases PubMed, Scopus, ProQuest, Web of Science, SURF, and SPONET to identify sources covering agility in youth. Among other inclusion criteria, only references applying unplanned agility concepts were included.ResultsUltimately, 41 reports were included comprising 23 observational studies, 14 experimental studies, and 4 references of secondary research. A total of 3,087 subjects were assessed in the included studies. Subject groups were predominantly male, above 10 years of age, and soccer athletes. Outcomes of observational studies indicate an effect of age and maturation on agility performance resulting in a non-linear “natural” development of agility. Furthermore, relationships between contributing perceptual-cognitive factors and agility performance tend to increase with progressing age, whereas relationships between physical factors and agility performance diminish. Evidence of training studies suggests that agility is trainable in youth, albeit with various underlying mechanisms.ConclusionsThis systematic scoping review is the first mapping of the body of literature about agility in youth. It outlines the current evidence base, reveals research gaps, and points out future directions to support researchers and practitioners in this field. Although, increasing research activity in this field is discernible, agility research in youth is still in its infancy. Considering the significance of agility for sports performance, future research is postulated to design evidence-based strategies for long-term agility development in young athletes.

Conclusions from doping prevention literature recommend tailored anti-doping education for athletes' specific needs. Newer approaches like the International Standard for Education of the World Anti-Doping Agency recommend a needs assessment before implementing measures. The International Standard for Education refers to the type of sports and its associated risk for doping. Following this idea, elite athletes from different types of sports should differ in their prerequisites for doping prevention. Consequently, the guiding research question focused on exploring the doping-prevention-related background of young athletes as a particular group for prevention efforts. Sixty young elite athletes (58.3% male) took part in a cross-sectional online survey, which was quantitatively analyzed. Participants included 26 athletes from a sport with low doping prevalence (sailing) and 34 athletes from a sport associated with high doping prevalence (wrestling). Sailors and wrestlers differed concerning the perceived resistance against doping temptations (p = 0.031, r = 0.31) and the estimated actual doping prevalence regarding sports in general (national frame: p < 0.001, r = 0.60; international frame: p = 0.013, r = 0.43). No differences between the two types of sports occurred, referring to doping attitudes, tendency to disengage morally, or topics athletes wish to learn about during doping prevention measures. All results indicated a good baseline for doping prevention with young elite athletes at the beginning of their careers. There is no sport-specific needs profile that could be used as a base for tailored measures. However, the data suggest that a differentiated consideration of gender could be helpful in the planning of doping prevention measures.

The aim of this study was to establish maturation-, age-, and sex-specific anthropometric and physical fitness percentile reference values of young elite athletes from various sports. Anthropometric (i.e., standing and sitting body height, body mass, body mass index) and physical fitness (i.e., countermovement jump, drop jump, change-of-direction speed [i.e., T-test], trunk muscle endurance [i.e., ventral Bourban test], dynamic lower limbs balance [i.e., Y-balance test], hand grip strength) of 703 male and female elite young athletes aged 8-18 years were collected to aggregate reference values according to maturation, age, and sex. Findings indicate that body height and mass were significantly higher (p

Dynamic postural control is challenged during many actions in sport such as when landing or cutting. A decrease of dynamic postural control is one possible risk factor for non-contact injuries. Moreover, these injuries mainly occur under loading conditions. Hence, to assess an athlete’s injury risk properly, it is essential to know how dynamic postural control is influenced by physical load. Therefore, the study’s objective was to examine the influence of maximal anaerobic load on dynamic postural control. Sixty-four sport students (32 males and 32 females, age: 24.11 ± 2.42, height: 175.53 ± 8.17 cm, weight: 67.16 ± 10.08 kg) were tested with the Y-Balance Test before and after a Wingate Anaerobic Test on a bicycle ergometer. In both legs, reach distances (anterior) and composite scores were statistically significantly reduced immediately after the loading protocol. The values almost returned to pre-load levels in about 20 min post-load. Overall, findings indicate an acute negative effect of load on dynamic postural control and a higher potential injury risk during a period of about 20 min post-load. To assess an athlete’s sports-specific injury risk, we recommend testing dynamic postural control under loaded conditions.

Understanding the shared genetic aetiology of psychiatric and medical comorbidity in neurodevelopmental disorders (NDDs) could improve patient diagnosis, stratification and treatment options. Rare tetratricopeptide repeat, ankyrin repeat and coiled-coil containing 2 (TANC2)-disrupting variants were disease causing in NDD patients. The post-synaptic scaffold protein TANC2 is essential for dendrite formation in synaptic plasticity and plays an unclarified but critical role in development. We here report a novel homozygous-viable Tanc2-disrupted function model in which mutant mice were hyperactive and had impaired sensorimotor gating consistent with NDD patient psychiatric endophenotypes. Yet, a multi-systemic analysis revealed the pleiotropic effects of Tanc2 outside the brain, such as growth failure and hepatocellular damage. This was associated with aberrant liver function including altered hepatocellular metabolism. Integrative analysis indicates that these disrupted Tanc2 systemic effects relate to interaction with Hippo developmental signalling pathway proteins and will increase the risk for comorbid somatic disease. This highlights how NDD gene pleiotropy can augment medical comorbidity susceptibility, underscoring the benefit of holistic NDD patient diagnosis and treatment for which large-scale preclinical functional genomics can provide complementary pleiotropic gene function information.

Invasive pulmonary aspergillosis is associated with high mortality. For diagnosis, galactomannan-antigen in serum and bronchoalveolar lavage fluid is recommended, with higher sensitivity in bronchoalveolar lavage fluid. Because of invasiveness, bronchoalveolar lavage might be withheld due to patients’ or technical limitations, leading to a delay in diagnosis while early diagnosis is crucial for patient outcome. To address this problem, we performed an analysis of patient characteristics of intubated patients with invasive pulmonary aspergillosis with comparison of galactomannan-antigen testing between non-directed bronchial lavage (NBL) and bronchoalveolar lavage fluid. A total of 32 intubated ICU patients with suspected invasive pulmonary aspergillosis could be identified. Mycological cultures were positive in 37.5% for A. fumigatus. Galactomannan-antigen in NBL (ODI 4.3 ± 2.4) and bronchoalveolar lavage fluid (ODI 3.6 ± 2.2) showed consistent results (p-value 0.697). Galactomannan-antigen testing for detection of invasive pulmonary aspergillosis using deep tracheal secretion showed comparable results to bronchoalveolar lavage fluid. Because of widespread availability in intubated patients, galactomannan-antigen from NBL can be used as a screening parameter in critical risk groups with high pretest probability for invasive aspergillosis to accelerate diagnosis and initiation of treatment. Bronchoalveolar lavage remains the gold standard for diagnosis of invasive aspergillosis to be completed to confirm diagnosis, but results from NBL remove time sensitivity.

Conventionally, hyperimmune globulin drugs manufactured from pooled immunoglobulins from vaccinated or convalescent donors have been used in treating infections where no treatment is available. This is especially important where multi-epitope neutralization is required to prevent the development of immune-evading viral mutants that can emerge upon treatment with monoclonal antibodies. Using microfluidics, flow sorting, and a targeted integration cell line, a first-in-class recombinant hyperimmune globulin therapeutic against SARS-CoV-2 (GIGA-2050) was generated. Using processes similar to conventional monoclonal antibody manufacturing, GIGA-2050, comprising 12,500 antibodies, was scaled-up for clinical manufacturing and multiple development/tox lots were assessed for consistency. Antibody sequence diversity, cell growth, productivity, and product quality were assessed across different manufacturing sites and production scales. GIGA-2050 was purified and tested for good laboratory procedures (GLP) toxicology, pharmacokinetics, and in vivo efficacy against natural SARS-CoV-2 infection in mice. The GIGA-2050 master cell bank was highly stable, producing material at consistent yield and product quality up to >70 generations. Good manufacturing practices (GMP) and development batches of GIGA-2050 showed consistent product quality, impurity clearance, potency, and protection in an in vivo efficacy model. Nonhuman primate toxicology and pharmacokinetics studies suggest that GIGA-2050 is safe and has a half-life similar to other recombinant human IgG1 antibodies. These results supported a successful investigational new drug application for GIGA-2050. This study demonstrates that a new class of drugs, recombinant hyperimmune globulins, can be manufactured consistently at the clinical scale and presents a new approach to treating infectious diseases that targets multiple epitopes of a virus.

Abstract Background Mesenchymal stem cells have potential applications in inflammatory bowel disease due to their immunomodulatory properties. Our aim was to evaluate the feasibility, safety and efficacy of endoscopic administration of adipose-derived mesenchymal stem cells (ASCs) in a colitis model in rats. Methods Colitis was induced in rats by rectal trinitrobenzenesulfonic acid (TNBS). After 24 h ASCs (107 cells) or saline vehicle were endoscopically injected into the distal colon. Rats were followed for 11 days. Daily weight, endoscopic score at days 1 and 11, macroscopic appearance at necropsy, colon length and mRNA expression of Foxp3 and IL-10 in mesenteric lymph nodes (MLN) were analyzed. Results Endoscopic injection was successful in all the animals. No significant adverse events or mortality due to the procedure occurred. Weight evolution was significantly better in the ASC group, recovering initial weight by day 11 (− 0.8% ± 10.1%, mean ± SD), whereas the vehicle group remained in weight loss (− 6.7% ± 9.2%, p = 0.024). The endoscopic score improved in the ASC group by 47.1% ± 5.3% vs. 21.8% ± 6.6% in the vehicle group (p < 0.01). Stenosis was less frequent in the ASC group (4.8% vs. 41.2%, p < 0.01). Colon length significantly recovered in the ASC group versus the vehicle group (222.6 ± 17.3 mm vs. 193.6 ± 17.9 mm, p < 0.001). The endoscopic score significantly correlated with weight change, macroscopic necropsy score and colon length. Foxp3 and IL-10 mRNA levels in MLN recovered with ASC treatment. Conclusions ASC submucosal endoscopic injection is feasible, safe and ameliorates TNBS-induced colitis in rats, especially stenosis.

Mesenchymal stem cells (MSCs) have a large potential in cell therapy for treatment of inflammatory and autoimmune diseases, thanks to their immunomodulatory properties. The encouraging results in animal models have initiated the translation of MSC therapy to clinical trials. In cell therapy protocols with MSCs, administered intravenously, several studies have shown that a small proportion of infused MSCs can traffic to the draining lymph nodes (LNs). This is accompanied with an increase of different types of regulatory immune cells in the LNs, suggesting the importance of migration of MSCs to the LNs in order to contribute to immunomodulatory response. Intranodal (IN), also referred as intralymphatic, injection of cells, like dendritic cells, is being proposed in the clinic for the treatment of cancer and allergy, showing that this route of administration is clinically safe and efficient. In this study, we investigated, for the first time, the biodistribution and the efficacy of Luciferase+ adipose-derived MSCs (Luci-eASCs), infused through the inguinal LNs (iLNs), in normal mice and in inflamed mice with colitis. Most of the Luci-eASCs remain in the iLNs and in the adipose tissue surrounding the inguinal LNs. A small proportion of Luci-eASCs can migrate to other locations within the lymphatic system and to other tissues and organs, having a preferential migration toward the intestine in colitic mice. Our results show that the infused Luci-eASCs protected 58% of the mice against induced colitis. Importantly, a correlation between the response to eASC treatment and a higher accumulation of eASCs in popliteal, parathymic, parathyroid, and mesenteric LNs were found. Altogether, these results suggest that IN administration of eASCs is feasible and may represent an effective strategy for cell therapy protocols with human adipose-derived MSCs in the clinic for the treatment of immune-mediated disorders.

Mesenchymal stem cells (MSCs) are multipotent stromal cells with immunomodulatory properties. They have emerged as a very promising treatment for autoimmunity and inflammatory diseases such as rheumatoid arthritis. Previous studies have demonstrated that MSCs, administered systemically, migrate to lymphoid tissues associated with the inflammatory site where functional MSC-induced immune cells with a regulatory phenotype were increased mediating the immunomodulatory effects of MSCs. These results suggest that homing of MSCs to the lymphatic system plays an important role in the mechanism of action of MSCs in vivo. Thus, we hypothesized that direct intralymphatic (IL) (also referred as intranodal) administration of MSCs could be an alternative and effective route of administration for MSC-based therapy. Here, we report the feasibility and efficacy of the IL administration of human expanded adipose mesenchymal stem cells (eASCs) in a mouse model of collagen-induced arthritis (CIA). IL administration of eASCs attenuated the severity and progression of arthritis, reduced bone destruction and increased the levels of regulatory T cells (CD25+Foxp3+CD4+ cells) and Tr1 cells (IL10+CD4+), in spleen and draining lymph nodes. Taken together, these results indicate that IL administration of eASCs is very effective in modulating established CIA and may represent an alternative treatment modality for cell therapy with eASCs.

BACKGROUND: The heart forms from a linear tube that is subject to complex remodeling during embryonic development. Hallmarks of this remodeling are the looping of the heart tube and the regionalization into chamber and non-chamber myocardium. Cardiomyocytes in the future chamber myocardium acquire different cellular and physiological characteristics through activation of a chamber-specific genetic program, which is in part mediated by T-box genes. METHODOLOGY/PRINCIPAL FINDING: We characterize two new zebrafish T-box transcription factors, tbx3b and tbx2a, and analyze their role during the development of the atrioventricular canal. Loss- and gain-of-function analyses demonstrate that tbx3b and tbx2a are necessary to repress the chamber-genetic program in the non-chamber myocardium. We also show that tbx3b and tbx2a are required to control cell proliferation in the atrioventricular canal and that misregulation of cell proliferation in the heart tube influences looping. Furthermore, we characterize the heart phenotype of a novel Tbx3 mutation in mice and show that both the control of cell proliferation and the repression of chamber-specific genetic program in the non-chamber myocardium are conserved roles of Tbx3 in this species. CONCLUSIONS/SIGNIFICANCE: Taken together, our results uncover an evolutionarily conserved role of Tbx2/3 transcription factors during remodeling of the heart myocardium and highlight the importance of controlling cell proliferation as a driving force of morphogenesis.