Normative Reference Centiles for Sprint Performance in High-Level Youth Soccer Players: The Need to Consider Biological Maturity.

PURPOSE: To compute reference centiles for 5- and 30-m sprint times relative to chronological and skeletal age in youth soccer players. Subsequently, to compare individual's sprint performance scores derived from the chronological and skeletal age reference centiles. METHODS: Sprint times were collected for a sample of male U11 to U19 soccer players (n = 1745 data points). Skeletal age data were available for a subsample (n = 776 data points). Reference centiles were fitted using generalized additive models for location, scale, and shape. Individual z scores relative to chronological and skeletal age reference centiles were computed and compared for each maturity group (late, on-time, early, and very early) using standardized mean differences (SMD). RESULTS: Reference centiles for chronological age increased more rapidly between 10.5 and 15.5 years, while reference centiles for skeletal age increased more rapidly between 13.0 and 16.5 years. Differences in chronological and skeletal z scores for very early (SMD: -0.73 to -0.43) and late (SMD: 0.58 to 1.29) maturing players were small to large, while differences for early (SMD: -0.30 to -0.19) and on-time (SMD: 0.16 to 0.28) were trivial to small. CONCLUSION: Reference centiles provide a valuable tool to assist the evaluation of sprint performance in relation to chronological and skeletal age for talent identification purposes in youth soccer players.

Combined telemonitoring and telecoaching for heart failure improves outcome.

Telemedicine has been shown to improve the outcome of heart failure (HF) patients in addition to medical and device therapy. We investigate the effectiveness of a comprehensive telehealth programme in patients with recent hospitalisation for HF on subsequent HF hospitalisations and mortality compared to usual care in a real-world setting. The telehealth programme consists of daily remote telemonitoring of HF signs/symptoms and regular individualised telecoaching sessions. Between January 2018 and September 2020, 119,715 patients of a German health insurer were hospitalised for HF and were eligible for participation in the programme. Finally, 6065 HF patients at high risk for re-hospitalisation were enroled. Participants were retrospectively compared to a propensity score matched usual care group (n = 6065). Median follow-up was 442 days (IQR 309-681). Data from the health insurer was used to evaluate outcomes. After one year, the number of hospitalisations for HF (17.9 vs. 21.8 per 100 patient years, p < 0.001), all-cause hospitalisations (129.0 vs. 133.2 per 100 patient years, p = 0.015), and the respective days spent in hospital (2.0 vs. 2.6 days per year, p < 0.001, and 12.0 vs. 13.4, p < 0.001, respectively) were significantly lower in the telehealth than in the usual care group. Moreover, participation in the telehealth programme was related to a significant reduction in all-cause mortality compared to usual care (5.8 vs. 11.0 %, p < 0.001). In a real-life setting of ambulatory HF patients at high risk for re-hospitalisation, participation in a comprehensive telehealth programme was related to a reduction of HF hospitalisations and all-cause mortality compared to usual care.

Soccer coaches vs. sport science and medicine staff: who can more accurately predict the skeletal age of high-level youth soccer players?

Biological maturity is an important aspect in the context of talent identification and development processes within elite youth soccer players. The aim of this study was to investigate the accuracy of soccer coaches (SC) as well as sports science and medicine staff (SSMS) to predict the skeletal age of high-level youth soccer players. We also aimed to evaluate the inter-rater reliability of the skeletal age predictions among the SC and SSMS. Skeletal ages were collected for 89 male academy soccer players registered for the U12 to U16 age groups at a professional German Bundesliga club. In addition, 12 SC and five SSMS provided their skeletal age predictions for each player of their respective age group. Standardised mean differences and equivalence testing were performed between actual and predicted skeletal ages. Intra-class correlations (ICC) were calculated to assess the inter-rater reliability. For the SC, differences between predicted and actual skeletal ages were trivial and equivalent to zero for the U12, U14, and entire sample, while for the SSMS, standardised mean differences ranged from trivial to small for all age groups and the entire sample. ICC for skeletal age predictions for the entire sample was good among the SC and excellent among the SSMS, but was somewhat lower when age groups were analysed separately. While, on average, predictions were close to the actual skeletal age, SC were slightly more accurate than the SSMS. However, variability among the SSMS was large on an individual level.

Overestimation of maximal aerobic speed by the Université de Montréal track test and a 1500-m-time trial in soccer.

Introduction: Maximal aerobic speed (MAS), usually measured by cardiopulmonary exercise testing (CPET) on a treadmill, is gaining popularity in soccer to determine aerobic performance. Several field tests are used to estimate MAS, although, gold standard methods are still not clarified. Therefore, this work aims 1) to compare two different CPET based methods to assess MAS and 2) to investigate the convergent validity of two common field tests to estimate MAS in soccer. Methods: Thirteen trained male soccer players completed an CPET on a treadmill to determine two VO2-kinetic based definitions of MAS (MASPlateau = speed at onset of VO2-plateau = gold standard; MAS30s = first speed of 30-s-interval of VO2max), the Université de Montreal Track Test (UMTT; VUMTT = speed of the last stage), and a 1500-m-time trial (1500-m-TT; V1500m = average speed). MASPlateau, MAS30s, VUMTT, and V1500m were compared using ANOVA. Additionally, limits of agreement analysis (LoA), Pearson's r, and ICC were calculated between tests. Results: MAS30s, VUMTT, and V1500m significantly overestimated MASPlateau by 0.99 km/h (ES = 1.61; p < 0.01), 1.61 km/h (ES = 2.03; p < 0.01) and 1.68 km/h (ES = 1.77; p < 0.01), respectively, with large LoA (-0.21 ≤ LoA≤3.55), however with large-to-very large correlations (0.65 ≤ r ≤ 0.87; p ≤ 0.02; 0.51 ≤ ICC≤ 0.85; p ≤ 0.03). Discussion: The overestimation and large LoA of MASPlateau by all estimates indicate that 1) a uniform definition of MAS is needed and 2) the UMTT and a 1500-m-TT seem questionable for estimating MAS for trained soccer players on an individual basis, while regression equations might be suitable on a team level. The results of the present work contribute to the clarification of acquisition of MAS in soccer.

Impact of Tele-Coaching During the COVID-19 Pandemic on Risk-Reduction Behavior of Patients with Heart Failure.

Introduction: Our study assessed the effectiveness of tele-coaching over written information in educating patients with chronic heart failure (CHF) at high risk of hospitalization about corona virus disease 2019 (COVID-19). We analyzed the impact on number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and self-reported behavior change. Methods: In April 2020, a tele-coaching module and written summary about COVID-19, risk-reduction measures for prevention of COVID-19, and appropriate consultation of medical attention during the pandemic were integrated into an established tele-coaching program. Three hundred seventy-eight patients who had received both tele-coaching and written information 3 weeks earlier were interviewed using a structured questionnaire and compared with 1,748 patients who had only received written information at this point. Results: Tele-coaching had no short-term effect on numbers of SARS-CoV-2 infections. However, patients receiving tele-coaching reported significantly more behavioral changes, including increased room ventilation (88% vs. 78%, p < 0.0001), surface cleaning (80% vs. 70%, p = 0.0006), wearing of face masks (59% vs. 51%, p = 0.013), and reduced usage of public transport (77% vs. 68%, p = 0.0003), despite no observed difference in recall about risk-reduction measures. Moreover, tele-coaching improved patients' knowledge about how to seek medical help in an emergency (46% vs. 36%, p = 0.0006), with a significant reduction in self-reported doctors' appointments (304 vs. 413 per 1,000 patients, p = 0.002) and hospital visits (50 vs. 87 per 1,000, p = 0.033) during the first peak of the pandemic. Conclusion: In a population of patients with CHF at high risk of hospitalization, COVID-19-specific tele-coaching effectively supported behavioral changes and significantly reduced face-to-face medical contacts in a short-term follow-up period.

Multimodal prevention of first psychotic episode through N-acetyl-l-cysteine and integrated preventive psychological intervention in individuals clinically at high risk for psychosis: Protocol of a randomized, placebo-controlled, parallel-group trial.

AIM: Meta-analyses indicate positive effects of both antipsychotic and cognitive-behavioural interventions in subjects clinically at high risk (CHR) for psychosis in terms of a delay or prevention of psychotic disorders. However, these effects have been limited regarding social functioning and the relative efficacy of both types of interventions remains unclear. Furthermore, neuroprotective substances seem to be a promising alternative agent in psychosis-prevention as they are associated with few and weak side-effects. METHODS: In this multi-centre randomized controlled trial (RCT), we investigate the effects of two interventions on transition to psychosis and social functioning: (a) an integrated preventive psychological intervention (IPPI) including stress-/symptom-management and social-cognitive remediation; (b) N-acetyl-l-cysteine (NAC) as a pharmacological intervention with glutamatergic, neuroprotective and anti-inflammatory capabilities. RESULTS: This is a double-blind, placebo-controlled RCT with regard to NAC and a single-blind RCT with regard to IPPI using a 2 × 2-factorial design to investigate the individual and combined preventive effects of both interventions. To this aim, a total of 200 CHR subjects will be randomized stratified by site to one of four conditions: (a) IPPI and NAC; (b) IPPI and Placebo; (c) NAC and psychological stress management; (d) Placebo and psychological stress management. Interventions are delivered over 26 weeks with a follow-up period of 12 months. CONCLUSION: This paper reports on the rationale and protocol of an indicated prevention trial to detect the most effective and tolerable interventions with regard to transition to psychosis as well as improvements in social functioning, and to evaluate the synergistic effects of these interventions.

Prolonged in vitro exposure to white wines enhances the erosive damage on human permanent teeth compared with red wines.

The aim of this in vitro study was to determine and compare the erosive potentials of red and white wines, exerted on enamel surfaces prepared from extracted human permanent teeth. European wines (50 red, 50 white wines) from different regions were purchased, and the pH values were measured. Eight wines with different pH values were selected. Enamel samples with an average surface area of 25 mm(2) were prepared from 25 extracted permanent teeth from male and female patients aged 40 to 65 years and incubated with wines for up to 24 hours; the amounts of released calcium were determined colorimetrically, and mean surface roughness was measured with a profilometer. A quantitative elemental analysis for Ca was carried out in various depths (5-50 microm), using an electron probe microanalyzer. Incubation of the enamel surfaces with different wines caused a time-dependent release of calcium. After 24 hours, white wines caused a significantly higher (P = .003) Ca release (range: 8.74-28.56 mg dL(-1) 25 mm(-2)) than red wines (range: 4.85-19.43 mg dL(-1) 25 mm(-2)), whereas the values for surface roughness were similar (white wines: 2.67 +/- 0.92 microm; red wines: 2.64 +/- 0.66 mum). Incubation with white wines resulted in a higher loss of Ca down to a depth of 60 microm. In this study, it was demonstrated that white wines have higher erosive potentials than red wines. Within the limits of this in vitro study, it can be predicted that a frequent consumption of white wines might lead to severe dental erosion.

Microvascular basal lamina antigen loss after traumatic brain injury in the rat.

The loss of microvascular basal lamina antigen is known to be a consequence of cerebral ischemia, but little information is available on its role in traumatic brain injury (TBI). The aim of our study was (1) to test the hypothesis that there is damage to the basal lamina of brain microvasculature after TBI, (2) to localize microvascular damage, and (3) to compare this loss with that in ischemia. Rats (n=14) were either sham operated (n=5) or subjected to fluid percussion injury (n=9; TBI=1.5 atm) and killed after 0 (n=5, sham), 12 (n=4), or 24 h (n=5). Collagen-type-IV immunoreactivity and a digital image-processing system were used to localize and quantify the number of stained vascular elements and the total collagen stained area. Western blot was used to compare collagen-type-IV content on the traumatic and nontraumatic brain side. The cortex of animals subjected to TBI and killed after 24 h showed a reduction in the area of stained collagen amounting to 19+/-4% (p<0.009) and a reduction in the total number of microvessels identified by collagen stain (29+/-6%; p<0.02). The Western blot revealed a 31+/-6% (p<0.03) reduction of collagen, compared to the mirror cortical area after 24 h. No significant reduction was found in the group that survived 12 h or in basal ganglia in both groups. TBI causes microvascular basal lamina damage. Whereas TBI affected only cortical areas, cerebral ischemia also induced microvascular basal lamina damage in the basal ganglia. After 24 h, the extent of severe basal lamina damage due to TBI was less severe than in ischemia.

Lymphocyte infiltration in the injured brain: role of proinflammatory cytokines.

Studies using mouse axotomised facial motoneuron model show a strong and highly selective entry of CD3+ lymphocytes into the affected nucleus, with a maximum at Day 14, which coincides with the peak of neuronal cell death, microglial phagocytosis, and increased synthesis of interleukin-1 beta (IL1beta), tumour necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma). We explored the possible involvement of these cytokines during the main phase of lymphocyte recruitment into the axotomised facial motor nucleus 7-21 days after nerve cut using mice homozygously deficient for IL1 receptor type 1 (IL1R1-/-), TNF receptor type 1 (TNFR1-/-), type 2 (TNFR2-/-) and type 1 and 2 (TNFR1&2-/-), IFNgamma receptor type 1 (IFNgammaR1-/-), and the appropriate controls for the genetic background. Transgenic deletion of IL1R1 led to a 54% decrease and that of TNFR2 to a 44% reduction in the number of CD3+ T-cells in the axotomised facial motor nucleus, with a similar relative decrease at Day 7, 14, and 21. Deletion of TNFR1 or IFNgammaR1 had no significant effect. Deletion of both TNFR1 and 2 (TNFR1&2-/-) caused a somewhat stronger, 63% decrease than did TNFR2 deletion alone, but this could be due to an almost complete inhibition of neuronal cell death. No mutations seemed to inhibit aggregation of CD3+ T-cells around glial nodules consisting of Ca-ion binding adaptor protein-1 (IBA1)+ phagocytotic microglia and neuronal debris. Altogether, the current data show the importance of IL1R1 and TNFR2 as the key players during the main phase of lymphocyte recruitment to the damaged part of the central nervous system.

Loss of microglial ramification in microglia-astrocyte cocultures: involvement of adenylate cyclase, calcium, phosphatase, and Gi-protein systems.

Reduction in microglial branching is a common feature in brain pathology and culminates in the transformation into small, rounded, microglia-derived phagocytes in the presence of neural debris. The molecular factors responsible for this transformation are unknown. Here we explored the effect of different classes of intra- and extracellular stimuli in vitro on the morphology of ramified microglia cultured on a confluent astrocyte substrate. These studies showed a strong dose-dependent effect for the Ca(2+) ionophore calcimycine/A21837 (50 microM) and for dibutyryl-cAMP (1 mM), with a loss of microglial ramification. Direct activation of the adenylate cyclase with forskolin (0.1 mM) also led to the disappearance of microglial branching. Okadaic acid (70 nM), the inhibitor of protein phosphatases 1 and 2A (PP1/PP2A), and pertussis toxin (12.5 microg/ml), a G(i)-protein inhibitor, also showed similar effects. No effect was observed for dibutyryl-cGMP or for UTP; addition of ATP had a moderate effect, but only at very high, probably nonphysiological concentrations (100 mM). Extracellular matrix components such as keratatan-sulfate, integrin receptor blockers, the disintegrins kistrin, echistatin, and flavoridin, or the serine protease thrombin all had no effect. Addition of prostaglandin D(2) (PGD(2)), a molecule produced by activated microglial cells, had a transforming effect, but at concentrations two orders of magnitude higher than that of established PGD(2) receptors. In summary, addition of agents causing intracellular elevation of Ca(2+) and cAMP or inhibition of G(i)-proteins and phosphatases to ramified microglia cultured on top of confluent astrocytes leads to a rapid loss of microglial branching. Signaling cascades controlled by these molecules may play an important role in the regulation of this common physiological process in the injured brain.

MRI predicts area of increased plasminogen activation in permanent focal cerebral ischemia.

To determine if MRI can predict intracerebral plasminogen activation after focal cerebral ischemia (FCI), ischemic regions detected by MRI after 48 h of permanent FCI in rats were compared with areas of increased plasminogen activation, defined by histological zymography after 72 h of ischemia. The overlap between areas of MRI alterations (64.5% +/- 5.4% of total ischemic hemisphere) and areas with increased plasminogen activation (62.2% +/- 3.6%) was significant for the hemisphere (p < 0.001), the cortex (p < 0.05), and the basal ganglia (p < 0.05). Thus, MRI can predict the extent of increased plasminogen activation, which may play a role in BBB-mediated post-ischemic brain edema and secondary hemorrhage.

Tissue-saving infarct volumetry using histochemistry validated by MRI in rat focal ischemia.

Lesion size is an important outcome parameter in experimental stroke research. However, most methods of measuring the infarct volume in rodents either require expensive equipment or render the brain tissue unusable for further analysis. We report on an inexpensive, tissue-saving method for quantifying the infarct volume in small rodents. After 3 h of middle cerebral artery occlusion (MCAO) and 24 h of reperfusion in male Wistar rats, the lesion was first identified using MRI with T2-weighted sequences. The infarct was then visualized in unfixed brain cryosections using microtubule associated protein 2 (MAP2)-immunohistochemistry and silver infarct staining. The lesion areas detected by all three different methods completely overlapped. The infarct volume was calculated for each method from the lesion area size on serial sections and the distance between them. Significant differences in lesion size were found between the individual animals (p = 0.000056), but not between different methods (p > 0.05). MAP2 immunohistochemistry is a convenient and valid method to measure stroke lesion volume; in addition 98% of the brain tissue is saved and available for use in further histological, immunohistochemical, and biochemical analysis.

Microvascular basal lamina injury after experimental focal cerebral ischemia and reperfusion in the rat.

To define the location and extent of microvascular damage of the basal lamina after cerebral ischemia and reperfusion in rats, the authors subjected animals (n = 16) to 3 hours of focal cerebral ischemia and 24 hours of reperfusion using the suture middle cerebral artery occlusion model; sham-operated animals served as controls (n = 6). The Western blot technique was used to define the collagen type IV protein content in various brain regions, whereas immunohistochemistry identified microvascular basal lamina loss (anticollagen type IV staining). The extent of damage was quantified by automatic morphometric video-imaging analysis. Statistical analysis was based on the Mann-Whitney test and the paired Student's t-test. The ischemic hemisphere showed a reduction of the collagen type IV protein content after ischemia and reperfusion in the Western blot (reduction compared with the nonischemic side: total hemisphere, 33% +/- 6%; basal ganglia, 25% +/- 7%; cortex 49% +/- 4%; P < 0.01) [corrected]. There was also a decrease in the number of cerebral microvessels between the ischemic and nonischemic hemispheres (20% +/- 2%), cortical (8% +/- 3%), and basal ganglia areas (31% +/- 3%) (P < 0.001). Besides a reduction of the vessel number, there was also a loss in basal lamina antigen-positive stained area in ischemic areas (hemisphere, 16% +/- 3%; cortex, 14% +/- 3%; basal ganglia, 21% +/- 4%; P < 0.01) [corrected]. Cortical areas had a less pronounced basal lamina loss than basal ganglia (P < 0.05). For the first time, microvascular basal lamina damage, indicated by collagen type IV loss, is proven in rats by biochemical and morphometric analysis. These changes are comparable with those found in nonhuman primates. The authors report novel data regarding microvascular ischemic changes in the cortex. These data provide a basis for future experiments to determine the mechanisms of ischemic microvascular damage and to devise new therapeutic strategies.

Prolonged cerebral transit time in CADASIL: a transcranial ultrasound study.

BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary angiopathy caused by mutations in Notch3. Cerebral microvessels show an accumulation of granular osmophilic material in the vicinity of degenerating vascular smooth muscle cells. In this study, we measured the arteriovenous cerebral transit time (CTT) to identify changes related to the microangiopathy in CADASIL. METHODS: CTT is the time that a contrast agent needs to pass from a cerebral artery to its corresponding vein. CTT was measured in 17 CADASIL individuals (mean age, 50.2+/-12.3 years) and an equal number of age- and sex-matched control subjects (mean age, 48.9+/-13.0 years) with transcranial color-coded duplex sonography. The intensity curves were recorded in the P2 segment of the posterior cerebral artery and the vein of Galen after injection of the ultrasound contrast agent Levovist. RESULTS: CTT was significantly prolonged in individuals with CADASIL (4.4+/-1.9 seconds) compared with control subjects (1.3+/-0.5 seconds, P<0.0001). This difference was also significant when only nondisabled CADASIL individuals (Rankin score=0, n=9) were analyzed (P<0.0001). There was a nonsignificant trend for a correlation between Rankin score and CTT (r=0.39, P=0.11). CONCLUSIONS: The prolonged CTT likely reflects microvascular changes in CADASIL. Measurements of the CTT may be used clinically to disclose small-vessel disease. Studies comparing CADASIL subjects with other patient populations seem warranted to determine possible differences in CTT between different types of small-vessel disease.