Association between eHealth literacy and health outcomes in German athletes using the GR-eHEALS questionnaire: a validation and outcome study.

BACKGROUND: Athletes face various sports-related stressors, which may increase their risk for physical and mental health symptoms. With the internet as an important source of (health) information, it is important for athletes to have eHealth literacy, i.e. the ability to access, understand and use electronic health information and services. However, it is presently uncertain whether eHealth literacy of athletes is linked to better health outcomes such as reduced injury frequency and behaviours like decreased substance abuse. METHODS: A cross-sectional study was conducted with N = 373 German athletes (229 females) from different types of sport (e.g., ball sports and water sports) who were included in the statistical analyses. The survey included medical, socio-demographic, eHealth- and sports-related data as well as the eHealth Literacy Scale (GR-eHEALS) questionnaire, which measures eHealth literacy. Confirmatory factor analyses and correlational analyses were performed to determine the convergent and discriminant (compared to the 8-item Impulsive Behavior-8 Scale) validity of the GR-eHEALS and to assess the relation between eHealth literacy scores and health outcomes. RESULTS: The more frequently athletes had sustained minor or moderate injuries in the past, the higher the level of eHealth literacy they reported. Furthermore, consumption frequency of painkillers (r = .18, p = .002), sedatives (r = .12, p = .040), and cannabis (r = .29, p = .000) was significantly correlated with eHealth literacy scores. The confirmatory factor analysis of the GR-eHEALS showed an acceptable model fit with a 2-factor solution (information seeking and information appraisal). The GR-eHEALS showed good discriminant (r = - .09, p = .21) and convergent validity (digital confidence; r = .28, p < .001). CONCLUSION: The GR-eHEALS is a valid instrument to assess eHealth literacy within the cohort of German athletes. Potential dangers of dealing with injury and psychological strain without reaching out for professional help should be considered.

Mental health symptoms in German elite athletes: a network analysis.

Introduction: Elite athletes are exposed to a variety of sport-specific stressors that may put them at particular risk for mental health symptoms and disorders. The aim of the present study was to assess data on mental health of elite athletes and investigate associations and interconnections among different variables using network analysis. Methods: A cross-sectional study was conducted from December 2021 to December 2022. The sample consisted of 275 German elite athletes (167 females) aged ≥18 years. Next to sociodemographic, medical and sport-related data, psychometric data such as psychological distress, symptoms of generalized anxiety, depression, and somatic symptom disorder have been gathered through questionnaires and analyzed by means of network analysis. Results: Over 95.0% of the athletes showed elevated distress and 28.6% reported symptoms of depression. Results of the network analysis show, among other findings, that symptoms of somatic symptom disorder were associated with severe injuries and substance use. Moreover, elite athletes who reported a better financial situation reported fewer symptoms of depression, generalized anxiety, and somatic symptom disorder. They also reported a lower incidence of mild to moderate injuries and severe injuries, fewer years spent in elite sports, less substance use, and fewer training sessions per week. Conversely, these athletes reported a higher level of distress. Furthermore, sex, financial situation and number of training units per week emerged as significant predictors for mental health symptoms. Discussion: Elite athletes showed increased numbers regarding mental health symptoms. Providing appropriate mental health interventions for elite athletes and further analysis of factors that influence the mental health of elite athletes and their interplay seem to be of central importance for the general well-being of elite athletes.

Carba-Sugar Analogs of Glucosamine-6-Phosphate: New Activators for the glmS Riboswitch.

Riboswitches are 5'-untranslated mRNA regions mostly found in bacteria. They are promising drug targets to overcome emerging bacterial resistance against commonly used antibiotics. The glmS riboswitch is unique among the family of riboswitches as it is a ribozyme that undergoes self-cleavage upon binding to glucosamine-6-phosphate (GlcN6P). Previously, we showed that carba glucosamine-6-phosphate (carba-GlcN6P) induces self-cleavage of the riboswitch with a potency similar to that of GlcN6P. Here, we report a synthetic approach to a new class of carba-GlcN6P derivatives with an alkoxy substituent in the carba position. Key features of the synthesis are a ring closing metathesis followed by a hydroboration. The strategy gives access to libraries of carba-GlcN6P derivatives. Ribozyme cleavage assays unraveled new activators for the glmS riboswitch from Listeria monocytogenes and Clostridium difficile.

Characterization of the glmS Ribozymes from Listeria Monocytogenes and Clostridium Difficile.

The glmS ribozyme regulates the expression of the essential GlmS enzyme being involved in cell wall biosynthesis. While >450 variants of the glmS ribozyme were identified by in silico approaches and homology searches, only a few have yet been experimentally investigated. Herein, we validate and characterize the glmS ribozymes of the human pathogens Clostridium difficile and Listeria monocytogenes. Both ribozymes, as their previous characterized homologs rely on glucosamine-6-phosphate as co-factor and the presence of divalent cations for exerting the cleavage reaction. The observed EC50 values in turn were found to be in the submicromolar range, at least an order of magnitude lower than observed for glmS ribozymes from other bacteria. The glmS ribozyme of L. monocytogenes was further shown to bear unique properties. It discriminates between co-factors very stringently and other than the glmS ribozyme of C. difficile retains activity at low temperatures. This finding illustrates that albeit being highly conserved, glmS ribozymes have unique characteristics.

Versatile enzymology and heterogeneous phenotypes in cobalamin complementation type C disease.

Nutritional deficiency and genetic errors that impair the transport, absorption, and utilization of vitamin B12 (B12) lead to hematological and neurological manifestations. The cblC disease (cobalamin complementation type C) is an autosomal recessive disorder caused by mutations and epi-mutations in the MMACHC gene and the most common inborn error of B12 metabolism. Pathogenic mutations in MMACHC disrupt enzymatic processing of B12, an indispensable step before micronutrient utilization by the two B12-dependent enzymes methionine synthase (MS) and methylmalonyl-CoA mutase (MUT). As a result, patients with cblC disease exhibit plasma elevation of homocysteine (Hcy, substrate of MS) and methylmalonic acid (MMA, degradation product of methylmalonyl-CoA, substrate of MUT). The cblC disorder manifests early in childhood or in late adulthood with heterogeneous multi-organ involvement. This review covers current knowledge on the cblC disease, structure-function relationships of the MMACHC protein, the genotypic and phenotypic spectra in humans, experimental disease models, and promising therapies.

Thiolatocobalamins repair the activity of pathogenic variants of the human cobalamin processing enzyme CblC.

Thiolatocobalamins are a class of cobalamins comprised of naturally occurring and synthetic ligands. Glutathionylcobalamin (GSCbl) occurs naturally in mammalian cells, and also as an intermediate in the glutathione-dependent dealkylation of methylcobalamin (MeCbl) to form cob(I)alamin by pure recombinant CblC from C. elegans. Glutathione-driven deglutathionylation of GSCbl was demonstrated both in mammalian as well as in C. elegans CblC. Dethiolation is orders of magnitude faster than dealkylation of Co-C bonded cobalamins, which motivated us to investigate two synthetic thiolatocobalamins as substrates to repair the enzymatic activity of pathogenic CblC variants in humans. We report the synthesis and kinetic characterization of cysteaminylcobalamin (CyaCbl) and 2-mercaptopropionylglycinocobalamin (MpgCbl). Both CyaCbl and MpgCbl were obtained in high purity (90-95%) and yield (78-85%). UV-visible spectral properties agreed with those reported for other thiolatocobalamins with absorbance maxima observed at 372 nm and 532 nm. Both CyaCbl and MpgCbl bound to wild type human recombinant CblC inducing spectral blue-shifts characteristic of the respective base-on to base-off transitions. Addition of excess glutathione (GSH) resulted in rapid elimination of the ß-ligand to give aquacobalamin (H2OCbl) as the reaction product under aerobic conditions. Further, CyaCbl and MpgCbl underwent spontaneous dethiolation thereby repairing the loss of activity of pathogenic variants of human CblC, namely R161G and R161Q. We posit that thiolatocobalamins could be exploited therapeutically for the treatment of inborn errors of metabolism that impair processing of dietary and supplemental cobalamin forms. While these disorders are targets for newborn screening in some countries, there is currently no effective treatment available to patients.

Synthesis of New Cyclomarin Derivatives and Their Biological Evaluation towards Mycobacterium Tuberculosis and Plasmodium Falciparum.

Cyclomarins are highly potent antimycobacterial and antiplasmodial cyclopeptides isolated from a marine bacterium (Streptomyces sp.). Previous studies have identified the target proteins and elucidated a novel mode of action, however there are currently only a few studies examining the structure-activity relationship (SAR) for both pathogens. Herein, we report the synthesis and biological evaluation of 17 novel desoxycyclomarin-inspired analogues. Optimization via side chain modifications of the non-canonical amino acids led to potent lead structures for each pathogen.

Corticosteroids inhibit Mycobacterium tuberculosis-induced necrotic host cell death by abrogating mitochondrial membrane permeability transition.

Corticosteroids are host-directed drugs with proven beneficial effect on survival of tuberculosis (TB) patients, but their precise mechanisms of action in this disease remain largely unknown. Here we show that corticosteroids such as dexamethasone inhibit necrotic cell death of cells infected with Mycobacterium tuberculosis (Mtb) by facilitating mitogen-activated protein kinase phosphatase 1 (MKP-1)-dependent dephosphorylation of p38 MAPK. Characterization of infected mixed lineage kinase domain-like (MLKL) and tumor necrosis factor receptor 1 (TNFR1) knockout cells show that the underlying mechanism is independent from TNFα-signaling and necroptosis. Our results link corticosteroid function and p38 MAPK inhibition to abrogation of necrotic cell death mediated by mitochondrial membrane permeability transition, and open new avenues for research on novel host-directed therapies (HDT).

Evaluation of multiple-session delay eyeblink conditioning comparing patients with focal cerebellar lesions and cerebellar degeneration.

The acquisition and timing of delay-conditioned eyeblink responses (CRs) have been shown to be significantly impaired in patients with disorders restricted to the cortex of the superior cerebellum. We were interested if patients improve incidences and timing of CRs across three sessions on three consecutive days. A standard delay paradigm was used in 9 patients with diffuse cerebellar degeneration, 13 patients with ischemic cortical cerebellar lesions and in 13 controls. High-resolution magnetic resonance imaging (MR imaging) was used to ensure that hemispheral lobules VI and/ or Crus I were lesioned in all stroke patients with the interposed nuclei being preserved. On day 1 patients with stroke but not with degenerative disorders showed significant CR acquisition, although total CR incidences remained significantly lower than in controls. No further improvement was visible on days 2 and 3 neither in patients with focal lesions nor in patients with cerebellar degeneration. CRs occurred earlier in cerebellar patients, most pronounced in patients with degenerative disorders. In patients with stroke but not in the degenerative group timing had improved on the third day close to values of the control subjects. Findings show that lesions of the cerebellar cortex produce permanent deficits in the acquisition of delay-conditioned eyeblink responses. Overall, mean CR incidence was higher in focal compared to degenerative disorders, most likely because the critical lobules (VI and Crus I) were lesioned only in part. Intact anterior lobe, which it thought to contribute to CR timing, may explain recovery of disordered timing in focal cerebellar patients.