High knee loading in male adolescent pre-professional football players: Effects of a targeted training programme

Objective: To assess whether targeted neuromuscular exercises can decrease knee loading of adolescent pre-professional footballers with high knee loading as identified with the field-based Drop Vertical Jump Test (DVJT). Design: Prospective controlled trial, conducted between August and November 2016 at Erasmus Medical Centre, The Netherlands. Methods: Pre-professional football players (aged 14–21 years) were evaluated at baseline and after 12 weeks follow-up with the field-based DVJT. The field-based DVJT is a standardised test in which a player drops from a box and jumps up immediately after landing; knee load is calculated based on five parameters. Players with high knee load (probability ≥ 0.75) from one club performed regular training(control group), and players with high knee load from another other club performed targeted neuromuscular exercises for 12 weeks (intervention group). The difference of change in knee load between both groups after 12 weeks was the primary outcome measure. Results: Of 107 eligible players, 75 had a high knee loading. Knee loading decreased in both groups after 12 weeks of training, but change in probability of high knee load was not significantly different between both groups (95% Confidence Interval [−0.012–0.082], p = 0.139). Conclusion: Targeted neuromuscular exercises had no additional effect in decreasing knee loading of adolescent male pre-professional football players compared to regular training. Trial registration number: The Netherlands Trial Register (ID number: 6044)

How dentists and oral and maxillofacial surgeons deal with tooth extraction without a valid clinical indication

Objectives: This study pertains to a secondary data analysis aimed at determining differences between oral and maxillofacial surgeons (OMFSs) and dentists handling dental extractions without an evident clinical indication. Study design: A survey of 18 questions was conducted among 256 OMFSs in the Netherlands and a random sample of 800 dentists Respondents could answer the questions in writing or online. The data was collected in the period from November 2019 to January 2020, during which two reminders were sent. Analysis of the data took place via descriptive statistics and Chi Square test. Results: The response rate was 28.1% (n = 72) for OMFSs and 30.3% (n = 242) for dentists. In the past three years, 81.9% (n = 59) of the OMFSs and 68.0% (n = 164) of the dentists received a request for extraction without a clinical indication. The most common reasons were financial and severe dental fear (OMFSs: 64.9 and 50.9% vs dentists: 77.4 and 36.5%). Dentists were significantly more likely (75.6%, n = 114) than OMFS (60.7%, n = 34) to comply with their last extraction request without a clinical indication. Almost none of them regretted the extraction afterwards. As for the request itself, it was found that 17.5% (n = 10) of the OMFSs and 12.5% (n = 20) of the dentists did not check for patients’ mental competency (p = 0.352). Conclusions: Given that most of the interviewed dental professionals complied with non-dental extraction requests when such extractions are ethically and legally precarious, recommendations for handling such requests are greatly needed

How many runners with new-onset Achilles tendinopathy develop persisting symptoms? A large prospective cohort study

Background: Achilles tendinopathy (AT) occurs in half of the elite runners. AT is a difficult-to-treat tendon disease, which may progress from new onset to a chronic state. It is unknown how many runners with new-onset AT develop persisting symptoms and which prognostic factors are associated with this course. Objective: To describe how many runners develop persisting symptoms 1 year after onset of reactive AT. Study Design: Prospective cohort study. Methods: Runners registering for a Dutch running event (5-42.2 km) were eligible for inclusion. Runners reporting new-onset AT between registration for the running event and 1 month after received a 1-year follow-up questionnaire. The 1-year follow-up questionnaire inquired about persisting symptoms (yes/no), running activity, and metabolic disorders. We calculated the percentage of runners with persisting symptoms and performed a multivariable logistic regression analysis to study the association between potential prognostic factors and persisting symptoms. Results: Of 1929 participants, 100 runners (5%) reported new-onset AT. A total of 62 runners (62%) filled in the 1-year follow-up questionnaire. Persisting symptoms were reported by 20 runners (32%). A higher running distance per week before new-onset AT was associated with a lower risk of developing persisting symptoms (odds ratio (OR): 0.9, 95% confidence interval (CI): [0.9;1.0]). There was a positive trend toward an association between metabolic disorders and persisting symptoms (OR: 5.7, 95% CI: [0.9;36.2]). Conclusion: One third of runners develop persisting symptoms 1 year after new-onset AT. Interestingly, a higher running distance per week before new-onset AT potentially lowers the risk of developing persisting symptoms

Salinomycin induces calpain and cytochrome c-mediated neuronal cell death

Salinomycin is a polyether antibiotic with properties of an ionophore, which is commonly used as cocciodiostatic drug and has been shown to be highly effective in the elimination of cancer stem cells (CSCs) both in vitro and in vivo. One important caveat for the potential clinical application of salinomycin is its marked neural and muscular toxicity. In the present study we show that salinomycin in concentrations effective against CSCs exerts profound toxicity towards both dorsal root ganglia as well as Schwann cells. This toxic effect is mediated by elevated cytosolic Na+ concentrations, which in turn cause an increase of cytosolic Ca2+ by means of Na+/Ca2+ exchangers (NCXs) in the plasma membrane as well as the mitochondria. Elevated Ca2+ then leads to calpain activation, which triggers caspase-dependent apoptosis involving caspases 12, 9 and 3. In addition, cytochrome c released from depolarized mitochondria directly activates caspase 9. Combined inhibition of calpain and the mitochondrial NCXs resulted in significantly decreased cytotoxicity and was comparable to caspase 3 inhibition. These findings improve our understanding of mechanisms involved in the pathogenesis of peripheral neuropathy and are important to devise strategies for the prevention of neurotoxic side effects induced by salinomycin

Mesenchymal Transition and PDGFRA Amplification/Mutation Are Key Distinct Oncogenic Events in Pediatric Diffuse Intrinsic Pontine Gliomas

Diffuse intrinsic pontine glioma (DIPG) is one of the most frequent malignant pediatric brain tumor and its prognosis is universaly fatal. No significant improvement has been made in last thirty years over the standard treatment with radiotherapy. To address the paucity of understanding of DIPGs, we have carried out integrated molecular profiling of a large series of samples obtained with stereotactic biopsy at diagnosis. While chromosomal imbalances did not distinguish DIPG and supratentorial tumors on CGHarrays, gene expression profiling revealed clear differences between them, with brainstem gliomas resembling midline/thalamic tumours, indicating a closely-related origin. Two distinct subgroups of DIPG were identified. The first subgroup displayed mesenchymal and pro-angiogenic characteristics, with stem cell markers enrichment consistent with the possibility to grow tumor stem cells from these biopsies. The other subgroup displayed oligodendroglial features, and appeared largely driven by PDGFRA, in particular through amplification and/or novel missense mutations in the extracellular domain. Patients in this later group had a significantly worse outcome with an hazard ratio for early deaths, ie before 10 months, 8 fold greater that the ones in the other subgroup (p = 0.041, Cox regression model). The worse outcome of patients with the oligodendroglial type of tumors was confirmed on a series of 55 paraffin-embedded biopsy samples at diagnosis (median OS of 7.73 versus 12.37 months, p = 0.045, log-rank test). Two distinct transcriptional subclasses of DIPG with specific genomic alterations can be defined at diagnosis by oligodendroglial differentiation or mesenchymal transition, respectively. Classifying these tumors by signal transduction pathway activation and by mutation in pathway member genes may be particularily valuable for the development of targeted therapies