The importance of nerve microenvironment for schwannoma development

Schwannomas are predominantly benign nerve sheath neoplasms caused by Nf2 gene inactivation. Presently, treatment options are mainly limited to surgical tumor resection due to the lack of effective pharmacological drugs. Although the mechanistic understanding of Nf2 gene function has advanced, it has so far been primarily restricted to Schwann cell-intrinsic events. Extracellular cues determining Schwann cell behavior with regard to schwannoma development remain unknown. Here we show pro-tumourigenic microenvironmental effects on Schwann cells where an altered axonal microenvironment in cooperation with injury signals contribute to a persistent regenerative Schwann cell response promoting schwannoma development. Specifically in genetically engineered mice following crush injuries on sciatic nerves, we found macroscopic nerve swellings in mice with homozygous nf2 gene deletion in Schwann cells and in animals with heterozygous nf2 knockout in both Schwann cells and axons. However, patient-mimicking schwannomas could only be provoked in animals with combined heterozygous nf2 knockout in Schwann cells and axons. We identified a severe re-myelination defect and sustained macrophage presence in the tumor tissue as major abnormalities. Strikingly, treatment of tumor-developing mice after nerve crush injury with medium-dose aspirin significantly decreased schwannoma progression in this disease model. Our results suggest a multifactorial concept for schwannoma formation-emphasizing axonal factors and mechanical nerve irritation as predilection site for schwannoma development. Furthermore, we provide evidence supporting the potential efficacy of anti-inflammatory drugs in the treatment of schwannomas

Successful one stage biventricular correction of aortic atresia with a ventricular septal defect and discordant ventriculo-arterial connections

Aortic atresia is rare in the setting of a normally developed left ventricle with a ventricular septal defect. In this combination, as far as we know, it has been described only with concordant ventriculo-arterial connections, for which seven one-stage biventricular repairs have now been described. We describe here the case of a 3 1/2-month-old male infant with a similar combination but with discordant ventriculo-arterial connections and severe pulmonary hypertension. It was the right ventricle which achieved normal size in this arrangement, presumably because of the ventricular septal defect. One-stage biventricular correction was accomplished, employing a single pulmonary allograft, aided by massive doses of Prostaglandin E1. As far as we know this is the first report of the combination of aortic atresia, discordant ventriculo-arterial connections, a ventricular septal defect and balanced ventricles. We complement our surgical account, nonetheless, with a description of a comparable specimen from our anatomic museum

White Paper: functionality and efficacy of wrist protectors in snowboarding—towards a harmonized international standard

The wrist is the most frequently injured body region among snowboarders. Studies have shown that the risk of sustaining a wrist injury can be reduced by wearing wrist protection. Currently, there are a wide variety of wrist protection products for snowboarding on the market that offer a range of protective features. However, there are no minimum performance standards for snowboarding wrist protectors worldwide. The International Society for Skiing Safety convened a task force to develop a White Paper to evaluate the importance and necessity of a minimum performance for all wrist protectors used in snowboarding. The White Paper outlines the need for a general framework for a harmonized international standard and reviews the existing evidence. Therefore, this White Paper may serve as a common base for future discussions. The broader goal of developing and implementing such a standard is to reduce the incidence and the severity of wrist injuries in snowboarding without increasing the risk of adverse events, such as upper arm or shoulder injury. The European standard for inline skating wrist protectors (EN 14120) can serve as a starting point for efforts related to a standard for snowboard wrist protectors, but certain modifications to the standard would be required. It is hypothesized that implementation of a snowboarding wrist protector standard would result in fewer and less severe wrist injuries in the sport and could translate into more riding days for healthy snowboarders and significant health-care costs savings

High malnutrition rate in Venezuelan Yanomami compared to Warao Amerindians and Creoles: significant associations with intestinal parasites and anemia

Contains fulltext : 125614.pdf (publisher's version ) (Open Access)BACKGROUND: Children in rural areas experience the interrelated problems of poor growth, anemia and parasitic infections. We investigated the prevalence of and associations between intestinal helminth and protozoan infections, malnutrition and anemia in school-age Venezuelan children. METHODS: This cross-sectional study was conducted in 390 children aged 4-16 years from three rural areas of Venezuela: the Amazon Region, Orinoco Delta and Carabobo State. Stool samples were collected for direct parasitic examinations. Anthropometric indicators of chronic (height-for-age Z score) and acute (weight-for-height and Body Mass Index (BMI)-for-age Z score in respectively children under 5 years of age and children aged 5 years and above) malnutrition were calculated. Multivariate linear and logistic regression models were built to determine factors associated with nutritional status and polyparasitism. RESULTS: Hookworm and Strongyloides stercoralis prevalences were highest in children from the Amazon rainforest (respectively 72% and 18%) while children from the Orinoco Delta and Carabobo State showed higher rates of Ascaris lumbricoides (respectively 28% and 37%) and Trichuris trichiura (40% in both regions). The prevalence of Giardia lamblia infection was not significantly different between regions (average: 18%). Anemia prevalence was highest in the Amazon Region (24%). Hemoglobin levels were significantly decreased in children with a hookworm infection. Malnutrition was present in respectively 84%, 30% and 13% of children from the Amazon Region, Orinoco Delta and Carabobo State. In multivariate analysis including all regions, G. lamblia and helminth infections were significantly and negatively associated with respectively height-for-age and weight-for-height/BMI-for-age Z scores. Furthermore, hemoglobin levels were positively associated with the height-for-age Z score (0.11, 95% CI 0.02 - 0.20). CONCLUSIONS: In rural populations in Venezuela helminthiasis and giardiasis were associated with acute and chronic nutritional status respectively. These data highlight the need for an integrated approach to control transmission of parasites and improve the health status of rural Venezuelan children