SHE mapping report Lessons learnt from policies and practices of SHE member countries

The Schools for Health in Europe Network Foundation mapping (SHE mapping) survey is a cross-national study to map the level of implementation of health promotion in schools of the SHE member countries and how this implementation is carried out. SHE mapping collected international data on: the integration of the national Health Promoting School (HPS) policy into other national policies; how national policies frame school practices in the whole school approach of HPS; how national policies contribute to a healthy physical environment in the school setting; the contributions of national policies to a school’s social environment, favourable to health promotion; the guidelines, tools and resources for a school to become a HPS; the national process of monitoring / evaluation of HPS; health topics included in the national HPS policy; health promoting school label; sources of funding for national HPS; main expectations of the SHE national coordinators for their national HPS scheme; number of HPS in SHE member countries; HPS facilities; how inclusion of health promotion is done in the school curriculum; health topics worked regularly in HPS; learning methods / strategies in HPS; practices and suggestions for the SHE School Manual and its two accompanying tools; facilitating factors and barriers faced by HPS in the SHE member countries. Data were collected using the Survey Monkey. All SHE national and regional coordinators from the 37 SHE member countries were invited to complete a questionnaire, upon completion of a statement of informed consent. Data were received from 75.7% of countries, but after removal of the incomplete questionnaires and two SHE regional coordinators who responded in duplicate for their country, because it was not possible to gather information from regions as there were only three regional coordinators who answered, 64.9% of countries were analysed.Este trabalho é financiado por Fundos Nacionais através da FCT – Fundação para a Ciência e a Tecnologia no âmbito do projeto do CIEC (Centro de Investigação em Estudos da Criança da Universidade do Minho) com a referência UID/CED/00317/2019

A novel push-pull central-lever mechanism reduces peak forces and energy-cost compared to hand-rim wheelchair propulsion during a controlled lab-based experiment

BACKGROUND: Hand-rim wheelchair propulsion is straining and mechanically inefficient, often leading to upper limb complaints. Previous push–pull lever propulsion mechanisms have shown to perform better or equal in efficiency and physiological strain. Propulsion biomechanics have not been evaluated thus far. A novel push–pull central-lever propulsion mechanism is compared to conventional hand-rim wheelchair propulsion, using both physiological and biomechanical outcomes under low-intensity steady-state conditions on a motor driven treadmill. METHODS: In this 5 day (distributed over a maximum of 21 days) between-group experiment, 30 able-bodied novices performed 60 min (5 × 3 × 4 min) of practice in either the push–pull central lever wheelchair (n = 15) or the hand-rim wheelchair (n = 15). At the first and final sessions cardiopulmonary strain, propulsion kinematics and force production were determined in both instrumented propulsion mechanisms. Repeated measures ANOVA evaluated between (propulsion mechanism type), within (over practice) and interaction effects. RESULTS: Over practice, both groups significantly improved on all outcome measures. After practice the peak forces during the push and pull phase of lever propulsion were considerably lower compared to those in the handrim push phase (42 ± 10 & 46 ± 10 vs 63 ± 21N). Concomitantly, energy expenditure was found to be lower as well (263 ± 45 vs 298 ± 59W), on the other hand gross mechanical efficiency (6.4 ± 1.5 vs 5.9 ± 1.3%), heart-rate (97 ± 10 vs 98 ± 10 bpm) and perceived exertion (9 ± 2 vs 10 ± 1) were not significantly different between modes. CONCLUSION: The current study shows the potential benefits of the newly designed push–pull central-lever propulsion mechanism over regular hand rim wheelchair propulsion. The much lower forces and energy expenditure might help to reduce the strain on the upper extremities and thus prevent the development of overuse injury. This proof of concept in a controlled laboratory experiment warrants continued experimental research in wheelchair-users during daily life

Long-term outcomes of slipped capital femoral epiphysis treated with in situ pinning

PURPOSE: Slipped capital femoral epiphysis (SCFE) is the commonest hip disorder in adolescents. In situ pinning is commonly performed, yet lately there has been an increase in procedures with open reduction and internal fixation. These procedures, however, are technically demanding with relatively high complication rates and unknown long-term outcomes. Nevertheless, reports on long-term results of in situ fixation are not equivocal. This study evaluates the possible higher risk of worse outcome after in situ pinning of SCFE. METHODS: All patients treated for SCFE with in situ fixation between 1980 and 2002 in four different hospitals were asked to participate. Patients were divided into three groups, based on severity of the slip. Patients were invited to the outpatient clinic for physical examination and X-rays, and to fill out the questionnaires HOOS, EQ5D, and SF36. ANOVA and chi-squared tests were used to analyze differences between groups. RESULTS: Sixty-one patients with 78 slips filled out the questionnaires. Patients with severe slips had worse scores on HOOS, EQ5D, and SF36. 75 % of patients with severe slips had severe osteoarthritis, compared to 2 % of mild and 11 % of moderate slips. CONCLUSION: Hips with mild and moderate SCFE generally had good functional and radiological outcome at a mean follow-up of 18 years, and for these hips there seems to be no indication for open procedures. However, severe slips have a significantly worse outcome, and open reduction and internal fixation could therefore be considered

Subtalar versus triple arthrodesis after intra-articular calcaneal fractures

Depending upon initial treatment, between 2 and 30% of patients with a displaced intra-articular calcaneal fracture require a secondary arthrodesis. The aim of this study was to investigate the effect of subtalar versus triple arthrodesis on functional outcome. A total of 33 patients with 37 secondary arthrodeses (17 subtalar and 20 triple) with a median follow-up of 116 months were asked to complete questionnaires regarding disease-specific functional outcome (Maryland Foot Score, MFS), quality of life (SF-36) and overall satisfaction with the treatment (Visual Analogue Scale, VAS). Patient groups were comparable considering median age at fracture, initial treatment (conservative or operative), time to arthrodesis, median follow-up, and post-arthrodesis radiographic angles. The MFS score was similar after subtalar versus triple arthrodesis (59 vs. 56 points; P = 0.79). No statistically significant difference was found for the SF-36 (84 vs. 83 points; P = 0.67) and the VAS (5 vs. 6; P = 0.21). Smoking was statistically significantly associated with a non-union (χ2 = 6.60, P = 0.017). The current study suggests that there is no significant difference in functional outcome between an in situ subtalar or triple arthrodesis as a salvage technique for symptomatic arthrosis after an intra-articular calcaneal fracture. Smoking is a risk factor for non-union

NQO2 is a reactive oxygen species generating off-target for acetaminophen

[Image: see text] The analgesic and antipyretic compound acetaminophen (paracetamol) is one of the most used drugs worldwide. Acetaminophen overdose is also the most common cause for acute liver toxicity. Here we show that acetaminophen and many structurally related compounds bind quinone reductase 2 (NQO2) in vitro and in live cells, establishing NQO2 as a novel off-target. NQO2 modulates the levels of acetaminophen derived reactive oxygen species, more specifically superoxide anions, in cultured cells. In humans, NQO2 is highly expressed in liver and kidney, the main sites of acetaminophen toxicity. We suggest that NQO2 mediated superoxide production may function as a novel mechanism augmenting acetaminophen toxicity

Glyphosate and AMPA in human urine of HBM4EU-aligned studies: part B adults

Within HBM4EU, human biomonitoring (HBM) studies measuring glyphosate (Gly) and aminomethylphosphonic acid (AMPA) in urine samples from the general adult population were aligned and quality-controlled/assured. Data from four studies (ESB Germany (2015-2020); Swiss HBM4EU study (2020); DIET-HBM Iceland (2019-2020); ESTEBAN France (2014-2016)) were included representing Northern and Western Europe. Overall, median values were below the reported quantification limits (LOQs) (0.05-0.1 microg/L). The 95th percentiles (P95) ranged between 0.24 and 0.37 microg/L urine for Gly and between 0.21 and 0.38 microg/L for AMPA. Lower values were observed in adults compared to children. Indications exist for autonomous sources of AMPA in the environment. As for children, reversed dosimetry calculations based on HBM data in adults did not lead to exceedances of the ADI (proposed acceptable daily intake of EFSA for Gly 0.1 mg/kg bw/day based on histopathological findings in the salivary gland of rats) indicating no human health risks in the studied populations at the moment. However, the controversy on carcinogenicity, potential endocrine effects and the absence of a group ADI for Gly and AMPA induce uncertainty to the risk assessment. Exposure determinant analysis showed few significant associations. More data on specific subgroups, such as those occupationally exposed or living close to agricultural fields or with certain consumption patterns (vegetarian, vegan, organic food, high cereal consumer), are needed to evaluate major exposure sources

EURL ECVAM Workshop on New Generation of Physiologically-Based Kinetic Models in Risk Assessment

The European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) Strategy Document on Toxicokinetics (TK) outlines strategies to enable prediction of systemic toxicity by applying new approach methodologies (NAM). The central feature of the strategy focuses on using physiologically-based kinetic (PBK) modelling to integrate data generated by in vitro and in silico methods for absorption, distribution, metabolism, and excretion (ADME) in humans for predicting whole-body TK behaviour, for environmental chemicals, drugs, nano-materials, and mixtures. In order to facilitate acceptance and use of this new generation of PBK models, which do not rely on animal/human in vivo data in the regulatory domain, experts were invited by EURL ECVAM to (i) identify current challenges in the application of PBK modelling to support regulatory decision making; (ii) discuss challenges in constructing models with no in vivo kinetic data and opportunities for estimating parameter values using in vitro and in silico methods; (iii) present the challenges in assessing model credibility relying on non-animal data and address strengths, uncertainties and limitations in such an approach; (iv) establish a good kinetic modelling practice workflow to serve as the foundation for guidance on the generation and use of in vitro and in silico data to construct PBK models designed to support regulatory decision making. To gauge the current state of PBK applications, experts were asked upfront of the workshop to fill a short survey. In the workshop, using presentations and discussions, the experts elaborated on the importance of being transparent about the model construct, assumptions, and applications to support assessment of model credibility. The experts offered several recommendations to address commonly perceived limitations of parameterization and evaluation of PBK models developed using non-animal data and its use in risk assessment, these include: (i) develop a decision tree for model construction; (ii) set up a task force for independent model peer review; (iii) establish a scoring system for model evaluation; (iv) attract additional funding to develop accessible modelling software.; (v) improve and facilitate communication between scientists (model developers, data provider) and risk assessors/regulators; and (vi) organise specific training for end users. The experts also acknowledged the critical need for developing a guidance document on building, characterising, reporting and documenting PBK models using non-animal data. This document would also need to include guidance on interpreting the model analysis for various risk assessment purposes, such as incorporating PBK models in integrated strategy approaches and integrating them with in vitro toxicity testing and adverse outcome pathways. This proposed guidance document will promote the development of PBK models using in vitro and silico data and facilitate the regulatory acceptance of PBK models for assessing safety of chemicals

Citrulline supplementation improves organ perfusion and arginine availability under conditions with enhanced arginase activity

Enhanced arginase-induced arginine consumption is believed to play a key role in the pathogenesis of sickle cell disease-induced end organ failure. Enhancement of arginine availability with l-arginine supplementation exhibited less consistent results; however, l-citrulline, the precursor of l-arginine, may be a promising alternative. In this study, we determined the effects of l-citrulline compared to l-arginine supplementation on arginine-nitric oxide (NO) metabolism, arginine availability and microcirculation in a murine model with acutely-enhanced arginase activity. The effects were measured in six groups of mice (n = 8 each) injected intraperitoneally with sterile saline or arginase (1000 IE/mouse) with or without being separately injected with l-citrulline or l-arginine 1 h prior to assessment of the microcirculation with side stream dark-field (SDF)-imaging or in vivo NO-production with electron spin resonance (ESR) spectroscopy. Arginase injection caused a decrease in plasma and tissue arginine concentrations. l-arginine and l-citrulline supplementation both enhanced plasma and tissue arginine concentrations in arginase-injected mice. However, only the citrulline supplementation increased NO production and improved microcirculatory flow in arginase-injected mice. In conclusion, the present study provides for the first time in vivo experimental evidence that l-citrulline, and not l-arginine supplementation, improves the end organ microcirculation during conditions with acute arginase-induced arginine deficiency by increasing the NO concentration in tissues