Ferroptosis is a form of programmed cell death associated with inflammation, neurodegeneration, and ischemia. Vitamin E (alpha-tocopherol) has been reported to prevent ferroptosis, but the mechanism ...by which this occurs is controversial. To elucidate the biochemical mechanism of vitamin E activity, we systematically investigated the effects of its major vitamers and metabolites on lipid oxidation and ferroptosis in a striatal cell model. We found that a specific endogenous metabolite of vitamin E, alpha-tocopherol hydroquinone, was a dramatically more potent inhibitor of ferroptosis than its parent compound, and inhibits 15-lipoxygenase via reduction of the enzyme's non-heme iron from its active Fe3+ state to an inactive Fe2+ state. Furthermore, a non-metabolizable isosteric analog of vitamin E which retains antioxidant activity neither inhibited 15-lipoxygenase nor prevented ferroptosis. These results call into question the prevailing model that vitamin E acts predominantly as a non-specific lipophilic antioxidant. We propose that, similar to the other lipophilic vitamins A, D and K, vitamin E is instead a pro-vitamin, with its quinone/hydroquinone metabolites responsible for its anti-ferroptotic cytoprotective activity.
Aim
These international clinical practice recommendations (CPR) for developmental coordination disorder (DCD), initiated by the European Academy of Childhood Disability (EACD), aim to address key ...questions on the definition, diagnosis, assessment, intervention, and psychosocial aspects of DCD relevant for clinical practice.
Method
Key questions in five areas were considered through literature reviews and formal expert consensus. For recommendations based on evidence, literature searches on ‘mechanisms’, ‘assessment’, and ‘intervention’ were updated since the last recommendations in 2012. New searches were conducted for ‘psychosocial issues’ and ‘adolescents/adults’. Evidence was rated according to the Oxford Centre for Evidence‐Based Medicine (level of evidence LOE 1–4) and transferred into recommendations. For recommendations based on formal consensus, two meetings of an international, multidisciplinary expert panel were conducted with a further five Delphi rounds to develop good clinical practice (GCP) recommendations.
Results
Thirty‐five recommendations were made. Eight were based on the evidence from literature reviews (three on ‘assessment’, five on ‘intervention’). Twenty‐two were updated from the 2012 recommendations. New recommendations relate to diagnosis and assessment (two GCPs) and psychosocial issues (three GCPs). Additionally, one new recommendation (LOE) reflects active video games as adjuncts to more traditional activity‐oriented and participation‐oriented interventions, and two new recommendations (one GCP, one LOE) were made for adolescents and adults with DCD.
Interpretation
The CPR–DCD is a comprehensive overview of DCD and current understanding based on research evidence and expert consensus. It reflects the state of the art for clinicians and scientists of varied disciplines. The international CPR–DCD may serve as a basis for national guidelines.
What this paper adds
Updated international clinical practice guidelines on developmental coordination disorder (DCD).
Refined and extended recommendations on clinical assessment and intervention for DCD.
A critical synopsis of current research on mechanisms of DCD.
A critical synopsis of psychosocial issues in DCD, with implications for clinical practice.
The first international recommendations to consider adolescents and adults with DCD.
Resumen
Recomendaciones internacionales para la práctica clínica sobre la definición, diagnóstico, evaluación, intervención y aspectos psicosociales del trastorno del desarrollo de la coordinación
Objetivo
Estas recomendaciones internacionales para la práctica clínica (RPC) sobre el trastorno del desarrollo de la coordinación (TDC), iniciadas por la Academia Europea de Discapacidad Infantil (EACD), tienen como objetivo abordar preguntas clave sobre la definición, diagnóstico, evaluación, intervención y aspectos psicosociales de TDC relevantes para la práctica clínica.
Método
Las preguntas clave en cinco áreas fueron tratadas a través de revisiones bibliográficas y consenso formal de expertos. Para las recomendaciones basadas en la evidencia, las búsquedas en la literatura sobre “mecanismos”, “evaluación” e “intervención” se actualizaron desde las últimas recomendaciones en 2012. Se realizaron nuevas búsquedas para “problemas psicosociales” y “adolescentes / adultos”. La evidencia se calificó de acuerdo con la gradación del Centro de Oxford para Medicina Basada en la Evidencia (nivel de evidencia LOE 1–4) y en ello se basaron las recomendaciones. Para recomendaciones basadas en el consenso formal, se llevaron a cabo dos reuniones de un panel multidisciplinario internacional de expertos con cinco rondas Delphi adicionales para desarrollar recomendaciones de buena práctica clínica (BPC).
Resultados
Se realizaron 35 recomendaciones. Ocho de ellas se basaron en la evidencia de las revisiones de la literatura (tres en “evaluación”, cinco en “intervención”). Veintidós fueron actualizadas a partir de las recomendaciones de 2012. Las nuevas recomendaciones se relacionan con el diagnóstico y la evaluación (dos BPC) y las cuestiones psicosociales (tres BPC). Además, una nueva recomendación (LOE) trata acerca de los videojuegos activos como complemento de las intervenciones más tradicionales orientadas a la actividad y la participación, y se hicieron dos nuevas recomendaciones (una BCP, una LOE) para adolescentes y adultos con TDC.
Interpretación
Estas recomendaciones internacionales para la práctica clínica sobre TDC aportan una visión general completa sobre TDC y el conocimiento actual basado en evidencia de investigación y consenso de expertos. Brinda actualización para clínicos y científicos de diversas disciplinas. Las recomendaciones internacionales para la práctica clínica TDC pueden servir como base para recomendaciones nacionales.
Recomendações internacionais para a prática clínica na definição, diagnóstico, avaliação, intervenção e aspectos psicossociais do transtorno do desenvolvimento da coordenação
Objetivo
Essas recomendações internacionais para a prática clínica (RPC) no transtorno do desenvolvimento da coordenação (TDC), iniciadas pela Academia Européia de Deficiência Infantil (EACD), objetiva direcionar questões chave na definição, diagnóstico, avaliação, intervenção e aspectos psicossociais do TDC relevantes para a prática clínica.
Métodos
Questões chave em cinco áreas foram consideradas através de revisões da literatura e consensos formais de especialistas. Para recomendações baseadas em evidências, buscas na literatura em “mecanismos”, “avaliação” e “intervenção” foram atualizadas desde as últimas recomendações de 2012. Novas buscas foram conduzidas para “problemas psicossociais” e “adolescentes/adultos”. Evidências foram classificadas de acordo com o Centro Oxford para Medicina Baseada em Evidência (nível de evidência NE 1‐4) e transferidas em recomendações. Para recomendações baseadas em consensos formais, dois encontros de um painel de especialistas internacional e multidisciplinar foram conduzidos com posteriormente cinco sessões Delphi para desenvolver recomendações de boa prática clínica (BPC).
Resultados
Trinta e cinco recomendações foram feitas. Oito foram baseadas em evidências de revisões da literatura (três em “avaliação”, cinco em “intervenção). Vinte e duas foram atualizadas das recomendações de 2012. Novas recomendações são relacionadas com diagnóstico e avaliação (duas BPC) e problemas psicossociais (três BPCs). Adicionalmente, uma nova recomendação (NE) se refere a jogos de videogame ativos como adjuntos à mais tradicional terapia orientada à tarefa e intervenção orientada à participação, e duas novas recomendações (uma BPC, um NE) foram feitas para adolescentes e adultos com TDC.
Interpretação
A RPC‐TDC apresenta uma visão geral do TDC e o conhecimento atual baseado em evidências de pesquisas e consenso de especialistas. Reflete o estado de arte dos clínicos e cientistas de disciplinas variadas. A RPC‐TDC internacional deverá servir como uma base para as diretrizes nacionais.
What this paper adds
Updated international clinical practice guidelines on developmental coordination disorder (DCD).
Refined and extended recommendations on clinical assessment and intervention for DCD.
A critical synopsis of current research on mechanisms of DCD.
A critical synopsis of psychosocial issues in DCD, with implications for clinical practice.
The first international recommendations to consider adolescents and adults with DCD.
This article's has been translated into Spanish and Portuguese.
Follow the links from the to view the translations.
A pocket version of these guidelines is available as Appendix S1 (https://onlinelibrary.wiley.com/doi/full/10.1111/dmcn.14132#support-information-section)
Dear Editor, I read the recent case report "Glucokinase maturity-onset diabetes of the young as a mimicker of stress hyperglycemia: a case report" by Nakasato et al. with interest (1). The authors ...present a case of hyperglycemia in the context of febrile seizure. Glucose levels, family history, and genetic testing on follow-up revealed the child has GCK-MODY. While the authors indicate this was not stress hyperglycemia after all, this may not be so.
Developmental coordination disorder (DCD) affects around 5% of children and commonly overlaps with other developmental disorders including: attention deficit hyperactivity disorder (ADHD), autism ...spectrum disorders (ASDs) and specific language impairment (SLI). There is evidence to demonstrate the wide-ranging impact on all areas of functioning including psychiatric and learning domains. There is increasing evidence of the continuing impact into adulthood and the long-term negative effects on relationships and employment. There is a need for early identification and intervention to limit the likelihood of these secondary consequences from emerging. This paper addresses the diagnosis of DCD.
We evaluated the diagnostic yield using genome‐slice panel reanalysis in the clinical setting using an automated phenotype/gene ranking system. We analyzed whole genome sequencing (WGS) data produced ...from clinically ordered panels built as bioinformatic slices for 16 clinically diverse, undiagnosed cases referred to the Pediatric Mendelian Genomics Research Center, an NHGRI‐funded GREGoR Consortium site. Genome‐wide reanalysis was performed using Moon™, a machine‐learning‐based tool for variant prioritization. In five out of 16 cases, we discovered a potentially clinically significant variant. In four of these cases, the variant was found in a gene not included in the original panel due to phenotypic expansion of a disorder or incomplete initial phenotyping of the patient. In the fifth case, the gene containing the variant was included in the original panel, but being a complex structural rearrangement with intronic breakpoints outside the clinically analyzed regions, it was not initially identified. Automated genome‐wide reanalysis of clinical WGS data generated during targeted panels testing yielded a 25% increase in diagnostic findings and a possibly clinically relevant finding in one additional case, underscoring the added value of analyses versus those routinely performed in the clinical setting.
Whole genome sequencing (WGS) data, produced from clinically ordered panels built as bioinformatic slices for 16 clinically diverse, undiagnosed cases, were reanalyzed using a machine‐learning‐based tool for variant prioritization and yielded additional potentially clinically significant variants in five out of 16 cases including a complex variant not detectable by exome.
Objective To evaluate the validity of the Beighton score as a generalized measure of hypermobility and to measure the prevalence of hypermobility and pain in a random population of school age ...children. Study design Prospective study of 551 children attending various Dutch elementary schools participated; 47% were males (258) and 53% (293) females, age range was 6 to 12 years. Children's joints and movements were assessed according to the Beighton score by qualified physiotherapists and by use of goniometry measuring 16 passive ranges of motion of joints on both sides of the body. Results More than 35% of children scored more than 5/9 on the Beighton score. Children who scored high on the Beighton score also showed increased range of motion in the other joints measured. Moreover 12.3% of children had symptoms of joint pain, and 9.1% complained of pain after exercise or sports. Importantly, this percentage was independent of the Beighton score. There were no significant differences in Beighton score for sex in this population. Conclusion The Beighton score, when goniometry is used, is a valid instrument to measure generalized joint mobility in school-age children 6 to 12 years. No extra items are needed to improve the scale.
Screening for vulnerability factors associated with historic suicidality and self-harm on entry to prison is critical to help prisons understand how to allocate extremely limited mental health ...resources. It has been established that having previous suicide attempts increases odds of future suicidality and self-harm in prison. We utilised administrative screening data from 665 adult male prisoners on entry to a category B prison in Wales, UK, collected using the Do-IT Profiler. This sample represents 16% of all prisoners who entered that prison during a 26-month period. 12% of prisoners reported a history of attempted suicide, 11% reported historic self-harm, and 8% reported a history of both. Historic traumatic brain injury and substance use problems were associated with a 3.3- and 1.9- times increased odds of a historic suicide attempt, respectively, but no significant increased risk of historic self-harm (95% CI: 1.51-6.60 and 1.02-3.50). However, those who were bullied at school had 2.7 times increased odds of reporting a history of self-harm (95% CI: 1.63-6.09). The most salient risk factors associated with both historic suicide and self-harm were higher levels of functional neurodisability (odds ratio 0.6 for a 1 standard deviation change in score, 95% CI: 0.35-0.75), and mood disturbance (odds ratio 2.1 for a 1 standard deviation change in score, 95% CI: 1.26-3.56). Therefore, it could be beneficial for prisons to screen for broader profiles of needs, to better understand how to provide appropriate services to prisoners vulnerable to suicide and self-harm. Multidisciplinary care pathways for prisoner mental health interventions are important, to account for complex multimorbidity. Adaptations may be needed for mental health interventions to be appropriate for, for example, a prisoner with a brain injury. Understanding this broad profile of vulnerability could also contribute to more compassionate responses to suicide and self-harm from prison staff.
Ectothermic animals are especially susceptible to temperature change, considering that their metabolism and core temperature are linked to the environmental temperature. As global water temperatures ...continue to increase, so does the need to understand the capacity of organisms to tolerate change. Sheepshead minnows (
Cyprinodon variegatus
) are the most eurythermic fish species known to date and can tolerate a wide range of environmental temperatures from − 1.9 to 43.0 °C. But little is known about the physiological adjustments that occur when these fish are subjected to acute thermal challenges and long-term thermal acclimation. Minnows were acclimated to 10, 21, or 32 °C for 4 weeks or acutely exposed to 10 and 32 °C and then assessed for swimming performance maximum sustained swimming velocity (
U
crit
), optimum swimming velocity (
U
opt
) and metabolic endpoints (extrapolated standard and maximum metabolic rate SMR, MMR), absolute aerobic scope (AS), and cost of transport (COT). Our findings show that the duration of thermal exposure (acute vs. acclimation) did not influence swimming performance. Rather, swimming performance was influenced by the exposure temperature. Swimming performance was statistically similar in fish exposed to 21 or 32 °C (approximately 7.0 BL s
−1
), but was drastically reduced in fish exposed to 10 °C (approximately 2.0 BL s
−1
), resulting in a left-skewed performance curve. There was no difference in metabolic end points between fish acutely exposed or acclimated to 10 °C. However, a different pattern was observed in fish exposed to 32 °C. MMR was similar between acutely exposed or acclimated fish, but acclimated fish had a 50% reduction in extrapolated SMR, which increased AS by 25%. However, this enhanced AS was not associated with changes in swimming performance, which opposes the oxygen-capacity limited thermal tolerance concept. Our findings suggest that sheepshead minnows may utilize two distinct acclimation strategies, resulting in different swimming performance and metabolic patterns observed between 10 and 32 °C exposures.
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