Energy expenditure at rest and during sleep in children with Prader-Willi syndrome is explained by body composition

Obesity in Prader-Willi syndrome (PWS) seems to be related to a low basal metabolic rate (BMR). In addition, abnormal sleep patterns reported in PWS might affect sleeping metabolic rate (SMR).Our objective was to assess BMR and SMR adjusted for fat-free mass in young PWS patients.Subjects were 17 PWS patients (10 females and 7 males aged 7.5-19.8 y) and 17 obese control subjects matched for sex and bone age. SMR was measured in a respiratory chamber, BMR with a ventilated-hood system, and body composition by deuterium dilution.BMR and SMR were significantly lower in the PWS group than in the control group (5.36 +/- 1.18 and 4.62 +/- 1.08 MJ/d compared with 6.38 +/- 1.55 and 5.60 +/- 1.52 MJ/d, respectively; P <0.05). When fat-free mass was included in the analysis, multiple regression showed no differences in BMR and SMR between groups. When weight was included in the analysis instead of fat-free mass, SMR was lower in the PWS group. Fat-free mass was lower in the PWS group both as an absolute value and when adjusted for height.BMR and SMR are low in young patients with PWS because of a low fat-free mass

Optimization of force in the Wingate Test for children with a neuromuscular disease.

Optimization of force in the Wingate Test for children with a neuromuscular disease. Van Mil E, Schoeber N, Calvert RE, Bar-or O. Children's Exercise and Nutrition Centre, McMaster University, Hamilton, Ontario, Canada. Determination of the optimal braking force (Fopt in the Wingate Anaerobic Test (WAnT) among healthy people has been determined based on total body mass. The abnormal muscle mass to total body mass ratio in individuals with neuromuscular disabilities invalidates this approach. This study was intended to validate the optimal force obtained from the Force Velocity Test (FVT) and from an estimate of lean arm volume as two alternative predictors for the Fopt. Twenty-eight 6- to 16-yr-old girls and boys with neuromuscular diseases performed the arm WAnT six times (three trials in each of two visits) against various braking forces to directly determine Fopt. They also performed the arm Force Velocity Test to assess optimal force (FoptFVT). Lean arm volume was determined by anthropometry (ALV) and water displacement (WLV). Correlations between Fopt on the one hand, and FoptFVT, WLV, and ALV on the other, were: R2 = 0.91, 0.81, and 0.82, respectively. Total body mass was the worst predictor (R2 = 0.65). Thus, Fopt obtained from either FVT or lean arm volume estimate is a useful predictor of the Fopt for mean power of the WAnT in children and adolescents with a neuromuscular disability

A complex system approach to address world challenges in food and agriculture

The quality and amount of the world food supply is crucial to the well-being of every human on the planet in the basic sense that we need food to live. It also has a profound impact on world economy, international trade, and global political stability. The choice of land used for agriculture, and the livestock and plants raised on the land, will impact the sustainable use of global resources. On a global scale, there are communities where insufficient food causes nutritional deficiencies, and at the same time, there are other communities eating too much food leading to obesity. Both conditions have accompanying diseases with associated financial consequences. The above issues relate to various scales, from local to global, and to a range of scientific disciplines. Moreover, their various elements are part of an interdependent, continuously changing, and adaptive system. This implies that the response of a combination of individual elements cannot usually be inferred from the response of each individual element or subsystem. This makes the identification of an appropriate intervention to change one or more elements a complex problem. We propose that a complex system approach should be used to address the global challenges of the agriculture and food system. The complex system approach accounts for the needs of stakeholders and policymakers in the agriculture and food system, and helps to determine which research programs will enable stakeholders to better anticipate and respond to emerging developments in the world. Moreover, the approach will enable them to determine effective intervention strategies to simultaneously optimise and safeguard their interests and the interests of the environment. The approach is formulated in terms of a roadmap of procedures. It encompasses an array of methods utilised in an integrative multi-scale and inter-disciplinary wa

A complex system approach to address world challenges in food and agriculture

The quality and amount of the world food supply is crucial to the well-being of every human on the planet in the basic sense that we need food to live. It also has a profound impact on world economy, international trade, and global political stability. The choice of land used for agriculture, and the livestock and plants raised on the land, will impact the sustainable use of global resources. On a global scale, there are communities where insufficient food causes nutritional deficiencies, and at the same time, there are other communities eating too much food leading to obesity. Both conditions have accompanying diseases with associated financial consequences. The above issues relate to various scales, from local to global, and to a range of scientific disciplines. Moreover, their various elements are part of an interdependent, continuously changing, and adaptive system. This implies that the response of a combination of individual elements cannot usually be inferred from the response of each individual element or subsystem. This makes the identification of an appropriate intervention to change one or more elements a complex problem. We propose that a complex system approach should be used to address the global challenges of the agriculture and food system. The complex system approach accounts for the needs of stakeholders and policymakers in the agriculture and food system, and helps to determine which research programs will enable stakeholders to better anticipate and respond to emerging developments in the world. Moreover, the approach will enable them to determine effective intervention strategies to simultaneously optimise and safeguard their interests and the interests of the environment. The approach is formulated in terms of a roadmap of procedures. It encompasses an array of methods utilised in an integrative multi-scale and inter-disciplinary wa

Variant location is a novel risk factor for individuals with arrhythmogenic cardiomyopathy due to a desmoplakin (DSP) truncating variant

Background:Truncating variants in desmoplakin (DSPtv) are an important cause of arrhythmogenic cardiomyopathy; however the genetic architecture and genotype-specific risk factors are incompletely understood. We evaluated phenotype, risk factors for ventricular arrhythmias, and underlying genetics of DSPtv cardiomyopathy. Methods:Individuals with DSPtv and any cardiac phenotype, and their gene-positive family members were included from multiple international centers. Clinical data and family history information were collected. Event-free survival from ventricular arrhythmia was assessed. Variant location was compared between cases and controls, and literature review of reported DSPtv performed. Results:There were 98 probands and 72 family members (mean age at diagnosis 43 +/- 8 years, 59% women) with a DSPtv, of which 146 were considered clinically affected. Ventricular arrhythmia (sudden cardiac arrest, sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator therapy) occurred in 56 (33%) individuals. DSPtv location and proband status were independent risk factors for ventricular arrhythmia. Further, gene region was important with variants in cases (cohort n=98; Clinvar n=167) more likely to occur in the regions resulting in nonsense mediated decay of both major DSP isoforms, compared with n=124 genome aggregation database control variants (148 [83.6%] versus 29 [16.4%]; P<0.0001). Conclusions:In the largest series of individuals with DSPtv, we demonstrate that variant location is a novel risk factor for ventricular arrhythmia, can inform variant interpretation, and provide critical insights to allow for precision-based clinical management.Cardiolog

Variant Location Is a Novel Risk Factor for Individuals With Arrhythmogenic Cardiomyopathy Due to a Desmoplakin (DSP) Truncating Variant.

BACKGROUND: Truncating variants in desmoplakin (DSPtv) are an important cause of arrhythmogenic cardiomyopathy; however the genetic architecture and genotype-specific risk factors are incompletely understood. We evaluated phenotype, risk factors for ventricular arrhythmias, and underlying genetics of DSPtv cardiomyopathy. METHODS: Individuals with DSPtv and any cardiac phenotype, and their gene-positive family members were included from multiple international centers. Clinical data and family history information were collected. Event-free survival from ventricular arrhythmia was assessed. Variant location was compared between cases and controls, and literature review of reported DSPtv performed. RESULTS: There were 98 probands and 72 family members (mean age at diagnosis 43±8 years, 59% women) with a DSPtv, of which 146 were considered clinically affected. Ventricular arrhythmia (sudden cardiac arrest, sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator therapy) occurred in 56 (33%) individuals. DSPtv location and proband status were independent risk factors for ventricular arrhythmia. Further, gene region was important with variants in cases (cohort n=98; Clinvar n=167) more likely to occur in the regions resulting in nonsense mediated decay of both major DSP isoforms, compared with n=124 genome aggregation database control variants (148 [83.6%] versus 29 [16.4%]; P<0.0001). CONCLUSIONS: In the largest series of individuals with DSPtv, we demonstrate that variant location is a novel risk factor for ventricular arrhythmia, can inform variant interpretation, and provide critical insights to allow for precision-based clinical management

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update

ObjectivesTo provide an update of the EULAR rheumatoid arthritis (RA) management recommendations addressing the most recent developments in the field. MethodsAn international task force was formed and solicited three systematic literature research activities on safety and efficacy of disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs). The new evidence was discussed in light of the last update from 2019. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned to and participants finally voted on the level of agreement with each item. ResultsThe task force agreed on 5 overarching principles and 11 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); GCs; biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab including biosimilars), abatacept, rituximab, tocilizumab, sarilumab and targeted synthetic (ts) DMARDs, namely the Janus kinase inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib. Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering in sustained clinical remission is provided. Safety aspects, including risk of major cardiovascular events (MACEs) and malignancies, costs and sequencing of b/tsDMARDs were all considered. Initially, MTX plus GCs is recommended and on insufficient response to this therapy within 3-6 months, treatment should be based on stratification according to risk factors; With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD should be added to the csDMARD; after careful consideration of risks of MACEs, malignancies and/or thromboembolic events tsDMARDs may also be considered in this phase. If the first bDMARD (or tsDMARD) fails, any other bDMARD (from another or the same class) or tsDMARD (considering risks) is recommended. With sustained remission, DMARDs may be tapered but should not be stopped. Levels of evidence and levels of agreement were high for most recommendations. ConclusionsThese updated EULAR recommendations provide consensus on RA management including safety, effectiveness and cost.Pathophysiology and treatment of rheumatic disease