Clinical pharmacogenetics of methotrexate

It is well known that interindividual variability can affect the response to many drugs in relation to age, gender, diet, and organ function. Pharmacogenomic studies have also documented that genetic polymorphisms can exert clinically significant effects in terms of drug resistance, efficacy and toxicity by modifying the expression of critical gene products (drug-metabolizing enzymes, transporters, and target molecules) as well as pharmacokinetic and pharmacodynamic parameters. A growing body of in vitro and clinical evidence suggests that common polymorphisms in the folate gene pathway are associated with an altered response to methotrexate (MTX) in patients with malignancy and autoimmune disease. Such polymorphisms may also induce significant MTX toxicity requiring expensive monitoring and treatment. Although the available data are not conclusive, they suggest that in the future MTX pharmacogenetics could play a key role in clinical practice by improving and tailoring treatment. This review describes the genetic polymorphisms that significantly influence MTX resistance, efficacy, and toxicity

Field-based tests for the assessment of physical fitness in children and adolescents practicing sport: A systematic review within the ESA program

High levels of physical fitness (PF) can positively affect both health and cognitive function, thus monitoring its levels in youth can help increase health and quality of life in adult populations later on. This systematic review aims to identify PF field-based tests used in young European populations practicing sport to find tools that are adequate for the considered target involving a new battery within the Enriched Sport Activities (ESA) project. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was followed. In the 83 identified articles, the main tests used were: vertical/horizontal jumps (for muscular strength/power); push-ups, running at maximum effort, sit-ups (for muscular strength/endurance); multistage non-intermittent and intermittent tests (for aerobic endurance); sit and reach (for flexibility); sprinting and agility T-tests (for speed and agility, respectively); 10 x 5 m shuttle run (SR) (for both speed and agility). Few studies assessed coordination, reaction time, power, and balance. Although the selected tests are widely used and validated, they do not determine all PF aspects and do not reflect sport-specific features. A final decision was made for the inclusion of the following tests: standing broad jump, seated medicine ball throw, 20 m SR test, 30 m sprint, Illinois test, and a new test, i.e., the crunning test, to assess different skill-related components at once. The use of this combination of tests allows for the assessment of all PF components and can help planning eective training programs and cultivate sporting talent

Effects of a physical activity intervention on physical fitness of schoolchildren: The enriched sport activity program

Background: Physical fitness in youth is a predictor of health in adulthood. The main objective of the present study was to understand if an enriched sport activity program could increase physical fitness in a population of schoolchildren. Methods: In a sample of 672 children aged 10.0 ± 1.90 years, different motor skills were tested by the 1 kg and 3 kg ball throw (BT), the standing broad jump (SBJ), the 30 m sprint (30mS), the leger shuttle run (LSR), the illinois agility test (IGT), and the quadruped test (QT). Within the controlled-trial, the intervention group (ESA) underwent an additional warm-up protocol, which included cognitive enhancing elements, for 14 weeks while the control group continued with ordinary exercise activity. Results: A significant increase was present regarding the 1 kg and 3 kg BT, the SBJ, the 30mS, and the IGT, while no significant difference was shown regarding the QT and the LSR in the ESA group between pre and post intervention. In the control group, no differences were present for any test except for the QT and the LSR post-test. Conclusion: A 14-week structured physical intervention had moderate effects regarding throwing, jumping, sprinting, and agility in a sample of schoolchildren

Cognitive and motivational monitoring during enriched sport activities in a sample of children living in Europe. The ESA program

Enriched Sport Activities (ESA) Program is an Evidence-based Practice Exercise Program cofounded by the Erasmus + Programme of the European Union (Key action: Sport-579661-EPP-1-2016-2-IT-SPO-SCP). It aims to enhance social inclusion, equal opportunities and psycho-physical wellbeing in children with typical development and special needs. This aim will be pursued through two ways: (1) Children and preadolescents’ participation in Enriched Sport Activities (ESA) Program; (2) Parents’ involvement and education on cognitive, motivational and social benefits of Physical Activities (PA) in their children. Recent research showed that high-level cognitive processes, such as inhibition, shifting, working memory and planning, can be improved by aerobic exercise programs following both single bouts of exercise and longer trainings from moderate to vigorous intensity [1]. Nevertheless, in the developmental age, structured sport activities, such as martial arts, basketball, soccer, rowing and dancing, act by delivering both physical and psychological benefits. The former involve physical fitness such as cardiorespiratory fitness, muscular strength, muscular endurance, flexibility and motor skills such as coordination, whilst the latter concern enjoyment, self-confidence and self-esteem, a sense of belonging and social support [2–4]. The effectiveness of PMA (Programma Motorio Arricchito), a structured motor program on coordination and executive functioning in kindergarten children, has been demonstrated [5]

Deep learning(s) in gaming disorder through the user-avatar bond: a longitudinal study using machine learning

Background and aims: Gaming disorder [GD] risk has been associated with the way gamers bond with their visual representation (i.e., avatar) in the game-world. More specifically, a gamer's relationship with their avatar has been shown to provide reliable mental health information about the user in their offline life, such as their current and prospective GD risk, if appropriately decoded. Methods: To contribute to the paucity of knowledge in this area, 565 gamers (Mage = 29.3 years; SD =10.6) were assessed twice, six months apart, using the User-Avatar-Bond Scale (UABS) and the Gaming Disorder Test. A series of tuned and untuned artificial intelligence [AI] classifiers analysed concurrently and prospectively their responses. Results: Findings showed that AI models learned to accurately and automatically identify GD risk cases, based on gamers' reported UABS score, age, and length of gaming involvement, both concurrently and longitudinally (i.e., six months later). Random forests outperformed all other AIs, while avatar immersion was shown to be the strongest training predictor. Conclusion: Study outcomes demonstrated that the user-avatar bond can be translated into accurate, concurrent and future GD risk predictions using trained AI classifiers. Assessment, prevention, and practice implications are discussed in the light of these findings

Can Dietary Patterns Impact Fertility Outcomes? A Systematic Review and Meta-Analysis.

There are conflicting results on the effect of diet on fertility. This study aimed to assess the effect of different dietary patterns on fertility outcomes in populations who conceive spontaneously and those requiring assisted reproductive technology (ART). A systematic search and meta-analysis were performed for studies investigating dietary patterns or whole diets in reproductive aged women requiring ART or conceived naturally. Outcomes were live births, pregnancy rates and infertility rates. In amount of 15,396 studies were screened with 11 eligible studies. Ten different diet patterns were grouped broadly into categories: Mediterranean, Healthy or Unhealthy. For the Mediterranean diet, on excluding high risk-of-bias studies (n = 3), higher adherence was associated with improved live birth/pregnancy rates in ART [OR 1.91 (95% CI 1.14-3.19, I2 43%)] (n = 2). Adherence to various Healthy diets was associated with improved ART outcomes (ProFertility diet and Dutch Dietary Guidelines) and natural conception outcomes (Fertility diet). However, due to the variability in Healthy diets' components, results were not pooled. Studies demonstrated preliminary evidence for the role of dietary patterns or whole diets in improving pregnancy and live birth rates. However, due to heterogeneity across the literature it is currently unclear which diet patterns are associated with improvements in fertility and ART outcomes.Hugo G. Winter, Daniel L. Rolnik, Ben W. J. Mol, Sophia Torkel, Simon Alesi, Aya Mousa, Nahal Habibi, Thais R. Silva, Tin Oi Cheung, Chau Thien Tay, Alejandra Quinteros, Jessica A. Grieger, and Lisa J. Mora

Breaking barriers: using the behavior change wheel to develop a tailored intervention to overcome workplace inhibitors to breaking up sitting time

© The Author(s). 2019. Background: The workplace is a prominent domain for excessive sitting. The consequences of increased sitting time include adverse health outcomes such as cardiovascular disease and poor mental wellbeing. There is evidence that breaking up sitting could improve health, however, any such intervention in the workplace would need to be informed by a theoretical evidence-based framework. The aim of this study was to use the Behaviour Change Wheel (BCW) to develop a tailored intervention to break up and reduce workplace sitting in desk-based workers. Methods: The BCW guide was followed for this qualitative, pre-intervention development study. Semi-structured interviews were conducted with 25 office workers (26–59years, mean age 40.9 [SD=10.8] years; 68% female) who were purposively recruited from local council offices and a university in the East of England region. The interview questions were developed using the Theoretical Domains Framework (TDF). Transcripts were deductively analysed using the COM-B (Capability, Opportunity, Motivation – Behaviour) model of behaviour. The Behaviour Change Technique Taxonomy Version 1 (BCTv1) was thereafter used to identify possible strategies that could be used to facilitate change in sitting behaviour of office workers in a future intervention. Results: Qualitative analysis using COM-B identified that participants felt that they had the physical Capability to break up their sitting time, however, some lacked the psychological Capability in relation to the knowledge of both guidelines for sitting time and the consequences of excess sitting. Social and physical Opportunity was identified as important, such as a supportive organisational culture (social) and the need for environmental resources (physical). Motivation was highlighted as a core target for intervention, both reflective Motivation, such as beliefs about capability and intention and automatic in terms of overcoming habit through reinforcement. Seven intervention functions and three policy categories from the BCW were identified as relevant. Finally, 39 behaviour change techniques (BCTs) were identified as potential active components for an intervention to break up sitting time in the workplace. Conclusions: The TDF, COM-B model and BCW can be successfully applied through a systematic process to understand the drivers of behaviour of office workers to develop a co-created intervention that can be used to break up and decrease sitting in the workplace. Intervention designers should consider the identified BCW factors and BCTs when developing interventions to reduce and break up workplace sitting

Global/local postbuckling failure analysis of composite stringer/skin panels

A finite element methodology for postbuckling failure analysis of composite stringer/skin panels is presented. The methodology employs a global two-dimensional plate finite element model for representing overall panel deformation and a local three-dimensional solid finite element model for representing stress within a critical panel region. Global and local models are connected with a two-dimensional/three-dimensional coupling methodology that is based on multipoint constraints. Analyses are carried out for two different panel designs utilizing both linear and nonlinear material models. Computational results for failure load, failure location, and failure mode compare favorably with results from earlier experimental test programs. The findings suggest that failure initiation in postbuckled composite stringer/skin panels can be effectively modeled with the developed finite element methodology