Multi-ethnic genome-wide association study for atrial fibrillation

Atrial fibrillation (AF) affects more than 33 million individuals worldwide and has a complex heritability. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF

Quantitative analysis of myocardial tissue with digital autofluorescence microscopy

Background: The opportunity offered by whole slide scanners of automated histological analysis implies an ever increasing importance of digital pathology. To go beyond the importance of conventional pathology, however, digital pathology may need a basic histological starting point similar to that of hematoxylin and eosin staining in conventional pathology. This study presents an automated fluorescence-based microscopy approach providing highly detailed morphological data from unstained microsections. This data may provide a basic histological starting point from which further digital analysis including staining may benefit. Methods: This study explores the inherent tissue fluorescence, also known as autofluorescence, as a mean to quantitate cardiac tissue components in histological microsections. Data acquisition using a commercially available whole slide scanner and an image-based quantitation algorithm are presented. Results: It is shown that the autofluorescence intensity of unstained microsections at two different wavelengths is a suitable starting point for automated digital analysis of myocytes, fibrous tissue, lipofuscin, and the extracellular compartment. The output of the method is absolute quantitation along with accurate outlines of above-mentioned components. The digital quantitations are verified by comparison to point grid quantitations performed on the microsections after Van Gieson staining. Conclusion: The presented method is amply described as a prestain multicomponent quantitation and outlining tool for histological sections of cardiac tissue. The main perspective is the opportunity for combination with digital analysis of stained microsections, for which the method may provide an accurate digital framework

The Impact of Intensified Training with a High or Moderate Carbohydrate Feeding Strategy on Resting and Exercise-induced Oxidative Stress

This study investigated the impact of intensified training (IT) and carbohydrate (CHO) supplementation on resting and exercise-induced oxidative stress

Children’s, parents’, and teachers’ experiences of the feasibility of a telerehabilitation intervention for children with acquired brain injury in the chronic phase – a qualitative study of acceptability and participation in the Child In Context Intervention (CICI)

Abstract Background This is a qualitative feasibility study of the Child in Context Intervention (CICI). The CICI is an individualized, goal-oriented and home-based tele-rehabilitation intervention which targets everyday functioning of children (6–16 years) with acquired brain injury in the chronic stage, and their families, one year or more after insult, who have ongoing challenges (physical, cognitive, behavioral, social and/or psychological). The aim of this study is to better understand how children, parents and teachers experienced participation and acceptability; to develop knowledge about the mechanisms of change, and to explore how the CICI was tailored to the context. Methods Six families and schools participated in the intervention, which comprised seven tele-rehabilitation sessions in which the child and parent participated, one in-person parent seminar and four digital school meetings. A multidisciplinary team delivered the intervention to 23 participants over a 4- to 5-month period. The intervention involved psychoeducation about targeted acquired brain injury-related problems, such as fatigue, pain, or social challenges. All but one consented to participate in the current digital interview study. The data were analyzed using content analysis. Results The experience of participation and acceptability varied among the children. Attendance was consistently high; the child participants felt mostly listened to and could influence goal setting and strategies. However, engaging and motivating the child participants proved somewhat challenging. The parents found the CICI rewarding, useful and relevant. However, they had different experiences regarding which intervention component they perceived as most helpful. Some argued in favor of the ‘whole intervention’, while others highlighted new knowledge, SMART goals or the school collaboration. The teachers found the intervention acceptable and useful but wanted a better meeting plan. They had difficulties in finding time for meetings, emphasized the involvement of school leaders, and appreciated the digital format. Conclusions Overall, the intervention was perceived as acceptable, and the participants felt that the various intervention components contributed to improvements. The CICI’s flexibility facilitated tailoring to different contexts based on the children’s functional level. The digital format saved time and provided flexibility regarding the amount of attendance but limited full participation from children with more severe cognitive impairments. Trial registration ClinicalTrials.gov Identifier: NCT04186182

Feasibility and Acceptability of a Complex Telerehabilitation Intervention for Pediatric Acquired Brain Injury: The Child in Context Intervention (CICI)

The current study is a feasibility study of a randomized controlled trial (RCT): the Child in Context Intervention (CICI). The CICI study is an individualized, goal-oriented and home-based intervention conducted mainly through videoconference. It targets children with ongoing challenges (physical, cognitive, behavioral, social and/or psychological) after acquired brain injury (ABI) and their families at least one year post injury. The CICI feasibility study included six children aged 11–16 years with verified ABI-diagnosis, their families and their schools. The aim was to evaluate the feasibility of the intervention components, child and parent perceptions of usefulness and relevance of the intervention as well as the assessment protocol through a priori defined criteria. Overall, the families and therapists rated the intervention as feasible and acceptable, including the videoconference treatment delivery. However, the burden of assessment was too high. The SMART-goal approach was rated as useful, and goal attainment was high. The parents’ ratings of acceptability of the intervention were somewhat higher than the children’s. In conclusion, the CICI protocol proved feasible and acceptable to families, schools and therapists. The assessment burden was reduced, and adjustments in primary outcomes were made for the definitive RCT

Rehabilitation for children with chronic acquired brain injury in the Child in Context Intervention (CICI) study: study protocol for a randomized controlled trial

Background Pediatric acquired brain injury (pABI) is associated with long-term cognitive, behavioral, social, and emotional problems, which may affect the quality of life, school, and family functioning. Yet, there is a lack of evidence-based community-centered rehabilitation programs for chronic pABI and these children do not systematically receive comprehensive rehabilitation. The Child In Context Intervention (CICI) study is a pragmatic randomized controlled trial (RCT) for children with chronic pABI, which aims to evaluate the effectiveness of an individualized and goal-oriented intervention targeting everyday functioning of the child and family. Methods Children aged 6–16 years with MRI/CT-verified intracranial abnormalities will be included in the CICI study if they have persistent self- or parent-reported cognitive, emotional, and/or behavioral challenges 1 year or more after insult and attend school regularly. A total of 70 families will be randomized 1:1 to an intervention or a control group. The intervention consists of seven family sessions, one parent seminar, and four school sessions delivered over approximately 6 months. The parent seminar will be held in person, and the other sessions will mainly be video based. The children’s and families’ self-reported major challenges in everyday life will be targeted using SMART goals. Evidence-based strategies, when available, will be applied to achieve the goals, combined with psychoeducation. Goal attainment scaling (GAS) will be used to evaluate goal attainment. Data is collected at baseline and after approximately 6 and 9 months. External assessors are blinded to group allocation. Primary outcomes are parent-reported brain injury symptoms in children and parenting self-efficacy at 9 months of follow-up. Secondary outcomes include child-reported brain injury symptoms, quality of life, executive functioning in daily life, parent emotional symptoms, family functioning, and unmet family health care needs. A process evaluation will be conducted. Discussion The current study provides an innovative approach to rehabilitation for children in the chronic phase of ABI and their families. This complex intervention may contribute to the development of evidence-based, high-quality rehabilitation for a large patient group, which is underrepresented in clinical research. It may also improve collaboration between specialized rehabilitation facilities, schools, and local health care services. Inclusion for the trial started in April 2021. Trial registration ClinicalTrials.gov NCT04798859 . Registered on March 15, 202