Search

Background: Increased gray matter volume (GMV) following electroconvulsive therapy (ECT) has been well-documented, with limited studies reporting a subsequent decrease in GMV afterwards. Objective: This study characterized the reversion pattern of GMV after ECT and its association with clinical depression outcome, using multi-site triple time-point data from the Global ECT-MRI Research Collaboration (GEMRIC). Methods: 86 subjects from the GEMRIC database were included, and GMV in 84 regions-of-interest (ROI) was obtained from automatic segmentation of T1 MRI images at three timepoints: pre-ECT (T0), within one-week post-ECT (T1), and one to six months post-ECT (T2). RM-ANOVAs were used to assess longitudinal changes and LMM analyses explored associations between GMV changes and demographical and clinical characteristics. Results: 63 of the 84 ROIs showed a significant increase-and-decrease pattern (RM-ANOVA, Bonferroni corrected p

Abstract Background Older people want to age in place. Despite advancing functional limitations and their desire of aging in place, they are not always faithful to therapy that maintains independence and promotes safety. Occupational therapists can facilitate aging in place. Occupational therapy is defined as the therapeutic use of everyday life occupations with persons, groups, or populations for the purpose of enhancing or enabling participation. Aim To describe the content a high-adherence-to-therapy and evidence-based occupational therapy intervention to optimize functional performance and social participation of home-based physically frail older adults and wellbeing of their informal caregiver, and the research activities undertaken to design this intervention. Methods A roadmap was created to develop the occupational therapy intervention. This roadmap is based on the Medical Research Council (MRC) framework and is supplemented with elements of the Intervention Mapping approach. The TIDieR checklist is applied to describe the intervention in detail. A systematic review and two qualitative studies substantiated the content of the intervention scientifically. Results The application of the first two phases of the MRC framework resulted in the ProMOTE intervention (Promoting Meaningful activities by Occupational Therapy in Elderly). The ProMOTE intervention is a high-adherence-to-therapy occupational therapy intervention that consists of six steps and describes in detail the evidence-based components that are required to obtain an operational intervention for occupational therapy practice. Conclusion This study transparently reflects on the process of a high-quality occupational therapy intervention to optimize the functional performance and social participation of the home-based physically frail older adult and describes the ProMOTE intervention in detail. The ProMOTE intervention contributes to safely aging in place and to maintaining social participation. The designed intervention goes beyond a description of the ‘what’. The added value lies in the interweaving of the ‘why’ and ‘how’. By describing the ‘how’, our study makes the concept of ‘therapeutic use-of-self’ operational throughout the six steps of the occupational therapy intervention. A further rigorous study of the effect of the ProMOTE intervention on adherence, functional performance and social participation is recommended based to facilitate the implementation of this intervention on a national level in Belgium.

Abstract Late-life depression has been consistently associated with lower gray matter volume, the origin of which remains largely unexplained. Recent in-vivo PET findings in early-onset depression and Alzheimer’s Disease suggest that synaptic deficits contribute to the pathophysiology of these disorders and may therefore contribute to lower gray matter volume in late-life depression. Here, we investigate synaptic density in vivo for the first time in late-life depression using the synaptic vesicle glycoprotein 2A receptor radioligand 11C-UCB-J. We included 24 currently depressed adults with late-life depression (73.0 ± 6.2 years, 16 female, geriatric depression scale = 19.5 ± 6.8) and 36 age- and gender-matched healthy controls (70.4 ± 6.2 years, 21 female, geriatric depression scale = 2.7 ± 2.9) that underwent simultaneous 11C-UCB-J positron emission tomography (PET) and 3D T1- and T2-FLAIR weighted magnetic resonance (MR) imaging on a 3-tesla PET-MR scanner. We used analyses of variance to test for 11C-UCB-J binding and gray matter volumes differences in regions implicated in depression. The late-life depression group showed a trend in lower gray matter volumes in the hippocampus (p = 0.04), mesial temporal (p = 0.02) and prefrontal cortex (p = 0.02) compared to healthy control group without surviving correction for multiple comparison. However, no group differences in 11C-UCB-J binding were found in these regions nor were any associations between 11C-UCB-J and depressive symptoms. Our data suggests that, in contrast to Alzheimer’s Disease, lower gray matter volume in late-life depression is not associated with synaptic density changes. From a therapeutic standpoint, preserved synaptic density in late-life depression may be an encouraging finding.

Abstract Background 5’ untranslated regions (5’UTRs) are essential modulators of protein translation. Predicting the impact of 5’UTR variants is challenging and rarely performed in routine diagnostics. Here, we present a combined approach of a comprehensive prioritization strategy and functional assays to evaluate 5’UTR variation in two large cohorts of patients with inherited retinal diseases (IRDs). Methods We performed an isoform-level re-analysis of retinal RNA-seq data to identify the protein-coding transcripts of 378 IRD genes with highest expression in retina. We evaluated the coverage of their 5’UTRs by different whole exome sequencing (WES) kits. The selected 5’UTRs were analyzed in whole genome sequencing (WGS) and WES data from IRD sub-cohorts from the 100,000 Genomes Project (n = 2397 WGS) and an in-house database (n = 1682 WES), respectively. Identified variants were annotated for 5’UTR-relevant features and classified into seven categories based on their predicted functional consequence. We developed a variant prioritization strategy by integrating population frequency, specific criteria for each category, and family and phenotypic data. A selection of candidate variants underwent functional validation using diverse approaches. Results Isoform-level re-quantification of retinal gene expression revealed 76 IRD genes with a non-canonical retina-enriched isoform, of which 20 display a fully distinct 5’UTR compared to that of their canonical isoform. Depending on the probe design, 3–20% of IRD genes have 5’UTRs fully captured by WES. After analyzing these regions in both cohorts, we prioritized 11 (likely) pathogenic variants in 10 genes (ARL3, MERTK, NDP, NMNAT1, NPHP4, PAX6, PRPF31, PRPF4, RDH12, RD3), of which 7 were novel. Functional analyses further supported the pathogenicity of three variants. Mis-splicing was demonstrated for the PRPF31:c.-9+1G>T variant. The MERTK:c.-125G>A variant, overlapping a transcriptional start site, was shown to significantly reduce both luciferase mRNA levels and activity. The RDH12:c.-123C>T variant was found in cis with the hypomorphic RDH12:c.701G>A (p.Arg234His) variant in 11 patients. This 5’UTR variant, predicted to introduce an upstream open reading frame, was shown to result in reduced RDH12 protein but unaltered mRNA levels. Conclusions This study demonstrates the importance of 5’UTR variants implicated in IRDs and provides a systematic approach for 5’UTR annotation and validation that is applicable to other inherited diseases.

In this article, we study the distance matrix as a representation of a phylogeny by way of hierarchical clustering. By defining a multivariate normal distribution on (a subset of) the entries in a matrix, this allows us to represent a distribution over rooted time trees. Here, we demonstrate tree distributions can be represented accurately this way for a number of published tree distributions. Though such a representation does not map to unique trees, restriction to a subspace, in particular one we call a “cube”, makes the representation bijective at the cost of not being able to represent all possible trees. We introduce an algorithm “cubeVB” specifically for cubes and show through well calibrated simulation study that it is possible to recover parameters of interest like tree height and length. Although a cube cannot represent all of tree space, it is a great improvement over a single summary tree, and it opens up exciting new opportunities for scaling up Bayesian phylogenetic inference. We also demonstrate how to use a matrix representation of a tree distribution to get better summary trees than commonly used maximum clade credibility trees. An open source implementation of the cubeVB algorithm is available from https://github.com/rbouckaert/cubevb as the cubevb package for BEAST 2.

Obstructive sleep apnoea (OSA) can occur in both rapid eye movement (REM) and non-REM sleep or be limited to REM sleep, when the upper airway is most prone to collapse due to REM sleep atonia. Respiratory events are usually longer and more desaturating in REM than in NREM sleep. The prevalence of REM OSA is higher in women than in men and REM OSA usually occurs in the context of mild–moderate OSA based on the apnoea–hypopnoea index calculated for the entire sleep study. Studies have highlighted some detrimental consequences of REM OSA; for example, its frequent association with systemic hypertension and a degree of excessive daytime sleepiness similar to that found in nonsleep-stage-dependent OSA. Moreover, REM OSA could increase cardiometabolic risk. Continuous positive airway pressure (CPAP) treatment aimed at preventing REM OSA should be longer than the 4 h usually considered as good compliance, since REM sleep occurs mostly during the second half of the night. Unfortunately, patients with REM OSA show poor adherence to CPAP. Alternative non-CPAP treatments might be a good choice for REM OSA, but data are lacking. This review summarises the available data on REM OSA and critically examines the weaknesses and strengths of existing literature.

Abstract Background This study investigated the perspectives of primary care professionals, in particular general practitioners, registered nurses, physiotherapists and occupational therapists, on inter-professional collaboration, the barriers and the facilitators they perceive in the care of the frail older population. Methods We conducted a qualitative study. In-depth interviews with healthcare professionals were performed, using open-ended questions about their perceptions on the care of frail older adults and inter-professional collaboration. Data was analyzed following the Basic Logical Model of Abduction and Creswell’s coding method. Results Healthcare professionals indicated that when they explored problems complementary to the reasons for older people to contact a healthcare professional, these additional problems often seemed to be the main problem. They also stated that there was too little inter-professional collaboration in the care of complex chronic issues and lack of a shared vision on collaboration. Collaboration is still limited too much to contacting established professions. Health information technology can support both, inter-professional collaboration and working on an evidence-based manner. It can also be a facilitator to inform patients. The availability and use of health information technology differs between the professions. Success factors and barriers for sustainable collaboration were identified on several levels, namely innovation, individual, professional, patient, social context, context of the organization, economic and political context. Conclusions Our study shed light on the willingness and barriers in collaboration of healthcare professionals in primary care for older adults. There is little inter-professional collaboration, despite the willingness of the healthcare professionals to collaborate.