Down syndrome (DS) is the most prevalent genetic cause of intellectual disability, resulting from trisomy 21. Recently, positron emission tomography (PET) imaging has been used to image synapses in ...vivo. The motivation for this pilot study was to investigate whether synaptic density in low functioning adults with DS can be evaluated using the PET radiotracer
CUCB-J. Data were acquired from low functioning adults with DS (n = 4) and older neurotypical (NT) adults (n = 37). Motion during the scans required the use of a 10-minute acquisition window for the calculation of synaptic density using SUVR
which was determined to be a suitable approximation for specific binding in this analysis using dynamic data from the NT group. Of the regions analyzed a large effect was observed when comparing DS and NT hippocampus and cerebral cortex synaptic density as well as hippocampus and cerebellum volumes. In this pilot study, PET imaging of
CUCB-J was successfully completed and synaptic density measured in low functioning DS adults. This work provides the basis for studies where synaptic density may be compared between larger groups of NT adults and adults with DS who have varying degrees of baseline cognitive status.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Alternative splicing is often subjected to complex regulatory control that involves many protein factors and cis-acting RNA sequence elements. One major challenge is to identify all of the protein ...players and define how they control alternative expression of a particular exon in a combinatorial manner. The Muscleblind-like (MBNL) and CUG-BP and ELAV-Like family (CELF) proteins are splicing regulatory proteins, which function as antagonists in the regulation of several alternative exons. Currently only a limited number of common targets of MBNL and CELF are known that are antagonistically regulated by these two groups of proteins.
Recently, we identified neurofibromatosis type 1 (NF1) exon 23a as a novel target of negative regulation by CELF proteins. Here we report that MBNL family members are positive regulators of this exon. Overexpression of MBNL proteins promote exon 23a inclusion in a low MBNL-expressing cell line, and simultaneous siRNA-mediated knockdown of MBNL1 and MBNL2 family members in a high MBNL-expressing cell line promotes exon 23a skipping. Importantly, these two groups of proteins antagonize each other in regulating inclusion of exon 23a. Furthermore, we analyzed the binding sites of these proteins in the intronic sequences upstream of exon 23a by UV cross-linking assays. We show that in vitro, in addition to the previously identified preferred binding sequence UGCUGU, the MBNL proteins need the neighboring sequences for optimal binding.
This study along with our previous work that demonstrated roles for Hu, CELF, and TIA-1 and TIAR proteins in the regulation of NF1 exon 23a establish that this exon is under tight, complex control.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Higher engagement in moderate-intensity physical activity (PA) is related to better cognitive functioning in neurotypical adults; however, little is known about the effect of PA on cognitive aging in ...adults with Down syndrome (DS). Individuals with DS have three copies of chromosome 21, which includes the gene involved in the production of the amyloid precursor protein, resulting in an increased risk for an earlier onset of Alzheimer's disease (AD). The goal of this study was to understand the relationship between engagement in moderate PA, memory, and hippocampal volume in adults with DS. Adults with DS participated in an ancillary Lifestyle study linked to the Alzheimer's Biomarkers Consortium for DS (ABC- DS;
= 71). A within-sample z-score memory composite was created from performance on the Cued Recall Test (CRT) and the Rivermead Picture Recognition Test. Participants wore a wrist-worn accelerometer (GT9X) to measure PA. Variables of interest included the average percentage of time spent in moderate PA and average daily steps. Structural MRI data were acquired within 18 months of actigraphy/cognitive data collection for a subset of participants (
= 54). Hippocampal volume was extracted using Freesurfer v5.3. Associations between moderate PA engagement, memory, and hippocampal volume were evaluated with hierarchical linear regressions controlling for relevant covariates age, body mass index, intellectual disability level, sex, and intracranial volume. Participants were 37.77 years old (SD = 8.21) and were 55.6% female. They spent 11.1% of their time engaged in moderate PA (SD = 7.5%) and took an average of 12,096.51 daily steps (SD = 4,315.66). After controlling for relevant covariates, higher memory composite score was associated with greater moderate PA engagement (
= 0.232,
= 0.027) and more daily steps (
= 0.209,
= 0.037). In a subset of participants, after controlling for relevant covariates, PA variables were not significantly associated with the hippocampal volume (all
-values ≥ 0.42). Greater hippocampal volume was associated with higher memory composite score after controlling for relevant covariates (
= 0.316,
= 0.017). More PA engagement was related to better memory function in adults with DS. While greater hippocampal volume was related to better memory performance, it was not associated with PA. Greater PA engagement may be a promising lifestyle behavior to preserve memory in adults with DS.
Palliative care in low- or middle-income country (LMIC) humanitarian settings is a new area, experiencing a degree of increased momentum over recent years. The review contributes to this growing body ...of knowledge, in addition to identifying gaps for future research. The overall aim is to systematically explore the evidence on palliative care needs of patients and/or their families in LMIC humanitarian settings.
Arksey and O'Malley's (Int J Soc Res Methodol. 8:19-32, 2005) scoping review framework forms the basis of the study design, following further guidance from Levac et al. (Implement Sci 5:1-9, 2010), the Joanna Briggs Institute (JBI) Peters et al. (JBI Reviewer's Manual JBI: 406-452, 2020), and the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) from Tricco et al. (Ann Intern Med 169:467-73, 2018). This incorporates a five-step approach and the population, concept, and context (PCC) framework. Using already identified key words/terms, searches for both published research and gray literature from January 2012 to October 2022 will be undertaken using databases (likely to include Cumulative Index of Nursing and Allied Health (CINAHL), MEDLINE, Embase, Global Health, Scopus, Applied Social Science Index and Abstracts (ASSIA), Web of Science, Policy Commons, JSTOR, Library Network International Monetary Fund and World Bank, Google Advanced Search, and Google Scholar) in addition to selected pre-print sites and websites. Data selection will be undertaken based on the inclusion and exclusion criteria and will be reviewed at each stage by two reviewers, with a third to resolve any differences. Extracted data will be charted in a table. Ethical approval is not required for this review.
Findings will be presented in tables and diagrams/charts, followed by a narrative description. The review will run from late October 2022 to early 2023. This is the first systematic scoping review specifically exploring the palliative care needs of patients and/or their family, in LMIC humanitarian settings. The paper from the review findings will be submitted for publication in 2023.
Context: Population ageing and projections that more people will die in care homes demand that care home staff are prepared for advance care planning (ACP). This is an update of a prior review, ...published in 2021, of ACP education interventions for healthcare professionals in care homes. Objective: We sought to address the questions: (1) What ACP education interventions exist for care home staff? and (2) How effective are these interventions? Method: The review adheres to PRISMA; PROSPERO (ID: CRD42022337865). Original research evaluating ACP education for care home staff, reporting any measurable outcome of effectiveness, was included. Extensive literature searches were performed from March 2018 to June 2022. The results were reported by narrative synthesis. Findings: We identified 10 studies (310 care homes), from the UK, Belgium, Norway and Canada. Major sources of heterogeneity between studies include intervention design, target population and outcome measure. More recent interventions target the wider multi-disciplinary team. There is a trend towards the adoption of more resident/family and staff-related outcomes. There was insufficient evidence to draw conclusions about the effectiveness of ACP education interventions. Limitations: Heterogeneity of the primary studies did not allow for meta-analysis. Implications: There is still insufficient data to determine the effectiveness of ACP education interventions for care home staff. Future researchers should aim to agree on outcomes that are specific to ACP education interventions for care home staff and develop standardised, validated outcome measures. Study design should consider an intervention’s ‘theory of change’ when considering outcomes.
Background
Adults with intellectual and developmental disabilities and their families have high need for support services. This study assessed resource utilization among caregivers of intellectual ...and developmental disabilities and other conditions.
Methods
We assessed 366 caregivers of adults with intellectual and developmental disabilities, dementia or other conditions Regressions assessed group differences in number of agency contacts and frequency of service use. A secondary analysis assessed reasons for underutilization of services.
Results
Caregivers of individuals with dementia contacted twice as many agencies as other caregivers and were more likely to report using suggested services. Agency contact and service utilization were similar among caregivers of adults with intellectual and developmental disabilities compared to other caregivers. Caregivers of adults with intellectual and developmental indicated that suggested services were unavailable to them.
Conclusion
The findings of this study shed light on challenges with access to and utilization of support services.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Adults with Down syndrome are at a high risk for disordered sleep. These sleep problems could have marked effects on aging and Alzheimer's disease, potentially altering white matter integrity. This ...study examined the associations between disordered sleep assessed via an actigraph accelerometer worn on 7 consecutive nights, presence of diagnosis of obstructive sleep apnea, and diffusion tensor imaging indices of white matter integrity in 29 non-demented adults with Down Syndrome (48% female, aged 33-54 years). Average total sleep time was associated with lower mean diffusivity in the left superior longitudinal fasciculus (
= -0.398,
= 0.040). Average sleep efficiency, length of awakenings, and movement index were related to fractional anisotropy in the right inferior longitudinal fasciculus (
= -0.614 to 0.387,
≤ 0.050). Diagnosis of obstructive sleep apnea was associated with fractional anisotropy in the right inferior longitudinal fasciculus (
= -0.373,
= 0.050). Findings suggest that more disrupted sleep is associated with lower white matter integrity in the major association tracts in middle-aged adults with Down syndrome. Longitudinal work is needed to confirm the directionally of associations. Sleep interventions could be an important component for promoting optimal brain aging in the Down syndrome population.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Expropriating Privacy Maxwell, Ferg; Fleming, Victoria
Persona Studies,
02/2023, Volume:
8, Issue:
2
Journal Article
Peer reviewed
During the winter of 2020, Toronto resident Khaleel Seivwright, began to construct small mobile shelters to provide insulation and privacy to unhoused residents living outdoors. Conditions produced ...by the COVID-19 pandemic increased demand on the city’s already underfunded and strained shelter system, subsequently accelerating development of encampments in parks throughout the city. From the outset, these “tiny shelters” served as a flashpoint in public discourse on the question of the relative health, safety, and beauty of unhoused privacy. Drawing on media coverage of Seivwright’s case, we address the question of the private persona as it emerges in relation to the unhoused, and to the practices of violent expropriation which daily police their existence. By examining the news discourses produced about Sievwrights tiny shelters, we interrogate how Sievwright’s public persona came to represent encampment residents as well as himself subsequently emerging as a boundary subject mediating the contradictory relations immanent to domesticity: between public and private space and public and private identity. Our analysis asks how the limits of privacy are actively imposed and managed under capitalism: who is allowed to have domestic space, where is that domestic space allowed to exist, and crucially what public personas emerge in relation to practices departing from the normative bounds of capitalism’s public/private distinction? Using critical discourse analysis (CDA), we examine the ways in which public personas are mediated by individuals and media institutions at the same time as addressing how personas themselves intervene in this process. CDA directs us to ask how personas are constituted through language. This emphasis on persona as both outcome of relations of power and as mediator in its own right permits us to address figures who are conventionally denied personas while simultaneously complicating and challenging the meanings behind domesticity within capitalist cities.
Expropriating Privacy Victoria Fleming; Fergus Maxwell
Persona Studies,
02/2023, Volume:
8, Issue:
2
Journal Article
Peer reviewed
Open access
During the winter of 2020, Toronto resident Khaleel Seivwright, began to construct small mobile shelters to provide insulation and privacy to unhoused residents living outdoors. Conditions produced ...by the COVID-19 pandemic increased demand on the city’s already underfunded and strained shelter system, subsequently accelerating development of encampments in parks throughout the city. From the outset, these “tiny shelters” served as a flashpoint in public discourse on the question of the relative health, safety, and beauty of unhoused privacy. Drawing on media coverage of Seivwright’s case, we address the question of the private persona as it emerges in relation to the unhoused, and to the practices of violent expropriation which daily police their existence. By examining the news discourses produced about Sievwrights tiny shelters, we interrogate how Sievwright’s public persona came to represent encampment residents as well as himself subsequently emerging as a boundary subject mediating the contradictory relations immanent to domesticity: between public and private space and public and private identity. Our analysis asks how the limits of privacy are actively imposed and managed under capitalism: who is allowed to have domestic space, where is that domestic space allowed to exist, and crucially what public personas emerge in relation to practices departing from the normative bounds of capitalism’s public/private distinction? Using critical discourse analysis (CDA), we examine the ways in which public personas are mediated by individuals and media institutions at the same time as addressing how personas themselves intervene in this process. CDA directs us to ask how personas are constituted through language. This emphasis on persona as both outcome of relations of power and as mediator in its own right permits us to address figures who are conventionally denied personas while simultaneously complicating and challenging the meanings behind domesticity within capitalist cities.
Chronic or persistent pain affects one's ability to work or be productive at work, generating high societal and economic burden. However, the provision of work-related advice and support for people ...with chronic pain is variable or lacking. The Pain-at-Work (PAW) Toolkit was cocreated with people who live with pain, health care professionals, and employers. It aims to increase knowledge about employee rights and how to access support for managing a painful chronic condition in the workplace and provides advice on lifestyle behaviors that facilitate the management of chronic pain.
We aimed to establish the feasibility of conducting a definitive cluster randomized controlled trial comparing access to the PAW Toolkit and telephone support calls from an occupational therapist (PAW) with treatment as usual (ie, standard support from their employer). Our primary outcomes are establishing parameters of feasibility, acceptability, usability, and safety of this digital workplace health intervention. We will assess the candidate primary and secondary outcomes' feasibility and test research processes for a definitive trial.
This is an open-label, parallel 2-arm pragmatic feasibility cluster randomized controlled trial with exploratory health economics analysis and a nested qualitative interview study. We aim to recruit 120 participants from at least 8 workplace clusters (any type, >10 employees) in England. The recruitment of workplaces occurs via personal approach, and the recruitment of individual participants is web based. Eligible participants are vocationally active adults aged ≥18 years with internet access and self-reporting chronic pain interfering with their ability to undertake or enjoy productive work. A restricted 1:1 cluster-level randomization is used to allocate employment settings to PAW or treatment as usual; participants are unblinded to group allocation. Following site- and individual-level consent, participants complete a web-based baseline survey (time 0), including measures of work capacity, health and well-being, and health care resource use. Follow-up is performed at 3 months (time 1) and 6 months (time 2). Feasibility outcomes relate to recruitment; intervention fidelity (eg, delivery, reach, uptake, and engagement); retention; and follow-up. Qualitative evaluation (time 2) is mapped to the Capability, Opportunity, Motivation-Behavior model and will explore intervention acceptability to employees and employers, along with individual and contextual factors influencing the delivery and uptake of the intervention.
Ethics approval was obtained in March 2023. Trial recruitment began in June 2023.
The PAW Toolkit is the first evidence-based digital health intervention aimed at supporting the self-management of chronic or persistent pain at work. This study will inform the design of a definitive trial, including sample size estimation, approaches to cluster site identification, primary and secondary outcomes' selection, and the final health economic model. Findings will inform approaches for the future delivery of this digital health intervention.
ClinicalTrials.gov NCT05838677; https://clinicaltrials.gov/study/NCT05838677.
DERR1-10.2196/51474.
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