RNA-binding proteins balance brain function in health and disease.

Posttranscriptional gene expression including splicing, RNA transport, translation, and RNA decay provides an important regulatory layer in many if not all molecular pathways. Research in the last decades has positioned RNA-binding proteins (RBPs) right in the center of posttranscriptional gene regulation. Here, we propose interdependent networks of RBPs to regulate complex pathways within the central nervous system (CNS). These are involved in multiple aspects of neuronal development and functioning, including higher cognition. Therefore, it is not sufficient to unravel the individual contribution of a single RBP and its consequences but rather to study and understand the tight interplay between different RBPs. In this review, we summarize recent findings in the field of RBP biology and discuss the complex interplay between different RBPs. Second, we emphasize the underlying dynamics within an RBP network and how this might regulate key processes such as neurogenesis, synaptic transmission, and synaptic plasticity. Importantly, we envision that dysfunction of specific RBPs could lead to perturbation within the RBP network. This would have direct and indirect (compensatory) effects in mRNA binding and translational control leading to global changes in cellular expression programs in general and in synaptic plasticity in particular. Therefore, we focus on RBP dysfunction and how this might cause neuropsychiatric and neurodegenerative disorders. Based on recent findings, we propose that alterations in the entire regulatory RBP network might account for phenotypic dysfunctions observed in complex diseases including neurodegeneration, epilepsy, and autism spectrum disorders.

People with disability and privacy in precision medicine research: what's at stake?

Re-identification from data used in precision medicine research is presumed to create minimal risk but may disproportionately impact health disparity populations. We consider plausible privacy risks and the negative ramifications thereof for people with disabilities, the largest health disparity population in the USA, and suggest measures to address these concerns.

Neurodevelopmental Outcomes for Individuals With Congenital Heart Disease: Updates in Neuroprotection, Risk-Stratification, Evaluation, and Management: A Scientific Statement From the American Heart Association.

Over the past decade, new research has advanced scientific knowledge of neurodevelopmental trajectories, factors that increase neurodevelopmental risk, and neuroprotective strategies for individuals with congenital heart disease. In addition, best practices for evaluation and management of developmental delays and disorders in this high-risk patient population have been formulated based on literature review and expert consensus. This American Heart Association scientific statement serves as an update to the 2012 statement on the evaluation and management of neurodevelopmental outcomes in children with congenital heart disease. It includes revised risk categories for developmental delay or disorder and an updated list of factors that increase neurodevelopmental risk in individuals with congenital heart disease according to current evidence, including genetic predisposition, fetal and perinatal factors, surgical and perioperative factors, socioeconomic disadvantage, and parental psychological distress. It also includes an updated algorithm for referral, evaluation, and management of individuals at high risk. Risk stratification of individuals with congenital heart disease with the updated categories and risk factors will identify a large and growing population of survivors at high risk for developmental delay or disorder and associated impacts across the life span. Critical next steps must include efforts to prevent and mitigate developmental delays and disorders. The goal of this scientific statement is to inform health care professionals caring for patients with congenital heart disease and other key stakeholders about the current state of knowledge of neurodevelopmental outcomes for individuals with congenital heart disease and best practices for neuroprotection, risk stratification, evaluation, and management.

Retrospective review of the code status of individuals with Down syndrome during the COVID-19 era.

Code status is a label in the medical record indicating a patient's wishes for end-of-life (EOL) care in the event of a cardiopulmonary arrest. People with intellectual disabilities had a higher risk of both diagnosis and mortality from coronavirus infections (COVID-19) than the general population. Clinicians and disability advocates raised concerns that bias, diagnostic overshadowing, and ableism could impact the allocation of code status and treatment options, for patients with intellectual disabilities, including Down syndrome (DS). To study this, retrospective claims data from the Vizient® Clinical Data Base (used with permission of Vizient, all rights reserved.) of inpatient encounters with pneumonia (PNA) and/or COVID-19 at 825 hospitals from January 2019 to June 2022 were included. Claims data was analyzed for risk of mortality and risk of "Do Not Resuscitate" (DNR) status upon admission, considering patient age, admission source, Elixhauser comorbidities (excluding behavioral health), and DS. Logistic regression models with backward selection were created. In total, 1,739,549 inpatient encounters with diagnoses of COVID-19, PNA, or both were included. After controlling for other risk factors, a person with a diagnosis of DS and a diagnosis of COVID-19 PNA had 6.321 odds ratio of having a DNR status ordered at admission to the hospital compared with those with COVID-19 PNA without DS. The diagnosis of DS had the strongest association with DNR status after controlling for other risk factors. Open and honest discussions among healthcare professionals to foster equitable approaches to EOL care and code status are needed.

De novo and bi-allelic variants in AP1G1 cause neurodevelopmental disorder with developmental delay, intellectual disability, and epilepsy.

Adaptor protein (AP) complexes mediate selective intracellular vesicular trafficking and polarized localization of somatodendritic proteins in neurons. Disease-causing alleles of various subunits of AP complexes have been implicated in several heritable human disorders, including intellectual disabilities (IDs). Here, we report two bi-allelic (c.737C>A [p.Pro246His] and c.1105A>G [p.Met369Val]) and eight de novo heterozygous variants (c.44G>A [p.Arg15Gln], c.103C>T [p.Arg35Trp], c.104G>A [p.Arg35Gln], c.229delC [p.Gln77Lys∗11], c.399_400del [p.Glu133Aspfs∗37], c.747G>T [p.Gln249His], c.928-2A>C [p.?], and c.2459C>G [p.Pro820Arg]) in AP1G1, encoding gamma-1 subunit of adaptor-related protein complex 1 (AP1γ1), associated with a neurodevelopmental disorder (NDD) characterized by mild to severe ID, epilepsy, and developmental delay in eleven families from different ethnicities. The AP1γ1-mediated adaptor complex is essential for the formation of clathrin-coated intracellular vesicles. In silico analysis and 3D protein modeling simulation predicted alteration of AP1γ1 protein folding for missense variants, which was consistent with the observed altered AP1γ1 levels in heterologous cells. Functional studies of the recessively inherited missense variants revealed no apparent impact on the interaction of AP1γ1 with other subunits of the AP-1 complex but rather showed to affect the endosome recycling pathway. Knocking out ap1g1 in zebrafish leads to severe morphological defect and lethality, which was significantly rescued by injection of wild-type AP1G1 mRNA and not by transcripts encoding the missense variants. Furthermore, microinjection of mRNAs with de novo missense variants in wild-type zebrafish resulted in severe developmental abnormalities and increased lethality. We conclude that de novo and bi-allelic variants in AP1G1 are associated with neurodevelopmental disorder in diverse populations.

Strategies for addressing the needs of children with or at risk of developmental disabilities in early childhood by 2030: a systematic umbrella review.

BACKGROUND: There are over 53million children worldwide under five with developmental disabilities who require effective interventions to support their health and well-being. However, challenges in delivering interventions persist due to various barriers, particularly in low-income and middle-income countries. METHODS: We conducted a global systematic umbrella review to assess the evidence on prevention, early detection and rehabilitation interventions for child functioning outcomes related to developmental disabilities in children under 5 years. We focused on prevalent disabilities worldwide and identified evidence-based interventions. We searched Medline, Embase, PsychINFO, and Cochrane Library for relevant literature from 1st January 2013 to 14th April 2023. A narrative synthesis approach was used to summarise the findings of the included meta-analyses. The results were presented descriptively, including study characteristics, interventions assessed, and outcomes reported. Further, as part of a secondary analysis, we presented the global prevalence of each disability in 2019 from the Global Burden of Disease study, identified the regions with the highest burden and the top ten affected countries. This study is registered with PROSPERO, number CRD42023420099. RESULTS: We included 18 reviews from 883 citations, which included 1,273,444 children under five with or at risk of developmental disabilities from 251 studies across 30 countries. The conditions with adequate data were cerebral palsy, hearing loss, cognitive impairment, autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder. ASD was the most prevalent target disability (n = 8 reviews, 44%). Most reviews (n = 12, 67%) evaluated early interventions to support behavioural functioning and motor impairment. Only 33% (n = 10/30) of studies in the reviews were from middle-income countries, with no studies from low-income countries. Regarding quality, half of reviews were scored as high confidence (n = 9/18, 50%), seven as moderate (39%) and two (11%) as low. CONCLUSIONS: We identified geographical and disability-related inequities. There is a lack of evidence from outside high-income settings. The study underscores gaps in evidence concerning prevention, identification and intervention, revealing a stark mismatch between the available evidence base and the regions experiencing the highest prevalence rates of developmental disabilities.

Disparities in Breast Cancer Screening Rates Among Adults With and Without Intellectual and Developmental Disabilities.

BACKGROUND: Individuals with intellectual and developmental disabilities may face barriers in accessing healthcare, including cancer screening and detection services. We sought to assess the association of intellectual and developmental disabilities (IDD) with breast cancer screening rates. METHODS: Data from 2018 to 2020 was used to identify screening-eligible individuals from Medicare Standard Analytic Files. Adults aged 65-79 years who did not have a previous diagnosis of breast cancer were included. Multivariable regression was used to analyze the differences in breast cancer screening rates among individuals with and without IDD. RESULTS: Among 9,383,349 Medicare beneficiaries, 11,265 (0.1%) individuals met the criteria for IDD. Of note, individuals with IDD were more likely to be non-Hispanic White (90.5% vs. 87.3%), have a Charlson Comorbidity Index score ≤ 2 (66.2% vs. 85.5%), and reside in a low social vulnerability index neighborhood (35.7% vs. 34.4%). IDD was associated with reduced odds of undergoing breast cancer screening (odds ratio (OR) 0.77, 95% confidence interval (CI) 0.74-0.80; p < 0.001). Breast cancer screening rates in individuals with IDD were further influenced by social vulnerability and belonging to a racial/ethnic minority. CONCLUSIONS: Individuals with IDD may face additional barriers to breast cancer screening. The combination of IDD and social vulnerability placed patients at particularly high risk of not being screened for breast cancer.

Home and Community-Based Services: A Systematic Review and Evidence Map.

BACKGROUND: Many adults aged 60 years or older have functional limitations and require home and community-based services (HCBS) to support their independence and delay the transition to an institutionalized setting. This systematic review provides an evidence map of the existing literature on HCBS identifying evidence gaps for policy and research. METHODS: A comprehensive literature search of multiple databases including Medline, Embase, and Scopus was conducted through December 7, 2023. Interviews with various stakeholders were conducted to solicit additional perspectives. Narrative and thematic synthesis was conducted to evaluate HCBS in terms of populations, interventions, outcomes, person-centeredness, and relevant quality measures. RESULTS: We identified 27 primary studies and 29 quality measures. Populations of HCBS studies can be categorized as those with functional disability, cognitive impairment, high-risk/frail conditions, and disease-specific conditions (Parkinson's disease, Alzheimer's disease, and post-stroke). HCBS interventions targeted optimization of person-centered planning, nonpharmacological approaches for dementia care, physical rehabilitation, self-directed home care, geriatric resources for practical support at home, and interdisciplinary care coordination for high-risk conditions. Person-centered planning and self-direction of HCBS services were not explicitly described in many studies and very few studies focused on addressing health-related social needs, whereas the majority reported primary clinical outcomes. Numerous quality measures exist for HCBS, some of which were validated, addressed multiple person-centered domains, and may apply across various conditions and populations. Key challenges in the literature on HCBS include limited number of randomized trials, inadequate descriptions of interventions to determine person-centeredness, limited information on facilitators and barriers, and limited information on workforce challenges in recruiting, retaining, and training personnel delivering HCBS. DISCUSSION: This evidence map describes the current state of HCBS and identifies evidence gaps for future research and policy decisions.

Participation in Special Olympics reduces the rate for developing diabetes in adults with intellectual and developmental disabilities.

AIM: Adults with intellectual and developmental disabilities (IDD) have a significantly higher prevalence of Type 2 diabetes than the general population. Evidence that lifestyle and/or behavioural interventions, such as participation in Special Olympics, decreases the risk of developing diabetes in adults with IDD could help minimize health disparities and promote overall health in this population. METHODS: This was a 20-year retrospective cohort study of adults with IDD (30-39 years) in the province of Ontario, Canada, that compared hazard rates of diabetes among Special Olympics participants (n = 4145) to non-participants (n = 31,009) using administrative health databases housed at ICES. Using cox proportional hazard models, crude and adjusted hazard ratios were calculated for the association between the primary independent variable (Special Olympics participation status) and the dependent variable (incident diabetes cases). RESULTS: After controlling for other variables, the hazard ratio comparing rates for developing diabetes between Special Olympics participants and non-participants was 0.85. This represents a 15% reduction in the hazard among Special Olympics participants when followed for up to 20 years. This result was statistically significant and represents a small effect size. CONCLUSIONS: Special Olympics could be considered a complex intervention that promotes physical activity engagement through sport participation, health screenings, and the promotion of healthy eating habits through educational initiatives. This study provides evidence that Special Olympics participation decreases the rate for developing diabetes.

Reproductive healthcare in adolescents with autism and other developmental disabilities.

BACKGROUND: Adults with developmental disabilities often have less access to reproductive health services than adults without these disabilities. However, little is known about how adolescents with developmental disabilities, including autism, access reproductive healthcare. OBJECTIVE: We aimed to characterize the use of reproductive healthcare services among adolescents with autism and those with other developmental disabilities in comparison with adolescents with typical development. STUDY DESIGN: We conducted a cohort study of a sample of adolescents who were continuously enrolled members of Kaiser Permanente Northern California, an integrated healthcare system, from ages 14 to 18 years. The final analytical sample included 700 adolescents with autism, 836 adolescents with other developmental disabilities, and 2187 typically developing adolescents who sought care between 2000 and 2017. Using the electronic health record, we obtained information on menstrual conditions, the use of obstetrical-gynecologic care, and prescriptions of hormonal contraception. We compared healthcare use between the groups using chi-square tests and covariate-adjusted risk ratios estimated using modified Poisson regression. RESULTS: Adolescents with autism and those with other developmental disabilities were significantly more likely to have diagnoses of menstrual disorders, polycystic ovary syndrome, and premenstrual syndrome than typically developing adolescents. These 2 groups also were less likely than typically developing peers to visit the obstetrician-gynecologist or to use any form of hormonal contraception, including oral contraception, hormonal implants, and intrauterine devices. Adolescents in all 3 groups accessed hormonal contraception most frequently through their primary care provider, followed by an obstetrician-gynecologist. CONCLUSION: Adolescents with autism and those with other developmental disabilities are less likely than their typically developing peers to visit the obstetrician-gynecologist and to use hormonal contraception, suggesting possible care disparities that may persist into adulthood. Efforts to improve access to reproductive healthcare in these populations should target care delivered in both the pediatric and obstetrics-gynecology settings.

Diverse learners: learning disabilities and quality of life following mind-body and health education interventions for adults with neurofibromatosis.

PURPOSE: Neurofibromatosis (NF) is associated with low quality-of-life (QoL). Learning disabilities are prevalent among those with NF, further worsening QoL and potentially impacting benefits from mind-body and educational interventions, yet research on this population is scarce. Here, we address this gap by comparing NF patients with and without learning disabilities on QoL at baseline and QoL-related gains following two interventions. METHODS: Secondary analysis of a fully-powered RCT of a mind-body program (Relaxation Response Resiliency Program for NF; 3RP-NF) versus an educational program (Health Enhancement Program for NF; HEP-NF) among 228 adults with NF. Participants reported QoL in four domains (Physical Health, Psychological, Social Relationships, and Environmental). We compare data at baseline, post-treatment, and 12-month follow-up, controlling for intervention type. RESULTS: At baseline, individuals with NF and learning disabilities had lower Psychological (T = -3.0, p = .001) and Environmental (T = -3.8, p < .001) QoL compared to those without learning disabilities. Both programs significantly improved all QoL domains (ps < .0001-0.002) from baseline to post-treatment, regardless of learning disability status. However, those with learning disabilities exceeded the minimal clinically important difference in only one domain (Psychological QoL) compared to three domains in individuals without learning disabilities. Moreover, those with learning disabilities failed to sustain statistically significant gains in Psychological QoL at 12-months, while those without learning disabilities sustained all gains. CONCLUSION: Adults with NF and learning disabilities have lower Psychological and Environmental QoL. While interventions show promise in improving QoL regardless of learning disabilities, additional measures may bolster clinical benefit and sustainability among those with learning disabilities.

Developmental surveillance and screening practices in a pediatric oncology clinic: Initial progress of a quality improvement study.

BACKGROUND: Pediatric cancer patients' oncology teams regularly take on a primary care role, but due to the urgent nature of cancer treatment, developmental screenings may be deprioritized. This leaves patients at risk of developmental diagnoses and referrals being delayed. AIMS: Clarify the current developmental surveillance and screening practices of one pediatric oncology team. MATERIALS AND METHODS: Researchers reviewed charts for patients (n = 66) seen at a pediatric oncology clinic in a suburban academic medical center to determine engagement in developmental screening (including functioning around related areas such as speech, neurocognition, etc.) and referrals for care in these areas. RESULTS: Developmental histories were collected from all patients through admission history and physical examination (H&P), but there was no routinized follow-up. Physicians did not conduct regular developmental screening per American Academy of Pediatrics guidelines for any patients but identified n = 3 patients with needs while the psychology team routinely surveilled all patients seen during this time (n = 41) and identified n = 18 patients as having delays. DISCUSSION: Physicians did not routinely screen for development needs beyond H&P and were inconsistent in developmental follow-up/referrals. Integrated psychologists were key in generating referrals for developmental-based care. However, many oncology patients were not seen by psychologists quickly or at all, creating a significant gap in care during a crucial developmental period. CONCLUSION: The case is made for further routinization of ongoing developmental screening in pediatric oncology care.

Neurocognitive mechanisms of co-occurring math difficulties in dyslexia: Differences in executive function and visuospatial processing.

Children with dyslexia frequently also struggle with math. However, studies of reading disability (RD) rarely assess math skill, and the neurocognitive mechanisms underlying co-occurring reading and math disability (RD+MD) are not clear. The current study aimed to identify behavioral and neurocognitive factors associated with co-occurring MD among 86 children with RD. Within this sample, 43% had co-occurring RD+MD and 22% demonstrated a possible vulnerability in math, while 35% had no math difficulties (RD-Only). We investigated whether RD-Only and RD+MD students differed behaviorally in their phonological awareness, reading skills, or executive functions, as well as in the brain mechanisms underlying word reading and visuospatial working memory using functional magnetic resonance imaging (fMRI). The RD+MD group did not differ from RD-Only on behavioral or brain measures of phonological awareness related to speech or print. However, the RD+MD group demonstrated significantly worse working memory and processing speed performance than the RD-Only group. The RD+MD group also exhibited reduced brain activations for visuospatial working memory relative to RD-Only. Exploratory brain-behavior correlations along a broad spectrum of math ability revealed that stronger math skills were associated with greater activation in bilateral visual cortex. These converging neuro-behavioral findings suggest that poor executive functions in general, including differences in visuospatial working memory, are specifically associated with co-occurring MD in the context of RD. RESEARCH HIGHLIGHTS: Children with reading disabilities (RD) frequently have a co-occurring math disability (MD), but the mechanisms behind this high comorbidity are not well understood. We examined differences in phonological awareness, reading skills, and executive function between children with RD only versus co-occurring RD+MD using behavioral and fMRI measures. Children with RD only versus RD+MD did not differ in their phonological processing, either behaviorally or in the brain. RD+MD was associated with additional behavioral difficulties in working memory, and reduced visual cortex activation during a visuospatial working memory task.

Inclusion of people with disabilities in Chilean health policy: a policy analysis.

BACKGROUND: Around 18% of the population in Chile has disabilities. Evidence shows that this population has greater healthcare needs, yet they face barriers to accessing healthcare due to health system failures. This paper aims to assess the inclusion of people with disabilities in health policy documents and to explore the perceptions of key national stakeholders regarding the policy context, policy processes, and actors involved. METHODS: A policy content analysis was conducted of 12 health policy documents using the EquiFrame framework, adapted to assess disability inclusion. Documents were reviewed and rated on their quality of commitment against 21 core concepts of human rights in the framework. Key national stakeholders (n = 15) were interviewed, and data were thematically analysed under the Walt and Gilson Policy Analysis Triangle, using NVivo R1. RESULTS: Core human rights concepts of disability were mentioned at least once in nearly all health policy documents (92%). However, 50% had poor policy commitments for disability. Across policies, Prevention of health conditions was the main human rights concept reflected, while Privacy of information was the least referenced concept. Participants described a fragmented disability movement and health policy, related to a dominant biomedical model of disability. It appeared that disability was not prioritized in the health policy agenda, due to ineffective mainstreaming of disability by the Government and the limited influence and engagement of civil society in policy processes. Moreover, the limited existing policy framework on disability inclusion is not being implemented effectively. This implementation gap was attributed to lack of financing, leadership, and human resources, coupled with low monitoring of disability inclusion. CONCLUSIONS: Improvements are needed in both the development and implementation of disability-inclusive health policies in Chile, to support the achievement of the right to healthcare for people with disabilities and ensuring that the health system truly "leaves no one behind".

INTRODUCCIóN: Alrededor del 18% de la población de Chile tiene discapacidad. Los datos demuestran que esta población tiene mayores necesidades de salud, pero se enfrenta a barreras para acceder a la salud debido a las deficiencias del sistema sanitario. El objetivo de este estudio es evaluar la inclusión de las personas con discapacidad en las políticas sanitarias y explorar las percepciones de actores nacionales en relación al contexto político, los procesos políticos y los actores implicados. MéTODOS: Se realizó un análisis de contenido de 12 políticas sanitarias utilizando el marco EquiFrame, adaptado para discapacidad. Se calificó la calidad de compromiso de las políticas con respecto a 21 conceptos de derechos humanos del EquiFrame. Se entrevistó a 15 actores nacionales, y los datos se analizaron temáticamente según el Triángulo de Políticas de Walt y Gilson, utilizando NVivo R1. RESULTADOS: Los conceptos de derechos humanos en materia de discapacidad se mencionaron al menos una vez en casi todas las políticas sanitarias (92%). Sin embargo, en el 50% de los casos los compromisos políticos en materia de discapacidad eran escasos. En todas las políticas, la Prevención de los problemas de salud fue el principal concepto de derechos humanos reflejado, mientras que la Privacidad de la información fue el concepto menos mencionado. Los participantes describieron un movimiento de la discapacidad y una política sanitaria fragmentados, relacionados con un modelo biomédico dominante de la discapacidad. Pareciera que la discapacidad no es prioritaria en la agenda política sanitaria, debido a su ineficaz integración por parte del Gobierno y a la limitada participación de la sociedad civil en los procesos políticos. Además, el limitado marco político existente sobre salud inclusiva no se está implementando eficazmente. Esta deficiencia en la implementación se atribuyó a la falta de financiamiento, liderazgo y recursos humanos, junto con el escaso monitoreo de la discapacidad. CONCLUSIONES: Se requieren mejoras tanto en el desarrollo como en la implementación de políticas de salud inclusivas de la discapacidad en Chile, para apoyar el alcance del derecho a la salud de las personas con discapacidad y asegurar que el sistema de salud realmente "no deje a nadie atrás".

EEG Microstates as Markers for Cognitive Impairments in Fragile X Syndrome.

Fragile X syndrome (FXS) is one of the most common inherited causes of intellectual disabilities. While there is currently no cure for FXS, EEG is considered an important method to investigate the pathophysiology and evaluate behavioral and cognitive treatments. We conducted EEG microstate analysis to investigate resting brain dynamics in FXS participants. Resting-state recordings from 70 FXS participants and 71 chronological age-matched typically developing control (TDC) participants were used to derive microstates via modified k-means clustering. The occurrence, mean global field power (GFP), and global explained variance (GEV) of microstate C were significantly higher in the FXS group compared to the TDC group. The mean GFP was significantly negatively correlated with non-verbal IQ (NVIQ) in the FXS group, where lower NVIQ scores were associated with greater GFP. In addition, the occurrence, mean duration, mean GFP, and GEV of microstate D were significantly greater in the FXS group than the TDC group. The mean GFP and occurrence of microstate D were also correlated with individual alpha frequencies in the FXS group, where lower IAF frequencies accompanied greater microstate GFP and occurrence. Alterations in microstates C and D may be related to the two well-established cognitive characteristics of FXS, intellectual disabilities and attention impairments, suggesting that microstate parameters could serve as markers to study cognitive impairments and evaluate treatment outcomes in this population. Slowing of the alpha peak frequency and its correlation to microstate D parameters may suggest changes in thalamocortical dynamics in FXS, which could be specifically related to attention control. (250 words).

IDcare - a longitudinal register study of pre-pandemic and pandemic health care utilization and diagnostic profiles among people with intellectual disabilities in southern Sweden.

The aim of the creation of this cohort was to investigate patterns of health and health care utilisation before and during the COVID-19 pandemic, overall and in relation to specific diagnoses, among people with intellectual disabilities (ID) compared to the general population. People living in Skåne, the southernmost region of Sweden, on 1st of January 2014 with at least one diagnosis of ID (ICD-10 codes F70-F79) or Down syndrome (DS; Q90), or support and/or services according to the LSS act comprised the ID cohort (n = 14 716). People living in the same family and/or household as a person in the ID cohort constituted the ID family cohort (n = 31 688), and those remaining comprised the general population cohort (gPop; n = 1 226 955). Data has been collected for all three cohorts from several national and regional registers. These include registers for health care (2014-2021), deaths (2014-2021), COVID-19-related health care (vaccinations, intensive care, palliative care, 2020-2021). The prevalence of ID was 1.2%. In the ID cohort, 77.9% had at least one measure of support, 5.8% at least one Q90-diagnosis and 63.8% had at least one F7-diagnosis (26.9% mild (F70), 7.4% moderate (F71), 2.8% severe (F72), 1.4% profound (F73), and 25.4% other/unknown (F78/F79)). Compared to the gPop there were more people in the younger age groups in the ID cohort. At this point, no additional collection of data will be carried out. However, there is a possibility to add data from the registers to include years after 2021 or from additional registers. Future publications will explore relevant research questions and report key findings in relation to health among people with ID. Future results will be used to inform policy and practice on people with ID.

Management of patients with epilepsy and Intellectual disabilities in group homes vs. Family Homes: Insights into polypharmacy and seizure characteristics.

OBJECTIVES: This study aimed to investigate the differences in ASMs prescription, seizure characteristics and predictors of polypharmacy in patients with epilepsy and Intellectual disabilities (IDs) residing in group homes versus family homes. METHODS: This nine-year retrospective study analyzed patients with epilepsy and IDs who were admitted to the EMU, epilepsy clinics at LHSC and rehabilitation clinics for patients with IDs at Parkwood Institution. The study included individuals aged 16 years and older residing in either group homes or family homes. Data on demographics, epilepsy characteristics, and ASMs use were collected and analyzed using the Statistical Package for Social Sciences. The study utilized binary logistic regression to identify predictors of polypharmacy in patients with epilepsy and IDs. RESULTS: The study enrolled a total of 81 patients, of which 59.3 % resided in family homes. Group home residents were significantly older (41 vs. 24.5 years; p = 0.0001) and were prescribed more ASMs (3 vs. 2; p = 0.002). Specific ASMs were more common in group homes, including valproic acid (54.5 % vs. 25.0 %), lacosamide (54.5 % vs. 22.9 %), topiramate (33.3 % vs. 14.6 %), and phenytoin (30.3 % vs. 6.2 %). Admission to the EMU was more prevalent in group homes (93.9 % vs. 52.1 %; p = 0.0001). Living in a group home increased the risk of polypharmacy (OR = 10.293, p = 0.005), as did older epilepsy onset age (OR = 1.135, p = 0.031) and generalized or focal & generalized epilepsy (OR = 7.153, p = 0.032 and OR = 10.442, p = 0.025, respectively). SIGNIFICANCE: Our study identified notable differences in the demographic and clinical characteristics of patients with epilepsy and IDs living in group homes versus family homes. Age of epilepsy onset, EMU admissions, epilepsy types, and residency setting were significant predictors of polypharmacy. These findings highlight the need for personalized care strategies and increased awareness of the potential risks associated with polypharmacy.

Aprepitant's roles in abating seizures, behavioral, and cognitive deficits in mice model of epilepsy.

BACKGROUND: Aprepitant (APR), a neurokinin 1 receptor antagonist, is an approved drug for treating chemotherapy-induced nausea and vomiting. OBJECTIVES: Investigate the beneficial roles of APR alone or in combination with sodium valproate (VPA) against lithium pilocarpine [li-pilo]-induced seizures, behavioral changes, and cognitive deficits. METHODS: Thirty male mice were divided into five groups, each containing 6. "Vehicle Group I," "Control Group II "li-pilo, " Valproate (VPA) group III (400 mg/kg/i.p.), "APR group IV, " and "Combination Group V." Videos of mice were recorded, and they were watched for episodes of spontaneous recurring seizures (SRS). Behavioral Tests were performed. At the end of the study, animal brains were taken for biochemical assays and gene expression studies. RESULTS: APR partially protected against SRS with partial restoration of average behavioral and standard cognitive skills associated with a significant increase in brain SOD activity and a significant decrease in MDA, IL-1ß, NF-КB, and SP-3 levels in relation to the control group. Interestingly, a combination of APR with VPA in epileptic mice showed complete protection against li-pilo-induced behavioral changes and cognitive deficits, a significant increase in brain SOD activity, and a considerable decrease in MDA, IL-1ß, NF-ΚB, and SP levels to normal. CONCLUSION: Using APR as an adjuvant to VPA is more effective in protecting against li-pilo-induced seizures, behavioral changes, and cognitive deficits due to its antioxidant, anti-inflammatory, and NK1 antagonist effects than using APR alone as drug therapy.

Examination of common and unique brain regions for atypical reading and math: a meta-analysis.

The purpose of this study is to identify consistencies across functional neuroimaging studies regarding common and unique brain regions/networks for individuals with reading difficulties (RD) and math difficulties (MD) compared to typically developing (TD) individuals. A systematic search of the literature, utilizing multiple databases, yielded 116 functional magnetic resonance imaging and positron emission tomography studies that met the criteria. Coordinates that directly compared TD with either RD or MD were entered into GingerALE (Brainmap.org). An activation likelihood estimate (ALE) meta-analysis was conducted to examine common and unique brain regions for RD and MD. Overall, more studies examined RD (n = 96) than MD (n = 20). Across studies, overactivation for reading and math occurred in the right insula and inferior frontal gyrus for atypically developing (AD) > TD comparisons, albeit in slightly different areas of these regions; however, inherent threshold variability across imaging studies could diminish overlying regions. For TD > AD comparisons, there were no similar or overlapping brain regions. Results indicate there were domain-specific differences for RD and MD; however, there were some similarities in the ancillary recruitment of executive functioning skills. Theoretical and practical implications for researchers and educators are discussed.

Nurse Supervised at Institutes versus Nurse Counseling Home-Based Resistance Exercise Training for Acute Pancreatitis.

BACKGROUND: The physical and mental quality of life of patients with acute pancreatitis is poor. Professional nurses have the necessary knowledge, art, and skills to aid in resistance exercise training. AIMS: To evaluate the effectiveness of 6 months of nurse-supervised resistance exercise training plus nutritional supplements and 6 months of nurse counseling home-based resistance exercise training plus nutritional supplements for patients with pancreatitis. METHODS: Patients with acute pancreatitis (age ≥ 18 years) received nurse-supervised resistance exercise training at the institute (NEN cohort, n = 103), nurse counseling for home-based resistance exercise (HEN cohort, n = 123), or usual care (UCN cohort, n = 155) for 6 months. All patients received advice regarding nutritional especially protein supplements. RESULTS: Before non-treatment intervention(s) (BL), quality of life score of patients was 53, mild-to-moderate self-reported pain episodes, or worse pain, and a total of 22% of patients were disabled. Patients in the NEN cohort had improved quality of life and decreased pain and disability after 6 months of non-treatment intervention(s) (EL) compared to their BL condition and those of the UCN and HEN cohorts at EL (p < 0.05 for all). A smaller number of patients were hospitalized and died in the NEN cohort than in the UCN and HEN cohorts (p ≤ 0.001 for both) during the follow-up period. CONCLUSION: The quality of life, pain, and disability condition(s) of patients with acute pancreatitis should be improved. Nurse-supervised resistance exercise training at the institute associated with improvement in the quality of life and decrease of pain, disability, hospitalization, and death of patients with acute pancreatitis.