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Thorax Jun 2024In adults and children with intellectual disability (ID), sleep -disordered breathing (SDB) is thought to be common. However, large epidemiological studies are lacking,... (Review)
Review
BACKGROUND
In adults and children with intellectual disability (ID), sleep -disordered breathing (SDB) is thought to be common. However, large epidemiological studies are lacking, and there are few studies on optimal methods of investigation and even fewer randomised, controlled intervention trials of treatment.
METHOD
Peer-reviewed publications from various databases were examined in line with search terms relevant to ID and SDB spanning the years 200-2024.
RESULTS
Findings suggest that, due to comorbid conditions, children and adults with ID may experience both an increased risk of SDB, as well as lower frequency of diagnosis. SDB can compromise the emotional, physical and mental health of individuals with ID. Appropriate treatment when tolerated leads to an improvement in health and well-being and several studies emphasized the importance of consistent follow-up of people with ID - something that is not universally occurring during childhood, in the transition to adulthood and during adulthood itself. As the most frequently occurring form of ID worldwide, we use Down syndrome as a specific example of how diagnosing and treating SDB can lead to improved outcomes.
CONCLUSIONS
This review highlights the importance of identifying SDB in this heterogenous population, recognising the multi-faceted, deleterious consequences of untreated SDB in people with ID, and presents some strategies that can be harnessed to improve diagnosis and management. Until further ID-specific research is available, we urge flexibility in the approach to people with ID and SDB based in guidelines and standard practice developed for the typically developing population.
PubMed: 38937106
DOI: 10.1136/thorax-2023-220032 -
Health Promotion International Jun 2024The article examines the experiences of family caregivers engaged in the provision of long-term care for their relatives with complex health needs within the Latvian...
The article examines the experiences of family caregivers engaged in the provision of long-term care for their relatives with complex health needs within the Latvian context. Semi-structured interviews were conducted with seven caregivers who provide care in cases of dementia, depression, schizophrenia, opioid use, Down syndrome and mild cognitive impairment. A thematic analysis of interview transcripts revealed common themes, such as the initial experiences when encountering a family member's disorder and the subsequent reactions, as well as the quest for support and resources. Variations mainly centered around differences in formal aspects and childhood experiences of care. Caregivers reported risk factors such as guilt, lack of support from family and friends, financial difficulties, deficiency of professional care and ignoring the caregiver's own needs. Awareness of personal resources, values and limits, coping with personal stigma and improved overall quality of life were identified as protective factors. The findings underscore several preventive measures that social and mental health services could implement to mitigate the adverse effects of caregiving on caregivers' lives.
Topics: Humans; Caregivers; Latvia; Female; Male; Middle Aged; Aged; Family; Adaptation, Psychological; Social Support; Interviews as Topic; Adult; Quality of Life; Qualitative Research; Social Stigma; Long-Term Care
PubMed: 38934478
DOI: 10.1093/heapro/daae070 -
Alzheimer's & Dementia : the Journal of... Jun 2024Cognitive impairment is a core feature of Down syndrome (DS), and the underlying neurobiological mechanisms remain unclear. Translation dysregulation is linked to...
INTRODUCTION
Cognitive impairment is a core feature of Down syndrome (DS), and the underlying neurobiological mechanisms remain unclear. Translation dysregulation is linked to multiple neurological disorders characterized by cognitive impairments. Phosphorylation of the translational factor eukaryotic elongation factor 2 (eEF2) by its kinase eEF2K results in inhibition of general protein synthesis.
METHODS
We used genetic and pharmacological methods to suppress eEF2K in two lines of DS mouse models. We further applied multiple approaches to evaluate the effects of eEF2K inhibition on DS pathophysiology.
RESULTS
We found that eEF2K signaling was overactive in the brain of patients with DS and DS mouse models. Inhibition of eEF2 phosphorylation through suppression of eEF2K in DS model mice improved multiple aspects of DS-associated pathophysiology including de novo protein synthesis deficiency, synaptic morphological defects, long-term synaptic plasticity failure, and cognitive impairments.
DISCUSSION
Our data suggested that eEF2K signaling dysregulation mediates DS-associated synaptic and cognitive impairments.
HIGHLIGHTS
Phosphorylation of the translational factor eukaryotic elongation factor 2 (eEF2) is increased in the Down syndrome (DS) brain. Suppression of the eEF2 kinase (eEF2K) alleviates cognitive deficits in DS models. Suppression of eEF2K improves synaptic dysregulation in DS models. Cognitive and synaptic impairments in DS models are rescued by eEF2K inhibitors.
PubMed: 38934363
DOI: 10.1002/alz.13916 -
Cytotechnology Aug 2024Fulminant hepatitis (FH) is a life-threatening clinical liver syndrome characterized by substantial hepatocyte necrosis and severe liver damage. FH is typically...
Fulminant hepatitis (FH) is a life-threatening clinical liver syndrome characterized by substantial hepatocyte necrosis and severe liver damage. FH is typically associated with severe oxidative stress, inflammation, and mitochondrial dysfunction. Pyrroloquinoline quinone (PQQ), a naturally occurring redox cofactor, functions as an essential nutrient and antioxidant and reportedly inhibits oxidative stress and exerts potent anti-inflammatory effects. In the present study, we aimed to evaluate the therapeutic efficacy of PQQ in murine hepatitis virus strain 3 (MHV-3)-induced FH and examined the underlying mechanism. An MHV-3-induced FH mouse model was established for in vivo examination Liver sinusoidal endothelial cells (LSECs) were used for in vitro experiments. Herein, we observed that PQQ supplementation significantly attenuated MHV-3-induced hepatic injury by suppressing inflammatory responses and reducing oxidative stress. Mechanistically, PQQ supplementation ameliorated MHV-3-induced hepatic damage by down-regulating the Keap1/Nrf2 signaling pathway in vivo and in vitro. Furthermore, Nrf2 small interfering RNA targeting LSECs abrogated the PQQ-mediated protective effects against MHV-3-related liver injury. Our results deepen our understanding of the hepatoprotective function of PQQ against MHV-3-induced liver injury and provide evidence that alleviating oxidative stress might afford a novel therapeutic strategy for treating FH.
PubMed: 38933874
DOI: 10.1007/s10616-024-00627-0 -
Cureus May 2024Trisomy 21 often leads to cardiac complications, usually associated with congenital heart disease, such as atrial septal defects, ventricular septal defects, and patent...
Trisomy 21 often leads to cardiac complications, usually associated with congenital heart disease, such as atrial septal defects, ventricular septal defects, and patent ductus arteriosus. This case describes an unexpected instance of infective endocarditis (IE) in a middle-aged patient with an incidentally discovered patent foramen ovale (PFO). The common risk factors for IE include previous valve surgery, artificial heart valves, pacemakers, prior IE, congenital defects like bicuspid aortic valve, IV drug use, and the congenital defects mentioned earlier.
PubMed: 38933636
DOI: 10.7759/cureus.61106 -
Children (Basel, Switzerland) May 2024Children with Down syndrome (DS) are at high risk of sleep-disordered breathing (SDB). The American Academy of Pediatrics recommends a polysomnogram (PSG) in children...
Children with Down syndrome (DS) are at high risk of sleep-disordered breathing (SDB). The American Academy of Pediatrics recommends a polysomnogram (PSG) in children with DS prior to the age of 4. This retrospective study examined the frequency of SDB, gas exchange abnormalities, co-morbidities, and surgical management in children with DS aged 2-4 years old at Seattle Children's Hospital from 2015-2021. A total of 153 children underwent PSG, with 75 meeting the inclusion criteria. The mean age was 3.03 years (SD 0.805), 56% were male, and 54.7% were Caucasian. Comorbidities included (n, %): cardiac (43, 57.3%), dysphagia or aspiration (24, 32.0%), prematurity (17, 22.7%), pulmonary (16, 21.3%), immune dysfunction (2, 2.7%), and hypothyroidism (23, 30.7%). PSG parameter data collected included (mean, SD): obstructive AHI (7.9, 9.4) and central AHI (2.4, 2.4). In total, 94.7% met the criteria for pediatric OSA, 9.5% met the criteria for central apnea, and 9.5% met the criteria for hypoventilation. Only one child met the criteria for hypoxemia. Overall, 60% had surgical intervention, with 88.9% of these being adenotonsillectomy. There was no statistically significant difference in the frequency of OSA at different ages. Children aged 2-4 years with DS have a high frequency of OSA. The most commonly encountered co-morbidities were cardiac and swallowing dysfunction. Among those with OSA, more than half underwent surgical intervention, with improvements in their obstructive apnea hypopnea index, total apnea hypopnea index, oxygen saturation nadir, oxygen desaturation index, total arousal index, and total sleep duration. This highlights the importance of early diagnosis and appropriate treatment. Our study also suggests that adenotonsillar hypertrophy is still a large contributor to upper airway obstruction in this age group.
PubMed: 38929231
DOI: 10.3390/children11060651 -
Brain Sciences May 2024: People with Down syndrome (DS) are deficient in verbal memory but relatively preserved in visuospatial perception. Verbal memories are related to semantic knowledge....
: People with Down syndrome (DS) are deficient in verbal memory but relatively preserved in visuospatial perception. Verbal memories are related to semantic knowledge. Receptive ability is better than expressive ability in people with DS but still seriously lags behind their age-matched controls. This lag may result in the weak semantic integration of people with DS. : This study aimed to examine the ability of semantic integration of people with DS by using false-memory tasks. Possible differences in the number of false memories induced by nouns and verbs were of focus. Two phases were involved in the false-memory task. In the study phase, ten-word lists with semantically related associates were presented. In the recognition phase, judgments were to be made about whether the words presented had been heard before. Three types of words were tested: previously presented associates, semantically related lures, and semantically unrelated new words. : People with DS overall showed the lowest accuracy among groups in response to tested word types. In the processing of lures, people with DS were worse in recognition than MA controls. In processing unrelated words, people with DS responded least accurately to all types of words compared to control groups. In the processing of associates, people with DS showed similar recognition rates as the MA controls but were less accurate than the CA controls. No difference was observed between nouns and verbs in recognizing word types among groups, though faster responses to nouns than to verbs emerged in college students. Further analyses on topic-wised comparisons of errors across syntactic categories revealed differences in specific concepts among groups, suggesting people with DS were atypical in semantic organization. : People with DS showed mixed patterns in semantic integration by false-memory tasks with delay to associates and deviance to lures together with unrelated words. People with DS showed distinct patterns in processing nouns and verbs while conducting topic-wise comparisons, suggesting that they formed false memories differently based on distinct syntactic categories. We concluded that people with DS develop a deviant semantic structure, hence showing problems in language and social cognition. Category-based rehabilitation is suggested to be implemented for people with DS to improve their semantic knowledge through lexical connections.
PubMed: 38928536
DOI: 10.3390/brainsci14060538 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024To screen interleukin (IL)-1β secretion-related membrane transporters by macrophage experiment and conventional knockout mice.
OBJECTIVE
To screen interleukin (IL)-1β secretion-related membrane transporters by macrophage experiment and conventional knockout mice.
METHODS
THP-1 cell line was differentiated to obtain human THP-1-derived macrophages, and the primary macrophages were obtained from human peripheral blood. wild-type mice with the same sex and age were used as the controls of knockout mice. The macrophages in abdominal cavity and bone marrow of mice were cultivated. The cells were treated with ABCC1/MRP1, ABCG2/BCRP, ABCB1/P-gp, OATP1B1, and MATE transporter inhibitors, then stimulated by lipopolysaccharide and adenosine triphosphate. The secretion level of IL-1β was detected by ELISA, Western blot, and immunofluorescence.
RESULTS
After inhibiting ABCC1/MRP1 transporter, the secretion of IL-1β decreased significantly, while inhibition of the other 4 transporters had no effect. In animal experiment, the level of IL-1β secreted by macrophages in bone marrow of knockout mice was significantly lower than control group ( < 0.05).
CONCLUSION
ABCC1/MRP1 transporter is a newly discovered IL-1β secretion pathway, which is expected to become a new target for solving clinical problems such as cytokine release syndrome.
Topics: Interleukin-1beta; Mice; Animals; Humans; Multidrug Resistance-Associated Proteins; Mice, Knockout; Macrophages; Down-Regulation; THP-1 Cells; Lipopolysaccharides
PubMed: 38926988
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.040 -
BMC Public Health Jun 2024People with serious mental illness (SMI) and people with intellectual disabilities/developmental disabilities (ID/DD) are at higher risk for COVID-19 and more severe... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
People with serious mental illness (SMI) and people with intellectual disabilities/developmental disabilities (ID/DD) are at higher risk for COVID-19 and more severe outcomes. We compare a tailored versus general best practice COVID-19 prevention program in group homes (GHs) for people with SMI or ID/DD in Massachusetts (MA).
METHODS
A hybrid effectiveness-implementation cluster randomized control trial compared a four-component implementation strategy (Tailored Best Practices: TBP) to dissemination of standard prevention guidelines (General Best-Practices: GBP) in GHs across six MA behavioral health agencies. GBP consisted of standard best practices for preventing COVID-19. TBP included GBP plus four components including: (1) trusted-messenger peer testimonials on benefits of vaccination; (2) motivational interviewing; (3) interactive education on preventive practices; and (4) fidelity feedback dashboards for GHs. Primary implementation outcomes were full COVID-19 vaccination rates (baseline: 1/1/2021-3/31/2021) and fidelity scores (baseline: 5/1/21-7/30/21), at 3-month intervals to 15-month follow-up until October 2022. The primary effectiveness outcome was COVID-19 infection (baseline: 1/1/2021-3/31/2021), measured every 3 months to 15-month follow-up. Cumulative incidence of vaccinations were estimated using Kaplan-Meier curves. Cox frailty models evaluate differences in vaccination uptake and secondary outcomes. Linear mixed models (LMMs) and Poisson generalized linear mixed models (GLMMs) were used to evaluate differences in fidelity scores and incidence of COVID-19 infections.
RESULTS
GHs (n=415) were randomized to TBP (n=208) and GBP (n=207) including 3,836 residents (1,041 ID/DD; 2,795 SMI) and 5,538 staff. No differences were found in fidelity scores or COVID-19 incidence rates between TBP and GBP, however TBP had greater acceptability, appropriateness, and feasibility. No overall differences in vaccination rates were found between TBP and GBP. However, among unvaccinated group home residents with mental disabilities, non-White residents achieved full vaccination status at double the rate for TBP (28.6%) compared to GBP (14.4%) at 15 months. Additionally, the impact of TBP on vaccine uptake was over two-times greater for non-White residents compared to non-Hispanic White residents (ratio of HR for TBP between non-White and non-Hispanic White: 2.28, p = 0.03).
CONCLUSION
Tailored COVID-19 prevention strategies are beneficial as a feasible and acceptable implementation strategy with the potential to reduce disparities in vaccine acceptance among the subgroup of non-White individuals with mental disabilities.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT04726371, 27/01/2021. https://clinicaltrials.gov/study/NCT04726371 .
Topics: Humans; COVID-19; Male; Female; Adult; Massachusetts; Middle Aged; Group Homes; Mental Disorders; COVID-19 Vaccines; Intellectual Disability
PubMed: 38926810
DOI: 10.1186/s12889-024-18835-w -
American Journal of Medical Genetics.... Jun 2024Mosaic Down syndrome is a triplication of chromosome 21 in some but not all cells. Little is known about the epidemiology of mosaic Down syndrome. We described...
BACKGROUND
Mosaic Down syndrome is a triplication of chromosome 21 in some but not all cells. Little is known about the epidemiology of mosaic Down syndrome. We described prevalence of mosaic Down syndrome and the co-occurrence of common chronic conditions in 94,533 Medicaid enrolled adults with any Down syndrome enrolled from 2016 to 2019.
METHODS
We identified mosaic Down syndrome using the International Classification of Diseases and Related Health Problems, tenth edition code for mosaic Down syndrome and compared to those with nonmosaic Down syndrome codes. We identified chronic conditions using established algorithms and compared prevalence by mosaicism.
RESULTS
In total, 1966 (2.08%) had claims for mosaic Down syndrome. Mosaicism did not differ by sex or race/ethnicity with similar age distributions. Individuals with mosaicism were more likely to present with autism (13.9% vs. 9.6%) and attention deficit hyperactivity disorder (17.7% vs. 14.0%) compared to individuals without mosaicism. In total, 22.3% of those with mosaic Down syndrome and 21.5% of those without mosaicism had claims for Alzheimer's dementia (Prevalence difference: 0.8; 95% Confidence interval: -1.0, 2.8). The mosaic group had 1.19 times the hazard of Alzheimer's dementia compared to the nonmosaic group (95% CI: 1.0, 1.3).
DISCUSSION
Mosaicism may be associated with a higher susceptibility to certain neurodevelopmental and neurodegenerative conditions, including Alzheimer's dementia. Our findings challenge previous assumptions about its protective effects in Down syndrome. Further research is necessary to explore these associations in greater depth.
PubMed: 38925597
DOI: 10.1002/ajmg.c.32097