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Aging Jun 2024Down Syndrome (DS) is a common genetic disorder characterized by an extra copy of chromosome 21, leading to dysregulation of various metabolic pathways. Oxidative stress...
Down Syndrome (DS) is a common genetic disorder characterized by an extra copy of chromosome 21, leading to dysregulation of various metabolic pathways. Oxidative stress in DS is associated with neurodevelopmental defects, neuronal dysfunction, and a dementia onset resembling Alzheimer's disease. Additionally, chronic oxidative stress contributes to cardiovascular diseases and certain cancers prevalent in DS individuals. This study investigates the impact of ageing on oxidative stress and liver fibrosis using a DS murine model (Ts2Cje mice). Our results show that DS mice show increased liver oxidative stress and impaired antioxidant defenses, as evidenced by reduced glutathione levels and increased lipid peroxidation. Therefore, DS liver exhibits an altered inflammatory response and mitochondrial fitness as we showed by assaying the expression of HMOX1, CLPP, and the heat shock proteins Hsp90 and Hsp60. DS liver also displays dysregulated lipid metabolism, indicated by altered expression of PPARα, PPARγ, FATP5, and CTP2. Consistently, these changes might contribute to non-alcoholic fatty liver disease development, a condition characterized by liver fat accumulation. Consistently, histological analysis of DS liver reveals increased fibrosis and steatosis, as showed by Col1a1 increased expression, indicative of potential progression to liver cirrhosis. Therefore, our findings suggest an increased risk of liver pathologies in DS individuals, particularly when combined with the higher prevalence of obesity and metabolic dysfunctions in DS patients. These results shed a light on the liver's role in DS-associated pathologies and suggest potential therapeutic strategies targeting oxidative stress and lipid metabolism to prevent or mitigate liver-related complications in DS individuals.
PubMed: 38942607
DOI: 10.18632/aging.205970 -
JACC. Advances Nov 2023
PubMed: 38938705
DOI: 10.1016/j.jacadv.2023.100673 -
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 -
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 -
Science Advances Jun 2024Caregiving for disabled individuals among Neanderthals has been known for a long time, and there is a debate about the implications of this behavior. Some authors...
Caregiving for disabled individuals among Neanderthals has been known for a long time, and there is a debate about the implications of this behavior. Some authors believe that caregiving took place between individuals able to reciprocate the favor, while others argue that caregiving was produced by a feeling of compassion related to other highly adaptive prosocial behaviors. The study of children with severe pathologies is particularly interesting, as children have a very limited possibility to reciprocate the assistance. We present the case of a Neanderthal child who suffered from a congenital pathology of the inner ear, probably debilitating, and associated with Down syndrome. This child would have required care for at least 6 years, likely necessitating other group members to assist the mother in childcare.
Topics: Down Syndrome; Humans; Animals; Neanderthals; Child; Female; Male; Child, Preschool
PubMed: 38924400
DOI: 10.1126/sciadv.adn9310 -
Case Reports in Dentistry 2024Managing dental care in children with special health care needs poses distinct challenges. This case report explores these challenges within the context of a 9-year-old...
BACKGROUND
Managing dental care in children with special health care needs poses distinct challenges. This case report explores these challenges within the context of a 9-year-old boy with Down syndrome (DS) facing dental treatment refusal. Over ten months and 13 visits, a tailored approach was devised for the patient who presented with multiple cavities and retained primary teeth. Key strategies included gradually introducing dental procedures, including tooth brushing, intraoral examination, tooth preparation, extraction, and myofunctional therapy. Behaviour guidance techniques include tell-show-do, desensitization, positive reinforcement, and close collaboration between dental professionals and the patient's mother. This methodical approach helped overcome the child's initial refusal without sedation or general anaesthesia, facilitating successful dental care.
CONCLUSION
This case emphasizes the effectiveness of patient-centred strategies and detailed communication in pediatric dentistry for children with DS, providing valuable insights for managing similar challenges in dental care.
PubMed: 38919976
DOI: 10.1155/2024/2966972 -
Iranian Journal of Public Health Mar 2024Most of the people with Down syndrome have short stature compared to general population. There is also a high prevalence of overweight and obesity, mainly in the...
BACKGROUND
Most of the people with Down syndrome have short stature compared to general population. There is also a high prevalence of overweight and obesity, mainly in the adolescence and in the adult life. The aim of this study was to compare some anthropometric parameters, heart rate and blood pressure of children with Down syndrome and those with normal development. Down syndrome is among the most commonly classified categories of mental sub normality, with the incidence at birth being around 1: 700 and 1: 750 in live births in most countries worldwide, with the risk of increasing with mother's age.
METHODS
The sample consisted of 82 children, 32 with Down syndrome and 50 healthy children, male, aged 14-15 yr from the population of Kosovo in 2022. There were no health problems present in the healthy children.
RESULTS
About 53% of children with Down syndrome have normal body mass, 15.62% are overweight, and 21.8 are obese. In terms of blood pressure, Down syndrome children have higher systolic pressure (121.94mm/hg), sd ±21.69 than healthy children (111.18mm/hg, sd ±10.88).
CONCLUSION
Children with Down syndrome had significantly higher body mass index, heart rate, and systolic pressure at rest compared to healthy children. However, after short physical activity, healthy children exhibited greater diastolic pressure than children with Down syndrome.
PubMed: 38919303
DOI: 10.18502/ijph.v53i3.15140 -
BioRxiv : the Preprint Server For... Jun 2024Fragile X syndrome (FXS) is an X-linked disorder that often leads to intellectual disability, anxiety, and sensory hypersensitivity. While sound sensitivity...
Fragile X syndrome (FXS) is an X-linked disorder that often leads to intellectual disability, anxiety, and sensory hypersensitivity. While sound sensitivity (hyperacusis) is a distressing symptom in FXS, its neural basis is not well understood. It is postulated that hyperacusis may stem from temporal lobe hyperexcitability or dysregulation in topdown modulation. Studying the neural mechanisms underlying sound sensitivity in FXS using scalp electroencephalography (EEG) is challenging because the temporal and frontal regions have overlapping neural projections that are difficult to differentiate. To overcome this challenge, we conducted EEG source analysis on a group of 36 individuals with FXS and 39 matched healthy controls. Our goal was to characterize the spatial and temporal properties of the response to an auditory chirp stimulus. Our results showed that males with FXS exhibit excessive activation in the frontal cortex in response to the stimulus onset, which may reflect changes in top-down modulation of auditory processing. Additionally, during the chirp stimulus, individuals with FXS demonstrated a reduction in typical gamma phase synchrony, along with an increase in asynchronous gamma power, across multiple regions, most strongly in temporal cortex. Consistent with these findings, we observed a decrease in the signal-to-noise ratio, estimated by the ratio of synchronous to asynchronous gamma activity, in individuals with FXS. Furthermore, this ratio was highly correlated with performance in an auditory attention task. Compared to controls, males with FXS demonstrated elevated bidirectional frontotemporal information flow at chirp onset. The evidence indicates that both temporal lobe hyperexcitability and disruptions in top-down regulation play a role in auditory sensitivity disturbances in FXS. These findings have the potential to guide the development of therapeutic targets and back-translation strategies.
PubMed: 38915683
DOI: 10.1101/2024.06.13.598957 -
Implementation Science Communications Jun 2024Implementation research generally assumes established evidence-based practices and prior piloting of implementation strategies, which may not be feasible during a public...
BACKGROUND
Implementation research generally assumes established evidence-based practices and prior piloting of implementation strategies, which may not be feasible during a public health emergency. We describe the use of a simulation model of the effectiveness of COVID-19 mitigation strategies to inform a stakeholder-engaged process of rapidly designing a tailored intervention and implementation strategy for individuals with serious mental illness (SMI) and intellectual/developmental disabilities (ID/DD) in group homes in a hybrid effectiveness-implementation randomized trial.
METHODS
We used a validated dynamic microsimulation model of COVID-19 transmission and disease in late 2020/early 2021 to determine the most effective strategies to mitigate infections among Massachusetts group home staff and residents. Model inputs were informed by data from stakeholders, public records, and published literature. We assessed different prevention strategies, iterated over time with input from multidisciplinary stakeholders and pandemic evolution, including varying symptom screening, testing frequency, isolation, contact-time, use of personal protective equipment, and vaccination. Model outcomes included new infections in group home residents, new infections in group home staff, and resident hospital days. Sensitivity analyses were performed to account for parameter uncertainty. Results of the simulations informed a stakeholder-engaged process to select components of a tailored best practice intervention and implementation strategy.
RESULTS
The largest projected decrease in infections was with initial vaccination, with minimal benefit for additional routine testing. The initial level of actual vaccination in the group homes was estimated to reduce resident infections by 72.4% and staff infections by 55.9% over the 90-day time horizon. Increasing resident and staff vaccination uptake to a target goal of 90% further decreased resident infections by 45.2% and staff infections by 51.3%. Subsequent simulated removal of masking led to a 6.5% increase in infections among residents and 3.2% among staff. The simulation model results were presented to multidisciplinary stakeholders and policymakers to inform the "Tailored Best Practice" package for the hybrid effectiveness-implementation trial.
CONCLUSIONS
Vaccination and decreasing vaccine hesitancy among staff were predicted to have the greatest impact in mitigating COVID-19 risk in vulnerable populations of group home residents and staff. Simulation modeling was effective in rapidly informing the selection of the prevention and implementation strategy in a hybrid effectiveness-implementation trial. Future implementation may benefit from this approach when rapid deployment is necessary in the absence of data on tailored interventions.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04726371.
PubMed: 38915130
DOI: 10.1186/s43058-024-00593-w