Comparing the Effectiveness of Octenidine Hydrochloride and Chlorhexidine Gluconate Mouthrinses in Reducing Plaque and Oxidative Stress in Institutionalized Children with Down Syndrome.

Background and objectives: Due to decreased manual dexterity, a lack of motivation, and difficulty on the part of the caregiver conducting efficient oral hygiene measures at home, patients with Down syndrome (DS) are badly affected. The objective of this study is to compare the efficacy of 0.1% octenidine (OCT) hydrochloride and 0.12% chlorhexidine (CHX) gluconate on plaque control and oxidative stress in institutionalized children with DS. Materials and methods: In 20 children, salivary samples were collected for analysis of the inflammatory marker high-sensitive C-reactive protein (hsCRP) and oxidative stress markers, specifically malondialdehyde (MDA). Plaque index (PlI) and gingival index (GI) were scored. After oral prophylaxis, the participants were randomly assigned to two groups, each consisting of 10 individuals (octenidol and CHX). Salivary oxidative stress marker assays were carried out using a modified version of Yagi's (1984) method, and absorbance was measured at 540 nm using an ultraviolet-visible spectrophotometer at 535 nm. hsCRP assays were conducted via latex turbidimetric immunoassay. Results: On comparison between the two groups, the OCT group showed a statistically significant reduction in GI, PlI, and MDA values (p < 0.05). Conclusion: It was seen that the use of 0.1% OCT hydrochloride could facilitate the maintenance of good oral hygiene and periodontal status, especially in patients with motor difficulties. Clinical trial registration: PMS/IEC/2016/02. How to cite this article: Raj AS, George S, S A, et al. Comparing the Effectiveness of Octenidine Hydrochloride and Chlorhexidine Gluconate Mouthrinses in Reducing Plaque and Oxidative Stress in Institutionalized Children with Down Syndrome. Int J Clin Pediatr Dent 2024;17(4):437-441.

Down syndrome and DYRK1A overexpression: relationships and future therapeutic directions.

Down syndrome is a genetic-based disorder that results from the triplication of chromosome 21, leading to an overexpression of many triplicated genes, including the gene encoding Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A (DYRK1A). This protein has been observed to regulate numerous cellular processes, including cell proliferation, cell functioning, differentiation, and apoptosis. Consequently, an overexpression of DYRK1A has been reported to result in cognitive impairment, a key phenotype of individuals with Down syndrome. Therefore, downregulating DYRK1A has been explored as a potential therapeutic strategy for Down syndrome, with promising results observed from in vivo mouse models and human clinical trials that administered epigallocatechin gallate. Current DYRK1A inhibitors target the protein function directly, which tends to exhibit low specificity and selectivity, making them unfeasible for clinical or research purposes. On the other hand, antisense oligonucleotides (ASOs) offer a more selective therapeutic strategy to downregulate DYRK1A expression at the gene transcript level. Advances in ASO research have led to the discovery of numerous chemical modifications that increase ASO potency, specificity, and stability. Recently, several ASOs have been approved by the U.S. Food and Drug Administration to address neuromuscular and neurological conditions, laying the foundation for future ASO therapeutics. The limitations of ASOs, including their high production cost and difficulty delivering to target tissues can be overcome by further advances in ASO design. DYRK1A targeted ASOs could be a viable therapeutic approach to improve the quality of life for individuals with Down syndrome and their families.

Strength versus aerobic program: effects on body composition and health-related physical fitness levels of youths with Down syndrome.

Aims: To determine the effect of a 16-week fitness program (strength vs. aerobic) on different indicators of body composition and components of health-related physical fitness in youths with Down syndrome. Methods and procedures outcomes: Fifty adolescents (19 girls and 31 boys; average age, 18.33 ± 1.42 years) with Down syndrome were recruited and randomized to two groups (strength group vs. aerobic group). Adolescents allocated in the aerobic group carried out a physical activity program three times a week for 16 weeks meanwhile adolescents allocated in the strength group performed a fitness program three times a week for 16 weeks. Results: The exercise group had significant improvements in all health-related physical fitness variables (p < .05) but not on body composition. Conclusions and implications: A sixteen week fitness program consisting of three sessions of 60 min is able to increase levels of health-related physical fitness but not on body composition in youths with Down syndrome. The aerobic program does not seem to show significant differences.

Combined sensory integration therapy plus neurodevelopmental therapy (NT) versus NT alone for motor and attention in children with Down syndrome: a randomized controlled trial.

In this study, we aimed to analyze the incremental effects of sensory integration therapy (SIT) plus neurodevelopmental therapy (NT) versus NT alone on the attention and motor skills in children with Down syndrome (DS). We randomly assigned into experimental (i.e. SIT + NT; n = 21) and control (i.e. NT alone; n = 21) groups. While NT was applied to both groups for six weeks, SIT was applied simultaneously to the experimental group for six weeks. Participants' motor functions (Bruininks-Oseretsky Test of Motor Proficiency-Short form (BOT-2 SF)) and attention skills (Stroop TBAG (Turkish Scientific and Technological Research Association) Form) were evaluated before and after treatment (6 weeks later). Stroop TBAG and BOT-2 SF scores of the groups were similar at the baseline (p > 0.05). Significant improvement from baseline was observed in both BOT-2 SF, and Stroop TBAG results in both groups (p < 0.05). In addition, the improvement in both BOT-2 SF and Stroop TBAG results was found to be greater in the experimental group compared to the control group (p < 0.01). There were clear advantages to adding SIT to NT alone when seeking to improve motor and attention skills in children with DS.

Case report: Down syndrome regression disorder, catatonia, and psychiatric and immunomodulatory interventions.

Down syndrome regression disorder (DSRD) is a rare condition involving subacute cognitive decline, loss of previously acquired developmental skills, and prominent neuropsychiatric symptoms, particularly catatonia, in people with Down syndrome. It is thought to involve both autoimmune and neuropsychiatric mechanisms. Research, however, is largely restricted to case studies and retrospective case series and is particularly limited in terms of prospective longitudinal follow-up. We report a case study of a person with DSRD who received both immunomodulatory (intravenous immunoglobulin; IVIG) and psychiatric interventions (electroconvulsive therapy, ECT) over two years with regular assessments using caregiver and clinician ratings. This revealed a small, unsustained response to IVIG and a rapid, sustained response once ECT was introduced. The case highlights the importance of multimodal assessment involving multiple medical specialties, the need to trial different therapies due to the condition's complexity, and the significant barriers that patients and their families face in accessing care.

Comparing research attitudes in Down syndrome and non-Down syndrome research decision-makers.

INTRODUCTION: Recruitment challenges in people with and without Down syndrome (DS) can delay research progress and risk sample bias. This study identified and quantified differences in research attitudes across populations of research enrollment decision-makers for individuals with and without DS. METHODS: We performed analyses using data from two registries: the University of California, Irvine Consent-to-Contact (C2C) Registry and DS-Connect. The former represented a sample of non-DS decision-makers (N = 4818), while for the latter, we excluded individuals with DS, leaving a population of DS family decision-makers (N = 976). We assessed scores on the Research Attitudes Questionnaire (RAQ) between DS and non-DS decision-makers. We compared total RAQ scores using linear regression and assessed item-level RAQ differences using proportional odds regression. RESULTS: Mean total RAQ scores were not statistically different between decision-makers in the two registries, after adjusting for age, sex, race and ethnicity, education, and the coronavirus disease 2019 (COVID-19) time frame (Est. Diff = 0.11, 95% confidence interval [CI]: -0.22, 0.43; p = 0.531). However, in a pre-specified analysis, we did find evidence of differential attitudes on item-level RAQ scores. Specifically, decision-makers for participants with DS had increased odds of a more favorable response to the question of responsibility to help others (DS vs. non-DS: odds ratio [OR] = 1.26, 95% CI: 1.08, 1.48) and decreased odds of a more favorable response to the question regarding the belief that medical research would find cures for major diseases during their lifetime (DS vs. non-DS: OR = 0.77, 95% CI: 0.66, 0.90). DISCUSSION: Our findings provide insights for researchers to develop strategies for recruiting individuals with and without DS into clinical research. The observed item-level differences warrant further investigation to instruct precise recruitment strategies. Highlights: Research attitudes between decision-makers for individuals with Down syndrome (DS) and decision-makers without DS were observed to be similar on average.Item-level differences in research attitudes were observed to differ for DS and non-DS decision-makers.These results can help facilitate precise recruitment strategies for populations with DS.

Sources of reduced visual acuity and spectacle treatment options for individuals with Down syndrome: Review of current literature.

Individuals with Down syndrome are known to have a greater prevalence of ocular conditions such as strabismus, nystagmus, elevated refractive error, poor accommodative function, elevated higher-order optical aberrations and corneal abnormalities. Related to these conditions, individuals with Down syndrome commonly have reduced best-corrected visual acuity at both far and near viewing distances across their lifespan. This review summarises the various optical sources of visual acuity reduction in this population and describes clinical trials that have evaluated alternative spectacle prescribing strategies to minimise these optical deficits. Although refractive corrections may still have limitations in their ability to normalise visual acuity for individuals with Down syndrome, the current literature provides evidence for eye care practitioners to consider in their prescribing practices for this population to maximise visual acuity. These considerations include accounting for the presence of elevated higher-order aberrations when determining refractive corrections and considering bifocal lens prescriptions, even for young children with Down syndrome.

Mature Cystic Teratoma in a Newborn With Down Syndrome.

Retroperitoneal teratomas are uncommon neoplasms that cause diagnostic dilemmas in neonates during the evaluation of abdominal cystic mass lesions. Down syndrome (DS) is a chromosomal abnormality with an extra third copy of chromosome 21. Due to chromosomal instability, DS is inferred to be a cancer predisposition syndrome. The malignancy pattern in DS is unique with higher incidence of hematological malignancies and solid tumors are rarely reported. Down syndrome neonate was incidentally diagnosed with a retroperitoneal cystic lesion along the left kidney during evaluation for poor feeding on ultrasonography, raising suspicion of an adrenal hemorrhagic cyst. CECT abdomen and pelvis revealed complex cystic lesions along the left renal hilum, with the possibility of cystic neuroblastoma, retroperitoneal cystic teratoma, and cystic lymphangioma. Tumor markers were within normal limits. Surgical exploration revealed a left renal hilar solitary cystic mass lesion, which was excised in toto with a probable intraoperative diagnosis of cystic lymphangioma. The postoperative course was uneventful. Histopathological examination confirmed that the lesion was a mature cystic teratoma. The child is doing well postoperatively at the one-year follow-up. Neonatal retroperitoneal teratomas are unusual neoplasms. A favorable outcome can be achieved, with early diagnosis and treatment.

Lamivudine modulates the expression of neurological impairment-related genes and LINE-1 retrotransposons in brain tissues of a Down syndrome mouse model.

Elevated activity of retrotransposons is increasingly recognized to be implicated in a wide range of neurodegenerative and neurodevelopmental diseases, including Down syndrome (DS), which is the most common chromosomal condition causing intellectual disability globally. Previous research by our group has revealed that treatment with lamivudine, a reverse transcriptase inhibitor, improved neurobehavioral phenotypes and completely rescued hippocampal-dependent recognition memory in a DS mouse model, Ts65Dn. We hypothesized that retrotransposition rates would increase in the Ts65Dn mouse model, and lamivudine could block retrotransposons. We analyzed the differentially expressed long interspersed element-1 (LINE-1 or L1) mapping on MMU16 and 17, and showed for the first time that retrotransposition could be associated with Ts65Dn's pathology, as misregulation of L1 was found in brain tissues associated with trisomy. In the cerebral cortex, 6 out of 26 upregulated L1s in trisomic treated mice were located in the telomeric region of MMU16 near Ttc3, Kcnj6, and Dscam genes. In the hippocampus, one upregulated L1 element in trisomic treated mice was located near the Fgd4 gene on MMU16. Moreover, two downregulated L1s rescued after treatment with lamivudine were located in the intronic region of Nrxn1 (MMU17) and Snhg14 (MMU7), implicated in a variety of neurodegenerative disorders. To gain further insight into the mechanism of this improvement, we here analyzed the gene expression profile in the hippocampus and cerebral cortex of trisomic mice treated and no-treated with lamivudine compared to their wild-type littermates. We found that treatment with lamivudine rescued the expression of 24% of trisomic genes in the cortex (located on mouse chromosome (MMU) 16 and 17) and 15% in the hippocampus (located in the human chromosome 21 orthologous regions), with important DS candidate genes such as App and Ets2, rescued in both regions.

Azacitidine treatment for myeloid leukemia associated with Down syndrome: A nationwide retrospective study in Japan.

Hypomethylating agent treatment for myeloid leukemia associated with Down syndrome (ML-DS) has been scarcely reported. Herein, we collected information on azacitidine treatment for ML-DS in Japan. Forty-eight cycles of azacitidine treatment were performed for 12 patients, including 11 relapsed or refractory (R/R) patients. In 40 cycles, azacitidine was used as monotherapy. No azacitidine-related death was observed. One cycle concurrently administered with methotrexate-based intrathecal therapy was discontinued due to toxicities. Only 4 of the 19 cycles given in non-remission achieved complete or partial remission. In conclusion, although most toxicities were acceptable, azacitidine monotherapy might be insufficient for R/R ML-DS cases.

Laboratory-based measures of executive function and daily living skills in young children with Down syndrome: informing future interventions.

BACKGROUND: Adaptive behaviour refers to the practical skills necessary for independence and is considered a high-priority intervention target for children with neurogenetic conditions associated with intellectual disability, like Down syndrome (DS). Daily living skills (DLS) are a critical aspect of adaptive behaviour, but they have received little intervention attention, possibly because they involve a wide variety of skills across many settings. The present study aimed to advance DLS intervention science by examining the concurrent and longitudinal association between DLS performances and a cognitive skillset hypothesised to support DLS skill acquisition, executive function (EF). METHODS: Participants were 71 children with DS between the ages of 2.5 and 8.7 years (M = 5.23 years; standard deviation = 1.65) who completed a battery of adapted EF tasks and a primary caregiver who completed the Vineland Adaptive Behavior Scales 3rd Edition Parent/Caregiver Comprehensive Report Form. A subset of caregivers also provided 6- and 12-month follow-up adaptive behaviour information. RESULTS: Results demonstrated a positive association between EF task performance and DLS standard scores and v-scores both concurrently and longitudinally. CONCLUSIONS: The findings have implications for potential future intervention approaches that aim to strengthen DLS performances by advancing EF skills in this population.

Correlation between fetal ventricular echogenic foci in pregnancy and fetus chromosomal anomaly: a case-control study in Bandar Abbas city.

Background: Ventricular echogenic foci are small structures within the hearts of some fetuses. These small areas result from increased echogenicity in the ventricles of fetuses located near the papillary muscles. An association between these foci and chromosomal abnormalities in fetuses has been reported. Considering that chromosomal abnormalities are a major cause of prenatal death, this study aimed to determine the value of fetal echogenic foci as markers for chromosomal abnormalities. Materials and methods: Fetal echocardiography was performed by an experienced cardiologist on 149 pregnant women in the second trimester. Of these, 75 were reported to have positive echogenic foci, and 74 were reported to have no echogenic foci. Subsequently, the three chromosomal anomalies including trisomies 21, 18, and 13 were examined. The information of the individuals, including gestational age and echogenic foci, was recorded. Results: Based on the findings of the present study, seven infants (4.7%) had trisomy 21, four infants (2.7%) had trisomy 13, and six infants (4.1%) had trisomy 18. The mean gestational age of pregnant women with positive and negative echogenic foci was 21.07±3.23 and 21.03±3.09, respectively. No significant relationship was found between ventricular echogenic foci and trisomy 21, 18, or 13. Conclusion: The present study suggests no significant relation between the presence of echogenic foci and chromosomal trisomies. This finding indicates that additional tests are required to confirm chromosomal abnormalities when echogenic intracardiac foci are present, especially in high-risk fetuses. Moreover, the absence of echogenic focus does not rule out chromosomal disorders.

Opioid and benzodiazepine requirements in critically ill post-surgical children with down syndrome: a systematic review and meta-analysis.

BACKGROUND: Down syndrome (DS), or Trisomy 21, is defined by the existence of an additional chromosome 21. Various physiological considerations in DS patients might lead to challenges in adequate pain management and sedation after surgery. The aim of this systematic review and meta-analysis is to evaluate the variations of the requirement needed for pain management and sedation in patients with DS who have undergone surgery compared to patients without DS. METHODS: A systematic review and meta-analysis of studies were conducted, focusing on critically ill patients with DS who were admitted to Intensive care units (ICUs) post-surgery and received opioids and/or benzodiazepines. Searches were conducted in four databases from their inception to November 18, 2023 (Pubmed, Scopus, Cochrane Library, and Web of Science). The primary outcome measured was the dosage of Oral Morphine Equivalent (OME) administered in the days following surgery. Fixed-effect models were used, an approach advisable when only a limited number of studies are available. RESULTS: Out of the 992 studies initially screened, the systematic review included ten studies, encompassing 730 patients, while the meta-analysis consisted of seven studies, encompassing 533 patients. Of the seven studies included in the analysis, 298 patients were identified to have DS, and 235 patients served as controls. Patients with DS showed a slight increase in OME needs on the first day, but this increase was not statistically significant (mean difference [MD] = 0.09; 95% Confidence Interval [CI]: [-0.02, 0.20]; P = 0.11). There was also no significant difference in the requirement for Midazolam on the first day among DS patients (MD = 0.01; CI [-0.16, 0.19]; P = 0.88). In addition, the duration of mechanical ventilation was not statistically significant in patients with DS compared with the control group (MD = -1.46 hours; 95% CI [-9.74, 6.82]; P = 0.73). CONCLUSION: Patients with Down syndrome did not require more sedation or analgesia in the first three days after surgery than patients without Down syndrome. Additionally, the two groups showed no significant difference in the duration of mechanical ventilation.

Characterization of white matter hyperintensities in Down syndrome.

INTRODUCTION: In Down syndrome (DS), white matter hyperintensities (WMHs) are highly prevalent, yet their topography and association with sociodemographic data and Alzheimer's disease (AD) biomarkers remain largely unexplored. METHODS: In 261 DS adults and 131 euploid controls, fluid-attenuated inversion recovery magnetic resonance imaging scans were segmented and WMHs were extracted in concentric white matter layers and lobar regions. We tested associations with AD clinical stages, sociodemographic data, cerebrospinal fluid (CSF) AD biomarkers, and gray matter (GM) volume. RESULTS: In DS, total WMHs arose at age 43 and showed stronger associations with age than in controls. WMH volume increased along the AD continuum, particularly in periventricular regions, and frontal, parietal, and occipital lobes. Associations were found with CSF biomarkers and temporo-parietal GM volumes. DISCUSSION: WMHs increase 10 years before AD symptom onset in DS and are closely linked with AD biomarkers and neurodegeneration. This suggests a direct connection to AD pathophysiology, independent of vascular risks. HIGHLIGHTS: White matter hyperintensities (WMHs) increased 10 years before Alzheimer's disease symptom onset in Down syndrome (DS). WMHs were strongly associated in DS with the neurofilament light chain biomarker. WMHs were more associated in DS with gray matter volume in parieto-temporal areas.

Morphometric analysis of atlas lateral mass in Down syndrome cases with relevance to surgical intervention.

PURPOSE: Surgical stabilization of the Atlas vertebrae is indicated for severe atlantoaxial instability (AAI) in patients with Down syndrome (DS). This study aims to evaluate the morphological characteristics of the Atlas lateral mass (ALM) in patients with DS with regard to safe instrumentation for surgical stabilization and to compare them with non-syndromic group. METHODS: This multicenter, retrospective, case-control study included age- and sex-matched patients with and without DS aged > 7 years with a cervical computed tomography (CT) scan. After three-dimensional CT reconstruction, nine parameters were evaluated for both groups. All included measurements were performed by a neuroradiologist who was blinded to clinical data. RESULTS: Forty-three of 3,275 patients with DS were included in this study. Matching number of consecutive patients without DS were identified (mean age: 16 years). Patients with DS were significantly shorter than those without DS. Seven of nine parameters related to ALM were significantly lower in patients with DS than in those in the control group, including anterior wall height (AH), posterior wall height (PH), their ratio, and arch-ALM angle. On adjusting data for patient height, patients with DS had a smaller PH, lower PH/AH ratio, and steeper arch-ALM angle than the control group. CONCLUSIONS: Patients with DS had a smaller posterior ALM wall and a steeper arch-ALM angle than the control group without DS. This information is important for surgical planning of safe posterior ALM exposure and safe instrumentation for surgical stabilization in patients with DS.

Unusual late-onset hypertrophic pyloric stenosis in an adolescent girl with down syndrome: Case report and review of the literature.

A 16-year-old girl with down syndrome came to our attention for recurrent postprandial vomiting and significant weight loss (>5 kgs). Diagnostic assessment (barium swallow study, ultrasonography, and CT) confirmed hypertrophic pyloric stenosis (HPS). Initial attempt with endoscopic dilation was not successful. The patient underwent Heineke-Mikulicz pyloroplasty. Full oral feeding was achieved by Day 7 postoperatively. At 6-month follow-up, the patient reported relief of symptoms, normal feeding habits and substantial weight gain. HPS should be considered in the differential diagnosis of recurrent vomiting, regardless of age. A comprehensive diagnostic work-up, including ultrasonography, endoscopy, and CT, is recommended to confirm the diagnosis.

Down syndrome and associated atrioventricular septal defects in a nationwide Norwegian cohort: Prevalence, time trends, and outcomes.

INTRODUCTION: The prevalence of Down syndrome (DS) is approximately 1 per 1000 births and is influenced by increasing maternal age over the last few decades. DS is strongly associated with congenital heart defects (CHDs), especially atrioventricular septal defect (AVSD). Our objectives were to investigate the prevalence of live-born infants with DS having a severe CHD in the Norwegian population over the last 20 years and compare outcomes in infants with AVSD with and without DS. MATERIAL AND METHODS: Information on all births from January 1, 2000 to December 31, 2019 was obtained from the Medical Birth Registry of Norway. We also obtained data on all infants with severe CHDs in Norway registered in Oslo University Hospital's Clinical Registry for Congenital Heart Defects during 2000-2019 and accessed individual-level patient data from the electronic hospital records of selected cases. Infants with AVSD and DS were compared to infants with AVSD without chromosomal defects. Crude and adjusted odds ratios (ORs) of infant mortality and need for surgery during the first year of life, with associated 95% confidence intervals (CIs), were estimated by logistic regression. RESULTS: A total of 1 177 926 infants were live-born in Norway during the study period. Among these, 1456 (0.1%) had DS. The prevalence of infants with DS having a severe CHDs was relatively stable, with a mean of 17 cases per year. The most common CHD associated with DS was AVSD (44.4%). Infants with AVSD and DS were more likely to have cardiac intervention during their first year of life compared to infants with AVSD without chromosomal defects (adjusted OR [aOR]: 2.52; 95% CI 1.27, 4.98). However, we observed no difference in infant mortality during first year of life between the two groups (aOR: 1.08; 95% CI 0.43, 2.70). CONCLUSIONS: The prevalence of live-born infants with severe CHDs and DS has been stable in Norway across 20 years. Infants with AVSD and DS did not have higher risk of mortality during their first year of life compared to infants with AVSD without chromosomal defects, despite a higher risk of operative intervention.

Analysis of microisolated frontal cortex excitatory layer III and V pyramidal neurons reveals a neurodegenerative phenotype in individuals with Down syndrome.

We elucidated the molecular fingerprint of vulnerable excitatory neurons within select cortical lamina of individuals with Down syndrome (DS) for mechanistic understanding and therapeutic potential that also informs Alzheimer's disease (AD) pathophysiology. Frontal cortex (BA9) layer III (L3) and layer V (L5) pyramidal neurons were microisolated from postmortem human DS and age- and sex-matched controls (CTR) to interrogate differentially expressed genes (DEGs) and key biological pathways relevant to neurodegenerative programs. We identified > 2300 DEGs exhibiting convergent dysregulation of gene expression in both L3 and L5 pyramidal neurons in individuals with DS versus CTR subjects. DEGs included over 100 triplicated human chromosome 21 genes in L3 and L5 neurons, demonstrating a trisomic neuronal karyotype in both laminae. In addition, thousands of other DEGs were identified, indicating gene dysregulation is not limited to trisomic genes in the aged DS brain, which we postulate is relevant to AD pathobiology. Convergent L3 and L5 DEGs highlighted pertinent biological pathways and identified key pathway-associated targets likely underlying corticocortical neurodegeneration and related cognitive decline in individuals with DS. Select key DEGs were interrogated as potential hub genes driving dysregulation, namely the triplicated DEGs amyloid precursor protein (APP) and superoxide dismutase 1 (SOD1), along with key signaling DEGs including mitogen activated protein kinase 1 and 3 (MAPK1, MAPK3) and calcium calmodulin dependent protein kinase II alpha (CAMK2A), among others. Hub DEGs determined from multiple pathway analyses identified potential therapeutic candidates for amelioration of cortical neuron dysfunction and cognitive decline in DS with translational relevance to AD.

Physicians, Public Discourse, and Passive Euthanasia of Infants with Down Syndrome in the Late-Twentieth Century.

Through the late-twentieth century, physicians endorsed the denial of life-saving surgeries to infants because they had Down syndrome. Grim physician assessments of the inevitable burden of Down syndrome found ideological footing in the 1970s crusade to eradicate the condition, a public health goal made possible by new genetic diagnostics and a weakened abortion law. What is most striking about this physician-sanctioned passive euthanasia is that it persisted even in an era of unprecedented expansion of disability rights. Physician endorsement of the euthanasia of infants with Down syndrome offers a powerful corrective to the notion that post-war Canada was marked by waning support for eugenics. Medically sanctioned euthanasia of babies because of their Down syndrome, eugenics of the most extreme type, thrived in late-twentieth century Canada.

Jusqu'à la fin du vingtième siècle, les médecins ont approuvé le refus de pratiquer des interventions chirurgicales vitales sur des nourrissons parce qu'ils étaient atteints du syndrome de Down. La sombre évaluation par les médecins du fardeau inévitable qu'entraînait le syndrome de Down a trouvé un fondement idéologique dans la croisade des années 1970 pour éradiquer la maladie, un objectif de santé publique rendu possible par les nouveaux diagnostics génétiques et grâce à une loi sur l'avortement moins sévère. L'aspect le plus frappant de cette euthanasie passive sanctionnée par les médecins est qu'elle a persisté à une époque d'expansion sans précédent des droits des personnes handicapées. L'approbation par les médecins de l'euthanasie des nourrissons atteints du syndrome de Down apporte un puissant correctif à l'idée que le Canada de l'après-guerre a été caractérisé par une baisse du soutien à l'eugénisme. L'euthanasie médicalement sanctionnée de bébés en raison du syndrome de Down, c'est-à-dire l'eugénisme le plus extrême, a au contraire prospéré dans le Canada de la fin du vingtième siècle.