Down syndrome is the most common chromosomal abnormality encountered in clinical practice with 50%of them having associated congenital heart disease(CHD).Shunt lesions account for around 75%of all CHDs in Down syndrom...Down syndrome is the most common chromosomal abnormality encountered in clinical practice with 50%of them having associated congenital heart disease(CHD).Shunt lesions account for around 75%of all CHDs in Down syndrome.Down syndrome patients,especially with large shunts are particularly predisposed to early development of severe pulmonary hypertension(PH)compared with shunt lesions in general population.This necessitates timely surgical correction which remains the only viable option to prevent long term morbidity and mortality.However,despite clear recommendations,there is wide gap between actual practice and fear of underlying PH which often leads to surgical refusals in Down syndrome even when the shunt is reversible.Another peculiarity is that Down syndrome patients can develop PH even after successful correction of shunt.It is not uncommon to come across Down syndrome patients with uncorrected shunts in adulthood with irreversible PH at which stage intracardiac repair is contraindicated and the only option available is a combined heartlung transplant.However,despite the guidelines laid by authorities,the rates of cardiac transplant in adult Down syndrome remain dismal largely attributable to the high prevalence of intellectual disability in them.The index case presents a real-world scenario highlighting the impact of severe PH on treatment strategies and discrimination driven by the fear of worse outcomes in these patients.展开更多
Down syndrome(DS)is a genetic condition characterized by intellectual disability,delayed brain development,and early onset Alzheimer’s disease.The use of primary neural cells and tissues is important for understandin...Down syndrome(DS)is a genetic condition characterized by intellectual disability,delayed brain development,and early onset Alzheimer’s disease.The use of primary neural cells and tissues is important for understanding this disease,but there are ethical and practical issues,including availability from patients and experimental manipulability.Moreover,there are significant genetic and physiological differences between animal models and humans,which limits the translation of the findings in animal studies to humans.Advancements in induced pluripotent stem cells(iPSC)technology have revolutionized DS research by providing a valuable tool for studying the cellular and molecular pathologies associated with DS.Induced pluripotent stem cells derived from cells obtained from DS patients contain the patient’s entire genome including trisomy 21.Trisomic iPSCs as well as their derived cells or organoids can be useful for disease modeling,investigating the molecular mechanisms,and developing potential strategies for treating or alleviating DS.In this review,we focus on the use of iPSCs and their derivatives obtained from DS individuals and healthy humans for DS research.We summarize the findings from the past decade of DS studies using iPSCs and their derivatives.We also discuss studies using iPSC technology to investigate DS-associated genes(e.g.,APP,OLIG1,OLIG2,RUNX1,and DYRK1A)and abnormal phenotypes(e.g.,dysregulated mitochondria and leukemia risk).Lastly,we review the different strategies for mitigating the limitations of iPSCs and their derivatives,for alleviating the phenotypes,and for developing therapies.展开更多
BACKGROUND Down syndrome(DS)is one of the most common causes of intellectual disability.Children with DS have varying intelligence quotient(IQ)that can predict their learning abilities.AIM To assess the brain metaboli...BACKGROUND Down syndrome(DS)is one of the most common causes of intellectual disability.Children with DS have varying intelligence quotient(IQ)that can predict their learning abilities.AIM To assess the brain metabolic profiles of children with DS and compare them to standard controls,using magnetic resonance spectroscopy(MRS)and correlating the results with IQ.METHODS This case-control study included 40 children with DS aged 6-15 years and 40 age and sex-matched healthy children as controls.MRS was used to evaluate ratios of choline/creatine(Cho/Cr),N-acetyl aspartic acid/creatine(NAA/Cr),and myoinositol/creatine(MI/Cr(in the frontal,temporal,and occipital lobes and basal ganglia and compared to controls and correlated with IQ.RESULTS Children with DS showed significant reductions in NAA/Cr and MI/Cr and a non-significant reduction in Cho/Cr in frontal lobes compared to controls.Additionally,we observed significant decreases in NAA/Cr,MI/Cr,and Cho/Cr in the temporal and occipital lobes and basal ganglia in children with DS compared to controls.Furthermore,there was a significant correlation between IQ and metabolic ratios in the brains of children with DS.CONCLUSION Brain metabolic profile could be a good predictor of IQ in children with DS.展开更多
BACKGROUND Pulmonary hypertension(PH)has serious short-and long-term consequences.PH is gaining increasing importance in high risk groups such as Down syndrome(DS)as it influences their overall survival and prognosis....BACKGROUND Pulmonary hypertension(PH)has serious short-and long-term consequences.PH is gaining increasing importance in high risk groups such as Down syndrome(DS)as it influences their overall survival and prognosis.Hence,there is a dire need to collate the prevalence rates of PH in order to undertake definitive measures for early diagnosis and management.AIM To determine the prevalence of PH in children with DS.METHODS The authors individually conducted a search of electronic databases manually(Cochrane library,PubMed,EMBASE,Scopus,Web of Science).Data extraction and quality control were independently performed by two reviewers and a third reviewer resolved any conflicts of opinion.The words used in the literature search were“pulmonary hypertension”and“pulmonary arterial hypertension”;“Down syndrome”and“trisomy 21”and“prevalence”.The data were analyzed by Comprehensive Meta-Analysis Software Version 2.Risk of bias assessment and STROBE checklist were used for quality assessment.RESULTS Of 1578 articles identified,17 were selected for final analysis.The pooled prevalence of PH in these studies was 25.5%.Subgroup analysis was carried out for age,gender,region,year of publication,risk of bias and etiology of PH.CONCLUSION This review highlights the increasing prevalence of PH in children with DS.It is crucial for pediatricians to be aware of this morbid disease and channel their efforts towards earlier diagnosis and successful management.Community-based studies with a larger sample size of children with DS should be carried out to better characterize the epidemiology and underlying etiology of PH in DS.展开更多
Background:Postoperative pulmonary hypertension limits the success of surgical treatment in some patients with unrestrictive congenital cardiac communications.Identifying patients at risk of developing postoperative p...Background:Postoperative pulmonary hypertension limits the success of surgical treatment in some patients with unrestrictive congenital cardiac communications.Identifying patients at risk of developing postoperative pulmonary hypertension is important to individualize follow-up strategies.Methods:We analyzed a prospective cohort of 52 pediatric patients(age 3 to 35 months)looking for perioperative predictors of mildly elevated pulmonary arterial pressure 6 months after surgery,defined as a systolic pressure greater than 30 mmHg by transthoracic echocardiography.This corresponds to a mean pulmonary arterial pressure of>20 mmHg.Clinical,echocardiographic and hemodynamic parameters were investigated.Perioperative hemodynamics was assessed by directly measuring pulmonary and systemic arterial pressures using indwelling catheters.Early postoperative pulmonary hemodynamics was defined as the mean pulmonary/systemic mean arterial pressure ratio(PAP/SAP)obtained per patient during the first 6 h of postoperative care.Results:Among the factors that were investigated as possible predictors,perioperative hemodynamics and the presence of Down syndrome were initially selected using univariate analysis(p<0.030).Early postoperative PAP/SAP was correlated with PAP/SAP obtained in the operating room just after cardiopulmonary bypass(r=0.70,p<0.001),and it was higher in subjects with Down syndrome than in nonsyndromic individuals(p=0.003).Early postoperative PAP/SAP was the only predictor selected using multivariate analysis.It was characterized as an independent predictor after adjustments for possible confounders.An early postoperative PAP/SAP of>0.35 was 76%sensitive and 74%specific at predicting a systolic pulmonary arterial pressure of>30 mmHg 6 months after surgery(hazard ratio with 95%CI 8.972[2.428–33.158],p=0.002).Conclusion:The hypertensive early postoperative behavior of the pulmonary circulation was strongly but not exclusively associated with Down syndrome,and it was characterized as an independent predictor of altered pulmonary arterial pressure after discharge from the hospital.展开更多
BACKGROUND Down syndrome(DS)is one of the most common chromosomal aneuploidy diseases.Prenatal screening and diagnostic tests can aid the early diagnosis,appropriate management of these fetuses,and give parents an inf...BACKGROUND Down syndrome(DS)is one of the most common chromosomal aneuploidy diseases.Prenatal screening and diagnostic tests can aid the early diagnosis,appropriate management of these fetuses,and give parents an informed choice about whether or not to terminate a pregnancy.In recent years,investigations have been conducted to achieve a high detection rate(DR)and reduce the false positive rate(FPR).Hospitals have accumulated large numbers of screened cases.However,artificial intelligence methods are rarely used in the risk assessment of prenatal screening for DS.AIM To use a support vector machine algorithm,classification and regression tree algorithm,and AdaBoost algorithm in machine learning for modeling and analysis of prenatal DS screening.METHODS The dataset was from the Center for Prenatal Diagnosis at the First Hospital of Jilin University.We designed and developed intelligent algorithms based on the synthetic minority over-sampling technique(SMOTE)-Tomek and adaptive synthetic sampling over-sampling techniques to preprocess the dataset of prenatal screening information.The machine learning model was then established.Finally,the feasibility of artificial intelligence algorithms in DS screening evaluation is discussed.RESULTS The database contained 31 DS diagnosed cases,accounting for 0.03%of all patients.The dataset showed a large difference between the numbers of DS affected and non-affected cases.A combination of over-sampling and undersampling techniques can greatly increase the performance of the algorithm at processing non-balanced datasets.As the number of iterations increases,the combination of the classification and regression tree algorithm and the SMOTETomek over-sampling technique can obtain a high DR while keeping the FPR to a minimum.CONCLUSION The support vector machine algorithm and the classification and regression tree algorithm achieved good results on the DS screening dataset.When the T21 risk cutoff value was set to 270,machine learning methods had a higher DR and a lower FPR than statistical methods.展开更多
The aim of the study was to investigate the effect of a hydrotherapy program on FVC, FEV, PEF, RR and SaO<sub>2</sub> on children with Down syndrome over six months and to compare it with a conventional re...The aim of the study was to investigate the effect of a hydrotherapy program on FVC, FEV, PEF, RR and SaO<sub>2</sub> on children with Down syndrome over six months and to compare it with a conventional respiratory physiotherapy program. Eighteen children, with Down Syndrome, aged 6 - 11 years (9.53 ± 0.454), divided into two groups of nine, the intervention group (IG), that participated in the hydrotherapy program and the control group (CG) participated in the classical physiotherapy program. We calculated mean values of FVC, FEV, PEF, RR and SaO2 before and after six months intervention for both groups. There was a statistically significant improvement in all factors for both groups. However, were statistically more significant for the intervention group (IG). Based on a specific protocol of intervention in the water and at the same time with a group of children who participated in a similar program of classical respiratory physiotherapy, it was found to be statistically more important than the second group in improving respiratory function. We recommend the use of hydrotherapy as a complementary therapy that should be part of the weekly program of these children in addition to the existing treatments they attend.展开更多
<strong>Background</strong>:<span> </span><span>Limited research concerns the study of continuity in the future of the physical and social status of elderly people with DS that is when pe...<strong>Background</strong>:<span> </span><span>Limited research concerns the study of continuity in the future of the physical and social status of elderly people with DS that is when people who take care of them will not be there anymore (“<i></i></span><i><i><span>after</span></i><span> </span><i><span>we</span></i><span> </span><i><span>have</span></i><span> </span><i><span>gone</span></i></i><span>”). </span><b><span>Objective</span></b><b><span>:</span></b><span> From a biopsychosocial perspective, to investigate the daily life of ageing people with Down Syndrome over 45 years old in order to identify the most important issues in better planning for their future. </span><b><span>Methods</span></b><b><span>:</span></b><span> A cross-sectional Italian national study was carried out. An <i></i></span><i><i><span>ad</span></i><span> </span><i><span>hoc</span></i></i><span> questionnaire was administered to formal and informal caregivers of aging people with Down Syndrome. </span><b><span>Results</span></b><b><span>:</span></b><span> 136 family members and health professionals were involved. Most of </span><span>the </span><span>people with Down Syndrome live at home, attend a daily center and do many activities. Most of them had never worked and she/he is not at all autonomous. 25% of caregivers declared that, nowadays, there is not planning for the future, and 30.9% of participants who planned their future collected information when it occurred (e.g. when the parents pass away). </span><b><span>Conclusions</span></b><b><span>:</span></b><span> </span><span>The a</span><span>ging of people with DS requires attention to the planning of their future. In order to better plan, it is necessary to avoid programming </span><span>“</span><span>in emergency</span><span>”</span><span>, but for time, keeping in mind of the activities developed by the people, their abilities and all of the elements that have allowed them to live well up to a point of their life.</span>展开更多
Purpose: To alert the medical community that whole exome sequencing can find accessory gene changes in well-known syndromes that alter preventive health care and management. Meaning: A collagen type VI gene change add...Purpose: To alert the medical community that whole exome sequencing can find accessory gene changes in well-known syndromes that alter preventive health care and management. Meaning: A collagen type VI gene change adds muscle weakness, hypermobility, and dysautonomia concerns to usual management considerations for Down syndrome. Methods: Commercial whole exome sequencing combined with clinical interpretation of DNA sequence change added new considerations to patient management and parental counsel. Results: An 11-year-old child with the trisomy 21 form of Down syndrome who was evaluated for extraordinary joint laxity had a heterozygous collagen type VI aspartic to glutamic acid (COL6A3 c.6360 C>G p.Asp2120Glu) gene change found by whole exome sequencing. The DNA variant was qualified as having strong relevance to the enhanced hypermobility due to prior association of collagen 6 gene changes with myopathy. Conclusions: Dual diagnosis of Ehlers-Danlos syndrome was not assigned because the patient lacked criteria like bruising, unusual scars, or selected dysautonomia symptoms. The concept of a hypermobility spectrum offers advantages for management of its constituent conditions if clinically guided ascertainment and DNA diagnostics are employed.展开更多
Down syndrome (DS) is the most common chromosomal abnormality in humans, and the most frequent cause of mental retardation. Patients affected by this syndrome show an increased prevalence of autoimmune diseases. The m...Down syndrome (DS) is the most common chromosomal abnormality in humans, and the most frequent cause of mental retardation. Patients affected by this syndrome show an increased prevalence of autoimmune diseases. The most common of those is Hypothyroidism. We present a case report describing the association of Down syndrome with Hyperthyroidism. An 18-year-old patient presented with a history of recurrent throat infections and intermittent diarrhea, having developed a total alopecia areata within one month from the first visit to the physician. After consultations with general practitioners, he was directed to an Endocrinology Ambulatory and diagnosed with a clear case of Graves’ disease associated with Down syndrome. Treatment was started with methimazole 20 mg/day, and after two months, was adjusted to 40 mg/day. The patient reached adequate clinical and laboratory balance after five months of treatment. Thus, the association between Down syndrome and Graves’ Disease is relevant in medical practice, due to its specific characteristics on diagnosis, and the need of an adequate treatment regarding this disease association.展开更多
Primary care physicians are in a unique position to provide a holistic and individualized care to their patients with Down Syndrome. These patients share common medical problems with general population;however, they o...Primary care physicians are in a unique position to provide a holistic and individualized care to their patients with Down Syndrome. These patients share common medical problems with general population;however, they often are medically complex and present with cardiac, orthopedic, and endocrine challenges such as overweight-obesity and related comorbidities that occur with more frequency in this unique population. The prevention of overweight-obesity is an important public health issue for both the general population and for the population of individuals with Down Syndrome. If abnormal weight gain is treated early and effectively many secondary comorbidities can be prevented or ameliorated. This case report discusses the impact of implementing a Consistent Individualized Carbohydrate controlled Anti-inflammatory Nutrition plan (C-ICAN) as part of the treatment plan for a young woman with Down Syndrome (DS). The C-ICAN meal plan is a low glycemic load meal plan with 30% to 35% calories from fat, 20% to 25% calories from protein, 40% to 45% calories from carbohydrate, and goal of 25 gm fiber per day. The C-ICAN meal plan combines the Mediterranean diet because of its well-established anti-inflammatory, and cardiovascular benefits, with a high protein and low glycemic-load meal plan to improve satiety and glycemic control. In this case the patient and her caregivers adjusted to a structured meal pattern well, weight balance resulted, and mealtime stress was reduced.展开更多
AIM: To describe human leukocyte antigen(HLA) alleles in individuals with Down syndrome and alopecia areata. METHODS: A cross-sectional study was conducted, which evaluated 109 individuals. Ten with down syndrome(DS) ...AIM: To describe human leukocyte antigen(HLA) alleles in individuals with Down syndrome and alopecia areata. METHODS: A cross-sectional study was conducted, which evaluated 109 individuals. Ten with down syndrome(DS) and alopecia areata(AA), ten with DS without AA and ten with AA without DS, and their fami-lies. The individuals were matched by gender and age. The following data were computed: gender, age, ethnic group, karyotype, clinical presentation and family history of alopecia areata. Descriptive analysis: measures of central tendency and frequency distribution. Inferential analysis: Fisher's exact test to compare categorical data between the three groups and Kruskal-Wallis ANOVA test for numerical data.RESULTS: Seventy per cent of evaluated individuals in the DS and AA group were male; presented mean age of 18.6(SD ± 7.2) years and 70% were Caucasian. We observed involvement of the scalp, with a single lesion in 10% and multiple in 90% of subjects. It was observed that there is no significant difference in the frequency distributions of the alleles HLA loci A, B, C, DRB1 and DQB1 of subjects studied. However, according to Fisher's exact test, there is a trend(P = 0.089) of DS group to present higher proportions of HLA-A 36 and HLA-B 15 than the AA group and AA and DS group.CONCLUSION: There was a tendency for the DS group, to present proportion of HLA-A 36 and HLA-B 15 higher than the AA group and group of individuals with AA and DS. However, there was no significant difference in the frequency distribution of the alleles.展开更多
Background:Down syndrome(DS)individuals,by the age of 40s,are at increased risk to develop Alzheimer-like dementia,with deposition in brain of senile plaques and neurofibrillary tangles.Our laboratory recently demonst...Background:Down syndrome(DS)individuals,by the age of 40s,are at increased risk to develop Alzheimer-like dementia,with deposition in brain of senile plaques and neurofibrillary tangles.Our laboratory recently demonstrated the disturbance of PI3K/AKT/mTOR axis in DS brain,prior and after the development of Alzheimer Disease(AD).The aberrant modulation of the mTOR signalling in DS and AD age-related cognitive decline affects crucial neuronal pathways,including insulin signaling and autophagy,involved in pathology onset and progression.Within this context,the therapeutic use of mTOR-inhibitors may prevent/attenuate the neurodegenerative phenomena.By our work we aimed to rescue mTOR signalling in DS mice by a novel rapamycin intranasal administration protocol(InRapa)that maximizes brain delivery and reduce systemic side effects.Methods:Ts65Dn mice were administered with InRapa for 12 weeks,starting at 6 months of age demonstrating,at the end of the treatment by radial arms maze and novel object recognition testing,rescued cognition.Results:The analysis of mTOR signalling,after InRapa,demonstrated in Ts65Dn mice hippocampus the inhibition of mTOR(reduced to physiological levels),which led,through the rescue of autophagy and insulin signalling,to reduced APP levels,APP processing and APP metabolites production,as well as,to reduced tau hyperphosphorylation.In addition,a reduction of oxidative stress markers was also observed.Discussion:These findings demonstrate that chronic InRapa administration is able to exert a neuroprotective effect on Ts65Dn hippocampus by reducing AD pathological hallmarks and by restoring protein homeostasis,thus ultimately resulting in improved cognition.Results are discussed in term of a potential novel targeted therapeutic approach to reduce cognitive decline and AD-like neuropathology in DS individuals.展开更多
Down syndrome(DS),as a typical genomic aneuploidy,is a common cause of various birth defects,among which is congenital heart disease(CHD).40e60%neonates with DS have some kinds of CHD.However,the molecular pathogenic ...Down syndrome(DS),as a typical genomic aneuploidy,is a common cause of various birth defects,among which is congenital heart disease(CHD).40e60%neonates with DS have some kinds of CHD.However,the molecular pathogenic mechanisms of DS associated CHD are still not fully understood.This review summarizes available studies on DS associated CHD from seven aspects so as to provide a crucial and updated overview of what we known so far in this domain.展开更多
Background:To assess the diagnostic ability of Pentacam HR(Oculus Optikgeräte,GmbH,Wetzlar,Germany)tomographic indices in discriminating keratoconus(KC)and KC suspect(KCS)in 10-to 30-year-old patients with Down s...Background:To assess the diagnostic ability of Pentacam HR(Oculus Optikgeräte,GmbH,Wetzlar,Germany)tomographic indices in discriminating keratoconus(KC)and KC suspect(KCS)in 10-to 30-year-old patients with Down syndrome(DS).Methods:In this study,DS patients were enrolled through special needs schools,the National Down Syndrome Society,and relevant non-profit organizations.Diagnoses were made independently by two experienced specialists.Forty Pentacam indices related to corneal thickness,volume,density,keratometry,power,shape,aberration,and elevation were extracted.For each index,the accuracy for KC and KCS diagnosis was evaluated using discriminant analysis and the area under receiver operating characteristic curve(AUROC).From each enrolled case,data from only one eye was entered in the analyses.Results:Analyses were performed on data from 25 KC,46 KCS,and 154 non-ectatic DS eyes.The best discriminants for KC were anterior higher order aberrations(HOA)(cutoff>0.643,AUROC=0.879),posterior vertical coma(cutoff>0.0702μm,AUROC=0.875),anterior vertical coma(cutoff>0.4124μm,AUROC=0.868),and total HOA(cutoff>0.608,AUROC=0.867).The difference between AUROCs were not statistically significant(all P>0.05).For KCS,the best discriminants were minimum corneal thickness(cutoff≤480.0μm,AUROC=0.775),corneal volume(cutoff≤55.3μm,AUROC=0.727)and Belin Ambrosio display-total deviation(BAD-D)(cutoff>2.23,AUROC=0.718)with no significant difference between AUROCs(all P>0.05).Conclusions:In this sample of DS patients,best KC discriminators were HOA and coma which showed good diagnostic ability.For KCS,best predictors were minimum corneal thickness,corneal volume,and BAD-D with relatively good diagnostic ability.Defining a new set of KC diagnostic criteria for DS patients is suggested.展开更多
Background:Extra genetic material in patients with Down syndrome(DS)may affect the function of any organ system.We evaluated cardiac functions using conventional tissue Doppler and two-dimensional speckle tracking ech...Background:Extra genetic material in patients with Down syndrome(DS)may affect the function of any organ system.We evaluated cardiac functions using conventional tissue Doppler and two-dimensional speckle tracking echocardiography in patients with DS in the absence of congenital and acquired heart disease in patients.Methods:A total of 115 patients with DS between 6 and 13 years of age with clinically and anatomically normal heart and 55 healthy children were included in this cross-sectional study.DS was diagnosed by a karyotype test.Patients with mosaic type were not included in this study.Systolic and diastolic functions were evaluated by echocardiography.Results:Pulsed waved Doppler transmitral early/late inflow velocity(E/A),tissue Doppler mitral annular early/late diastolic peak velocity(Ea/Aa),transtricuspid E/A and tricuspid valve annulus Ea/Aa,pulmonary venous Doppler systolic/diastolic(S/D)wave ratio were lower in patients with Down syndrome than in the control group(P=0.04,P=0.001,P<0.05,P<0.001,P<0.001,respectively).Mitral and tricuspid annular Ea were lower in patients with DS(P<0.001).The right and left ventricular myocardial performance indexes were higher in patients with DS than in the controls(P<0.01).They had significantly higher left ventricular mass,ejection fraction,the mitral annular plane systolic excursion values.However,the Down syndrome group compared with the controls had a lower strain values examined by two-dimensional longitudinal speckle-tracking strain echocardiography.Conclusion:These findings suggest conventional tissue Doppler and two-dimensional longitudinal speckletracking strain echocardiography were useful methods of investigating ventricular function and identifying a higher incidence of biventricular dysfunction in patients with Down syndrome compared with the healthy controls.展开更多
Background:To assess the diagnostic ability of Pentacam HR(Oculus Optikgerate,GmbH,Wetzlar,Germany)tomographic indices in discriminating keratoconus(KC)and KC suspect(KCS)in 10-to 30-year-old patients with Down syndro...Background:To assess the diagnostic ability of Pentacam HR(Oculus Optikgerate,GmbH,Wetzlar,Germany)tomographic indices in discriminating keratoconus(KC)and KC suspect(KCS)in 10-to 30-year-old patients with Down syndrome(DS).Methods:In this study,DS patients were enrolled through special needs schools,the National Down Syndrome Society,and relevant non-profit organizations.Diagnoses were made independently by two experienced specialists.Forty Pentacam indices related to corneal thickness,volume,density,keratometry,power,shape,aberration,and elevation were extracted.For each index,the accuracy for KC and KCS diagnosis was evaluated using discriminant analysis and the area under receiver operating characteristic curve(AUROC).From each enrolled case,data from onlyoneeyewas entered intheanalyses.Results:Analyses were performed on data from 25 KC,46 KCS,and 154 non-ectatic DS eyes.The best discriminants for KC were anterior higher-order aberrations(HOA)(cutoff>0.643μm,AUROC=0.879),posterior vertical coma(cutoff>0.0702μm,AUROC=0.875),anterior vertical coma(cutoff>0.4124μm,AUROC=0.868),and total HOA(cutoff>0.608μm,AUROC=0.867).The difference between AUROCs were not statistically significant(all P>0.05).For KCS,the best discriminants were minimum corneal thickness(cutoff≤480.0μm,AUROC=0.775),corneal volume(cutoff≤55.3μm,AUROC=0.727)and Belin Ambrosio display-total deviation(BAD-D)(cutoff>2.23,AUROC=0.718)with no significant difference between AUROCs(all P>0.05).Conclusions:In this sample of DS patients,the best KC discriminators were HOA and coma which showed good diagnostic ability.For KCS,the best predictors were minimum corneal thickness,corneal volume,and BAD-D with relatively good diagnostic ability.Defining a new set of KC diagnostic criteria for DS patients is suggested.展开更多
Backgrounds: Down syndrome (DS) is the most common chromosomal abnormality. The most important factor in DS is increased maternal age so after the age of 35, the risk of Down syndrome in pregnancy increases. Down synd...Backgrounds: Down syndrome (DS) is the most common chromosomal abnormality. The most important factor in DS is increased maternal age so after the age of 35, the risk of Down syndrome in pregnancy increases. Down syndrome can be diagnosed during pregnancy by prenatal screening. Nondisjunction in cell divisions is the main cause of the DS. Apo lipoprotein E is a 317 amino acid glycoprotein that plays an essential role in metabolism and cholesterol transport. Alzheimer’s disease (AD) is one of the symptoms of adults with DS. The apoE allele e4 has been identified as a risk factor for AD and also, played a main role in nondisjunction. An increased risk of AD in mothers of adults with DS has been reported. We hypothesized that young mothers of DS children (Methods: In this case-control study, 33 DS children and their parents were compared in case of age with 90 families without any history of DS. Genotyping was performed by ARMS-PCR technique. Statistical analysis was performed by SPSS v.21 software. Results: It indicated that there is a significant difference in allele distribution between case and control groups. The C allele for 112 codon of APOE gene and the C allele for 158 codon of APOE gene may associate with nondisjunction. In 112 codon of APOE gene, it seems having T allele reduces the risk of nondisjunction and in contrast C allele may be a risk factor in happening of nondisjunction. (p-value = 0.000006, OR = 2.66, 95% CI = 1.74 - 4.06). In 158 codon of APOE gene, it seems having T allele reduces the risk of nondisjunction and in contrast C allele may be a risk factor in happening of nondisjunction. (p-value = 0.0000, OR = 3.89, 95% CI = 2.38 - 6.34). E4 allele frequency in mothers of DS is about 14% more than those in control group. According to results of this study the C allele in 158 codon of APOE gene and the C allele in 112 codon of APOE gene could be considered as susceptibility genetic factors for nondisjunction in Northeast of Iran.展开更多
This paper presents the pathological voice detection and classification techniques using signal processing based methodologies and Feed Forward Neural Networks(FFNN).The important pathological voices such as Autism Sp...This paper presents the pathological voice detection and classification techniques using signal processing based methodologies and Feed Forward Neural Networks(FFNN).The important pathological voices such as Autism Spectrum Disorder(ASD)and Down Syndrome(DS)are considered for analysis.These pathological voices are known to manifest in different ways in the speech of children and adults.Therefore,it is possible to discriminate ASD and DS children from normal ones using the acoustic features extracted from the speech of these subjects.The important attributes hidden in the pathological voices are extracted by applying different signal processing techniques.In this work,three group of feature vectors such as perturbation measures,noise parameters and spectral-cepstral modeling are derived from the signals.The detection and classification is done by means of Feed For-ward Neural Network(FFNN)classifier trained with Scaled Conjugate Gradient(SCG)algorithm.The performance of the network is evaluated by finding various performance metrics and the the experimental results clearly demonstrate that the proposed method gives better performance compared with other methods discussed in the literature.展开更多
<strong>Background:</strong> Psoriasis, a chronic, systemic, inflammatory disease with prominent skin involvement, affects approximately 2% - 4% of the world population. Common variants of psoriasis are pl...<strong>Background:</strong> Psoriasis, a chronic, systemic, inflammatory disease with prominent skin involvement, affects approximately 2% - 4% of the world population. Common variants of psoriasis are plaque psoriasis, inverse psoriasis, guttate psoriasis, erythrodermic psoriasis, pustular form either palmoplantar pustular psoriasis or generalized pustular psoriasis, nail psoriasis, and psoriatic arthritis. Progressive Symmetrical Erythrokeratoderma (PSEK) is a rare genetic disorder, characterized by fixed, well-defined erythematous and hyperkeratotic plaques distributed predominantly on the elbows, knees, trunk, and dorsal surfaces of hands and feet. Clinically has the same presentation to psoriasis especially at early onset and could be confused with psoriasis but histopathological findings and progression of the psoriatic disease can differentiate between both conditions. <strong>Aim:</strong> To document a new variant of a severe, recalcitrant type of psoriasis with a history of recurrent attacks of exacerbations and partial remissions especially in lesions involving lower extremities that are clinically PSEK-like in presentation, but histopathologically consistent with psoriasis. <strong>Case report:</strong> A 12-year-old childhood male, known case of Down’s syndrome, presented to our clinic with a history of severely pruritic skin rashes involving the perioral area, corners of the mouth, bilateral elbows, dorsal hands, scrotum, and both lower extremities for 6 years duration. The rashes gradually progressed with time to form fixed lesions in the last 2 years. He was received multiple treatment modalities, including topical steroids, topical vitamin D derivatives, and narrowband UVB phototherapy without significant improvement and the lesions became more worsened over time. <strong>Conclusion:</strong> psoriasis can be presenting with a new variant of a severe, recalcitrant, and difficult to treat type in Down syndrome cases with a history of recurrent attacks of exacerbations and partial remissions especially in lesions involving lower extremities which are clinically PSEK-like in presentation, but histopathologically consistent with psoriasis. However, early diagnosis and strict management are important in controlling the severity of the condition.展开更多
文摘Down syndrome is the most common chromosomal abnormality encountered in clinical practice with 50%of them having associated congenital heart disease(CHD).Shunt lesions account for around 75%of all CHDs in Down syndrome.Down syndrome patients,especially with large shunts are particularly predisposed to early development of severe pulmonary hypertension(PH)compared with shunt lesions in general population.This necessitates timely surgical correction which remains the only viable option to prevent long term morbidity and mortality.However,despite clear recommendations,there is wide gap between actual practice and fear of underlying PH which often leads to surgical refusals in Down syndrome even when the shunt is reversible.Another peculiarity is that Down syndrome patients can develop PH even after successful correction of shunt.It is not uncommon to come across Down syndrome patients with uncorrected shunts in adulthood with irreversible PH at which stage intracardiac repair is contraindicated and the only option available is a combined heartlung transplant.However,despite the guidelines laid by authorities,the rates of cardiac transplant in adult Down syndrome remain dismal largely attributable to the high prevalence of intellectual disability in them.The index case presents a real-world scenario highlighting the impact of severe PH on treatment strategies and discrimination driven by the fear of worse outcomes in these patients.
基金supported by Shenzhen Science and Technology Planning Project(Grant No.JCYJ20210324093209024)Stable Support Project of Shenzhen(Grant No.20220812182215001).
文摘Down syndrome(DS)is a genetic condition characterized by intellectual disability,delayed brain development,and early onset Alzheimer’s disease.The use of primary neural cells and tissues is important for understanding this disease,but there are ethical and practical issues,including availability from patients and experimental manipulability.Moreover,there are significant genetic and physiological differences between animal models and humans,which limits the translation of the findings in animal studies to humans.Advancements in induced pluripotent stem cells(iPSC)technology have revolutionized DS research by providing a valuable tool for studying the cellular and molecular pathologies associated with DS.Induced pluripotent stem cells derived from cells obtained from DS patients contain the patient’s entire genome including trisomy 21.Trisomic iPSCs as well as their derived cells or organoids can be useful for disease modeling,investigating the molecular mechanisms,and developing potential strategies for treating or alleviating DS.In this review,we focus on the use of iPSCs and their derivatives obtained from DS individuals and healthy humans for DS research.We summarize the findings from the past decade of DS studies using iPSCs and their derivatives.We also discuss studies using iPSC technology to investigate DS-associated genes(e.g.,APP,OLIG1,OLIG2,RUNX1,and DYRK1A)and abnormal phenotypes(e.g.,dysregulated mitochondria and leukemia risk).Lastly,we review the different strategies for mitigating the limitations of iPSCs and their derivatives,for alleviating the phenotypes,and for developing therapies.
文摘BACKGROUND Down syndrome(DS)is one of the most common causes of intellectual disability.Children with DS have varying intelligence quotient(IQ)that can predict their learning abilities.AIM To assess the brain metabolic profiles of children with DS and compare them to standard controls,using magnetic resonance spectroscopy(MRS)and correlating the results with IQ.METHODS This case-control study included 40 children with DS aged 6-15 years and 40 age and sex-matched healthy children as controls.MRS was used to evaluate ratios of choline/creatine(Cho/Cr),N-acetyl aspartic acid/creatine(NAA/Cr),and myoinositol/creatine(MI/Cr(in the frontal,temporal,and occipital lobes and basal ganglia and compared to controls and correlated with IQ.RESULTS Children with DS showed significant reductions in NAA/Cr and MI/Cr and a non-significant reduction in Cho/Cr in frontal lobes compared to controls.Additionally,we observed significant decreases in NAA/Cr,MI/Cr,and Cho/Cr in the temporal and occipital lobes and basal ganglia in children with DS compared to controls.Furthermore,there was a significant correlation between IQ and metabolic ratios in the brains of children with DS.CONCLUSION Brain metabolic profile could be a good predictor of IQ in children with DS.
文摘BACKGROUND Pulmonary hypertension(PH)has serious short-and long-term consequences.PH is gaining increasing importance in high risk groups such as Down syndrome(DS)as it influences their overall survival and prognosis.Hence,there is a dire need to collate the prevalence rates of PH in order to undertake definitive measures for early diagnosis and management.AIM To determine the prevalence of PH in children with DS.METHODS The authors individually conducted a search of electronic databases manually(Cochrane library,PubMed,EMBASE,Scopus,Web of Science).Data extraction and quality control were independently performed by two reviewers and a third reviewer resolved any conflicts of opinion.The words used in the literature search were“pulmonary hypertension”and“pulmonary arterial hypertension”;“Down syndrome”and“trisomy 21”and“prevalence”.The data were analyzed by Comprehensive Meta-Analysis Software Version 2.Risk of bias assessment and STROBE checklist were used for quality assessment.RESULTS Of 1578 articles identified,17 were selected for final analysis.The pooled prevalence of PH in these studies was 25.5%.Subgroup analysis was carried out for age,gender,region,year of publication,risk of bias and etiology of PH.CONCLUSION This review highlights the increasing prevalence of PH in children with DS.It is crucial for pediatricians to be aware of this morbid disease and channel their efforts towards earlier diagnosis and successful management.Community-based studies with a larger sample size of children with DS should be carried out to better characterize the epidemiology and underlying etiology of PH in DS.
基金This work was supported by FAPESP-Foundation for Research Support of the State of São Paulo,São Paulo,Brazil[Grant#2015/21587-5].
文摘Background:Postoperative pulmonary hypertension limits the success of surgical treatment in some patients with unrestrictive congenital cardiac communications.Identifying patients at risk of developing postoperative pulmonary hypertension is important to individualize follow-up strategies.Methods:We analyzed a prospective cohort of 52 pediatric patients(age 3 to 35 months)looking for perioperative predictors of mildly elevated pulmonary arterial pressure 6 months after surgery,defined as a systolic pressure greater than 30 mmHg by transthoracic echocardiography.This corresponds to a mean pulmonary arterial pressure of>20 mmHg.Clinical,echocardiographic and hemodynamic parameters were investigated.Perioperative hemodynamics was assessed by directly measuring pulmonary and systemic arterial pressures using indwelling catheters.Early postoperative pulmonary hemodynamics was defined as the mean pulmonary/systemic mean arterial pressure ratio(PAP/SAP)obtained per patient during the first 6 h of postoperative care.Results:Among the factors that were investigated as possible predictors,perioperative hemodynamics and the presence of Down syndrome were initially selected using univariate analysis(p<0.030).Early postoperative PAP/SAP was correlated with PAP/SAP obtained in the operating room just after cardiopulmonary bypass(r=0.70,p<0.001),and it was higher in subjects with Down syndrome than in nonsyndromic individuals(p=0.003).Early postoperative PAP/SAP was the only predictor selected using multivariate analysis.It was characterized as an independent predictor after adjustments for possible confounders.An early postoperative PAP/SAP of>0.35 was 76%sensitive and 74%specific at predicting a systolic pulmonary arterial pressure of>30 mmHg 6 months after surgery(hazard ratio with 95%CI 8.972[2.428–33.158],p=0.002).Conclusion:The hypertensive early postoperative behavior of the pulmonary circulation was strongly but not exclusively associated with Down syndrome,and it was characterized as an independent predictor of altered pulmonary arterial pressure after discharge from the hospital.
基金Supported by Science and Technology Department of Jilin Province,No.20190302073GX.
文摘BACKGROUND Down syndrome(DS)is one of the most common chromosomal aneuploidy diseases.Prenatal screening and diagnostic tests can aid the early diagnosis,appropriate management of these fetuses,and give parents an informed choice about whether or not to terminate a pregnancy.In recent years,investigations have been conducted to achieve a high detection rate(DR)and reduce the false positive rate(FPR).Hospitals have accumulated large numbers of screened cases.However,artificial intelligence methods are rarely used in the risk assessment of prenatal screening for DS.AIM To use a support vector machine algorithm,classification and regression tree algorithm,and AdaBoost algorithm in machine learning for modeling and analysis of prenatal DS screening.METHODS The dataset was from the Center for Prenatal Diagnosis at the First Hospital of Jilin University.We designed and developed intelligent algorithms based on the synthetic minority over-sampling technique(SMOTE)-Tomek and adaptive synthetic sampling over-sampling techniques to preprocess the dataset of prenatal screening information.The machine learning model was then established.Finally,the feasibility of artificial intelligence algorithms in DS screening evaluation is discussed.RESULTS The database contained 31 DS diagnosed cases,accounting for 0.03%of all patients.The dataset showed a large difference between the numbers of DS affected and non-affected cases.A combination of over-sampling and undersampling techniques can greatly increase the performance of the algorithm at processing non-balanced datasets.As the number of iterations increases,the combination of the classification and regression tree algorithm and the SMOTETomek over-sampling technique can obtain a high DR while keeping the FPR to a minimum.CONCLUSION The support vector machine algorithm and the classification and regression tree algorithm achieved good results on the DS screening dataset.When the T21 risk cutoff value was set to 270,machine learning methods had a higher DR and a lower FPR than statistical methods.
文摘The aim of the study was to investigate the effect of a hydrotherapy program on FVC, FEV, PEF, RR and SaO<sub>2</sub> on children with Down syndrome over six months and to compare it with a conventional respiratory physiotherapy program. Eighteen children, with Down Syndrome, aged 6 - 11 years (9.53 ± 0.454), divided into two groups of nine, the intervention group (IG), that participated in the hydrotherapy program and the control group (CG) participated in the classical physiotherapy program. We calculated mean values of FVC, FEV, PEF, RR and SaO2 before and after six months intervention for both groups. There was a statistically significant improvement in all factors for both groups. However, were statistically more significant for the intervention group (IG). Based on a specific protocol of intervention in the water and at the same time with a group of children who participated in a similar program of classical respiratory physiotherapy, it was found to be statistically more important than the second group in improving respiratory function. We recommend the use of hydrotherapy as a complementary therapy that should be part of the weekly program of these children in addition to the existing treatments they attend.
文摘<strong>Background</strong>:<span> </span><span>Limited research concerns the study of continuity in the future of the physical and social status of elderly people with DS that is when people who take care of them will not be there anymore (“<i></i></span><i><i><span>after</span></i><span> </span><i><span>we</span></i><span> </span><i><span>have</span></i><span> </span><i><span>gone</span></i></i><span>”). </span><b><span>Objective</span></b><b><span>:</span></b><span> From a biopsychosocial perspective, to investigate the daily life of ageing people with Down Syndrome over 45 years old in order to identify the most important issues in better planning for their future. </span><b><span>Methods</span></b><b><span>:</span></b><span> A cross-sectional Italian national study was carried out. An <i></i></span><i><i><span>ad</span></i><span> </span><i><span>hoc</span></i></i><span> questionnaire was administered to formal and informal caregivers of aging people with Down Syndrome. </span><b><span>Results</span></b><b><span>:</span></b><span> 136 family members and health professionals were involved. Most of </span><span>the </span><span>people with Down Syndrome live at home, attend a daily center and do many activities. Most of them had never worked and she/he is not at all autonomous. 25% of caregivers declared that, nowadays, there is not planning for the future, and 30.9% of participants who planned their future collected information when it occurred (e.g. when the parents pass away). </span><b><span>Conclusions</span></b><b><span>:</span></b><span> </span><span>The a</span><span>ging of people with DS requires attention to the planning of their future. In order to better plan, it is necessary to avoid programming </span><span>“</span><span>in emergency</span><span>”</span><span>, but for time, keeping in mind of the activities developed by the people, their abilities and all of the elements that have allowed them to live well up to a point of their life.</span>
文摘Purpose: To alert the medical community that whole exome sequencing can find accessory gene changes in well-known syndromes that alter preventive health care and management. Meaning: A collagen type VI gene change adds muscle weakness, hypermobility, and dysautonomia concerns to usual management considerations for Down syndrome. Methods: Commercial whole exome sequencing combined with clinical interpretation of DNA sequence change added new considerations to patient management and parental counsel. Results: An 11-year-old child with the trisomy 21 form of Down syndrome who was evaluated for extraordinary joint laxity had a heterozygous collagen type VI aspartic to glutamic acid (COL6A3 c.6360 C>G p.Asp2120Glu) gene change found by whole exome sequencing. The DNA variant was qualified as having strong relevance to the enhanced hypermobility due to prior association of collagen 6 gene changes with myopathy. Conclusions: Dual diagnosis of Ehlers-Danlos syndrome was not assigned because the patient lacked criteria like bruising, unusual scars, or selected dysautonomia symptoms. The concept of a hypermobility spectrum offers advantages for management of its constituent conditions if clinically guided ascertainment and DNA diagnostics are employed.
文摘Down syndrome (DS) is the most common chromosomal abnormality in humans, and the most frequent cause of mental retardation. Patients affected by this syndrome show an increased prevalence of autoimmune diseases. The most common of those is Hypothyroidism. We present a case report describing the association of Down syndrome with Hyperthyroidism. An 18-year-old patient presented with a history of recurrent throat infections and intermittent diarrhea, having developed a total alopecia areata within one month from the first visit to the physician. After consultations with general practitioners, he was directed to an Endocrinology Ambulatory and diagnosed with a clear case of Graves’ disease associated with Down syndrome. Treatment was started with methimazole 20 mg/day, and after two months, was adjusted to 40 mg/day. The patient reached adequate clinical and laboratory balance after five months of treatment. Thus, the association between Down syndrome and Graves’ Disease is relevant in medical practice, due to its specific characteristics on diagnosis, and the need of an adequate treatment regarding this disease association.
文摘Primary care physicians are in a unique position to provide a holistic and individualized care to their patients with Down Syndrome. These patients share common medical problems with general population;however, they often are medically complex and present with cardiac, orthopedic, and endocrine challenges such as overweight-obesity and related comorbidities that occur with more frequency in this unique population. The prevention of overweight-obesity is an important public health issue for both the general population and for the population of individuals with Down Syndrome. If abnormal weight gain is treated early and effectively many secondary comorbidities can be prevented or ameliorated. This case report discusses the impact of implementing a Consistent Individualized Carbohydrate controlled Anti-inflammatory Nutrition plan (C-ICAN) as part of the treatment plan for a young woman with Down Syndrome (DS). The C-ICAN meal plan is a low glycemic load meal plan with 30% to 35% calories from fat, 20% to 25% calories from protein, 40% to 45% calories from carbohydrate, and goal of 25 gm fiber per day. The C-ICAN meal plan combines the Mediterranean diet because of its well-established anti-inflammatory, and cardiovascular benefits, with a high protein and low glycemic-load meal plan to improve satiety and glycemic control. In this case the patient and her caregivers adjusted to a structured meal pattern well, weight balance resulted, and mealtime stress was reduced.
文摘AIM: To describe human leukocyte antigen(HLA) alleles in individuals with Down syndrome and alopecia areata. METHODS: A cross-sectional study was conducted, which evaluated 109 individuals. Ten with down syndrome(DS) and alopecia areata(AA), ten with DS without AA and ten with AA without DS, and their fami-lies. The individuals were matched by gender and age. The following data were computed: gender, age, ethnic group, karyotype, clinical presentation and family history of alopecia areata. Descriptive analysis: measures of central tendency and frequency distribution. Inferential analysis: Fisher's exact test to compare categorical data between the three groups and Kruskal-Wallis ANOVA test for numerical data.RESULTS: Seventy per cent of evaluated individuals in the DS and AA group were male; presented mean age of 18.6(SD ± 7.2) years and 70% were Caucasian. We observed involvement of the scalp, with a single lesion in 10% and multiple in 90% of subjects. It was observed that there is no significant difference in the frequency distributions of the alleles HLA loci A, B, C, DRB1 and DQB1 of subjects studied. However, according to Fisher's exact test, there is a trend(P = 0.089) of DS group to present higher proportions of HLA-A 36 and HLA-B 15 than the AA group and AA and DS group.CONCLUSION: There was a tendency for the DS group, to present proportion of HLA-A 36 and HLA-B 15 higher than the AA group and group of individuals with AA and DS. However, there was no significant difference in the frequency distribution of the alleles.
基金This work was supported by the Ministry of Instruction,Universities and Research(MIUR)under the SIR program n°RBSI144MT to FDD,Jerome Lejeune Foundation with the grant#PERLUIGI/1484-PM2016A to MP and Fondi di Ateneo Progetti Grandi#RG116154C9214D1A from Sapienza University of Rome to FDD.
文摘Background:Down syndrome(DS)individuals,by the age of 40s,are at increased risk to develop Alzheimer-like dementia,with deposition in brain of senile plaques and neurofibrillary tangles.Our laboratory recently demonstrated the disturbance of PI3K/AKT/mTOR axis in DS brain,prior and after the development of Alzheimer Disease(AD).The aberrant modulation of the mTOR signalling in DS and AD age-related cognitive decline affects crucial neuronal pathways,including insulin signaling and autophagy,involved in pathology onset and progression.Within this context,the therapeutic use of mTOR-inhibitors may prevent/attenuate the neurodegenerative phenomena.By our work we aimed to rescue mTOR signalling in DS mice by a novel rapamycin intranasal administration protocol(InRapa)that maximizes brain delivery and reduce systemic side effects.Methods:Ts65Dn mice were administered with InRapa for 12 weeks,starting at 6 months of age demonstrating,at the end of the treatment by radial arms maze and novel object recognition testing,rescued cognition.Results:The analysis of mTOR signalling,after InRapa,demonstrated in Ts65Dn mice hippocampus the inhibition of mTOR(reduced to physiological levels),which led,through the rescue of autophagy and insulin signalling,to reduced APP levels,APP processing and APP metabolites production,as well as,to reduced tau hyperphosphorylation.In addition,a reduction of oxidative stress markers was also observed.Discussion:These findings demonstrate that chronic InRapa administration is able to exert a neuroprotective effect on Ts65Dn hippocampus by reducing AD pathological hallmarks and by restoring protein homeostasis,thus ultimately resulting in improved cognition.Results are discussed in term of a potential novel targeted therapeutic approach to reduce cognitive decline and AD-like neuropathology in DS individuals.
文摘Down syndrome(DS),as a typical genomic aneuploidy,is a common cause of various birth defects,among which is congenital heart disease(CHD).40e60%neonates with DS have some kinds of CHD.However,the molecular pathogenic mechanisms of DS associated CHD are still not fully understood.This review summarizes available studies on DS associated CHD from seven aspects so as to provide a crucial and updated overview of what we known so far in this domain.
文摘Background:To assess the diagnostic ability of Pentacam HR(Oculus Optikgeräte,GmbH,Wetzlar,Germany)tomographic indices in discriminating keratoconus(KC)and KC suspect(KCS)in 10-to 30-year-old patients with Down syndrome(DS).Methods:In this study,DS patients were enrolled through special needs schools,the National Down Syndrome Society,and relevant non-profit organizations.Diagnoses were made independently by two experienced specialists.Forty Pentacam indices related to corneal thickness,volume,density,keratometry,power,shape,aberration,and elevation were extracted.For each index,the accuracy for KC and KCS diagnosis was evaluated using discriminant analysis and the area under receiver operating characteristic curve(AUROC).From each enrolled case,data from only one eye was entered in the analyses.Results:Analyses were performed on data from 25 KC,46 KCS,and 154 non-ectatic DS eyes.The best discriminants for KC were anterior higher order aberrations(HOA)(cutoff>0.643,AUROC=0.879),posterior vertical coma(cutoff>0.0702μm,AUROC=0.875),anterior vertical coma(cutoff>0.4124μm,AUROC=0.868),and total HOA(cutoff>0.608,AUROC=0.867).The difference between AUROCs were not statistically significant(all P>0.05).For KCS,the best discriminants were minimum corneal thickness(cutoff≤480.0μm,AUROC=0.775),corneal volume(cutoff≤55.3μm,AUROC=0.727)and Belin Ambrosio display-total deviation(BAD-D)(cutoff>2.23,AUROC=0.718)with no significant difference between AUROCs(all P>0.05).Conclusions:In this sample of DS patients,best KC discriminators were HOA and coma which showed good diagnostic ability.For KCS,best predictors were minimum corneal thickness,corneal volume,and BAD-D with relatively good diagnostic ability.Defining a new set of KC diagnostic criteria for DS patients is suggested.
文摘Background:Extra genetic material in patients with Down syndrome(DS)may affect the function of any organ system.We evaluated cardiac functions using conventional tissue Doppler and two-dimensional speckle tracking echocardiography in patients with DS in the absence of congenital and acquired heart disease in patients.Methods:A total of 115 patients with DS between 6 and 13 years of age with clinically and anatomically normal heart and 55 healthy children were included in this cross-sectional study.DS was diagnosed by a karyotype test.Patients with mosaic type were not included in this study.Systolic and diastolic functions were evaluated by echocardiography.Results:Pulsed waved Doppler transmitral early/late inflow velocity(E/A),tissue Doppler mitral annular early/late diastolic peak velocity(Ea/Aa),transtricuspid E/A and tricuspid valve annulus Ea/Aa,pulmonary venous Doppler systolic/diastolic(S/D)wave ratio were lower in patients with Down syndrome than in the control group(P=0.04,P=0.001,P<0.05,P<0.001,P<0.001,respectively).Mitral and tricuspid annular Ea were lower in patients with DS(P<0.001).The right and left ventricular myocardial performance indexes were higher in patients with DS than in the controls(P<0.01).They had significantly higher left ventricular mass,ejection fraction,the mitral annular plane systolic excursion values.However,the Down syndrome group compared with the controls had a lower strain values examined by two-dimensional longitudinal speckle-tracking strain echocardiography.Conclusion:These findings suggest conventional tissue Doppler and two-dimensional longitudinal speckletracking strain echocardiography were useful methods of investigating ventricular function and identifying a higher incidence of biventricular dysfunction in patients with Down syndrome compared with the healthy controls.
文摘Background:To assess the diagnostic ability of Pentacam HR(Oculus Optikgerate,GmbH,Wetzlar,Germany)tomographic indices in discriminating keratoconus(KC)and KC suspect(KCS)in 10-to 30-year-old patients with Down syndrome(DS).Methods:In this study,DS patients were enrolled through special needs schools,the National Down Syndrome Society,and relevant non-profit organizations.Diagnoses were made independently by two experienced specialists.Forty Pentacam indices related to corneal thickness,volume,density,keratometry,power,shape,aberration,and elevation were extracted.For each index,the accuracy for KC and KCS diagnosis was evaluated using discriminant analysis and the area under receiver operating characteristic curve(AUROC).From each enrolled case,data from onlyoneeyewas entered intheanalyses.Results:Analyses were performed on data from 25 KC,46 KCS,and 154 non-ectatic DS eyes.The best discriminants for KC were anterior higher-order aberrations(HOA)(cutoff>0.643μm,AUROC=0.879),posterior vertical coma(cutoff>0.0702μm,AUROC=0.875),anterior vertical coma(cutoff>0.4124μm,AUROC=0.868),and total HOA(cutoff>0.608μm,AUROC=0.867).The difference between AUROCs were not statistically significant(all P>0.05).For KCS,the best discriminants were minimum corneal thickness(cutoff≤480.0μm,AUROC=0.775),corneal volume(cutoff≤55.3μm,AUROC=0.727)and Belin Ambrosio display-total deviation(BAD-D)(cutoff>2.23,AUROC=0.718)with no significant difference between AUROCs(all P>0.05).Conclusions:In this sample of DS patients,the best KC discriminators were HOA and coma which showed good diagnostic ability.For KCS,the best predictors were minimum corneal thickness,corneal volume,and BAD-D with relatively good diagnostic ability.Defining a new set of KC diagnostic criteria for DS patients is suggested.
文摘Backgrounds: Down syndrome (DS) is the most common chromosomal abnormality. The most important factor in DS is increased maternal age so after the age of 35, the risk of Down syndrome in pregnancy increases. Down syndrome can be diagnosed during pregnancy by prenatal screening. Nondisjunction in cell divisions is the main cause of the DS. Apo lipoprotein E is a 317 amino acid glycoprotein that plays an essential role in metabolism and cholesterol transport. Alzheimer’s disease (AD) is one of the symptoms of adults with DS. The apoE allele e4 has been identified as a risk factor for AD and also, played a main role in nondisjunction. An increased risk of AD in mothers of adults with DS has been reported. We hypothesized that young mothers of DS children (Methods: In this case-control study, 33 DS children and their parents were compared in case of age with 90 families without any history of DS. Genotyping was performed by ARMS-PCR technique. Statistical analysis was performed by SPSS v.21 software. Results: It indicated that there is a significant difference in allele distribution between case and control groups. The C allele for 112 codon of APOE gene and the C allele for 158 codon of APOE gene may associate with nondisjunction. In 112 codon of APOE gene, it seems having T allele reduces the risk of nondisjunction and in contrast C allele may be a risk factor in happening of nondisjunction. (p-value = 0.000006, OR = 2.66, 95% CI = 1.74 - 4.06). In 158 codon of APOE gene, it seems having T allele reduces the risk of nondisjunction and in contrast C allele may be a risk factor in happening of nondisjunction. (p-value = 0.0000, OR = 3.89, 95% CI = 2.38 - 6.34). E4 allele frequency in mothers of DS is about 14% more than those in control group. According to results of this study the C allele in 158 codon of APOE gene and the C allele in 112 codon of APOE gene could be considered as susceptibility genetic factors for nondisjunction in Northeast of Iran.
文摘This paper presents the pathological voice detection and classification techniques using signal processing based methodologies and Feed Forward Neural Networks(FFNN).The important pathological voices such as Autism Spectrum Disorder(ASD)and Down Syndrome(DS)are considered for analysis.These pathological voices are known to manifest in different ways in the speech of children and adults.Therefore,it is possible to discriminate ASD and DS children from normal ones using the acoustic features extracted from the speech of these subjects.The important attributes hidden in the pathological voices are extracted by applying different signal processing techniques.In this work,three group of feature vectors such as perturbation measures,noise parameters and spectral-cepstral modeling are derived from the signals.The detection and classification is done by means of Feed For-ward Neural Network(FFNN)classifier trained with Scaled Conjugate Gradient(SCG)algorithm.The performance of the network is evaluated by finding various performance metrics and the the experimental results clearly demonstrate that the proposed method gives better performance compared with other methods discussed in the literature.
文摘<strong>Background:</strong> Psoriasis, a chronic, systemic, inflammatory disease with prominent skin involvement, affects approximately 2% - 4% of the world population. Common variants of psoriasis are plaque psoriasis, inverse psoriasis, guttate psoriasis, erythrodermic psoriasis, pustular form either palmoplantar pustular psoriasis or generalized pustular psoriasis, nail psoriasis, and psoriatic arthritis. Progressive Symmetrical Erythrokeratoderma (PSEK) is a rare genetic disorder, characterized by fixed, well-defined erythematous and hyperkeratotic plaques distributed predominantly on the elbows, knees, trunk, and dorsal surfaces of hands and feet. Clinically has the same presentation to psoriasis especially at early onset and could be confused with psoriasis but histopathological findings and progression of the psoriatic disease can differentiate between both conditions. <strong>Aim:</strong> To document a new variant of a severe, recalcitrant type of psoriasis with a history of recurrent attacks of exacerbations and partial remissions especially in lesions involving lower extremities that are clinically PSEK-like in presentation, but histopathologically consistent with psoriasis. <strong>Case report:</strong> A 12-year-old childhood male, known case of Down’s syndrome, presented to our clinic with a history of severely pruritic skin rashes involving the perioral area, corners of the mouth, bilateral elbows, dorsal hands, scrotum, and both lower extremities for 6 years duration. The rashes gradually progressed with time to form fixed lesions in the last 2 years. He was received multiple treatment modalities, including topical steroids, topical vitamin D derivatives, and narrowband UVB phototherapy without significant improvement and the lesions became more worsened over time. <strong>Conclusion:</strong> psoriasis can be presenting with a new variant of a severe, recalcitrant, and difficult to treat type in Down syndrome cases with a history of recurrent attacks of exacerbations and partial remissions especially in lesions involving lower extremities which are clinically PSEK-like in presentation, but histopathologically consistent with psoriasis. However, early diagnosis and strict management are important in controlling the severity of the condition.
