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The stability of CR1 (complement receptor type 1) on ageing erythrocytes in vivo was examined in a group of normal subjects who had been genotyped using a restriction fragment length polymorphism (detected using a cDNA probe for CR1) that correlates with the numerical expression of CR1 on normal erythrocytes (H = allele correlating with high expression. L = low). Erythrocytes were separated into 5 fractions of increasing age on discontinuous Percoll gradients. Mean CR1 numbers on erythrocytes fell from 636 molecules per cell in the first fraction to 384 in the fifth in the HH group and from 478 lo 315 in the LL group. There was no difference in the rate of decline of CR1 numbers between the groups. A group of nine SLE patients was also studied in the same way; their genotypes were HH (four) and HL(five). Mean CR1 numbers amongst all of these patients fell from 477 to 232, a faster rate of decline than in a genotypically matched group of normal subjects. There was no difference in the prevalence of the different structural allotypes amongst 30 SLE patients compared with 21 normal subjects. These data provide further evidence that there are enhanced extracellular mechanisms for the removal of CR1 from erythrocytes of SLE patients and do not support the hypothesis that inherited variation in CR1 expression on erytliroeytes increases disease susceptibility to SLE. [ABSTRACT FROM AUTHOR]

Patients with IgA nephropathy often present a large array of antibodies against diet antigens and this disease can be experimentally induced by alimentary antigens. In this report, we have described the isolation from a patient with IgA nephropathy of antibovine serum albumin (BSA)-antibody idiotypes that are specifically recognized by auto-and heteroantiidiotypic antibodies. The fact that antigen (BSA) but not monomeric or aggregated human IgG inhibited the binding of antiidiotypic antibodies to the idiotypes, suggested that the idiotypic determinants are in or near the antigen binding site and that it is not a rheumatoid factor. By means of the heteroantiidiotypic antibodies raised in rabbits we observed the presence of increased levels of shared idiotypes in serum and/or immune complexes (IC) of 48 out of 70 (68.5%) genetically unrelated patients with IgA nephropathy. The close correlation (P < 0.005) between the presence of IgA-IC, measured by Raji cell assay, and the existence of high levels of serum idiotypes, suggest that a portion of circulating IC could consist of idiotype-antiidiotype. A strong concordance between the presence and levels of idiotypes and the clinical activity, as defined by the existence of haematuria, was also noted. The discrepancies and absence of correlation observed in our study among the levels of anti-BSA antibodies of different classes and serum levels of idiotypes, circulating IC and haematuria could suggest that the antibodies reacting with the heterologous antiidiotypic antibodies could be directed to other more pathogenic antigens than dietary antigens. All together, our results suggest that IgA nephropathy might belong to the group of diseases that occur in susceptible individuals with a limited potential in the immunological response repertoire. [ABSTRACT FROM AUTHOR]

Objectives: Characterise the circumstances associated with death during admission of adults with Down syndrome (DS) and to identify predictors of mortality., Patients and Methods: Observational study based on data on all emergent admissions of adults with DS to hospitals of the Spanish National Health System between 1997 and 2014. We analysed epidemiological and clinical variables., Results: We analysed admissions of 11,594 adults with DS, mean age 47 years. 1715 patients died (15%), being the highest mortality (35%) in individuals aged 50-59. A past medical history of cerebrovascular disease (aOR 2.95 [2.30-3.77]) or cancer (aOR 2.79 [2.07-3.75]), gross aspiration's admission (aOR 2.59 [2.20-3.04]), immobility (aOR 2.31 [1.46-3-62]), and readmission within 30 days (aOR 2.43 [2.06-2.86]) were identified as predictors of mortality., Conclusions: Adults with DS have a high in-hospital mortality rate. The main predictors of death were cerebrovascular disease, cancer, early readmission, and conditions commonly associated with advanced dementia., (© 2023 John Wiley & Sons Ltd.)

Objective: Alzheimer's disease (AD) is a major health concern for aging adults with Down syndrome (DS), but conventional diagnostic techniques are less reliable in those with severe baseline disability. Likewise, acquisition of magnetic resonance imaging to evaluate cerebral atrophy is not straightforward, as prolonged scanning times are less tolerated in this population. Computed tomography (CT) scans can be obtained faster, but poor contrast resolution limits its function for morphometric analysis. We implemented an automated analysis of CT scans to characterize differences across dementia stages in a cross-sectional study of an adult DS cohort., Methods: CT scans of 98 individuals were analyzed using an automatic algorithm. Voxel-based correlations with clinical dementia stages and AD plasma biomarkers (phosphorylated tau-181 and neurofilament light chain) were identified, and their dysconnectomic patterns delineated., Results: Dementia severity was negatively correlated with gray (GM) and white matter (WM) volumes in temporal lobe regions, including parahippocampal gyri. Dysconnectome analysis revealed an association between WM loss and temporal lobe GM volume reduction. AD biomarkers were negatively associated with GM volume in hippocampal and cingulate gyri., Interpretation: Our automated algorithm and novel dysconnectomic analysis of CT scans successfully described brain morphometric differences related to AD in adults with DS, providing a new avenue for neuroimaging analysis in populations for whom magnetic resonance imaging is difficult to obtain., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Immune dysregulation in individuals with Down syndrome (DS) leads to an increased risk for hospitalization and death due to coronavirus disease 2019 (COVID-19) and may impair the generation of protective immunity after vaccine administration., Methods: The cellular and humoral responses of 55 individuals with DS who received a complete SARS-CoV-2 vaccination regime at 1 to 3 (visit [V 1]) and 6 (V2) months were characterized., Results: SARS-CoV-2-reactive CD4+ and CD8+ T lymphocytes with a predominant Th1 phenotype were observed at V1 and increased at V2. Likewise, an increase in SARS-CoV-2-specific circulating Tfh (cTfh) cells and CD8+ CXCR5+ PD-1hi lymphocytes was already observed at V1 after vaccine administration. Specific immunoglobulin G (IgG) antibodies against SARS-CoV-2 S protein were detected in 96% and 98% of subjects at V1 and V2, respectively, although IgG titers decreased significantly between both time points., Conclusions: Our findings show that DS individuals develop an effective immune response to usual regimes of SARS-CoV-2 vaccination., Competing Interests: Potential conflicts of interest. E. P.-A. reports fees for Advisory Board participation from Pharmamar and AstraZeneca. D. R. d. A. reports grant number 19/00634 from Instituto Carlos III and grant number 2021A/2069 from Fondation Jerome Lejeune; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Universidad Complutense de Madrid (Título propio de experto en bioética clínica), Weill Cornell Medicine-Qatar (Division of Medical Ethics—several courses), Instituto Universitario de Investigación Ortega Y Gasset (Máster oficial en bioética clínica), Escuela Andaluza de Salud Pública (Curso Consultoría Ética Clínica [2022] y Máster en bioética [2021]), and Consejería de Salud, Comunidad De Madrid (Curso Consultoría Ética Clínica [November 2021]). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: To describe the clinical and epidemiological characteristics of adult patients with Down syndrome admitted to Spanish hospitals between 1997 and 2014. Secondary goals were to study trend changes over time, and to analyse differences between patients admitted to medical and surgical departments., Patients and Methods: Retrospective observational study on data collected from the Minimum Basic Dataset (MBDS, Conjunto Mínimo Básico de Datos [CMBD]) of admissions of adults with Down syndrome to hospitals belonging to the Spanish National Health System from 1 January 1997 through 31 December 2014. We analysed epidemiological and clinical variables., Results: We analysed 28,716 admissions of 16,874 adult patients with Down syndrome. Men accounted for 58.2% of the sample, and the mean age on admission was 41 ± 13 years, with an 11-year increase in mean age during the study period. Admissions among persons with Down syndrome increased by 5% during the study period, with a noticeable rise in admissions of older adults and to medical departments. Almost one-third of patients (31.8%) were admitted more than once. Age-adjusted mortality was 15.7%. The most common comorbid conditions were chronic obstructive pulmonary disease (25%), hypothyroidism (18.6%), and epilepsy (14.3%). The departments with the highest numbers of admissions were internal medicine (26.3%), pulmonary medicine (6.9%), and general surgery (5.25%)., Conclusion: Hospital admissions among Spanish adults with Down syndrome have increased in recent decades, especially in older patients. We identified substantial differences between patients admitted to medical and surgical departments., (© 2022 John Wiley & Sons Ltd.)

To describe congenital and acquired heart diseases in a Spanish cohort of adults with Down syndrome (DS), which could inform potential health recommendations for this population. Cross-sectional, observational study of adults with DS evaluated consecutively at a tertiary care, outpatient center between January 1 and December 31, 2019. The study population comprised 937 patients (51.8% men; median [IQR] age, 42 [18] years). An echocardiogram was available in the clinical chart of 420 patients (44.8%). The diagnosis of any form of heart disease was confirmed in 211 patients (22.5%): 101 (10.8%) had congenital heart defects, 80 (8.5%) simultaneous congenital and valvular heart diseases, and 30 (3.2%) isolated valvular heart disease. 111 patients (52.6% of those with congenital or valvular heart disease) had received corrective cardiac surgery. A total of 65 individuals were receiving medical management alone (30.8%), while 35 did not require any treatment because their cardiac disease was mild (16.6%). We found a high overall prevalence of heart disease in patients with DS, higher than previously reported for the pediatric population. Management of cardiovascular disease in adults with DS differs from that of the general population and should include universal echocardiography-based screening., (© 2022. The Author(s).)

Background: Down syndrome (DS) is considered the most frequent cause of early-onset Alzheimer's disease (AD), and the typical pathophysiological signs are present in almost all individuals with DS by the age of 40. Despite of this evidence, the investigation on the pre-dementia stages in DS is scarce. In the present study we analyzed the complexity of brain oscillatory patterns and neuropsychological performance for the characterization of mild cognitive impairment (MCI) in DS., Materials and Methods: Lempel-Ziv complexity (LZC) values from resting-state magnetoencephalography recordings and the neuropsychological performance in 28 patients with DS [control DS group (CN-DS) ( n = 14), MCI group (MCI-DS) ( n = 14)] and 14 individuals with typical neurodevelopment (CN-no-DS) were analyzed., Results: Lempel-Ziv complexity was lowest in the frontal region within the MCI-DS group, while the CN-DS group showed reduced values in parietal areas when compared with the CN-no-DS group. Also, the CN-no-DS group exhibited the expected pattern of significant increase of LZC as a function of age, while MCI-DS cases showed a decrease. The combination of reduced LZC values and a divergent trajectory of complexity evolution with age, allowed the discrimination of CN-DS vs. MCI-DS patients with a 92.9% of sensitivity and 85.7% of specificity. Finally, a pattern of mnestic and praxic impairment was significantly associated in MCI-DS cases with the significant reduction of LZC values in frontal and parietal regions ( p = 0.01)., Conclusion: Brain signal complexity measured with LZC is reduced in DS and its development with age is also disrupted. The combination of both features might assist in the detection of MCI within this population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fernández, Ramírez-Toraño, Bruña, Zuluaga, Esteba-Castillo, Abásolo, Moldenhauer, Shumbayawonda, Maestú and García-Alba.)

Background: Despite presenting higher risk of dementia, mild cognitive impairment (MCI) is not well defined in Down syndrome population., Objective: We aimed to describe cognitive and neuropsychological patterns associated with MCI in Down syndrome individuals., Method: Two groups of adults with Down syndrome (control and prodromal) were studied throughout 3 years. Two linear mixed models and a model including the variables that best predicted group membership were built., Results: Behavioural Regulation Index (BRI) (Behaviour Rating Inventory of Executive Function test) and the model composed of BRI, abstraction and delayed verbal memory were the variable and model best predicting group membership, respectively., Conclusion: Suggest a diagnosis of MCI when BRI is the earliest change perceived by caregivers and this is combined with low scores in abstract thinking, and when an amnesic pattern in delayed verbal memory is observed, but adaptive skills are preserved., (© 2021 John Wiley & Sons Ltd.)

Adults with Down syndrome (DS) have lower bone mineral density (BMD) than the general population. The objective of our study was to describe bone mineral status in DS population through volumetric BMD (vBMD) and trabecular bone score (TBS). Retrospective study of 297 subjects recruited from the Adult DS Outpatient Clinic of a tertiary care hospital in Spain, who underwent a bone densitometry for clinical purposes between January 2010 and June 2015. vBMD determination and TBS analysis on conventional DXA (Hologic QDR 4500) densitometer were performed in this cohort. The mean (±SD) age of our population was 34.3 (±10.9) years; 51% were women. Trabecular vBMD at total hip and femoral neck was lower in males than in females (191.7 ± 48.4 mg/cm 3 vs 206.9 ± 46.7 mg/cm 3 , p = 0.007, and 250.5 ± 70.1 mg/cm 3 vs 275.7 ± 66.2 mg/cm 3 , p = 0.002, respectively). Trabecular and cortical vBMD decreased with age, but age decline in trabecular vBMD was more pronounced in males. Likewise, lumbar TBS declined with age being normal in 63%, low in 29% and very low in 8% of subjects with DS, without differences between sexes. TBS showed a positive correlation (r = 0.37; p < 0.001, Kappa index= 0.275) with conventional DXA lumbar Z-score. vBMD at the hip showed lower values in DS subjects than in the general population, especially in males. Moreover, TBS was also lower at lumbar spine. Therefore, both assessments could be used as complementary tools to areal BMD (Z-score) to assess bone status in DS subjects., Competing Interests: Disclosures /Conflict of Interest The authors do not declare conflicts of interest regarding this article., (Copyright © 2021 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Patients with Down syndrome (DS) often have a high occurrence of obstructive sleep apnea-hypopnea (OSA) syndrome. We studied a large cohort of adults with DS attended due to clinical suspicion of OSA. A standardized questionnaire and full medical assessment were conducted, including a sleep study. One hundred and fifty-seven DS individuals were studied, with a mean ± SD age of 36 ± 10 years, 40.7% women, BMI 29.4 ± 5.6 kg/m 2 . The main clinical symptom was daytime sleepiness (64.9%). A sleep study was conducted in 114 patients. All 114 DS patients were diagnosed with OSA, with a predominance of obstructive and hypopnea events, (apnea-hypopnoea index, AHI, 35.0 ± 26.6), with an oxygen desaturation index of 32.9, and a Tc90% of 24.7%. Continuous positive airway pressure (CPAP) treatment was implemented in 75 (65.8%) of subjects. Tolerance was considered good in 75% of them, with a high compliance of 79.2% >4 hr/day (mean 7.1 hr/day), resulting in a symptomatic improvement in 58.7% of them. Obstructive sleep apnea is frequently confirmed in patients with DS when it clinically suspected. Treatment with CPAP in DS is feasible, and with higher adherence than in adults with normal cognitive functioning., (© 2020 Wiley Periodicals LLC.)

The paradigmatic relationship between aging and atherosclerotic cardiovascular events does not apply to all patient populations. Though trisomy 21 (T21) and its phenotypic expression, Down syndrome (DS), are conditions that involve premature aging, the cardiovascular system of adults with DS appears to be particularly spared from this early senescence. Despite a higher prevalence of some classic cardiovascular risk factors in adults with DS than in the general population, such as dyslipidemia, obesity, or sedentarism, these individuals do not develop hypertension or suffer major cardiovascular events as they age. The protective factors that prevent the development of hypertension in T21 are not well established. Genes like RCAN1 and DYRK1A, both on chromosome 21 and over-expressed in adults with DS, appear to play a major role in cardiovascular prevention. Their regulation of the renin-angiotensin-aldosterone system (RAAS) and neprilysin synthesis could underlie the constitutive protection against arterial hypertension in adults with DS and explain the absence of increased arterial stiffness in this population. A better understanding of these molecular pathways could have enormous implications for the clinical management of adults with DS and might foster the development of novel therapeutic targets in cardiovascular prevention for the general population., (© 2020 Wiley Periodicals LLC.)

Down syndrome (DS) has been considered a unique model for the investigation of Alzheimer's disease (AD) but intermediate stages in the continuum are poorly defined. Considering this, we investigated the neurophysiological (i.e., magnetoencephalography [MEG]) and neuropsychological patterns of mild cognitive impairment (MCI) and AD in middle-aged adults with DS. The sample was composed of four groups: Control-DS (n = 14, mean age 44.64 ± 3.30 years), MCI-DS (n = 14, 51.64 ± 3.95 years), AD-DS (n = 13, 53.54 ± 6.58 years), and Control-no-DS (healthy controls, n = 14, 45.21 ± 4.39 years). DS individuals were studied with neuropsychological tests and MEG, whereas the Control-no-DS group completed only the MEG session. Our results showed that the AD-DS group exhibited a significantly poorer performance as compared with the Control-DS group in all tests. Furthermore, this effect was crucially evident in AD-DS individuals when compared with the MCI-DS group in verbal and working memory abilities. In the neurophysiological domain, the Control-DS group showed a widespread increase of theta activity when compared with the Control-no-DS group. With disease progression, this increased theta was substituted by an augmented delta, accompanied with a reduction of alpha activity. Such spectral pattern-specifically observed in occipital, posterior temporal, cuneus, and precuneus regions-correlated with the performance in cognitive tests. This is the first MEG study in the field incorporating both neuropsychological and neurophysiological information, and demonstrating that this combination of markers is sensitive enough to characterize different stages along the AD continuum in DS., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Community-acquired pneumonia (CAP) is a common serious infection. This study aimed to evaluate the prognostic utility of neutrophil count percentage (NCP) and neutrophil-lymphocyte ratio (NLR) in patients with CAP., Methods: Retrospective study of hospitalized patients with CAP. Patients had a blood test at admission and 3-5 days after hospitalization (early-stage test). The main outcome variables were 30-day and 90-day mortality., Results: Two hundred and 9patients were included. Patients who survived had significant reductions in both NCP and NLR between admission and the day 3-5 blood tests (from 85.8% to 65.4% for NCP and from 10.1 to 3.2 for NLR). Twenty-five patients died in the first 90 days. Patients who died had lower, non-significant reductions in NCP (from 84.8% to 74%) and NLR (from 9.9 to 6.9) and significantly higher early-stage NCP and NLR than those who survived. NCP values higher than 85% and NLR values higher than 10 in the early-stage blood test were associated with a higher risk of mortality, even after multivariate adjustment (HR for NCP: 12; HR for NLR: 6.5)., Conclusion: NCP and NLR are simple, low-cost parameters with prognostic utility, especially when measured 3-5 days after CAP diagnosis. High NLR and/or NCP levels are associated with a greater risk of mortality at 90 days., (Copyright © 2019 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)