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Mitochondrial calcium (mCa2+) uptake occurs via the Mitochondrial Ca2+ Uniporter (MCU) complex and plays a critical role in mitochondrial dynamics, mitophagy, and apoptosis. MCU complex activity is in part modulated by the expression of its regulatory subunits. Cardiovascular disease models demonstrated altered gene/protein expression of one or multiple subunits in different cells, including vascular endothelial cells (ECs). MCU complex activity was found necessary for stable flow (s‐flow)‐induced mitophagy and promotion of an atheroprotective EC phenotype. Disturbed flow (d‐flow) is known to lead to an atheroprone phenotype. Despite the role of MCU in flow‐regulated EC function, flow‐induced alterations in MCU complex subunit expression are currently unknown. We exposed cultured human ECs to atheroprotective (steady shear stress, SS) or atheroprone flow (oscillatory shear stress, OS) and measured mRNA and protein levels of the MCU complex members. SS and OS differentially modulated subunit expression at gene/protein levels. Protein expression changes of the core MCU, mCa2+ uptake 1 (MICU1) and MCU regulator 1 (MCUR1) subunits in SS‐ and OS‐exposed, compared to static, ECs suggested an enhanced mCa2+ influx under each flow and a potential contribution to EC dysfunction under OS. In silico analysis of a single‐cell RNA‐sequencing dataset was employed to extract transcript values of MCU subunits in mouse carotid ECs from regions exposed to s‐flow or d‐flow. Mcu and Mcur1 genes showed significant differences in expression after prolonged exposure to each flow. The differential expression of MCU complex subunits indicated a tight regulation of the complex activity under physiological and pathological hemodynamic conditions. [ABSTRACT FROM AUTHOR]

Seventy-three subjects with mild and moderate intellectual disability (ID) of an unknown/idiopathic nature, who had no record of specific deficits in motor control, and 73 normal controls, matched for chronological age and sex, underwent evaluation of handedness. The results confirmed the previously reported excess of non-right handedness among subjects with ID, and suggested that this finding might be indicative of a deviant cerebral organization or atypical lateralization of cerebral representation of function in this group. However, it was noted that further research is needed to clarify how far this is a function of level of motor skill and how far is a syndrome-specific pathological phenomenon. [ABSTRACT FROM AUTHOR]

The mitochondrial calcium (Ca2+) uniporter (MCU) channel is responsible for mitochondrial Ca2+ influx. Its expression was found to be upregulated in endothelial cells (ECs) under cardiovascular disease conditions. Since the role of MCU in regulating cytosolic Ca2+ homeostasis in ECs exposed to shear stress (SS) is unknown, we studied mitochondrial Ca2+ dynamics (that is known to decode cytosolic Ca2+ signaling) in sheared ECs. To understand cause-and-effect, we ectopically expressed MCU in ECs. A higher percentage of MCU-transduced ECs exhibited mitochondrial Ca2+ transients/oscillations, and at higher frequency, under SS compared to sheared control ECs. Transients/oscillations correlated with mitochondrial reactive oxygen species (mROS) flashes and mitochondrial membrane potential (ΔΨm) flickers, and depended on activation of the mechanosensitive Piezo1 channel and the endothelial nitric oxide synthase (eNOS). A positive feedback loop composed of mitochondrial Ca2+ uptake/mROS flashes/ΔΨm flickers and endoplasmic reticulum Ca2+ release, in association with Piezo1 and eNOS, provided insights into the mechanism by which SS, under conditions of high MCU activity, may shape vascular EC energetics and function. [ABSTRACT FROM AUTHOR]

Williams (WS) and Down syndromes (DS) are two genetic disorders that involve intellectual disability (ID) and have been extensively studied over the past decades because of the unique linguistic profiles they exhibit. Recent investigations seek to explore the fractionation of linguistic components within the cognitive system using genetically based neurodevelopmental disorders such as WS and DS and to identify different profiles of linguistic function in these two groups of individuals.The‘expressive vocabulary’,‘receptive vocabulary’,‘word opposites’ and‘word definitions’ subtests (Level 1) of the Test of Word Knowledge (TOWK) were used to assess lexical skills in six children with WS and five children with DS.Our findings indicate that the two syndromes exhibit substantial differences on linguistic tasks with individuals with WS performing at a higher level compared to those with DS and producing atypical responses in word definitions. The pattern of errors for each syndrome is qualitatively different suggesting that their underlying linguistic mechanisms are distinctive even though ID is similar.This study supports the differential outcome of two chromosomal disorders with similar ID. It also argues in favour of the large within group variability of the two syndromes that is not related to mental age but rather to different underlying mechanisms supporting language. These findings are discussed in the light of the current evidence concerning linguistic knowledge of neurodevelopmental and genetic disorders. [ABSTRACT FROM AUTHOR]

Antibody-mediated rejection is characterized by deposits of complement (C) C4 and C3 split products on endothelial cells (ECs). C3 split products are critical mechanistically and diagnostically because they are deposited in amplified quantities, bind covalently to ECs and act as ligands for leukocytes. This study was designed to determine whether cultured vascular human ECs could clear covalently bound C3 split products from their surface. An immunoglobulin M (IgM) antibody against β2-microglobulin of major histocompatibility complex class I antigens was used to activate C in human serum. Some cells were exposed to hypoxia/reoxygenation and/or interleukin 1 β (IL-1 β) prior to incubation with antibody. C3b/iC3b and C3d deposition on the cell surface was measured by flow cytometry. Incubation with antibody followed by human serum caused a dose-dependent deposition of C3b/iC3b and C3d. Over half of deposited C3b/iC3b and one-third of C3d were cleared from the cell surface during a 3–7-h incubation period with human serum. Neither hypoxia/reoxygenation nor IL-1 β further increased the deposition of C3b/iC3b and C3d, and only slightly modulated their rates of clearance. In summary, human ECs rapidly clear iC3b and C3d from their surface. This finding may have important diagnostic and mechanistic implications to transplantation because C3d is used as a marker of antibody-mediated rejection. [ABSTRACT FROM AUTHOR]

Monocyte recruitment and fate specification after myocardial infarction. Am J Physiol Cell Physiol 319: C797-C806, 2020. First published September 2, 2020; doi:10.1152/ ajpcell.00330.2020.--Monocytes are critical mediators of the inflammatory response following myocardial infarction (MI) and ischemia-reperfusion injury. They are involved in both initiation and resolution of inflammation and play an integral role in cardiac repair. The antagonistic nature of their function is dependent on their subset heterogeneity and biphasic response following injury. New advancements in single-cell transcriptomics and mass cytometry have allowed us to identify smaller, transcriptionally distinct clusters that may have functional relevance in disease and homeostasis. Additionally, recent insights into the spatiotemporal dynamics of monocytes following ischemic injury and their subsequent interactions with the endothelium and other immune cells reveal a complex interplay between monocytes and the cardiac milieu. In this review, we highlight recent findings on monocyte functional heterogeneity, present new mechanistic insight into monocyte recruitment and fate specification following MI, and discuss promising therapeutic avenues targeting monocytes for the treatment of ischemic heart disease. [ABSTRACT FROM AUTHOR]

Endothelial cell dysfunction is the hallmark of every cardiovascular disease/condition, including atherosclerosis and ischemia/reperfusion injury. Fluid shear stress acting on the vascular endothelium is known to regulate cell homeostasis. Altered hemodynamics is thought to play a causative role in endothelial dysfunction. The dysfunction is associated with/preceded by mitochondrial oxidative stress. Studies by our group and others have shown that the form and/or function of the mitochondrial network are affected when endothelial cells are exposed to shear stress in the absence or presence of additional physico-chemical stimuli. The present review will summarize the current knowledge on the interconnections among intracellular Ca-nitric oxide-mitochondrial reactive oxygen species, mitochondrial fusion/fission, autophagy/mitophagy, and cell apoptosis vs. survival. More specifically, it will list the evidence on potential regulation of the above intracellular species and processes by the fluid shear stress acting on the endothelium under either physiological flow conditions or during reperfusion (following a period of ischemia). Understanding how the local hemodynamics affects mitochondrial physiology and the cell redox state may lead to development of novel therapeutic strategies for prevention or treatment of the endothelial dysfunction and, hence, of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Abstract: Ischemia (I)/reperfusion (RP)-induced endothelial cell (EC) injury is thought to be due to mitochondrial reactive oxygen species (mtROS) production. MtROS have been implicated in mitochondrial fission. We determined whether cultured EC exposure to simulated I/RP causes morphological changes in the mitochondrial network and the mechanisms behind those changes. Because shear stress results in nitric oxide (NO)-mediated endothelial mtROS generation, we simulated I/RP as hypoxia (H) followed by oxygenated flow over the ECs (shear stress of 10dyn/cm2). By exposing ECs to shear stress, H, H/reoxygenation (RO), or simulated I/RP and employing MitoTracker staining, we assessed the differential effects of changes in mechanical forces and/or O2 levels on the mitochondrial network. Static or sheared ECs maintained their mitochondrial network. H- or H/RO-exposed ECs underwent changes, but mitochondrial fission was significantly less compared to that in ECs exposed to I/RP. I/RP-induced fission was partially inhibited by antioxidants, a NO synthase inhibitor, or an inhibitor of the fission protein dynamin-related protein 1 (Drp1) and was accompanied by Drp1 oligomerization and phosphorylation (Ser616). Hence, shear-induced NO, ROS (including mtROS), and Drp1 activation are responsible for mitochondrial fission in I/RP-exposed ECs, and excessive fission may be an underlying cause of EC dysfunction in postischemic hearts. [Copyright &y& Elsevier]

Cultured vascular endothelial cell (EC) exposure to steady laminar shear stress results in peroxynitrite (ONOO-) formation intramitochondrially and inactivation of the electron transport chain. We examined whether the "hyperoxic state" of 21% O2, compared with more physiological O2 tensions (PO2), increases the shear-induced nitric oxide (NO) synthesis and mitochondrial superoxide (O2.-) generation leading to ONOO- formation and suppression of respiration. Electron paramagnetic resonance oximetry was used to measure O2 consumption rates of bovine aortic ECs sheared (10 dyn/cm², 30 min) at 5%, 10%, or 21% O2 or left static at 5% or 21% O2. Respiration was inhibited to a greater extent when ECs were sheared at 21% O2 than at lower PO2 or left static at different PO2. Flow in the presence of an endothelial NO synthase (eNOS) inhibitor or a ONOO- scavenger abolished the inhibitory effect. EC transfection with an adenovirus that expresses manganese superoxide dismutase in mitochondria, and not a control virus, blocked the inhibitory effect. Intracellular and mitochondrial O2.- production was higher in ECs sheared at 21% than at 5% O2, as determined by dihydroethidium and MitoSOX red fluorescence, respectively, and the latter was, at least in part, NO-dependent. Accumulation of NO metabolites in media of ECs sheared at 21% O2 was modestly increased compared with ECs sheared at lower PO2, suggesting that eNOS activity may be higher at 21% O2. Hence, the hyperoxia of in vitro EC flow studies, via increased NO and mitochondrial O2.- production, leads to enhanced ONOO- formation intramitochondrially and suppression of respiration. [ABSTRACT FROM AUTHOR]

The Parkinson's disease questionnaire (PDQ-39) is a well-validated British scale for the assessment of health-related quality of life (HQoL) in Parkinson's disease (PD). The PDQ-39 has been translated into Greek and it was applied to 119 Greek PD patients. These patients were classified in stages according to the Hoehn and Yahr (HY) scale and their motor disability was assessed by means of the Unified Parkinson's disease rating scale (UPDRS) as well as the Schwab and England activities of daily living scale (ADL). The Beck depression inventory (BDI) was applied for the evaluation of depression. The translated version of PDQ-39, designated PDQ-39GrV, was validated as follows: (1) Cronbach's alpha coefficient and item-total Spearman's rank-order correlations were calculated in order to estimate the internal consistency of PDQ-39GrV scales. (2) Validity of the PDQ-39GrV was examined in terms of agreement with the clinical assessment parameters (stage, UPDRS. ADL and BDI scores). (3) Sixty one PD patients were re-evaluated 3-7 days later in order to check test-retest reliability. The results showed the following: (1) The PDQ-39GrV demonstrated very good internal consistency (alpha 0.71-0.94). Item-total correlations were statistically significant (r: 0.52-0.93). Test-retest measurements correlated significantly (p = 0.001). (2) Clinically obtained motor parameters correlated well with PDQ-39GrV scales influenced by physical aspects of the disease, while emotionally and socially influenced ones correlated with depression. Our findings indicate that PDQ-39 GrV is a reliable, easy to administer scale for the assessment of HQoL in Greek PD patients. [ABSTRACT FROM AUTHOR]

ABSTRACT. The Test of Nonverbal Intelligence (TONI-2; L. Brown, R. J. Sherbenou, & S. Johnsen, 1990) and Raven's Colored Progressive Matrices (RCPM; J. C. Raven, 1965) are defined as language-free measures of cognitive ability. The purpose of the present study was to investigate the relation between the RCPM and the TONI-2 for samples of patients with Parkinson's disease (n = 75) and controls (n = 47). A regression equation was computed to evaluate the relation of the RCPM scores to the TONI-2 quotient. Regression equation results indicate that there is a significant overlapping linear variance between the two measures in both patients and controls. [ABSTRACT FROM AUTHOR]

This study explored potential factors of numeracy acquisition in young children with intellectual disabilities (IDs). Those factors are determined to assess parents' academic expectations and home practices that they use with their children daily. The sample consisted of 187 Greek-speaking couples, comprising a total number of 374 parents. All of them had a child with mild IDs aged between 4 and 7 years old. Since Greece is placed among European countries with the lowest median disposable income it is significant to assess the potential effects of each family's socioeconomic status. We employed structural equation modeling to identify potential factors affecting a child's with IDs numeracy outcomes. Analysis of moments structures (AMOS) revealed that there is a good fit for the suggested second-order structural equation model. Results are discussed regarding their practical implications., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Exploring individual differences and looking beyond averaged parameters of early numeracy in young children with mild intellectual disabilities has become an area of interest to many researchers worldwide. This study aimed to identify the different profiles of early numeracy skills in young children with mild intellectual disabilities. For this purpose, we assessed early numeracy through Utrecht early numeracy test and learning aptitude through Detroit Test, in a sample of 135 children diagnosed with intellectual disabilities. The mean of their mental age was 5:09 (years:months) . Two-step cluster analysis identified four homogenous groups of children with distinct early numeracy profiles as follows:C1 were fluent in relational and numerical skills up to 20, C2 were fluent in relational skills and numerical skills up to 10, C3 had basic knowledge of relational skills and inconsistent numerical skills up to 10 and C4 had inconsistent relational skills and numerical skills. Results are discussed with reference to their educational implications., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Exploring the individual differences of the longitudinal growth of early numeracy (EN) in young children with Intellectual disabilities (IDs) prerequires the critical stage of exploring and validating the potential factor structure. Despite the fact that Relational Skills (RS), Counting Skills (CS) and Operations (O) are expected to constitute distinct domains of EN, there is not sufficient evidence to support either the above position or the position that they are different means of assessing a general-informal numeracy skill construct. This study was designed to shed light in the field through the evaluation of a measurement model describing the structure of RS, CS and O domains of EN and their interrelation. The sample included N = 155 children with IDs, enrolled in special school classes, mentally aged between 5;02 (y;m) and 6;10 (M = 5.11, SD = 0.974). Confirmatory Factor Analysis indicated a "good fit" of the two-factor model (RS, CS + O) of EN in ID (RMSEA=.029 < 0.08, CFI = 0.98 ≥ 0.90 and SRMR = 0.000 < 0.08) . No measurement invariance across gender was reported for the proposed two-factor model of EN. The nested EN models validated full measurement invariance across gender. Finally, educational implications are discussed., Competing Interests: Authors declare that they have no conflict of interest., (© The British Society of Developmental Disabilities 2021.)

The current study explores the parental perspectives of children with intellectual disabilities (ID) on the effectiveness of inclusive education in Greek mainstream schools. The participants were 83 parents, whose children had different degrees of ID and all of them were attending mainstream schools at the time of the study. They completed a questionnaire examining their perspectives with regard to (a) the most effective educational placement in mainstream schools (special class, mainstream class or co-teaching), (b) their satisfaction with the inclusive mainstream education, (c) their cooperation with the teachers, (d) the perceived benefits of their children's educational placement and (e) their suggestions regarding the improvement of the inclusive educational model. Results indicated that most parents of children with ID would like their child to attend a mainstream class with a co-teaching arrangement. The perceived benefits are mostly related to the development of their children's social skills. Significant considerations regarding cooperation with the teachers, lack of individualized information and guidance, administrative and organizational issues were expressed., (© The British Society of Developmental Disabilities 2019.)

Teachers' interpersonal style is a new field of research in the study of students with intellectual disabilities and challenging behaviors in school context. In the present study, we investigate emotions and causal attributions of three basic types of challenging behaviors: aggression, stereotypy, and self-injury, in relation to teachers' interpersonal style. One hundred and seventy seven Greek general and special educator teachers participated in the study by completing a three-scaled questionnaire. Statistical analysis revealed that the type of challenging behaviors affected causal attributions. According to regression analysis, emotions, teaching experience, expertise in special education, and gender explained a significant amount of variance in interpersonal style. Emotions were found to have a mediating role in the relationship between causal attributions and interpersonal style of "willingness to support," when challenging behaviors were attributed to stable causes or causes under the control of the individual with intellectual disabilities., (© The Author(s) 2015.)

Purpose of the Study: Assess the N30 component of median nerve somatosensory evoked potentials (SEPs) in patients with Parkinson's disease (PD) and correlate its parameters with the severity of the disease, general cognitive ability and regional cerebral blood flow (rCBF)., Patients and Methods: Twenty-three non-demented, non-depressed PD patients (at stage II and III of the disease) and 23 age- and education-matched normal controls were enrolled in the study. SEPs were elicited by median nerve stimulation. PD patients' cognitive ability was assessed by means of: 1) Raven's Colored Progressive Matrices (RCPM); 2) the Test of Non-Verbal Intelligence (TONI-2); and 3) the Wisconsin Card Sorting Test (WCST). The patients' rCBF was evaluated by HMPAO SPECT., Results: There was no difference between SEP N30 latency in PD patients and controls (P > 0.05). The P20-N30 peak-to-peak amplitude was lower in PD patients bilaterally (P < 0.05), and the amplitude of N30-P40 was lower on the right side only (P < 0.05). A significant increase in the amplitude ratio P14-N20/P20-N30 was observed in PD patients (P < 0.05). The correlation of these findings with the clinical parameters of the disease, and notably motor signs, was not significant. Of the three neuropsychological tests only the RCPM showed a positive relation to right P20-N30 amplitude. Regression analysis between SEP parameters and rCBF showed a correlation of N30 amplitude with blood flow in parietal cortical areas, but not in frontal regions.

Two adjective pairs in comparative form, more-less and taller-shorter, were tested with moderately mentally retarded (MR) and nonretarded children (NR) matched on verbal mental age (MA) and socioeconomic status (SES) in a "show" and an "act-out" experimental condition. The data indicated that all the main effects, the group, the experimental condition, and the unmarked-marked relational terms were significant and so were the interactions of the Group x Experimental Conditions, Group x Unmarked Versus Marked Relational Terms, and Group x Experimental Conditions and Unmarked Versus Marked Relational Terms. A logistic regression analysis (LRA) showed that the relational term shorter in the act-out condition best predicted classification membership for the subjects in either group, suggesting that the MR children were less able to self-regulate behavior. The error types, however, mainly observed in the act-out experimental condition were the same from a semantic point of view in either group. The effect of the unmarked versus marked distinction cannot be considered independent of the experimental conditions applied.