MR Imaging Findings in 2 Cases of Late Infantile GM1 Gangliosidosis

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La educación temprana en Latinoamérica y las relaciones de la vulnerabilidad social con las funciones ejecutivas y la comunicación temprana en la primera infancia

Several studies have analysed the impact of attending early childhood education centres on communication, regulatory skills and social-emotional development. These educational institutions have increased in presence annually, partially due to the access of women to the labour market. It has been found that infant education may modulate development in vulnerable contexts (typically associated with negative cognitive outcomes), although the results are contradictory. We presented a study that evaluated Latin American dyads of mothers–infants aged 18 to 24 months regarding the influence of infant education and social vulnerability on Executive Functions (EF) and Communication Skills (CS). To address these goals, toddlers completed several EF tasks and the Early Social Communication Scales. Parents completed the Socioeconomic Level Scale from INDEC. Results revealed that social vulnerability was associated with both EF and CS, daycare attendance was positively related to CS and finally, the contribution of daycare varied by SES on EF. These findings highlight the importance of considering infant education and socioeconomic status to generate equal opportunities from the first months of life.Fil: Gago Galvagno, Lucas Gustavo. Universidad de Buenos Aires. Facultad de Psicología. Instituto de Investigaciones; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Abierta Interamericana. Facultad de Psicología; ArgentinaFil: Miller, Stephanie E.. University of Mississippi; Estados UnidosFil: de Grandis, María Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Abierta Interamericana. Facultad de Psicología; ArgentinaFil: Elgier, Angel Manuel. Universidad Abierta Interamericana. Facultad de Psicología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Psicología. Instituto de Investigaciones; Argentin

Regulation during the second year: Executive function and emotion regulation links to joint attention, temperament, and social vulnerability in a Latin American sample

© 2019 Gago Galvagno, De Grandis, Clerici, Mustaca, Miller and Elgier. Although a growing body of work has established developing regulatory abilities during the second year of life, more work is needed to better understand factors that influence this emerging control. The purpose of the present study was to examine regulation capacities in executive functions (i.e., EF or cognitive control) and emotion regulation (i.e., ER or control focused on modulating negative and sustaining positive emotions) in a Latin American sample, with a focus on how joint attention, social vulnerability, and temperament contribute to performance. Sixty Latin American dyads of mothers and children aged 18 to 24 months completed several EF tasks, a Still-Face Paradigm (SFP) to examine ER (Weinberg et al., 2008), and the Early Social Communication Scale to measure joint attention (Mundy et al., 2003). Parents completed the Early Childhood Behavior Questionnaire Very Short Form to measure temperament (ECBQ-VS, Putnam et al., 2010) and the Social Economic Level Scale (SES) from INDEC (2000). Results revealed the typical responses expected for toddlers of this age in these EF tasks and in the SFP. Also, we found associations between EF and ER and between non-verbal communication related to monitoring infants\u27 attention to objects (i.e., responding to joint attention) and initiation of pointing (e.g., pointing and showing of an object while the child alternates his gaze to an adult) with EF. Regarding social factors, family differences and type of housing contribute to regulation. For temperament, effortful control was associated with both regulatory capacities. Finally, only age predicted EF. These results suggest that many patterns regarding the development of these abilities are duplicated in the first months of life in a Latin American sample while further highlighting the importance of considering how the environment and the individual characteristics of infants may associate to these regulatory abilities, which is particularly relevant to developing public policies to promote their optimal development

A Feasibility Study of an Integral PWR for Space Applications

Fission space power systems are well suited to provide safe, reliable, economic and robust energy sources, in the order of 100 KWe. A preliminary feasibility study of a nuclear fission reactor is here presented with the following requirements: i) high reliability, ii) R&D program of moderate cost, iii) to be deployed within a reasonable period of time (e.g. 2015), iv) to be operated and controlled for a long time (10 years) without human intervention, v) possibly to be also used as a byproduct for some particular terrestrial application (or at least to share common technologies), vi) to start with stationary application. The driving idea is to extend as much as possible the PWR technology, by recurring to an integral type reactor. Two options are evaluated for the electricity production: a Rankine steam cycle and a Rankine organic fluid cycle. The neutronics calculation is based on WIMS code benchmarked with MCNP code. The reactivity control is envisaged by changing the core geometry. The resulting system appears viable and of reasonable size, well fit to the present space vector capabilities. Finally, a set of R&D needs has been identified: cold well, small steam turbines, fluid leakage control, pumps, shielding, steam generator in low-gravity conditions, self pressurizer, control system. A R&D program of reasonable extent may yield the needed answers, and some demanding researches are of interest for the new generation Light Water Reactors

Alternating hemiplegia of childhood: evolution over time and mouse model corroboration

Alternating hemiplegia of childhood is a rare neurodevelopmental disorder caused by ATP1A3 mutations. Some evidence for disease progression exists, but there are few systematic analyses. Here, we evaluate alternating hemiplegia of childhood progression in humans and in the D801N knock-in alternating hemiplegia of childhood mouse, Mashlool, model. This study performed an ambidirectional (prospective and retrospective data) analysis of an alternating hemiplegia of childhood patient cohort (n = 42, age 10.24 ± 1.48 years) seen at one US centre. To investigate potential disease progression, we used linear mixed effects models incorporating early and subsequent visits, and Wilcoxon Signed Rank test comparing first and last visits. Potential early-life clinical predictors were determined via multivariable regression. We also compared EEG background at first encounter and at last follow-up. We then performed a retrospective confirmation study on a multicentre cohort of alternating hemiplegia of childhood patients from France (n = 52). To investigate disease progression in the Mashlool mouse, we performed behavioural testing on a cohort of Mashlool- mice at prepubescent and adult ages (n = 11). Results: US patients, over time, demonstrated mild worsening of non-paroxysmal disability index scores, but not of paroxysmal disability index scores. Increasing age was a predictor of worse scores: P < 0.0001 for the non-paroxysmal disability index, intellectual disability scale and gross motor scores. Earliest non-paroxysmal disability index score was a predictor of last visit non-paroxysmal disability index score (P = 0.022), and earliest intellectual disability score was a predictor of last intellectual disability score (P = 0.035). More patients with EEG background slowing were noted at last follow-up as compared to initial (P = 0.015). Similar worsening of disease with age was also noted in the French cohort: age was a significant predictor of non-paroxysmal disability index score (P = 0.001) and first and last non-paroxysmal disability index score scores significantly differed (P = 0.002). In animal studies, adult Mashlool mice had, as compared to younger Mashlool mice, (i) worse balance beam performance; (ii) wider base of support; (iii) higher severity of seizures and resultant mortality; and (iv) no increased predisposition to hemiplegic or dystonic spells. In conclusion, (i) non-paroxysmal alternating hemiplegia of childhood manifestations show, on average over time, progression associated with severity of early-life non-paroxysmal disability and age. (ii) Progression also occurs in Mashlool mice, confirming that ATP1A3 disease can lead to age-related worsening. (iii) Clinical findings provide a basis for counselling patients and for designing therapeutic trials. Animal findings confirm a mouse model for investigation of underlying mechanisms of disease progression, and are also consistent with known mechanisms of ATP1A3-related neurodegeneration

Bi-allelic JAM2 Variants Lead to Early-Onset Recessive Primary Familial Brain Calcification.

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by a combination of neurological, psychiatric, and cognitive decline associated with calcium deposition on brain imaging. To date, mutations in five genes have been linked to PFBC. However, more than 50% of individuals affected by PFBC have no molecular diagnosis. We report four unrelated families presenting with initial learning difficulties and seizures and later psychiatric symptoms, cerebellar ataxia, extrapyramidal signs, and extensive calcifications on brain imaging. Through a combination of homozygosity mapping and exome sequencing, we mapped this phenotype to chromosome 21q21.3 and identified bi-allelic variants in JAM2. JAM2 encodes for the junctional-adhesion-molecule-2, a key tight-junction protein in blood-brain-barrier permeability. We show that JAM2 variants lead to reduction of JAM2 mRNA expression and absence of JAM2 protein in patient's fibroblasts, consistent with a loss-of-function mechanism. We show that the human phenotype is replicated in the jam2 complete knockout mouse (jam2 KO). Furthermore, neuropathology of jam2 KO mouse showed prominent vacuolation in the cerebral cortex, thalamus, and cerebellum and particularly widespread vacuolation in the midbrain with reactive astrogliosis and neuronal density reduction. The regions of the human brain affected on neuroimaging are similar to the affected brain areas in the myorg PFBC null mouse. Along with JAM3 and OCLN, JAM2 is the third tight-junction gene in which bi-allelic variants are associated with brain calcification, suggesting that defective cell-to-cell adhesion and dysfunction of the movement of solutes through the paracellular spaces in the neurovascular unit is a key mechanism in CNS calcification

Clinical profile of patients with ATP1A3 mutations in Alternating Hemiplegia of Childhood\u2014a study of 155 patients

Background: Mutations in the gene ATP1A3 have recently been identified to be prevalent in patients with alternating hemiplegia of childhood (AHC2). Based on a large series of patients with AHC, we set out to identify the spectrum of different mutations within the ATP1A3 gene and further establish any correlation with phenotype. Methods: Clinical data from an international cohort of 155 AHC patients (84 females, 71 males; between 3 months and 52 years) were gathered using a specifically formulated questionnaire and analysed relative to the mutational ATP1A3 gene data for each patient. Results: In total, 34 different ATP1A3 mutations were detected in 85 % (132/155) patients, seven of which were novel. In general, mutations were found to cluster into five different regions. The most frequent mutations included: p.Asp801Asn (43 %; 57/132), p.Glu815Lys (16 %; 22/132), and p.Gly947Arg (11 %; 15/132). Of these, p.Glu815Lys was associated with a severe phenotype, with more severe intellectual and motor disability. p.Asp801Asn appeared to confer a milder phenotypic expression, and p.Gly947Arg appeared to correlate with the most favourable prognosis, compared to the other two frequent mutations. Overall, the comparison of the clinical profiles suggested a gradient of severity between the three major mutations with differences in intellectual (p = 0.029) and motor (p = 0.039) disabilities being statistically significant. For patients with epilepsy, age at onset of seizures was earlier for patients with either p.Glu815Lys or p.Gly947Arg mutation, compared to those with p.Asp801Asn mutation (p &lt; 0.001). With regards to the five mutation clusters, some clusters appeared to correlate with certain clinical phenotypes. No statistically significant clinical correlations were found between patients with and without ATP1A3 mutations. Conclusions: Our results, demonstrate a highly variable clinical phenotype in patients with AHC2 that correlates with certain mutations and possibly clusters within the ATP1A3 gene. Our description of the clinical profile of patients with the most frequent mutations and the clinical picture of those with less common mutations confirms the results from previous studies, and further expands the spectrum of genotype-phenotype correlations. Our results may be useful to confirm diagnosis and may influence decisions to ensure appropriate early medical intervention in patients with AHC. They provide a stronger basis for the constitution of more homogeneous groups to be included in clinical trial