Electroencephalographic functional connectivity in extreme prematurity: a pilot study based on graph theory

Background: Connectivity studies based on functional magnetic resonance imaging (MRI) provided new insights in neonatal brain development but cannot be performed at bedside in the clinical setting. The electroencephalogram (EEG) connectivity has been less studied, particularly using the new approach based on graph theory. This study aimed to explore the functional EEG connectivity using graph theory analysis at an early post-conception age in extremely premature and late-preterm babies free of medical complications and overt brain damage. Methods: Sixteen neonates (8 extremely low gestational age (ELGA) and 8 late-preterm infants), both groups having performed multichannel EEG recordings at 35 weeks’ post-conception, were recruited in a single tertiary-level neonatal intensive care unit and well-baby nursery, respectively. Global (i.e., small-worldness) and local (i.e., clustering and strength) connectivity measures were calculated on a single-subject connectivity matrix of EEG data. Results: Both ELGA and late-preterm infants showed small-worldness organization at 35 weeks’ post-conception. The ELGA group had the strength parameter of the theta frequency band lower in the right than in the left hemisphere. This asymmetry did not emerge in the late-preterm group. Moreover, the mean strength parameter was significantly greater in the right hemisphere in the late preterms than in the ELGA group. Conclusion: EEG connectivity measures could represent an index of left-to-right maturation and developmental disadvantage in extremely preterm infants

Detecting neurodevelopmental trajectories in congenital heart diseases with a machine-learning approach

We aimed to delineate the neuropsychological and psychopathological profiles of children with congenital heart disease (CHD) and look for associations with clinical parameters. We conducted a prospective observational study in children with CHD who underwent cardiac surgery within five years of age. At least 18\ua0months after cardiac surgery, we performed an extensive neuropsychological (intelligence, language, attention, executive function, memory, social skills) and psychopathological assessment, implementing a machine-learning approach for clustering and influencing variable classification. We examined 74 children (37 with CHD and 37 age-matched controls). Group comparisons have shown differences in many domains: intelligence, language, executive skills, and memory. From CHD questionnaires, we identified two clinical subtypes of psychopathological profiles: a small subgroup with high symptoms of psychopathology and a wider subgroup of patients with ADHD-like profiles. No associations with the considered clinical parameters were found. CHD patients are prone to high interindividual variability in neuropsychological and psychological outcomes, depending on many factors that are difficult to control and study. Unfortunately, these dysfunctions are under-recognized by clinicians. Given that brain maturation continues through childhood, providing a significant window for recovery, there is a need for a lifespan approach to optimize the outcome trajectory for patients with CHD

Pre-surgery urine metabolomics may predict late neurodevelopmental outcome in children with congenital heart disease

Background: From fetal life until cardiac surgery, complex congenital heart diseases (CHD) exhibit different hemodynamic and oxygenation patterns that can lead to alteration of the metabolic profile. We used a metabolomic approach to identify urine metabolic markers before cardiac surgery, aiming to define the physiology of patients with complex CHD and to contribute to predict their neurodevelopmental outcome. Methods: In a prospective, observational, single-center study we enrolled 28 patients with complex biventricular and univentricular CHD aged less than 5 years, on stable hemodynamic conditions, and with no genetic anomalies. We analyzed urine samples, collected at the induction of anesthesia, by 1H NMR spectroscopy. Profiles of 1H NMR spectra were submitted to unsupervised (principal component) and supervised (partial least squares-discriminant) multivariate analysis. Neurodevelopment was assessed by neuropsychological and adaptive functioning testing. Results: Principal components analysis divided CHD patients metabolic profiles in two distinct clusters (RED and BLACK). Metabolic profiles belonging to the RED cluster showed higher levels of accumulation of citric acid cycle intermediates and glucose compared to the profiles in the BLACK cluster, indicating a possible switching to anaerobic metabolism. Patients belonging to the RED cluster were significantly more prone to show an adverse neurodevelopment pattern (p = 0.01). Conclusions: The application of metabolomic analysis to CHD children permitted a deeper insight on their metabolic status that could help to obtain a better understanding of the physiological implications and to predict long-term neurodevelopmental outcome. © 201

Trends in alcohol and tobacco use among Brazilian students: 1989 to 2010

Objective: To analyze temporal trends of the prevalence of alcohol and tobacco use among Brazilian students. Methods: We analyzed data published between 1989 and 2010 from five epidemiological surveys on students from the 6th to the 12th grade of public schools from the ten largest state capitals of Brazil. The total sample consisted of 104,104 students and data were collected in classrooms. The same collection tool – a World Health Organization self-reporting questionnaire – and sampling and weighting procedures were used in the five surveys. The Chi-square test for trend was used to compare the prevalence from different years. Results: The prevalence of alcohol and tobacco use varied among the years and cities studied. Alcohol consumption decreased in the 10 state capitals (p < 0.001) throughout 21 years. Tobacco use also decreased significantly in eight cities (p < 0.001). The highest prevalence of alcohol use was found in the Southeast region in 1993 (72.8%, in Belo Horizonte) and the lowest one in Belem (30.6%) in 2010. The highest past-year prevalence of tobacco use was found in the South region in 1997 (28.0%, in Curitiba) and the lowest one in the Southeast in 2010 (7.8%, in Sao Paulo). Conclusions: The decreasing trend in the prevalence of tobacco and alcohol use among students detected all over the Country can be related to the successful and comprehensive Brazilian antitobacco and antialcohol policies. Despite these results, the past-year prevalence of alcohol consumption in the past year remained high in all Brazilian regions

A Novel WAC Loss of Function Mutation in an Individual Presenting with Encephalopathy Related to Status Epilepticus during Sleep (ESES)

WAC (WW Domain Containing Adaptor With Coiled-Coil) mutations have been reported in only 20 individuals presenting a neurodevelopmental disorder characterized by intellectual disability, neonatal hypotonia, behavioral problems, and mildly dysmorphic features. Using targeted deep sequencing, we screened a cohort of 630 individuals with variable degrees of intellectual disability and identified five WAC rare variants: two variants were inherited from healthy parents; two previously reported de novo mutations, c.1661_1664del (p.Ser554*) and c.374C>A (p.Ser125*); and a novel c.381+2T>C variant causing the skipping of exon 4 of the gene, inherited from a reportedly asymptomatic father with somatic mosaicism. A phenotypic evaluation of this individual evidenced areas of cognitive and behavioral deficits. The patient carrying the novel splicing mutation had a clinical history of encephalopathy related to status epilepticus during slow sleep (ESES), recently reported in another WAC individual. This first report of a WAC somatic mosaic remarks the contribution of mosaicism in the etiology of neurodevelopmental and neuropsychiatric disorders. We summarized the clinical data of reported individuals with WAC pathogenic mutations, which together with our findings, allowed for the expansion of the phenotypic spectrum of WAC-related disorders

Análise da imunogenicidade e da estabilidade do surfactante pulmonar de origem porcina administrado em coelhos

PURPOSE: To study the immunogenicity and the stability of the porcine pulmonary surfactant preparation produced by the Instituto Butantan. METHOD: Immunogenicity assay: Sixteen New-Zealand-White rabbits (1000 g body weight) were divided into 4 study groups. Each group was assigned to receive either a) Butantan surfactant, b) Survanta® (Abbott Laboratories), c) Curosurf® (Farmalab Chiesi), or d) no surfactant. The surfactants were administered intratracheally, and the animals were collected immediately before and 60 and 180 days after surfactant administration. Sera were assayed for the presence of antisurfactant antibodies by enzyme-linked immunosorbent assay (ELISA). Stability assay: The Butantan surfactant used in this assay had been stored for one year in the refrigerator (4 to 8ºC) and its stability was evaluated in distinct assay conditions using a premature rabbit model. RESULTS: Immunogenicity assay: None of the surfactants analyzed triggered antibody immune responses against their components in any of the animals. Stability assay: The results of this study demonstrate that Butantan surfactant was as effective as Curosurf when both were submitted to the adverse circumstance of short- and long-term storage at room temperature. A similar level of efficacy for the Butantan surfactant, as compared to Curosurf was demonstrated by the pulmonary dynamic compliance, ventilatory pressure, and pressure-volume curve results. CONCLUSION: The results of our study demonstrate that Butantan surfactant may be a suitable alternative for surfactant replacement therapy.OBJETIVO: Estudar a imunogenicidade e a estabilidade do surfactante de origem porcina produzido pelo Instituto Butantan. MÉTODO: Experimento imunogenicidade: 16 coelhos da raça New-Zealand-White (Peso de 1000g) foram divididos em grupos de 4 animais. Cada grupo foi designado para receber: a) Surfactante do Butantan, b) Survanta® (Abbott Laboratories), c) Curosurf (Farmalab Chiesi) e d) nenhum tratamento com surfactante. Os surfactantes foram administrados via intratraqueal e o sangue dos animais foi coletado antes, 60 e 180 dias após a administração do surfactante. O soro obtido foi analisado quanto a presença de anticorpos anti-surfactante pelo método ELISA (enzyme-linked immunosorbent assay). Experimento estabilidade: O surfactante do Butantan usado neste experimento tinha sido armazenado por um ano em refrigerador (4 a 8&deg;C) e sua estabilidade foi analisada em condições distintas de experimentação, usando o modelo de coelho prematuro. RESULTADOS: Experimento imunogenicidade: Nenhum dos surfactantes analisados determinou a produção de anticorpos contra seus constituintes. Experimento estabilidade: Os resultados deste estudo demonstraram que o surfactante do Instituto Butantan mostrou eficácia semelhante a do Curosurf após ter sido submetido à condições adversas ao longo do tempo. A eficácia foi demonstrada através da complacência pulmonar dinâmica, pressão ventilatória e da curva pressão-volume. CONCLUSÃO: Os resultados deste estudo demonstraram que o surfactante do Instituto Butantan pode representar um tratamento alternativo de reposição de surfactante

An ecosystem service approach to license new run of the river hydropower plants

Freshwater ecosystems provide several services (ES) to society. Hydropower production is one of the most relevant ES supported by Alpine rivers, and it is often in conflict with other river uses and services. Recently, the demand by local authorities, public or private agencies for new small hydropower plants have been increasing, and new conflicts have been arousing. We propose an approach to model the alterations of selected ES which integrates hydrological and habitat models and evaluates possible variations of the selected ES under different withdrawal scenarios. The case-study is the Noce River, a gravel-bed river in the Italian Alps (Trentino, North East Italy) which is subject to hydropeaking. We selected four ES: habitat for juvenile and adult marble trout as biodiversity proxy, rafting as recreational services, and small hydropower production as provisioning service. We evaluated the variations of these services for maximum and no hydropower production, chosen as different boundary conditions. Moreover, we simulated the presence of four new different small hydropower plants with increasing withdrawals. Large hydropower is the key driver, affecting all the selected ES. Small hydropower decreases the potential for rafting up to 64%, while it is often negligible for other services