Expresión de ACE2 en cerebro durante el desarrollo y susceptibilidad de infección cerebral por SARS-COV-2 / ACE2 expression in the brain during development and susceptibility to brain infection by SARS-COV-2

Resumen La pandemia COVID-19 se extendió por todo por a la enorme capacidad del coronavirus SARS-CoV-2 para transmitirse entre humanos. El COVID-19 es una amenaza para la salud pública mundial. La entrada de este virus en las células se ve muy facilitada por la presencia de la enzima convertidora de angiotensina 2 (ACE2) en la membrana celular. Hoy en día no tenemos un conocimiento preciso de cómo se expresa este receptor en el cerebro durante el desarrollo humano y, como consecuencia, no sabemos si las células neurales en desarrollo son susceptibles de ser infectadas a través de la transmisión de madre a feto. Revisamos en este artículo los conocimientos sobre la expresión de ACE2 en el cerebro humano en desarrollo, con especial atención a la etapa fetal. Esta etapa corresponde al periodo de formación de la corteza cerebral. La posibilidad de infección por SARS-CoV-2 durante el periodo fetal puede alterar el desarrollo normal de la corteza cerebral. Así pues, aunque se han publicado pocos casos demostrando la transmisión vertical de la infección por SARS-CoV-2, el gran número de jóvenes infectados puede representar un problema sanitario que necesite seguimiento, por la posibilidad de que se originen alteraciones cognitivas y anomalías en el desarrollo de los circuitos corticales, que pueden representar predisposición a padecer problemas mentales a lo largo de la vida.

Abstract The COVID-19 pandemic spread around the world due to the enormous transmission of the SARS-CoV-2 among humans. COVID-19 represents a threat to global public health. The entry of this virus into cells is greatly facilitated by the presence of angiotensin-converting enzyme 2 (ACE2) in the cell membrane. Today we do not have a precise understanding of how this receptor expresses in the brain during human development and, as a consequence, we do not know whether neural cells in the developing brain are susceptible to infection. We review the knowledge about ACE2 expression in the developing human brain, with special attention to the fetal stage. This stage corresponds to the period of the cerebral cortex formation. Therefore, SARS-CoV-2 infection during the fetal period may alter the normal development of the cerebral cortex. Although few cases have been published demonstrating vertical transmission of SARS-CoV-2 infection, the large number of infected young people may represent a problem which requires health surveillance, due to the possibility of cognitive alterations and abnormalities in the development of cortical circuits that may represent a predisposition to mental problems later in life.

Variabilidad en el patrón de consumo de alimentos en una población de preescolares de Asunción, de nivel socioeconómico alto y su relación con el estado nutricional / The variability in feeding patterns of pre-schoolers living in Asunción, from families with high socioeconomic status and the relation with their nutritional status

Introducción: La diversidad alimentaria constituye una medida cualitativa del consumo de alimentos, tiene una asociación positiva con la calidad de la dieta y es un factor importante para alcanzar los requerimientos nutricionales. Objetivo: Evaluar la variabilidad en el patrón de consumo de los alimentos de niños pre escolares residentes en Asunción, de condición socioeconómica alta y su relación con el estado nutricional. Metodología: Diseño observacional, trasversal, cualitativo. Se realizó la evaluación de niños prescolares de 2-6 años de nivel socio económico alto de Asunción, de setiembre a octubre de 2014 mediante medición antropométrica y con dos encuestas: una de datos demográficos y otra con la lista de todos los alimentos disponibles en el mercado, mediante entrevista directa. Se evaluó estado nutricional y su relación con la diversidad alimentaria. Se utilizó medidas de frecuencia y el programa Anthro 3.2 de la Organización Mundial de la Salud. Resultados: Se estudiaron 67 niños, con predominó del sexo femenino. El 89,5 % de madres tuvo estudios terciarios concluidos. Se encontraban eutróficos (63% de los niños) y 31,5 % con malnutrición por exceso (sobrepeso y obesidad) Un 19% presentó riesgo de talla baja y el 1,5% talla baja. Se hallaron un total de 172 tipos de alimentos que se distribuyeron en 9 grupos, la media de número de alimentos consumidos por los niños pre escolares fue de 69,19 (IC 95%: 63,79- 74,59). El rango mínimo fue de 28 alimentos y el máximo 126 alimentos. No se encontró diferencias significativas con el Índice de Masa Corporal y la diversidad alimentaria; sin embargo la relación fue estadísticamente significativa entre diversidad de la alimentación y la talla alta. Conclusión: Se constató que existe poca variabilidad en el consumo de alimentos de niños pre escolares sin restricción socio económica. Se encontró relación significativa entre diversidad Alimentaria y la talla del niño

Introduction: Food diversity can be used to measure the quality of the feeding habits. It has a positive association with diet quality and constitutes an important factor to reach the nutritional requirements. Objectives: Assess the variability in feeding patterns of pre-schoolers living in Asunción, from families with high socioeconomic status and the relation with their nutritional status. Methodology: Observational, transversal in time, qualitative study. The researchers evaluated children from 2-6 years of age, from families with high socioeconomic status living in Asunción, from September to October of 2014, using antromopetric measures and two questionnaires applied in direct interview format: the first one with demographic data and the second one with a list of locally available food. The nutritional status and its relation with food diversity were assessed, measuring frequency. World's Health Organization's Software Anthro 3.2 was used for anthropometric evaluation. Results: In total, 67 children were included in the study, mainly female. 89,5% of the patient's mother had concluded tertiary education. 63% of patients were well-nourished and 31,5% had excess weight (overweight and obese). 19% were in risk of stumpting and 1,5% were in the range of stumpting. A total of 172 food varieties were found, distributed in 9 groups, the mean quantity of food varieties consumed by children was of 69,19 (CI: 95%, 63,79-74,59), ranging from 28 to 126 food varieties. Significant differences were not found in Body Mass Index and food diversity; but a statistically significant relation was found between food diversity and height. Conclusion: Low variability in feeding patterns was found in children with high socioeconomic status. There was a significant relation between food diversity and the child's height

Congenital central hypoventilation syndrome associated with Hirschsprung's Disease: case report and literature review / Síndrome de hipoventilação central congênita associada à doença de Hirschsprung: relato de caso e revisão de literatura

Abstract Objective: To report the case of a newborn with recurrent episodes of apnea, diagnosed with Congenital Central hypoventilation syndrome (CCHS) associated with Hirschsprung's disease (HD), configuring Haddad syndrome. Case description: Third child born at full-term to a non-consanguineous couple through normal delivery without complications, with appropriate weight and length for gestational age. Soon after birth he started to show bradypnea, bradycardia and cyanosis, being submitted to tracheal intubation and started empiric antibiotic therapy for suspected early neonatal sepsis. During hospitalization in the NICU, he showed difficulty to undergo extubation due to episodes of desaturation during sleep and wakefulness. He had recurrent episodes of hypoglycemia, hyperglycemia, metabolic acidosis, abdominal distension, leukocytosis, increase in C-reactive protein levels, with negative blood cultures and suspected inborn error of metabolism. At 2 months of age he was diagnosed with long-segment Hirschsprung's disease and was submitted to segment resection and colostomy through Hartmann's procedure. A genetic research was performed by polymerase chain reaction for CCHS screening, which showed the mutated allele of PHOX2B gene, confirming the diagnosis. Comments: This is a rare genetic, autosomal dominant disease, caused by mutation in PHOX2B gene, located in chromosome band 4p12, which results in autonomic nervous system dysfunction. CCHS can also occur with Hirschsprung's disease and tumors derived from the neural crest. There is a correlation between phenotype and genotype, as well as high intrafamilial phenotypic variability. In the neonatal period it can simulate cases of sepsis and inborn errors of metabolism.

Resumo Objetivo: Relatar caso de neonato com episódios de apneias recorrentes, diagnosticado com síndrome de hipoventilação central congênita (SHCC) associada à doença de Hirschsprung (DH), o que configurou síndrome de Haddad. Descrição do caso: Terceiro filho de casal não consanguíneo, nascido a termo, parto normal sem intercorrências, peso e comprimento adequados para idade gestacional. Logo após o nascimento apresentou bradipneia, bradicardia e cianose, foi submetido à intubação orotraqueal e iniciada antibioticoterapia empírica devido à suspeita de sepse neonatal precoce. Durante internação em UTI neonatal evoluiu com dificuldade de extubação devido a episódios de dessaturação durante sono e vigília. Apresentou quadros recorrentes de hipoglicemia, hiperglicemia, acidose metabólica, distensão abdominal, leucocitose, aumento de proteína C reativa, com hemoculturas negativas e suspeita de erro inato do metabolismo. Aos dois meses foi diagnosticada doença de Hirschsprung de segmento longo, foi submetido à ressecção do segmento e colostomia à Hartmann. Feita pesquisa genética por reação em cadeia da polimerase para pesquisa de SHCC, que evidenciou alelo mutado do gene PHOX2B e confirmou o diagnóstico. Comentários: Trata-se de doença genética rara, de herança autossômica dominante, causada por mutação no gene PHOX2B, localizado na banda cromossômica 4p12, que resulta em disfunção do sistema nervoso autônomo. A SHCC também pode cursar com doença de Hirschsprung e tumores derivados da crista neural. Há correlação entre fenótipo e genótipo, além de grande variabilidade fenotípica intrafamiliar. No período neonatal pode simular quadros de sepse e erros inatos do metabolismo.

Espectro fenotípico da síndrome de Kabuki em 23 pacientes brasileiros / Phenotypic spectrum of Kabuki syndrome in 23 Brazilian patients

Catalogar a variabilidade fenotípica dos pacientes com síndrome de Kabuki atendidos no Núcleo de Genética da Secretaria de Estado de Saúde do Distrito Federal, e comparar os resultados com os dados disponíveis na literatura.

To catalog the phenotypic variability of patients with Kabuki syndrome seen at the Clinical Genetics Service of Secretaria de Estado de Saúde do Distrito Federal, and to compare the results with data available in the literature.

Angiosarcoma in a 3-year-old child with congenital lymphedema

Angiosarcoma occurring in chronic lymphedema has been described in more than 200 cases, especially in the upper extremity following radical mastectomy (Stewart-Treves syndrome). However, angiosarcoma developing in congenital lymphedema is quite rare and the literature presents only 14 cases. Our patient is a girl with congenital lymphedema of the left lower limb that developed an angiosarcoma at 3 years of age, noted initially as a painful nodular lesion on the left thigh. This seems to be the earliest presentation of angiosarcoma associated with lymphedema. It claims attention to a careful evaluation of any lesions in a child with lymphedema to provide a better prognosis, which is allowed by precocious diagnosis and rapid interventions.

Evaluación de la conducta adolescente con las Escalas de Achenbach: ¿existe concordancia entre diferentes informantes?

resumen está disponible en el texto completo

Summary: Introduction Behavioural problems in adolescents are thought to be relevant as strong predictors for the detection of other psychological disorders. For this reason and due to the importance they present by themselves, carrying out an adequate assessment of them is fundamental. Mental health professionals have diverse opinions about the value and importance of the different informants. The majority choose of their sources according to the disorder and necessities of each evaluator. On the other hand, the need to obtain data about adolescents' functioning from multiple resources has been emphasised and numerous reasons have been exposed. Concretely, the fact of carrying out the most objective and complete evaluations as possible has been considered essential in those studies aimed at evaluating behavioural alteration in adolescents. For this reason, Achenbach developed three versions of his scale: one for the parents, another for the teachers and a third one for the adolescents themselves. Numerous investigations have studied the concordance between groups of informants about different behavioural alterations in adolescents, but none have carried out a complete analysis of all informants in all subscales (not only the total ones). For this reason, the current study has been developed with the aim of contributing to obtain an enriching vision for the professional in the field. Objectives. a) To systematically explore agreement patterns between adolescents, teachers and parents who inform of behavioural problems in adolescents in the general population and b) in those cases in which no agreement is found, to analyse the level of disagreement between each pair of informants for each subscale. Methodology. Cross-sectional and descriptive study Participants. The study was formed by 160 triads of parents, teachers and 13-16 year old adolescents selected from several schools in Barcelona. Instruments. The three forms of the Achenbach scale to measure behavioural alterations were applied. The scale was translated into Spanish by the Unit of Epidemiology and Diagnostic in Psychopathology of the Development of the Universidad Autónoma de Barcelona: Youth Self-Report, self-evaluated, Child Behaviour Checklist/4-18 and Teacher's Report Form, both heteroevaluated and completed by parents and teachers, respectively. These three forms contain a 89-item set that evaluates the same behaviour, where eight items are organised in scales of syndromes derived empirically and which are invariant throughout informants. The eight subscales are: withdrawn, somatic complaints, anxious/depressed, social problems, thought problems, attention problems, delinquent behaviour and aggressive behaviour. Some of them are grouped in second order factors: the first three in internalising, the last two in externalising, and the rest of them provide a total problems punctuation. Statistical procedure. Agreement values were analysed for each pair of informants and each subscale through the Intraclass Correlation Coefficient (ICC). A value below 0.40 indicates low concordance. In these cases, the statistical analysis proceeds with the discordance analysis by pairs of informants and for each subscale through the Bland Altman Method. Results. A low concordance (below 0.40) between informants was found especially in internalizing scales (0.230). A slightly higher value was found in attention (0.334), aggressive behaviour (0.371), externalizing (0.357), and total subscales (0.327). Secondly, it was observed that, when informing about somatic complains, thought and attention problems, internalising items and the total scale, parents reported more alterations, followed by adolescents and teachers. Also, parents indicated more withdrawal problems in adolescents, although in this case they were followed by teachers and adolescents themselves. Finally, in the evaluation of the anxiety/depression scales, social problems, delinquent behaviour, aggressiveness and externalising conducts, adolescents informed of more alterations followed by their parents, and then by the teachers. Regarding the agreement/disagreement variability throughout the scales scores, the discordance between different informants was higher when the punctuation was further away from normality, generally when the scales were scored higher. Discussion. The normative criteria of comparison and the reference frames for each group of informants are different. For instance, the fact that teachers report less behavioural alterations could be explained because of their familiarity in dealing with adolescents and a higher tolerance towards some behaviors. In general terms, this result fits in with most conclusions from investigations carried out in this field. On the other hand, the fact that parents inform of more internalising problems could be attributed to adolescent behaviour which would in turn alter the family context. Another explanation might be that parents are on the whole more implicated and more sensitive in detecting certain conducts or behavioural alterations in their offspring. In any case, it is disputable whether the lack of concordance between the different informants does really exist or, on the contrary, adolescent behaviour changes depending on the context. Finally, a result contradicting those found in the studies reviewed is that adolescents are the ones who report more externalising problems. Other authors have found that adolescents inform more about internalising problems, something which should be expected taking into account that they are the ones who know themselves better. This could be possibly explained by the presence of more social desirability/undesirability among the adolescents of our sample in front of their pair group when answering to the evaluation scales; this may be due to the group context in which the case was applied. The main limitation of the present study that it was carried out with a general population sample, although from another point of view this may be considered as a gain of the study. We recommend carrying out explicative studies about discordance, which could clarify the predictive validity of each informant group and make variations in the type of sample under study. Conclusions. Data from different sources contribute with specific information of relative validity. This is why a multidimensional, multisituational and mulitiinformant approach is fundamental. This is necessary not only to evaluate behavioural alterations in adolescents within a research context, but also when taking diagnostic decisions in a clinical context, because, depending on the chosen informant, the diagnostic criteria for one disorder or another might change. Also, our results imply that there may be an underdetection of behavioural problems in adolescents by the adults, which would result in a lower psychological demand than the necessary.

¿Explica la esquizotipia la discordancia entre informantes de alteraciones conductuales adolescentes?

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Summary: Introduction. Behavioural alterations are a quite potent predictor for schizophrenia. Very often, apparently healthy adolescents (who will later develop schizophrenia) present altered conducts similar to those manifested by schizophrenic subjects and as predictors for the disorder. There are studies that describe the relationship between these behavioural alterations and the features found in schizotypical personality disorder or schizophrenic symptoms. In this way, it has been established that those subjects who obtain high scores in schizotypy present more behavioural alterations. Concretely, the different behavioural alterations have been differentially related to the positive and negative subtypes of the schizotypical personality, suggesting continuity between the nature of premorbid conducts and the adult symptoms patterns in which the illness develops. On the other hand, comparing adolescents that will later develop schizophrenia with those who will not, it has been found that the best schizophrenia predictor is a poor behavioural adjustment. Moreover, if the teachers' reports are examined, there can be certain aspects such as the early behavioural patterns which will identify children who, for instance, will develop schizophrenia thirty years later, or even differential patterns according to the gender of the subjects. Therefore, if we want to carry out a schizophrenia prediction according to these behavioural criteria, knowing which informants are more useful and how their opinions match among them is of a great interest. Until this moment, the majority of studies have pointed out at the ability of teachers to identify conducts that can be used to select people at risk for schizophrenia. However, having into account that numerous studies conclude that there is a lack of agreement between these and other different informants for behavioural alterations in adolescents, the importance of studying the variables that can be influencing this matter must be raised. Following with the line of our research group a question is raised. We wonder if the presence of schizotypical personality traits makes the adolescents behaviour more ambiguous, with the consequent difficulty to define it in a coincident way from different evaluators and from themselves. Objectives. To analyse the influence of the schizotypical personality (assessed with the Oxford-Liverpool Inventory of Feelings and Experiences), the demographic variable gender and the interaction between them, in the discordance of different informants (parents, teachers and adolescents) when they inform about behavioural problems in adolescents (assessed with the Achenbach's scales). Methodology. This is an analytic transversal study that can be framed into a longitudinal study of 2 cohorts from the general population, which started on 2000 and has been then followed-up ("Psychoeducation program and early detection of schizophrenic disorders of adolescent onset"). Participants. 160 triads of parents, teachers and adolescents from 13 to 16 years old selected from 7 schools of Barcelona took part in the study. Instruments. The three forms of the Achenbach scale for the measure of behavioural alterations were applied: Youth Self- Report, Child Behaviour Checklist/4-18 and Teacher's Report Form. These forms contain 8 scales which are invariant throughout informants: Withdrawn, somatic complaints, anxious/depressed, social problems, thought problems, attention problems, delinquent behaviour and aggressive behaviour. Some of them are grouped in second order factors: Internalizing, externalizing and total. To evaluate the psychometrical schizotypical personality of adolescents we used the Oxford-Liverpool Inventory for Feelings and Experiences. It consists of an autoadministered inventory with 159 items that includes four schizotypical scales. The Unusual Experiences scale reflects the positive dimension of schizotypy and includes items of unusual perception aberrations and magical thinking. The Introvert Anhedonia Scale reflects the negative dimension of schizotypy and consists of items assessing restricted affect, social isolation and anhedonia. The Cognitive Disorganization Scale refers to disorganized aspects of the psychosis and it is composed of items assessing difficulties in concentration and decision-making. Finally, the Impulsive Nonconformity Scale reflects the characteristics of impulsive-type personality, social anxiety and maladjusted behaviours. Statistical proceed. Multiple regression analyses were carried out in order to revise the influence of the schizotypical personality, the demographic variable gender and the interaction between them as possible explicative variables, in the discordance between different informants about behavioural problems of adolescents. The dependent variable was a measure of the level of discordance between the three groups of informants. Results. A major discordance between informants of behavioural problems was found as schizotypy was higher. Concretely, a larger number of unusual experiences in adolescents increase the discordance for thought and internalizing problems. Discordance is also higher in aggressiveness and anxiety/depression as cognitive disorganization increases. Also, the higher the introverted anhedonia, the higher the discordance is for social problems, anxiety/depression, attention, externalizing problems, and for the total. To finish, a high score in non-conformity impulsivity increases the discordance for attention, delinquency and aggressive problems. About the influence of gender, discordance between informants for anxiety/depression is higher for females than for males. However, this varies when the interaction effects found are considered. In this way, a differential effect for the increase of non-conformity impulsivity and introvert anhedonia can be observed in males and females. Therefore, discordance between informants is higher when evaluating anxiety/ depression in males when non-conformity impulsivity is high. Just the opposite happens for girls. In addition, the discordance for the internalizing subscale increases just as the introverted anhedonia raises for females, but it decreases when evaluating males. Discussion. It seems clear that no source of data can be substituted for any other when evaluating behavioural problems in adolescents and much less when attention is centred in those adolescents who score high in schizotypy. Specifically, when evaluating the behaviour of those subjects who score high in the positive dimension of schizotypy, the agreement between informants decreases for thought and internalizing problems; and, when the behaviour of those who are defined for a more negative schizotypy is evaluated, the agreement decreases for social problems, anxiety/ depression, externalizing and total. Having all this into account and adding information that other authors have found related to each schizotypy subtype (which, besides, are the ones which more concordance show), some conclusions could be raised. It can be assumed as evident that schizotypical personality (and each trait type) and the subjacent conduct in these subjects can generate a difficulty in perceiving certain conducts which are not predominant in the subject, with the consequent discordance between informants. For future studies, it would be very interesting to carry out studies examined which group of informants augurs the behavioural predisposition for schizophrenia and its dimensions in the most accurately way possible. Conclusions. A most exact and objective method to assess behavioural problems as well-demonstrated predictor to schizophrenia, is necessary in order to select vulnerable teenagers to the illness and to develop programs of early intervention.

Tratamiento neuroquirúrgico de la agresividad irreductible: hipotalamotomía posteromedial estereotáxica / Stereotaxic posteromedial hypothalamotomy in the treatment of aggressive behaviour: a clinical case

Introducción: se describe el caso de un paciente de 30 años, portador de trastorno orgánico de la personalidad, que presentaba frecuentes accesos de agresividad patológica subtipo predatorio hacia otras personas. Estos episodios de descontrol fueron esporádicos en la infancia; a partir de los 15 años el síndrome fue empeorando a pesar de los tratamientos instituidos, siendo las crisis de agresividad imprevisibles cada vez más frecuentes y violentas. Se emplearon sucesivamente y en forma combinada terapéuticas farmacológicas (neurolépticos, antipsicóticos, benzodiacepinas, estabilizadores y betabloqueantes) a dosis plenas y en rango variable, electroconvulsoterapia y múltiples terapias de rehabilitación. Ante el fracaso terapéutico convencional se planteó como último recurso la neurocirugía. Procedimiento: la cirugía que se llevó a cabo fue una hipotalamotomía posteromedial bilateral estereotáxica por radiofrecuencia, bajo anestesia general, realizando la localización de los blancos a tratar con tomografía computada. No se observaron complicaciones posoperatorias. Resultados: en las semanas siguientes al posoperatorio el paciente se mantuvo en situación de mansedumbre, lo que permitió modificar el programa farmacológico, con suspensión de la megadosis de psicofármacos (haloperidol, olanzapina, lorazepam) y betabloqueantes (propranolol), y mantención del timorregulador anticomicial (valproato). En la evolución inmediata se reintegra precozmente y sin incidentes a la terapia grupal de rehabilitación y a actividades sociales con su familia. En la evolución diferida recupera paulatinamente rasgos personales y capacidades previas al comienzo de la refractariedad. La condición de mejoría clínica, respecto al objetivo del control de la agresividad patológica subtipo predatorio y la mejoría de la calidad de vida del paciente y su familia se mantienen durante el seguimiento de nueve meses, por lo que se decide publicar el reporte.

Elementos de análisis para la estructuración de un programa docente asistencial. Vereda el Zancudo (Fredonia, Antioquia), 1998. I Parte: Estado de Salud Bucal de Población / Elements of analysis for the design and implementation of a teaching assistance program, in the communities of El Zancudo y Fredonia in Colombia. Part I: Oral health status of the population

En este estudio se describe el estado de salud bucal de la población de la vereda el Zancudo (Fredonia- Antioquia). Se realizó examen clínico bucal a una muestra de 150 personas para determinar los niveles de caries dental, enfermedad periodontal y las necesidades de prótesis. En términos generales puede afirmarse que la situación de salud bucal de la población estudiada es un nivel aceptable principalmente en la población joven. Las personas menores de 20 años tienen alto grado de conservación dentaria, baja historia de caries dental y buena salud gingival. En los mayores de 20 años hay un deterioro evidente de estas condiciones pero los indicadores de enfermedad son más bajos que los reportados en el último estudio Nacional de salud bucal. Con base en estos resultados puede afirmarse que el programa docente asistencial debe estructurarse para responder a tres retos: -Mantener los buenos niveles de salud bucal encontrados en la población escolar, -Reformular programas educativos y de mercadeo social que tengan efectos sobre las conductas, hábitos y comportamiento de la población y -Garantizar actividades de recuperación de la salud para todos los grupos de edad...