Modulation of oxidative neurometabolism in ischemia/reperfusion by nitrite.

Nitrite has been viewed essentially as an inert metabolic endpoint of nitric oxide (•NO). However, under certain conditions, nitrite can be a source of •NO. In the brain, this alternative source of •NO production independent of nitric oxide synthase activity may be particularly relevant in ischemia/reperfusion (I/R), where low oxygen availability limits enzymatic production of •NO. Notably, in vivo concentration of nitrite can be easily increased with diet, through the ingestion of nitrate-rich foods, opening the window for a therapeutic intervention based on diet. Considering the modulation of mitochondrial respiration by •NO, we have hypothesized that the protective action of nitrite in I/R may also result from modulation of mitochondrial function. We used high-resolution respirometry to evaluate the effects of nitrite in two in vitro models of I/R. In both cases, an increase in oxygen flux was observed following reoxygenation, a phenomenon that has been coined "oxidative burst". The amplitude of this "oxidative burst" was decreased by nitrite in a concentration-dependent manner. Additionally, a pilot in vivo study in which animals received a nitrate-rich diet as a strategy to increase circulating and tissue levels of nitrite also revealed that the "oxidative burst" was decreased in the nitrate-treated animals. These results may provide mechanistic support to the observation of a protective effect of nitrite in situations of brain ischemia.

In vivo hydrogen peroxide diffusivity in brain tissue supports volume signaling activity.

Hydrogen peroxide is a major redox signaling molecule underlying a novel paradigm of cell function and communication. A role for H2O2 as an intercellular signaling molecule and neuromodulator in the brain has become increasingly apparent, with evidence showing this biological oxidant to regulate neuronal polarity, connectivity, synaptic transmission and tuning of neuronal networks. This notion is supported by its ability to diffuse in the extracellular space, from source of production to target. It is, thus, crucial to understand extracellular H2O2 concentration dynamics in the living brain and the factors which shape its diffusion pattern and half-life. To address this issue, we have used a novel microsensor to measure H2O2 concentration dynamics in the brain extracellular matrix both in an ex vivo model using rodent brain slices and in vivo. We found that exogenously applied H2O2 is removed from the extracellular space with an average half-life of t1/2 = 2.2 s in vivo. We determined the in vivo effective diffusion coefficient of H2O2 to be D* = 2.5 × 10-5 cm2 s-1. This allows it to diffuse over 100 µm in the extracellular space within its half-life. Considering this, we can tentatively place H2O2 within the class of volume neurotransmitters, connecting all cell types within the complex network of brain tissue, regardless of whether they are physically connected. These quantitative details of H2O2 diffusion and half-life in the brain allow us to interpret the physiology of the redox signal and lay the pavement to then address dysregulation in redox homeostasis associated with disease processes.

The bioactivity of neuronal-derived nitric oxide in aging and neurodegeneration: Switching signaling to degeneration.

The small and diffusible free radical nitric oxide (•NO) has fascinated biological and medical scientists since it was promoted from atmospheric air pollutant to biological ubiquitous signaling molecule. Its unique physical chemical properties expand beyond its radical nature to include fast diffusion in aqueous and lipid environments and selective reactivity in a biological setting determined by bioavailability and reaction rate constants with biomolecules. In the brain, •NO is recognized as a key player in numerous physiological processes ranging from neurotransmission/neuromodulation to neurovascular coupling and immune response. Furthermore, changes in its bioactivity are central to the molecular pathways associated with brain aging and neurodegeneration. The understanding of •NO bioactivity in the brain, however, requires the knowledge of its concentration dynamics with high spatial and temporal resolution upon stimulation of its synthesis. Here we revise our current understanding of the role of neuronal-derived •NO in brain physiology, aging and degeneration, focused on changes in the extracellular concentration dynamics of this free radical and the regulation of bioenergetic metabolism and neurovascular coupling.

Pediatric patients with COVID-19 admitted to intensive care units in Brazil: a prospective multicenter study / Pacientes pediátricos com COVID-19 admitidos em Unidades de Terapia Intensiva no Brasil: um estudo prospectivo multicêntrico

Abstract Objective: To describe the clinical characteristics of children and adolescents admitted to intensive care with confirmed COVID-19. Method: Prospective, multicenter, observational study, in 19 pediatric intensive care units. Patients aged 1 month to 19 years admitted consecutively (March-May 2020) were included. Demographic, clinical-epidemiological features, treatment, and outcomes were collected. Subgroups were compared according to comorbidities, age < 1 year, and need for invasive mechanical ventilation. A multivariable logistic regression model was used for predictors of severity. Results: Seventy-nine patients were included (ten with multisystemic inflammatory syndrome). Median age 4 years; 54% male (multisystemic inflammatory syndrome, 80%); 41% had comorbidities (multisystemic inflammatory syndrome, 20%). Fever (76%), cough (51%), and tachypnea (50%) were common in both groups. Severe symptoms, gastrointestinal symptoms, and higher inflammatory markers were more frequent in multisystemic inflammatory syndrome. Interstitial lung infiltrates were common in both groups, but pleural effusion was more prevalent in the multisystemic inflammatory syndrome group (43% vs. 14%). Invasive mechanical ventilation was used in 18% (median 7.5 days); antibiotics, oseltamivir, and corticosteroids were used in 76%, 43%, and 23%, respectively, but not hydroxychloroquine. The median pediatric intensive care unit length-of-stay was five days; there were two deaths (3%) in the non- multisystemic inflammatory syndrome group. Patients with comorbidities were older and comorbidities were independently associated with the need for invasive mechanical ventilation (OR 5.5; 95% CI, 1.43-21.12; p = 0.01). Conclusions: In Brazilian pediatric intensive care units, COVID-19 had low mortality, age less than 1 year was not associated with a worse prognosis, and patients with multisystemic inflammatory syndrome had more severe symptoms, higher inflammatory biomarkers, and a greater predominance of males, but only comorbidities and chronic diseases were independent predictors of severity.

Resumo Objetivo: Descrever as características clínicas de crianças e adolescentes internados em unidade de terapia intensiva com COVID-19 confirmada. Método: Estudo prospectivo, multicêntrico, observacional, em 19 unidades de terapia intensiva pediátrica. Foram incluídos pacientes entre um mês e 19 anos, admitidos consecutivamente (março a maio de 2020). As características demográficas, clínico-epidemiológicas, o tratamento e os resultados foram coletados. Os subgrupos foram comparados de acordo com as comorbidades, idade < 1 ano e necessidade de ventilação mecânica invasiva. Um modelo de regressão logística multivariável foi utilizado para preditores de gravidade. Resultados: Setenta e nove pacientes foram incluídos (10 com síndrome inflamatória multi-ssistêmica). Mediana de idade, quatro anos; 54% eram do sexo masculino (síndrome inflamatória multissistêmica, 80%); 41% tinham comorbidades (síndrome inflamatória multissistêmica, 20%). Febre (76%), tosse (51%) e taquipneia (50%) foram comuns nos dois grupos. Sintomas graves egastrointestinais e marcadores inflamatórios mais elevados foram mais frequentes na presença de síndrome inflamatória multissistêmica. Infiltrados intersticiais pulmonares foram comuns em ambos os grupos, mas o derrame pleural foi mais prevalente no grupo com síndrome inflamatória multissistêmica (43% vs. 14%). A ventilação mecânica invasiva foi utilizada em 18% (mediana 7,5 dias); antibióticos, oseltamivir e corticosteroides foram utilizados em 76%, 43% e 23%, respectivamente, mas não a hidroxicloroquina. A mediana do tempo de permanência na unidade de terapia intensiva pediátrica foi de 5 dias; duas mortes ocorreram (3%) no grupo não- síndrome inflamatória multissistêmica. Os pacientes com comorbidades eram mais velhos, e as comorbidades foram independentemente associadas à necessidade de ventilação mecânica invasiva(OR 5,5; IC95%, 1,43-21,12; P 0,01). Conclusões: Nas unidades de terapia intensiva pediátrica brasileiras, a COVID-19 apresentou baixa mortalidade, a idade inferior a um ano não foi associada a um pior prognóstico, os pacientes com síndrome inflamatória multissistêmica apresentaram sintomas mais graves, biomarcadores inflamatórios mais elevados e uma grande predominância no sexo masculino, mas apenas a presença de comorbidades e doenças crônicas foi um preditor independente de gravidade.

Pediatric patients with COVID-19 admitted to intensive care units in Brazil: a prospective multicenter study.

OBJECTIVE: To describe the clinical characteristics of children and adolescents admitted to intensive care with confirmed COVID-19. METHOD: Prospective, multicenter, observational study, in 19 pediatric intensive care units. Patients aged 1 month to 19 years admitted consecutively (March-May 2020) were included. Demographic, clinical-epidemiological features, treatment, and outcomes were collected. Subgroups were compared according to comorbidities, age < 1 year, and need for invasive mechanical ventilation. A multivariable logistic regression model was used for predictors of severity. RESULTS: Seventy-nine patients were included (ten with multisystemic inflammatory syndrome). Median age 4 years; 54% male (multisystemic inflammatory syndrome, 80%); 41% had comorbidities (multisystemic inflammatory syndrome, 20%). Fever (76%), cough (51%), and tachypnea (50%) were common in both groups. Severe symptoms, gastrointestinal symptoms, and higher inflammatory markers were more frequent in multisystemic inflammatory syndrome. Interstitial lung infiltrates were common in both groups, but pleural effusion was more prevalent in the multisystemic inflammatory syndrome group (43% vs. 14%). Invasive mechanical ventilation was used in 18% (median 7.5 days); antibiotics, oseltamivir, and corticosteroids were used in 76%, 43%, and 23%, respectively, but not hydroxychloroquine. The median pediatric intensive care unit length-of-stay was five days; there were two deaths (3%) in the non- multisystemic inflammatory syndrome group. Patients with comorbidities were older and comorbidities were independently associated with the need for invasive mechanical ventilation (OR 5.5; 95% CI, 1.43-21.12; p = 0.01). CONCLUSIONS: In Brazilian pediatric intensive care units, COVID-19 had low mortality, age less than 1 year was not associated with a worse prognosis, and patients with multisystemic inflammatory syndrome had more severe symptoms, higher inflammatory biomarkers, and a greater predominance of males, but only comorbidities and chronic diseases were independent predictors of severity.

Rio Birth Cohort Study on Environmental Exposure and Childhood Development - PIPA Project.

Background/Objective: As a developing country, Brazil presents a wide range of environmental risks that can constitute hazards to child health. The country also presents different socio-economic-cultural conditions that could be responsible for determining different vulnerability and susceptibility levels for the population, which can potentiate the effects of the environmental pollutants. The Rio Birth Cohort Study (PIPA project) is a prospective maternal-infant health study, hosted in the city of Rio de Janeiro (Southeastern Brazil), designed to investigate separate and combined effects of environmental chemical pollutants, as well as the interactions between these exposures and sociocultural environment and epigenetic patterns. This paper presents the learned lessons and strategies to address the shortcomings detected from this pilot study. Methods: The study population will be all children born at the Federal University of Rio de Janeiro Maternity Hospital from July 1st, 2020 to June 30th, 2021. The estimated population is of 2,500 children. The study will collect social, demographic, and health information from pregnant women and their children up to four years of age. Biological samples from both mothers and newborns will be collected to assess metal, pesticide and plasticizer exposure. All newborns will have their landmarks of physical, neurological, psychological, and cognitive development recorded at specific ages. Findings: A pilot study was carried out between September 2017 and August 2018, totaling 142 enrolled pregnant women, leading to 135 (95%) births and the collection of umbilical cord (126-93%,) and mother (139-98%) blood samples, as well as both mother (142-100%) and newborn (54-40%) urine samples and newborn meconium samples (117-86.7%). Conclusions: The study proposes a comprehensive assessment of pre- and postnatal exposure to environmental chemicals at multiple time points in a population living in a highly urbanized developing country. As far as we know, this is the only birth cohort in Brazil specifically designed for this purpose.

Bioactive Lipids and the Gut-Brain Axis: Diet as a Modulator of Bioactivity and Diversity of Lipids in the Brain.

The brain is highly rich in lipids, which accounts for roughly 50% of its dry weight. The brain lipidome, generally characterized over half a century ago, is comprised of thousands of biochemical structures expressed differentially as a function of brain region, structure, cell type and subcellular compartment. Lipids play diverse structural and functional roles in the brain, not only due to their chemical diversity but also due to the unique hydrophobic environment that they create. This lipophilic milieu promotes interactions involving reactive oxygen and nitrogen species that may not occur, at least at a similar extent, in aqueous environments.In the present chapter, we have focused on 3 distinct types of bioactive lipids and the roles played in brain physiology and pathology: nitrated fatty acids, cholesterol and endocannabinoids. These lipids are diverse in origin and bioactivity: (1) nitrated fatty acids result from biochemical modification of dietary fatty acids by nutrients and are proposed to play diverse physiological roles, namely by modulating NF-kB and Nfr2-dependent signaling cascades and post-translational modification of proteins. Produced in the gastric compartment, they are absorbed into circulation and can cross the blood-brain barrier, providing a new route for the interaction between the gastrointestinal tract and the brain; (2) cholesterol, synthetized de novo in the brain, not only regulates the biophysical properties of cellular membranes, but can also physically interact with neurotransmitter receptors and other membrane proteins and enzymes such as those involved in the processing and trafficking of the amyloid precursor protein (APP) and Aß peptide; (3) endocannabinoids, a class of neuromodulators derived from fatty acids that are synthetized and released upon demand and incite cellular responses by binding to specific membrane receptors.Being one of the most important and adjustable determinants of human health, our goal is to highlight the impact of diet on the bioactivity of lipids in the brain, discussing novel and provocative findings that advocate that lipids may modulate the gut-brain axis and therefore higher cortical functions such as motor function, learning and memory.

Genetic diversity of Saccharum complex using ISSR markers.

Sugarcane (Saccharum sp, Poaceae) is native to Southeast Asia, and due to growing demand as raw material, its cultivation recently expanded to new frontiers. The genetic diversity analysis is essential for targeting strategies in the formation and maintenance of a germplasm. This study aimed to assess the genetic diversity of 26 accessions of sugarcane from the Active Germplasm Bank of Embrapa Coastal Tablelands, using inter-simple sequence repeat (ISSR) molecular markers. Sixteen primers were used, resulting in 87 fragments with 91.13% of polymorphism. The similarity of the individuals ranged between 0.22 and 0.87. Individuals RB867515 and RB92579 were closer genetically, and the most distant ones were PI240785 and NSL 291970. Four distinct clusters were formed, using UPGMA. This information can be used to prioritize the selection of accessions for the conduction of hybridization in breeding and germplasm exchange actions.

Adaptación y validación de un cuestionario para medir las actitudes y percepciones hacia los hombres enfermeros / Cross-cultural adaptation and validation of the attitudes towards men in nursing scale (ATMINS)

Introducción. Para facilitar la detección de las posibles causas de los bajos niveles de ingreso de los hombres en enfermería, Bartfay et al., desarrollaron un cuestionario que llamaron Attitudes Towards Men in Nursing Scale (ATMINS). Objetivo. Realizar la adaptación transcultural y validación de la escala ATMINS para evaluar si los resultados con una muestra española son similares a los encontrados en la muestra canadiense. Participantes, material y método. Los sujetos se reclutaron en las Universidades de Alicante y del País Vasco. A todos los candidatos se les informó sobre el objetivo del estudio para que decidieran si deseaban participar en el mismo, una vez expuesto su contenido y dando tiempo suficiente para la lectura del cuestionario. Se ha utilizado el cuestionario ATMINS tras la pertinente traducción el español. La versión española de la escala ATMINS se proporcionó a un total de 142 participantes, que pertenecían al cuarto curso de Grado en Enfermería de la Universidad de Alicante y al Grado en Enfermería de la Universidad de Donostia. En ningún caso la cumplimentación de la escala por la muestra a estudio duró más de 5 minutos y no se detectó dificultad alguna en su implementación. Tras la administración de la escala, se realizó un análisis de consistencia interna mediante el Alfa de Cronbach con corrección mediante eliminación de ítem y posterior estudio de la validez de constructo mediante Análisis Factorial Exploratorio con rotación Varimax. Resultados. Los resultados muestran una fiabilidad que no alcanza el grado moderado. Se observa además, que, si se elimina el ítem 6, todas las submuestras, así como la muestra total, mejoran la consistencia interna. Este efecto no se obtiene tras la supresión de cualquiera de los otros cinco reactivos. El análisis factorial exploratorio apoya una estructura bifactorial del cuestionario con saturaciones muy altas en cada uno de los dos factores y con una carga negativa dentro del factor 2 para el ítem seis. La carga negativa del reactivo seis mantiene la saturación (.717) tras su inversión. Teniendo en cuenta solo los ítems del factor 1, se realiza el estudio de la consistencia interna, el cual revela que mejora la consistencia interna de la escala con puntuaciones próximas a .70. Conclusiones. La Escala revisada es un instrumento de fácil y rápida aplicación. Es válida para muestra española y posee una consistencia interna aceptable. Los resultados tanto en la Universidad de Ontario como en las de Alicante y Donostia (España) son equiparables (AU)

Aiming at detecting possible causes for the lack of male nursing professionals, Bartfay et al. developed a questionnaire named Attitudes Towards Men in Nursing Scale (ATMINS), which they tested in a university in Ontario, Canada. Objective. Achieve a cross-cultural adaptation and validation of the Attitudes Towards Men in Nursing Scale (ATMINS), in order to evaluate if results achieved using a Spanish sample are comparable with the Canadian study’s results. Participants, materials and method. Participants were recruited in universities of Alicante and Donostia (Basque Country). To assure voluntary participation in the study, all candidates were informed about the objective of the study and giving enough time to read the questionnaire. The questionnaire used was the Attitudes Toward Men in Nursing Scale (ATMINS), translated to Spanish. The Spanish version of the ARMINS scale was handed over to a total of 142 students from the Nursing Universities of Alicante and Donostia. Time needed to fill the questionnaires didn´t exceed 5 minutes in any case, and no difficulty was observed during implementation. After testing the scale, an internal consistency analysis was performed using Cronbach´s Alpha with correction by eliminating items. Validation of construct was done via Exploratory Factorial analysis with Varimax rotation. Results. The results show a reliability which does not reach a moderate degree. Eliminating item 6 in all subsamples, as well as in the total sample suppressing any of the other 5 items, increases internal consistency. The exploratory factorial analysis supports a bi-factorial structure of the questionnaire with very high saturation on each factor and a negative charge inside factor 2 for item 6. The negative charge of item 6 keeps the saturation (0.717) after its inversion. By performing an internal consistency analysis taking only into account items of factor 1, the scale’s consistency improves with results close to 0.70. Conclusions. The revised scale is a tool which enables easy and fast application. It is valid for the Spanish sample and provides an acceptable internal consistency. The results obtained in both universities in Spain and in Canada are comparable (AU)

Diversity and genetic stability in banana genotypes in a breeding program using inter simple sequence repeats (ISSR) markers.

Banana (Musa spp) is a fruit species frequently cultivated and consumed worldwide. Molecular markers are important for estimating genetic diversity in germplasm and between genotypes in breeding programs. The objective of this study was to analyze the genetic diversity of 21 banana genotypes (FHIA 23, PA42-44, Maçã, Pacovan Ken, Bucaneiro, YB42-47, Grand Naine, Tropical, FHIA 18, PA94-01, YB42-17, Enxerto, Japira, Pacovã, Prata-Anã, Maravilha, PV79-34, Caipira, Princesa, Garantida, and Thap Maeo), by using inter-simple sequence repeat (ISSR) markers. Material was generated from the banana breeding program of Embrapa Cassava & Fruits and evaluated at Embrapa Coastal Tablelands. The 12 primers used in this study generated 97.5% polymorphism. Four clusters were identified among the different genotypes studied, and the sum of the first two principal components was 48.91%. From the Unweighted Pair Group Method using Arithmetic averages (UPGMA) dendrogram, it was possible to identify two main clusters and subclusters. Two genotypes (Garantida and Thap Maeo) remained isolated from the others, both in the UPGMA clustering and in the principal cordinate analysis (PCoA). Using ISSR markers, we could analyze the genetic diversity of the studied material and state that these markers were efficient at detecting sufficient polymorphism to estimate the genetic variability in banana genotypes.

[Cross-Cultural Adaptaton and Validation of the Attitudes Towards Men in Nursing Scale (ATMINS)]. / Adaptación y validación de un cuestionario para medir las actitudes y percepciones hacia los hombres enfermeros.

Introduction: Aiming at detecting possible causes for the lack of male nursing professionals, Bartfay et al. developed a questionnaire named Attitudes Towards Men in Nursing Scale (ATMINS), which they tested a university in Ontario, Canada. Objective: Achieve a cross-cultural adaptation and validation of the Attitudes Towards Men in Nursing Scale (ATMINS), in order to evaluate if results achieved using a Spanish sample are comparable with the Canadian study's results. Participantsm, Materials, and Method: Participants were recruited in universities of Alicante and Donostia (Basque Country). To assure voluntary participation in the study, all candidates were informed about the objective of the study and giving enough time to read the questionnaire. The questionnaire used was the Attitudes Toward Men in Nursing Scale (ATMINS), translated to Spanish. The Spanish version of the ARMINS scale was handed over to a total of 142 students from the Nursing Universities of Alicante and Donostia. Time needed to fill the questionnaires didn't exceed 5 minutes in any case, and no difficulty was observed during implementation. After testing the scale, an internal consistency analysis was performed using Cronbach's Alpha with correction by eliminating items. Validation of construct was done via Exploratory Factorial analysis with Varimax rotation. Results: The results show a reliability which does not reach a moderate degree. Eliminating item 6 in all subsamples, as well as the total sample suppressing any of the other 5 items, increases internal consistency. The exploratory factorial analysis supports a bi-factorial structure of the questionnaire with very high saturation on each factor and a negative charge inside factor 2 for item 6. The negative charge of item 6 keeps the saturation (0.717) after its inversion. By performing an internal consistency analysis taking only into account items of factor 1, the scale's consistency improves with results close to 0.70. Conclusion: The revised scale is a tool which enables easy and fast application. It is valid for the Spanish sample and provides an acceptable internal consistency. The results obtained in both universities in Spain and in Canada are comparable.

Genetic diversity in natural populations of mangaba in Sergipe, the largest producer State in Brazil.

Mangaba (Hancornia speciosa Gomes) is found in areas of coastal tablelands in the Brazilian Northeast and Cerrado regions. This species has been subjected to habitat fragmentation that is mainly due to human activity, and requires conservation strategies. The aim of this study was to analyze the structure and inter- and intrapopulation genetic diversity of natural populations of H. speciosa Gomes using inter-simple sequence repeat (ISSR) molecular markers. A total of 155 individuals were sampled in 10 natural populations (ITA, PAC, IND, EST, BC, PIR, JAP, BG, NEO, and SANT) in the State of Sergipe, Brazil. Fifteen primers were used to generate 162 fragments with 100% polymorphism. Genetic analysis showed that the variability between populations (77%) was higher than within populations (23%). It was possible to identify five different groups by the unweighted pair group method with arithmetic mean and principal coordinate analysis, and only one individual (E10) remained isolated. Using ISSR markers it was possible to obtain a molecular profile of the populations evaluated, showing that these markers were effective and exhibited sufficient polymorphism to estimate the genetic variability of natural populations of H. speciosa Gomes.

Diversity and genetic structure of mangaba remnants in states of northeastern Brazil.

In this study, we analyzed the genetic diversity and structure of remnants of mangaba populations in states of northeastern Brazil by applying 9 microsatellite markers previously developed to establish conservation strategies for germplasm and species preservation. Six to 20 individuals per population were analyzed, with a total of 94 individuals and 6 populations from the states of Ceará, Pernambuco, and Sergipe, Brazil. The intra-population positive fixation index (f) in all populations indicated inbreeding resulting from the lack of random mating. The mean genetic diversity index values GST, FST, and RST estimated for divergence among the 6 populations were 0.14 (P < 0.05), revealing moderate genetic differentiation. The smallest FST value (P ≥ 0.05) was observed between the Jacarecoara and Tapera populations (0.005) and the highest between the Barra dos Coqueiros and Jacarecoara populations (0.287). The Jacarecoara population was the most divergent among the populations analyzed. According to analysis of molecular variance results, the largest variation percentage resulted from variability within populations (83.18%). Bayesian clustering analysis showed the formation of 2 sets (K = 2). Our results are important for developing strategies for in situ conservation of the species, seed collection, and ex situ conservation. For both methods, conservation of the greatest possible genetic variability of the species is essential.

Lethality by pneumonia and factors associated to death / Letalidade por pneumonia e fatores associados ao óbito

OBJECTIVE: To describe the case-fatality rate (CFR) and risk factors of death in children with community-acquired acute pneumonia (CAP) in a pediatric university hospital. METHOD: A longitudinal study was developed with prospective data collected from 1996 to 2011. Patients aged 1 month to 12 years were included in the study. Those who left the hospital against medical orders and those transferred to ICU or other units were excluded. Demographic andclinical-etiological characteristics and the initial treatment were studied. Variables associated to death were determined by bivariate and multivariate analysis using logistic regression. RESULTS: A total of 871 patients were selected, of whom 11 were excluded; thus 860 children were included in the study. There were 26 deaths, with a CFR of 3%; in 58.7% of these, penicillin G was the initial treatment. Pneumococcus was the most common pathogen (50.4%). From 1996 to 2000, there were 24 deaths (93%), with a CFR of 5.8% (24/413). From 2001 to 2011, the age group of hospitalized patients was older (p = 0.03), and the number of deaths (p = 0.02) and the percentage of disease severity were lower (p = 0.06). Only disease severity remained associated to death in the multivariate analysis (OR = 3.2; 95%CI: 1.2-8.9; p = 0.02). CONCLUSION: When the 1996-2000 and 2001-2011 periods were compared, a significant reduction in CFR was observed in the latter, as well as a change in the clinical profile of the pediatric in patients at the institute. These findings may be related to the improvement in the socio-economical status of the population. Penicillin use did not influence CFR. .

OBJETIVO: Descrever a taxa de letalidade (TL) e os fatores de risco de óbito em crianças com pneumonia grave adquirida na comunidade (CAP) em um hospital universitário pediátrico. MÉTODO: Foi desenvolvido um estudo longitudinal com dados prospectivos coletados de 1996 a2011. Foram incluídos no estudo pacientes com idade entre 1 mês e 12 anos de idade. Foram excluídos aqueles que deixaram o hospital desconsiderando as recomendações médicas e aqueles transferidos para UTI ou outras unidades. Foram estudadas as características demográficas, clínicas e etiológicas e o tratamento inicial. As variáveis associadas a óbito foram determinadas por análise bivariada e multivariada utilizando regressão logística. RESULTADOS: Foi selecionado um total de 871 pacientes, dos quais 11 foram excluídos; assim, foram incluídas no estudo 860 crianças. Houve 26 óbitos, com uma TL de 3%; em 58,7% desses, penicilina G foi o tratamento inicial. Pneumococo foi o patógeno mais comum (50,4%). De 1996 a 2000, houve 24 óbitos (93%), com uma TL de 5,8% (24/413). De 2001 a 2011, a faixa etária de pacientes internados foi mais velha (p = 0,03) e o número de óbitos (p = 0,02) e o percentual de gravidade das doenças foram menores (p = 0,06). Apenas a gravidade das doenças continuou associada a óbito na análise multivariada (RC = 3,2; IC de 95%: 1,2-8,9; p = 0,02). CONCLUSÃO: Quando os períodos de 1996-2000 e 2001-2011 foram comparados, foi observada uma redução significativa na TL no último período, bem como uma alteração no perfil clínico dos pacientes hospitalizados no instituto. Esses achados podem estar relacionados à melhora na situação socioeconômica da população. O uso de penicilina não influenciou a TL. .

Lethality by pneumonia and factors associated to death.

OBJECTIVE: To describe the case-fatality rate (CFR) and risk factors of death in children with community-acquired acute pneumonia (CAP) in a pediatric university hospital. METHOD: A longitudinal study was developed with prospective data collected from 1996 to 2011. Patients aged 1 month to 12 years were included in the study. Those who left the hospital against medical orders and those transferred to ICU or other units were excluded. Demographic and clinical-etiological characteristics and the initial treatment were studied. Variables associated to death were determined by bivariate and multivariate analysis using logistic regression. RESULTS: A total of 871 patients were selected, of whom 11 were excluded; thus 860 children were included in the study. There were 26 deaths, with a CFR of 3%; in 58.7% of these, penicillin G was the initial treatment. Pneumococcus was the most common pathogen (50.4%). From 1996 to 2000, there were 24 deaths (93%), with a CFR of 5.8% (24/413). From 2001 to 2011, the age group of hospitalized patients was older (p = 0.03), and the number of deaths (p = 0.02) and the percentage of disease severity were lower (p = 0.06). Only disease severity remained associated to death in the multivariate analysis (OR = 3.2; 95%CI: 1.2-8.9; p = 0.02). CONCLUSION: When the 1996-2000 and 2001-2011 periods were compared, a significant reduction in CFR was observed in the latter, as well as a change in the clinical profile of the pediatric inpatients at the institute. These findings may be related to the improvement in the socio-economical status of the population. Penicillin use did not influence CFR.

Quality of life and its domains in leprosy patients after neurolysis: a study using WHOQOL-BREF.

Surgical nerve decompression in leprosy is indicated to prevent or treat nerve damage, and to improve sensory motor function and quality of life (QoL). The purpose of this study was to describe QoL of leprosy patients after surgical nerve decompression. Participants who underwent neurolysis in the last 5 years were recruited. The assessment consisted of collecting demographic and clinical information, QoL and its domain scores. Descriptive statistical analysis of demographic and clinical data was presented. Included 33 patients (43 +/- 11.0 years) who had neurolysis with a total of 61 nerves operated. The results of WHOQOL-bref showed that overall QoL mean was 11.2 (+/- 3.63) and domains scored as follow: physical (11.0 +/- 3.56), environment (11.47 +/- 2.11), psychological (13.29 +/- 2.79) and social relations (15.03 +/- 3.66). Measures of QoL should become part of the standard battery of tools used to assess health and well-being and it may contribute to identifying patients' needs in rehabilitation.

Ethanol alters gene expression and cell organization during optic vesicle evagination.

Ethanol has been described as a teratogen in vertebrate development. During early stages of brain formation, ethanol affects the evagination of the optic vesicles, resulting in synophthalmia or cyclopia, phenotypes where the optic vesicles partially or totally fuse. The mechanisms by which ethanol affects the morphogenesis of the optic vesicles are however largely unknown. In this study we make use of in situ hybridization, electron microscopy and immunohistochemistry to show that ethanol has profound effects on cell organization and gene expression during the evagination of the optic vesicles. Exposure to ethanol during early eye development alters the expression patterns of some genes known to be important for eye morphogenesis, such as rx3/1 and six3a. Furthermore, exposure to ethanol interferes with the acquisition of neuroepithelial features by the eye field cells, which is clear at ultrastructual level. Indeed, ethanol disrupts the acquisition of fusiform cellular shapes within the eye field. In addition, tight junctions do not form and retinal progenitors do not properly polarize, as suggested by the mis-localization and down-regulation of zo1. We also show that the ethanol-induced cyclopic phenotype is significantly different to that observed in cyclopic mutants, suggesting a complex effect of ethanol on a variety of targets. Our results show that ethanol not only disrupts the expression pattern of genes involved in retinal morphogenesis, such as rx3 and rx1, but also disrupts the changes in cell polarity that normally occur during eye field splitting. Thus, ethylic teratology seems to be related not only to modifications in gene expression and cell death but also to alterations in cell morphology.

Chronic pain in leprosy: new aspects to be considered.

Leprosy is still considered to be endemic in several developing countries, such as India and Brazil. Infection with Mycobacterium leprae leads to chronic granulomatous inflammation in skin and peripheral nerves that can lead to sensory, motor and autonomic impairments. Since the disease causes severe sensory loss, little attention has been given to pain in leprosy. However, chronic pain in leprosy is being increasingly recognized as an important late complication of leprosy. This article discusses the assessment of pain in leprosy and suggests factors that can contribute to the chronicity. We also consider pain as a multiple system output, bringing the possibility of new treatment options for chronic pain in leprosy.

La formación de los dermatólogos: pasado, presente y futuro / Dermatology Residency Training: Past, Present, and Future

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