Causal inference in the closed-loop: marginal structural models for sequential excursion effects.

Optogenetics is widely used to study the effects of neural circuit manipulation on behavior. However, the paucity of causal inference methodological work on this topic has resulted in analysis conventions that discard information, and constrain the scientific questions that can be posed. To fill this gap, we introduce a nonparametric causal inference framework for analyzing "closed-loop" designs, which use dynamic policies that assign treatment based on covariates. In this setting, standard methods can introduce bias and occlude causal effects. Building on the sequentially randomized experiments literature in causal inference, our approach extends history-restricted marginal structural models for dynamic regimes. In practice, our framework can identify a wide range of causal effects of optogenetics on trial-by-trial behavior, such as, fast/slow-acting, dose-response, additive/antagonistic, and floor/ceiling. Importantly, it does so without requiring negative controls, and can estimate how causal effect magnitudes evolve across time points. From another view, our work extends "excursion effect" methods--popular in the mobile health literature--to enable estimation of causal contrasts for treatment sequences greater than length one, in the presence of positivity violations. We derive rigorous statistical guarantees, enabling hypothesis testing of these causal effects. We demonstrate our approach on data from a recent study of dopaminergic activity on learning, and show how our method reveals relevant effects obscured in standard analyses.

Reliability and predictability of phenotype information from functional connectivity in large imaging datasets.

One of the central objectives of contemporary neuroimaging research is to create predictive models that can disentangle the connection between patterns of functional connectivity across the entire brain and various behavioral traits. Previous studies have shown that models trained to predict behavioral features from the individual's functional connectivity have modest to poor performance. In this study, we trained models that predict observable individual traits (phenotypes) and their corresponding singular value decomposition (SVD) representations - herein referred to as latent phenotypes from resting state functional connectivity. For this task, we predicted phenotypes in two large neuroimaging datasets: the Human Connectome Project (HCP) and the Philadelphia Neurodevelopmental Cohort (PNC). We illustrate the importance of regressing out confounds, which could significantly influence phenotype prediction. Our findings reveal that both phenotypes and their corresponding latent phenotypes yield similar predictive performance. Interestingly, only the first five latent phenotypes were reliably identified, and using just these reliable phenotypes for predicting phenotypes yielded a similar performance to using all latent phenotypes. This suggests that the predictable information is present in the first latent phenotypes, allowing the remainder to be filtered out without any harm in performance. This study sheds light on the intricate relationship between functional connectivity and the predictability and reliability of phenotypic information, with potential implications for enhancing predictive modeling in the realm of neuroimaging research.

[Effects of the vaccination campaign on hospitalization and mortality linked to measles in Brazil in the last decade]. / Efeitos da campanha de vacinação nas internações e mortalidade relacionados ao sarampo no Brasil na última década.

Measles is one of the main causes of morbidity and mortality in the pediatric population and it can be prevented with 100% effectiveness by vaccination. However, the disease remains active in throughout Brazil. The scope of this article is to evaluate the population's adherence to vaccination and the potential connection with hospitalizations and mortality in relation to measles in Brazil. This is an ecological study based on secondary data on mortality and hospitalizations due to measles and vaccination coverage against the disease in Brazil from 2013 to 2022. The peak of adherence to the measles vaccination schedule occurred in the 3 years that preceded the eradication of the disease in the country, which occurred in 2016. In this interval, there are the lowest hospitalization rates, with zero mortality from 2014 to 2017. On the other hand, there has been a marked drop in vaccination rates since 2019, when the disease resurfaced in Brazil. Concomitantly, hospitalization and mortality rates reach the highest recorded values. Population adherence to the complete measles vaccination schedule, which is essential to control the disease and related deaths, is insufficient, which is reflected in hospitalization and mortality rates.

O sarampo é uma das principais causas de morbidade e mortalidade na população pediátrica e pode ser prevenido com 100% de eficácia pela vacinação. No entanto, a doença permanece ativa no território brasileiro. O objetivo do artigo é avaliar a adesão da população à vacinação e a possível relação com hospitalização e mortalidade em relação ao sarampo no Brasil. Trata-se de um estudo ecológico realizado a partir de dados secundários de mortalidade e internações acerca do sarampo e da cobertura vacinal contra a doença no Brasil nos anos de 2013 a 2022. O ápice de adesão ao calendário vacinal contra o sarampo se deu nos três anos que precederam a erradicação da doença no país, ocorrida em 2016. Nesse intervalo, tem-se as menores taxas de internação, com a mortalidade zerada de 2014 a 2017. Em contrapartida, verifica-se, desde então, queda na taxas de vacinação, acentuadas a partir de 2019, quando a doença reaparece no Brasil. Concomitantemente, as taxas de internação e mortalidade atingem os valores mais altos registrados. A adesão populacional ao calendário vacinal completo contra o sarampo, essencial ao controle da doença e dos óbitos relacionados, está insuficiente, o que se reflete nas taxas de internações e mortalidade.

Comparison of Different Pretreatment Processes Envisaging the Potential Use of Food Waste as Microalgae Substrate.

A significant fraction of the food produced worldwide is currently lost or wasted throughout the supply chain, squandering natural and economic resources. Food waste valorization will be an important necessity in the coming years. This work investigates the ability of food waste to serve as a viable nutritional substrate for the heterotrophic growth of Chlorella vulgaris. The impact of different pretreatments on the elemental composition and microbial contamination of seven retail food waste mixtures was evaluated. Among the pretreatment methods applied to the food waste formulations, autoclaving was able to eliminate all microbial contamination and increase the availability of reducing sugars by 30%. Ohmic heating was also able to eliminate most of the contaminations in the food wastes in shorter time periods than autoclave. However, it has reduced the availability of reducing sugars, making it less preferable for microalgae heterotrophic cultivation. The direct utilization of food waste containing essential nutrients from fruits, vegetables, dairy and bakery products, and meat on the heterotrophic growth of microalgae allowed a biomass concentration of 2.2 × 108 cells·mL-1, being the culture able to consume more than 42% of the reducing sugars present in the substrate, thus demonstrating the economic and environmental potential of these wastes.

Brain morphometry and estimation of aging brain in subjects with congenital untreated isolated GH deficiency.

PURPOSE: Individuals with isolated GH deficiency (IGHD) due to a mutation in the GHRH receptor gene have a normal life expectancy and above 50 years of age, similar total cognitive performance, with better attention and executive function than controls. Our objectives were to evaluate their brain morphometry and brain aging using MRI. METHODS: Thirteen IGHD and 14 controls matched by age, sex, and education, were enrolled. Quantitative volumetric data and cortical thickness were obtained by automatic segmentation using Freesurfer software. The volume of each brain region was normalized by the intracranial volume. The difference between the predicted brain age estimated by MRI using a trained neuronal network, and the chronological age, was obtained. p < 0.005 was considered significant and 0.005 < p < 0.05 as a suggestive evidence of difference. RESULTS: In IGHD, most absolute values of cortical thickness and regional brain volumes were similar to controls, but normalized volumes were greater in the white matter in the frontal pole and in the insula bilaterally, and in the gray matter, in the right insula and in left Caudate (p < 0.005 for all comparisons) We also noticed suggestive evidence of a larger volume in IGHD in left thalamus (p = 0.006), right thalamus (p = 0.025), right caudate (p = 0.046) and right putamen (p = 0.013). Predicted brain ages were similar between groups. CONCLUSION: IGHD is primarily associated with similar absolute brain measurements, and a set of larger normalized volumes, and does not appear to alter the process of brain aging.

Oestradiol and osteoclast differentiation: Effects on p53 and mitochondrial metabolism.

BACKGROUND: Oestrogen deficiency increases bone resorption, contributing to osteoporosis development. Yet, the mechanisms mediating the effects of oestrogen on osteoclasts remain unclear. This study aimed to elucidate the early metabolic alteration induced by RANKL, the essential cytokine in osteoclastogenesis and 17-beta-oestradiol (E2) on osteoclast progenitor cells, using RAW 264.7 macrophage cell line and primary bone marrow-derived macrophages as biological models. RESULTS: This research demonstrated that, in osteoclast precursors, RANKL stimulates complex I activity, oxidative phosphorylation (OXPHOS) and mitochondria-derived ATP production as early as 3 h of exposure. This effect on mitochondrial bioenergetics is associated with an increased capacity to oxidize TCA cycle substrates, fatty acids and amino acids. E2 inhibited all effects of RANKL on mitochondria metabolism. In the presence of RANKL, E2 also decreased cell number and stimulated the mitochondrial-mediated apoptotic pathway, detected as early as 3 h. Further, the pro-apoptotic effects of E2 during osteoclast differentiation were associated with an accumulation of p392S-p53 in mitochondria. CONCLUSIONS: These findings elucidate the early effects of RANKL on osteoclast progenitor metabolism and suggest novel p53-mediated mechanisms that contribute to postmenopausal osteoporosis.

Dissociable encoding of motivated behavior by parallel thalamo-striatal projections.

The successful pursuit of goals requires the coordinated execution and termination of actions that lead to positive outcomes. This process relies on motivational states that are guided by internal drivers, such as hunger or fear. However, the mechanisms by which the brain tracks motivational states to shape instrumental actions are not fully understood. The paraventricular nucleus of the thalamus (PVT) is a midline thalamic nucleus that shapes motivated behaviors via its projections to the nucleus accumbens (NAc)1,2,3,4,5,6,7,8 and monitors internal state via interoceptive inputs from the hypothalamus and brainstem.3,9,10,11,12,13,14 Recent studies indicate that the PVT can be subdivided into two major neuronal subpopulations, namely PVTD2(+) and PVTD2(-), which differ in genetic identity, functionality, and anatomical connectivity to other brain regions, including the NAc.4,15,16 In this study, we used fiber photometry to investigate the in vivo dynamics of these two distinct PVT neuronal types in mice performing a foraging-like behavioral task. We discovered that PVTD2(+) and PVTD2(-) neurons encode the execution and termination of goal-oriented actions, respectively. Furthermore, activity in the PVTD2(+) neuronal population mirrored motivation parameters such as vigor and satiety. Similarly, PVTD2(-) neurons also mirrored some of these parameters, but to a much lesser extent. Importantly, these features were largely preserved when activity in PVT projections to the NAc was selectively assessed. Collectively, our results highlight the existence of two parallel thalamo-striatal projections that participate in the dynamic regulation of goal pursuits and provide insight into the mechanisms by which the brain tracks motivational states to shape instrumental actions.

Clinical and molecular profiling of human visceral adipose tissue reveals impairment of vascular architecture and remodeling as an early hallmark of dysfunction.

Adipose tissue dysfunction is more related to insulin resistance than body mass index itself and an alteration in adipose tissue function is thought to underlie the shift from metabolically healthy to unhealthy obesity. Herein, we performed a clustering analysis that revealed distinct visceral adipose tissue gene expression patterns in patients with obesity at distinct stages of metabolic dysregulation. We have built a cross-sectional cohort that aims at reflecting the evolution of the metabolic sequelae of obesity with the main objective to map the sequential events that play a role in adipose tissue dysfunction from the metabolically healthy (insulin-sensitive) state to several incremental degrees of metabolic dysregulation, encompassing insulin resistance establishment, pre-diabetes, and type 2 diabetes. We found that insulin resistance is mainly marked by the downregulation of adipose tissue vasculature remodeling-associated gene expression, suggesting that processes like angiogenesis and adaptative expansion/retraction ability suffer early dysregulation. Prediabetes was characterized by compensatory growth factor-dependent signaling and increased response to hypoxia, while type 2 diabetes was associated with loss of cellular response to insulin and hypoxia and concomitant upregulation of inflammatory markers. Our findings suggest a putative sequence of dysregulation of biological processes that is not linear and has multiple distinct phases across the metabolic dysregulation process, ultimately culminating in the climax of adipose tissue dysfunction in type 2 diabetes. Several studies have addressed the transcriptomic changes in adipose tissue of patients with obesity. However, to the best of our knowledge, this is the first study unraveling the potential molecular mechanisms associated with the multi-step evolution of adipose tissue dysfunction along the metabolic sequelae of obesity.

Advancements in non-invasive microwave brain stimulation: A comprehensive survey.

This survey provides a comprehensive insight into the world of non-invasive brain stimulation and focuses on the evolving landscape of deep brain stimulation through microwave research. Non-invasive brain stimulation techniques provide new prospects for comprehending and treating neurological disorders. We investigate the methods shaping the future of deep brain stimulation, emphasizing the role of microwave technology in this transformative journey. Specifically, we explore antenna structures and optimization strategies to enhance the efficiency of high-frequency microwave stimulation. These advancements can potentially revolutionize the field by providing a safer and more precise means of modulating neural activity. Furthermore, we address the challenges that researchers currently face in the realm of microwave brain stimulation. From safety concerns to methodological intricacies, this survey outlines the barriers that must be overcome to fully unlock the potential of this technology. This survey serves as a roadmap for advancing research in microwave brain stimulation, pointing out potential directions and innovations that promise to reshape the field.

A Comparison of ChatGPT and Fine-Tuned Open Pre-Trained Transformers (OPT) Against Widely Used Sentiment Analysis Tools: Sentiment Analysis of COVID-19 Survey Data.

BACKGROUND: Health care providers and health-related researchers face significant challenges when applying sentiment analysis tools to health-related free-text survey data. Most state-of-the-art applications were developed in domains such as social media, and their performance in the health care context remains relatively unknown. Moreover, existing studies indicate that these tools often lack accuracy and produce inconsistent results. OBJECTIVE: This study aims to address the lack of comparative analysis on sentiment analysis tools applied to health-related free-text survey data in the context of COVID-19. The objective was to automatically predict sentence sentiment for 2 independent COVID-19 survey data sets from the National Institutes of Health and Stanford University. METHODS: Gold standard labels were created for a subset of each data set using a panel of human raters. We compared 8 state-of-the-art sentiment analysis tools on both data sets to evaluate variability and disagreement across tools. In addition, few-shot learning was explored by fine-tuning Open Pre-Trained Transformers (OPT; a large language model [LLM] with publicly available weights) using a small annotated subset and zero-shot learning using ChatGPT (an LLM without available weights). RESULTS: The comparison of sentiment analysis tools revealed high variability and disagreement across the evaluated tools when applied to health-related survey data. OPT and ChatGPT demonstrated superior performance, outperforming all other sentiment analysis tools. Moreover, ChatGPT outperformed OPT, exhibited higher accuracy by 6% and higher F-measure by 4% to 7%. CONCLUSIONS: This study demonstrates the effectiveness of LLMs, particularly the few-shot learning and zero-shot learning approaches, in the sentiment analysis of health-related survey data. These results have implications for saving human labor and improving efficiency in sentiment analysis tasks, contributing to advancements in the field of automated sentiment analysis.

Age-dependent energy metabolism and transcriptome changes in urine-derived stem cells.

The global population over 60 years old is projected to reach 1.5 billion by 2050. Understanding age-related disorders and gender-specificities is crucial for a healthy aging. Reliable age-related biomarkers are needed, preferentially obtained through non-invasive methods. Urine-derived stem cells (UDSCs) can be easily obtained, although a detailed bioenergetic characterization, according to the donor aging, remain unexplored. UDSCs were isolated from young and elderly adult women (22-35 and 70-94 years old, respectively). Surprisingly, UDSCs from elderly subjects exhibited significantly higher maximal oxygen consumption and bioenergetic health index than those from younger individuals, evaluated through oxygen consumption rate. Exploratory data analysis methods were applied to engineer a minimal subset of features for the classification and stratification of UDSCs. Additionally, RNAseq of UDSCs was performed to identify age-related transcriptional changes. Transcriptional analysis revealed downregulation of genes related to glucuronidation and estrogen metabolism, and upregulation of inflammation-related genes in UDSCs from elderly individuals. This study demonstrates unexpected differences in the UDSCs' OCR between young and elderly individuals, revealing improved bioenergetics in concurrent with an aged-like transcriptome signature. UDSCs offer a non-invasive model for studying age-related changes, holding promise for aging research and therapeutic studies.

Physical properties of Scarpa's fascia.

Preservation of Scarpa's fascia has improved clinical outcomes in abdominoplasty procedures and in other body contour surgeries. However, the physical properties of Scarpa's fascia have not yet been described, and grafts are still underexplored. Fresh surgical specimens from five female patients subjected to classical abdominoplasty were dissected and analyzed. A grid was drawn on the fascia surface, dividing it into equal upper and lower halves; four Scarpa's fascia samples (30 × 10 mm) were collected from each half, 40 mm apart. The thickness was measured with a caliper. A strain/stress universal testing machine was used for mechanical tests. Twenty-five samples were obtained (nine from the upper half, 16 from the lower). The average thickness was 0.56 ± 0.11 mm. The average values for stretch, stress, strain, and Young's Modulus were, respectively, 1.436, 4.198 MPa, 43.6%, and 23.14 MPa. The upper half showed significantly greater thickness and strain values (p = 0.020 and p = 0.048; Student's t-test). The physical and biomechanical properties of Scarpa's fascia can make it a donor area for fascial grafts as an alternative to fascia lata, as it is always available and has minimal donor-site morbidity. Further studies are needed to validate this statement. It seems advantageous to use the lower half of the abdomen instead of the upper part as a donor site.

Dissociable encoding of motivated behavior by parallel thalamo-striatal projections.

The successful pursuit of goals requires the coordinated execution and termination of actions that lead to positive outcomes. This process is thought to rely on motivational states that are guided by internal drivers, such as hunger or fear. However, the mechanisms by which the brain tracks motivational states to shape instrumental actions are not fully understood. The paraventricular nucleus of the thalamus (PVT) is a midline thalamic nucleus that shapes motivated behaviors via its projections to the nucleus accumbens (NAc)1-8 and monitors internal state via interoceptive inputs from the hypothalamus and brainstem3,9-14. Recent studies indicate that the PVT can be subdivided into two major neuronal subpopulations, namely PVTD2(+) and PVTD2(-), which differ in genetic identity, functionality, and anatomical connectivity to other brain regions, including the NAc4,15,16. In this study, we used fiber photometry to investigate the in vivo dynamics of these two distinct PVT neuronal types in mice performing a reward foraging-like behavioral task. We discovered that PVTD2(+) and PVTD2(-) neurons encode the execution and termination of goal-oriented actions, respectively. Furthermore, activity in the PVTD2(+) neuronal population mirrored motivation parameters such as vigor and satiety. Similarly, PVTD2(-) neurons, also mirrored some of these parameters but to a much lesser extent. Importantly, these features were largely preserved when activity in PVT projections to the NAc was selectively assessed. Collectively, our results highlight the existence of two parallel thalamo-striatal projections that participate in the dynamic regulation of goal pursuits and provide insight into the mechanisms by which the brain tracks motivational states to shape instrumental actions.

A Statistical Framework for Analysis of Trial-Level Temporal Dynamics in Fiber Photometry Experiments.

Fiber photometry has become a popular technique to measure neural activity in vivo, but common analysis strategies can reduce detection of effects because they condense within-trial signals into summary measures, and discard trial-level information by averaging across-trials. We propose a novel photometry statistical framework based on functional linear mixed modeling, which enables hypothesis testing of variable effects at every trial time-point, and uses trial-level signals without averaging. This makes it possible to compare the timing and magnitude of signals across conditions while accounting for between-animal differences. Our framework produces a series of plots that illustrate covariate effect estimates and statistical significance at each trial time-point. By exploiting signal autocorrelation, our methodology yields joint 95% confidence intervals that account for inspecting effects across the entire trial and improve the detection of event-related signal changes over common multiple comparisons correction strategies. We reanalyze data from a recent study proposing a theory for the role of mesolimbic dopamine in reward learning, and show the capability of our framework to reveal significant effects obscured by standard analysis approaches. Our method identifies two dopamine components with distinct temporal dynamics that may be hard to explain under currently competing learning theories. In simulation experiments, our methodology yields improved statistical power over common analysis approaches. Finally, we provide an open-source package implementing our framework.

Asistencia artroscópica y fijación interna percutánea en fracturas de Maisonneuve. Evaluación por imágenes de los resultados / Arthroscopy and percutaneous internal fixation in Maisonneuve fractures. Imaging evaluation

Introducción: La fractura de Maisonneuve es una lesión caracterizada por la fractura subcapital del peroné asociada a una lesión capsuloligamentaria de tobillo. Su tratamiento supone la restauración de la anatomía ósea y capsuloligamentaria normal para restablecer las fuerzas de contacto tibioastragalinas fisiológicas. Esta calidad de reducción puede ser difícil de alcanzar, sobre todo, con técnicas percutáneas. Objetivo: Evaluar mediante imágenes la calidad de la reducción de fracturas de Maisonneuve reducidas en forma cerrada (bajo visualización directa artroscópica) y fijadas por vía percutánea. Materiales y Métodos: Se analizaron radiografías e imágenes de tomografía computarizada preoperatorias y posoperatorias, comparativas de los tobillos operado y sano. Resultados: Se evaluaron 13 fracturas. Los parámetros radiográficos posoperatorios (espacio claro medial, solapamiento tibioperoneo distal, espacio claro tibioperoneo) no registraron diferencias, excepto por el intervalo tibioperoneo anterior que aumentó en un caso. La medición tomográfica posoperatoria del solapamiento tibioperoneo distal y el intervalo tibioperoneo anterior reveló que todas las reducciones eran satisfactorias. Dos pacientes tenían valores alterados en la sindesmosis tibioperonea distal con diferencia >2 mm respecto del tobillo sano. Conclusión: Recomendamos la asistencia artroscópica para el manejo de la fractura de Maisonneuve como herramienta de control intraoperatorio para una fijación percutánea más segura. Nivel de Evidencia: IV

Introduction: Maisonneuve fracture (MF) is an injury characterized by the subcapital fracture of the fibula associated with a capsuloligamentous injury of the ankle. Treatment involves the restoration of normal bone and capsuloligamentous anatomy in order to reestablish physiological tibiotalar contact forces. This quality of reduction can be difficult to achieve, especially with percutaneous techniques. Objective: To evaluate the quality of reduction in Maisonneuve fractures reduced in a closed manner (under direct arthroscopic visualization) and fixed percutaneously. Materials and Methods: We analyzed comparative preoperative and postoperative radiographs and CT scans of the operated and healthy ankles. Results: 13 fractures were evaluated. Radiographic parameters of postoperative procedures (medial clear space, distal tibiofibular overlap, tibiofibular clear space) did not register differences except for the anterior tibiofibular space, which had increased in 1 case. Postoperative tomographic measurements of tibiofibular clear space and anterior tibiofibular space showed 100% satisfactory reductions. Two patients presented altered distal tibiofibular overlap values with a difference greater than 2 mm compared to the healthy ankle. Conclusion: We recommend arthroscopy for the management of MF as an intraoperative control tool for safer percutaneous fixation. Level of Evidence: IV

Efeitos da campanha de vacinação nas internações e mortalidade relacionados ao sarampo no Brasil na última década / Effects of the vaccination campaign on hospitalization and mortality linked to measles in Brazil in the last decade

Resumo O sarampo é uma das principais causas de morbidade e mortalidade na população pediátrica e pode ser prevenido com 100% de eficácia pela vacinação. No entanto, a doença permanece ativa no território brasileiro. O objetivo do artigo é avaliar a adesão da população à vacinação e a possível relação com hospitalização e mortalidade em relação ao sarampo no Brasil. Trata-se de um estudo ecológico realizado a partir de dados secundários de mortalidade e internações acerca do sarampo e da cobertura vacinal contra a doença no Brasil nos anos de 2013 a 2022. O ápice de adesão ao calendário vacinal contra o sarampo se deu nos três anos que precederam a erradicação da doença no país, ocorrida em 2016. Nesse intervalo, tem-se as menores taxas de internação, com a mortalidade zerada de 2014 a 2017. Em contrapartida, verifica-se, desde então, queda na taxas de vacinação, acentuadas a partir de 2019, quando a doença reaparece no Brasil. Concomitantemente, as taxas de internação e mortalidade atingem os valores mais altos registrados. A adesão populacional ao calendário vacinal completo contra o sarampo, essencial ao controle da doença e dos óbitos relacionados, está insuficiente, o que se reflete nas taxas de internações e mortalidade.

Abstract Measles is one of the main causes of morbidity and mortality in the pediatric population and it can be prevented with 100% effectiveness by vaccination. However, the disease remains active in throughout Brazil. The scope of this article is to evaluate the population's adherence to vaccination and the potential connection with hospitalizations and mortality in relation to measles in Brazil. This is an ecological study based on secondary data on mortality and hospitalizations due to measles and vaccination coverage against the disease in Brazil from 2013 to 2022. The peak of adherence to the measles vaccination schedule occurred in the 3 years that preceded the eradication of the disease in the country, which occurred in 2016. In this interval, there are the lowest hospitalization rates, with zero mortality from 2014 to 2017. On the other hand, there has been a marked drop in vaccination rates since 2019, when the disease resurfaced in Brazil. Concomitantly, hospitalization and mortality rates reach the highest recorded values. Population adherence to the complete measles vaccination schedule, which is essential to control the disease and related deaths, is insufficient, which is reflected in hospitalization and mortality rates.

Intervenções não farmacológicas no manejo da obesidade infantil: uma overview / Non-pharmacological interventions in the management of childhood obesity: an overview / Intervenciones no farmacológicas en el tratamiento de la obesidad infantil: una visión general

Objetivo: Analisar na literatura científica a efetividade das intervenções não farmacológicas para o manejo da obesidade infantil. Método: Trata-se de uma revisão sistemática do tipo overview. As bases científicas para coleta de dados foram: Cinahl, Cochrane, Lilacs, Medline, Scopus, Scielo e Science direct, e todo o processo de seleção foi feito por pares e avaliado pelo teste Kappa. A análise dos estudos utilizou os instrumentos: AMSTAR para avaliação da qualidade metodológica, Robis 2.0 para avaliação do risco de viés, e o Sistema Grade para classificar nível de evidência. Resultado: 17 estudos foram considerados elegíveis, e avaliação das evidências demonstrou que as intervenções não farmacológicas são efetivas para o manejo da obesidade infantil, sendo classificadas pelo Sistema Grade com alto e moderado nível de evidência. Essas intervenções são caracterizadas como: comportamentais, educacional, familiar, nutricional e tecnológica e são capazes de promover mudanças no Índice de Massa Corporal e estilo de vida. Conclusão: As intervenções não farmacológicas são capazes de promover mudanças positivas quanto ao comportamento alimentar e manejo da obesidade, entretanto os resultados não são imediatos.

Objective: To analyze the effectiveness of non-pharmacological interventions for the management of childhood obesity in the scientific literature. Method: This is a systematic review of the overview type. The scientific databases for data collection were: Cinahl, Cochrane, Lilacs, Medline, Scopus, Scielo and Science direct, and the entire selection process was done by pairs and evaluated by Kappa test. The analysis of the studies used the instruments: AMSTAR to assess methodological quality, Robis 2.0 to assess risk of bias, and the Grade System to rank level of evidence. Results: 17 studies were considered eligible, and evaluation of the evidence showed that non- pharmacological interventions are effective for the management of childhood obesity, being classified by the Grade System with high and moderate level of evidence. These interventions are characterized as: behavioral, educational, family, nutritional, and technological, and are able to promote changes in Body Mass Index and lifestyle. Conclusion: Non-pharmacological interventions are able to promote positive changes in eating behavior and obesity management, but the results are not immediate.

Objetivo: Analizar la efectividad de las intervenciones no farmacológicas para el manejo de la obesidad infantil en la literatura científica. Método: Se trata de una revisión sistemática de tipo panorámica. Las bases de datos científicas para la recogida de datos fueron: Cinahl, Cochrane, Lilacs, Medline, Scopus, Scielo y Science direct, y todo el proceso de selección se realizó por parejas y se evaluó mediante el test de Kappa. En el análisis de los estudios se utilizaron los instrumentos AMSTAR para evaluar la calidad metodológica, Robis 2.0 para evaluar el riesgo de sesgo y el Grade System para clasificar el nivel de evidencia. Resultados: Se consideraron elegibles 17 estudios, y la evaluación de la evidencia mostró que las intervenciones no farmacológicas son efectivas para el manejo de la obesidad infantil, siendo clasificadas por el Sistema Grade con nivel de evidencia alto y moderado. Estas intervenciones se caracterizan por ser: conductuales, educativas, familiares, nutricionales y tecnológicas, y son capaces de promover cambios en el Índice de Masa Corporal y en el estilo de vida. Conclusiones: Las intervenciones no farmacológicas son capaces de promover cambios positivos en la conducta alimentaria y en el manejo de la obesidad, pero los resultados no son inmediatos.

Intervenção educativa para professores de creches sobre primeiros socorros: estudo quase-experimental / Educational intervention on first aid for kindergarten teachers: quasi-experimental study

Objetivo: Testar uma intervenção educativa para professores de creche sobre primeiros socorros, quanto aos desfechos de conhecimento e habilidade. Métodos: Estudo quase-experimental do tipo antes e depois, realizado em dez creches municipais públicas no Piauí, no período de setembro a outubro de 2019. A amostra foi composta de 36 professores e a coleta de dados foi realizada em três etapas: pré-teste acerca do conhecimento e habilidades em primeiros socorros; aplicação de atividade educativa teórico-prática; e pós-teste. Os dados foram analisados a partir do teste de Wilcoxon. Resultados:97,2% são do sexo feminino, a média de idade é de 41,47 (± 9,48) anos, 86,1% são apenas graduados e 13,9% têm pós-graduação. Ademais, 97,2% não realizaram curso de primeiros socorros e 58,3% já haviam presenciado alguma necessidade desse tipo de atendimento. Os participantes apresentaram aumento do conhecimento após a intervenção nos seguintes itens: acionamento de socorro (p=0,000); detecção e conduta na parada cardiorrespiratória (p=0,000; p=0,002); e conduta em hemorragias (p=0,001). A habilidade técnica dos profissionais apresentou aumento em todos os passos do atendimento em vítimas de parada cardiorrespiratória com p<0,05 na totalidade de itens avaliados. Conclusão: Após a intervenção, observou-se aumento do conhecimento e habilidade dos professores sobre situações de primeiros socorros. Descritores: Primeiros Socorros; Educação em Saúde; Professores Escolares; Capacitação de Professores.

Objective: To test an educational intervention for kindergarten teachers on first aid, regarding the outcomes of knowledge and skill. Methods:Quasi-experimental study of the before and after type, carried out in ten public municipal kindergarten centers in Piauí, during September to October 2019. The sample consisted of 36 teachers and data collection was carried out in three stages: pre-test on knowledge and skills in first aid; application of theoretical-practical educational activity; and post-test. Data were analyzed using the Wilcoxon test. Results:97.2% were female, the average age was 41.47 (± 9.48) years, 86.1% were only graduates and 13.9% had graduate degrees. 97.2% did not take a first aid course and 58.3% had already witnessed some need for this type of care. Participants showed an increase in knowledge after the intervention in the following items: emergency response (p=0.000); detection and management of cardiorespiratory arrest (p=0.000; p=0.002); and management of bleeding (p=0.001). The technical ability of professionals showed an increase in all stages of care in victims of cardiorespiratory arrest with p<0.05 in all items evaluated. Conclusion:After the intervention, there was an increase in teachers' knowledge and skill about first aid situations. Descriptors: First aid; Health education; School teachers; Teacher training.

Protocolo de intervenções nutricionais para o manejo da obesidade infantil na Atenção Primária à Saúde / Protocol to implement nutritional interventions for the management of childhood obesity in Primary Health Care

Objetivo: Construir e validar um protocolo de intervenções nutricionais para o manejo da obesidade infantil no âmbito da Atenção Primária à Saúde. Métodos: Trata-se de um estudo metodológico, organizado em três fases: elaboração de uma revisão sistemática do tipo overview, com uso das recomendações PRISMA, construção do protocolo clínico e validação do conteúdo com uso dos instrumentos AGREE II e AGREE-REX. Resultados: Foram incluídos 17 estudos para a construção do protocolo, indicando efetividade em intervenções com desfechos na redução significativa do IMC, mudança no comportamento e hábitos alimentares, aumento no nível de conhecimento sobre alimentação saudável. A avaliação do protocolo clínico obteve uma pontuação >70% e, conforme o parâmetro utilizado (≥50% qualidade alta), foi considerado adequado para implementação no campo da saúde da criança, mais especificamente no manejo da obesidade infantil. Conclusão: Um protocolo assistencial para o manejo da obesidade infantil no âmbito da Atenção Primária à Saúde representa de forma positiva uma estratégia sustentável e flexível com atuação de diversos atores sociais como profissionais da saúde e familiares, dentre outros, contribuindo para a redução de riscos de comorbidades associadas à obesidade e custos de saúde, bem como para promover comportamentos mais saudáveis na população pediátrica. Descritores: Atenção Primária à Saúde; Obesidade Infantil; Manejo da Obesidade; Protocolos Clínicos.

Objective: To create and validate a protocol to implement nutritional interventions for the management of childhood obesity in the Primary Health Care scope.Methods: This is a methodological study organized into three phases: elaboration of a systematic review of the "overview" type using the PRISMA recommendations; preparation of the clinical protocol; and content validation using the AGREE II and AGREE-REX instruments.Results: A total of 17 studies were included to create the protocol, indicating effectiveness in interventions with outcomes in a significant BMI reduction, change in eating behaviors and habits, and increase in the knowledge level about healthy eating. The clinical protocol assessment obtained a score >70% and, according to the parameter used (≥50% high quality), it was considered adequate for implementation in the children's health field, more specifically in the management of childhood obesity.Conclusion: A care protocol for the management of childhood obesity in the Primary Health Care scope positively represents a sustainable and flexible strategy with performance of several social actors such as health professionals and family members, among others, contributing to reducing risks of comorbidities associated with obesity and health costs, as well as to promoting healthier behaviors in the pediatric population. Descriptors: Primary Health Care; Pediatric Obesity; Obesity Management; Clinical Protocols.

Distinct brain-wide presynaptic networks underlie the functional identity of individual cortical neurons.

Neuronal connections provide the scaffolding for neuronal function. Revealing the connectivity of functionally identified individual neurons is necessary to understand how activity patterns emerge and support behavior. Yet, the brain-wide presynaptic wiring rules that lay the foundation for the functional selectivity of individual neurons remain largely unexplored. Cortical neurons, even in primary sensory cortex, are heterogeneous in their selectivity, not only to sensory stimuli but also to multiple aspects of behavior. Here, to investigate presynaptic connectivity rules underlying the selectivity of pyramidal neurons to behavioral state 1-12 in primary somatosensory cortex (S1), we used two-photon calcium imaging, neuropharmacology, single-cell based monosynaptic input tracing, and optogenetics. We show that behavioral state-dependent neuronal activity patterns are stable over time. These are not determined by neuromodulatory inputs but are instead driven by glutamatergic inputs. Analysis of brain-wide presynaptic networks of individual neurons with distinct behavioral state-dependent activity profiles revealed characteristic patterns of anatomical input. While both behavioral state-related and unrelated neurons had a similar pattern of local inputs within S1, their long-range glutamatergic inputs differed. Individual cortical neurons, irrespective of their functional properties, received converging inputs from the main S1-projecting areas. Yet, neurons that tracked behavioral state received a smaller proportion of motor cortical inputs and a larger proportion of thalamic inputs. Optogenetic suppression of thalamic inputs reduced behavioral state-dependent activity in S1, but this activity was not externally driven. Our results revealed distinct long-range glutamatergic inputs as a substrate for preconfigured network dynamics associated with behavioral state.