Genetic determinants of serum bilirubin using inferred native American gene variants in Chilean adolescents.

Gene variants in the UGT1A1 gene are strongly associated with circulating bilirubin levels in several populations, as well as other variants of modest effect across the genome. However, the effects of such variants are unknown regarding the Native American ancestry of the admixed Latino population. Our objective was to assess the Native American genetic determinants of serum bilirubin in Chilean admixed adolescents using the local ancestry deconvolution approach. We measured total serum bilirubin levels in 707 adolescents of the Chilean Growth and Obesity Cohort Study (GOCS) and performed high-density genotyping using the Illumina-MEGA array (>1.7 million genotypes). We constructed a local ancestry reference panel with participants from the 1000 Genomes Project, the Human Genome Diversity Project, and our GOCS cohort. Then, we inferred and isolated haplotype tracts of Native American, European, or African origin to perform genome-wide association studies. In the whole cohort, the rs887829 variant and others near UGT1A1 were the unique signals achieving genome-wide statistical significance (b = 0.30; p = 3.34 × 10-57). After applying deconvolution methods, we found that significance is also maintained in Native American (b = 0.35; p = 3.29 × 10-17) and European (b = 0.28; p = 1.14 × 10-23) ancestry components. The rs887829 variant explained a higher percentage of the variance of bilirubin in the Native American (37.6%) compared to European ancestry (28.4%). In Native American ancestry, carriers of the TT genotype of this variant averaged 4-fold higher bilirubinemia compared to the CC genotype (p = 2.82 × 10-12). We showed for the first time that UGT1A1 variants are the primary determinant of bilirubin levels in Native American ancestry, confirming its pan-ethnic relevance. Our study illustrates the general value of the local ancestry deconvolution approach to assessing isolated ancestry effects in admixed populations.

Prospective memory instruments for the assessment of children and adolescents: a systematic review.

BACKGROUND: Prospective memory is the ability to engage in an intention to be performed in the future. The main objective of this study was to identify instruments that assess both time-based and event-based prospective memory in children and adolescents and that have the potential to be clinically applicable. METHOD: Three databases (PubMed, Scopus, and PsycINFO) were searched to identify existing PM measures in original articles published until 2022. Literature searches were conducted using the following terms: (prospective memor* OR memor* for intentions) AND (neuropsychological assessment) AND (test* OR instrument* OR questionnaire* OR task*) AND (psychometric properties) AND (child* OR adolescen*). Relevant studies identified in the reference lists were also included in the review. RESULTS: Ten instruments were identified and classified into three categories: (a) test batteries, (b) experimental procedures, and (c) questionnaires. All the instruments identified were described concerning their content and the psychometric properties available. Some of the instruments presented empirical evidence regarding validity and reliability, but no one provided normative data. CONCLUSION: Besides the recent progress regarding studies publishing the development of a variety of novel measures, there are still many limitations surrounding the assessment of PM in the youth population because of the yet incipient psychometric properties presented by the majority of the PM instruments. Recommendations for a gold-standard PM instrument for assessing children and adolescents are provided.

Adducin Regulates Sarcomere Disassembly During Cardiomyocyte Mitosis.

BACKGROUND: Recent interest in understanding cardiomyocyte cell cycle has been driven by potential therapeutic applications in cardiomyopathy. However, despite recent advances, cardiomyocyte mitosis remains a poorly understood process. For example, it is unclear how sarcomeres are disassembled during mitosis to allow the abscission of daughter cardiomyocytes. METHODS: Here, we use a proteomics screen to identify adducin, an actin capping protein previously not studied in cardiomyocytes, as a regulator of sarcomere disassembly. We generated many adeno-associated viruses and cardiomyocyte-specific genetic gain-of-function models to examine the role of adducin in neonatal and adult cardiomyocytes in vitro and in vivo. RESULTS: We identify adducin as a regulator of sarcomere disassembly during mammalian cardiomyocyte mitosis. α/γ-adducins are selectively expressed in neonatal mitotic cardiomyocytes, and their levels decline precipitously thereafter. Cardiomyocyte-specific overexpression of various splice isoforms and phospho-isoforms of α-adducin in identified Thr445/Thr480 phosphorylation of a short isoform of α-adducin as a potent inducer of neonatal cardiomyocyte sarcomere disassembly. Concomitant overexpression of this α-adducin variant along with γ-adducin resulted in stabilization of the adducin complex and persistent sarcomere disassembly in adult mice, which is mediated by interaction with α-actinin. CONCLUSIONS: These results highlight an important mechanism for coordinating cytoskeletal morphological changes during cardiomyocyte mitosis.

Maternal mortality: protocol of a study integrated to the Birth in Brazil II survey. / Mortalidade materna: protocolo de um estudo integrado à pesquisa Nascer no Brasil II.

The Maternal Mortality Study conducts a hospital investigation of maternal deaths that occurred in 2020/2021 in the maternity hospitals sampled by the Birth in Brazil II survey, with the following objectives: estimate the maternal mortality underreporting; calculate a correction factor and the corrected (MMR); validate the causes of maternal mortality reported in the death certificate (DC); and analyze the factors associated with maternal mortality. The Birth in Brazil II includes approximately 24,250 puerperal women distributed in 465 public, private, and mixed hospitals with ≥ 100 live births/year in the five macroregions of Brazil. The Maternal Mortality Study data will be completed using the same Birth in Brazil II questionnaire, from the consultation of hospital records. Trained obstetricians will fill out a new DC (redone DC) from independent analysis of this questionnaire, comparing it to official data. The database of the investigated deaths will be related to the deaths listed in the Mortality Information System of the Brazilian Ministry of Health, allowing the estimation of underreporting and calculation of the corrected MMR. To calculate the reliability of the causes of death, the kappa test and prevalence-adjusted kappa with 95% confidence interval will be used. A case-control study to estimate the risk factors for maternal mortality will be developed with the investigated deaths (cases) and the controls obtained in the Birth in Brazil II survey, using conditional multiple logistic regression models. We expect this research to contribute to the correction of the underreporting of maternal mortality and to a better understanding of the determinants of the persistence of a high MMR in Brazil.

O Estudo da Mortalidade Materna conduz uma investigação hospitalar dos óbitos maternos ocorridos em 2020/2021 nas maternidades amostradas na pesquisa Nascer no Brasil II, com os seguintes objetivos: estimar o sub-registro da mortalidade materna e calcular um fator de correção e a razão de mortalidade materna (RMM) corrigida; validar as causas de mortalidade materna informadas na declaração de óbito (DO); e analisar os fatores associados à mortalidade materna. O Nascer no Brasil II inclui aproximadamente 24.255 puérperas distribuídas em 465 hospitais públicos, privados e mistos com ≥ 100 partos de nascidos vivos/ano nas cinco macrorregiões do país. Os dados do Estudo da Mortalidade Materna serão preenchidos utilizando o mesmo questionário do Nascer no Brasil II, a partir da consulta aos prontuários hospitalares. Obstetras treinados preencherão uma nova DO (DO refeita) a partir de análise independente desse questionário, comparando aos dados oficiais. A base de dados dos óbitos investigados será relacionada com os óbitos constantes no Sistema de Informações sobre Mortalidade do Ministério da Saúde, permitindo a estimativa do sub-registro e cálculo da RMM corrigida. Para o cálculo da confiabilidade das causas de morte, serão utilizados os testes kappa e kappa ajustado à prevalência com intervalo de 95% de confiança. Um estudo de caso-controle para estimar os fatores de risco para mortalidade materna será desenvolvido com os óbitos investigados (casos) e os controles obtidos na pesquisa Nascer no Brasil II, utilizando-se modelos de regressão logística múltipla condicional. Espera-se contribuir para a correção do sub-registro da mortalidade materna e para a melhor compreensão dos fatores determinantes da persistência de RMM elevada no Brasil.

El Estudio de Mortalidad Materna evalúa las muertes maternas ocurridas en 2020-2021 en las muestras de maternidades del encuesta Nacer en Brasil II con los objetivos de estimar el subregistro de mortalidad materna y calcular el factor de corrección y la tasa de mortalidad materna corregida (TMM); validar las causas de mortalidad materna reportadas en el certificado de defunción (CD); y analizar los factores asociados a la mortalidad materna. La Nacer en Brasil II incluye aproximadamente 24.250 mujeres puerperales, distribuidas en 465 hospitales públicos, privados y mixtos con ≥ 100 nacidos vivos/año en las cinco macrorregiones de Brasil. Los datos de Estudio de Mortalidad Materna se completarán con la información del cuestionario Nacer en Brasil II a partir de una búsqueda de los registros médicos hospitalarios. Los obstetras capacitados completarán un nuevo CD (CD rehecho) desde un análisis independiente de este cuestionario, comparándolo con los datos oficiales. La base de datos de muertes investigadas se relacionará con las muertes que constan en el Sistema de Informaciones sobre la Mortalidad del Ministerio de Salud para permitir la estimación del subregistro y el cálculo de la TMM corregida. Para calcular la exactitud de las causas de muerte, se utilizarán las pruebas kappa y kappa ajustada a la prevalencia con un intervalo de 95% de confianza. Un estudio de casos y controles se aplicará para estimar los factores de riesgo de las mortalidad materna con las muertes investigadas (casos) y los controles obtenidos en el estudio Nacer en Brasil II utilizando modelos de regresión logística múltiple condicional. Se espera que este estudio pueda contribuir a la corrección del subregistro de la mortalidad materna y a una mejor comprensión de los determinantes de la persistencia de alta TMM en Brasil.

Chiral hydroxymethyl-1H,3H-pyrrolo[1,2-c]thiazoles: the search for selective p53-activating agents for colorectal cancer therapy.

MANIO is an efficient p53-activating anticancer agent with remarkable selectivity to the p53 pathway and promising antitumor activity against colorectal cancer (CRC). Herein, a library of novel MANIO derivatives, including hydroxymethyl- and bis(hydroxymethyl)-1H,3H-pyrrolo[1,2-c]thiazoles, was synthesized by rational structural modulation. The antiproliferative activity of twenty derivatives was evaluated in a panel of human CRC cells with different p53 status. From this library, five compounds with R- and S-configuration and with aromatic or heteroaromatic groups at position 3, including the enantiomer of MANIO, were identified as selective towards p53-expressing cancer cells. On the other hand, two compounds with S-configuration, 6-hydroxymethyl- and 7-hydroxymethyl-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazoles, showed high cytotoxicity against WTp53-expressing HCT116 colon cells but, unlike MANIO, exhibited p53-independent inhibitory activity in CRC. The results described provide relevant structural and pharmacophoric data for the design of new p53-activating agents for precision therapy of CRC or other p53-related cancers harboring both wild-type or mutated p53 forms.

Improving the Properties of Gelatin-Based Films by Incorporation of "Pitanga" Leaf Extract and Crystalline Nanocellulose.

Biopolymer-based films can be activated by the incorporation of active compounds into their matrix. Plant extracts are rich in phenolic compounds, which have antimicrobial and/or antioxidant properties. The aim of this study was to produce gelatin-based active films and nanocomposite films incorporated with "pitanga" (Eugenia uniflora L.) leaf extract (PLE) and/or crystalline nanocellulose extracted from soybean straw (CN), and to study the physicochemical, functional, microstructural, thermal, UV/Vis light barrier, and antioxidant properties of these materials. PLE enhanced some film properties, such as tensile strength (from 30.2 MPa to 40.6 MPa), elastic modulus (from 9.3 MPa to 11.3 MPa), the UV/Vis light barrier, and antioxidant activity, in addition to affecting the microstructural, surface, and color properties. These improvements were even more significant in nanocomposites simultaneously containing PLE and CN (59.5 MPa for tensile strength and 15.1 MPa for elastic modulus), and these composites also had lower moisture content (12.2% compared to 13.5-14.4% for other treatments) and solubility in water (from 48.9% to 44.1%). These improvements may be the result of interactions that occur between PLE's polyphenols and gelatin, mainly in the presence of CN, probably due to the formation of a stable PLE-CN-gelatin complex. These results are relevant for the food packaging sector, as the activated nanocomposite films exhibited enhanced active, barrier, and mechanical properties due to the presence of PLE and CN, in addition to being entirely produced with sustainable components from natural and renewable sources.

Beyond restrictive: Sleeve Gastrectomy to Single Anastomosis Duodenoileal Bypass with Sleeve Gastrectomy as a spectrum of one single procedure.

INTRODUCTION: Single Anastomosis Duodenal-Ileal Bypass with Sleeve Gastrectomy (SADI-S) is a restrictive/hypoabsorptive procedure recommended for patients with obesity class 3. For safety reasons, SADI-S can be splited into a two-step procedure by performing a sleeve gastrectomy (SG) first. This stepwise approach also provides an unprecedented opportunity to disentangle the weight loss mechanisms triggered by each component. The objective was to compare weight trajectories and postprandial endocrine and metabolic responses of patients with obesity class 3 submitted to SADI-S or sleeve gastrectomy (SG) as the first step of SADI-S. METHODS: Subjects submitted to SADI-S (n=7) or SG (n=7) at a tertiary referral public academic hospital, underwent anthropometric evaluation and a liquid mixed meal tolerance test (MMTT) pre-operatively and at 3, 6, and 12 months post-operatively. RESULTS: Anthropometric parameters, as well as metabolic and micronutrient profiles, were not significantly different between groups, neither before nor after surgery. There were no significant differences in fasting or post-prandial glucose, insulin, C-peptide, ghrelin, insulin secretion rate (ISR) and insulin clearance during the MMTT between subjects submitted to SADI-S and SG. There was no lost to follow-up. CONCLUSIONS: The restrictive component seems to be the main driver for weight loss and metabolic adaptations observed during the first 12 months after SADI-S, given that the weight trajectories and metabolic profiles do not differ from SG. This data provides support for a surgeons' choice of a two-step SADI-S without jeopardizing the weight loss outcomes.

Metatranscriptome and Resistome of the Endodontic Microbiome.

INTRODUCTION: In this study, we used metatranscriptomics for the first time to investigate microbial composition, functional signatures, and antimicrobial resistance gene expression in endodontic infections. METHODS: Root canal samples were collected from ten teeth, including five primary and five persistent/secondary endodontic infections. RNA from endodontic samples was extracted, and RNA sequencing was performed on a NovaSeq6000 system (Illumina). Taxonomic analysis was performed using the Kraken2 bacterial database. Then, sequences with a taxonomic classification were annotated against the Universal Protein Knowledgebase for functional annotation and the Comprehensive Antibiotic Resistance Database for AR-like gene identification. RESULTS: Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria represented the dominant phyla, whereas Fusobacteria, Spirochetes, and Synergistetes were among the nondominant phyla. The top ten species were mainly represented by obligate (or quasiobligate) anaerobes, including Gram-negative (eg, Capnocytophaga sp. oral taxon 323, Fusobacterium nucleatum, Prevotella intermedia, Prevotella oris, Tannerella forsythia, and Tannerella sp. oral taxon HOT-286) and Gram-positive species (eg, Olsenella uli and Parvimonas micra). Transcripts encoding moonlighting proteins (eg, glycolytic proteins, translational elongation factors, chaperonin, and heat shock proteins) were highly expressed, potentially affecting bacterial adhesion, biofilm formation, host defense evasion, and inflammation induction. Endodontic bacteria expressed genes conferring resistance to antibiotic classes commonly used in dentistry, with a high prevalence and expression of tetracycline and lincosamide resistance genes. Antibiotic efflux and antibiotic target alteration/protection were the main resistance mechanisms. CONCLUSIONS: Metatranscriptomics revealed the activity of potential endodontic pathogens, which expressed putative virulence factors and a wide diversity of genes potentially involved in AR.

Effects of gallic acid and physical training on liver damage, force, and anxiety in obese mice: Hepatic modulation of Sestrin 2 (SESN2) and PGC-α expression.

Obesity and overweight are multifactorial diseases affecting more than one-third of the world's population. Physical inactivity contributes to a positive energy balance and the onset of obesity. Exercise combined with a balanced diet is an effective non-pharmacological strategy to improve obesity-related disorders. Gallic acid (GA), is a natural endogenous polyphenol found in a variety of fruits, vegetables, and wines, with beneficial effects on energetic homeostasis. The present study aims to investigate the effects of exercise training on obese mice supplemented with GA. Animal experimentation was performed with male Swiss mice divided into five groups: ST (standard control), HFD (obese control), HFD + GA (GA supplement), HFD + Trained (training), and HFD + GA + Trained (GA and training). The groups are treated for eight weeks with 200 mg/kg/body weight of the feed compound and, if applicable, physical training. The main findings of the present study show that GA supplementation improves liver fat, body weight, adiposity, and plasma insulin levels. In addition, animals treated with the GA and a physical training program demonstrate reduced levels of anxiety. Gene expression analyses show that Sesn2 is activated via PGC-1α independent of the GATOR2 protein, which is activated by GA in the context of physical activity. These data are corroborated by molecular docking analysis, demonstrating the interaction of GA with GATOR2. The present study contributes to understanding the metabolic effects of GA and physical training and demonstrates a new hepatic mechanism of action via Sestrin 2 and PGC-1α.

The TELEhealth Shared decision-making Coaching and Navigation in Primary carE (TELESCOPE) intervention: a study protocol for delivering shared decision-making for lung cancer screening by patient navigators.

Background: Lung cancer screening (LCS) can reduce lung cancer mortality but has potential harms for patients. A shared decision-making (SDM) conversation about LCS is required by the Centers for Medicare & Medicaid Services (CMS) for LCS reimbursement. To overcome barriers to SDM in primary care, this protocol describes a telehealth decision coaching intervention for LCS in primary care clinics delivered by patient navigators. The objective of the study is to evaluate the effectiveness of the intervention and its implementation potential, compared with an enhanced usual care (EUC) arm. Methods: Patients (n = 420) of primary care clinicians (n = 120) are being recruited to a cluster randomized controlled trial. Clinicians are randomly assigned to 1) TELESCOPE intervention: prior to an upcoming non-acute clinic visit, patients participate in a telehealth decision coaching session about LCS delivered by trained patient navigators and nurse navigators place a low-dose CT scan (LDCT) order for each TELESCOPE patient wanting LCS, or 2) EUC: patients receive enhanced usual care from a clinician. Usual care is enhanced by providing clinicians in both arms with access to a Continuing Medical Education (CME) webinar about LCS and an LCS discussion guide. Patients complete surveys at baseline and 1-week after the scheduled clinic visit to assess quality of the SDM process. Re-navigation is attempted with TELESCOPE patients who have not completed the LDCT within 3 months. One month before being due for an annual screening, TELESCOPE patients whose initial LCS showed low-risk findings are randomly assigned to receive a telehealth decision coaching booster session with a navigator or no booster. Electronic health records are abstracted at 6, 12 and 18 months after the initial decision coaching session (TELESCOPE) or clinic visit (EUC) to assess initial and annual LCS uptake, imaging results, follow-up testing for abnormal findings, cancer diagnoses, treatment, and tobacco treatment referrals. This study will evaluate factors that facilitate or interfere with program implementation using mixed methods. Discussion: We will assess whether a decision coaching and patient navigation intervention can feasibly support high-quality SDM for LCS and guideline-concordant LCS uptake for patients in busy primary care practices serving diverse patient populations. Trial Registration: This study was registered at ClinicalTrials.gov (NCT05491213) on August 4, 2022.

Perinatal mortality, severe maternal morbidity and maternal near miss: protocol of a study integrated with the Birth in Brazil II survey. / Mortalidade perinatal, morbidade materna grave e near miss materno: protocolo de um estudo integrado à pesquisa Nascer no Brasil II.

Brazil presents high maternal and perinatal morbidity and mortality. Cases of severe maternal morbidity, maternal near miss, and perinatal deaths are important health indicators and share the same determinants, being closely related to living conditions and quality of perinatal care. This article aims to present the study protocol to estimate the perinatal mortality rate and the incidence of severe maternal morbidity and maternal near miss in the country, identifying its determinants. Cross-sectional study integrated into the research Birth in Brazil II, conducted from 2021 to 2023. This study will include 155 public, mixed and private maternities, accounting for more than 2,750 births per year, participating in the Birth in Brazil II survey. We will collect retrospective data from maternal and neonatal records of all hospitalizations within a 30-day period in these maternities, applying a screening form to identify cases of maternal morbidity and perinatal deaths. Medical record data of all identified cases will be collected after hospital discharge, using a standardized instrument. Cases of severe maternal morbidity and maternal near miss will be classified based on the definition adopted by the World Health Organization. The perinatal deaths rate and the incidence of severe maternal morbidity and maternal near miss will be estimated. Cases will be compared to controls obtained in the Birth in Brazil II survey, matched by hospital and duration of pregnancy, in order to identify factors associated with negative outcomes. Results are expected to contribute to the knowledge on maternal morbidity and perinatal deaths in Brazil, as well as the development of strategies to improve care.

O Brasil apresenta elevada morbimortalidade materna e perinatal. Casos de morbidade materna grave, near miss materno e óbitos perinatais são indicadores importantes de saúde e compartilham dos mesmos determinantes sociais, tendo estreita relação com as condições de vida e qualidade da assistência perinatal. Este artigo pretende apresentar o protocolo de estudo que visa estimar a taxa de mortalidade perinatal e a incidência de morbidade materna grave e near miss materno no país, assim como identificar seus determinantes. Trata-se de estudo transversal integrado à pesquisa Nascer no Brasil II, realizada entre 2021 e 2023. Serão incluídas neste estudo 155 maternidades públicas, mistas e privadas, com mais de 2.750 partos por ano, participantes do Nascer no Brasil II. Nessas maternidades, será realizada coleta retrospectiva de dados de prontuário materno e neonatal de todas as internações ocorridas num período de 30 dias, com aplicação de uma ficha de triagem para identificação de casos de morbidade materna e de óbito perinatal. Dados de prontuário de todos os casos identificados serão coletados após a alta hospitalar, utilizando instrumento padronizado. Casos de morbidade materna grave e near miss materno serão classificados por meio da definição adotada pela Organização Mundial da Saúde. Será estimada a taxa de mortalidade perinatal e a incidência de morbidade materna grave e near miss materno. Os casos serão comparados a controles obtidos na pesquisa Nascer no Brasil II, pareados por hospital e duração da gestação, visando a identificação de fatores associados aos desfechos negativos. Espera-se que os resultados deste artigo contribuam para o conhecimento sobre a morbidade materna e a mortalidade perinatal no país, bem como para a elaboração de estratégias de melhoria do cuidado.

Brasil tiene una alta morbimortalidad materna y perinatal. Los casos de morbilidad materna severa, maternal near miss y muertes perinatales son importantes indicadores de salud y comparten los mismos determinantes sociales, y tienen una estrecha relación con las condiciones de vida y la calidad de la asistencia perinatal. Este artículo pretende presentar el protocolo de estudio que tiene como objetivo estimar la tasa de mortalidad perinatal y la incidencia de morbilidad materna severa y maternal near miss en el país, así como identificar sus determinantes. Se trata de un estudio transversal integrado a la investigación Nacer en Brasil II, realizada entre el 2021 y el 2023. Este estudio incluirá 155 maternidades públicas, mixtas y privadas, con más de 2.750 partos al año, que participan en el Nacer en Brasil II. En estas maternidades, se realizará una recopilación retrospectiva de datos de las historias clínicas maternas y neonatales de todas las hospitalizaciones ocurridas en un período de 30 días, con la aplicación de un formulario de triaje para identificar casos de morbilidad materna y de muerte perinatal. Los datos de las historias clínicas de todos los casos identificados se recopilarán tras el alta hospitalaria, mediante un instrumento estandarizado. Los casos de morbilidad materna severa y maternal near miss se clasificarán por medio de la definición adoptada por la Organización Mundial de la Salud. Se estimará la tasa de mortalidad perinatal y la incidencia de morbilidad materna severa y maternal near miss. Los casos se compararán con los controles obtenidos en el estudio Nacer en Brasil II, emparejados por hospital y duración del embarazo, para identificar factores asociados con desenlaces negativos. Se espera que los resultados de este artículo contribuyan al conocimiento sobre la morbilidad materna y la mortalidad perinatal en el país, así como a la elaboración de estrategias para mejorar el cuidado.

Birth in Brazil II: a postpartum maternal, paternal and child health research protocol. / Nascer no Brasil II: protocolo de investigação da saúde materna, paterna e da criança no pós-parto.

Pregnancy, parturition and birth bring major changes to the lives of mothers and fathers. This article presents a research protocol for estimating the prevalence of postpartum mental health outcomes in mothers and fathers, abuse and satisfaction in delivery/abortion care, and the correlations between them and socioeconomic, obstetric, and child health factors. As a 2-component research, it consists of a prospective cohort study with all postpartum women interviewed in the 465 maternity hospitals included at the Birth in Brazil II baseline survey conducted from 2021 to 2023, and a cross-sectional study with the newborns' fathers/partners. Interviews will be conducted via telephone or self-completion link sent by WhatsApp with the mother at 2 and 4 months after delivery/abortion. Partners will be approached three months after birth (excluding abortions, stillbirths and newborn death) using the telephone number informed by the mother at the maternity ward. Postpartum women will be inquired about symptoms of depression, anxiety and post-traumatic stress disorder, abuse during maternity care and quality of the mother-newborn bond. Maternal and neonatal morbidity, use of postnatal services, and satisfaction with maternity care are also investigated. Fathers will be asked to report on symptoms of depression and anxiety, and the quality of the relationship with the partner and the newborn. The information collected in this research stage may help to plan and improve care aimed at the postpartum health of the mother-father-child triad.

A gravidez, o parto e o nascimento são momentos de grandes mudanças na vida das mães e dos pais. Este artigo tem como objetivo apresentar o protocolo da pesquisa para estimar a prevalência dos desfechos em saúde mental nas mães e pais no pós-parto, dos maus tratos e satisfação na atenção ao parto/abortamento, e as inter-relações entre eles e fatores socioeconômicos, obstétricos e da saúde da criança. A pesquisa tem dois componentes: estudo de coorte prospectiva com todas as puérperas entrevistadas nas 465 maternidades incluídas na linha de base da pesquisa Nascer no Brasil II realizada entre 2021 e 2023, e estudo seccional com os companheiros/pais dos bebês. As entrevistas são realizadas por ligação telefônica ou link de autopreenchimento enviado por WhatsApp com as puérperas aos 2 e 4 meses após o parto/aborto. Os companheiros são abordados três meses após o nascimento (excluídos os abortos, natimortos e neomortos), a partir do telefone informado pela puérpera na maternidade. As entrevistas abordam, entre as puérperas, sintomas de depressão, ansiedade e transtorno de estresse pós-traumático, maus-tratos na atenção na maternidade e qualidade do vínculo mãe-bebê. São investigados também a presença de morbidade materna e neonatal, utilização de serviços pós-natais, e satisfação com o atendimento na maternidade. Entre os pais, é abordada a ocorrência de sintomas de depressão e ansiedade, e a qualidade do relacionamento com a esposa/companheira e o bebê. As informações coletadas nessa etapa da pesquisa poderão subsidiar o planejamento e melhoria do cuidado voltado para a saúde da tríade mãe-pai-filho após o nascimento.

El embarazo, el parto y el nacimiento son momentos de grandes cambios en la vida de madres y padres. Este artículo tiene como objetivo presentar el protocolo de investigación para estimar la prevalencia de los resultados de la salud mental en madres y padres en el posparto, maltratos y la satisfacción durante la atención del parto/aborto, y las interrelaciones entre ellos y los factores socioeconómicos, obstétricos y de salud infantil. La investigación tiene dos componentes: un estudio de cohorte prospectivo con todas las puérperas entrevistadas en las 465 maternidades incluidas en la línea de base de la encuesta Nacer en Brasil II realizada entre 2021 y 2023, y un estudio seccional con las parejas/padres de los bebés. Las entrevistas se efectúan mediante llamada telefónica o enlace de autocumplimentación enviado vía WhatsApp a las puérperas a los 2 y 4 meses después del parto/aborto. El contacto con la pareja se hace a los tres meses del nacimiento (excluyendo abortos, mortinatos y muertes de recién nacidos), a través del teléfono facilitado por la puérpera en la sala de maternidad. Las entrevistas abordan, entre las puérperas, los síntomas de depresión, ansiedad y trastorno de estrés postraumático, maltrato durante la atención en la maternidad y la calidad del vínculo madre-bebé. También se investiga la presencia de morbilidad materna y neonatal, uso de servicios posnatales y satisfacción con la atención en la maternidad. Entre los padres, se aborda la ocurrencia de síntomas de depresión y ansiedad, y la calidad de la relación con la esposa/pareja y el bebé. La información recopilada en esta etapa de la investigación puede apoyar la planificación y mejora de la atención dirigida a la salud de la tríada madre-padre-hijo después del nacimiento.

Protocol of Birth in Brazil II: National Research on Abortion, Labor and Childbirth. / Protocolo do Nascer no Brasil II: Pesquisa Nacional sobre Aborto, Parto e Nascimento.

Brazil has made advances in obstetric care in public and private hospitals; however, weaknesses in this system still require attention. The Brazilian Ministry of Health, aware of this need, funded the second version of the Birth in Brazil survey. This study aimed to evaluate: prenatal, labor and birth, postpartum, and abortion care, comparing the results with those of Birth in Brazil I; and analyze the main determinants of perinatal morbidity and mortality; evaluate the care structure and processes of obstetrics and neonatology services in maternity hospitals; analyze the knowledge, practices, and attitudes of health professionals who provide birth and abortion care; and identify the main barriers and facilitators related to care of this nature in Brazil. With a national scope and a 2-stage probability sample: 1-hospitals and 2-women, stratified into 59 strata, 465 hospitals were selected with a total planned sample of around 24,255 women - 2,205 for abortion reasons and 22,050 for labor reasons. Data collection was conducted using six electronic instruments during hospital admission for labor or abortion, with two follow-up waves, at two and four months. In order to expand the number of cases of severe maternal morbidity, maternal and perinatal mortality, three case control studies were incorporated into Birth in Brazil II. The fieldwork began in November 2021 and is scheduled to end in 2023. It will allow a comparison between current labor and birth care results and those obtained in the first study and will evaluate the advances achieved in 10 years.

Com o passar do tempo, o Brasil vem apresentando avanços na assistência obstétrica em hospitais públicos e privados; no entanto, ainda existem pontos frágeis que necessitam de atenção. O Ministério da Saúde, ciente dessa necessidade, financiou a segunda versão da pesquisa Nascer no Brasil. Os objetivos gerais são: avaliar a assistência pré-natal, ao parto e nascimento, ao puerpério e ao aborto, comparando com os resultados do Nascer no Brasil I, e analisar os principais determinantes da morbimortalidade perinatal; avaliar a estrutura e processos assistenciais dos serviços de obstetrícia e neonatologia das maternidades; analisar os conhecimentos, atitudes e práticas de profissionais de saúde que prestam assistência ao parto e ao aborto; e identificar as principais barreiras e facilitadores para essa assistência no país. Com escopo nacional e amostra probabilística em dois estágios (1-hospitais e 2-mulheres), dividida em 59 estratos, foram selecionados 465 hospitais com total planejado de, aproximadamente, 24.255 mulheres, 2.205 por motivo de aborto e 22.050 por motivo de parto. A coleta de dados, realizada por meio de seis instrumentos eletrônicos, ocorre durante a internação hospitalar para o parto ou aborto, com duas ondas de seguimento, aos dois e quatro meses. Com o intuito de expandir o número de casos de morbidade materna grave, mortalidade materna e perinatal, três estudos caso controle foram incorporados ao Nascer no Brasil II. O trabalho de campo foi iniciado em novembro de 2021 com término previsto para 2023. Os resultados permitirão comparar a atenção atual ao parto e ao nascimento com a retratada no primeiro inquérito e, com isso, avaliar os avanços alcançados no decorrer desses 10 anos.

Aunque Brasil ha presentado avances en la atención obstétrica en hospitales públicos y privados, todavía hay puntos débiles que necesitan atención. El Ministerio de Salud, consciente de esta necesidad, financió la segunda versión de la encuesta Nacer en Brasil. Los objetivos generales son: evaluar la atención prenatal, el parto y el nacimiento, el puerperio y el aborto, comparando con los resultados del Nacer en Brasil I, y analizar los principales determinantes de la morbimortalidad perinatal; evaluar la estructura y los procesos de atención de los servicios de obstetricia y neonatología en las maternidades; analizar los conocimientos, prácticas y actitudes de los profesionales de la salud que brindan atención para el parto y el aborto; e identificar las principales barreras y facilitadores para esta atención en el país. Tiene un alcance nacional y muestra probabilística en dos etapas (1-hospitales y 2-mujeres), la cual se dividió en 59 estratos; y se seleccionaron 465 hospitales con un total planificado de aproximadamente 24.255 mujeres, de las cuales 2.205 tuvieron procedimientos por aborto y 22.050 por parto. Para la recolección de datos se aplicó seis instrumentos electrónicos, que se realizó durante la hospitalización por parto o aborto, con dos rondas de seguimiento, a los dos y cuatro meses. Con el fin de ampliar el número de casos de morbilidad materna grave, mortalidad materna y perinatal, se incorporaron tres estudios de casos y controles en Nacer en Brasil II. El trabajo de campo comenzó en noviembre de 2021 y finalizará en 2023. Los resultados nos permitirán evaluar la atención al parto y al nacimiento actual con lo que se retrató en la primera encuesta, de esta manera se podrá evaluar los avances alcanzados a lo largo de estos 10 años.

Factors associated with the absence of postpartum consultations in a high-risk population.

Objective: To assess the rate of missed postpartum appointments at a referral center for high-risk pregnancy and compare puerperal women who did and did not attend these appointments to identify related factors. Methods: This was a retrospective cross-sectional study with all women scheduled for postpartum consultations at a high-risk obstetrics service in 2018. The variables selected to compare women were personal, obstetric, and perinatal. The variables of interest were obtained from the hospital's electronic medical records. Statistical analyses were performed using the Chi-square, Fisher's exact, or Mann-Whitney tests. For the variable of the interbirth interval, a receiver operating characteristic curve (ROC) was used to best discriminate whether or not patients attended the postpartum consultation. The significance level for the statistical tests was 5%. Results: A total of 1,629 women scheduled for postpartum consultations in 2018 were included. The rate of missing the postpartum consultation was 34.8%. A shorter interbirth interval (p = 0.039), previous use of psychoactive substances (p = 0.027), current or former smoking (p = 0.003), and multiparity (p < 0.001) were associated with non-attendance. Conclusion: This study showed a high rate of postpartum appointment non-attendance. This is particularly relevant because it was demonstrated in a high-risk obstetric service linked to clinical severity or social vulnerability cases. This highlights the need for new approaches to puerperal women before hospital discharge and new tools to increase adherence to postpartum consultations, especially for multiparous women.

Toxicity of REEs, Th, and U: A Biodisponibility, Cytotoxicity, and Bioaccumulation Assessment in Marine Sediment.

In this work, bioaccessibility tests for rare earth elements (REEs), Th, and U in marine sediment were carried out, in addition to complementary tests for cytotoxicity and bioaccumulation for the elements La, Ce, Eu, and Gd. The evaluation of human health risk through dermal absorption and oral ingestion was performed using the hazard quotient (HQ). According to the gastric digestion simulation (SBET), it was observed that the elements Ce and Nd exhibited higher absorption capacities in the human body (> 2 µg g-1). La and Sc presented intermediate concentrations (close to 1 µg g-1), while the remaining elements displayed concentrations below 0.5 µg g-1. In the gastrointestinal digestion extraction stage (PBET), all the elements maintained a similar absorption capacity to that observed in SBET, except for the absorption of Y which increased. The results of the bioaccumulation test conducted with fibroblast cells (L929) indicated that La and Eu had a 25% probability of intracellular accumulation. The cell viability test, with exposure to a standard REEs, Th, and U solution in 2% v v-1 HNO3 medium (until 100 µg mL-1) and an aqueous solution of La2O3, Gd(NO3)3, Ce(NO3)3, and Eu2O3 (until 1000 µg mL-1), did not demonstrate cytotoxic effects on fibroblast cells. Considering the ingestion hazard quotient (HQing) and dermal hazard quotient (HQderm) obtained, it was suggested that there is no significant risk of non-carcinogenic effects (< 1). However, they had higher HQing values compared to HQderm, indicating that REEs pose more significant risk to human health through oral ingestion absorption than dermal absorption.

[Assisting diabetics in Portugal: the structuring role of the Association to Protect Poor Diabetics, 1926-1946]. / A assistência aos diabéticos em Portugal: o papel estruturante da Associação Protetora dos Diabéticos Pobres, 1926-1946.

Assistance to diabetics in Portugal was quintessentially linked to the 1926 foundation of the Association to Protect Poor Diabetics (Associação Protetora dos Diabéticos Pobres) which was decisive in structuring diabetology in Portugal. This article shows how during the first half of the twentieth century, this association helped create a model of assistance for diabetics in this country based on the principles of modern diabetology. First, we examine its functional and clinical organization to comply with assistance policy during the New State period in Portugal. Next, we depict the organization of the assistance model, which included treatment and education of poor patients with diabetes.

A assistência aos diabéticos em Portugal esteve umbilicalmente ligada à fundação da Associação Protetora dos Diabéticos Pobres em 1926, a qual teve um papel determinante na estruturação da diabetologia portuguesa. O objetivo do artigo é demonstrar de que forma a associação contribuiu para a estruturação de um modelo de assistência aos diabéticos em Portugal, escorada nos princípios da diabetologia moderna na primeira metade do século XX. Primeiro explicaremos como a instituição se organizou em termos funcionais e clínicos atendendo às políticas assistenciais do período do Estado Novo em Portugal. Posteriormente mostraremos como estava organizado o modelo de assistência, que incluía o tratamento e a educação dos diabéticos pobres.

Case report: Primary CDK4/6 inhibitor and endocrine therapy in locally advanced breast cancer and its effect on gut and intratumoral microbiota.

Locally advanced breast cancer poses significant challenges to the multidisciplinary team, in particular with hormone receptor (HR) positive, HER2-negative tumors that classically yield lower pathological complete responses with chemotherapy. The increasingly significant use of CDK 4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET) in different breast cancer settings has led to clinical trials focusing on this strategy as a primary treatment, with promising results. The impact of the microbiota on cancer, and vice-versa, is an emerging topic in oncology. The authors report a clinical case of a postmenopausal female patient with an invasive breast carcinoma of the right breast, Luminal B-like, staged as cT4cN3M0 (IIIB). Since the lesion was considered primarily inoperable, the patient started letrozole and ribociclib. Following 6 months of systemic therapy, the clinical response was significant, and surgery with curative intent was performed. The final staging was ypT3ypN2aM0, R1, and the patient started adjuvant letrozole and radiotherapy. This case provides important insights on primary CDK4/6i plus ET in locally advanced unresectable HR+/HER2- breast cancer and its potential implications in disease management further ahead. The patient's gut microbiota was analyzed throughout the disease course and therapeutic approach, evidencing a shift in gut microbial dominance from Firmicutes to Bacteroidetes and a loss of microbial diversity following 6 months of systemic therapy. The analysis of the intratumoral microbiota from the surgical specimen revealed high microbial dissimilarity between the residual tumor and respective margins.

Time-specific impact of trace metals on breast density of adolescent girls in Santiago, Chile.

Whether trace metals modify breast density, the strongest predictor for breast cancer, during critical developmental stages such as puberty remains understudied. Our study prospectively evaluated the association between trace metals at Tanner breast stage B1 (n = 291) and at stages both B1 and B4 (n = 253) and breast density at 2 years post-menarche among Chilean girls from the Growth and Obesity Cohort Study. Dual-energy x-ray absorptiometry assessed the volume of dense breast tissue (absolute fibroglandular volume [FGV]) and percent breast density (%FGV). Urine trace metals included arsenic, barium, cadmium, cobalt, cesium, copper, magnesium, manganese, molybdenum, nickel, lead, antimony, selenium, tin, thallium, vanadium, and zinc. At B1, a doubling of thallium concentration resulted in 13.69 cm3 increase in absolute FGV (ß: 13.69, 95% confidence interval [CI]: 2.81, 24.52), while a doubling of lead concentration resulted in a 7.76 cm3 decrease in absolute FGV (ß: -7.76, 95%CI: -14.71, -0.73). At B4, a doubling of barium concentration was associated with a 10.06 cm3 increase (ß: 10.06, 95% CI: 1.44, 18.60), copper concentration with a 12.29 cm3 increase (ß: 12.29, 95% CI: 2.78, 21.56), lead concentration with a 9.86 cm3 increase (ß: 9.86, 95% CI: 0.73, 18.98), antimony concentration with a 12.97 cm3 increase (ß: 12.97, 95% CI: 1.98, 23.79) and vanadium concentration with a 13.14 cm3 increase in absolute FGV (ß: 13.14, 95% CI: 2.73, 23.58). Trace metals may affect pubertal breast density at varying developmental stages with implications for increased susceptibility for breast cancer.

An implementation analysis of a quality improvement project to reduce cesarean section in Brazilian private hospitals.

BACKGROUND: Brazil has one of the highest prevalence of cesarean sections in the world. The private health system is responsible for carrying out most of these surgical procedures. A quality improvement project called Adequate Childbirth Project ("Projeto Parto Adequado"- PPA) was developed to identify models of care for labor and childbirth, which place value on vaginal birth and reduce the frequency of cesarean sections without a clinical indication. This research aims to evaluate the implementation of PPA in private hospitals in Brazil. METHOD: Evaluative hospital-based survey, carried out in 2017, in 12 private hospitals, including 4,322 women. We used a Bayesian network strategy to develop a theoretical model for implementation analysis. We estimated and compared the degree of implementation of two major driving components of PPA-"Participation of women" and "Reorganization of care" - among the 12 hospitals and according to type of hospital (belonging to a health insurance company or not). To assess whether the degree of implementation was correlated with the rate of vaginal birth data we used the Bayesian Network and compared the difference between the group "Exposed to the PPA model of care" and the group "Standard of care model". RESULTS: PPA had a low degree of implementation in both components "Reorganization of Care" (0.17 - 0.32) and "Participation of Women" (0.21 - 0.34). The combined implementation score was 0.39-0.64 and was higher in hospitals that belonged to a health insurance company. The vaginal birth rate was higher in hospitals with a higher degree of implementation of PPA. CONCLUSION: The degree of implementation of PPA was low, which reflects the difficulties in changing childbirth care practices. Nevertheless, PPA increased vaginal birth rates in private hospitals with higher implementation scores. PPA is an ongoing quality improvement project and these results demonstrate the need for changes in the involvement of women and the care offered by the provider.

Polarization of HIV-1- and CMV-Specific IL-17-Producing T Cells among People with HIV under Antiretroviral Therapy with Cannabis and/or Cocaine Usage.

OBJECTIVE: This study evaluated the influence of cannabis and/or cocaine use in human immunodeficiency virus (HIV)- and cytomegalovirus (CMV)-specific T-cell responses of people with HIV (PWH). RESULTS: There was a higher percentage of IL-17-producing HIV-Gag-specific CD8+ T-cells in all drug users than that in PWH non-drug users. Stratifying the drug-user groups, increased percentages of IL-17-producing HIV-Gag-specific CD4+ and CD8+ T-cells were found in PWH cannabis plus cocaine users compared to PWH non-drug users. In response to CMV, there were higher percentage of IL-17-producing CMV-specific CD8+ T-cell in PWH cocaine users than that in PWH non-drug users. Considering all drug users together, there was a higher percentage of SEB-stimulated IL-17-producing CD4+ T-cells than that in PWH non-drug users, whereas cannabis users had higher percentages of IL-17-producing CD4+ T-cells compared to non-drug users. METHODS: Cryopreserved peripheral blood mononuclear cells from 37 PWH undergoing antiretroviral therapy (ART) using cannabis (10), cocaine (7), or cannabis plus cocaine (10) and non-drug users (10) were stimulated with HIV-1 Gag or CMV-pp65 peptide pools, or staphylococcal enterotoxin B (SEB) and evaluated for IFN-γ- and/or IL-17A-producing CD4+ and CD8+ T-cells using flow cytometry. CONCLUSIONS: Cannabis plus cocaine use increased HIV-specific IL-17 producing T-cells and cocaine use increased IL-17 CMV-specific CD8+ T-cell responses which could favor the inflammatory conditions associated with IL-17 overproduction.