Deep Learning in the Recognition of Activities of Daily Living Using Smartwatch Data.

The recognition of human activities (HAR) using wearable device data, such as smartwatches, has gained significant attention in the field of computer science due to its potential to provide insights into individuals' daily activities. This article aims to conduct a comparative study of deep learning techniques for recognizing activities of daily living (ADL). A mapping of HAR techniques was performed, and three techniques were selected for evaluation, along with a dataset. Experiments were conducted using the selected techniques to assess their performance in ADL recognition, employing standardized evaluation metrics, such as accuracy, precision, recall, and F1-score. Among the evaluated techniques, the DeepConvLSTM architecture, consisting of recurrent convolutional layers and a single LSTM layer, achieved the most promising results. These findings suggest that software applications utilizing this architecture can assist smartwatch users in understanding their movement routines more quickly and accurately.

Population pharmacokinetics of benznidazole in neonates, infants and children using a new pediatric formulation.

BACKGROUND: There is a major need for information on pharmacokinetics (PK) of benznidazole (BNZ) in children with Chagas disease (CD). We conducted a multicentre population PK, safety and efficacy study in children, infants and neonates with CD treated with BNZ (formulated in 100 mg tablets or 12.5 mg dispersible tablets, developed by the pharmaceutical company LAFEPE, in a collaboration with DNDi). METHODS: 81 children 0-12 years old were enrolled at 5 pediatric centers in Argentina. Diagnosis of T. cruzi infection was confirmed by direct microscopic examination, or at least two positive conventional serological tests. Subject enrolment was stratified by age: newborns to 2 years (minimum of 10 newborns) and >2-12 years. BNZ 7.5 mg/kg/d was administered in two daily doses for 60 days. Five blood samples per child were obtained at random times within pre-defined time windows at Day 0 at 2-5 h post-dose; during steady state, one sample at Day 7 and at Day 30; and two samples at 12-24 h after final BNZ dose at Day 60. The primary efficacy endpoint was parasitological clearance by qualitative PCR at the end of treatment. RESULTS: Forty-one (51%) patients were under 2 years of age (including 14 newborns <1 month of age). Median age at enrolment was 22 months (mean: 43.2; interquartile range (IQR) 7-72 months). The median measured BNZ Cmax was 8.32 mg/L (IQR 5.95-11.8; range 1.79-19.38). Median observed BNZ Cmin (trough) concentration was 2 mg/L (IQR 1.25-3.77; range 0.14-7.08). Overall median simulated Css was 6.3 mg/L (IQR 4.7-8.5 mg/L). CL/F increased quickly during the first month of postnatal life and reached adult levels after approximately 10 years of age. Negative qPCR was observed at the end of treatment in all 76 patients who completed the treatment. Five patients discontinued treatment (3 due to AEs and 2 due to lack of compliance). CONCLUSION: We observed lower BNZ plasma concentrations in infants and children than those previously reported in adults treated with comparable mg/kg doses. Despite these lower concentrations, pediatric treatment was well tolerated and universally effective, with a high response rate and infrequent, mild AEs. TRIAL REGISTRATION: Registered in clinicaltrials.gov #NCT01549236.

Cone-beam computed tomography texture analysis can help differentiate odontogenic and non-odontogenic maxillary sinusitis.

Purpose: This study aimed to assess texture analysis (TA) of cone-beam computed tomography (CBCT) images as a quantitative tool for the differential diagnosis of odontogenic and non-odontogenic maxillary sinusitis (OS and NOS, respectively). Materials and Methods: CBCT images of 40 patients diagnosed with OS (N=20) and NOS (N=20) were evaluated. The gray level co-occurrence (GLCM) matrix parameters, and gray level run length matrix texture (GLRLM) parameters were extracted using manually placed regions of interest on lesion images. Seven texture parameters were calculated using GLCM and 4 parameters using GLRLM. The Mann-Whitney test was used for comparisons between the groups, and the Levene test was performed to confirm the homogeneity of variance (α=5%). Results: The results showed statistically significant differences (P<0.05) between the OS and NOS patients regarding 3 TA parameters. NOS patients presented higher values for contrast, while OS patients presented higher values for correlation and inverse difference moment. Greater textural homogeneity was observed in the OS patients than in the NOS patients, with statistically significant differences in standard deviations between the groups for correlation, sum of squares, sum of entropy, and entropy. Conclusion: TA enabled quantitative differentiation between OS and NOS on CBCT images by using the parameters of contrast, correlation, and inverse difference moment.

Biosorption of bioactive compounds in bacterial nanocellulose: Mechanisms and physical-chemical properties.

Bacterial cellulose (BC) is a biomaterial produced by Gluconacetobacter xylinus, with wide applicability in different areas, such as biomedical, pharmaceutical, and food. BC production is usually carried out in a medium containing phenolic compounds (PC), such as teas, however, the purification process leads to the loss of such bioactive. Thus, the innovation of this research consists of the reincorporation of PC after the purification of the BC matrices through the biosorption process. In this context, the effects of the biosorption process in BC were evaluated to maximize the incorporation of phenolic compounds from a ternary mixture of hibiscus (Hibiscus sabdariffa), white tea (Camellia sinensis), and grape pomace (Vitis labrusca). The biosorbed membrane (BC-Bio) showed a great concentration of total phenolic compounds (TPC = 64.89 mg L-1) and high antioxidant capacity through different assays (FRAP: 130.7 mg L-1, DPPH: 83.4 mg L-1, ABTS: 158.6 mg L-1, TBARS: 234.2 mg L-1). The physical tests also indicated that the biosorbed membrane presented high water absorption capacity, thermal stability, low permeability to water vapor and improved mechanical properties compared to BC-control. These results indicated that the biosorption of phenolic compounds in BC efficiently increases bioactive content and improves physical membrane characteristics. Also, PC release in a buffered solution suggests that BC-Bio can be used as a polyphenol delivery system. Therefore, BC-Bio is a polymer with wide application in different industrial segments.

A Phase 2, Randomized, Multicenter, Placebo-Controlled, Proof-of-Concept Trial of Oral Fexinidazole in Adults With Chronic Indeterminate Chagas Disease.

BACKGROUND: Chagas disease (CD) has significant global health impact, but safe, effective treatments remain elusive. The nitroimidazole fexinidazole is a potential treatment. METHODS: This double-blind, randomized, placebo-controlled, dose-finding, proof-of-concept study was conducted in Bolivia. Adults with serologically confirmed chronic indeterminate CD and positive PCR were randomly assigned to 1 of 6 fexinidazole regimens (1200 or 1800 mg/day for 2, 4, or 8 weeks) or placebo. Target recruitment was 20 patients/arm. The primary endpoint was sustained parasitological clearance by serial negative qPCR from end of treatment (EOT) until 6 months follow-up in the intention-to-treat (ITT) population. Follow-up was extended to 12 months. RESULTS: Enrollment was interrupted after 4/47 patients presented with transient asymptomatic grade 3 and 4 neutropenia. Treatment of ongoing patients was stopped in all patients administered >2 weeks. A total of 40 patients received treatment with fexinidazole from 3 days to 8 weeks. Delayed-onset neutropenia (n = 8) and increased liver enzymes (n = 8) were found in fexinidazole patients vs none in the placebo arm. In the ITT analysis, sustained parasitological clearance from EOT to 12 months follow-up varied between 66.7% (1200 mg-2 week) and 100.0% (1800 mg-2 week). Rapid, sustained clearance of parasitemia was observed in all treated patients with available data, but not in any patients in the placebo group, at 12 months (P = .0056). Further exploratory exposure-response analysis suggested low dosages of fexinidazole may be safe and effective. CONCLUSIONS: Further evaluation is needed to establish fexinidazole's minimum effective dosage and risk-benefit relationship. Results suggest potential for effective treatment regimens <10 days. CLINICAL TRIALS REGISTRATION: NCT02498782.

Dependência, ciclo do capital e limites do fundo público no Brasil / Dependency, capital cycle and limits of the public fund in Brazil

Resumo: Este artigo visa identificar a participação e os limites do fundo público no ciclo do capital da economia dependente brasileira. Para isso, aborda as implicações do intercâmbio desigual, da transferência de valor e da superexploração da força de trabalho para a composição e direcionamento do fundo público no Brasil, utilizando-se da coleta e análise de dados acerca do sistema tributário brasileiro.

Abstract: This article aims to identify the participation and limits of the public fund in the capital cycle of the Brazilian dependent economy. To this end, it addresses the implications of unequal exchange, value transfer and overexploitation of the labor force for the composition and direction of public fund in Brazil, using the analysis of data about the Brazilian tax system.

O impacto de maus-tratos na saúde mental de crianças e adolescentes: revisão integrativa de literatura / The impact of maltreatment on the mental health of children and adolescents: an integrative literature review / El impacto del maltrato en la salud mental de niños y adolescentes: una revisión bibliográfica integradora

Os maus-tratos na infância e na adolescência consistem em abusos psicoló- gicos, físicos e sexuais, além de negligência dos cuidadores, gerando prejuízos psicoló- gicos nesses indivíduos. O objetivo do estudo foi analisar na literatura nacional e interna- cional o impacto dos maus-tratos na saúde mental de crianças e adolescentes. Trata-se de uma revisão integrativa da literatura realizada entre agosto e outubro de 2020, na Biblio- teca Virtual em Saúde (BVS), por meio da questão norteadora: "Quais são os estudos originais nacionais e internacionais que abordam o impacto de maus-tratos na saúde men- tal de crianças e adolescentes?". Foram incluídos artigos em inglês, disponíveis na ínte- gra, e correspondentes aos últimos três anos. Excluíram-se documentos que não apresen- tavam pertinência no estudo conduzido. Foram eleitos dezesseis artigos para análise, que foram divididos em quatro categorias:"I: Associação direta entre maus-tratos e problemas de saúde mental por crianças e adolescentes", a qual evidenciou prejuízos psicológicos como depressão e distúrbios do sono; "II: Fatores de proteção para a saúde mental de crianças e adolescentes vítimas de maus-tratos", que indicou atividades extracurriculares e ambiente familiar acolhedor como fatores de melhor prognóstico diante dos abusos; "III: Relação entre culpabilização da vítima de maus-tratos pela sociedade e sua saúde mental", a qual apresentou consequências negativas da cultura de culpabilização da ví- tima; e "IV: Influência da experiência pregressa de maus-tratos em cuidadores como fator preditor de perpetuação de abusos", que identificou a reprodução de estruturas familiares abusivas. Observa-se que os maus-tratos são uma problemática de saúde pública, o que afirma a necessidade de consolidação de políticas públicas no âmbito, a fim de garantir maior proteção a crianças e adolescentes.

Maltreatments in childhood and adolescence consists of psychological, physical and sexual absuses, in addition to negligence by caregivers, generating psycho- logical disturbs in these individuals. The objective of the study was to analyze in the national and international literature the impact of maltreatments in the mental health of children and adolescents. This is na integrative literature review conducted between Au- gust and October 2020, at the Biblioteca Virtual em Saúde (BVS), through the guiding question: "What are the original national and international studies that address the impact of maltreatments in the mental health of children and adolescents?". Articles in English, fully available, and corresponding to the last three years were included. Documents which were not relevant in the study conducted were excluded. Sixteen articles were chosen for analysis, which were divided into four categories: "I: Direct association between abuse and mental health problems by children and adolescents", which showed psychological damage such as depression and sleep disordes; "II: Protection factors for the mental health of children and adolescents who were victims of abuse", that indicated extracurricular activities and welcoming family environment as factors of better prognosis in the face of abuse; "III: Relationship between culpabilization of the victim of abuse by society and its mental health", which presented negative consequences of the culture of culpabilization of the victim; and "IV: Influence of the previous experience of maltreatment in caregivers as a predictor of perpetuation of abuse", that identified the reproduction of abusive family structures. It is observed that maltreatment is a public health problem, which affirms the need to consolidate public policies in the scope, in order to ensure greater protection for children and adolescents.

Los malos tratos en la infancia y adolescencia consisten en ausencias psico- lógicas, físicas y sexuales, además de negligencia por parte de los cuidadores, generando disturbios psico-lógicos en estos individuos. El objetivo del estudio fue analizar en la literatura nacional e internacional el impacto de los malos tratos en la salud mental de niños y adolescentes. Trata-se de uma revisão integrativa da literatura realizada entre ago- sto e outubro de 2020, na Biblioteca Virtual em Saúde (BVS), através da pergunta orien- tadora: "¿Cuáles son los estudios originales nacionales e internacionales que abordan el impacto de los malos tratos en la salud mental de niños y adolescentes?". Se incluyeron artículos en inglés, totalmente disponibles y correspondientes a los últimos tres años. Se excluyeron los documentos que no eran relevantes para el estudio realizado. Se eligieron 16 artículos para el análisis, que se dividieron en cuatro categorías: "I: Asociación directa entre maltrato y problemas de salud mental de niños y adolescentes", que mostraba daños psicológicos como depresión y trastornos del sueño; "II: Factores de protección para la salud mental de niños y adolescentes víctimas de maltrato", que indicaba las actividades extraescolares y el ambiente familiar acogedor como factores de mejor pronóstico ante el maltrato; "III: Relación entre la culpabilización de la víctima de maltrato por parte de la sociedad y su salud mental", que presentó las consecuencias negativas de la cultura de culpabilización de la víctima; y "IV: Influencia de la experiencia previa de maltrato en los cuidadores como predictor de perpetuación del maltrato", que identificó la reproduc- ción de estructuras familiares abusivas. Se observa que el maltrato es un problema de salud pública, lo que afirma la necesidad de consolidar políticas públicas en el ámbito, a fin de garantizar una mayor protección a los niños y adolescentes.

Aquisição de alimentos em domicílios brasileiros com e sem crianças / Food pourchase in brazilian households with and without child

-A construção dos hábitos alimentares infantis pode ser influenciada pela disponibilidade dos alimentos presentes nos domicílios. Não se sabe o quanto os pais modificam seu padrão de compra de alimentos para mais saudáveis quando há crianças em casa. Esta informação é importante para avaliar a percepção dos pais sobre a influência do ambiente domiciliar na formação de hábitos alimentares saudáveis em seus filhos. A renda familiar é uma variável que pode ter efeito na modificação dos hábitos alimentares dos pais, uma vez que reflete os recursos financeiros disponíveis para compra de alimentos. Investigar a aquisição de alimentos no Brasil em dois períodos com dez anos de diferença possibilita avaliar o efeito macroeconômico do engajamento dos pais na alimentação de seus filhos, uma vez que o país experimentou momentos econômicos distintos na última década. A fim de comparar a aquisição de alimentos saudáveis e não saudáveis em domicílios com e sem crianças no Brasil este estudo utilizou os dados da Pesquisa de Orçamentos Familiares (POF) conduzidos pelo IBGE, no Brasil, em seus inquéritos de 2008-2009 e 2017-2018. Os domicílios foram classificados em: i) presença ou não de crianças de um a cinco anos de idade e ii) maiores de cinco anos até dez anos de idade. Foram considerados todos os domicílios que compunham as amostras: 55.970 (POF 2007-2008) e 69.660 (POF 2017-2018), sem distinção por macrorregião ou zona urbana e rural, assim representando todo o território brasileiro. Os grupos de alimentos utilizados foram constituídos a partir das adaptações de agregados estipulados pela POF nas duas edições do inquérito. Foram estimadas as médias per capita em quilogramas da aquisição (Kg) de frutas, vegetais, refrigerantes e biscoitos num período de 7 dias consecutivos (uma semana). As diferenças das médias per capita da aquisição (Kg) dos alimentos entre domicílios com e sem criança foram estimadas por modelos de regressão de duas partes, combinando um modelo de regressão logística e um modelo linear generalizado de distribuição gama para valores positivos de aquisição, em função da distribuição assimétrica e inflada de zeros para compra de alguns itens alimentares. As análises foram estratificadas por quartos de renda domiciliar per capita, com ajustes pelo sexo e idade do morador de referência do domicílio, número de bebês, adolescentes, adultos e idosos vivendo no domicílio, e gasto mensal com alimentação. A comparação entre as médias de aquisição de alimentos entre os domicílios com e sem crianças foi dada pela intersecção dos intervalos de confiança de 95% e levou-se em consideração o peso amostral e o desenho complexo das POF. A média de aquisição de frutas em 2008-2009 foi maior nos domicílios com crianças das duas faixas etárias nos domicílios mais pobres. Em 2017-2018, a média de aquisição de frutas foi maior entre os domicílios com crianças de cinco a dez anos de idade pertencentes aos estratos socioeconômicos mais ricos. A compra de vegetais diferiu para menos em domicílios com crianças de 5-10 anos nos dois períodos. Houve uma maior média de aquisição per capita de biscoitos nos domicílios com crianças de todas as classes de rendimentos, em ambos os períodos avaliados.

The construction of children's eating habits can be influenced by the availability of food at the home. It's not known how much parents change their pattern of food purchase when there are children at household. That information is important in order to assess parents' perception of the home environment influence in the construction of healthy eating habits at their children. It's possible that family income have an effect on parents' eating habits, once reflects the financial resources available to food purchase. Investigating the food purchase in Brazil in two periods with ten years of diference leads to assess the macroeconomic effect of parental engagement in children's eating habits, since the country has experienced different moments in the last decade. In order to compare the food disponibility in households with and without children, this study utilized data from the Household Budget Surveys (POF) conducted by the Brazilian Institute of Geography and Statistics (IBGE), in Brazil, surveys 2008-2009 and 2017- 2018. The households were categorized into: i) presence or not of children aged between one and five years old and ii) children aged five and ten years old. The sample considered was 55,970 (POF 2007-2008) and 69,660 (POF 2017-2018). The food groups used were constituted from the recommendations of aggregates previously stipulated by the POF in the two editions of the survey. The means per capita were calculated in kilograms of purchase (Kg) of fruits, vegetables, soft drinks and cookies, over a period of 7 consecutive days (one week). Diferences in of food means per capita purchase (Kg) between households with and without children were estimated by using two-part regression models, that combines a logistic regression model and a generalized linear model with gamma distribution for positive values ​​of purchase, in function of the asymmetric and zero-inflated distribution for purchase of some food items. The analyzes were stratified by income quartiles per capita. With adjustments for sex and age of the household's main resident, number of babies, adolescents, adults and elderlys living in the household, and monthly expenditure on food purchase. The comparison between the means of food purchase between households with and without children was given by the intersection of the 95% confidence intervals, considering the weight sample. The means per capita purchase (Kg) of fruit in 2008-2009 was higher in households with children of both age groups in the poorest households. In 2017-2018, the average purchase of fruit was higher among households with children between five and ten years of age belonging to the elevates socioeconomic stratas. The purchase of vegetables were less in households with children aged 5-10 years in both periods. There was a higher purchase of cookies in households with children of all income classes, in both periods.

Impacts of technology on children's health: a systematic review / Impactos da tecnologia na saúde infantil: revisão sistemática

Abstract Objective: To identify the consequences of technology overuse in childhood. Data source: A systematic review was carried out in the electronic databases PubMed (National Library of Medicine of the National Institutes of Health) and BVS (Virtual Health Library), considering articles published from 2015 to 2020, in English, Portuguese and Spanish using the terms "Internet", "Child" and "Growth and Development". Data synthesis: 554 articles were found and 8 were included in the analysis. The studies' methodological quality was assessed by the Strobe and Consort criteria, being scored from 17 to 22 points. The articles showed positive and negative factors associated with the use of technology in childhood, although most texts emphasize the harmful aspects. Excessive use of internet, games and exposure to television are associated with intellectual deficits and mental health issues, but can also enable psychosocial development. Conclusions: Preventing the use of the internet is a utopic measure ever since society makes use of technologies. The internet is associated with benefits as well as with harms. It is important to optimize the use of internet and reduce risks with the participation of parents and caregivers as moderators, and training of health professionals to better guide them.

RESUMO Objetivo: Identificar as consequências do uso excessivo da tecnologia na infância. Fontes de dados: Foi realizada uma revisão sistemática nas bases de dados eletrônicas PubMed (National Library of Medicine — National Institutes of Health) e Biblioteca Virtual em Saúde (BVS) com artigos publicados de 2015 a 2020, em inglês, português e espanhol, utilizando os termos internet, child e growth and development. Síntese dos dados: Foram localizados 554 artigos, resultando em oito artigos incluídos nesta pesquisa. Os estudos foram avaliados quanto à sua qualidade metodológica pelos critérios Strengthening the Reporting of Observational Studies in Epidemiology (Strobe) e Consolidated Standards of Reporting Trials (Consort) e receberam pontuações que variaram de 17 a 22 pontos. Os artigos evidenciaram que há fatores positivos e negativos associados ao uso de tecnologias na infância, embora a maioria dos textos ressalte seu aspecto prejudicial. O uso excessivo de internet, jogos e exposição à televisão ocasionaram alterações intelectuais e da saúde mental, porém também possibilitaram o desenvolvimento psicossocial. Conclusões: Impedir o uso da internet é uma medida utópica, visto que a sociedade faz uso de tecnologias. Considerando que a internet pode trazer benefícios, mas também malefícios, são importantes a otimização do uso e a redução dos riscos, como a participação dos pais e responsáveis como moderadores dessa utilização, além da atualização dos profissionais da saúde para melhor orientá-los.

Is oral microbiota associated with overweight and obesity in children and adolescents? A systematic review.

This article aims to verify the relationship between the composition and diversity of oral microbiota with overweight and obese children and adolescents. This systematic review was registered in PROSPERO, followed PRISMA 2020, and included an electronic search until March 2022, in PubMed/MEDLINE, Web of Science, Scopus, and The Cochrane Library databases. Studies were eligible if they compared the oral microbiota according to nutrition status among children and adolescents. Independent peers using JBI Critical Appraisal Checklists assessed the quality of studies. Eleven studies were eligible to be included in this review, with a total of 1,695 children and adolescents, 224 were obese, 190 were overweight, 1,154 were eutrophics and 127 were underweight. The most frequent phyla in overweight and obese children and adolescents, in comparison to their counterparts were Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria and Fusobacteria. It was identified that nine of the eleven articles selected showed an association between oral microbiota and overweight and obesity in children and adolescents. We observed that there is an important association between oral bacterial composition diversity and overweight and obesity. This finding indicates the relevance of the evaluation and surveillance in oral health to control cases of overweight and obesity in children and adolescents.

Impacts of technology on children's health: a systematic review.

OBJECTIVE: To identify the consequences of technology overuse in childhood. DATA SOURCE: A systematic review was carried out in the electronic databases PubMed (National Library of Medicine of the National Institutes of Health) and BVS (Virtual Health Library), considering articles published from 2015 to 2020, in English, Portuguese and Spanish using the terms "Internet", "Child" and "Growth and Development". DATA SYNTHESIS: 554 articles were found and 8 were included in the analysis. The studies' methodological quality was assessed by the Strobe and Consort criteria, being scored from 17 to 22 points. The articles showed positive and negative factors associated with the use of technology in childhood, although most texts emphasize the harmful aspects. Excessive use of internet, games and exposure to television are associated with intellectual deficits and mental health issues, but can also enable psychosocial development. CONCLUSIONS: Preventing the use of the internet is a utopic measure ever since society makes use of technologies. The internet is associated with benefits as well as with harms. It is important to optimize the use of internet and reduce risks with the participation of parents and caregivers as moderators, and training of health professionals to better guide them.

Photobiomodulation using LLLT and LED of cells involved in osseointegration and peri-implant soft tissue healing.

This study evaluated the influence of photobiomodulation (PBM) using low-level laser therapy (PBM/LLLT) or light-emitting diode (PBM/LED) therapy on peri-implant tissue healing. A laboratory model was used to assess the adhesion and metabolism of osteoblasts (SaOs-2), human gingival fibroblasts (HGF), and normal oral keratinocytes (NOK) seeded on a titanium (Ti) surface. After seeding the cells on disks of Ti placed in wells of 24-well plates, three irradiations were performed every 24 h at energy density of 3 J/cm2. For PBM/LLLT, a LaserTABLE device was used with a wavelength of 780 nm and 25 mW, while for PBM/LED irradiation, a LEDTABLE device was used at 810 nm, 20 mW, at a density of 3 J/cm2. After irradiations, the number of cells (NC) attached and spread on the Ti surface, cell viability (CV), total protein (TP), and collagen (Col) synthesis were assessed. Alkaline phosphate activity (ALP) was evaluated only for SaOs-2. Data were submitted to ANOVA complemented by Turkey statistical tests at a 5% significance level. PBM significantly increased adherence of NOK to the Ti surface, while no significant effect was observed for SaOs-2 and HGF. PBM positively affected CV, as well as Col and TP synthesis, in distinct patterns according to the cell line. Increased ALP activity was observed only in those cells exposed to PBM/LLLT. Considering cell specificity, this investigation reports that photobiomodulation with low-power laser and LED at determined parameters enhances cellular functions related to peri-implant tissue healing in a laboratory model.

Childhood trauma is associated with onset of symptoms, functioning and cognition in patients with schizophrenia.

INTRODUCTION: Childhood trauma (CT) is known to be a vulnerability factor for schizophrenia, but the specific impacts of different trauma subtypes on the prognosis of these patients remains unclear. OBJECTIVE: To assess the relationships between the occurrence of overall CT and its subtypes with factors with known prognostic impact on schizophrenia, such as age at onset of symptoms, global functioning, and cognitive impairment in a sample of Brazilian patients. METHODS: One hundred and five stable patients diagnosed with schizophrenia according to DSM-5 criteria were evaluated using the Independent Living Skills Survey (ILSS; self-report global functioning), Schizophrenia Cognition Rating Scale (SCoRS; subjective cognitive impairment), and Childhood Trauma Questionnaire scales (CTQ; perceived overall CT, emotional neglect, physical neglect, physical abuse, and emotional and sexual abuse). Statistical analysis was performed with multivariate linear regression. RESULTS: After controlling for educational level and age, subjective cognitive impairment was directly correlated with overall perceived CT occurrence, emotional abuse, and sexual abuse. Self-report global functioning was inversely correlated with perceived overall CT occurrence, emotional abuse, and sexual abuse. Emotional abuse and physical abuse were also inversely correlated with age at onset of symptoms. CONCLUSIONS: CT can be related to more severe prognoses in schizophrenia, impacting on early onset of symptoms, lower global functioning, and greater cognitive impairment. Subtypes of trauma can be associated with different prognostic risks.

Genetic polymorphism of Trypanosoma cruzi bloodstream populations in adult chronic indeterminate Chagas disease patients from the E1224 clinical trial.

BACKGROUND: The role that the genetic diversity of natural Trypanosoma cruzi populations plays in response to trypanocidal treatment of chronic Chagas disease (CD) patients remains to be understood. We analysed the genetic polymorphisms of parasite bloodstream populations infecting chronic CD patients enrolled in the E1224 clinical trial. METHODS: A total of 506 baseline and post-treatment follow-up samples from 188 patients were analysed. T. cruzi satellite DNA (satDNA) was amplified and sequenced using cruzi1/cruzi2 primers, and samples with TcI/III, TcII, TcIV or hybrid satDNA sequences were identified. Minicircle signatures were obtained after kinetoplast DNA amplification using 121/122 primers and restriction enzyme digestion. Genetic distances between baseline and post-treatment minicircle signatures were estimated using the Jaccard coefficient. RESULTS: At baseline, 74.3% TcII, 17.9% hybrid and 7.8% TcI/III satDNA sequences were found, whereas at the end of follow-up the distribution was 55.2% TcII, 35.2% hybrid and 9.5% TcI/III. The placebo arm was the treatment group with the highest variation of satDNA sequences between baseline and post-treatment follow-up. Genetic distances between baseline and post-treatment minicircle signatures were similar among all treatment arms. No association between minicircle signature variability and satDNA type distribution was found. CONCLUSIONS: Genetic variability of T. cruzi bloodstream populations during post-treatment follow-up did not differ from that observed during chronic infection in the absence of treatment, suggesting that there were no selection events of E1224-resistant parasite populations. This is the first report documenting the genetic polymorphism of natural T. cruzi populations in chronic patients in the context of clinical trials with trypanocidal drugs.

Childhood trauma is associated with age at onset of symptoms, functioning, and cognition in patients with schizophrenia

Abstract Introduction Childhood trauma (CT) is known to be a vulnerability factor for schizophrenia, but the specific impacts of different trauma subtypes on the prognosis of these patients remains unclear. Objective To assess the relationships between the occurrence of overall CT and its subtypes with factors with known prognostic impact on schizophrenia, such as age at onset of symptoms, global functioning, and cognitive impairment in a sample of Brazilian patients. Methods One hundred and five stable patients diagnosed with schizophrenia according to DSM-5 criteria were evaluated using the Independent Living Skills Survey (ILSS; self-report global functioning), Schizophrenia Cognition Rating Scale (SCoRS; subjective cognitive impairment), and Childhood Trauma Questionnaire scales (CTQ; perceived overall CT, emotional neglect, physical neglect, physical abuse, and emotional and sexual abuse). Statistical analysis was performed with multivariate linear regression. Results After controlling for educational level and age, subjective cognitive impairment was directly correlated with overall perceived CT occurrence, emotional abuse, and sexual abuse. Self-report global functioning was inversely correlated with perceived overall CT occurrence, emotional abuse, and sexual abuse. Emotional abuse and physical abuse were also inversely correlated with age at onset of symptoms. Conclusions CT can be related to more severe prognoses in schizophrenia, impacting on early onset of symptoms, lower global functioning, and greater cognitive impairment. Subtypes of trauma can be associated with different prognostic risks.

Effects of EGF-coated titanium surfaces on adhesion and metabolism of bisphosphonate-treated human keratinocytes and gingival fibroblasts.

OBJECTIVE: To assess the effects of epidermal growth factor (EGF)-coated titanium (Ti) discs on the adhesion and metabolism of keratinocytes and gingival fibroblasts exposed to nitrogen-containing bisphosphonates. MATERIALS AND METHODS: Keratinocytes and fibroblasts were seeded (1 × 105 cells/disc) on Ti discs coated with EGF (100 nM). After 24 h, cells were exposed or not to sodium alendronate (SA) or zoledronic acid (ZA) at different concentrations (0 = control, 0.5, 1, or 5 µM) for 48 h. Cell adhesion to the substrates was evaluated by fluorescence microscopy. Cell viability (alamarBlue, n = 6) and synthesis of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2), and keratinocytes growth factor (KGF) (ELISA, n = 6) were assessed. Data were statistically analyzed by one-way ANOVA and Tukey tests (α = 0.05). RESULTS: Higher cell adhesion rate was observed when keratinocytes and fibroblasts were seeded onto EGF-coated discs in comparison to uncoated discs. ZA treatment hindered the adhesion of both cell lines on the Ti discs as well as reduced the viability and synthesis of VEGF, KGF and MMP-2 by cells (p < 0.05). SA treatment did not affect cell viability, but interfered negatively on the adhesion and synthesis of EGF and KGF by the cells (p < 0.05). EGF-coated surface increased cell viability and synthesis of growth factors as well as downregulated the synthesis of MMP-2 in comparison to control (p < 0.05). CONCLUSION: EGF applied on Ti surface improves the biological responses of oral mucosa cells exposed to SA and ZA. CLINICAL RELEVANCE: EGF-coating on titanium may be a suitable strategy to improve oral mucosa cellular events related to biological sealing, especially for patients under bisphosphonate therapy.

New regimens of benznidazole monotherapy and in combination with fosravuconazole for treatment of Chagas disease (BENDITA): a phase 2, double-blind, randomised trial.

BACKGROUND: Current treatment for Chagas disease with the only available drugs, benznidazole or nifurtimox, has substantial limitations, including long treatment duration and safety and tolerability concerns. We aimed to evaluate the efficacy and safety of new benznidazole monotherapy regimens and combinations with fosravuconazole, in the treatment of Chagas disease. METHODS: We did a double-blind, double-dummy, phase 2, multicentre, randomised trial in three outpatient units in Bolivia. Adults aged 18-50 years with chronic indeterminate Chagas disease, confirmed by serological testing and positive qualitative PCR results, were randomly assigned (1:1:1:1:1:1:1) to one of seven treatment groups using a balanced block randomisation scheme with an interactive response system. Participants were assigned to benznidazole 300 mg daily for 8 weeks, 4 weeks, or 2 weeks, benznidazole 150 mg daily for 4 weeks, benznidazole 150 mg daily for 4 weeks plus fosravuconazole, benznidazole 300 mg once per week for 8 weeks plus fosravuconazole, or placebo, with a 12-month follow-up period. The primary endpoints were sustained parasitological clearance at 6 months, defined as persistent negative qualitative PCR results from end of treatment, and incidence and severity of treatment-emergent adverse events, serious adverse events, and adverse events leading to treatment discontinuation. Primary efficacy analysis was based on the intention-to-treat and per-protocol populations and secondary efficacy analyses on the per-protocol population. Safety analyses were based on the as-treated population. Recruitment is now closed. This trial is registered with ClinicalTrials.gov, NCT03378661. FINDINGS: Between Nov 30, 2016, and July 27, 2017, we screened 518 patients, and 210 were enrolled and randomised. 30 patients (14%) were assigned to each treatment group. All 210 randomised patients were included in the intention-to-treat population, and 190 (90%) were included in the per-protocol population. In the intention-to-treat analysis, only one (3%) of 30 patients in the placebo group had sustained parasitological clearance at 6 months of follow-up. Sustained parasitological clearance at 6 months was observed in 25 (89%) of 28 patients receiving benznidazole 300 mg daily for 8 weeks (rate difference vs placebo 86% [95% CI 73-99]), 25 (89%) of 28 receiving benznidazole 300 mg daily for 4 weeks (86% [73-99]), 24 (83%) of 29 receiving benznidazole 300 mg daily for 2 weeks (79% [64-95]), 25 (83%) of 30 receiving benznidazole 150 mg daily for 4 weeks (80% [65-95]), 23 (85%) of 28 receiving benznidazole 150 mg daily for 4 weeks plus fosravuconazole (82% [67-97]), and 24 (83%) of 29 receiving benznidazole 300 mg weekly for 8 weeks plus fosravuconazole (79% [64-95]; p<0·0001 for all group comparisons with placebo). Six patients (3%) had ten serious adverse events (leukopenia [n=3], neutropenia [n=2], pyrexia, maculopapular rash, acute cholecystitis, biliary polyp, and breast cancer), eight had 12 severe adverse events (defined as interfering substantially with the patient's usual functions; elevated alanine aminotransferase [n=4], elevated gamma-glutamyltransferase [n=2], elevated aspartate aminotransferase [n=1], neutropenia [n=3], leukopenia [n=1], and breast cancer [n=1]), and 15 (7%) had adverse events that led to treatment discontinuation (most of these were in the groups who received benznidazole 300 mg daily for 8 weeks, benznidazole 300 mg once per week for 8 weeks plus fosravuconazole, and benznidazole 150 mg daily for 4 weeks plus fosravuconazole). No adverse events leading to treatment discontinuation were observed in patients treated with benznidazole 300 mg daily for 2 weeks or placebo. There were no treatment-related deaths. INTERPRETATION: Benznidazole induced effective antiparasitic response, regardless of treatment duration, dose, or combination with fosravuconazole, and was well tolerated in adult patients with chronic Chagas disease. Shorter or reduced regimens of benznidazole could substantially improve treatment tolerability and accessibility, but further studies are needed to confirm these results. FUNDING: Drugs for Neglected Diseases initiative (DNDi). TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Morphometric study of incisive canal and its anatomic variations in brazilian individuals.

Objective: To conduct a morphometric evaluation of the incisive canal, adjacent structures, and their anatomic variations in Brazilian individuals.Methods: A retrospective study was conducted using a sample of 157 multislice computed tomography images of adult Brazilian individuals of both sexes (20-96 years). The exam was performed with the RadiAnt DICOM Viewer 4.0.1 (64-bit) software that uses the DICOM PACS standard for visualization of medical and dental images.Results: The values for length and height of the canal, thickness of the palatine bone plate, and latero-lateral diameter of the incisive foramen were higher in men than in women (p < 0.05).Conclusion: The findings of this study demonstrated morphometric differences for the following parameters: latero-lateral diameter; width of canals at all levels measured; palatine bone plate height; canal length and palatine bone plate thickness in relation to the male and female sexes in the Brazilian population.

New chemotherapy regimens and biomarkers for Chagas disease: the rationale and design of the TESEO study, an open-label, randomised, prospective, phase-2 clinical trial in the Plurinational State of Bolivia.

INTRODUCTION: Chagas disease (CD) affects ~7 million people worldwide. Benznidazole (BZN) and nifurtimox (NFX) are the only approved drugs for CD chemotherapy. Although both drugs are highly effective in acute and paediatric infections, their efficacy in adults with chronic CD (CCD) is lower and variable. Moreover, the high incidence of adverse events (AEs) with both drugs has hampered their widespread use. Trials in CCD adults showed that quantitative PCR (qPCR) assays remain negative for 12 months after standard-of-care (SoC) BZN treatment in ~80% patients. BZN pharmacokinetic data and the nonsynchronous nature of the proliferative mammal-dwelling parasite stage suggested that a lower BZN/NFX dosing frequency, combined with standard or extended treatment duration, might have the same or better efficacy than either drug SoC, with fewer AEs. METHODS AND ANALYSIS: New ThErapies and Biomarkers for ChagaS infEctiOn (TESEO) is an open-label, randomised, prospective, phase-2 clinical trial, with six treatment arms (75 patients/arm, 450 patients). Primary objectives are to compare the safety and efficacy of two new proposed chemotherapy regimens of BZN and NFX in adults with CCD with the current SoC for BZN and NFX, evaluated by qPCR and biomarkers for 36 months posttreatment and correlated with CD conventional serology. Recruitment of patients was initiated on 18 December 2019 and on 20 May 2021, 450 patients (study goal) were randomised among the six treatment arms. The treatment phase was finalised on 18 August 2021. Secondary objectives include evaluation of population pharmacokinetics of both drugs in all treatment arms, the incidence of AEs, and parasite genotyping. ETHICS AND DISSEMINATION: The TESEO study was approved by the National Institutes of Health (NIH), U.S. Food and Drug Administration (FDA), federal regulatory agency of the Plurinational State of Bolivia and the Ethics Committees of the participating institutions. The results will be disseminated via publications in peer-reviewed journals, conferences and reports to the NIH, FDA and participating institutions. TRIAL REGISTRATION NUMBER: NCT03981523.

Profile of facial trauma in older adults cared for at a tertiary hospital of the Brazilian Federal District / Perfil do trauma de face em idosos atendidos em Hospital terciário do Distrito Federal

OBJECTIVES: The phenomenon of population aging and the remarkable inclusion of older adults in the economically active population has increased their participation in injuries and accidents, including facial trauma. The purpose of this study was to analyze the prevalence, etiology, and treatment of facial trauma in the older population of the Brazilian Federal District, as well as the gender, etiology, type of trauma, and treatment strategy regarding different age groups (60­69 years, 70­79 years, and 80 years or older). METHODS: This is a retrospective quantitative descriptive study using electronic medical records (Trackcare system) of older patients (aged ≥ 60 years) assisted at the Emergency Department of a tertiary hospital of the Federal District between 2016 and 2017 due to facial trauma. RESULTS: Out of 2382 records of patients with facial trauma, 139 (5.8%) were aged over 60 years. The main causes of facial trauma were falls, both in male and female patients. Facial contusion was the main diagnosis of facial trauma (25.2%), followed by fractures of the jaw (16.5%) and zygomatic complex (15.8%). Conservative treatment was the most common strategy adopted in the Emergency Department of Oral and Maxillofacial Surgery and Traumatology. CONCLUSIONS: This study showed a high prevalence of facial trauma in the geriatric population. Etiological factors such as falls and car accidents were highlighted in the studied groups. Conservative treatment and local guidelines were the preferred therapeutic approaches. Owing to the growth trend of the older population in the upcoming decades, exposure to risk factors for facial trauma tends to grow, thus requiring greater attention and specific knowledge from health professionals.

OBJETIVO: O envelhecimento da população e a inclusão marcante dos idosos na parcela economicamente ativa vêm aumentando a participação deles em traumatismos e acidentes, incluindo os que ocorrem na face. O objetivo deste trabalho foi analisar a prevalência, a etiologia e o tratamento do traumatismo de face na população idosa do Distrito Federal, assim como nas diferentes faixas etárias (60 ­ 69, 70 ­ 79 e 80 e mais), em relação a sexo, etiologia, tipo de trauma e tratamento. METODOLOGIA: Trata-se de estudo retrospectivo descritivo quantitativo, que utilizou prontuários eletrônicos (Sistema Trackcare) de pacientes idosos (≥ 60 anos) atendidos no pronto-socorro de hospital terciário do Distrito Federal, durante os anos de 2016 e 2017, por traumatismo de face. RESULTADOS: Do total de 2.382 prontuários de pacientes com traumatismo de face, 139 (5,8%) foram de idosos. O principal fator responsável pelo traumatismo na face foi a queda, tanto no sexo masculino como no feminino. A contusão na face foi o principal diagnóstico de traumatismo nessa região (25,2%), seguido por fratura de mandíbula (16,5%) e fratura do complexo zigomático (15,8%). O tratamento conservador foi o mais adotado no serviço de pronto-socorro de Cirurgia e Traumatologia Bucomaxilofacial. CONCLUSÕES: O presente estudo evidenciou uma elevada prevalência de traumas de face na população geriátrica. Fatores etiológicos como quedas e acidentes automobilísticos tiveram destaques nos grupos estudados. O tratamento conservador e orientações locais foram as condutas terapêuticas adotadas preferencialmente. Devido à tendência de crescimento da população idosa nas próximas décadas, bem como o perfil ativo que os idosos estão assumindo, a exposição a fatores de risco para traumas faciais tende a crescer, exigindo-se assim maior atenção e conhecimento específico por parte dos profissionais de saúde..