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O artigo tem como objetivo analisar a atuação do Poder Judiciário em três situações jurídicas distintas – o estabelecimento do toque de recolher para crianças e adolescentes por meio de Portarias Judiciais; a internação compulsória de dependentes em drogas e o julgamento de processos judiciais de estupro – verificando os sentidos de moralidade, normalidade e punição presentes no Sistema de Justiça em cada um desses casos. Nesse sentido, procura identificar o processo de construção de subjetividades relacionadas às situações descritas – o “menor”, o “louco” e a “mulher desonesta” –, verificando sob quais aspectos divergem da legislação atualmente em vigor no país. O trabalho foi realizado a partir da análise de documentos legislativos – Constituição Federal, Estatuto da Criança e do Adolescente, Lei nº 10.216/2001, dentre outros – e da pesquisa bibliográfica, destacando, no caso desta última, os conceitos trabalhados por Michel Foucault em suas obras. PALAVRAS-CHAVE: Poder Judiciário. Toque de recolher. Internação compulsória. Estupro. Subjetivação. Michel Foucault.

(1) Background: To analyze the prevalence and factors associated with diabetes mellitus in adults and the elderly in Rio Branco, Acre, Western Brazilian Amazon. (2) Methods: The R software version 4.0.5 was used for estimating the prevalence of diabetes mellitus, odds ratios, and 95% confidence intervals. Multiple analysis was conducted through hierarchical variable selection. (3) Results: 1.095 individuals aged 18 years and older participated in this study, with 6.4% of the respondents showing prevalence of diabetes mellitus. The prevalence of diabetes mellitus was positively associated with a prior medical diagnosis of obesity (OR: 3.2; 95% CI: 1.67–6.12), dyslipidemia (OR: 4.17; 95% CI: 2.08–8.36), and increasing age (OR: 1.07; 95% CI: 1.05–1.09). Conversely, an inverse association was observed with higher education (12 or more years of study; OR: 0.20; 95% CI: 0.07–0.61). (4) Conclusions: The prevalence of diabetes mellitus in the municipality of Rio Branco, Acre, Brazil, has significantly increased with advancing age. Education, obesity, and dyslipidemia were also identified as factors associated with diabetes mellitus in this population. Awareness campaigns regarding dietary patterns and lifestyle choices may serve as preventive and control measures.

Coagulation activation in immunothrombosis involves various pathways distinct from classical hemostasis, offering potential therapeutic targets to control inflammation-induced hypercoagulability while potentially sparing hemostasis. The Angiopoietin/Tie2 pathway, previously linked to embryonic angiogenesis and sepsis-related endothelial barrier regulation, was recently associated with coagulation activation in sepsis and COVID-19. This study explores the connection between key mediators of the Angiopoietin/Tie2 pathway and coagulation activation. The study included COVID-19 patients with hypoxia and healthy controls. Blood samples were processed to obtain platelet-free plasma, and frozen until analysis. Extracellular vesicles (EVs) in plasma were characterized and quantified using flow cytometry, and their tissue factor (TF) procoagulant activity was measured using a kinetic chromogenic method. Several markers of hemostasis were assessed. Levels of ANGPT1, ANGPT2, and soluble Tie2 correlated with markers of coagulation and platelet activation. EVs from platelets and endothelial cells were increased in COVID-19 patients, and a significant increase in TF+ EVs derived from endothelial cells was observed. In addition, ANGPT2 levels were associated with TF expression and activity in EVs. In conclusion, we provide further evidence for the involvement of the Angiopoietin/Tie2 pathway in the coagulopathy of COVID-19 mediated in part by release of EVs as a potential source of TF activity.

Este artigo baseia-se numa pesquisa realizada no contexto do Mestrado em Supervisão Pedagógica na Universidade Aberta, com o objetivo de entender qual o papel da supervisão pedagógica (SvP) nas práticas formativas, compreender o seu papel no desempenho profissional dos trabalhadores, analisar a perceção dos decisores da formação sobre modelos de supervisão e identificar os modelos de SvP presentes na formação contínua da Autoridade Tributária e Aduaneira (AT). No estudo, optou-se por uma abordagem mista de estudo de caso com finalidade exploratória e descritiva e foram empregues como técnicas de recolha de dados o inquérito por entrevista. Os resultados revelaram mudanças nas práticas formativas, visando preparar os funcionários para as suas funções atuais e futuras. A SvP da formação na AT mostrou-se pouco estruturada, com diferentes níveis e atores envolvidos, predominantemente vertical e diretiva, embora haja indícios de supervisão colaborativa.

Introdução. A COVID-19 impactou a garantia de uma alimentação adequada e saudável, inclusive entre universitários, que parecem constituir um grupo suscetível à Insegurança Alimentar (IA). Objetivo. Verificar a associação entre IA e marcadores de consumo alimentar em universitários durante a pandemia de COVID-19. Materiais e métodos. Estudo transversal com 5407 estudantes de instituições de ensino superior de todas as regiões do Brasil. Os dados foram coletados entre agosto/2020 e fevereiro/2021. O consumo alimentar foi avaliado por marcadores de alimentação saudável utilizados num inquérito nacional de saúde (VIGITEL). Os níveis de IA foram classificados pela Escala Brasileira de Insegurança Alimentar em Segurança Alimentar (SA) e IA leve, moderada e grave. A associação entre IA e marcadores de consumo foi avaliada por meio de regressão logística, considerando frequência semanal de consumo < 3 dias e ≥ 3 dias. Resultados. 37% dos universitários estavam em algum grau de IA. Verificou-se maior chance de baixa frequência de consumo de feijão (OR 1,81), verduras e legumes (OR 4,76), frutas (OR 3,99), lácteos (OR 3,98) e carnes (OR 3,41), e maiores chances de maior consumo de frango (OR 1,14) e ovos (OR 2,04) entre aqueles em IA (p

RESUMO Objetivos: Avaliar se a modelagem paterna, quanto à prática e/ou ao incentivo a dietas, pode predizer comportamentos de risco relacionados a transtornos alimentares (TAs) em crianças e adolescentes. Métodos: Foi realizada uma revisão sistemática dos estudos publicados até junho de 2022, disponíveis nas bases de dados indexadas — como PubMed, Biblioteca Virtual de Saúde, SciELO e Cochrane Library. Estudos transversais e longitudinais em línguas portuguesa, espanhola e inglesa foram incluídos e avaliados quanto ao risco de viés de acordo com a NewCastle – Ottawa Quality Assessment Scale . Resultados: Quatorze estudos foram considerados na revisão. A maioria deles é transversal (71,4%), proveniente dos Estados Unidos e de países europeus (57,1%), além de apresentar baixo risco de viés (85,7%). Grande parte dos trabalhos encontrou associações entre o incentivo a dietas por parte dos pais (modelagem direta) e comportamentos de risco em crianças e adolescentes, como o uso de métodos de controle de peso, a insatisfação corporal e a restrição alimentar. Poucos estudos relacionaram o hábito de o pai fazer dieta (modelagem indireta) com esses comportamentos. Conclusões: Os dados embasam a ideia de que a modelagem direta, ou seja, o incentivo verbal ao uso de dietas, pode ser muito danosa, principalmente em indivíduos que têm preocupações excessivas com peso e alimentação. Futuras pesquisas são necessárias para avaliar o impacto das práticas alimentares parentais e o desenvolvimento de possíveis ações de prevenção a problemas relacionados ao peso.

Objetivo: Estimar a prevalência e os fatores associados ao uso de suplementos alimentares por praticantes de atividades físicas em academias de Rio Branco, Acre. Materiais e Métodos: Estudo observacional analítico seccional desenvolvido em Rio Branco, em 2015. A coleta de dados foi realizada por entrevista semiestruturada com praticantes de atividade física em academias de Rio Branco. A variável dependente foi o uso autorreferido de suplemento alimentar e as variáveis independentes foram características socioeconômicas, demográficas, saúde e estilo de vida. Os fatores associados ao uso de suplementos alimentares foram identificados por meio de regressão logística não condicional. Resultados: Foram entrevistados 669 indivíduos com idade média de 27,89 anos (DP:10,11). Ao estratificar por sexo, 54,4% eram homens e 45,6% eram mulheres. A prevalência do uso de suplemento na semana da entrevista foi de 33%(IC95%:29,6–36,6), estando associado ao sexo masculino (ORaj:2,77; IC95%:1,94–3,96), ter entre 19 e 29 anos (ORaj:1,67; IC95%:1,01–2,77) e fazer academia a mais de um ano (ORaj:2,34; IC95%:1,64–3,34). Entre os que usaram suplementos na semana da entrevista, 79,7% referiram hipertrofia como objetivo da suplementação, 26,7% realizavam acompanhamento com profissional de saúde, 61,5% referiram não conhecer os efeitos do suplemento utilizado na saúde humana e 19,1% referiram algum efeito adverso. Conclusão: Observou-se elevado consumo de suplementos sem orientação profissional e desconhecimento dos efeitos na saúde humana. Como este foi o primeiro estudo com amostragem representativa das academias de Rio Branco, espera-se que possa contribuir para planejamento de novos estudos na Região Norte do Brasil e locais com características semelhantes.

The aim of the present study was to propose a quality prenatal (PN) care assessment model combining use and visit content (both adjusted for the weeks of gestation) to estimate inadequate PN care and associated factors in Rio Branco, Acre. A cross-sectional study was conducted using a population-based cohort of 1030 women in the city of Rio Branco in 2015. The use of PN care was classified according to the adapted Kotelchuck index by combining the performance of clinical-obstetric procedures adjusted for weeks of gestation. Levels of adequacy were built according to PN care use and content. Gross and adjusted odds ratios were estimated by using a logistic regression. The prevalence rates of inadequate prenatal care quality were 25.9% (Level-1), 54.8% (Level-2), 68.8% (Level-3), and 78.6% (Level-4). The factors associated with Level-1 were age ≤ 34 years (ORaj:3.74), not having a partner (ORaj:1.62), unplanned pregnancy (ORaj:1.73), and multiparity (ORaj:2.25); those for Level-2 comprised not having a partner (ORaj:1.82) and multiparity (ORaj:1.33); those for Level-3 were age ≤ 34 years (ORaj:3.31), not having a partner (Oraj:1.71), unplanned pregnancy (Oraj:1.45), PN in the private sector (Oraj:3.08), and multiparity (ORaj:2.17); those for Level 4 comprised not having a partner (ORaj:2.33), family income < 1 MW (ORaj:2.05), unplanned pregnancy (ORaj:1.41), PN in the private sector (ORaj:6.80), and multiparity (ORaj:1.49). The Kotelchuck index was proven efficient in assessing the combined effect of use and content in assessing PN care quality.

Objective: A sharp increase in pediatric thyroid cancer incidence is observed during adolescence, driven mainly by girls. Differences in disease pres entation across sexual maturity stages raise the question of whether sex steroids have a role in the heterogeneity. The aims of this study were to analyze the influe nce of puberty and sex on clinical presentation and prognosis and to evaluate the correlation between the expression of sex hormone receptors. Design and methods: Clinical records and immunohistochemical of specimens from 79 patients were analyzed. Puberty was analyzed by two criteria: end of puberty and beginning, in which the age of 10 was the cutoff. Results: Postpubertal were more frequently classified as having low-risk disease and a lower frequency of persistent disease, especially when the completion of puberty was used as the criteria. Male sex was associated with a higher ris k of persistent disease at the end of the observation period. Estrogen receptor α positivity was low in the entire sample, while progesterone receptor positivity was positive in 30% of the cases. Female hormone receptor expression was not associated with sex, American Thyroid Association risk score, persistent structural disease, or pubertal status. Conclusion: Our study showed that the completion of puberty correlated best with the clinical behaviour of pediatric thyroid cancer. It was also shown that postpubertal patients have a less aggressive initial presentation and better outcomes. However, this observation could not be explained by the expression of estrogen and progesterone receptors in the primary tumors.

ABSTRACT The amount of solar irradiation available in the growing environment can cause significant changes in physiology and leaf anatomy that enable crops to acclimate to different light conditions. In this sense, the objective was to characterize the leaf anatomy and to elucidate the morpho-physiological mechanisms of acclimation to high solar irradiance of heliconia genotypes during the initial stage of development under semiarid conditions. The experiment was conducted in the municipality of Petrolina, Pernambuco state, Brazil (09° 19’ 14” S, 40° 32’ 40” W, and 387 m of altitude) and the behavior of three heliconia genotypes (Heliconia rauliniana; H. bihai cv. Lobster Claw Two, and H. rostrata) grown in full sun and shading (50%) environments were evaluated. At 30 days after the implementation of the experiment, leaf anatomy, chlorophyll index, plant height, number of leaves, and number of tillers were analyzed. Heliconia leaves are characterized as amphistomatous with tetracytic stomata. In its main vein there are aerenchyma structures and hypodermis on the abaxial and adaxial sides. The responses to different light conditions in plants of H. bihai, H. rauliniana, and H. rostrata are genotype-specific. Furthermore, the anatomical structures and physiological changes observed in H. bihai and H. rauliniana plants demonstrate that these genotypes present greater plasticity and consequently greater potential for acclimation to high solar irradiation conditions. Thus, the genotypes H. rauliniana and H. bihai emerge as a potential alternative for cultivation in gardens or in open areas and for exploration as cut flower in regions with high solar irradiation availability.

BackgroundDiet quality is associated with psychobiological, psychological, biological, and physiological factors of individuals, and in the context of prolonged stress, such as the COVID-19 pandemic, it can lead to a worsening of the quality of food for undergraduates. This study aimed to analyze diet quality and associated factors in Brazilian undergraduates.MethodsData were collected from 4,799 undergraduate students from all Brazilian regions, from August 2020 to February 2021. The online questionnaire contained socioeconomic variables, the ESQUADA scale to assess diet quality, self-referred changes in weight, the Brazilian food insecurity scale (EBIA), sleep assessment and the perceived stress scale. Unconditional multiple logistic regression analysis was performed to study variables associated with poor and very poor diet quality.ResultsMost of participants presented a good diet quality (51.7%), while 9.8% had a poor or very poor diet quality and only 1.1% had an excellent diet quality. 58.2% of undergraduates reported to have an increase in weight during the pandemic and 74.3% of the students presented elevated stress during the pandemic. Logistic regressions showed students who gained weight during the pandemic presented the highest AOR = 1.56 (95% CI = 1.12–2.20) for poor or very poor diet quality. The elevated perceived stress was also associated with a higher AOR = 2.85 (95% CI = 1.71–4.74) for poor or very poor diet quality.ConclusionMost of the studied undergraduates presented a good diet quality. Nevertheless, poor/very poor diet quality was associated with higher perceived stress and weight gain. Our study indicated that policies should beaimed at the socioeconomically most vulnerable undergraduates, those in a situation of food and nutritional insecurity, high perceived stress, and who gained weight during the pandemic.

In this study, we developed functionalized polymeric micelles (FPMs) loaded with simvastatin (FPM-Sim) as a drug delivery system to target liver sinusoidal endothelial cells (LSECs) for preserving liver function in chronic liver disease (CLD). Polymeric micelles (PMs) were functionalized by coupling peptide ligands of LSEC membrane receptors CD32b, CD36 and ITGB3. Functionalization was confirmed via spectroscopy and electron microscopy. In vitro and in vivo FPM-Sim internalization was assessed by means of flow cytometry in LSECs, hepatocytes, Kupffer and hepatic stellate cells from healthy rats. Maximum tolerated dose assays were performed in healthy mice and efficacy studies of FPM-Sim were carried out in bile duct ligation (BDL) and thioacetamide (TAA) induction rat models of cirrhosis. Functionalization with the three peptide ligands resulted in stable formulations with a greater degree of in vivo internalization in LSECs than non-functionalized PMs. Administration of FPM-Sim in BDL rats reduced toxicity relative to free simvastatin, albeit with a moderate portal-pressure-lowering effect. In a less severe model of TAA-induced cirrhosis, treatment with FPM-CD32b-Sim nanoparticles for two weeks significantly decreased portal pressure, which was associated with a reduction in liver fibrosis, lower collagen expression as well as the stimulation of nitric oxide synthesis. In conclusion, CD32b-FPM stands out as a good nanotransporter for drug delivery, targeting LSECs, key inducers of liver injury.

Thrombotic primary antiphospholipid syndrome (t-PAPS) is an acquired condition characterized by heterogeneous thrombotic manifestations, which is intriguing since venous and arterial thrombosis appear to have distinct pathogenesis. Gene expression analysis may constitute a new approach to evaluate potential similarities or differences between the clinical manifestations of t-PAPS. Recently, dysregulation of the ANXA3, TNFAIP6, TXK, BACH2, and SERPINB2 genes has been associated with both arterial and venous thrombosis in the general population. Therefore, the aim of this study was to examine whether ANXA3, TNFAIP6, TXK, BACH2, and SERPINB2 expression was associated with t-PAPS. Gene expression was quantified by qPCR of total leukocyte mRNA. In this case-control study, 102 t-PAPS patients, 17 asymptomatic antiphospholipid (aPL) carriers and 100 controls were evaluated. Increased expression of ANXA3 (P = 0.008) and TNFAIP6 (P = 0.001) and decreased expression of the TXK gene (P = 0.0001) were associated with an increased risk of t-PAPS compared to the control. ANXA3 upregulation was more evident in cases of arterial thrombosis and multiple thrombotic events. There was no difference in the expression of these genes between triple and non-triple aPL positivity. ANXA3, TNFAIP6, TXK, BACH2, and SERPINB2 expression levels were also similar between aPL carriers and controls (P = 0.77; P = 0.48; P = 0.08; P = 0.73, and P = 0.13, respectively). In conclusion, our results showed that genes related to hemostasis (ANXA3) and immunity (TNFAIP6, TXK) are dysregulated in t-PAPS compared to controls. Gene dysregulation was not detected in aPL carriers and was not related to the aPL profile, suggesting that this gene signature is related to thrombotic manifestations rather than to aPL burden. Our results suggest that innate immunity and hemostasis pathways are associated with t-PAPS at a molecular level and may play a role in disease severity.

Endothelial barrier (EB) disruption contributes to acute lung injury in COVID-19, and levels of both VEGF-A and Ang-2, which are mediators of EB integrity, have been associated with COVID-19 severity. Here we explored the participation of additional mediators of barrier integrity in this process, as well as the potential of serum from COVID-19 patients to induce EB disruption in cell monolayers. In a cohort from a clinical trial consisting of thirty patients with COVID-19 that required hospital admission due to hypoxia we demonstrate that i) levels of soluble Tie2 were increase, and of soluble VE-cadherin were decreased when compared to healthy individuals; ii) sera from these patients induce barrier disruption in monolayers of endothelial cells; and iii) that the magnitude of this effect is proportional to disease severity and to circulating levels of VEGF-A and Ang-2. Our study confirms and extends previous findings on the pathogenesis of acute lung injury in COVID-19, reinforcing the concept that EB is a relevant component of this disease. Our results pave the way for future studies that can refine our understanding of the pathogenesis of acute lung injury in viral respiratory disorders, and contribute to the identification of new biomarkers and therapeutic targets for these conditions.

BackgroundAverse birth-outcomes still affect newborns worldwide. Although high-quality prenatal care is the main strategy to prevent these outcomes, the effect of prenatal care based on Kotelchuck index combined with consultation contents is still unclear. Thus, this article to evaluate the effect of the quality of prenatal care (PC) process on birth indicators in a cohort of puerperaes who attended maternity hospitals in Brazilian western Amazon, city of Rio Branco, in the state of Acre, Brazil, in 2015.MethodsThis research was a hospital-based cohort study. The sample consisted of 1,030 women who gave birth in maternity hospitals in the city between April 6 and June 30, 2015. This research was a hospital-based cohort study. The sample consisted of 1,030 women who gave birth in maternity hospitals in Rio Branco between April 6th. and June 30th., 2015. Prenatal care was classified as fully adequate when started ≤4th month; ≥80.0-109% expected consultations for GA according to the Kotelchuck Index; ≥5 records of blood pressure, weight, GA, fundal height, ≥4 records of fetal heart rate, fetal movements or equivalent to 75% of the number of consultations; in addition to recording ABO/RH, hemoglobin, VDRL, urine, glucose, anti-HIV and anti-toxoplamosis during the 1st trimester. The evaluated outcomes were low birth weight (LBW), preterm birth and vertical transmission of human immunodeficiency virus (HIV)/hepatitis/syphilis. Differences between proportions were assessed using the X² test, and the crude and adjusted odds ratios (OR) (95% CI) were estimated using unconditional logistic regression.ResultsOverall cohort, the outcomes incidences were 8.8% for LBW, 9.2% for preterm birth, and 1.1% for vertical transmission (syphilis/HIV/hepatitis). Crude and adjusted OR showed that inadequate PC increased the risk statistically significant of LBW (ORcrude: 1.84; 95%CI: 0.99-3.44; ORadjusted: 1.87; 95%CI: 1.00-3.52), and preterm birth (ORcrude: 1.79; 95%CI: 1.00-3.29; ORadjusted: 3.98; 95%CI: 1.40-11.29).ConclusionThe results draw attention to the importance of quality PC in reducing the risks of LBW, preterm birth, and vertical transmission of syphilis/HIV/hepatitis. Moreover, using this proposed quality prenatal care indicator based on Kotelchuck index combined with consultations contents adjusted by GA may accurately predict unfavorable outcomes.

Abstract Objective: to analyze the factors associated with positive self-perceived evaluation of prenatal care among users of Primary Health Care (PHC). Methods: the analytical cross-sectional study was carried out with secondary data from the 3rd Module of the 2nd cycle (2013 / 2014) of the External Evaluation of the Improvement of Access and Quality of Primary Care Program (PMAQ-AB – Portuguese acronym), collected from users in the Basic Health Units (BHU) that joined the PMAQ-AB in Brazil. The hierarchical analysis was performed using a theoretical model and logistic regression was performed between the self-perceived evaluation (positive - very good/good or negative - regular/poor/very bad) and the sociodemographic characteristics, prenatal care and health service evaluation (p

Objectives: To analyze the time trend of Diabetes mellitus in adults in Rio Branco, Acre in the years 2006 to 2020. Methods: This is an ecological observational study of time series, with data from the Surveillance System of Risk and Protection Factors for Chronic Diseases by Telephone Survey (VIGITEL). The Joinpoint Regression Analysis v.4.6.0.0 software was used to estimate the annual percentage change (APC) and 95% confidence intervals (95% CI). Results: In Rio Branco, the prevalence of diabetes mellitus (DM) in adults in the first year of the survey (2006) was 2.4%, with a higher prevalence in 2015 of 4.8%, and in the last year (2020) there was a reduction to 2.4%. In the elderly public, there was an increase from 16.2% in 2006 to 21.0% in 2020, with the highest frequency of DM in 2016, 24.6%. From 2006 to 2014, the annual percentage change (APC) of DM in the elderly showed a significant increase of 5.7% per year (95%CI: 2.6;8.9), as well as for schooling from 0 to 8 years of schooling (APC: 5.3%; 95%CI: 2.7;7.9) during the period from 2006 to 2015. Ascending trends in DM were observed among male adults, with an APC of 5.9% per year (95%CI: 0.9; 11.1) until 2018, as well as for non-consumption of soft drinks in this same public (APC: 5.2%; 95%CI: 0.5;10.1) until 2015. Conclusion: Government strategies against diabetes must be intensified in order to raise awareness among different age groups and population classes about the prevention, treatment and control of this disease.

Kirsten rat sarcoma (KRAS) is a small GTPase which acts as a molecular switch to regulate several cell biological processes including cell survival, proliferation, and differentiation. Alterations in KRAS have been found in 25% of all human cancers, with pancreatic cancer (90%), colorectal cancer (45%), and lung cancer (35%) being the types of cancer with the highest mutation rates. KRAS oncogenic mutations are not only responsible for malignant cell transformation and tumor development but also related to poor prognosis, low survival rate, and resistance to chemotherapy. Although different strategies have been developed to specifically target this oncoprotein over the last few decades, almost all of them have failed, relying on the current therapeutic solutions to target proteins involved in the KRAS pathway using chemical or gene therapy. Nanomedicine can certainly bring a solution for the lack of specificity and effectiveness of anti-KRAS therapy. Therefore, nanoparticles of different natures are being developed to improve the therapeutic index of drugs, genetic material, and/or biomolecules and to allow their delivery specifically into the cells of interest. The present work aims to summarize the most recent advances related to the use of nanotechnology for the development of new therapeutic strategies against KRAS-mutated cancers.

O projeto de extensão “Elas por Elas” foi criado em 2018, no âmbito do curso de Direito da Universidade Federal Fluminense (Campus Macaé). Dentro de uma perspectiva de Educação Jurídica Popular, a ação extensionista tem como escopo o desenvolvimento de um curso de formação e capacitação em direito das mulheres para líderes comunitárias e outras mulheres residentes no Município de Macaé (RJ), para que elas possam, posteriormente, atuar como multiplicadoras deste conhecimento em suas comunidades. O presente artigo tem como objetivo apresentar o projeto “Elas por Elas”, suas referências teóricas e metodológicas, bem como os resultados da atividade no ano de 2019. Para tanto, utiliza, a pesquisa bibliográfica e a análise de documentos produzidos pelas próprias participantes do curso durante a atividade extensionista. Conclui-se pela importância do projeto, bem como de outras atividades de educação jurídica popular, para a formação de redes de informação sobre os direitos das mulheres. http://dx.doi.org/10.35700/ca.2020.ano7n13.p24-34.2946

Resumo Objetivo Descrever, comparativamente, as prevalências de doenças crônicas não transmissíveis, consumo de alimentos ultraprocessados, álcool e tabaco, estimadas pelo Sistema de Vigilância de Fatores de Risco e Proteção para Doenças Crônicas por Inquérito Telefônico (Vigitel) e pela Pesquisa Nacional de Saúde (PNS), em Rio Branco, Acre, Brasil. Métodos Estudo transversal, sobre dados sociodemográficos, de saúde e estilo de vida de inquéritos realizados em 2019. Foram descritas as prevalências e intervalos de confiança de 95% (IC95%), e calculadas as diferenças percentuais. Resultados Dos 3.037 indivíduos avaliados, observaram-se prevalências similares com diferença para pessoas de raça/cor da pele parda, entre Vigitel (60,3%; IC95% 56,2;64,3) e PNS (70,8%; IC95% 67,4;73,9). Na estratificação por sexo, diferenças percentuais entre os inquéritos foram observadas para obesidade (masculino= 6,5%; feminino= 0,4%), tabagismo (masculino= 4,0%; feminino= -1,5%) e consumo abusivo de álcool (masculino= 6,9%; feminino= -2,5%), embora com IC95% sobrepostos. Conclusão As estimativas avaliadas em ambos os inquéritos foram similares.

Hemostatic abnormalities and thrombotic risk associated with coronavirus disease 2019 (COVID-19) are among the most discussed topics in the management of this disease. The aim of this position paper is to provide the opinion of Brazilian experts on the thromboprophylaxis and management of thrombotic events in patients with suspected COVID-19, in the sphere of healthcare in Brazil. To do so, the Brazilian Society of Thrombosis and Hemostasis (BSTH) and the Thrombosis and Hemostasis Committee of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy (ABHH) have constituted a panel of experts to carefully review and discuss the available evidence about this topic. The data discussed in this document was reviewed by May 9, 2020. Recommendations and suggestions reflect the opinion of the panel and should be reviewed periodically as new evidence emerges.

Background and purpose Thrombotic microangiopathy (TMA) is a group of microvascular occlusive disorders that presents with neurological involvement in up to 87% of the cases. Although the central nervous system (CNS) is an important target organ in TMA, the role of neurological manifestations in the disease clinical course is not well established. In this study, we described the neurological manifestations and CNS radiological aspects in patients with a first, acute TMA event. We also examined the association between severe neurological involvement and adverse clinical outcomes in TMA. Methods A cohort of patients diagnosed with a first TMA event between 1995 and 2016 was included, their medical charts and imaging tests were retrospectively evaluated. Results A total of 49 patients were included, 85.7% were women and the mean age was 36.5 years-old (SD 13.0). Neurological manifestations were described in 85.7% of the patients, most of them (88%) were considered severe and consisted of confusion, compromised sensorimotor function, stupor, seizures, and personality change. Imaging tests were performed in 62% of the patients with neurological manifestations and detected acute CNS lesions, such as posterior reversible encephalopathy syndrome, hemorrhagic and ischemic stroke were observed, in 7 (27%) of them. While the need for intensive care unit admission was greater and longer among patients with severe neurological manifestations, the number of plasma exchange sessions, the total duration of hospitalization and in-hospital death were similar between groups. Conclusions Severe neurological manifestations are common in first TMA events and are responsible for a worse disease presentation at admission. While the effect of neurological manifestations on acute TMA clinical course seems to be modest, these manifestations may have an important impact on the development of chronic cognitive impairment, which highlights the need for proper diagnosis and treatment.

Despite all the advances seen in recent years, the severe adverse effects and low specificity of conventional chemotherapy are still challenging problems regarding cancer treatment. Nanotechnology has helped to address these questions, making important contributions in the oncological field. The use of nanoparticles has allowed the improvement of the therapeutic index of several conventional drugs and facilitates the tumoral accumulation and intracellular delivery of complex biomolecules, such as genetic material. Among the wide range of nanotechnology-based drug delivery systems (nanoDDS), solid lipid nanoparticles (SLNs) have emerged as promising systems for delivering different types of cargo. Their solid lipid core, at room and body temperature, provides SLNs with higher stability than other formulations. Moreover, SLNs offer other important features, namely the possibility to perform active targeting, sustained and controlled release, and multifunctional therapy. Furthermore, with the possibility to use biocompatible and physiologic materials and easy scale-up and low-cost production methods, SLNs meet the principal requirements of an ideal nanoDDS. The present work aims to summarize the main aspects related to SLNs, including composition, production methods, and administration routes, as well as to show the most recent studies about the use of SLNs for cancer treatment.

In light of the growing bacterial resistance to antibiotics and in the absence of the development of new antimicrobial agents, numerous antimicrobial delivery systems over the past decades have been developed with the aim to provide new alternatives to the antimicrobial treatment of infections. However, there are few studies that focus on the development of a rational design that is accurate based on a set of theoretical-computational methods that permit the prediction and the understanding of hydrogels regarding their interaction with cationic antimicrobial peptides (cAMPs) as potential sustained and localized delivery nanoplatforms of cAMP. To this aim, we employed docking and Molecular Dynamics simulations (MDs) that allowed us to propose a rational selection of hydrogel candidates based on the propensity to form intermolecular interactions with two types of cAMPs (MP-L and NCP-3a). For the design of the hydrogels, specific building blocks were considered, named monomers (MN), co-monomers (CM), and cross-linkers (CL). These building blocks were ranked by considering the interaction with two peptides (MP-L and NCP-3a) as receptors. The better proposed hydrogel candidates were composed of MN3-CM7-CL1 and MN4-CM5-CL1 termed HG1 and HG2, respectively. The results obtained by MDs show that the biggest differences between the hydrogels are in the CM, where HG2 has two carboxylic acids that allow the forming of greater amounts of hydrogen bonds (HBs) and salt bridges (SBs) with both cAMPs. Therefore, using theoretical-computational methods allowed for the obtaining of the best virtual hydrogel candidates according to affinity with the specific cAMP. In conclusion, this study showed that HG2 is the better candidate for future in vitro or in vivo experiments due to its possible capacity as a depot system and its potential sustained and localized delivery system of cAMP.

ABSTRACT Objective: Because serum calcitonin (CT) is a reliable marker of the presence, volume, and extent of disease in medullary thyroid cancer (MTC), both the ATA and NCCN guidelines use the 2-3 month post-operative CT value as the primary response to therapy variable that determines the type and intensity of follow up evaluations. We hypothesized that the calcitonin would nadir to undetectable levels within 1 month of a curative surgical procedure. Subjects and methods: This retrospective review identified 105 patients with hereditary and sporadic MTC who had at least two serial basal CT measurements done in the first three months after primary surgery. Results: When evaluated one year after initial surgery, 42 patients (42/105, 40%) achieved an undetectable basal calcitonin level without additional therapies and 56 patients (56/84, 67%) demonstrated a CEA within the normal reference range. In patients destined to have an undetectable CT as the best response to initial therapy, the calcitonin was undetectable by 1 month after surgery in 97% (41/42 patients). Similarly, in patients destined to have a normalize their CEA, the CEA was within the reference range by 1 month post-operatively in 63% and by 6 months in 98%. By 6 months after curative initial surgery, 100% of patients had achieved a nadir undetectable calcitonin, 98% had reached the CEA nadir, and 97% had achieved normalization of both the calcitonin and CEA. Conclusion: The 1 month CT value is a reliable marker of response to therapy that allows earlier risk stratification than the currently recommended 2-3 month CT measurement.

ABSTRACT OBJECTIVE: To characterize breastfeeding patterns in the first six months of life and factors associated with early weaning in a birth-cohort in Rio Branco, state of Acre. METHODS: This is a prospective study with all babies born between April and June 2015. The mothers were interviewed soon after birth and between 6 and 15 months postpartum. At hospital discharge, breastfeeding was defined as exclusively (EBF), and breastfeeding (BF). In the follow-up, breastfeeding patterns were exclusive breastfeeding (EBF), predominant breastfeeding (PBF), and breastfeeding (BF). The interruption of breastfeeding in the first six months was classified as early weaning. The Kaplan Meier method (log-rank: 95%) was used to estimate the conditional probability of change in breastfeeding pattern, and early weaning risk. Crude and adjusted proportional Cox regression models, and their respective 95% confidence intervals (95%CI), were used to analyze the factors associated with early weaning. RESULTS: The study included 833 infants in EBF (95.4%) and BF (4.6%) at hospital discharge. During the first six months of life, the infant likely discharged in EBF remaining in EBF, becoming PBF, and BF, were respectively 16.4%, 32.3%, and 56.5%. The weaning likely at six months was statistically higher for infants discharged in BF (47.4%) when compared with those discharged in EBF (26%). Factors associated with early weaning were BF at hospital discharge (HR = 1.82; 95%CI 1.06–3.11), no mother cross-breastfeeding (HR = 2.50; 95%CI 1.59–3.94), pacifier use (HR = 6.23; 95%CI 4.52–8.60), less than six months of breastfeeding intention (HR = 1.93; 95%CI 1.25–2.98), lack of breastfeeding in the first hour of life (HR = 1.45; 95%CI 1.10–1.92), and pregnancy alcohol consumption (HR = 1.88; 95%CI 1.34–2.90). CONCLUSION: Compared to infants in EBF, those in BF at hospital discharge were more likely to wean. Public health efforts should prioritize EBF at hospital discharge, promote breastfeeding in the first hour of life, and prevent alcohol consumption risks during pregnancy, cross-breastfeeding and pacifier use.

BackgroundEfficient and early triage of hospitalized Covid-19 patients to detect those with higher risk of severe disease is essential for appropriate case management.MethodsWe trained, validated, and externally tested a machine-learning model to early identify patients who will die or require mechanical ventilation during hospitalization from clinical and laboratory features obtained at admission. A development cohort with 918 Covid-19 patients was used for training and internal validation, and 352 patients from another hospital were used for external testing. Performance of the model was evaluated by calculating the area under the receiver-operating-characteristic curve (AUC), sensitivity and specificity.ResultsA total of 363 of 918 (39.5%) and 128 of 352 (36.4%) Covid-19 patients from the development and external testing cohort, respectively, required mechanical ventilation or died during hospitalization. In the development cohort, the model obtained an AUC of 0.85 (95% confidence interval [CI], 0.82 to 0.87) for predicting severity of disease progression. Variables ranked according to their contribution to the model were the peripheral blood oxygen saturation (SpO2)/fraction of inspired oxygen (FiO2) ratio, age, estimated glomerular filtration rate, procalcitonin, C-reactive protein, updated Charlson comorbidity index and lymphocytes. In the external testing cohort, the model performed an AUC of 0.83 (95% CI, 0.81 to 0.85). This model is deployed in an open source calculator, in which Covid-19 patients at admission are individually stratified as being at high or non-high risk for severe disease progression.ConclusionsThis machine-learning model, applied at hospital admission, predicts risk of severe disease progression in Covid-19 patients.

La coagulopatía y la trombosis asociadas a la enfermedad por coronavirus 2019 (COVID-19) representan un problema importante en el manejo de esta enfermedad. Los estudios clínicos de los últimos meses han demostrado que los pacientes con COVID-19 presentan un estado de hipercoagulabilidad particular, en el que se observa un aumento notable del dímero D concomitante con niveles elevados de fibrinógeno. El estado de hipercoagulabilidad conduce a un mayor riesgo de trombosis, que parece ser mayor entre aquellos pacientes con síntomas críticos de COVID-19. El mejor enfoque terapéutico para prevenir los eventos trombóticos en esta nueva enfermedad aún no se ha determinado y han surgido varias preguntas con respecto a la tromboprofilaxia, como el momento adecuado para iniciar la anticoagulación, el tipo de anticoagulante y el régimen de dosis. Para abordar estas preocupaciones, varias sociedades médicas han publicado artículos de posición para brindar la opinión de expertos en trombosis sobre el manejo de la coagulopatía y trombosis asociadas a COVID-19. El Grupo Cooperativo Latinoamericano de Hemostasia y Trombosis (Grupo CLAHT) ha convocado a un panel de expertos en trombosis y hemostasia para discutir los datos disponibles sobre este tema. El objetivo de esta revisión es resumir la evidencia actual con respecto al deterioro hemostático y el riesgo trombótico en el COVID-19 y proporcionar una opinión cuidadosamente revisada de los expertos latinoamericanos sobre la tromboprofilaxis y el manejo de eventos trombóticos y coagulopatía en pacientes con sospecha de COVID-19.

This practical guidance, endorsed by the Brazilian Society of Thrombosis and Hemostasis and The Brazilian Society of Angiology and Vascular Surgery, the International Union of Angiology and the European Venous Forum, aims to provide physicians with clear guidance, based on current best evidence-based data, on clinical strategies to manage antithrombotic strategies in patients with coronavirus disease 2019.

Resumo O objetivo deste trabalho foi avaliar a eficácia de parte de um programa para promover a autorregulação da aprendizagem na educação superior. Participaram 26 ingressantes com idade média de 20,65 (DP = 3,35) provenientes de diferentes cursos de graduação de uma universidade pública, os quais participaram de uma atividade não obrigatória, organizada em seis encontros de 90 minutos cada um. Medidas de autorrelato foram aplicadas no pré e pós-teste a fim de comparar as variáveis dependentes: conhecimento das estratégias de aprendizagem, processos de autorregulação da aprendizagem, instrumentalidade percebida, autoeficácia para autorregular-se e para a formação superior. De acordo com a comparação entre o pré e pós-teste, os resultados são favoráveis no pós-teste para as variáveis conhecimento das estratégias de aprendizagem, autorregulação da aprendizagem e autoeficácia para autorregular-se. Esses resultados sugerem que a autorregulação da aprendizagem de ingressantes pode ser potencializada por meio do programa educacional “Cartas do Gervásio ao seu Umbigo”.

Development of RNA interference-based therapies with appropriate therapeutic window remains a challenge for advanced cancers. Because cancer stem cells (CSC) are responsible of sustaining the metastatic spread of the disease to distal organs and the progressive gain of resistance of advanced cancers, new anticancer therapies should be validated specifically for this subpopulation of cells. A new amphihilic-based gene delivery system that combines Pluronic® F127 micelles with polyplexes spontaneously formed by electrostatic interaction between anionic siRNA and cationic polyethylenimine (PEI) 10K, was designed (PM). Resultant PM gather the requirements for an efficient and safe transport of siRNA in terms of its physicochemical characteristics, internalization capacity, toxicity profile and silencing efficacy. PM were loaded with a siRNA against AKT2, an important oncogene involved in breast cancer tumorigenesis, with a special role in CSC malignancy. Efficacy of siAKT2-PM was validated in CSC isolated from two breast cancer cell lines: MCF-7 and Triple Negative MDA-MB-231 corresponding to an aggressive subtype of breast cancer. In both cases, we observed significant reduction on cell invasion capacity and strong inhibition of mammosphere formation after treatment. These results prompt AKT2 inhibition as a powerful therapeutic target against CSC and pave the way to the appearance of more effective nanomedicine-based gene therapies aimed to prevent CSC-related tumor recurrence.

Objetivo: Analisar a prevalência e possíveis fatores associados às anomalias congênitas em um município do estado do Acre. Métodos: Estudo transversal, descritivo, baseado nos dados do Sistema de Informações sobre Nascidos Vivos (SINASC) do município de Rio Branco, Acre, Brasil, no período de 2001 a 2013. A variável desfecho foi a presença de anomalias congênitas e as variáveis independentes estavam relacionadas à mãe e ao nascido vivo. Odds Ratio (OR) e intervalos de confiança de 95% foram estimados por regressão logística. Resultados: A prevalência de anomalias congênitas esteve presente em 0,2% dos nascidos vivos no período analisado, e as mais frequentes foram: as deformidades osteomusculares (41,3%), seguidas das malformações do sistema nervoso (17,9%); observando-se associação com a idade da mãe,

As alterações fisiológicas que ocorrem no organismo feminino durante o período gestacional é assunto bastante explorado pelos pesquisadores e encontra-se bem elucidado pela literatura; porém a temática relativa à farmacocinética e os mecanismos de teratogenicidade dos fármacos neste organismo em processo de alterações fisiológicas ainda encontra-se pouco explorado. O objetivo desta pesquisa foi revisar e contribuir para ampliar o conhecimento científico acerca da farmacocinética e dos mecanismos de teratogenicidade dos fármacos na gestação.

Objective: To determine the prevalence and to analyze factors associated with breastfeeding in the first hour of life in Rio Branco, Acre. Methods: A cross-sectional population-based study was conducted with 1144 mother / newborn binomials belonging to a maternal-infant cohort in Rio Branco, capital of Acre State, Brazil. The data were collected in the only two maternity hospitals in the capital. The dependent variable is breastfeeding in the first hour of life and its associated factors were identified through multiple and hierarchical logistic regression. Results: The prevalence of breastfeeding in the first hour of life in Rio Branco was 58.2% (95% CI: 55.2% - 61.2%). At distal and intermediate levels were associated with the outcome: maternal schooling, socioeconomic class, number of residents at home, maternal work and hypertension during pregnancy. In the proximal model, breastfeeding in the first hour of life was inversely associated with gestational hypertension (OR: 0.68, 95% CI: 0.47-0.98), cesarean section (OR: 0.15, 95% CI: 0.11-0.20) and low birth weight (OR: 0.32, 95% CI: 0.19 - 0.55). Conclusion: The main obstacles to breastfeeding in the first hour of life in Rio Branco are cesarean delivery and low birth weight. DOI: 10.12957/demetra.2019.43809

The biological relevance of fibrinolysis to the host response to sepsis is illustrated by pathogens such as S. pyogenes and Y. pestis, whose virulence factors are proteins that challenge the balance between pro- and anti-fibrinolytic factors of the host, and by the consistent finding of hypofibrinolysis in the early stages of sepsis. Whether this hypofibrinolytic response is beneficial or detrimental to the host, by containing the spread of pathogens while at the same time limiting the access of immune cell to infectious foci, is still a matter of debate. Tranexamic acid (TnxAc) is an antifibrinolytic agent that is being increasingly used to prevent and control bleeding in conditions such as elective orthopedic surgery, trauma, and post-partum-hemorrhage, which are frequently followed by infection and sepsis. Here we used a model of polymicrobial sepsis to evaluate whether hypofibrinolysis induced by TnxAc influenced survival, tissue injury and pathogen spread. Mice were treated with two doses of TnxAc bid for 48h, and then sepsis was induced by cecal ligation and puncture. Despite the induction of hypofibrinolysis by TnxAc, no difference could be observed in survival, tissue injury (measured by biochemical and histological parameters), cytokine levels or pathogen spread. Our results contribute with a new piece of data to the understanding of the complex interplay between fibrinolysis and innate immunity. While our results do not support the use of TnxAc in sepsis, they also address the thrombotic safety of TnxAc, a low cost and widely used agent to prevent bleeding.

The melon crop is normally developed in semiarid regions, where water resources are limited. This scarcity of water is a strong stressor on the crops, and requires the supplementation of existing water supplies with poor quality water, especially saline water. This can impede the growth and production of plants; however, the use of tolerant genotypes may minimize this problem. Thus, a greenhouse experiment was developed at the Federal University of Campina Grande - UFCG, Pombal Campus, Paraiba State, Brazil, in order to study the emergence, initial growth, and tolerance of melon cultivars irrigated with waters of different salt content. We studied three melon cultivars (Gaúcho Redondo, Gaúcho Casca de Carvalho and Halles Best Jumbo) irrigated with five levels of saline water (0.6; 1.2; 1.8; 2.4; and 3.0 dS m-1), arranged in a 3 x 5 factorial scheme, with the treatments distributed in a randomized block design with four replications. The plants seeds were monitored for 30 days after sowing, and at 30 days the growth and salinity tolerance index was evaluated. Cultivar Halles Best Jumbo was the most tolerant to saline water during initial stage of growth, while the Gaucho Redondo was more sensitive to salinity. It was found that saline waters up to 1.8 dS m-1 were suitable for irrigation of melon plants round Gaucho and waters up to 2.4 dS m-1 could be used for irrigation of Gaucho Casca de Carvalho and Halles Best Jumbo crops during the initial growth phase.

Within tumors, Cancer Stem Cell (CSC) subpopulation has an important role in maintaining growth and dissemination while preserving high resistance against current treatments. It has been shown that, when CSCs are eliminated, the surrounding Differentiated Cancer Cells (DCCs) may reverse their phenotype and gain CSC-like features to preserve tumor progression and ensure tumor survival. This strongly suggests the existence of paracrine communication within tumor cells. It is evidenced that the molecular crosstalk is at least partly mediated by Extracellular Vesicles (EVs), which are cell-derived membranous nanoparticles that contain and transport complex molecules that can affect and modify the biological behavior of distal cells and their molecular background. This ability of directional transport of small molecules prospects EVs as natural Drug Delivery Systems (DDS). EVs present inherent homing abilities and are less immunogenic than synthetic nanoparticles, in general. Currently, strong efforts are focused into the development and improvement of EV-based DDS. Even though EV-DDS have already reached early phases in clinical trials, their clinical application is still far from commercialization since protocols for EVs loading, modification and isolation need to be standardized for large-scale production. Here, we summarized recent knowledge regarding the use of EVs as natural DDS against CSCs and cancer resistance.

Inclusion bodies (IBs) are protein nanoclusters obtained during recombinant protein production processes, and several studies have demonstrated their potential as biomaterials for therapeutic protein delivery. Nevertheless, IBs have been, so far, exclusively sifted by their biological activity in vitro to be considered in further protein-based treatments in vivo. Matrix metalloproteinase-9 (MMP-9) protein, which has an important role facilitating the migration of immune cells, was used as model protein. The MMP-9 IBs were compared with their soluble counterpart and with MMP-9 encapsulated in polymeric-based micelles (PM) through ionic and covalent binding. The soluble MMP-9 and the MMP-9-ionic PM showed the highest activity values in vitro. IBs showed the lowest activity values in vitro, but the specific activity evolution in 50% bovine serum at room temperature proved that they were the most stable format. The data obtained with the use of an air-pouch mouse model showed that MMP-9 IBs presented the highest in vivo activity compared to the soluble MMP-9, which was associated only to a low and a transitory peak of activity. These results demonstrated that the in vivo performance is the addition of many parameters that did not always correlate with the in vitro behavior of the protein of interest, becoming especially relevant at evaluating the potential of IBs as a protein-based nanomaterial for therapeutic purposes.

Structural maintenance of chromosomes protein 2 (SMC2) is a central component of the condensin complex involved in DNA supercoiling, an essential process for embryonic stem cell survival. SMC2 over-expression has been related with tumorigenesis and cancer malignancy and its inhibition is regarded as a potential therapeutic strategy even though no drugs are currently available. Here, we propose to inhibit SMC2 by intracellular delivery of specific antibodies against the SMC2 protein. This strategy aims to reduce cancer malignancy by targeting cancer stem cells (CSC), the tumoral subpopulation responsible of tumor recurrence and metastasis. In order to prevent degradation and improve cellular internalization, anti-SMC2 antibodies (Ab-SMC2) were delivered by polymeric micelles (PM) based on Pluronic® F127 amphiphilic polymers. Importantly, scaffolding the Ab-SMC2 onto nanoparticles allowed its cellular internalization and highly increased its efficacy in terms of cytotoxicity and inhibition of tumorsphere formation in MDA-MB-231 and HCT116 breast and colon cancer cell lines, respectively. Moreover, in the case of the HCT116 cell line G1, cell-cycle arrest was also observed. In contrast, no effects from free Ab-SMC2 were detected in any case. Further, combination therapy of anti-SMC2 micelles with paclitaxel (PTX) and 5-Fluorouracil (5-FU) was also explored. For this, PTX and 5-FU were respectively loaded into an anti-SMC2 decorated PM. The efficacy of both encapsulated drugs was higher than their free forms in both the HCT116 and MDA-MB-231 cell lines. Remarkably, micelles loaded with Ab-SMC2 and PTX showed the highest efficacy in terms of inhibition of tumorsphere formation in HCT116 cells. Accordingly, our data clearly suggest an effective intracellular release of antibodies targeting SMC2 in these cell models and, further, strong cytotoxicity against CSC, alone and in combined treatments with Standard-of-Care drugs.

The search for an ideal gene delivery system is a long and laborious process in which several factors from the first idea to final formulation, including main challenges, peaks and troughs, should be deeply taken into consideration to ensure adequate biological safety and in vivo efficacy endpoints. Arachidonate 5-lipoxygenase (ALOX5), a crucial player related with cancer development and in particular with cancer stem cells malignancy. In this work we describe the process behind the development of a small interfering RNA (siRNA) delivery system to inhibit ALOX5 in cancer stem cells (CSC), as a model target gene. We started by screening chitosan polyplexes, among different types of chitosan in different complexation conditions. Due to the low silencing efficacy obtained, chitosan polyplexes were combined with Pluronic®-based polymeric micelles with recognized advantages regarding gene transfection. We tested different types of polymeric particles to improve the biological efficacy of chitosan polyplexes. Nevertheless, limited transfection efficiency was still detected. The well-established polyethyleneimine (PEI) cationic polymer was used in substitution of chitosan, in combination with polymeric micelles, originating PEI-siRNA-Pluronic® systems. The presence of Pluronic® F127 in the formulation showed to be of utmost importance because not only the silencing activity of the polyplexes was improved, but also PEI-associated toxicity was clearly reduced. This, allowed to increase the amount of PEI inside the system and its overall efficacy. Indeed, different types of PEI, N/P ratios and preparation methods were tested until an optimal formulation composed by PEI 10k branched-based polyplexes at an N/P ratio of 50 combined with micelles of Pluronic® F127 was selected. This combined micelle presented adequate technological properties, safety profile, and biological efficacy, resulting in high ALOX5 gene silencing and strong reduction of invasion and transformation capabilities of a stem cell subpopulation isolated from MDA-MB-231 triple negative breast cancer cells. [READ ARTICLE](https://precisionnanomedicine.com/article/6489)

ABSTRACT OBJECTIVE Analyze the trend of infant mortality in Rio Branco, state of Acre, from 1999 to 2015. METHODS An ecological observational study of a time series, in which data from deaths from the Information System on Mortality and Births of the Information System on Live Births were used. The annual percentage change was estimated using the Joinpoint software. RESULTS The infant mortality rate decreased from 26.99 in 1999 to 14.50 in 2015 per 1,000 live births, with an annual percentage change of -4.37 (95%CI -5.4– -3.4). When stratified by age components, the neonatal period presented an annual percentage change of -4.73 (95%CI -5.7– -3.7), and the post-neonatal period was -3.7 (95%CI -5.4– -2.0). Avoidability, avoidable causes and poorly defined causes showed a downward trend throughout the period and causes not clearly preventable showed an upward trend until 2008. The group of causes that contributed most to the infant deaths during the period studied was perinatal diseases, followed by malformations, infectious and parasitic diseases, and respiratory diseases. CONCLUSIONS Despite the decreasing trend in infant mortality rates in the capital compared to developed countries, it is relatively high.

There are remarkable similarities in the description of cancer stem cells (CSCs) and cancer cells with mesenchymal phenotype. Both cell types are highly tumorigenic, resistant against common anticancer treatment, and thought to cause metastatic growth. Moreover, cancer cells are able to switch between CSC and non-CSC phenotypes and vice versa, to ensure the necessary balance within the tumor. Likewise, cancer cells can switch between epithelial and mesenchymal phenotypes via well-described transition (EMT/MET) that is thought to be crucial for tumor propagation. In this review, we discuss whether, and to which extend, the CSCs and mesenchymal cancer cells are overlapping phenomena in terms of mechanisms, origin, and implication for cancer treatment. As well, we describe the dynamism of both phenotypes and involvement of the tumor microenvironment in CSC reversion and in EMT.

Resenha do livro recém-publicado da professora e crítica literária Leyla Perrone-Moisés.

A controlled cross-sectional study of family growers of fruit and vegetables was conducted between October 2009 and October 2010 to characterize the use of pesticides, establish the socio-demographic profile, and analyze cholinesterase activity in small-scale agricultural workers in Southern Brazil. Data was collected for 173 workers and 179 controls. A structured questionnaire was applied collecting socio-demographic information and determining knowledge and work practices in relation to pesticide use. The benchmarks for total cholinesterase (ChEs) and butyrylcholinesterase (BuChE) were obtained from the average enzymatic activity of the occupationally unexposed group (control). The mean age of the exposed population was 40.0 ± 11.2 years. The symptoms differed significantly (p30%) of ChEs activity, whereas no workers showed high inhibition (>50%) of BuChE. Potential factors involved include gender, education, pesticide orientation, exposure, and hygiene measures.

PURPOSE:To evaluate the antitumor and antimicrobial activity of ethanolic extract of Morinda citrifolia L. fruit cultivated in southeastern Brazil.METHODS:Preparation ethanolic extract of the fruit of Morinda citrifoliaL. Culture of melanoma cells B16-F10 for treatment with ethanolic extract of Morinda citrifolia L. fruit to determine cell viability by MTT and determination temporal effect of ethanolic extract fruit on the cell growth B16-F10 for 8 days. Evaluation of antimicrobial activity of ethanolic extract fruit against Staphylococcus aureusand Escherichia coli by determination of Minimum Inhibitory Concentration (MIC).RESULTS:The ethanolic extract of Morinda citrifolia L. fruit (10mg/mL) decreased cellular activity and inhibited 45% the rate of cell proliferation of B16-F10 melanoma treated during period studied. The ethanolic extract of Morinda citrifolia L. fruit demonstrated antimicrobial activity inhibiting the growth of both microorganisms studied. Staphylococcus aureuswas less resistant to ethanolic extract of Morinda citrifolia L. fruit than Escherichia coli, 1 mg/mL and 10 mg/mL, respectively.CONCLUSION: What these results indicate that the ethanolic extract of the fruit of Morinda citrifolia L. showed antitumor activity with inhibition of viability and growth of B16-F10 cells and also showed antibacterial activity as induced inhibition of growth of Staphylococcus aureusand Escherichia coli.

A disfunção femoropatelar é uma deficiência bastante comum entre indivíduos jovens que acomete, principalmente, o sexo feminino e pode ser caracterizada por dor, edema e creptação retropatelar. Sistematizar o conhecimento em relação ao aumento da força muscular do quadríceps e alívio de dor em pacientes com disfunção femoropatelar, através da utilização da estimulação elétrica neuromuscular e exercícios resistidos. Trata se de um estudo de revisão narrativa da literatura no período de 2005 a 2011. Os critérios de inclusão foram artigos de intervenção, dos últimos seis anos, nos idiomas inglês, espanhol e português, que utilizaram o fortalecimento muscular e a eletroestimulação neuromuscular para reabilitação obtidos através de buscas nos bancos de dados eletrônicos Medline, Lilacs e na biblioteca Bireme. A busca bibliográfica resultou em 28 referências, destes foram excluídos nove de acordo com os objetivos e critérios de inclusão e foram selecionados 16 artigos para leitura dos resumos e posterior análise. A Estimulação Elétrica Neuromuscular (EENM) de média frequência pode ser utilizada associada a exercícios resistidos como coadjuvante no tratamento da disfunção femoropatelar (DFP), tanto para se obter um reequilíbrio muscular quanto para o alívio da dor.Patellofemoral dysfunction is a fairly common deficiency among young individuals that primarily affects females and may be characterized by pain, swelling and retropatellar crepitation. The purpose of this review of literature from the period between 2005 and 2011 was to systematize knowledge in relation to the increase in quadriceps muscle strength and pain relief in patients with patellofemoral dysfunction, using neuromuscular electrical stimulation and resistance exercises. The inclusion criteria were intervention articles from the past six years, in English, Spanish and Portuguese, which used muscle strengthening and neuromuscular electrical stimulation for rehabilitation obtained through searches in the electronic databases Medline and Lilacs and in the Bireme library. The bibliographic search yielded 28 references, of which nine were excluded in accordance with the aims and inclusion criteria while 16 articles were selected for reading of the abstracts and subsequent analysis. Mediumfrequency Neuromuscular Electrical Stimulation (NMES) can be used in association with resistance exercises as an adjuvant in the treatment of patellofemoral dysfunction (PFD), both to achieve muscle rebalance and for pain relief.