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α-Lipoic acid (LA) is an antioxidant of endogenous production, also obtained exogenously. Oxidative stress is closely associated with hypertension, which causes kidney injury and endothelial dysfunction. Here, we evaluated the cardiovascular and renal effects of LA in the two-kidney-one-clip (2K1C) hypertension model. The rats were divided into four groups: Sham surgery (Sham), the two-kidneys-one-clip (2K1C) group, and groups treated with LA for 14 days (Sham-LA and 2K1C-LA). No changes were observed in the pattern of food, water intake, and urinary volume. The left/right kidney weight LKw/RKw ratio was significantly higher in 2K1C animals. LA treatment did not reverse the increase in cardiac mass. In relation to vascular reactivity, there was an increase in the potency of phenylephrine (PHE) curve in the hypertensive animals treated with LA compared to the 2K1C group and also compared to the Sham group. Vasorelaxation induced by acetylcholine (Ach) and sodium nitroprusside (SNP) were not improved by treatment with LA. Urea and creatinine levels were not altered by the LA treatment. In conclusion, the morphological changes in the aorta and heart were not reversed; however, the treatment with LA mitigated the contraction increase induced by the 2K1C hypertension.

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BACKGROUND/OBJECTIVES: Brazil and Mozambique face similar socioeconomic challenges, including common indicators of undernutrition and overnutrition among children. This study evaluated the similarity degree of the anthropometric and body composition variables of Brazilian and Mozambican children by using the Jaccard index. METHODS: A total of 1831 children of both genders aged 7-10 years from three Brazilian cities (Recife, Vitoria de Santo Antao, and Lagoa do Carro) and three Mozambican cities (Maputo, Boane, and Inhambane) participated in this study. Anthropometric (height, body mass, and waist circumference) and body composition (body fat percentage [%BF], lean mass, and fat mass) variables were measured and the Smoothed Jaccard Index Surface (SJIS) was used to evaluate the similarity degree. RESULTS: Brazilian children were taller and heavier and had a higher %BF and fat mass than Mozambican children. Children living in urban areas were taller than those living in rural zones in both countries. Brazilian and Mozambican children showed high similarity only between %BF and lean mass. Children from Recife and Maputo had high similarities among waist circumference, body mass, fat mass, height, and %BF. Finally, a high SJIS degree was observed among height and %BF for schoolchildren from rural and urban zones. CONCLUSION: Brazilian and Mozambican children exhibit differences in growth characteristics but a high degree of similarity when children from rural and urban zones are compared.

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Microscopy is integral to medical research, facilitating the exploration of various biological questions, notably cell quantification. However, this process's time-consuming and error-prone nature, attributed to human intervention or automated methods usually applied to fluorescent images, presents challenges. In response, machine learning algorithms have been integrated into microscopy, automating tasks and constructing predictive models from vast datasets. These models adeptly learn representations for object detection, image segmentation, and target classification. An advantageous strategy involves utilizing unstained images, preserving cell integrity and enabling morphology-based classification-something hindered when fluorescent markers are used. The aim is to introduce a model proficient in classifying distinct cell lineages in digital contrast microscopy images. Additionally, the goal is to create a predictive model identifying lineage and determining optimal quantification of cell numbers. Employing a CNN machine learning algorithm, a classification model predicting cellular lineage achieved a remarkable accuracy of 93%, with ROC curve results nearing 1.0, showcasing robust performance. However, some lineages, namely SH-SY5Y (78%), HUH7_mayv (85%), and A549 (88%), exhibited slightly lower accuracies. These outcomes not only underscore the model's quality but also emphasize CNNs' potential in addressing the inherent complexities of microscopic images.

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Snake venom metalloproteases (SVMPs) are hydrolytic enzymes dependent on metal binding, primarily zinc (Zn2+), at their catalytic site. They are classified into three classes (P-I to P-III). BjussuMP-II, a P-I SVMP isolated from Bothrops jararacussu snake venom, has a molecular mass of 24 kDa. It exhibits inhibitory activity on platelet aggregation and hydrolyzes fibrinogen. TNF-α upregulates the expression of adhesion molecules on endothelial cell surfaces, promoting leukocyte adhesion and migration during inflammation. Literature indicates that SVMPs may cleave the TNF-α precursor, possibly due to significant homology between metalloproteases from mammalian extracellular matrix and SVMPs. This study aimed to investigate BjussuMP-II's effects on human umbilical vein endothelial cells (HUVEC), focusing on viability, detachment, adhesion, release, and cleavage of TNF-α, IL-1ß, IL-6, IL-8, and IL-10. HUVEC were incubated with BjussuMP-II (1.5-50 µg/mL) for 3-24 h. Viability was determined using LDH release, MTT metabolization, and 7AAD for membrane integrity. Adhesion and detachment were assessed by incubating cells with BjussuMP-II and staining with Giemsa. Cytokines were quantified in HUVEC supernatants using EIA. TNF-α cleavage was evaluated using supernatants from PMA-stimulated cells or recombinant TNF-α. Results demonstrated BjussuMP-II's proteolytic activity on casein. It was not toxic to HUVEC at any concentration or duration studied but interfered with adhesion and promoted detachment. PMA induced TNF-α release by HUVEC, but this effect was not observed with BjussuMP-II, which cleaved TNF-α. Additionally, BjussuMP-II cleaved IL-1ß, IL-6, and IL-10. These findings suggest that the zinc metalloprotease BjussuMP-II could be a valuable biotechnological tool for treating inflammatory disorders involving cytokine deregulation.

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Cryptosporidium is a leading cause of severe diarrhea and mortality in young children and infants in Africa and southern Asia. More than twenty Cryptosporidium species infect humans, of which C. parvum and C. hominis are the major agents causing moderate to severe diarrhea. Relatively few genetic markers are typically applied to genotype and/or diagnose Cryptosporidium. Most infections produce limited oocysts making it difficult to perform whole genome sequencing (WGS) directly from stool samples. Hence, there is an immediate need to apply WGS strategies to 1) develop high-resolution genetic markers to genotype these parasites more precisely, 2) to investigate endemic regions and detect the prevalence of different genotypes, and the role of mixed infections in generating genetic diversity, and 3) to investigate zoonotic transmission and evolution. To understand Cryptosporidium global population genetic structure, we applied Capture Enrichment Sequencing (CES-Seq) using 74,973 RNA-based 120 nucleotide baits that cover ~92% of the genome of C. parvum. CES-Seq is sensitive and successfully sequenced Cryptosporidium genomic DNA diluted up to 0.005% in human stool DNA. It also resolved mixed strain infections and captured new species of Cryptosporidium directly from clinical/field samples to promote genome-wide phylogenomic analyses and prospective GWAS studies.

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Background: Attention-Deficit/Hyperactivity Disorder (ADHD) affects 5% of children and 2.5% of adults worldwide. Comorbidities are frequent, and Oppositional Defiant Disorder (ODD) reaches 50%. Family environment is crucial for the severity of behaviors and for prognosis. In middle-income countries, access to treatment is challenging, with more untreated children than those under treatment. Face-to-face behavioral parent training (PT) is a well-established intervention to improve child behavior and parenting. Method: A clinical trial was designed to compare PT-online and face-to-face effects to a waiting list group. Outcomes were the ADHD and ODD symptoms, parental stress and styles, and quality of life. Families were allocated into three groups: standard treatment (ST), ST + PT online, and ST + Face-to-Face PT. We used repeated measures ANOVA for pre × post treatment analysis corrected for multiple comparisons. Results and discussion: Parent training was effective in reducing symptoms of ADHD (p = 0.030) and ODD (p = 0.026) irrespective of modality (p = 1.000). The combination of ST and PT was also associated with better quality of life in the physical domain for patients (p = 0.009) and their parents (p = 0.050). In addition to preliminary data, online intervention seems effective for parenting and improving social acceptance of children. The potential to reach many by an online strategy with a self-directed platform may imply effectiveness with a low cost for public health to support parents' symptoms management.

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Abstract Several species of Cichla successfully colonized lakes and reservoirs of Brazil, since the 1960s, causing serious damage to local wildlife. In this study, 135 peacock bass were collected in a reservoir complex in order to identify if they represented a single dominant species or multiple ones, as several Cichla species have been reported in the basin. Specimens were identified by color pattern, morphometric and meristic data, and using mitochondrial markers COI, 16S rDNA and Control Region (CR). Overlapping morphological data and similar coloration patterns prevented their identification using the taxonomic keys to species identification available in the literature. However, Bayesian and maximum likelihood from sequencing data demonstrated the occurrence of a single species, Cichla kelberi. A single haplotype was observed for the 16S and CR, while three were detected for COI, with a dominant haplotype present in 98.5% of the samples. The extreme low diversity of the transplanted C. kelberi evidenced a limited number of founding maternal lineages. The success of this colonization seems to rely mainly on abiotic factors, such as increased water transparency of lentic environments that favor visual predators that along with the absence of predators, have made C. kelberi a successful invader of these reservoirs.

Resumo Muitas espécies de Cichla colonizaram com sucesso lagos e reservatórios do Brasil desde os anos 1960, causando graves prejuízos à vida selvagem nesses locais. Neste estudo, 135 tucunarés foram coletados em um complexo de reservatórios a fim de identificar se representavam uma espécie dominante ou múltiplas espécies, uma vez que diversas espécies de Cichla foram registradas na bacia. Os espécimes foram identificados com base na coloração, dados morfométricos e merísticos, e por marcadores mitocondriais COI, 16S rDNA e Região Controle (RC). A sobreposição dos dados morfométricos e o padrão similar de coloração impediram a identificação utilizando as chaves de identificação disponíveis na literatura. Entretanto, as análises bayesiana e de máxima verossimilhança de dados moleculares demonstraram a ocorrência de uma única espécie, Cichla kelberi. Um único haplótipo foi observado para o 16S e RC, enquanto três foram detectados para o COI, com um haplótipo dominante presente em 98,5% das amostras. A baixa diversidade nos exemplares introduzidos de C. kelberi evidenciou um número limitado de linhagens maternas fundadoras. O sucesso da invasão parece depender de fatores abióticos, como a maior transparência da água de ambientes lênticos que favorece predadores visuais que, atrelado à ausência de predadores, fez do C. kelberi um invasor bem-sucedido nesses reservatórios.

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Abstract Several species of Cichla successfully colonized lakes and reservoirs of Brazil, since the 1960's, causing serious damage to local wildlife. In this study, 135 peacock bass were collected in a reservoir complex in order to identify if they represented a single dominant species or multiple ones, as several Cichla species have been reported in the basin. Specimens were identified by color pattern, morphometric and meristic data, and using mitochondrial markers COI, 16S rDNA and Control Region (CR). Overlapping morphological data and similar coloration patterns prevented their identification using the taxonomic keys to species identification available in the literature. However, Bayesian and maximum likelihood from sequencing data demonstrated the occurrence of a single species, Cichla kelberi. A single haplotype was observed for the 16S and CR, while three were detected for COI, with a dominant haplotype present in 98.5% of the samples. The extreme low diversity of the transplanted C. kelberi evidenced a limited number of founding maternal lineages. The success of this colonization seems to rely mainly on abiotic factors, such as increased water transparency of lentic environments that favor visual predators that along with the absence of predators, have made C. kelberi a successful invader of these reservoirs.

Resumo Muitas espécies de Cichla colonizaram com sucesso lagos e reservatórios do Brasil desde os anos 1960, causando graves prejuízos à vida selvagem nesses locais. Neste estudo, 135 tucunarés foram coletados em um complexo de reservatórios a fim de identificar se representavam uma espécie dominante ou múltiplas espécies, uma vez que diversas espécies de Cichla foram registradas na bacia. Os espécimes foram identificados com base na coloração, dados morfométricos e merísticos, e por marcadores mitocondriais COI, 16S rDNA e Região Controle (RC). A sobreposição dos dados morfométricos e o padrão similar de coloração impediram a identificação utilizando as chaves de identificação disponíveis na literatura. Entretanto, as análises bayesiana e de máxima verossimilhança de dados moleculares demonstraram a ocorrência de uma única espécie, Cichla kelberi. Um único haplótipo foi observado para o 16S e RC, enquanto três foram detectados para o COI, com um haplótipo dominante presente em 98,5% das amostras. A baixa diversidade nos exemplares introduzidos de C. kelberi evidenciou um número limitado de linhagens maternas fundadoras. O sucesso da invasão parece depender de fatores abióticos, como a maior transparência da água de ambientes lênticos que favorece predadores visuais que, atrelado à ausência de predadores, fez do C. kelberi um invasor bem-sucedido nesses reservatórios.

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Health professionals play a significant role in identifying and reporting child physical abuse (CPA). However, several studies have pointed out non-reporting behavior among these professionals, evidencing difficulties identifying and reporting suspected cases. This review aimed to explore the frequency and possible barriers in identifying and reporting CPA by health professionals worldwide and to identify associated factors. This scoping review was conducted in the Pubmed, Web Of Science, Scopus, and SciELO databases between July 2019 and December 2020. Analytical and qualitative observational epidemiological studies were selected and published in English, Portuguese, and Spanish, with data on the identification and/or reporting of CPA by health professionals. Twenty studies fulfilled the criteria of this review. The studies were conducted with dentists, nurses, pediatricians, and general practitioners. The frequency of identification of CPA ranged from 50% to 89%, while the frequency of reporting ranged from 8% to 47%. This review revealed that health professionals had a low frequency of reporting of CPA, especially for dentists. In addition, several associated factors and barriers in the identification and reporting of CPA were identified in the studies. These were discussed in five main themes: training and continuing education in CPA, impact on professional practice, experiences and perceptions about child protection services, the threshold for suspicion of the professional, and the professional category.

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ABSTRACT Objective: to validate an educational technology as a teaching resource for teaching mental health nursing. Method: this is a methodological study, carried out through agreement among expert judges and the target audience, for content validity and appearance assessment of an educational game. A total of 11 expert judges and 114 students from two universities participated in the study. For validity, the Content Validity Index was used. Results: the teaching-pedagogical resource assessment reached an overall Content Validity Index equal to 88.5%. Items 7 and 9 obtained an Individual Content Validity Index of less than 78%. In view of this, these items were reassessed and adjusted according to suggested changes. For the domains assessed regarding educational game appearance, percentages were obtained that were between 85.9% and 97.3%. Conclusion: the assessments triggered adjustments to the game's theoretical-scientific content, making it capable of being used as an educational resource for the mental health discipline in nursing courses.

RESUMEN Objetivo: validar una tecnología educativa como recurso didáctico para la enseñanza de enfermería en salud mental. Método: estudio metodológico, realizado mediante acuerdo entre jueces expertos y el público objetivo, para validar el contenido y evaluar la apariencia de un juego educativo. En el estudio participaron 11 jueces expertos y 114 estudiantes de dos universidades. Para la validación se utilizó el Índice de Validez de Contenido. Resultados: la evaluación del recurso docente-pedagógico alcanzó un Índice Global de Validez de Contenido igual al 88,5%. Los ítems 7 y 9 obtuvieron un Índice de Validez de Contenido Individual inferior al 78%. Ante lo anterior, dichos ítems fueron reevaluados y ajustados de acuerdo a los cambios sugeridos. Para los dominios evaluados respecto a la apariencia del juego educativo se obtuvieron porcentajes que estuvieron entre 85,9% y 97,3%. Conclusión: las evaluaciones provocaron ajustes en el contenido teórico-científico del juego, haciéndolo apto para su uso como recurso educativo para la disciplina de salud mental en cursos de enfermería.

RESUMO Objetivo: Validar uma tecnologia educacional como recurso didático para o ensino de enfermagem em saúde mental. Método: Estudo metodológico, realizado através da concordância entre os juízes especialistas e do público-alvo, para a validação do conteúdo e avaliação da aparência de um jogo educacional. Participaram do estudo 11 juízes especialistas e 114 alunos de duas universidades. Para a validação, foi utilizado o Índice de Validade de Conteúdo. Resultados: A avaliação do recurso didático-pedagógico atingiu um Índice de Validade de Conteúdo Global igual a 88,5%. Os itens 7 e 9 obtiveram um Índice de Validade de Conteúdo Individual inferior a 78%. À vista disso, esses itens foram reavaliados e ajustados conforme as alterações sugeridas. Para os domínios avaliados referentes à aparência do jogo educacional, foram obtidos percentuais que estiveram entre 85,9% e 97,3%. Conclusão: As avaliações desencadearam adequações no conteúdo teórico-científico do jogo, tornando-o apto a ser empregado como recurso educacional da disciplina de saúde mental nos cursos de enfermagem.

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The objective was to identify the conditions of birth of children of women living with HIV in the period between 2009 and 2019, at the Regional Maternal and Child Hospital of Imperatriz (MA). Cross-sectional, quantitative, documentary study, with descriptive analysis of the data and carried out in a reference maternity hospital between August 2020 and July 2021. Information from the medical records of HIV-positive pregnant women and their newborn children was included. The results collected 314 medical records, of which 195 were eligible. Regarding the birth conditions of the newborns, in 56.41% the rapid test was negative; 72.82% used post-birth prophylaxis; 75.38% did not receive breast milk; 68.2% received vaccines at birth; 40.51% did not use any medication. 20.51% of the mothers were between 36 and 40 years old; 59.48% did not live in the municipality surveyed; 23.6% were housewives; 65.64 were multipara women; 46.15% were diagnosed with HIV during pregnancy; 67.17% had no coinfections; 82.05% underwent prenatal care; 60.51% used intrapartum prophylaxis; and 77.43% underwent cesarean section. The prenatal and childbirth follow-up of most of these women living with HIV reflected positively on the conditions of birth of their children, being an important strategy, aiming at the non-vertical transmission and prevention of the disease in children (AU).

Objetivou-se identificar as condições de nascimento de filhos de mulheres vivendo com HIV no período compreendido entre 2009 e 2019, no Hospital Regional Materno Infantil de Imperatriz (MA). Estudo transversal, quantitativo, documental, com análise descritiva dos dados e realizado em maternidade de referência entre os meses de agosto de 2020 e julho de 2021. Incluíram-se informações dos prontuários das gestantes soropositivas para HIV e de seus filhos recém-nascidos. Os resultados levantaram 314 prontuários, destes, 195 eram elegíveis. Sobre as condições de nascimento dos recém-nascidos, em 56,41% o teste rápido foi negativo; 72,82% usaram profilaxia pós-nascimento; 75,38% não receberam leite materno; 68,2% receberam vacinas logo ao nascer; 40,51% não faziam uso de nenhuma medicação; 20,51% das mães tinham entre 36 a 40 anos; 59,48% não residiam no município pesquisado; 23,6% eram donas de casa; 65,64 eram multigestas; 46,15% receberam o diagnóstico de HIV na gestação; 67,17% não tinham coinfecções; 82,05% realizaram o pré-natal; 60,51% fizeram uso da profilaxia intraparto; e 77,43% fizeram cesariana. O acompanhamento no pré-natal e parto da maioria dessas mulheres vivendo com HIV refletiu positivamente nas condições de nascimento de seus filhos, sendo uma importante estratégia, visando a não transmissão vertical e prevenção da doença nas crianças (AU).

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In France, the prevalence of hypertension is higher than 30%. Although treatment guidelines have been well established over the last twenty years, the national blood pressure control rate is below the average of high-income countries. This observational study aimed to describe the antihypertensive prescription behaviours of primary care physicians (PCPs) in France and to assess their compliance with current French guidelines, focusing on three specific prescription issues and their potential repercussions on blood pressure control: treatment initiation, treatment renewal or change and type of triple therapy. Prescription data were retrieved using the IQVIA longitudinal patient database (LPD), which delivers real-world data insights from French primary care electronic medical records (EMR). The average number of prescribed therapeutic agents was 1.9 per patient, with 39.3% monotherapy prescriptions. Treatment initiation represented 7.2% of all antihypertensive prescriptions. At treatment initiation, 22.5% of patients were prescribed dual therapy. The proportion of treatment renewal in the same therapeutic class was 74.3% while the proportion of treatment change was 18.5%. Of these, only 6.3% of patients received an additional therapy. Lastly, 35.7% of triple therapies were consistent with the recommended combinations. In conclusion, this study provides evidence of therapeutic gaps in hypertension management in France. The low blood control rate may be attributed to PCPs' therapeutic inertia and lack of knowledge of treatment guidelines. All stakeholders should commit to rapid corrective action in order to provide patients with the best care.

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The knowledge of the lithological context is necessary to interpret trace elements concentrations in the soil. Soil magnetic signature (χ) and soil X-ray fluorescence (XRF) are promising approaches in the study of the spatial variability of trace elements and the environmental monitoring of soil quality. This research aimed to assess the efficiency of measurements of χ and XRF sensors for spatial characterization of zinc (Zn), manganese (Mn), and copper (Cu) contents in soils of a sandstone-basalt transitional environment, using machine learning modeling. The studied area consisted of the Western Plateau of São Paulo (WPSP), with soils originating from sandstone and basalt. A total of 253 soil samples were collected at a depth of 0.0-0.2 m. The soils were characterized by particle size and chemical analysis: organic matter (OM), cation exchange capacity (CEC), ammonium oxalate-extracted iron (Feo), sodium dithionite-citrate-bicarbonate-extracted iron (Fed), and sulfuric acid-extracted iron (Fet). Hematite (Hm), goethite (Gt), kaolinite (Kt), and gibbsite (Gb) contents were obtained by X-ray diffraction (XRD). Magnetite (Mt) and maghemite (Mh) contents were obtained by soil χ, while trace elements contents were obtained by XRF and predicted by χ. Descriptive analysis, the test of means, and correlation were performed between attributes. Zn, Mn, and Cu contents were predicted using the machine learning algorithm random forest, and the spatial variability was obtained using the ordinary kriging interpolation technique. Landscape dissections influenced iron oxides, which had the highest contents in slightly dissected environments. Trace elements contents were not influenced by landscape dissections, demonstrating that lithological knowledge is necessary to characterize trace elements in soils. The prediction models developed through the machine learning algorithm random forest showed that χ can be used to characterize trace elements. The similar spatial pattern of trace elements obtained by XRF and χ measurements confirm the applicability of these sensors for mapping it under lithological and landscape transition, aiming for sustainable strategic planning of land use and occupation.

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This study was designed to characterize mice bone marrow (BM) and bone marrow-derived dendritic cells (BMDC) and to compare the surface markers expression and inflammatory cytokine liberation in response to LPS and Bothrops jararacussu venom (BjV) stimulation. Typical morphology was observed in BM and BMDCs from the 4th up to the 8th day of culture using recombinant mouse GM-CSF and IL-4. A high basal level of MHC-II, CD1d, CD83, CD11c, CD80, and low CD86 was expressed by BM cells. After stimulation with GM-CSF/IL-4 for BMDCs differentiation, the BM cells differentiated into BMDCs presented MHC-II, CD1d, CD83, CD11c, CD86, and CD80 expression on the 4th - 8th day accompanied with high levels of TNF-α liberated. The difference between the surface markers' expression was observed in this time course in which CD1d, CD11c, and CD80 remained in high levels of expression, while MHC-II and CD83 showed moderate expression during the differentiation period. Also, cytokines liberation was monitored over the period of the BMDCs culture, and on the 6th day, low levels of IL-6 and IL-1ß were found, while high levels of TNF-α on the 4th and 8th days, both of which contributed to the maturity of the BMDCs. Maturation of DCs with LPS showed significant upregulation of surface markers (MHC-II, CD1d, CD83, CD86, CD80) and pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α) liberation. On the other hand, BjV induced a decrease in CD1d, CD11c, CD83, and CD86 expression in mature BMDCs which was not observed when LPS was used to stimulate BMDCs which probably induces impairment in T-cell activation.

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PURPOSE: Early integration of pediatric palliative care (PPC) for children with cancer is critical to improving the quality of life of both the patient and family. Understanding physician perceptions of palliative care and perceived barriers to early integration is necessary to develop PPC in Brazil. METHODS: The Assessing Doctors' Attitudes on Palliative Treatment survey was modified for use in Brazil. The survey was open from January 2022 to June 2022 and distributed to physicians of all specialties from participating institutions who treat children with cancer. Statistical analysis was complemented by qualitative analysis of open-ended responses. RESULTS: A total of 272 respondents participated. Most respondents reported access to PPC experts for consultation (77.2%) and 34.5% indicated previous palliative care training. Physician knowledge of PPC was generally aligned with WHO guidance (median alignment, 93.0%; range, 80.5%-98.2%). However, about half (53.3%) felt comfortable addressing physical needs of patients receiving PPC, 35.3% addressing emotional needs, 25.8% addressing spiritual needs, and 33.5% addressing grief and bereavement needs. Most respondents (65.4%) felt palliative care should be involved from diagnosis, but only 10.3% stated that this occurred in their setting. The most important barriers identified were physician discomfort (89.0%), limited physician knowledge (88.6%), and lack of home-based services (83.8%). CONCLUSION: Despite a strong understanding of the role of palliative care, physicians in Brazil reported low confidence delivering PPC to children with cancer. Additionally, physicians generally believed that PPC should be integrated earlier in the disease trajectory of children with cancer. This work will direct educational and capacity building initiatives to ensure greater access to high-quality PPC for children with cancer in Brazil to address patient and family suffering.

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Essential oils extracted from many plant species have different biological activities, among which microbial activity stands out. Species of the genus Piper have antimicrobial potential against different species of bacteria and fungi. In this sense, the present study aimed to determine the chemical composition of the essential oil from the leaves of Piper gaudichaudianum (EOPG), as well as to investigate their antimicrobial activity and their modulatory effect on the Norfloxacin resistance in the Staphylococcus aureus SA1199B strain overproducer of the NorA efflux pump. Furthermore, their inhibitory activities on the biofilm formation as well as on the cellular differentiation of C. albicans were evaluated. Gas chromatography analysis identified 24 compounds, such as hydrocarbon sesquiterpenes (54.8%) and oxygenated sesquiterpenes (28.5%). To investigate the antimicrobial potential of EOPG against S. aureus, E. coli, and C. albicans, a microdilution assay was performed, and no intrinsic antimicrobial activity was observed. On the other hand, the oil potentiated the activity of Norfloxacin against the SA1199B strain, indicating that EOPG could be used in association with Norfloxacin against S. aureus strains resistant to this antibiotic. EOPG also inhibited S. aureus biofilm formation, as evidenced by the crystal violet assay. In the dimorphism assay, EOPG was able to inhibit the cell differentiation process in C. albicans. Results indicate that EOPG could be used in association with Norfloxacin in the treatment of infections caused by resistant S. aureus strains overproducing the NorA efflux pump. Furthermore, its ability to inhibit the formation of hyphae by C. albicans suggests that EOPG could also be applied in the prevention and/or treatment of fungal infections.

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Lectins are a large group of proteins found in many snake venoms. BjcuL is a C-type lectin from Bothrops jararacussu snake venom that does not present cytotoxicity action on human peripheral blood mononuclear cells (PBMCs) at concentrations of 5 and 10 µg/mL. BjcuL demonstrates an immunomodulatory role in PBMCs with the production of pro- and anti-inflammatory cytokines (IL-2, IL-10, IFN-γ, IL-6, TNF-α, and IL-17) in addition to stimulate T cells to produce reactive oxygen species (ROS) that could play a role in the acute inflammatory reaction observed in the victims. Inflammasomes are an essential arm in cells of innate immunity to detect and sense a range of endogenous or exogenous, sterile, or infectious stimuli to elicit cellular responses and effector mechanisms. NLRP3 inflammasome is a significant target for this study, because the lectin is responsible for leukocyte activation stimulating the release of inflammatory mediators, which results in dynamic cellular responses to remove the detrimental process to the body in snakebites. Thus, this study aimed to investigate how isolated BjcuL from B. jararacussu venom affects NLRP3 inflammasome activation on PBMCs. For this, the cells were isolated by density gradient and incubated with BjcuL at different periods and concentrations for the evaluation of the activation of the NLRP3 inflammasome through gene and protein expressions of ASC, CASPASE-1, and NLRP3 by RT-qPCR, Western blot, and immunofluorescence, as well as the participation of Toll-like receptor 4 (TLR4) and ROS in the IL-1ß production, a product resultant of the NLRP3 inflammasome activation. Herein, BjcuL interacts with TLR4 as demonstrated by in vitro and in silico studies and induces cytokines release via NF-κB signaling. By genic and protein expression assays, BjcuL activates NLRP3 inflammasome, and the pharmacological modulation with LPS-RS, an antagonist of TLR4; LPS-SM, an agonist of TLR4; MCC950, a specific NLRP3 inhibitor, and rotenone, an inhibitor of mitochondrial ROS, confirmed the participation of TLR4 and ROS in the NLRP3 inflammasome activation and IL-1ß liberation. The effects of BjcuL on the regulation and activation of the NLRP3 inflammasome complex via TLR4 activation with ROS participation may be determinant for the development of the inflammatory local effects seen in snakebite victims. In addition, in silico together with in vitro studies provide information that may be useful in the rational design of TLR agonists as well as new adjuvants for immunomodulatory therapy.

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BACKGROUND: Data on post-acute COVID-19 in autoimmune rheumatic diseases (ARD) are scarce, focusing on a single disease, with variable definitions of this condition and time of vaccination. The aim of this study was to evaluate the frequency and pattern of post-acute COVID-19 in vaccinated patients with ARD using established diagnosis criteria. METHODS: Retrospective evaluation of a prospective cohort of 108 ARD patients and 32 non-ARD controls, diagnosed with SARS-CoV-2 infection (RT-PCR/antigen test) after the third dose of the CoronaVac vaccine. Post-acute COVID-19 (≥ 4 weeks and > 12 weeks of SARS-CoV-2 symptoms) were registered according to the established international criteria. RESULTS: ARD patients and non-ARD controls, balanced for age and sex, had high and comparable frequencies of ≥ 4 weeks post-acute COVID-19 (58.3% vs. 53.1%, p = 0.6854) and > 12 weeks post-acute COVID-19 (39.8% vs. 46.9%, p = 0.5419). Regarding ≥ 4 weeks post-acute COVID-19, frequencies of ≥ 3 symptoms were similar in ARD and non-ARD controls (54% vs. 41.2%, p = 0.7886), and this was also similar in > 12 weeks post-acute COVID-19 (68.3% vs. 88.2%, p = 0.1322). Further analysis of the risk factors for ≥ 4 weeks post-acute COVID-19 in ARD patients revealed that age, sex, clinical severity of COVID-19, reinfection, and autoimmune diseases were not associated with this condition (p > 0.05). The clinical manifestations of post-acute COVID-19 were similar in both groups (p > 0.05), with fatigue and memory loss being the most frequent manifestations. CONCLUSION: We provide novel data demonstrating that immune/inflammatory ARD disturbances after third dose vaccination do not seem to be a major determinant of post-acute COVID-19 since its pattern is very similar to that of the general population. Clinical Trials platform (NCT04754698).

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