Oropouche Virus Exposure in Febrile Patients during Chikungunya Virus Introduction in the State of Amapá, Amazon Region, Brazil.

Oropouche orthobunyavirus (OROV) is an arbovirus transmitted by midges that has been involved in outbreaks throughout Central and South America. In Brazil, human cases have been historically concentrated in the northern region of the country. Oropouche fever in humans range from mild clinical signs to rare neurological events, and is considered a neglected tropical disease in Brazil. Due to the clinical similarities to other arboviruses, such as chikungunya and dengue viruses, OROV infections are likely to be underreported. Chikungunya virus (CHIKV) cases in Brazil were first recognized in 2014 in the states of Amapá and Bahia in the north and northeast regions, respectively. Both OROV and CHIKV cause nonspecific symptoms, making clinical diagnosis difficult in a scenario of arbovirus cocirculation. Aiming to investigate OROV transmission during the CHIKV introduction in the state of Amapá located in the Brazilian Amazon, we conducted a retrospective molecular (RT-qPCR) and serological investigation in febrile cases (N = 166) collected between August 2014 and May 2015. All acute serum samples were negative for OROV RNA using RT-qPCR. However, neutralizing antibodies for OROV were detected using a plaque reduction neutralization test (PRNT90) in 10.24% (17/166) of the patients, with neutralizing antibody titers ranging from 20 to ≥640, suggesting the previous exposure of patients to OROV. Regarding CHIKV, recent exposure was confirmed by the detection of CHIKV RNA in 20.25% (33/163) of the patients and by the detection of anti-CHIKV IgM in 28.57% (44/154) of the patients. The additional detection of anti-CHIKV IgG in 12.58% (19/151) of the febrile patients suggests that some individuals had been previously exposed to CHIKV. Whether the OROV exposure reported here occurred prior or during the CHIKV circulation in Amapá, is unknown, but because those arboviral infections share similar clinical signs and symptoms, a silent circulation of enzootic arboviruses during the introduction of exotic arboviruses may occur, and highlights the importance of syndromic cases' surveillance to arboviruses in Brazil.

Effectiveness of non-pharmacological interventions in reducing pain in preterm infants: A systematic review and network meta-analysis.

OBJECTIVE: To identify the most effective non-pharmacological measures for pain control in preterm infants in the Neonatal Intensive Care Unit (NICU). METHODS: A Systematic review and network meta-analysis of randomized clinical trials published in English, Portuguese, and Spanish from April 2020 to December 2023. The data sources used were MedLine via PubMed, LILACS, EMBASE, The Cochrane Central Register of Controlled Trials, and Pedro. We performed the risk of bias analysis with Rob 2 and the certainty of the evidence and strength of the recommendation using the Grading of Recommendations Assessment, Development, and Evaluation system. We assessed heterogeneity using the Higgins and Thompson I2 test, the classification of interventions using the P-score, and inconsistencies using the Direct Evidence Plot. RESULTS: From 210 publications identified, we utilized 12 studies in analysis with 961 preterm infants, and we combined ten studies in network meta-analysis with 716 preterm infants, and 12 combinations of non-pharmacological measures. With moderate confidence, sensory saturation, sugars, non-nutritive sucking, maternal heart sound, lullaby, breast milk odor/taste, magnetic acupuncture, skin-to-skin contact, and facilitated tucking have been shown to reduce pain in preterm infants when compared to no intervention, placebo, proparacaine or standard NICU routine: sensory saturation [SMD 5,25 IC 95%: -8,98; -1,53], sugars [SMD 2,32 IC 95%: -3,86; -0,79], pacifier [SMD 3,74 IC 95%: -7,30; 0,19], and sugars and pacifier SMD [3,88 IC 95% -7,72; -0,04]. CONCLUSION: Non-pharmacological measures are strongly recommended for pain management in preterm infants in the NICU. IMPLICATIONS FOR CLINICAL PRACTICE: The findings of this study have important implications for policy and practice. This is the only systematic review that compared the effectiveness of non-pharmacological measures, thus making it possible to identify which measure presents the best results and could be the first choice in clinical decision making.

Antiviral and Virucidal Activities of Uncaria tomentosa (Cat's Claw) against the Chikungunya Virus.

Uncaria tomentosa (UT) is a medicinal plant popularly known as cat's claw belonging to the Rubiaceae family that has been reported to display antiviral and anti-inflammatory activities. The chikungunya virus (CHIKV) outbreaks constitute a Brazilian public health concern. CHIKV infection develops an abrupt onset of fever, usually accompanied by a skin rash, besides incapacitating polyarthralgia. There is no vaccine available or treatment for CHIKV infection. The present study evaluates the hydroalcoholic extract of UT bark as a potential antiviral against CHIKV. The in vitro antiviral activity of the UT extract against the Brazilian CHIKV strain was assessed using quantitative reverse transcription polymerase chain reaction, flow cytometry, and plaque assay. Results obtained demonstrated that UT inhibits CHIKV infection in a dose-dependent manner. At the non-cytotoxic concentration of 100 µg/mL, UT exhibited antiviral activity above 90% as determined by plaque reduction assay, and it reduced the viral cytopathic effect. Similarly, a significant virucidal effect of 100 µg/mL UT was observed after 24 and 48 h post-infection. This is the first report on the antiviral activity of UT against CHIKV infection, and the data presented here suggests UT as a potential antiviral to treat CHIKV infection.

Investigating USP42 Mutation as Underlying Cause of Familial Non-Medullary Thyroid Carcinoma.

In a family with Familial Non-Medullary Thyroid Carcinoma (FNMTC), our investigation using Whole-Exome Sequencing (WES) uncovered a novel germline USP42 mutation [p.(Gly486Arg)]. USP42 is known for regulating p53, cell cycle arrest, and apoptosis, and for being reported as overexpressed in breast and gastric cancer patients. Recently, a USP13 missense mutation was described in FNMTC, suggesting a potential involvement in thyroid cancer. Aiming to explore the USP42 mutation as an underlying cause of FNMTC, our team validated the mutation in blood and tissue samples from the family. Using immunohistochemistry, the expression of USP42, Caspase-3, and p53 was assessed. The USP42 gene was silenced in human thyroid Nthy-Ori 3-1 cells using siRNAs. Subsequently, expression, viability, and morphological assays were conducted. p53, Cyclin D1, p21, and p27 proteins were evaluated by Western blot. USP42 protein was confirmed in all family members and was found to be overexpressed in tumor samples, along with an increased expression of p53 and cleaved Caspase-3. siRNA-mediated USP42 downregulation in Nthy-Ori 3-1 cells resulted in reduced cell viability, morphological changes, and modifications in cell cycle-related proteins. Our results suggest a pivotal role of USP42 mutation in thyroid cell biology, and this finding indicates that USP42 may serve as a new putative target in FNMTC.

High-Throughput Drug Screening Revealed That Ciclopirox Olamine Can Engender Gastric Cancer Stem-like Cells.

Cancer stem cells (CSCs) are relevant therapeutic targets for cancer treatment. Still, the molecular circuits behind CSC characteristics are not fully understood. The low number of CSCs can sometimes be an obstacle to carrying out assays that explore their properties. Thus, increasing CSC numbers via small molecule-mediated cellular reprogramming appears to be a valid alternative tool. Using the SORE6-GFP reporter system embedded in gastric non-CSCs (SORE6-), we performed a high-throughput image-based drug screen with 1200 small molecules to identify compounds capable of converting SORE6- to SORE6+ (CSCs). Here, we report that the antifungal agent ciclopirox olamine (CPX), a potential candidate for drug repurposing in cancer treatment, is able to reprogram gastric non-CSCs into cancer stem-like cells via activation of SOX2 expression and increased expression of C-MYC, HIF-1α, KLF4, and HMGA1. This reprogramming depends on the CPX concentration and treatment duration. CPX can also induce cellular senescence and the metabolic shift from oxidative phosphorylation (OXPHOS) to glycolysis. We also disclose that the mechanism underlying the cellular reprogramming is similar to that of cobalt chloride (CoCl2), a hypoxia-mimetic agent.

Using a Dual CRISPR/Cas9 Approach to Gain Insight into the Role of LRP1B in Glioblastoma.

LRP1B remains one of the most altered genes in cancer, although its relevance in cancer biology is still unclear. Recent advances in gene editing techniques, particularly CRISPR/Cas9 systems, offer new opportunities to evaluate the function of large genes, such as LRP1B. Using a dual sgRNA CRISPR/Cas9 gene editing approach, this study aimed to assess the impact of disrupting LRP1B in glioblastoma cell biology. Four sgRNAs were designed for the dual targeting of two LRP1B exons (1 and 85). The U87 glioblastoma (GB) cell line was transfected with CRISPR/Cas9 PX459 vectors. To assess LRP1B-gene-induced alterations and expression, PCR, Sanger DNA sequencing, and qRT-PCR were carried out. Three clones (clones B9, E6, and H7) were further evaluated. All clones presented altered cellular morphology, increased cellular and nuclear size, and changes in ploidy. Two clones (E6 and H7) showed a significant decrease in cell growth, both in vitro and in the in vivo CAM assay. Proteomic analysis of the clones' secretome identified differentially expressed proteins that had not been previously associated with LRP1B alterations. This study demonstrates that the dual sgRNA CRISPR/Cas9 strategy can effectively edit LRP1B in GB cells, providing new insights into the impact of LRP1B deletions in GBM biology.

Factors Associated with Mortality after Percutaneous Endoscopic Gastrostomy.

Introduction: Percutaneous endoscopic gastrostomy (PEG) is a common procedure performed world-wide on patients with different comorbidities, with many indications and overall low morbidity. However, studies showed an elevated early mortality in patients undergoing PEG placement. In this systematic review, we review the factors associated with early mortality after PEG. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The methodological index for nonrandomized studies (MINORS) score system was used to perform qualitative assessment of all included studies. Recommendations were summarized for predefined key items. Results: The search found 283 articles. A refined total of 21 studies were included; 20 studies cohort studies and 1 case-control study. For the cohort studies, MINORS score ranged from 7 to 12 out of 16. The single case-control study scored 17 out of 24. The number of study patients ranged from 272 to 181,196. Thirty-day mortality rate varied from 2.4% to 23.5%. Albumin, age, body mass index, C-reactive protein, diabetes mellitus, and dementia were the most frequently associated factors to early mortality in patients undergoing PEG placement. Five studies reported procedure related deaths. Infection was the most commonly reported complication of PEG placement. Conclusions: PEG tube insertion is a fast, safe and effective procedure, but is not free of complications and can have a high early mortality rate as demonstrated in this review. Patient selection should be a key factor and the identification of factors associated with early mortality is important in the elaboration of a protocol to benefit patients.

High VEGFA Expression Is Associated with Improved Progression-Free Survival after Bevacizumab Treatment in Recurrent Glioblastoma.

Glioblastoma (GB) is one of the deadliest human cancers. Many GB patients do not respond to treatment, and inevitably die within a median of 15-18 months post-diagnosis, highlighting the need for reliable biomarkers to aid clinical management and treatment evaluation. The GB microenvironment holds tremendous potential as a source of biomarkers; several proteins such as MMP-2, MMP-9, YKL40, and VEGFA have been identified as being differentially expressed in GB patient samples. Still to date, none of these proteins have been translated into relevant clinical biomarkers. This study evaluated the expression of MMP-2, MMP-9, YKL40, and VEGFA in a series of GBs and their impact on patient outcome. High levels of VEGFA expression were significantly associated with improved progression-free survival after bevacizumab treatment, thus having potential as a tissue biomarker for predicting patients' response to bevacizumab. Noteworthily, VEGFA expression was not associated with patient outcome after temozolomide treatment. To a lesser extent, YKL40 also provided significant information regarding the extent of bevacizumab treatment. This study highlights the importance of studying secretome-associated proteins as GB biomarkers and identifies VEGFA as a promising marker for predicting response to bevacizumab.

Improving the quality of external cause of death data in Brazil: evaluation and validation of a new form to investigate garbage codes.

Garbage codes, such as external causes with no specific information, indicate poor quality cause of death data. Investigation of garbage codes via an effective instrument is necessary to convert them into useful data for public health. This study analyzed the performance and suitability of the new investigation of deaths from external causes (IDEC) form to improve the quality of external cause of death data in Brazil. The performance of the IDEC form on 133 external garbage codes deaths was compared with a stratified matched sample of 992 (16%) investigated deaths that used the standard garbage codes form. Consistency between these two groups was checked. The percentage of garbage codes from external causes reclassified into valid causes with a 95% confidence interval (95%CI) was analyzed. Reclassification for specific causes has been described. Qualitative data on the feasibility of the form were recorded by field investigators. Investigation using the new form reduced all external garbage codes by -92.5% (95%CI: -97.0; -88.0), whereas the existing form decreased garbage codes by -60.5% (95%CI: -63.5; -57.4). The IDEC form presented higher effectivity for external-cause garbage codes of determined intent. Deaths that remained garbage codes mainly lacked information about the circumstances of poisoning and/or vehicle accidents. Despite the fact that field investigators considered the IDEC form feasible, they suggested modifications for further improvement. The new form was more effective than the current standard form in improving the quality of defined external causes.

Assessing the Antitumor Potential of Variants of the Extracellular Carbohydrate Polymer from Synechocystis ΔsigF Mutant.

Cancer is a leading cause of death worldwide with a huge societal and economic impact. Clinically effective and less expensive anticancer agents derived from natural sources can help to overcome limitations and negative side effects of chemotherapy and radiotherapy. Previously, we showed that the extracellular carbohydrate polymer of a Synechocystis ΔsigF overproducing mutant displayed a strong antitumor activity towards several human tumor cell lines, by inducing high levels of apoptosis through p53 and caspase-3 activation. Here, the ΔsigF polymer was manipulated to obtain variants that were tested in a human melanoma (Mewo) cell line. Our results demonstrated that high molecular mass fractions were important for the polymer bioactivity, and that the reduction of the peptide content generated a variant with enhanced in vitro antitumor activity. This variant, and the original ΔsigF polymer, were further tested in vivo using the chick chorioallantoic membrane (CAM) assay. Both polymers significantly decreased xenografted CAM tumor growth and affected tumor morphology, by promoting less compact tumors, validating their antitumor potential in vivo. This work contributes with strategies for the design and testing tailored cyanobacterial extracellular polymers and further strengths the relevance of evaluating this type of polymers for biotechnological/biomedical applications.

A systemic framework of energy efficiency in schools: experiences from six European countries.

Schools are complex physical and social institutions within national education systems. They account for significant energy consumption and like other buildings can demonstrate inefficient patterns of energy use. Poor energy performance of educational facilities is an intricate issue driven by complex causality of interconnected and dynamic factors. Addressing this issue requires a systemic approach, which is heretofore lacking. The aim of this research is to present and describe a systemic framework to facilitate energy reduction in schools across different European contexts. This transdisciplinary approach to sustainable energy use has been piloted in 13 post-primary schools located in six countries in northwest Europe. The research implements a series of planned activities and interventions, which help to unveil a systemic approach to improving energy efficiency in schools. The findings demonstrate how this approach, together with its ensuing methodologies and strategies, can contribute to reducing carbon emissions and improve knowledge and awareness around sustainable energy.

Early death, morbidity and pharmacotherapy in extremely premature and very premature in neonatal intensive care units / Morte precoce, morbidade e farmacoterapia em prematuros extremos e muito prematuros em unidades de terapia intensiva neonatal

Abstract Objectives: to evaluate the evolution of extremely preterm and very preterm infants admitted to neonatal intensive care units, regarding the use of ventilatory support, morbidities, medication use, death, survival and viability. Methods: a non-concurrent cohort study, with 163 very premature and extreme newborns hospitalized in three neonatal intensive care units, during 2016 and 2017. A descriptive analysis of the data obtained from the medical records was performed. The outcomes studied were the use of ventilatory support, morbidities, medication use, death and causes of death. A survival curve was constructed and a viability limit was defined. Results: in the study, 28.2% were extreme and 71.8% were very premature. In this order of subgroups, the need for mechanical ventilation was higher for the extremes (65.2% and 41.0%) and the main diagnosis was early sepsis (78.6% and 82.6). Off-label (60.5% and 47.9%) and off-license (25.3% and 29.0%) medications were used. Most deaths (57.8%) occurred between the extremes, mainly due to septic shock. Survival was lower for the lowest gestational ages and the limit of viability was between 26 and 27 weeks. Conclusions: the main morbidities were from the respiratory system, with high use of off-label and unlicensed medications. Extremes had a greater demand for intensive care in addition to needing more drugs and progressing more to death.

Resumo Objetivos: avaliar a evolução dos prematuros extremos e muito prematuros internados em unidades de terapia intensiva neonatais, quanto ao uso de suporte ventilatório e de medicamentos, óbito, sobrevida e viabilidade. Métodos: estudo de coorte não concorrente, com 163 recém-nascidos muito prematuros e extremos internados em três unidades de terapia intensiva neonatais, durante 2016 e 2017. Realizou-se análise descritiva dos dados obtidos dos prontuários. Os desfechos estudados foram o uso de suporte ventilatório, morbidades, uso de medicamentos, óbito e causas de óbito. Foi construída curva de sobrevivência e delimitado um limite de viabilidade. Resultados: no estudo, 28,2% eram extremos e 71,8% muito prematuros. Nessa ordem de subgrupos, a necessidade de ventilação mecânica foi maior para os extremos (65,2% e 41,0%) e o principal diagnóstico foi sepse precoce (78,6% e 82,6).Medicamentos off-label (60,5% e 47,9%) e sem-licença (25,3% e 29,0%) foramutilizados. A maioria dos óbitos (57,8%) ocorreu entre os extremos, principalmente por choque séptico. A sobrevivência foi menor para as menores idades gestacionais e o limite de viabilidade ficou entre 26 e 27 semanas. Conclusões: as principais morbidades foram do sistema respiratório, com alto uso de medicamentos off-label e sem licença. Extremos tiveram maior demanda de cuidados intensivos além de necessitarem de mais medicamentos e evoluírem mais ao óbito.

Improving the quality of external cause of death data in Brazil: evaluation and validation of a new form to investigate garbage codes / Melhorando a qualidade dos dados de causa externa de morte no Brasil: avaliação e validação de um novo formulário para investigar códigos garbage / Mejora en la calidad de los datos de causa externa de muerte en Brasil: evaluación y validación de un nuevo formulario para investigar códigos garbage

Garbage codes, such as external causes with no specific information, indicate poor quality cause of death data. Investigation of garbage codes via an effective instrument is necessary to convert them into useful data for public health. This study analyzed the performance and suitability of the new investigation of deaths from external causes (IDEC) form to improve the quality of external cause of death data in Brazil. The performance of the IDEC form on 133 external garbage codes deaths was compared with a stratified matched sample of 992 (16%) investigated deaths that used the standard garbage codes form. Consistency between these two groups was checked. The percentage of garbage codes from external causes reclassified into valid causes with a 95% confidence interval (95%CI) was analyzed. Reclassification for specific causes has been described. Qualitative data on the feasibility of the form were recorded by field investigators. Investigation using the new form reduced all external garbage codes by -92.5% (95%CI: -97.0; -88.0), whereas the existing form decreased garbage codes by -60.5% (95%CI: -63.5; -57.4). The IDEC form presented higher effectivity for external-cause garbage codes of determined intent. Deaths that remained garbage codes mainly lacked information about the circumstances of poisoning and/or vehicle accidents. Despite the fact that field investigators considered the IDEC form feasible, they suggested modifications for further improvement. The new form was more effective than the current standard form in improving the quality of defined external causes.

Códigos garbage (códigos inespecíficos ou incompletos), como causas externas sem informações específicas, indicam dados de má qualidade sobre a causa da morte. É necessário investigar os códigos garbage com um instrumento efetivo para convertê-los em dados úteis para a saúde pública. Este estudo analisou o desempenho e a adequação do novo formulário de investigação de óbitos por causas externas (IDEC) para melhorar a qualidade dos dados de causa externa de morte no Brasil. O desempenho deste formulário em 133 óbitos com códigos garbage de causas externas foi comparado com uma amostra estratificada e pareada de 992 (16%) óbitos investigados que utilizaram o formulário padrão de códigos garbage existente. A consistência entre esses dois grupos foi verificada. Analisou-se o percentual de códigos garbage de causas externas reclassificados em causas válidas com um intervalo de 95% de confiança (IC95%). A reclassificação para causas específicas foi descrita. Dados qualitativos sobre a viabilidade do formulário foram registrados por pesquisadores de campo. A investigação com o novo formulário reduziu todos os códigos garbage de causas externas em -92,5% (IC95%: -97,0; -88,0) enquanto o formulário existente diminuiu os códigos garbage em -60,5% (IC95%: -63,5; -57,4). O formulário IDEC foi mais eficaz para os códigos garbage de causa externa sem intenção indeterminada. As mortes que permaneceram como códigos garbage careciam principalmente de informações detalhadas sobre as circunstâncias do envenenamento e dos acidentes de trânsito. O formulário IDEC foi considerado viável pelos investigadores de campo, no entanto, eles sugeriram modificações para um maior aperfeiçoamento. O novo formulário foi mais eficaz do que o formulário padrão atual na melhoria da qualidade das causas externas definidas.

Códigos garbage (códigos inespecíficos o incompletos), como causas externas inespecíficas, son los indicadores de datos de mala calidad sobre la causa de muerte. Es necesario investigar los códigos garbage con un instrumento eficaz para convertirlos en datos útiles para la salud pública. Este estudio analizó el desempeño y la adecuación del nuevo formulario de investigación de muertes por causas externas (IDEC) para mejorar la calidad de los datos de causa externa de muerte en Brasil. El desempeño de este formulario en 133 muertes con códigos garbage de causas externas se comparó con una muestra estratificada y emparejada de 992 (16%) muertes investigadas que usaron el formulario estándar de códigos garbage existente. Se comprobó la consistencia entre estos dos grupos. Se analizó el porcentaje de códigos garbage por causas externas reclasificados en causas válidas con un intervalo del 95% de confianza (IC95%). Se procedió a una reclasificación por causas específicas. Los datos cualitativos sobre la viabilidad del formulario fueron registrados por investigadores de campo. La investigación con el nuevo formulario tuvo una reducción de todos los códigos garbage de causas externas en -92,5% (IC95%: -97,0; -88,0), mientras que el formulario existente redujo todos los códigos garbage de causas externas en -60,5% (IC95%: -63,5; -57,4). El formulario IDEC fue el más efectivo para códigos garbage de causa externa sin intención indeterminada. Las muertes que quedaron como códigos garbage carecían principalmente de información detallada sobre las circunstancias de envenenamiento y de accidentes de tránsito. Los investigadores de campo confirmaron la viabilidad del formulario IDEC, además de sugerir modificaciones para mejorarlo. El nuevo formulario fue el más efectivo que el formulario estándar actual en cuanto a la mejora de la calidad de las causas externas definidas.

Ensino e pesquisa em saúde mental na atenção básica: Portfólio de Práticas Inspiradoras em Atenção Psicossocial / Mental Health teaching and research in primary care: Portfolio of Inspiring Practices in Psychosocial Care / Enseñanza e investigación en salud mental en atención primaria: Portafolio de Prácticas Inspiradoras en Atención Psicosocial

Resumo Neste artigo, discutimos o processo de trabalho da pesquisa, a metodologia participativa e colaborativa para a construção do site para uso ampliado na Atenção, Ensino e Pesquisa nos campos da Saúde Mental Atenção Básica, o qual intitulamos 'Portfólio de Práticas Inspiradoras em Atenção Psicossocial', bem como as ações em curso para sua gestão compartilhada. O conjunto da pesquisa analisou, sistematizou e categorizou práticas na atenção básica e espaços comunitários, construindo mecanismos de busca e disseminação científica para experiências inovadoras e inspiradoras em todo o país, no período de 2015 a 2020. O site dá visibilidade e relevância às abordagens psicossociais de acolhimento, cuidado e potencialização da vida presentes no Sistema Único de Saúde. Experiências alternativas ao modelo biomédico, base para uma perspectiva interdisciplinar e desinstitucionalizante de Saúde Mental na Atenção Básica.

Abstract In this article, we discuss the working process of the research, the participatory and collaborative methodology for the construction of the website for expanded use in Care, Teaching and Research in the fields of Mental Health Primary Care, which we titled 'Portfolio of Inspiring Practices in Psychosocial care', as well as the ongoing actions for its shared management. The whole research analyzed, systematized and categorized practices in primary care and community spaces, building search engines and scientific dissemination for innovative and inspiring experiences throughout the country, in the period from 2015 to 2020. The website gives visibility and relevance to the psychosocial approaches of reception, care and enhancement of life present in the Unified Health System. Alternative experiences to the biomedical model, the basis for an interdisciplinary and deinstitutionalizing perspective of Mental Health in Primary Care.

Resumen En este artículo discutimos el proceso de trabajo de la investigación, la metodología participativa y colaborativa para la construcción del site de uso ampliado en la Atención, Enseñanza e Investigación en los campos de la Atención Primaria de Salud Mental, que denominamos 'Portafolio de Prácticas Inspiradoras en Atención Psicosocial', así como las acciones en curso para su gestión compartida. El conjunto de investigación analizó, sistematizó y categorizó prácticas en la atención primaria y en los espacios comunitarios, construyendo mecanismos de búsqueda y divulgación científica de experiencias innovadoras e inspiradoras en todo el país, de 2015 a 2020. El site confere visibilidad y relevancia a los enfoques psicosociales de acogida, cuidado y potenciación de vida presentes en el Sistema Único de Salud. Experiencias alternativas al modelo biomédico, base para una perspectiva interdisciplinar y desinstitucionalizadora de la Salud Mental en Atención Primaria.

Retrospective molecular investigation of Mayaro and Oropouche viruses at the human-animal interface in West-central Brazil, 2016-2018.

Mayaro virus (MAYV, Togaviridae) and Oropouche orthobunyavirus (OROV, Peribunyaviridae) are emerging enzootic arboviruses in Latin America. Outbreaks of febrile illness associated with MAYV and OROV have been reported among humans mainly in the northern region of Brazil since the 1980s, and recent data suggest these viruses have circulated also in more populated areas of western Brazil. MAYV shares mosquito vectors with yellow fever virus and it has been historically detected during yellow fever epidemics. Aiming to investigate the transmission of OROV and MAYV at the human-animal interface during a yellow fever, chikungunya and Zika outbreaks in Brazil, we conducted a retrospective molecular investigation in 810 wild and domestic animals, 106 febrile patients, and 22.931 vectors collected from 2016 to 2018 in Cuiaba and Campo Grande metropolitan regions, western Brazil. All samples tested negative for OROV and MAYV RNA by RT-qPCR. Findings presented here suggest no active circulation of MAYV and OROV in the sampled hosts. Active surveillance and retrospective investigations are instrumental approaches for the detection of cryptic and subclinical activity of enzootic arboviruses and together serve as a warning system to implement appropriate actions to prevent outbreaks.

The Role of Growth Factors in the Pathogenesis of Dengue: A Scoping Review.

Growth factors (GFs) have a role in tissue repair and in the modulation of the expression of inflammatory cells in damage caused by pathogens. This study aims to systematize the evidence on the role of GFs in the pathogenesis of dengue. This scoping review considered all published peer-reviewed studies in the MEDLINE and Embase databases. Ultimately, 58 studies that analyzed GFs in dengue patients, published between 1998 and 2021, were included. DENV-2 infection and secondary infection were more frequent in the patients studied. ELISA and multiplex immunoassay (Luminex) were the most used measurement techniques. Increased levels of vascular endothelial growth factor, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, transforming growth factor beta, and hepatocyte growth factor as well as reduced levels of platelet-derived growth factor and epidermal growth factor were observed in severe dengue in most studies. Vascular endothelial growth factor and hepatocyte growth factor were identified as biomarkers of severity. In addition, there is evidence that the dengue virus can use the growth factor pathway to facilitate its entry into the cell and promote its viral replication. The use of tyrosine kinase inhibitors is an alternative treatment for dengue that is being studied.

Robotic Intracorporeal Rectus Aponeuroplasty: Early Experience of a New Surgical Technique for Ventral Hernia Repair.

Introduction: The laparoscopic intracorporeal rectus aponeuroplasty (LIRA) was developed as an alternative for minimally invasive ventral hernia repair. This technique allows the closure of the defect and restoration of the midline without tension by plication of both aponeurosis of the abdominal rectus muscles combined with a minimally invasive intraperitoneal underlay mesh repair. The objective of this study is to report our early experience with the Robotic-LIRA (R-LIRA) technique and its safety and short-term efficacy. Methods: We performed a retrospective analysis of patients undergoing R-LIRA repair for ventral hernias from March 2019 to April 2022. Results: Eight patients underwent R-LIRA from March 2019 to April 2022. Median age was 47 years (interquartile range [IQR] 34.5-62.8). Median body mass index was 34.2 kg/m2 (IQR 29.9-35.2). Four patients (50%) had a primary ventral hernia being one M2, two M3, and one M2/M3. There were three incisional hernias, being one recurrent, 6 patients (75%) had associated diastasis of the rectus muscle and 1 patient presented pure diastasis. The median hernia width was 4 cm (IQR 2-6), and the median defect area was 16 cm2 (IQR 4-42). The median mesh area was 290 cm2 (IQR 211.2-300). In all cases, a barbed suture was also used for mesh fixation, and tackers were added in 4 cases. The median operative time was 172 minutes (IQR 139.8-293.3). The median length of stay was 0.5 days (IQR 0-1.8), and the median follow-up was 20 days (IQR 16-46). Conclusion: The R-LIRA has been shown to be safe and feasible for ventral and incisional hernia repairs with or without Diastasis of the Rectus Abdominis Muscle in the short term.

A Chikungunya Virus Multiepitope Recombinant Protein Expressed from the Binary System Insect Cell/Recombinant Baculovirus Is Useful for Laboratorial Diagnosis of Chikungunya.

Chikungunya virus (CHIKV) is an arbovirus currently distributed worldwide, causing a disease that shares clinical signs and symptoms with other illnesses, such as dengue and Zika and leading to a challenging clinical differential diagnosis. In Brazil, CHIKV emerged in 2014 with the simultaneous introduction of both Asian and East/Central/South African (ECSA) genotypes. Laboratorial diagnosis of CHIKV is mainly performed by molecular and serological assays, with the latter more widely used. Although many commercial kits are available, their costs are still high for many underdeveloped and developing countries where the virus circulates. Here we described the development and evaluation of a multi-epitope recombinant protein-based IgG-ELISA (MULTREC IgG-ELISA) test for the specific detection of anti-CHIKV antibodies in clinical samples, as an alternative approach for laboratorial diagnosis. The MULTREC IgG-ELISA showed 86.36% of sensitivity and 100% of specificity, and no cross-reactivity with other exanthematic diseases was observed. The recombinant protein was expressed from the binary system insect cell/baculovirus using the crystal-forming baculoviral protein polyhedrin as a carrier of the target recombinant protein to facilitate recovery. The crystals were at least 10 times smaller in size and had an amorphous shape when compared to the polyhedrin wild-type crystal. The assay uses a multi-epitope antigen, representing two replicates of 18 amino acid sequences from the E2 region and a sequence of 17 amino acids from the nsP3 region of CHIKV. The recombinant protein was highly expressed, easy to purify and has demonstrated its usefulness in confirming chikungunya exposure, indeed showing a good potential tool for epidemiological surveillance.

Terapias inovadoras para reparo tecidual em pessoas com pé diabético / Innovative therapies for tissue repair in people with diabetic feet / Terapias innovadoras para la reparación de tejidos en personas con pie diabético

Objetivo: Identificar as terapias inovadoras para reparo tecidual em pessoas com pé diabético. Método: Revisão integrativa, conduzida nas bases de dados/portal: Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) e Base de Dados de Enfermagem (BDENF) via Biblioteca Virtual em Saúde (BVS), Scientific Electronic Library Online (SciELO), SCOPUS e PubMed. Foram utilizadas estratégias de buscas, com utilização de descritores do Descritores em Ciências da Saúde (DeSC) e Medical Subject Headings (MeSH), em associação com os operadores booleanos AND e OR. As buscas foram efetuadas em fevereiro de 2022. A triagem e seleção dos artigos contou com auxílio do software Rayyan. Os principais resultados do estudo foram distribuídos em quadros e descritos de forma narrativa. Resultados: Foram incluídos 18 artigos, que evidenciaram 13 terapias inovadoras, sendo duas terapias de origem vegetal: extrato de kiwi e biomembrana de proteínas do látex de Calotropis procera; seis terapias advindas de tecidos humanos: cimento ósseo carregado com antibiótico, plasma autólogo rico em plaquetas, membrana amniótica, derivados do cordão umbilical, enxerto de pele e células mesenquimais derivadas de placenta humana; e cinco terapias permeadas por tecnologias duras: terapia por pressão negativa, ozonioterapia, heberprot-P ®, oxigenoterapia hiperbárica e laserterapia. Foram identificados diversos benefícios no uso dessas terapias, como melhor taxa de cicatrização, redução da taxa de amputação e no tamanho da úlceras. Conclusão: Diversas terapias podem ser utilizadas para tratamento do pé diabético em associação com o tratamento padrão, coadjuvado as chances de cicatrização total, menor risco de amputações, melhora da marcha e qualidade de vida das pessoas com diabetes mellitus e úlceras nos pés.

Objective:To identify innovative therapies for tissue repair in people with diabetic feet. Method:Integrative review, conducted in the databases/portal: Latin American and Caribbean Literature on Health Sciences (LILACS) and Nursing Database (BDENF) via the Virtual Health Library (BVS), Scientific Electronic Library Online (SciELO), SCOPUS, and PubMed. Search strategies were used, using descriptors from the Descriptors in Health Sciences (DeSC) and Medical Subject Headings (MeSH), in association with the Boolean operators AND/OR. The searches were carried out in February 2022. The screening and selection of articles were aided by the Rayyan software. The main results of the study were distributed in tables and described in a narrative way. Results:Eighteen articles were included, which showed 13 innovative therapies, two of which were of plant origin: kiwi extract and Calotropis procera latex protein biomembrane; six therapies derived from human tissues: bone cement loaded with antibiotics, autologous platelet-rich plasma, amniotic membrane, umbilical cord derivatives, skin graft and mesenchymal cells derived from the human placenta; and five therapies permeated by hard technologies: negative pressure therapy, ozone therapy, heberprot-P®, hyperbaric oxygen therapy, and laser therapy. Several benefits were identified in the use of these therapies, such as better healing rate, reduced amputation rate, and ulcer size. Conclusion:Several therapies can be used to treat diabetic feet in association with standard treatment, helping the chances of total healing, lower risk of amputations, improved gait, and quality of life for people with diabetes mellitus and foot ulcers.

Objetivo:Identificar terapias innovadoras para la reparación de tejidos en personas con pie diabético. Método:Revisión integradora, realizada en las bases de datos/portal: Literatura Latinoamericana y del Caribe en Ciencias de la Salud (LILACS) y Base de Datos de Enfermería (BDENF) a través de la Biblioteca Virtual en Salud (BVS), Scientific Electronic Library Online (SciELO), SCOPUS y PubMed. Se utilizaron estrategias de búsqueda, utilizando descriptores de Descriptors in Health Sciences (DeSC) y Medical Subject Headings (MeSH), en asociación con los operadores booleanos AND y OR. Las búsquedas se realizaron en febrero de 2022. El software Rayyan ayudó a la selección y selección de artículos. Los principales resultados del estudio se distribuyeron en tablas y se describieron de forma narrativa. Resultados:Se incluyeron dieciocho artículos, que mostraron 13 terapias innovadoras, dos de las cuales fueron de origen vegetal: extracto de kiwi y biomembrana de proteína de látexde Calotropis procera; seis terapias derivadas de tejidos humanos: cemento óseo cargado con antibióticos, plasma autólogo rico en plaquetas, membrana amniótica, derivados de cordón umbilical, injerto de piel y células mesenquimales derivadas de placenta humana; y cinco terapias permeadas por tecnologías duras: terapia de presión negativa, ozonoterapia, heberprot-P®, oxigenoterapia hiperbárica y láserterapia. Se identificaron varios beneficios en el uso de estas terapias, como una mejor tasa de cicatrización, una tasa de amputación y un tamaño de úlcera reducidos. Conclusión:Varias terapias pueden ser utilizadas para tratar el pie diabético en asociación con el tratamiento estándar, lo que ayuda a las posibilidades de curación total, menor riesgo de amputaciones, mejora de la marcha y calidad de vida de las personas con diabetes mellitus y úlceras en los pies.

BAG2 prevents Tau hyperphosphorylation and increases p62/SQSTM1 in cell models of neurodegeneration.

BACKGROUND: Protein aggregates are pathological hallmarks of many neurodegenerative diseases, however the physiopathological role of these aggregates is not fully understood. Protein quality control has a pivotal role for protein homeostasis and depends on specific chaperones. The co-chaperone BAG2 can target phosphorylated Tau for degradation by an ubiquitin-independent pathway, although its possible role in autophagy was not yet elucidated. In view of this, the aim of the present study was to investigate the association among protein aggregation, autophagy and BAG2 levels in cultured cells from hippocampus and locus coeruleus as well as in SH-SY5Y cell line upon different protein aggregation scenarios induced by rotenone, which is a flavonoid used as pesticide and triggers neurodegeneration. METHODS AND RESULTS: The present study showed that rotenone exposure at 0.3 nM for 48 h impaired autophagy prior to Tau phosphorylation at Ser199/202 in hippocampus but not in locus coeruleus cells, suggesting that distinct neuron cells respond differently to rotenone toxicity. Rotenone induced Tau phosphorylation at Ser199/202, together with a decrease in the endogenous BAG2 protein levels in SH-SY5Y and hippocampus cell culture, which indicates that rotenone and Tau hyperphosphorylation can affect this co-chaperone. Finally, it has been shown that BAG2 overexpression, increased p62/SQSTM1 levels in cells from hippocampus and locus coeruleus, stimulated LC3II recycling as well as prevented the raise of phosphorylated Tau at Ser199/202 in hippocampus. CONCLUSIONS: Results demonstrate a possible role for BAG2 in degradation pathways of specific substrates and its importance for the study of cellular aspects of neurodegenerative diseases.