Multinational experience with next-generation sequencing: opportunity to identify transthyretin cardiac amyloidosis and Fabry disease.

Background: Sarcomeric hypertrophic cardiomyopathy (HCM) must be differentiated from phenotypically similar conditions because clinical management and prognosis may greatly differ. Patients with unexplained left ventricular hypertrophy require an early, confirmed genetic diagnosis through diagnostic or predictive genetic testing. We tested the feasibility and practicality of the application of a 17-gene next-generation sequencing (NGS) panel to detect the most common genetic causes of HCM and HCM phenocopies, including treatable phenocopies, and report detection rates. Identification of transthyretin cardiac amyloidosis (ATTR-CA) and Fabry disease (FD) is essential because of the availability of disease-specific therapy. Early initiation of these treatments may lead to better clinical outcomes. Methods: In this international, multicenter, cross-sectional pilot study, peripheral dried blood spot samples from patients of cardiology clinics with an unexplained increased left ventricular wall thickness (LVWT) of ≥13 mm in one or more left ventricular myocardial segments (measured by imaging methods) were analyzed at a central laboratory. NGS included the detection of known splice regions and flanking regions of 17 genes using the Illumina NextSeq 500 and NovaSeq 6000 sequencing systems. Results: Samples for NGS screening were collected between May 2019 and October 2020 at cardiology clinics in Colombia, Brazil, Mexico, Turkey, Israel, and Saudi Arabia. Out of 535 samples, 128 (23.9%) samples tested positive for pathogenic/likely pathogenic genetic variants associated with HCM or HCM phenocopies with double pathogenic/likely pathogenic variants detected in four samples. Among the 132 (24.7%) detected variants, 115 (21.5%) variants were associated with HCM and 17 (3.2%) variants with HCM phenocopies. Variants in MYH7 (n=60, 11.2%) and MYBPC3 (n=41, 7.7%) were the most common HCM variants. The HCM phenocopy variants included variants in the TTR (n=7, 1.3%) and GLA (n=2, 0.4%) genes. The mean (standard deviation) ages of patients with HCM or HCM phenocopy variants, including TTR and GLA variants, were 42.8 (17.9), 54.6 (17.0), and 69.0 (1.4) years, respectively. Conclusions: The overall diagnostic yield of 24.7% indicates that the screening strategy effectively identified the most common forms of HCM and HCM phenocopies among geographically dispersed patients. The results underscore the importance of including ATTR-CA (TTR variants) and FD (GLA variants), which are treatable disorders, in the differential diagnosis of patients with increased LVWT of unknown etiology.

CD20+ T cells in monoclonal B cell lymphocytosis and chronic lymphocytic leukemia: frequency, phenotype and association with disease progression.

Introduction: In monoclonal B cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL), the expansion of malignant B cells disrupts the normal homeostasis and interactions between B cells and T cells, leading to immune dysregulation. CD20+ T cells are a subpopulation of T cells that appear to be involved in autoimmune diseases and cancer. Methods: Here, we quantified and phenotypically characterized CD20+ T cells from MBL subjects and CLL patients using flow cytometry and correlated our findings with the B-cell receptor mutational status and other features of the disease. Results and discussion: CD20+ T cells were more represented within the CD8+ T cell compartment and they showed a predominant memory Tc1 phenotype. CD20+ T cells were less represented in MBL and CLL patients vs healthy controls, particularly among those with unmutated IGVH gene. The expansion of malignant B cells was accompanied by phenotypic and functional changes in CD20+ T cells, including an increase in follicular helper CD4+ CD20+ T cells and CD20+ Tc1 cells, in addition to the expansion of the TCR Vß 5.1 in CD4+ CD20+ T cells in CLL.

Biomechanical Assessment Methods Used in Chronic Stroke: A Scoping Review of Non-Linear Approaches.

Non-linear and dynamic systems analysis of human movement has recently become increasingly widespread with the intention of better reflecting how complexity affects the adaptability of motor systems, especially after a stroke. The main objective of this scoping review was to summarize the non-linear measures used in the analysis of kinetic, kinematic, and EMG data of human movement after stroke. PRISMA-ScR guidelines were followed, establishing the eligibility criteria, the population, the concept, and the contextual framework. The examined studies were published between 1 January 2013 and 12 April 2023, in English or Portuguese, and were indexed in the databases selected for this research: PubMed®, Web of Science®, Institute of Electrical and Electronics Engineers®, Science Direct® and Google Scholar®. In total, 14 of the 763 articles met the inclusion criteria. The non-linear measures identified included entropy (n = 11), fractal analysis (n = 1), the short-term local divergence exponent (n = 1), the maximum Floquet multiplier (n = 1), and the Lyapunov exponent (n = 1). These studies focused on different motor tasks: reaching to grasp (n = 2), reaching to point (n = 1), arm tracking (n = 2), elbow flexion (n = 5), elbow extension (n = 1), wrist and finger extension upward (lifting) (n = 1), knee extension (n = 1), and walking (n = 4). When studying the complexity of human movement in chronic post-stroke adults, entropy measures, particularly sample entropy, were preferred. Kinematic assessment was mainly performed using motion capture systems, with a focus on joint angles of the upper limbs.

Synthesis and In Vitro and Silico Anti-inflammatory Activity of New Thiazolidinedione-quinoline Derivatives.

BACKGROUND: Inflammation is a series of complex defense-related reactions. The inflammation cascade produces various pro-inflammatory mediators. Unregulated production of these pro-inflammatory mediators can lead to a wide range of diseases, including rheumatoid arthritis, sepsis, and inflammatory bowel disease. In the literature, the anti-inflammatory action of quinoline and thiazolidinedione nuclei are well established, alone, and associated with other nuclei. The synthesis of hybrid molecules is a strategy for obtaining more efficient molecules due to the union of pharmacophoric nuclei known to be related to pharmacological activity. OBJECTIVE: Based on this, this work presents the synthesis of thiazolidinedione-quinoline molecular hybrids and their involvement in the modulation of cytokines involved in the inflammatory reaction cascade. METHODS: After synthesis and characterization, the compounds were submitted to cell viability test (MTT), ELISA IFN-γ and TNF-α, adipogenic differentiation, and molecular docking assay with PPARy and COX-2 targets. RESULTS: LPSF/ZKD2 and LPSF/ZKD7 showed a significant decrease in the concentration of IFN- γ and TNF-α, with a dose-dependent behavior. LPSF/ZKD4 at a concentration of 50 µM significantly reduced IL-6 expression. LPSF/ZKD4 demonstrates lipid accumulation with significant differences between the untreated and negative control groups, indicating a relevant agonist action on the PPARγ receptor. Molecular docking showed that all synthesized compounds have good affinity with PPARγ e COX-2, with binding energy close to -10,000 Kcal/mol. CONCLUSION: These results demonstrate that the synthesis of quinoline-thiazolidinedione hybrids may be a useful strategy for obtaining promising candidates for new anti-inflammatory agents.

Wearables for Monitoring and Postural Feedback in the Work Context: A Scoping Review.

Wearables offer a promising solution for simultaneous posture monitoring and/or corrective feedback. The main objective was to identify, synthesise, and characterise the wearables used in the workplace to monitor and postural feedback to workers. The PRISMA-ScR guidelines were followed. Studies were included between 1 January 2000 and 22 March 2023 in Spanish, French, English, and Portuguese without geographical restriction. The databases selected for the research were PubMed®, Web of Science®, Scopus®, and Google Scholar®. Qualitative studies, theses, reviews, and meta-analyses were excluded. Twelve studies were included, involving a total of 304 workers, mostly health professionals (n = 8). The remaining studies covered workers in the industry (n = 2), in the construction (n = 1), and welders (n = 1). For assessment purposes, most studies used one (n = 5) or two sensors (n = 5) characterised as accelerometers (n = 7), sixaxial (n = 2) or nonaxialinertial measurement units (n = 3). The most common source of feedback was the sensor itself (n = 6) or smartphones (n = 4). Haptic feedback was the most prevalent (n = 6), followed by auditory (n = 5) and visual (n = 3). Most studies employed prototype wearables emphasising kinematic variables of human movement. Healthcare professionals were the primary focus of the study along with haptic feedback that proved to be the most common and effective method for correcting posture during work activities.

Logical model of reception and risk classification for women with pre-eclampsia and eclampsia.

OBJECTIVE: To describe the validation of the Logical Model of Reception and Risk Classification for women with pre-eclampsia/eclampsia in a high-risk maternity hospital. METHOD: Evaluative research with a quantitative approach. The elaboration and validation of the Logical Model were systematized in stages related to the scope review, preparation of the document guided by the Donabedian model and validation by 12 stakeholders, aiming at the assessment of the Content Validation Index. RESULTS: The problem that gave rise to the intervention was elaborated, supporting the construction of the Logical Model. Agreement was reached on 24 items, reaching a Content Validation Index of 0.99. Stakeholders included contributions regarding correlations between elements of the structure and process. CONCLUSION: The document achieved high content validity and could contribute to decision-making by managers in the Reception and Risk Classification sectors for women with pre-eclampsia and/or eclampsia.

Aquimarina aquimarini sp. nov. and Aquimarina spinulae sp. nov., novel bacterial species with versatile natural product biosynthesis potential isolated from marine sponges.

This study describes two Gram-negative, flexirubin-producing, biofilm-forming, motile-by-gliding and rod-shaped bacteria, isolated from the marine sponges Ircinia variabilis and Sarcotragus spinosulus collected off the coast of Algarve, Portugal. Both strains, designated Aq135T and Aq349T, were classified into the genus Aquimarina by means of 16S rRNA gene sequencing. We then performed phylogenetic, phylogenomic and biochemical analyses to determine whether these strains represent novel Aquimarina species. Whereas the closest 16S rRNA gene relatives to strain Aq135T were Aquimarina macrocephali JAMB N27T (97.8 %) and Aquimarina sediminis w01T (97.1 %), strain Aq349T was more closely related to Aquimarina megaterium XH134T (99.2 %) and Aquimarina atlantica 22II-S11-z7T (98.1 %). Both strains showed genome-wide average nucleotide identity scores below the species level cut-off (95 %) with all Aquimarina type strains with publicly available genomes, including their closest relatives. Digital DNA-DNA hybridization further suggested a novel species status for both strains since values lower than 70 % hybridization level with other Aquimarina type strains were obtained. Strains Aq135T and Aq349T grew from 4 to 30°C and with between 1-5 % (w/v) NaCl in marine broth. The most abundant fatty acids were iso-C17 : 03-OH and iso-C15 : 0 and the only respiratory quinone was MK-6. Strain Aq135T was catalase-positive and ß-galactosidase-negative, while Aq349T was catalase-negative and ß-galactosidase-positive. These strains hold unique sets of secondary metabolite biosynthetic gene clusters and are known to produce the peptide antibiotics aquimarins (Aq135T) and the trans-AT polyketide cuniculene (Aq349T), respectively. Based on the polyphasic approach employed in this study, we propose the novel species names Aquimarina aquimarini sp. nov. (type strain Aq135T=DSM 115833T=UCCCB 169T=ATCC TSD-360T) and Aquimarina spinulae sp. nov. (type strain Aq349T=DSM 115834T=UCCCB 170T=ATCC TSD-361T).

An Intestinal FXR Agonist Mitigates Dysbiosis, Intestinal Tight Junctions, and Inflammation in High-Fat Diet-Fed Mice.

SCOPE: To analyze the effects of fexaramine (FEX), as an intestinal FXR agonist, on the modulation of the intestinal microbiota and ileum of mice fed a high-fat (HF) diet. METHODS AND RESULTS: Three-month-old C57Bl/6 male mice are divided into two groups and received a control (C, 10% of energy from lipids) or HF (50% of energy from lipids) diet for 12 weeks. They are subdivided into the C, C + FEX, HF, and HF + FEX groups. FEX is administered (FEX-5 mg kg-1 ) via orogastric gavage for three weeks. Body mass (BM), glucose metabolism, qPCR 16S rRNA gene expression, and ileum gene expression, bile acids (BAs), tight junctions (TJs), and incretin are analyzed. FEX reduces BM and glucose intolerance, reduces plasma lipid concentrations and the Firmicutes/Bacteroidetes ratio, increases the Lactobacillus sp. and Prevotella sp. abundance, and reduces the Escherichia coli abundance. Consequently, the ileal gene expression of Fxr-Fgf15, Tgr5-Glp1, and Cldn-Ocldn-Zo1 is increased, and Tlr4-Il6-Il1beta is decreased. CONCLUSION: FEX stimulates intestinal FXR and improves dysbiosis, intestinal TJs, and the release of incretins, mitigating glucose intolerance and BM increases induced by an HF diet. However, FEX results in glucose intolerance, insulin resistance, and reduces intestinal TJs in a control group, thus demonstrating limitations to this dietary model.

Avaliação normativa do atendimento obstétrico emergencial na prevenção da COVID-19 / Evaluación normativa de la asistencia obstétrica de emergencia en la prevención de COVID-19 / Normative evaluation of emergency obstetric care in the prevention of COVID-19

Resumo Objetivo Avaliar a estrutura e o fluxo assistencial do acolhimento - classificação de risco e emergência obstétrica em uma maternidade pública no contexto da COVID-19. Métodos Estudo do tipo avaliação normativa e observacional nos setores de Acolhimento (Classificação de Risco e Emergência Obstétrica) de uma maternidade pública no Rio de Janeiro. A coleta de dados foi realizada de junho a agosto de 2020 por 480 horas de observação direta não participante, com registros sistematizados em checklist contendo variáveis relacionadas à disponibilidade e conformidade dos recursos estruturais, e à conformidade do fluxo assistencial. Os dados foram organizados em planilhas (Microsoft Excel® 2010) e analisados usando a estatística descritiva. Resultados A avaliação da estrutura obteve 80,3% de disponibilidade, resultando em classificação de alta disponibilidade e 91,1% de conformidade, obtendo conformidade adequada. O fluxo assistencial mostrou 72,7% de conformidade total; 9,1% de conformidade parcial e 18,2% de não cumprimento, configurando-se como alta conformidade. Conclusão A avaliação normativa indicou altas disponibilidade e conformidade em estrutura e fluxo assistencial nos cenários estudados.

Resumen Objetivo Evaluar la estructura y el flujo de asistencia de recepción, clasificación de riesgo y emergencia obstétrica, en una maternidad pública en el contexto del COVID-19. Métodos Estudio tipo evaluación normativa y observacional en los sectores de Recepción (clasificación de riesgo y emergencia obstétrica) de una maternidad pública en Rio de Janeiro. La recopilación de datos se realizó de junio a agosto de 2020 durante 480 de observación directa no participante, con registros sistematizados en una checklist con variables relacionadas con la disponibilidad y conformidad de los recursos estructurales y con la conformidad del flujo de asistencia. Los datos se organizaron en planillas (Microsoft Excel® 2010) y se analizaron usando la estadística descriptiva. Resultados La evaluación de la estructura obtuvo un 80,3 % de disponibilidad, que tuvo como resultado una clasificación de alta disponibilidad, y un 91,1 % de conformidad, con una conformidad adecuada. El flujo de asistencia mostró un 72,7 % de conformidad total, un 9,1 % de conformidad parcial y un 18,2 % de no cumplimiento, lo que se configura como alta conformidad. Conclusión La evaluación normativa indicó alta disponibilidad y alta conformidad en estructura y flujo de asistencia en los escenarios estudiados.

Abstract Objective Evaluate the structure and care flow - risk classification and obstetric emergency in a public maternity hospital in the context of COVID-19. Methods Normative and observational evaluation study in the Care sectors (Risk Classification and Obstetric Emergency) of a public maternity hospital in Rio de Janeiro. Data collection was carried out from June to August 2020 for 480 hours of non-participant direct observation, with records systematized in a checklist containing variables related to the availability and compliance of structural resources, and the compliance of the care flow. Data were organized into spreadsheets (Microsoft Excel® 2010) and analyzed using descriptive statistics. Results The framework assessment scored 80.3% availability, resulting in a high availability rating, and 91.1% compliance, achieving adequate compliance. The care flow showed 72.7% of total compliance; 9.1% of partial compliance and 18.2% of non-compliance, configuring high compliance. Conclusion Normative evaluation indicated high availability and compliance in structure and care flow in the studied scenarios.

Natural product biosynthetic potential reflects macroevolutionary diversification within a widely distributed bacterial taxon.

IMPORTANCE: This is the most comprehensive study performed thus far on the biosynthetic potential within the Flavobacteriaceae family. Our findings reveal intertwined taxonomic and natural product biosynthesis diversification within the family. We posit that the carbohydrate, peptide, and secondary metabolism triad synergistically shaped the evolution of this keystone bacterial taxon, acting as major forces underpinning the broad host range and opportunistic-to-pathogenic behavior encompassed by species in the family. This study further breaks new ground for future research on select Flavobacteriaceae spp. as reservoirs of novel drug leads.

Dieta mediterrânea para prevenção de doenças cardiovasculares: overview de revisões sistemáticas / Mediterranean diet for prevention of cardiovascular diseases: overview of systematic reviews

Contextualização: As doenças cardiovasculares (DCV) representam a principal causa de morte no Brasil e no mundo e a dieta mediterrânea (DM) surgiu como possibilidade de prevenção dessas doenças. Ela envolve o alto consumo de frutas, vegetais, frutos do mar, nozes, legumes, grãos e azeite, e ingestão moderada de vinho nas refeições, além de menor ingestão de carnes vermelhas e processadas, gordura saturada, doces e bebidas açucaradas. Objetivo: Avaliar a efetividade da DM para prevenção de DCV. Métodos: Trata-se de overview de revisões sistemáticas. Procedeu-se à busca por estudos que associavam a DM às DCV em quatro bases eletrônicas de dados: Cochrane - Central de Registros de Ensaios Clínicos - CENTRAL (2023), PubMed (1966-2023), Portal BVS (1982-2023) e EMBASE (1974-2023). Dois pesquisadores, independentemente extraíram os dados e avaliaram a qualidade dos estudos para a síntese. O desfecho primário de análise envolveu a prevenção de doença cardiovascular e a redução de mortalidade. Resultados: 5 revisões sistemáticas foram incluídas, totalizando 74 ensaios clínicos (n = 124.820) e 16 coortes prospectivas (n = 722.495). Discussão: Embora os estudos incluídos relatem benefícios favoráveis à DM para prevenção de DCV, as evidências são de baixa a moderada qualidade, diante da heterogeneidade e fragilidades metodológicas. Sugere-se a realização de novos estudos clínicos com padronização de relato dos resultados. Conclusão: Parece haver benefício da DM para prevenção de DCV, mas diante das evidências limitadas, há incertezas que tornam lícita a recomendação por novos ensaios clínicos com comparação a outras dietas, para maior robustez dos achados.

Analysis of the Mutational Landscape of Osteosarcomas Identifies Genes Related to Metastasis and Prognosis and Disrupted Biological Pathways of Immune Response and Bone Development.

Osteosarcoma (OS) is the most prevalent type of bone tumor, but slow progress has been achieved in disentangling the full set of genomic events involved in its initiation and progression. We assessed by NGS the mutational spectrum of 28 primary OSs from Brazilian patients, and identified 445 potentially deleterious SNVs/indels and 1176 copy number alterations (CNAs). TP53 was the most recurrently mutated gene, with an overall rate of ~60%, considering SNVs/indels and CNAs. The most frequent CNAs (~60%) were gains at 1q21.2q21.3, 6p21.1, and 8q13.3q24.22, and losses at 10q26 and 13q14.3q21.1. Seven cases presented CNA patterns reminiscent of complex events (chromothripsis and chromoanasynthesis). Putative RB1 and TP53 germline variants were found in five samples associated with metastasis at diagnosis along with complex genomic patterns of CNAs. PTPRQ, KNL1, ZFHX4, and DMD alterations were prevalent in metastatic or deceased patients, being potentially indicative of poor prognosis. TNFRSF11B, involved in skeletal system development and maintenance, emerged as a candidate for osteosarcomagenesis due to its biological function and a high frequency of copy number gains. A protein-protein network enrichment highlighted biological pathways involved in immunity and bone development. Our findings reinforced the high genomic OS instability and heterogeneity, and led to the identification of novel disrupted genes deserving further evaluation as biomarkers due to their association with poor outcomes.

[Care in a natural birth center and due compliance with national guidelines]. / O cuidado na casa de parto e sua conformidade com as diretrizes nacionais.

The scope of this article is to analyze the compliance of the care offered by Casa de Parto David Capistrano Filho-RJ with the recommendations of the National Guidelines for Care in Natural Childbirth. It involved a descriptive cross-sectional study with 952 observations, from 2014 to 2018. This included analysis of compliance using a judgment matrix and then classified as total compliance (≥75.0%), partial compliance (50.0%-74.9%), incipient compliance (49.9%-25.0%) and non-compliance (less than 24.9%). The results of the judgment matrix show that care in the aspects of labor, delivery and newborn care is in full compliance with the recommendations of the Guidelines. The care at the Casa de Parto Birth Center, conducted by obstetric nurses, follows the recommendations of the national guidelines, and has been seen to incorporate a de-medicalized, personalized form of care, which respects the physiology of childbirth. They also develop a model of their own technologies of care, constituting non-invasive technologies of obstetric nursing care.

O objetivo deste artigo é analisar a conformidade do cuidado oferecido pela Casa de Parto David Capistrano Filho-RJ às recomendações das Diretrizes Nacionais de Assistência ao Parto Normal. Estudo transversal descritivo com 952 observações, no período de 2014 a 2018. Análise de conformidade através de matriz de julgamento e classificada como conformidade total (≥75,0%), conformidade parcial (50,0%-74,9%), conformidade incipiente (49,9%-25,0%) e não conformidade (menor que 24,9%). Os resultados da matriz de julgamento mostram que o cuidado na atenção ao trabalho de parto, parto e assistência ao recém-nascido apresenta conformidade total em relação às recomendações das Diretrizes. O cuidado na Casa de Parto, conduzido por enfermeiras obstétricas, segue as recomendações das diretrizes nacionais, e vem evidenciando uma prática desmedicalizada, autônoma, que respeita a fisiologia do parto. Desenvolvem também um modelo de tecnologias próprias de cuidar, constituindo as tecnologias não invasivas de cuidado de enfermagem obstétrica.

O cuidado na casa de parto e sua conformidade com as diretrizes nacionais / Care in a natural birth center and due compliance with national guidelines

Resumo O objetivo deste artigo é analisar a conformidade do cuidado oferecido pela Casa de Parto David Capistrano Filho-RJ às recomendações das Diretrizes Nacionais de Assistência ao Parto Normal. Estudo transversal descritivo com 952 observações, no período de 2014 a 2018. Análise de conformidade através de matriz de julgamento e classificada como conformidade total (≥75,0%), conformidade parcial (50,0%-74,9%), conformidade incipiente (49,9%-25,0%) e não conformidade (menor que 24,9%). Os resultados da matriz de julgamento mostram que o cuidado na atenção ao trabalho de parto, parto e assistência ao recém-nascido apresenta conformidade total em relação às recomendações das Diretrizes. O cuidado na Casa de Parto, conduzido por enfermeiras obstétricas, segue as recomendações das diretrizes nacionais, e vem evidenciando uma prática desmedicalizada, autônoma, que respeita a fisiologia do parto. Desenvolvem também um modelo de tecnologias próprias de cuidar, constituindo as tecnologias não invasivas de cuidado de enfermagem obstétrica.

Abstract The scope of this article is to analyze the compliance of the care offered by Casa de Parto David Capistrano Filho-RJ with the recommendations of the National Guidelines for Care in Natural Childbirth. It involved a descriptive cross-sectional study with 952 observations, from 2014 to 2018. This included analysis of compliance using a judgment matrix and then classified as total compliance (≥75.0%), partial compliance (50.0%-74.9%), incipient compliance (49.9%-25.0%) and non-compliance (less than 24.9%). The results of the judgment matrix show that care in the aspects of labor, delivery and newborn care is in full compliance with the recommendations of the Guidelines. The care at the Casa de Parto Birth Center, conducted by obstetric nurses, follows the recommendations of the national guidelines, and has been seen to incorporate a de-medicalized, personalized form of care, which respects the physiology of childbirth. They also develop a model of their own technologies of care, constituting non-invasive technologies of obstetric nursing care.

Experiencias de aprendizaje orientadas al bienestar / Wellbeing-oriented learning experiences

Introducción: En la educación médica, las estrategias de enseñanza orientadas al bienestar comienzan a generar interés, y las experiencias artísticas, de acuerdo con la bibliografía, pueden ser una alternativa. Materiales y métodos: Este estudio tuvo como propósito describir la experiencia del curso electivo virtual ‘Bienestar, arte y salud' en una escuela de medicina en Colombia, que se realizó durante 2021-2022. Se aplicó la metodología para la evaluación de programas en las profesiones de salud. Resultados: Las actividades de aprendizaje buscaron: cambios en la percepción de los estudiantes sobre la relación bienestar, salud y arte; generar procesos reflexivos sobre la experiencia estética y artística; promover la comprensión de la experiencia estética y su impacto en la salud de las personas; y reflexionar sobre el bienestar propio y el bienestar de otros. Los conocimientos previos y las experiencias de los estudiantes en relación con el bienestar propio y el de personas cercanas son importantes para la comprensión de los contenidos del curso. Los proyectos propuestos por los estudiantes se relacionan con experiencias propias y reflexiones sobre situaciones como problemas de salud mental y asociados con el estudio y la práctica médica. Conclusiones: El estudio concluye que el interés por el autocuidado, la transdisciplinariedad y la flexibilidad académica puede beneficiar aprendizajes relacionados con el bienestar.(AU)

Introduction: In medical education, well-being oriented teaching strategies are beginning to generate interest and artistic experiences, according to the literature, can be an alternative. Materials and methods: The purpose of this study was to describe the experience of the virtual elective course: ‘Well-being, art and health', in a medical school in Colombia, which took place during 2021-2022. We applied the methodology for the evaluation of programs in the health professions. Results: The learning activities sought: to change students' perception of the relationship between wellbeing, health and art; to generate reflective processes on the aesthetic and artistic experience; to promote understanding of the aesthetic experience and its impact on people's health; and to reflect on one's own wellbeing and the wellbeing of others. Students' prior knowledge and experiences in relation to the wellbeing of self and others close to them are important for the understanding of the course content. The projects proposed by the students are related to own experiences and reflections on situations such as mental health problems and associated with medical study and practice. Conclusions: The study concludes that interest in self-care, transdisciplinarity and academic flexibility can benefit learning related to wellbeing.(AU)

Saline extract of Portulaca elatior leaves with photoprotective and antioxidant activities does not show acute oral and dermal toxicity in mice.

The present study aimed to evaluate saline extracts from the leaves (LE) and stem (SE) of Portulaca elatior in relation to their phytochemical composition and photoprotective and antioxidant effects, as well as to evaluate the toxicity of the leaf extract. The extracts were characterized for protein concentration and phenol and flavonoid contents, as well as for thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC) profiles. Total antioxidant capacity and DPPH and ABTS+ scavenging activities were determined. In the photoprotective activity assay, the sun protection factor (SPF) was calculated. The toxicity evaluation of LE included in vitro hemolytic assay and in vivo oral and dermal acute toxicity assays in Swiss mice. LE showed the highest protein, phenol, and flavonoid (8.79 mg/mL, 323.46 mg GAE/g, and 101.96 QE/g, respectively). TLC revealed the presence of flavonoids, reducing sugars, terpenes, and steroids in both extracts. In HPLC profiles, LE contained flavonoids, while SE contained flavonoids and ellagic tannins. The antioxidant activity assays showed the lowest IC50 values ​(34.15-413.3 µg/mL) for LE, which presented relevant SPF (> 6) at 50 and 100 µg/mL. LE demonstrated low hemolytic capacity, and no signs of intoxication were observed in mice treated orally or topically at 1000 mg/kg. However, at 2000 mg/kg, an increase in the mean corpuscular volume of erythrocytes and a reduction in lymphocytes were observed; animals treated topically with 2000 mg/kg displayed scratching behavior during the first hour of observation and showed edema and erythema that regressed after six days. In conclusion, LE did not present acute oral or dermal toxicity in Swiss mice at a dose of 1000 mg/kg and showed slight toxicity in animals treated with 2000 mg/kg. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-022-00160-2.

DNA methylation patterns suggest the involvement of DNMT3B and TET1 in osteosarcoma development.

DNA methylation may be involved in the development of osteosarcomas. Osteosarcomas commonly arise during the bone growth and remodeling in puberty, making it plausible to infer the involvement of epigenetic alterations in their development. As a highly studied epigenetic mechanism, we investigated DNA methylation and related genetic variants in 28 primary osteosarcomas aiming to identify deregulated driver alterations. Methylation and genomic data were obtained using the Illumina HM450K beadchips and the TruSight One sequencing panel, respectively. Aberrant DNA methylation was spread throughout the osteosarcomas genomes. We identified 3146 differentially methylated CpGs comparing osteosarcomas and bone tissue samples, with high methylation heterogeneity, global hypomethylation and focal hypermethylation at CpG islands. Differentially methylated regions (DMR) were detected in 585 loci (319 hypomethylated and 266 hypermethylated), mapped to the promoter regions of 350 genes. These DMR genes were enriched for biological processes related to skeletal system morphogenesis, proliferation, inflammatory response, and signal transduction. Both methylation and expression data were validated in independent groups of cases. Six tumor suppressor genes harbored deletions or promoter hypermethylation (DLEC1, GJB2, HIC1, MIR149, PAX6, and WNT5A), and four oncogenes presented gains or hypomethylation (ASPSCR1, NOTCH4, PRDM16, and RUNX3). Our analysis also revealed hypomethylation at 6p22, a region that contains several histone genes. Copy-number changes in DNMT3B (gain) and TET1 (loss), as well as overexpression of DNMT3B in osteosarcomas provide a possible explanation for the observed phenotype of CpG island hypermethylation. While the detected open-sea hypomethylation likely contributes to the well-known osteosarcoma genomic instability, enriched CpG island hypermethylation suggests an underlying mechanism possibly driven by overexpression of DNMT3B likely resulting in silencing of tumor suppressors and DNA repair genes.

Prevalence and factors associated with low back pain in warehouse workers: A cross-sectional study.

BACKGROUND: Low back pain is a highly prevalent musculoskeletal disorder that leads to functional incapacity and absence from work. OBJECTIVE: To analyze warehouse workers' prevalence and factors associated with low back pain. METHODS: Cross-sectional study design with 204 male warehouse workers (stocker, separator, checker, and packer) from motor parts companies. Age, body mass, marital status, education, the practice of physical exercise, presence of pain, low back pain intensity, comorbidities, time away from work, handgrip strength, flexibility, and trunk muscle strength were collected and analyzed. Data are presented as mean, standard deviation, absolute and relative frequency. A binary logistic regression was performed, with low back pain (yes or no) as the dependent variable. RESULTS: 24.0% of the workers reported low back pain with an average intensity of 4.7 (± 2.4) points. The participants were young, had completed high school education, were single and married, and had normal body weight. There was a more likely low back pain presence in separator tasks. Greater handgrip strength in the dominant (right) hand and trunk muscle is associated with no low back pain. CONCLUSION: Low back pain prevalence was 24% among young warehouse workers, more likely in separation tasks. A greater handgrip and trunk strength can be a protective factor to no low back pain.