Association between exposure to plasma mixture of essential and toxic elements and the lipid profile in institutionalized older adults.

BACKGROUND: Older adults have a progressive deficiency in the ability to detoxify chemical elements and are susceptible to dyslipidemia and changes in glycemic control. The objective was to evaluate the association of the mixture of essential and toxic elements in the plasma of institutionalized older adults and test the associations with lipid profile variables and glycemic control. METHODS: Data were obtained from 149 Brazilian older adults aged ≥60 living in nursing homes (NH) in Natal, Brazil. The concentrations of sixteen chemical elements in plasma and lipid profile parameters and glycemic control of 149 institutionalized older adults were measured. Bayesian kernel machine regression was used to estimate the associations of the mixture of chemical elements with total cholesterol (TC), high-density lipoprotein (HDL-c), low-density lipoprotein (LDL-c), triglycerides (TG), fasting glucose, and glycated hemoglobin. RESULTS: Non-linear responses to exposure were observed for iron (Fe) about TC, LDL-c, and TG, and for barium (Ba) and copper (Cu) about TG. The concentration of the mixture of chemical elements below the 35th percentile was associated with a decrease in TC. Fe was the main element in the effect of the mixture associated with TC. CONCLUSIONS: The lower concentrations of the mixture of chemical elements in plasma had a protective effect on the increase in TC, with Fe being the main element. Considering the results, the levels of essential and toxic elements in the plasma of older adults require extensive screening, mainly to prevent dyslipidemia and monitor clinical interventions.

The added value of the long-term ecological research network to upscale restoration in Europe.

Achieving global restoration targets poses challenges including the need for long-term research and effective monitoring of success, fostering collaborations across diverse fields and actors, ensuring the availability of suitable reference ecosystems, and securing sustained funding. Yet, these conditions are often lacking, limiting the effectiveness of restoration. We provide an overview of ecological restoration practices in the pan-European region of the Long-term Ecological Research Network (eLTER) and demonstrate the importance of eLTER and its potential contributions to support the implementation of the EU Nature Restoration Law. We developed an online questionnaire to collect information on eLTER restoration experts and restoration projects details including the use of eLTER contributions (e.g. infrastructure, data and knowledge), between November 2021 and March 2022. We identified 62 restoration experts and 42 restoration projects from 18 countries. Our results show that eLTER restoration expertise covers most of the European habitats, diverse degradation states and restoration techniques. Most restoration projects (78%) involved long-term monitoring exceeding the average project lifespan, which has proven necessary to achieve restoration success. No common protocol was used for monitoring and evaluation or cost-benefit estimates, but respondents reported effective projects, mostly financed from national funds, and benefits in five ecosystem services on average covered per project. Key eLTER contributions included providing reference ecosystems, biotic and abiotic background data, and interdisciplinary discussion or stakeholder management. Ecological restoration is time intensive and requires long-term research and monitoring standardization to fully understand the restoration process and to ensure comparability across ecosystems. The eLTER network can help address these challenges providing added-value contributions through its infrastructure, long-term datasets, diversity of expertise and strategies that can help identify best restoration practices and support the EU Nature Restoration Law. Finally, additional and long-term funding from the EU and the private sector is needed to achieve global larger-scale restoration targets.

Selenium biomarkers and miR-7-5p in overweight/obese women.

INTRODUCTION: Chronic low-grade inflammation and oxidative stress are pivotal contributors to the metabolic complications associated with obesity. Selenoprotein P (SELENOP) and glutathione peroxidase 1 (GPx1) are selenoproteins involved in the reduction of reactive oxygen species and pro-inflammatory cytokines levels. Nutritional epigenomics revealed the interaction of microRNAs and nutrients with an important impact on metabolic pathways involved in obesity. However, the knowledge regarding the influence of microRNA on selenium biomarkers and its impact on metabolic pathways related to obesity remains scarce. Thus, the aim of this study was to investigate the association of plasma miR-7-5p expression with selenium and inflammatory biomarkers in women with overweight/obesity. MATERIAL AND METHODS: Anthropometric evaluations were performed and blood samples were collected for the analysis of fasting glucose, insulin, inflammatory and selenium biomarkers, and miR-7-5p expression in 54 women with overweight/obesity. Gene expression of SELENOP and GPX1 were evaluated in peripheral mononuclear blood cells. RESULTS: This study observed a negative correlation between SELENOP levels and miR-7-5p (rho = -0.350; p = 0.018). Additionally, it was observed that body fat (OR = 0.737; p = 0.011), age (OR = 1.214; p = 0.007), and miR-7-5p (OR = 0.990; p = 0.015) emerged as significant predictors of SELENOP levels. CONCLUSIONS: In conclusion, we observed a significant inverse association between miR-7-5p expression and SELENOP concentration in overweight/obese women, suggesting that age and percentage of body fat are also associated. TRIAL REGISTRATION NUMBER: Brazilian Registry of Clinical Trials (ReBEC) number RBR-2nfy5q.

Relined fiberglass posts: influence of resin opacity on the bond strength to intraradicular dentin.

This study aimed to evaluate the bond strength between relined fiberglass posts with different composite resin opacities in different thirds of the intraradicular dentin. Thirty single-rooted premolars were endodontically treated and divided into three groups (n=10): fiberglass posts relined with translucent composite resin, fiberglass posts relined with opaque composite resin, and fiberglass posts without relining. After cementation of the posts, the specimens were cut perpendicular to the long axis of the tooth in slices of approximately 1.3 mm of each third to be analyzed (cervical, middle, and apical) and then subjected to the push-out test. The bond strength (MPa) data were subjected to Shapiro-Wilk normality tests and two-way repeated measures analysis of variance, considering the experimental groups and different regions as study factors. Tukey's post-hoc test (p<.05) was applied for comparisons between the groups. In the cervical third, higher values of bond strength were found for the group relined with translucent resin, with a statistically significant difference for the other groups. In the other regions, both opaque and translucent resins showed similar results, but both showed higher values of bond strength compared to fiberglass posts without relining. The bond strength of fiberglass posts to different thirds of intraradicular dentin is influenced by composite resin relining as well as the opacity of the resin. The use of translucent composite resin is a more effective alternative for fiberglass posts relining.

Solidagenone from Solidago chilensis Meyen Protects against Acute Peritonitis and Lipopolysaccharide-Induced Shock by Regulating NF-κB Signaling Pathway.

Anti-inflammatory agents are widely used for the treatment of inflammatory diseases. Nevertheless, the associated side effects of the available drugs make it necessary to search for new anti-inflammatory drugs. Here, we investigated the anti-inflammatory activity of solidagenone. Initially, we observed that a single dose of 30, 60, or 90 mg/kg of solidagenone did not result in mortality or elicit any discernible signs of toxicity in mice. At the same doses, solidagenone promoted a significant reduction in the migration of neutrophils in an acute peritonitis model and decreased mortality in a lipopolysaccharide-induced endotoxic shock model. Interestingly, treatment with solidagenone conferred a protective effect against leukopenia and thrombocytopenia, hematological disorders commonly observed in sepsis conditions. In addition, treatment with all the doses of solidagenone promoted a significant reduction in nitric oxide, TNF-α, and IL-1ß levels relative to the LPS-stimulated vehicle-treated cultures. Furthermore, gene expression and in silico analyses also supported the modulation of the NF-κB pathway by solidagenone. Finally, in silico pharmacokinetics predictions indicated a favorable drugability profile for solidagenone. Taken together, the findings of the present investigation show that solidagenone exhibits significant anti-inflammatory properties in acute experimental models, potentially through the modulation of the NF-κB signaling pathway.

Relined fiberglass posts: influence of resin opacity on the bond strength to intraradicular dentin

Abstract This study aimed to evaluate the bond strength between relined fiberglass posts with different composite resin opacities in different thirds of the intraradicular dentin. Thirty single-rooted premolars were endodontically treated and divided into three groups (n=10): fiberglass posts relined with translucent composite resin, fiberglass posts relined with opaque composite resin, and fiberglass posts without relining. After cementation of the posts, the specimens were cut perpendicular to the long axis of the tooth in slices of approximately 1.3 mm of each third to be analyzed (cervical, middle, and apical) and then subjected to the push-out test. The bond strength (MPa) data were subjected to Shapiro-Wilk normality tests and two-way repeated measures analysis of variance, considering the experimental groups and different regions as study factors. Tukey's post-hoc test (p<.05) was applied for comparisons between the groups. In the cervical third, higher values of bond strength were found for the group relined with translucent resin, with a statistically significant difference for the other groups. In the other regions, both opaque and translucent resins showed similar results, but both showed higher values of bond strength compared to fiberglass posts without relining. The bond strength of fiberglass posts to different thirds of intraradicular dentin is influenced by composite resin relining as well as the opacity of the resin. The use of translucent composite resin is a more effective alternative for fiberglass posts relining.

Resumo Este estudo teve como objetivo avaliar a resistência de união entre pinos de fibra de vidro anatomizados com resinas compostas de diferentes opacidades em diferentes terços da dentina intrarradicular. Trinta pré-molares uniradiculares foram tratados endodonticamente e divididos em três grupos (n=10): pinos de fibra de vidro anatomizados com resina composta translúcida, pinos de fibra de vidro anatomizados com resina composta opaca e pinos de fibra de vidro sem anatomização. Após a cimentação dos pinos, os corpos de prova foram cortados perpendicularmente ao longo eixo do dente em fatias de aproximadamente 1,3 mm de cada terço a ser analisado (cervical, médio e apical) e posteriormente submetidos ao teste de push-out. Os dados de resistência de união (MPa) foram submetidos a testes de normalidade de Shapiro-Wilk e ANOVA dois fatores para análises repetidas, considerando os grupos experimentais e diferentes regiões como fatores de estudo. O teste post-hoc de Tukey (p=0,05) foi aplicado para comparações entre os grupos. No terço cervical foram encontrados maiores valores de resistência de união no grupo com anatomização com resina translúcida, com diferença estatisticamente significativa para os demais grupos. Nas demais regiões, tanto as resinas opacas quanto as translúcidas apresentaram resultados semelhantes, mas ambas apresentaram valores de resistência de união superiores aos pinos de fibra de vidro sem anatomização. A resistência de união dos pinos de fibra de vidro aos diferentes terços da dentina intrarradicular é influenciada pela anatomização da resina composta, bem como pela opacidade da resina. A utilização de resina composta translúcida é uma alternativa mais eficaz para a anatomização de pinos de fibra de vidro.

Estratégias de ensino-aprendizagem de neuroanatomia: uma revisão integrativa da literatura / Strategies for teaching-learning neuroanatomy: an integrative literature review

Resumo Introdução: Uma significativa parcela dos estudantes de Medicina considera a neuroanatomia um conteúdo de difícil compreensão, muitas vezes desprovido de aplicações práticas devido à sua extensa e monótona apresentação. Além disso, ao longo das últimas décadas, houve uma redução no tempo dedicado à apresentação teórica da neuroanatomia. Corroborando tal afirmativa, durante a pandemia de Covid-19, observou-se um distanciamento crescente entre professores e alunos, o que, por sua vez, agravou ainda mais os desafios no ensino da disciplina. Objetivo: Este estudo possui como objetivo realizar uma revisão integrativa da literatura no intuito de explorar estratégias para aperfeiçoamento do ensino da neuroanatomia no curso superior de Medicina. Método: Para atingir esse objetivo, os subscritores efetivaram uma pesquisa integrativa de artigos publicados sobre estratégias de ensino-aprendizagem de neuroanatomia para estudantes de Medicina no período entre 1º de janeiro de 2000 e 26 de maio de 2023. Para obtenção de tais dados, os autores utilizaram três bases de dados - PubMed, SciELO e BVS -, empregando os seguintes descritores e o operador booleano "AND" em ambos os idiomas (português e inglês): "ensino", "aprendizagem", "neuroanatomia", "estudantes de medicina", "learning", "teaching", "neuroanatomy" e "medical students". Resultado: A revisão da literatura revelou uma crescente exploração de novas abordagens de ensino e aprendizado em neuroanatomia, destacando-se o uso de tecnologias como realidade virtual, cursos de neuroanatomia assistidos por computadores, modelos anatômicos de argila e a aplicação de estudos de casos clínicos. Conclusão: Nota-se nos últimos anos um notável surgimento de novas estratégias de ensino-aprendizagem no cenário acadêmico, que, por sua vez, visam aprimorar o conhecimento e a experiência dos alunos nos mais variados campos, inclusive na neuroanatomia.

Abstract Introduction: Most medical students consider neuroanatomy to be a challenging subject, often lacking practical applications due to its extensive and monotonous presentation. Furthermore, over the past few decades, there has been a reduction in the time allocated to the theoretical presentation of neuroanatomy. Recently, during the COVID-19 pandemic, there has been a growing disconnect between teachers and students, exacerbating the challenges in teaching this discipline. Objective: This study aimed to conduct an integrative literature review to explore strategies for enhancing the teaching of neuroanatomy in medical undergraduate programs. Method: To achieve this objective, we conducted an integrative search of articles published on teaching and learning strategies in neuroanatomy for medical students. We utilized three databases: PubMed, SciELO, and BVS, employing the following keywords and the boolean operator "AND" in both Portuguese and English: "ensino," "aprendizagem," "neuroanatomia," "estudantes de medicina," and "learning," "teaching," "neuroanatomy," and "medical students." Result: The literature review revealed a growing exploration of new approaches to teaching and learning in neuroanatomy, with a focus on the utilization of technologies such as virtual reality, computer-assisted neuroanatomy courses, anatomical clay models, and the application of clinical case studies. Conclusion: In recent years, there has been a noticeable emergence of new teaching and learning strategies in the academic environment, aimed at enhancing students' knowledge and experience, particularly in the field of neuroanatomy.

The let-7b-5p, miR-326, and miR-125a-3p are associated with left ventricular systolic dysfunction in post-myocardial infarction.

Background: Acute ST-elevation myocardial infarction (STEMI) can lead to adverse cardiac remodeling, resulting in left ventricular systolic dysfunction (LVSd) and heart failure. Epigenetic regulators, such as microRNAs, may be involved in the physiopathology of LVSd. Objective: This study explored microRNAs in peripheral blood mononuclear cells (PBMC) of post-myocardial infarction patients with LVSd. Methods: Post-STEMI patients were grouped as having (LVSd, n = 9) or not LVSd (non-LVSd, n = 16). The expression of 61 microRNAs was analyzed in PBMC by RT-qPCR and the differentially expressed microRNAs were identified. Principal Component Analysis stratified the microRNAs based on the development of dysfunction. Predictive variables of LVSd were investigated through logistic regression analysis. A system biology approach was used to explore the regulatory molecular network of the disease and an enrichment analysis was performed. Results: The let-7b-5p (AUC: 0.807; 95% CI: 0.63-0.98; p = 0.013), miR-125a-3p (AUC: 0.800; 95% CI: 0.61-0.99; p = 0.036) and miR-326 (AUC: 0.783; 95% CI: 0.54-1.00; p = 0.028) were upregulated in LVSd (p < 0.05) and discriminated LVSd from non-LVSd. Multivariate logistic regression analysis showed let-7b-5p (OR: 16.00; 95% CI: 1.54-166.05; p = 0.020) and miR-326 (OR: 28.00; 95% CI: 2.42-323.70; p = 0.008) as predictors of LVSd. The enrichment analysis revealed association of the targets of these three microRNAs with immunological response, cell-cell adhesion, and cardiac changes. Conclusion: LVSd alters the expression of let-7b-5p, miR-326, and miR-125a-3p in PBMC from post-STEMI, indicating their potential involvement in the cardiac dysfunction physiopathology and highlighting these miRNAs as possible LVSd biomarkers.

Are Phosphatidylcholine and Lysophosphatidylcholine Body Levels Potentially Reliable Biomarkers in Obesity? A Review of Human Studies.

Phosphatidylcholines (PCs) are the major components of biological membranes in animals and are a class of phospholipids that incorporate choline as a headgroup. Lysophosphatidylcholines (LPCs) are a class of lipid biomolecules derived from the cleavage of PCs, and are the main components of oxidized low-density lipoproteins (oxLDLs) that are involved in the pathogenesis of atherosclerosis. Since obesity is associated with a state of chronic low-grade inflammation, one can anticipate that the lipidomic profile changes in this context and both PCs and LPCs are gaining attention as hypothetically reliable biomarkers of obesity. Thus, a literature search is performed on PubMed, Latin American and Caribbean Health Science Literature (LILACS), and Excerpta Medica DataBASE (Embase) to obtain the findings of population studies to clarify this hypothesis. The search strategy resulted in a total of 2403 reports and 21 studies were included according to the eligibility criteria. Controversial data on the associations of PCs and LPCs with body mass index (BMI) and body fat parameters have been identified. There is an inverse relationship between BMI and most species of PCs, and a majority of studies exhibited negative associations between BMI and LPCs. Other findings regarding the differences between PCs and LPCs in obesity are presented, and the associated uncertainties are discussed in detail.

Plasma Concentration of Essential and Toxic Trace Elements After Brazil Nut Intake: Results from a Randomized Controlled Trial.

Brazil nut (BN) is a good source of essential nutrients, but little is known about the content of other components, such as toxic elements. Moreover, the high consumption of BN could probably contribute to increased levels of toxic and essential elements in the blood. Thus, this study aimed to evaluate the concentration of essential and toxic trace elements in BN and their concentration in plasma of obese women after regular intake of BN. A randomized controlled clinical trial was carried out with 55 subjects that were randomly assigned to either the Brazil nut group (BN) (n = 29) or the control group (CO) (n = 26) and followed up for 2 months. The BN group consumed one unit of Brazil nut per day, and the CO group did not receive any intervention. The concentration of essential elements (zinc, copper, manganese, and cobalt) and toxic (barium, lead, and cadmium) in BN samples and plasma of obese women (before and after the intervention) were determined by inductively coupled plasma mass spectrometry. Barium followed by copper, and manganese were the trace elements present in higher amounts in Brazil nuts. After the BN intervention period was observed an increase in plasma cadmium (p = 0.002) and a reduction of plasma manganese (p < 0.001) levels. In conclusion, our findings suggest that the regular consumption of BN from the Brazilian Amazon rainforest contributes to the intake of essential trace elements and can be considered safe regarding the content of heavy metals.

Experiences of women with advanced cervical cancer before starting the treatment: Systematic review of qualitative studies.

BACKGROUND: Advanced stage and high mortality are characteristics of cervical cancer in developing countries. Comprehension of the diagnosis itinerary is one of the main strategies to control the disease impact. OBJECTIVES: To identify reasons for the delay in diagnosing symptomatic cervical cancer according to the patient's perspectives reported in qualitative studies. We searched four databases (PubMed, Embase, CINAHL, and Web of Science). SELECTION CRITERIA: We included qualitative studies of women with advanced cervical cancer that explored their experiences before treatment. We excluded unoriginal, non-qualitative, and duplicated studies. DATA COLLECTION AND ANALYSIS: We selected 39 articles for a full-text reading and included 15 in the present review. We chose the Consolidated Criteria for Reporting Qualitative Research (COREQ) for quality assessment and The Model of Pathways to Treatment to guide the codifying process. MAIN RESULTS: Four main themes emerged from the synthesis: (1) Health-seeking motivators; (2) Obstacles to seeking medical care; (3) Diagnosis delay; and (4) Coping with the disease. These themes were derived from patients' personal knowledge and beliefs, social relationships, socioeconomic status, and healthcare system characteristics. CONCLUSIONS: Individual behavior, social factors, and healthcare organization contribute to the delay in diagnosing advanced cervical cancer.

Trajetórias juvenis e a construção de intelectuais orgânicos/as , / Young people's trajectories and the construction of organic intellectuals ,

Resumo A partir do acompanhamento de uma trajetória de vida juvenil, buscou-se apreender de que forma e quais experiências colaboram para constituir jovens mais ativos socialmente - em uma perspectiva gramsciniana: intelectuais orgânicos/as. Questiona-se, portanto: quais seriam as experiências que incidem/incidiram sobre as vidas juvenis que contribuem/contribuíram para a construção de processos na direção da emancipação social? Assim, utilizou-se do acompanhamento singular e territorial — tecnologia social descrita e elaborada pela terapia ocupacional social — resultando nas descrições e análises de situações para que uma jovem engendrasse movimentos de catarse, destacando sua participação em ações de extensão universitária, ambientes virtuais, grêmio estudantil e atividades vinculadas ao programa de iniciação científica do ensino médio (PIBIC-EM). Projeta-se que este estudo ofereça referências para estratégias de fortalecimento das redes de jovens e fomento a criação e ampliação de diferentes espaços coletivos por onde os jovens transitam, sejam eles presenciais ou virtuais, de tal modo que possam enfrentar as diferentes vulnerabilidades que cercam seus cotidianos.

Abstract Based on the follow-up of a young woman, we sought to understand how and what experiences contribute to the formation of more socially active young people - from a Gramscian perspective, organic intellectuals. The question is, therefore, which experiences have or have had an influence on the lives of young people that contribute or have contributed to constructing processes towards social emancipation? To this end, an individual territorial follow-up—a social technology developed by social occupational therapy—was used, resulting in descriptions and analyses of situations so that this young woman could engender movements of catharsis, highlighting her participation and protagonism in university extension actions, virtual environments, student guild events, and activities linked to a high school research program. It is expected that this study will provide references for strategies to strengthen youth networks and foster the creation and expansion of different collective spaces where young people move about, whether in person or virtually so that they can cope with the vulnerabilities that surround their everyday life.

Molecular Hybridization Strategy on the Design, Synthesis, and Structural Characterization of Ferrocene-N-acyl Hydrazones as Immunomodulatory Agents.

Immunomodulatory agents are widely used for the treatment of immune-mediated diseases, but the range of side effects of the available drugs makes necessary the search for new immunomodulatory drugs. Here, we investigated the immunomodulatory activity of new ferrocenyl-N-acyl hydrazones derivatives (SintMed(141−156). The evaluated N-acyl hydrazones did not show cytotoxicity at the tested concentrations, presenting CC50 values greater than 50 µM. In addition, all ferrocenyl-N-acyl hydrazones modulated nitrite production in immortalized macrophages, showing inhibition values between 14.4% and 74.2%. By presenting a better activity profile, the ferrocenyl-N-acyl hydrazones SintMed149 and SintMed150 also had their cytotoxicity and anti-inflammatory effect evaluated in cultures of peritoneal macrophages. The molecules were not cytotoxic at any of the concentrations tested in peritoneal macrophages and were able to significantly reduce (p < 0.05) the production of nitrite, TNF-α, and IL-1ß. Interestingly, both molecules significantly reduced the production of IL-2 and IFN-γ in cultured splenocytes activated with concanavalin A. Moreover, SintMed150 did not show signs of acute toxicity in animals treated with 50 or 100 mg/kg. Finally, we observed that ferrocenyl-N-acyl hydrazone SintMed150 at 100 mg/kg reduced the migration of neutrophils (44.6%) in an acute peritonitis model and increased animal survival by 20% in an LPS-induced endotoxic shock model. These findings suggest that such compounds have therapeutic potential to be used to treat diseases of inflammatory origin.

Diagnostic Performance of Three ELISAs for Detection of Antibodies against SARS-CoV-2 in Human Samples.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that causes coronavirus disease 2019 (COVID-19) is a disease with a high rate of transmission. Serological tests are important to perform surveys and to determine the immunological status of the population. Based on this, we evaluated three enzyme-linked immunoassays (ELISAs) using different antigens from SARS-CoV-2 in a cohort of 161 patients. The performance of the ELISA developed for immunoglobulin G (IgG) measurement against SARS-CoV-2 was evaluated based on sensitivity, specificity, and accuracy. We found specificities of 0.98, 0.98, and 0.99 and sensitivities of 0.99, 0.91, and 0.87 for the nucleocapsid (N) protein, spike protein, and receptor binding domain (RBD) fraction, respectively. The accuracy assessment indicated the N protein (accuracy = 0.98) as the antigen most likely to give a correct diagnosis. Overall, the antibody responses were present for all three proteins in subjects with confirmed SARS-CoV-2 infections, showing a similar pattern of antibody production for different antigens. In summary, these highly sensitive and specific ELISAs, with a more competitive price, appear to be a valid approach for the serodiagnosis of COVID-19.

Anti-Inflammatory Activities of Betulinic Acid: A Review.

Inflammatory diseases have a high prevalence and has become of great interest due to the increase in life expectancy and the costs to the health care system worldwide. Chronic diseases require long-term treatment frequently using corticosteroids and non-steroidal anti-inflammatory drugs, which are associated with diverse side effects and risk of toxicity. Betulinic acid, a lupane-type pentacyclic triterpene, is a potential lead compound for the development of new anti-inflammatory treatments, and a large number of derivatives have been produced and tested. The potential of betulinic acid and its derivatives has been shown in a number of pre-clinical studies using different experimental models. Moreover, several molecular mechanisms of action have also been described. Here we reviewed the potential use of betulinic acid as a promissory lead compound with anti-inflammatory activity and the perspectives for its use in the treatment of inflammatory conditions.

Therapeutic Applications of Physalins: Powerful Natural Weapons.

Physalins, or 16,24-cyclo-13,14-seco steroids, are compounds belonging to the class of withanolides that can be found in plants of Solanaceae family, mainly in species belonging to the genus Physalis spp., which are annual herbaceous plants widely distributed in tropical and subtropical regions of the world. Physalins are versatile molecules that act in several cell signaling pathways and activate different mechanisms of cell death or immunomodulation. A number of studies have shown a variety of actions of these compounds, including anticancer, anti-inflammatory, antiparasitic, antimicrobial, antinociceptive, and antiviral activities. Here we reviewed the main findings related to the anticancer, immunomodulatory, and antiparasitic activities of physalins and its mechanisms of action, highlighting the \challenges and future directions in the pharmacological application of physalins.

Prognostic Nutritional Index and Oxygen Therapy Requirement Associated With Longer Hospital Length of Stay in Patients With Moderate to Severe COVID-19: Multicenter Prospective Cohort Analyses.

Purpose: To evaluate whether the prognostic nutritional index (PNI) is related to the oxygen therapy requirement at hospital admission and to ascertain the prognostic effect of the PNI and the oxygen therapy requirement as predictors of hospital length of stay in patients with moderate to severe coronavirus disease 2019 (COVID-19). Methods: This is a post-hoc analysis in hospitalized patients with moderate to severe COVID-19. The participants were categorized: (1) non-oxygen therapy (moderate COVID-19 not requiring oxygen therapy); (2) nasal cannula therapy (severe COVID-19 requiring nasal cannula oxygen therapy); and (3) high-flow therapy (severe COVID-19 requiring high-flow oxygen therapy). PNI was calculated for each patient according to the following equation: serum albumin [g/dL] × 10 + total lymphocyte count [per mm3] × 0.005. The participants were categorized into malnutrition (PNI <40), mild malnutrition (PNI 40-45), and non-malnutrition (PNI > 45). Results: According to PNI, malnutrition was more prevalent in the high-flow therapy group (94.9%; P < 0.001) with significantly lower PNI compared to both groups even after adjusting for the center and C-reactive protein. Patients in the high-flow therapy group [9 days (95% CI 7.2, 10.7), P < 0.001] and malnutrition status [7 days (95% CI 6.6, 7.4), P = 0.016] showed a significant longer hospital length of stay compared to their counterparts. The multivariable Cox proportional hazard models showed significant associations between both oxygen therapy requirement and PNI categories and hospital discharge. Conclusion: In addition to oxygen therapy requirement, low PNI was associated with longer hospital length of stay. Our findings suggest that PNI could be useful in the assessment of nutritional status related to the prognosis of patients with moderate to severe COVID-19.

Phenolic Compound Profile by UPLC-MS/MS and Encapsulation with Chitosan of Spondias mombin L. Fruit Peel Extract from Cerrado Hotspot-Brazil.

Taperebá (Spondias mombin L.) is a native species of the Brazilian Cerrado that has shown important characteristics such as a significant phenolic compound content and biological activities. The present study aimed to characterize the phenolic compound profile and antioxidant activity in taperebá peel extract, as well as microencapsulating the extract with chitosan and evaluating the stability of the microparticles. The evaluation of the profile of phenolic compounds was carried out by UPLC-MS/MS. The in vitro antioxidant activity was evaluated by DPPH and ABTS methods. The microparticles were obtained by spray drying and were submitted to a stability study under different temperatures. In general, the results showed a significant content of polyphenols and antioxidant activity. The results of UPLC-MS/MS demonstrated a significant content of polyphenols in taperebá peel, highlighting the high content of ellagic acid and quercetin compounds. There was significant retention of phenolic compounds when microencapsulated, demonstrating high retention at all evaluated temperatures. This study is the first to microencapsulate the extract of taperebá peel, in addition to identifying and quantifying some compounds in this fruit.

Epidemiologia do câncer cervical no Brasil: uma revisão integrativa / Epidemiología del cáncer de cuello uterino en Brasil: una revisión integradora / Epidemiology of cervical cancer in Brazil: an integrative review

Objetivo: avaliar as publicações científicas que apresentam informações sobre a tendência da incidência e da mortalidade por câncer de co lo de útero no Brasil. Método: revisão integrativa de artigos publicados entre os anos de 2011 e 2020, a partir de busca na Biblioteca Virtual em Saúde , utilizando os descritores "incidência", "câncer do colo do útero" e "mortalidade". Resultados: foram se lecionados 37 artigos. Esta revisão tornou evidente que a maioria dos estudos demonstrou uma tendência decrescente da incidência e mortalidade por câncer do colo do útero no Brasil. Entretanto, esses indicadores ainda são considerados elevados, sobretudo n as regiões Norte e Nordeste do país. Conclusão: apesar da tendência da redução da incidência e mortalidade , o câncer cervical continua sendo um problema de saúde pública no Brasil.(AU)

Objective: to evaluate scientific publications that present information on trends in cervical cancer incidence and mortality in Brazil. Metho d: an integrative review of articles published between 2011 and 2020 was carried out, from a search in the Virtual Health Lib rary using the descriptors "incidence", "cancer of the cervix" and "mortality". Results: 37 articles were selected. This review made it evident that most studies showed a decreasing trend in cervical cancer incidence and mortality in Brazil. However, these indicators are still considered high, especially in the North and Northeast regions of the country. Conclusion: despite the trend of reduced incidence and mortality, cervical cancer remains a public health problem in Brazil.(AU)

Objetivo: evaluar publicaciones científicas que presenten informaciones sobre tendencias en la incidencia y mortalidad por cáncer de cuello uterino en Brasil. Método: se realizó una revisión integradora de artículos publicados entre 2011 y 2020, a partir de una búsqueda en la Biblioteca Virtual en Salud utilizando los descriptor es "incidencia", "cáncer de cuello uterino" y "mortalidad". Resultados : se seleccionaron 37 artículos. Esta revisión hizo evidente que la mayo ría de los estudios mostraron una tendencia decreciente en la incidencia y mortalidad por cáncer de cuello uterino en Brasil. Sin embargo, estos indicadores aún se consideran altos, especialmente en las regiones Norte y Nordeste del país. Conclusión: a pes ar de la tendencia de reducción de la incidencia y la mortalidad, el cáncer de cuello uterino sigue siendo un problema de salud pública en Brasil.(AU)

Effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in patients with moderate to severe COVID-19.

BACKGROUND: The modulating effect of vitamin D on cytokine concentrations in severe coronavirus disease 2019 (COVID-19) remains unknown. OBJECTIVES: We aimed to investigate the effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19. METHODS: This is a post hoc, ancillary, and exploratory analysis from a multicenter, double-blind, placebo-controlled, randomized clinical trial. Patients with moderate to severe COVID-19 were recruited from 2 hospitals in São Paulo, Brazil. Of 240 randomly assigned patients, 200 were assessed in this study and randomly assigned to receive a single oral dose of 200,000 IU vitamin D3 (n = 101) or placebo (n = 99). The primary outcome was hospital length of stay, which has been published in our previous study. The prespecified secondary outcomes were serum concentrations of IL-1ß, IL-6, IL-10, TNF-α, and 25-hydroxyvitamin D. The post hoc exploratory secondary outcomes were IL-4, IL-12p70, IL-17A, IFN-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-8, IFN-inducible protein-10 (IP-10), macrophage inflammatory protein-1ß (MIP-1ß), monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and leukocyte count. Generalized estimating equations for repeated measures, with Bonferroni's adjustment, were used for testing all outcomes. RESULTS: The study included 200 patients with a mean ± SD age of 55.5 ± 14.3 y and BMI of 32.2 ± 7.1 kg/m2, of which 109 (54.5%) were male. GM-CSF concentrations showed a significant group-by-time interaction effect (P = 0.04), although the between-group difference at postintervention after Bonferroni's adjustment was not significant. No significant effects were observed for the other outcomes. CONCLUSIONS: The findings do not support the use of a single dose of 200,000 IU vitamin D3, compared with placebo, for the improvement of cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19.This trial was registered at clinicaltrials.gov as NCT04449718.