Antarctic marine sediment as a source of filamentous fungi-derived antimicrobial and antitumor compounds of pharmaceutical interest.

Antarctica harbors a microbial diversity still poorly explored and of inestimable biotechnological value. Cold-adapted microorganisms can produce a diverse range of metabolites stable at low temperatures, making these compounds industrially interesting for biotechnological use. The present work investigated the biotechnological potential for antimicrobial and antitumor activity of filamentous fungi and bacteria isolated from marine sediment samples collected at Deception Island, Antarctica. A total of 89 microbial isolates were recovered from marine sediments and submitted to an initial screening for L-glutaminase with antitumoral activity and for antimicrobial metabolites. The isolates Pseudogymnoascus sp. FDG01, Pseudogymnoascus sp. FDG02, and Penicillium sp. FAD33 showed potential antiproliferative action against human pancreatic carcinoma cells while showing no toxic effect on non-tumor cells. The microbial extracts from unidentified three bacteria and four filamentous fungi showed antibacterial activity against at least one tested pathogenic bacterial strain. The isolate FDG01 inhibited four bacterial species, while the isolate FDG01 was active against Micrococcus luteus in the minimal inhibitory concentration of 0.015625 µg mL -1. The results pave the way for further optimization of enzyme production and characterization of enzymes and metabolites found and reaffirm Antarctic marine environments as a wealthy source of compounds potentially applicable in the healthcare and pharmaceutical industry.

Knowledge and attitudes regarding contraceptive methods and sex education in students and parents of eight Colombian schools 2020-2021: a mixed methods study.

Background: In Colombia, the average age of first sexual intercourse is between 14 and 15, and it has one of the highest fertility rates among adolescents in Latin America, which reflects poor access to health services and a lack of knowledge about contraception. Some laws support comprehensive sex education as a learning process that families and schools should provide. The objective of this work was to assess the frequency of adequate knowledge and attitudes of acceptance towards contraception in students, their associated factors, sexual behaviours in sexually active students, and experiences with sex education. Methods: Mixed methods study consisting of an analytical cross-sectional study and a qualitative hermeneutic phenomenological study. The former included students who completed a questionnaire with sociodemographic variables, surveys on knowledge and attitudes toward contraception, and questions about sexual behaviour. Focus groups were used in the qualitative study to evaluate students' and parents' sex education experiences. Findings: 827 students were surveyed, of whom 52.3% had adequate knowledge about contraceptives and 80.1% had attitudes of acceptance. Talking with parents about sex education, receiving sex education, and being in the eleventh grade increased the likelihood of having adequate knowledge. Each year of age, being male, being a victim of forced displacement, and studying in a public school were associated with lower possibilities of attitudes of acceptance. Using condoms, compared to other contraceptives, was associated with less adequate knowledge and attitudes of acceptance (p < 0.05). Experiences with sex education, contraception, and sexual and reproductive rights were three emerging categories in the focus groups. Interpretation: In a group of Colombian high school students, half of them had adequate knowledge, eight out of 10 had attitudes of acceptance about contraception, and both were associated with having received sex education. Nevertheless, different types of barriers to sexual education were identified at home and in schools. The results will allow the generation of educational policies that modify the educational model as well as new strategies by health professionals to raise awareness about responsible sexuality. Funding: This project was financed by internal research of the Fundación Universitaria de Ciencias de la Salud-FUCS (DI-I-0392-20).

Bioprospecting the potential of the microbial community associated to Antarctic marine sediments for hydrocarbon bioremediation.

Microorganisms that inhabit the cold Antarctic environment can produce ligninolytic enzymes potentially useful in bioremediation. Our study focused on characterizing Antarctic bacteria and fungi from marine sediment samples of King George and Deception Islands, maritime Antarctica, potentially affected by hydrocarbon influence, able to produce enzymes for use in bioremediation processes in environments impacted with petroleum derivatives. A total of 168 microorganism isolates were obtained: 56 from sediments of King George Island and 112 from Deception Island. Among them, five bacterial isolates were tolerant to cell growth in the presence of diesel oil and gasoline and seven fungal were able to discolor RBBR dye. In addition, 16 isolates (15 bacterial and one fungal) displayed enzymatic emulsifying activities. Two isolates were characterized taxonomically by showing better biotechnological results. Psychrobacter sp. BAD17 and Cladosporium sp. FAR18 showed pyrene tolerance (cell growth of 0.03 g mL-1 and 0.2 g mL-1) and laccase enzymatic activity (0.006 UL-1 and 0.10 UL-1), respectively. Our results indicate that bacteria and fungi living in sediments under potential effect of hydrocarbon pollution may represent a promising alternative to bioremediate cold environments contaminated with polluting compounds derived from petroleum such as polycyclic aromatic hydrocarbons and dyes.

Technology transfer during the COVID-19 pandemic: report on the first face-to-face practical training course in Brazil.

MAIN RESULTS: Technology transfer can take place at large events, as long as safety protocols are strictly enforced. It is important to disseminate, at these events, the concepts of the Responsible Research and Innovation (RRI). Implications for services: Face-to-face training course is fundamental for training public health professionals. Technology transfer between research institutions and health services results in updating and improving health system performance. PERSPECTIVES: Based on the success of the reported technology transfer, a new module will be incorporated into the next edition of VEME (Panama 2022), entitled Virus Evolution to Public Health Policy Makers. The objective of this report was to describe the first face-to-face course aimed at training public health professionals in performing real-time genomic surveillance during the pandemic period. Experience report on a theoretical-practical course focusing on genomic research and surveillance, including mobile sequencing technologies, bioinformatics, phylogenetics and epidemiological modeling. There were 162 participants in the event and it was the first major face-to-face training course conducted during the COVID-19 epidemic in Brazil. No cases of SARS-CoV-2 infection was detected among the participants at the end of the event, suggesting the safety and effectiveness of all safety measures adopted. The results of this experience suggest that it is possible to conduct professional training safely during pandemics, as long as all safety protocols are followed.

SMC3 epigenetic silencing regulates Rab27a expression and drives pancreatic cancer progression.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is expected to soon surpass colorectal cancer as a leading cause of cancer mortality in both males and females in the US, only lagging behind lung cancer. The lethality of PDAC is driven by late diagnosis and inefficient therapies. The complex biology of PDAC involves various cellular components, including exosomes that carry molecular information between cells. Thus, recipient cells can be reprogrammed, impacting tumorigenesis. Rab27a is a GTPase responsible for the last step of exosomes biogenesis. Hence, dissecting the mechanisms that regulate the expression of Rab27a and that control exosomes biogenesis can provide fundamental insights into the molecular underpinnings regulating PDAC progression. METHODS: To assess the mechanism that regulates Rab27a expression in PDAC, we used PDAC cell lines. The biological significance of these findings was validated in PDAC genetically engineered mouse models (GEMMs) and human samples. RESULTS: In this work we demonstrate in human PDAC samples and GEMMs that Rab27a expression decreases throughout the development of the disease, and that Rab27a knockout promotes disease progression. What is more, we demonstrate that Rab27a expression is epigenetically regulated in PDAC. Treatment with demethylating agents increases Rab27a expression specifically in human PDAC cell lines. We found that SMC3, a component of the cohesin complex, regulates Rab27a expression in PDAC. SMC3 methylation is present in human PDAC specimens and treatment with demethylating agents increases SMC3 expression in human PDAC cell lines. Most importantly, high levels of SMC3 methylation are associated with a worse prognosis in PDAC. Mechanistically, we identified an enhancer region within the Rab27a gene that recruits SMC3, and modulates Rab27a expression. CONCLUSION: Overall, we dissected a mechanism that regulates Rab27a expression during PDAC progression and impacts disease prognosis.

Seroprevalence of Dengue, Chikungunya and Zika at the epicenter of the congenital microcephaly epidemic in Northeast Brazil: A population-based survey.

BACKGROUND: The four Dengue viruses (DENV) serotypes were re-introduced in Brazil's Northeast region in a couple of decades, between 1980's and 2010's, where the DENV1 was the first detected serotype and DENV4 the latest. Zika (ZIKV) and Chikungunya (CHIKV) viruses were introduced in Recife around 2014 and led to large outbreaks in 2015 and 2016, respectively. However, the true extent of the ZIKV and CHIKV outbreaks, as well as the risk factors associated with exposure to these viruses remain vague. METHODS: We conducted a stratified multistage household serosurvey among residents aged between 5 and 65 years in the city of Recife, Northeast Brazil, from August 2018 to February 2019. The city neighborhoods were stratified and divided into high, intermediate, and low socioeconomic strata (SES). Previous ZIKV, DENV and CHIKV infections were detected by IgG-based enzyme linked immunosorbent assays (ELISA). Recent ZIKV and CHIKV infections were assessed through IgG3 and IgM ELISA, respectively. Design-adjusted seroprevalence were estimated by age group, sex, and SES. The ZIKV seroprevalence was adjusted to account for the cross-reactivity with dengue. Individual and household-related risk factors were analyzed through regression models to calculate the force of infection. Odds Ratio (OR) were estimated as measure of effect. PRINCIPAL FINDINGS: A total of 2,070 residents' samples were collected and analyzed. The force of viral infection for high SES were lower as compared to low and intermediate SES. DENV seroprevalence was 88.7% (CI95%:87.0-90.4), and ranged from 81.2% (CI95%:76.9-85.6) in the high SES to 90.7% (CI95%:88.3-93.2) in the low SES. The overall adjusted ZIKV seroprevalence was 34.6% (CI95%:20.0-50.9), and ranged from 47.4% (CI95%:31.8-61.5) in the low SES to 23.4% (CI95%:12.2-33.8) in the high SES. The overall CHIKV seroprevalence was 35.7% (CI95%:32.6-38.9), and ranged from 38.6% (CI95%:33.6-43.6) in the low SES to 22.3% (CI95%:15.8-28.8) in the high SES. Surprisingly, ZIKV seroprevalence rapidly increased with age in the low and intermediate SES, while exhibited only a small increase with age in high SES. CHIKV seroprevalence according to age was stable in all SES. The prevalence of serological markers of ZIKV and CHIKV recent infections were 1.5% (CI95%:0.1-3.7) and 3.5% (CI95%:2.7-4.2), respectively. CONCLUSIONS: Our results confirmed continued DENV transmission and intense ZIKV and CHIKV transmission during the 2015/2016 epidemics followed by ongoing low-level transmission. The study also highlights that a significant proportion of the population is still susceptible to be infected by ZIKV and CHIKV. The reasons underlying a ceasing of the ZIKV epidemic in 2017/18 and the impact of antibody decay in susceptibility to future DENV and ZIKV infections may be related to the interplay between disease transmission mechanism and actual exposure in the different SES.

Transferência tecnológica durante a pandemia de covid-19: relato do primeiro treinamento prático presencial no Brasil / Technology transfer during the COVID-19 pandemic: report on the first face-to-face practical training course in Brazil / Transferencia de tecnología durante la epidemia de COVID-19 en Brasil: informe de la primera formación práctica presencial

O relato descreveu o primeiro curso presencial visando capacitar profissionais de saúde pública na realização de vigilância genômica em tempo real, durante períodos pandêmicos. Relato de experiência sobre um curso teórico-prático com foco em pesquisa e vigilância genômica, incluindo tecnologias de sequenciamento móvel, bioinformática, filogenética e modelagem epidemiológica. O evento contou com 162 participantes e foi o primeiro grande treinamento presencial realizado durante a epidemia de covid-19 no Brasil. Não foi detectada infecção pelo SARS-CoV-2 ao final do evento em nenhum participante, sugerindo a segurança e efetividade de todas as medidas de segurança adotadas. Os resultados do evento sugerem que é possível executar capacitação profissional com segurança durante pandemias, desde que seguidos todos os protocolos de segurança.

The objective of this report was to describe the first face-to-face course aimed at training public health professionals in performing real-time genomic surveillance during the pandemic period. Experience report on a theoretical-practical course focusing on genomic research and surveillance, including mobile sequencing technologies, bioinformatics, phylogenetics and epidemiological modeling. There were 162 participants in the event and it was the first major face-to-face training course conducted during the COVID-19 epidemic in Brazil. No cases of SARS-CoV-2 infection was detected among the participants at the end of the event, suggesting the safety and effectiveness of all safety measures adopted. The results of this experience suggest that it is possible to conduct professional training safely during pandemics, as long as all safety protocols are followed.

Este estudio tuvo como objetivo describir el primer curso presencial para capacitar a los profesionales de la salud pública para llevar a cabo la vigilancia genómica en tiempo real durante los períodos de pandemia. Este es un informe de experiencia en un curso teórico-práctico centrado en la investigación y vigilancia genómica, que incluye secuenciación móvil, bioinformática, filogenética y tecnologías de modelado epidemiológico. Este evento contó con la asistencia de 162 participantes y fue la primera gran capacitación presencial realizada durante la epidemia de COVID-19 en Brasil. No se detectó infección por SARS-CoV-2 al final del evento en ningún participante, lo que sugiere la seguridad y efectividad de todas las medidas de seguridad adoptadas. Por lo tanto, los resultados del evento sugieren que es posible realizar entrenamientos profesionales de manera segura durante pandemias, siempre y cuando se sigan todos los protocolos de seguridad.

Comparative metabolomic profiling of women undergoing in vitro fertilization procedures reveals potential infertility-related biomarkers in follicular fluid.

Infertility is a worldwide concern, affecting one in six couples throughout their reproductive period. Therefore, enhancing the clinical tools available to identify the causes of infertility may save time, money, and emotional distress for the involved parties. This study aims to annotate potential biomarkers in follicular fluid that are negatively affecting pregnancy outcomes in women suffering infertility-related diseases such as endometriosis, tuboperitoneal factor, uterine factor, and unexplained infertility, using a metabolomics approach through high-resolution mass spectrometry. Follicular fluid samples collected from women who have the abovementioned diseases and managed to become pregnant after in vitro fertilization procedures [control group (CT)] were metabolically compared with those from women who suffer from the same diseases and could not get pregnant after the same treatment [infertile group (IF)]. Mass spectrometry analysis indicated 10 statistically relevant differential metabolites in the IF group, including phosphatidic acids, phosphatidylethanolamines, phosphatidylcholines, phosphatidylinositol, glucosylceramides, and 1-hydroxyvitamin D3 3-D-glucopyranoside. These metabolites are associated with cell signaling, cell proliferation, inflammation, oncogenesis, and apoptosis, and linked to infertility problems. Our results indicate that understanding the IF's metabolic profile may result in a faster and more assertive female infertility diagnosis, lowering the costs, and increasing the probability of a positive pregnancy outcome.

Pharmacokinetics of Intramuscularly Administered Thermoresponsive Polymers.

Aqueous solutions of some polymers exhibit a lower critical solution temperature (LCST); that is, they form phase-separated aggregates when heated above a threshold temperature. Such polymers found many promising (bio)medical applications, including in situ thermogelling with controlled drug release, polymer-supported radiotherapy (brachytherapy), immunotherapy, and wound dressing, among others. Yet, despite the extensive research on medicinal applications of thermoresponsive polymers, their biodistribution and fate after administration remained unknown. Thus, herein, they studied the pharmacokinetics of four different thermoresponsive polyacrylamides after intramuscular administration in mice. In vivo, these thermoresponsive polymers formed depots that subsequently dissolved with a two-phase kinetics (depot maturation, slow redissolution) with half-lives 2 weeks to 5 months, as depot vitrification prolonged their half-lives. Additionally, the decrease of TCP of a polymer solution increased the density of the intramuscular depot. Moreover, they detected secondary polymer depots in the kidneys and liver; these secondary depots also followed two-phase kinetics (depot maturation and slow dissolution), with half-lives 8 to 38 days (kidneys) and 15 to 22 days (liver). Overall, these findings may be used to tailor the properties of thermoresponsive polymers to meet the demands of their medicinal applications. Their methods may become a benchmark for future studies of polymer biodistribution.

Replacement of the Gamma by the Delta variant in Brazil: Impact of lineage displacement on the ongoing pandemic.

The coronavirus disease 2019 (COVID-19) epidemic in Brazil was driven mainly by the spread of Gamma (P.1), a locally emerged variant of concern (VOC) that was first detected in early January 2021. This variant was estimated to be responsible for more than 96 per cent of cases reported between January and June 2021, being associated with increased transmissibility and disease severity, a reduction in neutralization antibodies and effectiveness of treatments or vaccines, and diagnostic detection failure. Here we show that, following several importations predominantly from the USA, the Delta variant rapidly replaced Gamma after July 2021. However, in contrast to what was seen in other countries, the rapid spread of Delta did not lead to a large increase in the number of cases and deaths reported in Brazil. We suggest that this was likely due to the relatively successful early vaccination campaign coupled with natural immunity acquired following prior infection with Gamma. Our data reinforce reports of the increased transmissibility of the Delta variant and, considering the increasing concern due to the recently identified Omicron variant, argues for the necessity to strengthen genomic monitoring on a national level to quickly detect the emergence and spread of other VOCs that might threaten global health.

Performance-Cost Trade-Off in Auto-Scaling Mechanisms for Cloud Computing.

Cloud computing has been widely adopted over the years by practitioners and companies with a variety of requirements. With a strong economic appeal, cloud computing makes possible the idea of computing as a utility, in which computing resources can be consumed and paid for with the same convenience as electricity. One of the main characteristics of cloud as a service is elasticity supported by auto-scaling capabilities. The auto-scaling cloud mechanism allows adjusting resources to meet multiple demands dynamically. The elasticity service is best represented in critical web trading and transaction systems that must satisfy a certain service level agreement (SLA), such as maximum response time limits for different types of inbound requests. Nevertheless, existing cloud infrastructures maintained by different cloud enterprises often offer different cloud service costs for equivalent SLAs upon several factors. The factors might be contract types, VM types, auto-scaling configuration parameters, and incoming workload demand. Identifying a combination of parameters that results in SLA compliance directly in the system is often sophisticated, while the manual analysis is prone to errors due to the huge number of possibilities. This paper proposes the modeling of auto-scaling mechanisms in a typical cloud infrastructure using a stochastic Petri net (SPN) and the employment of a well-established adaptive search metaheuristic (GRASP) to discover critical trade-offs between performance and cost in cloud services.The proposed SPN models enable cloud designers to estimate the metrics of cloud services in accordance with each required SLA such as the best configuration, cost, system response time, and throughput.The auto-scaling SPN model was extensively validated with 95% confidence against a real test-bed scenario with 18.000 samples. A case-study of cloud services was used to investigate the viability of this method and to evaluate the adoptability of the proposed auto-scaling model in practice. On the other hand, the proposed optimization algorithm enables the identification of economic system configuration and parameterization to satisfy required SLA and budget constraints. The adoption of the metaheuristic GRASP approach and the modeling of auto-scaling mechanisms in this work can help search for the optimized-quality solution and operational management for cloud services in practice.

Extracellular Vesicles from Pancreatic Cancer Stem Cells Lead an Intratumor Communication Network (EVNet) to fuel tumour progression.

OBJECTIVE: Intratumor heterogeneity drives cancer progression and therapy resistance. However, it has yet to be determined whether and how subpopulations of cancer cells interact and how this interaction affects the tumour. DESIGN: We have studied the spontaneous flow of extracellular vesicles (EVs) between subpopulations of cancer cells: cancer stem cells (CSC) and non-stem cancer cells (NSCC). To determine the biological significance of the most frequent communication route, we used pancreatic ductal adenocarcinoma (PDAC) orthotopic models, patient-derived xenografts (PDXs) and genetically engineered mouse models (GEMMs). RESULTS: We demonstrate that PDAC tumours establish an organised communication network between subpopulations of cancer cells using EVs called the EVNet). The EVNet is plastic and reshapes in response to its environment. Communication within the EVNet occurs preferentially from CSC to NSCC. Inhibition of this communication route by impairing Rab27a function in orthotopic xenographs, GEMMs and PDXs is sufficient to hamper tumour growth and phenocopies the inhibition of communication in the whole tumour. Mechanistically, we provide evidence that CSC EVs use agrin protein to promote Yes1 associated transcriptional regulator (YAP) activation via LDL receptor related protein 4 (LRP-4). Ex vivo treatment of PDXs with antiagrin significantly impairs proliferation and decreases the levels of activated YAP.Patients with high levels of agrin and low inactive YAP show worse disease-free survival. In addition, patients with a higher number of circulating agrin+ EVs show a significant increased risk of disease progression. CONCLUSION: PDAC tumours establish a cooperation network mediated by EVs that is led by CSC and agrin, which allows tumours to adapt and thrive. Targeting agrin could make targeted therapy possible for patients with PDAC and has a significant impact on CSC that feeds the tumour and is at the centre of therapy resistance.

Molecular mimicry of NF-κB by vaccinia virus protein enables selective inhibition of antiviral responses.

Infection of mammalian cells with viruses activates NF-κB to induce the expression of cytokines and chemokines and initiate an antiviral response. Here, we show that a vaccinia virus protein mimics the transactivation domain of the p65 subunit of NF-κB to inhibit selectively the expression of NF-κB-regulated genes. Using co-immunoprecipitation assays, we found that the vaccinia virus protein F14 associates with NF-κB co-activator CREB-binding protein (CBP) and disrupts the interaction between p65 and CBP. This abrogates CBP-mediated acetylation of p65, after which it reduces promoter recruitment of the transcriptional regulator BRD4 and diminishes stimulation of NF-κB-regulated genes CXCL10 and CCL2. Recruitment of BRD4 to the promoters of NFKBIA and CXCL8 remains unaffected by either F14 or JQ1 (a competitive inhibitor of BRD4 bromodomains), indicating that BRD4 recruitment is acetylation-independent. Unlike other viral proteins that are general antagonists of NF-κB, F14 is a selective inhibitor of NF-κB-dependent gene expression. An in vivo model of infection demonstrated that F14 promotes virulence. Molecular mimicry of NF-κB may be conserved because other orthopoxviruses, including variola, monkeypox and cowpox viruses, encode orthologues of F14.

Genomic epidemiology of the SARS-CoV-2 epidemic in Brazil

The high numbers of COVID-19 cases and deaths in Brazil have made Latin America an epicentre of the pandemic. SARS-CoV-2 established sustained transmission in Brazil early in the pandemic, but important gaps remain in our understanding of virus transmission dynamics at a national scale. We use 17,135 near-complete genomes sampled from 27 Brazilian states and bordering country Paraguay. From March to November 2020, we detected co-circulation of multiple viral lineages that were linked to multiple importations (predominantly from Europe). After November 2020, we detected large, local transmission clusters within the country. In the absence of effective restriction measures, the epidemic progressed, and in January 2021 there was emergence and onward spread, both within and abroad, of variants of concern and variants under monitoring, including Gamma (P.1) and Zeta (P.2). We also characterized a genomic overview of the epidemic in Paraguay and detected evidence of importation of SARS-CoV-2 ancestor lineages and variants of concern from Brazil. Our findings show that genomic surveillance in Brazil enabled assessment of the real-time spread of emerging SARS-CoV-2 variants.

Plasma membrane permeabilization to explain erythrosine B phototoxicity on in vitro breast cancer cell models.

Lipid oxidation is ubiquitous in cell life under oxygen and essential for photodynamic therapy (PDT) of carcinomas. However, the mechanisms underlying lipid oxidation in rather complex systems such as plasma membranes remain elusive. Herein, Langmuir monolayers were assembled with the lipid extract of glandular breast cancer (MCF7) cells and used to probe the molecular interactions allowing adsorption of the photosensitizer (PS) erythrosine B and subsequent photooxidation outcomes. Surface pressure (π) versus area (cm2/mL) isotherms of MCF7 lipid extract shifted to larger areas upon erythrosine incorporation, driven by secondary interactions that affected the orientation of the carbonyl groups and lipid chain organization. Light-irradiation increased the surface area of the MCF7 lipid extract monolayer containing erythrosine owing to the lipid hydroperoxidation, which may further undergo decomposition, resulting in the chain cleavage of phospholipids and membrane permeabilization. Incorporation of erythrosine by MCF7 cells induced slight toxic effects on in vitro assays, differently of the severe phototoxicity caused by light-irradiation, which significantly decreased cell viability by more than 75% at 2.5 × 10-6 mol/L of erythrosine incubated for 3 and 24 h, reaching nearly 90% at 48 h of incubation. The origin of the phototoxic effects is in the rupture of the plasma membrane shown by the frontal (FSC) and side (SSC) light scattering of flow cytometry. Consistent with hydroperoxide decomposition, membrane permeabilization was also confirmed by cleaved lipids detected in mass spectrometry and subsidizes the necrotic pathway of cell death.

Metabolic Evaluation in Patients With Hepatitis C Treated With Direct Antiviral Agents.

Epidemiological data clearly indicate a link between hepatitis C virus (HCV) and altered glucose homeostasis. Objective: To evaluate the response of treatment with direct antiviral agents (DAAs) on metabolic variables of patients with hepatitis C. Methods: Observational, cross-sectional study in a sample of patients with hepatitis C starting therapy with DAAs followed on the hepatology division of Federal University of Rio de Janeiro State. Data were collected in two stages: before the start of therapy and between 12 and 52 weeks after obtaining the sustained virological response. Results: In the baseline assessment of the 97 patients selected, 19.3% were obese, 38.6% were overweight, 50% were hypertensive, 43.8% were pre-diabetic, 12.5% were diabetic, 31.2% were dyslipidemic, and 21.8% had metabolic syndrome. There was an increase in total cholesterol and LDL levels (p < 0.001), and a non-significant reduction in blood glucose, glycated hemoglobin, insulin, and HOMA-IR levels after treatment. In the post-treatment, there was a reduction in fibrosis (p = 0.016), with a reduction in the levels of GGT, AST, and ALT (all with p < 0.001), as well as in the FIB4 and APRI scores (both with p < 0.001) and in the degree of fibrosis evaluated by elastography represented in kPa (p = 0.006). The blood glucose level was higher in patients with steatosis (p = 0.039) after treatment. There was a positive pre-treatment correlation between the degree of fibrosis (kPa) and FIB4 (r = 0.319, p = 0.004), APRI (r = 0.287, p = 0.010), and the NAFLD score (r = 0.275, p = 0.016). Conclusion: Patients with hepatitis C had a high prevalence of metabolic disturbance in the pre-treatment phase, but the therapy did not show beneficial effects, especially on glucose metabolism.

Síndrome de Tako-Tsubo en perioperatorio: Una variante rara. Reporte de caso / Tako-Tsubo syndrome in perioperative: A rare variant. Case report

Tako-Tsubo syndrome or stress-induced cardiomyopathy has been described as a transient left ventricular apical dyskinesia with chest pain and ST-segment elevation on electrocardiogram in the absence of obstructive lesions in coronary arteriography, most commonly in perimenopausal women. It is a rare pathology, with five reported variations and debated pathophysiological mechanisms. The current most accepted theory is a surge of catecholaminergic discharge, associated with genetic predisposition and an emotional or physical stress factor as trigger. We report a case of a 27-year-old woman with a history of uncontrolled asthma and a brother with early heart disease. She underwent appendectomy under general anesthesia and immediately after extubation, she presented a drop in oxygen saturation, respiratory distress, oppressive chest pain, severe arterial hypotension and acute pulmonary edema, requiring reintubation. ST depression on electrocardiogram, positive troponins, coronary arteriography without obstructive lesions, and mid-ventricular hypokinesia was observed in the complementary cardiac studies. Based in these findings, stress cardiomyopathy was diagnosed. The patient progressed favorably, four months after discharge, the patient remained asymptomatic with no changes in the cardiac studies.

El síndrome de Tako-Tsubo o miocardiopatía por estrés es descrito como una discinesia apical transitoria con cuadro de dolor torácico típico y electrocardiograma con elevación del segmento ST ante ausencia de lesiones en arteriografía coronaria, presentada principalmente en mujeres perimenopáusicas. Se reconoce como una patología poco frecuente, con 5 variaciones reportadas y de la que aún se debaten los mecanismos fisiopatológicos, siendo la descarga catecolaminérgica, asociada a predisposición genética y un factor emocional y/o físico desencadenante, la teoría más aceptada hoy en día. Se presenta el caso de una mujer de 27 años con antecedente de asma no controlada y hermano con enfermedad cardiaca temprana, que es llevada a apendicectomía abierta bajo anestesia general e inmediatamente a la extubación presenta caída de la saturación de oxígeno, dificultad respiratoria, refiere dolor torácico opresivo, hipotensión arterial severa y edema agudo de pulmón, con requerimiento de nueva intubación; electrocardiograma con infradesnivel del ST, troponinas positivas, arteriografía coronaria sin lesiones e hipocinesia medioventricular, con lo que se diagnostica miocardiopatía por estrés. Evolución favorable y egreso, y seguimiento a los 4 meses con exámenes normales.

The obscurance of the greatest sylvatic yellow fever epidemic and the cooperation of the Pan American Health Organization during the COVID-19 pandemic.

INTRODUCTION: Since 2016, Brazil has been in the midst of its largest sylvatic yellow fever epidemic ever, found predominantly outside the Amazon region. Cases originating from Brazil have been reported in France, the Netherlands, Romania, Switzerland, Argentina, and Chile. The epidemic began in the Central-West region of Brazil in 2014, spreading into the Southern region, with significant non-human primate transmission continuing towards Paraguay and Argentina. METHODS: This report is an integrative review of Pan American Health Organization cooperation during a sylvatic yellow fever epidemic. RESULTS: The Pan American Health Organization has played a central role in handling the yellow fever emergency, collaborating with the Ministry of Health and various research groups in supporting interventions of different response areas. The Pan American Health Organization's technical cooperation included: training and workshops to exchange experiences, carrying out technical cooperation in patient management and epidemiological, entomological, laboratory, and epizootic surveillance, organizing the assistance network, and acquiring strategic inputs. The Pan American Health Organization's technical cooperation supported the Ministry of Health's decision to adopt a single-dose vaccine and use fractional doses to support the vaccination needs of more than 39,000,000 people. The coronavirus disease 2019 pandemic contributed to the failure of reaching the yellow fever vaccination goals and made it difficult to integrate the yellow fever vaccine into recommended areas. CONCLUSIONS: Given the ongoing coronavirus disease 2019 pandemic, it is necessary to strengthen measures for the surveillance, prevention, and control of yellow fever with multilateral cooperation between countries.

Update on the treatment of musculoskeletal manifestations in chikungunya fever: a guideline.

Since the emergence of the chikungunya virus in Brazil in 2014, more than 700,000 cases have been reported throughout the country, corresponding to one-third of all cases reported in the Americas. In addition to its high attack rates, resulting in hundreds of thousands of cases, the disease has high chronicity rates with persistent joint manifestations for more than 3 months, which can spread to more than half of the patients affected in the acute phase. Pain associated with musculoskeletal manifestations, often disabling, has an effect on patients' quality of life at different stages of the disease. Currently, the challenge faced by specialists is identifying the best therapy to be instituted for symptom relief despite the limited number of published intervention studies. In 2016, a multidisciplinary group published pharmacological treatment protocols for pain in patients with chikungunya, which was incorporated into the guidelines for clinical management of the Brazilian Ministry of Health in 2017; in that same year, a consensus was published by the Brazilian Society of Rheumatology about diagnosis and treatment. After 5 years of experience with chikungunya epidemics, in 2019, specialists involved in the protocols of the Brazilian Society of Rheumatology and Brazilian Ministry of Health prepared an update with the main objective of developing flowcharts for the therapeutic approach of musculoskeletal manifestations in adult patients to enable specialists at different levels of healthcare to spread and apply this guideline in a systematic and simplified manner.

Does leukotriene F4 play a major role in the infection mechanism of Candida sp.?

Candidiasis is the most common fungal infection affecting hospitalized patients, especially immunocompromised and critical patients. Limitations regarding the assertive diagnosis of both Candidemia and Candidiasis not only impairs the introduction of effective treatments but also lays a heavy financial burden over the health system. Furthermore, it is still challenging to ascertain whether diagnostic methods are accurate and whether treatment is effective for patients with Candidemia. These constraints come from the uncertainty of the pathophysiological mechanism by which the pathogen establishes the opportunistic infection. Additionally, it is the reason why some patients present positive blood culture results, and others do not, and why it is very difficult during clinical routines to prove Candidemia or invasive candidiasis. Taking into account the current situation, this contribution proposes two markers that may help to understand the mechanisms of infection by the pathogen: Leukotriene F4 and 5,6-dihydroxy-eicosatetraenoic. These two lipids putatively modulate the host's immune response, and the initial data presented in this contribution suggest that these lipids allow the opportunistic infection to be installed. The study was carried out using an omics-based platform using direct-infusion high-resolution mass spectrometry and allied with bioinformatics tools to provide accurate and reliable results for biomarker candidates screening.