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BACKGROUND: Halofuginone (PJS-539) is an oral prolyl-tRNA synthetase inhibitor that has a potent in vitro activity against SARS-CoV-2 virus. The safety and efficacy of halofuginone in Covid-19 patients has not been studied. METHODS: We conducted a phase II, randomized, double-blind, placebo-controlled, dose ranging, safety and tolerability trial of halofuginone in symptomatic (≤ 7 days), mostly vaccinated, non-hospitalized adults with mild to moderate Covid-19. Patients were randomized in a 1:1:1 ratio to receive halofuginone 0.5mg, 1mg or placebo orally once daily for 10 days. The primary outcome was the decay rate of the SARS-CoV-2 viral load logarithmic curve within 10 days after randomization. RESULTS: From September 25, 2021, to February 3, 2022, 153 patients were randomized. The mean decay rate in SARS-CoV-2 viral load log10 within 10 days was -3.75 (95% CI, -4.11; -3.19) in the placebo group, -3.83 (95% CI, -4.40; -2.27) in the halofuginone 0.5mg group and -4.13 (95% CI, -4.69; -3.57) in the halofuginone 1mg group, with no statistically significant difference in between placebo vs. halofuginone 0.5mg (mean difference -0.08; 95% CI -0.82 to 0.66, p = 0.96) and between placebo vs. halofuginone 1mg (mean difference -0.38; 95% CI, -1.11; 0.36, p = 0.41). There was no difference on bleeding episodes or serious adverse events at 28 days. CONCLUSIONS: Among non-hospitalized adults with mild to moderate Covid-19 halofuginone treatment was safe and well tolerated but did not decrease SARS-CoV-2 viral load decay rate within 10 days.

(Series Information) European Papers - A Journal on Law and Integration, 2024 9(1), 121-129 | European Forum Insight of 18 June 2024 | (Table of Contents) I. Introduction. - II. Signature of international agreements: the (in)consistent practice. - III. Solving the indeterminacy of art. 218 TFEU. - iii.1. Scope, institutional balance and sincere cooperation. - iii.2 Signature of non-binding agreements. - IV. Case C-551-21: insights and commentaries. - iv.1. Understanding the arguments. - iv.2. The Court’s Findings. - V. Conclusions | (Abstract) The current Insight analyses the judgment of the European Court of Justice in Case C-551/21, which up-held the Commission's claim regarding its right to exercise the external act of treaty signature. The deci-sion sheds light on the signature procedure outlined in art. 218 TFEU and adds to previous cases, clari-fying the proper contours and roles of each institution in relation to the procedure set in the article. An initial observation of the practice appears to indicate the Permanent Representative of the country holding the Council's presidency as the responsible party to sign international agreements with third parties representing the Union. However, a more in-depth analysis reveals a lack of consistent and standardised practice. The judgment correctly recalibrates the institutional balance and is coherent with the reforms of the Lisbon Treaty, which sought to bring about an evolution of the principles of the Treaties without a formal amendment process.

microRNAs (miRNAs) are small endogenous noncoding RNAs, and alterations in their expression may contribute to oncogenesis. Discovering a unique miRNA pattern holds the potential for early detection and novel treatment possibilities in cancer. This study aimed to evaluate miRNA expression in pediatric patients with gonadal germ cell tumors (GCTs), focusing on characterizing the miRNA profiles of each histological subtype and identifying a distinct histological miRNA signature for a total of 42 samples of pediatric gonadal GCTs. The analysis revealed distinct miRNA expression profiles for all histological types, regardless of the primary site. We identified specific miRNA expression signatures for each histological type, including 34 miRNAs for dysgerminomas, 13 for embryonal carcinomas, 25 for yolk sac tumors, and one for immature teratoma, compared to healthy controls. Furthermore, we identified 26 miRNAs that were commonly expressed in malignant tumors, with six miRNAs (miR‐302a‐3p, miR‐302b‐3p, miR‐371a‐5p, miR‐372‐3p, miR‐373‐3p, and miR‐367‐3p) showing significant overexpression. Notably, miR‐302b‐3p exhibited a significant association with all the evaluated clinical features. Our findings suggest that miRNAs have the potential to aid in the diagnosis, prognosis, and management of patients with malignant GCTs.

IntroductionInfections acquired during healthcare setting stay pose significant public health threats. These infections are known as Healthcare-Associated Infections (HAI), mostly caused by pathogenic bacteria, which exhibit a wide range of antimicrobial resistance. Currently, there is no knowledge about the global cleaning process of hospitals and the bacterial diversity found in ICUs of Brazilian hospitals contributing to HAI.ObjectiveCharacterize the microbiome and common antimicrobial resistance genes present in high-touch Intensive Care Unit (ICU) surfaces, and to identify the potential contamination of the sanitizers/processes used to clean hospital surfaces.MethodsIn this national, multicenter, observational, and prospective cohort, bacterial profiles and several antimicrobial resistance genes from 41 hospitals across 16 Brazilian states were evaluated. Using high-throughput 16S rRNA amplicon sequencing and real-time PCR, the bacterial abundance and resistance genes presence were analyzed in both ICU environments and cleaning products.ResultsWe identified a wide diversity of microbial populations with a recurring presence of HAI-related bacteria among most of the hospitals. The median bacterial positivity rate in surface samples was high (88.24%), varying from 21.62 to 100% in different hospitals. Hospitals with the highest bacterial load in samples were also the ones with highest HAI-related abundances. Streptococcus spp., Corynebacterium spp., Staphylococcus spp., Bacillus spp., Acinetobacter spp., and bacteria from the Flavobacteriaceae family were the microorganisms most found across all hospitals. Despite each hospital particularities in bacterial composition, clustering profiles were found for surfaces and locations in the ICU. Antimicrobial resistance genes mecA, blaKPC-like, blaNDM-like, and blaOXA-23-like were the most frequently detected in surface samples. A wide variety of sanitizers were collected, with 19 different active principles in-use, and 21% of the solutions collected showed viable bacterial growth with antimicrobial resistance genes detected.ConclusionThis study demonstrated a diverse and spread pattern of bacteria and antimicrobial resistance genes covering a large part of the national territory in ICU surface samples and in sanitizers solutions. This data should contribute to the adoption of surveillance programs to improve HAI control strategies and demonstrate that large-scale epidemiology studies must be performed to further understand the implications of bacterial contamination in hospital surfaces and sanitizer solutions.

Abstract: Background: The release of neutrophil extracellular traps (NETs) is associated with inflammation, coagulopathy, and organ damage found in severe cases of COVID-19. However, the molecular mechanisms underlying the release of NETs in COVID-19 remain unclear. Objectives: We aim to investigate the role of the Gasdermin-D (GSDMD) pathway on NETs release and the development of organ damage during COVID-19. Methods: We performed a single-cell transcriptome analysis in public data of bronchoalveolar lavage. Then, we enrolled 63 hospitalized patients with moderate and severe COVID-19. We analyze in blood and lung tissue samples the expression of GSDMD, presence of NETs, and signaling pathways upstreaming. Furthermore, we analyzed the treatment with disulfiram in a mouse model of SARS-CoV-2 infection. Results: We found that the SARS-CoV-2 virus directly activates the pore-forming protein GSDMD that triggers NET production and organ damage in COVID-19. Single-cell transcriptome analysis revealed that the expression of GSDMD and inflammasome-related genes were increased in COVID-19 patients. High expression of active GSDMD associated with NETs structures was found in the lung tissue of COVID-19 patients. Furthermore, we showed that activation of GSDMD in neutrophils requires active caspase1/4 and live SARS-CoV-2, which infects neutrophils. In a mouse model of SARS-CoV-2 infection, the treatment with disulfiram inhibited NETs release and reduced organ damage. Conclusion: These results demonstrated that GSDMD-dependent NETosis plays a critical role in COVID-19 immunopathology and suggests GSDMD as a novel potential target for improving the COVID-19 therapeutic strategy.

Background: Systemic inflammatory responses mimicking infectious complications are often present in surgical patients. Methods: The objective was to assess the association between withholding early antimicrobial therapy while investigating alternative diagnoses and worse outcomes in nonseptic patients with suspected nosocomial infection in a retrospective cohort of critically ill surgical patients. The initiation of antibiotic therapy within 24 h of the suspicion of infection was defined as the Early Empirical Antibiotic strategy (EEA) group and the initiation after 24 h of suspicion or not prescribed was defined as the Conservative Antibiotic strategy (CA) group. Primary outcome was composite: death, sepsis, or septic shock within 14 days. Main exclusion criteria were sepsis or an evident source of infection at inclusion. Results: Three hundred and forty patients were eligible for inclusion (74% trauma patients). Age, sex, reason for hospital admission, SAPS3 score, SOFA score, and use of vasopressors or mechanical ventilation were not different between the groups. Within 14 days of inclusion, 100% (130/130) of EEA patients received antibiotics compared to 57% (120/210) of CA patients. After adjusting for confounding variables, there was no association between primary outcome and the groups. In a post hoc subgroup analysis including only patients with a posteriori confirmed infection (by microbiological cultures), delay in initiation of adequate antimicrobial therapy was independently associated with the primary outcome (Odds Ratio = 1.19 per day of delay; 95% CI 1.05–1.37). Conclusions: Withholding early empiric antibiotic therapy was not associated with progression of organ dysfunction within 14 days in nonseptic surgical patients with suspected nosocomial infection without an obvious source.

Escalating industrial CO2 emissions necessitate innovative carbon capture and utilization strategies. This study explores the potential of mineral-carbonation of steelmaking slags, particularly White Slag (WS) and various Refractory Wastes (RWs), to mitigate CO2 emissions and valorize industrial wastes. Experiments were performed with waste materials from the production lines at CELSA (Barcelona, Spain). We delved into direct aqueous carbonation, evaluating the performance and characteristics of these wastes under different experimental conditions. Our findings reveal that all slags can effectively sequester CO2. This process is effective not only for pure CO2 but also for diluted flue gases under mild conditions (≤ 100 ºC, ≤ 6 bar). Specifically, WS exhibited peak CO2 sequestration capacities (SC) of 359.79 gCO2/kgslag (pure CO2) and 276.65 gCO2/kgslag (diluted flue gas). In contrast, the RWs presented different kinetic, reaching a maximum SC of 311 gCO2/kgslag after prolonged times. Given the large inhomogeneity of RWs, individual analysis of distinct RW fractions revealed significant variations in carbonation performance. Tundish RW exhibited the highest CO2 sequestration capacity, emphasizing the importance of waste source and mineral composition in the carbonation. Chemical and morphological evaluations confirmed the transformation of CaO to CaCO3, with MgO remaining largely inert. Additionally, the process indicated potential environmental benefits by reducing the mobility of toxic metals, particularly Pb, suggesting an ancillary avenue for waste treatment. This study underscores the utility of CO2 mineralization as a dual-benefit approach within the circular economy framework, offering insights into its application for sustainable waste management and CO2 emission reduction in the steel industry.

Abstract Introduction Shorter courses of antimicrobials have been shown to be non-inferior to longer, “traditional” duration of therapies, including for some severe healthcare-associated infections, with a few exceptions. However, evidence is lacking regarding shorter regimes against severe infections by multidrug-resistant Gram-negative bacteria (MDR-GNB), which are often caused by distinct strains and commonly treated with second-line antimicrobials. In the duratiOn of theraPy in severe infecTIons by MultIdrug-reSistant gram-nEgative bacteria (OPTIMISE) trial, we aim to assess the non-inferiority of 7-day versus 14-day antimicrobial therapy in critically ill patients with severe infections caused by MDR-GNB. Methods This is a randomized, multicenter, open-label, parallel controlled trial to assess the non-inferiority of 7-day versus 14-day of adequate antimicrobial therapy for intensive care unit (ICU)-acquired severe infections by MDR-GNB. Adult patients with severe infections by MDR-GNB initiated after 48 h of ICU admission are screened for eligibility. Patients are eligible if they proved to be hemodynamically stable and without fever for at least 48 h on the 7th day of adequate antimicrobial therapy. After consenting, patients are 1:1 randomized to discontinue antimicrobial therapy on the 7th (± 1) day or to continue for a total of 14th (± 1) days. Planned Outcomes The primary outcome is treatment failure, defined as death or relapse of infection within 28 days after randomization. Non-inferiority will be achieved if the upper edge of the two-tailed 95% confidence interval of the difference between the clinical failure rate in the 7-day and the 14-day group is not higher than 10%. Conclusion The OPTIMISE trial is the first randomized controlled trial specifically designed to assess the duration of antimicrobial therapy in patients with severe infections by MDR-GNB. Trial Registration ClinicalTrials.gov, NCT05210387. Registered on 27 January 2022. Seven Versus 14 Days of Antibiotic Therapy for Multidrug-resistant Gram-negative Bacilli Infections (OPTIMISE).

Chemical and physical denudation rates have been assessed in areas with different lithologies. Surprisingly, there are no studies that attempt to document these rates in the Poços de Caldas Alkaline Massif (PC), the largest alkaline magmatism in South America and an important Al supergene deposit in Brazil. Therefore, the chemical and physical denudation rates were assessed and explained in the PC. Surface water and rainwater samples were collected at the Amoras Stream basin, covering one complete hydrological cycle (2016). All samples were analyzed for dissolved cations, silica, anions, total dissolved solids (TDS), and total suspended solids (TSS). The results reflected the seasonal variation on discharge, water temperature, and electrical conductivity in the Amoras Stream, with most of the cations, anions, silica TDS, and TSS being carried in the wet season. Partial hydrolysis and silicate incongruent dissolution are the main water/rock interactions in the PC, with an atmospheric/soil CO2 consumption rate of 1.6 × 105 mol/km2/a. The annual fluxes of Cl−, PO43−, NO3−, and Al3+ were significantly influenced from rainwater. Chemical and physical weathering rates were 4 ± 0.8 and 3.0 ± 0.6 m/Ma in the PC, respectively, indicating that under the current climatic condition, the weathering profile is in dynamic equilibrium.

BackgroundHalofuginone (PJS-539) is an oral prolyl-tRNA synthetase inhibitor that has a potent in vitro activity against SARS-CoV-2 virus. The safety and efficacy of halofuginone in Covid-19 patients has not been studied.MethodsWe conducted a phase II, randomized, double-blind, placebo-controlled, dose ranging, safety and tolerability trial of halofuginone in symptomatic (≤ 7 days), mostly vaccinated, non-hospitalized adults with mild to moderate Covid-19. Patients were randomized in a 1:1:1 ratio to receive halofuginone 0.5mg, 1mg or placebo orally once daily for 10 days. The primary outcome was the decay rate of the SARS-CoV-2 viral load logarithmic curve within 10 days after randomization.ResultsFrom September 25, 2021, to February 3, 2022, 153 patients were randomized. The mean decay rate in SARS-CoV-2 viral load log10 within 10 days was -3.75 (95% CI, -4.11; -3.19) in the placebo group, -3.83 (95% CI, -4.40; -2.27) in the halofuginone 0.5mg group and -4.13 (95% CI, -4.69; -3.57) in the halofuginone 1mg group, with no statistically significant difference in between placebo vs. halofuginone 0.5mg (mean difference -0.08; 95% CI -0.82 to 0.66, p = 0.96) and between placebo vs. halofuginone 1mg (mean difference -0.38; 95% CI, -1.11; 0.36, p = 0.41). There was no difference on bleeding episodes or serious adverse events at 28 days.ConclusionsAmong non-hospitalized adults with mild to moderate Covid-19 halofuginone treatment was safe and well tolerated but did not decrease SARS-CoV-2 viral load decay rate within 10 days.

The coronavirus disease (COVID-19) pandemic leveraged telemedicine worldwide mainly due to the need for social distancing, patient safety, and infection prevention. The Hospital das Cl?nicas da Faculdade de Medicina da Universidade de S?o Paulo (HCFMUSP) was a key reference site in the treatment of COVID-19 severe cases in the country. To continue patient's health care, it became necessary to increase the number of teleconsultations and standardize it institutionally. Herein, we briefly described how the HCFMUSP improved the teleconsultation health care service during the COVID-19 pandemic, highlighting the implementation of important innovations and the throughout standardization process, including patients and professional workflow. We also detailed the methodology used to implement or improve teleconsultation in a medical/multidisciplinary specialty at HCFMUSP. All these efforts made the HCFMUSP reach the goal of converting 15% of all face-to-face consultations into teleconsultations only in 2021. In addition, there were more than 370,000 teleconsultations until the end of 2022. Our experience has shown that having a supporting team, a digital certification process, and the data integration were key factors toward the successful implementation of the teleconsultation services. We believe that progressing toward teleconsultation will improve the population covered by health care services in Brazil, as well as contribute to a reduction of waiting time, and solving costs to health care institutions and patients. We expect this report of our experience in teleconsultation implementation could inspire and guide other health care institutions in the development of telemedicine.

The shikimate pathway is crucial for the biosynthesis of aromatic amino acids in plants and represents a promising target for developing new herbicides. This work aimed to identify inhibitors of shikimate dehydrogenase (SDH), a key enzyme of the shikimate pathway that catalyzes the conversion of 3-dehydroshikimate to shikimate. Virtual screening and molecular dynamic simulations were performed on the SDH active site of Arabidopsis thaliana (AtSDH), and 6-nitroquinazoline-2,4-diol (NQD) was identified as a potential inhibitor. In vitro assays showed that NQD decreased the activity of AtSDH by reducing Vmax while keeping KM unchanged, indicating non-competitive inhibition. In vivo, hydroponic experiments revealed that NQD reduced the root length of soybean and maize. Additionally, NQD increased the total protein content and certain amino acids. Soybean roots uptake NQD more efficiently than maize roots. Furthermore, NQD reduced shikimate accumulation in glyphosate-treated soybean roots, suggesting its potential to restrict the flow of metabolites along the shikimate pathway in soybean. The simultaneous treatment of maize seedlings with glyphosate and NQD accumulated gallic acid in the roots, indicating that NQD inhibits SDH in vivo. Overall, the data indicate that NQD inhibits SDH both in vitro and in vivo, providing valuable insights into the potential development of herbicides targeting SDH.

Introduction Certain criteria for ventilator-associated events (VAE) definition might influence the type of an event, its detection rate and consequently the resource expenditure in intensive care unit. The Impact of Infections by Antimicrobial-Resistant Microorganisms - Ventilator-Associated Pneumonia (IMPACTO MR-PAV) aims to evaluate the incidence and diagnostic accuracy of ventilator-associated pneumonia (VAP) using the current criteria for VAP surveillance in Brazil versus the VAE criteria defined by the US National Healthcare Safety Network-Center for Diseases Control and Prevention (CDC) criteria.Methods and analysis The study will be conducted in around 15 centres across Brazil from October 2022 to December 2023. Trained healthcare professionals will collect data and compare the incidence of VAP using both the current criteria for VAP surveillance in Brazil and the VAE criteria defined by the CDC. The accuracy of the two criteria for identifying VAP will also be analysed. It will also characterise other events associated with mechanical ventilation (ventilator-associated condition, infection-related ventilator-associated complication) and adjudicate VAP reported to the Brazilian Health Regulatory Agency (ANVISA) using current epidemiological diagnostic criteria.Ethics and dissemination This study was approved by the Institutional Review Board under the number 52354721.0.1001.0070. The study’s primary outcome measure will be the incidence of VAP using the two different surveillance criteria, and the secondary outcome measures will be the accuracy of the two criteria for identifying VAP and the adjudication of VAP reported to ANVISA. The results will contribute to the improvement of VAP surveillance in Brazil and may have implications for other countries that use similar criteria.Trial registration number NCT05589727; Clinicaltrials.gov.

Objetivos: O cromossomo Philadelphia (Ph) é uma translocação recíproca entre os cromossomos 9 e 22, formando o rearranjo gênico BCR-ABL. Objetiva-se descrever o caso de uma paciente, portadora dessa anormalidade citogenética, com leucemia mieloide crônica (LMC), dez anos após quimiorradioterapia por leucemia linfoide aguda (LLA). Materiais e métodos: Estudo do prontuário da paciente. Resultados: S.G.S., menina de 15 anos, em ago/2006, com queixa de astenia, febre, palidez e adenomegalia cervical. Ao exame físico, úlceras necróticas em gengiva e hepatomegalia, confirmada por USG. Ao hemograma, anemia (10,4 g/dL), leucocitose (35.000/mm3) e trombocitopenia (23.000/mm3). Ao mielograma, medula óssea hipocelular, com espículas hipocelulares, raras células com núcleo de cromatina frouxa, citoplasma não muito escasso e esboço de nucléolos, concluindo diagnóstico de LLA, classificação FAB L1. À imunofenotipagem celular, expressão de HLA-DR, CD19, CD56, CD58, definindo LLA pró-B - CD10 negativo. A quimioterapia seguiu o protocolo GBTLI-93 para pacientes com alto risco. Foi submetida a radioterapia craniana (líquor não infiltrado), 18 Gy em 12 frações, de fev. a mar/2007, sem intercorrências, dando início à fase de manutenção do tratamento em maio/2007, encerrando tratamento em ago/2009, em acompanhamento periódico, sem sinais de recaída, até 2012. Sem registros de exame de biologia molecular à época. Em jan/2019, S.G.S., com 28 anos, apresentando quadro gripal, realizou hemograma, que revelou leucocitose (80.040 mm3). Ao mielograma, medula óssea hipercelular, com espículas hipercelulares, relação leuco:eritroblástica 50:1, setor eritrocitário extremamente hipocelular, setor leucocitário hipercelular com escalonamento, sugerindo LMC. O exame de biologia molecular (RT-PCR) revelou translocação BCR-ABL, isoforma p190 positiva, sendo negativa a isoforma p210. Instaurado tratamento com o inibidor da tirosina-quinase (TKI) imatinibe, alcançando resposta molecular completa (BCR-ABL indetectável) em jul/2022. Discussão: A LLA Ph-positivo apresenta, mais comumente, translocação BCR-ABL subtipo e1a2, que codifica a proteína p190, que está associada a pior prognóstico. Na LMC, observa-se a translocação BCR-ABL em subtipos de transcrição e13a2 e e14a2, que codificam proteínas p210, também sendo possível encontrar as isoformas p210 e p190 presentes simultaneamente. No entanto, a isoforma p190 isoladamente é rara na LMC, além de ser fator de risco importante, pois pacientes costumam apresentar respostas menos satisfatórias ao uso de TKI.Segundas neoplasias hematológicas são raras em pacientes previamente tratados por leucemia. LMC pode ocorrer como neoplasia secundária por danos genéticos causados por quimiorradioterapia prévia, contudo, a LMC Ph-positivo raramente é descrita como neoplasia secundária, sugerindo a predisposição gênica como causa. Conclusão: O surgimento de uma segunda neoplasia hematológica, relacionada a um raro rearranjo gênico e possivelmente associada a danos genéticos causados por quimiorradioterapia prévia, fomenta o debate sobre o caráter multifatorial da oncogênese na leucemia. Mais estudos são necessários para determinar as repercussões clínicas e o prognóstico das leucemias associadas à mutação BCR-ABL de subtipo p190, assim como a relação entre a quimiorradioterapia para LLA e LMC secundária.

Introdução: De acordo com ministério da saúde, o serviço de hemoterapia deve realizar os seguintes exames imuno-hematológicos para qualificação do sangue do doador, a fim de garantir a eficácia terapêutica e a segurança da futura doação: tipagem ABO; tipagem RhD; e pesquisa de anticorpos antieritrocitários irregulares (PAI). A PAI é comumente utilizada para identificar a presença de anticorpos com significados clínicos ou não presentes no soro de doadores e receptores de transfusões sanguíneas e através da técnica indireta da antiglobulina. Se um paciente receber a transfusão de hemocomponentes com estes anticorpos, pode ser exposto, tanto à um risco de hemólise, como também interferir nos testes pré-transfusionais realizados antes de uma nova transfusão. A identificação dos doadores é importante para uma seleção de hemocomponentes seguros e orientação desses doadores para uma eventual necessidade transfusional. Objetivos: Analisar o perfil dos doadores do Banco de Sangue de Ribeirão Preto, que apresentaram resultado de PAI positivo e identificar quais os anticorpos mais frequentes no período de 2021 a 2022. Material e métodos: Em uma análise retrospectiva dos resultados de PAI positivos dos doadores sangue no período de janeiro de 2021 até dezembro de 2022, fizemos classificação de acordo com gênero, idade, identificação do anticorpo, tipagem sanguínea e histórico gestacional e transfusional. Resultados: Tivemos um total de 32.651 doadores, desses 39 apresentaram a PAI positiva, representando 0,12%, em que 41% foram do grupo O positivo, 15,4% A positivos, 15,4% O negativos, 10,25% A negativos, 7,7% B positivos, 7,7% AB positivos e 2,55% AB negativo. Visto que 71,7% eram do gênero feminino e 28,2% masculino. A faixa etária que apresentou maior frequência de resultados positivos foi de 40 a 49 anos, com 46%, seguido de 30 a 39 anos com 18%. Os anticorpos irregulares identificados foram: 23% anti-D, 23% Anti-M, 15,3% anti-E, 12,8% anti-K, 10,2% anti-c, 7,6% anti-C, 5,1% anti-JKa e 5,1% anti-DIA e outros em menores frequências. Ao analisarmos o histórico de gestacional e transfusional, verificamos que 46% relatam ter tido gestações, 20% dos doadores relatam ter recebido transfusão e 34% não relatam nenhum histórico. Discussão: De acordo com a literatura a presença de anticorpos irregulares na população em geral é de 0,3 a 2%, e o o presente trabalho identificou um resultado abaixo desse esperado. Também é conhecido que o anti-D é o anticorpo mais frequente na população, entretanto, neste estudo, o anti-M apareceu com mesma frequência do anti-D. O resultado obtido com mais de 70% dos doadores serem do sexo feminino, sugere um anti-D de origem gestacional. A presença de doadores com anti-M induz a suspeita de um provável IgM de origem natural. Conclusão: A identificação de aloimunização eritrocitária em doadores de sangue é importante ferramenta para permitir uma seleção segura de concentrados de hemácias devidamente identificados e descarte correto de plasmas e plaquetas, para manutenção de estoque adequado e redução e gastos com descartes.

Objetivo: O Banco de Sangue GSH de Ribeirão Preto, realizou no ano anterior a caracterização do perfil epidemiológico dos doadores de sangue que apresentaram reações adversas sistêmicas à doação, sendo a maior incidência em doadores de primeira vez e faixa etária dos 16 a 29 anos. A partir da identificação doadores com perfil de maior risco, foram estabelecidas algumas ações de prevenção, visando minimizar o risco das reações adversas sistêmicas deste grupo. Desta forma, o objetivo do atual estudo é avaliar a efetividade dessas ações na prevenção de reações adversas relacionadas à doação de sangue em doadores com perfil de maior risco. Material e métodos: Estudo coorte prospectivo através da randomização aleatória de doadores de primeira vez e faixa etária jovem dos 16 a 29 anos no período de 3 meses. Após seleção dos doadores, realizado a aplicação de ações preventivas, análise observacional da eficácia das ações e avaliação da redução de risco absoluto e relativo. Resultados: No período de maio a julho de 2023, houveram 552 doadores de primeira vez e faixa etária jovem dos 16 a 29 anos. Através da seleção aleatória durante o processo de triagem clínica, aplicamos duas ações de prevenção, sendo elas, orientação assertiva sobre o ciclo do sangue ao qual 4% dos doadores desenvolveram reações adversas relacionadas à doação de sangue. A segunda ação aplicada, realizamos a posição trendelenburg após a coleta ao qual apenas 2,6% desenvolveram reações adversas relacionadas à doação de sangue. Os doadores que não aplicamos as ações de prevenção, a incidência de reações adversas foi de 5,5%. Discussão: Ao avaliar a efetividade da aplicação das ações preventivas propostas, através do cálculo de redução de risco absoluto (RAR) o estudo obteve resultado de 2,5%. A ação preventiva de orientação assertiva sobre o ciclo do sangue aos doadores, obteve resultado de risco absoluto (RAR) em 1,5%, não havendo relevância estatística significativa. Em destaque, a ação preventiva ao qual realizamos a posição trendelenburg após a coleta obteve maior impacto positivo devido ao resultado de risco absoluto (RAR) em 2,9%. Sendo assim, quando avaliamos o impacto para minimizar as reações adversas sistêmicas relacionadas à doação de sangue em doadores com perfil de risco que aplicamos as ações e em doadores com perfil de risco que não aplicamos, houve uma redução de risco relativo (RRR) de 53% com respectivo intervalo de confiança de 95%. Portanto, estabelecer ações de prevenção que reduzem o risco de reação adversa sistêmica relacionada à doação de sangue com este perfil de doadores, gerou maior segurança durante o processo de doação dos doadores, garantiu melhor qualidade em nosso atendimento e consequentemente agregou confiança para motivá-los a retornarem para futuras doações. Conclusão: O estudo permitiu a promoção de ações de prevenção que reduziram a incidência de reações adversas sistêmicas relacionadas à doação de sangue em doadores com perfil de maior risco, ao qual a posição trendelemburg após a coleta obteve maior destaque para redução das reações adversas sistêmica. Garantindo assim, um processo seguro e de qualidade que viabiliza a fidelização dos doadores de maior risco.

Introdução: A transfusão de sangue é uma prática médica muito importante e frequente no cotidiano do cuidado dos pacientes. O uso de hemocomponentes são variados: politraumatizados, doenças crônicas, cirurgias, neoplasias hematológicas, hemoglobinopatias, entre outras. O ato da doação de sangue é a única forma de mantermos esse recurso, porém segundo o Ministério da Saúde apenas 1,6% da população brasileira doa sangue, número abaixo do esperado pela Organização Mundial da Saúde (OMS), estimado de 3 a 5%. Temos em nosso serviço em média 16 mil doadores por ano, onde 38,8% são doadores de repetição e 43,3% são de primeira vez. Do total de doadores, 30% são motivados por conhecer um paciente em específico, 44% foram mobilizados por campanhas ou convocados pelo banco de sangue e 25% são doadores espontâneos. Para a manutenção dos estoques de sangue e atender a demanda hospitalar é necessário um trabalho contínuo para fidelização de doadores. Objetivos: Este trabalho teve como objetivo identificar os fatores que na visão dos doadores são importantes para seu retorno em nosso serviço. Material e métodos: Por meio de pesquisa descritiva, foram distribuídosn 100 questionários na recepção do banco de sangue de forma aleatória para doadores que já haviam doado pelo menos uma vez, no período de maio a junho de 2023. O questionário continha as perguntas: quantidade de doações, estacionamento, cordialidade, limpeza, infraestrutura, tempo de espera, a contato da equipe de captação e o lanche. Os doadores assinalavam se aquele item foi extremamente, muito, moderadamente, pouco ou nada importante para seu retorno ao banco de sangue. Resultados: Do total de 100 questionários, foram 52 sexo masculino e 48 feminino, 60% tinham entre 30 e 50 anos de idade. Com relação ao número de doações, 37% já fizeram mais de 10 doações, 29% entre 5 e 10 doações, 21% de 3 a 5 doações e 13% estavam realizando a segunda doação. Em relação aos fatores perguntados, a limpeza, cordialidade e infraestrutura foi extremamente importante para seu retorno, com 60, 57 e 53 % respectivamente, sendo que aproximadamente 95% dos doadores assinalaram “extremamente” ou “muito” para esse 3 fatores. Já os fatores de tempo de atendimento, contato e o lanche, a maioria dos doadores sinalizou a opção “muito” para seu retorno com 40, 44 e 42%. No fator de ter um estacionamento, 15% assinalaram como “nada”. Verificou-se que o sexo masculino são mais motivamos pela limpeza (extremamente), porém o contato da captação e tempo de doação também influenciaram muito no seu retorno. Já o sexo feminino, a limpeza e cordialidade são extremamente importantes, porém os demais fatores foram bem distribuídos. Discussão: Esta pesquisa evidenciou que a faixa etária de doadores mais fidelizados estão entre 30 e 50 anos e que independente do sexo, a limpeza, cordialidade e infraestrutura são os fatores que mais motivaram os doadores a retornarem ao nosso serviço. Assim, o investimento no cuidado da limpeza e a garantia de um bom relacionamento com o doador são pontos de sucesso para a fidelização. Possuir um estacionamento conveniado foi o menos importante na nossa pesquisa, mas sabemos que essa importância pode ser variável a depender da localização de cada banco de sangue. Conclusão: Este estudo nos permitiu analisar a visão dos doadores sobre dos fatores que os deixam seguros e motivados a voltarem ao nosso serviço e assim melhorarmos os pontos para o aumento da fidelização.

Gastrointestinal signs and symptoms are the first signs of toxicity due to exposure to fluoride (F). This suggests the possibility that lower levels of subchronic F exposure may affect the gut. The aim of this study was to evaluate changes in the morphology, proteome and microbiome of the ileum of rats, after subchronic exposure to F. Male rats ingested water with 0, 10, or 50 mgF/L for thirty days. Treatment with F, regardless of the dose, significantly decreased the density of HuC/D-IR neurons, whereas CGRP-IR and SP-IR varicosities were significantly increased compared to the control group. Increased VIP-IR varicosities were significantly increased only in the group treated with 50 mgF/L. A significant increase in thickness of the tunica muscularis, as well as in the total thickness of the ileum wall was observed at both F doses when compared to controls. In proteomics analysis, myosin isoforms were increased, and Gastrotopin was decreased in F-exposed mice. In the microbiome metagenomics analysis, Class Clostridia was significantly reduced upon exposure to 10 mgF/L. At the higher F dose of 50 mg/L, genus Ureaplasma was significantly reduced in comparison with controls. Morphological and proteomics alterations induced by F were marked by changes associated with inflammation, and alterations in the gut microbiome. Further studies are needed to determine whether F exposure increases inflammation with secondary effects of the gut microbiome, and/or whether primary effects of F on the gut microbiome enhance changes associated with inflammation.

Abstract In this large cohort of healthcare workers, we aimed to estimate the rate of reinfections by SARS-CoV-2 over 2 years of the COVID-19 pandemic. We investigated the proportion of reinfections among all the cases of SARS-CoV-2 infection from March 10, 2020 until March 10, 2022. Reinfection was defined as the appearance of new symptoms that on medical evaluation were suggestive of COVID-19 and confirmed by a positive RT-PCR. Symptoms had to occur more than 90 days after the previous infection. These 2 years were divided into time periods based on the different variants of concern (VOC) in the city of São Paulo. There were 37,729 medical consultations due to COVID-19 at the hospital’s Health Workers Services; and 25,750 RT-PCR assays were performed, of which 23% (n = 5865) were positive. Reinfection by SARS-CoV-2 was identified in 5% (n = 284) of symptomatic cases. Most cases of reinfection occurred during the Omicron period (n = 251; 88%), representing a significant increase on the SARS-CoV-2 reinfection rate before and during the Omicron variant period (0.8% vs. 4.3%; p

Objectives To develop a Brazilian public hospital, Sao Paulo University Medical School Clinics Hospital, HCFMUSP, informational model to link and improve multiple patients' health data, care pathways and outcomes, to build a living real world ecosystem aiming to subsidize policy decision-making, support research and promote patients' engagement and involvement. Methods Policy-relevant linkage data including demography, diagnostics, outpatient and emergency room visits, hospitalizations, intensive care evolution, assisted mechanical ventilation or special equipment’s uses, electronic prescriptions, imaging and clinical laboratory tests results, surgery records, blood components use, and medical and multidisciplinary teams’ evolutions. Telemedicine-based hub developed for patient’s access to his own visits or procedures schedule, comprehensive data and results temporal series, and specific communications channels. Anonymized data sharing for Sao Paulo State Health Secretariat policy decision-making and SP Research Agency multicenter Data Lake for Covid-19 pandemic research. Stratified impact and economic analysis regarding clinical and co-morbid conditions research were published. Results Since March 2020, this informational model example comprises over 10,000 Covid-19 patient’s related data with more than 100,000 events registered. During the first pandemic trimester, upon SP Health Secretariat policy, the HCFMUSP Central Institute’s 900 ward and 300 ICU beds were the SP central reference for severe and critical admissions. In this first evaluation 88.4% had co-morbidities (e.g. 48.1% hypertension, 30.5% diabetes), 51.7% required ICU admission and 28.9% died. Average hospital length of stay was 10.7 days, mean cost per admission was US$12,637.42, and the overall daily cost was US$919.24. Age strata >69 years confirmed COVID-19, ICU, elevated C-reactive protein (inflammation) adjusted by D-dimer levels (thrombosis biomarker), higher mSOFA, mechanical ventilation, dialysis, surgery and comorbidities, remained significantly associated with higher (24%-200%) costs and poorer outcomes. Conclusion The informational model is proving to be beneficial for all stakeholders. Technology-based organized systems increased management accuracy and efficiency, emergency preparedness, facilitates patient’s involvement and participation, promote medical and multi-professionals teams’ knowledge development, and permits to subsidize policy decisions and to improve public health.

Introduction SARS-CoV-2 has been identified as the cause of the disease officially named COVID-19, primarily a respiratory illness. COVID-19 was characterised as a pandemic on 11 March 2020. It has been estimated that approximately 20% of people with COVID-19 require oxygen therapy. Oxygen has been listed on the WHO Model List of Essential Medicines List and Essential Medicines List for Children for almost two decades. The COVID-19 pandemic has highlighted, more than ever, the acute need for scale-up of oxygen therapy. Detailed data on the use of oxygen therapy in low-and-middle income countries at the patient and facility level are needed to target interventions better globally.Methods and analysis We aim to describe the requirements and use of oxygen at the facility and patient level of approximately 4500 patients with COVID-19 in 30 countries. Our objectives are specifically to characterise type and duration of different modalities of oxygen therapy delivered to patients; describe demographics and outcomes of hospitalised patients with COVID-19; and describe facility-level oxygen production and support. Primary analyses will be descriptive in nature. Respiratory support transitions will be described in Sankey plots, and Kaplan-Meier models will be used to estimate probability of each transition. A multistate model will be used to study the course of hospital stay of the study population, evaluating transitions of escalating respiratory support transitions to the absorbing states.Ethics and dissemination WHO Ad Hoc COVID-19 Research Ethics Review Committee (ERC) has approved this global protocol. When this protocol is adopted at specific country sites, national ERCs may make require adjustments in accordance with their respective national research ethics guidelines. Dissemination of this protocol and global findings will be open access through peer-reviewed scientific journals, study website, press and online media.Trial registration number NCT04918875.

Introduction: Olfactory changes are quite common in the population, causing a significant impact on the quality of life. Documentation of the olfactory function is essential for the diagnosis, treatment and follow-up of patients with inflammatory diseases of the upper airways, neurodegenerative diseases or viral infections. Among the different existing smell tests, the CCCRC is an inexpensive test, easy to apply, but it has not yet been evaluated on a large scale in the Brazilian population. Objective: To validate the CCCRC smell test, after adaptation for the Brazilian population, evaluating the performance of healthy volunteers and the stability of the test in retests. Methods: In this study, we carried out a cultural adaptation of the CCCRC test to Brazil. To validate and determine the normality scores, we applied the test to 334 healthy volunteers, aged >18 years of age. The retest was also carried out in up to four weeks on 34 additional volunteers to assess validity of the results. Results: When evaluating the participants’ performance, normosmia and mild hyposmia values were obtained in more than 95% of them. Women (58.4%) showed better accuracy than men (41.6%): p

Visceral adiposity is a risk factor for severe COVID-19, and infection of adipose tissue by SARS-CoV-2 has been reported. Here the authors confirm that human adipose tissue is a possible site for SARS-CoV-2 infection, but the degree of adipose tissue infection and the way adipocytes respond to the virus depend on the adipose tissue depot and the viral strain.

Abstract Background The release of neutrophil extracellular traps (NETs) is associated with inflammation, coagulopathy, and organ damage found in severe cases of COVID-19. However, the molecular mechanisms underlying the release of NETs in COVID-19 remain unclear. Objectives We aim to investigate the role of the Gasdermin-D (GSDMD) pathway on NETs release and the development of organ damage during COVID-19. Methods We performed a single-cell transcriptome analysis in public data of bronchoalveolar lavage. Then, we enrolled 63 hospitalized patients with moderate and severe COVID-19. We analyze in blood and lung tissue samples the expression of GSDMD, presence of NETs, and signaling pathways upstreaming. Furthermore, we analyzed the treatment with disulfiram in a mouse model of SARS-CoV-2 infection. Results We found that the SARS-CoV-2 virus directly activates the pore-forming protein GSDMD that triggers NET production and organ damage in COVID-19. Single-cell transcriptome analysis revealed that the expression of GSDMD and inflammasome-related genes were increased in COVID-19 patients. High expression of active GSDMD associated with NETs structures was found in the lung tissue of COVID-19 patients. Furthermore, we showed that activation of GSDMD in neutrophils requires active caspase1/4 and live SARS-CoV-2, which infects neutrophils. In a mouse model of SARS-CoV-2 infection, the treatment with disulfiram inhibited NETs release and reduced organ damage. Conclusion These results demonstrated that GSDMD-dependent NETosis plays a critical role in COVID-19 immunopathology and suggests GSDMD as a novel potential target for improving the COVID-19 therapeutic strategy.

ABSTRACT Objective: COVID-19 has been associated with a significant burden to those who survive the acute phase. We aimed to describe the quality of life and symptoms of anxiety, depression, and posttraumatic stress disorder (PTSD) at 90 days after hospital discharge of COVID-19 patients. Methods: Patients with COVID-19 admitted to a private hospital in the city of São Paulo, Brazil, between April of 2020 and April of 2021 were interviewed by telephone at 30 and 90 days after discharge to assess the quality of life and symptoms of depression, anxiety, and PTSD. Results: A total of 2,138 patients were included. The mean age was 58.6 ± 15.8 years, and the median length of hospital stay was 9.0 (5.0-15.8) days. Between the two time points, depression increased from 3.1% to 7.2% (p < 0.001), anxiety increased from 3.2% to 6.2% (p < 0.001), and PTSD increased from 2.3% to 5.0% (p < 0.001). At least one physical symptom related to COVID-19 diagnosis persisted in 32% of patients at day 90. Conclusions: Persistence of physical symptoms was high even at 90 days after discharge. Although the prevalence of symptoms of anxiety, depression, and PTSD was low, these symptoms persisted for three months, with a significant increase between the time points. This finding indicates the need to identify at-risk patients so that they can be given an appropriate referral at discharge.