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Renata Galetti,1 Rafael Antonio Casarin Penha Filho,2 Joseane Cristina Ferreira,1 Alessandro M Varani,2 Ana Lúcia Costa Darini11Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil; 2Faculdade de Ciências Agrárias e Veterinárias, Universidade Estadual Paulista “Júlio de Mesquita Filho” (UNESP), Jaboticabal, BrazilAbstract: We describe the mobilome of Escherichia fergusonii 40A isolated from poultry, consisting of four different plasmids, p46_40A (IncX1, 45,869 bp), p80_40A (non-typable, 79,635 bp), p150_40A (IncI1-ST1, 148,340 bp) and p280_40A (IncHI2A-ST2, 279,537 bp). The mobilome-40A carries a blend of several different resistance and virulence genes, heavy metal tolerance operons and conjugation system. This mobilome 40A is a perfect tool to preserve and disseminate antimicrobial resistance and makes the bacterial isolate incredibly adapted to survive under constant antimicrobial pressure.Keywords: plasmids, antibiotic resistance, heavy metal tolerance, poultry

Background: Noninvasive positive-pressure ventilation (NPPV) modes are currently available on bilevel and ICU ventilators. However, little data comparing the performance of the NPPV modes on these ventilators are available.Methods: In an experimental bench study, the ability of nine ICU ventilators to function in the presence of leaks was compared with a bilevel ventilator using the IngMar ASL5000 lung simulator (IngMar Medical; Pittsburgh, PA) set at a compliance of 60 mL/cm H(2)O, an inspiratory resistance of 10 cm H(2)O/L/s, an expiratory resistance of 20 cm H(2)O/ L/s, and a respiratory rate of 15 breaths/min. All of the ventilators were set at 12 cm H(2)O pressure support and 5 cm H(2)O positive end-expiratory pressure. The data were collected at baseline and at three customized leaks.Main Results: At baseline, all of the ventilators were able to deliver adequate tidal volumes, to maintain airway pressure, and to synchronize with the simulator, without missed efforts or auto-triggering. As the leak was increased, all of the ventilators (except the Vision [Respironics; Murrysville, PA] and Servo I [Maquet; Solna, Sweden]) needed adjustment of sensitivity or cycling criteria to maintain adequate ventilation, and some transitioned to backup ventilation. Significant differences in triggering and cycling were observed between the Servo I and the Vision ventilators.Conclusions: The Vision and Servo I were the only ventilators that required no adjustments as they adapted to increasing leaks. There were differences in performance between these two ventilators, although the clinical significance of these differences is unclear. Clinicians should be aware that in the presence of leaks, most ICU ventilators require adjustments to maintain an adequate tidal volume. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Comparison of contingent, step-wise and integrated screening policies. METHODS: Mid-trimester Down syndrome risks were retrospectively calculated from FaSTER trial data. For contingent screening, initial risk was calculated from ultrasound measurement of nuchal translucency (NT), maternal serum pregnancy-associated plasma protein (PAPP)-A and free beta-human chorionic gonadotrophin (hCG) at 11-13 weeks, and classified positive (>1 in 30), borderline (1 in 30-1500) or negative. Borderline risks were recalculated using alpha-fetoprotein, hCG, unconjugated estriol (uE3) and inhibin at 15-18 weeks, and reclassified as positive (>1 in 270) or negative. For step-wise screening, initial negative risks were also recalculated. For integrated screening, a single risk was calculated from NT, PAPP-A and the second trimester markers. RESULTS: There were 86 Down syndrome and 32,269 unaffected pregancies. The detection rate for contingent screening was 91% and false-positive rate was 4.5%; initial detection rate was 60%, initial false-positive rate was 1.2% and borderline risk was 23%. Step-wise screening had 92% detection rate and 5.1% false-positive rate; integrated screening had 88% and 4.9% respectively. CONCLUSION: As predicted by modelling, the contingent screening detection rate for a fixed false-positive rate is comparable with step-wise and integrated screening, but substantially reduces the number needing to return for second trimester testing. [ABSTRACT FROM AUTHOR]

Vinasse, a dark-colored aqueous byproduct of bioethanol production, contains a variety of organic compounds and inorganic salt ions. In this study, the photoreforming of vinasse was investigated using Pt/TiO 2 as a catalyst under UV irradiation. The gaseous products generated were analyzed, revealing the formation of hydrogen (H 2 ) along with other gases, including CO 2 , CH 4 , CO, C 2 H 6 , C 2 H 4 , C 3 H 8 , and C 4 H 10 . When using filtered vinasse, H 2 and other gaseous products were produced solely through photolysis, even in the presence of the Pt/TiO 2 photocatalyst. Notably, photocatalytic H 2 production was observed when inorganic salt ions were removed from the vinasse, and a lower concentration of vinasse was employed in the reaction medium., Competing Interests: The authors declare that no competing financial interests or personal relationships influenced the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Background: Serratia marcescens, an opportunistic nosocomial Gram-negative bacterium pathogen, has emerged as an important cause of healthcare-associated infections owing to its acquisition of antimicrobial resistance genes (ARGs) and virulence factor determinants., Methods: Four carbapenem-resistant S. marcescens strains were recovered from patients admitted to different hospitals in 2017 and 2018. We assessed the antimicrobial resistance and virulence context, as well as the genetic similarities of four Brazilian S. marcescens strains, and compared the genomes of these S. marcescens isolates with whole genome data of 428 S. marcescens strains available in the NCBI Reference Sequence. Antimicrobial susceptibility testing was performed by disk diffusion and broth microdilution methods according to CLSI recommendations. Whole genome sequencing was performed using Illumina NextSeq 250-bp paired-end sequencing for two isolates, Sm424 and Sm613, which presented representative phenotypes., Results: The pathogenicity of both sequenced strains was predicted using the Pathogen Finder tool. Both isolates carried efflux system genes (RND, SMR, MFS, ABC-family) and resistance genes (bla STR-2 , aac(6')-Ic, fos). Virulence factor genes involved in motility, regulation, capsule formation, acid resistance, and acriflavine resistance were also found. The Pathogen Finder tool predicted a >71% probability of being a human pathogen for Sm424 and Sm613., Conclusion: S. marcescens has shown increased adaptive, resistance, and pathogenic potential, being responsible for different nosocomial infections., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2025. Published by Elsevier Ltd.)

Antimicrobial resistance is a major healthcare problem and a concern for global public health. In this current scenario, the use of non-antibiotic antimicrobials, such as heavy metals and biocides, has increased aiming to control the spread of antibiotic-resistant bacteria. Consequently, heavy metal tolerance genes (HMTG) and biocides tolerance genes (BTG) have been more frequently detected in Gram-negative bacilli. In this study, we searched for acquired HMTG, BTG and acquired antibiotic-resistance genes (ARG) and determined the minimum inhibitory concentration (MIC) of common heavy metals and biocides in multidrug-resistant and susceptible Gram-negative bacilli clinical isolates. High frequency of silA and pcoD genes was detected mainly among Klebsiella spp. and E. cloacae, regardless of their susceptible profile. merA gene was also found in isolates carrying silA-pcoD genes. ARG were detected in isolates that harbor silA and/or pcoD genes. BTG (qacΔE, ydgE, ydgF, mdfA, and emrE) were detected mostly in K. pneumoniae and E. cloacae isolates, regardless of their susceptible profile, and these isolates often co-harbored HMTG and/or ARG. Higher CuSO 4 MIC values were obtained in aerobic conditions, regardless of the presence or absence of pcoD and/or silA genes. Nevertheless, in most isolates carrying pcoD/silA, higher CuSO 4 MIC values were determined under anaerobic conditions. Regarding AgNO 3 , no significant differences in MIC values were observed for isolates with or without silA gene. Our results show a broad distribution of HMTG, BTG, and ARG in bacteria causing healthcare-associated infections, and this can contribute to the co-selection of hospital pathogens multiresistant to multiple and diverse antimicrobials., Competing Interests: Declaration of competing interes The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Ltd.)

Background: Mechanical ventilation (MV) skills are crucial for clinicians who care for critically ill patients; however, few training programs incorporate structured curricula and appropriate assessments. The use of virtual simulators for teaching and assessments has not been evaluated and can offer advantages. Objective: To create an MV competency-based course for internal medicine residents using a virtual simulator and to evaluate course impact. Methods: We developed an online, 8 month, competency-based MV course for internal medicine residents, including virtual simulation. Each module included a 1-hour session (20 min of lecture, 40 min of virtual simulation) and self-directed learning material. Engagement was reinforced through live meetings, an online platform, and group chats. To evaluate competency, we adapted a validated simulation-based assessment to a virtual MV simulator (virtual simulation-based assessment [SBA]). Course impact was evaluated using the four-level Kirkpatrick model, including surveys for satisfaction and confidence (level 1), knowledge assessment with a multiple-choice examination (level 2), and deliberate practice with the simulator and clinical competence on the virtual SBA (level 3). Results: Eighty-one residents out of 103 completed the course and rated it as effective, with a net promoter score of 9.2. The use of virtual simulation was rated as very useful by most participants. Confidence in caring for patients under MV in different scenarios before and after the course significantly increased. On a 10-point scale, the multiple-choice examination score increased 1.19 points (95% confidence interval, 0.91-1.47; P  < 0.001) from baseline to the end of the course, and the virtual SBA score at the end of the course was 6.15 ± 1.26 for post-graduate year 1 residents and 6.48 ± 1.56 for post-graduate year 2 residents ( P  = 0.33). Performance on different competencies varied, with lower scores on tasks such as asynchrony correction. Ninety-nine percent of residents reported a very positive (58%) or positive (41%) impact of the course in their practice. Conclusion: We developed a satisfactory and effective MV course including virtual simulation for internal medicine residents during the COVID-19 pandemic. Confidence and knowledge increased by the end of the course, although performance on complex MV skills was suboptimal. The use of virtual simulators for teaching and assessment are valuable new tools for teaching MV.

Perioperative risk assessment helps inform clinical practice for older people with hip fractures. This is a cohort study, where perioperative risk screening, including NHFS, was performed at admission, followed by an evaluation of 30-day outcomes. 503 patients were included, 73% female, 79.4 ± 9.3 years old; 58% presented extracapsular and 42% intracapsular fractures, with a 30-day mortality of 9%. The NHFS was higher in the patients who died at 5.6 ± 1.1 compared to survivals at 4.3 ± 1.5 (p-value < 0.001). NHFS > 4 was associated with 30-day mortality observed by Cox regression adjusted by fracture type: HR 4.55 (95% CI 2.10-9.82) (p-value < 0.001) and Kaplan-Meyer Curve (HR 3.94; 95% CI 2.19-7.07; p-value < 0.001). ROC curve showed the accuracy of NHFS in explaining 30-day mortality (AUC 0.74; 95% CI 0.67-0.81). Complications were higher among patients with NHFS > 4. The performance of NHFS was better than the traditional perioperative risk ASA score. Therefore, NHFS can be implemented in real-world clinical practice to estimate the 30-day mortality risk for hip fracture in older patients in Brazil. NHFS > 4 is critical for 30-day mortality and complications; this cutoff helps inform clinical practice. The present study might motivate other centers to consider NHFS in their perioperative risk assessment routine., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Mechanical ventilation can be a life-saving intervention, but its implementation requires a multidisciplinary approach, with an understanding of its indications and contraindications due to the potential for complications. The management of mechanical ventilation should be part of the curricula during clinical training; however, trainees and practicing professionals frequently report low confidence in managing mechanical ventilation, often seeking additional sources of knowledge. Review articles, consensus statements and clinical practice guidelines have become important sources of guidance in mechanical ventilation, and although clinical practice guidelines offer rigorously developed recommendations, they take a long time to develop and can address only a limited number of clinical questions. The Associação de Medicina Intensiva Brasileira and the Sociedade Brasileira de Pneumologia e Tisiologia sponsored the development of a joint statement addressing all aspects of mechanical ventilation, which was divided into 38 topics. Seventy-five experts from all regions of Brazil worked in pairs to perform scoping reviews, searching for publications on their specific topic of mechanical ventilation in the last 20 years in the highest impact factor journals in the areas of intensive care, pulmonology, and anesthesiology. Each pair produced suggestions and considerations on their topics, which were presented to the entire group in a plenary session for modification when necessary and approval. The result was a comprehensive document encompassing all aspects of mechanical ventilation to provide guidance at the bedside. In this article, we report the methodology used to produce the document and highlight the most important suggestions and considerations of the document, which has been made available to the public in Portuguese.

The increasing digitalisation of healthcare has created a pressing need for health professionals to develop robust digital skills. This paper explores the imperative of equipping health professionals with the necessary digital proficiency to enhance their daily workflows and improve patient care. The expanding use of digital technologies, including electronic health records, telehealth, and artificial intelligence, has transformed the healthcare landscape. However, the adoption of these technologies has been hindered by barriers, such as a lack of interoperability and hesitancy among healthcare providers. To address these challenges, this paper argues that digital skill development must be a core component of healthcare education and professional training. Medical schools and healthcare organisations must prioritise the integration of digital health curricula and continuous learning opportunities to ensure that the next generation of healthcare providers is well-equipped to navigate the digital healthcare ecosystem. Additionally, this paper highlights the importance of fostering a culture of digital innovation and collaboration within healthcare settings. By empowering health professionals to actively participate in the development and testing of new digital health applications, the industry can unlock the full potential of digital technologies to enhance daily workflows and improve patient outcomes.

Purpose: Tolerance and persistence occur "silently" in bacteria categorized as susceptible by antimicrobial susceptibility testing in clinical microbiology laboratories. They are different from resistance phenomena, not well-studied, and often remain unnoticeable. We aimed to investigate and characterize ceftazidime-avibactam (CZA) tolerance/persistence in 80 Klebsiella pneumoniae isolates from bloodstream infections., Methods: We used the Tolerance Disk Test (TDtest) to detect CZA tolerance/persistence and investigate the avibactam (AVI) influence on them, and time-kill assays with minimal duration for killing (MDK) determination to characterize/differentiate CZA tolerance from persistence, for selected isolates. Whole genome sequencing was performed for 49/80 selected isolates to investigate genes related to beta-lactam tolerance/persistence and resistance as well as phylogeny studies., Results: Tolerance/persistence to CZA was detected in 48/80 (60%) isolates, all extensively drug-resistant (XDR) or multidrug-resistant, carbapenem-resistant K. pneumoniae (CRKp), KPC producers, and previously categorized as susceptible (not resistant) to CZA. No heteroresistance was detected. CZA tolerance/persistence occurred due to ceftazidime tolerance/persistence and was not related to AVI in the CZA combination. 5/11 isolates were characterized as CZA-tolerant and 5/11 as CZA-persistent. The single (1/11) XDR and CRKp non-KPC producer was truly susceptible. All the CZA-tolerant/persistent isolates (ST11, ST258, ST340, ST437, ST16, ST17, and ST307) harbored the carbapenemase-encoding gene bla KPC-2 . Mutation in only two genes (rpoS and degQ) related to beta-lactam tolerance/persistence was found in only 7/49 CZA-tolerant/persistent isolates, suggesting the presence of yet unknown beta-lactam tolerance/persistence genes., Conclusion: Among the K. pneumoniae bloodstream isolates studied, 60%, previously categorized as susceptible to CZA, were, actually, tolerant/persistent to this antibiotic, all these KPC producers., Competing Interests: Declarations. Ethical approval: This study was approved by the Ethics Committee of the Ribeirao Preto School of Pharmaceutical Sciences– University of São Paulo (CAAE: 57488422.0.0000.5403– Protocol CEP/FCFRP nº 5.443.849) and by the Ethics Committee of the University Hospital, Ribeirão Preto Medical School– University of São Paulo (CAAE: 57488422.0.3001.5440– Protocol CEP/HCFMRP n° 5.462.049). Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Epidemiology, ventilator management, and outcomes in patients with acute respiratory distress syndrome (ARDS) because of coronavirus disease 2019 (COVID-19) have been described extensively but have never been compared between countries. We performed an individual patient data analysis of four observational studies to compare epidemiology, ventilator management, and outcomes. We used propensity score weighting to control for confounding factors. The analysis included 6,702 patients: 1,500 from Argentina, 844 from Brazil, 975 from the Netherlands, and 3,383 from Spain. There were substantial differences in baseline characteristics between countries. There were small differences in ventilation management. Intensive care unit mortality was higher in Argentina and Brazil compared with the Netherlands and Spain (59.6% and 56.6% versus 32.1% and 34.7%; P <0.001). The median number of days free from ventilation and alive at day 28 was equally low (0 [0-7], 0 [0-18], 1 [0-16], and 0 [0-16] days, respectively; P = 0.03), and the median number of days free from ventilation and alive at day 60 was higher in the Netherlands and Spain (0 [0-37], 0 [0-50], 33 [0-48], and 26 [0-48] days, respectively; P <0.001). Propensity score matching confirmed the outcome differences. Thus, the outcome of COVID-19 ARDS patients in Argentina and Brazil was substantially worse compared with that of patients in the Netherlands and Spain. It is unlikely that this results from differences in case mix or ventilation management.

Objective: To evaluate the available evidence comparing the use of the bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) regimen for 6 months with that of standard-of-care regimens for patients with multidrug-resistant or rifampin-resistant tuberculosis (MDR/RR-TB)., Methods: This was a systematic review of clinical trials comparing the use of the BPaLM regimen with the standard of care in patients with MDR/RR-TB. The main outcome measure was an unfavorable endpoint (a composite of death, treatment failure, treatment discontinuation, loss to follow-up, and recurrence), and secondary outcome measures included adverse events and serious adverse events. We searched the MEDLINE, EMBASE, Google Scholar, LILACS, and ClinicalTrials.gov databases, from their inception to January 31, 2024, with no limitation as to language or year of publication. The risk of bias was assessed by using the Cochrane risk-of-bias tool, and the quality of evidence was based on the Grading of Recommendations Assessment, Development and Evaluation approach., Results: A total of 3,668 studies were retrieved; only one (a randomized clinical trial) met the inclusion criteria and was included. In patients with MDR/RR-TB, treatment with the BPaLM regimen, when compared with the standard of care, reduced the risk of an unfavorable outcome (composite, number needed to treat [NNT] = 7); early treatment discontinuation (NNT = 8); adverse events and discontinuation (NNT = 12); and serious adverse events (NNT = 5)., Conclusions: This systematic review of the use of BPaLM in patients with MDR/RR-TB, although it included only one study, showed that BPaLM is more effective than is the standard of care and has a better safety profile. That has major implications for guidelines on the treatment of MDR/RR-TB.

Importance: High-flow nasal oxygen (HFNO) and noninvasive ventilation (NIV) are commonly used respiratory support therapies for patients with acute respiratory failure (ARF)., Objective: To assess whether HFNO is noninferior to NIV on the rates of endotracheal intubation or death at 7 days in 5 patient groups with ARF., Design, Setting, and Participants: This noninferiority, randomized clinical trial enrolled hospitalized adults (aged ≥18 years; classified as 5 patient groups with ARF: nonimmunocompromised with hypoxemia, immunocompromised with hypoxemia, chronic obstructive pulmonary disease [COPD] exacerbation with respiratory acidosis, acute cardiogenic pulmonary edema [ACPE], or hypoxemic COVID-19, which was added as a separate group on June 26, 2023) at 33 hospitals in Brazil between November 2019 and November 2023 (final follow-up: April 26, 2024)., Interventions: High-flow nasal oxygen (n = 883) or NIV (n = 883)., Main Outcomes and Measures: The primary outcome was endotracheal intubation or death within 7 days assessed using a bayesian hierarchical model with dynamic borrowing across patient groups. Noninferiority was defined by a posterior probability of 0.992 or greater for an odds ratio (OR) less than 1.55., Results: Among 1800 patients, 1766 completed the study (mean age, 64 [SD, 17] years; 707 [40%] were women). The primary outcome of endotracheal intubation or death at 7 days occurred in 39% (344/883) in the HFNO group vs 38% (336/883) in the NIV group. In the immunocompromised with hypoxemia patient group, the primary outcome occurred in 57.1% (16/28) in the HFNO group vs 36.4% (8/22) in the NIV group; enrollment was stopped for futility (final OR, 1.07; 95% credible interval [CrI], 0.81-1.39; noninferiority posterior probability [NPP], 0.989). In the nonimmunocompromised with hypoxemia group, the primary outcome occurred in 32.5% (81/249) in the HFNO group vs 33.1% (78/236) in the NIV group (OR, 1.02 [95% CrI, 0.81-1.26]; NPP, 0.999). In the ACPE group, the primary outcome occurred in 10.3% (14/136) in the HFNO group vs 21.3% (29/136) in the NIV group (OR, 0.97 [95% CrI, 0.73-1.23]; NPP, 0.997). In the hypoxemic COVID-19 group, the primary outcome occurred in 51.3% (223/435) in the HFNO group vs 47.0% (210/447) in the NIV group (OR, 1.13 [95% CrI, 0.94-1.38]; NPP, 0.997). In the COPD exacerbation with respiratory acidosis group, the primary outcome occurred in 28.6% (10/35) in the HFNO group vs 26.2% (11/42) in the NIV group (OR, 1.05 [95% CrI, 0.79-1.36]; NPP, 0.992). However, a post hoc analysis without dynamic borrowing across the 5 ARF patient groups revealed some qualitatively different results in patients with COPD, immunocompromised patients, and patients with ACPE. The incidence of serious adverse events was similar (9.4% of patients in HFNO group vs 9.9% in NIV group)., Conclusions and Relevance: Compared with NIV, HFNO met prespecified criteria for noninferiority for the primary outcome of endotracheal intubation or death within 7 days in 4 of the 5 patient groups with ARF. However, the small sample sizes in some patient groups and the sensitivity of the findings to the choice of analysis model suggests the need for further study in patients with COPD, immunocompromised patients, and patients with ACPE., Trial Registration: ClinicalTrials.gov Identifier: NCT03643939.

The natural products 7-hydroxycoumarin (7HC) and 7-hydroxy-4-methylcoumarin (7H4MC), known as umbelliferone and hymecromone, respectively, are one of the simplest structural examples from coumarin's family, showing several biological activities. Bovine serum albumin (BSA) is the main model protein used in laboratory experiments to characterize the biophysical capacity of potential drugs to be carried until the target in the bloodstream. Thus, the interaction BSA:7HC and BSA:7H4MC was biophysically characterized by circular dichroism (CD), steady-state, and time-resolved fluorescence techniques combined with molecular docking calculations via cross-docking approach to better correlate with the biological medium. There is a ground-state association BSA:7HC/7H4MC, and the presence of the methyl group in the coumarin core did not change the binding affinity and trend to BSA significantly. However, comparing the obtained data with those reported to benzo-α-pyrone there is evidence that the incorporation of the hydroxyl group in the aromatic ring A of the coumarin core improves the binding affinity to albumin around 10-folds and changes the binding site from subdomain IIA to IIIA or IB. In addition, the presence of other drugs, e.g., naproxen or ketoprofen, might interfere with the binding capacity of 7HC and 7H4MC, resulting in perturbations on the residence time of some clinically used drugs in the bloodstream., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Lapachol (LAP), a natural 1,4-naphthoquinone used in popular medicine in South America, is an antioxidant and antimicrobial compound in teas and infusions and used as a food additive; however, its interactive profile with the main protein carrier of compounds in the human bloodstream (human serum albumin, HSA) was not still characterized. Additionally, the impact of LAP in binding clinically drugs to albumin is still unknown. Thus, the present work describes the interaction HSA:LAP using different biophysical techniques, i.e., 1 H saturation-transfer difference nuclear magnetic resonance ( 1 H STD-NMR), isothermal titration calorimetry (ITC), steady-state and time-resolved fluorescence measurements combined with molecular docking calculations. LAP interacts with subdomain region IIA (site I), mainly driven by enthalpy effects, while subdomain region IB (site III) was identified as the second binding site, mainly driven by entropy effects. The binding is spontaneous, strong (binding constant average, K average ≈ 4.45 × 10 5  M -1 ), and there is a positive cooperativity in the presence of ibuprofen, with the LAP structure fully buried into the protein cavities. Overall, LAP might impact the residence time (pharmacokinetic profile) of drugs that bind to subdomains regions IIA and IB of albumin, e.g., warfarin, phenylbutazone, diflunisal, naproxen, camptothecin, doxorubicin, daunorubicin, suramin, and tyrosine kinase inhibitors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Competing Interests: Competing interests: The authors declare no competing interests.

Background: This study aimed to assess whether a driving pressure-limiting strategy based on positive end-expiratory pressure (PEEP) titration according to best respiratory system compliance and tidal volume adjustment increases the number of ventilator-free days within 28 days in patients with moderate to severe acute respiratory distress syndrome (ARDS)., Methods: This is a multi-centre, randomised trial, enrolling adults with moderate to severe ARDS secondary to community-acquired pneumonia. Patients were randomised to a driving pressure-limiting strategy or low PEEP strategy based on a PEEP:FiO 2 table. All patients received volume assist-control mode until day 3 or when considered ready for spontaneous modes of ventilation. The primary outcome was ventilator-free days within 28 days. Secondary outcomes were in-hospital and intensive care unit mortality at 90 days., Results: The trial was stopped because of recruitment fatigue after 214 patients were randomised. In total, 198 patients (n=96 intervention group, n=102 control group) were available for analysis (median age 63 yr, [interquartile range 47-73 yr]; 36% were women). The mean difference in driving pressure up to day 3 between the intervention and control groups was -0.7 cm H 2 O (95% confidence interval -1.4 to -0.1 cm H 2 O). Mean ventilator-free days were 6 (sd 9) in the driving pressure-limiting strategy group and 7 (9) in the control group (proportional odds ratio 0.72, 95% confidence interval 0.39-1.32; P=0.28). There were no significant differences regarding secondary outcomes., Conclusions: In patients with moderate to severe ARDS secondary to community-acquired pneumonia, a driving pressure-limiting strategy did not increase the number of ventilator-free days compared with a standard low PEEP strategy within 28 days., Clinical Trial Registration: NCT04972318., Competing Interests: Declaration of interest The authors declare that they have no conflicts of interest., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Coronaviruses such as SARS-CoV-2 encode a conserved papain-like protease (PLpro) that is crucial for viral replication and immune evasion, making it a prime target for antiviral drug development. In this study, three surface pockets on SARS-CoV-2 PLpro that may function as sites for allosteric inhibition were computationally identified. To evaluate the effects of these pockets on proteolytic activity, 52 residues were separately mutated to alanine. In Pocket 1, located between the Ubl and thumb domains, the introduction of alanine at T10, D12, T54, Y72, or Y83 reduced PLpro activity to <12% of that of WT. In Pocket 2, situated at the interface of the thumb, fingers, and palm domains, Q237A, S239A, H275A, and S278A inactivated PLpro. Finally, introducing alanine at five residues in Pocket 3, between the fingers and palm domains, inactivated PLpro: S212, Y213, Y251, K254, and Y305. Pocket 1 has a higher druggability score than Pockets 2 and 3. MD simulations showed that interactions within and between domains play critical roles in PLpro activity and thermal stability. The essential residues in Pockets 1 and 2 participate in a combination of intra- and inter-domain interactions. By contrast, the essential residues in Pocket three predominantly participate in inter-domain interactions. The most promising targets for therapeutic development are Pockets one and 3, which have the highest druggability score and the largest number of essential residues, respectively. Non-competitive inhibitors targeting these pockets may be antiviral agents against COVID-19 and related coronaviruses., Competing Interests: Conflict of interests The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Patient medical information often exists in unstructured text containing abbreviations and acronyms deemed essential to conserve time and space but posing challenges for automated interpretation. Leveraging the efficacy of Transformers in natural language processing, our objective was to use the knowledge acquired by a language model and continue its pre-training to develop an European Portuguese (PT-PT) healthcare-domain language model., Methods: After carrying out a filtering process, Albertina PT-PT 900M was selected as our base language model, and we continued its pre-training using more than 2.6 million electronic medical records from Portugal's largest public hospital. MediAlbertina 900M has been created through domain adaptation on this data using masked language modelling., Results: The comparison with our baseline was made through the usage of both perplexity, which decreased from about 20 to 1.6 values, and the fine-tuning and evaluation of information extraction models such as Named Entity Recognition and Assertion Status. MediAlbertina PT-PT outperformed Albertina PT-PT in both tasks by 4-6% on recall and f1-score., Conclusions: This study contributes with the first publicly available medical language model trained with PT-PT data. It underscores the efficacy of domain adaptation and offers a contribution to the scientific community in overcoming obstacles of non-English languages. With MediAlbertina, further steps can be taken to assist physicians, in creating decision support systems or building medical timelines in order to perform profiling, by fine-tuning MediAlbertina for PT- PT medical tasks., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Miguel Nunes reports financial support was provided by PRR. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The coronavirus disease-2019 (COVID-19) pandemic has affected different sectors of society, and healthcare workers have been particularly impacted. This study aimed to describe the clinical, epidemiological, and molecular characteristics of SARS-CoV-2 infections among healthcare workers in Evandro Chagas Institute, a research reference center in Brazil, from October 2020 to July 2022. 845 samples were collected from individuals who presented clinical symptoms of respiratory infection. Nasopharyngeal positive samples were submitted through genome sequencing. Clinical, epidemiological, and the SARS-CoV-2 lineages (or variants) were analyzed. SARS-CoV-2 positivity was detected in 31.8% (269/845) of samples with a higher prevalence of females (60.2%). The highest SARS-CoV-2 positivity rates were reported in March 2021 (39%), January 2022 (65%), and July 2022 (56%). On clinical symptoms, arthralgia, chills, and diarrhea were statistically significantly detected in 2020; fever, runny nose, and arthralgia in 2021; runny nose, and cough in 2022. On molecular analysis of SARS-CoV-2, 66 samples (25.3%, 66/269) were sequenced and the most prevalent lineage was the Omicron, representing 57.6%. Studies on the epidemiological and clinical characteristics of HCW are essential to propose control measures and work management since research centers play a major role in surveillance to identify and monitor infectious diseases., (© 2024. The Author(s).)

Background: In response to the intricate language, specialized terminology outside everyday life, and the frequent presence of abbreviations and acronyms inherent in health care text data, domain adaptation techniques have emerged as crucial to transformer-based models. This refinement in the knowledge of the language models (LMs) allows for a better understanding of the medical textual data, which results in an improvement in medical downstream tasks, such as information extraction (IE). We have identified a gap in the literature regarding health care LMs. Therefore, this study presents a scoping literature review investigating domain adaptation methods for transformers in health care, differentiating between English and non-English languages, focusing on Portuguese. Most specifically, we investigated the development of health care LMs, with the aim of comparing Portuguese with other more developed languages to guide the path of a non-English-language with fewer resources., Objective: This study aimed to research health care IE models, regardless of language, to understand the efficacy of transformers and what are the medical entities most commonly extracted., Methods: This scoping review was conducted using the PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) methodology on Scopus and Web of Science Core Collection databases. Only studies that mentioned the creation of health care LMs or health care IE models were included, while large language models (LLMs) were excluded. The latest were not included since we wanted to research LMs and not LLMs, which are architecturally different and have distinct purposes., Results: Our search query retrieved 137 studies, 60 of which met the inclusion criteria, and none of them were systematic literature reviews. English and Chinese are the languages with the most health care LMs developed. These languages already have disease-specific LMs, while others only have general-health care LMs. European Portuguese does not have any public health care LM and should take examples from other languages to develop, first, general-health care LMs and then, in an advanced phase, disease-specific LMs. Regarding IE models, transformers were the most commonly used method, and named entity recognition was the most popular topic, with only a few studies mentioning Assertion Status or addressing medical lexical problems. The most extracted entities were diagnosis, posology, and symptoms., Conclusions: The findings indicate that domain adaptation is beneficial, achieving better results in downstream tasks. Our analysis allowed us to understand that the use of transformers is more developed for the English and Chinese languages. European Portuguese lacks relevant studies and should draw examples from other non-English languages to develop these models and drive progress in AI. Health care professionals could benefit from highlighting medically relevant information and optimizing the reading of the textual data, or this information could be used to create patient medical timelines, allowing for profiling., (©Miguel Nunes, Joao Bone, Joao C Ferreira, Luis B Elvas. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 21.10.2024.)

Bacterial antibiotic resistance is a public health problem affecting humans and animals. This study focuses on identifying Gram-negative bacilli (GNB) (MALDI-TOF MS and Klebsiella MALDI TypeR) resistant to antimicrobials in freshly emitted feces of healthy captive and rescued wild birds from a zoo in Brazil. Birds from the zoo and rescued from sixteen different orders were investigated. Resistant bacteria from feces were selected (MacConkey agar with 2 μg/mL cefotaxime). Genomic similarity and plasmid were investigated by Pulsed-Field Gel Electrophoresis of XbaI fragments (XbaI-PFGE) and S1-PFGE. Polymerase Chain Reaction (PCR) was performed to search for beta-lactamase genes. From 80 birds included, 26 from the zoo (50 %) and 18 rescued wild birds (64 %) presented cefotaxime-resistant GNB. E. coli and Klebsiella spp were the most prevalent species. Among 65 isolates from the zoo and rescued wild birds, 75 % were considered multidrug-resistant (MDR). The majority of the isolates were extended-spectrum beta-lactamases (ESBL) producing and resistant to enrofloxacin. bla CTX-M-GROUP-1 , bla TEM , and bla SHV were the most detected genes, and bla KPC was detected in K. pneumoniae complex. According to genomic similarity results, some identical profiles were found in birds with no known contact among the zoo or rescued birds. Several isolates carried one to three plasmids (15-350 kb). The presence of multidrug-resistant (MDR) isolates from healthy captive and wild birds brings novel data on the dissemination of these elements to the environment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)