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Daniel FC Mazo,1 Marcelo G de Oliveira,2 Isabel VA Pereira,1 Bruno Cogliati,3 José T Stefano,1 Gabriela FP de Souza,2 Fabíola Rabelo,1 Fabiana R Lima,4 Venâncio A Ferreira Alves,4 Flair J Carrilho,1 Claudia PMS de Oliveira1 1University of São Paulo School of Medicine, Department of Gastroenterology, Clinical Division, Hepatology Branch (LIM-07), Sao Paulo, Brazil; 2Institute of Chemistry, University of Campinas, Campinas, Sao Paulo, Brazil; 3University of Sao Paulo School of Veterinary Medicine and Animal Science, Department of Pathology, Sao Paulo, Brazil; 4University of São Paulo School of Medicine, Department of Pathology (LIM14), São Paulo, Brazil Abstract: S-Nitroso-N-acetylcysteine (SNAC) is a water soluble primary S-nitrosothiol capable of transferring and releasing nitric oxide and inducing several biochemical activities, including modulation of hepatic stellate cell activation. In this study, we evaluated the antifibrotic activity of SNAC in an animal model of nonalcoholic steatohepatitis (NASH) induced in Sprague-Dawley rats fed with a choline-deficient, high trans fat diet and exposed to diethylnitrosamine for 8 weeks. The rats were divided into three groups: SNAC, which received oral SNAC solution daily; NASH, which received the vehicle; and control, which received standard diet and vehicle. Genes related to fibrosis (matrix metalloproteinases [MMP]-13, -9, and -2), transforming growth factor ß-1 [TGFß-1], collagen-1a, and tissue inhibitors of metalloproteinase [TIMP-1 and -2] and oxidative stress (heat-shock proteins [HSP]-60 and -90) were evaluated. SNAC led to a 34.4% reduction in the collagen occupied area associated with upregulation of MMP-13 and -9 and downregulation of HSP-60, TIMP-2, TGFß-1, and collagen-1α. These results indicate that oral SNAC administration may represent a potential antifibrotic treatment for NASH. Keywords: nitric oxide, S-nitroso-N-acetylcysteine, fibrogenesis, NASH, diethylnitrosamine

Angelino Julio Cariello,1 Paulo José Martins Bispo,2 Gabriela Freitas Pereira de Souza,3 Antonio Carlos Campos Pignatari,2 Marcelo Ganzarolli de Oliveira,3 Ana Luisa Hofling-Lima11Department of Ophthalmology, 2Division of Infectious Diseases, Federal University of São Paulo, 3Institute of Chemistry, University of Campinas, Campinas, São Paulo, BrazilBackground: The purpose of this study was to evaluate the antimicrobial activity of two nitric oxide donors, ie, S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylcysteine (SNAC), against clinical isolates from patients with infectious keratitis.Methods: Reference broth microdilution assays were performed to determine the minimum inhibitory and bactericidal concentrations for GSNO and SNAC against four American Type Culture Collection strains and 52 clinical isolates from patients with infectious keratitis as follows: 14 (26.9%) Pseudomonas species; 13 (25.0%) coagulase-negative Staphylococci; 10 (19.2%) Staphylococcus aureus; nine (17.3%) Serratia marcescens; and six (11.5%) Enterobacter aerogenes. Sterility control and bacterial growth control were also performed.Results: SNAC showed lower minimum inhibitory and bactericidal concentrations than GSNO for all clinical isolates from patients with infectious keratitis. For Gram-positive bacteria, mean minimum inhibitory and bactericidal concentrations were 2.1 ± 1.3 and 8.6 ± 3.8 mM for SNAC and 4.6 ± 3.2 and 21.5 ± 12.5 mM for GSNO (P < 0.01). For Gram-negative bacteria, mean minimum inhibitory and bactericidal concentrations were 3.3 ± 1.4 and 6.1 ± 3.4 mM for SNAC and 12.4 ± 5.4 and 26.5 ± 10.1 mM for GSNO (P < 0.01). The minimum bactericidal to inhibitory concentration ratio was ≤8 in 100% of all isolates tested for SNAC and in 94.2% tested for GSNO.Conclusions: SNAC and GSNO had effective inhibitory and bactericidal effects against bacterial isolates from keratitis. SNAC showed greater antimicrobial activity than GSNO against all bacteria. Gram-positive bacteria were more susceptible to the inhibitory and bactericidal effects of the S-nitrosothiols.Keywords: antimicrobial activity, S-nitroso-N-acetylcysteine, S-nitrosoglutathione, nitric oxide donors, infectious keratitis

Background: Oropouche virus is an arthropod-borne virus that has caused outbreaks of Oropouche fever in central and South America since the 1950s. This study investigates virological factors contributing to the re-emergence of Oropouche fever in Brazil between 2023 and 2024., Methods: In this observational epidemiological study, we combined multiple data sources for Oropouche virus infections in Brazil and conducted in-vitro and in-vivo characterisation. We collected serum samples obtained in Manaus City, Amazonas state, Brazil, from patients with acute febrile illnesses aged 18 years or older who tested negative for malaria and samples from people with previous Oropouche virus infection from Coari municipality, Amazonas state, Brazil. Basic clinical and demographic data were collected from the Brazilian Laboratory Environment Management System. We calculated the incidence of Oropouche fever cases with data from the Brazilian Ministry of Health and the 2022 Brazilian population census and conducted age-sex analyses. We used reverse transcription quantitative PCR to test for Oropouche virus RNA in samples and subsequently performed sequencing and phylogenetic analysis of viral isolates. We compared the phenotype of the 2023-24 epidemic isolate (AM0088) with the historical prototype strain BeAn19991 through assessment of titre, plaque number, and plaque size. We used a plaque reduction neutralisation test (PRNT 50 ) to assess the susceptibility of the novel isolate and BeAn19991 isolate to antibody neutralisation, both in serum samples from people previously infected with Oropouche virus and in blood collected from mice that were inoculated with either of the strains., Findings: 8639 (81·8%) of 10 557 laboratory-confirmed Oropouche fever cases from Jan 4, 2015, to Aug 10, 2024, occurred in 2024, which is 58·8 times the annual median of 147 cases (IQR 73-325). Oropouche virus infections were reported in all 27 federal units, with 8182 (77·5%) of 10 557 infections occurring in North Brazil. We detected Oropouche virus RNA in ten (11%) of 93 patients with acute febrile illness between Jan 1 and Feb 4, 2024, in Amazonas state. AM0088 had a significantly higher replication at 12 h and 24 h after infection in mammalian cells than the prototype strain. AM0088 had a more virulent phenotype than the prototype in mammalian cells, characterised by earlier plaque formation, between 27% and 65% increase in plaque number, and plaques between 2·4-times and 2·6-times larger. Furthermore, serum collected on May 2 and May 20, 2016, from individuals previously infected with Oropouche virus showed at least a 32-fold reduction in neutralising capacity (ie, median PRNT 50 titre of 640 [IQR 320-640] for BeAn19991 vs <20 [ie, below the limit of detection] for AM0088) against the reassortant strain compared with the prototype., Interpretation: These findings provide a comprehensive assessment of Oropouche fever in Brazil and contribute to an improved understanding of the 2023-24 Oropouche virus re-emergence. Our exploratory in-vitro data suggest that the increased incidence might be related to a higher replication efficiency of a new Oropouche virus reassortant for which previous immunity shows lower neutralising capacity., Funding: São Paulo Research Foundation, Burroughs Wellcome Fund, Wellcome Trust, US National Institutes of Health, and Brazilian National Council for Scientific and Technological Development., Translation: For the Portuguese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The variability in trophic position and carbon isotopic signatures can provide information about their dietary flexibility and its ability to adapt to changing environmental conditions. The impact of the invasive blue crab Callinectes sapidus was assessed by estimating its trophic position and isotopic niche using stable isotopes (δ 1 ³C, δ 1 ⁵N, δ³⁴S) across different invaded Atlantic coastal areas. This study, the first of its kind in the eastern Atlantic range, reveals the crab's omnivorous behavior with a wide trophic position (TP = 2-4), consistent with findings from its native range. Significant spatial variability in trophic roles was observed between habitats, with salt marshes showing enriched δ 1 ³C and lower TP due to differences in primary producers like Spartina detritus and phytoplankton. Estuaries exhibited higher and broader δ 1 ⁵N and TP ranges, influenced by prey availability and anthropogenic nitrogen inputs, that implies a significant impact on marine benthic and pelagic animal communities. Seasonal changes in the Guadalquivir estuary, linked to overwintering and brooding migrations, showed sexual differences in isotopic signatures, with males more enriched in δ 1 ⁵N than females, indicating varied prey availability or metabolic differences. Overall, the Atlantic invaded range displayed broader and lower TP compared to the Mediterranean, underlining the blue crab's flexible and diverse trophic role across different habitats and trophic levels. The variability in trophic position and carbon isotopic signatures reflects the dietary flexibility of this invasive species and its potential effects on native fauna. These findings emphasize the need to consider trophic interactions in ecosystem management and conservation efforts., 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 © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Amphotericin B (AmB) is a commonly utilized antifungal agent, which is also recommended for the treatment of certain neglected tropical diseases, including leishmaniasis. However, its clinical application is constrained because of its poor oral bioavailability and adverse effects, prompting the investigation of alternative drug delivery systems. Polymeric nanoparticles (PNPs) have gained attention as a potential drug delivery vehicle, providing advantages such as sustained release and enhanced bioavailability, and could have potential as AmB carriers. However, concerns persist regarding nanomaterials' toxicity, requiring more studies. Zebrafish ( Danio rerio ) embryos were used as a valuable model for toxicity testing, especially because of their genetic similarity to humans and standardized developmental assessments. Methods: In this study, we produced and characterized AmB loaded and non-loaded PNPs by nanoprecipitation, dynamic light scattering, transmission electron microscopy, atomic force microscopy and spectroscopy. Afterwards, we verified their toxicity through in vitro MTT assays in three cell lines (HEK293, HepG2, and J774 A1) and in vivo tests with zebrafish embryos. Results: In both trials, it was noted that nanoencapsulation of the drug led to increased toxicity when compared to non-encapsulated AmB, possibly indicating that they penetrated the embryo's chorion. Nevertheless, it was demonstrated that the polymers used are safe and they are not the cause of toxicity, neither are the nanostructures per se. Conclusions: Therefore, it is believed that the objective of improving the bioavailability of AmB may have been achieved, and the observed toxicity was probably linked to AmB's ability to destabilize cell membranes.

Immunosensors based on electrical impedance spectroscopy allow for label-free, real-time detection of biologically relevant molecules and pathogens, without requiring electro-active materials. Here, we investigate the influence of bare gold nanoparticles (AuNPs), synthesized via laser ablation in solution, on the performance of an impedimetric immunosensor for detecting severe acute respiratory syndrome coronavirus (SARS-CoV-2). Graphene acetic acid (GAA) was used in the active layer for immobilizing anti-SARS-CoV-2 antibodies, owing to its high density of carboxylic groups. Immunosensors incorporating AuNPs exhibited superior performance compared to those relying solely on GAA, achieving a limit of detection (LoD) of 3 x 10 -20  g/mL to detect the Spike Receptor Binding Domain (RBD) protein of SARS-CoV-2 and of 2 PFU/mL for inactivated virus. Moreover, these immunosensors presented high selectivity against the H1N1 influenza virus. We anticipate that this platform will be versatile and applicable in the early diagnosis of various diseases and viral infections, thereby facilitating Point-of-Care testing., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Osvaldo Novais de Oliveira Jr. reports financial support was provided by Coordination of Higher Education Personnel Improvement (CAPES). Osvaldo Novais de Oliveira Jr. reports financial support was provided by National Council for Scientific and Technological Development (CNPq). Osvaldo Novais de Oliveira Jr. reports financial support was provided by State of Sao Paulo Research Foundation (FAPESP). Rafael Cintra Hensel reports financial support was provided by State of Sao Paulo Research Foundation. Stefano Casalini reports financial support was provided by Nanochemistry for Energy and Health. Stefano Casalini reports financial support was provided by Nexus. Stefano Casalini reports financial support was provided by Complessità Chimica C2. Stefano Casalini reports financial support was provided by Government of Italy Commission for the Selection of Excellence University Departments. 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. Published by Elsevier B.V.)

Bed regulation within Brazil's National Health System (SUS) plays a crucial role in managing care for patients in need of hospitalization. In Rio Grande do Norte, Brazil, the RegulaRN Leitos Gerais platform was the information system developed to register requests for bed regulation for COVID-19 cases. However, the platform was expanded to cover a range of diseases that require hospitalization. This study explored different machine learning models in the RegulaRN database, from October 2021 to January 2024, totaling 47,056 regulations. From the data obtained, 12 features were selected from the 24 available. After that, blank and inconclusive data were removed, as well as the outcomes that had values other than discharge and death, rendering a binary classification. Data was also correlated, balanced, and divided into training and test portions for application in machine learning models. The results showed better accuracy (87.77%) and recall (87.77%) for the XGBoost model, and higher precision (87.85%) and F1-Score (87.56%) for the Random Forest and Gradient Boosting models, respectively. As for Specificity (82.94%) and ROC-AUC (82.13%), the Multilayer Perceptron with SGD optimizer obtained the highest scores. The results evidenced which models could adequately assist medical regulators during the decision-making process for bed regulation, enabling even more effective regulation and, consequently, greater availability of beds and a decrease in waiting time for patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Barreto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Certain situations and contexts during early years of life and childhood can have a significant impact on the health of older individuals. Studies have demonstrated that adversities such as poverty, neglect, abuse, and exposure to chronic stress conditions during the early years of life are associated with a range of health problems in adulthood., Objective: To systematically identify the literature on the impact of circumstances and/or conditions in early life/childhood on the health of older adults., Materials and Methods: A systematic literature review guided by the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was conducted. The databases used were PUBMED, LILACS, Scielo, Embase, and Web of Science. Longitudinal studies published without language or publication date restrictions, related to the proposed theme, were included. Editorial letters, review protocols, reflective studies, literature reviews, and articles without available online abstracts or full texts were excluded. The quality assessment of the studies was conducted using tools and guidelines provided by the Joanna Briggs Institute. The database search conducted between May and August 2023 resulted in 8,224 articles found. After completing the steps of duplicate exclusion and reading titles and abstracts, 35 articles were selected for full reading, culminating in a final sample of 10 eligible articles for this review., Results: These studies highlighted various early-life circumstances, including socioeconomic status, exposure to adverse childhood experiences, and environmental factors, demonstrating significant associations with health outcomes in older adults. The findings collectively emphasize the critical role that early adversities play in influencing chronic diseases, mental health, and overall well-being in later life., Final Considerations: Understanding social determinants, early-life adversities, and socioeconomic factors is essential for promoting healthy and equitable aging, with effective interventions and public policies aimed at reducing inequalities and ensuring the well-being of the adults and older adults., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: To access to reproductive health information on the Internet helps patients understand their infertility journey and make decisions about their treatment. This study aimed to evaluate the quality of fertility clinic websites accredited by the Latin American Network for Assisted Reproduction (REDLARA) using the QUality Evaluation Scoring Tool (QUEST)., Methods: This observational, cross-sectional, and online study evaluated the clinic websites registered as accredited centers on the REDLARA website. The QUEST was used for the quality assessment of the websites. Data were collected from the available websites of all accredited fertility clinics between September 2023 and January 2024., Results: A total of 173 websites from fertility clinics accredited by REDLARA were evaluated, and 152 (87.8%) clinics had functioning websites. The majority of analyzed websites were from Brazilian fertility clinics (n=58; 38.1%), followed by Mexican (n=23; 15.1%) and Argentine (n=21; 13.8%). No indication of authorship or username was observed on most websites. Some form of support for the patient-physician relationship was reported by 86.8% of websites. The mean (standard deviation±SD) of the total score obtained by all fertility clinics was 12.73±4.7 (range: 1-26). Brazil had the highest total score (mean±SD=16.03±4.6), whereas Peru had the lowest (6.42±1.7). Statistical analysis revealed a difference in the quality of websites among Latin American countries., Conclusions: The health information disseminated by fertility clinic websites in Latin America is of poor quality. Therefore, REDLARA should implement rules for building good-quality websites.

This study provides a comprehensive analysis of the eco-physiological responses of the blue crab (Callinectes sapidus) to variations in salinity, shedding light on its adaptability and invasive success in aquatic environments. Gender-specific differences in osmoregulation and Electron Transport System (ETS) activity highlight the importance of considering sex-specific aspects when understanding the physiological responses of invasive species. Females exhibited increased ETS activity at lower salinities, potentially indicative of metabolic stress, while males displayed constant ETS activity across a range of salinities. Osmoregulatory capacity which depended on gender and salinity, was efficient within meso-polyhaline waters but decreased at higher salinities, particularly in males. These findings provide valuable understandings into how C. sapidus specimens in an invaded area responds to salinity changes, important for considerate its distribution through saline pathways during tidal cycle fluctuations. This study shows the importance of interdisciplinary research for effective management of invasive species and conservation of affected aquatic ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known conflicts of interest or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Oropouche virus (OROV; species Orthobunyavirus oropoucheense ) is an arthropod-borne virus that has caused outbreaks of Oropouche fever in Central and South America since the 1950s. This study investigates virological factors contributing to the reemergence of Oropouche fever in Brazil between 2023 and 2024., Methods: In this study, we combined OROV genomic, molecular, and serological data from Brazil from 1 January 2015 to 29 June 2024, along with in vitro and in vivo characterization. Molecular screening data included 93 patients with febrile illness between January 2023 and February 2024 from the Amazonas State. Genomic data comprised two genomic OROV sequences from patients. Serological data were obtained from neutralizing antibody tests comparing the prototype OROV strain BeAn 19991 and the 2024 epidemic strain. Epidemiological data included aggregated cases reported to the Brazilian Ministry of Health from 1 January 2014 to 29 June 2024., Findings: In 2024, autochthonous OROV infections were detected in previously non-endemic areas across all five Brazilian regions. Cases were reported in 19 of 27 federal units, with 83.2% (6,895 of 8,284) of infections in Northern Brazil and a nearly 200-fold increase in incidence compared to reported cases over the last decade. We detected OROV RNA in 10.8% (10 of 93) of patients with febrile illness between December 2023 and May 2024 in Amazonas. We demonstrate that the 2023-2024 epidemic was caused by a novel OROV reassortant that replicated approximately 100-fold higher titers in mammalian cells compared to the prototype strain. The 2023-2024 OROV reassortant displayed plaques earlier than the prototype, produced 1.7 times more plaques, and plaque sizes were 2.5 larger compared to the prototype. Furthermore, serum collected in 2016 from previously OROV-infected individuals showed at least a 32-fold reduction in neutralizing capacity against the reassortment strain compared to the prototype., Interpretation: These findings provide a comprehensive assessment of Oropouche fever in Brazil and contribute to a better understanding of the 2023-2024 OROV reemergence. The recent increased incidence may be related to a higher replication efficiency of a new reassortant virus that also evades previous immunity., Competing Interests: Declaration of interests The authors declare no competing interests.

Perovskite nanocrystals hold significant promise for a wide range of applications, including solar cells, LEDs, photocatalysts, humidity and temperature sensors, memory devices, and low-cost photodetectors. Such technological potential stems from their exceptional quantum efficiency and charge carrier conduction capability. Nevertheless, the underlying mechanisms of photoexcitation, such as phase segregation, annealing, and ionic diffusion, remain insufficiently understood. In this context, we harnessed hyperspectral fluorescence microspectroscopy to advance our comprehension of fluorescence enhancement triggered by UV continuous-wave (cw) laser irradiation of CsPbBr 3 colloidal nanocrystal thin films. Initially, we explored the kinetics of fluorescence enhancement and observed that its efficiency (φ ph ) correlates with the laser power ( P ), following the relationship φ ph = 7.7⟨ P ⟩ 0.47±0.02 . Subsequently, we estimated the local temperature induced by the laser, utilizing the finite-difference method framework, and calculated the activation energy ( E a ) required for fluorescence enhancement to occur. Our findings revealed a very low activation energy, E a ∼ 9 kJ/mol. Moreover, we mapped the fluorescence photoenhancement by spatial scanning and real-time static mode to determine its microscale length. Below a laser power of 60 μW, the photothermal diffusion length exhibited nearly constant values of approximately (22 ± 5) μm, while a significant increase was observed at higher laser power levels. These results were ascribed to the formation of nanocrystal superclusters within the film, which involves the interparticle spacing reduction, creating the so-called quantum dot solid configuration along with laser-induced annealing for higher laser powers.

Objective: to map and synthesize the main evidence on the use of bioelectrical impedance (BIA) and its variables in the assessment of sarcopenia in community-dwelling older adults., Methods: This is a scoping review carried out by searching for articles available in four databases: PUBMED, LILACS, Web of Science and CINAHL, with the following search strategy: Body Composition AND Sarcopenia AND ″electric impedance'' OR ″bioelectrical impedance analysis'' AND Aged., Results: A total of 27,660 older adults made up the sum of the samples of the included studies. Most studies included participants of both sexes (75.6%), used the variable skeletal and/or appendicular skeletal muscle mass (ASMM) (75.6%), followed by body fat (8.1%), and phase angle (8.1%) in the assessment of the body composition of subjects with sarcopenia., Conclusion: The data from this research show that ASMM and phase angle are the main variables related to sarcopenia screening in community-dwelling older adults. Whereas total extracellular water/body water is still considered a confounding variable in the screening of sarcopenia in the elderly, but it can be considered useful regarding the health conditions of the elderly in the community., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The Atlantic croaker Micropogoniasundulatus , a sciaenid fish native to the North Atlantic American coast, holds importance in recreational and commercial fisheries. Moreover, its potential as an invasive species should be noted, given its expansion and establishment in Atlantic European waters. This study reports its southernmost occurrence in Europe, in the Gulf of Cadiz. Morphological and molecular analysis confirmed its identity, revealing genetic similarities to US sequences. A comprehensive review of historical non-native distribution records underscored the species' expansion throughout European waters, suggesting human-mediated introduction. The escalating frequency of such arrivals emphasises the critical need for effective monitoring and management efforts in order to control non-native species in this region., Competing Interests: No conflict of interest to declare Disclaimer: This article is (co-)authored by any of the Editors-in-Chief, Managing Editors or their deputies in this journal., (Gustavo Freire de Carvalho-Souza, Cristóbal Lobato Gómez, Enrique González-Ortegón.)

We detected Mayaro virus (MAYV) in 3.4% (28/822) of febrile patients tested during 2018-2021 from Roraima State, Brazil. We also isolated MAYV strains and confirmed that these cases were caused by genotype D. Improved surveillance is needed to better determine the burden of MAYV in the Amazon Region.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes acute, subacute, and chronic human arthritogenic diseases and, in rare instances, can lead to neurological complications and death. Here, we combined epidemiological, virological, histopathological, cytokine, molecular dynamics, metabolomic, proteomic, and genomic analyses to investigate viral and host factors that contribute to chikungunya-associated (CHIK) death. Our results indicate that CHIK deaths are associated with multi-organ infection, central nervous system damage, and elevated serum levels of pro-inflammatory cytokines and chemokines compared with survivors. The histopathologic, metabolite, and proteomic signatures of CHIK deaths reveal hemodynamic disorders and dysregulated immune responses. The CHIKV East-Central-South-African lineage infecting our study population causes both fatal and survival cases. Additionally, CHIKV infection impairs the integrity of the blood-brain barrier, as evidenced by an increase in permeability and altered tight junction protein expression. Overall, our findings improve the understanding of CHIK pathophysiology and the causes of fatal infections., Competing Interests: Declaration of interests M.S.D. is a consultant or advisor for Inbios, Ocugen, Vir Biotechnology, Topspin Therapeutics, Moderna, Merck, and Immunome. The Diamond laboratory has received funding support from Emergent BioSolutions, Moderna, and Vir Biotechnology., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The COVID-19 pandemic was initiated by the rapid spread of a SARS-CoV-2 strain. Though mainly classified as a respiratory disease, SARS-CoV-2 infects multiple tissues throughout the human body, leading to a wide range of symptoms in patients. To better understand how SARS-CoV-2 affects the proteome from cells with different ontologies, this work generated an infectome atlas of 9 cell models, including cells from brain, blood, digestive system, and adipocyte tissue. Our data shows that SARS-CoV-2 infection mainly trigger dysregulations on proteins related to cellular structure and energy metabolism. Despite these pivotal processes, heterogeneity of infection was also observed, highlighting many proteins and pathways uniquely dysregulated in one cell type or ontological group. These data have been made searchable online via a tool that will permit future submissions of proteomic data ( https://reisdeoliveira.shinyapps.io/Infectome&#95;App/ ) to enrich and expand this knowledgebase., (© 2024. The Author(s).)

The discovery of disease-specific biomarkers, such as microRNAs (miRNAs), holds the potential to transform the landscape of Amyotrophic Lateral Sclerosis (ALS) by facilitating timely diagnosis, monitoring treatment response, and accelerating drug discovery. Such advancement could ultimately improve the quality of life and survival rates for ALS patients. Despite more than a decade of research, no miRNA biomarker candidate has been translated into clinical practice. We conducted a systematic review and meta-analysis to quantitatively synthesize data from original studies that analyzed miRNA expression from liquid biopsies via PCR and compared them to healthy controls. Our analysis encompasses 807 miRNA observations from 31 studies, stratified according to their source tissue. We identified consistently dysregulated miRNAs in serum (hsa-miR-3665, -4530, -4745-5p, -206); blood (hsa-miR-338-3p, -183-5p); cerebrospinal fluid (hsa-miR-34a-3p); plasma (hsa-miR-206); and neural-enriched extracellular vesicles from plasma (hsa-miR-146a-5p, -151a-5p, -10b-5p, -29b-3p, and -4454). The meta-analyses provided further support for the upregulation of hsa-miR-206, hsa-miR-338-3p, hsa-miR-146a-5p and hsa-miR-151a-5p, and downregulation of hsa-miR-183-5p, hsa-miR-10b-5p, hsa-miR-29b-3p, and hsa-miR-4454 as consistent indicators of ALS across independent studies. Our findings provide valuable insights into the current understanding of miRNAs' dysregulated expression in ALS patients and on the researchers' choices of methodology. This work contributes to the ongoing efforts towards discovering disease-specific biomarkers., Competing Interests: None., (© 2024 The Authors.)

Climate change may enhance the establishment of introduced species, as well as the poleward shift in distribution of numerous species over decades. Long-term research and monitoring of an ecosystem at the southernmost point of the Atlantic coast of Europe should be an important priority in order to detect and understand trends in species composition and the related environmental changes. The Guadalquivir estuary (South West Spain) is more likely to suffer the exacerbated effects of climate change due to its location in the Mediterranean-climate zone. The long-term data set between 1997 and 2006 has allowed us to analyse the variability of the natural and anthropogenic stressors. The mean interannual dissimilarity of the estuarine fauna (Bray-Curtis dissimilarity index) has showed important differences throughout the years, and the species that most contributed to these differences were the exotic species capable of completing their life cycles. This long-term monitoring of the estuarine community has allowed us to anticipate future events and ecological risk assessment in European waters., (© 2023. The Author(s).)

Recurrent miscarriage (RM) affects up to 2.5% of couples of reproductive age. Up to 10% of couples using assisted reproductive technology experience recurrent implantation failure (RIF). Immunosuppressive drugs, such as calcineurin inhibitors (CNIs), has been proposed for RM and RIF management. This systematic review and meta-analysis (SRMA) aimed to evaluate the efficacy and safety of CNIs in RM and RIF treatment. We searched in the three databases. Review Manager 5.4.1 was used for statistical analysis. This review included 8 studies involving 1042 women (485 women in the CNIs group and 557 women in the control group). CNI treatment (cyclosporine [CsA] and tacrolimus [TAC]) increases live birth rate (LBR, odds ratio [OR]: 2.52; 95% confidence interval [CI]: 1.93-3.28, p < 0.00001) and clinical pregnancy rate (OR: 2.25; 95% CI: 1.54-4.40, p < 0.0001) and decreases miscarriage rate (OR: 0.45 95% CI: 0.32-0.63, p < 0.00001) when compared to the control. Side effects and obstetric and neonatal complications was similar in both groups. In conclusion, CNIs increased LBR in women with RM and RIF but there is a moderate risk of bias. Subgroup analysis revealed that CNIs improved LBR in women with RM with a low risk of bias. However, in women with RIF, with moderate to high risk of bias. The use of CsA and TAC, in low doses and for a short period, for managing reproductive failures in women seems to be safe, not causing serious side effects nor increasing the risk of obstetric and neonatal complications., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

One of the main factors limiting tilapia's production is the occurrence of infections caused by Aeromonas and Streptococcus species. This work intended to evaluate a bivalent vaccine against A. hydrophila and S. agalactiae by intraperitoneal (i.p) administration in Nile tilapia ( Oreochromis niloticus ) in Brazil. The study was carried out in two phases: one in the laboratory, on a small scale, and from the results obtained, the study was expanded to a large scale in a production system in cages. The vaccine proved to be safe and effective in laboratory tests, with a vaccine efficacy (VE) of 93.66%. However, in large-scale tests with 12,000 tilapias, the VE was 59.14%, with a better food conversion ratio (1.54 kg) in the vaccinated group compared to the control group (1.27 kg). These results corroborate the efficiency of this tested vaccine; however, they indicate the need for field tests to attest to real protection.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4 + T helper cells, but not CD8 + T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS- CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients., Competing Interests: NB, GD, Dd, AF, GS, SM, TK, VB, LM, JV, GP, NW, LN, VC, AD, FV, LT, JF, IC, LS, AP, EM, RU, AB, TN, LR, MA, MM, LB, FC, RL, JG, NM, AM, RS, MA, DT, PP, MM, KB, CS, FG, VS, Ed, VF, MC, BC, AP, LC, MD, PR, AG, FP, LS, LB, SS, MP, SW, AS, RC, AV, MV, AD, LV, AF, Ld, TC, HN, HM, RM, DM, MS, JP, PM, MM, AF No competing interests declared, (© 2023, Brunetti, Davanzo, de Moraes et al.)

Occurrence of hyperglycemia upon infection is associated with worse clinical outcome in COVID-19 patients. However, it is still unknown whether SARS-CoV-2 directly triggers hyperglycemia. Herein, we interrogated whether and how SARS-CoV-2 causes hyperglycemia by infecting hepatocytes and increasing glucose production. We performed a retrospective cohort study including patients that were admitted at a hospital with suspicion of COVID-19. Clinical and laboratory data were collected from the chart records and daily blood glucose values were analyzed to test the hypothesis on whether COVID-19 was independently associated with hyperglycemia. Blood glucose was collected from a subgroup of nondiabetic patients to assess pancreatic hormones. Postmortem liver biopsies were collected to assess the presence of SARS-CoV-2 and its transporters in hepatocytes. In human hepatocytes, we studied the mechanistic bases of SARS-CoV-2 entrance and its gluconeogenic effect. SARS-CoV-2 infection was independently associated with hyperglycemia, regardless of diabetic history and beta cell function. We detected replicating viruses in human hepatocytes from postmortem liver biopsies and in primary hepatocytes. We found that SARS-CoV-2 variants infected human hepatocytes in vitro with different susceptibility. SARS-CoV-2 infection in hepatocytes yields the release of new infectious viral particles, though not causing cell damage. We showed that infected hepatocytes increase glucose production and this is associated with induction of PEPCK activity. Furthermore, our results demonstrate that SARS-CoV-2 entry in hepatocytes occurs partially through ACE2- and GRP78-dependent mechanisms. SARS-CoV-2 infects and replicates in hepatocytes and exerts a PEPCK-dependent gluconeogenic effect in these cells that potentially is a key cause of hyperglycemia in infected patients.

Introduction: Chikungunya fever is an infection transmitted by the Chikungunya virus (CHIKV), which is an arbovirus that is transmitted by the mosquitoes Aedes aegypti and Aedes albopictus. The most common sequelae caused by CHIKV are chronic musculoskeletal pain, nerve damage, joint deformation and functional impairment., Objective: To systematically identify the literature on the contributions of physiotherapy in the treatment of patients with CHIKV sequelae., Materials and Methods: Systematic review of the literature, guided by the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). The databases used were PUBMED, LILACS, Scielo and PEDro. Experimental studies and/or full case studies published without language restriction or publication data were included, in which they stood out as contributions of musculoskeletal functional rehabilitation in the treatment of patients with the condition in question. Analytical observational studies, editorial letters, review protocols, reflective studies, literature reviews and articles that do not have an abstract and/or full text available online were excluded., Results: The search in the databases was carried out between July and August 2022. A total of 4,782 articles were found on the platforms used and 10 articles from the gray literature search. After the duplicate analysis, 2,027 studies were excluded, leaving 2,755 articles that had their titles and abstracts read, of which 600 articles were selected for full reading. After this step, a final sample of 13 articles was eligible for this review., Final Considerations: The most consolidated approaches used in the literature demonstrate that kinesiotherapy, associated or not with electrothermophototherapy, the pilates method and auriculotherapy are useful resources in the treatment of these individuals, significantly inspired by pain relief, improved quality of life and of functionality., (© 2023. The Author(s).)

The COVID-19 pandemic was triggered by the coronavirus SARS-CoV-2, whose peak occurred in the years 2020 and 2021. The main target of this virus is the lung, and the infection is associated with an accentuated inflammatory process involving mainly the innate arm of the immune system. Here, we described the induction of a pulmonary inflammatory process triggered by the intranasal (IN) instillation of UV-inactivated SARS-CoV-2 in C57BL/6 female mice, and then the evaluation of the ability of vitamin D (VitD) to control this process. The assays used to estimate the severity of lung involvement included the total and differential number of cells in the bronchoalveolar lavage fluid (BALF), histopathological analysis, quantification of T cell subsets, and inflammatory mediators by RT-PCR, cytokine quantification in lung homogenates, and flow cytometric analysis of cells recovered from lung parenchyma. The IN instillation of inactivated SARS-CoV-2 triggered a pulmonary inflammatory process, consisting of various cell types and mediators, resembling the typical inflammation found in transgenic mice infected with SARS-CoV-2. This inflammatory process was significantly decreased by the IN delivery of VitD, but not by its IP administration, suggesting that this hormone could have a therapeutic potential in COVID-19 if locally applied. To our knowledge, the local delivery of VitD to downmodulate lung inflammation in COVID-19 is an original proposition.

Background and Aims: Low-density lipoprotein (LDL) plasma concentration decline is a biomarker for acute inflammatory diseases, including coronavirus disease-2019 (COVID-19). Phenotypic changes in LDL during COVID-19 may be equally related to adverse clinical outcomes., Methods: Individuals hospitalized due to COVID-19 (n = 40) were enrolled. Blood samples were collected on days 0, 2, 4, 6, and 30 (D0, D2, D4, D6, and D30). Oxidized LDL (ox-LDL), and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity were measured. In a consecutive series of cases (n = 13), LDL was isolated by gradient ultracentrifugation from D0 and D6 and was quantified by lipidomic analysis. Association between clinical outcomes and LDL phenotypic changes was investigated., Results: In the first 30 days, 42.5% of participants died due to Covid-19. The serum ox-LDL increased from D0 to D6 (p < 0.005) and decreased at D30. Moreover, individuals who had an ox-LDL increase from D0 to D6 to over the 90th percentile died. The plasma Lp-PLA2 activity also increased progressively from D0 to D30 (p < 0.005), and the change from D0 to D6 in Lp-PLA2 and ox-LDL were positively correlated (r = 0.65, p < 0.0001). An exploratory untargeted lipidomic analysis uncovered 308 individual lipids in isolated LDL particles. Paired-test analysis from D0 and D6 revealed higher concentrations of 32 lipid species during disease progression, mainly represented by lysophosphatidyl choline and phosphatidylinositol. In addition, 69 lipid species were exclusively modulated in the LDL particles from non-survivors as compared to survivors., Conclusions: Phenotypic changes in LDL particles are associated with disease progression and adverse clinical outcomes in COVID-19 patients and could serve as a potential prognostic biomarker., Competing Interests: Declaration of Competing Interest Dr. Miguel Sáinz-Jaspeado works at Mercodia company (Mercodia AB, Uppsala, Sweden) as product Manager & Medical Science Liaison and, kindly provided the enzyme-linked immunoassay (ELISA) kits for oxidized low-density lipoprotein measures., (Copyright © 2023. Published by Elsevier Inc.)

Cardiovascular diseases are the leading cause of mortality worldwide, requiring support to manage symptoms and improve prognosis. Home-based cardiac rehabilitation is a realistic resource for this purpose, but it requires patients' self-management skills in order to change behaviours. Smartphones are considered mHealth technology (mobile technological resources in healthcare) and have the potential to provide modalities for delivery of cardiac rehabilitation. This systematic review aims to examine these modalities and identify those that are most effective for improving exercise capacity, quality of life, and patient compliance. Randomized controlled trials (1994 to 2022) performed with adults with coronary artery disease (post-myocardial infarction, angina, post-coronary artery bypass graft surgery) or heart failure eligible for home-based cardiac rehabilitation (mHealth) will be selected. Studies published in English, Spanish, or Portuguese that compare rehabilitation-specific mobile apps or smartphone-based features with conventional cardiac rehabilitation will be included. Searches will be conducted in MEDLINE, CENTRAL, EMBASE, LILACS, PEDro, grey literature, and ongoing or recently completed studies. Data and risk of bias will be assessed, and if appropriate, a meta-analysis will be carried out., (© 2023 The Authors.)

A significant fraction of patients are affected by persistent fear and anxiety. Currently, there are several anxiolytic drug options, however their clinical outcomes do not fully manage the symptoms. Here, we evaluated the effects of a bromazepam‑palladium derivative [2-{(7-bromo-2-oxo-1,3-dihydro-2H-1,4-benzodiazepin-5-il)pyridinyl-κ 2 -N,N}chloropalladium(II)], [(BMZ)PdCl 2 ], on fear/anxiety and memory-related behavior in mice. For this, female Swiss mice were treated intraperitoneally (i.p.) with saline (NaCl 0.9%) or [(BMZ)PdCl 2 ] (0.5, 5.0, or 50 μg/kg). After 30 min, different tests were performed to evaluate anxiety, locomotion, and memory. We also evaluated the acute toxicity of [(BMZ)PdCl 2 ] using a cell viability assay (neutral red uptake assay), and whether the drugs mechanism of action involves the γ-aminobutyric acid type A (GABA A ) receptor complex by pre-treating animals with flumazenil (1.0 mg/kg, i.p., a competitive antagonist of GABA A -binding site). Our results demonstrate that [(BMZ)PdCl 2 ] induces an anxiolytic-like phenotype in the elevated plus-maze test and that this effect can be blocked by flumazenil. Furthermore, there were no behavioral alterations induced by [(BMZ)PdCl 2 ], as evaluated in the light-dark box, open field, and step-down passive avoidance tests. In the acute toxicity assay, [(BMZ)PdCl 2 ] presented IC 50 and LD 50 values of 218 ± 60 μg/mL and 780 ± 80 mg/kg, respectively, and GSH category 4. Taken together, our results show that the anxiolytic-like effect of acute treatment with [(BMZ)PdCl 2 ] occurs through the modulation of the benzodiazepine site in the GABA A receptor complex. Moreover, we show indications that [(BMZ)PdCl 2 ] does not promote sedation and amnesia and presents the same toxicity as the bromazepam prototype., 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 © 2022 Elsevier Inc. All rights reserved.)

Since the COVID-19 pandemic emerged, vaccination has been the core strategy to mitigate the spread of SARS-CoV-2 in humans. This paper analyzes the impact of COVID-19 vaccination on hospitalizations and deaths in the state of Rio Grande do Norte, Brazil. We analyzed data from 23,516 hospitalized COVID-19 patients diagnosed between April 2020 and August 2021. We excluded the data from patients hospitalized through direct occupancy, unknown outcomes, and unconfirmed COVID-19 cases, resulting in data from 12,635 patients cross-referenced with the immunization status during hospitalization. Our results indicated that administering at least one dose of the immunizers was sufficient to significantly reduce the occurrence of moderate and severe COVID-19 cases among patients under 59 years. Considering the partially or fully immunized patients, the mean age is similar between the analyzed groups, despite the occurrence of comorbidities and higher than that observed among not immunized patients. Thus, immunized patients present lower Unified Score for Prioritization (USP) levels when diagnosed with COVID-19. Our data suggest that COVID-19 vaccination significantly reduced the hospitalization and death of elderly patients (60+ years) after administration of at least one dose. Comorbidities do not change the mean age of moderate/severe COVID-19 cases and the days required for the hospitalization of these patients.

Visceral adiposity is a risk factor for severe COVID-19, and a link between adipose tissue infection and disease progression has been proposed. Here we demonstrate that SARS-CoV-2 infects human adipose tissue and undergoes productive infection in fat cells. However, susceptibility to infection and the cellular response depends on the anatomical origin of the cells and the viral lineage. Visceral fat cells express more ACE2 and are more susceptible to SARS-CoV-2 infection than their subcutaneous counterparts. SARS-CoV-2 infection leads to inhibition of lipolysis in subcutaneous fat cells, while in visceral fat cells, it results in higher expression of pro-inflammatory cytokines. Viral load and cellular response are attenuated when visceral fat cells are infected with the SARS-CoV-2 gamma variant. A similar degree of cell death occurs 4-days after SARS-CoV-2 infection, regardless of the cell origin or viral lineage. Hence, SARS-CoV-2 infects human fat cells, replicating and altering cell function and viability in a depot- and viral lineage-dependent fashion., (© 2022. The Author(s).)