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Emergency medical services often serve as the initial point of contact for septic patients, offering crucial pre-hospital intervention opportunities. However, the efficacy of pre-hospital interventions remains uncertain. From this perspective, we'll talk about the available evidence of pre-hospital sepsis and septic shock treatment and the barriers to its implementation., 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).)

Although various tools provide proteomic information, each tool has limitations related to execution platforms, libraries, versions, and data output format. Integrating data generated from different software is a laborious process that can prolong analysis time. Here, we present FastProtein, a protein analysis pipeline that is user-friendly, easily installable, and outputs important information about subcellular location, transmembrane domains, signal peptide, molecular weight, isoelectric point, hydropathy, aromaticity, gene ontology, endoplasmic reticulum retention domains, and N-glycosylation domains. It also helps determine the presence of glycosylphosphatidylinositol and obtain functional information from InterProScan, PANTHER, Pfam, and alignment-based annotation searches. FastProtein provides the scientific community with an easy-to-use computational tool for proteomic data analysis. It is applicable to both small datasets and proteome-wide studies. It can be used through the command line interface mode or a web interface installed on a local server. FastProtein significantly enhances proteomics analysis workflows by producing multiple results in a single-step process, thereby streamlining and accelerating the overall analysis. The software is open-source and freely available. Installation and execution instructions, as well as the source code and test files generated for tool validation, are available at https://github.com/bioinformatics-ufsc/FastProtein., Competing Interests: The authors declare there are no competing interests., (©2024 Moreira et al.)

Refractory black carbon (rBC) has great potential to increase melting when deposited on snow and ice surfaces. Previous studies attributed sources and impacts of rBC in the northern Antarctic Peninsula region by investigating long-range atmospheric transport from South Hemisphere biomass burning and industrial regions or by assessing impacts from local tourism and research activities. We used high-resolution measurements of refractory rBC in a firn core collected near the northern tip of the Antarctic Peninsula, as well as atmospheric rBC from Modern-Era Retrospective Analysis for Research and Applications, Version 2, satellite measurements, modeling, burned area data, and tourism statistics, to assess combined impacts of both long-range transported rBC and locally emitted rBC. Our findings suggest that tourism activities have a regional rather than local impact and the increase in rBC concentrations during late spring-summer, influenced by tourism activities and fires in the Southern Hemisphere, can enhance ice melt. This highlights the need for strategies to reduce local and distant rBC emissions.

Background: Osteoarthritis (OA) is the most common degenerative joint disease and affects millions of people worldwide, particularly the elderly population. The pathophysiology of OA is complex and involves multiple factors. Methods: Several studies have emphasized the crucial role of inflammation in this process. The receptor activator of NF-κB ligand (RANKL), the receptor activator of NF-κB (RANK), and osteoprotegerin (OPG) trigger a signaling cascade that leads to the excessive production of RANKL in the serum. Conclusions: The aim of this narrative review is (i) to assess the role of the RANK/RANKL/OPG signaling pathway in the context of OA progression, focusing especially on the physiopathology and on all the mechanisms leading to the activation of the inflammatory cascade, and (ii) to evaluate all the potential therapeutic strategies currently available that restore balance to bone formation and resorption, reducing structural abnormalities and relieving pain in patients with OA.

Introduction: The microbial-induced restoration of ferruginous crusts ( canga ), which partially cover iron deposits and host unique ecosystems, is a promising alternative for reducing the environmental impacts of the iron mining industry., Methods: To investigate the potential of microbial action to accelerate the reduction and oxidation of iron in substrates rich in hematite and goethite, four different microbial treatments (water only as a control - W; culture medium only - MO; medium + microbial consortium - MI; medium + microbial consortium + soluble iron - MIC) were periodically applied to induce iron dissolution and subsequent precipitation. Except for W, all the treatments resulted in the formation of biocemented blocks., Results: MO and MI treatments resulted in significant goethite dissolution, followed by precipitation of iron oxyhydroxides and an iron sulfate phase, due to iron oxidation, in addition to the preservation of microfossils. In the MIC treatment, biofilms were identified, but with few mineralogical changes in the iron-rich particles, indicating less iron cycling compared to the MO or MI treatment. Regarding microbial diversity, iron-reducing families, such as Enterobacteriaceae, were found in all microbially treated substrates., Discussion: However, the presence of Bacillaceae indicates the importance of fermentative bacteria in accelerating the dissolution of iron minerals. The acceleration of iron cycling was also promoted by microorganisms that couple nitrate reduction with Fe(II) oxidation. These findings demonstrate a sustainable and streamlined opportunity for restoration in mining areas., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 da Silva, Cardoso, Angelica, Bitencourt, Moreira, Lucheta, Prado, Candela and Gastauer.)

Objectives: To characterise Portuguese cancer-related patient organisations and analyse their views, motivations and experiences on patient involvement in cancer research., Design: A multistakeholder group, comprising patient representatives and researchers, codesigned a questionnaire after a literature review, online sessions and collaborative mind maps. In May 2021, a survey was conducted among representatives of Portuguese cancer-related patient organisations, focusing on four dimensions: experience in cancer research; perception of its outcomes; motivations and expectations on patient involvement in research; and organisation characteristics., Participants: Twenty-seven representatives from Portuguese cancer-related patient organisations responded to the questionnaire, corresponding to a 64% response rate., Results: Among the surveyed organisations, 26% have participated in clinical studies. Their involvement occurred in few stages of the research process and, mostly, with low levels of engagement. They showed 'great interest' in participating in most research steps, although this is not reflected in a high perception of influence over these same steps. More than half claimed to have contributed to the increase in patient recruitment and to a better understanding of informed consent by patients involved. Ensuring that research results are more aligned with the true needs of patients is the greatest motivation. Also, our results suggest that the organisation's number of employees and its integration into a European/International network play a relevant role in patient involvement in research., Conclusions: This study provides the first in-depth characterisation of Portuguese cancer-related patient organisations and their views, motivations and experiences on patient involvement in cancer research. Most importantly, this study revealed that most of these organisations show great interest in being involved in different R&D stages to ensure that research results are aligned with patients' needs. Their motivation should be turned into greater and more meaningful involvement in practice, so that the cancer community can benefit from the outcomes of truly patient-centred research., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Healthy aging encompasses more than the absence of disease, emphasizing the preservation of functional abilities for enhanced well-being and quality of life. Nature-based interventions are scientifically proven contributors to healthy aging., Objective: To develop an evidence map showcasing nature-based interventions targeting older individuals' health and well-being., Methods: The evidence map was developed through critical analysis of systematic reviews and clinical trials utilizing the tools AMSTAR2 and CONSORT. A systematic search spanning the past decade was conducted across databases: Cochrane, SCOPUS, PubMed, Web of Science, Embase, and LILACS., Results: Twelve articles met the eligibility criteria. Nature-based interventions such as forest bathing, hiking, therapeutic gardens, virtual reality, and forest sounds were identified. Outcomes were categorized into physical aspects (cardiovascular and pulmonary; neuro-immuno-endocrinological) and mental/behavioral aspects. The final map integrated interventions, outcomes, and quality assessments., Conclusions: The survey highlights the positive impact of nature-based interventions on the health of the elderly. This study provides insights across various domains, fostering the development of programs and policies in management to promote healthy aging. Regarding healthcare, it encourages discourse among professionals regarding the integration of nature-based practices for equitable care in both individual and group settings. Furthermore, it underscores the need for research in the Southern Hemisphere, particularly in Brazil, where the study was conducted.

Introduction: Peroneal disorders are a common cause of ankle pain and lateral instability and have been described in as much as 77% of patients with lateral ankle instability. Clicking, swelling, pain, and tenderness in the peroneal tendons track are frequent symptoms, but they can be confused with other causes of lateral ankle pain. The management of peroneal disorders can be conservative or surgical. When the conservative treatment fails, surgery is indicated, and open or tendoscopic synovectomy, tubularization, tenodesis or tendon transfers can be performed. The authors present a surgical technique of tendoscopy associated to minimally invasive tenodesis for the treatment of peroneal tendon tears, as well as the preliminary results of patients submitted to this procedure. Methods: Four patients with chronic lateral ankle pain who were diagnosed with peroneal brevis pathology were treated between 2020 and 2022 with tendoscopic-assisted minimally invasive synovectomy and tenodesis. Using a 2.7 mm 30° arthroscope and a 3.0 mm shaver blade, the entire length of the peroneus brevis tendon and most parts of the peroneus longus tendon can be assessed within Sammarco's zones 1 and 2. After the inspection and synovectomy, a minimally invasive tenodesis is performed. Results: All patients were evaluated at least six months after surgery. All of them reported improvement in daily activities and in the Foot Function Index (FFI) questionnaire (pre-surgery mean FFI = 23.86%; post-surgery mean FFI = 6.15%), with no soft tissue complications or sural nerve complaints. Conclusion: The tendoscopy of the peroneal tendons allows the surgeon to assess their integrity, confirm the extent of the lesion, perform synovectomy, prepare the tendon for tenodesis, and perform it in a safe and minimally invasive way, reducing the risks inherent to the open procedure.

Introduction: The CA1 region of the hippocampus has an important role in learning and memory. It has been shown that estrogen deficiency may reduce the synaptic density in the region and that hormone replacement therapy may attenuate the reduction., Objectives: This study aimed to evaluate the effects of estrogen and raloxifene on the synaptic density profile in the CA1 region of the hippocampus in ovariectomized rats., Methods: Sixty ovariectomized three-month-old virgin rats were randomized into six groups (n = 10). Treatments started either three days (early treatment) or sixty days (late treatment) after ovariectomy. The groups received propylene glycol vehicle (0.5 mL/animal/day), equine conjugated estrogens (50 μg/animal/day), or raloxifene (3 mg/kg/day) either early or late after ovariectomy. The drugs were administered orally by gavage for 30 days. At the end of the treatments, the animals were anesthetized and transcardially perfused with ether and saline solution. The brains were removed and prepared for analysis under transmission electron microscopy and later fixed., Results: Results showed a significant increase in the synaptic density profile of the hippocampal CA1 region in both the early estrogen (0.534 ± 0.026 µ/m 2 ) and the early raloxifene (0.437 ± 0.012 µ/m 2 ) treatment groups compared to the early or late vehicle-treated control groups (0.338 ± 0.038 µ/m 2 and 0.277 ± 0.015 µ/m 2 respectively)., Conclusions: The present data suggest that the raloxifene effect may be lower than that of estrogen, even early or late treatment, on synaptic density in the hippocampus., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2023 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

This study presents the first integrated study on total Hg (THg) level in surface soil (SS), bottom soil (BS), stream sediments (SD), lake sediments (LS), stream water (SW), and lake water (LW) of Itacaiúnas River Watershed (IRW), Brazil to investigate the source and distribution of Hg in different environmental media considering contrasts of geological domains and sub-basins and its potential ecological and human risk. Hg content in most of the soils and sediments were above the upper crustal average values (56 μg/kg), however, when compared to the legal limits set by the Resolution CONAMA (Conselho Nacional de Meio Ambiente: soil 500 μg/kg; sediment 486 μg/kg), only 1 soil sample from Parauapebas sub-basin and 4 sediment samples from Violão Lake exceeded the limit. None of the SW and LW samples (<0.2 μg/L; CONAMA limit for Class II freshwater) are markedly contaminated by Hg. The SS and BS show similar contents and spatial distribution of Hg with higher contents being registered mostly in the Itacaiúnas and Parauapebas sub-basins, which are closely correlated with SD. This suggests that Hg levels are largely of geogenic origin and anthropogenic effect is highly limited. Principal Component Analysis (PCA) results show that Hg is strongly associated with total organic carbon (TOC), loss on ignition (LOI), and SO 3 , indicating organic matter as the main factor controlling the distribution of Hg and this is the major cause of accentuated Hg enrichment in lake sediments. The ecological risk index revealed a low pollution risk for most of the solid samples, except 11% LS and <1.5% SS and SD samples, which registered moderate risk. Health risk assessment indicated no adverse non-carcinogenic health effect on either adults and children in terms of Hg contamination. This information will be useful for Hg risk assessment in the Carajás region and future environmental research in this direction in the Amazonia., 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 © 2023 Elsevier Inc. All rights reserved.)

The expansion of areas of human occupation and the increase in economic activity and deforestation are negatively impacting the Amazon ecosystem. Situated in the Carajás Mineral Province in the southeastern Amazon, the Itacaiúnas River Watershed (IRW) encompasses several active mines and has a historical record of intense deforestation primarily linked with the expansion of pasturelands, but also of urban areas, and mining activities. Industrial mining projects are subjected to strict environmental control, but artisanal mining (ASM; 'garimpos') sites have not been controlled, despite their known environmental impacts. In recent years, the opening and expansion of ASM in the IRW for the exploitation of mineral resources (Au, Mn, and Cu) have been remarkable. This study presents evidence of anthropogenic impacts, mainly caused by ASM, on the quality and hydrogeochemical characteristics of the IRW surface water. The hydrogeochemical data sets of two projects carried out in the IRW, during 2017 and from 2020 until present, were used to evaluate these impacts within the region. Water quality indices were calculated for the surface water samples. For the whole IRW, water collected during the dry season tended to yield better quality indicators in comparison to those collected during the rainy season. Two sampling sites at Sereno Creek showed very poor water quality and extremely high concentrations of Fe, Al, and potentially toxic elements over time. From 2016 to 2022, ASM sites increased markedly. Moreover, there are indications that Mn exploitation via ASM in Sereno hill is the main source of contamination in the area. New trends of ASM expansion were observed along the main watercourses, related to the exploitation of Au from alluvial deposits. Similar anthropogenic impacts are registered in other regions of the Amazon and environmental monitoring should be encouraged to assess the chemical safety of strategic areas., 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 © 2023 Elsevier Ltd. All rights reserved.)

Although there are many studies on the health effects of methylmercury (MeHg) toxicity during in utero and early development, little is known about its effects on mineralized tissues present in the oral cavity, such as enamel structure. Therefore, this study evaluated the effects of MeHg exposure on the physico-chemical, ultrastructural and functional properties of mature tooth enamel. Specifically, we studied offspring of mothers exposed to MeHg during the prenatal and postnatal periods which are the developmental stages associated with tooth enamel formation. Female rats were exposed to MeHg at a dose of 40 μg/kg/day for 42 days of pregnancy and lactation. The enamel of offspring was analyzed by (1) Fourier Transform Infrared Spectroscopy and Raman to assess physicochemical composition, (2) Scanning Electron Microscopy for ultrastructural evaluation, (3) Transmitted Polarizing Light Microscopy for analysis of the enamel extracellular matrix, and (4) resistance and hardness were evaluated by microhardness. The results showed that MeHg exposure during this sensitive enamel formation period induced changes in inorganic and organic content and enamel prisms ultrastructure alterations and disturbed the organic extracellular matrix due to a decreased enamel strength. These novel findings establish for the first time that maternal exposure to MeHg pre and postnatal promoted relevant changes in mature enamel of their offspring rats., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chemelo, Bittencourt, Nascimento, Paiva, Delbem, Pessan, do Espírito Santo, Albuquerque, Angélica, Crespo-Lopez, Pessanha, Aschner and Lima.)

Objectives: The aim of this study was to evaluate CD56 immunostaining in the stroma of benign and malignant ovarian epithelial neoplasms and associate the CD56 immunostaining with prognostic factors and survival in ovarian cancer., Methods: Patients with ovarian epithelial neoplasia (n=77) were studied with a prospective cohort. The CD56 immunostaining was evaluated in the peritumoral stroma. Two groups were evaluated: benign ovarian neoplasms (n=40) and malignant ovarian neoplasms (n=37). Data were recorded for histological type and grade, International Federation of Gynecology and Obstetrics staging, molecular subtype, and lymph node metastases. Fisher's exact test and Kaplan-Meier survival curves were used, with a significance level of ≤0.05., Results: We found greater CD56 stromal immunostaining in malignant neoplasms when compared to the group of benign neoplasms (p=0.00001). There was no significant difference in relation to the prognostic factors and survival., Conclusion: Malignant ovarian neoplasms showed higher stromal CD56 immunostaining. As the prognostic value of natural killer in ovarian cancer is controversial, knowing the specific function of each cell present both in the tumor tissue and systemically may help guide successful immunotherapies in the near future.

Pesticides offer stakeholders cost-effective solutions to control weeds. Nevertheless, such active compounds can manifest as severe environmental pollutants when escaping from agroecosystems into surrounding natural ecosystems, driving the need to remediate them. We, hence, analyzed whether Mucuna pruriens can develop a potential phytoremediator for treating tebuthiuron (TBT) in soil with vinasse. We exposed M. pruriens to microenvironments containing tebuthiuron at 0.5, 1, 1.5, and 2 (standard dose) L ha -1 and vinasse at 75, 150 (industrial recommendation), and 300 m 3 ·ha -1 . Experimental units without organic compounds represented controls. We assessed M. pruriens for morphometrical features, such as plant height and stem diameter and shoot/root dry mass, over approximately 60 days. We obtained evidence for M. pruriens not effectively removing tebuthiuron from the terrestrial medium. Such a pesticide developed phytotoxicity, significantly limiting its germination and growth. The higher the dose, the more negatively the tebuthiuron impacted the plant. In addition, introducing vinasse into the system, irrespective of volume, intensified the damage to photosynthetic and non-photosynthetic structures. Equally important, its antagonist action further decreased the production and accumulation of biomass. As M. pruriens could not effectively extract tebuthiuron from the soil, it could allow neither Crotalaria juncea nor Lactuca sativa to grow on synthetic media containing residual pesticide. An atypical performance of such testing (tebuthiuron-sensitive) organisms over independent ecotoxicological bioassays validated inefficient phytoremediation. Hence, M. pruriens could not offer a functional remediative option to treat environmental pollution by tebuthiuron in agroecosystems where vinasse occurs, such as sugarcane-producing areas. Although M. pruriens considered a tebuthiuron phytoremediator as cited in the literature, satisfactory results did not occur in our research due to high concentrations of vinasse in the soil. Therefore, this information requires more specific studies about the influence of high concentrations of organic matter on M. pruriens productivity and phytoremediation performance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Frias, Lima, Aragão, Nantes, Moreira, Cruz, Tomaz and Lopes.)

SARS-CoV-2 genome surveillance is important for monitoring risk groups and health workers as well as data on new cases and mortality rate due to COVID-19. We characterized the circulation of SARS-CoV-2 variants from May 2021 to April 2022 in the state of Santa Catarina, southern Brazil, and evaluated the similarity between variants present in the population and healthcare workers (HCW). A total of 5291 sequenced genomes demonstrated the circulation of 55 strains and four variants of concern (Alpha, Delta, Gamma and Omicron-sublineages BA.1 and BA.2). The number of cases was relatively low in May 2021, but the number of deaths was higher with the Gamma variant. There was a significant increase in both numbers between December 2021 and February 2022, peaking in mid-January 2022, when the Omicron variant dominated. After May 2021, two distinct variant groups (Delta and Omicron) were observed, equally distributed among the five Santa Catarina mesoregions. Moreover, from November 2021 to February 2022, similar variant profiles between HCW and the general population were observed, and a quicker shift from Delta to Omicron in HCW than in the general population. This demonstrates the importance of HCW as a sentinel group for monitoring disease trends in the general population.

Hormonal and metabolic factors may influence endometrial quality and interfere with the action of progesterone. Therefore, the aim of our study was to address this issue. Participants were recruited from an outpatient reproductive endocrinology clinic at an academic tertiary medical care centre. All subjects underwent endometrial biopsy (EB) in the follicular phase of the cycle prior to treatment. Thereafter, they were treated with micronized progesterone (400 mg/day × 10 days intravaginally) from days 14-28 of the next cycle. A second EB was performed between days 21-24 of the cycle (the second phase). The metabolic and hormonal serum levels were evaluated during the implantation window. EB samples were analysed using light microscopy for histomorphometric analysis. The endometrium of women with Polycystic Ovarian Syndrome (PCOS) in the second phase demonstrated a uniform surface epithelium with less leukocyte infiltration and an absence of apoptotic figures compared to the control group. ( p < 0.021). The thickness of the surface epithelium in the second phase of the PCOS group correlated positively with free and bioavailable testosterone values. The number of stromal cells increases with increasing insulin levels. Our results suggest that histomorphometric abnormalities of the endometrium persist and are linked to androgen and insulin levels despite progesterone supplementation in PCOS.

Background: Trypanosoma evansi infects a large number of wild and domestic animals and causes a spoliative disease known as surra. It is mechanically transmitted, mainly by biting flies of the genera Tabanus and Stomoxys. The detection of T. evansi DNA in the feeding apparatus of Dichelacera alcicornis and Dichelacera januarii from South America is reported, to the best of our knowledge, for the first time., Methods: Tabanids were collected weekly from February 2018 to February 2019 from two sites. The feeding apparatus was removed and DNA extraction, polymerase chain reaction and sequencing were performed., Results: A 205-base pair fragment of the variant surface protein RoTat 1.2 gene, confirmed by DNA sequencing, was amplified from the feeding apparatus of D. alcicornis and D. januarii., Conclusions: This is, to the best of our knowledge, the first record of T. evansi DNA in South American tabanids., (© 2022. The Author(s).)

Introduction: The control of Salmonella spp. in poultry involves different biosecurity actions and lately has been complicated by the emergence of multidrug resistant serovars. The application of organic acids and essential oils has been used with different approaches due to the antibacterial properties as food preservatives. The use of these molecules in animal feed to control enteric pathogens is a major interest within the poultry industry., Methods: The use of a blend containing nature-identical compounds of sorbic acid (25%), thymol (9.5%) and carvacrol (2.5%) microencapsulated in a lipid matrix, was investigated in the present work, for the control of three Salmonella serovars ( S . ser. Typhimurium, S . ser. Heidelberg and S . ser. Minnesota). Commercial broilers were challenged at 3 or at 33 days of age. Groups SH-1, SM-1 and ST-1, received treatment in the feed, at 2 kg/ton from 1-21 days of age and at 1 kg/ton from 35-42 days of age (last week), while groups SH-2, SM-2 and ST-2, were treated only during the last week receiving 2 kg/ton. Each treated group had an untreated control group, that was challenged at the same moment with the respective serovar (groups PCH, PCM and PCT). The challenge strains were enumerated in liver and cecal contents, weekly after challenge, at 7, 14, 21, 28, 35 and 42 days-of-age., Results and Discussion: Significant reduction was noticed at 7 and 14 days of age in all groups that received treatment during the initial phase ( p < 0.05). Moreover, the body weight was significantly higher at the last experimental day ( p < 0.05) in chickens that received treatment at the initial and at the final growth stages., Competing Interests: GS, RS, and AM were employed by Farmabase Animal Health. AP serves as professor at the University of Bologna and is a member of the board of directors of Vetagro SpA (Reggio Emilia, Italy) which funded the project. EG serves as an advisor of Vetagro SpA. Vetagro, as funder of the study, was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Stingelin, Scherer, Machado, Piva, Grilli and Penha Filho.)

Cardiac arrest is an important public health issue, with a survival rate of approximately 15 to 22%. A great proportion of these deaths occur after resuscitation due to post-cardiac arrest syndrome, which is characterized by the ischemia-reperfusion injury that affects the role body. Understanding physiopathology is mandatory to discover new treatment strategies and obtain better results. Besides improvements in cardiopulmonary resuscitation maneuvers, the great increase in survival rates observed in recent decades is due to new approaches to post-cardiac arrest care. In this review, we will discuss physiopathology, etiologies, and post-resuscitation care, emphasizing targeted temperature management, early coronary angiography, and rehabilitation.

Chikungunya virus (CHIKV) belongs to the genus Alphaviridae, with a single-stranded positive-sense RNA genome of 11.8 kbp encoding a polyprotein that generates both non-structural proteins and structural proteins. The virus is transmitted by the Aedes aegypti and A. albopictus mosquitoes, depending on the location. CHIKV infection leads to dengue-like musculoskeletal symptoms and has been responsible for several outbreaks worldwide since its discovery in 1952. Patients often experience fever, headache, muscle pain, joint swelling, and skin rashes. However, the ultrastructural and mechanical properties of CHIKV have not been fully characterized. Thus, this study aims to apply a physical approach to investigate CHIKV's ultrastructural morphology and mechanical properties, using atomic force microscopy and Raman spectroscopy as the main tools. Using nanomechanical assays of AFM and a gold nanoparticles substrate for Raman signal enhancement, we explored the conformational plasticity, morphology, vibrational signature, and nanomechanical properties of the chikungunya virus, providing new information on its ultrastructure at the nanoscale and offering a novel understanding of the virus' behavior upon mechanical disruptions besides its molecular composition.

Methylmercury (MeHg) is the most common organic form of mercury (Hg) that humans are exposed and is considered an environmental pollutant. Several populations that live in endemic regions of MeHg exposure are subject to the toxicant for long periods, including pregnant women and children, causing damage to several organs during early periods of development. Alveolar bone is an essential structure for the oral cavity, responsible for supporting teeth and masticatory forces. However, evidence on the effects of MeHg on alveolar bone and the intrauterine and lactation period is lacking. Thus, this study aimed to investigate the effects of MeHg exposure during gestation and lactation on the developing alveolar bone of offspring rats after maternal exposure. Dams were exposed during 41 days of pregnancy and lactation, and the mandibles of the offspring were collected. The alveolar bone was analyzed by Fourier Transform Infrared Spectroscopy to evaluate the physicochemical composition; by Scanning Electron Microscopy for ultrastructural evaluation; by histopathological, histochemical, and morphometric for tissue analyses. In addition, bone quality was assessed by X-ray microtomography. MeHg exposure altered the mineral composition and caused histological damage associated with a lower quantity and thickness of bone trabeculae, as well as reduced osteocyte density and collagen fiber content. A reduction in trabecular thickness and bone volume and an increase in trabecular spaces were observed and were associated with anatomical compromise of the vertical bone dimensions. Thus, the results suggest that the developing alveolar bone is susceptible to the toxic effects of MeHg when organisms are exposed during intrauterine and lactation periods. From a translational perspective, these changes in the alveolar bone can help us understand possible abnormalities induced by toxic metals and highlight the need for care for structures other than those already seen as targets for damage triggered by environmental MeHg exposure., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Assignment of gene function has been a crucial, laborious, and time-consuming step in genomics. Due to a variety of sequencing platforms that generates increasing amounts of data, manual annotation is no longer feasible. Thus, the need for an integrated, automated pipeline allowing the use of experimental data towards validation of in silico prediction of gene function is of utmost relevance. Here, we present a computational workflow named AnnotaPipeline that integrates distinct software and data types on a proteogenomic approach to annotate and validate predicted features in genomic sequences. Based on FASTA (i) nucleotide or (ii) protein sequences or (iii) structural annotation files (GFF3), users can input FASTQ RNA-seq data, MS/MS data from mzXML or similar formats, as the pipeline uses both transcriptomic and proteomic information to corroborate annotations and validate gene prediction, providing transcription and expression evidence for functional annotation. Reannotation of the available Arabidopsis thaliana , Caenorhabditis elegans, Candida albicans, Trypanosoma cruzi, and Trypanosoma rangeli genomes was performed using the AnnotaPipeline, resulting in a higher proportion of annotated proteins and a reduced proportion of hypothetical proteins when compared to the annotations publicly available for these organisms. AnnotaPipeline is a Unix-based pipeline developed using Python and is available at: https://github.com/bioinformatics-ufsc/AnnotaPipeline., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Maia, Filho, Kawagoe, Teixeira Soratto, Moreira, Grisard and Wagner.)

Purpose: Neutrophils play a role during the oncogenic process, and their count can be a prognostic marker. The objective was to evaluate the association of band and segmented neutrophils with prognostic factors, overall survival, and disease-free survival in advanced uterine cervical cancer (IIB to IVB staging)., Methods: This study evaluated 88 patients diagnosed with uterine cervical cancer staging IIB to IVB. The recorded data from medical records were age, parity, staging, histological type, absolute count of total neutrophils, band neutrophils and segmented neutrophils, disease-free survival, and overall survival. Receiver-operating characteristic (ROC) curve was used to obtain the area under the curve (AUC) and determine the best cut-off values for each parameter. Survival was verified by the Kaplan-Meier method, and multivariate analysis was performed by Cox regression. The level of significance was ≤ 0.05., Results: Regarding the total neutrophils, band, and segmented neutrophils count, a cut-off value of 6187/mm 3 , 273 mm 3 and 6062/mm 3 were found, respectively. Overall survival was shorter in patients with total neutrophils greater than 6187/mm 3 (p = 0.012), band neutrophils greater than 273/mm 3 (p = 0.001), and segmented neutrophils greater than 6062/mm 3 (p = 0.013). After multivariate analysis considering the two types of neutrophils, only band neutrophils greater than 273/mm 3 remained as an independent factor for shorter overall survival., Conclusion: The absolute count of band neutrophils greater than 273/mm 3 was a potential predictor of shorter overall survival in women with invasive cervical cancer. This count can be of great clinical use, in addition to being inexpensive, less invasive, and easy to perform., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: We have examined the impact of changes in modifiable risk factors on CVD mortality in 26 Brazilian states from 2005 to 2017., Methods: Data were acquired from the Global Burden of Diseases study (GBD) and official sources of the Brazilian government, totalling 312 state-year observations. Population attributable fractions (PAFs) were calculated to determine the number of deaths attributed to changes in each risk factor. Fixed-effects multivariable linear regression models were performed, adjusting for income, income inequality, poverty and access to healthcare., Results: Between 2005 and 2017, CVD deaths reduced by 21.42%, accompanied by a decrease in smoking (-33%) and increases in hyperglycaemia (+9.5%), obesity (+31%) and dyslipidaemia (+5.2%). Reduction in smoking prevented or postponed almost 20,000 CVD deaths in this period, while increased hyperglycaemia exposure resulted in more than 6,000 CVD deaths. The association between hyperglycaemia and CVD mortality was 5 to 10 times higher than those found for other risk factors, especially in women (11; 95%CI 7 to 14, deaths per 1-point increase in hyperglycaemia exposure). Importantly, the association between hyperglycaemia and CVD mortality was independent of socioeconomic status and access to healthcare, while associations for other risk factors after the same adjustments., Conclusion: Reduction in smoking was the risk factor that led to the highest number of CVD deaths prevented or postponed, while hyperglycaemia showed the most deleterious association with CVD mortality. Health policies should aim to directly reduce the prevalence of hyperglycaemia to mitigate the population burden of CVD in Brazil in the future., Competing Interests: The authors have declared that no competing interests exist.

Abstract: Stigma remains a feature that influences the lifestyle of people with mental illness. Negative attitudes, stereotypes, and discrimination are still prevalent in these people's life. Stigma is considered a public health problem that occurs unconsciously in society, categorizing people. Portugal is the seventh-worst country concerning stigma in Mental Health. There have been few improvements in reducing stigma over time, and there is a great need to create investigations and validate instruments that measure stigma in the population., Aim: This study aims to address the gaps in the level of studies and normative instruments that measure the stigma of the Portuguese population in the face of mental illness. It, therefore, aims to adapt and validate community attitudes toward people with mental illness (CAMI) culturally and examine its psychometric properties., Method: The 27-item version of CAMI was translated and back-translated into English, which was analyzed and evaluated by a panel of experts. A sociodemographic survey and CAMI were applied in an online format, in which participated 427 adults representing the Portuguese population in general. Finally, the reliability and validity of the instrument were analyzed., Results: CAMI showed positive values of reliability and validity but not optimal. The confirmatory factor analysis values satisfactory values that indicate good quality of fit: x 2 /df = 3.296; comparative fit index = 0.601; goodness of fit index = 0.817; and root mean square error of approximation = 0.073, indicates good quality of fit. Cronbach alpha was different for each factor, but it was positive. Spearman coefficient (ρ = -0.343) obtained a negative but consistent value., Conclusions: This study contributed to the achievement and validation of new measures to assess the stigma of the general population related to people with mental illness. We must continue to analyze this theme, complete the validation of this instrument, and understand the existing levels of stigma, its predominance in society, and the possible creation and implementation of new measures that support literacy in mental illness and anti-stigma., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of PBJ-Associação Porto Biomedical/Porto Biomedical Society. All rights reserved.)

Epitopes are portions of a protein that are recognized by antibodies. These small amino acid sequences represent a significant breakthrough in a branch of bioinformatics called immunoinformatics. Various software are available for linear B-cell epitope (BCE) prediction such as ABCPred , SVMTrip , EpiDope , and EpitopeVec ; a well-known BCE predictor is BepiPred-2.0. However, despite the prediction, there are several essential steps, such as epitope assembly, evaluation, and searching for epitopes in other proteomes. Here, we present EpiBuilder (https://epibuilder.sourceforge.io), a user friendly software that assists in epitope assembly, classifying and searching using input results of BepiPred-2.0. EpiBuilder generates several output results from these data and supports a proteome-wide processing approach. In addition, this software provides the following features: Chou & Fasman beta-turn prediction, Emini surface accessibility prediction, Karplus and Schulz flexibility prediction, Kolaskar and Tongaonkar antigenicity, Parker hydrophilicity prediction, N -glycosylation domains, and hydropathy. These information generate a unique topology for each epitope, visually demonstrating its characteristics. The software can search the entire epitope sequence in various FASTA files, and it allows to use BLASTP to identify epitopes that eventually have sequence variations. As an EpiBuilder application, we developed a epitope dataset from the protozoan Trypanosoma brucei gambiense , the gram-positive bacterium Clostridioides difficile , and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Virtual Reality (VR) has been identified as one of the most promising resources for developing empathy towards stigmatized groups as it allows individuals to experience a situation close to reality from another person's perspective. This quasi-experimental study aimed to examine the impact on empathy, knowledge, and attitudes towards people with schizophrenia of a VR simulation that reproduces the experience of psychotic symptoms while performing a cognitive task compared with watching a 2D video and, thus, how these experiences could reduce stigma towards people diagnosed with schizophrenia. The sample comprised of 102 higher education health students, distributed by the experimental and control groups. The impact of the program was measured by completing multiple questionnaires on levels of empathy, attitudes, and mental health knowledge. Both methods (VR and 2D video) were, to a certain extent, effective. However, VR was more effective at eliciting attitudes and knowledge change compared to the control group. These findings suggest that not only VR but also 2D videos could be interesting strategies to enhance empathy and improve attitudes towards people with schizophrenia in higher education health students., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Marques, Gomes Veloso, Araújo, Simões de Almeida, Correia, Pereira, Queiros, Pimenta, Pereira and Silva.)

The western mesoregion of the state of Santa Catarina (SC), Southern Brazil, was heavily affected as a whole by the COVID-19 pandemic in early 2021. This study aimed to evaluate the dynamics of the SARS-CoV-2 virus spreading patterns in the SC state from March 2020 to April 2021 using genomic surveillance. During this period, there were 23 distinct variants, including Beta and Gamma, among which the Gamma and related lineages were predominant in the second pandemic wave within SC. A regionalization of P.1-like-II in the Western SC region was observed, concomitant to the increase in cases, mortality, and the case fatality rate (CFR) index. This is the first evidence of the regionalization of the SARS-CoV-2 transmission in SC and it highlights the importance of tracking the variants, dispersion, and impact of SARS-CoV-2 on the public health systems.

Background: In comparison to organic mercury (MeHg), the environmental inorganic mercury (IHg) can be found in some skin-lightening cosmestics were considered "harmless" for a long time. However, recent studies have shown that long-term exposure to low doses of IHg may affect biological systems. Therefore, this study investigated the effects of IHg long-term exposure to the alveolar bone of adult rats., Methods: Adult Wistar rats were distributed in control and HgCl 2 exposed (0.375 mg/kg/day). After 45 days, the rats were euthanized and both blood and hemimandibles were collected. Total blood Hg levels were measured and both inorganic and organic components of the alveolar bone were determined through XRD and ATR-FTIR. The microstructure of the alveolar bone was assessed by using micro-CT and the morphometric analysis was performed by using stereomicroscopy., Results: Alterations in the physicochemical components of the alveolar bone of exposed animals were observed. The bone changes represented a tissue reaction at the microstructural level, such as bone volume increase. However, no significant dimensional changes (bone height) were observed., Conclusion: Exposure to IHg at this dose can promote microstructural changes and alteration in the organic and inorganic components in the alveolar bone., Competing Interests: The authors declare that they have no competing interests., (© 2022 Nunes et al.)

Mineralogical and technological characterization of ceramic raw materials from a new deposit located at Caxias city, Maranhão State-Brazil, was accomplished to determine their potential as raw materials for the ceramics industry in northeastern Brazil. The ceramic raw materials were collected from three different locations on the site and characterized by X-ray fluorescence (XRF), X-ray diffraction (XRD), differential thermal analysis (DTA), and thermogravimetry (TG). The XRF analysis of the fraction < 2 μm revealed that most samples had SiO 2 (35-51 wt%), Al 2 O 3 (19-29 wt%), Fe 2 O 3 (2-21 wt%), MgO (0.7 to 4.5 wt%) and K 2 O (0.9 to 5 wt%) as components. Quartz, kaolinite, illite, hematite and montmorillonite were the main mineral phases identified. DTA and TG analysis confirmed the mineral identification. The technological potential of the ceramic raw materials was investigated by: cation exchange capacity (CEC), plastic behavior (Atterberg Limits), linear shrinkage at 950 °C (LS F ), flexural strength (FS), apparent porosity (AP), water absorption (WA) and bulk density (BD). The main experimental results-WA (9-17%), AP (19-31%), FS (2.0-23 MPa), and the Atterberg limits-indicated that the ceramic raw materials investigated have high potential to be used to develop mass for red or structured ceramics, such as bricks and roof tiles.

Purpose: To evaluate the effect of hyperbaric oxygenation (HBO) on angiogenesis in random rat skin flaps, by immunoexpression of vascular endothelial growth factor A (VEGF-A)., Methods: Forty adult rats were divided into four groups: GE) epilated; GE/HBO) epilated subjected to HBO; GER) epilated submitted to dorsal skin flap; GER/HBO) epilated subjected to dorsal skin flap + HBO. HBO was performed with rats inside a chamber under atmosphere close to 100% oxygen and pressure of 2.4 absolute atmospheres, 2h per day during seven consecutive days. GE and GER groups were placed in the hyperbaric chamber without HBO. Then, under anesthesia, skin flaps were removed and separated into three portions relative to pedicle fixation. The samples were fixed in formalin and processed for paraffin embedding. Histological sections were submitted to immunohistochemistry for VEGF-A detection. The number of immunostained-blood vessels were counted under light microscopy., Results: GE and GE/HBO groups showed normal and similar skin morphology in the three flap portions. A fibrin-leukocyte crust, along with denatured collagen and intense leukocyte infiltrate, was mainly observed in the dermis of the medial and distal flap portions of GER group. Meanwhile, the GER/HBO group presented more regions with intact collagen and small areas of leukocyte infiltrate in the three flap regions. VEGF-A-immunostained blood vessels were largely seen in all regions of GE and GE/HBO groups, whereas no significant differences were found between these groups. A decrease in vascularization was noticed in GER and GER/HBO groups, which was more evident in the most distal portion of the flaps. However, the number of VEGF-A-immunostained blood vessels in GER/HBO group was significantly higher when compared to GER group., Conclusions: Hyperbaric oxygenation was associated with increased angiogenesis and improved viability of rat skin flaps.

Physical activity levels during the COVID-19 pandemic have been decreasing and this may be a risk factor for development of emotional eating and its associated factors. The aim of the study was to analyze the factors associated with emotional eating among individuals with different physical activity levels during the COVID-19 pandemic. Data relating to the pandemic on physical activity, emotional eating, sociodemographic data, perceptions about lifestyle habits, body satisfaction, and perceptions about eating habits and food consumption were collected. Factors associated with emotional eating in the group of active and inactive individuals were observed using multiple linear regression controlled for age, sex, BMI, and monthly income. Emotional eating for the active group was associated with perceived stress, body dissatisfaction, and increased consumption of sweets and desserts. In addition to these factors found among the active group, working or studying >8 h/day, sleep worsening, increased amount of food consumed, increased purchase of food through delivery, and increased vegetable consumption were also associated with emotional eating for the inactive group. These findings suggest a potential protective role of physical activity in the appearance of factors associated with emotional eating during the COVID-19 pandemic.

Background: Income inequality can negatively affect population health by increasing social stress and conflict, and reducing trust, public goods and healthcare access. However there is limited evidence from low and middle-income countries (LMICs) with high levels of inequality. This study investigates the association between income inequality, morbimortality and risk factors of non-communicable diseases (NCDs) in 26 Brazilian states from 2002 to 2017., Methods: Data was acquired for men and women from the Global Health Data Exchange, the Brazilian Institute of Geography and Statistics, and the Brazilian Ministry of Health, totalling 416 state-year observations. Disability-adjusted life years (DALYs) and risk factors of NCDs were the dependent variables. Gini Index was the main independent variable. Multivariate linear panel regressions were performed, controlling for state and time fixed effects, gross domestic product per capita, population ageing, poverty and access to healthcare., Findings: A 1% increase in the Gini Index was associated with increases in alcohol abuse (of 923•4 DALYs per 100,000 people, 95%CI 217•6 to 1629•0) and diabetes mellitus morbidity (of 893•3 DALYs per 100,000 people, 95%CI 127•7 to 1659•0), and decreases in morbidity from attention disorder (of -4•0 DALYs per 100,000 people, 95%CI -7•4 to -0•5) and autism spectrum (of -2•4 DALYs per 100,000 people, 95%CI -4•3 to -0•5). These associations were greater for men, further supported by associations with alcohol use as a risk factor., Interpretation: This study provides evidence from a highly unequal LMIC, Brazil, of negative associations between income inequality and NCDs, and the importance of addressing wider social determinants of health., Funding: This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brazil (CAPES) - Finance Code 001 as a Brazilian CAPES scholarship to AZD and by the São Paulo Research Foundation (FAPESP), grant 2020/15944-8 to RSG., Competing Interests: We declared no competing interests., (© 2021 The Author(s). Published by Elsevier Ltd.)

Clostridioides difficile BI/NAP1/ribotype 027 is an epidemic hypervirulent strain found worldwide, including in Latin America. We examined the genomes and exoproteomes of two multilocus sequence type (MLST) clade 2 C. difficile strains considered hypervirulent: ICC-45 (ribotype SLO231/UK[CE]821), isolated in Brazil, and NAP1/027/ST01 (LIBA5756), isolated during a 2010 outbreak in Costa Rica. C. difficile isolates were cultured and extracellular proteins were analyzed using high-performance liquid chromatography-tandem mass spectrometry. Genomic analysis revealed that these isolates shared most of the gene composition. Only 83 and 290 NAP1/027 genes were considered singletons in ICC-45 and NAP1/027, respectively. Exoproteome analysis revealed 197 proteins, of which 192 were similar in both strains. Only five proteins were exclusive to the ICC-45 strain. These proteins were involved with catalytic and binding functions and indirectly interacted with proteins related to pathogenicity. Most proteins, including TcdA, TcdB, flagellin subunit, and cell surface protein, were overrepresented in the ICC-45 strain; 14 proteins, including mature S-layer protein, were present in higher proportions in LIBA5756. Data are available via ProteomeXchange with identifier PXD026218. These data show close similarity between the genome and proteins in the supernatant of two strains with hypervirulent features isolated in Latin America and underscore the importance of epidemiological surveillance of the transmission and emergence of new strains.

Background: To compare the maxillary dentoalveolar changes of patients treated with three distalization force systems: Jones Jig, Distal Jet and First Class appliances, using digitized models., Material and Methods: The retrospective sample comprised 118 digitized models of 59 patients with Class II malocclusion divided into three groups: Group 1 consisted of 22 patients treated with the Jones Jig appliance; Group 2 consisted of 20 patients treated with the Distal Jet, and Group 3 comprised 17 patients treated with the First Class appliance. Pretreatment and post-distalization plaster models of all patients were digitized and evaluated with OrthoAnalyzerTM software. The pretreatment and post-distalization variables regarding sagittal, rotational and transverse changes were compared by the One-way Analysis of Variance (ANOVA) and Kruskal-Wallis tests, depending on normality., Results: All appliances presented similar amounts of distalization. The Distal Jet appliance promoted significantly smaller mesial displacement of premolars and greater expansion of posterior teeth. The First Class presented the smallest rotation of the maxillary molars and treatment time., Conclusions: The distalizers were effective in correcting Class II molar relationship, however, a palatal force seems to provide fewer undesirable effects. Additionally, the degree of rotation and expansion was associated with the side of force application. Key words: Malocclusion, Angle Class II, Orthodontics, Corrective, Distalizers., Competing Interests: Conflicts of interest The authors declare that no conflict of interest exist., (Copyright: © 2021 Medicina Oral S.L.)

Background: The metabolic syndrome (MetS) is correlated with disorders of the reproductive system, such as the polycystic ovary syndrome (PCOS). While consumption of a diet rich in carbohydrates is linked to the development of MetS, it is still unclear if this diet leads to ovarian dysfunction and PCOS., Objectives: We investigated the influence of a high-sucrose diet (HSD) on the ovarian milieu of Wistar rats and studied the correlation between high consumption of sugary drinks and the prevalence of PCOS in women., Methods: Wistar rats were given a standard laboratory diet (CTR, 10% sucrose, n = 8) or HSD (HSD, 25% sucrose, n = 8) from postnatal day 21 to 120. Animals were evaluated weekly to calculate food intake, feed efficiency and weight gain. Both onset of puberty and estrous cycle were monitored. Metabolic serum biochemistry, organ morphometry and ovarian histology were performed upon euthanasia. In parallel, a fixed-effects multiple linear regression analysis was performed using data from Brazilian states (459 state-year observations) to test the correlation between the consumption of sugar-sweetened beverages (surrogate for HSD intake) and the prevalence of PCOS (surrogate for ovarian dysfunction)., Results: HSD animals showed increased adipose tissue accumulation, hyperglycaemia and insulin resistance when compared to CTR. Interestingly HSD rats also entered puberty earlier than CTR. Moreover, ovaries from HSD animals had an increased number of atretic antral follicles and cystic follicles, which were correlated with the hypertrophy of periovarian adipocytes. Finally, there was a positive correlation between the intake of sugary drinks and prevalence of PCOS in women of reproductive age., Conclusions: HSD ingestion leads to ovarian dysfunction in rats and could be correlated with PCOS in women, suggesting these alterations could lead to public health issues. Therefore, we reinforce the deleterious impact of HSD to the ovarian system and suggest that the reduction of added sugars intake could be beneficial to ovarian health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 de Melo, Soares, Costa, Benevides, Vale, Paes and Gaspar.)

Background: Protein disulphide isomerase (PDI) and NADPH oxidase 1 (Nox-1) regulate platelet function and reactive oxygen species (ROS) generation, suggesting potentially interdependent roles. Increased platelet reactivity and ROS production have been correlated with cardiometabolic disease risk factors., Objectives: To establish whether PDI and Nox-1 cooperate to control platelet function., Methods: Immunofluorescence microscopy was utilised to determine expression and localisation of PDI and Nox-1. Platelet aggregation, fibrinogen binding, P-selectin exposure, spreading and calcium mobilization were measured as markers of platelet function. A cross-sectional population study ( n = 136) was conducted to assess the relationship between platelet PDI and Nox-1 levels and cardiometabolic risk factors., Results: PDI and Nox-1 co-localized upon activation induced by the collagen receptor GPVI. Co-inhibition of PDI and Nox-1 led to additive inhibition of GPVI-mediated platelet aggregation, activation and calcium flux. This was confirmed in murine Nox-1 -/- platelets treated with PDI inhibitor bepristat, without affecting bleeding. PDI and Nox-1 together contributed to GPVI signalling that involved the phosphorylation of p38 MAPK, p47phox, PKC and Akt. Platelet PDI and Nox-1 levels were upregulated in obesity, with platelet Nox-1 also elevated in hypertensive individuals., Conclusions: We show that PDI and Nox-1 cooperate to control platelet function and are associated with cardiometabolic risk factors.

Background: Coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 strain, was first identified in late 2019 in China. The outcomes of patients affected by the virus can worsen, developing acute respiratory failure and other serious complications, especially in older individuals and people with obesity and comorbidities. Thus, obese patients tend to have a more severe course of COVID-19. Thus, this review aims to synthesize the evidence in the literature that associates COVID-19 and the severity of clinical outcomes in infected obese patients., Methods: This protocol was designed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols Statement. Scientific and gray literature will be systematically selected from PubMed/MEDLINE, Latin American Literature in Health Sciences, Online Scientific Electronic Library, Scopus, ScienceDirect, Web of Science, Embase, and Cochrane. The selection of articles will be limited to studies published in English, Portuguese, and Spanish from December 2019 onwards. The main clinical outcomes will be clinical severity in obese patients with COVID-19 as tachypnea (respiratory rate, ≥ 30 breaths per minute), hypoxemia (oxygen saturation, ≤ 93%), the ratio of the partial pressure of arterial oxygen to fraction of inspired oxygen (< 300), lung infiltrate (> 50% of the lung field involved within 24-48 h), diagnosis of the severe acute respiratory syndrome, need of invasive mechanical ventilation, and mortality. Two reviewers will independently screen all citations, full-text articles, and abstract data. Selection bias will be minimized by excluding studies published before December 2019. Conflicts will be resolved through a third reviewer and consensus-building. Moreover, findings will be reported using narrative synthesis and tabulation of the summaries., Discussion: Given the need for early detection of the possible implications and treatment for patients with obesity diagnosed with COVID-19, the scoping review will be useful to capture the state of the current literature, identify the gaps, and make recommendations for future research for directing the conduct and optimization of therapies in these patients by the multiprofessional teams., Systematic Review Registration: Open Science Framework: https://osf.io/xrkec.