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Rickettsiosis is a disease caused by bacteria belonging to the genus Rickettsia, and is a potentially fatal zoonotic disease of great medical and veterinary importance. Given the urgent need to develop new diagnostic methods for detecting this disease, the present review aimed to evaluate the number of publications dedicated to the identification of Rickettsia spp. in human samples using molecular methods, such as polymerase chain reaction and its variations. To this end, a bibliographical survey covering articles published in the past ten years was conducted using the PudMed platform with the keywords "spotted fever" and "Rickettsia," both combined with "diagnosis." A growing number of publications in this area reflects an increasing interest in research, especially since 2015. From 2015 to February 2024, several promising results were tested and many studies were able to detect the genetic sequences of interest. Therefore, the absence of a standard diagnosis method highlights the critical need for developing an effective technique capable of accurately detecting the etiological agent and ensuring accurate diagnosis of the disease.

Background: Human immunodeficiency virus (HIV) infection is a health problem in Brazil and worldwide. Without treatment, the infection can progress to Acquired Immunodeficiency Syndrome (AIDS), with a high mortality potential. The objective of this study was to analyze the time trend of AIDS mortality in Brazil, macro-regions, federal units and their respective capitals, from 2012 to 2022., Methods: This is a time-series study of all AIDS deaths in Brazil from 2012 to 2022. The study included the annual number of deaths and the crude and standardized mortality rates. The Joinpoint regression model was used for the time analysis of the standardized rates. Annual percentage change (APC) and average annual percentage change (AAPC) were calculated. A 95% confidence interval (CI) and a 5% significance level were used., Results: During the period analyzed, 128,678 AIDS deaths were recorded in Brazil, with a crude mortality rate of 6.3/100,000 and a standardized mortality rate of 5.3/100,000. From 2012 to 2020, three regions showed a declining trend in AIDS mortality: Central-West (AAPC - 2.3%; 95%CI -4.3 to -0.21; p = 0.03), Southeast (AAPC - 5.6%; 95%CI -6.8 to -4.0; p < 0.001), and South (AAPC - 4.4%; 95%CI -5.27 to -3.6; p < 0.001). There was also a downward trend in 10 states and 10 capitals. There was an increase in the number of deaths from 2020 onwards in the North, Northeast and Southeast regions compared to 2019., Conclusion: There was a downward trend in AIDS mortality from 2012 to 2020 and an upward trend from 2020 to 2022. The regional differences observed could reflect the social disparities that exist in Brazil. In addition, the Covid-19 pandemic has had an impact on the process of dealing with HIV in Brazil., (© 2024. The Author(s).)

Cocoa beans contain a variety of nutritional compounds and are rich in biologically active substances. The aim of this study was to utilize cocoa nibs (roasted and unroasted) as the main ingredient in the development of an attractive and convenient product. The produced nibs were analyzed for total phenolics, flavonoids, and antioxidant capacity using DPPH, ABTS, and FRAP methods. The primary phenolic compounds and methylxanthines were analyzed by LC/MS. Subsequently, cereal bars were developed, including a control sample (without nibs) and five formulations containing 41% nibs, using various proportions of roasted and unroasted nibs. The influence of the origin of the beans on the product characteristics was also evaluated. The results showed that the roasting process led to a reduction in epicatechin, caffeine, and caffeic acid. Furthermore, the reduction in total phenolics, flavonoids, and antioxidant capacity after roasting was more pronounced in beans from Bahia compared to those from Espírito Santo. Regarding the cereal bars, the results demonstrated that using cocoa from Bahia, the formulation with a higher proportion of unroasted nibs (F80) significantly increased the total phenolic content (1968.85 mg of gallic acid/100 g) and total flavonoids (39.26 mg of quercetin/100 g). This initial study suggests that the use of cocoa nibs as a functional ingredient in cereal bars may be a viable and advantageous option for creating a product with greater antioxidant potential.

The skin is a tissue constantly exposed to the risk of damage, such as cuts, burns, and genetic disorders. The standard treatment is autograft, but it can cause pain to the patient being extremely complex in patients suffering from burns on large body surfaces. Considering that there is a need to develop technologies for the repair of skin tissue like 3D bioprinting. Skin is a tissue that is approximately 1/16 of the total body weight and has three main layers: epidermis, dermis, and hypodermis. Therefore, there are several studies using cells, biomaterials, and bioprinting for skin regeneration. Here, we provide an overview of the structure and function of the epidermis, dermis, and hypodermis, and showed in the recent research in skin regeneration, the main cells used, biomaterials studied that provide initial support for these cells, allowing the growth and formation of the neotissue and general characteristics, advantages and disadvantages of each methodology and the landmarks in recent research in the 3D skin bioprinting., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Invasive infections caused by non-albicans Candida are increasing worldwide. However, there is still a lack of information on invasive candidiasis (IC) in the pediatric setting, including susceptibility profiles and clonal studies. We investigated the clinical, epidemiologic, and laboratory characteristics of IC, possible changes in antifungal susceptibility profiles over time, and the occurrence of clonality in our tertiary children's hospital. We analyzed 123 non-duplicate Candida isolates from sterile sites of pediatric patients in a tertiary hospital in southern Brazil, between 2016 and 2021. Data on demographics, comorbidities, and clinical outcomes were collected. Candida species distribution, antifungal susceptibility profiles, biofilm production, and molecular epidemiology of isolates were assessed using reference methods. The range of IC incidence was 0.88-1.55 cases/1000 hospitalized patients/year, and the IC-related mortality rate was 20.3%. Of the total IC cases, 42.3% were in patients aged < 13 months. Mechanical ventilation, parenteral nutrition, and intensive care unit (ICU) admission were common in this group. In addition, ICU admission was identified as a risk factor for IC-related mortality. The main site of Candida spp. isolation was blood, and non-albicans Candida species were predominant (70.8%). No significant clonal spread was observed among isolates of the three most commonly isolated species, and 99.1% of all isolates were biofilm producers. Non-albicans Candida species were predominant in this study. Notably, clonal expansion and emergence of antifungal drug resistance were not observed in our pediatric setting., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

The objective of this systematic review (SR) was to select studies on the use of gene editing by CRISPR technology related to plant resistance to biotic stresses. We sought to evaluate articles deposited in six electronic databases, using pre-defined inclusion and exclusion criteria. This SR demonstrates that countries such as China and the United States of America stand out in studies with CRISPR/Cas. Among the most studied crops are rice, tomatoes and the model plant Arabidopsis thaliana . The most cited biotic agents include the genera, Xanthomonas, Manaporthe, Pseudomonas and Phytophthora . This SR also identifies several CRISPR/Cas-edited genes and demonstrates that plant responses to stressors are mediated by many complex signaling pathways. The Cas9 enzyme is used in most articles and Cas12 and 13 are used as additional editing tools. Furthermore, the quality of the articles included in this SR was validated by a risk of bias analysis. The information collected in this SR helps to understand the state of the art of CRISPR/Cas aimed at improving resistance to diseases and pests to understand the mechanisms involved in most host-pathogen relationships. This SR shows that the CRISPR/Cas system provides a straightforward method for rapid gene targeting, providing useful information for plant breeding programs.

We describe the geographical variation in tree species composition across Amazonian forests and show how environmental conditions are associated with species turnover. Our analyses are based on 2023 forest inventory plots (1 ha) that provide abundance data for a total of 5188 tree species. Within-plot species composition reflected both local environmental conditions (especially soil nutrients and hydrology) and geographical regions. A broader-scale view of species turnover was obtained by interpolating the relative tree species abundances over Amazonia into 47,441 0.1-degree grid cells. Two main dimensions of spatial change in tree species composition were identified. The first was a gradient between western Amazonia at the Andean forelands (with young geology and relatively nutrient-rich soils) and central-eastern Amazonia associated with the Guiana and Brazilian Shields (with more ancient geology and poor soils). The second gradient was between the wet forests of the northwest and the drier forests in southern Amazonia. Isolines linking cells of similar composition crossed major Amazonian rivers, suggesting that tree species distributions are not limited by rivers. Even though some areas of relatively sharp species turnover were identified, mostly the tree species composition changed gradually over large extents, which does not support delimiting clear discrete biogeographic regions within Amazonia., (© 2024. The Author(s).)

Background and Objective: Buprenorphine is an opioid drug indicated for the management of severe and persistent pain. The buprenorphine transdermal patch provides a non-invasive method of rate-controlled drug release, ensuring constant and predictable drug plasma levels over an extended period. This study aimed to assess the bioequivalence, skin adhesion non-inferiority, and tolerability of two buprenorphine transdermal patches to meet the regulatory requirements for the registration of a generic product in Brazil. Methods: A randomized, single-dose, two-period, two-sequence crossover trial was performed involving healthy subjects of both genders. The subjects received a single dose of either the test formulation or the reference formulation (Restiva ® ), separated by a 29-day washout period. For pharmacokinetic analysis, blood samples were collected up to 12 days post-dose and quantified using a validated bioanalytical method. Skin adhesion was assessed over a 7-day period (dosing interval) following patch application. Seventy-six subjects were enrolled and fifty-two completed the study. Results and Conclusion: The 90% confidence intervals for Cmax, AUC 0-t , and partial AUCs were within the acceptable bioequivalence limits of 80 to 125%. Adhesion comparison showed the non-inferiority of the test formulation. Based on ANVISA's regulatory requirements, the test and reference formulations were considered bioequivalent and could be interchangeable in clinical practice.

Tubular aggregates (TA) are skeletal muscle structures that arise from the progressive accumulation of sarcoplasmic reticulum proteins, mainly with aging. Muscle regeneration plays a role in TA formation. TA quantification may aid in the evaluation of muscle aging and genetic muscle degeneration. TA form over time, appears in aging in normal murine muscles. TA reduction in injured conditions may be due to the degeneration-regeneration process in muscles, with loss of damaged muscle fibers and formation of new fibers that do not present protein aggregation. These new regenerated fibers do not improve the function capacity of the aged muscle. Here, we present a methodology for labeling and identifying tubular aggregates in muscle fibers and also the standardization of its quantification., (© 2024. Springer Science+Business Media, LLC.)

Procyanidins (PCs) have emerged as agents with potential antimicrobial and antibiofilm activities, although their mechanisms of action and structure-activity relationships remain poorly understood. This review assessed the potential mechanisms of action and applications of these compounds to explore these aspects. Studies on the antimicrobial properties of PCs suggest that they are involved in osmotic imbalance, DNA interactions and metabolic disruption. Although less studied, their antibiofilm activities include antiadhesive effects and the modulation of mobility and quorum sensing. However, most research has used uncharacterized plant extracts for in vitro assays, limiting the understanding of the structure-activity relationships of PCs and their in vivo mechanisms. Clinical trials on the antimicrobial and antibiofilm properties of PCs have not clarified these issues due to nonstandardized methodologies, inadequate chemical characterization, and the limited number of studies, preventing a consensus and evaluation of the in vivo effects. Additionally, patent analysis revealed that technological developments in the antimicrobial and antibiofilm uses of PCs are concentrated in health care and dental care, but new biotechnological uses are emerging. Therefore, while PCs are promising antimicrobial and antibiofilm compounds, further research into their chemical structures and mechanisms of action is crucial for evidence-based applications in biotechnology and health care.

Risk factors for the development of severe COVID-19 include several comorbidities, but age was the most striking one since elderly people were disproportionately affected by SARS-CoV-2 infection. Among the reasons for this markedly unfavorable response in the elderly, immunosenescence and inflammaging appear as major drivers of this outcome. A finding that was also notable was that hospitalized patients with severe COVID-19 have an accumulation of senescent T cells, suggesting that immunosenescence may be aggravated by SARS-CoV-2 infection. The present work was designed to examine whether these immunosenescence changes are characteristic of COVID-19 and whether it is dependent on disease severity using cross-sectional and longitudinal studies. Our cross-sectional data show that COVID-19, but not other respiratory infections, rapidly increased cellular senescence and exhaustion in CD4 and CD8 T cells during early infection. In addition, longitudinal analyses with patients from Brazil and Portugal provided evidence of increased frequencies of senescent and exhausted T cells over a 7-d period in patients with mild/moderate and severe COVID-19. Altogether, the study suggests that accelerated immunosenescence in CD4 and especially CD8 T-cell compartments may represent a common and unique outcome of SARS-CoV2 infection., Competing Interests: Conflict of interest statement. No conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Cyanoacrylate-based adhesives are widely used in wound closure, providing good cosmetic results and little discomfort. However, reports in the literature are found about negative effects that include the release of cytotoxic chemicals during biodegradation. In this study, we sought to evaluate and compare the effectiveness of four cyanoacrylate-based adhesives on the closure of skin incisions in Rattus norvegicus . The animals ( n = 140) were divided into five groups of 28 animals each according to the wound closure technique: G1 and G2 (n-2-ethyl-cyanoacrylate); G3 (n-2-butyl-cyanoacrylate); G4 (n-2-octyl-cyanoacrylate); and G5 (5 nylon stitches). Midline incisions measuring 5.0 cm in length were created and closed using the different materials evaluated, and on D3, D7, D14, and D21, tensiometric and histopathological analyses were performed. Shorter wound closure and adhesion times were observed in G4 animals. At D3 and D7, G5 presented greater tensiometric resistance in the animals of G5, with a decrease in D14 and D21 compared to the other groups. On the other hand, the wounds of G3 and G4 were more resistant in D14 and D21, reaching maximum resistance values. Polymorphonuclear and mononuclear cells are more prevalent and more granulation tissue was observed in G5. The deposition of type III collagen was more evident in G5, whilst there was no difference in the amount of type I collagen in any of the groups treated with cyanoacrylate adhesives. Larger areas stained positive for VEGF-α in G2 and smaller areas in G4, with peaks at D7 and D14. In general, cyanoacrylate adhesives cause less intense inflammatory reactions, resulting in shorter healing times when compared to nylon sutures.

Background: Wheelchair racing is a traditional modality of Paralympic athletics. In general, racing wheelchairs are customized according to the athletes' anthropometric conditions, based on pre-established dimensions according to the manufacturer's manual. Usually, athletes choose the dimensions for their new sports wheelchairs, and when they are delivered for use, they often have problems due to incorrect body adjustments., Purpose: To develop a new customization methodology that is made possible through a new multi-adjustable racing wheelchair prescription equipment (RWPE) for athletics. This equipment performs several measurements and adjustments according to the athlete's anthropometric characteristics, evaluating the best-fit athlete to obtain better performance in the personalized wheelchair., Materials and Methods: Customizing racing wheelchairs is based on anthropometric measurements of the individual and specific ergonomic adjustments for better performance and safety. The RWPE is a multi-adjustment device composed of modules that use measuring instruments to guarantee maximum precision and accuracy of the assessments. This project's innovation is associated with the multi-regulation equipment itself and a conventional process of manufacturing a racing wheelchair through an online form. The RWPE has a robust and rigid structure for conducting race-track experimental tests., Results and Conclusions: The experimental tests allowed the equipment to be validated regarding safety, comfort, and prescription methodology. A high-performance athlete validated the equipment and prescription methodology, and as a result, a new version of a parameterized wheelchair was also developed using the prescription methodology. A comparison between prescription tests showed better athlete performance regarding estimated average power, considering dimensions optimized through RWPE.

Products derived from the latex of Euphorbia tirucalli were obtained through hydrolysis and column chromatography, resulting in products rich in triterpenes, ingenol 3-esters (I3E), and other derivatives from hydrolysed latex. These products underwent evaluation for their cytotoxic activity against gastric adenocarcinoma cells (AGS). Triterpene derivatives were synthesised, and the selectivity of each product was assessed. The results were compared with the previously described crude latex. Triterpenes and I3E were analysed in silico for their affinity with the active site of PKCδC1b. The hydrolysed latex (free of I3E) exhibited high cytotoxicity, albeit with reduced selectivity. Triterpenes and acetylated triterpenes were more cytotoxic than I3E, although the latter showed greater selectivity. Euphol benzoates and cinnamates showed no cytotoxicity. I3E demonstrated high affinity for the PKCδC1b. In summary, triterpenes exhibited higher cytotoxicity against AGS cells, while I3E displayed greater selectivity. Hydrolysed latex shows promise as a potential candidate for future gastric cancer treatment.

Introduction: The efficient and effective management of gastrostomy patients should be based on best practices., Objective: This project aimed to improve gastrostomy management in a semi-intensive care unit of a private hospital in São Paulo, Brazil., Methods: This study followed the JBI Evidence Implementation Framework. The JBI approach to evidence implementation is grounded in an audit, feedback, and re-audit strategy. A baseline audit was conducted to measure current practices against recommended best practices. Feedback from the audit was used to identify barriers and design implement strategies to improve practice. A follow-up audit was then conducted to measure changes in compliance with best practices., Results: The baseline audit involved an evaluation of 33 nurses and 90 nursing technicians, as well as 10 gastrostomy patients. The follow-up audit evaluated 37 nurses and 80 nursing technicians, as well as 10 gastrostomy patients. The follow-up audit revealed that compliance increased to 90% for three of the eight criteria. For the remainder, it varied between 20% and 50%., Conclusion: The baseline audit and feedback strategy led to improved compliance in five of the eight criteria. Future audits will be necessary to maintain these results., Spanish Abstract: http://links.lww.com/IJEBH/A259., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the University of Adelaide, JBI.)

Research Background: In a country where millions of people have nutritional needs, innovative ways of producing food from commonly wasted agro-industrial by-products, can be an important alternative for the production of fermented beverages. In light of this, the aim of this study is to evaluate the potential of fruit by-products from acerola, guava and tamarind for the production of fermented beverages., Experimental Approach: Physicochemical and microbiological parameters, total antioxidant capacity and fermentation kinetics were investigated during the first (at 0, 48, 72, 96 and 168 h) and second fermentation (at 0 and 24 h). The acid profile of fermented beverages was determined by chromatography, and the sensory profile was determined by consumer acceptance test., Results and Conclusions: Physicochemical parameters of all formulations complied with current legislation and were of satisfactory microbiological quality. The reslts of fermentation kinetics showed that both pH and soluble solids content decreased - with an average final pH of 3.12, 2.85 and 2.78 for the acerola, guava and tamarind formulations, respectively - while acidity increased with final values of 0.94, 0.75 and 1 % for the same formulations. Of all formulations, tamarind had the highest total soluble solids content (8.17 g/100 g), and acerola had the highest antioxidant potential determined as Trolox equivalents ((20.0±0.8) μM/g). Organic acids were found in all samples, with mainly glucuronic acid detected in the kombucha beverages. All formulations showed satisfactory sensory acceptability, although the results were better for guava. The fruit by-products can be used as raw materials for the development of alternative kombucha beverages., Novelty and Scientific Contribution: As consumers are increasingly selective in their food choices, the development of food products with high nutritional value has increased significantly in recent years. New types of fermentable beverages such as kombucha - using tropical fruit by-products to enhance their chemical composition, sensory properties and nutritional value - have created new opportunities for beverage consumption and offer greater health benefits than the traditional version, where only Camellia sinensis is used. The promotion of these co-products and their respective beverages is an excellent opportunity for sustainability and their commercialisation., Competing Interests: CONFLICT OF INTEREST There is no conflict of interest., (Authors.)

Major tailings dam failures have occurred recently around the world and resulted in severe environmental impacts, such as metal contamination. Manganese is a metal highly associated with mining activities, largely detected in mining dam collapses. This metal is considered necessary for different organisms, but it can be toxic and cause oxidative stress and genetic damage in fishes. In this study, we investigated the toxic effects of manganese on Astyanax lacustris, by exposing the fish individually to different concentrations of this metal (2.11, 5.00, and 10.43 mg/L) for 96 h. To assess the effects of manganese, we used biochemical biomarkers (glutathione S-transferase, catalase, and acetylcholinesterase enzyme activity) and the manganese bioaccumulation in different tissues (liver and gills). The obtained data showed that only at concentrations of 5.00 mg/L and 10.43 mg/L the activity of glutathione S-transferase differed significantly. Additionally, the acetylcholinesterase activity in the brain tissue was inhibited. The highest level of manganese bioaccumulation was observed in the liver and branchial tissue. Overall, we concluded that high concentrations of manganese may cause physiological changes in Astyanax lacustris., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: The study aimed to assess the impact of diphenyliodonium hexafluorophosphate (DPI) on the physicochemical properties of experimental resin composites (ECRs) featuring reduced concentrations of camphorquinone (CQ)/amine., Methods: Five concentrations of CQ (0.125, 0.25, 0.5, 0.75, and 1 mol%) with dimethylaminoethyl amine benzoate (EDAB) in a 1:2 mol% ratio (CQ:EDAB) were incorporated into a 50:50 mass% monomer blend of bisphenol glycidyl methacrylate (BisGMA) and triethyleneglycol dimethacrylate (TEGDMA). An additional 5 groups with the same CQ:EDAB concentrations had 0.5 mol% DPI added. Each resin group contained 60 wt% of 0.7 µm barium-alumino-silicate glass. Light transmission (n = 3), real-time degree of polymerization (n = 3), temperature change during polymerization (n = 5), polymerization shrinkage strain (n = 3), flexural strength, and modulus (n = 12), as well as water sorption and solubility (n = 5), were evaluated. Data were analyzed using two-way ANOVA and Tukey's post-hoc test (α = 0.05)., Results: Light transmission was reduced in groups containing 0.125 and 0.25 mol% of CQ without DPI. DPI increased temperature, degree and rate of polymerization, despite the reduction in CQ/amine concentration. Additionally, there was an increase in polymerization shrinkage strain, flexural strength and modulus, and a reduction in water sorption and solubility in ECRs with DPI, even with lower concentrations of CQ/EDAB., Significance: DPI improved the assessed properties of composites across various concentrations of CQ/EDAB, showing the benefit of reducing the quantity of CQ used without compromising the properties and curing of the resin composites., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: to investigate the influence of the leukoreduction moment (preor post-storage) of blood components on the clinical outcomes of patients transfused in the emergency department., Methods: retrospective cohort study of patients aged 18 years or older who received preor post-storage leukoreduced red blood cell or platelet concentrate in the emergency department and remained in the institution for more than 24 hours. A generalized mixed-effects model was applied in the analyses., Results: in a sample of 373 patients (63.27% male, mean age 54.83) and 643 transfusions (69.98% red blood cell), it was identified that the leukoreduction moment influenced the length of hospital stay (p<0.009), but was not dependent on the transfused blood component (p=0.124). The leukoreduction moment had no effect (p>0.050) on transfusion reactions, healthcare-associated infections, or mortality., Conclusions: patients who received pre-storage leukoreduced blood components in the emergency department had a shorter length of hospital stay.

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.

Objectives: To describe the historical series of admissions to the Intensive Care Unit of older adults with femoral fractures, and verify the association between age and injury characteristics and treatment, nursing workload, severity, and clinical evolution in the unit., Method: Retrospective cohort of 295 older adults (age ≥60 years) admitted to the Intensive Care Unit of a hospital in São Paulo, between 2013 and 2019, and who presented with a femur fracture as the main cause of hospitalization. Variables regarding demographic characteristics, cause, and type of fracture, treatment provided, severity, nursing workload, and medical outcome of patients were analyzed. The Shapiro-Wilk, Wilcoxon-Mann-Whitney, Kruskal-Wallis tests and Pearson correlation were applied., Results: There was an increase in older adults admission to the Intensive Care Unit from 2017 on. Female patients with distal femur fractures who died in the Intensive Care Unit had significantly (p < 0.05) higher median age than men, patients with shaft or proximal femur fractures, and survivors., Conclusion: The study findings highlight essential information for structuring care for older adults with femoral fractures who require intensive care.

Cisplatin (CP) is a chemotherapy drug widely prescribed to treat various neoplasms. Although fundamental for the therapeutic action of the drug, its cytotoxic mechanisms trigger adverse effects in several tissues, such as the kidney, liver, and heart, which limit its clinical use. In this sense, studies point to an essential role of damage to nuclear and mitochondrial DNA associated with oxidative stress, inflammation, and apoptosis in the pathophysiology of tissue injuries. Due to the limitation of effective preventive and therapeutic measures against CP-induced toxicity, new strategies with potential cytoprotective effects have been studied. Therefore, this article is timely in reviewing the characteristics and main molecular mechanisms common to renal, hepatic, and cardiac toxicity previously described, in addition to addressing the main validated strategies for the current management of these adverse events in clinical practice. We also handle the main promising antioxidant substances recently presented in the literature to encourage the development of new research that consolidates their potential preventive and therapeutic effects against CP-induced cytotoxicity., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Therapeutic anticoagulation showed inconsistent results in hospitalized patients with COVID-19 and selection of the best patients to use this strategy still a challenge balancing the risk of thrombotic and hemorrhagic outcomes. The present post-hoc analysis of the ACTION trial evaluated the variables independently associated with both bleeding events (major bleeding or clinically relevant non-major bleeding) and the composite outcomes thrombotic events (venous thromboembolism, myocardial infarction, stroke, systemic embolism, or major adverse limb events). Variables were assessed one by one with independent logistic regressions and final models were chosen based on Akaike information criteria. The model for bleeding events showed an area under the curve of 0.63 (95% confidence interval [CI] 0.53 to 0.73), while the model for thrombotic events had an area under the curve of 0.72 (95% CI 0.65 to 0.79). Non-invasive respiratory support was associated with thrombotic but not bleeding events, while invasive ventilation was associated with both outcomes (Odds Ratio of 7.03 [95 CI% 1.95 to 25.18] for thrombotic and 3.14 [95% CI 1.11 to 8.84] for bleeding events). Beyond respiratory support, creatinine level (Odds Ratio [OR] 1.01 95% CI 1.00 to 1.02 for every 1.0 mg/dL) and history of coronary disease (OR 3.67; 95% CI 1.32 to 10.29) were also independently associated to the risk of thrombotic events. Non-invasive respiratory support, history of coronary disease, and creatinine level may help to identify hospitalized COVID-19 patients at higher risk of thrombotic complications.ClinicalTrials.gov: NCT04394377., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: This study aimed to determine the median age at natural menopause and analyze lifestyle, anthropometric, and dietary characteristics associated with the age at natural menopause among Brazilian women., Methods: This cross-sectional study involved 2,731 women 50 years and over, drawn from the baseline of the Brazilian Longitudinal Study of Aging (ELSI-Brazil, 2015/16). Nonparametric Kaplan-Meier cumulative survivorship estimates were used to assess the median timing of natural menopause. Cox proportional hazards regression models were employed to estimate the associations between age at natural menopause and exposure variables., Results: The overall median age at natural menopause was 50 years. In the adjusted Cox model, current smoking (hazard ratio [HR], 1.11; 95% CI, 1.01-1.23) and underweight (HR, 1.34; 95% CI, 1.12-1.61) were associated with earlier natural menopause. Conversely, performing recommended levels of physical activity in the last week (HR, 0.88; 95% CI, 0.80-0.97), being overweight (HR 0.86; 95% CI, 0.74-0.99), and adhering to two or three healthy eating markers (HR, 0.80; 95% CI, 0.66-0.97; HR, 0.76; 95% CI, 0.61-0.94, respectively) were associated with later age at natural menopause. Binge drinking and waist circumference were not associated with age at natural menopause., Conclusions: Lifestyle, anthropometric, and dietary characteristics are significant factors that affect the age at natural menopause. Our findings can contribute to public policies targeted at Brazilian women's health., Competing Interests: Financial disclosure/conflicts of interest: None reported., (Copyright © 2024 by The Menopause Society.)

Objective: This case-control study evaluated the association of sociodemographic profile, mental health disorders and oral health-related quality of life (OHRQoL) with periodontitis., Methods: Patients with periodontitis (PP, n = 50) and control patients (CP, n = 50) were allocated into 2 groups after a complete periodontal examination. Data collection included age, sex, marital status, education and application of 2 questionnaires: Hospital Anxiety and Depression Scale for the diagnosis of anxiety/depression and Impact Profile on Oral Health (OHIP-14) for classification of well-being. An adjusted multiple binary logistic regression analysis was performed to assess the effect of all studied covariates on periodontitis., Results: The results show that mean clinical attachment loss and periodontal probing depth were 5.92 (SD = 0.42) and 5.46 (SD = 0.78) in PP and 0.00 (SD = 0.00) and 2.85 (SD = 0.23) in CP, respectively (p < 0.001). The regression analysis demonstrated a significant effect on periodontitis for age (OR = 1.13; p < 0.0001; 95% CI: 1.07-1.20), with the PP having more people aged 50 years or older than CP, anxiety (OR = 1.25; p = 0.020; 95% CI: 1.04-1.50) and OHIP-14 (OR = 1.17; p < 0.0001; 95% CI: 1.08-1.226)., Conclusions: The findings showed a positive association between anxiety, OHRQoL and age with periodontitis., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Several studies have investigated the correlation between the effects of different surgical treatments and laboratory exams for schistosomal portal hypertension, especially concerning portal system thrombosis. The etiopathogenic factors of this thrombosis are not fully understood. In this study, the correlation between surgical treatment for schistosomal portal hypertension and the occurrence of postoperative portal system thrombosis was investigated., Methods: A total of 61 patients who underwent surgical treatment for schistosomal portal hypertension were distributed into four groups: Patients in Group 1 (n=12) underwent portal variceal disconnection associated with splenic artery ligation and spleen preservation. Patients in Group 2 (n=20) underwent portal variceal disconnection and total splenectomy. Patients in Group 3 (n=20) underwent portal variceal disconnection with subtotal splenectomy, preserving the upper splenic pole supplied by the splenogastric vessels. Patients in Group 4 (n=9) underwent portal variceal disconnection with total splenectomy and autogenous splenic implants on the greater omentum. Late postoperative portal vein thrombosis was diagnosed using Doppler ultrasound., Results: Over the 10-year follow-up, portal vein thrombosis occurred in 26 operated patients (42.6%), with no significant difference observed among the four surgical groups (p=0.217). Most of the thrombi only partially occluded the portal system veins. All the patients presented with a thrombus inside the portal vein. There was no difference in hematological and biochemical tests between groups with or without portal vein thrombosis., Conclusions: Portal vein thrombosis is often observed in the late postoperative period, irrespective of the surgical treatment employed, and is not associated with patient characteristics or any hematological and biochemical tests.

Stress exposure can lead to post-traumatic stress disorder (PTSD) in male and female rats. Social-Single Prolonged Stress (SPS) protocol has been considered a potential PTSD model. This study aimed to pharmacologically validate the Social-SPS as a PTSD model in male and female rats. Male and female Wistar rats (60-day-old) were exposed to Social-SPS protocol and treated with fluoxetine (10 mg/Kg) or saline solution intraperitoneally 24 h before euthanasia. Two cohorts of animals were used; for cohort 1, male and female rats were still undisturbed until day 7 post-Social-SPS exposure, underwent locomotor and conditioned fear behaviors, and were euthanized on day 9. Animals of cohort 2 were subjected to the same protocol but were re-exposed to contextual fear behavior on day 14. Results showed that fluoxetine-treated rats gained less body weight than control and Social-SPS in both sexes. Social-SPS effectively increased the freezing time in male and female rats on day eight but not on day fourteen. Fluoxetine blocked the increase of freezing in male and female rats on day 8. Different mechanisms for fear behavior were observed in males, such as Social-SPS increased levels of glucocorticoid receptors and Beclin-1 in the amygdala. Social-SPS was shown to increase the levels of NMDA2A, GluR-1, PSD-95, and CAMKII in the amygdala of female rats. No alterations were observed in the amygdala of rats on day fourteen. The study revealed that Social-SPS is a potential PTSD protocol applicable to both male and female rats., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Rocky Mountain or Brazilian spotted fever, caused by Rickettsia rickettsii , is a fulminant, seasonal, and neglected disease that occurs in focal points of North America and South America. Its rapid detection is essential for the better prognosis and survival rate of infected individuals. However, disease diagnosis still faces challenges as the accuracy of many of the available laboratory tests fluctuates. This review aimed to analyze methods for antibody or antigen detection, their gaps, and their evolution over time. A search was conducted to find all studies in the Pubmed database that described the antibody or antigen detection of R. rickettsii infections. Initially, a total of 403 articles were screened. Of these articles, only 17 fulfilled the pre-established inclusion criteria and were selected. Among the different methods applied, the IFA technique was the one most frequently found in the studies. However, it presented varied results such as a low specificity when using the indirect method. Other techniques, such as ELISA and immunohistochemistry, were also found, although in smaller numbers and with their own limitations. Although some studies showed promising results, there is a pressing need to find new techniques to develop a rapid and effective diagnosis of R. rickettssi infection.

This study revealed the potential of magnesium whitlockite [WH: Ca 18 Mg 2 (HPO 4 ) 2 (PO 4 ) 12 ] nanoparticles (WH NPs) for anti-inflammatory and anti-cancer therapies. Although magnesium whitlockite possesses promising biological properties, its effects on inflammation and cancer remain unexplored. In this study, we address this gap by synthesizing WH NPs and demonstrating their multifaceted functionalities. Through detailed characterization, we revealed the synthesis pathway involving brushite as a precursor, with magnesium ions incorporated during hydrothermal treatment. WH NPs exhibited anti-inflammatory properties by significantly reducing the production of key inflammatory markers (NO, TNF-α, and IL-6). Furthermore, they display promising anti-cancer activity by inhibiting the proliferation of MDA-MB-231 breast cancer cells. Our findings not only establish a deeper understanding of WH NP synthesis but also highlight their potential for the development of innovative cancer and inflammatory treatments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Antibiotics may induce super-resistant bacteria if they are available in the environment. Therefore, the removal of aqueous nitrofurantoin (NFT), and more importantly, the removal of the remaining antimicrobial activity after treatment, by the photo-Fenton process, was herein studied. Degradation experiments were performed according to an experimental design (0.5% error; factors: concentrations of NFT, Fe 3+ , and H 2 O 2 ). Degradation conditions were: 20 mg NFT L -1 , 10 mg Fe 3+ L -1 , and 170 mg H 2 O 2 L -1 . Fixed parameters were: 100 mL of the NFT solution, pH 2.5, 15-min stirring, and 25.0 ± 0.5°C. The initial rate constant ( k 0 ) and the maximum oxidation capacity (MOC) of the system were 0.61 min -1 and 100%, respectively ( R 2  = 0.986). 97% of the NFT and 93% of the organic carbon initially present were removed. Five degradation products (DPs) were detected by HPLC-MS and their endpoints estimated by the ECOSAR (ECOlogical Structure-Activity Relationships) 2.0 software. NFT and its DPs presented no toxicity towards Lactuca sativa . The antimicrobial activity ( Escherichia coli ) of NFT and/or DPs was completely removed in 15 min. Structures were proposed for the detected DPs. In short, the tested advanced oxidation technology (AOP), besides being capable of removing and mineralizing aqueous NFT in a short time, 15 min, also rendered the treated water biologically inactive (no ecotoxicity, no antimicrobial activity).

Statement of the Problem: Biological complications of implant-supported prostheses remain a concern. Therefore, standardizing hygiene protocols to promote their maintenance is important., Purpose: The purpose of this scoping review was to identify available hygiene guidance for home care procedures, as well as periodicity and protocols for the professional maintenance of implant-supported prostheses., Material and Methods: This study was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the study protocol was made available at: https://osf.io/5jdeh/. The search was last performed in the PubMed database on March 15, 2022 and was undertaken by 2 independent researchers. Clinical studies and reviews that evaluated home care and maintenance protocols for dental implant-supported prostheses (fixed or removable), without language restriction or year of publication, were included. A descriptive analysis was performed considering study characteristics (study design, restorative assembly, maintenance strategies, eligibility criteria, number of included studies, quality/level of evidence, and main findings)., Results: The initial search yielded 3138 studies, of which 18 were included for descriptive analysis (6 critical reviews, 4 clinical trials, 3 systematic reviews, 2 guideline reports, 2 retrospective studies, and 1 transversal study). The main instrument recommended for home care was the use of a conventional toothbrush associated with triclosan-containing toothpaste in addition to interproximal aids (brushes or floss) for all types of restorations. The use of irrigation instruments was also frequently considered. For professional maintenance, almost all studies reported a positive effect of regular recalls every 3 months during the first year, followed by less regular recalls according to the motivation of the patient and home care efficacy. At each recall, the professional should evaluate the patient history, oral tissues, implant, abutments, and restorations, as well as perform professional cleaning of the prostheses with appropriate instruments so that the implants and abutments may be preserved., Conclusions: Establishing an adequate hygiene protocol is indispensable for implant-supported restorations. To do so, the professional must guide and support the patient's home care by taking into account the patient's motivation and efficacy during the hygiene procedures. Also, for professional maintenance, the periodicity of recalls should be constant and include an evaluation of the condition of the restoration and adjacent tissues, followed by professional cleaning of prostheses, implants, and abutments, in addition to new instructions to improve patient home care., (Copyright © 2022 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Vulvovaginal candidiasis (VVC) remains a prevalent fungal disease, characterized by challenges, such as increased fungal resistance, side effects of current treatments, and the rising prevalence of non- albicans Candida spp. naturally more resistant. This study aimed to propose a novel therapeutic approach by investigating the antifungal properties and toxicity of 2-hydroxychalcone (2-HC) and 3'-hydroxychalcone (3'-HC), both alone and in combination with fluconazole (FCZ) and clotrimazole (CTZ). A lipid carrier (LC) was also developed to deliver these molecules. The study evaluated in vitro anti- Candida activity against five Candida species and assessed cytotoxicity in the C33-A cell line. The safety and therapeutic efficacy of in vivo were tested using an alternative animal model, Galleria mellonella . The results showed antifungal activity of 2-HC and 3'-HC, ranging from 7.8 to 31.2 as fungistatic and 15.6 to 125.0 mg/L as fungicide effect, with cell viability above 80% from a concentration of 9.3 mg/L (2-HC). Synergistic and partially synergistic interactions of these chalcones with FCZ and CTZ demonstrated significant improvement in antifungal activity, with MIC values ranging from 0.06 to 62.5 mg/L. Some combinations reduced cytotoxicity, achieving 100% cell viability in many interactions. Additionally, two LCs with suitable properties for intravaginal application were developed. These formulations demonstrated promising therapeutic efficacy and low toxicity in Galleria mellonella assays. These results suggest the potential of this approach in developing new therapies for VVC.

We aimed to estimate the proportions of childhood parental neglect, abuse, and rejection and to evaluate the co-occurrence of these experiences among transgender women in Rio de Janeiro, Brazil. This was a cross-sectional study with a convenience sample enrolled between July 2019 and March 2020, using an adapted version of the Childhood Trauma Questionnaire. Proportions and corresponding confidence intervals (CI) were calculated. Kendall correlation with Tau-b estimator was used in the bivariate analyses. We gathered data from 139 participants. The most prevalent types of childhood traumas were emotional abuse (60.43%, 95% CI [51.79, 68.62]), physical abuse (57.55%, 95% CI [48.90, 65.89]) and sexual abuse (44.60%, 95% CI [36.18, 53.27]). Severe to extreme physical and emotional abuse occurred among 40.29% (95% CI [32.06, 48.93]) and 5.75% (95% CI [2.51, 11.02]) of participants, respectively. The proportion of parental rejection (eviction) was 32.37% (95% CI [25.04, 40.69]) and occurred with the other forms of abuse, except sexual abuse. Multiple types of childhood abuse, neglect, and parental rejection were observed among transgender women in our sample. The harmful effects of childhood abuse on the mental and physical health of people in the transgender population are of concern, particularly considering the cumulative effect produced by the co-occurrence of such events and their harmful lifetime effects. It is urgently necessary to debate and formulate public policies to ensure the right to gender expression from childhood., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interests with respect to the authorship and/or publication of this article.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) exhibit high mortality rates in pediatric patients and usually belong to international high-risk clones. This study aimed to investigate the molecular epidemiology and carbapenem resistance mechanisms of K. pneumoniae isolates recovered from pediatric patients, and correlate them with phenotypical data. Twenty-five CRKP isolates were identified, and antimicrobial susceptibility was assessed using broth microdilution. Carbapenemase production and β-lactamase genes were detected by phenotypic and genotypic tests. Multilocus sequence typing was performed to differentiate the strains and whole-genome sequencing was assessed to characterize a new sequence type. Admission to the intensive care unit and the use of catheters were significantly positive correlates of CRKP infection, and the mortality rate was 36%. Almost all isolates showed multidrug-resistant phenotype, and most frequent resistant gene was bla KPC . We observed the dissemination of ST307 and clones belonging to CG258, which are considered high risk. In pediatric patients, these clones present with high genomic plasticity, favoring adaptation of the KPC and NDM enzymes to healthcare environments., (© 2024. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

It is unclear whether muscle blood flow (MBF) is altered in long-term Hodgkin lymphoma (HL) survivors. We tested the hypothesis that 1 ) MBF response during mental stress (MS) is impaired in long-term HL survivors and 2 ) aerobic exercise training combined with local strength exercise (ET) restores MBF responses during MS in these survivors. Eighteen 5-year HL survivors and 10 aged-paired healthy subjects (HC) were studied. Twenty HL survivors were randomly divided into two groups: exercise-trained (HLT, n = 10) and untrained (HLUT, n = 10). Maximal aerobic capacity was evaluated by a cardiopulmonary exercise test and forearm blood flow (FBF) by venous occlusion plethysmography. MS was elicited by Stroop color and word test. ET was conducted for 4 mo, 3/wk for 60 min each session. The aerobic exercise intensity corresponded to anaerobic threshold up to 10% below the respiratory compensation point. The strength exercises consisted of two to three sets of chest press, pulley and squat exercises, 12-15 repetitions each exercise at 30-50% of the maximal voluntary contraction. Baseline was similar in HL survivors and HC, except peak oxygen consumption (peak V̇o 2 , P = 0.013) and FBF ( P = 0.006) that were lower in the HL survivors. FBF responses during MS were lower in HL survivors ( P < 0.001). ET increased peak V̇o 2 (11.59 ± 3.07%, P = 0.002) and FBF at rest (33.74 ± 5.13%, P < 0.001) and during MS (24 ± 5.31%, P = 0.001). Further analysis showed correlation between the changes in peak V̇o 2 and the changes in FBF during MS (r = 0.711, P = 0.001). In conclusion, long-term HL survivors have impaired MBF responses during MS. ET restores MBF responses during MS. NEW & NOTEWORTHY Long-term Hodgkin lymphoma (HL) survivors have impaired muscle blood flow responses during mental stress and decreased maximal aerobic capacity. Supervised aerobic exercise training combined with local strength exercises restores muscle blood flow responses during mental stress and maximal aerobic capacity in these survivors. These findings provide evidence of safety and effectiveness of exercise training in HL survivors. Moreover, they highlight the importance of exercise training in the treatment of this set of patients.

The drug-resistant temporal lobe epilepsy (TLE) has recently been associated with single nucleotide variants (SNVs) in microRNA(miR)-146a ( MIR-146A ) (rs2910164) and Sodium Voltage-Gated Channel Alpha Subunit 1 ( SCN1A ) (rs2298771 and rs3812718) genes. Moreover, no studies have shown an association between these SNVs and susceptibility to drug-resistant and drug-responsive TLE in Brazil. Thus, deoxyribonucleic acid (DNA) samples from 120 patients with TLE (55 drug-responsive and 65 drug-resistant) were evaluated by real-time polymerase chain reaction (RT-PCR). A total of 1171 healthy blood donor individuals from the Online Archive of Brazilian Mutations (ABraOM, from Portuguese Arquivo Brasileiro On-line de Mutações), a repository containing genomic variants of the Brazilian population, were added as a control population for the studied SNVs. MIR-146A and SCN1A relative expression was performed by quantitative RT-PCR (qRT-PCR). The statistical analysis protocol was performed using an alpha error of 0.05. TLE patient samples and ABraOM control samples were in Hardy-Weinberg equilibrium for all studied SNVs. For rs2910164, the frequencies of the homozygous genotype (CC) (15.00% vs. 9.65%) and C allele (37.80% vs. 29.97%) were superior in patients with TLE compared to controls with a higher risk for TLE disease [odds ratio (OR) = 1.89 (95% confidence interval (95%CI) = 1.06-3.37); OR = 1.38 (95%CI = 1.04-1.82), respectively]. Drug-responsive patients also presented higher frequencies of the CC genotype [21.81% vs. 9.65%; OR = 2.58 (95%CI = 1.25-5.30)] and C allele [39.09% vs. 29.97%; OR = 1.50 (95%CI = 1.01-2.22)] compared to controls. For rs2298771, the frequency of the heterozygous genotype (AG) (51.67% vs. 40.40%) was superior in patients with TLE compared to controls with a higher risk for TLE disease [OR = 2.42 (95%CI = 1.08-5.41)]. Drug-resistant patients presented a higher AG frequency [56.92% vs. 40.40%; OR = 3.36 (95%CI = 1.04-17.30)] compared to the control group. For rs3812718, the prevalence of genotypes and alleles were similar in both studied groups. The MIR-146A relative expression level was lower in drug-resistant compared to drug-responsive patients for GC (1.6 vs. 0.1, p -value = 0.049) and CC (1.8 vs. 0.6, p -value = 0.039). Also, the SCN1A relative expression levels in samples from TLE patients were significantly higher in AG [2.09 vs. 1.10, p -value = 0.038] and GG (3.19 vs. 1.10, p -value < 0.001) compared to the AA genotype. In conclusion, the rs2910164-CC and rs2298771-AG genotypes are exerting significant risk influence, respectively, on responsive disease and resistant disease, probably due to an upregulated nuclear factor kappa B (NF-kB) and SCN1A loss of function.

The present study aimed to determine the genetic diversity of isolates of Mycobacterium tuberculosis (Mtb) from presumed drug-resistant tuberculosis patients from several states of Brazil. The isolates had been submitted to conventional drug susceptibility testing for first- and second-line drugs. Multidrug-resistant (MDR-TB) (54.8%) was the most frequent phenotypic resistance profile, in addition to an important high frequency of pre-extensive resistance (p-XDR-TB) (9.2%). Using whole-genome sequencing (WGS), we characterized 298 Mtb isolates from Brazil. Besides the analysis of genotype distribution and possible correlations between molecular and clinical data, we determined the performance of an in-house WGS pipeline with other online pipelines for Mtb lineages and drug resistance profile definitions. Sub-lineage 4.3 (52%) was the most frequent genotype, and the genomic approach revealed a p-XDR-TB level of 22.5%. We detected twenty novel mutations in three resistance genes, and six of these were observed in eight phenotypically resistant isolates. A cluster analysis of 170 isolates showed that 43.5% of the TB patients belonged to 24 genomic clusters, suggesting considerable ongoing transmission of DR-TB, including two interstate transmissions. The in-house WGS pipeline showed the best overall performance in drug resistance prediction, presenting the best accuracy values for five of the nine drugs tested. Significant associations were observed between suffering from fatal disease and genotypic p-XDR-TB ( p = 0.03) and either phenotypic ( p = 0.006) or genotypic ( p = 0.0007) ethambutol resistance. The use of WGS analysis improved our understanding of the population structure of MTBC in Brazil and the genetic and clinical data correlations and demonstrated its utility for surveillance efforts regarding the spread of DR-TB, hopefully helping to avoid the emergence of even more resistant strains and to reduce TB incidence and mortality rates.

Nuclear magnetic resonance (NMR) longitudinal rotating frame relaxation time (T 1ρ ), rarely used in low-field NMR, can be more effective than conventional T 1 and T 2 relaxation times to differentiate polymorphic forms of solid pharmaceuticals. This could be attributed to T 1ρ sensibility to structural and molecular dynamics that can be enhanced by changing the strength of the oscillating magnetic field ( B 1 ) of spinlock pulses. Here, we compared the capacity of T 1 , T 2 , and T 1ρ to differentiate inactive (A) and active (C) crystalline forms of the World Health Organization essential drug Mebendazole. The results showed that T 1 and T 2 values of both forms were statistically identical at 0.47 T. Conversely, T 1ρ of both forms measured with weak spinlock B 1 fields, ranging from 0.08 to 0.80 mT were statistically different in the same spectrometer. The T 1ρ also has the limit of detection to detect the presence of at least 10% of inactive A form in the active C form. Therefore, T 1ρ , measured with weak spinlock B 1 fields can be an effective, streamlined, and complementary approach for characterizing not only solid active pharmaceutical ingredients but other solid-state materials as well.

Recombinant multiepitope proteins (RMPs) are a promising alternative for application in diagnostic tests and, given their wide application in the most diverse diseases, this review article aims to survey the use of these antigens for diagnosis, as well as discuss the main points surrounding these antigens. RMPs usually consisting of linear, immunodominant, and phylogenetically conserved epitopes, has been applied in the experimental diagnosis of various human and animal diseases, such as leishmaniasis, brucellosis, cysticercosis, Chagas disease, hepatitis, leptospirosis, leprosy, filariasis, schistosomiasis, dengue, and COVID-19. The synthetic genes for these epitopes are joined to code a single RMP, either with spacers or fused, with different biochemical properties. The epitopes' high density within the RMPs contributes to a high degree of sensitivity and specificity. The RMPs can also sidestep the need for multiple peptide synthesis or multiple recombinant proteins, reducing costs and enhancing the standardization conditions for immunoassays. Methods such as bioinformatics and circular dichroism have been widely applied in the development of new RMPs, helping to guide their construction and better understand their structure. Several RMPs have been expressed, mainly using the Escherichia coli expression system, highlighting the importance of these cells in the biotechnological field. In fact, technological advances in this area, offering a wide range of different strains to be used, make these cells the most widely used expression platform. RMPs have been experimentally used to diagnose a broad range of illnesses in the laboratory, suggesting they could also be useful for accurate diagnoses commercially. On this point, the RMP method offers a tempting substitute for the production of promising antigens used to assemble commercial diagnostic kits., (© 2024. The Author(s).)