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Hantavirus pulmonary syndrome (HPS) is an increasing health problem in Brazil because of encroachment of sprawling urban, agricultural, and cattle-raising areas into habitats of subfamily Sigmodontinae rodents, which serve as hantavirus reservoirs. From 1993 through June 2007, a total of 884 cases of HPS were reported in Brazil (case-fatality rate 39%). To better understand this emerging disease, we collected 89 human serum samples and 68 rodent lung samples containing antibodies to hantavirus from a 2,500-km-wide area in Brazil. RNA was isolated from human samples and rodent tissues and subjected to reverse transcription-PCR. Partial sequences of nucleocapsid protein and glycoprotein genes from 22 human and 16 rodent sources indicated only Araraquara virus and Juquitiba virus lineages. The case-fatality rate of HPS was higher in the area with Araraquara virus. This virus, which may be the most virulent hantavirus in Brazil, was associated with areas that have had greater anthropogenic changes. [ABSTRACT FROM AUTHOR]

Current treatments of visceral leishmaniasis face limitations due to drug side effects and/or high cost, along with the emergence of parasite resistance. Novel and low-cost antileishmanial agents are therefore required. We report herein the antileishmanial activity of β-acetyl-digitoxin (b-AD), a cardenolide isolated from Digitalis lanata leaves, assayed in vitro and in vivo against Leishmania infantum. Results showed direct action of b-AD against parasites, as well as efficacy for the treatment of Leishmania-infected macrophages. In vivo experiments using b-AD-containing Pluronic® F127 polymeric micelles (b-AD/Mic) to treat L. infantum-infected mice showed that this composition reduced the parasite load in distinct organs in more significant levels. It also induced the development of anti-parasite Th1-type immunity, attested by high levels of IFN-γ, IL-12, TNF-α, GM-CSF, nitrite and specific IgG2a antibodies, in addition to low IL-4 and IL-10 contents, along with higher IFN-γ-producing CD4+ and CD8+ T-cell frequency. Furthermore, low toxicity was found in the organs of the treated animals. Comparing the therapeutic effect between the treatments, b-AD/Mic was the most effective in protecting animals against infection, when compared to the other groups including miltefosine used as a drug control. Data found 15 days after treatment were similar to those obtained one day post-therapy. In conclusion, the results obtained suggest that b-AD/Mic is a promising antileishmanial agent and deserves further studies to investigate its potential to treat visceral leishmaniasis.

A clioquinol (ICHQ)-containing Pluronic® F127 polymeric micelle system (ICHQ/Mic) was recently shown to be effective against Leishmania amazonensis infection in a murine model. In the present study, ICHQ/Mic was tested against L. infantum infection. BALB/c mice (n = 12 per group) were infected with L. infantum stationary promastigotes through subcutaneous injection and, 45 days after challenge, received saline or were treated via the subcutaneous route with empty micelles, ICHQ or ICHQ/Mic. In addition, animals were treated with miltefosine by the oral route, as a drug control. Half of the animals were euthanized 1 and 15 days after treatment, aiming to evaluate two endpoints after therapy, when parasitological and immunological parameters were investigated. Results showed that the treatment using miltefosine, ICHQ or ICHQ/Mic induced significantly higher anti-parasite IFN-γ, IL-12, GM-CSF, nitrite and IgG2a isotype antibody levels, which were associated with low IL-4 and IL-10 production. In addition, a higher frequency of IFN-γ and TNF-α-producing CD4+ and CD8+ T-cells was found in these animals. The parasite load was evaluated in distinct organs, and results showed that the treatment using miltefosine, ICHQ or ICHQ/Mic induced significant reductions in organic parasitism in the treated and infected mice. A comparison between the treatments suggested that ICHQ/Mic was the most effective in inducing a highly polarized Th1-type response, as well as reducing the parasite load in significant levels in the treated and infected animals. Data obtained 15 days after treatment suggested maintenance of the immunological and parasitological responses. In conclusion, ICHQ/Mic could be considered in future studies for the treatment of visceral leishmaniasis.

Com o objetivo de conhecer p estabelecimento e duração do aleitamento materno total e exclusivo em comunidades rurais do Semi-Árido Baiano, Brasil, foram estudadas 226 crianças de O a 2 anos de idade, filhas de pequenos produtores rurais que vivem numa das regiões mais secas do nordeste brasileiro, de pobreza absoluta. Os dados referem-se a todas as crianças da família que à data do estudo tinham até 2 anos de idade. Os dados foram coletados por meio de formulários aplicados às mães ou responsáveis pelo menor, no período de 1988 a 1989. A tábua de vida foi o recurso estatístico utilizado para o cálculo da duração mediana do evento. Das 226 crianças que integraram o estudo, 91,6 iniciaram a amamentação ao peito. A duração mediana do aleitamento total foi de 90,28 dias e o aleitamento exclusivo apresentou duração mediana de 0,1 dia. Ainda que o estabelecimento da amamentação ao peito possa ser considerado alto, a duração mediana do aleitamento total foi extrememente curta, e o aleitamento exclusivo foi desprezível.

Alterations in miRNAs, p53, and sphingolipid metabolism are associated with head and neck squamous cell carcinoma (HNSCC). However, the role of sphingosine kinase (SK)-2, an enzyme crucial for sphingolipid metabolism, is poorly understood in HNSCC. The aim of this study was to investigate how SK2 and p53 interact to regulate miRNAs miR-205 and miR-296. Analysis of small-RNA sequencing data from nontumor oral keratinocytes with SK2 overexpression (NOK-SK2) compared to controls (NOK-Ø) revealed differential expression of >100 miRNAs being half-regulated by p53. The expression of miR-205 was down-regulated, and miR-296 was up-regulated, in NOK-SK2 cells; however, cells with SK2 knockdown and p53 overexpression showed an opposite profile. Proteins involved in miRNA biogenesis were increased in NOK-SK2 cells, while levels were decreased in NOK-SK2 cells with p53 overexpression. Transfection with miR-205 mimic and miR-296 inhibitor decreased the aggressiveness and the number of cancer stem-like cells in oral keratinocytes and oral carcinoma cells with SK2 regulation. Overexpression of miR-205 in HN12-SK2 cells decreased tumor-formation capacity, and NOK-SK2 cells abrogated tumor growth in mice. The results indicate crosstalk between SK2 and p53 in regulating miRNAs 205 and 296, which could be potential therapeutic targets in the treatment of HNSCC., Competing Interests: Disclosure Statement None declared., (Copyright © 2025 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Pantoea agglomerans is one of four Pantoea species reported in the USA to cause bacterial rot of onion bulbs. However, not all P. agglomerans strains are pathogenic to onion. We characterized onion-associated strains of P. agglomerans to elucidate the genetic and genomic signatures of onion-pathogenic P. agglomerans. We collected >300 P. agglomerans strains associated with symptomatic onion plants and bulbs from public culture collections, research laboratories, and a multi-year survey in 11 states in the USA. Combining the 87 genome assemblies with 100 high-quality, public P. agglomerans genome assemblies we identified two well-supported P. agglomerans phylogroups. Strains causing severe symptoms on onion were only identified in Phylogroup II and encoded the HiVir pantaphos biosynthetic cluster, supporting the role of HiVir as a pathogenicity factor. The P. agglomerans HiVir cluster was encoded in two distinct plasmid contexts: 1) as an accessory gene cluster on a conserved P. agglomerans plasmid (pAggl), or 2) on a mosaic cluster of plasmids common among onion strains (pOnion). Analysis of closed genomes revealed that the pOnion plasmids harbored alt genes conferring tolerance to Allium thiosulfinate defensive chemistry and many harbored cop genes conferring resistance to copper. We demonstrated that the pOnion plasmid pCB1C can act as a natively mobilizable pathogenicity plasmid that transforms P. agglomerans Phylogroup I strains, including environmental strains, into virulent pathogens of onion. This work indicates a central role for plasmids and plasmid ecology in mediating P. agglomerans interactions with onion plants, with potential implications for onion bacterial disease management., (Published by Oxford University Press on behalf of the International Society for Microbial Ecology [2025].)

Objective: Cancer cells undergo adaptive processes that favor their survival and proliferation when subjected to different types of cellular stress. These changes are linked to oncogenic processes such as genetic instability, tumor proliferation, therapy resistance, and invasion. Therefore, this study aimed to review studies that discuss possible morphological and genetic changes acquired by neoplastic cells under stressful conditions., Methods: The articles used in this integrative review were searched on PubMed, Web of Science, CAPES, BVS and Scopus. Studies that discussed how cells undergo morphogenetic changes as an adaptive response to stress in cancer were included., Results: This article reviewed 82 studies that highlighted multiple types of stress to which cancer can be subjected, such as oxidative, thermal and mechanical stress; glucose and other nutrients deficiency; hypoxia and chemotherapy. Neoplastic cells under stress can undergo adaptive changes that make it possible to overcome this obstacle. In this adaptive process, the acquisition of certain mutations implies cellular morphological changes such as Epithelial-Mesenchymal Transition, polyploidy, mitochondrial and cytoskeletal changes. These adaptive changes occur concomitantly with processes related to oncogenesis such as gene instability, tumor proliferation, resistance to therapy and invasion., Conclusions: This study reveals that adaptations to cellular stress promote morphological and functional changes that accompany or accelerate oncogenesis. It has been revised how epithelial-mesenchymal transition, polyploidy and mitochondrial dysfunctions not only reinforce the survival of tumor cells in adverse environments, but also increase therapeutic resistance and invasive capacity. Also noteworthy are the contributions on genomic instability associated with stress and the potential of senescent cells in tumor heterogeneity, both as factors of tumor resistance and progression. These insights suggest new therapeutic targets and prognostic biomarkers, expanding the possibilities for more effective strategies to combat cancer., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Introduction: Sexual and gender minority (SGM) youth have higher rates of nicotine vaping than other youth in the United States. While social media can be effective in reaching youth and discouraging vaping, informed cultural tailoring is necessary to ensure effective messaging to SGM youth. This study aimed to understand SGM youth perspectives on anti-vaping social media messages and tailoring approaches., Aims and Methods: In-depth, qualitative videoconference interviews were conducted from February to July 2022 with 34 SGM youth recruited in the United States via social media ads. The interview guide addressed participants' beliefs about vaping, the context of vaping, perspectives on tailoring messages, and responses to examples of social media anti-vaping messages. Coding and thematic analysis followed a team-based approach., Results: SGM youth perspectives fell into four categories-representation and diversity, facts and evidence, empowering messages, and source credibility. Participants stressed the importance of accurate, genuine representation of SGM youth in messages, but also noted that more overt representation may be seen as tokenizing. Participants recommended partnering with known LGBTQ + influencers who can promote or share anti-vaping messages on social media platforms. They also recommended using culturally tailored language, including statistics specific to SGM youth, and invoking themes of empowerment to improve the relevance, reach, and effectiveness of anti-vaping campaigns., Conclusions: Findings can inform future efforts to develop anti-vaping messages for SGM youth with effective reach through social media. Nuanced perspectives on SGM representation in messages suggest a careful approach to tailoring. Concerns around inauthenticity may be minimized by ensuring SGM youth are included in message development and dissemination., Implications: This study describes the importance of being attentive to the tailoring preferences among the current generation of SGM youth. Findings will inform social media-based messaging strategies that discourage nicotine vaping tailored for SGM youth in health campaign material design and evaluation, ensuring that tailored messages are designed in ways that avoid unintended consequences. The study also describes methods for effectively engaging SGM youth in research to improve the relevance of health education materials for this population and increase reach, which in turn can lead to a reduction in vaping practices among SGM youth., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. 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.)

The pan-cancer and multi-omics approach is motivated by the genetic and molecular complexity inherent in the varied types of cancer. This method presents itself as a crucial resource for advancing early diagnosis, defining prognoses and identifying treatments that share common bases between different forms of tumors. The aim of this article is to explore pan-cancer analysis in conjunction with multi-omics strategies, evaluating laboratory, computational, clinical procedures and their consequences, as well as examining the tumor microenvironment, epigenetics and future directions of these technologies in patient management. To this end, a literature review was conducted using PUBMED, resulting in the selection of 260 articles, of which 81 were carefully chosen to support this analysis. The pan-cancer methodology is applied to the study of this microenvironment with the aim of investigating its common characteristics through multiomics data. The development of new therapies depends on understanding the oncogenic pathways associated with different cancers. Thus, the integration of multi-omics and pan-cancer analyzes offers an innovative perspective in the search for new control points, metabolic pathways and markers, in addition to facilitating the identification of patterns common to multiple cancer types, allowing the development of targeted treatments. In this way, the convergence of multiomics and clinical approaches promotes a broad view of cancer biology, leading to more effective and personalized therapies., Competing Interests: Declarations. Conflict of interest: The authors declare no conflicts of interest. Ethical approval: Not applicable. Informed consent: Not applicable. Institutional review board: Not applicable., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Background: As Indian states consider HPV testing for cervical screening, there is a need to review evidence from prior studies to inform program design and evaluate implementation research gaps., Design: We conducted a systematic review of original articles in Medline, Embase, Global Health and Web of Science, published from 2000 to May 4, 2024. Articles describing use of HPV as a primary cervical screening test in India, in either community-based programs for the general population, or among women living with HIV, were included. We describe approaches to invitation, education, screening, and follow-up, and map determinants and outcomes to the RE-AIM and the Consolidated Framework for Implementation Research frameworks., Results: Of 71 included articles (51 unique studies), 19 reported on screening among women living with HIV, while 52 were community-based (general population of women). Self-collection was offered by 15 studies and was acceptable to most screened women. Community-based programs were mainly facility or outreach-based, with three studies offering only home-based self-collection, including one that integrated with cardiovascular risk screening. Studies from northeastern and tribal populations were scarce. Only one self-collection study used a screen and treat (at second visit) approach, but did not report follow-up, while none offered immediate treatment following a point-of-care test., Conclusions: Community-based HPV testing, including self-collection, is feasible in India, with more research needed among underrepresented populations. Further implementation research is needed on integrating HPV screening with existing health systems, feasibility of HPV test and treat models and genotyping triage, to improve follow-up in low resource settings., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Julia ML Brotherton reports a relationship with Australian Centre for the Prevention of Cervical Cancer that includes: employment. JMLB was previously employed by the Australian Centre for the Prevention of Cervical Cancer (ACPCC). ACPCC/VCS Pathology has received equipment or supplies from Abbott, AusDiagnostics, BD, Cepheid, Copan, Hologic, Microbiologics, MicroBix, NRL, Qiagen, Rovers, Roche, and Seegene for research and validation studies. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: This study aimed to evaluate the effectiveness and safety of direct-acting antivirals (DAAs) for hepatitis C treatment by measuring sustained virologic response (SVR) and serious adverse events to help design effective interventions for reducing disease prevalence., Methods: This was a retrospective, observational, real-life study of patients with chronic hepatitis C receiving DAA treatment in the state of Ceará, Brazil. Data were collected in REDCap and analyzed using R® software by the Student's t, chi-square, and Fisher's exact tests, with a significance level of 5%., Results: In this study, 1075 patients who were diagnosed with hepatitis C infection between October 2015 and October 2023 were included. The mean age of the participants was 56.6 ± 11 years and 60.2% were men. The sample included 51 HIV-infected patients (6.6%), 166 (15,4%) liver transplant recipients, 34 (3,1%) kidney transplant recipients, and 446 patients with cirrhosis (41.4%). The overall SVR rate was 96.4%. The sofosbuvir/daclatasvir/ribavirin regimen used in 354 (32.9%) patients achieved an SVR of 96%. The cure rate was 96.5%, with a lower SVR in patients with cirrhosis (93.4%) than in those with less severe fibrosis (97.9%) (p=0.0015). Serious adverse events associated with ribavirin use occurred in 3.5% of patients., Conclusions: DAA treatment for hepatitis C achieved SVR in real life in all patient profiles, including transplant recipients, HIV carriers, and patients with cirrhosis. Although these drugs are safe, a few decompensated patients with cirrhosis died during treatment.

The epidemic of obesity has increased worldwide and is associated with comorbidities such as diabetes and cardiovascular disease. In this context, strategies that modulate body weight and improve glycemic metabolism have increased, and bariatric surgeries such as Sleeve Gastrectomy (SG) have been highlighted in obesity treatment. However, the mechanism by which SG reduces body weight and improves glycemic control remains unknown. Thus, in this study, we aimed to evaluate food intake and the expression of hypothalamic genes involved with the regulation of this process in diet-induced obese mice submitted to SG. For this, we used C57BL/6 mice submitted to a 10-week high-fat diet protocol and submitted to SG. Food intake, fed and fasted glycemia, as well as hypothalamic anorexigenic and orexigenic gene expression were evaluated 4 weeks after the surgical procedure. First, we observed that SG reduces body weight (44.19 ± 0.47 HFD, 43.51 ± 0.71 HFD-SHAM, and 38.22 ± 1.31 HFD-SG), fasting glycemia (115.0 ± 4.60 HFD, 122.4 ± 3.48 HFD-SHAM, and 93.43 ± 4.67 HFD-SG), insulinemia (1.77 ± 0.15 HFD, 1.92 ± 0.27 HFD-SHAM, and 0.93 ± 0.05 HFD-SG), and leptinemia (5.86 ± 1.38 HFD, 6.44 ± 1.51 HFD-SHAM, and 1.43 ± 0.35 HFD-SG) in obese mice. Additionally, SG reduces food (5.15 ± 0.18 HFD, 5.49 ± 0.32, HFD-SHAM, and 3.28 ± 0.26 HFD-SG) and total (16.88 ± 0.88 HFD, 17.05 ± 0.42, HFD-SHAM, and 14.30 ± 0.73 HFD-SG) calorie intake without alterations in anorexigenic and orexigenic gene expression. In conclusion, these data indicate that SG improves obesity-associated alterations at least in part by a reduction in food intake. This effect is not associated with the canonical food intake pathway in the hypothalamus, indicating the involvement of non-canonical pathways in this process.

Emerging evidence suggests that aberrant expression levels of Sigma1 ( SIGMAR1 , also known as sigma-1 receptor) have been implicated in the progression of various diseases, including cancer. However, its significance in oral cancer (OC) has not been thoroughly explored. To advance in this field, the present study aimed to investigate the impact of SIGMAR1 knockdown in oral cancer cells. To do so, we included in this study our cohort of human OC samples and OC cell lines, which were utilized for experimental verification through several in vitro assays. Our findings revealed that SIGMAR1 overexpression was associated with poor survival rates and positively correlated with PD-L1 overexpression in human oral cancer samples. Furthermore, SIGMAR1 inhibition led to a decrease in PD-L1 expression and sensitized oral cancer cells to cisplatin treatment by enhancing apoptosis. These results suggest that SIGMAR1 knockdown may present a promising strategy worthy of further exploration in the management of oral cancer.

The use of Structured Diagnostic Assessments (SDAs) is a solution for unreliability in psychiatry and the gold standard for diagnosis. However, except for studies between the 50 s and 70 s, reliability without the use of Non-SDAs (NSDA) is seldom tested, especially in non-Western, Educated, Industrialized, Rich, and Democratic (WEIRD) countries. We aim to measure reliability between examiners with NSDAs for psychiatric disorders. We compared diagnostic agreement after clinician change, in an outpatient academic setting. We used inter-rater Kappa measuring 8 diagnostic groups: Depression (DD: F32, F33), Anxiety Related Disorders (ARD: F40-F49, F50-F59), Personality Disorders (PD: F60-F69), Bipolar Disorder (BD: F30, F31, F34.0, F38.1), Organic Mental Disorders (Org: F00-F09), Neurodevelopment Disorders (ND: F70-F99) and Schizophrenia Spectrum Disorders (SSD: F20-F29). Cohen's Kappa measured agreement between groups, and Baphkar's test assessed if any diagnostic group have a higher tendency to change after a new diagnostic assessment. We analyzed 739 reevaluation pairs, from 99 subjects who attended IPUB's outpatient clinic. Overall inter-rater Kappa was moderate, and none of the groups had a different tendency to change. NSDA evaluation was moderately reliable, but the lack of some prevalent hypothesis inside the pairs raised concerns about NSDA sensitivity to some diagnoses. Diagnostic momentum bias (that is, a tendency to keep the last diagnosis observed) may have inflated the observed agreement. This research was approved by IPUB's ethical committee, registered under the CAAE33603220.1.0000.5263, and the UTN-U1111-1260-1212., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Objectives: Whole-grain pearl millet is a nutritious cereal source of dietary fiber, vitamins, minerals, and bioactive compounds. It offers health benefits such as glycemic control and satiety. Extrusion cooking for diverse formulations, including beverages, can alter its chemical composition, impacting the nutritional value. This study aimed to evaluate the sensory acceptability of an extruded millet flour beverage and its acute effects on glycemic index (GI), glycemic and insulinemic response, food intake, and subjective appetite sensations in euglycemic and eutrophic adults., Methods: This is an acute, single-blind, randomized, controlled, cross-over clinical study comprising 14 euglycemic and eutrophic adults. Initially, beverages based on whole extruded millet flour were developed, and sensorially and chemically analyzed. Next, a clinical trial was conducted with participants undergoing four sessions and consuming one of the following options: extruded millet beverage, a maltodextrin control beverage, or a glucose solution administered in two separate sessions. Blood glucose, insulin, and appetite responses were assessed over a 2-h period, in addition to determining the GI of the beverages and analyzing food intake in the 24 h following each session., Results: The extruded millet flour strawberry-flavored beverage had the best sensory acceptance and was classified as having as high GI. Consumption of the extruded millet beverage showed similar glycemic and insulinemic responses, as well as appetite control and food intake of the subjects, when compared with consumption of the maltodextrin control beverage., Conclusions: Intake of the extruded millet beverage maintained glycemic and insulinemic responses, appetite control, and food intake in euglycemic and eutrophic subjects., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Benign peripheral nerve sheath tumors (BPNSTs) are a vast, common, heterogeneous group of lesions that are often diagnostically challenging. The head and neck region is recognized as the second most common location for these lesions, especially the tongue. However, BPNSTs occurring centrally within the jaw bones are exceedingly rare. To date, approximately 161 cases of intraosseous BPNSTs have been reported in the jaws. This group mainly includes the relatively more common neurofibromas and schwannomas, and the less common perineuriomas and hybrid forms. Unlike soft tissues, schwannomas are the most common BPNSTs occurring within the jaws, followed by neurofibromas and perineuriomas. These neoplasms can present as a well-defined unilocular lesion or as an ill-defined multilocular image, resembling several types of benign and malignant lesions of odontogenic origin. The aim of the current study was to report 4 new cases of intraosseous BPNSTs and a comprehensive literature review., Competing Interests: Declarations of 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 article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

We identified a novel mouse plasmacytoid dendritic cell (pDC) lineage derived from the common lymphoid progenitors (CLPs) that is dependent on expression of Bcl11a . These CLP-derived pDCs, which we refer to as 'B-pDCs', have a unique gene expression profile that includes hallmark B cell genes, normally not expressed in conventional pDCs. Despite expressing most classical pDC markers such as SIGLEC-H and PDCA1, B-pDCs lack IFN-α secretion, exhibiting a distinct inflammatory profile. Functionally, B-pDCs induce T cell proliferation more robustly than canonical pDCs following Toll-like receptor 9 (TLR9) engagement. B-pDCs, along with another homogeneous subpopulation of myeloid-derived pDCs, display elevated levels of the cell surface receptor tyrosine kinase AXL, mirroring human AXL + transitional DCs in function and transcriptional profile. Murine B-pDCs therefore represent a phenotypically and functionally distinct CLP-derived DC lineage specialized in T cell activation and previously not described in mice., Competing Interests: AA, JD, KG, ZS, CR, ZH, BL, DO, JL, VI, LE, GG, GI, SY, HT No competing interests declared, (© 2024, Araujo, Dekker et al.)

Background: Cardiometabolic diseases cover a spectrum of interrelated conditions linked to metabolic dysfunctions and/or cardiovascular disorders, including systemic arterial hypertension, diabetes mellitus, dyslipidemia, and obesity. Cocoa is a rich source of dietary polyphenols and has been associated with cardiovascular health benefits. However, beneficial effects of cocoa consumption and appropriate quantities in decreasing cardiometabolic risk factors have yet to be established. Therefore, we will conduct a systematic review and meta-analysis to examine the effects of cocoa consumption on cardiometabolic risk markers (total cholesterol, HDL, LDL, triglycerides, blood glucose, glycated hemoglobin, waist circumference, abdominal circumference, body mass index, systolic blood pressure and diastolic blood pressure) in adults with or without established cardiovascular risk factors., Methods: Our review will include all randomized controlled trials published in English, Portuguese and Spanish with no date of publication restrictions evaluating the effects of cocoa consumption on cardiometabolic risk markers selected from the databases MEDLINE (PubMed), LILACS, Cochrane, EMBASE, Web of Science and SciELO, and gray literature. Eligible studies must involve adults (age ≥18y), and the consumption of cocoa or dark chocolate (≥ 70% cocoa), include a control group and evaluate blood pressure, anthropometric measurements, and lipid or glycemic profiles. We will use risk-of-bias 2 (RoB2) tool to assess the risk of bias and the GRADE system to assess the strength of evidence. Statistical analyses will be performed using RStudio for Windows and R package meta., Discussion: This meta-analysis will summarize existing evidence on the effects of cocoa consumption on cardiometabolic health in adults. Better understanding the effects of cocoa consumption on anthropometric measurements, blood pressure, and lipid and glycemic profiles can provide valuable insights for health professionals to improve dietary recommendations regarding appropriate quantities., Trial Registration: Systematic Review Registration: PROSPERO CRD42023484490., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Arisi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Doxorubicin (DOX) has been widely used in the treatment of breast cancer, but it is directly associated with late-onset cardiovascular disease (CVD). Whether anthropometric, food intake or other risk factors together with DOX-based chemotherapy can increase the risk of developing cardiotoxicity remains uncertain. We examined the association between anthropometric variables with doxorubicin-induced cardiotoxicity in women with breast cancer., Methods: Twenty-six women (53.7 ± 9.6 y) undergoing DOX-based chemotherapy (408.3 ± 66.7 mg/m 2 ) participated in the study. We collected data on body composition (bioimpedance), dietary intake (24 h) and cardiac function (echocardiographic assessment of left ventricular ejection fraction, LVEF). All measurements were taken at baseline, one month of treatment completion and one-year follow-up after start of treatment. DOX-induced cardiotoxicity was defined as ≥ 10% absolute decrease in LVEF. Thus, the participants were then grouped as DOX-induced (DIC) or non-DOX-induced (non-DIC) cardiotoxicity. Data are shown as mean ± SD (standard deviation). We performed comparisons between the two groups using Student's t-test for independent samples or Generalized Estimating Equations (groups + 3 evaluation time points) with Bonferroni post-hoc test. Lastly, the correlations were analyzed using Pearson correlation; p < 0.05 for all tests., Results: At baseline the participants' body mass index (BMI) was 29.9 ± 7.9 kg/m 2 and LVEF was 67.4 ± 6.2%. Seven of them (26.9%) developed therapy-induced cardiotoxicity (ΔLVEF - 3.2 ± 2.6%; p < 0.001). Postmenopausal status and family history of CVD were more prevalent in the DIC group than non-DIC group. We found no consistent BMI changes in the groups over time. Interestingly, the non-DIC group showed a small increase in visceral fat at treatment completion and increased waist circumference at one-year follow-up compared to baseline. These same changes were not seen in the DIC group. We also observed a pattern of correlation of some anthropometric variables with LVEF: the more unfavorable the body composition the more pronounced the LVEF decrease at one-year follow-up, though not associated with cardiotoxicity., Conclusions: Our study did not provide sufficient evidence to support that anthropometric variables, food intake or other risk factors increase the risk of developing cardiotoxicity. However, there are apparent trends that need to be further investigated in larger samples., (© 2024. The Author(s).)

Background: Penile squamous cell carcinoma (PSCC) is a rare malignancy. However, in developing countries the incidence rate is higher. The understanding of molecular alterations is essential for evaluating possible targets for more effective systemic therapies., Methods: We retrospectively collected clinical data of metastatic PSCC (mPSCC) patients who had received at least one prior systemic treatment from 3 Brazilian hospitals. Tumor samples were evaluated using the next-generation sequencing (NGS) Foundation One DX and immunohistochemistry (IHC). The objective was to identify and describe somatic genomic alterations known to be functional or pathogenic and their association with survival outcomes., Results: Twenty-three patients were identified, 22 and 18 patients had tumor samples analyzed by IHC and NGS, respectively. PD-L1 expression (CPS ≥ 1%) was positive in 14 patients (63.6%). Regarding the genomic alterations, 16 patients (88.9%) had some clinically relevant genomic alterations. TP53, TERT, CDKN2A, PIK3CA, NOTCH1, and CDKN2B loss were identified in 66.7%, 50%, 50%, 33.3%, 27.8%, and 22.2% of the patients, respectively. No MSI or TMB high (≥10 mutations/MB) cases were identified. NOTCH1 mutation was identified only in HPV-negative patients and it was associated with worse OS (yes: 5.5 vs no: 12.8 months, P = .049) and progression-free survival (yes: 5.5 vs no: 11.7 months, P = .032)., Conclusion: This study demonstrated that molecular alterations in mPSCC from developing countries are similar to those from developed countries. Predictive biomarkers for immunotherapy response such as TMB high or MSI were not identified. Specific gene mutations may identify patients with worse prognoses and open new avenues for therapeutic development., (© The Author(s) 2024. Published by Oxford University Press.)

Despite the numerous studies on biocompatibility with nano-biomaterials, the biological effects of strontium-substituted HA nanoparticles (nSrHA) need to be better understood. So, we conducted an embryotoxicity test using zebrafish (Danio rerio) according to the OECD 236 guideline, a model that represents a viable alternative that bridges the gap between in vitro and mammalian models. Zebrafish embryos were exposed for 120 h to microspheres containing nSrHA nanoparticles with low and high crystallinity, synthesized at temperatures of 5°C (nSrHA5) and 90°C (nSrHA90). We evaluated lethality, developmental parameters, and reactive oxygen species (ROS) production. The larval behavior was assessed at 168 hpf to determine if the biomaterials affected motor responses and anxiety-like behavior. The results showed that the survival rate decreased significantly for the nSrHA5 group (low crystalline particles), and an increase in ROS was also observed in this group. However, none of the biomaterials caused morphological changes indicative of toxicity during larval development. Additionally, the behavioral tests did not reveal any alterations in all experimental groups, indicating the absence of neurotoxic effects from exposure to the tested biomaterials. These findings provide valuable insights into the biosafety of modified HA-based nanostructured biomaterials, making them a promising strategy for bone tissue repair. As the use of hydroxyapatite-based biomaterials continues to grow, it is crucial to ensure rigorous control over the quality, reliability, and traceability of these materials., (© 2024 Wiley Periodicals LLC.)

Background: There are 2 extraction techniques for follicular units (FUs) in hair transplantation: strip harvesting follicular unit transplantation (FUT) and follicular unit excision (FUE). Currently, no extant studies have demonstrated that one technique is superior in extraction and donor area optimization for a dense result., Objective: This study compares the FUT and FUE techniques by evaluating the percentage of FUs with 3 or more hairs and the hairs-to-follicular-unit ratio in patients who underwent both procedures at different times., Materials and Methods: The medical records of patients who underwent at least 1 FUT procedure and at least 1 FUE procedure (with this being the second surgical procedure) were reviewed. The surgeries were performed in the same clinic with the same surgeon and surgical team., Results: There was a higher percentage of FUs with 3 or more hairs and a higher hairs-to-follicular-unit ratio with the FUE technique than with the FUT technique., Conclusion: In FUE, surgeons tend to choose better-looking FUs with thick, plentiful hairs. Even with these results, it is impossible to declare one procedure superior because the correct indication considers multiple factors., (Copyright © 2024 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This case report examines the clinical presentation, diagnosis, treatment, and outcomes of mucocutaneous leishmaniasis with primary oral involvement in HIV-positive and HIV-negative patients diagnosed in Brazil., Methods: We discuss the clinical manifestations, diagnostic methods, and therapeutic strategies, highlighting the clinical and histopathologic diagnostic features and distinct progression patterns based on HIV status. Our findings are compared with patterns observed in other countries, emphasizing the differences between the Americas and Europe, Asia, and Africa., Results: In the Americas, particularly in Brazil, mucocutaneous leishmaniasis often presents with localized oral lesions, even in the presence of systemic immunosuppression, whereas in the Europe, Asia, and Africa, oral involvement is typically associated with visceral leishmaniasis in immunocompromised patients. These differences were due to variations in the parasite species involved., Conclusion: This comparison underscores the importance of regional and immunological factors in diagnosing and managing this neglected infectious disease., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Resistance exercise training (RET) is considered an excellent tool for preventing diseases with an inflammatory background. Its neuroprotective, antioxidant, and anti-inflammatory properties are responsible for positively modulating cholinergic and oxidative systems, promoting neurogenesis, and improving memory. However, the mechanisms behind these actions are largely unknown. In order to investigate the pathways related to these effects of exercise, we conducted a 12-week long-term exercise training protocol and used lipopolysaccharide (LPS) to induce damage to the cortex and hippocampus of male Wistar rats. The cholinergic system, oxidative stress, and histochemical parameters were analyzed in the cerebral cortex and hippocampus, and memory tests were also performed. It was observed that LPS: (1) caused memory loss in the novel object recognition (NOR) test; (2) increased the activity of acetylcholinesterase (AChE) and Iba1 protein density; (3) reduced the protein density of brain-derived neurotrophic factor (BDNF) and muscarinic acetylcholine receptor M1 (CHRM1); (4) elevated the levels of lipid peroxidation (TBARS) and reactive species (RS); and (5) caused inflammatory damage to the dentate gyrus. RET, on the other hand, was able to prevent all alterations induced by LPS, as well as increase per se the protein density of the alpha-7 nicotinic acetylcholine receptor (nAChRα7) and Nestin, and the levels of protein thiols (T-SH). Overall, our study elucidates some mechanisms that support resistance physical exercise as a valuable approach against LPS-induced neuroinflammation and memory loss., (© 2024 Wiley Periodicals LLC.)

Objective: Sulfonylureas have been used to improve performance in strength sports. However, this hypothetical effect has not been proven. We examined the ergogenic acute effect of gliclazide on resistance training performance and muscle recovery., Subjects and Methods: We conducted a double-blind, randomized, crossover pilot study with 10 healthy resistance-trained adults (29.3 ± 4.4 years), nonusers of anabolic steroids. The participants were randomized to two exercise sessions. In the first session, five participants received placebo and the other five received gliclazide modified release, both administered 8 hours before the session. Session two was performed in a crossover fashion a week later. The volume load was calculated as the maximum number of repetitions of four sets multiplied by load (65% 1-RM). Blood samples were collected before and after exercise, as well as 24 hours and 48 hours after exercise for measurement of creatine kinase (CK-MM) and lactate dehydrogenase (LDH) activity. Blood glucose was measured with a glucometer before, during, and after the exercise sessions., Results: Gliclazide did not enhance volume load for bench press (placebo: 2,698.0 ± 923.0 kg; gliclazide: 2,675.0 ± 1,088.0 kg; p = 0.073) or leg press (placebo: 10,866.0 ± 2,671.0 kg; gliclazide: 10,817.0 ± 2,888.0 kg; p = 0.135). However, CK-MM (-27.7%; p = 0.034) and LDH (-21.1%; p = 0.021) activities were decreased with gliclazide 48 hours after exercise. There was also a decrease in blood glucose in the gliclazide compared with the placebo session (p = 0.018)., Conclusion: Gliclazide did not enhance performance in a single resistance training session, but promoted faster muscle recovery. The decrease in blood glucose post-exercise with gliclazide was an undesirable effect that could lead to long-term glucose metabolism disorders. Registered in ClinicalTrials.gov under number NCT04443777., Competing Interests: Competing interests: the authors declare that they have no competing interests. Disclosure: no potential conflict of interest relevant to this article was reported.

Xeroderma Pigmentosum (XP) is a genetic disorder characterized by photosensitivity, dyschromia, and high risk of skin cancer. From a clinical and histologic view, it can be difficult to diagnose cutaneous melanoma (CM) in XP patients and to define its resection margins. We aimed to study the role of PRAME (PReferentially Expressed Antigen in MElanoma) in differentiating intraepidermal CM from superficial atypical melanocytic proliferation of uncertain significance (SAMPUS) and evaluating the histological margins of CMs. We included XP patients. melanocitic and nonmelanocytic lesions with adjacent skin, and, as control groups, sun-damaged skin from non-XP individuals. Melanocytic lesions with a consensus diagnosis were grouped into CM, SAMPUS, or benign. The selected samples were PRAME-immunoshistochemically stained, and the ratio between immuno-positive cells/mm was recorded, according to Olds and colleagues for intraepidermal lesions. Lezcano and colleagues' method was used for intradermal lesions. Clinical data from XP patients were reviewed. All 9 patients were alive and well at the study closure, even those who developed melanoma metastases. Positive/diffuse PRAME expression was found in 29% (7/24) of intraepidermal CMs and 20% (1/5) SAMPUS samples. All 103 XP control samples and 24 adjacent lesions skin of non-XP patients were PRAME negative. This was a single-center and retrospective study, using a relatively small sample, limiting our conclusions. In XP patients' lesions, PRAME expression could help in the setting of challenging melanocytic tumors and surgical margins evaluation. It is also possible that the method can avoid overdiagnosis and, consequently, more aggressive treatment recommendation in unequivocal CM cases., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Deforestation and high human mobility due to mining activities have been key to the increase in malaria cases in the Americas. Here, we review the epidemiological and control aspects of malaria in the Amazon mining areas. Epidemiological evidence shows: 1) a positive correlation between illegal mining activity and malaria incidence, mostly in the Amazon region; 2) most Brazilian miners are males aged 15-29 years who move between states and even countries; 3) miners do not fear the disease and rely on medical care, diagnosis, and medication when they become ill; 4) illegal mining has emerged as the most reported anthropogenic activity within indigenous lands and is identified as a major cause of malaria outbreaks among indigenous people in the Amazon; and 5) because mining is largely illegal, most areas are not covered by any healthcare facilities or activities, leading to little assistance in the diagnosis and treatment of malaria. Our review identified five strategies for reducing the malaria incidence in areas with mining activities: 1) reviewing legislation to control deforestation and mining expansion, particularly in indigenous lands; 2) strengthening malaria surveillance by expanding the network of community health agents to support rapid diagnosis and treatment; 3) reinforcing vector control strategies, such as the use of insecticide-treated nets; 4) integrating deforestation alerts into the national malaria control program; and 5) implementing multi-sectoral activities and providing prompt assistance to indigenous populations. With this roadmap, we can expect a decrease in malaria incidence in the Amazonian mining areas in the future.

Background: Tracheal grafts have been investigated for over a century, aiming to replace various lesions. However, tracheal reconstruction surgery remains a challenge, primarily due to anatomical considerations, intraoperative airway management, the technical complexity of reconstruction, and the potential postoperative morbidity and mortality. Due to research development, the amniotic membrane (AM) and Wharton's Jelly (WJ) arise as alternatives within the new set of therapeutic alternatives. These structures hold significant therapeutic potential for tracheal defects. This study analyzed the capacity of tracheal tissue regeneration after 60 days of decellularized WJ and AM implantation in rabbits submitted to conventional tracheostomy., Methods: An in vivo experimental study was carried out using thirty rabbits separated into three groups (Control, AM, and WJ) (n = 10). The analyses were performed 60 days after surgery through immunohistochemistry., Results: Different immunomarkers related to scar regeneration, such as aggrecan, TGF-β1, and α-SMA, were analyzed. However, they highlighted no significant difference between the groups. Collagen type I, III, and Aggrecan also showed no significant difference between the groups., Conclusions: Both scaffolds appeared to be excellent frameworks for tissue engineering, presenting biocompatibility and a desirable microenvironment for cell survival; however, they did not display histopathological benefits in trachea tissue regeneration.

Background: We conducted a systematic review and meta-analysis to examine the effect of dietary intake of cocoa on anthropometric measurements, lipid and glycemic profiles, and blood pressure levels in adults, with and without comorbidities., Methods: The databases used were MEDLINE (PubMed), EMBASE, Web of Science, Cochrane, LILACS, and SciELO. The eligible studies were randomized clinical trials (RCTs) involving adults undergoing cocoa consumption (cocoa extract or ≥70% cocoa dark chocolate) for ≥4 weeks that evaluated at least one of the following markers: body weight, body mass index (BMI), waist/abdominal circumference, total cholesterol, LDL-c, triglycerides, HDL-c, blood glucose, glycated hemoglobin (HbA1c), and systolic and diastolic blood pressure (SBP/DBP)., Results: Thirty-one studies were included, totaling 1986 participants. Cocoa consumption showed no effects on body weight, BMI, waist circumference, triglycerides, HDL-c and HbA1c. Yet, there was a reduction in total cholesterol (-8.35 mg/dL, 95% CI -14.01; -2.69 mg/dL), LDL-c (-9.47 mg/dL, 95% CI -13.75; -5.20 mg/dL), fasting blood glucose (-4.91 mg/dL, 95% CI -8.29; -1.52 mg/dL), SBP (-2.52 mmHg, 95% CI -4.17; -0.88 mmHg), and DBP (-1.58 mmHg, 95% CI -2.54; -0.62 mmHg)., Conclusions: The consumption of cocoa showed protective effects on major cardiometabolic risk markers that have a clinical impact in terms of cardiovascular risk reduction.

Freshwater ecosystems are among the most endangered ecosystems worldwide. While numerous taxa are on the verge of extinction as a result of global changes and direct or indirect anthropogenic activity, genomic and transcriptomic resources represent a key tool for comprehending species' adaptability and serve as the foundation for conservation initiatives. The Loire grayling, Thymallus ligericus, is a freshwater European salmonid endemic to the upper Loire River basin. The species is comprised of fragmented populations that are dispersed over a small area and it has been identified as a vulnerable species. Here, we provide a multi-tissue de novo transcriptome assembly of T. ligericus. The completeness and integrity of the transcriptome were assessed before and after redundancy removal with lineage-specific libraries from Eukaryota, Metazoa, Vertebrata, and Actinopterygii. Relative gene expression was assessed for each of the analyzed tissues, using the de novo assembled transcriptome and a genome-based analysis using the available T. thymallus genome as a reference. The final assembly, with a contig N50 of 1221 and Benchmarking Universal Single-Copy Orthologs (BUSCO) scores above 94%, is made accessible along with structural and functional annotations and relative gene expression of the five tissues (NCBI SRA and FigShare databases). This is the first transcriptomic resource for this species, which provides a foundation for future research on this and other salmonid species that are increasingly exposed to environmental stressors., (© 2024. The Author(s).)

Cervical Cancer (CC) is one of the most prevalent neoplasms among women, considered the leading cause of gynecological death worldwide, and the fourth most common type of cancer. Regional metastasis is closely related to the low effectiveness of treatment, and validating biomarkers can optimize accuracy in diagnosis and prognosis. Among the potential biomarkers associated with disease metastasis are circular RNAs (circRNAs), whose altered expression has been linked to CC progression. In this context, this systematic review aims to compile information on the clinical-pathological significance and describe the biological function of circRNAs. Inclusion and exclusion criteria were used to include relevant literature, followed by in silico analysis. Additionally, we employed the UALCAN tools to search for host genes of circRNAs and expression data, miRTargetLink 2.0 to predict interactions of microRNA target genes and the Cytoscape software to predict possible interactions of microRNA target genes. According to the research, most circRNAs were found to be overexpressed and described as regulators of processes such as invasion, cell proliferation, apoptosis and migration. They were also implicated in clinical significance, including metastasis, TNM staging and microRNA interactions. CircRNAs may participate in critical processes in tumorigenesis; therefore, understanding the underlying molecular mechanisms of gene regulation in CC can contribute to the accuracy of diagnosis, prognosis and therapy., 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 © 2024 Matos, Silva, Barbosa, de Andrade, Santos Lages, Corrêa, Oliveira, Teixeira, da Silva, Fonseca, Teixeira-Júnior, Alves, Alencar Junior, Khayat and Pinho.)

Sepsis represents a complex clinical syndrome that results from a harmful host response to infection. The infections most associated with sepsis are pneumonia, intra-abdominal infection, and urinary tract infection. Tea tree oil (TTO) has shown high antibacterial activity; however, it exhibits low aqueous solubility and high volatility, which have motivated its nanoencapsulation. In this study, the performance of nanoemulsions (NE) and nanocapsules (NC) loaded with TTO was compared. These systems were prepared by spontaneous emulsification and nanoprecipitation methods, respectively. Poly-ε-caprolactone or Eudragit ® RS100 were tested as polymers for NCs whereas Tween ® 80 or Pluronic ® F68 as surfactants in NE preparation. Pluronic ® F68 and Eudragit ® RS100 resulted in more homogeneous and stable nanoparticles. In accelerated stability studies at 4 and 25 °C, both colloidal suspensions (NC and NE) were kinetically stable. NCs showed to be more stable to photodegradation and less cytotoxic than NEs. After sepsis induction by the cecal ligation and puncture (CLP) model, both NE and NC reduced neutrophil infiltration into peritoneal lavage (PL) and kidneys. Moreover, the systems increased group thiols in the kidney and lung tissue and reduced bacterial growth in PL. Taken together, both systems showed to be effective against injury induced by sepsis; however, NCs should be prioritized due to advantages in terms of cytotoxicity and physicochemical stability., (© 2024. Controlled Release Society.)

Competing Interests: The author or authors declare that they have no conflict of interest.

Background: Some maternal characteristics are related to alcohol intake during pregnancy, which irreversibly compromises the maternal-fetal binomial integrity., Objectives: To identify the frequency, impact, and factors associated with alcohol consumption during pregnancy., Design and Setting: A cross-sectional study was performed at the Hospital Materno Infantil Presidente Vargas (HMIPV) in Porto Alegre/RS between March and December 2016., Methods: A structured questionnaire was administered along with a medical records review. They refer to the maternal sociodemographic and gestational status, alcohol consumption patterns, and characteristics of the fetus/newborn. In the statistical analysis, P values < 0.05 were considered significant., Results: The frequency of alcohol intake was 37.3%; this was characterized by the consumption of fermented beverages (89.3%), especially during the first trimester (79.6%). Risky consumption (high and/or early) occurred for 30.2% of participants. Risk factors associated with maternal alcohol consumption during pregnancy were tobacco use (P < 0.001) and abortion attempt (P = 0.023). Living with a partner (P = 0.002) and planning pregnancy (P = 0.009) were protective factors. Risky consumption was related to all of the aforementioned variables as well as threatened abortion (P = 0.023)., Conclusions: Alcohol intake during pregnancy is common and affects nearly one-third of pregnant women. Knowledge of the population at risk and protective factors is essential for the development of campaigns that seek to reduce consumption and, therefore, its consequences for the mother and fetus.

Objective: Our objective was to check if the ICD-10 operational criteria application changes non-operational, prototype-based diagnoses obtained in a real-life scenario., Methods: Psychiatry residents applied the diagnostic criteria of the ICD-10 as a "diagnostic test" to five outpatient patients they were already following who had a prototype-based diagnosis. Tests were used to ascertain whether changes in opinion were significant and if any of the diagnostic groups were more prone to change than others. The present paper is part of the study with UTN U1111-1260-1212., Results: Seventeen residents reviewed their last five case files, retrieving 85 diagnostic pairs of non-operational-based vs. operational-based diagnoses. The Stuart-Maxwell test did not indicate a significant opinion change ( χ 2 = 5.25, p = 0.39; power = 0.94) besides 30% of diagnostic changes. Despite not being statistically significant, 20.2% of all evaluations resulted in a change that would affect treatment choices. Using ICD-10 operational criteria slightly increased the number of observed diagnoses, but probably without clinical relevance. None of the non-operational diagnoses have a higher tendency to change with operational criteria application ( χ 2 = 11.6, p = 0.07). The female gender was associated with a higher diagnostic change tendency., Conclusion: Applying ICD-10 operational criteria as a diagnostic test does not induce a statistically significant diagnostic opinion change in residents and no diagnostic group seems more sensible to diagnostic change. Gender-related differences in diagnostic opinion changes might be evidence of sunk cost bias. Although not statistically significant, using operational criteria after diagnostic elaboration might help to deal with subjects without adequate treatment response., Competing Interests: HGRN receives a monthly wage from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazilian Education Ministry, due to his PhD dedication. The present manuscript is also part of his PhD research. The remaining 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 © 2024 Rocha Neto, Lessa, Koiller, Pereira, Gomes, Veloso Filho, Casado Telleria, Cavalcanti and Telles-Correia.)

Purpose: Renal cell carcinoma is an aggressive disease with a high mortality rate. Management has drastically changed with the new era of immunotherapy, and novel strategies are being developed; however, identifying systemic treatments is still challenging. This paper presents an update of the expert panel consensus from the Latin American Cooperative Oncology Group and the Latin American Renal Cancer Group on advanced renal cell carcinoma management in Brazil., Methods: A panel of 34 oncologists and experts in renal cell carcinoma discussed and voted on the best options for managing advanced disease in Brazil, including systemic treatment of early and metastatic renal cell carcinoma as well as nonclear cell tumours. The results were compared with the literature and graded according to the level of evidence., Results: Adjuvant treatments benefit patients with a high risk of recurrence after surgery, and the agents used are pembrolizumab and sunitinib, with a preference for pembrolizumab. Neoadjuvant treatment is exceptional, even in initially unresectable cases. First-line treatment is mainly based on tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs); the choice of treatment is based on the International Metastatic Database Consortium (IMCD) risk score. Patients at favourable risk receive ICIs in combination with TKIs. Patients classified as intermediate or poor risk receive ICIs, without preference for ICI + ICIs or ICI + TKIs. Data on nonclear cell renal cancer treatment are limited. Active surveillance has a place in treating favourable-risk patients. Either denosumab or zoledronic acid can be used for treating metastatic bone disease., Conclusion: Immunotherapy and targeted therapy are the standards of care for advanced disease. The utilization and sequencing of these therapeutic agents hinge upon individual risk scores and responses to previous treatments. This consensus reflects a commitment to informed decision-making, drawn from professional expertise and evidence in the medical literature., (© 2024. The Author(s).)

Introduction: Mutations of the phosphatase and tensin homolog (PTEN) gene have been associated with a spectrum of disorders called PTEN hamartoma tumor syndrome, which predisposes the individual to develop various types of tumors and vascular anomalies. Its phenotypic spectrum includes Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), Proteus syndrome, autism spectrum disorders (ASD), some sporadic cancers, Lhermitte-Duclos disease (LDD), and various types of associated vascular anomalies., Clinical Presentation: A previously healthy 27-year-old woman was experiencing visual scintillating scotomas and mild chronic headaches for the past 2 years. The initial computed tomographic (CT) and magnetic resonance imaging (MRI) scans did not reveal any abnormalities, but the possibility of pseudotumor cerebri was considered. Furthermore, a cerebral angiogram showed a posterior fossa dural arteriovenous fistula (dAVF), which was initially treated through embolization. However, in spite of proper treatment, this patient experienced multiple recurrent dAVFs in different locations, requiring multiple embolizations and surgeries. Despite exhibiting altered cerebral perfusion and hemodynamics, the patient did not display any significant symptoms until she experienced a sudden stroke resulting from deep venous thrombosis, which was not associated with any medical procedures or medication use. A comprehensive analysis was performed due to the aggressive nature of the dAVFs. Surprisingly, exome sequencing of a blood sample revealed a PTEN gene variant in chromosome 10, indicative of Cowden syndrome. However, no tumors or other vascular lesions were detected in other systems that would constitute Cowden syndrome., Conclusion: The rapid formation of multiple and complex dAVFs, coupled with not meeting the criteria for any other PTEN-related syndrome, unequivocally leads to the presentation of a novel phenotype of the PTEN germline variant., 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 © 2024 Jong-A-Liem, Sarti, dos Santos, Giacon, Wuo-Silva, Baeta, de Campos Filho and Chaddad-Neto.)

The Annelida phylum is composed of a myriad of species exhibiting key phenotypic adaptations. They occupy key ecological niches in a variety of marine, freshwater and terrestrial ecosystems. Importantly, the increment of omic resources is rapidly modifying the taxonomic landscape and knowledge of species belonging to this phylum. Here, we comprehensively characterised and annotated a transcriptome of the common ragworm, Hediste diversicolor (OF Müller). This species belongs to the family Nereididae and inhabits estuarine and lagoon areas on the Atlantic coasts of Europe and North America. Ecologically, H. diversicolor plays an important role in benthic food webs. Given its commercial value, H. diversicolor is a promising candidate for aquaculture development and production in farming facilities, under a circular economy framework. We used Illumina next-generation sequencing technology, to produce a total of 105 million (M) paired-end (PE) raw reads and generate the first whole-body transcriptome assembly of H. diversicolor species. This high-quality transcriptome contains 69,335 transcripts with an N50 transcript length of 2313 bp and achieved a BUSCO gene completeness of 97.7% and 96% in Eukaryota and Metazoa lineage-specific profile libraries. Our findings offer a valuable resource for multiple biological applications using this species., Competing Interests: Declaration of competing interest The authors declare no competing interests (financial, professional, or personal relationships) that could influence the work here reported., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Coriander is a medicinal and aromatic plant (MAP) traditionally cultivated and used in Alentejo, Portugal. However, few publications are available about its ethnobotanical applications. Four independent ethnobotanical surveys were carried out: throughout the region (2002-2003), in three villages (2013), and in city markets (2007 and 2022). Coriander was the most common fresh cultivated MAP (75% of the total area) and also the most representative MAP fresh herb in city markets. The leaves, mostly, were used fresh or frozen or transformed in piso . Some of the recipes have agro-industrial potential, such as piso and aromatized olive oil. Coriander essential oils (EOs) were isolated by hydrodistillation from aerial parts with inflorescence emergence (APIs) and from fruits, and fatty acids (FA) by solvent extraction from the fruits. Gas chromatography and gas chromatography-mass spectrometry analysis showed EOs dominated by n -decanal (21-24%), 2- trans -decenal (12-18%) and n -nonane (10-17%) in APIs, and linalool dominance (73-78%) in the fruits. Petroselinic acid (32-55%) was the dominant fatty acid. A literature survey on conventional and nonconventional extraction techniques showed a constancy in the dominant compounds isolated, highlighted piso as a home-made green-extraction procedure, but also reflected the relevance of coriander as a MAP with diverse industrial potential uses.

Hypertension, a critical global health concern, is characterized by persistent high blood pressure and is a major cause of cardiovascular events. This perspective explores the multifaceted implications of hypertension, its association with cardiovascular diseases, and the emerging role of the gut microbiota. The gut microbiota, a dynamic community in the gastrointestinal tract, plays a pivotal role in hypertension by influencing blood pressure through the generation of antioxidant, anti-inflammatory, and short-chain fatty acids metabolites, and the conversion of nitrates into nitric oxide. Antihypertensive medications interact with the gut microbiota, impacting drug pharmacokinetics and efficacy. Prebiotics and probiotics present promising avenues for hypertension management, with prebiotics modulating blood pressure through lipid and cholesterol modulation, and probiotics exhibiting a general beneficial effect. Personalized choices based on individual factors are crucial for optimizing prebiotic and probiotic interventions. In conclusion, the gut microbiota's intricate influence on blood pressure regulation offers innovative perspectives in hypertension therapeutics, with targeted strategies proving valuable for holistic blood pressure management and health promotion., Competing Interests: The author declared that there are no conflicts of interest., (© The Author(s) 2024.)

This study analyzed the effects of a physical exercise program compared to the complexity of the motor task on the cognitive function, brain-derived neurotrophic factor (BDNF) levels, and lipid profile of older adults with mild cognitive impairment (MCI). Twenty-seven participants were randomized into three intervention groups: Physical Exercise (PE), Motor Task (MT), and Physical Exercise associated with Motor Task (PE + MT). Six months of intervention twice a week resulted in improvements in cognitive function, total cholesterol (TC), and LDL cholesterol (LDL-C) in the PE (p < 0.05). In the PE + MT, in addition to improved cognitive capacity, there was also a reduction in non-HDL cholesterol (NHDL-C) and LDL cholesterol (LDL-C) levels (p < 0.05), while in the MT, the values of TC, NHDL-C, and LDL-C decreased as a result of the intervention. BDNF levels were not affected by the interventions. In conclusion, PE alone or combined with MT is effective in promoting improvements in overall cognitive function and lipid profile in older adults with MCI; and BDNF seems not to be a sensitive marker for people with mild cognitive impairment., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

There is a known correlation between cancer and changes in sphingolipids, specifically the production of sphingosine-1-phosphate (S1P) by sphingosine kinases 1 and 2 (SPHK1/SPHK2). However, a potential relationship between bioactive lipid molecules, SPHK, and the response to DNA damage is unknown. We aimed to evaluate the response of oral keratinocytes and head and neck cancer cell lines with SPHK2/S1P alterations to DNA damage. This assessment is intended to establish a link between these alterations and tumorigenesis as well as resistance to therapy. SPHK2 overexpression in oral squamous cells promoted evasion of apoptosis and cell cycle control, which increased the resistance to genotoxic agents (chemical and physical). Cells that have SPHK2 overexpression are more prone to DNA damage, which allows those damaged cells to survive and multiply. This is associated with a decrease in overall DNA methylation. These discoveries help to clarify the connection between SPHK2 and the response to DNA damage, as well as its capacity to aid in the resistance against genotoxic agents, including those used in cancer treatment., 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. Published by Elsevier B.V.)

The remission of obesity-related diseases following bariatric surgery appears to result from the reorganization of metabolic and hormonal pathways involving adipokines. This study aimed to investigate the relationship between changes in body adiposity and serum adipokine levels, as well as the association between variations in adiponectin or resistin levels and cardiometabolic risk blood biomarkers before and after Roux-en-Y gastric bypass. A longitudinal and prospective study was conducted with bariatric surgery patients. Anthropometric, body composition and blood biochemical parameters were measured before and at 2 and 6 months post-surgery. The data were analyzed using ANOVA, Pearson or Spearman correlation, and simple linear regression with a significance level of p < 0.05. Among 36 mostly female patients aged 30 to 39 years, significant reductions in body weight (-26.8%), fat mass (-50%), waist circumference (-18%) and waist-to-height ratio (-22%) were observed post-surgery. Serum adiponectin levels increased (+107%), while resistin (-12.2%), TNF-α (-35%), and PAI-1 (-11.1%) decreased. Glucose, insulin, CRP, cholesterol, LDL-c, triglycerides, and vitamin D also decreased. Waist circumference variation showed a positive correlation with PAI-1 and TNF-α and a negative correlation with adiponectin. The total fat mass showed a positive correlation with PAI-1. Adiponectin variation correlated negatively with glucose, resistin, and CRP but positively with HDL-c. Resistin showed a positive correlation with insulin and CRP. In conclusion, 6 months post-bariatric surgery, reducing abdominal adiposity had a more significant impact on serum adipokine levels than total fat mass. Adiponectin increase and resistin decrease acted as endocrine mediators driving the remission of cardiometabolic risk biomarkers in individuals with obesity following Roux-en-Y gastric bypass.

Introduction: Instruments to manage adverse effects of endocrine therapy with Aromatase inhibitors (AI) may improve adherence and persistence to treatment and Health-Related Quality of Life (HRQL). The 31-item Cervantes Scale (CS-31) is an HRQL questionnaire with particularities of the perimenopausal and postmenopausal period that could be an appropriate instrument to assess HRQL in Breast Cancer (BC) survivors., Objective: This study aimed to perform additional validation of the CS-31 for BC survivors undergoing adjuvant endocrine therapy., Methods: This prospective study was performed at three time points named T0, T1, and T2: initial, intermediate, and final follow-up period, respectively, totaling 24 months of follow-up. At each time point, the participants completed the CS-31, Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F), and Hospital Anxiety and Depression Scale (HADS). The internal consistency, construct validity, responsiveness analyses, and known-group validity of CS-31 were evaluated., Results: This study included 89 postmenopausal women diagnosed with hormone receptor-positive early BC in adjuvant endocrine therapy with AI. The internal consistency was good (Cronbach's alpha = 0.89). Construct validity received a positive rating, with 100% of results consistent with prior hypotheses. A prospective improvement in HRQL was identified for the CS-31 Global Score and FACIT-F Total Score and for most of their domains. Furthermore, women with anxiety and depression by HADS presented worse HRQL by CS-31., Conclusion: The authors identified that the CS-31 seems to be appropriate for use in oncology medical routine and may help to monitor adverse effects and HRQL of BC survivors during adjuvant endocrine therapy., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

The SET gene has four transcripts reported in NCBI, coding two isoforms of SET proteins. The most known function of SET protein is inhibiting protein phosphatase 2A, a tumor suppressor, which has been associated with different biological processes. In this review, our focus was on exploring the other SET functions related to epigenetic mechanisms, which impact cellular migration, cell cycle and apoptosis.

This study evaluated clinical features of individuals with long COVID (5-8 months after diagnosis) who reported sleep and memory problems (62 cases) compared to those without (52 controls). Both groups had a similar mean age (41 vs. 39 years). Around 86% of the participants were non-hospitalized at the time of infection, and none of them were vaccinated at that point. Subsequently, both cases and controls received the vaccine; however, the vaccination rates differed significantly between the groups (30.7% vs. 51.0%). Cases and controls had similar rates of symptoms at acute COVID phase. However, cases were more likely to experience coryza, dyspnea, headache, and nausea/vomiting during long COVID. Regarding new-onset symptoms in long COVID, 12.9% of cases had dyspnea, and 14.5% experienced nausea/vomiting, whereas in the control group there were only 1.9% and 0.0%, respectively. Cases also had a significantly higher prevalence of persistent headache (22.6% vs. 7.7%), and dyspnea (12.9% vs. 0.0). In addition, cases also showed an increased rate of mental health complaints: disability in daily activities (45.2% vs. 9.6%; P  < 0.001); concentration/sustained attention difficulties (74.2% vs. 9.6%; P  < 0.001); anxiety-Generalized Anxiety Disorder 2-item scale (GAD-2) ≥ 3 (66.1% vs. 34.6%; P  = 0.0013); and "post-COVID sadness" (82.3% vs. 40.4%; P  < 0.001). We observed a significant correlation between sadness and anxiety in cases, which was not observed in controls (P=0.0212; Spearman correlation test). Furthermore, the frequency of concomitant sadness and anxiety was markedly higher in cases compared to controls (59.7% vs. 19.2%) ( P  < 0.0001; Mann-Whitney test). These findings highlight a noteworthy association between sadness and anxiety specifically in cases. In conclusion, our data identified concurrent psychological phenotypes in individuals experiencing sleep and memory disturbances during long COVID. This strengthens the existing evidence that SARS-CoV-2 causes widespread brain pathology with interconnected phenotypic clusters. This finding highlights the need for comprehensive medical attention to address these complex issues, as well as major investments in testing strategies capable of preventing the development of long COVID sequelae, such as vaccination., Competing Interests: The authors declare there are no competing interests., (©2024 Titze-de-Almeida et al.)

The European sardine ( Sardina pilchardus , Walbaum 1792) is indisputably a commercially important species. Previous studies using uneven sampling or a limited number of makers have presented sometimes conflicting evidence of the genetic structure of S. pilchardus populations. Here, we show that whole genome data from 108 individuals from 16 sampling areas across 5000 km of the species' distribution range (from the Eastern Mediterranean to the archipelago of Azores) support at least three genetic clusters. One includes individuals from Azores and Madeira, with evidence of substructure separating these two archipelagos in the Atlantic. Another cluster broadly corresponds to the center of the distribution, including the sampling sites around Iberia, separated by the Almeria-Oran front from the third cluster that includes all of the Mediterranean samples, except those from the Alboran Sea. Individuals from the Canary Islands appear to belong to the Mediterranean cluster. This suggests at least two important geographical barriers to gene flow, even though these do not seem complete, with many individuals from around Iberia and the Mediterranean showing some patterns compatible with admixture with other genetic clusters. Genomic regions corresponding to the top outliers of genetic differentiation are located in areas of low recombination indicative that genetic architecture also has a role in shaping population structure. These regions include genes related to otolith formation, a calcium carbonate structure in the inner ear previously used to distinguish S. pilchardus populations. Our results provide a baseline for further characterization of physical and genetic barriers that divide European sardine populations, and information for transnational stock management of this highly exploited species towards sustainable fisheries.

We show, for the first time, radio measurements of the depth of shower maximum (X&#95;{max}) of air showers induced by cosmic rays that are compared to measurements of the established fluorescence method at the same location. Using measurements at the Pierre Auger Observatory we show full compatibility between our radio and the previously published fluorescence dataset, and between a subset of air showers observed simultaneously with both radio and fluorescence techniques, a measurement setup unique to the Pierre Auger Observatory. Furthermore, we show radio X&#95;{max} resolution as a function of energy and demonstrate the ability to make competitive high-resolution X&#95;{max} measurements with even a sparse radio array. With this, we show that the radio technique is capable of cosmic-ray mass composition studies, both at Auger and at other experiments.