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Nontuberculous mycobacteria (NTM) are emerging human pathogens linked to severe pulmonary diseases. Current treatments involve the prolonged use of multiple drugs and are often ineffective. Bacterial dihydrofolate reductase (DHFR) is a key enzyme targeted by antibiotics in Gram-negative bacterial infections. However, existing DHFR inhibitors designed for Gram-negative bacteria often fail against mycobacterial DHFRs. Here, we detail the rational design of NTM DHFR inhibitors based on P218 , a malarial DHFR inhibitor. We identified compound 8 , a 2,4-diaminopyrimidine exhibiting improved pharmacological properties and activity against purified DHFR, and whole cell cultures of two predominant NTM species: Mycobacterium avium and Mycobacterium abscessus . This study underscores the potential of compound 8 as a promising candidate for the in vivo validation of DHFR as an effective treatment against NTM infections.

Background: Groin hernia repair (GHR) is a performed procedure worldwide, with approximately 20 million surgeries carried out each year. Despite being less common in females, there is a lack of research on how sex influences the outcomes of GHR. This systematic review and meta-analysis aim to assess how patient sex impacts results in GHR., Methods: We performed a systematic review and meta-analysis according to Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. We searched for studies up to October 2023 in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. The studies included focused on sex outcomes for both robotic and open GHR procedures. Data extraction and quality assessment were conducted using the Risk of Bias in Non-Randomized Studies - Of Interventions tool. Our statistical analysis was performed using the metafor package in RStudio., Results: After screening a total of 3917 articles, we identified 29 studies that met our criteria, comprising a total of 1,236,694 patients. Among them, 98,641 (7.98%) patients were females. Our findings showed that females had higher rates of hernia recurrence (RR 1.28), chronic pain (RR 1.52), and surgical site infections (SSIs) (RR 1.46) compared to males. Females showed a lower tendency to undergo minimally invasive surgery (MIS) with a relative risk of 0.82 (95% CI 0.69-0.97; p = 0.02)., Conclusion: Females tend to face higher rates of complications after GHR such as an elevated risk of chronic pain, recurrence, and surgical site infections (SSI). Moreover, they undergo fewer MIS options compared to males. These results underscore the importance of research to enhance outcomes for women undergoing GHR., (© 2024 International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Objectives: This study aimed to evaluate the association between the sociodemographic characteristics of caregivers and patients with stroke, clinical data on stroke, and disability with caregiver burden, hopelessness, and anxiety., Materials and Methods: This cross-sectional study included patients with stroke of either sex, aged >18 years. Data were collected between January 2020 and July 2021. Patient demographic included age, sex, stroke type, severity, etiology, topography, treatment, and stroke recurrence. Stroke disability was assessed using the modified Rankin Scale and Barthel Index at 90 days post-discharge. Additionally, caregiver burden, hopelessness, and anxiety were evaluated during patient consultations using the Zarit Burden Interview (ZBI), Beck Hopelessness Scale (BHS), and Beck Anxiety Inventory (BAI)., Results: We included 104 patients with stroke and their caregivers. Overall caregiver burden was moderate (ZBI: 24 [25]), with mild hopelessness (BHS: 4 [4]) and minimal to mild anxiety (BAI: 8 [13]). The linear regression model presented in Table 3 showed that female caregivers scored up to 11 points higher on the Zarit Burden Interview (p = 0.011). Additionally, increased patient age was associated with a higher caregiver burden (p = 0.002) on the Zarit Burden Interview. Posterior circulation stroke and total anterior circulation stroke were also associated with higher Zarit Burden Interview scores compared to lacunar stroke (p = 0.017). Age was not associated with caregiver burden in the entire sample. However, an association between age and caregiver burden was found only in the female group. Furthermore, women aged 65 years and older experienced a more severe burden than women aged 18 to 64 years (p<0.001). Stroke disability was not associated with caregiver burden., Conclusions: Older female caregivers were significantly affected when caring for stroke patients. Total anterior circulation stroke and Posterior circulation stroke increased Zarit Burden Interview scores. However, no association was observed between stroke disability and the caregiver burden., 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.)

Fibroepithelial polyps (FEPs) are rare benign tumors that can occur in the urinary tract and are especially uncommon in the urethra. This report presents a case of a young man with obstructive symptoms caused by a urethral polyp, which was treated endoscopically. Fibroepithelial polyps can be a cause of urethral stenosis in young men and may also be encountered during the treatment of other causes of urethral narrowing., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Pseudomonas aeruginosa frequently causes antibiotic-recalcitrant pneumonia, but the mechanisms driving its adaptation during human infections remain unclear. To reveal the selective pressures and adaptation strategies at the mucosal surface, here we investigated P. aeruginosa growth and antibiotic tolerance in tissue-engineered airways by transposon insertion sequencing (Tn-seq). Metabolic modelling based on Tn-seq data revealed the nutritional requirements for P. aeruginosa growth, highlighting reliance on glucose and lactate and varying requirements for amino acid biosynthesis. Tn-seq also revealed selection against biofilm formation during mucosal growth in the absence of antibiotics. Live imaging in engineered organoids showed that biofilm-dwelling cells remained sessile while colonizing the mucosal surface, limiting nutrient foraging and reduced growth. Conversely, biofilm formation increased antibiotic tolerance at the mucosal surface. Moreover, mutants with exacerbated biofilm phenotypes protected less tolerant but more cytotoxic strains, contributing to phenotypic heterogeneity. P. aeruginosa must therefore navigate conflicting physical and biological selective pressures to establish chronic infections., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Biological clocks and other molecular biomarkers of aging are difficult to implement widely in a clinical setting. In this study, we used routinely collected hematological markers to develop an aging clock to predict blood age and determine whether the difference between predicted age and chronologic age (aging gap) is associated with advanced aging in mice. Data from 2,562 mice of both sexes and three strains were drawn from two longitudinal studies of aging. Eight hematological variables and two metabolic indices were collected longitudinally (12,010 observations). Blood age was predicted using a deep neural network. Blood age was significantly correlated with chronological age, and aging gap was positively associated with mortality risk and frailty. Platelets were identified as the strongest age predictor by the deep neural network. An aging clock based on routinely collected blood measures has the potential to provide a practical clinical tool to better understand individual variability in the aging process., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The use of C-type natriuretic peptide (CNP) in the interaction with the oocyte and in the temporary postponement of spontaneous meiosis resumption has already been well described. However, its action in pre-implantation developmental-stage embryos is yet to be understood. Thus, our study aimed to detect the presence of the canonical CNP receptor (natriuretic peptide receptor, NPR2) in germinal vesicle (GV)-, metaphase II (MII)-, presumptive zygote (PZ)-, morula (MO)-, and blastocyst (BL)-stage embryos and, later, to observe possible modulations on the embryos when co-cultured with CNP. In Experiment I, we detected and quantified NPR2 on the abovementioned embryo stages. Further, in Experiment II, we intended to test different concentrations (100, 200, or 400 nM of CNP) at different times of inclusion in the in vitro culture (IVC; inclusion from the beginning, i.e., day 1, or from day 5). In Experiment III, 400 nM of CNP was used on day 1 (D1) in the IVC, which was not demonstrated to be embryotoxic, and it showed potentially promising results in the blastocyst production rate when compared to the control. Thus, we analyzed the embryonic development rates of bovine embryos (D7) and hatching kinetics (D7, D8, and D9). Subsequently, morula and blastocyst were collected and evaluated for transcript abundance of their competence and quality (apoptosis, oxidative stress, proliferation, and differentiation) and lipid metabolism. Differences with probabilities less than p < 0.05, and/or fold change (FC) > 1.5, were considered significant. We demonstrate the presence of NPR2 until the blastocyst development stage, when there was a significant decrease in membrane receptors. There was no statistical difference in the production rate after co-culture with 400 nM CNP. However, when we evaluated the abundance of morula transcripts, there was an upregulated transcription in ADCY6 ( p = 0.057) and downregulated transcripts in BMP15 ( p = 0.013), ACAT1 ( p = 0.040), and CASP3 ( p = 0.082). In addition, there was a total of 12 transcriptions in morula that presented variation FC > 1.5. In blastocysts, the treatment with CNP induced upregulation in BID , CASP3 , SOX2 , and HSPA5 transcripts and downregulation in BDNF , NLRP5 , ELOVL1 , ELOVL4 , IGFBP4 , and FDX1 transcripts (FC > 1.5). Thus, our study identified and quantified the presence of NPR2 in bovine pre-implantation embryos. Furthermore, 400 nM of CNP in IVC, a concentration not previously described in the literature, modulated some transcripts related to embryonic metabolism, and this was not embryotoxic morphologically.

Objective: To describe the locations of food and beverage acquisition in Brazil, according to the level of food processing and household location (urban/rural)., Methods: Data from 49,489 households from the Household Budget Survey 2017-2018 were used. Information regarding food and beverages was collected through a collective acquisition booklet over 7 consecutive days. Locations were classified into 10 groups on the basis of similarities in sales structure and mode of food offering, and food and beverages were categorized according to the NOVA classification. The frequency of households acquiring food in each location was estimated, as well as the acquisition frequency according to processing level, considering significance through non-overlapping 95% confidence intervals., Results: Half of the households (51.9%) acquired food in supermarkets, contributing to both the acquisition of fresh and minimally processed foods (92.2% in urban; 90.2% in rural) and ultra-processed foods (78.6% in urban; 74.1% in rural). For the urban area, the Supermarket (55.0%), Bakery (46.5%) and Small markets (43.1%) are among the places with the highest frequency of food acquisition, while for rural areas, it is found that Small Markets (53%), Supermarkets (32.3%) and Home production (31.0%) presented the highest frequencies., Conclusion: The acquisition of food and beverages for household consumption in Brazil differs according to household location (urban/rural), indicating the importance of the community food environment in the consumption patterns of ultra-processed foods.

The first interactions among the embryo, endometrium, and corpus luteum (CL) are essential for pregnancy success. Small extracellular vesicles (sEVs) are part of these interactions. We previously demonstrated that sEVs from in vivo- or in vitro-produced bovine embryos contain different miRNA cargos. Herein we show: 1) the presence and origin (in vivo or in vitro) of the blastocyst differentially reprograms endometrial transcriptional profiles; 2) the endometrial explant (EE) cultured with in vivo or in vitro embryos release sEVs with different miRNA contents, and; 3) the luteal explant (CLE) exposed to these sEVs have distinct mRNA and miRNA profiles. To elucidate this, the EE were cultured in the presence or absence of a single Day-7 in vivo (EE-AI) or in vitro (EE-IVF) embryo. After of culture we found, in the EE, 45 and 211 differentially expressed genes (DEGs) associated with embryo presence and origin, respectively. SEVs were recovered from the conditioned media (CM) in which EE and embryos were co-cultured. Four miRNAs were differentially expressed between sEVs from CM-EE-AI and CM-EE-IVF. Luteal explants exposed in culture to these sEVs showed 1360 transcripts, and fifteen miRNAs differentially expressed. The DEGs associated with embryo presence and origin, modulating cells' proliferation, and survival. These results demonstrate that in vivo- or in vitro-produced bovine embryos induce molecular alterations in the endometrium; and that the embryo and endometrium release sEVs capable of modifying the mRNA and miRNA profile in the CL. Therefore, the sEVs-mediated embryo-endometrium-CL interactions possibly regulate the CL viability to ensure pregnancy success., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Biomaterials derived from biological matrices have been widely investigated due to their great therapeutic potential in regenerative medicine, since they are able to induce cell proliferation, tissue remodeling, and angiogenesis in situ . In this context, highly vascularized and proliferative tissues, such as the uterine wall, present an interesting source to produce acellular matrices that can be used as bioactive materials to induce tissue regeneration. Therefore, this study aimed to establish an optimized protocol to generate decellularized uterine scaffolds (dUT), characterizing their structural, compositional, and biomechanical properties. In addition, in vitro performance and in vivo biocompatibility were also evaluated to verify their potential applications for tissue repair. Results showed that the protocol was efficient to promote cell removal, and dUT general structure and extracellular matrix composition remained preserved compared with native tissue. In addition, the scaffolds were cytocompatible, allowing cell growth and survival. In terms of biocompatibility, the matrices did not induce any signs of immune rejection in vivo in a model of subcutaneous implantation in immunocompetent rats, demonstrating an indication of tissue integration after 30 days of implantation. In summary, these findings suggest that dUT scaffolds could be explored as a biomaterial for regenerative purposes, which is beyond the studies in the reproductive field.

Objective: We developed an in-house bioinformatics pipeline to improve the detection of respiratory pathogens in metagenomic sequencing data. This pipeline addresses the need for short-time analysis, high accuracy, scalability, and reproducibility in a high-performance computing environment., Results: We evaluated our pipeline using ninety synthetic metagenomes designed to simulate nasopharyngeal swab samples. The pipeline successfully identified 177 out of 204 respiratory pathogens present in the compositions, with an average processing time of approximately 4 min per sample (processing 1 million paired-end reads of 150 base pairs). For the estimation of all the 470 taxa included in the compositions, the pipeline demonstrated high accuracy, identifying 420 and achieving a correlation of 0.9 between their actual and predicted relative abundances. Among the identified taxa, 27 were significantly underestimated or overestimated, including only three clinically relevant pathogens. We also validated the pipeline by applying it to a clinical dataset from a study on metagenomic pathogen characterization in patients with acute respiratory infections and successfully identified all pathogens responsible for the diagnosed infections. These findings underscore the pipeline's effectiveness in pathogen detection and highlight its potential utility in respiratory pathogen surveillance., (© 2024. The Author(s).)

Progesterone (P4) is predicted to act as a negative regulatory hormone for oocyte maturation events; however, its local effects during follicular development remain poorly understood in bovine. The complex process of oocyte meiosis progression is dependent on cellular communication among follicular cells. Besides, the breakdown of this communication, mainly between cumulus cells (CC) and oocyte, through the retraction of cumulus projections connecting these cells can impact oocyte maturation. In our study, we observed that follicles from the ovary ipsilateral to the corpus luteum (CL) containing high intrafollicular P4 concentrations enhance the abundance of proteins detected in follicular-derived small extracellular vesicles (sEVs) predicted to be involved in the retraction of membrane projections based on actin filaments, such as transzonal projections (TZPs). Conversely, we found that follicles from the ovary contralateral to the CL, which contained low intrafollicular P4 concentrations, had a high detection of proteins predicted to regulate the maintenance of TZPs. We also performed RNAseq analysis which demonstrated that 177 genes were differentially expressed in CC under the different P4 environments. Bioinformatic analysis points to changes associated to cell metabolism in cells from follicles ipsilateral to the CL in comparison to genes involved in cell communication in CC from follicles contralateral to the CL. Our functional analysis experiment confirmed that supplementation of cumulus-oocyte complexes during in vitro maturation with P4 at concentration similar to ipsilateral follicles reduces the number of TZPs. In summary, our study underscores a direct association between P4 concentration and cumulus-oocyte interaction, with potential consequences for the acquisition of oocyte competence., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Juliano Coelho da Silveira reports financial support was provided by São Paulo Research Foundation - FAPESP. Juliano Coelho da Silveira reports financial support was provided by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES). Juliano Coelho da Silveira reports financial support was provided by National Council for Scientific and Technological Development. 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 Elsevier B.V. All rights reserved.)

The plasma proteome can mediate poor oral health problems (POHP)'s link to incident dementia. We screened 37,269 UK Biobank participants 50-74 years old (2006-2010) for prevalent POHP, further tested against 1463 plasma proteins and incident dementia over up to 15 years of follow-up. Total effect (TE) of POHP-dementia through plasma proteomic markers was decomposed into pure indirect effect (PIE), interaction referent (INTREF), controlled direct effect (CDE), or mediated interaction (INTMED). POHP increased the risk of all-cause dementia by 17% (P < 0.05). Growth differentiation factor 15 (GDF15) exhibited the strongest mediating effects (PIE > 0, P < 0.001), explaining 28% the total effect of POHP on dementia, as a pure indirect effect. A first principal component encompassing top 4 mediators (GDF15, IL19, MMP12, and ACVRL1), explained 11% of the POHP-dementia effect as a pure indirect effect. Pathway analysis including all mediators (k = 173 plasma proteins) revealed the involvement of the immune system, signal transduction, metabolism, disease, and gene expression, while STRING analysis indicated that top mediators within the first principal component were also represented in the two largest proteomic clusters. The dominant biological GO pathway for the GDF15 cluster was GO:0007169 labeled as "transmembrane receptor protein tyrosine kinase signaling pathway." Dementia is linked to POHP mediated by GDF15 among several proteomic markers., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: We aimed to conduct a meta-analysis of randomized trials comparing the immediate vs delayed provision of long-acting reversible contraceptives in postpartum subjects, focusing on short-interval pregnancies, utilization rates, and adverse events., Data Sources: Cochrane Central, Embase, PubMed, and ClinicalTrials.gov were systematically searched from inception up to December 19, 2023, without filters or language limitation., Study Eligibility Criteria: We selected randomized controlled trials assessing the immediate insertion of long-acting reversible contraceptives in women during postpartum period in comparison with the delayed provision., Study Appraisal and Synthesis Methods: We calculated relative risks with 95% confidence intervals to analyze the primary outcome of utilization rates and secondary endpoints, including initiation rates, pregnancy, any breastfeeding, exclusive breastfeeding, and serious adverse events. A random-effects model was employed in the R software. Moreover, we assessed the risk of bias of selected randomized controlled trials using version 2 of the Cochrane Risk of Bias Assessment Tool., Results: We included 24 randomized trials comprising 2507 participants, of whom 1293 (51.6%) were randomized to the immediate insertion. Postpartum women in the immediate group had lower risk of pregnancy (relative risk 0.16; 95% confidence interval 0.04-0.71; P=.02) compared with delayed group, and higher rates of long-acting reversible contraceptives at 6 months of follow-up (relative risk 1.23; 95% confidence interval 1.09-1.37; P<.01)., Conclusion: Inserting long-acting reversible contraceptives before hospital discharge was associated with a reduction in the risk of pregnancy, and increased rates of its utilization at 6 months of follow-up. This intervention may be an effective contraception strategy for postpartum women., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The expansion of sequencing technologies as a result of the response to the COVID-19 pandemic enabled pathogen (meta)genomics to be deployed as a routine component of surveillance in many countries. Scaling genomic surveillance, however, comes with associated costs in both equipment and sequencing reagents, which should be optimized. Here, we evaluate the cost efficiency and performance of different read lengths in identifying pathogens in metagenomic samples. We carefully evaluated performance metrics, costs, and time requirements relative to choices of 75, 150 and 300 base pairs (bp) read lengths in pathogen identification., Results: Our findings revealed that moving from 75 bp to 150 bp read length approximately doubles both the cost and sequencing time. Opting for 300 bp reads leads to approximately two- and three-fold increases, respectively, in cost and sequencing time compared to 75 bp reads. For viral pathogen detection, the sensitivity median ranged from 99% with 75 bp reads to 100% with 150-300 bp reads. However, bacterial pathogens detection was less effective with shorter reads: 87% with 75 bp, 95% with 150 bp, and 97% with 300 bp reads. These findings were consistent across different levels of taxa abundance. The precision of pathogen detection using shorter reads was comparable to that of longer reads across most viral and bacterial taxa., Conclusions: During disease outbreak situations, when swift responses are required for pathogen identification, we suggest prioritizing 75 bp read lengths, especially if detection of viral pathogens is aimed. This practical approach allows better use of resources, enabling the sequencing of more samples using streamlined workflows, while maintaining a reliable response capability., (© 2024. The Author(s).)

Objective: To provide cutting-edge information on the impact and risks of using Electronic Nicotine Delivery Systems (ENDS) by children and adolescents, based on the latest evidence published in the literature., Data Source: A comprehensive search was carried out on PubMed, using the expressions ''electronic cigarettes'' OR ''electronic nicotine delivery systems" OR "vaping" AND ''adolescent'' AND "risks" AND ''acute lung injury'. All retrieved articles had their titles and abstracts read to identify and fully read the papers reporting the most recent evidence on each subject., Summary of Findings: The use of ENDS has alarmingly increased in Brazil and around the world. The possibility of customizing use, the choice of flavors and nicotine content, and the general notion that these devices are harmless when compared to conventional cigarettes are some of the factors responsible for this increase. Numerous scientific studies have proven that electronic cigarettes have serious consequences for the respiratory system, such as EVALI (E-cigarette or Vaping-Associated Lung Injury) and difficult-to-control asthma, as well as harmful effects on the neurological, cardiovascular, gastrointestinal, and immunological systems. High concentrations of nicotine make many young people addicted to this substance. In Brazil, commercialization, import, and advertising are prohibited. The viable interventions to address the use of these devices in children and adolescents are prevention and behavioral counseling., Conclusion: There is clear scientific evidence that these devices pose a risk to the physical and mental health of children and adolescents., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2024 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

Objective: To investigate fatigue methods for the evaluation of translucent zirconia and to associate in vitro failures with clinically reported ones., Data: Studies published in English that used fatigue tests on dental translucent zirconia., Sources: Two databases (MEDLINE/PubMed and Scopus) were electronically searched without any restriction on year of publication., Study Selection: A total of 4555 studies were identified. After removal of duplicates (78) and irrelevant articles (4316) that did not meet the inclusion criteria, 161 articles were considered eligible based on their titles and abstracts. These articles were fully read, leading to the inclusion of 41 studies in the review., Results: The most widely used fatigue method for evaluation of translucent zirconia was step-stress (18 articles), followed by staircase (seven articles), and step-wise (two articles). Most studies had been conducted in a wet environment with the use of a stainless steel piston to apply load to cemented structures on a dentin-like substrate. Most fracture analyses indicated the fracture originated on the cementation or contact surface where the load was applied. Moreover, studies that utilized anatomical structures (dental crowns) reported fractures starting at the cervical margin of the crowns., Conclusion: Most studies used the step-stress method. Only three studies reported failures similar to those found in clinical trials that used translucent zirconia restorations., Clinical Significance: The study findings can assist on correlating clinical failures to the ones observed in vitro., Competing Interests: Declaration of competing interest The author (ADB) is an Editorial Board Member of Journal of Dentistry and was not involved in the editorial review or the decision to publish this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To evaluate how ventilatory support, the duration of invasive ventilatory support use and lung mechanics are related to barotrauma development in patients who are severely infected with COVID-19 and who are admitted to the intensive care unit and develop pulmonary barotrauma., Methods: Retrospective cohort study of patients who were severely infected with COVID-19 and who developed pulmonary barotrauma secondary to mechanical ventilation., Results: This study included 60 patients with lung barotrauma who were divided into two groups: 37 with early barotrauma and 23 with late barotrauma. The early barotrauma group included more individuals who needed noninvasive ventilation (62.2% versus 26.1%, p = 0.01). The tidal volume/kg of predicted body weight on the day of barotrauma was measured, and 24 hours later, it was significantly greater in the late barotrauma group than in the early barotrauma group. During the day, barotrauma was accompanied by plateau pressure and driving pressure accompanied by tidal volume, which significantly increased in the late barotrauma group. According to the SAPS 3, patients in the early barotrauma group had more pulmonary thromboembolism and more severe illness. However, the intensive care unit mortality rates did not significantly differ between the two groups (66.7% for early barotrauma versus 76.9% for late barotrauma)., Conclusion: We investigated the effect of respiratory mechanics on barotrauma in patients with severe COVID-19 and found that 25% of patients were on nonprotective ventilation parameters when they developed barotrauma. However, 50% of patients were on protective ventilation parameters, suggesting that other nonventilatory factors may contribute to barotrauma.

This study explored the migration of follicular fluid (FF)-derived extracellular vesicles (EVs) of the uterine environment to the bloodstream and their interaction with neutrophils in vivo and in vitro . For the in vivo experiment, six Nellore heifers ( Bos indicus ) received an intrauterine infusion seven days after ovulation with 1X PBS only (sham group; n=1), 1X PBS stained with lipophilic dye PKH26 (control group; n=2), or FF-derived EVs stained with PKH26 (treated group; n=3). Plasma was collected at 0, 10, 30, 60-, 180-, 360-, 720-, and 1440-min post-infusion to obtained EVs for analysis by nano flow cytometry. Labeled EVs were present in the bloodstream at 30- and 60-min post-infusion in the treatment group. Additionally, plasma derived-EVs from all groups were positive for Calcein-AM, Alix, Syntenin, and Calnexin, which confirm the presence of EVs. The second experiment utilized the plasma-derived EVs from the heifers from 30 and 60 min timepoints to evaluate if neutrophils can uptake EVs in vitro . As results, it was possible to observe the presence of labeled EVs in neutrophils treated with plasma derived-EVs from the treatment group. In summary, our results suggest that labeled EVs can migrate from the uterine environment rapidly and interact with circulating immune cells in bovine., Competing Interests: Conflicts of interest: The authors have no conflict of interest to declare., (Copyright © The Author(s).)

Conjugation of the naturally occurring product piplartine (PPT, 1), which is a potent cytotoxic compound and ROS inducer, with a diphenyl sulfonyl-substituted furoxan moiety (namely, 3,4-bis(phenylsulfonyl)-1,2,5-oxadiazole-2-oxide), an important type of NO donor, via an ether linker of different chain lengths is described, characterized and screened for the anticancer potential. The cytotoxicity of the new hybrids was evaluated on a panel of human cancer cell lines (MCF-7, PC3 and OVCAR-3) and two non-cancer human cells (MCF10A and PNT2). In general, the synthesized hybrids were more cytotoxic and selective compared to their furoxan precursors 4-6 and PPT in the above cancer cells. Particularly, PC3 cells are the most sensitive to hybrids 7 and 9 (IC 50 values of 240 nM and 50 nM, respectively), while a lower potency was found for the prostate normal cells (IC 50 = 17.8 μM and 14.1 μM, respectively), corresponding to selectivity indices of ca. 75 and 280, respectively. NO generation by the PPT-furoxan compounds in PC3 cells was confirmed using the Griess reaction. Furthermore, the cell growth inhibitory effect of 9 was significantly attenuated by the NO scavenger carboxy-PTIO. The intracellular ROS generation by 7 and 9 was also verified, and different assays showed that co-treatment with the antioxidant N -acetyl-l-cysteine (NAC) provided protection against PPT-induced ROS generation. Further mechanistic studies revealed that 7 and 9 had strong cytotoxicity to induce apoptosis in PC3 cells, being mediated, at least in part, by the NO-release and increase in ROS production. Notably, the ability of 9 to induce apoptosis was stronger than that of 7, which may be attributed to higher levels of NO released by 9. Compounds 7 and 9 modulated the expression profiles of critical regulators of cell cycle, such as CDKN1A (p21), c-MYC , and CCND1 (cyclin D1), as well as induced DNA damage. Overall, tethering the furoxan NO-releasing moiety to the cytotoxic natural product PPT had significant impact on the potential anticancer activity and selectivity of the novel hybrid drug candidates, especially 9, as a result of synergistic effects of both furoxan and PPT's ability to release NO, generate ROS, induce DNA damage, and trigger apoptosis., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Maximal oxygen uptake (VO 2 max) is a determining indicator for cardiorespiratory capacity in endurance athletes, and epigenetics is crucial in its levels and variability. This initial study examined a broad plasma miRNA profile of twenty-three trained elite endurance athletes with similar training volumes but different VO 2 max in response to an acute maximal graded endurance test. Six were clustered as higher/lower levels based on their VO 2 max (75.4 ± 0.9 and 60.1 ± 5.0 mL.kg -1 .min -1 ). Plasma was obtained from athletes before and after the test and 15 ng of total RNA was extracted and detected using an SYBR-based 1113 miRNA RT-qPCR panel. A total of 51 miRNAs were differentially expressed among group comparisons. Relative amounts of miRNA showed a clustering behavior among groups regarding distinct performance/time points. Significantly expressed miRNAs were used to perform functional bioinformatic analysis (DIANA tools). Fatty acid metabolism pathways were strongly targeted for the significantly different miRNAs in all performance groups and time points ( p < 0.001). Although this pathway does not solely determine endurance performance, their significant contribution is certainly achieved through the involvement of miRNAs. A highly genetically dependent gold standard variable for performance evaluation in a homogeneous group of elite athletes allowed genetic/epigenetic aspects related to fatty acid pathways to emerge.

Selection strategies are performed post-fertilization when the random combination of paternal and maternal genomes has already occurred. It would be greatly advantageous to eliminate meiotic uncertainty by selecting genetically superior gametes before fertilization. To achieve this goal, haploid embryonic cells and embryonic stem cell lineages could be derived, genotyped, and used to substitute gametes. On the paternal side, androgenetic development can be achieved by removing the maternal chromosomes from the oocyte before or after fertilization. We have shown that once developed into an embryo, haploid cells can be removed for genotyping and, if carrying the selected genome, be used to replace sperm at fertilization. A similar strategy can be used on the maternal side by activating the oocyte parthenogenetically and using some embryonic cells for genotyping while the remaining are used to produce diploid embryos by fertilization. Placed together, both androgenetic and parthenogenetic haploid cells that have been genotyped to identify optimal genomes can be used to produce offspring with predetermined genomes. Successes and problems in developing such a breeding platform to achieve this goal are described and discussed below., Competing Interests: Conflicts of interest: The authors have no conflict of interest to declare., (Copyright © The Author(s).)

Background and Purpose: Leishmaniasis is a globally prevalent vector-borne disease caused by parasites of the genus Leishmania. The available chemotherapeutic drugs present problems related to efficacy, emergence of parasite resistance, toxicity and high cost, justifying the search for new drugs. Several classes of compounds have demonstrated activity against Leishmania, including icetexane-type diterpenes, previously isolated from Salvia and other Lamiaceae genera. Thus, in this study, compounds of Salvia procurrens were investigated for their leishmanicidal and immunomodulatory activities., Methods: The exudate of S. procurrens was obtained by rapidly dipping the aerial parts in dichloromethane. The compounds were isolated by column and centrifugal planar chromatography over silica gel. The effects on L. amazonensis growth, survival, membrane integrity, reactive oxygen species (ROS) generation, mitochondrial membrane potential and cytotoxicity of the compounds towards human erythrocytes, peripheral blood mononuclear cells and macrophages were evaluated. The effects on intracellular amastigote forms, nitric oxide (NO) and TNF-α production were also investigated., Results: The exudate from the leaves afforded the novel icetexane 7-hydroxyfruticulin A (1) as well as the known demethylisofruticulin A (2), fruticulin A (3) and demethylfruticulin A (4). The compounds (1-4) were tested against promastigotes of L. amazonensis and showed an effective inhibition of the parasite survival (IC 50 = 4.08-16.26 μM). In addition, they also induced mitochondrial ROS production, plasma membrane permeability and mitochondrial dysfunction in treated parasites, and presented low cytotoxicity against macrophages. Furthermore, all diterpenes tested reduced the number of parasites inside macrophages, by mechanisms involving TNF-α, NO and ROS., Conclusion: The results suggest the potential of 7-hydroxyfruticulin A (1) as well as the known demethylisofruticulin A (2),fruticulin A (3) and demethylfruticulin A (4) as candidates for use in further studies on the design of anti-leishmanial drugs., Competing Interests: Declaration of competing interest The authors declare that is no competing financial interest., (Copyright © 2024. Published by Elsevier GmbH.)

Skeletal muscle regeneration after injury is a complex process involving inflammatory signaling and myoblast activation. Pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α) are key mediators, but their effects on gene expression in proliferating myoblasts are unclear. We performed the RNA sequencing of TNF-α treated C2C12 myoblasts to elucidate the signaling pathways and gene networks regulated by TNF-α during myoblast proliferation. The TNF-α (10 ng/mL) treatment of C2C12 cells led to 958 differentially expressed genes compared to the controls. Pathway analysis revealed significant regulation of TNF-α signaling, along with the chemokine and IL-17 pathways. Key upregulated genes included cytokines (e.g., IL-6), chemokines (e.g., CCL7), and matrix metalloproteinases (MMPs). TNF-α increased myogenic factor 5 (Myf5) but decreased MyoD protein levels and stimulated the release of MMP-9, MMP-10, and MMP-13. TNF-α also upregulates versican and myostatin mRNA. Overall, our study demonstrates the TNF-α modulation of distinct gene expression patterns and signaling pathways that likely contribute to enhanced myoblast proliferation while suppressing premature differentiation after muscle injury. Elucidating the mechanisms involved in skeletal muscle regeneration can aid in the development of regeneration-enhancing therapeutics.

During oocyte meiosis resumption, a coordinated program of transcript translation and decay machinery promotes a remodeling of mRNA stores, which determines the success of the acquisition of competence and early embryo development. We investigated levels of two genes related to mRNA translation ( CPEB1 and CPEB4 ) and two related to mRNA degradation ( CNOT7 and ZFP36L2 ) machinery and found ZFP36L2 downregulated in in vitro -matured bovine oocytes compared to in vivo counterparts. Thereafter, we tested the effects of a pre-IVM step with NPPC and a modified IVM with AREG on the modulation of members of mRNA translation and degradation pathways in cumulus cells and oocytes. Our data showed a massive upregulation of genes associated with translational and decay processes in cumulus cells, promoted by NPPC and AREG supplementation, up to 9h of IVM. The oocytes were less affected by NPPC and AREG, and even though ZFP36L2 transcript and protein levels were downregulated at 9 and 19h of IVM, only one ( KDM4C ) from the ten target genes evaluated was differently expressed in these treatments. These data suggest that cumulus cells are more prone to respond to NPPC and AREG supplementation in vitro , regarding translational and mRNA decay programs. Given the important nursing role of these cells, further studies could contribute to a better understanding of the impact of these modulators in maternal mRNA modulation and improve IVM outcomes., Competing Interests: Conflicts of interest: The authors have no conflict of interest to declare., (Copyright © The Author(s).)

This prospective, blinded, randomized crossover study aimed to assess the anesthetic effects of the combination of 30 mg/kg ketamine and 2 mg/kg midazolam via intranasal (IN) or intramuscular (IM) routes in twelve domestic chickens. Physiological parameters (respiratory rate - RR, heart rate - HR, and cloacal temperature -Tºcloacal) were monitored throughout the experiment, along with recovery time and sedation level (S0: awake, no recumbency, responsive to stimuli; S1: blinking eyes, recumbency, relaxed, response to stimulus, mild movement; S2: open eyes, recumbency, relaxed, mild response to stimuli; S3: closed eyes, recumbency, relaxed, no movement). In the IM group, all birds reached S3, while in IN 5/12 reached S3, 4/12 reached at most S1, and 1/12 at most S2. IM administration showed higher sedation at 5, 10, 15, 20, 30, 35, 40, and 45 minutes (p<0.05). IN administration exhibited a shorter total recovery time (26.3±21.4 min vs. 92.9±33.4 min; p<0.001). No time, group, or time-group interaction effects were observed in HR and cloacal Tº, with a trend to a decrease in RR both groups (p<0.001). Increased incidences of vocalization and agitation was observed via IM (4/12 vs. 0/12; p=0.028), with no difference in salivation. Despite faster recovery with less agitation and vocalization, the ketamine and midazolam combination via IN provided less consistent sedation compared to the IM route in chickens., Competing Interests: Conflict of interests: Authors declare no conflicts of interest.

Background: The study examined how plasma proteome indicators may explain the link between poor cardiovascular health (CVH) and dementia risk., Methods: The present study involved 28,974 UK Biobank participants aged 50-74y at baseline (2006-2010) who were followed-up for ≤ 15 y for incidence of dementia. CVH was calculated using Life's Essential 8 (LE8) total scores. The scores were standardized and reverse coded to reflect poor CVH (LE8z&#95;rev). OLINK proteomics was available on this sample (k = 1,463 plasma proteins). The study primarily tested the mediating effects of the plasma proteome in LE8z&#95;rev-dementia effect. The total effect was decomposed into "mediation only" or pure indirect effect (PIE), "interaction only" or interaction referent (INTREF), "neither mediation nor interaction" or controlled direct effect (CDE), and "both mediation and interaction" or mediated interaction (INTMED)., Results: The study found poorer CVH assessed by LE8z&#95;rev increased the risk of all-cause dementia by 11 % [per 1 SD, hazard ratio, (HR) = 1.11, 95 % CI: 1.03-1.20, p = 0.005). The study identified 11 plasma proteins with strong mediating effects, with GDF15 having the strongest association with dementia risk (per 1 SD, HR = 1.24, 95 % CI: 1.16, 1.33, P < 0.001 when LE8z&#95;rev is set at its mean value) and the largest proportion mediated combining PIE and INTMED (62.6 %; 48 % of TE is PIE), followed by adrenomedullin or ADM. A first principal component with 10 top mediators (TNFRSF1A, GDF15, FSTL3, COL6A3, PLAUR, ADM, GFRAL, ACVRL1, TNFRSF6B, TGFA) mediated 53.6 % of the LE8z&#95;rev-dementia effect. Using all the significant PIE (k = 526) proteins, we used OLINK Insight pathway analysis to identify key pathways, which revealed the involvement of the immune system, signal transduction, metabolism, disease, protein metabolism, hemostasis, membrane trafficking, extracellular matrix organization, developmental biology, and gene expression among others. STRING analysis revealed that five top consistent proteomic mediators were represented in two larger clusters reflecting numerous interconnected biological gene ontology pathways, most notably cytokine-mediated signaling pathway for GDF15 cluster (GO:0019221) and regulation of peptidyl-tyrosine phosphorylation for the ADM cluster (GO:0050730)., Conclusion: Dementia is linked to poor CVH mediated by GDF15 and ADM among several key proteomic markers which collectively explained ∼ 54 % of the total effect., 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., (Published by Elsevier Inc.)

Objective: The present study aimed to determine the magnitude and intervention time of resistance training required to generate adaptations in the muscle thickness of the quadriceps muscle obtained by ultrasound in healthy adults., Method: A systematic review with meta-analysis was conducted on studies recovered from Pubmed, Web of Science, and Scopus databases up to March 2022. The study selection process was carried out by two independent researchers, with the presence of a third researcher in case of disagreements. The methodological quality of the studies was determined with the TESTEX scale, and the risk of bias analysis was determined using Cochrane's RoB 2.0 tool. The meta-analysis used the inverse of the variance with a fixed model, and the effect size was reported by the standardized mean difference (SMD) with a confidence interval of 95%., Results: Ten studies were included in a meta-analysis. The overall analysis of the studies demonstrated an SMD = 0.35 [95% CI: 0.13-0.56] (P = 0.002), with a low heterogeneity of I 2  = 0% (P = 0.52). No publication bias was detected using a funnel plot followed by Egger's test (P = 0.06). The degree of certainty of the meta-analysis was high using the GRADE tool., Conclusion: We found that resistance training can generate significant average increases of 16.6% in muscle thickness obtained by ultrasound in the quadriceps femoris muscles of healthy adults. However, the subgroup analysis showed that significant effect sizes were only observed after eight weeks of training., Competing Interests: Declarations of interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The aim was to evaluate the frequency, clinicopathological features, and HPV status of oropharyngeal squamous cell carcinoma (OP-SCC) and benign HPV-related epithelial lesions of the oropharynx over the last 25 years. Moreover, a literature review was performed to investigate HPV frequency in OP-SCC samples diagnosed in Brazilian Centers., Material and Methods: A cross-sectional study analyzed OP-SCC, squamous papilloma, verruca vulgaris, and condyloma accuminatum, diagnosed from 1997 to 2021. HPV status of OP-SCC was determined by immunohistochemistry and "in situ" hybridization. Bivariate statistics were performed (p≤0.05). For the literature review, MEDLINE/PubMed, Web of Science, EMBASE, and Scopus were searched. Two independent reviewers assessed the studies for eligibility., Results: Cross-sectional: 211 OP-SCC (63.0%) and 124 benign lesions (37.0%) were included. OP-SCC frequency increased gradually over time, whereas benign lesions had steady trends. OP-SCC affected more males (n= 171; 81.0%), though the relative frequency in females rose over time. Smoking (n= 127; 60.2%) was common in OP-SCC. Nineteen OP-SCC (13.0%) were positive for HPV. HPV-positive and HPV-negative tumors had similar clinicopathological features (p>0.05). Benign lesions predominated in middle-aged (n= 32; 26.7%) women (n= 71; 57.3%), in the soft palate (n=101; 81.5%)., Literature Review: 32 studies were included, and in 60% of them, HPV frequency in OP-SCC was less than 25%., Conclusions: OP-SCC prevalence has been increasing, and it was mostly associated with smoking and alcohol rather than with HPV infection in Brazil. Benign lesions had a stationary frequency over the evaluated period.

The uterine tube extracellular matrix is a key component that regulates tubal tissue physiology, and it has a region-specific structural distribution, which is directly associated to its functions. Considering this, the application of biological matrices in culture systems is an interesting strategy to develop biomimetic tubal microenvironments and enhance their complexity. However, there are no established protocols to produce tubal biological matrices that consider the organ morphophysiology for such applications. Therefore, this study aimed to establish region-specific protocols to obtain decellularized scaffolds derived from porcine infundibulum, ampulla, and isthmus to provide suitable sources of biomaterials for tissue-engineering approaches. Porcine uterine tubes were decellularized in solutions of 0.1% SDS and 0.5% Triton X-100. The decellularization efficiency was evaluated by DAPI staining and DNA quantification. We analyzed the ECM composition and structure by optical and scanning electronic microscopy, FTIR, and Raman spectroscopy. DNA and DAPI assays validated the decellularization, presenting a significative reduction in cellular content. Structural and spectroscopy analyses revealed that the produced scaffolds remained well structured and with the ECM composition preserved. YS and HEK293 cells were used to attest cytocompatibility, allowing high cell viability rates and successful interaction with the scaffolds. These results suggest that such matrices are applicable for future biotechnological approaches in the reproductive field.

Illicit drug use is a serious and complex public health problem, not only due to the severity of the health damage but also to the social implications, such as marginalization and drug trafficking. Currently, cocaine (COC) is among the most abused drugs worldwide with about 22 million users. Drug abuse has also been found in women during the pregnancy period, which has shed light on a new group for epidemiology. The diagnosis of COC use in these cases usually depends largely on the mother's reports, which in several cases omit or deny consumption. Therefore, considering physical-chemical methods of sample preparation and exposure biomarkers, the development of analytic toxicological methods can help to confirm drug use during pregnancy. Thus, the objective of the present work was to develop an analytical method based on dispersive liquid-liquid microextraction for the determination of COC analytes, using umbilical cord tissue as an alternative biological matrix, and detection by gas chromatography coupled to mass spectrometry. Therefore, after optimization, the dispersive liquid-liquid microextraction method was fully validated for quantification of COC, benzoylecgonine, cocaethylene, ecgonine, ecgonine methyl ester and norcocaine. The limits of detection were between 15 and 25 ng/g, the limits of quantification were 30 ng/g for ecgonine and 25 ng/g for the other analytes. Linearity ranged from the limits of quantification to 1,000 ng/g. Coefficients of variation for intra-assay precision were <18.5%, inter-assay was <8.75% and bias was <16.4% for all controls. The developed method was applied in 10 suspected positive samples, based on the mother's report and maternal urine screening and confirmation. COC, benzoylecgonine, ecgonine and ecgonine methyl ester were quantified in four umbilical cords with concentrations that ranged from 39.6 to 420.5 ng/g., (© The Author(s) 2024. Published by Oxford University Press. 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.)

Background: This systematic review was conducted to assess the effects of whole-body vibration (WBV) exercises on muscles responses and on risk of falls in elderly individuals., Methods: Searches were conducted in MEDLINE/PubMed, Physiotherapy Evidence Database (PEDro), Web of Science, CINAHL and Scopus databases in Feb 2023 to identify studies with the potential to be included according to the eligibility criteria. Relevant data from included studies were extracted. The methodological quality was evaluated for each study included by PEDro scale, risk of bias (Cochrane Collaboration's tool), and the level of evidence by National Health and Medical Research Council (NHMRC)., Results: Six randomized clinical trial (RCT) were included. In respect of the level of evidence, all studies were classified as Level II (NHMRC) and regarding to the methodological quality (PEDro scale), four studies were considered 'high' and two were 'fair'. Two publications presented low risk of bias, three with high risk of bias and one unclear. All the selected studies reported positive effects and improvements on risk of falls and muscle response after WBV exercise., Conclusion: WBV exercise may contribute to reduce the risk of falls and improve muscle responses in the elderly individuals., (Copyright© 2024 Meirelles et al. Published by Tehran University of Medical Sciences.)

Background: Studing the nutritional needs and dietary habits of primates is essential to ensure their health and well-being. This includes the understanding of the use of nutrients and its correlation with health parameters., Methods: Diet and nutritional parameters of 13 captive capuchin monkeys (Sapajus sp.) were assesed. Apparent digestibility of dry matter and nutrients were evaluated. Nutritional status was established based on body condition score (BCS) and muscle mass score (MMS)., Results: High apparent digestibility coefficients (ADC) were observed for crude protein and ether extract, but low for minerals and crude fiber. The ADC of EE and CF were related to MMS, and the biochemical parameters did not correlate with the AD coefficients obtained in the group. The nutritional status of the animals remained inadequate in 84.6% of the individuals, suggesting a reformulation of the diet and nutritional management., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The study aims to describe six subgemmal neurogenous plaque (SNP) cases and compile the previously available data on SNP. Searches on PubMed, Web of Science, Embase, Scopus, and a two-step study selection were performed to compile data from case reports/series of SNP published in English literature. Our six patients (range 29-63 years) had SNP in the posterior lateral border of the tongue. Four of them were associated with lymphoepithelial cysts. A total of 15 studies, comprising 116 patients, were included in this overview. There was a slight predilection for female patients (56.0%) in the 5th (22.4%) and the 7th (23.9%) decades. The lateral border of the tongue (66.4%) was the most common anatomical location. The major manifestation was nodule/papule. Histologically, the presence of taste buds (n = 40/ 34.5%), superficial neural plexus (n = 32/ 27.6%), deep nerve fascicles (n = 32/ 27.6%), ganglion cells (n = 41/ 35.3%), and lymphoid tissue (n = 22/ 19.0%) was mainly reported. Surgical removal was the primary approach, with a low recurrence rate. Although largely unknown, SNP is a regular and likely frequent structure located in the tongue. The findings emphasize the importance of describing clinicopathological patterns of SNP as a differential diagnosis of neural lesions that affect the tongue., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

While cryopreservation of cauda epididymal sperm (SpCau) allows the preservation of post-mortem bulls' gametes, the process triggers sperm damage. Although improving post-thaw sperm quality, using egg yolk extenders (EY) raises biosafety concerns which forces the use of EY-free extenders (EYFE). Since EYFE are less efficient in preserving post-thaw sperm quality, a strategy for ejaculated sperm (SpEj) frozen with EYFE is to add an Equilibrium Time (ET) step period to the cryopreservation process. However, the ET effect on the quality of SpCau cryopreserved in EYFE remains unknown. Distinct from SpEJ, SpCau physiologically displays cytoplasmic droplets (CDs) in the flagellum that may benefit cell exchange during ET. We hypothesized that using ET in SpCau cryopreserved with EYFE impacts sperm morphofunctional features, CD area, and in vitro fertility ability. Extender nanoparticles were also assessed. Following collection from the cauda epididymis of six Nellore bulls by retrograde flow, SpCau were cryopreserved in EYFE BoviFree® (Minitube, Germany) using three ET protocols: ET0 (no-ET); ET2.5 (2.5 h-ET); and ET5 (5 h-ET). SpCau from ET2.5 and ET5 showed a higher (P ≤ 0.05) percentage of motility and integrity of plasma and acrosome membranes and a smaller (P ≤ 0.05) distal CD area. There are no differences in sperm abnormalities, oxidative stress, capacitation-like events, and in vitro fertility ability. However, a better sperm recovery was found after Percoll® selection for ET2.5 and ET5. Interestingly, the number of nanoparticles in the extender decreased in post-thawed samples. In conclusion, an ET of 2.5 or 5 h is required for an efficient SpCau cryopreservation using an EYFE., Competing Interests: Declaration of competing interest The authors affirm that they have no competing or conflicts of interest., (Copyright © 2024 Society for Cryobiology. Published by Elsevier Inc. All rights reserved.)

Objectives: Magnetic resonance imaging (MRI) is the modality of choice for rectal cancer initial staging and restaging after neoadjuvant chemoradiation. Our objective was to perform a meta-analysis of the diagnostic performance of the split scar sign (SSS) on rectal MRI in predicting complete response after neoadjuvant therapy., Methods: MEDLINE, EMBASE, and Cochrane databases were searched for relevant published studies through June 2023. Primary studies met eligibility criteria if they evaluated the diagnostic performance of the SSS to predict complete response on pathology or clinical follow-up in patients undergoing neoadjuvant chemoradiation. A meta-analysis with a random-effects model was used to estimate pooled sensitivity and specificity, area under the curve (AUC), and diagnostic odds ratio (DOR) of the SSS., Results: A total of 4 studies comprising 377 patients met the inclusion criteria. The prevalence of complete response in the studies was 21.7-52.5%. The pooled sensitivity and specificity of the SSS to predict complete response were 62.0% (95% CI, 43.5-78.5%) and 91.9% (95% CI, 78.9-97.2%), respectively. The estimated AUC for SSS was 0.83 (95% CI, 0.56-0.94) with a DOR of 18.8 (95% CI, 3.65-96.5)., Conclusion: The presence of SSS on rectal MRI demonstrated high specificity for complete response in patients with rectal cancer after neoadjuvant chemoradiation. This imaging pattern can be a valuable tool to identify potential candidates for organ-sparing treatment and surveillance., Clinical Relevance Statement: SSS presents high specificity for complete response post-neoadjuvant. This MRI finding enhances rectal cancer treatment assessment and aids clinicians and patients in choosing watch-and-wait over immediate surgery, which can potentially reduce costs and associated morbidity., Key Points: •Fifteen to 50% of rectal cancer patients achieve complete response after neoadjuvant chemoradiation and may be eligible for a watch-and-wait strategy. •The split scar sign has high specificity for a complete response. •This imaging finding is valuable to select candidates for organ-sparing management., (© 2024. The Author(s).)

We tested the hypothesis that the biosensor capability of the endometrium is mediated in part, by the effect of different cargo contained in the extracellular vesicles secreted by the conceptus during the peri-implantation period of pregnancy. We transferred Bos taurus taurus embryos of different origin, in vivo (high developmental potential (IV)), in vitro (intermediate developmental potential (IVF)), or cloned (low developmental potential (NT)), into Bos taurus indicus recipients. Extracellular vesicles (EVs) recovered from Day 16 conceptus-conditioned medium were characterized and their microRNA (miRNA) cargo sequenced alongside RNA sequencing of their respective endometria. There were substantial differences in the endometrial response to in vivo versus in vitro and in vivo versus cloned conceptuses (1153 and 334DEGs respectively) with limited differences between in vitro Vs cloned conceptuses (36 DEGs). The miRNA cargo contained in conceptus-derived EVs was similar between all three groups (426 miRNA in common). Only 8 miRNAs were different between in vivo and cloned conceptuses, while only 6 miRNAs were different between in vivo and in vitro-derived conceptuses. Treatment of endometrial epithelial cells with mimic or inhibitors for miR-128 and miR-1298 changed the proteomic content of target cells (96 and 85, respectively) of which mRNAs are altered in the endometrium in vivo (PLXDC2, COPG1, HSPA12A, MCM5, TBL1XR1, and TTF). In conclusion, we have determined that the biosensor capability of the endometrium is mediated in part, by its response to different EVs miRNA cargo produced by the conceptus during the peri-implantation period of pregnancy., (© 2024 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Extracranial cerebrovascular disease has been the subject of intense research throughout the world, and is of paramount importance for vascular surgeons. This guideline, written by the Brazilian Society of Angiology and Vascular Surgery (SBACV), supersedes the 2015 guideline. Non-atherosclerotic carotid artery diseases were not included in this document. The purpose of this guideline is to bring together the most robust evidence in this area in order to help specialists in the treatment decision-making process. The AGREE II methodology and the European Society of Cardiology system were used for recommendations and levels of evidence. The recommendations were graded from I to III, and levels of evidence were classified as A, B, or C. This guideline is divided into 11 chapters dealing with the various aspects of extracranial cerebrovascular disease: diagnosis, treatments and complications, based on up-to-date knowledge and the recommendations proposed by SBACV., Competing Interests: Conflicts of interest: No conflicts of interest declared concerning the publication of this article., (Copyright© 2024 The authors.)

Climate change can have direct and indirect effects on human health. Direct effects can include an increase in extreme weather events, such as heatwaves and floods, as well as an increase in the spread of vector-borne and infectious diseases, which may lead to a set of health problems and diseases. Indirect effects can include changes in air quality, water availability, and food production and distribution. These changes can lead to an increase in respiratory problems, malnutrition, and increased food insecurity. There is a perceived need to investigate the extent to which Higher Education Institutions (HEIs) are engaged in efforts to foster a greater understanding of the connections between climate change and health. In this context, this preliminary investigation offers an overview of the relationships between climate change and health. By means of a survey among teaching staff and researchers at HEIs from 42 countries across all continents working on the connection between climate change and health. The study has investigated the extent to which current provisions for education and training on the connection between climate change and health are being considered and how current needs in terms of policy development, research, and training are being met. A series of case studies illustrate how universities worldwide are actively developing strategies and implementing measures to address climate change and health. The study concludes by providing specific recommendations aimed at facilitating the handling of issues related to climate change and health in a higher education context., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Leal Filho 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: Inflammation in the lungs and other vital organs in COVID-19 is characterized by the presence of neutrophils and a high concentration of neutrophil extracellular traps (NETs), which seems to mediate host tissue damage. However, it is not known whether NETs could have virucidal activity against SARS-CoV-2., Methods: We investigated whether NETs could prevent SARS-CoV-2 replication in neutrophils and epithelial cells and what the consequence of NETs degradation would be in K18-humanized ACE2 transgenic mice infected with SARS-CoV-2., Results: Here, by immunofluorescence microscopy, we observed that viral particles colocalize with NETs in neutrophils isolated from patients with COVID-19 or healthy individuals and infected in vitro. The inhibition of NETs production increased virus replication in neutrophils. In parallel, we observed that NETs inhibited virus abilities to infect and replicate in epithelial cells after 24 hours of infection. Degradation of NETs with DNase I prevented their virucidal effect in vitro. Using K18-humanized ACE2 transgenic mice, we observed a higher viral load in animals treated with DNase I. However, the virucidal effect of NETs was not dependent on neutrophil elastase or myeloperoxidase activity., Conclusions: Our results provide evidence of the role of NETosis as a mechanism of SARS-CoV-2 viral capture and inhibition., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Ethnopharmacological Relevance: Monteverdia ilicifolia (Maytenus ilicifolia, Celastraceae), known as "espinheira-santa", has been widely used in Brazil to manage mainly gastrointestinal diseases. This species has been listed in the Brazilian Pharmacopeia and in the National List of Essential Medicines (RENAME). Considering that clinical studies about M. ilicifolia are rare, our group has been performing a broader project designed to evaluate the efficacy of M. ilicifolia capsules in a clinical trial, for this reason, approaches to provide safety to those patients are relevant., Aim of the Study: We aimed to investigate the potential pharmacokinetic interaction and hepatotoxicity and intestinal toxicity of an aqueous extract of M. ilicifolia and its main phytocompounds, catequin, epicatequin, and quercetin., Methods and Materials: Slices of liver and intestine of Wistar rats were incubated with different concentrations of M. ilicifolia extract or isolated compounds (catechin, epicatechin and quercetin). Commercial kits were used to evaluate enzyme activities of CYP2D6 and CYP3A4 isoforms, as well as cell viability (MTT) assay and intracellular enzymes leakage, specifically lactate dehydrogenase (LDH), alkaline phosphatase (AP), aspartate aminotransferase (AST), alanine aminotransferase (ALT) were studied., Results: Incubation with M. ilicifolia extract, catechin, epicatechin and quercetin did not affect significantly any evaluated parameter in intestines. The intracellular enzymes leakages, CYP2D6, LDH and AST, were increased with M. ilicifolia extract and quercetin in liver slices., Conclusions: Our in vitro findings highlighted, for the first time, the potential hepatotoxicity induced by an aqueous extract of M. ilicifolia, consequently this species and its products should be avoided in liver diseases, supporting that studies of safety must be performed including in the context of traditional medicinal plants., 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.)

Aims: Despite the established use of palatal tissue grafts for mucogingival procedures, there are no studies on the effect of extraoral storage time on graft outcomes. This prospective split-mouth randomized experimental clinical trial aimed to assess whether gingival graft extraoral storage time affects graft healing., Methods: Standardized grafts were harvested from the palate and stored extraorally for 2 (Control) or 40 (Test) minutes before being placed at recipient beds. Intraoral scans, clinical photographs, and tissue blood perfusion were obtained preoperatively, postoperatively, and at follow-up visits (Days 2 (PO2), 3 (PO3), 7 (PO7), and 14 (PO14)). Healing Score Index (HSI) and wound fluid (WF) biomarkers (angiogenin, IL-6, IL-8 (CXCL8), IL-33, VEGF-A, and ENA-78 (CXCL5)) were also assessed., Results: Twenty-three participants completed all study visits. Extraoral storage time was 2.3 ± 1.1 min and 42.8 ± 3.4 min for C and T grafts, respectively (p < .0001). Recipient beds remained open for 21.4 ± 1.7 min. No graft underwent necrosis or failed to heal by PO14. Minimal volumetric changes were observed, without significant intergroup differences (p ≥ .11). Graft perfusion initially decreased post-harvesting before peaking on PO7 for both C and T grafts, with no significant intergroup differences (p ≥ .14). HSI values progressively increased, with no significant intergroup differences (p ≥ .22). WF analysis revealed detectable levels for all biomarkers tested, without significant intergroup differences (p ≥ .23)., Conclusion: Extraoral storage time of 40 min has neither statistically significant nor clinically discernible effects on autologous graft revascularization, early healing, or survival, as determined by physiological, wound healing, and molecular parameters., (© 2024 The Authors. Journal of Periodontal Research published by John Wiley & Sons Ltd.)

Trypanosoma cruzi is the etiologic agent of the most prevalent human parasitic disease in Latin America, Chagas disease. Its genome is rich in multigenic families that code for virulent antigens and are present in the rapidly evolving genomic compartment named Disruptive. DNA replication is a meticulous biological process in which flaws can generate mutations and changes in chromosomal and gene copy numbers. Here, integrating high-throughput and single-molecule analyses, we were able to identify Predominant, Flexible, and Dormant Orc1Cdc6-dependent origins as well as Orc1Cdc6-independent origins. Orc1Cdc6-dependent origins were found in multigenic family loci, while independent origins were found in the Core compartment that contains conserved and hypothetical protein-coding genes, in addition to multigenic families. In addition, we found that Orc1Cdc6 density is related to the firing of origins and that Orc1Cdc6-binding sites within fired origins are depleted of a specific class of nucleosomes that we previously categorized as dynamic. Together, these data suggest that Orc1Cdc6-dependent origins may contribute to the rapid evolution of the Disruptive compartment and, therefore, to the success of T. cruzi infection and that the local epigenome landscape is also involved in this process.IMPORTANCE Trypanosoma cruzi , responsible for Chagas disease, affects millions globally, particularly in Latin America. Lack of vaccine or treatment underscores the need for research. Parasite's genome, with virulent antigen-coding multigenic families, resides in the rapidly evolving Disruptive compartment. Study sheds light on the parasite's dynamic DNA replication, discussing the evolution of the Disruptive compartment. Therefore, the findings represent a significant stride in comprehending T. cruzi 's biology and the molecular bases that contribute to the success of infection caused by this parasite., Competing Interests: The authors declare no conflict of interest.

This article tried, from an intersectional standpoint, to grasp the challenges experienced by health professionals and service users of human milk banks in provision of care for transgender men chestfeeding. This exploratory, descriptive qualitative study drew on interviews of six human milk bank staff, who had previously assisted trans men in relation to chestfeeding and two bisexual trans men, who chestfed. The data was treated by thematic analysis, supported by Atlas.ti software, version 9.0. Lacunas in the educational, institutional and management spheres, associated with personal and social issues, reproduce a pre-conceived normative model and disregard the special demands of providing chestfeeding care for the trans population. Cisheteronormativity and "professional supremacy" operate in personal, social and institutional respects to segregate transgender men in lactation support services. Intersectional analysis of these challenges affords an overall view of segregative factors and enables public policies to be introduced to promote social justice.

Background: Graft loss increases the risk of patient death after simultaneous pancreas-kidney (SPK) transplantation. The relative risk of each graft failure is complex due to the influence of several competing events., Methods: This retrospective, single-center study compared 4-year patient survival according to the graft status using Kaplan-Meier (KM) and Competing Risk Analysis (CRA). Patient survival was also assessed according to five eras (Era 1: 2001-2003; Era 2: 2004-2006; Era 3: 2007-2009; Era 4: 2010-2012; Era 5: 2012-2015)., Results: Between 2000 and 2015, 432 SPK transplants were performed. Using KM, patient survival was 86.5% for patients without graft loss (n = 333), 93.4% for patients with pancreas graft loss (n = 46), 43.7% for patients with kidney graft loss (n = 16), and 25.4% for patients with pancreas and kidney graft loss (n = 37). Patient survival was underestimated using KM versus CRA methods in patients with pancreas and kidney graft losses (25.4% vs. 36.2%), respectively. Induction with lymphocyte depleting antibodies was associated with 81% reduced risk (HR.19, 95% CI.38-.98, p = .0048), while delayed kidney function (HR 2.94, 95% CI 1.09-7.95, p = .033) and surgical complications (HR 2.94, 95% CI 1.22-7.08, p = .016) were associated with higher risk of death. Four-year patient survival increased from Era 1 to Era 5 (79% vs. 87.9%, p = .047)., Conclusion: In this cohort of patients, kidney graft loss, with or without pancreas graft loss, was associated with higher mortality after SPK transplantation. Compared to CRA, the KM model underestimated survival only among patients with pancreas and kidney graft losses. Patient survival increased over time., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Currently, in Brazil, all researchers involved in animal experimentation must undergo training in laboratory animal science to stay updated on biology, methodology, ethics, and legal considerations related to the use of animals. The training program presented in this study not only aims to fulfill a legal obligation but also intends to train students and professionals to effectively care for their biomodels. It seeks to help them understand the importance of this care, both for the welfare of the animals and for the results of their projects. In total, 58 participants were present at the event (pre-event and full-time course). These participants consisted students and professionals from 11 institutions and 5 different countries. These numbers demonstrate the successful attainment of the desired capillarity in the scientific community and the posterior dissemination of knowledge. Through this course, it was possible to train the participants and raise their awareness about the importance of applying scientific knowledge in their daily practices to maintain the animals, ensuring the welfare of the models and refining the research. Finally, the program presented in this study, as well as the strategies adopted, can serve as a model for other institutions aiming to achieve similar results.

This study evaluated the feasibility of an automated method to delimit the required area to quantitatively analyze root filling voids and gaps from cross-sectional confocal laser scanning microscopy (CLSM) images. Root canals of maxillary canines were prepared with rotary instruments and filled by lateral compaction technique using gutta-percha and AH Plus sealer. The roots were stored (100% humidity, 37 °C) for a period of 24 h and then transversally sectioned to obtain 2-mm-thick slices from the apical and middle thirds. The areas corresponding to filling materials, gaps, and voids were manually delimited or automatically demarked by ImageJ software after converting the images to the RGB color system. Based on manual and automatic delimitations, the percentages of voids and gaps were calculated. Data of voids and gaps between middle and apical thirds were individually compared by paired t-test. Pearson`s correlation test was used to assess the correlation of data between the methods. Irrespective of the method of area delimitation, no difference was observed between the root thirds for both voids and gaps, while the p-values calculated for each method were similar. Almost perfect correlations between the methods were observed for both outcomes. The proposed method to automatically delimit the areas corresponding to filling material, voids, and gaps appears to be a valid method to facilitate the quantitative analysis of defects in root canal fillings using topographic CSLM images., (© 2023. The Author(s), under exclusive licence to The Society of The Nippon Dental University.)

Internet-delivered cognitive-behavioral therapy (I-CBT) is effective in treating post-traumatic stress disorder (PTSD) symptoms, offering enhanced accessibility and cost-effectiveness. However, it's important to note that these technologies may not be suitable for all age groups. Therefore, we conducted a systematic review and meta-analysis to determine if the effectiveness of I-CBT in treating PTSD varies based on the patients' mean age. We conducted a systematic review of the literature, focusing on randomized controlled trials (RCTs) in the ISI Web of Science, PubMed/MEDLINE, and PsycINFO databases. Following this, we performed a meta-analysis and evaluated the risk of bias using the Cochrane risk of bias quality assessment tool. In this study, we examined patient-related factors (civil or military status, age, and gender), clinical characteristics (baseline PTSD severity and type of trauma), and treatment characteristics (type of intervention, synchronous or asynchronous delivery, and the number of sessions) as independent variables. The dependent variable was the reduction in mean PTSD symptoms. Five RCTs out of 1,552 screened studies were included in this review, all of which showed some level of concern regarding potential bias. Our meta-analysis indicates that I-CBT is equally effective regardless of patients' mean age. Since all RCTs included only provide the mean age of the patients, further randomized controlled trials should address the effectiveness of I-CBT among different age groups.