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ABSTRACT: Our objectives were to evaluate the endometrial responsiveness of dairy heifers to an intrauterine infusion of recombinant bovine interferon-tau (rbIFN-τ) and to associate endometrial responses to rbIFN-τ with subsequent reproductive performance. In experiments 1 and 2, cyclic heifers were enrolled in a program for synchronization of the estrous cycle, and blood sampling and ultrasonography examinations were performed on d 0, 4, 7, 11, and 14 of the estrous cycle. In experiment 1, heifers were randomly assigned to receive an intrauterine infusion containing 2 µg of rbIFN-τ (rbIFN-τ = 19) or saline control (CTRL = 19) into the uterine horn ipsilateral to the corpus luteum (CL) on d 14 of the estrous cycle. Then, 6 hours after the infusion, the infused uterine horn was flushed for sampling of the uterine luminal fluid (ULF) for composition analysis, and the endometrium was biopsied for transcriptomics. In experiment 2, 100 heifers received an intrauterine infusion of rbIFN-τ, and the same procedures for uterine sample collection were performed as described in experiment 1. After the intrauterine test, heifers were enrolled in a breeding program and classified as highly fertile (HF; pregnant at first AI) or subfertile (SF; not pregnant at first AI). Statistical analyses were performed using regression models, which included the effects of treatment (experiment 1: CTRL vs. rbIFN-τ) or fertility group (experiment 2: HF vs. SF) and block of samples. Intrauterine infusion of rbIFN-τ increased the expression of classical interferon-stimulated genes in the endometrium (e.g., ISG15, MX1, OAS2, IRF9, and USP18), and an antiviral response was predicted to be the main downstream effect of the transcriptome changes. In addition, rbIFN-τ increased the abundance of cholesterol, glycerol, and the overall concentration of oxylipins in the ULF. Analysis of endometrial transcriptome between HF and SF heifers revealed important differences in the expression of genes associated with cell signaling, metabolism, attachment, and migration, with a large representation of genes encoding extracellular matrix proteins. In general, differentially expressed genes were expected to be downregulated by IFN-τ but seemed to fail to be downregulated in SF heifers, resulting in higher expression in SF compared with HF heifers. Subfertile heifers had lower concentrations of glycerol and an altered profile of oxylipins in the ULF, with a lower abundance of oxylipins derived from arachidonic acid and dihomo-γ-linolenic acid, and a greater abundance of oxylipins derived from linoleic acid. Measurements of ovarian function did not differ between groups and, therefore, did not influence the observed results in uterine biology. Overall, the endometrial responsiveness to IFN-τ is variable among individuals and associated with subsequent fertility of heifers, indicating that communication between conceptus and endometrium is critical for the uterine receptivity and survival of pregnancy.

ABSTRACT: The objective of this prospective cohort study was to determine if progesterone (P4) profiles differed between dairy cows with or without inflammatory disorders early postpartum. A total of 708 cows from 2 commercial herds were enrolled 3 wk before parturition and examined for clinical health disorders (difficult calving, retained placenta, metritis, displaced abomasum, mastitis, or lameness) until 5 wk postpartum. Serum haptoglobin (Hp) was measured in blood at 2 and 6 DIM (range ±2 d); metritis was assessed at 4, 8, 11, and 15 DIM; and purulent vaginal discharge and endometritis (≥6% PMN in endometrial cytology sampled by cytobrush) were assessed at 35 ± 3 DIM. As Hp ≥0.8 g/L or endometritis were associated with ovarian dysfunction in previous studies, cows with serum Hp ≥0.8 g/L at either time point and endometritis, regardless of clinical disease, were classified as the cohort with inflammatory disorders (INFLAM; n = 139). Clinically healthy cows without difficult calving, with singleton birth, with Hp

Objective: Despite the increasing reports of blaNDM in Enterobacterales in Brazil, comprehensive whole genome sequencing (WGS) data remain scarce. To address this knowledge gap, our study focuses on the characterization of the genome of an New Delhi Metallo-β-lactamase (NDM)-1-producing Klebsiella quasipneumoniae subsp. quasipneumoniae (KQPN) clinical strain isolated in Brazil. Methods: The antimicrobial susceptibility profile of the A-73.113 strain was performed by agar dilution or broth microdilution following the Brazilian Antimicrobial Susceptibility Testing Committee/European Committee on Antimicrobial Susceptibility Testing recommendations. WGS was performed using the Illumina® NextSeq platform and the generated reads were assembled using the SPAdes software. The sequences obtained were submitted to the bioinformatics pipelines to determine the sequence type, resistome, plasmidome, and virulome. Results: The A-73.113 strain was identified as KQPN and was susceptible to polymyxins (MICs, ≤0.25 µg/mL), tigecycline (MIC, 0.5 µg/mL), ciprofloxacin (MIC, 0.5 µg/mL), and levofloxacin (MIC, 1 µg/mL). WGS analysis revealed the presence of genes conferring resistance to β-lactams (blaNDM-1, blaCTX-M-15, blaOXA-9, blaOKP-A-5, blaTEM-1), aminoglycosides [aph(3′)-VI, aadA1, aac(6′)-Ib], and fluoroquinolones (oqxAB, qnrS1, aac(6′)-Ib-cr]. Additionally, the presence of the plasmid replicons Col(pHAD28), IncFIA(HI1), IncFIB(K) (pCAV1099-114), IncFIB(pQil), and IncFII(K), as well as virulence-encoding genes fimABCDEFGHIK (type 1 fimbria), pilW (type IV pili), iutA (aerobactin), entABCDEFS/fepABCDG/fes (Ent siderophores), iroE (salmochelin), and allABCDRS (allantoin utilization) was verified. Furthermore, we found that the A-73.113 strain belongs to ST1040. Conclusions: Here we report the genomic characteristics of an NDM-1-producing KQPN ST1040 strain isolated from blood cultures in Brazil. These data will enhance our comprehension of how this species contributes to the acquisition and dissemination of blaNDM-1 in Brazilian nosocomial settings.

Summary: Levodopa-induced dyskinesia (LID) refers to involuntary motor movements of chronic use of levodopa in Parkinson’s disease (PD) that negatively impact the overall well-being of people with this disease. The molecular mechanisms involved in LID were investigated through whole-blood transcriptomic analysis for differential gene expression and identification of new co-expression and differential co-expression networks. We found six differentially expressed genes in patients with LID, and 13 in patients without LID. We also identified 12 co-expressed genes exclusive to LID, and six exclusive hub genes involved in 23 gene-gene interactions in patients with LID. Convergently, we identified novel genes associated with PD and LID that play roles in mitochondrial dysfunction, dysregulation of lipid metabolism, and neuroinflammation. We observed significant changes in disease progression, consistent with previous findings of maladaptive plastic changes in the basal ganglia leading to the development of LID, including a chronic pro-inflammatory state in the brain.

Summary: Background: It is unknown if early COVID-19 monoclonal antibody (mAb) therapy can reduce risk of Long COVID. The mAbs amubarvimab/romlusevimab were previously demonstrated to reduce risk of hospitalization/death by 79%. This study assessed the impact of amubarvimab/romlusevimab on late outcomes, including Long COVID. Methods: Non-hospitalized high-risk adults within 10 days of COVID-19 symptom onset enrolled in a randomized, double-blind, placebo-controlled phase 2/3 trial of amubarvimab/romlusevimab for COVID-19 treatment. Late symptoms, assessed using a participant-completed symptom diary, were a pre-specified exploratory endpoint. The primary outcome for this analysis was the composite of Long COVID by participant self-report (presence of COVID-19 symptoms as recorded in the diary at week 36) or hospitalization or death by week 36. Inverse probability weighting (IPW) was used to address incomplete outcome ascertainment, giving weighted risk ratios (wRR) comparing amubarvimab/romlusevimab to placebo. Findings: Participants received amubarvimab/romlusevimab (n = 390) or placebo (n = 390) between January and July 2021. Median age was 49 years, 52% were female, 18% Black/African American, 49% Hispanic/Latino, and 9% COVID-19-vaccinated at entry. At week 36, 103 (13%) had incomplete outcome ascertainment, and 66 (17%) on amubarvimab/romlusevimab and 92 (24%) on placebo met the primary outcome (wRR = 0.70, 95% confidence interval (CI) 0.53–0.93). The difference was driven by fewer hospitalizations/deaths with amubarvimab/romlusevimab (4%) than placebo (13%). Among 652 participants with available diary responses, 53 (16%) on amubarvimab/romlusevimab and 44 (14%) on placebo reported presence of Long COVID. Interpretation: Amubarvimab/romlusevimab treatment, while highly effective in preventing hospitalizations/deaths, did not reduce risk of Long COVID. Additional interventions are needed to prevent Long COVID. Funding: National Institute of Allergy and Infectious Diseases of the National Institutes of Health. Amubarvimab and romlusevimab supplied by Brii Biosciences.

Background and aims: Cardiovascular disease remains a leading cause of mortality, with statins widely used to reduce its risk. Despite extensive research, the nuanced impact of statin therapy on cardiorespiratory fitness, particularly the reduction in peak oxygen consumption (VO2), is still an open question. This study aims to contribute fresh insights to the ongoing discussion, highlighting the unresolved nature of this clinical matter. Methods: We retrospectively analyzed maximal cardiopulmonary exercise test (CPET) in male and female participants over 18 years of age who were under statins treatment. They were categorized as physically active or inactive according to self-report of physical activity. From 33,804 CPET, 4,941 participants (76 % men, age 42 ± 13 years; and 24 % women, age 41 ± 13 years) were included in the study. Results: The multivariate linear regression model showed that statins were associated with a significant reduction in VO2 peak (−4.2 [-4.8, −3.5] mL/kg/min, p 600 min/week: 6.9 [5.4; 8.4] mL/kg/min, all p 150 min/week). Future research should explore the mechanisms behind this interaction and identify optimal exercise regimens for individuals on statin therapy.

European catfish is a large-bodied apex predator, a key species in native areas, but invasive in others where it negatively impacts local aquatic fauna necessitates catfish regulation. However, traditional ichthyological methods face challenges in capturing it. The study presents a detailed description of the efficient long-line method, refined through 48 sampling campaigns across twelve European water bodies. This method proves cost-effective and technically undemanding, requiring an average of 5.6 bait fish to catch one European catfish per day. The long-lines outperform other techniques, with the highest Biomass per unit effort (BPUE) of 6.205 kg of catfish per man-hour and minimal by-catch (0.276 kg per man-hour). In contrast, fyke nets, the second most efficient method, achieve a BPUE of 0.621 kg of catfish per man-hour with 3.953 kg of by-catch per man-hour. To optimize long-line catches, a 15 m distance between branch lines and regular relocation is recommended. Live fish is the most effective bait with no significant differences observed among species. However, earthworms, a less controversial alternative, are also efficient, especially for smaller catfish. Our recapture approach using various ichthyological methods revealed no hook avoidance behavior by catfish after a previous catch or avoidance by a certain part of the population. The long-line method is suitable for population regulation, scientific research, and conservation efforts and is the most effective means of capturing live European catfish.

Summary: Background: Mucositis is a common and highly impactful side effect of conventional and emerging cancer therapy and thus the subject of intense investigation. Although common practice, mucositis assessment is heterogeneously adopted and poorly guided, impacting evidence synthesis and translation. The Multinational Association of Supportive Care in Cancer (MASCC) Mucositis Study Group (MSG) therefore aimed to establish expert recommendations for how existing mucositis assessment tools should be used, in clinical care and trials contexts, to improve the consistency of mucositis assessment. Methods: This study was conducted over two stages (January 2022–July 2023). The first phase involved a survey to MASCC-MSG members (January 2022–May 2022), capturing current practices, challenges and preferences. These then informed the second phase, in which a set of initial recommendations were prepared and refined using the Delphi method (February 2023–May 2023). Consensus was defined as agreement on a parameter by >80% of respondents. Findings: Seventy-two MASCC-MSG members completed the first phase of the study (37 females, 34 males, mainly oral care specialists). High variability was noted in the use of mucositis assessment tools, with a high reliance on clinician assessment compared to patient reported outcome measures (PROMs, 47% vs 3%, 37% used a combination). The World Health Organization (WHO) and Common Terminology Criteria for Adverse Events (CTCAE) scales were most commonly used to assess mucositis across multiple settings. Initial recommendations were reviewed by experienced MSG members and following two rounds of Delphi survey consensus was achieved in 91 of 100 recommendations. For example, in patients receiving chemotherapy, the recommended tool for clinician assessment in clinical practice is WHO for oral mucositis (89.5% consensus), and WHO or CTCAE for gastrointestinal mucositis (85.7% consensus). The recommended PROM in clinical trials is OMD/WQ for oral mucositis (93.3% consensus), and PRO-CTCAE for gastrointestinal mucositis (83.3% consensus). Interpretation: These new recommendations provide much needed guidance on mucositis assessment and may be applied in both clinical practice and research to streamline comparison and synthesis of global data sets, thus accelerating translation of new knowledge into clinical practice. Funding: No funding was received.

Anti-CD19 CAR-T cell therapy represents a breakthrough in the treatment of B-cell malignancies, and it is expected that this therapy modality will soon cover a range of solid tumors as well. Therefore, a universal cheap and sensitive method to detect CAR expression is of foremost importance. One possibility is the use of epitope tags such as c-Myc, HA or FLAG tags attached to the CAR extracellular domain, however, it is important to determine whether these tags can influence binding of the CAR with its target molecule. Here, we conducted in-silico structural modelling of an FMC63-based anti-CD19 single-chain variable fragment (scFv) with and without a c-Myc peptide tag added to the N-terminus portion and performed molecular dynamics simulation of the scFv with the CD19 target. We show that the c-Myc tag presence in the N-terminus portion does not affect the scFv’s structural equilibrium and grants more stability to the scFv. However, intermolecular interaction potential (IIP) analysis reveals that the tag can approximate the complementarity-determining regions (CDRs) present in the scFv and cause steric impediment, potentially disturbing interaction with the CD19 protein. We then tested this possibility with CAR-T cells generated from human donors in a Nalm-6 leukemia model, showing that CAR-T cells with the c-Myc tag have overall worse antitumor activity, which was also observed when the tag was added to the C-terminus position. Ultimately, our results suggest that tag addition is an important aspect of CAR design and can influence CAR-T cell function, therefore its use should be carefully considered.

Purpose: This prospective study evaluated the effects of the metal-free crowns on the periodontal tissues of abutment teeth during a 12-month follow-up. Materials and Methods:: A sample of 24 patients (N = 32 abutment teeth) who needed a single-tooth restoration were enrolled to receive either a metal-ceramic (n = 21) or lithium disilicate (n = 11). The single-unit crowns were evaluated at baseline, 3-and 12-month follow-up. The periodontal parameters were evaluated: plaque index (PI), gingival bleeding index (GBI), bleeding on probing (BOP), probing depth (PD), clinical attachment loss (CAL), radiographically and clinical crown fitting, bone resorption, and marginal finish lines. Statistical analyses were performed using the Exact Fisher and Mann-Whitney tests, and the Wilcoxon signed-rank test as a post hoc test for Friedman (95 % confidence interval). Results:: The marginal finish line showed a statistical difference with a biomaterial type (p =.004). After a 12-months, a significant increase was observed in PI and mean PD for abutment teeth of metal-ceramic crowns. The metal-free crowns presented higher values for GBI and CAL (p2

Background: Mitotane is employed as adjuvant therapy in managing adrenocortical carcinoma in pediatric patients. While various adverse effects, such as estrogen-like manifestations, are well-documented in adults, there is limited knowledge regarding pediatric-specific toxicity. This report details an uncommon case of isosexual precocious pseudopuberty induced during childhood due to the estrogen-like effects of mitotane. Case report: A 2.8-year-old female diagnosed with adrenocortical carcinoma (pT4 pN0 M0) underwent adjuvant treatment with mitotane and cytotoxic chemotherapy following incomplete resection (tumor stage III). Approximately eight months into mitotane treatment, she exhibited signs of puberty (Tanner stage 2), including progressive breast development, uterine enlargement, vaginal discharge, and an advancement of bone age by nearly two years. Gonadotrophin-dependent puberty and endogenous estrogen production were ruled out. The precocious pseudopuberty was attributed to previously reported estrogen-like effects of mitotane therapy. Subsequent administration of the aromatase inhibitor anastrozole in combination with mitotane led to a reduction in clinical signs of puberty. Conclusion: Monitoring for estrogen-like effects of mitotane is crucial, particularly in pre-pubertal children, to avert potentially irreversible changes associated with precocious pseudopuberty. Aromatase inhibitors may serve as a prompt therapeutic option, enabling the continuation of mitotane treatment.

In recent years, there has been a growing interest in improving energy efficiency and thermal comfort in low-income housing, especially in regions prone to extreme climatic conditions. Conventional construction materials such as bricks and concrete exhibit shortcomings in energy efficiency, resulting in high indoor temperatures. This scenario not only impacts residents' well-being but also increases energy consumption, especially for air conditioning systems, potentially straining the electrical infrastructure in hot climate areas, leading to power outages and adverse consequences for the community and local industry. This study proposes an innovative and sustainable solution: the use of expanded styrene-butadiene rubber (SBR) with micronized leather shavings, possessing thermal insulation properties. The thermal insulation capacity of the composites was evaluated using heat flow methods, hot/cold plate heat flow analysis, and impedance tube acoustic method. The SBR/Leather waste composite at 20 phr emerges as a viable, promising, and sustainable alternative, exhibiting significant thermal insulation capacity with a thermal conductivity of 0.073 Wm-1.K−1 and temperature attenuation close to 15 °C, potentially enhancing comfort and quality of life in urban areas. The thermal insulation results of the other composites also surpassed traditional construction materials such as building boards, plywood, fiberglass, asphalt roofing, and cement tiles. The study demonstrates the feasibility of reusing leather as a reinforcing filler in rubber-based foams to produce thermal insulation materials, offering a sustainable solution to mitigate urban heating and improve quality of life in cities.

Objectives: To analyze bone mineral content (BMC) and area bone mineral density (aBMD) accrual in adolescent male footballers who started their first football season. Methods: 17 athletes (14.8 ± 0.4 years) were monitored across 15 weeks of football training. Participants were evaluated for somatic maturation (HPHV), BMC, and aBMD at three time points: before (M1) and after (M2) a preparatory phase, and at the end of the competitive phase (M3). BMC and aBMD were measured using DXA scans. Participants were divided into groups according to maturation status (circa-PHV and post-PHV), and the amount of accumulated training load (median split). Results: A significant effect (12.1 g/week, standard error (SE) = 2.6 g/week) was observed for lower limbs BMC across the three time points. There were no significant effects of time for upper limbs BMC. There was a significant effect of time for total body aBMD (0.007, SE = 0.003 g/cm2/week) across the three time points. Adolescents at post-PHV had a significant 245.6 g (SE = 56.1 g) higher BMC compared to adolescents at circa-PHV. No significant effects were observed for the accumulated training load. Conclusion: Systematic football training, even during the growth spurt, has a positive impact on adolescent bone markers despite the accumulated training load and maturation.

ABSTRACT: Our objective was to investigate associations of postpartum health with serum progesterone (P4) concentrations after first artificial insemination (AI), expression of interferon-stimulated genes (ISG) in blood leukocytes, and serum pregnancy-associated glycoprotein (PAG) during early pregnancy in dairy cows. In this observational study, Holstein cows (n = 475) from 2 commercial herds were enrolled 3 wk before expected parturition. Body condition score (BCS) and lameness were assessed at enrollment, and total Ca, haptoglobin, and nonesterified fatty acids (NEFA) were measured in serum at 2 and 6 ± 2 d in milk (DIM). Blood β-hydroxybutyrate and metritis were evaluated at 4, 8, 11, and 15 ± 2 DIM, and purulent vaginal discharge (PVD) and endometritis based on endometrial cytology were diagnosed at 35 DIM. Onset of cyclicity was assessed by biweekly P4 measurements. The BCS was assessed at enrollment and at 63 DIM, and lameness at enrollment and at 21 and 49 DIM. First AI was based on estrus detection until ∼75 DIM, or synchronization for timed AI thereafter. Serum P4 was measured at d 8 and 12 after first AI; expression of ISG (ISG15 and RTP4) in blood leukocytes was assessed at d 19; and PAG in serum of pregnant cows was measured at d 29, 33, and 40. Multivariable linear regression models were built including health variables (with metabolites categorized via receiver operating characteristic curve analysis) and covariates (season, milk yield, AI method, DIM), accounting for pregnancy status (for ISG and PAG models), repeated measures (for P4 and PAG models), and herd as random. Results are reported comparing cows affected versus unaffected by each predictor. Serum P4 concentrations were lesser at d 8 after AI in cows that had total Ca ≤2.09 mM (3.6 vs. 4.0 ± 0.2 ng/mL) at 2 DIM or a clinical disease (3.7 vs. 4.0 ± 0.2 mg/mL), and P4 tended to be lesser at d 8 in cows that had PVD (3.6 vs. 4.0 ± 0.2 ng/mL) or any uterine disease (3.7 vs. 4.1 ± 0.2 ng/mL). Among cows pregnant at d 29, relative ISG15 expression (fold change) at d 19 was greater in cows that had lameness (5.10 [4.18–6.18] vs. 3.14 [3.10–3.19]) but tended to be lesser in cows that had endometritis (3.20 [2.89–3.54] vs. 4.29 [4.20–4.35]), and relative expression of RTP4 tended to be lesser in cows that had displaced abomasum (1.02 [0.62–1.67] vs. 1.75 [1.73–1.78]). Serum PAG was lesser at d 29 (3.8 vs. 4.2 ± 0.2 sample-to-positive ratio [S:P]) in cows that had NEFA ≥0.73 mM at 6 DIM, and lesser at d 33 (3.9 vs. 4.5 ± 0.2 S:P) and 40 (3.1 vs. 3.7 ± 0.2 S:P) in cows that had prepartum BCS ≥3.75. These findings suggest long-term effects of metabolic or reproductive tract disorders on luteal function after first AI, pregnancy recognition signaling, and placental function during early pregnancy. These associations may partially explain some of the pathways linking postpartum health and fertility in dairy cows.

This article presents a study on the use of natural fibers and kaolin waste as sustainable alternatives in the manufacture of polymer matrix composites. In the present research, isophthalic unsaturated polyester matrix composites were manufactured in association with bamboo fibers (Bambusa vulgaris) and kaolin waste. The kaolin waste was used with a particle size of 50–100 MESH and the fibers in lengths of 15 mm and 30 mm, randomly arranged within the matrix. Bamboo fibers were used fresh and treated with NaOH (5%/2 h). The chemical characterization of the fibers was obtained followed by the morphological characterization using Scanning Electron Microscopy (SEM). The composites were mechanically evaluated through flexural and tensile tests. The mechanical properties obtained were treated by analysis of variance (ANOVA) and Tukey test. The fracture surfaces of the composites were verified by SEM. Bamboo fibers had a chemical composition similar to other natural fibers already studied, with 7.55% extractives, 17.95% total lignin and 74.5% holocellulose. Composites with 30 mm long treated fibers and 30% kaolin showed better flexural strength (137.0 MPa), with deformation of (1.59 mm) and flexural modulus of (19.27 GPa). Through tensile tests, it was possible to identify that the addition of kaolin waste provided a significant improvement in tensile strength of 66% (15BTKW20) and 54% (30BTKW20) compared to neat polyester. SEM micrographs of bamboo fibers, surface roughness, starch granules, micropores and parenchyma cells were identified. ANOVA reinforced the reliability of the results, highlighting the feasibility of manufacturing kaolin waste/bamboo fiber hybrid composites.

Introduction: This study evaluated outcomes and risk factors for COVID-19 in 91 Brazilian multiple myeloma (MM) patients between April 2020 and January 2022. Results: Of the 91 MM patients diagnosed with COVID-19, 64% had comorbidities and 66% required hospitalization due to COVID-19, with 44% needing ventilatory support and 37% intensive care. Age (OR 2.02; 95%CI 1.02 – 7.7) and hypertension OR 4.5; 95%CI 1.3 – 15.5) were independently associated with hospitalization and certain MM therapies (corticosteroids and monoclonal drugs) were associated with ventilatory support (OR 4.3; 95%CI 1.3 – 14 and OR 5.7; 95%CI 1.8 – 18, respectively), while corticosteroids and immunomodulatory drugs were linked to ICU admission (OR 5.1; 95% CI 1.4 – 18 and OR 3.4; 95%CI 1.1 – 10, respectively). The overall mortality rate was 30%, with the highest rate observed in the ICU (73%). Additionally, the ECOG performance status was linked to increased mortality (OR 11.5; 95%CI 1.9 – 69). The MM treatment was delayed in 63% of patients who recovered from COVID-19. Conclusions: The findings highlight the need for preventing COVID-19 and prioritizing vaccination among MM patients, as they have high rates of severe outcomes in the event of COVID-19. It is also essential to monitor the potential clinical impacts of COVID-19 on MM patients in the long-term. Given the limited resources available in treating MM patients in Brazil during the COVID-19 pandemic, outcomes might be worse in this population.

Exacerbated inflammation and coagulation are a hallmark of COVID-19 severity. Extracellular vesicles (EVs) are intercellular transmitters involved in inflammatory conditions, which are capable of triggering prothrombotic mechanisms. Since the release of EVs is potentially associated with COVID-19-induced coagulopathy, the aim of this study was to evaluate changes in inflammation- and hypercoagulability-related EVs during the first month after symptom onset and to determine whether they are associated with disease severity. Blood samples of patients with mild or severe forms of the disease were collected on three occasions: in the second, third and fourth weeks after symptom onset for the quantification by flow cytometry of CD41A (platelet glycoprotein IIb/IIIa), CD162 (PSGL-1), CD31 (PECAM-1) and CD142 cells (tissue factor). Analysis of variance (ANOVA) with repeated measures, Kruskal-Wallis and correlation tests were used. Eighty-five patients were enrolled, 71% of whom had mild disease. Seventeen uninfected individuals served as controls. Compared to controls, both mild and severe COVID-19 were associated with higher EV-CD31+, EV-CD41+ and EV-CD142+ levels. All EV levels were higher in severe than in mild COVID-19 only after the third week from symptom onset, as opposed to C-reactive protein and D-dimer levels, which were higher in severe than in mild COVID-19 earlier during disease progression. EV levels were also associated with C-reactive protein and D-dimer levels only after the third week of symptoms. In conclusion, EVs expressing CD41A, CD31, TF, and CD162 appear as late markers of COVID-19 severity. This finding may contribute to the understanding of the pathogenesis of acute and possibly long COVID-19.

Background: Infective endocarditis continues to be a significant concern and may be undergoing an epidemiological transition. Methods: Were studied 1804 consecutive episodes of infective endocarditis between 1978 and 2022. The mean age was 48 ( ± 19), and 1162 (64%) patients were male. Temporal trends in demographic data, comorbidities, predisposing conditions, microorganisms, complications and in-hospital death have been studied over the decades (1978–1988, 1989–1999, 2000–2010 and 2011–2022). The outcomes and clinical characteristics were modeled using nonlinear cubic spline functions. Findings: Valve surgery was performed in 50% of the patients and overall in-hospital mortality was 30%. From the first to the fourth decade studied, the average age of patients increased from 29 to 57 years (p

Summary: Background and aims: A healthy diet is one of the pillars of familial hypercholesterolemia (FH) treatment. However, the best dietary pattern and indication for specific supplementation have not been established. Our aim is to conduct a pilot study to assess the effect of an adapted cardioprotective diet with or without phytosterol and/or krill oil supplement in participants with a probable or definitive diagnosis of FH, treated with moderate/high potency statins. Methods: A national, multicenter, factorial, and parallel placebo-controlled randomized clinical trial with a superiority design and 1:1:1:1 allocation rate will be conducted. The participants will undergo whole exome sequencing and be allocated into four treatment groups: 1) a cardioprotective diet adapted for FH (DICA-FH) + phytosterol placebo + krill oil placebo; 2) DICA-FH + phytosterol 2 g/day + krill oil placebo; 3) DICA-FH + phytosterol placebo + krill oil 2 g/day; or 4) DICA-FH + phytosterol 2 g/day + krill oil 2 g/day. The primary outcomes will be low-density lipoprotein (LDL)-cholesterol and lipoprotein (a) levels and adherence to treatment after a 120-day follow-up. LDL- and high-density lipoprotein (HDL)-cholesterol subclasses, untargeted lipidomics analysis, adverse events, and protocol implementation components will also be assessed. Results: A total of 58 participants were enrolled between May–August 2023. After the end of the follow-up period, the efficacy and feasibility results of this pilot study will form the basis of the design of a large-scale randomized clinical trial. Conclusions: This study's overall goal is to recommend dietary treatment strategies in the context of FH.

Objectives: This study aimed to analyze the knowledge of dental surgeons concerning the pharmacological effects of bisphosphonates (BP) and their impact on the health of patients undergoing oral surgery treatment. Materials and methods: A quantitative study was conducted with professionals in the Cariri region of Ceará, Brazil. The data were collected using a semi-structured questionnaire to interview the dental surgeons who met the inclusion criteria. The data were analyzed by Chi-square and Fischer's Exact tests using the SPSS program version 22.0. Results: The results indicated that most interviewed subjects have no experience with the dental treatment of individuals under treatment with bisphosphonates. When a sample of the medication was presented, a significant number of the participants (65.3%) did not recognize the drug. Among those who recognized it, 66.5% did not know how to treat bisphosphonate-using patients in the clinical routine. However, 95.1% of the professionals who recognized the need to discontinue these drugs admitted contacting the prescriber to establish the best dental conduct. Our results also showed that recently graduated professionals better understood the need to stop BP use before invasive treatment, although they did not know the protocol. Conclusion: In conclusion, a better knowledge of the pharmacological effects of BP is crucial for conducting adequate anamnesis, requesting additional tests, and performing medical monitoring, which has a significant impact on the clinical practice of dental surgeons.

ABSTRACT: The objective of the present study was to evaluate a blend of functional oils (FO) composed of copaiba and garlic essential oils, pepper oleoresin and cashew nut liquid to mitigate the effects of heat stress on productivity, egg quality, organ morphology of the gastrointestinal tract, serum biochemical profile, nutrient metabolism and body temperature of Japanese quail. A completely randomized design was used in a 3 × 2 factorial scheme (without additive; 300 and 500 mg FO/kg of feed x birds raised in a thermal comfort (TC) and heat stress (HS) environment), with 6 replicates of 8 birds per plot. The birds under HS had lower feed intake (P = 0.0000), egg mass (P = 0.0000), laying rate (P = 0.0000) and higher percentage of infertile non-commercial eggs (P = 0.0004), lower head temperature amplitude (P = 0.0000) and higher average of body temperature (P = 0.0312). HS worsened the external and internal quality of the eggs. Birds kept in HS showed higher values of cholesterol (P = 0.0000) and glutamic-pyruvic transaminase (P = 0.0272). The use of 300 and 500 g FO/ton of feed improved the feed conversion (P = 0.0000) and egg mass (P = 0.0000) of the quail bred under HS, respectively, by 8.4 and 7.2% and increased the relative weight of liver (P = 0.0064) and pancreas (P = 0.0492). The use of such additives also provided a higher % of yolk (P = 0.0018) and reduced the percentage of albumen (P = 0.0029) of the eggs produced in TC, in addition to reducing the amplitude of head temperature (P = 0.0484) of birds bred under HS. The breeding of Japanese quail under HS results in negative impacts on the production, physiological and qualitative aspects of the eggs. The use of 300 g/ton of FO in the diet of Japanese quail leads to improvements in feed conversion, increased liver capacity in nutritional metabolism and results in eggs with a higher proportion of yolks, being, therefore, an alternative for feeding quail in a hot climate.

Background: Chagas Disease (CD) can cause Chagas cardiomyopathy. The new coronavirus disease (COVID-19) also affects the cardiovascular system and may worsen Chagas cardiomyopathy. However, the cardiac evolution of patients with CD infected by COVID-19 is not known. Thus, the objective of this study is to assess, within one year, whether there was cardiac progression after COVID-19 in CD. Methods: Longitudinal study with CD patients. The outcome was cardiac progression, defined as the appearance of new major changes in the current ECG compared to the previous ECG considered from the comparison of electrocardiograms (ECGs) performed with an interval of one year. Positive Anti-SARS-CoV2 Serology was the independent variable of interest. For each analysis, a final multiple model was constructed, adjusted for sociodemographic, clinical, and pandemic-related characteristics. Results: Of the 404 individuals included, 22.8 % had positive serology for COVID-19 and 10.9 % had cardiac progression. In the final model, positive serology for COVID-19 was the only factor associated with cardiac progression in the group as a whole (OR = 2.65; 95 % CI = 1.27–5.53) and for new-onset cardiomyopathy in the group with normal previous ECG (OR = 3.50; 95 % CI = 1.21–10.13). Conclusion: Our study shows an association between COVID-19 and progression of Chagas cardiomyopathy, evaluated by repeated ECGs, suggesting that COVID-19 accelerated the natural history of CD.

Summary: Eukaryotic initiation factor 2B (eIF2B) controls translation initiation by recycling inactive eIF2-GDP to active eIF2-GTP. Under cellular stress, the integrated stress response (ISR) is activated inhibiting eIF2B activity resulting in the translation attenuation and reprogramming of gene expression to overcome the stress. The ISR can dictate cell fate wherein chronic activation has pathological outcomes. Vanishing white matter disease (VWMD) is a chronic ISR-related disorder with mutations in eIF2B targeting astrocyte and oligodendrocyte cells. Regulation of eIF2B localization (eIF2B bodies) has been implicated in the ISR. We present evidence that neuronal and glial cell types possess distinct patterns of eIF2B bodies which change in a manner correlating to acute and chronic ISR activation. We also demonstrate that while neural and glial cell types respond similarly to the acute induction of the ISR a chronic ISR exerts cell-type specific differences. These findings provide key insights into neural cell responses and adaptation to cellular stress.

Summary: Gene editing of human pluripotent stem cells is a promising approach for developing targeted gene therapies for metabolic diseases. Here, we present a protocol for generating a CRISPR-Cas12a gene knockout of protein tyrosine phosphatases in human embryonic stem cells. We describe steps for differentiating the edited clones into pancreatic islet-like spheroids rich in β-like cells. We then detail procedures for implanting these spheroids under the murine kidney capsule for in vivo maturation. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

A 78-year-old woman presented to hospital with altered mental status. Hyponatremia was diagnosed and treated. She maintained mental confusion despite normal sodium. No headache, fever or focal signs were present. CSF analysis showed chronic meningitis; MRI demonstrated basilar enhancement. She was empirically treated for tuberculosis, with no improvement. PCR for Sporothrix in the CSF was positive. After treatment with Amphotericin followed by oral itraconazole, she completely recovered her cognitive abilities. Follow-up CSF was normal. This report illustrates the need to consider sporotrichosis in the differential diagnosis of chronic meningitis in immunocompetent, and the importance of PCR as a diagnostic tool.

Background: Alzheimer's disease (AD) is an incurable condition characterized by cognitive and neurochemical impairments, necessitating the exploration of alternative interventions. Physical exercise shows promise, but the effects of high-intensity protocols on the neurochemical aspects of AD-related neurodegeneration remain poorly explored. Objective: This study examines the effects of high-intensity body weight interval training (PMED) on brain-derived neurotrophic factor (BDNF) and phosphorylated-TAU protein (p-TAU) in AD disease. Methods: Thirty-four elderly individuals diagnosed with AD disease were divided into two groups of 17 subjects: GCP, which participated in PMED (30 min at 80–90 % of maximal cardiac frequency three times per week), and GCS, which had no interventions. Pre- and post-measurements of BDNF and p-TAU were conducted. Results: The GCS group showed no changes in his neurochemical factors (p > 0.05). In contrast, the GCP group experienced increased BDNF levels and decreased p-TAU blood concentrations (p < 0.0001 for both). Conclusions: PMED increased BDNF and reduced p-TAU concentrations, improving neurochemistry in AD disease. This can open an avenue of new interventions using high-intensity body weight interval training, including, in home base programs, which can be an advantage to engagement.

Background: Doxorubicin (DOX) is a highly effective chemotherapy drug widely used to treat cancer, but its use is limited due to multisystemic toxicity. Lipid metabolism is also affected by doxorubicin. Orange juice can reduce dyslipidemia in other clinical situations and has already been shown to attenuate cardiotoxicity. Our aim is to evaluate the effects of Pera orange juice (Citrus sinensis L. Osbeck) on mitigating lipid metabolism imbalance, metabolic pathways, and DOX induced cytotoxic effects in the heart and liver. Methods: Twenty-four male Wistar rats were allocated into 3 groups: Control (C); DOX (D); and DOX plus Pera orange juice (DOJ). DOJ received orange juice for 4 weeks, while C and D received water. At the end of each week, D and DOJ groups received 4 mg/kg/week DOX, intraperitoneal. At the end of 4 weeks animals were submitted to echocardiography and euthanasia. Results: Animals treated with DOX decreased water intake and lost weight over time. At echocardiography, DOX treated rats presented morphologic alterations in the heart. DOX increased aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol, high density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides. It also reduced superoxide dismutase (SOD) activity, increased protein carbonylation in the heart and dihydroethidium (DHE) expression in the liver, decreased glucose transporter type 4 (GLUT4) and the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ1) in the heart, and reduced carnitine palmitoyltransferase I (CPT1) in the liver. Conclusion: DOX caused dyslipidemia, liver and cardiac toxicity by increasing oxidative stress, and altered energy metabolic parameters in both organs. Despite not improving changes in left ventricular morphology, orange juice did attenuate oxidative stress and mitigate the metabolic effects of DOX.

Background: Selective cyclooxygenase-2 inhibitor anti-inflammatory drugs (coxibs) are associated with the development of adverse events, mainly gastrointestinal and cardiovascular, but renal effects are less known. Objective: To assess the renal risks of coxibs compared to placebo by means of a systematic review and meta-analysis. Methods: Randomized controlled trials that assessed renal effects of coxibs (celecoxib, etoricoxib, lumiracoxib, parecoxib, and valdecoxib) were searched in PubMed, Embase, Scopus and other sources up to March 2024. Two independent reviewers performed study screening, data extraction, and risk of bias assessment. Random effect meta-analysis was employed to calculate the relative risks (RR) and 95% confidence intervals (CI) of renal effects of coxibs compared to placebo and inconsistency among studies (I2). Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. Results: Out of 5284 retrieved records, 49 studies (comprising 46 reports) were included. Coxibs increased the risk of edema (RR 1.46; 95% CI 1.15, 1.86; I2 = 0%; 34 studies, 19,754 participants; moderate-certainty evidence), and celecoxib increased hypertensive or renal events (RR 1.24; 95% CI 1.08, 1.43; I2 = 0%; 2 studies, 3589 participants; moderate-certainty evidence). Etoricoxib increased the risk of hypertension (RR 1.98; 95% CI 1.14, 3.46; I2 = 34%; 13 studies, 6560 participants; moderate-certainty evidence); no difference was observed when pooling all coxibs (RR 1.26; 95% CI 0.91, 1.76; I2 = 26%; 30 studies, 16,173 participants; moderate-certainty evidence). Conclusions: Coxibs likely increase the renal adverse effects, including hypertension and edema. Awareness about the renal risks of coxibs should be increased, mainly in high-risk patient.

Summary: Background: Ethno-racial inequalities are critical determinants of health outcomes. We quantified ethnic-racial inequalities on adverse birth outcomes and early neonatal mortality in Brazil. Methods: We conducted a cohort study in Brazil using administrative linked data between 2012 and 2019. Estimated the attributable fractions for the entire population (PAF) and specific groups (AF), as the proportion of each adverse outcome that would have been avoided if all women had the same baseline conditions as White women, both unadjusted and adjusted for socioeconomics and maternal risk factors. AF was also calculated by comparing women from each maternal race/skin colour group in different groups of mothers’ schooling, with White women with 8 or more years of education as the reference group and by year. Findings: 21,261,936 newborns were studied. If all women experienced the same rate as White women, 1.7% of preterm births, 7.2% of low birth weight (LBW), 10.8% of small for gestational age (SGA) and 11.8% of early neonatal deaths would have been prevented. Percentages preventable were higher among Indigenous (22.2% of preterm births, 17.9% of LBW, 20.5% of SGA and 19.6% of early neonatal deaths) and Black women (6% of preterm births, 21.4% of LBW, 22.8% of SGA births and 20.1% of early neonatal deaths). AF was higher in groups with fewer years of education among Indigenous, Black and Parda for all outcomes. AF increased over time, especially among Indigenous populations. Interpretation: A considerable portion of adverse birth outcomes and neonatal deaths could be avoided if ethnic-racial inequalities were non-existent in Brazil. Acting on the causes of these inequalities must be central in maternal and child health policies. Funding: Bill & Melinda Gates Foundation and Wellcome Trust.

Gender-based violence is a global scourge advancing unchecked, penetrating all social and cultural strata. Physical, sexual and emotional abuse seriously affects women's freedom, with consequences not only psychological and physical but also economic, in the form of health, labour, legal and police costs. Therefore, society demands effective governmental measures based on respect for human rights and aimed at promoting equality to avoid intimidation and ill-treatment. This paper proposes to carry out a bibliometric analysis of the literature to investigate the state of the art of public policy and gender violence or domestic violence or violence against women to detect the patterns of behaviour that have marked the lines of study over the last two decades (2001–2022), by analysing a sample of 355 articles. The results reveal that scientific production has grown exponentially recently, with Brazil and the USA having the most significant involvement. Furthermore, three clearly differentiated lines of research are evident: the detection of risk factors and prevention measures; feminist movements aimed at empowering women, seeking their independence; and the qualification of care services supported by public policies. However, they all have the same objective, to achieve gender homogeneity and stop any type of violence against women and girls.

The transplacental transmission of parasites and hemoparasites is crucial for understanding the epidemiology of diseases. This study aimed to assess the prevalence of hemopathogens in bovine fetuses at various gestational periods. Samples were obtained from a slaughterhouse in the state of Minas Gerais, Brazil, and a total of 236 fetuses were collected. DNA extracted from blood samples (145) and organ samples (a pool of brain and spleen) (236) underwent a nested PCR (nPCR) assay to detect Babesia spp., Theileria spp., Trypanosoma vivax, Anaplasma marginale, Anaplasma bovis, Anaplasma phagocytophilum, Ehrlichia minasensis, and hemotropic Mycoplasma spp. Additionally, serological analysis of 145 plasma samples was conducted using the indirect fluorescent antibody test-IFAT to detect IgG against Babesia bovis, Babesia bigemina, A. marginale, and Trypanosoma vivax. The observed prevalence of transplacental transmission was 19.3 %, 6.2 %, 42.7 % and 2.7 %, for A. marginale, B. bigemina, 'Candidatus M. haemobos', and Mycoplasma wenyonii, respectively. The prevalence of A. marginale by gestational trimester was 16 % (13/81) in the second trimester and 23 % (14/60) in the third trimester, with no positive samples in the first trimester. Regarding the species B. bovis and B. bigemina, all evaluated animals tested negative by nPCR, and no serological evidence for B. bovis was found by the IFAT. Babesia bigemina demonstrated an overall seroprevalence of 6.2 % (9/145), with 4.8 % (7/145) in the last trimester and 1.3 % (2/145) in the second trimester of pregnancy. In total, 42.7 % (62/145) of blood samples were positive for 'Candidatus M. haemobos’, with 42 % (34/81) in the middle trimester, and 43 % (26/60) in the final trimester of pregnancy. Mycoplasma wenyonni was detected in 2.7 % (4/145) blood samples, all in coinfection with ‘C. M. haemobos’. The prevalence by pregnancy trimester was 25 % (1/4) in the first trimester; 1.2 % (1/81) in the second trimester and 3.3 % (2/60) in the third trimester of pregnancy. Hemopathogen DNA was detected in fetus blood samples but not the brain or spleen samples. All the samples were negative for T. vivax, Theileria spp., Anaplasma spp. and Ehrlichia spp. Overall, in this study, approximately 70 % of fetuses were positive for one or more of the studied parasites. No significant associations were observed between pairs of pathogens, except ‘C. M. haemobos’ and A. marginale.

The aging population reveals the need to develop self-care interventions that promote autonomy and well-being. The current systematic review aimed to assess the association between the implementation of structured home-based rehabilitation programs to promote self-care in older adults and health-related outcomes among people aged 60 years or older. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature review was performed. Three electronic databases (MEDLINE, CINAHL and Psychology and Behavioral Sciences Collection) were searched. Randomized experimental studies, that implemented a home-based rehabilitation program to promote self-care in older adults, and were published between 2019 and 2024, were retrieved. Data on health-related outcomes were collected. Eight studies were included; all eight studies implemented a monitored, progressive and customized rehabilitation program. The studies varied greatly regarding the sample size, the duration of the intervention, the rehabilitation program implemented and the instruments used. The implementation of structured home-based rehabilitation programs may contribute to improve physical and psychological health-related outcomes among older adults by promoting functional capacity, self-care and knowledge.

Three-dimensional (3D) printing is an innovative manufacturing method with the potential to revolutionize topical and transdermal dosage forms. Nowadays, it is established that Vat-based photopolymerization (VP) 3D printing technologies offer superior printing efficiency and versatility compared to other 3D printing technologies available on the market. However, there are some limitations that impair their full application in pharmaceutical contexts, such as the lack of a range of biocompatible materials for topical and transdermal applications. This review article explores all types of VP-based 3D printing and discusses the relevance of implementing this kind of technology. We start with a detailed description of the printing process, focusing on the commercial materials available and lab-made resins proposed by different authors. We also review recent studies in this field, which mainly focus on the fabrication of transdermal devices based on microneedle arrays. In the future, it is expected that the manufacturers of 3D printers invest in modifications to the printing apparatus to allow the simultaneous printing of different resins and/or compound types, which will open frontiers to the personalization of treatment approaches.

Summary: N-methyl-D-aspartate receptors are ionotropic glutamate receptors that mediate synaptic transmission and plasticity. Variable GluN2 subunits in diheterotetrameric receptors with identical GluN1 subunits set very different functional properties. To understand this diversity, we use single-molecule fluorescence resonance energy transfer (smFRET) to measure the conformations of the ligand binding domain and modulatory amino-terminal domain of the common GluN1 subunit in receptors with different GluN2 subunits. Our results demonstrate a strong influence of the GluN2 subunits on GluN1 rearrangements, both in non-agonized and partially agonized activation intermediates, which have been elusive to structural analysis, and in the fully liganded state. Chimeric analysis reveals structural determinants that contribute to these subtype differences. Our study provides a framework for understanding the conformational landscape that supports highly divergent levels of activity, desensitization, and agonist potency in receptors with different GluN2s and could open avenues for the development of subtype-specific modulators.

This study investigates the use of satellite-derived Christiansen Uniformity Coefficient (SDCUC) values for evaluating irrigation uniformity. In the context of global water scarcity and the imperative for sustainable water management, we explore the potential of remote sensing methods to evaluate irrigation uniformity across large agricultural areas. The findings reveal a consistent tendency for SDCUC to overestimate irrigation uniformity, with an average overestimation rate of 7.83 %. However, accuracy improved with the appropriate method, vegetation index, or spectral band selection. Employing the entire satellite image for SDCUC (SDCUCTOT) assessment improved accuracy. For Sentinel-1 (S1), using the dual-band cross-polarization horizontal transmit/vertical receive band (VH), the bias confidence interval was −0.39–0.69 %, while for Sentinel-2 (S2), using the normalized difference red edge 3 index (NDRE3), it was −1.47–0.66 %, and for Landsat 8 (L8) and Landsat 9 (L9) using the shortwave infrared water stress index (SIWSI) it ranged from 0.36 % to 2.28 %. Improved results were also observed when the normalized difference vegetation index (NDVI) ranged between 0.4 and 0.8 or the evapotranspiration and potential evapotranspiration ratio (ET/PET) ranged between 0.30 and 0.55. In these conditions, SDCUCTOT for the S2, L8, and L9 using the simple ratio index (SR) ranged from 1.00 % to 2.33 %, 0.00–1.83 %, 0.23–2.00 %, respectively, and for S2, the normalized difference water index (NDWI) and NDRE3 ranged from −1.39–0.71 %, and −1.43–2.31 % respectively. These findings underscore the potential of remote sensing techniques to revolutionize water resource management and promote sustainable agriculture, emphasizing the synergistic role of ground-based measurements and the need for continued methodological refinements to improve accuracy. Further advancements and research are warranted to refine the methodology and enhance the accuracy and reliability of remote sensing-based irrigation uniformity assessment, ultimately contributing to more sustainable agricultural irrigation practices.

Summary: Investigations involving high-intensity interval training (HIIT) have proven to be efficient in controlling diabesity. This study aimed to assess the impact of discontinuing HIIT and retraining within the context of diabesity. 75 C57BL6 mice went through 5 stages: baseline, induction of diabesity with Western diet, training, detraining, and retraining (6 weeks each period). Detraining led to elevated adiposity, exacerbated metabolic parameters and intestinal health, and altered gut microbiota composition. Retraining restored blood glucose regulation and enhanced intestinal health yet did not induce fat reduction. While both training and retraining exerted an effect on the composition of the gut microbiota, the impact of diet demonstrates a more substantial potency compared to that of exercise concerning intestinal health and microbiome. These findings may contribute to a broader understanding of diabesity management and introduce perspectives for the use of specific physical training to enhance patient outcomes and intestine health.

The Neotropical freshwater stingrays of Potamotrygon genus present a unique and complex natural history and biogeographical pattern that can be traced to a marine origin and the colonization of the continental environment during the Miocene. During the evolution of potamotrygonids, several species of the parasitic fauna coevolved and co-opted concomitantly to their hosts during the colonization of the new environments. One striking example can be observed during the colonization of the upper Paraná River region. However, few studies explored the ecological and taxonomic aspects of potamotrygonid parasites. In this work, we investigate aspects of the ecology and taxonomy of the species of Monogenea and Cestoda that are parasites the species of freshwater stingrays of the genus Potamotrygon in the upper Paraná River. Our results indicate that at least six species of parasites are present in potamotrygonids in the region. Two of the observed parasites are putative new species and three of the parasitic species were identified for the first time in the region, hence expanding their geographic distributions. We quantified ecological aspects at different levels of communities for the collected parasite species. We compared the diversity in different locations and hosts and performed an exploratory analysis to investigate the differences in parasite abundance. Additionally, an identification key for the Monogenea and Cestoda species of the sampled region is provided.

The teaching profession has always been recognized as one that requires a greater vocational calling. However, education professionals have had to adapt to and manage phenomenons which have arisen due to more demanding work contexts that require them to participate in work, even when they are ill (presenteeism), and to a global-wide digital transformation. Such phenomenons include cyberbullying, which has proliferated in school environments. It is crucial to understand the impact this type of phenomenon can have on these professionals. Accordingly, the main objective of this study was to identify the needs felt by teachers to deal effectively with incidents of cyberbullying and its potential impact on and reduce presenteeism. Two studies were developed, with the intention that the hypotheses posed by the quantitative study could be enriched with the inferences drawn from the qualitative study. A sample of 542 middle school teachers responded to questionnaires and 63 participated in interviews. The results showed that teachers’ professional calling led to a lower loss of productivity, due to a lower frequency of presenteeism. This effect was more pronounced in the presence of cyberbullying observation. This study provides a contribution to the calling and presenteeism literature since it focuses on the impact of observing cyberbullying on sickness presence. It is relevant because by knowing the demands that teachers feel and the resources they lack, it is possible to implement tailored intervention and prevention programs to help professionals deal with cyberbullying.

Purpose: Most studies assessing hair cortisol were conducted with adults. As specific guidelines for infant hair collection are lacking, we developed a hair collection protocol for 12-month-old infants and assessed its acceptability and feasibility. Results: Out of the total (N = 45), 95.6 % (n = 43) of caregivers consented to the procedure, while one caregiver did not consent (2.2 %), and another requested the procedure to be halted before required amount of hair had been reached (2.2 %). Furthermore, two (4.4 %) infants did not have enough hair for collection. There was no attrition due to infant fussiness/crying. Discussion: We learned five lessons which can help to enhance reproducibility, mother's consent, and mother-infant comfort and acceptance of the procedure. The first lesson is to have the infant sit on the caregiver's lap to ensure the infant feels safe and remains relatively still. The second is to reassure caregivers by showing hair samples representing the amount to be cut as well as by clarifying no unaesthetic gaps would be visible. The third is to caress the infant's head to habituate them to the hair manipulation and to make soap bubbles as distractors. The fourth is to take extra care when securing the lock of hair for cutting because the infant scalp is thin and malleable. The fifth is to place a precision scale in the collection room to ensure the necessary weight is reached. Conclusion: Our hair collection protocol developed for 12-month-old infants was deemed feasible and acceptable, filled an important literature gap concerning the absence of published protocols for infants, and will contribute to increase the replicability and collection efficiency for other research teams.

The first evidence for the standard model production of a top quark in association with a W boson and a Z boson is reported. The measurement is performed in multilepton final states, where the Z boson is reconstructed via its decays to electron or muon pairs. At least one W boson, associated or from top quark decay, decays leptonically, too. The analysed data were recorded by the CMS experiment at the CERN LHC in 2016–2018 in proton-proton collisions at s=13 TeV, and correspond to an integrated luminosity of 138 fb−1. The measured cross section is 354±54(stat)±95(syst) fb, and corresponds to a statistical significance of 3.4 standard deviations.

Cutaneous leishmaniasis (CL) is a neglected disease caused by Leishmania parasites. The oral drug miltefosine is effective, but there is a growing problem of drug resistance, which has led to increasing treatment failure rates and relapse of infections. Photodynamic therapy (PDT) combines a light source and a photoactive drug to promote cell death by oxidative stress. Although PDT is effective against several pathogens, its use against drug-resistant Leishmania parasites remains unexplored. Herein, we investigated the potential of organic light-emitting diodes (OLEDs) as wearable light sources, which would enable at-home use or ambulatory treatment of CL. We also assessed its impact on combating miltefosine resistance in Leishmania amazonensis-induced CL in mice. The in vitro activity of OLEDs combined with 1,9-dimethyl-methylene blue (DMMB) (OLED-PDT) was evaluated against wild-type and miltefosine-resistant L. amazonensis strains in promastigote (EC50 = 0.034 μM for both strains) and amastigote forms (EC50 = 0.052 μM and 0.077 μM, respectively). Cytotoxicity in macrophages and fibroblasts was also evaluated. In vivo, we investigated the potential of OLED-PDT in combination with miltefosine using different protocols. Our results demonstrate that OLED-PDT is effective in killing both strains of L. amazonensis by increasing reactive oxygen species and stimulating nitric oxide production. Moreover, OLED-PDT showed great antileishmanial activity in vivo, allowing the reduction of miltefosine dose by half in infected mice using a light dose of 7.8 J/cm2 and 15 μM DMMB concentration. In conclusion, OLED-PDT emerges as a new avenue for at-home care and allows a combination therapy to overcome drug resistance in cutaneous leishmaniasis.

The wild boar, an impactful invasive species in Brazil, is subject to population control activities, which often include the use of hunting dogs. Hunters commonly consume wild boar meat, which is also used to feed their dogs, posing a risk of Toxoplasma gondii infection for humans and both T. gondii and Neospora caninum for dogs. The study aimed to investigate the prevalence of infection in wild boars (n = 127) and hunting dogs (n = 73) from São Paulo, Rio Grande do Sul, and Paraná states. We employed histopathological, serological (indirect fluorescent antibody test), and molecular techniques (endpoint polymerase chain reaction). Histopathology slides of wild boar tissue (central nervous system, heart, skeletal muscle, liver, spleen, kidney, gastrointestinal tract, pancreas, lymph nodes, and thyroid) sections revealed no T. gondii or N. caninum cysts (0/47). Antibodies anti-T. gondii were detected in 35/108 (32.4%) and anti-N. caninum in 45/108 (41.7%) wild boars. Only 2/18 (11.1%) wild boar tissue homogenate samples tested positive for T. gondii on endpoint PCR. Hunting dogs showed antibodies against T. gondii in 62/73 (85%) and against N. caninum in 31/73 (42%). The presence of antibodies against T. gondii and N. caninum in wild boars and hunting dogs, along with T. gondii DNA detection in wild boars, indicates the circulation of these parasites. Educating hunters on preventing these foodborne diseases, including zoonotic risks, is crucial.

The present study aimed to compare V̇O2max (absolute, adjusted to total body mass, and adjusted to lean mass) in recreational runners and sedentary women < and > 50 yr and verify the effect of aging and physical activity level on the three types of V̇O2 max expression. The study included 147 women:85 runners (45.7 ± 14.1 yr) and 62 sedentary controls (48.8 ± 9.8 yr). They were subjected to cardiopulmonary exercise testing for V̇O2 max measurement and a body composition test by dual-emission X-ray absorptiometry system. V̇O2max were expressed as absolute values (L/min), relative to total body mass values (mL/kg/min), and relative to lean mass values (mL/kgLM/min). The two-way analysis of variance revealed a significant interaction [F(2,131) = 4.43, p

Fat mass and obesity-related (FTO) gene single nucleotide polymorphisms (SNPs) interferes with food preferences that impact macronutrient intake. Few studies have investigated the relationship of this polymorphisms with the intake of micronutrients. Moreover, studies have shown multiple micronutrient deficiencies in patients with obesity. This work evaluated the effect of the FTO rs9939609 gene polymorphism on dietary nutritional quality and food intake of macronutrients and vitamins in of women with obesity candidates for metabolic surgery. The study included 106 women (24 to 60 years old) with BMIs of 36.1 to 64.8 kg/m2. A food frequency questionnaire validated for the local population was applied to obtain information about food intake. The Index of Nutritional Quality (INQ) was used to assess the adequacy of macronutrient and vitamin intake. Energy, protein and lipid intakes were higher in carriers of the A allele compared to TT in the younger age groups but were similar in the class of subjects aged ≥45 years. The INQ for protein was higher in carriers of the A allele than in carriers of the TT allele. The INQs for protein, carbohydrate, vitamins B2, B3 and B6 decreased, whereas the INQ for vitamin C increased with advancing age. The INQ for vitamin A was lower in AA than in TT, regardless of age, whereas vitamin E was higher in younger AA than in older AA. The INQ for vitamin B9 was higher in younger women than in older women. In conclusion, the FTO gene contributed to the intake of more energy, protein and lipids and interfered with the intake of vitamins B9, A and E. With the exception of vitamin A, the effect of the genotype was attenuated with ageing.

Introduction: The financial impact of breast cancer has been discussed due to its high incidence and the increased costs of systemic therapy and is even more relevant in countries with low and medium socioeconomic development. Objective: To evaluate the financial viability of using the MammaPrint™ (MP) genetic signature in a public and private system in a country with a medium socioeconomic development index. Material and method: A pharmacoeconomic trial with a cost-benefit analysis evaluating the reduction in costs of chemotherapy, support drugs, and materials used during chemotherapy infusion in high-risk hormone receptor-positive (HR+) breast cancer patients submitted to analysis using the MammaPrint™ genetic signature. Results: The value of using MammaPrint™ in the Unified Health System (SUS) would bring an additional cost of US$ 1,334.56 per patient in the over-50 age group. In private medicine, the use of MammaPrint™ in the same population would result in cost savings ranging from US$ 2,422.53 to US$ 9,989.95 per patient. Conclusion: The use of MP in RH + breast cancer patients with high clinical risk and low genomic risk in Brazil leads to significant savings in resources when applied to supplementary healthcare. In the SUS, reducing the costs of MP for large-scale use could make its application viable. These values need to be re-evaluated in each institution, using the methodology applied in the trial, adjusting according to costs, to obtain a result that reflects its reality.

Objective: Determine the prevalence and risk factors for anxiety, stress and depression among higher education students in a sample from Portugal and Brazil. Methods: Students from Portugal (n = 709) and Brazil (n = 487) answered the Depression, Anxiety and Stress Scale (DASS-21) and demographic and academic characteristics questions. Results: Rates of anxiety, stress, and depression were 55.3 %, 55.9 % and 56.3 % for Portuguese students and 71.5 %, 75.6 % and 68.2 % for Brazilian students, respectively. In the total sample, being Brazilian was found to predict anxiety, stress and depression. In both samples, being female was found to predict anxiety and stress. Being displaced was also found to affect mental health: anxiety for the Portuguese sample; stress for the Brazilian sample. Furthermore, in the Portuguese sample, fields of study were found to affect mental health: Education and Human Motricity protected from anxiety, stress and depression; Psychology protected from anxiety and depression; Medicine protected from depression. Non-working status was also found to predict depression in this sample. Limitations: The cross-sectional design prevents the establishment of causal relationships; self-report measures may be susceptible to response bias; the recruitment of participants may be susceptible to selection bias; cultural factors and institutional differences between these countries may affect mental health. Conclusions: Country, gender, displacement, field of study, and working status were found to affect higher education students’ mental health. From a clinical perspective, specific programs addressing anxiety, stress and depression in university students should be tested, as these disorders have a noteworthy prevalence in this population.

Since December 2019, a new form of Severe Acute Respiratory Syndrome (SARS) has emerged worldwide, caused by SARS coronavirus 2 (SARS-CoV-2). This disease was called COVID-19 and was declared a pandemic by the World Health Organization in March 2020. Symptoms can vary from a common cold to severe pneumonia, hypoxemia, respiratory distress, and death. During this period of world stress, the medical and scientific community were able to acquire information and generate scientific data at unprecedented speed, to better understand the disease and facilitate vaccines and therapeutics development. Notably, bioinformatics tools were instrumental in decoding the viral genome and identifying critical targets for COVID-19 diagnosis and therapeutics. Through the integration of omics data, bioinformatics has also improved our understanding of disease pathogenesis and virus-host interactions, facilitating the development of targeted treatments and vaccines. Furthermore, molecular biology techniques have accelerated the design of sensitive diagnostic tests and the characterization of immune responses, paving the way for precision medicine approaches in treating COVID-19. Our analysis highlights the indispensable contributions of bioinformatics and molecular biology to the global effort against COVID-19. In this review, we aim to revise the COVID-19 features, diagnostic, prevention, treatment options, and how molecular biology, modern bioinformatic tools, and collaborations have helped combat this pandemic. An integrative literature review was performed, searching articles on several sites, including PUBMED and Google Scholar indexed in referenced databases, prioritizing articles from the last 3 years. The lessons learned from this COVID-19 pandemic will place the world in a much better position to respond to future pandemics.

Objectiveto evaluate the effectiveness of using music to relieve pain, anxiety, and change in vital signs in adult and older adult patients undergoing cardiac catheterization.Methodsthis is a systematic review with meta-analysis carried out in October 2022, using 12 data sources, without time or language restrictions. The study followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The “Risk-of-bias tool” was used to assess the risk of bias, the “R CORE Team program: A language and environment for statistical computing” was used to perform the meta-analysis, and the “Grading of Recommendations Assessment, Development and Evaluation” was used to assess the quality of evidence in the studies. Results: a total of nine studies were included, totaling 1456 participants. The most used tools for measuring anxiety were the State-Trait Anxiety Inventory and Numerical Rating Scale. This was also used to measure pain, in addition to the Visual Analogue Scale. The use of instrumental, classical and relaxing music prevailed, applied using headphones during the painful procedure, at a frequency of 60 to 100bpm and sound intensity of 60–70 dB. There was statistical significance in the use of music in reducing pain, anxiety and systolic blood pressure. Conclusion: music interventions are effective in relieving pain, reducing systolic pressure and anxiety, but indifferent in terms of heart rate, respiratory rate and diastolic pressure. They provide humanization of care, can reduce hospital costs and length of hospital stay.