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This study aimed to characterize the epidemiological aspects of PrEP use and barriers to accessing this prophylaxis. This cross-sectional study was conducted between January 2021 and April 2022, encompassing 140 PrEP users treated at the Testing and Counseling Center (CTA) in Campo Grande, Mato Grosso do Sul. Data on sociodemographic characteristics and factors associated with PrEP discontinuation were obtained using a standardized questionnaire. Most PrEP users were cisgender men (92.00%), predominantly white (51.00%), over 30 years of age (56.50%), homosexual-oriented (76.50%), and had a minimum of 12 years of education (77.50%). Approximately 60.00% admitted to inconsistent condom use in recent sexual encounters, primarily involving anal intercourse. Approximately 88.00% perceived themselves as at risk of contracting STIs in the upcoming year. Regarding new presentation forms, 54.00% indicated a willingness to use "on-demand PrEP," and 92.00% expressed interest in using "injectable PrEP." After 6 months of follow-up, 43.60% (95.00% CI: 35.50-52.00) discontinued PrEP use, primarily due to changes in sexual behavior (38.30%) and difficulties accessing healthcare services (21.28%). This study underscores the need to involve diverse key populations and highlights the significance of PrEP as an ongoing monitoring strategy for HIV/STI prevention in addition to the importance of incorporating new formulations such as daily oral PrEP into the Brazilian National Health System (SUS).

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Considering the lack of consensus related to the impact of selective IL-6 receptor inhibition on bone remodeling and the scarcity of reports, especially on large bone defects, this study proposed to evaluate the biological impact of the selective inhibitor of interleukin-6 receptor (tocilizumab) in an experimental model of critical calvarial defect in rats. In this preclinical and in vivo study, 24 male Wistar rats were randomly divided into two groups (n=12/group): defect treated with collagen sponge (CG) and defect treated with collagen sponge associated with 2 mg/kg tocilizumab (TCZ). The defect in the parietal bone was created using an 8-mm diameter trephine drill. After 90 days, the animals were euthanized, and tissue samples (skull caps) were evaluated through micro-CT, histological, immunohistochemistry, cytokines, and RT-qPCR analyses. Tocilizumab reduced mononuclear inflammatory infiltration (P<0.05) and tumor necrosis factor (TNF)-α levels (P<0.01) and down-regulated tissue gene expression of BMP-2 (P<0.001), RUNX-2 (P<0.05), and interleukin (IL)-6 (P<0.05). Moreover, it promoted a stronger immunostaining of cathepsin and RANKL (P<0.05). Micro-CT and histological analyses revealed no impact on general bone formation (P>0.05). The bone cells (osteoblasts, osteoclasts, and osteocytes) in the defect area were similar in both groups (P>0.05). Tocilizumab reduced inflammatory cytokines, decreased osteogenic protein, and increased proteases in a critical bone defect in rats. Ninety days after the local application of tocilizumab in the cranial defect, we did not find a significant formation of bone tissue compared with a collagen sponge.

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Screener, a board game supplemented with online resources, was introduced and distributed by the Brazilian Society of Pharmacology and Experimental Therapeutics to postgraduate programs as an instructional tool for the process of drug discovery and development (DDD). In this study, we provided a comprehensive analysis of five critical aspects for evaluating the quality of educational games, namely: 1) description of the intervention; 2) underlying pedagogical theory; 3) identification of local educational gaps; 4) impact on diverse stakeholders; and 5) elucidation of iterative quality enhancement processes. We also present qualitative and quantitative assessments of the effectiveness of this game in 11 postgraduate courses. We employed the MEEGA+ online survey, comprising thirty-three close-ended unipolar items with 5-point Likert-type response scales, to assess student perceptions of the quality and utility of Screener. Based on 115 responses, the results indicated a highly positive outlook among students. In addition, we performed a preliminary evaluation of learning outcomes in two courses involving 28 students. Pre- and post-quizzes were applied, each consisting of 20 True/False questions directly aligned with the game's content. The analysis revealed significant improvement in students' performance following engagement with the game, with scores rising from 8.4 to 13.3 (P<0.0001, paired t-test) and 9.7 to 12.7 (P<0.0001, paired t-test). These findings underscore the utility of Screener as an enjoyable and effective tool for facilitating a positive learning experience in the DDD process. Notably, the game can also reduce the educational disparities across different regions of our continental country.

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Computational materials research is vital in improving our understanding of various class of materials and their properties, contributing valuable information that helps predict innovative structures and complement empirical investigations. In this context, DHQ-graphene recently emerged as a stable two-dimensional carbon allotrope composed of decagonal, hexagonal, and quadrilateral carbon rings. Here, we employ density functional theory calculations to investigate the mechanical, electronic, and optical features of its boron nitride counterpart (DHQ-BN). Our findings reveal an insulating band gap of 5.11 eV at the HSE06 level and good structural stability supported by phonon calculations and ab initio molecular dynamics simulations. Moreover, DHQ-BN exhibits strong ultraviolet (UV) activity, suggesting its potential as a highly efficient UV light absorber. Its mechanical properties, including Young's modulus (230 GPa) and Poisson's ratio (0.7), provide insight into its mechanical resilience and structural stability.

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BACKGROUND: The differentiation between primary and metastatic salivary gland neoplasms (SGNs) helps in determining appropriate management strategies, including the need for additional diagnostic tests, surveillance, or aggressive treatment. The purpose of this study was to identify and quantify the immature and mature dendritic cells (DCs) in metastatic and no metastatic SGNs and determine its association with clinicopathological findings. MATERIAL AND METHODS: Cross-sectional, observational, and descriptive study that includes 33 malignant salivary gland neoplasms [MSGN (6, 18.1% metastatic)], and 22 pleomorphic adenomas (PA), as a control group. Clinical and histopathological characteristics were obtained. Immunohistochemistry for human leukocyte antigen D-related (HLA-DR), CD1a, CD83, and Ki-67 proteins was done. Positive intra- and peritumoral DCs were counted. RESULTS: Individuals with MSGN had a lower density of intratumoral HLA-DR+ cells than those with PA (p=0.001), Ki-67 immunostaining was significantly higher in MSGN than in PA (6% vs. 1.4%, p<0.001). Metastatic MSGN showed less intratumoral CD1a+ than non-metastatic (3.2 vs. 165.1, p=0.001). No differences in intra- and peritumoral CD83+ cells were found between benign and malignant SGN. CONCLUSIONS: These results suggest that the immune-protective function of intratumoral DCs is compromised in MSGNs. DCs markers may represent useful prediction tools for metastases in salivary gland malignancies, with crucial implications in the implementation of appropriate disease management strategies.

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Screener, a board game supplemented with online resources, was introduced and distributed by the Brazilian Society of Pharmacology and Experimental Therapeutics to postgraduate programs as an instructional tool for the process of drug discovery and development (DDD). In this study, we provided a comprehensive analysis of five critical aspects for evaluating the quality of educational games, namely: 1) description of the intervention; 2) underlying pedagogical theory; 3) identification of local educational gaps; 4) impact on diverse stakeholders; and 5) elucidation of iterative quality enhancement processes. We also present qualitative and quantitative assessments of the effectiveness of this game in 11 postgraduate courses. We employed the MEEGA+ online survey, comprising thirty-three close-ended unipolar items with 5-point Likert-type response scales, to assess student perceptions of the quality and utility of Screener. Based on 115 responses, the results indicated a highly positive outlook among students. In addition, we performed a preliminary evaluation of learning outcomes in two courses involving 28 students. Pre- and post-quizzes were applied, each consisting of 20 True/False questions directly aligned with the game's content. The analysis revealed significant improvement in students' performance following engagement with the game, with scores rising from 8.4 to 13.3 (P<0.0001, paired t-test) and 9.7 to 12.7 (P<0.0001, paired t-test). These findings underscore the utility of Screener as an enjoyable and effective tool for facilitating a positive learning experience in the DDD process. Notably, the game can also reduce the educational disparities across different regions of our continental country.

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Leishmaniasis is a vector-transmitted zoonosis caused by different species of the genus Leishmania, with a wide clinical spectrum. It is a public health problem aggravated by a series of limitations regarding treatment. In the search for new therapeutic alternatives, scorpion venoms are a source of multifunctional molecules that act against the natural resistance of pathogens. This work evaluated the antileishmanial potential of Brotheas amazonicus and Tityus metuendus venoms against the promastigote forms of Leishmania amazonensis e Leishmania guyanensis. The venoms of B. amazonicus and T. metuendus were evaluated for their constituents using Fourier Transform Infrared (FTIR). Growth inhibition and death of promastigotes were evaluated in the presence of diferente crude venom concentrations (100 µg/mL, 50 µg/mL, 10 µg/mL, 1 µg/mL) after one hour of incubation at 25 °C. The FTIR spectra of both venoms exhibited bands in approximate regions, revealing that both exhibit similar functional groups. Crude venom from both scorpion species showed similar or superior leishmanicidal effects to the standart drug N-methylglucamine antimoniate. At the highest concentration of 100 µg/mL, cultures of L. guyanensis treated with the venom of B. amazonicus showed the highest mortality percentages, above 28%, while T. metuendus venom showed the highest activity against L. amazonensis, with mortality above 7%. This preliminar study demonstrates that B. amazonicus and T. metuendus venoms can be important tools in the search for new drugs Against leishmaniasis. Next step involves evaluating the activity against the amastigote forms and purifying the venom proteins in order to identify the best anti-leishmania candidates.

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BACKGROUND: Trastuzumab deruxtecan (T-DXd) has been shown to benefit progression-free survival and overall survival in patients with metastatic breast cancer (mBC) after progression on ≥1 human epidermal growth factor receptor 2 (HER2)-targeted therapies. However, interstitial lung disease (ILD) and cardiotoxicity are the most significant toxicities associated with T-DXd. Therefore, we conducted a systematic review and meta-analysis to assess the incidence and severity of these toxicities in mBC patients treated with T-DXd. MATERIALS AND METHODS: We searched PubMed, Cochrane, and Scopus databases, and conferences websites for randomized clinical trials and nonrandomized studies of intervention including HER2-low or HER2-positive mBC patients who received at least one dose of T-DXd. Statistical analysis was carried out using R software. RESULTS: We included 15 studies comprising 1970 patients with a mean follow-up of 13.3 months. Median age ranged from 53 to 59 years, 61.9% were non-Asian, and 67.4% had hormone receptor-positive mBC. In a pooled analysis, the incidence of ILD was 11.7% [222 patients; 95% confidence interval (CI) 9.1% to 15.0%]. Patients receiving T-DXd dose of 6.4 mg/kg developed a significantly higher rate of ILD (22.7%) compared to those receiving a dose of 5.4 mg/kg (9.3%) (P < 0.01). Most cases of ILD (80.2%; 174/217 patients) were mild (grade 1 or 2). Grade 3 or 4 ILD was reported in 29 patients (13.4%), and grade 5 in 14 patients (6.4%). The incidence of decreased left ventricular ejection fraction (LVEF) was 1.95% (95% CI 0.65% to 3.73%), and the QT interval (QTi) prolongation was 7.77% (95% CI 2.74% to 20.11%). Most patients were asymptomatic, but four had LV dysfunction and heart failure (0.26%). CONCLUSIONS: In this meta-analysis of 1970 patients with mBC, treatment with T-DXd was associated with a 11.7% incidence of ILD, 7.7% incidence of prolonged QTi, and 1.9% incidence of reduced LVEF. Early detection and management of T-DXd-related toxicity by a multidisciplinary team may ultimately improve patient outcomes.

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The aim of this study was to evaluate the antibacterial and antioxidant activities of essential oil (EO) from fresh leaves of Psidium rufum. The EO was extracted by hydrodistillation and identified by gas chromatography coupled to mass spectrometry. The antibacterial activity was evaluated by determining the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Antioxidant activity was determined by ß-carotene/linoleic acid co-oxidation system, 2,2-diphenyl-1-picrylhydrazyl radical scavenging and iron reduction methods. Hydrocarbon sesquiterpenes were the predominant class, indicating 1,8 cineole, α-longipinene as major. The EO was tested against the bacteria Staphylococcus aureus and Pseudomonas aeruginosa (MIC = 2,500 µg/mL and MBC = 20,000 µg/mL); Enterococcus faecalis (MIC = 2,500µg/mL and MBC > 20,000µg/mL) and Escherichia coli (MIC > 20,000µg/mL and MBC > 20,000µg/mL). The EO showed antioxidant potential due to ß-carotene/linoleic acid co-oxidation system, with 76.63% of oxidation inhibition (1.0mg/mL) and due to the iron reduction power (5,38 µmol Fe 2+ /mg sample). The results are promising in recommending this species for the development of food, cosmetic and pharmaceutical products.

O objetivo deste estudo foi avaliar as atividades antibacteriana e antioxidante do óleo essencial (OE) das folhas frescas de Psidium rufum. O OE foi extraído por hidrodestilação e identificado por cromatografia gasosa acoplada à espectrometria de massas. Foi avaliada a atividade antibacteriana, determinando-se a concentração inibitória mínima (CIM) e a concentração bactericida mínima (CBM). A atividade antioxidante foi determinada pelo sistema de co-oxidação ß-caroteno/ácido linoleico, pelos métodos de sequestro do radical 2,2-difenil-1-picrilhidrazil e de redução do ferro. Sesquiterpenos hidrocarbonetos foram a classe predominante, indicando 1,8 cineol, α-longipineno como majoritário. O OE foi testado contra as bactérias Staphylococcus aureus e Pseudomonas aeruginosa (CIM = 2,500µg/mL e CBM = 20.000µg/mL); Enterococcus faecalis (CIM=2,500µg/mL e CBM > 20.000µg/mL) e Escherichia coli (CIM > 20.000µg/mL e CBM > 20.000µg/mL). O OE apresentou potencial antioxidante pelo sistema co-oxidação ß-caroteno/ácido linoleico com 76,63% de inibição da oxidação (1,0mg/mL) e pelo poder de redução de ferro (5,38 µmol Fe2+/mg amostra). Os resultados são promissores em indicar essa espécie para o desenvolvimento de produtos alimentícios, cosméticos e farmacêuticos.

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In the present study, the cryoprotective effects of Lolium perenne antifreeze protein (LpAFP) on the vitrification of bovine embryos were evaluated. In vitro-produced blastocysts were divided into two groups: the control group (CG) without the addition of LpAFP and the treatment group (TG) with the addition of 500 ng/ml of LpAFP in the equilibrium and vitrification solution. Vitrification was carried out by transferring the blastocysts to the equilibrium solution [7.5% ethylene glycol (EG) and 7.5% dimethyl sulfoxide (DMSO)] for 2 min and then to the vitrification solution (15% EG, 15% DMSO and 0.5M sucrose). The blastocysts were deposited on a cryotop device and submerged in liquid nitrogen. Warming was carried out in three steps in solutions with different sucrose concentrations (1.0, 0.5, and 0.0 M, respectively). Embryos were evaluated for re-expansion/hatching, the total cell count, and ultrastructural analysis. There was no significant difference in the re-expansion rate 24 h after warming; however, there was variation (P < 0.05) in the hatching rate in the TG and the total number of cells 24 h after warming was higher in the TG (114.87 ± 7.24) when compared with the CG (91.81 ± 4.94). The ultrastructural analysis showed changes in organelles related to the vitrification process but, in the TG, there was less damage to mitochondria and rough endoplasmic reticulum compared with the CG. In conclusion, the addition of 500 ng/ml of LpAFP during the vitrification of in vitro-produced bovine embryos improved the hatching rate and total cell number of blastocysts after warming and mitigated intracellular damage.

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