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This study investigated crotamine (CTA), a peptide derived from the venom of the South American rattlesnake Crotalus durissus terrificus, known for its exceptional cell penetration potential. The objective was to explore the antibacterial and antifungal activity of CTA, its ability to inhibit efflux pumps and evaluate the effectiveness of its pharmacological combination with antibiotics and antifungals. In microbiological assays, CTA in combination with antibiotics was tested against strains of S. aureus and the inhibition of NorA, Tet(K) and MepA efflux pumps was also evaluated. CTA alone did not present clinically relevant direct antibacterial action, presenting MIC > 209.7 µM against strains S. aureus 1199B, IS-58, K2068. The standard efflux pump inhibitor CCCP showed significant effects in all negative relationships to assay reproducibility. Against the S. aureus 1199B strain, CTA (20.5 µM) associated with norfloxacin diluted 10 × (320.67 µM) showed a potentiating effect, in relation to the control. Against the S. aureus IS-58 strain, the CTA associated with tetracycline did not show a significant combinatorial effect, either with 2304 or 230.4 µM tetracycline. CTA at a concentration of 2.05 µM associated with ciprofloxacin at a concentration of 309.4 µM showed a significant potentiating effect. In association with EtBr, CTA at concentrations of 2.05 and 20.5 µM potentiated the effect in all strains tested, reducing the prevention of NorA, Tet(K) and MepA efflux pumps. In the C. albicans strain, a potentiating effect of fluconazole (334.3 µM) was observed when combined with CTA (2.05 µM). Against the C. tropicalis strain, a significant effect was also observed in the association of fluconazole 334.3 µM, where CTA 2.05 µM considerably reduced fungal growth and decreased the potentiation of fluconazole. Against the C. krusei strain, no significant potentiating effect of fluconazole was obtained by CTA. Our results indicate that CTA in pharmacological combination potentiates the effects of antibiotics and antifungal. This represents a new and promising antimicrobial strategy for treating a wide variety of infections.

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BACKGROUND Evidence from randomized studies support complete over culprit-only revascularization for patients with acute coronary artery syndrome (ACS) and multivessel coronary artery diseases (MVD). Whether these findings extend to elderly patients, however, has not been thoroughly explored. METHODS We conducted a systematic review and meta-analysis comparing clinical outcomes of elderly individuals (defined as age ≥75 years) with ACS and MVD submitted to complete vs partial-only percutaneous coronary intervention (PCI). PubMed, Embase, and Cochrane were searched. We computed pooled hazard ratios with 95% confidence intervals (CI) to preserve time time-to-event data. RESULTS We included 7 studies, of which 2 were RCT and 5 were multivariable adjusted cohorts, comprising a total 10 147, of whom 43.8% underwent complete revascularization. As compared with partial-only PCI, complete revascularization was associated with a lower all-cause mortality (hazard ratio 0.71; 95% CI 0.60­0.85; P < 0.01), cardiovascular mortality (hazard ratio 0.64; 95% CI 0.52­0.79; P < 0.01), and recurrent myocardial infarction (hazard ratio 0.65; 95% CI 0.50­0.85; P < 0.01). There was no significant difference between groups regarding the risk of revascularizations (hazard ratio 0.80; 95% CI 0.53­1.20; P = 0.28). CONCLUSION Among elderly patients with ACS and multivessel CAD, complete revascularization is associated with a lower risk of all-cause mortality, cardiovascular mortality, and recurrent myocardial infarction.

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BACKGROUND: Diabetic retinopathy (DR) stands as the foremost cause of preventable blindness in adults. Despite efforts to expand DR screening coverage in the Brazilian public healthcare system, challenges persist due to various factors including social, medical, and financial constraints. Our objective was to evaluate the quality of images obtained with the AirDoc, a novel device, compared to Eyer portable camera which has already been clinically validated. METHODS: Images were captured by two portable retinal devices: AirDoc and Eyer. The included patients had their fundus images obtained in a screening program conducted in Blumenau, Santa Catarina. Two retina specialists independently assessed image's quality. A comparison was performed between both devices regarding image quality and the presence of artifacts. RESULTS: The analysis included 129 patients (mean age of 61 years), with 29 (43.28%) male and an average disease duration of 11.1 ± 8 years. In Ardoc, 21 (16.28%) images were classified as poor quality, with 88 (68%) presenting artifacts; in Eyer, 4 (3.1%) images were classified as poor quality, with 94 (72.87%) presenting artifacts. CONCLUSIONS: Although both Eyer and AirDoc devices show potential as screening tools, the AirDoc images displayed higher rates of ungradable and low-quality images, that may directly affect the DR and DME grading. We must acknowledge the limitations of our study, including the relatively small sample size. Therefore, the interpretations of our analyses should be approached with caution, and further investigations with larger patient cohorts are warranted to validate our findings.

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The objective of this study was to compare the indirect methods of obtaining digestibility with the direct method of total fecal collection to estimate the apparent digestibility of nutrients in sheep and goats supplemented with non-protein nitrogen. Five goats and five sheep with no defined racial pattern were used, distributed in two 5 × 5 Latin squares, with split plots, considering the diets as plots and the apparent digestibility determination methodologies as subplots. The diets were composed of buffelgrass hay and the addition, via ruminal infusion, of increasing amounts of nitrogen supplementation in order to gradually raise the CP level of the basal diet in intervals of 2% points, that is, + 2, +4, + 6 and + 8%. Samples of the feeds offered, and the leftovers were collected daily during the five days of collection to determine the nutrient intake, as well as the total collection of feces to determine the apparent digestibility of the nutrients. The amount of fecal dry matter excreted was estimated by the concentration of Indigestible Acid Detergent Fiber (ADFi), Indigestible Neutral Detergent Fiber (NDFi), Indigestible Dry Matter at 244 h (DMi 244 h) and Indigestible Dry Matter at 264 h (DMi 264 h). Among the evaluated markers, DMi 264 h had the lowest accuracy in estimating fecal excretion and nutrient digestibility. For the goat species, the markers ADFi and DMi 244 h proved to be able to adequately predict fecal excretion and digestibility indices, while NDFi stood out for both species. Among the evaluated markers, NDFi is the one that most accurately estimates the nutrient digestibility of the diet for goats and sheep.

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OBJECTIVE: To evaluate whether coating enamel with a polymeric primer (PPol) containing titanium tetrafluoride (TiF4) before applying a bleaching gel with 35% H2O2 (35% BG) increases esthetic efficacy, prevents changes in morphology and hardness of enamel, as well as reduces the cytotoxicity from conventional in-office bleaching. MATERIALS AND METHODS: Standardized enamel/dentin discs were stained and bleached for 45 min (one session) with 35% BG. Groups 2TiF4, 6TiF4, and 10TiF4 received the gel on the enamel previously coated with PPol containing 2 mg/mL, 6 mg/mL, or 10 mg/mL, respectively. No treatment or application of 35% BG directly on enamel were used as negative control (NC), and positive control (PC), respectively. UV-reflectance spectrophotometry (CIE L*a*b* system, ΔE00, and ΔWI, n = 8) determined the bleaching efficacy of treatments. Enamel microhardness (Knoop, n = 8), morphology, and composition (SEM/EDS, n = 4) were also evaluated. Enamel/dentin discs adapted to artificial pulp chambers (n = 8) were used for trans-amelodentinal cytotoxicity tests. Following the treatments, the extracts (culture medium + bleaching gel components diffused through the discs) were collected and applied to odontoblast-like MDPC-23 cells, which were assessed concerning their viability (alamarBlue, n = 8; Live/Dead, n = 4), oxidative stress (n = 8), and morphology (SEM). The amount of H2O2 in the extracts was also determined (leuco crystal violet/peroxidase, n = 8). The numerical data underwent one-criterion variance analysis (one-way ANOVA), followed by Tukey's test, at a 5% significance level. RESULTS: Regarding the ΔE00, no difference was observed among groups 2TiF4, 6TiF4, and PC (p > 0.05). The ΔWI was similar between groups 2TiF4 and PC (p > 0.05). The ΔWI of group 6TiF4 was superior to PC (p < 0.05), and group 10TiF4 achieved the highest ΔE00 and ΔWI values (p < 0.05). Besides limiting enamel microstructural changes compared to PC, group 10TiF4 significantly increased the hardness of this mineralized dental tissue. The highest cellular viability occurred in 10TiF4 compared to the other bleached groups (p < 0.05). Trans-amelodentinal H2O2 diffusion decreased in groups 2TiF4, 6TiF4, and 10TiF4 in comparison with PC (p < 0.05). CONCLUSION: Coating enamel with a PPol containing TiF4 before applying a 35% BG may increase enamel microhardness and esthetic efficacy and reduce the trans-amelodentinal cytotoxicity of conventional in-office tooth bleaching. The PPol containing 10 mg/mL of TiF4 promoted the best outcomes.

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This study aimed to assess the impact of adding forage cactus as an additive to the production of corn silage without the cob on the performance of feedlot sheep and subsequent silage losses. The experimental design was completely randomized, consisting of three treatments: corn silage without cob; 0% = 100% corn plant without the cob; 10% = 90% corn plant without cob + 10% forage cactus; 20% = 80% corn plant without cob + 20% forage cactus. Significant effects were observed for dry matter intake (P = 0.0201), organic matter (P = 0.0152), ether extract (P = 0.0001), non-fiber carbohydrates (P = 0.0007). Notably, nutrient digestibility showed significant differences in organic matter (P = 0.0187), ether extract (P = 0.0095), neutral detergent fiber (P = 0.0005), non-fiber carbohydrates (P = 0.0001), and metabolizable energy (P = 0.0001). Performance variables, including total weight gain (P = 0.0148), average daily weight gain (P = 0.0148), feeding efficiency, and rumination efficiency of dry matter (P = 0.0113), also exhibited significant effects. Consequently, it is recommended to include 20% forage cactus in corn silage, which, based on natural matter, helps meet animals' water needs through feed. This inclusion is especially vital in semi-arid regions and aids in reducing silage losses during post-opening silo disposal.

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The aim was to evaluate the chemical composition, carbohydrates, protein fractionation and in vitro gas production of silages composed of spineless cactus and tropical forages and their effect on sheep performance. Treatments consisted of silages: corn silage (CS), spineless cactus silage (SCS), spineless cactus + gliricidia (SCG), spineless cactus + buffel grass silage (SCBG) and spineless cactus + pornunça (SCP). Silos were opened 60 days after ensiling, and analyses were carried out. The digestibility test lasted for 36 days, with eight animals per treatment. A completely randomized design was adopted. Considering carbohydrate fractionation, CS, SCS and SCBG silages had higher total carbohydrate content (p = 0.001). The SCS silage presented a higher A + B1 fraction (p = 0.001). The SCBG and SCG silages showed a higher B2 fraction (p < 0.0001) compared to the CS and SCS silages. The SCBG and SCP silages presented a higher C fraction (p = 0.001). For protein fractionation, the SCP and SCG silages showed higher crude protein contents (p = 0.001). The CS and SCS silages showed a higher A fraction (p = 0.001). The SCBG silage presented a higher B1 + B2 fraction (p = 0.001). The SCG silage showed a higher B3 fraction (p = 0.006) compared to SCBG silage. The SCS and SCP silages showed a higher C fraction (p = 0.001). Exclusive SCS silage showed higher in vitro dry matter digestibility (p = 0.001), dry matter degradability (p = 0.001) and total gas production (p = 0.001). The use of the SCBG, SCP and SCG silages to feed sheep increased the dry matter intake (p < 0.001). Sheep fed the SCG silage showed greater dry matter and crude protein digestibility compared to the sheep fed the CS, SCS and SCP silages (p = 0.002). There was a higher water intake (p < 0.001) with the use of the SCS and SCG silages to feed the sheep. The SCP and SCG silages provided a greater intake (p < 0.001) and excretion (p < 0.001) of nitrogen by the animals. Although there were no differences between the treatments for daily gains, lambs that received the spineless cactus-based silage associated with tropical forages showed higher gains (160-190 g/day) than lambs that received CS silage (130 g/day). Thus, the use of spineless cactus associated with buffelgrass, pornunça and gliricidia to prepare mixed silages (60:40) to feed sheep has potential use to feed sheep, with positive effects on nutrient degradation and increases in dry matter intake. Under experimental conditions, we recommend the exclusive use of spineless cactus silage associated with buffel grass, pornunça and gliricidia in feeding sheep in semi-arid regions, as it provides nutrients, water and greater daily gains compared to corn silage.

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DEAD-box helicases are global regulators of liquid-liquid phase separation (LLPS), a process that assembles membraneless organelles inside cells. An outstanding member of the DEAD-box family is DDX3X, a multi-functional protein that plays critical roles in RNA metabolism, including RNA transcription, splicing, nucleocytoplasmic export, and translation. The diverse functions of DDX3X result from its ability to bind and remodel RNA in an ATP-dependent manner. This capacity enables the protein to act as an RNA chaperone and an RNA helicase, regulating ribonucleoprotein complex assembly. DDX3X and its orthologs from mouse, yeast (Ded1), and C. elegans (LAF-1) can undergo LLPS, driving the formation of neuronal granules, stress granules, processing bodies or P-granules. DDX3X has been related to several human conditions, including neurodevelopmental disorders, such as intellectual disability and autism spectrum disorder. Although the research into the pathogenesis of aberrant biomolecular condensation in neurodegenerative diseases is increasing rapidly, the role of LLPS in neurodevelopmental disorders is underexplored. This review summarizes current findings relevant for DDX3X phase separation in neurodevelopment and examines how disturbances in the LLPS process can be related to neurodevelopmental disorders.

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This study aimed to evaluate the effect of increasing levels of red propolis extract (RPE) in the diet of confined sheep on performance and histomorphometric parameters of rumen and intestine and histopathological parameters of liver and kidney. Thirty-five male sheep (17.08 ± 2.36 kg) were used, distributed in a completely randomized design, with five treatments (0, 7, 14, 21, and 28 mL day-1 RPE) and seven replications, submitted to 68 days of experiment. At the end of the experimental period, the animals were euthanized, and samples of rumen, intestine, liver, and kidney were collected to histomorphometry and histopathology analyzes. Higher RPE inclusions (21 and 28 mL day-1) maintained dry matter intake and increased total weight (5.78 x 6.14 and 6.95 kg, respectively) gain up to 20.24%. In the rumen, the inclusion of RPE led to an increase in the thickness of the epithelium and the highest level also increased the thickness of the keratinized portion of this epithelium (21.71 x 32.15 µm). The level of 21 mL day-1 provided larger ruminal papillae (1620.68 x 1641.70 µm) and greater ruminal absorption area (561791.43 x 698288.50 µm2). In intestine 21 and 28 mL-1 of RPE provided greater mucosal thickness (468.54 x 556.20 and 534.64 µm), higher goblet cell index (23.32 x 25.82 and 25.64) and higher hepatic glycogen index (1.47 x 1.64 and 1.62), supporting higher nutrients absortion and glicogenolise and intestinal health, corroborating the weight gain indices. The inclusion of RPE did not cause renal histopathological lesions. Therefore, levels of 21 and 28 mL day-1 of RPE can be used in sheep diets, promoting greater final weight gain, causing positive histomorphological changes in the rumen, intestine and liver, without causing kidney or liver damage.

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In the Amazon, some species of Loricariidae are at risk of extinction due to habitat loss and overexploitation by the ornamental fish market. Cytogenetic data related to the karyotype and meiotic cycle can contribute to understanding the reproductive biology and help management and conservation programs of these fish. Additionally, chromosomal mapping of repetitive DNA in Loricariidae may aid comparative genomic studies in this family. However, cytogenetics analysis is limited in Amazonian locariids. In this study, chromosomal mapping of multigenic families was performed in Scobinancistrus aureatus, Scobinancistrus pariolispos and Spatuloricaria sp. Meiotic analyzes were performed in Hypancistrus zebra and Hypancistrus sp. "pão". Results showed new karyotype for Spatuloricaria sp. (2n=66, NF=82, 50m-10sm-6m). Distinct patterns of chromosomal organization of histone H1, histone H3 and snDNA U2 genes were registered in the karyotypes of the studied species, proving to be an excellent cytotaxonomic tool. Hypotheses to explain the evolutionary dynamics of these sequences in studied Loricariidae were proposed. Regarding H. zebra and H. sp. "pão", we describe the events related to synapse and transcriptional activity during the meiotic cycle, which in both species showed 26 fully synapsed bivalents, with high gene expression only during zygotene and pachytene. Both Hypancistrus species could be used may be models for evaluating changes in spermatogenesis of Loricariidae.

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