Effectiveness of self-etching bonding systems on dentin after radiotherapy: perspectives on microtensile and microshear bond strength.

OBJECTIVE: Self-etching dental adhesives bond with dentin through chemical reactions with calcium. This study assessed bond strength (BS) using microtensile (µTBS) and microshear (µSBS) tests on sound and post-radiotherapy dentin, with dental adhesives containing different functional monomers. METHODS: Sound dentin (SD) and post-radiotherapy irradiated dentin (ID) were tested with two adhesive systems: Clearfil SE Bond (SE, 10-MDP-based) and FL Bond II (FL, containing carboxylic and phosphonic monomers with S-PRG bioactive particles). The tests occurred initially (24 h) and six months later; fracture mode was also analyzed (40x). Ninety-six human molars were randomly assigned (n = 12), and half were irradiated with a 70 Gy radiation dose. For µTBS test, teeth were bonded, restored and sectioned them into beams (0.64 mm2). The µSBS test used filled transparent cylindrical matrices with resin composite and light-cured them after dental adhesive applications. Three-way ANOVA and Tukey's test (p < 0.05) analyzed the data. RESULTS: µTBS showed a significant substrate x adhesive interaction (p < 0.001), while µSBS was significant for all factors (p = 0.006). SE and FL performed better on SD and ID, respectively, in the µTBS test. As for µSBS, SE showed higher values on ID (p < 0.05). Lower BS values occurred for SD-FL and ID-SE after six months. CONCLUSION: Dental adhesive performance varied based on substrate type and test method. FL was more stable for ID in µTBS, while SE excelled in µSBS. CLINICAL RELEVANCE: As post-radiotherapy irradiated dentin becomes more vulnerable, self-etching systems based on functional monomer and bioactive ingredients may exhibit appropriate bonding to this altered substrate.

Hemodynamic Assessment via Echocardiography During Propofol Anesthetic Induction in Healthy Dogs.

Introduction: Propofol is an intravenous anesthetic administered as a bolus or continuous infusion during anesthetic induction and maintenance. Its pharmacokinetic characteristics include hepatic and extrahepatic metabolism with a rapid onset of action and short duration, which provides a smooth anesthetic induction without excitatory effects. Objective: To evaluate whether the isolated use of propofol in anesthetic induction in dogs changes the hemodynamic variables assessed via echocardiography. Study Design: Prospective clinical study. Animals: Twelve healthy dogs. Methods: The dogs were induced with propofol (dose/effect) at 3 mg/kg/minute, and echocardiographic evaluations were performed immediately before anesthetic induction (MB) and immediately after its interruption (MI), at the end of the supply of the anesthetic agent. Results: A significant reduction was observed between the values of the following hemodynamic variables: Ejection Fraction (EF%), which varied from 70% to 65% (p=0.011) between moments, and the Doppler Ejection Index (DEI), which ranged from 27.1 mL/beat/m2 to 22.4 mL/beat/m2 (p=0.044). The heart rate (HR) and the other studied hemodynamic variables showed no significant differences between the evaluated moments. Conclusion and Clinical Relevance: Propofol was a safe anesthetic-inducing agent, maintaining stable hemodynamic indices during anesthetic induction at the used rate.

Interleukin-27 Regulates Adaptative Immune Responses Associated With Control of Parasite Replication in Canine Leishmaniasis.

Interleukin 27 (IL-27) is a cytokine that regulates susceptibility to Leishmania infantum infection in humans and experimental models. This cytokine has not yet been described in canine leishmaniasis (CanL). Therefore, we investigated whether IL-27 has a regulatory role in CanL. The EBI3 and p28 subunits of IL-27 were measured in splenic leukocytes culture supernatant from dogs with CanL and compared to control dogs. We also correlated EBI3 and p28 levels with IL-21, anti-L. infantum antibodies and parasite loads. We performed functional assays followed by IL-27 blockade and measured parasite loads, production of cytokines in splenic leukocytes culture supernatant, and the expression of PD-1, CTLA-4, phospho-Stat-1/3, T-bet, GATA3 and nitric oxide production (NO). Both IL-27 subunits increased in the supernatant of dogs with CanL compared to control dogs. EBI3 and p28 levels showed a moderate positive correlation with IL-21 (r = 0.67, p < 0.0001 and r = 0.45, p < 0.012, respectively), and the EBI3 subunit was positively associated with anti-L. infantum IgG antibodies (r = 0.38, p < 0.040) and parasite load (r = 0.47, p < 0.009). IL-27 and IL-21 participate of immune responses in CanL. IL-27 may be associated with the failure of immunity to control parasite replication via upregulation of the expression of PD-1, CTLA-4, T-bet and NO in splenic leukocytes from dogs with CanL. These findings suggest that the pathways regulated by IL-27 are involved in CanL pathogenesis in the host, and may be targets for new therapies.

hACE2 upregulation and participation of macrophages and clear cells in the immune response of epididymis to SARS-CoV-2 in K18-hACE2 mice.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus caused the coronavirus disease 2019 pandemic, and the prevalence of deaths among men is higher than among women. The epididymis, divided into caput, corpus, and cauda, shows a region-specific immunity. The K18-hACE2 mouse expresses human angiotensin-converting enzyme 2 (hACE2), the receptor that allows SARS-CoV-2 infection. However, studies using this transgenic mouse to evaluate the impact of this viral infection in epididymis have not yet been performed. OBJECTIVES: We evaluated the expression of hACE2 in the epididymis of SARS-CoV-2-infected K18-hACE2 mice, and assessed the epididymal immune response, focusing on F4/80+ mononuclear phagocytes and tumor necrosis factor-alpha expression. MATERIALS AND METHODS: The following analyses were performed in the epididymal sections of infected mice: epithelial height and duct diameter, birefringent collagen, Terminal deoxynucleotidyl Transferase-mediated dUTP Nick End Labelling, immunoreactions for detection of hACE2, spike, FGF, V-ATPase, F4/80, tumor necrosis factor-alpha, and iNOS. Viral particles were identified under electron microscopy. hACE2, Rigi, Tgfb1 and Tnfa expression were also evaluated by real-time quantitative polymerase chain reaction. RESULTS: All epididymal regions expressed hACE2, which increased in all epididymal regions in the infected mice. However, the caput appeared to be the most infected region. Despite this, the caput region showed minimal changes while the cauda showed significant epithelial changes associated with increased iNOS immunoexpression. The F4/80+ mononuclear phagocyte area increased significantly in both stroma and epithelium. In addition to the epithelial and stromal mononuclear phagocytes, tumor necrosis factor-alpha was also detected in clear cells, whose cytoplasm showed a significant increase of this cytokine in the infected animals. DISCUSSION AND CONCLUSION: The K18-hACE2 mouse is a useful model for evaluating the impact of SARS-CoV-2 infection in the epididymis. The infection induced hACE2 upregulation, favoring the virulence in the epididymis. The epididymal regions responded differentially to infection, and the activation of F4/80+ mononuclear phagocytes associated with the increased tumor necrosis factor-alpha immunolabeling in clear cells indicates a role of clear cells/mononuclear phagocytes immunoregulatory mechanisms in the epididymal immune response to SARS-CoV-2 infection.

Diastereoselective Synthesis of Highly Functionalized γ-Lactams via Ugi Reaction/Michael Addition.

The γ-lactam ring is a prominent feature in medicinal chemistry, and its synthesis has garnered significant interest due to its valuable properties. Among the γ-lactams, 2-oxopyrrolidine-3-carbonitrile derivatives stand out as versatile synthons that can be readily transformed into a variety of other functional groups. In this work, we successfully synthesized highly functionalized 3-cyano-2-pyrrolidinones with moderate to good overall yields using the Ugi reaction followed by intramolecular Michael addition. The process demonstrated excellent diastereoselectivity and showed good tolerance to a range of isonitriles and carbonyl compounds.

Calcium silicate-based intracanal medication: Physicochemical properties and effectiveness of techniques for removing medication from the human root canal.

OBJECTIVE: Our purpose was to investigate the physicochemical properties of Bio-C Temp, a bioceramic intracanal medication, and whether its residues remain adhered to the dentine walls after conventional manual irrigation (CMI) or passive ultrasonic irrigation (PUI) in comparison to Calen. METHODS: The pH after 12 hours, 1 day, 3 days, 7 days, 14 days, 21 days and 28 days, and the flow, radiopacity, and the solubility of the medications after immersion for 7 and 30 days in distilled water (dH2O) or phosphate-buffered saline (PBS) solution were evaluated. Filling capacity, and volumetric changes after 14 days were assessed by micro-computed tomography (micro-CT). The residues of medications after CMI or PUI were analysed with scanning electron microscopy. Statistical analysis was performed using ANOVA and Tukey's post-hoc test, Student's t test or the Kruskal-Wallis and Dunn post-hoc test (α = 0.05). RESULTS: Bio-C Temp presented a lower pH, flow, volumetric change, and weight loss after immersion in PBS on the 7th and 14th days (p < 0.05) and greater radiopacity and filling capacity (p < 0.05) than Calen. Both medications showed lower solubility in PBS than in dH2O (p < 0.05). There was no difference in the residue content of the two medications between two irrigation methods in three-thirds of the roots (p > 0.05). CONCLUSION: Although Bio-C Temp had less volumetric loss and satisfactory filling capacity, this medication provided lower alkalinity than did Calen. Furthermore, neither CMI nor PUI completely removed the medicament residues within the human root canal.

Bacterial and Symbiodiniaceae communities' variation in corals with distinct traits and geographical distribution.

Coral microbiomes play crucial roles in holobiont homeostasis and adaptation. The host's ability to populate broad ecological niches and to cope with environmental changes seems to be related to the flexibility of the coral microbiome. By means of high-throughput DNA sequencing we characterized simultaneously both bacterial (16S rRNA) and Symbiodiniaceae (ITS2) communities of four reef-building coral species (Mussismilia braziliensis, Mussismilia harttii, Montastraea cavernosa, and Favia gravida) that differ in geographic distribution and niche specificity. Samples were collected in a marginal reef system (Abrolhos, Brazil) in four sites of contrasting irradiance and turbidity. Biological filters governed by the host are important in shaping corals' microbiome structure. More structured associated microbial communities by reef site tend to occur in coral species with broader geographic and depth ranges, especially for Symbiodiniaceae, whereas the endemic and habitat-specialist host, M. braziliensis, has relatively more homogenous bacterial communities with more exclusive members. Our findings lend credence to the hypothesis that higher microbiome flexibility renders corals more adaptable to diverse environments, a trend that should be investigated in more hosts and reef areas.

Systemic and Environmental Risk Factors Associated with Molar Incisor Hypomineralisation.

The etiology of molar incisor hypomineralisation (MIH) has been attributed to systemic and environmental factors since 2001. The identification of MIH etiology is fundamental to better understand this condition, for differential diagnosis, and to identify the patient group at risk of MIH. Although the etiology of MIH is still unclear, it is stated as a multifactorial origin, with an overlap of systemic and genetic risk factors. The aim of this chapter was to discuss the systemic and environmental factors associated with MIH according to scientific evidence in the literature, relating it to the basic knowledge of amelogenesis and tooth development chronology. In this chapter, amelogenesis is described and illustrated in detail. Some characteristics of the amelogenesis process could explain some clinical features of the developmental defect of enamel, especially MIH. The chronology of tooth development was also referred to as a characteristic for the occurrence of MIH. Finally, the literature about systemic and environmental risk factors was revised, and the prenatal, perinatal, and postnatal factors associated with MIH were discussed. During the prenatal period, maternal health status, including illnesses during pregnancy and maternal smoking, are the main investigated factors associated with MIH. Prematurity (<37 weeks), low birth weight, and cesarean delivery are the factors associated with MIH during the perinatal period. Moreover, postnatal factors, such as common childhood illnesses, respiratory disease, infections, and antibiotic use, have been associated with MIH. New longitudinal studies that consider the synergy between exposure to environmental factors and biological susceptibility are likely to provide a new understanding of the etiology of MIH.

Prevalence and factors associated with dyslipidemia in children aged 6 to 42 months in a Brazilian capital.

This study aimed to assess the prevalence and factors associated with lipid profile abnormalities of children aged 6 to 42 months in a Central-West Brazilian capital city. This cross-sectional study used data from the baseline of a cluster-randomized clinical trial conducted in parallel. It evaluated the lipid profile, usual nutrients intake (direct food-weighing method and 24-hour dietary recall), anthropometric parameters, and socioeconomic aspects of 169 children from early childhood education centers. Poisson regression with robust variance analysis was conducted. Of the total sample, 85% had dyslipidemia, 72% had high-density lipoproteins (HDL-c) levels below the desired range, 49% had increased triglycerides (TG), 17% exhibited elevated low-density lipoproteins (LDL-c), and 15% showed high total cholesterol (TC). An increase in the body mass index (BMI) for age z-score was associated with a higher prevalence of increased TG (PR = 1.22; 95%CI: 1.05-1.41; p = 0.009). Higher age in children was associated with an increased prevalence of high LDL-c (PR = 1.037; 95%CI: 1.01-1.07; p = 0.022) and TC (PR = 1.036; 95%CI: 1.00-1.07; p = 0.037), however it was a protective factor against low HDL-c (PR = 0.991; 95%CI: 0.98-1.00; p = 0.042). High energy intake was associated with low HDL-c (PR = 1.001; 95%CI: 1.00-1.00; p = 0.023). A higher prevalence of increased LDL-c (PR = 1.005; 95%CI: 1.00-1.01; p = 0.006) and decreased HDL-c (PR = 1.002; 95%CI: 1.00-1.00; p < 0.001) were associated with dietary cholesterol intake. Most of the children presented at least one alteration in serum lipids. Lipid profile abnormalities were associated with higher BMI, older age, and increased caloric and cholesterol intake.

Prevalence and associated factors related to sarcopenia in people living with HIV/AIDS.

BACKGROUND: The use of antiretrovirals has increased the survival of People Living with HIV/AIDS (PLWHA), resulting in an aging population and a rise in the incidence of sarcopenia. The lack of uniformity among the prevalences found in studies may be associated with the use of different diagnostic criteria, highlighting the need for local studies to determine the prevalence of sarcopenia. METHODS: Cross-sectional study to estimate the prevalence and associated factors of sarcopenia using the revised criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2). This study included PLWHA of both sexes, aged 40 years or older, who were treated at the infectious disease outpatient clinic of a tertiary hospital from 2019 to 2021. Muscle mass was quantified through electrical bioimpedance, using resistance and reactance to calculate appendicular lean mass (ALM) in kg/m². Muscle strength, measured in kg, was assessed using a manual dynamometer, and muscle function was evaluated using the gait speed test (m/s). Numerical variables were analyzed using measures of central tendency and dispersion. The chi-square test was used to assess associations in categorical variables. Odds ratios (OR) and 95% Confidence Intervals (CI) were calculated to evaluate the strength of associations. RESULTS: Among the 218 PLWHA, the prevalence of sarcopenia was 8.7% (95% CI: 5.6 to 13.3). The mean age of the study population was 51.8 ± 8.3 years; 53.7% were male, 72.9% were brown/Black, 97.7% reported not using illicit drugs, and 24.8% were classified as obese. Multivariate analysis showed that the time since HIV diagnosis (P = 0.022) and the use of illicit drugs were associated with the diagnosis of sarcopenia. CONCLUSION: The prevalence of sarcopenia using the EWGSOP2 criteria was low. People with a longer duration of HIV infection and those using illicit drugs were more likely to develop sarcopenia.

Influence of irradiated dentin, biofilm and different artificial saliva formulations on root dentin demineralization.

The aim of this study was evaluated the influence of radiation as well as of new formulations of artificial saliva on the development of root dentin lesions. Bovine root samples were divided into: irradiated (70 Gy) dentin or not; the type of biofilm (from irradiated patient-experimental or non-irradiated patient-control) and the type of artificial saliva (for the condition irradiated dentin/biofilm from irradiated patient): Control Artificial Saliva (inorganic); Control Saliva + 1 mg/ml hemoglobin; Control Saliva +0.1 mg/ml cystatin; Control Saliva + hemoglobin + cystatin; Bioextra (positive control) and deionized water (DiW, negative control) (n = 12/group). Biofilm was produced using human biofilm and McBain saliva (0.2 % of sucrose, 37o C and 5 % CO2); the treatments were done 1x/day, for 5 days. Colony-forming units (CFU) counting was performed; demineralization was quantified by transversal microradiography. Two-way ANOVA/Bonferroni or Sidak test for the comparison between biofilm x dentin and ANOVA/Tukey or Kruskal-Wallis/Dunn for comparing artificial saliva were done (p < 0.05). The type of biofilm had no influence on CFU and demineralization. Sound dentin under control biofilm presented the lowest Lactobacillus ssp. and Streptococcus mutans CFU and the lowest mean mineral loss (R) (25.6 ± 2.2; 23.7 ± 2.9 %) compared to irradiated dentin (26.1 ± 2.8; 28.1 ± 3.3, p < 0.004) for both types of biofilms (experimental and control, respectively). Bioextra was the only artificial saliva that reduced R (10.8 ± 2.5 %) and Lesion Depth (LD) (35 ± 15 µm) compared to DiW (17.3 ± 3.3 %, 81 ± 18 µm, p < 0.0001). Irradiation has impact on caries development; the experimental saliva were unable to reduce its occurrence.

Elucidating the underlying mechanisms of silicon to suppress the effects of nitrogen deficiency in pepper plants.

In many regions, nitrogen (N) deficiency limits pepper cultivation, presenting significant cultivation challenges. This study investigates the impact of N deficiency and silicon (Si) supplementation on physiological responses and antioxidant modulation in pepper plants, focusing particularly on the homeostasis of carbon (C), nitrogen, and phosphorus (P), and their effects on growth and biomass production. Conducted in a factorial design, the experiment examined pepper plants under conditions of N sufficiency and deficiency, with and without Si supplementation (0.0 mM and 2.0 mM). Results showed that N deficiency sensitizes pepper plants, leading to increased electrolyte leakage (39.59%) and disrupted C, N, and P homeostasis. This disruption manifests as reductions in photosynthetic pigments (-64.53%), photochemical efficiency (-14.92%), and the synthesis of key metabolites such as total free amino acids (-86.97%), sucrose (-53.88%), and soluble sugars (-39.96%), ultimately impairing plant growth. However, Si supplementation was found to alleviate these stresses. It modulated the antioxidant system, enhanced the synthesis of ascorbic acid (+30.23), phenolic compounds (+33.19%), and flavonoids (+7.52%), and reduced cellular electrolyte leakage (-25.02%). Moreover, Si helped establish a new homeostasis of C, N, and P, optimizing photosynthetic and nutritional efficiency by improving the utilization of C (+17.46%) and N (+13.20%). These Si-induced modifications in plant physiology led to increased synthesis of amino acids (+362.20%), soluble sugars (+51.34%), and sucrose (77.42%), thereby supporting enhanced growth of pepper plants. These findings elucidate the multifaceted biological roles of Si in mitigating N deficiency effects, offering valuable insights for more sustainable horticultural practices.

Multiple PDT sessions with chlorin-e6 and LL-37 loaded-nanoemulsion provide limited benefits to periodontitis in rats.

BACKGROUND: The combination of photodynamic therapy (PDT) and LL-37 has never been tested in an animal study and our research team background suggests this strategy might be a promising alternative to intensify periodontitis resolution. This study aimed to assess the effects of multiple sessions of PDT with chlorin-e6 conjugated to the antimicrobial peptide LL-37 loaded nanoemulsion, as adjunctive therapy in experimental periodontitis in rats. METHODS: Experimental periodontitis was induced in 81 rats. After disease establishment, animals were assigned to three groups: SRP (scaling and root planning); SRP + 1PDT, SRP followed by a single PDT session; SRP + 4PDT (n = 27), SRP followed by four PDT sessions at 0, 24, 48 and 72 h after SRP. Animals were subjected to euthanasia at 7, 14 and 28 days, and samples were submitted to osteoclast quantification, immunological and microtomography analysis. RESULTS: All treatments resulted in significant periodontal improvements and there was no significant difference between the groups in both local inflammatory response and healing process. Minimal adjunctive effects could be found for the combined therapy in terms of cytokine levels (IL-1ß and IL-10), with no statistical significance. However, the number of TRAP-positive osteoclasts per mm of alveolar bone linear surface for the group treated with PDT sessions was significantly lower than those treated with SRP only. CONCLUSIONS: Multiple PDT sessions with chlorin-e6 and LL-37 nanoemulsion as an adjunct to scaling and root planning reduced the presence of osteoclast in the local site but did not contribute towards bone regeneration and IL-1ß and IL-10 levels.

Impact of functional monomers, bioactive particles, and HEMA, on the adhesive performance of self-etch adhesive systems applied to simulated altered dentin.

OBJECTIVES: This study aimed to evaluate how self-etching/universal dental adhesive systems (DASs) with differing compositions interact with sound (S), post-radiotherapy (irradiated; I), and artificially eroded (E) dentin in terms of bonding properties. METHODS: The DASs tested were Adper Scotchbond Multipurpose (MP; control), Clearfil SE Bond (SE), FL Bond II (FL), Adper Single Bond Universal (SU) and BeautiBond Xtreme (BX). They were analyzed for initial and 6-month microtensile bond strength (µTBS, n = 12), mode of failure (40 x), scanning electron microscopy (SEM), surface wettability (W, n = 10), and degree of conversion (DC, n = 3) via Fourier-transform infrared spectroscopy (FTIR). Normal and homogeneous distribution of the data allowed their analyses through ANOVA and Tukey tests (p < 0.05). RESULTS: All DASs except BX exhibited higher µTBS for S decreasing for I and E. BX demonstrated the greatest stability among the altered substrates. FL showed the most hydrophobic properties, likely due to its bioactive components. Universal DASs achieved higher DC, regardless of composition. CONCLUSIONS: HEMA-free formulation combined with carboxylic and phosphoric acids in BX, achieved the most stable performance for altered substrates. CLINICAL SIGNIFICANCE: Since radiotherapy and erosion affect dentin, their characteristics compromise adhesive performance and impair the achievement of durable and satisfactory restorations. The use of universal adhesives less dependent on calcium seems less susceptible to hydrolytic degradation and may be a promising option for maintaining adhesive stability over time.

Cryopreservation and transplantation of spermatogonia stem cells in piracanjuba Brycon orbignyanus (Characiformes: Characidae), an endangered fish species.

Piracanjuba (Brycon orbignyanus) is an endangered fish species from the Neotropical region. The establishment of a cryobank using spermatogonial stem cells (SSCs) and subsequent production of a germline chimera is thus a promising strategy for such species. In the present work, procedures for the isolation and cryopreservation of piracanjuba SSCs and subsequent transplantation into sterile recipients were established. The piracanjuba SSCs were obtained by Percoll density gradient centrifugation and differential plating. SSC fractions were evaluated by relative ddx4 expression, alkaline phosphatase activity, and light microscopy. SSC cryopreservation was performed using five cryoprotectants at three different concentrations. The mix of the cells from the 20% and 30% Percoll density gradients showed 58.35 ± 0.03% purity of SSCs. The purity of SSCs increased to 66.00 ± 0.01% after differential plating. The relative ddx4 expression was 3.5 times higher in cells from the Percoll density gradient centrifugation than in the gonad and cells after differential plating. Propanediol (1 M) was the most effective cryoprotector evaluated (P = 1.000), showing 90.75 ± 1.85% cell viability. Freshly isolated and cryopreserved cells from the Percoll density gradient centrifugation were transplanted into a sterile male adult triploid hybrid with germ cell-less gonads. SSCs were observed in the germinal epithelium of the testes of recipients 20 days after transplantation. The results are promising for obtaining functional germline chimeras in Neotropical fish. Consequently, although the number of males used for the experiment was borderline, the procedures established here can be applied in future actions for the conservation and reconstitution of the piracanjuba in case of extinction.

Short Communication: Rotavirus Group A Occurrence in Rural Water Source Samples in a Midwest Region State of Brazil, Comparing Wet and Dry Seasons.

Identified as a potential reference pathogen by the WHO Guidelines for Drinking-Water Quality, Rotavirus (RV) is among the main enteric viruses that cause waterborne diseases. The aim of this study was to identify and correlate the presence of RV in collective and individual water sources of rural communities in the state of Goiás, within the seasons in which the collections were made (rainy and dry seasons). For this, 86 water samples in the dry period and 160 samples in the rainy period were collected. Concentration of water samples, extraction of viral genetic material and molecular tests were performed. When analyzing the presence of RV in the samples, taking into consideration the period studied, RV was found to be more prevalent in the dry season (54.7%) than in the rainy season (20%), showing a strong statistical association with the dry season (p-value < 0.001). The presence of pathogenic microorganisms in water is a public risk issue, enabling the emergence of outbreaks, endemics and epidemics. In the present research, there was an association between the presence of Rotavirus and the dry period of the year when compared to the rainy period.

Predicting of novel homoserine dehydrogenase inhibitors against Paracoccidioides brasiliensis: integrating in silico and in vitro approaches.

Aim: To search for potential inhibitors to homoserine dehydrogenase (HSD) in Paracoccidioides brasiliensis the causative agent of paracoccidioidomycosis, an infection with a high mortality rate in Brazil.Materials & methods: The enzyme was modeled and used in the virtual screening of the compounds. The library was first screened by the Autodock, in which 66 molecules were better ranked than substrate, and then, also evaluated by the Molegro and Gold programs.Results: The HS23 and HS87 molecules were selected in common by the three programs, and ADME/Tox evaluation indicates they are not toxic. The molecular dynamics of PbHSD bonded to ligands showed stable complexes until 50 ns. To validate the results, compounds were purchased for assays of minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), synergic profile with Amphotericin B (AmB) and cytotoxicity. The two molecules presented MIC of 32 µg/ml and MFC of 64 µg/ml against the P. brasiliensis (strain Pb18). They also showed synergistic activity with AmB and a lack of toxicity against Hela and Vero cell lines.Conclusion: These results suggest that the HS23 and HS87 are promising candidates as PbHSD inhibitors and may be used as hits for the development of new drugs against paracoccidioidomycosis.

[Box: see text].

Relationship between autophagy and NLRP3 inflammasome during articular cartilage degradation in oestrogen-deficient rats with streptozotocin-induced diabetes.

BACKGROUND: Estrogen deficiency and Diabetes mellitus (DM) cause joint tissue deterioration, although the mechanisms are uncertain. This study evaluated the immunoexpression of autophagy and NLRP3-inflammasome markers, in rat articular cartilage with estrogen deficiency and DM. METHODS: Twenty rats were sham-operated (SHAM) or ovariectomized (OVX) and equally allocated into four groups: SHAM and OVX groups administered with vehicle solution; SHAM and OVX groups treated with 60 mg/kg/body weight of streptozotocin, intraperitoneally, to induce DM (SHAM-DM and OVX-DM groups). After seven weeks, the rats were euthanized, and their joint knees were processed for paraffin embedding. Sections were stained with haematoxylin-eosin, toluidine blue, safranin-O/fast-green or subjected to picrosirius-red-polarisation method; immunohistochemistry to detect beclin-1 and microtubule-associated protein 1B-light chain 3 (autophagy markers), NLRP3 and interleukin-1ß (IL-1ß) (inflammasome activation markers), along with matrix metalloproteinase-9 (MMP-9), Nuclear factor-kappa B (NFκB), and Vascular endothelial growth factor A (VEGF-A) were performed. RESULTS: Deterioration of articular cartilage and subchondral bone were greater in SHAM-DM and OVX-DM groups. Higher percentages of immunolabeled chondrocytes to NLRP3, IL-1ß, MMP-9, NFκB, and VEGF-A, as well as lower percentages of chondrocytes immunolabeled to autophagy markers, were noticed in estrogen-deficient and diabetic groups. These differences were greater in the OVX-DM group. Percentages of immunolabeled chondrocytes showed negative correlation between autophagy markers v.s IL-1ß, NLRP-3, MMP-9, NFκB, and VEGF-A, along with positive correlation between VEGF-A vs. MMP-9, NFκB, IL-1ß, and NLRP3, and MMP-9 vs. NFκB. CONCLUSIONS: In conclusion, autophagy reduction and NLRP3 inflammasome activation in chondrocytes may be implicated in articular cartilage degradation, under estrogen-deficient and DM conditions. Moreover, the combination of estrogen deficiency and DM may potentiate those effects.

Translation and Validation of the Brazilian Version of the European Obesity Academy Questionnaire on Patients' Motivations for Seeking Metabolic and Bariatric Surgery.

PURPOSE: Understanding patients' motives for undergoing metabolic and bariatric surgery (MBS) is key to managing postoperative expectations. We aimed to translate and validate the 14-item European Obesity Academy Questionnaire on Expectations about Surgical Treatment (EOAQ-EST) to Brazilian Portuguese for research and clinical use. MATERIALS AND METHODS: This study included a total of 198 candidates for MBS at a reference academic hospital in Brazil from January 2021 to February 2022. We followed Beaton and Bombardier's guidelines for translation and cultural adaptation, including translation, back-translation, comparative analysis, expert review, pilot testing, and the creation of the final version of the questionnaire. Reliability was tested with McDonald's omega, and internal validity was assessed using confirmatory factor analysis (CFA). RESULTS: The final version was applied to 161 patients, 85% female, with a mean age of 46.4 ± 10.3 years and a mean BMI of 48.3 ± 8.2 kg/m2. Validity was supported by a bifactorial model (95% CI 0.044-0.104, p = 0.08), excluding one item (improved fertility) due to a floor effect. The reliability analysis showed that the 13 remaining items were internally consistent, with a McDonald's ω of 0.625. CONCLUSIONS: The Brazilian-Portuguese version of EOAQ-EST proved to be user-friendly, consistent, and reliable. This questionnaire may assist multidisciplinary teams in effectively addressing patients' expectations concerning metabolic and bariatric surgery (MBS) outcomes.