Fusarium keratitis in a Brazilian tropical semi-arid area: Clinical-epidemiological features, molecular identification and antifungal susceptibility.

BACKGROUND: Fungal keratitis is a severe eye infection that can result in blindness and visual impairment, particularly in developing countries. Fusarium spp. are the primary causative agents of this condition. Diagnosis of Fusarium keratitis (FK) is challenging, and delayed treatment can lead to serious complications. However, there is limited epidemiological data on FK, especially in tropical areas. OBJECTIVES: This study aimed to describe the clinical, laboratorial and epidemiological characteristics of FK in a tropical semi-arid region of Brazil. PATIENTS/METHODS: Adult patients with laboratory-confirmed FK diagnosed between October 2019 and March 2022 were evaluated. Fusarium isolates were characterized at molecular level and evaluated regarding antifungal susceptibility. RESULTS: A total of 226 clinical samples from patients suspected of keratitis were evaluated; fungal growth was detected in 50 samples (22.12%); out of which 42 were suggestive of Fusarium spp. (84%). Molecular analysis of a randomly selected set of 27 isolates identified F. solani species complex (n = 14); F. fujikuroi sensu lato (n = 6) and F. dimerum sensu lato (n = 7); a total of 10 haplotypes were identified among the strains. All but one Fusarium strains were inhibited by amphotericin B, natamycin and fluconazole. Most patients were male (71.42%; 30 out of 42), aged from 27 to 73 years old. Trauma was the most important risk factor for FK (40.47%; 17 out of 42). Patients were treated with antifungals, corticoids and antibiotics; keratoplasty and eye enucleation were also performed. CONCLUSIONS: The study provided insights into the characteristics of FK in tropical regions and emphasized the importance of enhanced surveillance and management strategies.

Access to dental services in an elder population of African descent in Brazil.

OBJECTIVES: We investigated access to dental services and associated factors in a community of Quilombola older people. BACKGROUND: Quilombola populations are groups of individuals descended from black Africans subjected to slavery during part of Brazilian history. As marginalised and neglected individuals, they have high rates of negative indicators and require further attention to the social determinants that affect their health reality. MATERIALS AND METHODS: A cross-sectional quantitative study was conducted in the Quilombola community of Castainho, in the Northeast region of Brazil. In this community, 34 older people aged between 65 and 74 resided. We collected self-report data on sociodemographic and economic characteristics, along with oral examinations by the researchers. The primary dependent variable was regular access to dental services. Statistical analysis used Fisher's exact test (P = .05). RESULTS: Among the 32 participants in the final sample, 18.8% (n = 6) reported accessing dental services in the previous 6 months. Self-declared individuals of mixed race, with positive self-assessment of oral health, and those who did not self-perceive the need for treatment had lower rates of regular access to dental services (P < .05). CONCLUSION: Use of dental services by older Quilombola people is low, and there are differences by ethnicity and individual perception of oral health.

Might Zika virus-associated microcephaly's severity impact deciduous tooth eruption and orofacial structures?

OBJECTIVE: to investigate the impact of the severity of microcephaly caused by the Zika virus (MCZ) on tooth eruption and orofacial structures of children. DESIGN: This case series study developed the research at the Mens Sana Rehabilitation Center, Arcoverde, Brazil. The study included 27 children diagnosed with MCZ. We performed the data collection in June 2018 through a questionnaire answered by the legal guardians, followed by a clinical examination of the children. The data were analyzed by the Mann-Whitney and Fisher's exact tests (p = 0.05). RESULTS: The final sample was composed of 20 children. Of these, 13 (35.0%) had severe microcephaly, 5 (30.0%) had altered sequence of tooth eruption, 10 (50.0%) had delayed eruption, and the mean number of decayed teeth was 2.3. The most identified orofacial changes were teeth grinding habit (65.0%), difficult chewing (50.0%), and non-nutritive sucking (50.0%). The Mann-Whitney test showed that the severity of microcephaly did not affect tooth eruption (p = 0.581). The Fisher's exact test showed that the severity of microcephaly was not associated with orofacial changes (p > 0.05). CONCLUSIONS: The severity of MCZ does not seem to influence changes in deciduous tooth eruption and the presence of orofacial anomalies.

In silico affinity between analgesic/anti-inflammatory drugs and the transient receptor potential A1 to predict potential pharmacological managing approaches for bleaching sensitivity.

Reducing in-office tooth bleaching sensitivity represents a challenge for professionals. Researchers have associated the block of the pain receptor TRPA1 with reducing bleaching sensitivity. However, the chemical affinity of analgesic/anti-inflammatory drugs to the TRPA1 needs to be verified. To perform a virtual screening of multiple drugs (analgesic and anti-inflammatory drugs) to verify chemical affinity for the TRPA1 receptor. The crystal structure of the TRPA1 receptor proteins was retrieved from the Protein Data Bank. The SMILES codes of the ligands were extracted from PubChem. The binding energy of the complex was obtained in ∆G - kcal/mol by AutoDock Vina© and replicated in the webservers SwissDock©, Dockthor©, and CbDock©. LigPlus© confirmed the binding sites. Codeine and dexamethasone showed regularity among all servers, even showing binding energy values of -7.9 kcal/mol for codeine and -8.1 kcal/mol for dexamethasone. Codeine and dexamethasone may be potential drugs to manage tooth bleaching sensitivity if they reach the dental pulp TRPA1 receptor.

A Study on the Influence of Sensors in Frequency and Time Domains on Context Recognition.

Adaptive AI for context and activity recognition remains a relatively unexplored field due to difficulty in collecting sufficient information to develop supervised models. Additionally, building a dataset for human context activities "in the wild" demands time and human resources, which explains the lack of public datasets available. Some of the available datasets for activity recognition were collected using wearable sensors, since they are less invasive than images and precisely capture a user's movements in time series. However, frequency series contain more information about sensors' signals. In this paper, we investigate the use of feature engineering to improve the performance of a Deep Learning model. Thus, we propose using Fast Fourier Transform algorithms to extract features from frequency series instead of time series. We evaluated our approach on the ExtraSensory and WISDM datasets. The results show that using Fast Fourier Transform algorithms to extract features performed better than using statistics measures to extract features from temporal series. Additionally, we examined the impact of individual sensors on identifying specific labels and proved that incorporating more sensors enhances the model's effectiveness. On the ExtraSensory dataset, the use of frequency features outperformed that of time-domain features by 8.9 p.p., 0.2 p.p., 39.5 p.p., and 0.4 p.p. in Standing, Sitting, Lying Down, and Walking activities, respectively, and on the WISDM dataset, the model performance improved by 1.7 p.p., just by using feature engineering.

Orofacial features in children with microcephaly associated with Zika virus: A scoping review.

OBJECTIVE: To analyze published scientific evidence about the most common orofacial disorders in children with microcephaly associated with ZIKV infection. METHODS: Through a scoping review, we respond to the search question was formulated: "What are the orofacial alterations in children with microcephaly associated with ZIKV?" It was performed a search in PubMed, EMBASE, Scopus, and Health Virtual Library. It was selected papers wrote in English, Portuguese, or Spanish. An evidence quality analysis was performed using the Agency for Healthcare Research and Quality classification. RESULTS: It was included 11 studies performed in the Brazilian Northeast region. The studies were carried out between 2018 and 2020. The main related alterations were delay in the tooth-eruption and deformation in the oral structures. CONCLUSION: The results observed in our work show moderate scientific evidence regarding the association of ZIKV with orofacial alterations in children with microcephaly due to the classifications of the quality of evidence of each one of the included studies. The main changes reported were in the chronology of tooth eruption, alteration in teeth, and oral structures.

Stimulation of Osteoclast Formation by Oncostatin M and the Role of WNT16 as a Negative Feedback Regulator.

Oncostatin M (OSM), which belongs to the IL-6 family of cytokines, is the most potent and effective stimulator of osteoclast formation in this family, as assessed by different in vitro assays. Osteoclastogenesis induced by the IL-6 type of cytokines is mediated by the induction and paracrine stimulation of the osteoclastogenic cytokine receptor activator of nuclear factor κ-B ligand (RANKL), expressed on osteoblast cell membranes and targeting the receptor activator of nuclear factor κ-B (RANK) on osteoclast progenitor cells. The potent effect of OSM on osteoclastogenesis is due to an unusually robust induction of RANKL in osteoblasts through the OSM receptor (OSMR), mediated by a JAK-STAT/MAPK signaling pathway and by unique recruitment of the adapter protein Shc1 to the OSMR. Gene deletion of Osmr in mice results in decreased numbers of osteoclasts and enhanced trabecular bone caused by increased trabecular thickness, indicating that OSM may play a role in physiological regulation of bone remodeling. However, increased amounts of OSM, either through administration of recombinant protein or of adenoviral vectors expressing Osm, results in enhanced bone mass due to increased bone formation without any clear sign of increased osteoclast numbers, a finding which can be reconciled by cell culture experiments demonstrating that OSM can induce osteoblast differentiation and stimulate mineralization of bone nodules in such cultures. Thus, in vitro studies and gene deletion experiments show that OSM is a stimulator of osteoclast formation, whereas administration of OSM to mice shows that OSM is not a strong stimulator of osteoclastogenesis in vivo when administered to adult animals. These observations could be explained by our recent finding showing that OSM is a potent stimulator of the osteoclastogenesis inhibitor WNT16, acting in a negative feedback loop to reduce OSM-induced osteoclast formation.

Access to information on oral hygiene and mothers' practices of children with microcephaly caused by Zika virus.

OBJECTIVE: To verify whether access to information about oral hygiene influenced the practices of caregivers of children with microcephaly caused by Zika virus (ZIKV). METHODS: A case series study was developed at the Mens Sana Rehabilitation Center, in the municipality of Arcoverde, Pernambuco, Brazil. The study universe included the mothers of 32 children with microcephaly caused by Zika virus. Data collection took place in June 2018 and was carried out through a structured questionnaire. The variables studied comprised socioeconomic issues, habits, diet, and knowledge about oral hygiene. Fisher's Exact and Pearson's Chi-square tests were used with a significance level of 5%. RESULTS: Out of 32 individuals eligible to participate in the study, only 27 were selected. Most mothers reported receiving information about oral hygiene from their infants (63.0%). Fisher's Exact and Pearson's Chi-square tests showed that access to oral hygiene information was associated with mother's education, family income, regular visits to the dentist, frequency of tooth brushing, age at which the infant started brushing, and brushing time (p < 0.05). CONCLUSION: Access to information about oral hygiene positively influenced the oral health care of mothers with their children with microcephaly caused by ZIKV.

Identification of docosahexaenoic and eicosapentaenoic acids multiple targets facing periodontopathogens.

The eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) play a substantial role in Periodontal Disease (PD) due to their antimicrobial and immunomodulatory actions. However, their antimicrobial mechanism of action against bacteria involved in PD remains unclear. We aimed to estimate the probable targets of EPA and DHA against the seven periodontopathogens. Through in silico analyses, the protein-acids interactions, protein characterization, and molecular docking were performed. We identified 165 proteins from periodontopathogens that may interact with EPA and DHA. Fusobacterium nucleatum has the highest number of predicted proteins among analyzed bacteria (n = 43, 26.06%). The EPA shows more interactions than DHA. The EPA and DHA interact mainly with proteins involved in the metabolism (n = 69, 41.81%). Also, the EPA and DHA interact with proteins located in any subcellular location. The affinities between acids and pathogenic proteins were moderate (binding energy was lower than -4.0 kcal/mol). The interactions between EPA and DHA and periodontopathogens occur in multiples proteins. There is not a predilection about the functional class of pathogenic proteins targeting EPA and DHA. However, there are moderate binding affinities between EPA or DHA and essential pathogenic proteins (TolC, CRISPR, FusA).

Micronutrients and bioactive compounds in the immunological pathways related to SARS-CoV-2 (adults and elderly).

The new coronavirus pandemic is affecting the entire world with more than 25 million confirmed cases in August 2020 according to the World Health Organization. It is known that the virus can affect several tissues and can progress to a respiratory failure in severe cases. To prevent the progression to this stage of the disease and minimize all the damage caused by coronavirus (SARS-CoV-2) the immune system must be in its integrity. A healthy nutritional status are fundamental to efficient immunological protection and consequently a good response to SARS-CoV-2. Micronutrients and bioactive compounds perform functions in immune cells that are extremely essential to stop SARS-CoV-2. Their adequate consumption is part of a non-pharmacological intervention to keep the immune system functioning. This review has as main objective to inform how micronutrients and bioactive compounds could act in the essential immunological pathways could stop SARS-CoV-2, focusing on the functions that have already established in the literature and transposing to this scenario.

Two phytocompounds from Schinopsis brasiliensis show promising antiviral activity with multiples targets in Influenza A virus.

Influenza A virus, the main flu agent, affects billions of people worldwide. Conventional treatments still present limitations related to drug-resistance and severe side effects. As a result, natural product-derived molecules have been increasingly investigated as prospect drug candidates. Therefore, the aim of this study was to investigate the possible anti-flu activity and to evaluate the toxicity and pharmacokinetic parameters, by in silico approaches, of the Schinopsis brasiliensis Engl. phytochemical compounds. Nine phytocompounds and six antiviral drugs (Amantadine, Umifenovir, Favipiravir, Nitazoxanide, Oseltamivir, Zanamivir) were selected for the analyses against four Influenza A proteins: neuraminidase, polymerase basic protein 2, hemagglutinin and M2 ion channel protein. The molecular docking, the predicted antiviral activity, the predicted toxicity and the pharmacokinetics investigations were conducted. The obtained results demonstrated that Syringaresinol and Cycloartenone display promising in silico antiviral activity (binding energy < 5.0 and ≥ 9.0 kcal/mol) and safety (low toxicity than commercial anti-flu drugs). Overall, this study corroborated the hypothesis that S. brasiliensis barks extract has a biological activity against Influenza A virus. Additionally, Syringaresinol and Cycloartenone have multiple targets in Influenza A virus and showed themselves as the most promising phytocompounds to be isolated and considered for the therapeutic arsenal against the flu.

Schinopsis brasiliensis Engl. to combat the biofilm-dependents diseases in vitro.

Dental caries and periodontal disease are the most prevalent of the biofilm-dependent diseases. With numerous side effects on the use of chlorhexidine, the search for new safe therapeutic alternatives for microorganisms involved with these diseases increases every day. This study aimed to evaluate the antimicrobial activity and cytotoxicity of extracts made from the bark of Schinopsis brasiliensis Engl. against five oral microorganisms and analyze their phytochemical and thermal degradation profile. The liquid-liquid partition was performed with hexane, chloroform and ethyl acetate. The identification and quantification of the chemical marker was done. Antimicrobial activity was evaluated based on the minimum inhibitory concentration. The cytotoxicity was analyzed based on the hemolysing potential of the samples. The thermal degradation profile was performed by two different methods. Gallic acid was identified as the main compound of the samples and showed the highest amount in the chloroform fraction. All samples were able to inhibit the growth of the microorganisms tested and showed no cytotoxicity. The ethanol extract absorbs less heat than the fractions. All samples exhibited exothermic peak consistent with degradation of gallic acid. Based on the results, the samples used are potential candidates for use in dental formulations for biofilm control.

Extracellular Matrix Derived from High Metastatic Human Breast Cancer Triggers Epithelial-Mesenchymal Transition in Epithelial Breast Cancer Cells through αvß3 Integrin.

Alterations in the composition and architecture of the extracellular matrix (ECM) can influence cancer growth and dissemination. During epithelial-mesenchymal transition (EMT), epithelial cells assume a mesenchymal cell phenotype, changing their adhesion profiles from cell-cell contacts to cell-matrix interactions, contributing to metastasis. Breast cancer cells present at different stages of differentiation, producing distinct ECMs in the same tumor mass. However, the contribution of ECM derived from metastatic tumor cells to EMT is unclear. Here, we showed the mechanisms involved in the interaction of MCF-7, a low-metastatic, epithelial breast cancer cell line, with the ECM produced by a high metastatic breast tumor cell, MDA-MB-231 (MDA-ECM). MDA-ECM induced morphological changes in MCF-7 cells, decreased the levels of E-cadherin, up-regulated mesenchymal markers, and augmented cell migration. These changes were accompanied by the activation of integrin-associated signaling, with increased phosphorylation of FAK, ERK, and AKT and activation canonical TGF-ß receptor signaling, enhancing phosphorylation of SMAD2 and SMAD4 nuclear translocation in MCF-7 cells. Treatment with Kistrin (Kr), a specific ligand of integrin αvß3 EMT induced by MDA-ECM, inhibited TGF-ß receptor signaling in treated MCF-7 cells. Our results revealed that after interaction with the ECM produced by a high metastatic breast cancer cell, MCF-7 cells lost their characteristic epithelial phenotype undergoing EMT, an effect modulated by integrin signaling in crosstalk with TGF-ß receptor signaling pathway. The data evidenced novel potential targets for antimetastatic breast cancer therapies.

Antimicrobial Activity of Schinopsis brasiliensis Engler Extract-Loaded Chitosan Microparticles in Oral Infectious Disease.

Enterococcus faecalis infections represent a health concern, mainly in oral diseases, in which treatments with chlorhexidine solution (0.2%) are often used; however, it presents high toxicity degree and several side effects. Based on this, the use of natural products as an alternative to treatment has been explored. Nonetheless, plant extracts have poor organoleptic characteristics that impair theirs in natura use. Therefore, this work aimed to evaluate the analytical profile, biological activity, and cytotoxicity in vitro of S. brasiliensis-loaded chitosan microparticles (CMSb) produced using different aspersion flow rates. The analytical fingerprint was obtained by FTIR and NIR spectra. Principal components analysis (PCA) was used to verify the similarity between the samples. The crystallinity degree was evaluated by X-ray diffraction (XRD). Phytochemical screening (PS) was performed to quantify phytocompounds. Antimicrobial activity was evaluated by minimum inhibitory concentration (MIC). Antibiofilm activity and bactericidal kinetics against E. faecalis (ATCC 29212 and MB 146-clinical isolated) were also assessed. The hemolytic potential was performed to evaluate the cytotoxicity. Data provided by FTIR, NIR, and PCA analyses revealed chemical similarity between all CMSb. Furthermore, the results from XRD analysis showed that the obtained CMSb present amorphous characteristic. Tannins and polyphenols were accurately quantified by the PS, but methodology limitations did not allow the flavonoid quantification. The low hemolytic potential assay indicates that all samples are safe. Antimicrobial assays revealed that CMSb were able to inhibit not only the E. faecalis ATCC growth but also the biofilm formation. Only one CMSb sample was able to inhibit the clinical strain. These results highlighted the CMSb antimicrobial potential and revealed this system as a promising product to treat infections caused by E. faecalis.

Mesenchymal Stem Cells are Recruited and Activated into Carcinoma-Associated Fibroblasts by Prostate Cancer Microenvironment-Derived TGF-ß1.

Tumor stromal cells can supply appropriate signals that may develop aggressive phenotypes of carcinoma cells and establish a complex scenario which culminates in metastasis. Recent works proposed that bone marrow-derived mesenchymal stem cells (MSC) are recruited to primary tumors. However, the exact functions of these cells in the tumor microenvironment are not well characterized, as it is reported that MSC can either promote or inhibit tumor progression. In the present study, we aim at investigating the signaling molecules which regulate the interplay between MSC, prostate carcinoma (PCa) cells and two important cellular types constituting the tumor-associated stroma, macrophages and fibroblasts, during their progression toward malignancy. We identified TGF-ß1 as a crucial molecule able to attract MSC recruitment both to PCa cells as well as to tumor stroma components. Moreover, PCa- and tumor stroma-secreted TGF-ß1 is important to induce MSC transdifferentiation into carcinoma-associated fibroblast (CAF)-like cells. Consequently, the CAF-like phenotype acquired by MSC is central to promote tumor progression related effects. Thus, tumor-educated MSC enhance PCa invasiveness compared to nonactivated MSC. Additionally, differing from normal MSC, CAF-like MSC perform vascular mimicry and recruit monocytes, which can be further polarized to M2 macrophages within the PCa environment. Our findings indicate a prominent role for TGF-ß1 in MSC mobilization and activation strengthened by the fact that the blockade of TGF-ß1 signaling impairs MSC promotion of PCa progression. Stem Cells 2016;34:2536-2547.

Physical and chemical characteristics of the longissimus dorsi from swine reared in climate-controlled and uncontrolled environments.

The aim of this study was to evaluate the effect of ambient temperature on the physical and chemical characteristics of the longissimus dorsi muscle by comparing the quality of meat from pigs reared in a controlled and in an uncontrolled environment, the latter provided with a shallow pool. Twenty castrated male pigs of the Topigs line were randomly allotted to two treatments: a controlled environment, with constant temperature (22 °C) and relative humidity (70%); and an uncontrolled environment in a conventional shed for rearing pigs equipped with a shallow pool, where pigs were subject to climatic variations. Meat from pigs kept in the controlled environment showed a greater capacity to retain intracellular water, higher tenderness, and lower cholesterol levels than meat from pigs reared in the uncontrolled environment, but displayed higher lipid oxidation and a lower concentration of DHA. Treatments had no effect on color, pH, chemical composition, or fatty acid profile (except DHA concentration). Rearing pigs in sheds equipped with a shallow pool minimizes the effects of environmental heat on meat quality, allowing the production of high-quality meat in warm climate regions without expensive investments. Animals reared in an uncontrolled environment equipped with a shallow pool are able to produce meat with characteristics within the quality standards and with similar quality to that of meat from animals raised in controlled environment.

Growing-finishing performance and carcass yield of pigs reared in a climate-controlled and uncontrolled environment.

The objective of this study was to evaluate the effect of temperature on the performance and carcass yield of pigs housed in different environments. Twenty castrated male pigs of the Topigs line were assigned to two treatments: T1, controlled environment, and T2, uncontrolled environment containing a shallow pool. A completely randomized design consisting of two treatments and ten repetitions each was used. The data were submitted to analysis of variance, and means were compared by the Tukey test at a level of significance of 5 % using the SAS 9.2 program (SAS Institute, Inc., NC, USA). The results showed that rearing pigs in an uncontrolled environment during the growing and finishing phases reduced daily feed intake (1.722 and 3.164 kg, respectively) and improved feed conversion (2.15 and 2.70 kg, respectively), but did not influence the carcass yield of the animals. In conclusion, rearing pigs under different environmental conditions during the growing and finishing phases influenced animal performance without interfering with carcass yield.

Tumor microenvironment: bone marrow-mesenchymal stem cells as key players.

Tumor progression is a multistep phenomenon in which tumor-associated stromal cells perform an intricate cross-talk with tumor cells, supplying appropriate signals that may promote tumor aggressiveness. Among several cell types that constitute the tumor stroma, the discovery that bone marrow-derived mesenchymal stem cells (BM-MSC) have a strong tropism for tumors has achieved notoriety in recent years. Not only are the BM-MSC recruited, but they can also engraft at tumor sites and transdifferentiate into cells such as activated fibroblasts, perivascular cells and macrophages, which will perform a key role in tumor progression. Whether the BM-MSC and their derived cells promote or suppress the tumor progression is a controversial issue. Recently, it has been proposed that proinflammatory stimuli can be decisive in driving BM-MSC polarization into cells with either tumor-supportive or tumor-repressive phenotypes (MSC1/MSC2). These considerations are extremely important both to an understanding of tumor biology and to the putative use of BM-MSC as "magic bullets" against tumors. In this review, we discuss the role of BM-MSC in many steps in tumor progression, focusing on the factors that attract BM-MSC to tumors, BM-MSC differentiation ability, the role of BM-MSC in tumor support or inhibition, the immunomodulation promoted by BM-MSC and metastatic niche formation by these cells.