Transcutaneous Electric Nerve Stimulation in Animal Model Studies: From Neural Mechanisms to Biological Effects for Analgesia.

OBJECTIVE: This systematic and meta-analysis review evaluated the transcutaneous electrical nerve stimulation (TENS)-induced action mechanisms for animal analgesia. MATERIALS AND METHODS: Two independent investigators identified relevant articles published until February 2021 through a literature review, and a random-effects meta-analysis was performed to synthesize the results. RESULTS: Of the 6984 studies found in the data base search, 53 full-text articles were selected and used in the systematic review. Most studies used Sprague Dawley rats (66.03%). High-frequency TENS was applied to at least one group in 47 studies, and most applications were performed for 20 minutes (64.15%). Mechanical hyperalgesia was analyzed as the primary outcome in 52.83% of the studies and thermal hyperalgesia in 23.07% of studies using a heated surface. More than 50% of the studies showed a low risk of bias on allocation concealment, random housing, selective outcome reporting, and acclimatization before the behavioral tests. Blinding was not performed in only one study and random outcome assessment in another study; acclimatization before the behavioral tests was not performed in just one study. Many studies had an uncertain risk of bias. Meta-analyses indicated no difference between low-frequency and high-frequency TENS with variations among the pain models. CONCLUSIONS: This systematic review and meta-analysis suggests that TENS has presented a substantial scientific foundation for its hypoalgesic effect in preclinical studies for analgesia.

Social isolation due to COVID-19: impact on loneliness, sedentary behavior, and falls in older adults.

OBJECTIVES: The World Health Organization has recommended social isolation to prevent the transmission of COVID-19. Thus, feelings of loneliness, sedentary behavior, and predisposition to falls have been reported more often due to the adoption of social isolation, especially for older adults. The objective of this study was to compare older adults' loneliness, sedentary behavior, and occurrence of falls before and during social isolation due to the pandemic as well as to analyze the association of loneliness with sedentary lifestyle and falls in older adults. METHOD: Retrospective analytical study conducted through an online survey with older adults from Brazilian states in social isolation, approved by the Research Ethics Committee (number 32168920.0.0000.0068). RESULTS: There was a significant increase in loneliness and sedentary behavior during social isolation (p-value < 0.05 for both), but no increase was observed for falls (p-value = 0.615). There was no correlation between the outcomes, nor was there a correlation between the outcomes and the number of days in social isolation. CONCLUSION: The results of this research show that adoption of social isolation due to the COVID-19 pandemic brought an increase in sedentary behavior and loneliness for older adults but had no effect on the number of falls.

Effect of sanitizing solutions on cobalt-chromium alloys for dental prostheses: A systematic review of in vitro studies.

STATEMENT OF PROBLEM: Given the wide use of cobalt-chromium (Co-Cr) alloys, especially for removable partial dentures, and the importance of chemical solutions to complement the cleaning of dental prostheses, safe disinfection products should be identified for the regular decontamination of Co-Cr dental prostheses. PURPOSE: The purpose of this systematic review of in vitro studies was to determine the effects on the properties of Co-Cr dental alloys of the various chemical agents used to clean dental prostheses. MATERIAL AND METHODS: In vitro studies were included based on a literature search conducted in March 2022 in the Medline/PubMed, SCOPUS, Web of Science, Virtual Health Library, and Embase databases. Independent reviewers performed the search, selection, extraction, and analysis of the data. The review was performed based on the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. The quality of the included articles was evaluated by using parameters adapted from the Consolidated Standards of Reporting Trials (CONSORT) guidelines, and the risk of bias analysis was performed based on previous studies. RESULTS: Among the 15 included studies, the chemical agents evaluated were alkaline peroxides and hypochlorites, mouthwashes containing cetylpyridinium chloride and chlorhexidine, diluted acids, and enzymes. Some peroxides produced increased ion release, surface roughness, and mass loss of the alloys. The hypochlorites were responsible for the greatest surface corrosion, yielding dark stains, rough regions, and depressions. Acetic and peracetic acids and mouthwashes containing chlorhexidine and cetylpyridinium did not produce significant changes in Co-Cr alloys. Most studies presented moderate risk of bias. CONCLUSIONS: According to the included studies, mouth rinses containing cetylpyridinium chloride or chlorhexidine and solutions with acetic and peracetic acid could be safely used to chemically sanitize Co-Cr prostheses. Alkaline peroxides should be used with caution, and alkaline hypochlorite solutions should be avoided.

Food and nutritional insecurity is associated with depressive symptoms mediated by NR3C1 gene promoter 1F methylation.

The aim of this study was to investigate socioeconomic stressors predictive of depressive symptoms and possible epigenetic changes in the glucocorticoid receptor - NR3C1-1F - an encoding gene involved in depressive symptoms. A total of 321 adult volunteers from southeastern Brazil were recruited to evaluate depressive symptoms, socio-demographic and economic factors, including food and nutritional security (FNS) or insecurity (FNiS) status, and NR3C1-1F region methylation by pyrosequencing. Depressive symptom determinants were investigated using a Poisson regression model with robust variance. Mann-Whitney tests and structural mediation equation models were used to evaluate the relationship between NR3C1 DNA methylation, FNiS, and depressive symptoms. Multivariate Poisson regression with robust variance adjusted for sex and FNiS and NR3C1-1F region methylation predicted risk factors for depressive symptoms. Mediation analysis revealed that NR3C1-1F region methylation mediated the relationship between FNiS exposure and depressive symptoms as an outcome, and depressive volunteers and FNiS individuals exhibited a significant increase in NR3C1 methylation when compared to healthy individuals and FNS volunteers, respectively. Therefore, we suggest that stress caused by FNiS may lead to depressive symptoms and that NR3C1-1F DNA methylation can act as a mediator of both FNiS and depressive symptoms.

"Macho food": Masculinities, food preferences, eating practices history and commensality among gay bears in São Paulo, Brazil.

This article describes and explore eating practices and food preferences among gay men who call themselves bears in São Paulo, Brazil, and their relation with their life history, masculinities representations, and sexuality. It is a qualitative and quantitative research within an ethnographic perspective. A purposive sample of thirty-five self-declared gay bears. The data were analyzed identifying the regular, expressive and meaningful significance units collected through the interviews. We identified that the self-declared bears in São Paulo, Brazil, build a solid relation between food preferences, eating practices, masculinity, and group belonging. From the bear's perspective, meat, especially bovine, is related to masculinity and extensively understood as a strong common bond within the community, leveraging their sexuality. For these persons, eating meat as well as drinking beer can build the ideal mannish and unfeminine body that is overvalue. Being gay and "eating like a man," as well as exposing a "macho" body while disdaining other body types constructions could represent a strategy to avoid discrimination, shame and humiliation. On the other way, this community does not just linearly imitate heterosexual men although their conducts can reproduce patriarchal representations and meanings through eating practices. These findings could be used to understand the complexity of alimentary practices, particularly food preferences as well as commensalities, among specific communities or membership groups.

Production of xylanases by Bacillus sp. TC-DT13 in solid state fermentation using bran wheat.

Xylanases have gained increasing importance due to their diverse applications in the food, paper, and pharmaceutical industries, however, the production of these enzymes currently uses expensive substrates. It has already been estimated that more than 30% of the enzyme production cost originates from the substrate. The present study aimed to optimize the production of extracellular xylanases by the Bacillus sp. TC-DT 13 using solid-state fermentation with agro-industrial residues, with a view at reducing the production cost of these enzymes. All the agro-industrial residues were tested in submerged fermentation to select the best inductor to produce xylanase. Among these residues, wheat bran was selected as the best inducer of xylanase production with 1500 U/mL. Regarding solid-state fermentation, the use of wheat bran as the only fermentation substrate was used and a ratio of 1:4 moisture over a time of 144 hours induced higher amount of xylanase reaching 2943 U/g. The use of carbon and nitrogen sources did not result in the increase in production of xylanolitic enzymes. The use of agro-industrial residues in the solid-state fermentation, besides increasing the production of xylanase, reduces the cost of production and is an environmentally friendly alternative.

Antimicrobial activity of Lippia gracilis essential oils on the plant pathogen Xanthomonas campestris pv. campestris and their effect on membrane integrity.

Xanthomonas campestris pv.campestris (Xcc) is the causative agent of black rot, a disease that causes serious damage to plants from Brassicaceae family. However, there are no chemicals or biological agent commercially registered for the control of this disease. Thus, this study aimed to evaluate the antimicrobial activity and chemical composition of Lippia gracilis essential oils (EOs) on Xcc aiming its use as effective biological control. We also investigated the effect of EOs on the integrity of the bacterial cytoplasmic membrane. Chemical analysis by GC/MS showed that the major compounds of the seven EOs of L. gracilis are thymol or carvacrol. The seven genotypes showed inhibition of bacterial growth with MIC from 700 µg.ml-1 to 1000 µg.ml-1, with the genotype LGRA-106 (rich in Thymol) with higher antimicrobial activity. The MIC for thymol and carvacrol were 250 µg.ml-1. After exposure to LGRA-106 EO (2×, 1×, 1/2×, 1/4×, and 1/8 x MIC for 5 min, it was observed a decreased cell viability and increased pI fluorescence, which indicates damage to the cytoplasmic cell membrane. This study demonstrates that L. gracilis EOs have antimicrobial activity and have a potential to be used in the control of black rot. Furthermore this antimicrobial activity is due, at least in part, to bacterial cytoplasmic membrane damage.

PAI-1, CAIX, and VEGFA expressions as prognosis markers in oral squamous cell carcinoma.

BACKGROUND: In oral squamous cell carcinoma (OSCC), the HIF-1 complex promotes the expression of genes involved in specific mechanisms of cell survival under hypoxic conditions, such as plasminogen activator inhibitor-1 (PAI-1), carbonic anhydrase 9 (CAIX), and vascular endothelial growth factor A (VEGFA). The study aimed to investigate the presence and prognostic value of PAI-1, CAIX, and VEGFA in OSCC. MATERIALS AND METHODS: Immunohistochemistry was used to analyze the expressions of these proteins in 52 tumoral tissue samples of patients with OSCC, surgically treated and followed by a minimum of 24 months after surgery. The correlations between protein expressions and clinicopathological parameters and prognosis were analyzed. RESULTS: Positive PAI-1 membrane expression was significantly associated with local disease relapse (P = .027). Multivariate analysis revealed that the positive PAI-1 membrane expression is an independent marker for local disease relapse, with approximately 14-fold increased risk when compared to negative expression (OR = 14.49; CI = 1.40-150.01, P = .025). Strong PAI-1 cytoplasmic expression was significantly associated with the less differentiation grade (P = .027). Strong CAIX membrane expression was significantly associated with local disease-free survival (P = .038). Positive CAIX cytoplasmic expression was significantly associated with lymph node affected (P = .025) and with disease-specific survival (P = .022). Multivariate analysis revealed that the positive CAIX cytoplasmic expression is an independent risk factor for disease-related death, increasing their risk approximately 3-fold when compared to negative expression (HR = 2.84; CI = 1.02-7.87, P = .045). Positive VEGFA cytoplasmic expression was significantly associated with less differentiation grade (P = .035). CONCLUSION: Our results suggest a potential role for these expressions profiles as tumor prognostic markers in OSCC patients.

Food-based dietary guidelines: a comparative analysis between the Dietary Guidelines for the Brazilian Population 2006 and 2014.

OBJECTIVE: In 2014, the Brazilian Ministry of Health launched the second edition of the Dietary Guidelines for the Brazilian Population (DGBP), which deploys the new food classification NOVA. It esteems that the second DGBP overcomes the limitations in the previous food guide, reformulating the diet concepts, food pattern, culture and system. The present paper analyses the advances and limits established in the second edition, contrasting with its first edition. DESIGN: The study employs a discourse analysis. The corpus was established through four stages: (i) floating reading of the empirical materials; (ii) deepening readings; (iii) selected discursive sequences; and (iv) organization of the discursive sequences into a matrix for analysis. The data analysis used three steps: (i) identification of similar texts in external materials; (ii) elucidation of linguistic effect through deepening readings of the external materials; and (iii) systematic analysis to identify sequences that expressed equivalence or disparities. SETTING: Brazil. SUBJECTS: DGBP 2006 and 2014. RESULTS: Adoption of the NOVA food classification, based on food processing level, enabled the development of dietary guidelines that consider the limitations of the nutritional discourse and may incorporate the sociocultural and social-environmental discourses, evoking pleasure in food, diversity of feeding habits and stimulating culinary practices as promoters of healthy eating practices. CONCLUSIONS: The second DGBP enables a new way of thinking about meals and foods, on the strengthening of socio-cultural dimensions of feeding, and on addressing food and nutritional guidelines on culinary practices, eating and edibility.

Vulvar Tuberculosis Cutis Orificialis Concomitant to Pulmonary Tuberculosis: A Case Report.

Tuberculosis (TB) is a common condition with increasing incidence worldwide. Cutaneous TB represents a small portion of extrapulmonary TB. Health care professionals must be aware of cutaneous forms of TB to avoid delay in diagnosis and treatment. We present a case of a 59-year-old woman with vulvar TB cutis orificialis in association with pulmonary TB without any other involvement of genitourinary system. We discuss epidemiological aspects, classification, treatment, range of histopathological patterns, and use of ancillary techniques for diagnosis.

Undernutrition during pregnancy and lactation increases the number of fos-cells in the reward system in response to a 5-HT6 receptor agonist in male adolescent rats.

Undernutrition promotes morphofunctional adaptations in neuroanatomical circuits, leading to behavioural changes. Adolescence is a period of vulnerability for these adaptations, such as the control of food intake and the serotonergic system. The serotonergic system is capable of promoting satiety. However, its role in hedonic control has not been fully elucidated. The involvement of the 5-HT6 receptor in motivational feeding behaviours was recently observed. Therefore, we aimed to evaluate the effect of a 5-HT6 receptor agonist on food intake and neuronal activation in areas of the reward system in adolescent rats subjected to perinatal protein undernutrition. Wistar rats were divided into two groups according to nutritional manipulation during gestation and lactation. It has been observed that undernourished animals present greater neuronal activation in response to the 5HT-6 receptor agonist in areas of the food reward system.

Selection of Lactic Acid Bacteria with Probiotic Potential Isolated from the Fermentation Process of "Cupuaçu" (Theobroma grandiflorum).

In the present study, nine lactic acid bacteria isolated from the fermentation process of "cupuaçu" (Theobroma grandiflorum) were selected for probiotic use. In vitro (resistance to gastrointestinal environment, in vitro antagonism and co-aggregation with pathogens) and in vivo (intestinal colonization and ex vivo antagonism in germ-free mice, cumulative mortality, translocation to liver and spleen, histopathological examination of liver and ileum and mRNA cytokine gene expression during an experimental infection with S. Typhimurium) assays were used. Among the nine Lactobacillus strains isolated from the "cupuaçu" fermentation, L. plantarum 81 and L. plantarum 90 were selected as potential probiotics based on better results obtained in in vitro evaluations (production of diffusible inhibitory compounds and co-aggregation) as well as in vivo experiments (resistance to gastrointestinal environment, ex vivo antagonism, higher survival after enteropathogen challenge, lower hepatic translocation of enteropathogen, lower histopathological lesions in ileum and liver and anti-inflammatory pattern of immunological response). Concluding, L. plantarum 81 and L. plantarum 90 showed in vitro and in vivo capacities for probiotic use through different mechanisms of protection and its origin would allow an easier adaptation in an alimentary matrix for its administration.

Ocellatin-PT antimicrobial peptides: High-resolution microscopy studies in antileishmania models and interactions with mimetic membrane systems.

Although the mechanism of action of antimicrobial peptides (AMPs) is not clear, they can interact electrostatically with the cell membranes of microorganisms. New ocellatin-PT peptides were recently isolated from the skin secretion of Leptodactylus pustulatus. The secondary structure of these AMPs and their effect on Leishmania infantum cells, and on different lipid surface models was characterized in this work. The results showed that all ocellatin-PT peptides have an α-helix structure and five of them (PT3, PT4, PT6 to PT8) have leishmanicidal activity; PT1 and PT2 affected the cellular morphology of the parasites and showed greater affinity for leishmania and bacteria-mimicking lipid membranes than for those of mammals. The results show selectivity of ocellatin-PTs to the membranes of microorganisms and the applicability of biophysical methods to clarify the interaction of AMPs with cell membranes.

Microbiological, physicomechanical, and surface evaluation of an experimental self-curing acrylic resin containing halloysite nanotubes doped with chlorhexidine.

OBJECTIVE: The objective was to synthesize halloysite nanotubes loaded with chlorhexidine (HNT/CHX) and evaluate the antimicrobial activity, microhardness, color change, and surface characteristics of an experimental self-curing acrylic resin containing varying concentrations of the synthesized nanomaterial. METHODS: The characterization of HNT/CHX was carried out by calculating incorporation efficiency, morphological and compositional, chemical and thermal evaluations. SAR disks were made containing 0 %, 3 %, 5 %, and 10 % of HNT/CHX. Specimens (n = 3) were immersed in distilled water and spectral measurements were carried out using UV/Vis spectroscopy to evaluate the release of CHX for up to 50 days. The antimicrobial activity of the composite against Candida albicans and Streptococcus mutans was evaluated by disk-diffusion test. Microhardness, color analyses (ΔE), and surface roughness (Ra) (n = 9) were performed before and after 30 days of immersion. Data were analyzed using ANOVA/Bonferroni. {Results.} The incorporation efficiency of CHX into HNT was of 8.15 %. All test groups showed controlled and cumulative CHX release up to 30 or 50 days. Significant antimicrobial activity was verified against both microorganisms (p < 0.001). After the 30-day immersion period, the 10 % HNT/CHX group showed a significant increase in hardness (p < 0.05) and a progressive color change (p < 0.001). At T0, the 5 % and 10 % groups exhibited Ra values similar to the control group (p > 0.05), while at T30, all groups showed similar roughness values (p > 0.05). {Significance.} The modification of a SAR with HNT/CHX provides antimicrobial effect and controlled release of CHX, however, the immediate surface roughness in the 3 % group was compromised when compared to the control group.

Senescence on Dental Pulp Cells: Effects on Morphology, Migration, Proliferation, and Immune Response.

INTRODUCTION: Evidence indicates that senescence can affect essential dental pulp functions, such as defense capacity and repair, consequently affecting the successes of conservative endodontic treatments. This study aims to evaluate the effects of senescence on the morphology, migration, proliferation, and immune response of human dental pulp cells. METHODS: Cells were treated with doxorubicin to induce senescence, confirmed by ß-galactosidase staining. Morphological changes, cellular proliferation, and migration were evaluated by scanning electron microscopy, trypan blue cells, and the scratch method, respectively. Modifications in the immune response were evaluated by measuring the genes for pro-inflammatory cytokines tumor necrosis factor alpha and interleukin (IL)-6 and anti-inflammatory cytokines transforming growth factor beta 1 and IL-10 using the real time polymerase chain reaction assay. RESULTS: An increase in cell size and a decrease in the number of extensions were observed in senescent cells. A reduction in the proliferative and migratory capacity was also found in senescent cells. In addition, there was an increase in the gene expression of inflammatory cytokines tumor necrosis factor alpha and IL-6 and a decrease in the gene expression of IL-10 and transforming growth factor beta-1, suggesting an exacerbated inflammatory situation associated with immunosuppression. CONCLUSIONS: Cellular senescence is possibly a condition that affects prognoses of conservative endodontic treatments, as it affects primordial cellular functions related to this treatment.

Multi-target Phenylpropanoids Against Epilepsy.

Epilepsy is a neurological disease with no defined cause, characterized by recurrent epileptic seizures. These occur due to the dysregulation of excitatory and inhibitory neurotransmitters in the central nervous system (CNS). Psychopharmaceuticals have undesirable side effects; many patients require more than one pharmacotherapy to control crises. With this in mind, this work emphasizes the discovery of new substances from natural products that can combat epileptic seizures. Using in silico techniques, this review aims to evaluate the antiepileptic and multi-target activity of phenylpropanoid derivatives. Initially, ligand-based virtual screening models (LBVS) were performed with 468 phenylpropanoid compounds to predict biological activities. The LBVS were developed for the targets alpha- amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), voltage-gated calcium channel Ttype (CaV), gamma-aminobutyric acid A (GABAA), gamma-aminobutyric acid transporter type 1 (GAT-1), voltage-gated potassium channel of the Q family (KCNQ), voltage-gated sodium channel (NaV), and N-methyl D-aspartate (NMDA). The compounds that had good results in the LBVS were analyzed for the absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters, and later, the best molecules were evaluated in the molecular docking consensus. The TR430 compound showed the best results in pharmacokinetic parameters; its oral absorption was 99.03%, it did not violate any Lipinski rule, it showed good bioavailability, and no cytotoxicity was observed either from the molecule or from the metabolites in the evaluated parameters. TR430 was able to bind with GABAA (activation) and AMPA (inhibition) targets and demonstrated good binding energy and significant interactions with both targets. The studied compound showed to be a promising molecule with a possible multi-target activity in both fundamental pharmacological targets for the treatment of epilepsy.

Mechanisms Involved in the Therapeutic Effect of Cannabinoid Compounds on Gliomas: A Review with Experimental Approach.

INTRODUCTION: Brain tumors have high morbidity and mortality rates, accounting for 1.4% of all cancers. Gliomas are the most common primary brain tumors in adults. Currently, several therapeutic approaches are used; however, they are associated with side effects that affect patients'quality of life. Therefore, further studies are needed to develop novel therapeutic protocols with a more favorable side effect profile. In this context, cannabinoid compounds may serve as potential alternatives. OBJECTIVE: This study aimed to review the key enzymatic targets involved in glioma pathophysiology and evaluate the potential interaction of these targets with four cannabinoid derivatives through molecular docking simulations. METHODS: Molecular docking simulations were performed using four cannabinoid compounds and six molecular targets associated with glioma pathophysiology. RESULTS: Encouraging interactions between the selected enzymes and glioma-related targets were observed, suggesting their potential activity through these pathways. In particular, cannabigerol showed promising interactions with epidermal growth factor receptors and phosphatidylinositol 3- kinase, while Δ-9-tetrahydrocannabinol showed remarkable interactions with telomerase reverse transcriptase. CONCLUSION: The evaluated compounds exhibited favorable interactions with the analyzed enzymatic targets, thus representing potential candidates for further in vitro and in vivo studies.

Methyleugenol Has an Antidepressant Effect in a Neuroendocrine Model: In Silico and In Vivo Evidence.

Major depressive disorder is a severe mood disorder characterized by different emotions and feelings. This study investigated the antidepressant activity of the phenylpropanoid methyleugenol (ME) in adult female mice exposed to a stress model induced by dexamethasone. The animals were randomly divided into groups containing eight animals and were pre-administered with dexamethasone (64 µg/kg subcutaneously). After 165 and 180 min, they were treated with ME (25, 50 and 100 mg/kg intraperitoneally) or imipramine (10 mg/kg intraperitoneally) after 45 min and 30 min, respectively; they were then submitted to tests which were filmed. The videos were analyzed blindly. In the tail suspension test, ME (50 mg/kg) increased latency and reduced immobility time. In the splash test, ME (50 mg/kg) decreased grooming latency and increased grooming time. In the open field, there was no statistical difference for the ME groups regarding the number of crosses, and ME (50 mg/kg) increased the number of rearing and time spent in the center. Regarding in silico studies, ME interacted with dopaminergic D1 and α1 adrenergic pathway receptors and with tryptophan hydroxylase inhibitor. In the in vivo evaluation of the pathways of action, the antidepressant potential of ME (50 mg/kg) was reversed by SCH23390 (4 mg/kg intraperitoneally) dopaminergic D1 receptor, Prazosin (1 mg/kg intraperitoneally) α1 adrenergic receptor, and PCPA (4 mg/kg intraperitoneally) tryptophan hydroxylase inhibitor. Our findings indicate that ME did not alter with the locomotor activity of the animals and shows antidepressant activity in female mice with the participation of the D1, α1 and serotonergic systems.