What has a year of social isolation due to the COVID-19 pandemic influenced oral parafunctional habits and temporomandibular disorders? A case-control study.

OBJECTIVE: Few studies investigated the influence of oral parafunctional habits during the COVID-19 pandemic. Since some studies have demonstrated that signs and symptoms of temporomandibular disorder (TMD), as well as psychological alterations, increased during the COVID-19 pandemic lockdown, the aim of this study was to investigate whether social isolation is a situation that increases the prevalence of oral parafunctional habits. METHODS: This was an observational case-control study. An online survey with questions about TMD symptoms (Diagnostic Criteria Symptom Questionnaire) and oral parafunctional habits (Oral Behaviours Checklist [OBC]) was administered to Brazilian residents at two different times (2020 and 2021). The participants were divided according to social isolation practices into study groups (GI: 2020, n = 507; GIII: 2021, n = 282) and control groups (GII: 2020, n = 98; GIV: 2021, n = 202). RESULT: In each group, we evaluated the association of the frequency of oral parafunctional habits with the symptoms of TMD, and we observed that individuals with a greater presence of painful TMD present a greater number of oral parafunctional habits. Despite the literature showing that individuals who practiced social isolation developed more oral parafunctional habits, when analysing the association of the OBC questions in Groups GI × GII and GIII × GIV, only 'sustained talking' (p = .0022) and 'hold telephone between your hand and shoulders' (p = .0124) showed a significant difference in GI × GII. Kendall's coefficient of concordance revealed that there was a very strong concordance (GI × GII 0.9515 (p = .0087) and GIII × GIV 0.9655 (p = .0074)) between the ranks of the analysed oral parafunctional habits in all groups. CONCLUSION: We can state that Individuals who practiced social isolation did not present more oral parafunctional habits than individuals who did not.

The Trypanosoma cruzi pleiotropic protein P21 orchestrates the intracellular retention and in-vivo parasitism control of virulent Y strain parasites.

P21 is a protein secreted by all forms of Trypanosoma cruzi (T. cruzi) with recognized biological activities determined in studies using the recombinant form of the protein. In our recent study, we found that the ablation of P21 gene decreased Y strain axenic epimastigotes multiplication and increased intracellular replication of amastigotes in HeLa cells infected with metacyclic trypomastigotes. In the present study, we investigated the effect of P21 in vitro using C2C12 cell lines infected with tissue culture-derived trypomastigotes (TCT) of wild-type and P21 knockout (TcP21-/-) Y strain, and in vivo using an experimental model of T. cruzi infection in BALB/c mice. Our in-vitro results showed a significant decrease in the host cell invasion rate by TcP21-/- parasites as measured by Giemsa staining and cell count in bright light microscope. Quantitative polymerase chain reaction (qPCR) analysis showed that TcP21-/- parasites multiplied intracellularly to a higher extent than the scrambled parasites at 72h post-infection. In addition, we observed a higher egress of TcP21-/- trypomastigotes from C2C12 cells at 144h and 168h post-infection. Mice infected with Y strain TcP21-/- trypomastigotes displayed higher systemic parasitemia, heart tissue parasite burden, and several histopathological alterations in heart tissues compared to control animals infected with scrambled parasites. Therewith, we propose that P21 is important in the host-pathogen interaction during invasion, cell multiplication, and egress, and may be part of the mechanism that controls parasitism and promotes chronic infection without patent systemic parasitemia.

Fluconazole and levofloxacin prophylaxis are ineffective strategies for preventing infections in acute myeloid leukemia patients undergoing chemotherapy.

INTRODUCTION: Acute myeloid leukemia patients are at high risk for infections, which contribute to increased mortality rates of up to 70%. The use of antimicrobial prophylaxis has been shown to significantly lower rates of infection. Therefore, this retrospective study aimed to evaluate the effect of two agents that showed effective results in the literature, levofloxacin and fluconazole, as prophylaxis strategies in AML patients. METHODOLOGY: A total of 85 AML patients' medical records treated with a 7+3 induction chemotherapy protocol in the Cancer Hospital of Uberlândia from 2017 to 2021 were screened and their data was collected. Within these patients, groups for analysis were created based on whether the acting physician included an antibacterial or antifungal prophylaxis protocol during induction. Contingency tables with χ² and odds ratio tests were realized to verify associations between prophylaxis and infection. Additionally, Kaplan-Meier curves with Cox regression were developed to analyze survival. RESULTS: The use of prophylaxis with either fluconazole or levofloxacin did not lower rates of infection, as those who with prophylaxis did not demonstrate significant differences when compared to those without (20.3-29.7%, and 12.3-23.3%, respectively). Patients who suffered a bacterial infection during induction were shown to have lower overall survival, with a similar trend seen in fungal infections. CONCLUSION: Bacterial and fungal infections were associated with higher rates of induction mortality and lower overall survival, and prophylaxis using fluconazole and levofloxacin did not present any significant difference in preventing these infections in this study, contrasting results found in the literature. The individuality of each treatment center should be taken into consideration and future studies should be realized to better determine the most effective methods and agents for prophylaxis.

PLA2-MjTX-II from Bothrops moojeni snake venom exhibits antimetastatic and antiangiogenic effects on human lung cancer cells.

Phospholipases A2 (PLA2s) from snake venom possess antitumor and antiangiogenic properties. In this study, we evaluated the antimetastatic and antiangiogenic effects of MjTX-II, a Lys49 PLA2 isolated from Bothrops moojeni venom, on lung cancer and endothelial cells. Using in vitro and ex vivo approaches, we demonstrated that MjTX-II reduced cell proliferation and inhibited fundamental processes for lung cancer cells (A549) growth and metastasis, such as adhesion, migration, invasion, and actin cytoskeleton decrease, without significantly interfering with non-tumorigenic lung cells (BEAS-2B). Furthermore, MjTX-II caused cell cycle alterations, increased reactive oxygen species production, modulated the expression of pro- and antiangiogenic genes, and decreased vascular endothelial growth factor (VEGF) expression in HUVECs. Finally, MjTX-II inhibited ex vivo angiogenesis processes in an aortic ring model. Therefore, we conclude that MjTX-II exhibits antimetastatic and antiangiogenic effects in vitro and ex vivo and represents a molecule that hold promise as a pharmacological model for antitumor therapy.

A tomato B-box protein regulates plant development and fruit quality through the interaction with PIF4, HY5, and RIN transcription factors.

During the last decade, knowledge about BBX proteins has greatly increased. Genome-wide studies identified the BBX gene family in several ornamental, industry, and food crops; however, reports regarding the role of these genes as regulators of agronomically important traits are scarce. Here, by phenotyping a knockout mutant, we performed a comprehensive functional characterization of the tomato locus Solyc12g089240, hereafter called SlBBX20. The data revealed the encoded protein as a positive regulator of light signaling affecting several physiological processes during the life span of plants. Through inhibition of PHYTOCHROME INTERACTING FACTOR 4 (SlPIF4)-auxin crosstalk, SlBBX20 regulates photomorphogenesis. Later in development, it controls the balance between cell division and expansion to guarantee correct vegetative and reproductive development. In fruits, SlBBX20 is transcriptionally induced by the master transcription factor RIPENING INHIBITOR (SlRIN) and, together with ELONGATED HYPOCOTYL 5 (SlHY5), up-regulates flavonoid biosynthetic genes. Finally, SlBBX20 promotes the accumulation of steroidal glycoalkaloids and attenuates Botrytis cinerea infection. This work clearly demonstrates that BBX proteins are multilayer regulators of plant physiology because they affect not only multiple processes during plant development but they also regulate other genes at the transcriptional and post-translational levels.

Antiangiogenic properties of BthMP, a P-I metalloproteinase from Bothrops moojeni snake venom by VEGF pathway in endothelial cells.

Angiogenesis is a process that is controlled by a delicate combination of proangiogenic and antiangiogenic molecules and can be disrupted in various illnesses, including cancer. Non-cancerous diseases can also have an abnormal or insufficient vascular growth, inflammation and hypoxia, which exacerbate angiogenesis. These conditions include atherosclerosis, psoriasis, endometriosis, asthma, obesity and AIDS. Based on that, the present work assessed the in vitro and ex vivo antiangiogenic properties stemming from BthMP, a P-I metalloproteinase from Bothrops moojeni snake venom, via the VEGF pathway. BthMP at a concentration of 5 and 40 µg/mL showed no toxicity to endothelial cells (HUVEC) in the MTT assay and was not able to induce necrosis and colony proliferation. Interestingly, BthMP inhibited adhesion, migration and invasion of HUVECs in Matrigel and arrested in vitro angiogenesis by reducing the average number of nodules in toxin-treated cells by 9.6 and 17.32 at 5 and 40 µg/mL, respectively, and the number of tubules by 15.9 at 5 µg/mL and 21.6 at 40 µg/mL in a VEGF-dependent way, an essential proangiogenic property. Furthermore, BthMP inhibited the occurrence of the angiogenic process in an ex vivo aortic ring test by decreasing new vessel formation by 52% at 5 µg/mL and by 66% at 40 µg/mL and by increasing the expression of an antiangiogenic gene, SFLT-1, and decreasing the expression of the proangiogenic genes VEGFA and ANGPT-1. Finally, this toxin reduces the production of nitric oxide, a marker that promotes angiogenesis and VEGF modulation, and decreases the protein expression of VEGFA in the supernatant of the HUVEC culture by about 30 %. These results suggest that BthMP has a promising antiangiogenic property and proves to be a biotechnological mechanism for understanding the antiangiogenic responses induced by snake venom metalloproteinases, which could be applied to a variety of diseases that exhibit an imbalance of angiogenesis mechanisms.

Overweight and Blood Pressure in Pre-Pubertal Children: A Longitudinal Study.

OBJECTIVE: To analyze the longitudinal relationship between overweight and hypertension in school children. METHODS: This cohort study enrolled children 6-8 years of age who were then prospectively followed up over a 24 months period with repeat assessments performed at an interval of 11-13 months. Information on participation in physical education classes in school, sports practice outside of school, and economic status were obtained through questionnaires answered by parents/guardians. The measurement of blood pressure, weight, height, and waist circumference was performed during the serial follow-up visits in school. RESULTS: The proportion of hypertension did not change significantly over the 24 months (7.1% to 8.2%; P = 0.690). However, children with overweight and obesity throughout the period, had a 198% [HR (95% CI) 2.98 (1.40, 6.35)] higher risk of having hypertension diagnosed during follow-up when compared to eutrophic children in the same period. CONCLUSION: The development trajectory of overweight and obesity in children aged 6-8 years was associated with hypertension.

A potential antiviral against COVID-19 obtained from Byrsonima coccolobifolia leaves extract.

In this study, we specifically focused on the crude methanolic leaf extract of Byrsonima coccolobifolia, investigating its antifungal potential against human pathogenic fungi and its antiviral activity against COVID-19. Through the use of high-performance liquid chromatography coupled with electrospray ionization ion trap tandem mass spectrometry, direct infusion electrospray ionization ion trap tandem mass spectrometry, and chromatographic dereplication procedures, we identified galloyl quinic acid derivatives, catechin derivatives, proanthocyanidins, and flavonoid glycosides. The broth dilution assay revealed that the methanolic leaf extract of B. coccolobifolia exhibits antifungal activity against Cryptococcus neoformans (IC50 = 4 µg/mL). Additionally, docking studies were conducted to elucidate the interactions between the identified compounds and the central residues at the binding site of biological targets associated with COVID-19. Furthermore, the extract demonstrated an in vitro half-maximum effective concentration (EC50 = 7 µg/mL) and exhibited significant selectivity (>90%) toward SARS-CoV-2.

Skin donation for transplantation: Social representations of family members who (do not) give consent for collection.

Despite the advantages of using deceased donor skin in the treatment of burns, it is not easy to obtain these grafts due to low tissue donation rates. In order to discover the social representations of family members of organ donors regarding skin donation and to analyze the convergences and divergences of these representations between family members who consented and those who refused to allow skin to be donated for transplantation, we conducted interviews with 20 family members of organ donors in a situation of brain death. Data were obtained through interviews and submitted to the Collective Subject Discourse Analysis Technique. This study shows that in the opinion of family members who consented and those who did not authorize skin donation, the consideration contains both positive and negative representations, which can have different weights and influence decision-making. This study also highlights, in an unprecedented way, the representation of the animalization of the donor, which can be a reason for the refusal to allow skin to be donated.

The Impact of Bleomycin Deficit on Survival in Hodgkin's Lymphoma Patients: A Retrospective Study.

PURPOSE: Hodgkin's lymphoma is currently treated with a chemotherapy protocol consisting of doxorubicin, bleomycin, vinblastine, and dacarbazine. Due to Brazil facing a bleomycin shortage in 2017, and this drug's high toxicity, this retrospective study evaluates the effect that the absence of bleomycin had on treatment response and overall survival of Hodgkin's lymphoma patients. METHODS: The medical records of 126 HL patients treated between 2007 and 2021 were reviewed and their data collected, followed by grouping into ABVD and AVD groups according to bleomycin use. Data concerning the patient's characteristics, cancer type, and treatment plan were analyzed with proportion tests, Kaplan-Meier curves. univariate Cox regression, and χ2 tests. RESULTS: No discernible differences were found in this study between the overall survival and recurrence rate of patients treated with bleomycin compared to those without. Additionally, there was an increased risk of death in each subsequent cycle of chemotherapy of the complete ABVD protocol, demonstrating a risk of toxicity. Among the variables analyzed, hypertension and the presence of B symptoms were also associated with an increased risk of death, while the use of radiotherapy significantly improved survival. CONCLUSION: The results of this study suggest that bleomycin did not impact the outcome of Hodgkin's lymphoma treatment. Moreover, the increased risk of death associated with its toxicity during each cycle of treatment raises concerns about its role as an essential component of the gold standard for Hodgkin's lymphoma treatment. Therefore, further research and consideration are needed to reassess the use of bleomycin in Hodgkin's lymphoma treatment protocols.

Recusa familiar para doação de córneas para transplante: fatores associados e tendência / Negativa familiar para donación de córneas para trasplante: factores asociados y tendencia / Family refusal to donate a cornea for transplantation: associated factors and trends

Resumo Objetivo Analisar a recusa familiar de doação de córnea para transplante em uma Organização de Procura de Órgãos. Métodos Estudo quantitativo do tipo transversal sobre as recusas de córnea de doadores em situação de morte encefálica. A fonte de dados foi constituída pelos Termos de Autorização de Doação de Órgãos e Tecidos firmados entre janeiro de 2001 a dezembro de 2020 em uma Organização de Procura de Órgãos. Os dados foram coletados, tabulados e analisados de forma descritiva e inferencial. O presente estudo foi aprovado pelo Comitê de Ética em Pesquisa. Resultados Dos 2.447 Termos de Autorização de Doação de Órgãos e Tecidos firmados no período, 620 (25.34%) recusaram a doação de córneas. Com relação à tendência temporal de recusas de doação de córneas, o único período que apresentou significância foi de 2001 a 2009, quando as faixas etárias de zero a 11 anos e 12 a 19 anos demonstraram tendência decrescente, e a faixa etária maior ou igual a 60 anos, mostrou-se crescente. No período total de 2001 a 2020, as faixas etárias dos 20 a 40 anos, 41 a 59 anos e maior ou igual a 60 anos apresentaram, 48%, 59% e 73%, respectivamente, menores chances de recusa da doação de córneas. Conclusão A faixa etária apresentou associação com a recusa, tendo em vista que os indivíduos de maior idade apresentaram maiores índices.

Resumen Objetivo Analizar la negativa familiar de donación de córneas para trasplante en una Organización de Búsqueda de Órganos. Métodos: Estudio cuantitativo tipo transversal sobre la negativa de córnea de donantes en situación de muerte encefálica. La fuente de datos estuvo compuesta por los Términos de Autorización de Donación de Órganos y Tejidos firmados entre enero de 2001 y diciembre de 2020 en una Organización de Búsqueda de Órganos. Se recopilaron los datos, luego se tabularon y se analizaron de forma descriptiva e inferencial. El presente estudio fue aprobado por el Comité de Ética en Investigación. Resultados De los 2447 Términos de Autorización de Donación de Órganos y Tejidos firmados en el período, 620 (25,34 %) negaron la donación de córneas. Con relación a la tendencia temporal de negativas de donación de córneas, el único período que presentó significación fue de 2001 a 2009, cuando los grupos de edad de 0 a 11 años y de 12 a 19 años demostraron una tendencia decreciente, y el grupo de edad mayor o igual a 60 años se mostró creciente. En el período total de 2001 a 2020, los grupos de edad de 20 a 40 años, de 41 a 59 años y mayor o igual a 60 años presentaron un 48 %, un 59 % y un 73 %, respectivamente, menor probabilidad de negativa de donación de córneas. Conclusión El grupo de edad presentó relación con la negativa, considerando que los individuos de mayor edad presentan mayores índices.

Abstract Objective To analyze family refusals to donate a cornea for transplantation in an Organ Procurement Organization. Methods This was a quantitative cross-sectional study on corneal donation refusals from potential brain-dead donors. The data source was based on the Terms of Authorization for Donation of Organs and Tissues signed from January 2001 to December 2020 in an Organ Procurement Organization. Data were collected, tabulated, and analyzed in a descriptive and inferential manner. The present study was approved by the Research Ethics Committee. Results Of the 2,447 Terms of Authorization for Donation of Organs and Tissues signed in the above period, 620 (25.34%) of them refused to donate a cornea. Regarding the time trend of corneal donation refusals, the period 2001-2009 was the only one that showed significance, when the 0-11 and 12-19 age groups showed a decreasing trend and that of 60 years or older showed an increasing trend. In the period 2001-2020, the age groups of 20-40, 41-59, and 60 years or older had lower rates of refusal to donate a cornea (48%, 59%, and 73%, respectively). Conclusion The age group is associated with refusal because older individuals had the highest refusal rates.

Evaluation of Brazilian women's participation in the CNPQ in the field of medical research / Avaliação da participação das mulheres brasileiras no CNPQ na área de pesquisa médica

Abstract Introduction: Brazilian scientific production has shown substantial growth and achieved international visibility. However, in general, the participation of women in scientific activities remains limited. Objective: This study aimed to evaluate the indicators of scientific productivity of women fellows of the Council for Scientific and Technological Development (CNPq) in the field of Medicine. Method: This cross-sectional study was conducted on 541 (211 women, 39%) researchers registered as recipients of CNPq research productivity (PQ) scholarships in Medicine according to a list provided in December 2022. Results: There was a predominance of male researchers (n=330; 61%). In both the male and female groups, most researchers were at level 2, with 62.5% women and 47.2% men (p=0.018). All 211 female PQ scholars were distributed among 37 different institutions and published 34,969 papers in scientific journals, averaging 165.7 articles per researcher. In the last five years of the study period (from 2018 to 2022), 9,679 papers were published. Over their careers, the 211 researchers supervised 5,440 undergraduate research students, 4,144 master's degree students, and 2,923 PhD candidates. There was a significant difference between the scholarship levels for the development of human resources in undergraduate research (p=0.040), master's degree (p=0.027), and PhD. (p<0.001). Conclusion: There are still less women participating in CNPq medical research than men. However, we observed a substantial participation of women in all the assessed items, including technical and scientific production and the human resources training.

Resumo Introdução: A produção científica brasileira apresentou crescimento substancial e visibilidade internacional. Contudo, em geral, a participação das mulheres em atividades científicas ainda é limitada. Objetivo: Este estudo objetivou avaliar os indicadores de produtividade científica de mulheres bolsistas do Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) na área de medicina. Método: Foi realizado estudo transversal com 541 (211 mulheres, 39%) pesquisadores cadastrados como bolsistas de produtividade em medicina do CNPq conforme lista disponibilizada em dezembro de 2022. Resultado: Houve predomínio de pesquisadores do sexo masculino (n = 330; 61%). Em ambos os grupos, masculino e feminino, a maioria dos investigadores encontra-se no nível 2, sendo 62,5% mulheres e 47,2% homens (p = 0,018). Todos os 211 pesquisadores foram distribuídos em 37 instituições diferentes e publicaram 34.969 artigos em revistas científicas, com média de 165,7 artigos por pesquisador. De 2018 a 2022, foram publicados 9.679 artigos. Ao longo de suas carreiras, os 211 pesquisadores orientaram 5.440 alunos de iniciação científica, 4.144 alunos de mestrado e 2.923 alunos de doutorado. Houve diferença significativa entre os níveis de bolsas quanto ao desenvolvimento de recursos humanos em iniciação científica (p = 0,040), mestrado (p = 0,027) e doutorado (p < 0,001). Conclusão: Ainda há menor participação de mulheres do que de homens entre os pesquisadores médicos do CNPq. Contudo, foi possível observar participação substancial das mulheres em todos os quesitos avaliados, incluindo a produção técnica e científica e a formação de recursos humanos.

Morphological aspects of rumen papillae of lambs fed agro-industrial wastes.

Sheep meet production systems require roughage feed of good nutritional quality. However, the production of sorghum or corn silage, besides expensive, also depends on large cultivable areas and favorable weather conditions. Thus, agro-industrial residues have stood out as a feed alternative that contribute to the reduction of production costs and to the conservation of the environment. Fragments of the ruminal mucosa of 30 healthy lambs fed with agro-industrial residues and slaughtered with a final weight of 36 kg were analyzed by light and scanning electron microscopy. We observed that the coproducts grape residue and wet brewery residue affected the shape, dimensions, and cytoarchitecture of the rumen epithelium in contrast to traditional sorghum silage. The rumen papillae of lambs fed grape waste were larger, and their epithelium was thinner when compared to the papillae of lambs fed wet brewery waste and sorghum silage. It can be assumed that the increased mucosal surface area of the rumen contributed to greater weight gain and reduced time to slaughter. The use of a greater variety of agro-industrial residues as a substitute for traditional feedstuffs contributes to the increase in animal protein production in many countries, making the confinement of sheep more viable and sustainable.

Identifying the Risk Factors for Malignant Mammary Tumors in Dogs: A Retrospective Study.

Mammary cancer is one of the main causes of death in female dogs worldwide, considering that many risk factors are involved in its development. This study aimed to elucidate the relationship between epidemiological and clinical risk factors with the histopathological diagnosis of malignant mammary tumors in dogs treated at the Veterinary Hospital of the Federal University of Uberlândia, which has one of the first veterinary oncology services in Brazil. A retrospective matched case-control study was conducted to identify risk factors for the development of malignant mammary tumors in dogs. The variables analyzed were size dog, breed, housing, type of diet, and body score. Potential risk factors were selected by univariate analysis (p < 0.25) before multivariate forward binary logistic regression. The most frequent benign tumor was the benign mixed tumor (35.2%), and the most frequent malignant tumor was the mixed carcinoma (27.4%). Size dog, breed, housing, and overweight are predictors of malignant mammary tumors in dogs. The highest risk of developing malignant mammary tumors is associated with large female dogs, Yorkshire or Poodle breeds, living outside the home, or being overweight.

Dental Caries, Tooth Loss and Quality of Life of Individuals Exposed to Social Risk Factors in Northeast Brazil.

This study aimed to investigate the impact of dental caries and tooth loss on oral health-related quality of life (OHRQoL) in socioeconomically disadvantaged people. A population-based, cross-sectional survey was conducted in 28 cities at social risk in Northeast Brazil. All permanent residents aged 12, 15-19, 35-44, and 65-74 years were eligible, and 3063 were included. Participants answered a questionnaire on socioeconomic status, beliefs, and behaviors. Trained local dentists performed oral clinical examinations during home visits. Caries and tooth loss were evaluated using the decayed, missing, and filled teeth (DMFT) index and OHRQoL was evaluated using the Oral Health Impact Profile-14 (OHIP-14). Poisson regression analysis was performed to assess the relationship between individual domains, OHIP-14 scores, dental caries, tooth loss, and socioeconomic/demographic characteristics. Mean DMFT (standard deviation) scores were 2.68 (4.01), 4.84 (4.30), 15.35 (7.26), and 26.72 (8.03) for groups aged 12, 15-19, 35-44, and 65-74 years, respectively. Most participants (70%) were partially edentulous and 13% were completely edentulous. Caries and tooth loss significantly increased with age and impacted OHRQoL. Physical pain (5.8%) and psychological discomfort (5.8%) were the most commonly reported on the OHIP-14. Untreated caries (prevalence ratio (PR), 1.54; 95% confidence interval (CI), 1.37-1.72) and edentulism (PR, 1.29; 95% CI, 1.08-1.53) had a significant negative impact on OHRQoL. Income, level of education, sex, age, and oral hygiene habits were also related to OHRQoL. There was a high prevalence of dental caries and edentulism in all age groups except 12-year-olds. OHRQoL was negatively impacted by these oral conditions across the lifespan, with a trend towards more negative scores and higher impact in older adults.

Dual nanocarrier of chlorhexidine and fluconazole: Physicochemical characterization and effects on microcosm biofilms and oral keratinocytes.

OBJECTIVES: This study assembled and characterized a dual nanocarrier of chlorhexidine (CHX) and fluconazole (FLZ), and evaluated its antibiofilm and cytotoxic effects. METHODS: CHX and FLZ were added to iron oxide nanoparticles (IONPs) previously coated by chitosan (CS) and characterized by physical-chemical analyses. Biofilms from human saliva supplemented with Candida species were grown (72 h) on glass discs and treated (24 h) with IONPs-CS carrying CHX (at 39, 78, or 156 µg/mL) and FLZ (at 156, 312, or 624 µg/mL) in three growing associations. IONPs and CS alone, and 156 µg/mL CHX + 624 µg/mL FLZ (CHX156-FLZ624) were tested as controls. Next, microbiological analyses were performed. The viability of human oral keratinocytes (NOKsi lineage) was also determined (MTT reduction assay). Data were submitted to ANOVA or Kruskal-Wallis, followed by Fisher's LSD or Tukey's tests (α=0.05). RESULTS: Nanocarriers with spherical-like shape and diameter around 6 nm were assembled, without compromising the crystalline property and stability of IONPs. Nanocarrier at the highest concentrations was the most effective in reducing colony-forming units of Streptococcus mutans, Lactobacillus spp., Candida albicans, and Candida glabrata. The other carriers and CHX156-FLZ624 showed similar antibiofilm effects, and significantly reduced lactic acid production (p<0.001). Also, a dose-dependent cytotoxic effect against oral keratinocytes was observed for the dual nanocarrier. IONPs-CS-CHX-FLZ and CHX-FLZ significantly reduced keratinocyte viability at CHX and FLZ concentrations ≥7.8 and 31.25 µg/mL, respectively (p<0.05). CONCLUSION: The nanotherapy developed outperformed the effect of the combination CHX-FLZ on microcosm biofilms, without increasing the cytotoxic effect of the antimicrobials administered. CLINICAL SIGNIFICANCE: The dual nanocarrier is a promising topically-applied therapy for the management of oral candidiasis considering that its higher antibiofilm effects allow the use of lower concentrations of antimicrobials than those found in commercial products.

Rottlerin impairs early and late steps of Toxoplasma gondii infection in human trophoblast cells and villous explants.

Congenital toxoplasmosis, caused by the opportunistic protozoan parasite T. gondii, can cause stillbirths, miscarriages and fetal abnormalities, as well as encephalitis and chorioretinitis in newborns. Available treatment options rely on antiparasitic drugs that have been linked to serious side effects, high toxicity and the development of drug-resistant parasites. The search for alternative therapeutics to treat this disease without acute toxicity for the mother and child is essential for the advancement of current therapeutic procedures. The present study aimed to unravel the mode of the anti-T. gondii action of Rottlerin, a natural polyphenol with multiple pharmacological properties described. Herein, we further assessed the antiparasitic activity of Rottlerin against T. gondii infection on the human trophoblastic cells (BeWo cells) and, for the first time, on human villous explants. We found that non-cytotoxic doses of Rottlerin impaired early and late steps of parasite infection with an irreversible manner in BeWo cells. Rottlerin caused parasite cell cycle arrest in G1 phase and compromised the ability of tachyzoites to infect new cells, thus highlighting the possible direct action on parasites. An additional and non-exclusive mechanism of action of Rottlerin involves the modulation of host cell components, by affecting lipid droplet formation, mitochondrial function and upregulation of the IL-6 and MIF levels in BeWo cells. Supporting our findings, Rottlerin also controlled T. gondii proliferation in villous explants with low toxicity and reduced the IL-10 levels, a cytokine associated with parasite susceptibility. Collectively, our results highlighted the potential use of Rottlerin as a promising tool to prevent and/or treat congenital toxoplasmosis.

Health promotion competencies in the multidisciplinary residency: capacity for change and health advocacy. / Competências em promoção da saúde na residência multiprofissional: capacidade de mudanças e advocacia em saúde.

Health Promotion consists of individual and group strategies to achieve equity and reduce risks related to the Social Determinants of Health. This study aims to analyze the Capacity for Change and Health Advocacy domains of the CompHP in the reality of a Multidisciplinary Residency Program in Family and Community Health. This qualitative exploratory research was conducted with twenty-one participants. Data were interpreted through Discourse Analysis under the lens of Depth Hermeneutics. In the capacity for change, we identified that promoting healthy lifestyles is insufficient to develop autonomous and emancipated individuals in the search for decent living conditions. Concerning health advocacy, residents guide clients on the importance of popular participation in spaces intended for social control in Primary Health Care.

A Promoção da Saúde consiste em estratégias individuais e coletivas, com vistas ao alcance da equidade e redução dos riscos relacionados aos Determinantes Sociais em Saúde. Este estudo objetiva analisar os domínios Capacidade de Mudança e Advocacia em Saúde do CompHP na realidade de uma Residência Multiprofissional em Saúde da Família e Comunidade. Trata-se de uma pesquisa qualitativa, de caráter exploratório. Participaram vinte e um participantes. Os dados foram interpretados através da Análise de Discurso à luz da Hermenêutica de Profundidade. No domínio capacidade de mudanças, foi identificado que promover hábitos de vida saudáveis não é suficiente, sendo necessário desenvolver indivíduos autônomos e emancipados para a busca de condições de vida dignas. Para o domínio advocacia em saúde, os residentes orientam os usuários sobre a importância da participação popular nos espaços destinados ao controle social no âmbito da Atenção Primária em Saúde.

Lipopeptides from an isolate of Bacillus subtilis complex have inhibitory and antibiofilm effects on Fusarium solani.

Bacillus subtilis species complex is known as lipopeptide-producer with biotechnological potential for pharmaceutical developments. This study aimed to identify lipopeptides from a bacterial isolate and evaluate their antifungal effects. Here, we isolated and identified a lipopeptide-producing bacterium as a species of Bacillus subtilis complex (strain UL-1). Twenty lipopeptides (six iturins, six fengycins, and eight surfactins) were identified in the crude extract (CE) and fractions (F1, F2, F3, and F4), and the highest content of total lipopeptides was observed in CE and F2. The chemical quantification data corroborate with the hemolytic and antifungal activities that CE and F2 were the most hemolytic and inhibited the fungal growth at lower concentrations against Fusarium spp. In addition, they caused morphological changes such as shortening and/or atypical branching of hyphae and induction of chlamydospore-like structure formation, especially in Fusarium solani. CE was the most effective in inhibiting the biofilm formation and in disrupting the mature biofilm of F. solani reducing the total biomass and the metabolic activity at concentrations ≥ 2 µg/mL. Moreover, CE significantly inhibited the adherence of F. solani conidia on contact lenses and nails as well as disrupted the pre-formed biofilms on nails. CE at 100 mg/kg was nontoxic on Galleria mellonella larvae, and it reduced the fungal burden in larvae previously infected by F. solani. Taken together, the lipopeptides obtained from strain UL-1 demonstrated a potent anti-Fusarium effect inducing morphological alterations and antibiofilm activities. Our data open further studies for the biotechnological application of these lipopeptides as potential antifungal agents. KEY POINTS: • Lipopeptides inhibit Fusarium growth and induce chlamydospore-like structures. • Lipopeptides hamper the adherence of conidia and biofilms of Fusarium solani. • Iturins, fengycins, and surfactins were associated with antifungal effects.

Influence of atherosclerosis risk factors on the anatomical distribution of peripheral arterial disease in patients with chronic limb-threatening ischemia: a cross-sectional study.

Background: Atherosclerosis risk factors can have different impacts on cardiovascular diseases and on the anatomical distribution of Peripheral Arterial Disease (PAD). Objectives: To study the influence of atherosclerosis risk factors on the anatomical distribution of PAD in patients with chronic limb-threatening ischemia (CLTI). Methods: We performed an observational, cross-sectional, and analytical study that included 476 hospitalized patients with CLTI due to PAD. We compared the presence of atherosclerosis risk factors (age, gender, diabetes mellitus, smoking, and hypertension) in patients with PAD involving three different anatomic areas (aortoiliac, femoropopliteal, and infrapopliteal). Multivariate analysis was performed to identify associations between atherosclerosis risk factors and PAD distribution. Results: The mean age of the 476 patients was 69 years, 249 (52%) were men, and 273 (57%) had diabetes. Seventy-four percent (353) had minor tissue loss. Multivariate analysis identified three risk factors associated with PAD anatomical distribution (gender, smoking, and DM). Women had a 2.7 (CI: 1.75-4.26) times greater chance of having femoropopliteal disease. Smokers had a 3.6-fold (CI: 1.54-8.30) greater risk of aortoiliac disease. Diabetic patients were 1.8 (CI: 1.04-3.19) times more likely to have isolated infrapopliteal occlusive disease. Conclusions: The study showed that gender, DM, and smoking impact on the anatomical distribution of PAD in patients with CLTI. Diabetic patients were more likely to have only infrapopliteal disease, women had a greater risk of femoropopliteal PAD, and smokers had a greater risk of aortoiliac occlusive disease.