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Candida species are among the priority pathogens in the area of research and development. Due to the problems associated with resistance to antifungals, new therapeutic alternatives are necessary. In this regard, drug repositioning has gained prominence. The objective of this study was to evaluate the activity of three tricyclic antidepressants (TCAs) - amitriptyline (AMT), nortriptyline (NOR) and clomipramine (CLO) - isolated or associated with antifungals against strains of Candida spp., as well as to analyze the possible mechanism of action. Among the methods used were broth microdilution tests, tolerance level assessment, checkerboard assays, flow cytometry and fluorescence microscopy. Furthermore, Candida cells were visualized after treatments by scanning electron microscopy (SEM). AMT presented MIC 50% in the range of 16 to 128 µg/mL, NOR from 8 to 128 µg/mL, and CLO from 8 to 64 µg/mL, with all three TCAs having a fungicidal inhibitory action profile. For these TCAs, there was synergism with amphotericin B (AMB) in 100% of the isolates. In association with fluconazole (FLC) and itraconazole (ITR), there were mostly indifferent interactions. TCAs isolated and associated with AMB reduced cell viability, promoted DNA fragmentation and damage, caused mitochondrial depolarization, externalization of phosphatidylserine, produced reactive oxygen species (ROS), decreased reduced glutathione (GSH) and increased carbonyl protein levels, causing morphological changes. The results suggest the antifungal mechanism of the TCAs works via the apoptotic pathway., (© 2024. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Background: Patients with immune-mediated rheumatic diseases (IMRDs) have been prioritized for COVID-19 vaccination to mitigate the infection severity risks. Patients with rheumatoid arthritis (RA) are at a high risk of severe COVID-19 outcomes, especially those under immunosuppression or with associated comorbidities. However, few studies have assessed the safety of the COVID-19 vaccine in patients with RA., Objective: To evaluate the safety of vaccines against SARS-CoV-2 in patients with RA., Methods: This data are from the study "Safety and Efficacy on COVID-19 Vaccine in Rheumatic Diseases," a Brazilian multicentric prospective phase IV study to evaluate COVID-19 vaccine in IMRDs in Brazil. Adverse events (AEs) in patients with RA of all centers were assessed after two doses of ChAdOx1 (Oxford/AstraZeneca) or CoronaVac (Sinovac/Butantan). Stratification of postvaccination AEs was performed using a diary, filled out daily and returned at the end of 28 days for each dose., Results: A total of 188 patients with RA were include, 90% female. CoronaVac was used in 109 patients and ChAdOx1 in 79. Only mild AEs were observed, mainly after the first dose. The most common AEs after the first dose were pain at the injection (46,7%), headache (39,4%), arthralgia (39,4%), myalgia (30,5%) and fatigue (26,6%), and ChAdOx1 had a higher frequency of pain at the injection (66% vs 32 %, p < 0.001) arthralgia (62% vs 22%, p < 0.001) and myalgia (45% vs 20%, p < 0.001) compared to CoronaVac. The more common AEs after the second dose were pain at the injection (37%), arthralgia (31%), myalgia (23%), headache (21%) and fatigue (18%). Arthralgia (41,4% vs 25%, p = 0.02) and pain at injection (51,4% vs 27%, p = 0.001) were more common with ChAdOx1. No serious AEs were related. With Regard to RA activity level, no significant difference was observed between the three time periods for both COVID-19 vaccines., Conclusion: In the comparison between the two immunizers in patients with RA, local reactions and musculoskeletal symptoms were more frequent with ChAdOx1 than with CoronaVac, especially after the first dose. In summary, the AE occurred mainly after the first dose, and were mild, like previous data from others immunizing agents in patients with rheumatoid arthritis. Vaccination did not worsen the degree of disease activity., (© 2024. The Author(s).)

Introduction. The development of new antifungal drugs has become a global priority, given the increasing cases of fungal diseases together with the rising resistance to available antifungal drugs. In this scenario, drug repositioning has emerged as an alternative for such development, with advantages such as reduced research time and costs. Gap statement. Propafenone is an antiarrhythmic drug whose antifungal activity is poorly described, being a good candidate for further study. Aim. This study aims to evaluate propafenone activity against different species of Candida spp. to evaluate its combination with standard antifungals, as well as its possible action mechanism. Methodology. To this end, we carried out tests against strains of Candida albicans , Candida auris , Candida parapsilosis , Candida tropicalis , Candida glabrata and Candida krusei based on the evaluation of the MIC, minimum fungicidal concentration and tolerance level, along with checkerboard and flow cytometry tests with clinical strains and cell structure analysis by scanning electron microscopy (SEM). Results. The results showed that propafenone has a 50% MIC ranging from 32 to 256 µg ml -1 , with fungicidal activity and positive interactions with itraconazole in 83.3% of the strains evaluated. The effects of the treatments observed by SEM were extensive damage to the cell structure, while flow cytometry revealed the apoptotic potential of propafenone against Candida spp. Conclusion. Taken together, these results indicate that propafenone has the potential for repositioning as an antifungal drug.

Introduction: Superficial laryngeal hydration, obtained through nebulization, is related to the moisture level on the epithelial surfaces of the vocal folds, modifying their biomechanical and aerodynamic properties. Through high-speed videolaryngoscopy it is possible to obtain objective data for laryngeal analysis after nebulization and a better understanding of this phenomenon OBJECTIVE: To verify the effects of nebulization with saline solution on laryngeal parameters of digital videokymography obtained by high-speed videolaryngoscopy examination in women and men with and without laryngeal alterations METHOD: This is a clinical, comparative intra-subject study. Fifty-nine adults were selected, with and without laryngeal alterations, 30 females and 29 males. Digital videokymographs in the anterior, middle and posterior thirds of the vocal folds of the participants were analyzed before and after nebulization with 0.9% saline solution., Results: Women without laryngeal alterations showed more parameters changes after nebulization, in which there was a decrease in maximum and medium opening, amplitude of opening of the left and right vocal fold in the anterior glottal third, and an increase of the percentage of closure of the vocal folds. These results indicate a minor extent of lateral excursion of the vocal folds during phonation. In women with laryngeal alterations, the parameters that changed after nebulization were the increased frequency of opening of the left and right vocal folds in the topography of the posterior third. In men, nebulization did not change the variables studied, except for the amplitude of the right vocal fold in men with laryngeal alterations, in the analysis of the posterior glottic third., Conclusion: The results suggest that surface hydration modifies laryngeal dynamics differently between genders. After nebulization with saline solution, women without laryngeal alterations showed a decrease in the lateralization of the vocal folds during phonation, suggesting a better phonatory efficiency., (Copyright © 2022 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction. Antibiotic resistance is a major threat to public health, particularly with methicillin-resistant Staphylococcus aureus (MRSA) being a leading cause of antimicrobial resistance. To combat this problem, drug repurposing offers a promising solution for the discovery of new antibacterial agents. Hypothesis. Menadione exhibits antibacterial activity against methicillin-sensitive and methicillin-resistant S. aureus strains, both alone and in combination with oxacillin. Its primary mechanism of action involves inducing oxidative stress. Methodology. Sensitivity assays were performed using broth microdilution. The interaction between menadione, oxacillin, and antioxidants was assessed using checkerboard technique. Mechanism of action was evaluated using flow cytometry, fluorescence microscopy, and in silico analysis. Aim. The aim of this study was to evaluate the in vitro antibacterial potential of menadione against planktonic and biofilm forms of methicillin-sensitive and resistant S. aureus strains. It also examined its role as a modulator of oxacillin activity and investigated the mechanism of action involved in its activity. Results. Menadione showed antibacterial activity against planktonic cells at concentrations ranging from 2 to 32 µg ml -1 , with bacteriostatic action. When combined with oxacillin, it exhibited an additive and synergistic effect against the tested strains. Menadione also demonstrated antibiofilm activity at subinhibitory concentrations and effectively combated biofilms with reduced sensitivity to oxacillin alone. Its mechanism of action involves the production of reactive oxygen species (ROS) and DNA damage. It also showed interactions with important targets, such as DNA gyrase and dehydroesqualene synthase. The presence of ascorbic acid reversed its effects. Conclusion. Menadione exhibited antibacterial and antibiofilm activity against MRSA strains, suggesting its potential as an adjunct in the treatment of S. aureus infections. The main mechanism of action involves the production of ROS, which subsequently leads to DNA damage. Additionally, the activity of menadione can be complemented by its interaction with important virulence targets.

Purpose: To verify the effect of nebulization on the voice of dysphonic and non-dysphonic individuals on acoustic, perceptual-auditory, aerodynamic, electroglottographic, laryngeal parameters and on the self-perception of vocal discomfort., Materials and Methods: All the research subjects were submitted to vocal evaluation, laryngeal and voice self-perception. Then, the participants remained in vocal rest for a period of 10 minutes and the analysis mentioned above were again performed. After this first stage, the participants were submitted to the nebulization for a period of 10 minutes and the all analysis above were again performed. Descriptive analysis of the variables was carried. In the comparison of the pre- and post-nebulization groups, the Paired T-Student Test was used for variables with non-dysphonic distribution and the Wilcoxon Test for variables with asymmetric distribution. When categorical variables were evaluated (perceptual-auditory evaluation and laryngeal assessment), the Pearson's Chi-square test was used. In all analysis, a significance level of 5% was considered. The intra-rater agreement in the auditory-perceptual and perceptual-visual assessment was assessed using the AC1 statistic, using the R program. For this purpose, 20% of the voice samples and laryngeal images were replicated blindly and interpreted by the evaluators at the time evaluations., Results: The results of this research show that non-dysphonic individuals have more positive vocal and laryngeal effects after nebulization than dysphonic ones. It is also observed that the EGG measurement was the most sensitive to the effect of nebulization, with an increase in the Closed quotient (CQ) in all groups evaluated. Regarding acoustic measurements, it is noted that the effect of nebulization in men is more evident than in women. After nebulization, there was an increase in fundamental frequency in the group of non-dysphonic women and dysphonic and non-dysphonic men. A decrease in the amplitude perturbation quotient values is observed in all groups, besides a reduction in the pitch perturbation quotient values after nebulization in non-dysphonic men groups. There was improves aerodynamic efficiency in groups of dysphonic and non-dysphonic men and in the self-perception of vocal discomfort in all groups studied after the hydration procedure. The results of this study demonstrate a significant improvement in the mucosal wave after nebulization in the groups of women and men who are not dysphonic., Conclusion: The nebulization procedure with saline solution improves acoustic measurements, the electroglottographic closed quotient and vocal self-perception of dysphonic and non-dysphonic women and men. Nebulization increases the mucosal wave of the vocal folds in non-dysphonic women and men and improves the aerodynamic efficiency of men., (Copyright © 2021 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the acoustic and self-perception modifications obtained after the first, third, fifth and seventh minutes of voice oral high-frequency oscillation practice accomplished with the Shaker® device., Methodology: Twenty-seven women aged between 18 and 41 years with and without vocal complaint participated in the study. The sustained vowel / ε / was recorded at maximum phonation time before (pre-exercise) and after the first, third, fifth and seventh minutes of voice oral high-frequency oscillation practice accomplished with Shaker®. The acoustic analysis of the following parameters was performed: noise, fundamental frequency, glottal to noise excitation, Jitter, Shimmer and number of harmonics., Results: There were no significant differences in the comparison of the acoustic parameters between the participants with and without vocal symptoms. It was observed an improvement in the self-perception of vocal discomfort in the groups of women with and without vocal symptoms, comparing the moment before the practice with the first and third minutes of practice. There was a reduction in Jitter values when comparing the time before practice with the moments after one and seven minutes and when comparing the moments after five and seven minutes of exercise in the group of women with vocal symptoms., Conclusion: The Shaker® technique showed positive results both in individuals with symptoms and in individuals without vocal symptoms.

Objective: The objective of this study was to evaluate if noise interferes with the vocal dose in women without vocal complaints., Study Design: This is an experimental and comparative study., Methods: Data were collected on 27 women between 22 and 50 years of age without vocal complaints in a university classroom. Speech-language pathology evaluation was performed employing auditory-perceptual analysis and a vocal symptom questionnaire. The acoustics of the classroom were evaluated via both observation of the characteristics of the room and the quantification of background noise and reverberation time. Two distinctive acoustic conditions were created for evaluations: condition 1, a room without acoustic treatment and without noise reproduction, and condition 2, a room without acoustic treatment with noise reproduction. Each participant was evaluated individually in both acoustic conditions. To obtain vocal dose data, a vocal dosimeter was used. Subjects were asked to perform two 10-minute readings, one in each acoustic condition. The order of conditions was randomized between subjects. Subjects were instructed to complete the reading tasks at the vocal intensity deemed appropriate to be heard by a listener in the back of the room. t Tests and the Wilcoxon test were employed to compare parameters across subjects and conditions., Results: Fundamental frequency, vocal intensity, percentage of phonation, and cycle dose significantly increased in the background noise condition., Conclusion: A positive relation between vocal dose and the presence of excessive noise in the environment was observed., (Copyright © 2019 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The vestibular evoked myogenic potential triggered by galvanic vestibular stimulation (galvanic-VEMP) has been used to assess the function of the vestibulospinal motor tract and is a candidate biomarker to predict and monitor the human T-cell lymphotropic virus type 1 (HTLV-1) associated myelopathy (HAM). This study determined the agreement and reliability of this exam., Methods: Galvanic-VEMP was performed in 96 participants, of which 24 patients presented HAM, 27 HTLV-1-asymptomatic carriers, and 45 HTLV-1-negative asymptomatic controls. Galvanic vestibular stimulation was achieved by passing a binaural and bipolar current at a 2 milliamperes (mA) intensity for 400 milliseconds (ms) between the mastoid processes. Galvanic-VEMP electromyographic wave responses of short latency (SL) and medium latency (ML) were recorded from the gastrocnemius muscle. Intrarater (test-retest) and interrater (two independent examiners) agreement and reliability were assessed by standard error of measurement (SEM), coefficient of repeatability (CR), intraclass correlation coefficient (ICC), and Kappa coefficient., Results: In the total sample (n = 96), SL and ML medians were 56 ms (IQR 52-66) and 120 ms (IQR 107-130), respectively. The intrarater repeatability measures for SL and ML were, respectively: SEM of 6 and 8 ms; CR of 16 and 22 ms; ICC of 0.80 (p<0.001) and 0.91 (p<0.001); and a Kappa coefficient of 0.53 (p<0.001) and 0.82 (p<0.001). The interrater reproducibility measures for SL and ML were, respectively: SEM of 3 and 10 ms; CR of 8 and 27 ms; ICC of 0.95 (p<0.001) and 0.86 (p<0.001); and a Kappa coefficient of 0.77 (p<0.001) and 0.88 (p<0.001)., Conclusion: Galvanic-VEMP is a reliable and reproducible method to define the integrity of the vestibulospinal tract. Longitudinal studies will clarify its validity in the clinical context, aimed at achieving an early diagnosis and the monitoring of HAM., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Analyze the effects of the Comprehensive Vocal Rehabilitation Program (CVRP) and the motivational stages during speech therapy in teachers with behavioral dysphonia., Methods: Retrospective, longitudinal, observational study using data from the medical records of 33 teachers regarding auditory-perceptual, acoustic, self-perception analyses and the Voice Handicap Index (VHI-10) protocol in pre- and post-speech therapy situations, and motivational stages of adherence to treatment., Results: Auditory-perceptual assessment of the voice showed that 64.7% of the participants improved voice quality post-speech therapy. Comparison between the pre- and post-speech therapy moments showed that 82.4% of the teachers improved their voice according to self-perception. The VHI-10 showed no statistically significant difference between the pre- and post-speech therapy moments (p=0.879). Acoustic analysis of the voice showed improvement in the means of all evaluated parameters. Statistically significant correlation was observed in the analysis between the pre- and post-speech therapy moments only for the variables maximum phonation time and shimmer. Most of the teachers were at the stage of contemplation on the URICA-VOICE scale. No statistical significance was observed in the correlation analysis between VHI-10, auditory-perceptual assessment of the voice, maximum phonation time, and parameters of acoustic analysis with vocal self-perception of teachers and with auditory-perceptual assessment of voice., Conclusion: The use of CVRP for the treatment of behavioral dysphonia presented positive results in the pre- and post-speech therapy evaluation. As for motivation, the teachers strongly believed in the possibility of facing the problem, but still without much effort to change this situation.

Background: Vestibular-evoked myogenic potential triggered by galvanic vestibular stimulation (galvanic-VEMP) evaluates the motor spinal cord and identifies subclinical myelopathies. We used galvanic-VEMP to compare spinal cord function in individuals infected with human T-cell lymphotropic virus type 1 (HTLV-1) from asymptomatic status to HTLV-1-associated myelopathy (HAM)., Methodology/principal Findings: This cross-sectional study with 122 individuals included 26 HTLV-1-asymptomatic carriers, 26 individuals with possible HAM, 25 individuals with HAM, and 45 HTLV-1-seronegative individuals (controls). The groups were similar regarding gender, age, and height. Galvanic stimuli (duration: 400 ms; intensity: 2 mA) were applied bilaterally to the mastoid processes and VEMP was recorded from the gastrocnemius muscle. The electromyographic parameters investigated were the latency and amplitude of the short-latency (SL) and medium-latency (ML) responses. While SL and ML amplitudes were similar between groups, SL and ML latencies were delayed in the HTLV-1 groups compared to the control group (p<0.001). Using neurological examination as the gold standard, ROC curve showed an area under the curve of 0.83 (p<0.001) for SL and 0.86 (p<0.001) for ML to detect spinal cord injury. Sensibility and specificity were, respectively, 76% and 86% for SL and 79% and 85% for ML. Galvanic-VEMP disclosed alterations that were progressive in HTLV-1-neurological disease, ranging from SL delayed latency in HTLV-1-asymptomatic carriers, SL and ML delayed latency in possible HAM group, to absence of VEMP response in HAM group., Conclusions/significance: The worse the galvanic-VEMP response, the more severe the myelopathy. Galvanic-VEMP alteration followed a pattern of alteration and may be a prognostic marker of progression from HTLV-1-asymptomatic carrier to HAM., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To analyze the voice-related quality of life of children with dysphonia and without voice disorders in a population sample of Belo Horizonte, Minas Gerais state, Brazil., Methods: Study participants were 420 children, 98 with dysphonia and 322 without voice disorders, aged six to 10 years, enrolled in public and private elementary schools. The random sample was divided into two groups: dysphonic children (study group - SG) and children without vocal disorders (control group - CG). Assessment of the children's voices was performed by four voice-expert speech-language pathologists with more than 10 years of experience in this field, using the auditory-perceptual parameter of overall severity of dysphonia graded in four points. The results were analyzed based on the evaluation of children's voices conducted by the speech-language pathologist that presented the highest intra-rater agreement, using the Kappa statistical method. The Pediatric Voice-related Quality-of-Life (PVRQoL) survey was answered by the children's parents/legal guardians. Descriptive statistical analysis of the data was conducted using the Student's t-Test., Results: Of the 420 children evaluated, 98 were dysphonic (SG) and 322 presented no voice alteration (CG). Analysis of the three PVRQoL scores (total, physical, and social-emotional) showed no difference between the groups tested (SG and CG). No difference was observed in PVRQoL values regarding the degree of vocal deviation., Conclusion: Dysphonia does not have a negative impact on the voice-related quality of life of children considering the response of secondary informants.

Both neurons and astrocytes are known to affect local vascular response in the brain following neuronal activity. In order to differentiate the contributions of each cell type to the hemodynamic response during stimulation and resting state, intrinsic optical signal (IOI) was recorded synchronized with fluorescence imaging of calcium concentration sensitive dye Oregon Green BAPTA-1 AM. By changing the stimulation parameters (frequency and duration), it was possible to individually promote neuronal and glial responses and to compare them to levels of oxy (HbO), deoxy (HbR) and total (HbT) hemoglobin concentrations. Finally, resting state recordings were done to investigate the possible correlation between hemoglobin fluctuation and calcium transients, based on different frequency bands associated either with neuronal or glial activity., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

In October 2010, 2-year-old papaya (cv. Hawaii) trees with high incidence of stem rot were observed during a survey conducted in Rio Grande do Norte state, northeastern Brazil. Stems showing reddish brown-to-dark brown symptoms were collected and small pieces (4 to 5 mm) of necrotic tissues were surface sterilized for 1 min in 1.5% NaOCl, washed twice with sterile distilled water, and plated onto potato dextrose agar (PDA) amended with 0.5 g liter -1 streptomycin sulfate. Plates were incubated at 25°C with a 12-h photopheriod for 4 days. Pure cultures with white, fluffy aerial mycelia were obtained by subculturing hyphal tips onto PDA. Identification was made using morphological characteristics and DNA based molecular techniques. Colonies grown on PDA and Spezieller Nährstoffarmer agar (SNA) for 10 days at 25°C with a 12-h photoperiod were used for morphological identification (3). The fungus produced cream sporodochia and two types of spores: microconidia were thin-walled, hyaline, ovoid, one-celled, and 6.8 to 14.6 × 2.3 to 4.2 μm; macroconidia were thick walled, hyaline, slightly curved, 3- to 5-celled, and 25.8 to 53.1 × 3.9 to 5.7 μm. Fifty spores of each type were measured. Rounded, thick-walled chlamydospores were produced, with two to four arranged together. On the basis of morphological characteristics (1), three fungal isolates (CMM-3825, CMM-3826, and CMM-3827) were identified as Fusarium solani (Mart.) Sacc. and were deposited in the Culture Collection of Phytopathogenic Fungi of the Universidade Federal Rural de Pernambuco (Recife, Brazil). Single-spore isolates were obtained and genomic DNA of the isolates was extracted and a portion of the translation elongation factor 1-alpha (EF1-α) gene of the isolates was amplified and sequenced (2). When compared with sequences available in the GenBank and Fusarium-ID databases, DNA sequences of the three isolates shared 99 to 100% sequence identity with F. solani species complex (GenBank Accession Nos. JF740784.1, DQ247523.1, and DQ247017.1). Representative sequences of the isolates were deposited in GenBank (Accession Nos. JQ808499, JQ808500, and JQ808501). Pathogenicity tests were conducted with four isolates on 3-month-old papaya (cv. Hawaii) seedlings. Mycelial plugs taken from the margin of actively growing colonies (PDA) of each isolate were applied in shallow wounds (0.4 cm in diameter) on the stem (center) of each plant. Inoculation wounds were wrapped with Parafilm. Control seedlings received sterile PDA plugs. Inoculated and control seedlings (10 each) were kept in a greenhouse at 25 to 30°C. After 2 weeks, all inoculated seedlings showed reddish brown necrotic lesions in the stems. No symptoms were observed in the control plants. The pathogen was successfully reisolated from symptomatic plants to fulfill Koch's postulates. To our knowledge, this is the first report of F. solani species complex causing papaya stem rot in Brazil. Papaya is an important fruit crop in the northeastern Brazil and the occurrence of this disease needs to be taken into account in papaya production. References: (1) C. Booth. Fusarium Laboratory Guide to the Identification of the Major Species. CMI, Kew, England, 1977. (2) D. M. Geiser et al. Eur. J. Plant Pathol. 110:473, 2004. (3) J. F. Leslie and B. A. Summerell. The Fusarium Laboratory Manual. Blackwell Publishing, Ames, IA, 2006.

Ticks infesting amphibians and reptiles in the State of Pernambuco are reviewed, based on the current literature and new collections recently carried out by the authors. To date, three tick species have been found on amphibians and reptiles in Pernambuco. Amblyomma fuscum appears to be exclusively associated with Boa constrictor, its type host. Amblyomma rotundatum has a relatively low host-specificity, being found on toads, snakes, and iguana. Amblyomma dissimile has been found on a lizard and also small mammals (i.e., rodents and marsupials). New tick-host associations and locality records are given.