Influence of carbonyl cyanide m-chlorophenyl hydrazone on biofilm dynamics, protease, and siderophore production by Burkholderia pseudomallei.

Efflux pump inhibitors are a potential therapeutic strategy for managing antimicrobial resistance and biofilm formation. This article evaluated the effect of carbonyl cyanide m-chlorophenyl hydrazone (CCCP) on the biofilm growth dynamics and the production of virulence factors by Burkholderia pseudomallei. The effects of CCCP on planktonic, growing, and mature biofilm, interaction with antibacterial drugs, and protease and siderophore production were assessed. CCCP MICs ranged between 128 and 256 µM. The CCCP (128 µM) had a synergic effect with all the antibiotics tested against biofilms. Additionally, CCCP reduced (p < .05) the biomass of biofilm growth and mature biofilms at 128 and 512 µM, respectively. CCCP also decreased (p < .05) protease production by growing (128 µM) and induced (p < .05) siderophore release by planktonic cells (128 µM) growing biofilms (12.8 and 128 µM) and mature biofilms (512 µM). CCCP demonstrates potential as a therapeutic adjuvant for disassembling B. pseudomallei biofilms and enhancing drug penetration.

Repurposing approved drugs as potential efflux pump inhibitors in multidrug-resistant Pseudomonas aeruginosa.

Aim: To evaluate the action of promethazine, fluoxetine and carbonyl cyanide 3-chlorophenylhydrazone as efflux pump inhibitors (EPIs) against multidrug-resistant Pseudomonas aeruginosa. Methods: The effect of the compounds was evaluated in planktonic cells and bacterial biofilms. Accumulation tests were performed with ethidium bromide to prove their action as EPIs. Then, they were associated with antimicrobials. Results: Effect on planktonic cells and biofilms was found. Assays with ethidium bromide indicate their action as EPIs. Significant reductions in the metabolic activity of biofilms were observed after the association with the antimicrobials, especially for meropenem. Conclusion: It is possible to prove the action of these compounds as EPIs for P. aeruginosa and demonstrate the relevance of efflux pumps in antimicrobial resistance.

[Box: see text].

Ternary (molybdenum disulfide/graphene)/carbon nanotube nanocomposites assembled via a facile colloidal electrostatic path as electrocatalysts for the oxygen reduction reaction: Composition and nitrogen-doping play a key role in their performance.

Nanocomposites have garnered attention for their potential as catalysts in electrochemical reactions vital for technologies like fuel cells, water splitting, and metal-air batteries. This work focuses on developing three-dimensional (3D) nanocomposites through aqueous phase exfoliation, non-covalent functionalization of building blocks with surfactants and polymers, and electrostatic interactions in solution leading to the nanocomposites assembly and organization. By combining molybdenum disulfide (MoS2) layers with graphene nanoplatelets (GnPs) to form a binary 2D composite (MoS2/GnP), and subsequently incorporating multiwalled carbon nanotubes (MWNTs) to create ternary 3D composites, we explore their potential as catalysts for the oxygen reduction reaction (ORR) critical in fuel cells. Characterization techniques such as X-ray photoelectron spectroscopy, scanning electron microscopy, and X-ray diffraction elucidate material composition and structure. Our electrochemical studies reveal insights into the kinetics of the reactions and structure-activity relationships. Both the (MoS2/GnP)-to-MWNT mass ratio and nitrogen-doping of GnPs (N-GnPs) play a key role on the electrocatalytic ORR performance. Notably, the (MoS2/N-GnP)/MWNT material, with a 3:1 mass ratio, exhibits the most effective ORR activity. All catalysts demonstrate good long-term stability and methanol crossover tolerance. This facile fabrication method and observed trends offer avenues for optimizing composite electrocatalysts further.

Anthraquinones against Cryptococcus neoformans sensu stricto: antifungal interaction, biofilm inhibition and pathogenicity in the Caenorhabditis elegans model.

Introduction. Cryptococcal biofilms have been associated with persistent infections and antifungal resistance. Therefore, strategies, such as the association of natural compounds and antifungal drugs, have been applied for the prevention of biofilm growth. Moreover, the Caenorhabditis elegans pathogenicity model has been used to investigate the capacity to inhibit the pathogenicity of Cryptococcus neoformans sensu stricto.Hypothesis. Anthraquinones and antifungals are associated with preventing C. neoformans sensu stricto biofilm formation and disrupting these communities. Antraquinones reduced the C. neoformans sensu stricto pathogenicity in the C. elegans model.Aim. This study aimed to evaluate the in vitro interaction between aloe emodin, barbaloin or chrysophanol and itraconazole or amphotericin B against growing and mature biofilms of C. neoformans sensu stricto.Methodology. Compounds and antifungal drugs were added during biofilm formation or after 72 h of growth. Then, the metabolic activity was evaluated by the MTT reduction assay, the biomass by crystal-violet staining and the biofilm morphology by confocal laser scanning microscopy. C. neoformans sensu stricto's pathogenicity was investigated using the nematode C. elegans. Finally, pathogenicity inhibition by aloe emodin, barbarloin and chrysophanol was investigated using this model.Results. Anthraquinone-antifungal combinations affected the development of biofilms with a reduction of over 60 % in metabolic activity and above 50 % in biomass. Aloe emodin and barbaloin increased the anti-biofilm activity of antifungal drugs. Chrysophanol potentiated the effect of itraconazole against C. neoformans sensu stricto biofilms. The C. elegans mortality rate reached 76.7 % after the worms were exposed to C. neoformans sensu stricto for 96 h. Aloe emodin, barbaloin and chrysophanol reduced the C. elegans pathogenicity with mortality rates of 61.12 %, 65 % and 53.34 %, respectively, after the worms were exposed for 96 h to C. neoformans sensu stricto and these compounds at same time.Conclusion. These results highlight the potential activity of anthraquinones to increase the effectiveness of antifungal drugs against cryptococcal biofilms.

Frequency of Stroke in Intermediate-Risk Patients in the Long-Term Undergoing TAVR vs SAVR: A Systematic Review and Meta-Analysis.

The aim of this research is to compare the long-term incidence of stroke in intermediate-risk patients who have undergone either transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) procedures. The objective is to identify which method exhibits a higher propensity for stroke occurrence, potentially contributing to disability or stroke-related mortality. We conducted a systematic review and meta-analysis to evaluate the frequency of stroke post-TAVR and SAVR procedures. Data were compiled from a diverse array of research articles, retrieved from the Embase, Cochrane Library, and PubMed databases. Conclusions were derived from the comprehensive analysis of forest plots. The analysis indicates no significant reduction in stroke incidence among patients undergoing TAVR compared to those receiving SAVR. This conclusion, underscored by a P-value of 0.76 and a 95% confidence interval (CI) ranging from 0.80 to 1.17, arises from a careful review of multiple pertinent studies. The meta-analysis of pooled data does not reveal a significant decrease in stroke frequency associated with TAVR. For intermediate-risk patients, both TAVR and SAVR present similar stroke risks, indicating no procedure is inherently safer. Healthcare providers must take this into account when counseling patients, considering each procedure's benefits and drawbacks. This study focuses specifically on intermediate-risk individuals, so results may not apply universally. Further research across different risk categories is needed. This study emphasizes the need for individualized patient care and informed decision-making in aortic stenosis management.

Antifungal Activity of Chitosan against Histoplasma capsulatum in Planktonic and Biofilm Forms: A Therapeutic Strategy in the Future?

Histoplasmosis is a respiratory disease caused by Histoplasma capsulatum, a dimorphic fungus, with high mortality and morbidity rates, especially in immunocompromised patients. Considering the small existing therapeutic arsenal, new treatment approaches are still required. Chitosan, a linear polysaccharide obtained from partial chitin deacetylation, has anti-inflammatory, antimicrobial, biocompatibility, biodegradability, and non-toxicity properties. Chitosan with different deacetylation degrees and molecular weights has been explored as a potential agent against fungal pathogens. In this study, the chitosan antifungal activity against H. capsulatum was evaluated using the broth microdilution assay, obtaining minimum inhibitory concentrations (MIC) ranging from 32 to 128 µg/mL in the filamentous phase and 8 to 64 µg/mL in the yeast phase. Chitosan combined with classical antifungal drugs showed a synergic effect, reducing chitosan's MICs by 32 times, demonstrating that there were no antagonistic interactions relating to any of the strains tested. A synergism between chitosan and amphotericin B or itraconazole was detected in the yeast-like form for all strains tested. For H. capsulatum biofilms, chitosan reduced biomass and metabolic activity by about 40% at 512 µg/mL. In conclusion, studying chitosan as a therapeutic strategy against Histoplasma capsulatum is promising, mainly considering its numerous possible applications, including its combination with other compounds.

Chitosan microparticles loaded with essential oils inhibit duo-biofilms of Candida albicans and Streptococcus mutans

Abstract Oral candidiasis is a common fungal infection that affects the oral mucosa, and happens when Candida albicans interacts with bacteria in the oral microbiota, such as Streptococcus mutans, causing severe early childhood caries. C. albicans and S. mutans mixed biofilms are challenging to treat with conventional antimicrobial therapies, thus, new anti-infective drugs are required. Objective This study aimed to test a drug delivery system based on chitosan microparticles loaded with geranium and lemongrass essential oils to inhibit C. albicans and S. mutans mixed biofilms. Methodology Chitosan microparticles loaded with essential oils (CM-EOs) were obtained by spray-drying. Susceptibility of planktonic were performed according CLSI at 4 to 2,048 µg/mL. Mixed biofilms were incubated at 37ºC for 48 h and exposed to CM-EOs at 256 to 4,096 µg/mL. The antimicrobial effect was evaluated using the MTT assay, with biofilm architectural changes analyzed by scanning electron microscopy. RAW 264.7 cell was used to evaluate compound cytotoxicity. Results CM-EOs had better planktonic activity against C. albicans than S. mutans. All samples reduced the metabolic activity of mixed C. albicans and S. mutans biofilms, with encapsulated oils showing better activity than raw chitosan or oils. The microparticles reduced the biofilm on the slides. The essential oils showed cytotoxic effects against RAW 264.7 cells, but encapsulation into chitosan microparticles decreased their toxicity. Conclusion This study demonstrates that chitosan loaded with essential oils may provide an alternative method for treating diseases caused by C. albicans and S. mutans mixed biofilm, such as dental caries.

Prevalência do consumo de bebidas alcoólicas e fatores associados em população adulta / Prevalencia del consumo de bebidas alcohólicas y factores asociados en población adulta / Prevalence of alcohol drink consumption and associated factors in the adult population

RESUMO Objetivo: estimar a prevalência do consumo de álcool e fatores associados em população adulta, assistida na Atenção Primária à Saúde, de uma capital do Nordeste brasileiro. Método: estudo de corte transversal, realizado com 391 adultos, faixa etária de 20 a 59 anos, atendidos pelas Equipes de Saúde da Família do Município de Teresina, Piauí. Os dados foram obtidos por meio de entrevistas estruturadas no período de Abril a Julho de 2019 e analisados no SPSS versão 20.0. Resultados: a amostra foi composta majoritariamente por mulheres, idade de 30 a 39 anos, escolarizados, mas sem trabalho, com filhos, e religiosos. A prevalência do consumo de álcool foi de 59,3%, dos quais 15,3% fizeram uso de risco, 2,1% uso nocivo e 3,1% apresentaram possível dependência. Houve associação estatisticamente significativa entre consumo de álcool e as variáveis independentes: sexo, faixa etária e trabalho. Conclusão: os resultados mostram elevada prevalência do consumo de álcool associado a homens, apesar da predominância de mulheres, adultos jovens e com trabalho. Considerando os malefícios que o consumo nocivo provoca, destaca-se a importância da aplicação rotineira de instrumentos durante as consultas realizadas na Atenção Primária que identifiquem o padrão de consumo de álcool, permitindo uma intervenção precoce e eficaz.

RESUMEN Objetivo: estimar la prevalencia del consumo de alcohol y factores asociados en población adulta, asistida en la Atención Primaria a la Salud, de una capital del Nordeste brasileño. Método: estudio de corte transversal, realizado con 391 adultos, franja de edad de 20 a 59 años, atendidos por los Equipos de Salud de la Familia del Municipio de Teresina, Piauí-Brasil. Los datos fueron obtenidos por medio de entrevistas estructuradas en el período de abril a julio de 2019 y analizados en elSPSS versión 20.0. Resultados: la muestra fue compuesta mayoritariamente por mujeres, edad de 30 a 39 años, escolarizados, pero sin trabajo, conhijos, y religiosos. La prevalencia del consumo de alcohol fue de 59,3%, del cual 15,3% hizo uso de riesgo, 2,1% uso nocivo y 3,1% presentó posible dependencia. Hubo asociación estadísticamente significativa entre consumo de alcohol ylas variables independentes: sexo, franja de edad y trabajo. Conclusión: los resultados demuestran elevada prevalencia del consumo de alcohol asociado a hombres, apesar de la predominancia de mujeres, adultos jóvenes y con trabajo. Considerando los males que el consumo nocivo provoca, se destaca la importancia de la aplicación rutinaria de instrumentos durante las consultas realizadas en la Atención Primaria que identifiquenel patrón de consumo de alcohol, permitiendo una intervención precoz y eficaz.

ABSTRACT Objective: to estimate the prevalence of alcohol consumption and associated factors in an adult population, assisted in Primary Health Care, in a capital city of Northeastern Brazil. Method: a cross-sectional study, carried out with 391 adults, between 20 and 59 years old, assisted by the Family Health Teams in the city of Teresina, Piauí. Data were obtained through structured interviews from April to July 2019 and analyzed in SPSS version 20.0. Results: The sample was mostly composed of women, between 30 and 39 years old, educated but without a job, with children, and religious. The prevalence of alcohol consumption was 59.3%, of which 15.3% made risky use, 2.1% harmful use, and 3.1% presented possible dependence. There was a statistically significant association between alcohol consumption and the independent variables: gender, age group, and work. Conclusion: the results show a high prevalence of alcohol consumption associated with men, despite the predominance of women, young adults, and those with work. Considering the harmful consumption causes, the importance of the routine application of instruments during consultations carried out in Primary Care that identify the pattern of alcohol consumption is highlighted, allowing for early and effective intervention.

Yeast microbiota of free-ranging amphibians and reptiles from Caatinga biome in Ceará State, Northeast Brazil: High pathogenic potential of Candida famata / Leveduras da microbiota de anfíbios e répteis do bioma Caatinga no Ceará, Nordeste do Brasil: alto potencial patogênico de Candida famata

ABSTRACT: Studies on the fungal microbiota of reptiles and amphibians are necessary to better understand of host-microbe interactions and the establishment of fungal disease in these animals. However, these studies are limited. The present researchidentified yeasts from free-ranging reptiles and amphibians from the Caatinga biome andevaluated the virulence factors production, the antifungal susceptibility in planktonic and biofilm growth and the pathogenicity of Candida famata isolates. Twenty-nine isolates of the genera Candida, Cryptococcus and Rhodotorula were identified by phenotypic and/or molecular methods and production of hydrolytic enzymes in vitro by these genera of fungi was evaluated. In addition, susceptibility of planktonic cells and biofilms to azoles and amphotericin B was evaluated. The pathogenicity of C. famata, the most prevalent yeast species isolated, was evaluated using Caenorhabditis elegans model. C. famata was the most prevalent yeast in amphibian and reptilian microbiota. Phospholipase and protease production was observed in 18/29 and 11/29 of the yeast isolates, respectively, while 100% formed biofilms. Itraconazole presented high minimal inhibitory concentrations against C. famata and C. tropicalis. Amphotericin B reduced the biomass and metabolic activity of biofilms. C. famata induced the mortality of C. elegans. In conclusion, reptiles and amphibians are colonized by yeasts capable of producing important virulence factors, especially by Candida spp. that present low susceptibility to azoles which may result from imbalances in ecosystem. Finally, C. famata isolated from these animals presented high pathogenicity, showing the importance of the study of reptile and amphibians fungal microbiota.

RESUMO: Estudos sobre a microbiota fúngica de répteis e anfíbios são necessários para melhor compreender as interações hospedeiro-microrganismo e o estabelecimento de doenças fúngicas nesses animais. No entanto, esses estudos são limitados. O objetivo da presente pesquisa foi identificar leveduras isoladas de répteis e anfíbios do bioma Caatinga e avaliar a produção de fatores de virulência, a sensibilidade a antifúngicos no crescimento planctônico e de biofilme e a patogenicidade de Candida famata. Vinte e nove isolados dos gêneros Candida, Cryptococcus e Rhodotorula foram identificados por métodos fenotípicos e/ou moleculares e a produção de enzimas hidrolíticas in vitro por esses gêneros de fungos foi avaliada. Além disso, foi avaliada a suscetibilidade de células planctônicas e biofilmes a azólicos e anfotericina B. A patogenicidade de C. famata, a espécie de levedura isolada mais prevalente, foi avaliada usando Caenorhabditis elegans. C. famata foi a levedura mais prevalente na microbiota de anfíbios e répteis. A produção de fosfolipase e protease foi observada em 18/29 e 11/29 dos isolados de levedura, respectivamente, enquanto 100% formaram biofilmes. O itraconazol apresentou altas concentrações inibitórias mínimas contra C. famata e C. tropicalis. A anfotericina B reduziu a biomassa e atividade metabólica dos biofilmes. C. famata induziu a mortalidade de C. elegans. Em conclusão, répteis e anfíbios são colonizados por leveduras capazes de produzir importantes fatores de virulência, especialmente por cepas de Candida spp. que apresentam baixa suscetibilidade a azólicos que podem resultar de desequilíbrio no ecossistema. Por fim, C. famata isolados desses animais apresentaram alta patogenicidade, mostrando a importância do estudo da microbiota fúngica de répteis e anfíbios.

Age estimation in Brazilian adults by Kvaals and Camerieres methods

Abstract The aim of this study was to verify the precision and applicability of two methods of age estimation, Kvaal's and Cameriere's methods, among Brazilian adults. A sample composed of periapical radiographs of canine teeth belonging to 320 Brazilian adults was analyzed, divided into groups according to sex (male and female) and age group (20-29 years, 30-39 years, 40-49 years and 50-59 years). Kvaal's method presented better results when compared to the results of Cameriere's method in the general evaluation of each canine tooth, except for the upper left canine (tooth 23), which presented a mean error (ME) with no statistically significant difference between the methods (Kvaal: ME = 7.43, p = 0.4991, Cameriere: ME = 7.55, p = 0.6982). In the evaluation by age groups, Kvaal's method presented a lower variation between the real age and estimated age when applied to the age groups of 20-29 years and 30-39 years compared to the results provided by Cameriere's method. With respect to the groups aged 40 to 49 years and 50 to 59 years, Cameriere's method presented better performance than the results provided by Kvaal's method. The methods of estimating age proposed by Kvaal and Cameriere are simple and nondestructive and have demonstrated reproducibility and reliability. The Kvaal method was more accurate for the age groups of 20-29 and 30-39 years, and for those over 40 years, the Cameriere method was the most accurate.

A census of laparoscopic and robotic urological practice: a survey of minimally invasive surgery department of the Brazilian Society of Urology

ABSTRACT Minimally invasive urologic surgery has been developing in Brazil and now is a routine part of care in many regions and patients with different conditions benefit from it. Training in laparoscopic and robotic surgery has evolved and concerns exist both over the quality of surgical training and the practical effect on results of the urological training. This is an unprecedented study which undertook a census to determinate the current state of laparoscopic and robotic urological practice and to know the mains barriers to adequate practice in Brazil. In august 2017, surveys, consisting of an anonymous questionnaire with 15 questions, were sent via internet to the mailing list of the Brazilian Society of Urology (SBU). With these data, activities related to laparoscopy and robotic surgery of our urologists and the mains difficulties and barriers to practice laparoscopy and robotic surgery were evaluated. In our survey, 413 questionnaires were completed. Majority of the responders were currently working in the southeast region of Brazil (52.1%) and 75.5% of the surgeons performed laparoscopic surgery while, only 12.8%, robotic surgery. The lack of experience on the technique and the lack of equipment were the mains barriers and difficulties for not executing laparoscopic and robotic surgeries, respectively. Proper longitudinal training and access to good equipment in minimally invasive surgery are still barriers for urologists in our country.

Effect of temperature and substrate moisture on group survival of Constrictotermes sp. (Isoptera: Termitidae) under laboratory conditions

ABSTRACT Laboratory bioassays should be performed under appropriate conditions that minimize stress and promote greater longevity to tested animals. For social insects, for instance, the stress triggered by removal individuals from nests may result in changes in their survival and behavior. Here we analyzed the effects of variations of different combinations of temperature and substrate moisture (mL of water/g of nest substrate) on group survival of Constrictotermes sp. (Termitidae: Nasutitermitinae). In general, lower substrate moisture resulted in faster mortality. On the other hand, groups survival longer at a temperature of 26 ºC and under higher substrate moisture (2-3 mL/7 g of nest substrate). The result of this study may contribute to the establishment of bioassay protocols performed with Constrictotermes sp. in the laboratory.

Phenotype-driven strategies for screening Candida parapsilosis complex for molecular identification

Abstract In this study, phenotypic methods presented >80% agreement with the molecular identification of 59 Candida parapsilosis complex. Growth at 15% NaCl or pH 7.0 significantly reduced cfu-counts of Candida orthopsilosis, suggesting these conditions may support the development of phenotypic methods for the differentiation of the cryptic species of C. parapsilosis complex.

Phenotype-driven strategies for screening Candida parapsilosis complex for molecular identification

Abstract In this study, phenotypic methods presented >80% agreement with the molecular identification of 59 Candida parapsilosis complex. Growth at 15% NaCl or pH 7.0 significantly reduced cfu-counts of Candida orthopsilosis, suggesting these conditions may support the development of phenotypic methods for the differentiation of the cryptic species of C. parapsilosis complex.

Terpinen-4-ol, tyrosol, and ß-lapachone as potential antifungals against dimorphic fungi

Abstract This study aimed to evaluate the in vitro antifungal activity of terpinen-4-ol, tyrosol, and β-lapachone against strains of Coccidioides posadasii in filamentous phase (n = 22) and Histoplasma capsulatum in both filamentous (n = 40) and yeast phases (n = 13), using the broth dilution methods as described by the Clinical and Laboratory Standards Institute, to determine the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of these compounds. The mechanisms of action of these compounds were also investigated by analyzing their effect on cell membrane permeability and ergosterol synthesis. The MIC and MFCf these compounds against C. posadasii, mycelial H. capsulatum, and yeast-like H. capsulatum, were in the following ranges: 350-5720 µg/mL, 20-2860 µg/mL, and 40-1420 µg/mL, respectively for terpinen-4-ol; 250-4000 µg/mL, 30-2000 µg/mL, and 10-1000 µg/mL, respectively, for tyrosol; and 0.48-7.8 µg/mL, 0.25-16 µg/mL, and 0.125-4 µg/mL, respectively for β-lapachone. These compounds showed a decrease in MIC when the samples were subjected to osmotic stress, suggesting that the compounds acted on the fungal membrane. All the compounds were able to reduce the ergosterol content of the fungal strains. Finally, tyrosol was able to cause a leakage of intracellular molecules.

Antiretroviral drugs saquinavir and ritonavir reduce inhibitory concentration values of itraconazole against Histoplasma capsulatum strains in vitro

Abstract Recent studies have shown that some drugs that are not routinely used to treat fungal infections have antifungal activity, such as protease inhibitor antiretroviral drugs. This study investigated the in vitro susceptibility of Histoplasma capsulatum var. capsulatum to saquinavir and ritonavir, and its combination with the antifungal itraconazole. The susceptibility assay was performed according to Clinical and Laboratory Standards Institute guidelines. All strains were inhibited by the protease inhibitor antiretroviral drugs. Saquinavir showed minimum inhibitory concentrations ranging from 0.125 to 1 μg mL−1 for both phases, and ritonavir presented minimum inhibitory concentrations ranging from 0.0312 to 4 μg mL−1and from 0.0625 to 1 μg mL−1 for filamentous and yeast phase, respectively. Concerning the antifungal itraconazole, the minimum inhibitory concentration values ranged from 0.0019 to 0.125 μg mL−1 and from 0.0039 to 0.0312 μg mL−1 for the filamentous and yeast phase, respectively. The combination of saquinavir or ritonavir with itraconazole was synergistic against H. capsulatum, with a significant reduction in the minimum inhibitory concentrations of both drugs against the strains (p < 0.05). These data show an important in vitro synergy between protease inhibitors and itraconazole against the fungus H. capsulatum.

Azole resistance in Candida spp. isolated from Catú Lake, Ceará, Brazil: an efflux-pump-mediated mechanism

Abstract Since, there is no study reporting the mechanism of azole resistance among yeasts isolated from aquatic environments; the present study aims to investigate the occurrence of antifungal resistance among yeasts isolated from an aquatic environment, and assess the efflux-pump activity of the azole-resistant strains to better understand the mechanism of resistance for this group of drugs. For this purpose, monthly water and sediment samples were collected from Catú Lake, Ceará, Brazil, from March 2011 to February 2012. The obtained yeasts were identified based on morphological and biochemical characteristics. Of the 46 isolates, 37 were Candida spp., 4 were Trichosporon asahii, 3 were Cryptococcus laurentii, 1 Rhodotorula mucilaginosa, and 1 was Kodamaea ohmeri. These isolates were subjected to broth microdilution assay with amphotericin B, itraconazole, and fluconazole, according to the methodology standardized by the Clinical and Laboratory Standards Institute (CLSI). The minimum inhibitory concentrations (MICs) of amphotericin B, itraconazole, and fluconazole were 0.03125–2 µg/mL, 0.0625 to ≥16 µg/mL, and 0.5 to ≥64 µg/mL, respectively, and 13 resistant azole-resistant Candida isolates were detected. A reduction in the azole MICs leading to the phenotypical reversal of the azole resistance was observed upon addition of efflux-pump inhibitors. These findings suggest that the azole resistance among environmental Candida spp. is most likely associated with the overexpression of efflux-pumps.

Risk Factors for Cardiovascular Disease, Metabolic Syndrome and Sleepiness in Truck Drivers / Fatores de Risco para Doença Cardiovascular, Síndrome Metabólica e Sonolência em Motoristas de Caminhão

Abstract Background: Truck driver sleepiness is a primary cause of vehicle accidents. Several causes are associated with sleepiness in truck drivers. Obesity and metabolic syndrome (MetS) are associated with sleep disorders and with primary risk factors for cardiovascular diseases (CVD). We analyzed the relationship between these conditions and prevalence of sleepiness in truck drivers. Methods: We analyzed the major risk factors for CVD, anthropometric data and sleep disorders in 2228 male truck drivers from 148 road stops made by the Federal Highway Police from 2006 to 2011. Alcohol consumption, illicit drugs and overtime working hours were also analyzed. Sleepiness was assessed using the Epworth Sleepiness Scale. Results: Mean age was 43.1 ± 10.8 years. From 2006 to 2011, an increase in neck (p = 0.011) and abdominal circumference (p < 0.001), total cholesterol (p < 0.001), triglyceride plasma levels (p = 0.014), and sleepiness was observed (p < 0.001). In addition, a reduction in hypertension (39.6% to 25.9%, p < 0.001), alcohol consumption (32% to 23%, p = 0.033) and overtime hours (52.2% to 42.8%, p < 0.001) was found. Linear regression analysis showed that sleepiness correlated closely with body mass index (β = 0.19, Raj2 = 0.659, p = 0.031), abdominal circumference (β = 0.24, Raj2 = 0.826, p = 0.021), hypertension (β = -0.62, Raj2 = 0.901, p = 0.002), and triglycerides (β = 0.34, Raj2 = 0.936, p = 0.022). Linear multiple regression indicated that hypertension (p = 0.008) and abdominal circumference (p = 0.025) are independent variables for sleepiness. Conclusions: Increased prevalence of sleepiness was associated with major components of the MetS.

Resumo Fundamento: A sonolência de motoristas de caminhão, que pode resultar de diferentes causas, é a principal causa de acidentes com veículos. Obesidade e síndrome metabólica (SMet) estão associadas a distúrbios do sono e fatores de risco primários para doença cardiovascular (DCV). Este estudo verificou a relação entre essas condições e a prevalência de sonolência em motoristas de caminhão. Métodos: Este estudo analisou os principais fatores de risco para DCV, dados antropométricos e distúrbios do sono em 2.228 motoristas de caminhão do sexo masculino a partir de informação coletada de 148 paradas efetuadas em rodovias pela Polícia Rodoviária Federal entre 2006 e 2011. Consumo de álcool e de drogas ilícitas e excesso de horas trabalhadas também foram analisados. Sonolência foi avaliada com a Escala de Sonolência de Epworth. Resultados: A idade média foi de 43,1 ± 10,8 anos. De 2006 a 2011, observou-se aumento de: circunferências cervical (p = 0,011) e abdominal (p < 0,001); colesterol total (p < 0,001); níveis séricos de triglicerídeos (p = 0,014); sonolência (p < 0,001). Além disso, houve redução de hipertensão (de 39,6% para 25,9%, p < 0,001), consumo de álcool (de 32% para 23%, p = 0,033) e excesso de horas trabalhadas (de 52,2% para 42,8%, p < 0,001). A análise de regressão linear mostrou correlação íntima de sonolência com índice de massa corporal (β = 0,19, Raj2 = 0,659, p = 0,031), circunferência abdominal (β = 0,24, Raj2 = 0,826, p = 0,021), hipertensão (β = -0,62, Raj2 = 0,901, p = 0,002) e triglicerídeos (β = 0,34, Raj2 = 0,936, p = 0,022). Regressão linear múltipla indicou que hipertensão (p = 0,008) e circunferência abdominal (p = 0,025) são variáveis independentes para sonolência. Conclusões: Elevada prevalência de sonolência foi associada com os principais componentes da SMet.

Simvastatin inhibits planktonic cells and biofilms ofCandida and Cryptococcusspecies

ABSTRACTThe antifungal activity of some statins against different fungal species has been reported. Thus, at the first moment, the in vitro antifungal activity of simvastatin, atorvastatin and pravastatin was tested againstCandida spp. and Cryptococcus spp. Then, in a second approach, considering that the best results were obtained for simvastatin, this drug was evaluated in combination with antifungal drugs against planktonic growth and tested against biofilms ofCandida spp. and Cryptococcus spp. Drug susceptibility testing was performed using the microdilution broth method, as described by the Clinical and Laboratory Standards Institute. The interaction between simvastatin and antifungals against planktonic cells was analyzed by calculating the fractional inhibitory concentration index. Regarding biofilm susceptibility, simvastatin was tested against growing biofilm and mature biofilm of one strain of each tested yeast species. Simvastatin showed inhibitory effect against Candida spp. andCryptococcus spp. with minimum inhibitory concentration values ranging from 15.6 to 1000 mg L-1 and from 62.5 to 1000 mg L-1, respectively. The combination of simvastatin with itraconazole and fluconazole showed synergism against Candidaspp. and Cryptococcus spp., while the combination of simvastatin with amphotericin B was synergistic only againstCryptococcus spp. Concerning the biofilm assays, simvastatin was able to inhibit both growing biofilm and mature biofilm ofCandida spp. and Cryptococcus spp. The present study showed that simvastatin inhibits planktonic cells and biofilms ofCandida and Cryptococcus species.