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When quality of life questionnaires are used as measures of treatment outcomes, it is essential to know how well these can respond to clinical changes. The objective of this study is to examine the responsiveness of the Brazilian-Portuguese version of the Oswestry Disability Index (ODI-Brazil) in subjects with chronic low back pain submitted to a physical therapy program. Thirty subjects with chronic low back pain completed the ODI-Brazil questionnaire, along with an 11-point pain visual analogue scale (Pain VAS), and the Brazilian-Portuguese version of Roland-Morris disability questionnaire before and after the program. All patients also completed a global perception of change Likert scale in condition after the program. This scale was collapsed to produce a dichotomous variable outcome: improved and non-improved. Responsiveness was determined using effect size statistics and receiver operating characteristic curve (ROC curve), with best cut-point analysis. The best change score cut-off was identified when equally balanced sensitivity and specificity was found, as an expression of the minimum clinically important difference (MCID). After treatment, 19 patients considered themselves improved. Both the effect size (0.37) and the area under the ROC curve (0.73) for ODI-Brazil score in relation to global outcome after program indicated that the ODI-Brazil showed responsiveness. The ROC curve for ODI-Brazil was distributed at the upper corners of the diagonal line, indicating that the questionnaire presents discriminative ability. The best cut-off point for ODI-Brazil was approximately 4.45 points (63.2% sensitivity, 81.8% specificity). The Brazilian-Portuguese version of ODI has comparable responsiveness to other commonly used functional status measures and is appropriate for use in chronic low back pain patients receiving conservative care. [ABSTRACT FROM AUTHOR]

The demand for therapeutic proteins is growing annually. Novel approaches for the production of these molecules on a large scale are necessary, especially in plants. Plant laticifers could help provide an in vivo cell system for protein production expression that can reduce costs of production and downstream processing., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: This study aimed to identify COVID-19 cases among people living with HIV (PLWH) in Brazil in 2020, describe their clinical, sociodemographic, and epidemiological profiles, and evaluate the factors associated with disease severity., Methods: This cross-sectional study used secondary data obtained from the Brazilian healthcare system. Probabilistic and deterministic data linkage methods were used to identify coinfected patients. Descriptive statistical analysis was conducted, and factors associated with severe cases were evaluated using Pearson's chi-squared test, Student's t-test, and logistic regression., Results: In 2020, 36,746 coinfections were identified, making it one of the largest coinfection databases described worldwide. In total, 4,502 (12.25%) patients had severe cases and 32,244 (87.75%) had non-severe cases. The covariates age (OR=1.05; 95% CI: 1.05-1.06), nonwhite ethnicity (OR=1.68; 95% CI: 1.56-1.81), history of AIDS diagnosis (OR=1.17; 95% CI: 1.08-1.28), recent HIV diagnosis (OR=5.47; 95% CI: 4.25-7.02), absence of antiretroviral therapy (OR=1.70; 95% CI: 1.57-1.84), CD4+ < 200 (OR=6.41; 95% CI: 5.09-8.08), detectable HIV viral load (OR=2.61; 95% CI: 2.21-3.05), ≥ 1 comorbidity (OR=4.09; 95% CI: 3.79-4.41), and ≥ 4 symptoms were associated with increased severity., Conclusions: Multiple factors were linked to severe COVID-19, including uncontrolled HIV infection, age > 50 years, comorbidities, and racial disparities. This study reinforces the importance of maintaining public policies focused on early HIV diagnosis, access and adherence to treatment, especially for minority ethnic groups, and focusing on premature aging in PLWH.

Background: Auranofin is an approved anti-rheumatic drug that has a broad-range inhibitory action against several microorganisms, including human pathogenic fungi. The auranofin activity against Histoplasma capsulatum, the dimorphic fungus that causes histoplasmosis, has not been properly addressed. Since there are few therapeutic options for this life-threatening systemic mycosis, this study evaluated the effects of auranofin on H. capsulatum growth and expression of virulence factors., Methodology/principal Findings: Minimal inhibitory and fungicidal concentrations (MIC and MFC, respectively) of auranofin against 15 H. capsulatum strains with distinct genetic backgrounds were determined using the yeast form of the fungus and a microdilution protocol. Auranofin activity was also assessed on a macrophage model of infection and on a Tenebrio molitor invertebrate animal model. Expression of virulence-related genes was compared between auranofin treated and untreated H. capsulatum yeast cells using a quantitative PCR assay. Auranofin affected the growth of different strains of H. capsulatum, with MIC and MFC values ranging from 1.25 to 5.0 μM and from 2.5 to >10 μM, respectively. Auranofin was able to kill intracellular H. capsulatum yeast cells and conferred protection against the fungus in the experimental animal model of infection. Moreover, the expression of catalase A, HSP70, superoxide dismutase, thioredoxin reductase, serine proteinase, cytochrome C peroxidase, histone 2B, formamidase, metallopeptidase, Y20 and YPS3 proteins were reduced after six hours of auranofin treatment. CONCLUSIONS/SIGNIFICANCE: Auranofin is fungicidal against H. capsulatum and reduces the expression of several virulence-related genes, which makes this anti-rheumatic drug a good candidate for new medicines against histoplasmosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 de Abreu Almeida et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Over the past two decades, zoonotic sporotrichosis transmitted by naturally infected cats has become hyperendemic in Rio de Janeiro, Brazil. Sporothrix brasiliensis is the main agent involved. However, there are other forms of transmission of sporotrichosis. The aim of this study was to evaluate and associate the epidemiological, clinical and therapeutic data and the susceptibility of Sporothrix spp. to antifungal drugs in 43 non-zoonotic sporotrichosis cases. Forty-three clinical strains of Sporothrix were identified by partial sequencing of the calmodulin gene. An antifungal susceptibility test of amphotericin B, terbinafine, itraconazole, posaconazole and isavuconazole was performed according to the broth microdilution method. Most patients were male (55.8%). Regarding the source of infection, 21 patients (48.8%) reported trauma involving plants and/or contact with soil. Sporothrix brasiliensis was the predominant species (n = 39), followed by S. globosa (n = 3) and S. schenckii (n = 1). Sporothrix brasiliensis was associated with all the sources of infection, reinforcing previous data showing the presence of this species in environmental sources, as well as with all the clinical forms, including severe cases. One clinical strain of Sporothrix brasiliensis was classified as a non-wild-type strain for amphotericin B and another for itraconazole. S. schenckii was classified as non-WT for all the antifungals tested. In this context, it is important to emphasize that non-zoonotic sporotrichosis still occurs in the state of Rio de Janeiro, with S. brasiliensis as the main etiological agent, primarily associated with infections acquired after traumatic inoculation with plants and/or soil contact, followed by S. globosa and S. schenckii . In addition, non-WT strains were found, indicating the need to monitor the antifungal susceptibility profile of these species. It is crucial to investigate other natural sources of S. brasiliensis to better understand this fungal pathogen and its environment and host cycle.

Mucormycosis is a severe fungal infection that demands immediate and decisive intervention upon suspicion. The causative agents of mucormycosis exhibit inherent resistance to echinocandins and voriconazole, and their in vitro susceptibility to terbinafine is highly variable and species-specific. Considering these factors and the limitations of currently available antifungal therapies, the identification of novel antifungals with potent activity against mucormycosis is of paramount importance. This study aims to identify compounds from the MMV Pathogen Box® presenting antifungal activity against selected mucormycosis agents and to evaluate their potential synergistic effects when combined with antifungal drugs. A screening of the Pathogen Box® compounds was conducted, isolated or in combination with sub-inhibitory concentrations of amphotericin B, isavuconazole or posaconazole, against a Rhizopus oryzae strain. Hits from the screenings were further evaluated against eight Mucoralean strains for minimal inhibitory and fungicidal concentration determinations and to confirm synergistic interactions using the checkerboard method. Ultrastructural studies were performed using scanning electron microscopy. MMV675968 exhibited fungicidal activity against a R. oryzae strain. All but one Rhizopus spp. strains presented MIC ≤ 1 μg/mL, with a geometric mean of 0.78 μg/mL observed across all isolates for this compound, which did not change significantly the cellular structure of this fungus. The combination screening with antifungal drugs revealed six additional compounds potentially active against the R. oryzae strain, two of them demonstrated proven synergism through the checkerboard assay. This first study with the MMV Pathogen Box® and Zigomycetes highlights promising new treatment options for mucormycosis in the future., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

Chromoblastomycosis (CBM) and pheohyphomycosis (PHM) are the most common implantation mycoses caused by dematiaceous fungi. In the past, flucytosine (5-FC) has been used to treat CBM, but development of resistance is common. Carmofur belongs to the same class as 5-FC and has in vitro inhibitory activity against the main agents of CBM and PHM. The aim of this study was to compare the action of these two pyrimidine analog drugs against CBM and PHM agents. The minimum inhibitory concentration (MIC) and the selectivity index based on cytotoxicity tests of these two drugs against some agents of these mycoses were determined, with carmofur presenting a higher selectivity index than 5-FC. Carmofur demonstrated here synergistic interactions with itraconazole and amphotericin B against Exophiala heteromorpha, Fonsecaea pedrosoi, Fonsecaea monophora, and Fonsecaea nubica strains. Additionally, carmofur plus itraconazole demonstrated here synergism against a Phialophora verrucosa strain. To evaluate the development of carmofur resistance, passages in culture medium containing subinhibitory concentrations of this pyrimidine analog were carried out, followed by in vitro susceptibility tests. Exophiala dermatitidis quickly developed resistance, whereas F. pedrosoi took seven passages in carmofur-supplemented medium to develop resistance. Moreover, resistance was permanent in E. dermatitidis but transient in F. pedrosoi. Hence, carmofur has exhibited certain advantages, albeit accompanied by limitations such as the development of resistance, which was expected as with 5-FC. This underscores its therapeutic potential in combination with other drugs, emphasizing the need for a meticulous evaluation of its application in the fight against dematiaceous fungi., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Background: Sporothrix brasiliensis causes sporotrichosis, an important infection in some groups of patients. Aims: This work was designed to investigate the effects of isavuconazole against this species. Methods: An antifungal susceptibility test was performed to compare MIC values with other antifungal drugs used to treat sporotrichosis. A checkerboard assay was performed to understand isavuconazole interactions. Furthermore, isavuconazole growth inhibition on an itraconazole-resistant strain was tested. Results: Isavuconazole had similar MICs to other azoles against S. brasiliensis , presenting fungistatic activity. Isavuconazole did not interact in vitro with antifungals or immunosuppressive drugs and inhibited the growth of an itraconazole-resistant strain. Conclusion: Isavuconazole inhibits S. brasiliensis , its pharmacologic characteristics make it a candidate for patients with sporotrichosis and it may be useful to combat sporotrichosis caused by resistant isolates.

Background: Eliminating mother-to-child transmission (MTCT) of HIV, hepatitis B, and syphilis is a challenge in Brazil. Many policies have been implemented since 1986, but important gaps remain. This study aimed to describe the trends of MTCT in Brazil and evaluate the gaps and perspectives in this scenario., Methods: This is a descriptive study conducted with secondary data publicly available in the information systems of the Brazilian Ministry of Health regarding data on HIV, syphilis, and hepatitis B in pregnant women and children from 2011 to 2021., Results: HIV and hepatitis B have had constant rates over the years in pregnant women, with the detection rates around 2.5/1,000 live birth (LB) and 0.5/1.000LB, respectively. The same did not happen with syphilis, which has shown an increasing line in the last decade. In 2011, the detection rate of syphilis in pregnancy was 4.7/1,000LB, and in 2021 it reached 27.1/1,000LB. Regarding the trends in children, an important decrease was observed in HIV/AIDS (incidence rate from 0.18/1,000 in 2011 to 0.04/1,000 in 2021) and Hepatitis B (incidence rate from 0.9/1,000LB in 2011 to 0.5/1,000LB in 2021). For congenital syphilis, there is a continuous increase, being 3.3/1,000LB in 2011 and 9.9/1,000LB in 2021. Data from the HIV clinical monitoring showed that antiretroviral treatment coverage among pregnant women identified increased slightly between 2011 and 2021, in Brazil, from 92.3% to 94.3%. For syphilis, 82.5% of pregnant women were treated with benzathine penicillin, and 88.7% in 2011. The historical series of hepatitis B vaccination coverage in children has decreased over the years; it was 96% in 2013 and 76% in 2021., Conclusion: These data show many gaps and some perspectives in the MTCT program in Brazil. The country is close to reaching MTCT HIV elimination, but there are many challenges regarding HBV and syphilis. These data can be used to organize the strategies to improve the Brazilian response to MTCT elimination of HIV, hepatitis B, and syphilis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Miranda, Santos, Coelho, Pascom, de Lannoy, Ferreira, Gaspar, Maciel, Barreira and Pereira.)

Chromoblastomycosis (CBM) is a neglected human implantation mycosis caused by several dematiaceous fungal species. Currently available therapy is usually associated with physical methods, especially surgery, and with high refractoriness. Therefore, drug discovery for CBM is essential. Drug repositioning is a strategy used to facilitate the discovery of new treatments for several diseases. The aim of this study was to discover substances with antifungal activity against CBM agents from a collection of drugs previously approved for use in human diseases. A screening was performed with the NIH Clinical Collection against Fonsecaea pedrosoi . Ten substances, with clinical applicability in CBM, inhibited fungal growth by at least 60%. The minimum inhibitory concentration (MIC) of these substances was determined against other CBM agents, and the benzimidazoles albendazole, mebendazole and thiabendazole presented the lowest MIC values. The selectivity index, based on MIC and cytotoxicity of these substances, revealed albendazole to be more selective. To investigate a possible synergism of this benzimidazole with itraconazole and terbinafine, the chequerboard method was used. All interactions were classified as indifferent. Our current results suggest that benzimidazoles have repositioning potential against CBM agents. Albendazole seems to be the most promising, since it presented the highest selectivity against all dematiaceous fungi tested.

Dried and milled eggplant fruit peel and calyces (PC) and mesocarp, placenta and core (Mes) were utilized as natural sources of valuable chemicals. Pectins were extracted with 0.1 M Na 2 CO 3 (1 h; 23 °C). A high-power ultrasound (US) pretreatment (10 min net time; 12.76 W/cm 2 power intensity) in 10:200 (g/mL) powder:water ratio led to the lowest solvent and energy consumptions after the subsequent 0.1 M Na 2 CO 3 stirring, permitting the highest recoveries of uronic acid (UA) from PC and Mes (80.25 and 93.8 %, respectively). Homogalacturonans (>65 % w/w UA) of low degree of methylesterification, of acetylation, and 90,214-138,184 Da molecular weights with low polydispersity (≈1.32-1.40) were obtained. They included released ferulate (≈3.5 mg/100 g) esterified pectins. Antioxidants (caffeoylquinic acid, putrescine and spermidine derivatives, β-carotene, lutein) gave additional technological value to their thickening effect as pectins protected tryptophan, tyrosine, alkyl side chains and sulfhydryl of skim milk proteins from UV-C photo-oxidation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The Trichosporonaceae family comprises a large number of basidiomycetes widely distributed in nature. Some of its members, especially Trichosporon asahii, have the ability to cause human infections. This ability is related to a series of virulence factors, which include lytic enzymes production, biofilm formation, resistance to oxidising agents, melanin and glucuronoxylomannan in the cell wall, metabolic plasticity and phenotypic switching. The last two are poorly addressed within human pathogenic Trichosporonaceae., Objective: These factors were herein studied to contribute with the knowledge of these emerging pathogens and to uncover mechanisms that would explain the higher frequency of T. asahii in human infections., Methods: We included 79 clinical isolates phenotypically identified as Trichosporon spp. and performed their molecular identification. Lactate and N-acetyl glucosamine were the carbon sources of metabolic plasticity studies. Morphologically altered colonies after subcultures and incubation at 37°C indicated phenotypic switching., Results and Conclusion: The predominant species was T. asahii (n = 65), followed by Trichosporon inkin (n = 4), Apiotrichum montevideense (n = 3), Trichosporon japonicum (n = 2), Trichosporon faecale (n = 2), Cutaneotrichosporon debeurmannianum (n = 1), Trichosporon ovoides (n = 1) and Cutaneotrichosporon arboriforme (n = 1). T. asahii isolates had statistically higher growth on lactate and N-acetylglucosamine and on glucose during the first 72 h of culture. T. asahii, T. inkin and T. japonicum isolates were able to perform phenotypic switching. These results expand the virulence knowledge of Trichosporonaceae members and point for a role for metabolic plasticity and phenotypic switching on the trichosporonosis pathogenesis., (© 2022 Wiley-VCH GmbH.)

Histoplasmosis is a frequent mycosis in people living with HIV/AIDS and other immunocompromised hosts. Histoplasmosis has high rates of mortality in these patients if treatment is unsuccessful. Itraconazole and amphotericin B are used to treat histoplasmosis; however, both antifungals have potentially severe pharmacokinetic drug interactions and toxicity. The present study determined the minimal inhibitory and fungicidal concentrations of mebendazole, a drug present in the NIH Clinical Collection, to establish whether it has fungicidal or fungistatic activity against Histoplasma capsulatum . Protein extracts from H. capsulatum yeasts, treated or not with mebendazole, were analyzed by proteomics to understand the metabolic changes driven by this benzimidazole. Mebendazole inhibited the growth of 10 H. capsulatum strains, presenting minimal inhibitory concentrations ranging from 5.0 to 0.08 µM. Proteomics revealed 30 and 18 proteins exclusively detected in untreated and mebendazole-treated H. capsulatum yeast cells, respectively. Proteins related to the tricarboxylic acid cycle, cytoskeleton, and ribosomes were highly abundant in untreated cells. Proteins related to the nitrogen, sulfur, and pyrimidine metabolisms were enriched in mebendazole-treated cells. Furthermore, mebendazole was able to inhibit the oxidative metabolism, disrupt the cytoskeleton, and decrease ribosomal proteins in H. capsulatum . These results suggest mebendazole as a drug to be repurposed for histoplasmosis treatment., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Sporotrichosis is a subcutaneous mycosis with worldwide distribution and caused by eight pathogenic species of the Sporothrix genus. Different ex situ preservation methods are used around the world to maintain the survival, morphophysiological and genetic traits of fungal strains isolated from patients with sporotrichosis for long terms. The main aim of the present study was to evaluate the survival, phenotypic and genotypic stability of Sporothrix strains after preservation on PDA slant stored at 4 °C, sterile water and cryopreservation at -80 °C, for a period of time of 6, 12, 18 and 24 months of storage. Eight clinical Sporothrix isolates were identified based on a polyphasic approach consisting of classical macro- and micro-morphological traits, biochemical assays, proteomic profiles by MALDI-TOF MS and molecular biology. According to the final identification, one strain was identified as S. schenckii (CMRVS 40428) and seven strains were re-identified as S. brasiliensis (CMRVS 40421, CMRVS 40423, CMRVS 40424, CMRVS 40425, CMRVS 40426, CMRVS 40427 and CMRVS 40433). In addition, it was observed that the isolates survived after the different time points of storage in distilled water, PDA slant and cryopreservation at -80 °C. For fungi preserved in water, low polymorphisms were detected by the partial sequencing of β-tubulin. Cryopreservation at -80 °C induced morphological changes in one single isolate. The proteomic profiles obtained by MALDI-TOF MS after preservation showed differences among the methods. In conclusion, preservation on agar slant stored at 4 °C was the most effective method to preserve the eight clinical Sporothrix strains. This method produced less change in the phenotypic traits and kept the genetic integrity of all strains. Agar slant stored at 4 °C is a simple and inexpensive method and can be especially used in culture collections of limited funding and resources.

Background: Black fungi of the Herpotrichiellaceae family are agents of chromoblastomycosis and phaeohyphomycosis. There are few therapeutic options for these infections and it is common to associate antifungal drugs in their treatment., Objectives: To investigate the Medicines for Malaria Venture (MMV) Pathogen Box® for possible compounds presenting synergism with antifungal drugs used to treat black fungal infections., Methods: An initial screening of the Pathogen Box® compounds was performed in combination with itraconazole or terbinafine at sub-inhibitory concentrations against Fonsecaea pedrosoi. Hits were further tested against eight Herpotrichiellaceae using the checkerboard method., Findings: No synergism was observed with terbinafine. MMV687273 (SQ109) and MMV688415 showed synergism with itraconazole against F. pedrosoi. Synergism of these compounds was confirmed with some black fungi by the checkerboard method. SQ109 and itraconazole presented synergism for Exophiala dermatitidis, F. pedrosoi, F. monophora and F. nubica, with fungicidal activity for F. pedrosoi and F. monophora. MMV688415 presented synergism with itraconazole only for F. pedrosoi, with fungicidal activity. The synergic compounds had high selectivity index values when combined with itraconazole., Main Conclusions: These compounds in combination, particularly SQ109, are promising candidates to treat Fonsecaea spp. and E. dermatitidis infections, which account for most cases of chromoblastomycosis and phaeohyphomycosis.

Introduction: HIV incidence estimates are essential to monitor the progress of prevention and control interventions., Methods: Data collected by Brazilian surveillance systems were used to derive HIV incidence estimates by age group (15-24; 25+) and sex from 1986 to 2018. This study used a back-calculation method based on the first CD4 count among treatment-naïve cases. Incidence estimates for the population aged 15 years or over were compared to Global Burden of Disease Study (GBD) estimates from 2000 to 2018., Results: Among young men (15-24 years), HIV incidence increased from 6,400 (95% CI: 4,900-8,400), in 2000, to 12,800 (95% CI: 10,800-15,900), in 2015, reaching incidence rates higher than 70/100,000 inhabitants and an annual growth rate of 3.7%. Among young women, HIV incidence decreased from 5,000 (95% CI: 4,200-6,100) to 3,200 (95% CI: 3,000-3,700). Men aged ≥25 years and both female groups showed significant annual decreases in incidence rates from 2000 to 2018. In 2018, the estimated number of new infections was 48,500 (95% CI: 45300-57500), 34,800 (95% CI: 32800-41500) men, 13,600 (95% CI: 12,500-16,000) women. Improvements in the time from infection to diagnosis and in the proportion of cases receiving antiretroviral therapy immediately after diagnosis were found for all groups. Comparison with GBD estimates shows similar rates for men with overlapping confidence intervals. Among women, differences are higher mainly in more recent years., Conclusions: The results indicate that efforts to control the HIV epidemic are having an impact. However, there is an urgent need to address the vulnerability of young men.

Glucuronoxylomannan (GXM) participates in several immunoregulatory mechanisms, which makes it an important Cryptococcus virulence factor that is essential for the disease. Trichosporon asahii and Trichosporon mucoides share with Cryptococcus species the ability to produce GXM. To check whether other opportunistic species in the Trichosporonaceae family produce GXM-like polysaccharides, extracts from 28 strains were produced from solid cultures and their carbohydrate content evaluated by the sulfuric acid / phenol method. Moreover, extracts were assessed for cryptococcal GXM cross-reactivity through latex agglutination and lateral flow assay methods. Cryptococcus neoformans and Saccharomyces cerevisiae were used as positive and negative controls, respectively. In addition to T. asahii, the species Trichosporon inkin, Apiotrichum montevideense, Trichosporon japonicum, Trichosporon faecale, Trichosporon ovoides, Cutaneotrichosporon debeurmannianum, and Cutaneotrichosporon arboriformis are also producers of a polysaccharide immunologically similar to the GXM produced by human pathogenic Cryptococcus species. The carbohydrate concentration of the extracts presented a positive correlation with the GXM contents determined by titration of both methodologies. These results add several species to the list of fungal pathogens that produce glycans of the GXM type and bring information about the origin of potential false-positive results on immunological tests for diagnosis of cryptococcosis based on GXM detection.

Bloodstream infections (BSI) caused by Candida species are the fourth cause of healthcare associated infections worldwide. Non-albicans Candida species emerged in the last decades as agents of serious diseases. In this study, clinical and microbiological aspects of six patients with BSI due to the Meyerozyma (Candida) guilliermondii species complex from an oncology reference center in Brazil, were evaluated. To describe demographic and clinical characteristics, medical records of the patients were reviewed. Molecular identification of the isolates was performed by ITS1-5.8S-ITS2 region sequencing. Antifungal susceptibility was evaluated by the EUCAST method and the minimal inhibitory concentrations (MIC) assessed according to the epidemiological cutoff values. Virulence associated phenotypes of the isolates were also studied. Ten isolates from the six patients were evaluated. Five of them were identified as Meyerozyma guilliermondii and the others as Meyerozyma caribbica. One patient was infected with two M. caribbica isolates with different genetic backgrounds. High MICs were observed for fluconazole and echinocandins. Non-wild type isolates to voriconazole appeared in one patient previously treated with this azole. Additionally, two patients survived, despite infected with non-wild type strains for fluconazole and treated with this drug. All isolates produced hemolysin, which was not associated with a poor prognosis, and none produced phospholipases. Aspartic proteases, phytase, and esterase were detected in a few isolates. This study shows the reduced antifungal susceptibility and a variable production of virulence-related enzymes by Meyerozyma spp. In addition, it highlights the poor prognosis of neutropenic patients with BSI caused by this emerging species complex., Lay Abstract: Our manuscript describes demographic, clinical and microbiological characteristics of patients with bloodstream infection by the Meyerozyma guilliermondii species complex at a reference center in oncology in Brazil., (© The Author(s) 2020. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Sporotrichosis in immunocompromised patients has a high morbidity and may cause deaths. Particularly, patients with acquired immunodeficiency syndrome (AIDS) with low T CD4 counts develop a chronic disease, with severe and widespread forms. Recently, the ability of Sporothrix brasiliensis, the main agent of zoonotic sporotrichosis, to increase its virulence in a diabetic patient without HIV infection was described. Since it was a unique finding, it is not known how often this occurs in patients with chronic and refractory sporotrichosis. The aim of this study is to compare sequential Sporothrix isolates obtained from patients with sporotrichosis and AIDS in order to detect changes in virulence-related phenotypes and acquisition of antifungal resistance during the evolution of the disease. Fungal growth in different substrates, antifungal susceptibility, thermotolerance, resistance to oxidative stress, and production of hydrolytic enzymes were evaluated. Correlations were assessed between clinical and phenotypic variables. Sixteen isolates, all identified as S. brasiliensis, obtained from five patients were studied. They grew well on glucose and N-acetyl-D-glucosamine, but poorly on lactate. Except from isolates collected from two patients, which were non-wild type for terbinafine, they were considered wild type for the antifungal drugs tested. Thermotolerance of the isolates was moderate to high. Except for phytase and phospholipase, isolates were able to produce virulence-related enzymes on different levels. Changes in all studied phenotypes were observed during the course of the disease in some patients. The results show that the HIV-driven immunosuppression is more relevant than fungal phenotypes on the unfavorable outcomes of disseminated sporotrichosis.

Calotropis procera produces a milky sap containing proteolytic enzymes. At low concentrations, they induce milk-clotting (60 µg/ml) and to dehair hides (0.05 and 0.1%). A protocol for obtaining the enzymes is reported. The latex was mixed with distilled water and the mixture was cleaned through centrifugation. It was dialyzed with distilled water and centrifuged again to recover the soluble fraction [EP]. The dialyze is a key feature of the process. EP was characterized in terms of protein profile, chemical stability, among other criteria. Wild plants belonging to ten geographic regions and grown in different ecological conditions were used as latex source. Collections were carried out, spaced at three-month, according to the seasons at the site of the study. Proteolytic activity was measured as an internal marker and for determining stability of the samples. EP was also analyzed for metal content and microbiology. EP showed similar magnitude of proteolysis, chromatographic and electrophoretic profiles of proteins. Samples stored at 25 °C exhibited reduced solubility (11%) and proteolytic capacity (11%) after six months. Enzyme autolysis was negligible. Microbiological and metal analyses revealed standard quality of all the samples tested. EP induced milk clotting and hide dehairing after storage for up to six months.

Background: Anxiety is almost always present before medical interventions and may play a role in pain perception. We aim to evaluate factors associated with pain intensity reported by patients submitted to Office Hysteroscopy (OH)., Methods: Cross-sectional observational study, with data from April to November 2015. It included patients attended at the Assis Chateaubriand Maternity School (MEAC/UFC) with an indication of office hysteroscopy. Before the examination, the patients answered a validated questionnaire about anxiety (STAI). After the examination, women answered the Visual Analogue Scale (VAS). The data were analyzed using the Statistical Package for the Social Sciences (SPSS) 15.0, with Spearman correlation, Mann-Whitney U-test, and analyses of variance., Results: 252 patients were included, with a mean age of 45.7 years, of whom 29% were postmenopausal (mean pain 5.5) and 71% were in menacme (mean pain 5.1) (p = 0.258). The anxiety trait and state showed a significant influence on the pain scale (p <0.001 and p=0.001), but age or endometrial sample did not. 27% of the patients were nulliparous. Less pain was associated with the number (p=0.01) and vaginal (p=0.005) of deliveries. The main indication for the procedure was abnormal uterine bleeding (54.4%)., Conclusion: OH may be associated with moderate but tolerable discomfort. There was a significant correlation between higher scores on the pain scale and anxiety. There was evidence of reduced pain with parity and type of delivery, but not with reproductive age or endometrial biopsy.

Microsporum canis is a zoophilic dermatophyte and the most common fungus isolated from dogs and cats worldwide. To invade skin, this pathogen uses different enzymes, which may be associated with virulence, that contribute to the fungal pathogenicity. The aim of this study is to compare the expression of enzymes that may be associated with virulence, and thermotolerance of M. canis strains isolated from dogs, cats, and humans. The in vitro expression of the enzymes keratinase, catalase, urease, hemolysin, and aspartic protease was evaluated in 52 M. canis strains recently isolated from 14 human patients, 12 dogs, 15 symptomatic, and 11 asymptomatic cats. In addition, thermotolerance was assessed by comparative analysis of fungal growth at 25 °C and 35 °C. Keratinase activity was low in 34 and moderate in 18 strains. Aspartic-protease activity was low in 7, moderate in 33, and high in 12 strains. Hemolysin activity was low in 44 and moderate in 8 strains. All strains were classified as low producers of catalase. All but three strains produced urease in vitro, with a broad range of activity. The strains presented in vitro growth at the two studied temperatures were classified as presenting low (36.5%), medium (44.3%), or high (19.2%) thermotolerance. There was no statistically significant difference in the new putative virulence-associated factors studied among the different hosts, which suggests that they may have a similar role on human, cat, and dog infection. Also, no difference was observed between strains isolated from symptomatic and asymptomatic cats. This suggests that these factors have a limited impact on the fate of feline dermatophytosis caused by M. canis.

Competing Interests: The authors have no conflict of interests to declare.

Chromoblastomycosis (CBM) is a chronic subcutaneous mycosis caused by traumatic implantation of many species of black fungi. Due to the refractoriness of some cases and common recurrence of CBM, a more effective and less time-consuming treatment is mandatory. The aim of this study was to identify compounds with in vitro antifungal activity in the Pathogen Box® compound collection against different CBM agents. Synergism of these compounds with drugs currently used to treat CBM was also assessed. An initial screening of the drugs present in this collection at 1 μM was performed with a Fonsecaea pedrosoi clinical strain according to the EUCAST protocol. The compounds with activity against this fungus were also tested against other seven etiologic agents of CBM (Cladophialophora carrionii, Phialophora verrucosa, Exophiala jeanselmei, Exophiala dermatitidis, Fonsecaea monophora, Fonsecaea nubica, and Rhinocladiella similis) at concentrations ranging from 0.039 to 10 μM. The analysis of potential synergism of these compounds with itraconazole and terbinafine was performed by the checkerboard method. Eight compounds inhibited more than 60% of the F. pedrosoi growth: difenoconazole, bitertanol, iodoquinol, azoxystrobin, MMV688179, MMV021013, trifloxystrobin, and auranofin. Iodoquinol produced the lowest MIC values (1.25-2.5 μM) and MMV688179 showed MICs that were higher than all compounds tested (5 - >10 μM). When auranofin and itraconazole were tested in combination, a synergistic interaction (FICI = 0.37) was observed against the C. carrionii isolate. Toxicity analysis revealed that MMV021013 showed high selectivity indices (SI ≥ 10) against the fungi tested. In summary, auranofin, iodoquinol, and MMV021013 were identified as promising compounds to be tested in CBM models of infection., Competing Interests: The authors have declared that no competing interests exist.

Infections caused by Rhodotorula spp. are increasing worldwide. This study identified, through the light of the new taxonomic advances on the subphylum Pucciniomycotina, 16 isolates from blood cultures and compared their antifungal susceptibility on microdilution and gradient diffusion methods. Internal transcriber spacer sequencing identified Rhodotorula mucilaginosa (n = 12), Rhodotorula toruloides (n = 2), Rhodotorula dairenensis (n = 1), and Cystobasidium minutum (n = 1). Amphotericin B was the most effective drug. A good essential agreement was observed on MIC values of amphotericin B and voriconazole determined by the two methods. Therefore, the gradient method is useful for susceptibility tests of R. mucilaginosa against these drugs.

Objective: To analyze the distribution of health care services for viral hepatitis and reported cases of viral hepatitis according to the health regions of Northern Brazil., Method: It is an evaluative, descriptive and quantitative research considering viral hepatitis care services and reported cases in the Northern region of Brazil, using data collected from the National Registry of Health Establishments and the Notifiable Diseases Information System. Descriptive statistics and georeferencing, through software, were used to demonstrate the spatial distribution of services and reported cases., Results: Viral hepatitis health services are distributed in a differentiated way; rapid tests are capillaries in the states; confirmatory tests and treatment are performed in some health regions, with a greater grouping of services in the capitals and their surroundings. Cases were reported across all regions, with areas of higher concentration near services., Conclusion: The availability of services can favor access to prevention, diagnosis and monitoring of cases. However, organizational peculiarities of the health system and services highlight fragilities that have repercussions on the access and entirety of viral hepatitis care.

Objective: The goal of this study was to explore the surveillance data about mandatory reporting diseases, included in the official information systems, and evaluate the historical trend analysis in prisoners in Brazil., Design: A time trends study was performed using secondary data from prisons' health units., Setting: Nationwide representative data of Brazilian prisoners obtained from 2007 to 2014 health and prison information systems database were analysed. These data are carried out by units identified as prison health facilities., Primary Outcome Measures: Diseases diagnosis and individual data were available at the National System of Disease Notification (in Portuguese SINAN), Mortality Information System (in Portuguese SIM) and Prison Registration Systems (in Portuguese INFOPEN and GEO prisons). Analyses of the notification data performed in the SINAN at the national level. SINAN was consolidated with SIM, INFOPEN and GEO prison data., Results: A total of 23 235 cases of compulsory disease notification causing morbidity were reported in prison units in Brazil; of these cases, 20 003 (85.6%) were men and 3362 (14.4%) were women. Over time, the proportion of prisoners increased from 1.92 per 1000 inhabitants in 2007 to 2.77 per 1000 inhabitants in 2014 (rising trend). From a total of 27 states, 12 of them presented a growth in disease notifications, 14 were stable and in only one state was there a decrease in notifications. There was an increase in notifications in the country as a whole. Tuberculosis (64.4%), dengue (9.1%), AIDS (9.0%) and viral hepatitis (5.9%) were among the most frequently reported diseases during the study period., Conclusion: Despite showing stable tendencies, our results show high rates of diseases in Brazilian prisons. Prison health services should not be isolated but integrated into regional and national health and justice systems., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Chromoblastomycosis (CBM) is a difficult-to-treat chronic subcutaneous mycosis. In Brazil, the main agent of this disease is Fonsecaea pedrosoi, which is phenotypically very similar to other Fonsecaea species, differing only genetically. The correct species identification is relevant since different species may differ in their epidemiologic aspects, clinical presentation, and treatment response., Methodology/principal Findings: Partial sequencing of the internal transcribed spacer (ITS) was used to identify twenty clinical isolates of Fonsecaea spp. Their in vitro antifungal susceptibility was determined using the broth microdilution method, according to the M38-A2 protocol. Amphotericin B (AMB), flucytosine (5FC), terbinafine (TRB), fluconazole (FLC), itraconazole (ITC), ketoconazole (KTC), posaconazole (POS), voriconazole (VRC), ravuconazole (RVC), caspofungin (CAS), and micafungin (MFG) were tested. The association between ITC/TRB, AMB/5FC, and ITC/CAS was studied by the checkerboard method to check synergism. The available patients' data were correlated with the obtained laboratory results. Fonsecaea monophora (n = 10), F. pedrosoi (n = 5), and F. nubica (n = 5) were identified as CBM' agents in the study. TRB and VRC were the drugs with the best in vitro activity with minimal inhibitory concentrations (MIC) lower than 0.25 mg/L. On the other hand, FLC, 5FC, AMB, and MFG showed high MICs. The AMB/5FC combination was synergistic for three F. monophora strains while the others were indifferent. Patients had moderate or severe CBM, and ITC therapy was not sufficient for complete cure in most of the cases, requiring adjuvant surgical approaches., Conclusions/significance: F. monophora, the second most frequent Fonsecaea species in South America, predominated in patients raised and born in Rio de Janeiro, Brazil, without cerebral involvement in these cases. TRB, VRC, and the AMB/5FC combination should be further investigated as a treatment option for CBM., Competing Interests: The authors have declared that no competing interests exist.

Background: Paracoccidioidomycosis (PCM) is one of the most important systemic mycoses in Latin America and the leading fungal cause of mortality in non-immunosuppressed individuals in Brazil. However, HIV/PCM co-infection can increase the clinical severity in these co-infected patients. This co-infection is rarely reported in the literature mainly because of the different epidemiological profiles of these infections. Furthermore, PCM is a neglected and non-notifiable disease, which may underestimate the real importance of this disease. The advent of molecular studies on the species of the genus Paracoccidioides has expanded the knowledge regarding the severity and the clinical spectrum in PCM. In this context, the development of studies to describe the association of the Paracoccidioides phylogenetic cryptic species in vulnerable populations, such as HIV-infected patients, appears relevant., Objective: To describe the clinical, epidemiological, therapeutic and prognostic aspects in HIV/PCM co-infected patients, along with the molecular identification of the Paracoccidioides species involved in these cases., Methods: The investigators performed a molecular and clinical retrospective study involving HIV/PCM co-infected patients, from a reference centre for PCM care in the endemic area of Rio de Janeiro, Brazil, from 1998 to 2015. Molecular identification of the fungal strains was done by amplification of partial sequences of arf and gp43 genes., Findings: Of 89 patients diagnosed with PCM by fungal isolation in the culture, a viable isolate was recovered for molecular analysis from 44 patients. Of these 44 patients, 28 (63.6%) had their serum samples submitted for enzyme immunoassay tests for screening of HIV antibodies, and 5 (17.9%) had a positive result. All cases were considered severe, with a variable clinical presentation, including mixed, acute/subacute clinical forms and a high rate of complications, requiring combination therapy. Paracoccidioides brasiliensis S1 was the species identified in all cases., Conclusions: HIV/PCM co-infection can change the natural history of this fungal disease. The authors reinforce the need to include HIV screening diagnostic tests routinely for patients with PCM.

Tinea capitis caused by Microsporum audouinii is reported herein from two Brazilian schoolchildren, which are brothers. Arthroconidia were evidenced on direct examination of scalp hair, and a fungus of the genus Microsporum was isolated from cultures of each patient. The isolated fungi were classified as M. audouinii by visualization of species-specific structures, including: pectinate hyphae, chlamydospores, and fusiform macroconidia, sterile growth with characteristic brown pigment in rice grains, and through DNA sequencing of the internal transcriber spacer region. Patients were refractory to ketoconazole, but the two cases had a satisfactory response to oral terbinafine. All M. audouinii infections described in this century were reviewed, and to our knowledge, this is the first literature description of this species from South America. Misidentification of M. audouinii with Microsporum canis can occur in this area, leading to erroneous data about the occurrence of this species.

This study evaluated the influence of bleaching protocols on intrapulpal temperature and fracture strength of the bleached teeth. Ninety maxillary incisors were assigned to 9 groups (n=10): G1: 35% carbamide peroxide (35% CP), G2: 38% hydrogen peroxide (38% HP), G3: halogen light, G4: LED-laser, G5: 35% CP + halogen light, G6: 38% HP + halogen light, G7: 35% CP + LED-laser, G8: 38% HP + LED-laser, and G9: no treatment (control). Pulp space was widened, a thermocouple was introduced through the apex up to the pulp chamber and the temperature was recorded (°C). The fracture strength (kN) was determined using an Instron machine. Data were analyzed by ANOVA and Tukey's test (p<0.05). The halogen light alone (1.10 ± 0.24) (G3) and associated with 38% HP (1.15 ± 0.30) (G6) produced the highest temperature increase, statistically different (p<0.05) from the other groups. G1 (0.15 ± 0.06) and G6 (0.19 ± 0.07) produced the lowest values, statistically different (p<0.05) from G5 (0.65 ± 0.49). The bleaching protocols increased the temperature, but no increment exceeded the critical value of 5.6°C. Neither 35% CP nor 38% HP or the light sources alone altered the fracture strength of the teeth.

Objective: To evaluate whether treatment of venous congenital vascular malformations with the use of laser technology provides lightening or disappearance of lesions with a high degree of satisfaction reported by patients and observed by the physician., Methods: A retrospective study gathered 26 patients suffering from vascular malformation, of which 73.07% were female and were treated with the PhotoDerm® device. The treatment of vascular malformations needed an average of 6.43 sessions, with intervals of six to eight weeks. Patients included in this study had skin type II (57.40%) and type III (42.30%), according to the Fitzpatric's classification. The mean age ranged from 14 to 61 years, averaging 36.70 years. Data were obtained through the completion of an informed protocol by the patient., Results: High satisfaction rates were reported (96.16%) and only one case (3.84%) was partially satisfied when considering lightening or disappearance of lesions. When evaluated by medical professionals, lesions disappeared in 80.76% and became lighter in 19.24%., Conclusion: The treatment of venous vascular malformations with Photo-Derm® is safe and effective as it offered a high degree of patient satisfaction and good results in the disappearance of the lesions.

Purpose: To study the relationship between topoisomerase IIalpha, active caspase-3 expressions and HPV DNA in uterine cervices with low-grade squamous intraepithelial lesions (LSIL)., Methods: Forty women with LSIL and 32 without cervical neoplasia diagnosed through cytologic and histopathologic examination were evaluated regarding topoisomerase IIalpha and active caspase-3 expressions and HPV DNA detection using PCR (GP5/GP6) in cervicovaginal smears., Results: The mean percentage of cells immunomarked by topoisomerase in the group with LSIL was 11.62% while in the control it was 4.13% (p < 0.0001). In the presence of HPV DNA, topoisomerase expression was higher in the group with productive viral infection than in nonneoplastic tissue (p = 0.004). Caspase-3 expression was observed in 17 patients with LSIL (42.5%) and in five without cervical neoplasia (15.63%)., Conclusion: The use of topoisomerase IIalpha and active caspase-3 in cervical biopsies may help to define the prognosis of HPV cervical infection.

This study evaluated rapid maxillary expansion (RME) dentoskeletal effects by means of computed tomography (CT), comparing tooth tissue-borne and tooth-borne expanders. The sample comprised eight girls aged 11 to 14 years presenting Class I or II malocclusions with posterior unilateral or bilateral crossbite that were randomly divided into two treatment groups, palatal acrylic (Haas-type) and hygienic (Hyrax) expanders. All appliances were activated up to the full seven mm capacity of the expansion screw. The patients were subjected to a spiral CT scan before expansion and after a three-month retention period when the expander was removed. One-millimeter-thick axial sections were scanned parallel to the palatal plane, comprising the dentoalveolar area and the base of the maxilla up to the inferior third of the nasal cavity. Multiplanar reconstruction was used to measure maxillary transverse dimensions and posterior teeth inclination by means of a computerized method. The results showed that RME produced a significant increase in all measured transverse linear dimensions, decreasing in magnitude from dental arch to basal bone. The transverse increase at the level of the nasal floor corresponded to one-third of the amount of screw activation. Tooth-borne (Hyrax) and tooth tissue-borne (Haas-type) expanders tended to produce similar orthopedic effects. In both methods, RME led to buccal movement of the maxillary posterior teeth, by tipping and bodily translation. The second premolars displayed more buccal tipping than the appliance-supporting teeth. The tooth tissue-borne expander produced a greater change in the axial inclination of appliance-supporting teeth, especially first premolars, compared with the tooth-borne expander.

The prototyping is a method for reconstruction of human body segments by computer software. It has been used in neurosurgery for cranial reproduction in patients allowing the programming of surgical procedures and the production of prosthesis to reconstruct bone failures in the skull. We present two cases of cranioplasty performed with the use of acrylic prosthesis constructed by prototyping. After 10 months of follow-up, they do not present signs of infection and show good aesthetic result. The advantages pointed at the literature for this method (reduction of surgical time, easy technical handle, and good aesthetic result) were confirmed.

By direct immunoflurescence, deposits of immunoglubins and complement were investigated at the dermal epidermal junction in skin specimens from 210 patients divided into three groups: A--134 patients without lupus; B--54 patients with Systemic Lupus Erythematosus (SLE); C--22 patients with Discoid Lupus Erythematosus. Twenty two patients from group B were submitted to renal biopsy: 20 of these demonstrated a positive lupus band test and data suggested a positive correlation between the intensity of immunoglobulin and complement deposition at the dermal epidermal junction with more severe renal involvement. The other 32 patients were not submitted to renal biopsy; in sediment and band test, may be of value in the prevision of patients with higher probability of developing more serious renal lesions. Our results revealed a high specificity (85.5%) and sensitivity (87%). Test positivity was uninfluenced by steroid and immunosuppressive therapy. The test appears to be of great interest for use on all patients who fail to meet the criteria for the diagnosis of SLE but whose condition suggest such a diagnosis.

The expression of CR-1 complement receptors on glomerular epithelial cells, was studied in 77 renal biopsies from patients with (74) or without (3) glomerular diseases, employing an anti-CR-1 monoclonal antibody, and an indirect immunoperoxidase technique. Four patterns of CR-1 expression were recognised: normal (18); generally decreased (6); focal/segmental partial loss (44); and complete loss (9). Normal expression was detected in all three biopsies with non-glomerular diseases, and in glomerular diseases with normal glomeruli on light microscopy, but also in several glomerulonephritic biopsies (13), including diffuse proliferative lupus nephritis (1 of 7) and idiopathic membranous nephritis (5 of 14). However, the majority of biopsies from patients with glomerular diseases showed abnormal CR-1 expression (59 of 74), most evident in proliferative biopsies (43 of 49), with or without crescent formation (respectively, 18 of 20 and 25 of 29). Complete loss of CR-1 expression was almost restricted to crescentic biopsies (8 of 9). The abnormal CR-1 expression was unrelated to the presence of capillary immune deposits of Ig or C. More intraglomerular monocytes, assessed by monoclonal antibodies, were encountered in glomerulonephritic biopsies with partial CR-1 loss (median 6.2, P less than 0.05) or complete loss (median 14, P less than 0.03), than in biopsies with normal receptor expression (median 1.4). Thus, changes in glomerular CR-1 expression are frequently seen in many glomerular diseases and are associated with glomerular proliferative changes and monocyte infiltration, but not with the presence of capillary immune deposits.(ABSTRACT TRUNCATED AT 250 WORDS)

Interstitial foam cells are occasionally seen in patients with the nephrotic syndrome. In a group of patients with the nephrotic syndrome we were able to demonstrate that these cells express markers characteristic of the monocyte/macrophage lineage. Their presence was related to the previous duration of proteinuria, but they had no apparent influence on the subsequent evolution of renal function. The mechanisms leading to their presence are unknown.