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Histoplasmosis is a widespread systemic disease caused by Histoplasma capsulatum, prevalent in the Americas. Despite its significant morbidity and mortality rates, no vaccines are currently available. Previously, five vaccine targets and specific epitopes for H. capsulatum were identified. Immunoinformatics has emerged as a novel approach for determining the main immunogenic components of antigens through in silico methods. Therefore, we predicted the main helper and cytotoxic T lymphocytes and B-cell epitopes for these targets to create a potential multi-epitope vaccine known as HistoVAC-TSFM. A total of 38 epitopes were found: 23 common to CTL and B-cell responses, 11 linked to HTL and B cells, and 4 previously validated epitopes associated with the B subunit of cholera toxin, a potent adjuvant. In silico evaluations confirmed the stability, non-toxicity, non-allergenicity, and non-homology of these vaccines with the host. Notably, the vaccine exhibited the potential to trigger both innate and adaptive immune responses, likely involving the TLR4 pathway, as supported by 3D modeling and molecular docking. The designed HistoVAC-TSFM appears promising against Histoplasma, with the ability to induce important cytokines, such as IFN-γ, TNF-α, IL17, and IL6. Future studies could be carried out to test the vaccine's efficacy in in vivo models.

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Histoplasma capsulatum is a thermodymorphic fungus that causes histoplasmosis, a systemic mycosis that presents different clinical manifestations, ranging from self-limiting to acute lung infection, chronic lung infection and disseminated infection. Usually, it affects severely immunocompromised patients although immunocompetent patients can also be infected. Currently, there are no vaccines to prevent histoplasmosis and the available antifungal treatment presents moderate to high toxicity. Additionally, there are few options of antifungal drugs. Thus, the aim of this study was to predict possible protein targets for the construction of potential vaccine candidates and predict potential drug targets against H. capsulatum. Whole genome sequences from four previously published H. capsulatum strains were analyzed and submitted to different bioinformatic approaches such as reverse vaccinology and subtractive genomics. A total of four proteins were characterized as good protein candidates (vaccine antigens) for vaccine development, three of which are membrane-bound and one is secreted. In addition, it was possible to predict four cytoplasmic proteins which were classified as good protein candidates and, through molecular docking performed for each identified target, we found four natural compounds that showed favorable interactions with our target proteins. Our study can help in the development of potential vaccines and new drugs that can change the current scenario of the treatment and prevention of histoplasmosis.

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In recent decades, emerging fungal infections have changed the clinical mycology scenario as a consequence of the advances in medical diagnostics and therapeutic procedures, long hospitalization times, and the growing number of individuals with debilitating chronic diseases and impaired immune systems. This report presents a 19 months old Brazilian female patient who developed a severe fungal sepsis by an uncommon yeast. She was admitted at the intensive care unit with severe pneumonia, bronchopulmonary dysplasia, and weight-for-age z score of less than -2. She remained more than 30 days in the intensive care unit where she had a femoral venous catheter placement, enteral nutrition, broad-spectrum antibiotic therapy, and prophylaxis with fluconazole. Moreover, pericardiocentesis was performed due to cardiac tamponade. She had a previous history of prematurity, cardiac surgery due to patent ductus arteriosus, and a long period of hospital stay. Despite the antifungal prophylaxis, two yeast isolates were recovered from blood and then identified by classical mycological methods and internal transcribed spacer (ITS) sequencing as Wickerhamomyces anomalus. Both isolates exhibited susceptibility to amphotericin B, ketoconazole, itraconazole, voriconazole, and fluconazole. Her clinical state worsened, presenting anasarca, epistaxis, and hemorrhagic suffusions in the mouth, sclera, oliguria, and bradycardia. Two days after the first positive culture, she presented a gradual reduction of the white blood cells count, with severe leukopenia and neutropenia. She died five days after.

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BACKGROUND: Statins are used as cholesterol-lowering drugs and may also have direct antimicrobial effects. OBJECTIVE: To evaluate synergic interactions between simvastatin and both amphotericin B and fluconazole, against environmental strains of Cryptococcus neoformans isolated from captive birds' droppings. DESIGNAND SETTING: Experimental study conducted at Federal University of Piauí, Parnaíba, in collaboration with Federal University of Triângulo Mineiro, Uberaba, Brazil. METHODS: Statin susceptibility tests of Cryptococcus neoformans samples were performed as prescribed in standards. Interactions of simvastatin with amphotericin and fluconazole were evaluated using the checkerboard microdilution method. Presence of these interactions was quantitatively detected through determining the fractional inhibitory concentration index (FICI). RESULTS: Isolates of Cryptococcus neoformans were obtained from 30 of the 206 samples of dry bird excreta (14.5%) that were collected from pet shops and houses. Ten isolates were selected for susceptibility tests. All of them were susceptible to amphotericin and fluconazole. All presented minimum inhibitory concentration (MIC) > 128 µg/ml and, thus, were resistant in vitro to simvastatin. An in vitro synergic effect was shown through combined testing of amphotericin B and simvastatin, such that six isolates (60%) presented FICI < 0.500. Two isolates showed considerable reductions in MIC, from 1 µg/ml to 0.250 µg/ml. No synergic effect was observed through combining fluconazole and simvastatin. CONCLUSION: These results demonstrate that simvastatin should be considered to be a therapeutic alternative, capable of potentiating the action of amphotericin B. However, further studies are necessary to clarify the real effect of simvastatin as an antifungal agent.

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BACKGROUND: Statins are used as cholesterol-lowering drugs and may also have direct antimicrobial effects. OBJECTIVE: To evaluate synergic interactions between simvastatin and both amphotericin B and fluconazole, against environmental strains of Cryptococcus neoformans isolated from captive birds' droppings. DESIGNAND SETTING: Experimental study conducted at Federal University of Piauí, Parnaíba, in collaboration with Federal University of Triângulo Mineiro, Uberaba, Brazil. METHODS: Statin susceptibility tests of Cryptococcus neoformans samples were performed as prescribed in standards. Interactions of simvastatin with amphotericin and fluconazole were evaluated using the checkerboard microdilution method. Presence of these interactions was quantitatively detected through determining the fractional inhibitory concentration index (FICI). RESULTS: Isolates of Cryptococcus neoformans were obtained from 30 of the 206 samples of dry bird excreta (14.5%) that were collected from pet shops and houses. Ten isolates were selected for susceptibility tests. All of them were susceptible to amphotericin and fluconazole. All presented minimum inhibitory concentration (MIC) > 128 µg/ml and, thus, were resistant in vitro to simvastatin. An in vitro synergic effect was shown through combined testing of amphotericin B and simvastatin, such that six isolates (60%) presented FICI < 0.500. Two isolates showed considerable reductions in MIC, from 1 µg/ml to 0.250 µg/ml. No synergic effect was observed through combining fluconazole and simvastatin. CONCLUSION: These results demonstrate that simvastatin should be considered to be a therapeutic alternative, capable of potentiating the action of amphotericin B. However, further studies are necessary to clarify the real effect of simvastatin as an antifungal agent.

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Trypanosoma cruzi and Helicobacter pylori (HP) are pathogens that cause chronic diseases and have been associated with hypergastrinemia. The aim of this study was to evaluate the fasting gastrin levels in patients with different clinical forms of Chagas disease (CD), coinfected or not by HP. The enrolled individuals were outpatients attending at the university hospital. HP infection was assessed by serology and 13 C-urea breath test. Fasting serum gastrin concentration was measured by chemiluminescence assay. Gastric endoscopic and histological features were also evaluated. Associations between CD and serum gastrin level were evaluated in a logistical model, adjusting for age, gender and HP status. A total of 113 patients were evaluated (45 with Chagas disease and 68 controls). In the multivariate analysis, increasing serum gastrin levels (OR= 1.02; 95% CI= 1.01-1.12), increasing age (OR= 1.05; 95% CI= 1.02 - 1.09) and HP-positive status (OR = 2.88; 95% CI = 1.10 - 7.51) remained independently associated with CD. The serum gastrin levels were significantly higher in the group of patients with the cardiodigestive form ( P = 0.03) as well as with digestive form ( P = <0.001) of Chagas disease than in the controls. In conclusion, patients with cardiodigestive and digestive clinical forms of CD have increased basal serum gastrin levels in comparison with controls. Moreover, we also demonstrated that H. pylori coinfection contributes to the hypergastrinemia shown in CD.

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Objective: This study aimed to evaluate the physical and social factors that influence the quality of life of patients with chronic kidney disease (CKD) on hemodialysis (HD). Study Design: Descriptive and cross-sectional. Methods: There were 149 patients with CKD routinely submitted to HD that answered a questionnaire adapted (Medical Results Survey; SF-36) about the presence of symptoms during and after the HD sessions, main diseases concomitant, and the presence of factors that influence the quality of life. Results: According to the multivariate analysis, the presence of symptoms after the HD contributes to a decrease in the quality of life (p=0.04). However, emotional well-being was positively associated with social activities (p=0.01). The daily activities and the absence of concomitant diseases are associated with good health and, therefore, a better quality of life for patients with CKD (p<0.05). Patients with chronic diseases such as hypertension and diabetes should be better observed, since such illnesses are always associated with renal dysfunction. Conclusion: The results of the present study demonstrate that the chronic renal patients should be inserted into social environments and should perform daily activities despite the limitations of the treatment since an active lifestyle contributes positively to their well-being and quality of life (AU)

Objetivo: O objetivo deste estudo foi avaliar os fatores físicos e sociais que influenciam a qualidade de vida de pacientes com doença renal crônica (DRC) em hemodiálise (HD). Modelo de estudo: Descritivo e transversal. Métodos: Foram incluídos 149 pacientes com DRC rotineiramente submetidos a HD que responderam ao questionário adaptado (Medical Results Survey; SF-36) sobre a presença de sintomas durante e após as sessões de HD, principais doenças concomitantes e presença de fatores que influenciam a qualidade de vida. Resultados: De acordo com a análise multivariada, a presença de sintomas após a HD contribui para uma diminuição da qualidade de vida (p=0,04). Entretanto, o bem-estar emocional foi positivamente relacionado com as atividades sociais (p=0,01). As atividades diárias e a ausência de doenças concomitantes estão associadas com uma boa saúde e assim, a uma melhor qualidade de vida dos pacientes com DRC (p<0,05). Pacientes com doenças crônicas como hipertensão e diabetes devem ser melhor acompanhados, uma vez que, estas doenças estão constantemente associadas a disfunção renal. Conclusão: Os resultados do presente estudo demonstram que os pacientes crônicos renais devem ser inseridos no ambiente social e devem realizar atividades cotidianas, apesar das limitações do tratamento, uma vez que um estilo de vida ativo contribui positivamente para a melhora da qualidade de vida. (AU)

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Cryptococcal infections are mainly caused by members of the Cryptococcus neoformans species complex (molecular types VNI, VNII, VNB, VNIV and the AD hybrid VNIII). PCR of the mating type loci and MLST typing using the ISHAM-MLST consensus scheme were used to evaluate the genetic relationship of 102 (63 clinical and 39 environmental) C. neoformans isolates from Uberaba, Brazil and to correlate the obtained genotypes with clinical, antifungal susceptibility and virulence factor data. All isolates were mating type alpha. MLST identified 12 known and five new sequence types (ST). Fourteen STs were identified within the VNI isolates, with ST93 (57/102, 56%) and ST77 (19/102, 19%) being the most prevalent. From the nine VNII isolates previously identify by URA5-RFLP only four (ST40) were confirmed by MLST. The remaining five grouped within the VNB clade in the phylogenetic analysis corresponding to the sequence type ST504. Other two environmental isolates also grouped within VNB clade with the new sequence type ST527. The four VNII/ST40 isolates were isolated from CSF. The two VNIV sequence types (ST11 and ST160) were isolated from blood cultures. Two of six patients evaluated with more than one isolates had mixed infections. Amongst the VNI isolates 4 populations were identified, which showed differences in their susceptibility profiles, clinical outcome and virulence factors. These results reinforce that ST93 is the most prevalent ST in HIV-infected patients in the Southeastern region of Brazil. The finding of the VNB molecular type amongst environmental Brazilian isolates highlights that this genotype is not restricted to the African continent.

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Introdução: Apesar dos avanços científicos e tecnológicos na área de cuidados de saúde, a infecção hospitalar (IH) ainda é considerada como um grave problema de saúde pública. A IH pode ser definida como uma infecção adquirida após a admissão hospitalar do paciente e que se manifesta durante a internação ou após a sua alta. Objetivos: O estudo apresentou como objetivo avaliar o conhecimento dos estudantes técnicos e universitários em saúde sobre as IHs, suas formas de divulgação e prevenção, para promover, assim, a consciência dos riscos relacionados com a má conduta na atividade profissional. Material e Métodos: A coleta de dados foi realizada através de um questionário com questões sobre o assunto, seguido pela apresentação de palestras. Um total de 34 estudantes do ensino superior e 100 estudantes de ensino técnico foi incluído no estudo. Resultados: A definição correta de IH foi observada no primeiro questionário de 33 (97,1%) estudantes do ensino superior e em 86 (86,0%) alunos do ensino técnico, alcançando 100% nos dois casos, após a palestra. Foi observado uma melhora na compreensão dos alunos sobre a importância da diminuição do uso indiscriminado de antibióticos e da contribuição da higienização das mãos para a prevenção da IH, após a palestra, em 85,3% e 87,0% dos estudantes de ensino superior e técnico, respectivamente. Conclusão: Houve um aumento significativo na melhora do conhecimento dos alunos sobre o conceito e causas das IHs após as palestras.(AU)

Introduction: Despite the scientific and technological advances in the field of healthcare, nosocomial infections (NI) remain a serious public health issue. NI can be defined as an infection acquired after hospital admission and manifested during patient hospitalization or after discharge. Objective: To evaluate the knowledge of higher and technical education health students about NI, as well as about dissemination and prevention strategies. Ultimately, it is aimed to promote the awareness of risks related to misconduct in professional practice. Material and Methods: The data were collected using a questionnaire, followed by a lecture. A total of 34 students of higher education and 100 students of technical education were included. Results: A correct definition of NI was reported based on the first questionnaire by 33 (97.1%) students of higher education and 86 (86%) students of technical education. After the lecture, 100% of participants from both groups reported the correct definition of NI. After the lecture, 85.3% and 87% of higher and technical education students, respectively, showed an improved understanding of the importance of decreasing the indiscriminate use of antibiotics as well as of hand hygiene for NI prevention. Conclusion: There was a significant increase in the improvement of students' knowledge about the concept and causes of NI after the lectures. (AU)

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