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The secreted aspartic peptidases (Saps) of Candida albicans play crucial roles in various steps of fungal-host interactions. Using a flow cytometry approach, this study investigated the expression of Saps1-3 antigens after (i) incubation with soluble proteins, (ii) interaction with mammalian cells, and (iii) infection in immunosuppressed BALB/c mice. Supplementation strategies involving increasing concentrations of bovine serum albumin (BSA) added to yeast carbon base (YCB) medium as the sole nitrogenous source revealed a positive and significant correlation between BSA concentration and both the growth rate and the percentage of fluorescent cells (%FC) labeled with anti-Saps1-3 antibodies. Supplementing the YCB medium with various soluble proteins significantly modulated the expression of Saps1-3 antigens in C. albicans. Specifically, immunoglobulin G, gelatin, and total bovine/human sera significantly reduced the %FC, while laminin, human serum albumin, fibrinogen, hemoglobin, and mucin considerably increased the %FC compared to BSA. Furthermore, co-cultivating C. albicans yeasts with either live epithelial or macrophage cells induced the expression of Saps1-3 antigens in 78% (mean fluorescence intensity [MFI] = 152.1) and 82.7% (MFI = 178.2) of the yeast cells, respectively, compared to BSA, which resulted in 29.3% fluorescent cells (MFI = 50.9). Lastly, the yeasts recovered from the kidneys of infected immunosuppressed mice demonstrated a 4.8-fold increase in the production of Saps1-3 antigens (MFI = 246.6) compared to BSA, with 95.5% of yeasts labeled with anti-Saps1-3 antibodies. Altogether, these results demonstrated the positive modulation of Saps' expression in C. albicans by various key host proteinaceous components, as well as by in vitro and in vivo host challenges.

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Background: Dengue virus (DENV) is an arbovirus transmitted by Aedes aegypti mosquitoes, which can cause severe conditions such as hemorrhagic fever and dengue shock syndrome. These conditions are associated with adverse social, clinical, and economic consequences in Brazil. Herein, the Wolbachia mosquito replacement method is a promising dengue control strategy. Methods: We estimated the economic impact of implementing the Wolbachia mosquito replacement method in seven Brazilian cities. A mathematical microsimulation model tracked nearly 23 million inhabitants over a 20-year period, considering the transitions between five different health states (susceptible, inapparent, outpatient, hospitalised and death). Direct costs included local dengue control programs, Wolbachia implementation and dengue care. Indirect costs related to death and productivity loss, as well as disability-adjusted life-years (DALY) averted were also considered. Findings: Without Wolbachia, the model projected 1,762,688 reported dengue cases over 20 years. Implementing the Wolbachia method would avert at least 1,295,566 dengue cases, resulting in lower costs and greater effectiveness in all simulated cities. On average, for every 1000 inhabitants followed for 20 years, the Wolbachia method yielded a cost difference of USD 538,233.68 (BRL 2,691,168.40) and averted 5.56 DALYs. Net monetary benefits (NMB) were positive in all seven cities, ranging from USD 110.72 (BRL 553.59) to USD 1399.19 (BRL 6995.95) per inhabitant. Alternative scenarios have also shown a favourable return on investment with a positive benefit-cost ratio (BCR). Interpretation: Wolbachia is likely a cost-effective strategy in the Brazilian context, consistent with international studies. Sensitivity analysis and alternative scenarios confirmed the robustness of the results. Funding: This study was funded by the Wellcome Trust under a grant (224459/Z/21/Z).

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We conducted a comprehensive comparative analysis of extracellular vesicles (EVs) from two Acanthamoeba castellanii strains, Neff (environmental) and T4 (clinical). Morphological analysis via transmission electron microscopy revealed slightly larger Neff EVs (average = 194.5 nm) compared to more polydisperse T4 EVs (average = 168.4 nm). Nanoparticle tracking analysis (NTA) and dynamic light scattering validated these differences. Proteomic analysis of the EVs identified 1,352 proteins, with 1,107 common, 161 exclusive in Neff, and 84 exclusively in T4 EVs. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) mapping revealed distinct molecular functions and biological processes and notably, the T4 EVs enrichment in serine proteases, aligned with its pathogenicity. Lipidomic analysis revealed a prevalence of unsaturated lipid species in Neff EVs, particularly triacylglycerols, phosphatidylethanolamines (PEs), and phosphatidylserine, while T4 EVs were enriched in diacylglycerols and diacylglyceryl trimethylhomoserine, phosphatidylcholine and less unsaturated PEs, suggesting differences in lipid metabolism and membrane permeability. Metabolomic analysis indicated Neff EVs enrichment in glycerolipid metabolism, glycolysis, and nucleotide synthesis, while T4 EVs, methionine metabolism. Furthermore, RNA-seq of EVs revealed differential transcript between the strains, with Neff EVs enriched in transcripts related to gluconeogenesis and translation, suggesting gene regulation and metabolic shift, while in the T4 EVs transcripts were associated with signal transduction and protein kinase activity, indicating rapid responses to environmental changes. In this novel study, data integration highlighted the differences in enzyme profiles, metabolic processes, and potential origins of EVs in the two strains shedding light on the diversity and complexity of A. castellanii EVs and having implications for understanding host-pathogen interactions and developing targeted interventions for Acanthamoeba-related diseases.IMPORTANCEA comprehensive and fully comparative analysis of extracellular vesicles (EVs) from two Acanthamoeba castellanii strains of distinct virulence, a Neff (environmental) and T4 (clinical), revealed striking differences in their morphology and protein, lipid, metabolites, and transcripts levels. Data integration highlighted the differences in enzyme profiles, metabolic processes, and potential distinct origin of EVs from both strains, shedding light on the diversity and complexity of A. castellanii EVs, with direct implications for understanding host-pathogen interactions, disease mechanisms, and developing new therapies for the clinical intervention of Acanthamoeba-related diseases.

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Up to 25% of pediatric cataract cases are inherited. There is sparse information in the literature regarding the cost of whole-exome sequencing (WES) for suspected hereditary pediatric cataracts. Molecular diagnosis of suspected hereditary pediatric cataracts is important for comprehensive genetic counseling. We performed a partial economic evaluation with a mixed costing analysis, using reimbursement data and microcosting approach with a bottom-up technique to estimate the cost of using WES for genetic diagnosis of suspected hereditary pediatric cataracts from the perspective of the Brazilian governmental health care system. One hundred and ten participants from twenty-nine families in Rio de Janeiro (RJ) were included. Costs of consumables, staff and equipment were calculated. Two scenarios were created: (1) The reference scenario included patients from RJ with suspected hereditary pediatric cataracts plus two family members. (2) The alternative scenario considered other genetic diseases, resulting in 5,280 exams per month. Sensitivity analysis was also performed. In the reference scenario, the total cost per exam was 700.09 United States dollars (USD), and in the alternative scenario, the total cost was 559.23 USD. The cost of WES alone was 527.85 USD in the reference scenario and 386.98 USD in the alternative scenario. Sensitivity analysis revealed that the largest costs were associated with consumables in both scenarios. Economic evaluations can help inform policy decisions, especially in middle-income countries such as Brazil.

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Introducción: La influencia de la clorhexidina sobre la fuerza de unión de los sistemas adhesivos es aún muy controversial. Objetivo: Determinar la fuerza de unión de dos adhesivos universales en dentina previa aplicación de la clorhexidina al 2 % en tiempos de aplicación diferentes. Métodos: Se empleó treinta incisivos y se desgastó la superficie vestibular para exponer la dentina. Posteriormente, se dividió aleatoriamente en seis grupos (n = 5). Se emplearon los adhesivos Single Bond Universal (SBU) y All-Bond Universal (ABU) con/sin clorhexidina. Grupo SBU-0: Single Bond Universal; Grupo SBU-30: clorhexidina por 30 segundos + Single Bond Universal; Grupo SBU-60: clorhexidina por 60 segundos + Single Bond Universal; Grupo ABU-0: All-Bond Universal; Grupo ABU-30: clorhexidina por 30 segundos + All-Bond Universal y Grupo ABU-60: clorhexidina por 60 segundos + All-Bond Universal. La resistencia adhesiva se analizó mediante ANOVA mixto de dos factores y post hoc de Tukey (p < 0,05). Resultados: La fuerza de unión para el grupo SBU-60 aumentó significativamente respecto al grupo control (p = 0,032). Igualmente, para los grupos ABU-30 y ABU-60, la fuerza de unión aumentó significativamente respecto al grupo control (p = 0,001) y (p = 0,000), respectivamente. Conclusión: La aplicación previa de clorhexidina al 2 % durante 60 segundos aumenta la fuerza de unión de los sistemas adhesivos Single Bond Universal y All-Bond Universal.

Introduction: The influence of chlorhexidine on the bond strength of adhesive systems is still very controversial. Objective: To determine the bond strength of two universal adhesives on dentin after application of 2% chlorhexidine at different application times. Methods: Thirty incisors were used and the vestibular surface was abraded to expose the dentin. Subsequently, they were randomly divided into six groups (n = 5). Single Bond Universal (SBU) and All-Bond Universal (ABU) adhesives with/without chlorhexidine were used. Group SBU-0: Single Bond Universal; Group SBU-30: chlorhexidine for 30 seconds + Single Bond Universal; Group SBU-60: chlorhexidine for 60 seconds + Single Bond Universal; Group ABU-0: All-Bond Universal; Group ABU-30: chlorhexidine for 30 seconds + All-Bond Universal and Group ABU-60: chlorhexidine for 60 seconds + All-Bond Universal. Adhesive strength was analyzed by two-factor mixed ANOVA and Tukey's post hoc (p < 0.05). Results: The bond strength for the SBU-60 group increased significantly with respect to the control group (p = 0.032). Similarly, for the ABU-30 and ABU-60 groups, the bond strength increased significantly with respect to the control group (p = 0.001) and (p = 0.000), respectively. Conclusion: Pre-application of 2% chlorhexidine for 60 seconds increases the bond strength of Single Bond Universal and All-Bond Universal adhesive systems.

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We aimed to identify the reports of symptoms of depression, anxiety, and stress among caregivers of children without visual impairment, with low vision, and with blindness and their relationship with the degree of social, emotional, material, and affective support. This cross-sectional and multicenter study was conducted in the municipality of Rio de Janeiro, Brazil, from 2019 to 2020. A questionnaire was applied to obtain caregivers' sociodemographic and economic data. The Medical Outcomes Study Social Support Scale (MOS-SSS) and The Depression, Anxiety, and Stress Scale (DASS-21) were used. Tests were used for multiple comparisons of these scales. The prevalence ratio of symptoms of depression, anxiety, and stress was estimated. Of all caregivers (N = 355), more than 90% were women-mothers. Caregivers of children with visual impairment show the highest proportion of no schooling, incomplete elementary education, or lower average monthly income. Most caregivers of children with blindness reported symptoms of depression, anxiety, and stress (66.7%, 73.3%, and 80%, respectively) as did those of children with low vision. The evaluation of the relationship between MOS-SSS and DASS-21 results shows greater support and lower scores of reports of depression, anxiety, and stress for caregivers of children without disabilities or with less visual impairment. For caregivers of blind children, the highest prevalence of such reports was independent of the received support. Results indicate the need for a care policy with mechanisms to protect the mental health of caregivers of visually impaired children.

O objetivo foi identificar os relatos de sintomas de depressão, ansiedade e estresse entre cuidadores de crianças sem deficiência visual, com baixa visão e com cegueira e sua relação com o grau de apoio social, emocional, material e afetivo. Estudo transversal e multicêntrico, realizado no Município do Rio de Janeiro, Brasil, entre 2019 e 2020. Aplicou-se um questionário para obter dados sociodemográficos e econômicos do cuidador. Foram utilizadas a Escala de Apoio Social (The Medical Outcomes Study Social Support Scale - MOS-SSS) e a Escala de Depressão, Ansiedade e Estresse (The Depression, Anxiety, and Stress Scale - DASS-21). Na comparação entre as escalas, foram utilizados testes para comparações múltiplas. Estimou-se a razão de prevalência de sintomas de depressão, ansiedade e estresse. Do total de cuidadores (N = 355), mais de 90% eram mulheres-mães e a maior proporção de cuidadores sem instrução ou Ensino Fundamental incompleto e com menor renda média mensal foi daqueles de crianças com deficiência visual. A maioria dos cuidadores de crianças com cegueira relatou sintomas de depressão, ansiedade e estresse (respectivamente, 66,7%, 73,3% e 80%), mesmo comportamento observado no grupo de cuidadores de crianças com baixa visão. Na avaliação da relação entre os resultados das escalas MOS-SSS e DASS-21, entre os cuidadores de crianças sem deficiência ou com menor comprometimento visual, observou-se maiores apoios e menores escores de relatos de depressão, ansiedade e estresse. Entre os cuidadores de crianças cegas, as maiores prevalências não dependeram dos apoios recebidos. Os resultados indicam a necessidade de uma política de cuidado com mecanismos de proteção à saúde mental dos cuidadores de crianças com deficiência visual.

El objetivo fue identificar los relatos de síntomas de depresión, ansiedad y estrés entre cuidadores de niños sin discapacidad visual, con baja visión y con ceguera y su relación con el grado de apoyo social, emocional, material y afectivo. Estudio transversal y multicéntrico realizado en la ciudad de Río de Janeiro, Brasil, entre el 2019 y el 2020. Se aplicó un cuestionario para obtener datos sociodemográficos y económicos del cuidador. Se utilizaron la Escala de Apoyo Social (The Medical Outcomes Study Social Support Scale - MOS-SSS) y Escala de Depresión, Ansiedad y Estrés (The Depression, Anxiety, and Stress Scale - DASS-21). Al comparar las escalas, se utilizaron pruebas para comparaciones múltiples. Se estimó la razón de prevalencia de síntomas de depresión, ansiedad y estrés. Del total de cuidadores (N = 355), más del 90% eran mujeres madres y la mayor proporción de cuidadores sin escolaridad o con primaria incompleta y con menor ingreso mensual promedio fueron los de niños con discapacidad visual. La mayoría de los cuidadores de niños con ceguera reportó síntomas de depresión, ansiedad y estrés, respectivamente, 66,7%, 73,3% y 80%, mismo comportamiento observado en el grupo de cuidadores de niños con baja visión. Al evaluar la relación entre los resultados de las escalas MOS-SSS y DASS-21, entre los cuidadores de niños sin discapacidad o con menor compromiso visual, se observó mayor apoyo y menores puntajes de relatos de depresión, ansiedad y estrés. Entre los cuidadores de niños ciegos, la mayor prevalencia de tales relatos no dependió del apoyo recibido. Los resultados indican la necesidad de una Política de Cuidado con mecanismos para proteger la salud mental de los cuidadores de niños con discapacidad visual.

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Objetivo: Comparar o implante transcateter de valva aórtica (TAVI) ao tratamento conservador em pacientes inoperáveis ou à cirurgia de troca valvar (SAVR) em pacientes com risco cirúrgico alto ou intermediário conforme a Society of Thoracic Surgeons (STS), por meio de uma revisão sistemática de avaliações econômicas completas. Avaliar a variabilidade de modelos econômicos, parâmetros, pressupostos e sua influência nos resultados finais. Métodos: Foi realizada uma busca da literatura nas bases Medline, EMBASE, Cochrane Library, Web of Science, SciELO e International HTA Base e busca manual. Foram incluídas análises econômicas completas baseadas em modelos econômicos publicadas entre 2011 e 2022, em português, inglês e espanhol. A qualidade dos estudos foi avaliada usando o instrumento QHES (Quality of Health Economic Studies). Resultados: Foram incluídos 36 estudos, majoritariamente análises de custo-utilidade (64%), da Europa (41%), utilizando dados de eficácia dos estudos PARTNER. O modelo de Markov (61%) foi predominante. O custo da prótese do TAVI foi um parâmetro de impacto na análise de sensibilidade nos três grupos. Os estudos alcançaram uma boa qualidade no instrumento QHES. Conclusão: O TAVI tendeu a ser custo-efetivo em relação aos comparadores. Os modelos não foram homogêneos nos parâmetros, horizontes temporais e taxa de desconto, podendo impactar a custo-efetividade do TAVI e dificultar a comparação dos resultados entre diferentes países e perspectivas.

ABSTRACT Objective: To compare transcatheter aortic valve implantation (TAVI) to conservative treatment in inoperable patients or to valve replacement surgery (SAVR) in patients at high or intermediate surgical risk according to the Society of Thoracic Surgeons (STS), through a systematic review of comprehensive economic evaluations. Evaluate the variability of economic models, parameters, assumptions and their influence on final results. Methods: A literature search was performed in Medline, EMBASE, Cochrane Library, Web of Science, SciELO and International HTA Base and manual search. Complete economic analyzes based on economic models published between 2011 and 2022 in Portuguese, English and Spanish were included. The quality of the studies was evaluated using the QHES (Quality of Health Economic Studies) instrument. Results: Thirty-six studies were included, mostly cost-utility analyses (64%), from Europe (41%), and using efficacy data from the PARTNER studies. The Markov model (61%) was predominant. The cost of the TAVI prosthesis was the most important parameter in the sensitivity analysis in the three groups. The studies achieved a good quality in QHES instrument. Conclusion: TAVI tended to be cost-effective relative to comparators. The models were not homogeneous in parameters, time horizons and discount rate, which may have an impact on the cost-effectiveness of TAVI, making it difficult to compare the results between different countries and perspectives.

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OBJECTIVE: To investigate the tobacco-attributable burden on disease, medical costs, productivity losses and informal caregiving; and to estimate the health and economic gains that can be achieved if the main tobacco control measures (raising taxes on tobacco, plain packaging, advertising bans and smoke-free environments) are fully implemented in eight countries that encompass 80% of the Latin American population. DESIGN: Markov probabilistic microsimulation economic model of the natural history, costs and quality of life associated with the main tobacco-related diseases. Model inputs and data on labour productivity, informal caregivers' burden and interventions' effectiveness were obtained through literature review, surveys, civil registrations, vital statistics and hospital databases. Epidemiological and economic data from January to October 2020 were used to populate the model. FINDINGS: In these eight countries, smoking is responsible each year for 351 000 deaths, 2.25 million disease events, 12.2 million healthy years of life lost, US$22.8 billion in direct medical costs, US$16.2 billion in lost productivity and US$10.8 billion in caregiver costs. These economic losses represent 1.4% of countries' aggregated gross domestic products. The full implementation and enforcement of the four strategies: taxes, plain packaging, advertising bans and smoke-free environments would avert 271 000, 78 000, 71 000 and 39 000 deaths, respectively, in the next 10 years, and result in US$63.8, US$12.3, US$11.4 and US$5.7 billions in economic gains, respectively, on top of the benefits being achieved today by the current level of implementation of these measures. CONCLUSIONS: Smoking represents a substantial burden in Latin America. The full implementation of tobacco control measures could successfully avert deaths and disability, reduce healthcare spending and caregiver and productivity losses, likely resulting in large net economic benefits.

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Trichophyton, Microsporum, Nannizzia and Epidermophyton genera cause dermatophytosis, the most common and highly contagious infectious skin disease. Rio de Janeiro is one of the most visited cities in the Southern Hemisphere, located in the most visited state of Brazil. This retrospective study investigated epidemiological and laboratorial aspects of dermatophytosis in Rio de Janeiro state, Brazil, by using spatiotemporal analysis. More than half of all individuals were infected by one or more dermatophytes. A variation between 18 and 106 years-old of the studied population was verified, and women more frequently affected. Patients were more frequently infected by Trichophyton spp., most of them T. rubrum, followed by T. mentagrophytes. M. canis and N. gypsea were more frequently isolated in the age group between 40 and 60 years old, while T. rubrum predominates among younger patients. All species presented homogeneous distribution while T. tonsurans appears to be restricted to the Rio de Janeiro capital and E. floccosum to the municipality of Macaé (190 Km apart from RJ). Rio de Janeiro state presented spatial clusters of dermatophytosis with high density in Guanabara Bay (E. floccosum, M. canis, N. gypsea, T. tonsurans) and Niterói (T. rubrum, T. mentagrophytes) but low density in Macaé (E. floccosum). Significant spatiotemporal clusters on dermatophytosis cases were detected in distinct municipalities (p-value ≤ 0.05). The Vulnerability Index (r = 0.293) and Demographic Density (r = 0.652) distributed according to neighborhoods in Niterói were direct related with dermatophytosis cases whereas Income (r = -0.306) was inversely correlated (p-value ≤ 0.05). The dermatophytosis spatiotemporal distinct distribution after two major international events in Rio de Janeiro, Brazil, highlight the pressing need for specific measures of its prevention and controlling. This is particularly relevant in touristic tropical localities which must consider both socio-economical and traveler's medicine variables.

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Resumo O objetivo do estudo foi estimar o custo da implantação de um centro de reprodução humana em um hospital público de referência nacional localizado no Rio de Janeiro. A população elegível foi a de homens e mulheres que possuem diagnóstico das causas mais frequentes de infertilidade. Os itens de custos incluídos foram consultas, exames, equipamentos, recursos humanos e insumos. Os custos foram identificados e quantificados a partir de consulta a clínicas de reprodução assistida, especialistas e literatura. Foram valorados através de bases públicas. A análise dos dados foi realizada através de um modelo de decisão analítico. A perspectiva do estudo foi do SUS provedor. O custo por procedimento na alta complexidade foi de R$ 18.829 para a fertilização in vitro com injeção intracitoplasmática de espermatozoide e de R$ 5.649 para a inseminação artificial. O investimento inicial necessário para funcionamento do centro de alta complexidade para a realização de 480 ciclos foi de R$ 15.903.361 no primeiro ano, o qual incluiu a estruturação do ambiente físico. A estimativa do investimento necessário para a incorporação e manutenção dos serviços no SUS é indispensável para a gestão financeira.

Abstract This study aimed to estimate the cost of implementing a center for assisted human reproduction in a public reference hospital in Rio de Janeiro. The cost analysis was carried out from the perspective of the SUS provider of assistance. The eligible population was men and women diagnosed with the most frequent causes of infertility. The cost items included in primary care and medium complexity were consultations and examinations and in high complexity were equipment, human resources and supplies. Costs were identified and quantified through consultation with assisted reproduction clinics, specialists and literature. They have been valued through public databases. Data analysis was performed using an analytical decision model that included costs of assisted reproduction and effectiveness procedures. The cost per procedure in high complexity was R$ 18,829 for in vitro fertilization with intracytoplasmic sperm injection and R$ 5,649 for artificial insemination. The initial investment required to operate the high complexity center for 480 cycles was R$ 15,903,361 in the first year, which included structuring the physical environment. Estimating the investment required for the incorporation and maintenance of services in SUS is essential for the management of available financial resources.