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Abstract Cryptic fungal pathogens pose disease management challenges due to their morphological resemblance to known pathogens. Here, we investigated the genomes and phenotypes of 53 globally distributed isolates of Aspergillus section Nidulantes fungi and found 30 clinical isolates—including four isolated from COVID-19 patients—were A. latus, a cryptic pathogen that originated via allodiploid hybridization. Notably, all A. latus isolates were misidentified. A. latus hybrids likely originated via a single hybridization event during the Miocene and harbor substantial genetic diversity. Transcriptome profiling of a clinical isolate revealed that both parental subgenomes are actively expressed and respond to environmental stimuli. Characterizing infection-relevant traits—such as drug resistance and growth under oxidative stress—revealed distinct phenotypic profiles among A. latus hybrids compared to parental and closely related species. Moreover, we identified four features that could aid A. latus taxonomic identification. Together, these findings deepen our understanding of the origin of cryptic pathogens.

Background: Approximately 60% of individuals with cystic fibrosis (CF) are affected by Aspergillus fumigatus infection. This condition is correlated with a decline in lung function and is identified as an independent risk factor contributing to hospital admissions among CF patients. This study investigates the dynamic interplay of A. fumigatus within the context of CF patients, tracing its evolution over time, with a specific emphasis on colonization dynamics. Methods: An analysis was conducted on 83 sequential A. fumigatus isolates derived from sputum samples of six patients receiving care at a renowned CF hospital in Brazil. Employing microsatellite genotyping techniques, alongside an investigation into cyp51A gene mutations, this research sheds light on the genetic variations, colonization, and resistance of A. fumigatus within the CF respiratory environment. Results: Our research findings indicate that CF patients can harbor A. fumigatus strains from the same clonal complexes for prolonged periods. Additionally, we identified that clinical isolates have the potential to spread among patients in the same healthcare facility, evidencing hospital contamination. Two patients who underwent long-term Itraconazole treatment did not show phenotypic resistance. However, one of these patients exhibited mutations in the cyp51A gene, indicating the need to monitor resistance to azoles in these patients colonized for long periods by A. fumigatus. We also observed co-colonization or co-infection involving multiple genotypes in all patients over time. Conclusion: This comprehensive examination offers valuable insights into the pathogenesis of A. fumigatus infections in CF patients, potentially shaping future therapeutic strategies and management approaches. This enhanced understanding contributes to our knowledge of A. fumigatus impact on disease progression in individuals with cystic fibrosis. Additionally, the study provides evidence of cross-contamination among patients undergoing treatment at the same hospital.

Background: Aspergillus fumigatus is an important concern for immunocompromised individuals, often resulting in severe infections. With the emergence of resistance to azoles, which has been the therapeutic choice for Aspergillus infections, monitoring the resistance of these microorganisms becomes important, including the search for mutations in the cyp51A gene, which is the gene responsible for the mechanism of action of azoles. We conducted a retrospective analysis covering 478 A. fumigatus isolates. Methods: This comprehensive dataset comprised 415 clinical isolates and 63 isolates from hospital environmental sources. For clinical isolates, they were evaluated in two different periods, from 1998 to 2004 and 2014 to 2021; for environmental strains, one strain was isolated in 1998, and 62 isolates were evaluated in 2015. Our primary objectives were to assess the epidemiological antifungal susceptibility profile; trace the evolution of resistance to azoles, Amphotericin B (AMB), and echinocandins; and monitor cyp51A mutations in resistant strains. We utilized the broth microdilution assay for susceptibility testing, coupled with cyp51A gene sequencing and microsatellite genotyping to evaluate genetic variability among resistant strains. Results: Our findings reveal a progressive increase in Minimum Inhibitory Concentrations (MICs) for azoles and AMB over time. Notably, a discernible trend in cyp51A gene mutations emerged in clinical isolates starting in 2014. Moreover, our study marks a significant discovery as we detected, for the first time, an A. fumigatus isolate carrying the recently identified TR46/F495I mutation within a sample obtained from a hospital environment. The observed cyp51A mutations underscore the ongoing necessity for surveillance, particularly as MICs for various antifungal classes continue to rise. Conclusions: By conducting resistance surveillance within our institution’s culture collection, we successfully identified a novel TR46/F495I mutation in an isolate retrieved from the hospital environment which had been preserved since 1998. Moreover, clinical isolates were found to exhibit TR34/L98H/S297T/F495I mutations. In addition, we observed an increase in MIC patterns for Amphotericin B and azoles, signaling a change in the resistance pattern, emphasizing the urgent need for the development of new antifungal drugs. Our study highlights the importance of continued monitoring and research in understanding the evolving challenges in managing A. fumigatus infections.

We present a case of a 55-year-old man with a heart transplant who acquired Invasive Aspergillosis by Aspergillus fumigatus with the focus in the kidney. During about two years of antifungal treatment, most of the time with voriconazole, it was possible to obtain nine isolates of A. fumigatus, with the same genotypic characteristics, but with an increase in MIC for several azoles. The two last isolates presented high MICs for Voriconazole (>8 μg/mL>). Sequencing of the CYP51A gene showed G448S amino acid substitution in the same two isolates. In long-term treatments with antifungals, it would be important to regularly evaluate the susceptibility of isolated strains, as resistance to azoles has been increasingly described around the world.

RESUMO Objetivo Verificar a frequência e a gravidade de disfagia pós-acidente vascular cerebral isquêmico na fase aguda com e sem trombólise e a associação entre a disfagia e as características demográficas, comprometimentos neurológico e funcional e a realização da trombólise. Método Estudo retrospectivo de análise de prontuário de 94 pacientes pós-acidente vascular cerebral isquêmico na fase aguda, destes, 52 pacientes realizaram trombólise e 42 não receberam o tratamento. Os dados coletados foram: idade, sexo, comorbidades, janela terapêutica para realização da trombólise, nível de consciência, grau de comprometimento neurológico, nível de dependência funcional, avaliação clínica da deglutição. Foram realizadas análise descritiva das variáveis categóricas e contínuas e análise de associação pelo teste Quiquadrado de Pearson, sendo consideradas como associações estatisticamente significantes as que apresentaram valor de p ≤ 0,05. Resultados A frequência de disfagia nos pacientes trombolizados foi de 67,3%. Os pacientes trombolizados apresentaram 4,6 vezes mais chance de apresentarem disfagia do que os pacientes não trombolizados. A gravidade da disfagia não apresentou associação com a realização da trombólise. Houve associação entre a presença de disfagia e a dependência funcional. As características demográficas e o comprometimento neurológico não apresentaram associação com o transtorno da deglutição. Conclusão Os pacientes trombolizados apresentaram maior tendência de desenvolverem disfagia do que os não trombolizados na fase aguda do acidente vascular cerebral, estando a disfagia associada à dependência funcional.

OBJETIVOS: comparar o desempenho de bons e maus leitores e escritores de escola pública e privada na leitura em voz alta e escrita sob ditado quanto aos parâmetros de escrita e fluência de leitura, além de verificar as estratégias de leitura e escrita utilizadas por essas crianças. MÉTODO: 61escolares, do 4º e 5º ano do Ensino Fundamental de uma escola da rede pública (GPU) e outra de ensino privado (GPr) foram submetidos ao Teste de Desempenho Escolar, para classificação em bom e mau leitor e escritor; e à leitura em voz alta e escrita de palavras e pseudopalavras, para verificação do desempenho quanto ao total de acertos em leitura e escrita, taxa e acurácia de leitura e acurácia de escrita, bem como as estratégias de leitura/escrita utilizadas. RESULTADOS: de maneira geral, o desempenho dos participantes de escola privada foi superior aos de escola pública. Observou-se melhor desempenho na leitura que na escrita; em palavras que em pseudopalavras; em palavras de alta frequência que em palavras de baixa frequência; e em palavras regulares que em irregulares. Os efeitos encontrados na leitura e na escrita foram os mesmos para escola pública e privada. CONCLUSÃO: os aspectos sociais e pedagógicos influenciam no desempenho de leitura e escrita. No grupo estudado foram observados os efeitos de lexicalidade, regularidade e frequência, não evidenciando o uso preferencial de uma ou outra rota de leitura e escrita. O tipo de escola não parece interferir na estratégia de leitura/escrita usada pelas crianças.

ABSTRACT Sporotrichosis, the cutaneous mycosis most commonly reported in Latin America, is caused by the Sporothrix clinical clade species, including Sporothrix brasiliensis and Sporothrix schenckii sensu stricto. Due to its zoonotic transmission in Brazil, S. brasiliensis represents a significant health threat to humans and domestic animals. Itraconazole, terbinafine, and amphotericin B are the most used antifungals for treating sporotrichosis. However, many strains of S. brasiliensis and S. schenckii have shown resistance to these agents, highlighting the importance of finding new therapeutic options. Here, we demonstrate that milteforan, a commercial veterinary product against dog leishmaniasis, whose active principle is miltefosine, is a possible therapeutic alternative for the treatment of sporotrichosis, as observed by its fungicidal activity in vitro against different strains of S. brasiliensis and S. schenckii. Fluorescent miltefosine localizes to the Sporothrix cell membrane and mitochondria and causes cell death through increased permeabilization. Milteforan decreases S. brasiliensis fungal burden in A549 pulmonary cells and bone marrow-derived macrophages and also has an immunomodulatory effect by decreasing TNF-α, IL-6, and IL-10 production. Our results suggest milteforan as a possible alternative to treat feline sporotrichosis.IMPORTANCESporotrichosis is an endemic disease in Latin America caused by different species of Sporothrix. This fungus can infect domestic animals, mainly cats and eventually dogs, as well as humans. Few drugs are available to treat this disease, such as itraconazole, terbinafine, and amphotericin B, but resistance to these agents has risen in the last few years. Alternative new therapeutic options to treat sporotrichosis are essential. Here, we propose milteforan, a commercial veterinary product against dog leishmaniasis, whose active principle is miltefosine, as a possible therapeutic alternative for treating sporotrichosis. Milteforan decreases S. brasiliensis fungal burden in human and mouse cells and has an immunomodulatory effect by decreasing several cytokine production.

Purposes: to compare the performance of good and bad readers and writers of public and private schools in reading aloud and writing under dictation regarding the parameters of writing and reading fluency, besides to verify the reading and writing strategies used by these children. Method: 61 students of the 4th and 5th grade from a public (GPu) and a private (GPr) elementary school were submitted to a School Performance Test, for classification into good and bad reader and writer; and to reading aloud and writing words and pseudo words in order to verify their performance regarding the total number of successes in reading and writing, rate and accuracy in reading and accuracy in writing, as well as strategies for reading/writing used. Results: in a general overview, the performance of participants from private school was higher than from public school. There was better performance in reading than in writing; in words than in pseudo words; in high frequency words than in low-frequency words; in regular words than in irregular words. The effects found in reading and writing were the same for public and private schools. Conclusion: social and pedagogical aspects influence the performance of reading and writing. In the group studied, it was observed the effects of lexicality, regularity and frequency; it was not showed the preferential use of one or another route of reading and writing. The type of school does not seem to interfere in the strategy of reading / writing used by these children. [ABSTRACT FROM AUTHOR]

Abstract Background Although oncological palliative care is increasingly being offered by multidisciplinary teams, there is still a lack of data about some symptoms handled by these teams, such as dysphagia, in patients with advanced cancer outside swallow regions. This study aimed to estimate the occurrence of dysphagia in prognosis studies of adults with advanced cancer outside the head, neck, and upper gastrointestinal tract, and to determine if there is an association with mortality. Methods A systematic review of studies that evaluated dysphagia and mortality was conducted (PROSPERO: CRD42021257172). Data sources BVS, PubMed, CINAHL, Web of Science, and Scopus. Data between 2011 and 2023 were selected. Results Among the 608 articles screened, only 14 were included, which covered different types of cancer, primarily Lung, and Genitourinary, Skin, Hematological, and Central Nervous System as well. Dysphagia demonstrated a variable frequency, and almost half of the studies found a percentage of dysphagia above 60%, appearing most as a symptom that affects health-related quality of life and prove to be a toxicity of treatment. The association between dysphagia and mortality was only evaluated in three articles that studied advanced lung cancer, in which, after controlling for covariates, swallowing disorders were associated with worse survival, with prevalences of dysphagia and hazard ratios of 78.5% (1.12 [1.04–1.20]), 4% (1.34 [1.28–1.35]), and 3% (1.40 [1.07–1.81]), respectively. Conclusions The occurrence of dysphagia in advanced cancer outside the head, neck, and upper GI tract is common, and there seems to be an association with significantly decreased survival in patients with advanced lung cancer.