Search

Background: Frailty is associated with several unfavorable outcomes after kidney transplantation (KTx). However, limited information is available regarding the transitions in frailty state and its components after KTx. This study aimed to evaluate the transitions in physical frailty phenotype and its components over a period of 12 months after KTx., Methods: In this prospective single-center cohort study, we measured physical frailty phenotype (PFP) and its components at the time of admission for KTx and 12 months after KTx. The evaluation includes five components: weakness (grip strength analysed by sex and body mass index quartiles), physical activity (kcals/week based on the Minnesota Leisure Time Physical Activity questionnaire), exhaustion (self-report using the Center for Epidemiological Studies Depression Scale), gait speed (time taken to walk 15 feet based on sex and height-specific cutoff), and unintentional weight loss (self-report of unintentional weight loss > 10 lbs in the last year). The exhaustion and physical activity components are validated in the Brazilian population. Each component is scored as 0 or 1 according to its presence or absence, and a PFP score of 3-5 defines frailty, 2 is intermediate, and 0-1 is rated as non-frail. We used the McNemar and Wilcoxon test to compare physical frailty phenotype and its components between the two periods., Results: Among 87 patients included in the study, 16.1% were classified as frail, 20.7% as intermediately frail, and 63.2% as non-frail. Sixty-four patients were included in the analysis to evaluate transitions in frailty. At the time of admission for KTx, 15.6% of patients were defined as frail compared to 4.7% of patients at 12 months after KTx (p = 0.023). Among the physical frailty phenotype components, the proportion of patients who scored in the weight loss category 12 months after KTx was significantly lower than that at the time of KTx (6.3% vs 34.4%, p < 0.001)., Conclusions: There was a 69.9% reduction in the prevalence of frail patients at the end of the 12-month follow-up after KTx. Among the components of frailty, weight loss showed a significant improvement., (© 2022. The Author(s) under exclusive licence to Italian Society of Nephrology.)

The genus Paracoccidioides consist of dimorphic fungi geographically limited to the subtropical regions of Latin America, which are responsible for causing deep systemic mycosis in humans. However, the molecular mechanisms by which Paracoccidioides spp. causes the disease remain poorly understood. Paracoccidioides spp. harbor genes that encode proteins involved in host cell interaction and mitochondrial function, which together are required for pathogenicity and mediate virulence. Previously, we identified TufM (previously known as EF-Tu) in Paracoccidioides brasiliensis (PbTufM) and suggested that it may be involved in the pathogenicity of this fungus. In this study, we examined the effects of downregulating PbTUFM using a silenced strain with a 55% reduction in PbTUFM expression obtained by antisense-RNA (aRNA) technology. Silencing PbTUFM yielded phenotypic differences, such as altered translation elongation, respiratory defects, increased sensitivity of yeast cells to reactive oxygen stress, survival after macrophage phagocytosis, and reduced interaction with pneumocytes. These results were associated with reduced virulence in Galleria mellonella and murine infection models, emphasizing the importance of PbTufM in the full virulence of P. brasiliensis and its potential as a target for antifungal agents against paracoccidioidomycosis.

MicroRNAs (miRNAs) are small RNAs (length, 19-24 nucleotides) that regulate gene expression by either mRNA degradation or translational inhibition of proteins. Circulating miRNAs, which are extremely stable and protected from RNAse-mediated degradation in body fluids, have appeared as candidate biomarkers for numerous diseases. However, little is known about circulating miRNAs in fungal infections. Paracoccidioidomycosis (PCM) is caused by the Paracoccidioides species, and is endemic in Central and South America, with predominance in adult male workers from rural areas. The current study aimed to identify a serum miRNA expression profile that could serve as a novel diagnostic biomarker for PCM. Total RNA was isolated and the levels of circulating miRNAs were compared between patients with PCM and healthy control subjects using reverse transcription-quantitative polymerase chain reaction. Bioinformatic analysis was used to evaluate the potential roles of these miRNAs in PCM. Eight miRNAs were differentially expressed in serum samples from patients with PCM. These miRNAs are associated with apoptosis and immune response. The identified miRNAs facilitate with understanding the regulatory mechanisms involved in the host-parasite interaction of PCM. Furthermore, considering that the diagnosis of PCM presents difficulties, these miRNAs may serve as novel biomarkers for this disease.