Understanding the mechanism of action of protease inhibitors in controlling the growth of the Candida Genus: potential candidates for development of new antifungal molecules.

There is a growing imperative for research into alternative compounds for the treatment of the fungal infections. Thus, many studies have focused on the analysis of antifungal proteins and peptides from different plant sources. Among these molecules are protease inhibitors (PIs). Previously, PIs present in the peptide-rich fractions called PEF1, PEF2 and PEF3 were identified from Capsicum chinense seeds, which have strong activity against phytopathogenic fungi. The aim of this study was to evaluate the mechanism of action and antimicrobial activity of PIs from PEF2 and PEF3 on the growth of yeasts of the genus Candida. In this work, analyses of their antimicrobial activity and cell viability were carried out. Subsequently, the mechanism of action by which the PIs cause the death of the yeasts was evaluated. Cytotoxicity was assessed in vitro by erythrocytes lysis and in vivo in Galleria mellonella larvae. PEF2 and PEF3 caused 100% of the growth inhibition of C. tropicalis and C. buinensis. For C. albicans inhibition was approximately 60% for both fractions. The PEF2 and PEF3 caused a reduction in mitochondrial functionality of 54% and 46% for C. albicans, 26% and 30% for C. tropicalis, and 71% and 68% for C. buinensis, respectively. These fractions induced morphological alterations, led to membrane permeabilization, elevated ROS levels, and resulted in necrotic cell death in C. tropicalis, whilst demonstrating low toxicity toward host cells. From the results obtained here, we intend to contribute to the understanding of the action of PIs in the control of fungal diseases of medical importance.

Cardiac and Liver Fibrosis Assessed by Multiparametric MRI in Patients with Fontan Circulation.

The abnormal hemodynamics in Fontan circulation due to persistently increased systemic venous pressure results in hepatic venous congestion and Fontan-associated liver disease. Combined assessment of cardiac and liver fibrosis and cardiac remodeling using multiparametric MRI in this context have not been fully explored. To evaluate cardiac and liver fibrosis and cardiac remodeling using multiparametric MRI in patients who have undergone Fontan procedures. Thirty-eight patients and 23 controls underwent cardiac and liver MRI examinations in a 3.0-T scanner. Mann-Whitney, Fisher exact test, and Spearman's correlation were applied to evaluate myocardial volumes, function, native cardiac and liver T1 mapping, ECVs and liver stiffness. The mean native cardiac T1 value (p = 0.018), cardiac ECV (p < 0.001), liver native T1 (p < 0.001), liver ECV (p < 0.001), and liver stiffness (p < 0.001) were higher in patients than controls. The indexed end-diastolic volume (EDVi) correlated with the myocardial ECV (r = 0.356; p = 0.033), native liver T1 (r = 0.571; p < 0.001), and with liver stiffness (r = 0.391; p = 0.015). In addition, liver stiffness correlated with liver ECV (r = 0.361; p = 0.031) and native liver T1 (r = 0.458; p = 0.004). An association between cardiac remodeling and cardiac and liver fibrosis were found in this population. The usefulness of MRI to follow cardiac and liver involvement in these patients is critical to improve treatment strategies and to prevent the need for combined liver and heart transplantation.

Multiparametric magnetic resonance imaging of the liver and spleen in Gaucher disease.

PURPOSE: To assess liver and spleen characteristics of a population with Gaucher disease (GD) using multiparametric MRI and MR elastography (MRE) for evaluation of diffuse liver and spleen disease, which includes liver fat fraction, liver and spleen volume and iron deposition, and liver and spleen stiffness correlated with DS3 Severity Scoring System for Gaucher disease (GD-DS3). METHODS: We prospectively evaluated 41 patients with type 1 Gaucher disease using a 3.0 T MRI and MRE between January 2019 and February 2020. Clinical, laboratory, and imaging data was collected. Mann-Whitney, Kruskal-Wallis, and Spearman's correlation were applied to evaluate liver and spleen MRI and MRE, clinical and laboratory variables, and GD-DS3. ERT and SRT treatment groups were compared. RESULTS: Hepatomegaly was seen in 15% and splenomegaly in 42% of the population. Moderate and strong and correlations were found between liver and spleen iron overload (rho = 0.537; p = 0.002); between liver and spleen volume (rho = 0.692, p < 0.001) and between liver and spleen stiffness (rho = 0.453, p = 0.006). Moderate correlations were found between liver stiffness and GD-DS3 (rho = 0.559; p < 0.001) and between splenic volume and GD-DS3 (rho = 0.524; p = 0.001). CONCLUSION: The prevalence of hepatosplenomegaly, liver fibrosis, and liver iron overload in treated patients with GD is low, which may be related to the beneficial effect of treatment. Liver MRE and splenic volume correlate with severity score and may be biomarkers of disease severity.

Defensin-like peptides from Capsicum chinense induce increased ROS, loss of mitochondrial functionality, and reduced growth of the fungus Colletotrichum scovillei.

In the present study, we identified and characterized two defensin-like peptides in an antifungal fraction obtained from Capsicum chinense pepper fruits and inhibited the growth of Colletotrichum scovillei, which causes anthracnose. AMPs were extracted from the pericarp of C. chinense peppers and subjected to ion exchange, molecular exclusion, and reversed-phase in a high-performance liquid chromatography system. We investigated the endogenous increase in reactive oxygen species (ROS), the loss of mitochondrial functioning, and the ultrastructure of hyphae. The peptides obtained from the G3 fraction through molecular exclusion chromatography were subsequently fractionated using reverse-phase chromatography, resulting in the isolation of fractions F1, F2, F3, F4, and F5. The F1-Fraction suppressed C. scovillei growth by 90, 70.4, and 44% at 100, 50, and 25 µg mL-1, respectively. At 24 h, the IC50 and minimum inhibitory concentration were 21.5 µg mL-1 and 200 µg mL-1, respectively. We found an increase in ROS, which may have resulted in an oxidative burst, loss of mitochondrial functioning, and cytoplasm retraction, as well as an increase in autophagic vacuoles. MS/MS analysis of the F1-Fraction indicated the presence of two defensin-like proteins, and we were able to identify the expression of three defensin sequences in our C. chinense fruit extract. The F1-Fraction was also found to inhibit the activity of insect α-amylases. In summary, the F1-Fraction of C. chinense exhibits antifungal activity against a major pepper pathogen that causes anthracnose. These defensin-like compounds are promising prospects for further research into antifungal and insecticide biotechnology applications. © 2024 Society of Chemical Industry.

How Cardiac Fibrosis Assessed via T1 Mapping Is Associated with Liver Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease.

(1) Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. Although cardiovascular and NAFLD risk factors overlap, an independent association between these conditions may exist. Hepatic and cardiac fibrosis are important markers of mortality, but the correlation between these markers in patients with NAFLD has not been well studied. Our main objective was to determine the degree of myocardial fibrosis in patients with NAFLD and its correlation with the severity of liver fibrosis. (2) Methods: In this cross-sectional study, patients with NAFLD were allocated to two groups according to the stage of liver fibrosis assessed using MRI: no or mild fibrosis (F0-F1) and significant fibrosis (F2-F4). Framingham risk scores were calculated to evaluate cardiovascular risk factors, and patients underwent multiparametric cardiac and abdominal MRIs. (3) Results: The sample comprised 44 patients (28 with no or mild liver fibrosis and 16 with significant liver fibrosis). The mean age was 57.9 ± 12 years, and 41% were men. Most patients had high cardiac risk factors and carotid disease. Relative to patients with no or mild liver fibrosis, those with significant fibrosis had a higher median calcium score (p = 0.05) and increased myocardial extracellular volume (ECV; p = 0.02). Liver fibrosis correlated with cardiac fibrosis, represented by the ECV (r = 0.49, p < 0.001). The myocardial ECV differentiated patients with and without significant liver fibrosis (AUC = 0.78). (4) Conclusion: This study showed that diffuse myocardial fibrosis is associated with liver fibrosis in patients with NAFLD.

Association between clinical, serological, functional and radiological findings and ventilatory distribution heterogeneity in patients with rheumatoid arthritis.

BACKGROUND: In rheumatoid arthritis (RA), the involvement of the pulmonary interstitium can lead to structural changes in the small airways and alveoli, leading to reduced airflow and maldistribution of ventilation. The single-breath nitrogen washout (SBN2W) test is a measure of the ventilatory distribution heterogeneity and evaluates the small airways. This study aimed to find out which clinical, serological, functional and radiological findings are useful to identify RA patients with pathological values of the phase III slope (SIII) measured by the SBN2W test. METHODS: This was a cross-sectional study in which RA patients were assessed using the Health Assessment Questionnaire-Disability Index (HAQ-DI) and the Clinical Disease Activity Index (CDAI) and underwent serological analysis of autoantibodies and inflammatory markers. In addition, they underwent pulmonary function tests (including the SBN2W test) and chest computed tomography (CT). RESULTS: Of the 60 RA patients evaluated, 39 (65%) had an SIII >120% of the predicted value. There were significant correlations between SIII and age (r = 0.56, p<0.0001), HAQ-DI (r = 0.34, p = 0.008), forced vital capacity (FVC, r = -0.67, p<0.0001), total lung capacity (r = -0.46, p = 0.0002), residual volume/total lung capacity (TLC) (r = 0.44, p = 0.0004), and diffusing capacity of the lungs for carbon monoxide (r = -0.45, p = 0.0003). On CT scans, the subgroup with moderate/severe disease had a significantly higher SIII than the normal/minimal/mild subgroup (662 (267-970) vs. 152 (88-283)% predicted, p = 0.0004). In the final multiple regression model, FVC, extent of moderate/severe involvement and age were associated with SIII, explaining 59% of its variability. CONCLUSIONS: In patients with RA, FVC, extent of lung involvement and age, all of which are easily obtained variables in clinical practice, identify poorly distributed ventilation. In addition, the presence of respiratory symptoms and deteriorated physical function are closely related to the distribution of ventilation in these patients.

Preoperative evaluation of prostate cancer by 68Ga-PMSA positron emission tomography/computed tomography: comparison with magnetic resonance imaging and with histopathological findings.

Objective: To evaluate the accuracy of preoperative positron emission tomography/computed tomography with 68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA PET/CT) for staging prostate cancer and compare it with magnetic resonance imaging (MRI) using histopathology of surgical specimens as the gold standard. Materials and Methods: In this retrospective study, 65 patients with prostate cancer were analyzed. Results: The accuracy of 68Ga-PSMA PET/CT for tumor detection was 95%, and that of MRI was 91%. There was no difference between 68Ga-PSMA PET/CT and MRI regarding localization of the lesion. The sensitivity of 68Ga-PSMA PET/CT for detecting extraprostatic extension was quite low (14%). For detection of seminal vesicle invasion, 68Ga-PSMA PET/CT showed a sensitivity of 57% and accuracy of 91%. There was a moderate correlation between the maximum standardized uptake value (SUVmax) and the serum level of prostate-specific antigen (p < 0.01; ρ = 0.368) and between the SUVmax and the International Society of Urological Pathology (ISUP) grade (p < 0.01; ρ = 0.513). Conclusion: 68Ga-PSMA PET/CT is a promising tool for detecting and evaluating the primary tumor, which can alter the staging and management of the disease.

Objetivo: Avaliar a acurácia da tomografia por emissão de pósitrons/tomografia computadorizada com PSMA (PET-PMSA) pré-operatória para estadiamento do câncer de próstata e compará-la com a ressonância magnética (RM) utilizando o histopatológico cirúrgico como padrão ouro. Materiais e Métodos: Neste estudo retrospectivo foram analisados 65 pacientes com câncer de próstata. Resultados: A acurácia da PET-PSMA para a detecção tumoral foi de 95% e a da RM foi de 91%. Não houve diferença entre a PET-PSMA e a RM quanto à localização da lesão. A PET-PSMA apresentou baixa sensibilidade (14%) para detecção de extensão extraprostática em comparação ao histopatológico. Para detecção de invasão de vesícula seminal, a PET-PSMA apresentou sensibilidade de 57% e acurácia de 91% em comparação ao histopatológico. Houve correlação moderada entre o SUVmax e o PSA (p < 0,01; ρ = 0,368) e entre o SUVmax e o ISUP (p < 0,01; ρ = 0,513). Conclusão: A PET-PSMA é uma ferramenta promissora para detecção e avaliação do tumor primário, alterando o estadiamento e a conduta do paciente.

Natural Language Processing for the Identification of Incidental Lung Nodules in Computed Tomography Reports: A Quality Control Tool.

PURPOSE: To evaluate the diagnostic performance of a natural language processing (NLP) model in detecting incidental lung nodules (ILNs) in unstructured chest computed tomography (CT) reports. METHODS: All unstructured consecutive reports of chest CT scans performed at a tertiary hospital between 2020 and 2021 were retrospectively reviewed (n = 21,542) to train the NLP tool. Internal validation was performed using reference readings by two radiologists of both CT scans and reports, using a different external cohort of 300 chest CT scans. Second, external validation was performed in a cohort of all random unstructured chest CT reports from 57 different hospitals conducted in May 2022. A review by the same thoracic radiologists was used as the gold standard. The sensitivity, specificity, and accuracy were calculated. RESULTS: Of 21,542 CT reports, 484 mentioned at least one ILN (mean age, 71 ± 17.6 [standard deviation] years; women, 52%) and were included in the training set. In the internal validation (n = 300), the NLP tool detected ILN with a sensitivity of 100.0% (95% CI, 97.6 to 100.0), a specificity of 95.9% (95% CI, 91.3 to 98.5), and an accuracy of 98.0% (95% CI, 95.7 to 99.3). In the external validation (n = 977), the NLP tool yielded a sensitivity of 98.4% (95% CI, 94.5 to 99.8), a specificity of 98.6% (95% CI, 97.5 to 99.3), and an accuracy of 98.6% (95% CI, 97.6 to 99.2). Twelve months after the initial reports, 8 (8.60%) patients had a final diagnosis of lung cancer, among which 2 (2.15%) would have been lost to follow-up without the NLP tool. CONCLUSION: NLP can be used to identify ILNs in unstructured reports with high accuracy, allowing a timely recall of patients and a potential diagnosis of early-stage lung cancer that might have been lost to follow-up.

Structural and Biochemical Characterization of Three Antimicrobial Peptides from Capsicum annuum L. var. annuum Leaves for Anti-Candida Use.

The emergence of resistant microorganisms has reduced the effectiveness of currently available antimicrobials, necessitating the development of new strategies. Plant antimicrobial peptides (AMPs) are promising candidates for novel drug development. In this study, we aimed to isolate, characterize, and evaluate the antimicrobial activities of AMPs isolated from Capsicum annuum. The antifungal potential was tested against Candida species. Three AMPs from C. annuum leaves were isolated and characterized: a protease inhibitor, a defensin-like protein, and a lipid transporter protein, respectively named CaCPin-II, CaCDef-like, and CaCLTP2. All three peptides had a molecular mass between 3.5 and 6.5 kDa and caused morphological and physiological changes in four different species of the genus Candida, such as pseudohyphae formation, cell swelling and agglutination, growth inhibition, reduced cell viability, oxidative stress, membrane permeabilization, and metacaspase activation. Except for CaCPin-II, the peptides showed low or no hemolytic activity at the concentrations used in the yeast assays. CaCPin-II inhibited α-amylase activity. Together, these results suggest that these peptides have the potential as antimicrobial agents against species of the genus Candida and can serve as scaffolds for the development of synthetic peptides for this purpose.

Artificial intelligence to predict the need for mechanical ventilation in cases of severe COVID-19.

Objective: To determinate the accuracy of computed tomography (CT) imaging assessed by deep neural networks for predicting the need for mechanical ventilation (MV) in patients hospitalized with severe acute respiratory syndrome due to coronavirus disease 2019 (COVID-19). Materials and Methods: This was a retrospective cohort study carried out at two hospitals in Brazil. We included CT scans from patients who were hospitalized due to severe acute respiratory syndrome and had COVID-19 confirmed by reverse transcription-polymerase chain reaction (RT-PCR). The training set consisted of chest CT examinations from 823 patients with COVID-19, of whom 93 required MV during hospitalization. We developed an artificial intelligence (AI) model based on convolutional neural networks. The performance of the AI model was evaluated by calculating its accuracy, sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve. Results: For predicting the need for MV, the AI model had a sensitivity of 0.417 and a specificity of 0.860. The corresponding area under the ROC curve for the test set was 0.68. Conclusion: The high specificity of our AI model makes it able to reliably predict which patients will and will not need invasive ventilation. That makes this approach ideal for identifying high-risk patients and predicting the minimum number of ventilators and critical care beds that will be required.

Objetivo: Determinar a acurácia da tomografia computadorizada (TC), avaliada por redes neurais profundas, na ventilação mecânica, de pacientes hospitalizados por síndrome respiratória aguda grave por COVID-19. Materiais e Métodos: Trata-se de estudo de coorte retrospectivo, realizado em dois hospitais brasileiros. Foram incluídas TCs de pacientes hospitalizados por síndrome respiratória aguda grave e COVID-19 confirmada por RT-PCR. O treinamento consistiu em TC de tórax de 823 pacientes com COVID-19, dos quais 93 foram submetidos a ventilação mecânica na hospitalização. Nós desenvolvemos um modelo de inteligência artificial baseado em redes de convoluções neurais. A avaliação do desempenho do uso da inteligência artificial foi baseada no cálculo de acurácia, sensibilidade, especificidade e área sob a curva ROC. Resultados: A sensibilidade do modelo foi de 0,417 e a especificidade foi de 0,860. A área sob a curva ROC para o conjunto de teste foi de 0,68. Conclusão: Criamos um modelo de aprendizado de máquina com elevada especificidade, capaz de prever de forma confiável pacientes que não precisarão de ventilação mecânica. Isso significa que essa abordagem é ideal para prever com antecedência pacientes de alto risco e um número mínimo de equipamentos de ventilação e de leitos críticos.

Crohn's disease: review and standardization of nomenclature.

Crohn's disease is an inflammatory bowel disease that can affect any segment of the gastrointestinal tract. It has a variable clinical course, with alternating periods of disease activity and remission. Because the incidence and prevalence of Crohn's disease have been increasing, evaluation by imaging methods has become more important. The most widely used methods are computed tomography enterography, magnetic resonance enterography (as an elective examination), and contrast-enhanced computed tomography (in the context of emergency). Computed tomography enterography and magnetic resonance enterography are useful for diagnosis, follow-up, evaluation of complications, and prognosis. Both can be used in order to evaluate the small bowel loops and the associated mesenteric findings, as well as to evaluate other abdominal organs. They both also can detect signs of disease activity, fibrosis, penetrating disease, and complications. The interpretation of such changes is essential to the multidisciplinary approach, as is the standardization of the nomenclature employed in the reports. In this paper, we review and illustrate the imaging findings of Crohn's disease, using the standardized nomenclature proposed in the multidisciplinary consensus statement issued by the Society of Abdominal Radiology, the Society of Pediatric Radiology, and the American Gastroenterology Association, with recommendations for descriptions, interpretations, and impressions related to those findings.

Doença de Crohn é uma doença inflamatória intestinal que pode acometer qualquer segmento do trato gastrointestinal, com curso clínico variado, alternando períodos de atividade de doença e remissão. Sua incidência e prevalência vêm aumentando, tornando a avaliação por métodos de imagem mais importante. Os métodos mais utilizados são enterotomografia computadorizada, enterorressonância magnética eletivamente e tomografia computadorizada com contraste no contexto da emergência. A enterotomografia computadorizada e a enterorressonância magnética são úteis para diagnóstico, seguimento, avaliação de complicações e para prognóstico. Avaliam as alças intestinais delgadas e os achados mesentéricos associados, além dos demais órgãos abdominais. Detectam sinais de atividade de doença, sinais de cronicidade e doença penetrante e complicações, importantes para a escolha do melhor tratamento. A interpretação dessas alterações é fundamental para que a equipe multidisciplinar trabalhe conjuntamente com compreensão da linguagem utilizada nos relatórios. Neste artigo, apresentamos uma revisão dos achados de imagem da doença de Crohn e ilustramos os possíveis achados dessa doença utilizando a nomenclatura padronizada proposta no consenso multidisciplinar composto pelas Sociedade de Radiologia Abdominal, Sociedade de Radiologia Pediátrica e a Associação Americana de Gastroenterologia, com recomendações de descrição, interpretação dos achados e recomendações de impressão.

Artificial Intelligence for Cardiothoracic Imaging: Overview of Current and Emerging Applications.

Artificial intelligence algorithms can learn by assimilating information from large datasets in order to decipher complex associations, identify previously undiscovered pathophysiological states, and construct prediction models. There has been tremendous interest and increased incorporation of artificial intelligence into various industries, including healthcare. As a result, there has been an exponential rise in the number of research articles and industry participants producing models intended for a variety of applications in medical imaging, which can be challenging to navigate for radiologists. In thoracic imaging, multiple applications are being evaluated for chest radiography and computed tomography and include applications for lung nodule evaluation and cancer imaging, quantifying diffuse lung disorders, and cardiac imaging, to name a few. This review aims to provide an overview of current clinical AI models, focusing on the most common clinical applications of AI in cardiothoracic imaging.

Crohn's disease: review and standardization of nomenclature / Doença de Crohn: revisão e padronização da nomenclatura

Abstract Crohn's disease is an inflammatory bowel disease that can affect any segment of the gastrointestinal tract. It has a variable clinical course, with alternating periods of disease activity and remission. Because the incidence and prevalence of Crohn's disease have been increasing, evaluation by imaging methods has become more important. The most widely used methods are computed tomography enterography, magnetic resonance enterography (as an elective examination), and contrast-enhanced computed tomography (in the context of emergency). Computed tomography enterography and magnetic resonance enterography are useful for diagnosis, follow-up, evaluation of complications, and prognosis. Both can be used in order to evaluate the small bowel loops and the associated mesenteric findings, as well as to evaluate other abdominal organs. They both also can detect signs of disease activity, fibrosis, penetrating disease, and complications. The interpretation of such changes is essential to the multidisciplinary approach, as is the standardization of the nomenclature employed in the reports. In this paper, we review and illustrate the imaging findings of Crohn's disease, using the standardized nomenclature proposed in the multidisciplinary consensus statement issued by the Society of Abdominal Radiology, the Society of Pediatric Radiology, and the American Gastroenterology Association, with recommendations for descriptions, interpretations, and impressions related to those findings.

Resumo Doença de Crohn é uma doença inflamatória intestinal que pode acometer qualquer segmento do trato gastrointestinal, com curso clínico variado, alternando períodos de atividade de doença e remissão. Sua incidência e prevalência vêm aumentando, tornando a avaliação por métodos de imagem mais importante. Os métodos mais utilizados são enterotomografia computadorizada, enterorressonância magnética eletivamente e tomografia computadorizada com contraste no contexto da emergência. A enterotomografia computadorizada e a enterorressonância magnética são úteis para diagnóstico, seguimento, avaliação de complicações e para prognóstico. Avaliam as alças intestinais delgadas e os achados mesentéricos associados, além dos demais órgãos abdominais. Detectam sinais de atividade de doença, sinais de cronicidade e doença penetrante e complicações, importantes para a escolha do melhor tratamento. A interpretação dessas alterações é fundamental para que a equipe multidisciplinar trabalhe conjuntamente com compreensão da linguagem utilizada nos relatórios. Neste artigo, apresentamos uma revisão dos achados de imagem da doença de Crohn e ilustramos os possíveis achados dessa doença utilizando a nomenclatura padronizada proposta no consenso multidisciplinar composto pelas Sociedade de Radiologia Abdominal, Sociedade de Radiologia Pediátrica e a Associação Americana de Gastroenterologia, com recomendações de descrição, interpretação dos achados e recomendações de impressão.

Artificial intelligence to predict the need for mechanical ventilation in cases of severe COVID-19 / Inteligência artificial na predição de necessidade de ventilação mecânica em casos graves de COVID-19

Abstract Objective: To determinate the accuracy of computed tomography (CT) imaging assessed by deep neural networks for predicting the need for mechanical ventilation (MV) in patients hospitalized with severe acute respiratory syndrome due to coronavirus disease 2019 (COVID-19). Materials and Methods: This was a retrospective cohort study carried out at two hospitals in Brazil. We included CT scans from patients who were hospitalized due to severe acute respiratory syndrome and had COVID-19 confirmed by reverse transcriptionpolymerase chain reaction (RT-PCR). The training set consisted of chest CT examinations from 823 patients with COVID-19, of whom 93 required MV during hospitalization. We developed an artificial intelligence (AI) model based on convolutional neural networks. The performance of the AI model was evaluated by calculating its accuracy, sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve. Results: For predicting the need for MV, the AI model had a sensitivity of 0.417 and a specificity of 0.860. The corresponding area under the ROC curve for the test set was 0.68. Conclusion: The high specificity of our AI model makes it able to reliably predict which patients will and will not need invasive ventilation. That makes this approach ideal for identifying high-risk patients and predicting the minimum number of ventilators and critical care beds that will be required.

Resumo Objetivo: Determinar a acurácia da tomografia computadorizada (TC), avaliada por redes neurais profundas, na ventilação mecânica, de pacientes hospitalizados por síndrome respiratória aguda grave por COVID-19. Materiais e Métodos: Trata-se de estudo de coorte retrospectivo, realizado em dois hospitais brasileiros. Foram incluídas TCs de pacientes hospitalizados por síndrome respiratória aguda grave e COVID-19 confirmada por RT-PCR. O treinamento consistiu em TC de tórax de 823 pacientes com COVID-19, dos quais 93 foram submetidos a ventilação mecânica na hospitalização. Nós desenvolvemos um modelo de inteligência artificial baseado em redes de convoluções neurais. A avaliação do desempenho do uso da inteligência artificial foi baseada no cálculo de acurácia, sensibilidade, especificidade e área sob a curva ROC. Resultados: A sensibilidade do modelo foi de 0,417 e a especificidade foi de 0,860. A área sob a curva ROC para o conjunto de teste foi de 0,68. Conclusão: Criamos um modelo de aprendizado de máquina com elevada especificidade, capaz de prever de forma confiável pacientes que não precisarão de ventilação mecânica. Isso significa que essa abordagem é ideal para prever com antecedência pacientes de alto risco e um número mínimo de equipamentos de ventilação e de leitos críticos.

Trypsin/α-Amylase Inhibitors from Capsicum chinense Seeds: Characterization and Antifungal Activity against Fungi of Agronomic Importance.

BACKGROUND: Protease inhibitors (PIs) have attracted attention due to their important roles in plant defense. OBJECTIVE: The objective of this work was to characterize and evaluate the antimicrobial activity of the peptides of a family of serine PIs from Capsicum chinense Jacq. seeds. METHODS: Initially, PIs were extracted from the seeds and subjected to purification by chromatography, resulting in three different peptide enriched fractions (PEFs) termed PEF1, PEF2 and PEF3. Subsequently, the PEF3 was subjected to trypsin inhibition assays, α-amylase activity assays, antimicrobial activity assays on phytopathogenic fungi, and assays to determine the likely mechanisms of action. RESULTS: The PEF3 was composed of three protein bands with molecular masses ranging between 6 and 14 kDa. The amino acid residues of the ~6 kDa band showed high similarity with serine PIs. PEF3 inhibited the activity of the enzymes trypsin, human salivary α-amylase, and Tenebrio molitor larval α-amylase and inhibited the growth of phytopathogenic fungi, showing 83.7% loss of viability in Fusarium oxysporum. PEF3 induced reactive oxygen species in Colletotrichum lindemuthianum and F. oxysporum to dissipate their mitochondrial membrane potential and activated caspases in C. lindemuthianum. CONCLUSION: Our results reinforce the importance of PIs in plant defense mechanisms against phytopathogenic fungi as well as in their biotechnological applications for the control of plant pathogens.

Relative enhancement index can be used to quantify liver function in cirrhotic patients that undergo gadoxetic acid-enhanced MRI.

OBJECTIVES: To evaluate MRI with gadoxetic acid to quantify liver function in cirrhotic patients using the relative enhancement index (REI) compared with Child-Pugh score (CPS), MELD score, and indocyanine green plasma disappearance rate (ICG-PDR) and to establish cutoffs for REI to stratify cirrhotic patients into good and poor liver function groups. METHODS: We prospectively evaluated 60 cirrhotic patients and calculated CPS, MELD score, ICG-PDR, and REI for each patient. Spearman's correlation coefficient was used to assess correlation between REI, CPS, MELD, and ICG-PDR. Good and poor liver function groups were created by k-means clustering algorithm using CPS, MELD, and ICG-PDR. ROC curve analysis was performed and optimal cutoff was identified for group differentiation. RESULTS: Good correlations were found between REI and other liver function biomarkers: REI and CPS (rho = - 0.816; p < 0.001); REI and MELD score (rho = - 0.755; p < 0.001); REI and ICG-PDR (rho = 0.745; p < 0.001)]. REI correlation was stronger for patients with Child-Pugh A (rho = 0.642, p = 0.002) and B (rho = 0.798, p < 0.001) than for those with Child-Pugh C (rho = 0.336, p = 0.148). REI is significantly lower in patients with poor liver function (p < 0.001). ROC curve showed an AUC 0.94 to discriminate patients with poor liver function (REI cutoff < 100; 100% sensitivity; 76% specificity). CONCLUSIONS: REI is a valuable non-invasive index for liver function quantification that has good correlations with other liver function biomarkers. REI can be easily calculated and can be used to estimate liver function in clinical practice in the routine evaluation of cirrhotic patients that undergo MR imaging with gadoxetic acid contrast. KEY POINTS: • REI is a valuable non-invasive index for liver function quantification that has good correlations with other liver function biomarkers. • REI can be easily calculated in the routine evaluation of cirrhotic patients that undergo gadoxetic acid-enhanced MRI. • The REI enables stratification of cirrhotic patients into good and poor liver function groups and can be used as additional information, together with morphological and focal liver lesion evaluation.

Inhibition of Serine Protease, α-Amylase and Growth of Phytopathogenic Fungi by Antimicrobial Peptides from Capsicum chinense Fruits.

Plant fungal diseases cause major problems for the global economy. Antimicrobial peptides have aroused great interest in the control of phytopathogens, as they are natural molecules and have a broad spectrum of inhibitory activity. Herein, we have tried to identify and characterize antimicrobial peptides present in fruits of Capsicum chinense and to evaluate their enzymatic and antifungal activities. The retained fraction obtained in the anion exchange chromatography with strong antifungal activity was subjected to molecular exclusion chromatography and obtained four fractions named G1, G2, G3, and G4. The 6.0-kDa protein band of G2 showed similarity with protease inhibitors type II, and it was able to inhibit 100% of trypsin and α-amylase activities. The protein band with approximately 6.5 kDa of G3 showed similarity with sequences of protease inhibitors from genus Capsicum and showed growth inhibition of 48% for Colletotrichum lindemuthianum, 49% for Fusarium lateritium, and 51% for F. solani and F. oxysporum. Additionally, G3 causes morphological changes, membrane permeabilization, and ROS increase in F. oxysporum cells. The 9-kDa protein band of G4 fraction was similar to a nsLTP type 1, and a protein band of 6.5 kDa was similar to a nsLTP type 2. The G4 fraction was able to inhibit 100% of the activities of glycosidases tested and showed growth inhibition of 35 and 50% of F. oxysporum and C. lindemuthianum, respectively. C. chinense fruits have peptides with antifungal activity and enzyme inhibition with biotechnological potential.

Anti-Candida Potential of Peptides from Immature and Ripe Fruits of Capsicum chinense Jacq.

The objective of this work was to purify and evaluate the antifungal potential of peptides present in immature and ripe fruits of Capsicum chinense Jacq. (accession UENF 1706) on the medical importance yeasts. Initially the proteins of these seedless fruits were extracted, precipitated with ammonium sulfate at 70% saturation, followed by heating at 80 °C. Subsequently, the peptide-rich extract was fractionated by DEAE-Sepharose anion exchange. The whole process was monitored by tricine-SDS-PAGE. The results revealed that the fraction retained in anion exchange column, called D2, of immature and ripe fruits significantly inhibit the growth of Candida albicans and C. tropicalis yeasts. Due to the higher yield, the D2 fraction of immature fruits was selected for further purification by reverse phase chromatography on HPLC, where sixteen different fractions (H1-H16) were obtained and these were subjected to antifungal assay at 50 µg mL-1. Although almost all fractions tested had significant growth inhibition, the HI9 fraction inhibit 99% of the two yeasts tested. The effect of treatment with HI3, HI8, HI9, and HI14 fractions on the viability of yeast cells was analyzed due to their strong growth inhibition. We observed that only 50 µg mL-1 of the HI9 fraction is the lethal dose for 100% of the cells of C. albicans and C. tropicalis in the original assay. Although the HI9 fraction had a fungicidal effect on both tested yeasts, we only observed membrane permeabilization for C. tropicalis cells treated with 50 µg mL-1 of this fraction. Through mass spectrometry, we identified that the 6 kDa peptide band of HI9 fraction showed similarity with antimicrobial peptides belonging to the plant defensin family.

Preoperative evaluation of prostate cancer by 68Ga-PMSA positron emission tomography/computed tomography: comparison with magnetic resonance imaging and with histopathological findings / Avaliação pré-operatória do câncer de próstata pela tomografia por emissão de pósitrons/tomografia computadorizada com PSMA-68Ga: comparação com ressonância magnética e com achados histopatológicos

Abstract Objective: To evaluate the accuracy of preoperative positron emission tomography/computed tomography with 68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA PET/CT) for staging prostate cancer and compare it with magnetic resonance imaging (MRI) using histopathology of surgical specimens as the gold standard. Materials and Methods: In this retrospective study, 65 patients with prostate cancer were analyzed. Results: The accuracy of 68Ga-PSMA PET/CT for tumor detection was 95%, and that of MRI was 91%. There was no difference between 68Ga-PSMA PET/CT and MRI regarding localization of the lesion. The sensitivity of 68Ga-PSMA PET/CT for detecting extraprostatic extension was quite low (14%). For detection of seminal vesicle invasion, 68Ga-PSMA PET/CT showed a sensitivity of 57% and accuracy of 91%. There was a moderate correlation between the maximum standardized uptake value (SUVmax) and the serum level of prostate-specific antigen (p < 0.01; ρ = 0.368) and between the SUVmax and the International Society of Urological Pathology (ISUP) grade (p < 0.01; ρ = 0.513). Conclusion: 68Ga-PSMA PET/CT is a promising tool for detecting and evaluating the primary tumor, which can alter the staging and management of the disease.

Resumo Objetivo: Avaliar a acurácia da tomografia por emissão de pósitrons/tomografia computadorizada com PSMA (PET-PMSA) pré-operatória para estadiamento do câncer de próstata e compará-la com a ressonância magnética (RM) utilizando o histopatológico cirúrgico como padrão ouro. Materiais e Métodos: Neste estudo retrospectivo foram analisados 65 pacientes com câncer de próstata. Resultados: A acurácia da PET-PSMA para a detecção tumoral foi de 95% e a da RM foi de 91%. Não houve diferença entre a PET-PSMA e a RM quanto à localização da lesão. A PET-PSMA apresentou baixa sensibilidade (14%) para detecção de extensão extraprostática em comparação ao histopatológico. Para detecção de invasão de vesícula seminal, a PET-PSMA apresentou sensibilidade de 57% e acurácia de 91% em comparação ao histopatológico. Houve correlação moderada entre o SUVmax e o PSA (p < 0,01; ρ = 0,368) e entre o SUVmax e o ISUP (p < 0,01; ρ = 0,513). Conclusão: A PET-PSMA é uma ferramenta promissora para detecção e avaliação do tumor primário, alterando o estadiamento e a conduta do paciente.