Complex and Controversial Roles of Eicosanoids in Fungal Pathogenesis

The prevalence of fungal infections has increased in immunocompromised patients, leading to millions of deaths annually. Arachidonic acid (AA) metabolites, such as eicosanoids, play important roles in regulating innate and adaptative immune function, particularly since they can function as virulence factors enhancing fungal colonization and are produced by mammalian and lower eukaryotes, such as yeasts and other fungi (Candida albicans, Histoplasma capsulatum and Cryptococcus neoformans). C. albicans produces prostaglandins (PG), Leukotrienes (LT) and Resolvins (Rvs), whereas the first two have been well documented in Cryptococcus sp. and H. capsulatum. In this review, we cover the eicosanoids produced by the host and fungi during fungal infections. These fungal-derived PGs have immunomodulatory functions analogous to their mammalian counterparts. Prostaglandin E2 (PGE2) protects C. albicans and C. parapsilosis cells from the phagocytic and killing activity of macrophages. H. capsulatum PGs augment the fungal burden and host mortality rates in histoplasmosis. However, PGD2 potentiates the effects and production of LTB4, which is a very potent neutrophil chemoattractant that enhances host responses. Altogether, these data suggest that eicosanoids, mainly PGE2, may serve as a new potential target to combat diverse fungal infections

A reliable and valid tool to assess the sexual acceptability of contraceptive methods

Introduction: Adequate identification of the sexual acceptability of contraceptive methods is key for designing health promotion interventions, assessing their impacts, and increasing their effectiveness. This study aimed to develop and validate a questionnaire to explore the preferences of women depending on their epidemiological characteristics and their partner relationships-the Sexual Acceptability of Contraceptive Methods Questionnaire [in Spanish, Aceptabilidad Sexual de los Métodos Anticonceptivos (ASMA)]. Methods: Psychometric validation was conducted using Exploratory Factorial Analysis (EFA) and confirmatory factor analysis (CFA). The reliability of the final version of the questionnaire was explored using Cronbach's alpha and McDonald omega to estimate internal consistency. Results: A three-factor model was identified. Factor 1 (explaining 28.32% of the model) corresponds to questions concerning the use and placement of the contraceptive and includes 6 items; Factor 2 (explaining 24.23%) corresponds to other factors that affect the relationship such as bleeding and side effects of the contraceptive method and includes 10 items; and Factor 3 (explaining 18.94%) corresponds to the couple relationship and includes 8 items. Conclusion and implications: The ASMA questionnaire provides a valid and reliable tool for assessing the sexual acceptability of various contraceptive methods. This instrument gathers data that provide information on various aspects of women's sexuality, health, education, and beliefs, all of which can determine the preference for one contraceptive method over another. Moreover, the tool can help to identify profiles of women who have different preferences when selecting a particular method

A reliable and valid tool to assess the sexual acceptability of contraceptive methods

Introduction: Adequate identification of the sexual acceptability of contraceptive methods is key for designing health promotion interventions, assessing their impacts, and increasing their effectiveness. This study aimed to develop and validate a questionnaire to explore the preferences of women depending on their epidemiological characteristics and their partner relationships—the Sexual Acceptability of Contraceptive Methods Questionnaire [in Spanish, Aceptabilidad Sexual de los Métodos Anticonceptivos (ASMA)]. Methods: Psychometric validation was conducted using Exploratory Factorial Analysis (EFA) and confirmatory factor analysis (CFA). The reliability of the final version of the questionnaire was explored using Cronbach’s alpha and McDonald omega to estimate internal consistency. Results: A three-factor model was identified. Factor 1 (explaining 28.32% of the model) corresponds to questions concerning the use and placement of the contraceptive and includes 6 items; Factor 2 (explaining 24.23%) corresponds to other factors that affect the relationship such as bleeding and side effects of the contraceptive method and includes 10 items; and Factor 3 (explaining 18.94%) corresponds to the couple relationship and includes 8 items. Conclusion and implications: The ASMA questionnaire provides a valid and reliable tool for assessing the sexual acceptability of various contraceptive methods. This instrument gathers data that provide information on various aspects of women’s sexuality, health, education, and beliefs, all of which can determine the preference for one contraceptive method over another. Moreover, the tool can help to identify profiles of women who have different preferences when selecting a particular method

Assessment of ELISA F29 as a marker of etiological treatment efficacy for Chagas disease

La proteína flagelar F29 es una proteína ligadora de calcio del Trypanosoma cruzi. En el presente trabajo se realizó un estudio transversal en sueros de pacientes con infección crónica por T. cruzi tratados con nifurtimox (Nx) o benznidazol (Bz) y no tratados, para evaluar el antígeno F29 como marcador de eficacia terapéutica. Se utilizó un ensayo inmuno-enzimático con la proteína recombinante F29 (ELISA F29) y se analizó su relación con la serología convencional (SC) y la evolución parasitológica y clínica en esos pacientes. Se estudiaron 118 sueros de pacientes que formaban parte de una cohorte, de los cuales se disponía de información retrospectiva, serológica, parasitológica y clínica.Los pacientes se dividieron en 3 grupos: A) 30 tratados negativizaron SC post-tratamiento; B) 34 tratados permanecieron con SC reactiva; C) 54 no tratados. Las muestras de suero se procesaron a doble ciego en forma simultánea mediante serología convencional (hemoaglutinación indirecta, aglutinación directa e inmunofluorescencia indirecta) y ELISA F29. El test ELISA F29 resultó no reactivo en: 100% del grupo A, 82,4% del grupo B y 13% del grupo C. Los infectados con alteraciones electrocar-diográficas compatibles con miocardiopatía chagásica crónica (n = 11) fueron reactivos al ELISA F29. Los pacientes en quienes los estudios parasitológicos (xenodiagnóstico y/o strout) fueron (+) presentaron elevada reactividad al ELISA F29. La correlación entre ELISA F29 y SC en los pacientes tratados con SC no reactiva (grupo A) y no tratados (grupo C), fue significativa (p of group C. The infected patients who presented electrocardiographic alterations compatible with chronic chagasic myocardiopathy (n = 11) were reactive for ELISA F29. All patients whose parasitological studies (xenodiagnosis and/or strout method) were positive presented a high reactivity to the ELISA F29 test. The correlation between ELISA F29 and CS was statistically significant (p . These results suggest that the fast and user-friendly ELISA F29 test could be useful to monitor changes after trypanocidal treatment.Fil: Fabbro, Diana. Universidad Nacional del Litoral. Centro de Investigaciones Endemias Nacionales (CIEN); Argentina.Fil: Velázquez, Elsa. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología Dr. Mario Fatala Chaben; Argentina.Fil: Mendoza, Norberto. Universidad Nacional del Litoral. Centro de Investigaciones Endemias Nacionales (CIEN); Argentina.Fil: Streiger, Mirtha. Universidad Nacional del Litoral. Centro de Investigaciones Endemias Nacionales (CIEN); Argentina.Fil: Arias, Enrique. Universidad Nacional del Litoral. Centro de Investigaciones Endemias Nacionales (CIEN); Argentina.Fil: Denner, Susana. Universidad Nacional del Litoral. Centro de Investigaciones Endemias Nacionales (CIEN); Argentina.Fil: Del Barco, Mónica. Universidad Nacional del Litoral. Centro de Investigaciones Endemias Nacionales (CIEN); Argentina.Fil: Amicone, Norberto. Universidad Nacional del Litoral. Centro de Investigaciones Endemias Nacionales (CIEN); Argentina.Fil: Pravia, Carlos. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología Dr. Mario Fatala Chaben; Argentina.Fil: Malagrino, Nora. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología Dr. Mario Fatala Chaben; Argentina.Fil: Ruiz, Andres Mariano. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología Dr. Mario Fatala Chaben; Argentina

Assessment of ELISA F29 as a marker of etiological treatment efficacy for Chagas disease

La proteína flagelar F29 es una proteína ligadora de calcio del Trypanosoma cruzi. En el presente trabajo se realizó un estudio transversal en sueros de pacientes con infección crónica por T. cruzi tratados con nifurtimox (Nx) o benznidazol (Bz) y no tratados, para evaluar el antígeno F29 como marcador de eficacia terapéutica. Se utilizó un ensayo inmuno-enzimático con la proteína recombinante F29 (ELISA F29) y se analizó su relación con la serología convencional (SC) y la evolución parasitológica y clínica en esos pacientes. Se estudiaron 118 sueros de pacientes que formaban parte de una cohorte, de los cuales se disponía de información retrospectiva, serológica, parasitológica y clínica.Los pacientes se dividieron en 3 grupos: A) 30 tratados negativizaron SC post-tratamiento; B) 34 tratados permanecieron con SC reactiva; C) 54 no tratados. Las muestras de suero se procesaron a doble ciego en forma simultánea mediante serología convencional (hemoaglutinación indirecta, aglutinación directa e inmunofluorescencia indirecta) y ELISA F29. El test ELISA F29 resultó no reactivo en: 100% del grupo A, 82,4% del grupo B y 13% del grupo C. Los infectados con alteraciones electrocar-diográficas compatibles con miocardiopatía chagásica crónica (n = 11) fueron reactivos al ELISA F29. Los pacientes en quienes los estudios parasitológicos (xenodiagnóstico y/o strout) fueron (+) presentaron elevada reactividad al ELISA F29. La correlación entre ELISA F29 y SC en los pacientes tratados con SC no reactiva (grupo A) y no tratados (grupo C), fue significativa (p of group C. The infected patients who presented electrocardiographic alterations compatible with chronic chagasic myocardiopathy (n = 11) were reactive for ELISA F29. All patients whose parasitological studies (xenodiagnosis and/or strout method) were positive presented a high reactivity to the ELISA F29 test. The correlation between ELISA F29 and CS was statistically significant (p . These results suggest that the fast and user-friendly ELISA F29 test could be useful to monitor changes after trypanocidal treatment.Fil: Fabbro, Diana. Universidad Nacional del Litoral. Centro de Investigaciones Endemias Nacionales (CIEN); Argentina.Fil: Velázquez, Elsa. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología Dr. Mario Fatala Chaben; Argentina.Fil: Mendoza, Norberto. Universidad Nacional del Litoral. Centro de Investigaciones Endemias Nacionales (CIEN); Argentina.Fil: Streiger, Mirtha. Universidad Nacional del Litoral. Centro de Investigaciones Endemias Nacionales (CIEN); Argentina.Fil: Arias, Enrique. Universidad Nacional del Litoral. Centro de Investigaciones Endemias Nacionales (CIEN); Argentina.Fil: Denner, Susana. Universidad Nacional del Litoral. Centro de Investigaciones Endemias Nacionales (CIEN); Argentina.Fil: Del Barco, Mónica. Universidad Nacional del Litoral. Centro de Investigaciones Endemias Nacionales (CIEN); Argentina.Fil: Amicone, Norberto. Universidad Nacional del Litoral. Centro de Investigaciones Endemias Nacionales (CIEN); Argentina.Fil: Pravia, Carlos. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología Dr. Mario Fatala Chaben; Argentina.Fil: Malagrino, Nora. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología Dr. Mario Fatala Chaben; Argentina.Fil: Ruiz, Andres Mariano. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología Dr. Mario Fatala Chaben; Argentina

Lymphangioleiomyomatosis: Searching for potential biomarkers

Biomarkers; Lymphangioleiomyomatosis; MetalloproteinasesBiomarcadores; Linfangioleiomiomatosis; MetaloproteinasasBiomarcadors; Limfangioleiomiomatosi; MetaloproteinasesBackground: Vascular endothelial growth factor-D (VEGF-D) is the most commonly used biomarker for diagnosing lymphangioleiomyomatosis (LAM). However, lung biopsy is often necessary as well; therefore, defining new biomarkers for LAM is crucial. The aim of this study was to describe the diagnostic accuracy of a variety of biomarkers. Methods: We assessed 13 analytes in serum related to extracellular matrix remodeling, lymphatic involvement and angiogenesis in a cohort of patients with LAM, comparing them with patients with other cystic lung diseases (OCLD) and healthy women. A scoring method based on the cut-point of each VEGF-D and metalloproteinase-2 (MMP-2) was used to evaluate the diagnostic performance of the marker combination. Results: A total of 97 subjects were recruited: 59 (61%) LAM patients, 18 (19%) OCLD patients, and 20 (20%) healthy female controls. MMP-2 was the only extracellular matrix remodeling biomarker able to differentiate LAM patients from OCLD and healthy patients. Serum MMP-2 was higher in LAM patients [median 578 (465–832) ng/ml] than in patients with OCLD and healthy controls [medians 360 (314–546) and 427 (365–513) ng/ml, respectively (p < 0.0001)]. The area under ROC curve (AUC) of MMP-2 was 0.785 and that of VEGF-D 0.815 (p = 0.6214). The sensitivity/specificity profiles of each biomarker (54/92% for MMP-2, 59/95% for VEGF-D) yielded a composite score (−6.36 + 0.0059 × VEGF-D + 0.0069 × MMP-2) with higher accuracy than each component alone (AUC 0.88 and sensitivity/specificity 79/87%). Conclusion: Combining MMP-2 and VEGF-D may increase diagnostic accuracy for LAM.This project was supported by the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR), grant number: PI 638/2018. The funders have no role in study design, data and analysis collection, decision to publish, or preparation of the manuscript

Soluble co-signaling molecules predict long-term graft outcome in kidney-transplanted patients

Co-signaling molecules are responsible for full T-cell activation after solid organ transplantation. Their increased expression can lead to the release of a soluble form that can modulate the immune response post-transplantation. We analyzed the presence of co-signaling molecules (sCD30, sCD40, sCD137, sCTLA-4, sCD80, sCD28, sCD40L, sPD-1, and sPD-L1) in serum from kidney-transplanted patients (n = 59) obtained at different times (before transplantation, and 15 days, 3 months and 1 year post-transplantation) and their contribution to graft outcome was evaluated using principal component analysis. Before transplantation, high levels of soluble co-signaling molecules (mainly sCD30, sCD137 and sCD40) were detected in all patients. These molecules were modulated soon after receiving an allograft but never attained similar levels to those of healthy controls. A signature based on the determination of six soluble co-stimulatory (sCD30, sCD40, sCD137 and sCD40L) and co-inhibitory (sPD-1 and sPD-L1) molecules at 3 months post-transplantation allowed a group of patients to be identified (27.12%) with a worse long-term graft outcome. Patients with high levels of soluble molecules showed a progressive and gradual deterioration of kidney function (increased creatinine and proteinuria levels and decreased estimated glomerular filtration rate) over time and a higher risk of graft loss at 6 years post-transplantation than patients with low levels of these molecules (62.55% versus 5.14%, p<0.001). Thus, our data show an aberrant expression of soluble co-signaling molecules in kidney-transplanted patients whose quantification at 3 months post-transplantation might be a useful biomarker of immune status and help to predict long-term graft evolution

A reliable and valid tool to assess the sexual acceptability of contraceptive methods

IntroductionAdequate identification of the sexual acceptability of contraceptive methods is key for designing health promotion interventions, assessing their impacts, and increasing their effectiveness. This study aimed to develop and validate a questionnaire to explore the preferences of women depending on their epidemiological characteristics and their partner relationships—the Sexual Acceptability of Contraceptive Methods Questionnaire [in Spanish, Aceptabilidad Sexual de los Métodos Anticonceptivos (ASMA)].MethodsPsychometric validation was conducted using Exploratory Factorial Analysis (EFA) and confirmatory factor analysis (CFA). The reliability of the final version of the questionnaire was explored using Cronbach’s alpha and McDonald omega to estimate internal consistency.ResultsA three-factor model was identified. Factor 1 (explaining 28.32% of the model) corresponds to questions concerning the use and placement of the contraceptive and includes 6 items; Factor 2 (explaining 24.23%) corresponds to other factors that affect the relationship such as bleeding and side effects of the contraceptive method and includes 10 items; and Factor 3 (explaining 18.94%) corresponds to the couple relationship and includes 8 items.Conclusion and implicationsThe ASMA questionnaire provides a valid and reliable tool for assessing the sexual acceptability of various contraceptive methods. This instrument gathers data that provide information on various aspects of women’s sexuality, health, education, and beliefs, all of which can determine the preference for one contraceptive method over another. Moreover, the tool can help to identify profiles of women who have different preferences when selecting a particular method

Clustering COVID-19 ARDS patients through the first days of ICU admission. An analysis of the CIBERESUCICOVID Cohort

Background Acute respiratory distress syndrome (ARDS) can be classified into sub-phenotypes according to different inflammatory/clinical status. Prognostic enrichment was achieved by grouping patients into hypoinflammatory or hyperinflammatory sub-phenotypes, even though the time of analysis may change the classification according to treatment response or disease evolution. We aimed to evaluate when patients can be clustered in more than 1 group, and how they may change the clustering of patients using data of baseline or day 3, and the prognosis of patients according to their evolution by changing or not the cluster.Methods Multicenter, observational prospective, and retrospective study of patients admitted due to ARDS related to COVID-19 infection in Spain. Patients were grouped according to a clustering mixed-type data algorithm (k-prototypes) using continuous and categorical readily available variables at baseline and day 3.Results Of 6205 patients, 3743 (60%) were included in the study. According to silhouette analysis, patients were grouped in two clusters. At baseline, 1402 (37%) patients were included in cluster 1 and 2341(63%) in cluster 2. On day 3, 1557(42%) patients were included in cluster 1 and 2086 (57%) in cluster 2. The patients included in cluster 2 were older and more frequently hypertensive and had a higher prevalence of shock, organ dysfunction, inflammatory biomarkers, and worst respiratory indexes at both time points. The 90-day mortality was higher in cluster 2 at both clustering processes (43.8% [n = 1025] versus 27.3% [n = 383] at baseline, and 49% [n = 1023] versus 20.6% [n = 321] on day 3). Four hundred and fifty-eight (33%) patients clustered in the first group were clustered in the second group on day 3. In contrast, 638 (27%) patients clustered in the second group were clustered in the first group on day 3.Conclusions During the first days, patients can be clustered into two groups and the process of clustering patients may change as they continue to evolve. This means that despite a vast majority of patients remaining in the same cluster, a minority reaching 33% of patients analyzed may be re-categorized into different clusters based on their progress. Such changes can significantly impact their prognosis

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation