Identification of Mir-182-3p/FLI-1 Axis as a Key Signaling in Immune Response in Cervical Cancer: A Comprehensive Bioinformatic Analysis.

miRNAs modulate gene expression and play critical functions as oncomiRs or tumor suppressors. The miR-182-3p is important in chemoresistance and cancer progression in breast, lung, osteosarcoma, and ovarian cancer. However, the role of miR-182-3p in cervical cancer (CC) has not been elucidated. AIM: To analyze the role of miR-182-3p in CC through a comprehensive bioinformatic analysis. METHODS: Gene Expression Omnibus (GEO) databases were used for the expression analysis. The mRNA targets of miR-182-3p were identified using miRDB, TargetScanHuman, and miRPathDB. The prediction of island CpG was performed using the MethPrimer program. The transcription factor binding sites in the FLI-1 promoter were identified using ConSite+, Alibaba2, and ALGGEN-PROMO. The protein-protein interaction (PPI) analysis was performed in STRING 11.5. RESULTS: miR-182-3p was significantly overexpressed in CC patients and has potential as a diagnostic. We identified 330 targets of miR-182-3p including FLI-1, which downregulates its expression in CC. Additionally, the aberrant methylation of the FLI-1 promoter and Ap2a transcription factor could be involved in downregulating FLI1 expression. Finally, we found that FLI-1 is a possible key gene in the immune response in CC. CONCLUSIONS: The miR-182-3p/FLI-1 axis plays a critical role in immune response in CC.

NT-pro-BNP is predictive of morbidity and mortality after pulmonary thromboendarterectomy and is independent of preoperative hemodynamics.

Current predictors of clinical outcomes after pulmonary thromboendarterectomy (PTE) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) are largely limited to preoperative clinical characteristics. N-terminal-pro-brain natriuretic peptide (NT-pro-BNP), a biomarker of right ventricular dysfunction, has not yet been well described as one such predictor. From 2017 to 2021, 816 patients with CTEPH referred to the University of California, San Diego for PTE were reviewed for differences in NT-pro-BNP to predict preoperative characteristics and postoperative outcomes up to 30 days post-PTE. For analysis, NT-pro-BNP was dichotomized to less than/equal to or greater than 1000 pg/mL based on the mean of the study population. Mean NT-pro-BNP was 1095.9 ±1783.4 pg/mL and median was 402.5 pg/mL (interquartile range: 119.5-1410.8). Of the 816 patients included, 250 had NT-pro-BNP > 1000 pg/mL. Those with NT-pro-BNP > 1000 pg/mL were significantly more likely to have worse preoperative functional class (III-IV) and worse preoperative hemodynamics. Patients with NT-pro-BNP > 1000 pg/mL also tended to have more postoperative complications including reperfusion pulmonary edema (22% vs. 5.1%, p < 0.001), airway hemorrhage (8.4% vs. 4.9%, p = 0.075), residual pulmonary hypertension (11.9% vs. 3.1%, p < 0.001), and 30-day mortality (4.8% vs. 1.1%, p = 0.001). Even after adjusting for confounders, patients with NT-pro-BNP > 1000 pg/mL had a 2.48 times higher odds (95% confidence interval: 1.45-4.00) of reaching a combined endpoint that included the above complications. Preoperative NT-pro-BNP > 1000 pg/mL is a strong predictor of more severe preoperative hemodynamics and identifies patients at higher risk for postoperative complications.

Repeat pulmonary thromboendarterectomy outcomes: A 15-year single-center retrospective review.

OBJECTIVE: Chronic thromboembolic pulmonary hypertension is potentially curable via pulmonary thromboendarterectomy. A minority of patients experience recurrence of their symptoms and are eligible for repeat pulmonary thromboendarterectomy. However, little data exist regarding risk factors and outcomes for this patient population. METHODS: We performed a retrospective review of the University of California San Diego chronic thromboembolic pulmonary hypertension quality improvement database, including all patients who underwent pulmonary thromboendarterectomy from December 2005 to December 2020. Of the 2019 cases performed during this period, 46 were repeat pulmonary thromboendarterectomy procedures. Demographics, preoperative and postoperative hemodynamics, and surgical complications were compared between the repeat pulmonary thromboendarterectomy group and 1008 first pulmonary thromboendarterectomy group. RESULTS: Repeat pulmonary thromboendarterectomy recipients were more likely to be younger, to have an identified hypercoagulable state, and to have higher preoperative right atrial pressure. Etiologies of recurrent disease include incomplete initial endarterectomy, discontinuation of anticoagulation (noncompliance or for medical reasons), and anticoagulation treatment failure. Patients who received repeat pulmonary thromboendarterectomy had significant hemodynamic improvement, but less pronounced compared with patients who received first pulmonary thromboendarterectomy. Repeat pulmonary thromboendarterectomy was associated with an increased risk of postoperative bleeding, reperfusion lung injury, residual pulmonary hypertension, and increased ventilator, intensive care unit, and hospital days. However, hospital mortality was similar between the groups (2.2% vs 1.9%). CONCLUSIONS: This is the largest reported series of repeat pulmonary thromboendarterectomy surgery. Despite an increase in postoperative complications, this study demonstrates that repeat pulmonary thromboendarterectomy surgery can result in significant hemodynamic improvement with acceptable surgical mortality in an experienced center.

Airway Hemorrhage Complicating Pulmonary Thromboendarterectomy: Risk Factors and Outcomes.

BACKGROUND: Airway hemorrhage is a known complication of pulmonary thromboendarterectomy (PTE) in patients with chronic thromboembolic pulmonary hypertension. Predisposing factors for postoperative airway hemorrhage have not been well described. The aims of this study were to determine the incidence and outcomes of airway hemorrhage after PTE and to identify potential risk factors. METHODS: This was a retrospective chart review of subjects undergoing PTE between 2015 and 2019. Postoperative airway hemorrhage was defined as significant endobronchial bleeding requiring withholding anticoagulation, bronchial blocker placement, and/or extracorporeal membrane oxygenation (ECMO). RESULTS: Of 877 subjects who underwent PTE, 58 subjects (6.6%) developed postoperative airway hemorrhage. Subjects with hemorrhage were more likely to be women (60% vs 45%, P = .03), to be older (57.8 vs 54.0 years, P = .04), and to have a higher incidence of preoperative hemoptysis (19.0% vs 7.6%, P = .006) compared with control subjects (subjects without airway hemorrhage). Those with hemorrhage had significantly higher preoperative right atrial pressure (P = .002) and pulmonary vascular resistance (P < .001) and a higher incidence of residual pulmonary hypertension (P = .005). Airway hemorrhage management included ECMO with bronchial blocker (n = 2), bronchial blocker without ECMO (n = 26), or withholding anticoagulation alone until bleeding subsided (n = 30). Mortality was significantly higher in those with airway hemorrhage compared with control subjects (13.8% vs 1.2%, P < .001). CONCLUSIONS: The incidence of postoperative airway hemorrhage is low but associated with significant mortality. Older age, female sex, preoperative hemoptysis, and worse preoperative pulmonary hypertension were associated with an increased risk of developing postoperative airway hemorrhage.

Prácticas y estrategias didácticas en el modelo pedagógico constructivista en enfermería / Didactic practices and strategies in the constructivist pedagogical model in nursingconstructivist pedagogical model in nursing

Objetivo: analizar la relación de las prácticas pedagógicas y estrategias didácticas utilizadas en el aula y los escenarios de práctica clínica de V semestre de la facultad de enfermería de la Fundación Universitaria de Ciencias de la Salud de Bogotá, con el modelo pedagógico institucional. Método: estudio cualitativo con enfoque etnográfico en el que participaron directivos, docentes y estudiantes, aplicando técnicas de observación no participante y entrevista semiestructurada. Se utilizó la herramienta ATLAS. Ti y se realizó triangulación entre documentos institucionales, entrevistas y la observación no participante. Resultados: se partió de cuatro categorías predeterminadas y emergieron cuatro adicionales, que dan cuenta de la relación entre el modelo pedagógico institucional con las prácticas pedagógicas y estrategias didácticas utilizadas por los docentes. Conclusiones: la institución en su trayectoria ha pasado por varios modelos pedagógicos sin que se haya realizado un estudio que evidencie el tránsito de un modelo a otro; ahora se están implementando varias estrategias para que docentes y estudiantes se apropien del modelo constructivista, lo que ha derivado en dificultades en la implementación, confusiones y tensiones. Este trabajo en conjunto con directivos, docentes y estudiantes, propone estrategias para facilitar la apropiación del modelo y su incorporación en las prácticas y estrategias didácticas.

Objective: to analyze the relationship between the pedagogical practices and teaching strategies used in the classroom and clinical practice scenarios of the 5th semester of the School of Nursing at Fundación Universitaria de Ciencias de la Salud in Bogotá, and the institutional pedagogical model. Method: ethnographic qualitative study with the participation of the directive staff, teachers and students, applying non-participant observation and semi-structured interview techniques. The ATLAS.Ti software was used and triangulation comparing institutional documents, interviews and non-participant observation was conducted. Results: four predetermined categories were used as a starting point and four additional categories emerged, showing the relationship between the institutional pedagogical model and the pedagogical practices and teaching strategies used by teachers. Conclusions: the institution has used several pedagogical models without conducting a study that evidences the transition from one model to another; currently, several strategies are being implemented for teachers and students to appropriate the constructivist model, causing difficulties, confusion and tension during its implementation. This work, with the participation of the directive staff, teachers and students, proposes strategies to facilitate the appropriation of the model and its integration in didactic practices and strategies.

Determinación de factores de adhesión asociados a la formación de biopelícula en aislamientos clínicos de Staphylococcus aureus y Staphylococcus epidermidis / Determination of adhesion factors associated with biofilm formation in clinical isolates of Staphylococcus aureus and Staphylococcus epidermidis

Resumen Los factores de adhesión son determinantes de virulencia que se expresan en microorganismos que tienen la capacidad de formar biopelícula, contribuyendo a la gravedad de infecciones intrahospitalarias. Dentro de estos componentes de la superficie microbiana que reconocen moléculas de adhesión de matriz conocidas como MSCRAMMs, se incluyen el factor de unión a fibronectina A y B, (FnbA y B) factor de aglutinación A y B (ClfA y B) y factor de unión a fibrinógeno (Fib), que se han descrito en Staphylococcus aureus y reaccionan con proteínas de la matriz extracelular humana. El objetivo de este estudio fue determinar la presencia de estos factores de adhesión relacionados con la formación de biopelicula en Staphylococcus. Método. Se caracterizaron fenotípica y genotípicamente 30 aislamientos clínicos de Staphylococcus aureus y Staphylococcus epidermidis, provenientes de pacientes inmunocomprometidos en tres instituciones hospitalarias de Bogotá. La producción de Biopelícula se determinó mediante Rojo Congo y Cristal violeta y mediante PCR convencional y múltiplex se amplificaron los genes FnbA y B, ClfA y B y Fib, así como los genes del operón ica ADBC. Resultados. Todos los aislamientos clínicos fueron positivos genotípica y fenotípicamente para la producción de Biopelícula, encontrándose la presencia del operón completo en el 88.9%, los factores ClfA y ClfB en un 70%; Fib en un 60%, FnbB en un 23% y FnbA en el 17%. Conclusiones. En este estudio se evidenció la presencia de estos factores de virulencia en S. epidermidis, los cuáles hasta el momento se han reportado únicamente en S.aureus. Este hallazgo es importante ya que se sugiere la relación con transferencia horizontal de genes entre estas especies, siendo el S. epidermidis un importante reservorio genético, y un importante patobionte causal de infecciones nosocomiales, asociado con dispositivos médicos.

Abstract Adhesion factors are virulence determinants that are expressed in microorganisms with the ability to form biofilms, contributing to the severity of nosocomial infections. Among these microbial surface components recognizing adhesive matrix molecules (MSCRAMMs), are fibronectin binding A and B (fnbA and B) clumping A and B (ClfA and B) and fibrinogen binding (Fib) factors. All of these have been described in Staphylococcus aureus and react with human extracellular matrix proteins. The goal of this study was to determine adhesion factors related to the biofilm formation in Staphylococcus. Method. For these purpose, 30 clinical isolates of Staphylococcus aureus and Staphylococcus epidermidis, from immunocompromised patients in three hospitals in Bogotá were characterized both, genotypically and phenotypically. The biofilm formation was determined through Congo Red and Violet Crystal and the genes FnbA, B, ClfA, B, Fib and operon ica ADBC were amplified through conventional and multiplex PCR. Results. Every clinical isolate were genotypically and phenotypically positive for the biofilm formation, being found the presence of the whole ica ADBC operon in 88,9%. The ClfA and ClfB were found by 70%; Fib 60%, fnbB 23% and 17% offnbA. Conclusions. This study proved the presence of these virulence factors in S. epidermidis, which so far have only been reported in S. aureus. This finding is important because it suggestes the relationship with horizontal gene transfer between these species, being the S. epidermidis an important genetic reservoir and a causal patobiont of nosocomial infections associated with medical devices.

Nasal nitric oxide and nasal eosinophils decrease with levocetirizine in subjects with perennial allergic rhinitis.

BACKGROUND: Allergic rhinitis is commonly treated with antihistamines. Monitoring improvement of airway inflammation noninvasively using nasal nitric oxide (nNO) would be clinically useful. To determine the anti-inflammatory effect of oral levocetirizine dihydrochloride (LC), we measured nNO and nasal eosinophils (nEos) in perennial allergic rhinitis (PAR) subjects. METHODS: A randomized double-blind placebo-controlled crossover design was used. Inclusion criteria consisted of subjects having a PAR history, exam and diary scores consistent with active symptoms, and positive skin testing. Subjects taking allergy medications 1 month before the study were not enrolled. After consenting, 31 subjects (24 female subjects; mean age, 29 years) were randomized to either oral LC (5 mg) or matching placebo for 2 weeks. After 2 week washout, subjects started the other 2-week treatment. At each visit, nNO was measured by aspiration at each nare using a nasal kit from NIOX (Aerocrine, Sweden) in parts per billion; nEos was collected from nasal smears and measured by microscopy using the scoring system (0-4+) and symptoms were self-reported using the allergic Rhinitis Quality of Life Questionnaire (RQLQ). Daily allergy symptom scores (total symptom score [TSS] 4) were collected at each visit. RESULTS: During LC, mean baseline nNO was 807 ± 317 parts per billion (ppb; left) and 831 ± 332 ppb (right) and decreased significantly to 688 ± 266 ppb and 702 ± 286 ppb, respectively (p < 0.05). No significance was found during placebo treatment (778 ± 270 ppb, 808 ± 299 ppb to 802 ± 271 ppb, 813 ± 273 ppb). The mean nNO change was also significant compared with placebo (-125 ppb versus +14 ppb; p < 0.05). There was a significant decrease in nEos with LC compared with placebo (3.1-2.5 versus 2.9-2.6; p < 0.05). RQLQ scores were significantly improved with LC only. In TSS-4 scoring, a trend toward improvement during LC and significant worsening during placebo was found. Baseline nNO predicted changes in nasal eosinophils (nEos) and RQLQ. CONCLUSION: We showed that oral LC therapy decreased objective markers of rhinitis inflammation, nNO and nEos, in patients with PAR. Improvement in symptom scoring was also found with LC treatment.