Genetic Determinants for Prediction of Outcome of Patients with Papillary Thyroid Carcinoma

Aggressive metastatic disease is rare in papillary thyroid carcinoma (PTC), a neoplasia that usually carries an excellent prognosis. BRAF, RAS, and TERT promoter (TERTp) genes are altered in PTC, and their impact on patient outcomes remains controversial. We performed Sanger sequencing on a series of 241 PTCs to determine the role of genetic mutations (BRAF, RAS, and TERTp) in PTC patient outcomes. The implication of RAS mut tumors remain uncertain in clinical terms. BRAF mut /TERTp wt tumors were prone to be associated with local aggressiveness (recurrent, persistent/disease), whereas TERTp mut tumors were predisposed to recurrent/persistent structural disease, and disease-specific mortality. Our results indicate that different molecular markers play a distinct role in predicting PTC patient outcomes. Papillary thyroid carcinoma (PTC) usually presents an excellent prognosis, but some patients present with aggressive metastatic disease. BRAF, RAS, and TERT promoter (TERTp) genes are altered in PTC, and their impact on patient outcomes remains controversial. We aimed to determine the role of genetic alterations in PTC patient outcomes (recurrent/persistent disease, structural disease, and disease-specific mortality (DSM)). The series included 241 PTC patients submitted to surgery, between 2002-2015, in a single hospital. DNA was extracted from tissue samples of 287 lesions (primary tumors and metastases). Molecular alterations were detected by Sanger sequencing. Primary tumors presented 143 BRAF, 16 TERTp, and 13 RAS mutations. Isolated TERTp mut showed increased risk of structural disease (HR = 7.0, p < 0.001) and DSM (HR = 10.1, p = 0.001). Combined genotypes, BRAF wt /TERTp mut (HR = 6.8, p = 0.003), BRAF mut /TERTp mut (HR = 3.2, p = 0.056) and BRAF mut /TERTp wt (HR = 2.2, p = 0.023) showed increased risk of recurrent/persistent disease. Patients with tumors BRAF wt /TERTp mut (HR = 24.2, p < 0.001) and BRAF mut /TERTp mut (HR = 11.5, p = 0.002) showed increased risk of structural disease. DSM was significantly increased in patients with TERTp mut regardless of BRAF status (BRAF mut /TERTp mut, log-rank p < 0.001; BRAF wt /TERTp mut, log-rank p < 0.001). Our results indicate that molecular markers may have a role in predicting PTC patients' outcome. BRAF mut /TERTp wt tumors were prone to associate with local aggressiveness (recurrent/persistent disease), whereas TERTp mut tumors were predisposed to recurrent structural disease and DSM

Trained immunity induction by the inactivated mucosal vaccine MV130 protects against experimental viral respiratory infections.

MV130 is an inactivated polybacterial mucosal vaccine that confers protection to patients against recurrent respiratory infections, including those of viral etiology. However, its mechanism of action remains poorly understood. Here, we find that intranasal prophylaxis with MV130 modulates the lung immune landscape and provides long-term heterologous protection against viral respiratory infections in mice. Intranasal administration of MV130 provides protection against systemic candidiasis in wild-type and Rag1-deficient mice lacking functional lymphocytes, indicative of innate immune-mediated protection. Moreover, pharmacological inhibition of trained immunity with metformin abrogates the protection conferred by MV130 against influenza A virus respiratory infection. MV130 induces reprogramming of both mouse bone marrow progenitor cells and in vitro human monocytes, promoting an enhanced cytokine production that relies on a metabolic shift. Our results unveil that the mucosal administration of a fully inactivated bacterial vaccine provides protection against viral infections by a mechanism associated with the induction of trained immunity.We are grateful to members of the D.S. laboratory for discussions and critical reading of the manuscript. We thank the CNIC facilities and personnel for assistance. P.B. is funded by grant BES-2014-069933 (‘‘Ayudas para Contratos Predoctorales para la Formacio´ n de Doctores 2014’’) from the Spanish Ministry of Economy, Industry and Competitiveness (MINECO). L.C. was a recipient of a European Respiratory Society Fellowship (RESPIRE2-2013- 3708). G.D. is supported by a European Molecular Biology Organization Long-term Fellowship (ALTF 379-2019). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sk1odowska-Curie grant agreement No. 892965. Work in the D.S. laboratory is funded by the CNIC; by the European Research Council (ERC-2016-consolidator grant 725091); by the European Commission (635122-PROCROP H2020); by Ministerio de Ciencia e Innovacio´ n (MICINN), Agencia Estatal de Investigacio´ n (AEI), and Fondo Europeo de Desarrollo Regional (FEDER) (SAF2016-79040-R); by AEI (PID2019-108157RB); by Comunidad de Madrid (B2017/BMD-3733 Immunothercan-CM); by FIS-Instituto de Salud Carlos III, MICINN and FEDER (RD16/0015/0018-REEM); by a collaboration agreement with Inmunotek; by Atresmedia (Constantes y Vitales prize); by Fundacio´ La Marato´ de TV3 (201723); and by Fondo Solidario Juntos (Banco Santander). The CNIC is supported by the Instituto de Salud Carlos III, the MICINN, and the Pro CNIC Foundation.S

Cortisol secretion after adrenocorticotrophin (ACTH) and Dexamethasone tests in healthy female and male dogs

<p>Abstract</p> <p>Background</p> <p>For the conclusive diagnosis of Cushing's Syndrome, a stimulating ACTH test or a low suppressive Dexamethasone test is used. Reports in other species than the dog indicate that plasma cortisol concentration after ACTH administration is affected by gender. We investigated the effect of gender on the cortisol response to ACTH and Dexamethasone tests in dogs.</p> <p>Methods</p> <p>Seven healthy adult Cocker Spaniels (4 females and 3 males) were assigned to a two by two factorial design: 4 dogs (2 females and 2 males) received IV Dexamethasone 0.01 mg/kg, while the other 3 dogs received an IV saline solution (control group). Two weeks later the treatments were reversed. After one month, ACTH was given IV (250 μg/animal) to 4 dogs (2 female and 2 males) while the rest was treated with saline solution (control group). Cortisol concentrations were determined by a direct solid-phase radioimmunoassay and cholesterol and triglycerides by commercial kits.</p> <p>Results and Discussion</p> <p>No effect of treatment was observed in metabolite concentrations, but females presented higher cholesterol concentrations. ACTH-treated dogs showed an increase in cortisol levels in the first hour after sampling until 3 hours post injection. Cortisol concentrations in Dexamethasone-treated dogs decreased one hour post injection and remained low for 3 hours, thereafter cortisol concentrations increased. The increase in cortisol levels from one to two hours post ACTH injection was significantly higher in females than males. In Dexamethasone-treated males cortisol levels decreased one hour post injection up to 3 hours; in females the decrease was more pronounced and prolonged, up to 5 hours post injection.</p> <p>Conclusion</p> <p>We have demonstrated that cortisol response to ACTH and Dexamethasone treatment in dogs differs according to sex.</p

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Gestión del conocimiento. Perspectiva multidisciplinaria. Volumen 17

El libro “Gestión del Conocimiento. Perspectiva Multidisciplinaria”, Volumen 17 de la Colección Unión Global, es resultado de investigaciones. Los capítulos del libro, son resultados de investigaciones desarrolladas por sus autores. El libro es una publicación internacional, seriada, continua, arbitrada, de acceso abierto a todas las áreas del conocimiento, orientada a contribuir con procesos de gestión del conocimiento científico, tecnológico y humanístico. Con esta colección, se aspira contribuir con el cultivo, la comprensión, la recopilación y la apropiación social del conocimiento en cuanto a patrimonio intangible de la humanidad, con el propósito de hacer aportes con la transformación de las relaciones socioculturales que sustentan la construcción social de los saberes y su reconocimiento como bien público

Rotavírus: um importante agente de infecção pediátrica

Uma das causas mais comuns de desidratação provocada por diarréia em crianças em todo mundo é a infecção por rotavirus. Este agente etiológico lidera as causas de gastrenterites não bacterianas, podendo infectar crianças em qualquer idade e também adultos. Devido à existência de um grande número de genótipos e sorogrupos, o estudo epidemiológico e o diagnóstico da doença causada por rotavirus tornam-se difíceis. A grande incidência global da gastrenterite por rotavirus, especialmente em países em desenvolvimento, levou ao desenvolvimento de vacinas, procurando diminuir a morbidade e a mortalidade ligada aesta infecção. O objetivo desta revisão é atualizar o profissional da saúde sobre os aspectos clínicos e laboratoriais, auxiliando no reconhecimento e rápido diagnóstico desta patologia

Aula abierta

Resumen tomado de la publicaciónEl grit es una variable importante para predecir indicadores de éxito en diversos contextos entre los que se encuentra el académico. Sin embargo, son escasos los instrumentos de medida de grit bien validados en apoyo a la investigación. El objetivo del presente estudio es consolidar la validación de la Escala Grit de Oviedo (EGO) presentando datos de su validación en Portugal. Se empleó una muestra de 285 participantes portugueses (M años= 18.46; DT años= 1.30). Además, se empleó una muestra de población española para analizar la invarianza de medida (330 participantes; M años= 23.01 y DT años= 3.22). Se confirmó la unidimensionalidad de la escala EGO en el contexto portugués, mostrando además invarianza escalar entre ambas poblaciones. La fiabilidad de la escala EGO fue excelente (ω = .96), y mostró una correlación moderada con el bienestar subjetivo (r = .28) y con la confianza para terminar el curso académico (r = .33). La escala EGO puede ser empleada para estudiar el grit en Portugal.ES