Análisis de las vías de carcinogénesis del cáncer colorrectal sincrónico no hereditario

El cáncer colorrectal (CCR), es la tercera neoplasia más común y la segunda causa de mortalidad por cáncer en los países desarrollados. Desde una perspectiva molecular, la formación de un tumor es consecuencia de la acumulación de múltiples alteraciones tanto a nivel genético como epigenético. La mayoría de los CCR son esporádicos y aparecen como consecuencia de mutaciones a nivel somático. Sin embargo, pueden existir mutaciones a nivel germinal que transmiten la susceptibilidad para el CCR a las generaciones posteriores, produciendo los diferentes síndromes de CCR hereditario. Se han identificado tres grandes vías de carcinogénesis en el desarrollo del CCR: vía supresora o de inestabilidad cromosómica (INC), vía mutadora o de inestabilidad de microsatélites (IMS) vía metiladora o del fenotipo metilador de islas de CpG (CIMP). La vía supresora o de INC es la alteración más frecuente. No sólo se encuentra en la mayor parte de los casos de CCR esporádicos, sino también en síndromes hereditarios como la poliposis adenomatosa familiar (PAF). Este tipo de tumores se caracterizan por el desequilibrio cromosómico (aneuploidía), con deleciones, amplificaciones y una alta frecuencia de pérdida de heterocigosidad (LOH, Loss of Heterozygosity). Existen dos tipos de alteraciones: 1. la activación de oncogenes, como K-RAS y c-MYC 2. la inactivación de genes supresores del crecimiento tumoral, APC, DCC, p53, TGFBR o PIK3CA..

Prevalence and distribution of infectious and parasitic agents in roe deer from Spain and their possible role as reservoirs

In order to provide up-to-date information about the prevalence of infectious and parasitic agents in Spanish roe deer (Capreolus capreolus), samples from 93 animals hunted from January 2013 to April 2015 were collected and analysed by parasitological, serological and molecular techniques. Sampled animals came from four roe deer populations corresponding to Oceanic, Continental, Mediterranean and Mountainous ecosystems of Spain. Data regarding sex, age and year were also considered. A high percentage of roe deer (95.7%) resulted positive for at least one agent. Sarcocystis spp. was the most frequently diagnosed genus (88.8%), followed by gastrointestinal nematodes (62.9%) and Schmallenberg virus (53.5%). Varestrongylus capreoli (38%), Anaplasma phagocitophylum (34.2%), Eimeria spp. (29.2%), Toxoplasma gondii (25%) and Cephenemyia stimulator (23.8%) displayed medium prevalences and, finally low percentages were registered for Moniezia spp. (6.7%), Dictyocaulus noerneri (2.4%) and Mycobacterium avium subsp. paratuberculosis (1.5%). No infections by Neospora caninum, Bovine herpesvirus, pestivirus or Coxiella burnetii were found. Climate was significantly associated with the prevalence of T. gondii, C. stimulator and A. phagocitophylum, with higher prevalences in animals from Oceanic and Mediterranean areas. Our results suggest that infections affecting Spanish roe deer, especially those of parasitic aetiology, represent one of the causes of the descent in the abundance of this ungulate in the last years. Moreover, the high prevalence of zoonotic agents such as T. gondii and A. phagocitophylum could also have a great relevance in the environmental and/or Public Health.This research was supported by a Programme for consolidating and structuring competitive research groups (GRC2015/003, Xunta de Galicia) and by the Research Project ‘RUMIGAL: Rede de estudo multidisciplinar dos ruminantes en Galicia’ (R2014/005, Xunta de Galicia, Spain)S

Fasciola hepatica ectópica en pulmón de bovinos sacrificados en el Centro de Beneficio Municipal de Cajamarca, Perú

The aim of this study was the evaluate the frequency and morphometric characterization of ectopic Fasciola hepatica in the lung. For this, 2066 lungs of cattle were evaluated in the municipal abattoir of Cajamarca, Peru, between July and August 2018. The lungs presenting macroscopic lesions were reviewed to determine the presence or absence of ectopic Fasciola hepatica. The frequency of erratic pulmonary fasciolosis was 3.68 ± 0.8%. Morphometrically, the ectopic Fasciola hepatica maintains a foliaceous shape, with pale pinkish to grey-brown coloration, measuring 10.36 ± 3.44 mm long and 4.31 ± 0.97 mm wide, and without evidence of oviposition.Con el objetivo de evaluar la frecuencia y caracterización morfométrica de Fasciola hepatica ectópica en pulmón, se evaluaron 2066 bovinos en el centro de beneficio municipal de Cajamarca, Perú, entre julio y agosto de 2018. Los pulmones que presentaron lesiones macroscópicas fueron revisados para determinar la presencia o ausencia de Fasciola hepatica ectópica. Se determinó una frecuencia de la fasciolosis errática pulmonar de 3.68 ± 0.8%. Morfométricamente, se observó que la Fasciola hepatica ectópica mantiene una forma foliácea, con coloraciones de rosado-pálido a marrón-grisáceo y con dimensiones de 10.36 ± 3.44 mm de largo y 4.31 ± 0.97 mm de ancho, y sin evidencia de ovoposición

Antenatal Betamethasone Every 12 Hours in Imminent Preterm Labour

Background: Benefits of antenatal corticosteroids have been established for preterm infants who have received the full course. In imminent preterm labours there is no time to administer the second dose 24 h later. Objective: To determine whether the administration of two doses of betamethasone in a 12 h interval is equivalent to the effects of a full maturation. Methods: We performed a retrospective cohort study including preterm infants ≤34 weeks gestational age at birth and ≤1500 g, admitted to an NICU IIIC level in a tertiary hospital from 2015 to 2020. The population was divided into two cohorts: complete maturation (CM) (two doses of betamethasone 24 h apart), or advanced maturation (AM) (two doses of betamethasone 12 h apart). The primary outcomes were mortality or survival with severe morbidities. The presence of respiratory distress syndrome and other morbidities of prematurity were determined. These variables were analysed in the neonates under 28 weeks gestational age cohort. Neurodevelopment at 2 years was evaluated with the validated Ages and Stages Questionnaires®, Third Edition (ASQ®-3). Multiple regression analyses were performed and adjusted for confounding factors. Results: A total of 275 preterm neonates were included. Serious outcomes did not show differences between cohorts, no increased incidence of morbidity was found in AM. A lower percentage of hypotension during the first week (p = 0.04), a tendency towards lower maximum FiO2 (p = 0.14) and to a shorter mechanical ventilation time (p = 0.14) were observed for the AM cohort. Similar results were found in the subgroup of neonates under 28 weeks gestational age. There were no differences in cerebral palsy or sensory deficits at 24 months of corrected age, although the AM cohort showed a trend towards better scores on the ASQ3 scale. Conclusions: Administration of betamethasone every 12 h showed similar results to the traditional pattern with respect to mortality and severe morbidities. (...)This research received no external funding. Partial funding for open access charge: Universidad de Málag

Proper assignation of reactivation in a COVID-19 recurrence initially interpreted as a reinfection

A 77-year-old-male (Case R) who had had a previous diagnosis of mild COVID-19 episode, was hospitalized 35 days later. On Day 23 post-admission, he developed a second COVID-19 episode, now severe, and finally died. Initially, Case R COVID-19 recurrence was interpreted as a reinfection due to the exposure to a SARS-CoV-2 RT-PCR-positive room-mate. However, whole-genome-sequencing indicated that case R recurrence corresponded to a reactivation of the strain involved in his first episode. Case R reactivation had major consequences, leading to a more severe episode, and causing a subsequent transmission to another two hospitalized patients, one of them with fatal outcome.Peer reviewe

YES1 drives lung cancer growth and progression and predicts sensitivity to dasatinib

Rationale: The characterization of new genetic alterations is essential to assign effective personalized therapies in non–small cell lung cancer (NSCLC). Furthermore, finding stratification biomarkers is essential for successful personalized therapies. Molecular alterations of YES1, a member of the SRC (proto-oncogene tyrosine-protein kinase Src) family kinases (SFKs), can be found in a significant subset of patients with lung cancer. Objectives: To evaluate YES1 (v-YES-1 Yamaguchi sarcoma viral oncogene homolog 1) genetic alteration as a therapeutic target and predictive biomarker of response to dasatinib in NSCLC. Methods: Functional significance was evaluated by in vivo models of NSCLC and metastasis and patient-derived xenografts. The efficacy of pharmacological and genetic (CRISPR [clustered regularly interspaced short palindromic repeats]/Cas9 [CRISPR-associated protein 9]) YES1 abrogation was also evaluated. In vitro functional assays for signaling, survival, and invasion were also performed. The association between YES1 alterations and prognosis was evaluated in clinical samples. Measurements and Main Results: We demonstrated that YES1 is essential for NSCLC carcinogenesis. Furthermore, YES1 overexpression induced metastatic spread in preclinical in vivo models. YES1 genetic depletion by CRISPR/Cas9 technology significantly reduced tumor growth and metastasis. YES1 effects were mainly driven by mTOR (mammalian target of rapamycin) signaling. Interestingly, cell lines and patient-derived xenograft models with YES1 gene amplifications presented a high sensitivity to dasatinib, an SFK inhibitor, pointing out YES1 status as a stratification biomarker for dasatinib response. Moreover, high YES1 protein expression was an independent predictor for poor prognosis in patients with lung cancer. Conclusions: YES1 is a promising therapeutic target in lung cancer. Our results provide support for the clinical evaluation of dasatinib treatment in a selected subset of patients using YES1 status as predictive biomarker for therapy

Risk Factors for COVID-19 in Inflammatory Bowel Disease: A National, ENEIDA-Based Case–Control Study (COVID-19-EII)

(1) Scant information is available concerning the characteristics that may favour the acquisition of COVID-19 in patients with inflammatory bowel disease (IBD). Therefore, the aim of this study was to assess these differences between infected and noninfected patients with IBD. (2) This nationwide case-control study evaluated patients with inflammatory bowel disease with COVID-19 (cases) and without COVID-19 (controls) during the period March-July 2020 included in the ENEIDA of GETECCU. (3) A total of 496 cases and 964 controls from 73 Spanish centres were included. No differences were found in the basal characteristics between cases and controls. Cases had higher comorbidity Charlson scores (24% vs. 19%; p = 0.02) and occupational risk (28% vs. 10.5%; p < 0.0001) more frequently than did controls. Lockdown was the only protective measure against COVID-19 (50% vs. 70%; p < 0.0001). No differences were found in the use of systemic steroids, immunosuppressants or biologics between cases and controls. Cases were more often treated with 5-aminosalicylates (42% vs. 34%; p = 0.003). Having a moderate Charlson score (OR: 2.7; 95%CI: 1.3-5.9), occupational risk (OR: 2.9; 95%CI: 1.8-4.4) and the use of 5-aminosalicylates (OR: 1.7; 95%CI: 1.2-2.5) were factors for COVID-19. The strict lockdown was the only protective factor (OR: 0.1; 95%CI: 0.09-0.2). (4) Comorbidities and occupational exposure are the most relevant factors for COVID-19 in patients with IBD. The risk of COVID-19 seems not to be increased by immunosuppressants or biologics, with a potential effect of 5-aminosalicylates, which should be investigated further and interpreted with caution

La influencia de la tecnología en los procesos de producción musical: análisis de la grabación sonora y sus aplicaciones en el ámbito docente

Memoria de las actividades del proyecto de Innova-Docencia nº256, coordinado por el Dr. Marco Antonio Juan de Dios Cuartas, profesor del Departamento de Musicología de la Universidad Complutense de Madrid