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El judaísmo y el cristianismo han legado escritos pertenecientes al género apocalíp­tico, interesantes para el conocimiento de las ideas sobre el fin del mundo y sobre las expectativas de futuro que judíos y cristianos albergaban en los momentos más críticos de su existencia. Sin embargo, los temas y motivos de las obras características de este género se encuentran en otros escritos que, a priori, no podrían ser calificados como “apocalipsis”. El texto de Sulpicio Severo sobre el pensamiento apocalíptico de Martin de Tours se ha convertido en objeto de debate por los múltiples ejemplos literarios que elevan a Nerón a una categoría escatológica y lo asocian al Anticristo. En el presente trabajo se compara el contenido de las ideas de Martín con otros textos de semejante contenido para demostrar si las ideas de Martín pueden definirse como una reutilización o destacan por su originalidad.

Large studies in von Willebrand disease patients, including Spanish and Portuguese registries, led to the identification of >250 different mutations. It is a challenge to determine the pathogenic effect of potential splice site mutations on VWF mRNA. This study aimed to elucidate the true effects of 18 mutations on VWF mRNA processing, investigate the contribution of next-generation sequencing to in vivo mRNA study in von Willebrand disease, and compare the findings with in silico prediction. RNA extracted from patient platelets and leukocytes was amplified by RT-PCR and sequenced using Sanger and next generation sequencing techniques. Eight mutations affected VWF splicing: c.1533+1G>A, c.5664+2T>C and c.546G>A (p.=) prompted exon skipping; c.3223-7_3236dup and c.7082-2A>G resulted in activation of cryptic sites; c.3379+1G>A and c.7437G>A) demonstrated both molecular pathogenic mechanisms simultaneously; and the p.Cys370Tyr missense mutation generated two aberrant transcripts. Of note, the complete effect of three mutations was provided by next generation sequencing alone because of low expression of the aberrant transcripts. In the remaining 10 mutations, no effect was elucidated in the experiments. However, the differential findings obtained in platelets and leukocytes provided substantial evidence that four of these would have an effect on VWF levels. In this first report using next generation sequencing technology to unravel the effects of VWF mutations on splicing, the technique yielded valuable information. Our data bring to light the importance of studying the effect of synonymous and missense mutations on VWF splicing to improve the current knowledge of the molecular mechanisms behind von Willebrand disease. clinicaltrials.gov identifier:02869074.

The multimeric analysis (MA) of plasma von Willebrand factor (VWF) evaluates structural integrity and helps in the diagnosis of von Willebrand disease (VWD). This assay is a matter of controversy, being considered by some investigators cumbersome and only slightly informative. The centralised study 'Molecular and Clinical Profile of von Willebrand Disease in Spain (PCM-EVW-ES)' has been carried out by including the phenotypic assessment and the genetic analysis by next generation sequencing (NGS) of the VWF gene (VWF). The aim of the present study was to evaluate the role of MA to the diagnosis of these patients and their potential discrepancies. Two hundred and seventy out of 480 patients centrally diagnosed with VWD had normal multimers, 168 had abnormal multimers and 42 a total absence of multimers. VWF MA was of great significance in the diagnosis of 83 patients (17.3%), it was also of help in the diagnosis achieved in 365 additional patients (76%) and was not informative in 32 cases (6.7%). With regard to discrepancies, 110 out of 480 (23%) patients centrally diagnosed with VWD presented some kind of discordance between VWF:RCo/VWF:Ag and/or VWF:CB/VWF:Ag ratios, multimeric study and/or genetic results. The VWF MA was key in the presence of novel mutations as well as in cases with phenotypic discrepancies. A comparison between the contribution of MA and VWF:CB showed a clearly higher contribution of the former in the diagnostic process. These data seem to reinforce the relevance of the VWF MA in VWD diagnosis, despite all its limitations.

Molecular diagnosis of patients with von Willebrand disease is pending in most populations due to the complexity and high cost of conventional molecular analyses. The need for molecular and clinical characterization of von Willebrand disease in Spain prompted the creation of a multicenter project (PCM-EVW-ES) that resulted in the largest prospective cohort study of patients with all types of von Willebrand disease. Molecular analysis of relevant regions of the VWF, including intronic and promoter regions, was achieved in the 556 individuals recruited via the development of a simple, innovative, relatively low-cost protocol based on microfluidic technology and next-generation sequencing. A total of 704 variants (237 different) were identified along VWF, 155 of which had not been previously recorded in the international mutation database. The potential pathogenic effect of these variants was assessed by in silico analysis. Furthermore, four short tandem repeats were analyzed in order to evaluate the ancestral origin of recurrent mutations. The outcome of genetic analysis allowed for the reclassification of 110 patients, identification of 37 asymptomatic carriers (important for genetic counseling) and re-inclusion of 43 patients previously excluded by phenotyping results. In total, 480 patients were definitively diagnosed. Candidate mutations were identified in all patients except 13 type 1 von Willebrand disease, yielding a high genotype-phenotype correlation. Our data reinforce the capital importance and usefulness of genetics in von Willebrand disease diagnostics. The progressive implementation of molecular study as the first-line test for routine diagnosis of this condition will lead to increasingly more personalized and effective care for this patient population.

Resumen: Los cristianos, desde la época de las persecuciones, se opusieron a admitir que los emperadores romanos pudieran poseer una naturaleza divina, negándose a participar en el culto imperial. Paralelamente, diversas corrientes ideológicas abogaron por afirmar que la autoridad y el poder del emperador tendrían su origen en la Divina Providencia cristiana. De este modo, el cristianismo primitivo se vio en la tesitura de rehusar a intervenir en la manifestación pública de la divinidad de los emperadores y aceptar a la vez que la máxima autoridad política de Roma había sido colocada por Dios para dirigir el Imperio romano. En el presente trabajo, se expondría como ambas ideas serían retomadas en el siglo V por Paulo Orosio en sus Historiae Adversus Paganos a través de los textos sobre Domiciano y Augusto, pudiéndose demostrar que el pensamiento político cristiano sobre el “carácter divino” del emperador roma­no continuaría vigente, aunque fuese desde una óptica historiográfica. Abstract: Christians, from the Persecution’s age, opposed to admit Roman empe­rors could have a divine nature, refu­sing to participate in the imperial cult. In parallel, various ideological currents advocated for affirming the authority and power of the emperor would have their origin in Christian Divine Provi­dence. Thus, Early Christianity was in the position of refusing to intervene in the public demonstration of the divini­ty of the emperors and accept that the most important political authority of Rome had been placed by God to lead the Roman Empire. This paper would expose as both ideas would be taken up in the fifth century by Paulus Orosius in his Historiae Adversus Paganos through the texts about Domitian and Augustus, being able to demonstrate the Christian political thought on the “divine charac­ter” of the Roman emperor would con­tinue in force, even if it were from a his­toriographical optical. Palabras clave: Emperador romano, naturaleza divi­na, culto imperial, Paulo Orosio, Domi­ciano, Augusto Key words: Roman emperor, divine nature, im­perial cult, Paulus Orosius, Domitian, Augustus.

En las Actas de los Mártires (Acta Martyrum) se relata la muerte de los cristianos durante el período de las persecuciones. Proliferan los relatos en los que el protagonismo lo ejercen los cristianos de forma aislada o en pequeños grupos, siendo excepcional la muerte de los cristianos en masa. En dos textos, extraídos de la obra de Eusebio de Cesarea (Historia Eclesiástica), se describe el violento ataque a toda una comunidad, protagonizado por grupos incontrolados, ubicados cronológica y geográficamente en dos momentos claves en la historia de las persecuciones anticristianas del Imperio romano. En el presente trabajo se analizan estos acontecimientos, atendiendo también al contexto socio-religioso, sin olvidar las hipotéticas repercusiones que estos u otros podrían haber desencadenado en la literatura cristiana, principalmente en la apocalíptica y en el pensamiento escatológico de los testigos oculares. Tampoco se obvia un factor que pudo haber influido en la mentalidad de los cristianos que vivieron entre un episodio y otro (177-249). Para este tramo cronológico se han datado los primeros textos de la leyenda del Nero Redivivus o colocación en un plano escatológico del designado desde autores como Tertuliano o Melitón de Sardes como el primer emperador perseguidor, vinculado a partir del siglo III al Anticristo.

Background and objectives: Social distancing and quarantine implanted during the COVID-19 outbreak could have delayed the accession of oncologic patients to hospitals and treatments. This study analysed the management of sarcoma patients during this period in five Spanish hospitals. Design and methods: Clinical data from adult sarcoma patients, soft tissue and bone sarcomas, managed during the COVID-19 outbreak, from 15 March to 14 September 2020 (Covid cohort), were retrospectively collected and time for diagnosis, surgery and active treatments were compared with sarcoma patients managed during the same pre-pandemic period in 2018 (Control cohort). Results: A total of 126 and 182 new sarcoma patients were enrolled in the Covid and Control cohorts, respectively, who were mainly diagnosed as soft tissue sarcomas (81.0% and 80.8%) and at localized stage (80.2% and 79.1%). A diagnostic delay was observed in the Covid cohort with a median time for the diagnosis of 102.5 days (range 6–355) versus 83 days (range 5–328) in the Control cohort ( p = 0.034). Moreover, a delay in surgery was observed in cases with localized disease from the Covid cohort with a median time of 96.0 days (range 11–265) versus 54.5 days (range 2–331) in the Control cohort ( p = 0.034). However, a lower delay for neoadjuvant radiotherapy was observed in the Covid cohort with a median time from the diagnosis to the neoadjuvant radiotherapy of 47 days (range 27–105) versus 91 days (range 27–294) in the Control cohort ( p = 0.039). No significant differences for adjuvant radiotherapy, neoadjuvant/adjuvant chemotherapy and neoadjuvant/adjuvant palliative chemotherapy were observed between both cohorts. Neither progression-free survival (PFS) nor overall survival (OS) was significantly different. Conclusion: Delays in diagnosis and surgery were retrospectively observed in sarcoma patients during the COVID-19 outbreak in Spain, while the time for neoadjuvant radiotherapy was reduced. However, no impact on the PFS and OS was observed.