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Abstract Background Germline heterozygous pathogenic variants (PVs) in TP53 cause Li-Fraumeni syndrome (LFS), a condition associated with increased risk of multiple tumor types. As the associated cancer risks were refined over time, clinical criteria also evolved to optimize diagnostic yield. The implementation of multi-gene panel germline testing in different clinical settings has led to the identification of TP53 PV carriers outside the classic LFS-associated cancer phenotypes, leading to a broader cancer phenotypic redefinition and to the renaming of the condition as “heritable TP53-related cancer syndrome” (hTP53rc). Germline TP53 variant interpretation is challenging due to the diverse nature of TP53 PVs, variable penetrance of the syndrome, possible occurrence of TP53 somatic mosaicism, and TP53 involvement in clonal hematopoiesis of indeterminate potential (CHIP). Here we aim to assess the relevance and impact of these issues on the diagnostic routine, and to evaluate the sensitivity of the different LFS clinical criteria to identify hTP53rc. Methods TP53 was analyzed in 6161 suspected hereditary cancer non-related patients categorized into three subgroups: (1) 495 patients fulfilling any LFS/Chompret clinical criteria; (2) 2481 patients diagnosed with early-onset breast/colorectal cancer; (3) 3185 patients without clinical criteria suggestive of hTP53rc. Ancillary tests were performed when TP53 PVs were identified in individuals not meeting LFS/Chompret criteria and/or when the variant was identified at low variant allele frequency (VAF). Results TP53 PVs were identified in blood DNA of 45 probands. Variant origin was elucidated in 39 of these: 72% patients had a constitutional PV, 10% were mosaics, and 18% had CHIP-associated PVs. Notably, two of the seven CHIP-TP53 PVs identified were detected at high allelic frequencies (VAF > 35%). Twenty-nine percent of germline TP53 PV did not meet any of the LFS clinical criteria. Among the clinical criteria, Chompret 2009 showed the highest sensitivity in our cohort (68% vs. 54% for Chompret 2015), highlighting the relevance of considering lung cancer in the criteria. Conclusions Our data supports performing TP53 ancillary testing for the identification of potential mosaicisms and CHIP-associated PVs, particularly in patients not meeting clinical criterial for LFS, irrespective of the VAF, and the application of clinical criteria that include lung cancer diagnosis.

Throughout the Genetic Counselling process a great emphasis is done on the need to communicate the familial risk information and the genetic study to the relatives. In addition, the clinical reports specify the relatives at risk situation. However, the familial communication pattern of genetic results after the counselling remains unknown. Objective: To conduct a descriptive study about the communication pattern of results of the diagnostic genetic test in hereditary predisposition to cancer at the ICO Genetic Counselling Unit. Methods: A descriptive study has been performed by telephone interview on a sample of index individuals attended at the Genetic Counselling Unit. Patients were asked whether if they had communicated their genetic study results and to whom. Similarly, demographic, personal and genetic result itself variables have been collected to explore whether any of them could modify the communication pattern. Results: Most patients report the results of the genetic studies to their relatives. However, this communication is not complete, so it is possible to design intervention strategies which may improve the communication pattern of the patients who receive diagnostic genetic tests in the context of the hereditary predisposition to cancer.

Directive speech acts in the 18th century comedy of manners: Toward modern patterns and conditions of use? II. Indirect formulations This paper is the second part of the study developed in Iglesias (2022). It consists of a pragmalinguistic analysis of indirect formulations of the directive speech acts from five plays of the so-called bourgeois comedy of customs introduced in Spain by Enlightenment authors in the second half of the 18th century. The different linguistic expressions of these acts and their conditions of use are studied in some detail. The analysis shows that, despite the fact that quantitative data could invite us to think of a pragmalinguistic continuity respect to the 16th and 17th centuries, we can find in these texts the first manifestations of form and meaning strategies belonging to non-impositive negative politeness (Jucker 2012, 2020), and a distribution of linguistic and usage directive patterns approaching to nowadays usage. *Este trabajo se enmarca dentro del Proyecto de Investigación Los procesos de gestión de la imagen y la (des)cortesía: perspectivas históricas, lingüísticas y discursivas (PID2019-107668GB-I00), financiado por el MINECO.

Directive act of speech in the bourgeois comedy of customs from 17th century: Toward modern language and usage patterns? I. Direct formulations This paper is meant as a contribution to the Spanish historical pragmatics. It consists of a pragmalinguistic analysis of directive speech acts from five plays of the so-called bourgeois comedy of customs introduced in Spain by Enlightenment authors in the second half of the 18th century. The different linguistic expressions of these acts, their illocutionary values and their conditions of use are studied in detail. * Este trabajo se enmarca dentro del Proyecto de Investigación Los procesos de gestión de la imagen y la (des)cortesía: perspectivas históricas, lingüísticas y discursivas (PID2019-107668GB-I00), financiado por el MINECO.

Abstract Germline mutations in BUB1 and BUB3 have been reported to increase the risk of developing colorectal cancer (CRC) at young age, in presence of variegated aneuploidy and reminiscent dysmorphic traits of mosaic variegated aneuploidy syndrome. We performed a mutational analysis of BUB1 and BUB3 in 456 uncharacterized mismatch repair-proficient hereditary non-polyposis CRC families and 88 polyposis cases. Four novel or rare germline variants, one splice-site and three missense, were identified in four families. Neither variegated aneuploidy nor dysmorphic traits were observed in carriers. Evident functional effects in the heterozygous form were observed for c.1965-1G>A, but not for c.2296G>A (p.E766K), in spite of the positive co-segregation in the family. BUB1 c.2473C>T (p.P825S) and BUB3 c.77C>T (p.T26I) remained as variants of uncertain significance. As of today, the rarity of functionally relevant mutations identified in familial and/or early onset series does not support the inclusion of BUB1 and BUB3 testing in routine genetic diagnostics of familial CRC.

Se realizó la modelación de la dispersión del Dióxido de Azufre (SO2) en el Centro Histórico de Riobamba, por cuanto no existe una semejante para la investigación proyectiva del caso; esto, para una pequeña ciudad ubicada en la Región Interandina, a 2754 msnm, que de a poco se proyecta hacia los suburbios, por la caótica coyuntura central. Debido al parque automotor y al conglomerado de instituciones públicas y educativas, que a la vez concentra gran cantidad de gente en el sector en las horas laborables, se generaría enfermedades respiratorias según datos clínicos, producidos probablemente por inhalación de SO2 y otros contaminantes. Se realizaron a la vez, diversos monitoreos técnicos para determinar la prevalencia de los principales contaminantes en el ambiente; se analizaron los datos bajo el esquema del diseño de componentes principales para caracterizar tendencias de correlación; y, se estableció un modelo matemático de dispersión a partir del diseño descrito con fines proyectivos.

En este trabajo mostramos cómo se adaptan y se utilizan en La Celestina determinadas secuencias típicamente conversacionales y las construcciones o formatos lingüísticos asociados a ellas. En concreto, nos centramos en las secuencias de reparación y estudiamos sus formas lingüísticas y sus funciones conversacionales y textuales para poner de manifiesto cómo contribuyen de manera decisiva a la verosimilitud del diálogo celestinesco. Abstract In this paper we show how some typically conversational sequences and the linguistic formats related to them are adapted and exploited for the construction of dramatic dialogue. Especifically we focus on repair sequences in Celestina and we study their linguistic formats and conversational and textual functioning to reveal their crucial contribution to verosimility of Celestina ‘s dialogue.

A Síndrome de Klippel-Trenaunay-Weber representa a associação de hemangiomas planos, ectasias venosas e hipertrofia do segmento corpóreo afetado. Apresenta-se o caso de um paciente de 39 anos, sexo masculino, seguido desde 1993 no serviço da Disciplina de Cirurgia Vascular da Escola Paulista de Medicina (Unifesp), por quadro inicial da síndrome em membro inferior esquerdo. O paciente foi tratado apenas por elastocompressão e medidas gerais. Neste período, ele evoluiu com piora da estase venosa, da hipertrofia óssea e da hiperpigmentação de pele. Na ultrassonografia Doppler colorida venosa dos membros inferiores havia perviedade do sistema venoso profundo, hiperfluxo venoso, insuficiência segmentar de veia safena magna com sinais de tromboflebite e tributárias insuficientes. Indicou-se, para a melhora da estase venosa, ligadura da junção safeno-femoral esquerda e escleroterapia (polidocanol 3%) retrógrada da mesma, com exérese das ectasias venosas. O paciente recebeu alta hospitalar no primeiro dia pós-operatório e atualmente está em acompanhamento ambulatorial com melhora significativa dos sintomas.The Klippel-Trenaunay-Weber Syndrome is the association of hemangioma, venous ectasia, and hypertrophy of the affected body segment. We report the case of a 39-year-old male followed-up since 1993 due to onset of symptoms in the left lower limb. He was treated only with the use of elastic stockings and general measures. Over the years, he had worsening of venous stasis, of bone hypertrophy, and of skin hyperpigmentation. Color-coded Doppler ultrasonography of the lower limbs showed patency of the deep venous system, venous overflow, segmentar insufficiency of the greater saphenous vein with signs of thrombophlebitis, and insufficient tributary veins. In order to improve venous stasis, ligation of the left sapheno-femoral junction and retrograde foam sclerotherapy (polidocanol 3%) with resection of tributary veins were performed. The patient was discharged in the first postoperative day and has been followed as an outpatient, presenting significant improvement of the symptoms.

La Atención Bioquímica plantea una actualización y una reconversión del ejercicio profesional basada en un cambio de paradigma, de uno centrado en la técnica analítica a uno centrado en el paciente. El nuevo paradigma debe instalar un nuevo eje para la enseñanza y el ejercicio profesional, optimizando las fases preanalítica y posanalítica del análisis clínico. La atención al paciente en la fase preanalítica implica: capacitar al personal técnico y administrativo, informar al paciente respecto de los estudios requeridos, y controlar la adecuada prescripción médica de las determinaciones, esto último originado en una entrevista previa con el paciente. La optimización posanalítica del ensayo, integra e interpreta los datos obtenidos para lograr una conclusión analítico-bioquímica, que a su vez, se integra en el diagnóstico médico y ayuda al paciente en un mejor manejo de su situación clínica y personal. El gran desafío actual y futuro de la profesión bioquímica essu efectiva participación en la medicina preventiva, a través de estudios analíticos de baja complejidad y en vínculo directo con el paciente. La Atención Bioquímica es, fi nalmente, una cuestión de relaciones personales, directas, profesionales y responsables entre el bioquímico y la población, con el objetivo de asegurarle una mejor calidad de vida.

El objetivo de este artículo es dar a conocer los resultados del estudio de investigación llevado en la Universidad Nacional Mayor de San Marcos en el año 2013. Uno de los objetivos del estudio fue la evaluación de la calidad ambiental del ecosistema de la bahía de Ancón, que se realizó mediante un monitoreo de los principales parámetros físicos, químicos y biológicos en la zona litoral y zona marina de la bahía. Los resultados fueron contrastados con los límites máximos permisibles establecidos en el estándar de calidad ambiental de agua correspondiente a la categoría 2 (actividades marino costeras) y 4 (conservación del medio ambiente acuático) del D.S. N° 002-2008-MINAM. La bahía de Ancón es un ecosistema natural, valioso por su complejidad, belleza paisajística y sustento de actividades como la pesca, el turismo y el comercio. Sin embargo, está sujeta a posibles impactos ambientales producto de actividades humanas. Los resultados de la evaluación muestran que las condiciones de temperatura presentes en este estudio fueron normales, con ligero proceso de enfriamiento por debajo del promedio en 0.6°C; las condiciones de distribución de oxígeno disuelto, pH, sólidos suspendidos totales y DBO5 indican que el ecosistema funciona relativamente normal en la bahía. Respecto a los parámetros de fosfatos y silicatos se hallaron en altas concentraciones; además de la presencia de 2,000 a 3,100 NMP de coliformes fecales, que indicarían niveles de contaminación en la zona próxima al muelle artesanal de Ancón, donde se han observado dos zonas con influencia de cargas orgánicas antrópicas provenientes del aporte del río Rímac, Chillón y colector de Comas (Estaciones 1, 4 y 5).

The total and free fatty acid contents were studied in ready for consumption samples of four different varieties of traditional dry-fermented sausages made in Galicia (NW of Spain): Chorizo gallego, Chorizo de cebolla, Androlla and Botillo. No significant differences (p>0.05) were observed in the content of the different total fatty acids among the four sausage varieties. The total fatty acids profile was very similar in the four varieties: the most abundant total fatty acid was oleic (45% of total fatty acids), followed by palmitic (21%), linoleic (14%), estearic (13%) and palmitoleic (2%); this profile basically coincides with those described by other authors in pork fat. The total average content of free fatty acids was 2176 mg/100 g of fat in Chorizo gallego, 5223 mg/100 g of fat in Chorizo de cebolla, 2308 mg/100 g of fat in Androlla and 183 mg/100 g of fat in Botillo. These average values in Chorizo gallego, Chorizo de cebolla and Androlla were found in the range of values described for other dry-fermented sausage varieties; the average value in Botillo was clearly lower than those decribed for other fermented sausages. In the four sausage varieties the most abundant free fatty acid was oleic, followed by linoleic, palmitic and estearic. This free fatty acid profile coincides with those described in literature for other dry-fermented sausages. The average content of each individual free fatty acid was significantly (p

Durante el parto, frecuentemente, la zona perineal sufre daños, de forma espontánea (desgarro perineal), o como resultado de una incisión quirúrgica realizada por los profesionales (episiotomía). Estos traumatismos originan alta morbilidad, dolor, malestar y repercusiones negativas sobre la musculatura del suelo pélvico. El conocimiento de estas consecuencias, da lugar a la búsqueda y utilización, por parte de las matronas, de diferentes técnicas con el objetivo de reducirlas, protegiendo el periné de desgarros y evitando la episiotomía. Entre ellas está el uso de termoterapia, aplicada en el periné durante el periodo expulsivo del parto, en forma de compresas húmedas y calientes, que producen vasodilatación y tienen propiedades sedantes, relajantes musculares y analgésicas. Se realiza una revisión bibliográfica con el objetivo de conocer la evidencia científica que existe sobre del efecto de la aplicación de calor local en el periné durante el periodo expulsivo de un parto normal en la frecuencia y el tipo de traumatismos del periné, así como en la percepción del dolor. En la búsqueda bibliográfica, se encontraron 10 publicaciones: 4 estudios experimentales, 2 estudios observacionales, 2 revisiones bibliográficas, un documento de consenso y una Guía de Práctica Clínica. La literatura revisada demuestra que hay datos razonables para apoyar la técnica descrita, ya que ha mostrado una reducción en el traumatismo perineal grave, alivio el dolor, aumento de la comodidad y reducción de la incidencia de incontinencia urinaria. El procedimiento, se puede ofrecer, porque no tiene efectos perjudiciales, es barato y es aceptado por las usuarias y las matronas. Abstract: Perineum is damaged quite often during labor, spontaneously (perineal tear), or as a result of a surgical incision made by professionals (episiotomy) . These injuries originate high morbidity, pain, discomfort and adverse effects on the pelvic floor muscles. The knowledge of these consequences has made midwives look for different techniques and interventions, trying to decrease damage, protect perineum from tears, and prevent/avoid episiotomies. Among them, we may highlight the use of thermotherapy applied on the perineum during second stage of labor, in the form of warm, moist compresses, which produce vasodilatation and also has sedative, muscle relaxant and analgesic properties. A literature review was performed in order to find out acute scientific evidence. The subject was “Effects of applying hot on perineum during second stage of a normal delivery: focusing on frequency, type of perinea tear, and pain perception”. Ten studies were found: 4 experimental studies, 2 observational studies, 2 literature reviews, one consensus document and Clinical Practice: The use of warm compresses on the perineum is associated with a decreased occurrence on severe perineal trauma and the incidence of urinary incontinence. This technique seems to provide more pain relief and comfort to the women. Therefore, the procedure may be offered to pregnant women as it is cheap and not harmful, not forgetting that it has been well accepted by women and midwives. Palabra Clave: Parto; Periné; Dolor; Traumatismo Perineal; Compresas Calientes. Key Words: Delivery; Perineum; Perineal Trauma; Pain; Warm Pads.