The Relationship between Telomere Length and Mortality in Chronic Obstructive Pulmonary Disease (COPD)

Some have suggested that chronic obstructive pulmonary disease (COPD) is a disease of accelerated aging. Aging is characterized by shortening of telomeres. The relationship of telomere length to important clinical outcomes such as mortality, disease progression and cancer in COPD is unknown. Using quantitative polymerase chain reaction (qPCR), we measured telomere length of peripheral leukocytes in 4,271 subjects with mild to moderate COPD who participated in the Lung Health Study (LHS). The subjects were followed for approximately 7.5 years during which time their vital status, FEV1 and smoking status were ascertained. Using multiple regression methods, we determined the relationship of telomere length to cancer and total mortality in these subjects. We also measured telomere length in healthy “mid-life” volunteers and patients with more severe COPD. The LHS subjects had significantly shorter telomeres than those of healthy “mid-life” volunteers (p<.001). Compared to individuals in the 4th quartile of relative telomere length (i.e. longest telomere group), the remaining participants had significantly higher risk of cancer mortality (Hazard ratio, HR, 1.48; p = 0.0324) and total mortality (HR, 1.29; p = 0.0425). Smoking status did not make a significant difference in peripheral blood cells telomere length. In conclusion, COPD patients have short leukocyte telomeres, which are in turn associated increased risk of total and cancer mortality. Accelerated aging is of particular relevance to cancer mortality in COPD

Telomerase promoter mutations in cancer: an emerging molecular biomarker?

João Vinagre, Vasco Pinto and Ricardo Celestino contributed equally to the manuscript.Cell immortalization has been considered for a long time as a classic hallmark of cancer cells. Besides telomerase reactivation, such immortalization could be due to telomere maintenance through the “alternative mechanism of telomere lengthening” (ALT) but the mechanisms underlying both forms of reactivation remained elusive. Mutations in the coding region of telomerase gene are very rare in the cancer setting, despite being associated with some degenerative diseases. Recently, mutations in telomerase (TERT) gene promoter were found in sporadic and familial melanoma and subsequently in several cancer models, notably in gliomas, thyroid cancer and bladder cancer. The importance of these findings has been reinforced by the association of TERT mutations in some cancer types with tumour aggressiveness and patient survival. In the first part of this review, we summarize the data on the biology of telomeres and telomerase, available methodological approaches and non-neoplastic diseases associated with telomere dysfunction. In the second part, we review the information on telomerase expression and genetic alterations in the most relevant types of cancer (skin, thyroid, bladder and central nervous system) on record, and discuss the value of telomerase as a new biomarker with impact on the prognosis and survival of the patients and as a putative therapeutic target

L'Islam sciita. Storia di una minoranza

Il volume presenta una storia della comunità musulmana sciita nelle sue varie ramificazioni, dalle origini all'età contemporanea. Lo sciismo, quale componenete religiosa di minoranza, ha sempre rappresentato una costante istanza di opposizione e di ribellione, dando vita ad espressioni intellettuali e politiche di dissenso, sfociate spesso in forme d ipensiero "eterodosso". In epoca moderna e contemporanea lo sciismo è stato ed è tuttora voce tra le più attive e interessanti del pluralismo politico e religioso che caratterizza il mondo islamico

Familial non-medullary thyroid cancer: a critical review

Background: Familial non-medullary thyroid carcinoma (FNMTC), mainly of papillary histotype (FPTC), is defined by the presence of the disease in two or more first-degree relatives in the absence of other known familial syndromes. With the increasing incidence of PTC in the recent years, the familial form of the disease has also become more common than previously reported and constitutes nearly 10% of all thyroid cancers. Many aspects of FNMTC are debated, concerning both clinical and genetic aspects. Several studies reported that, in comparison with sporadic PTCs, FPTCs are more aggressive at disease presentation, while other authors reported no differences in the clinical behavior of sporadic and familial PTCs. For this reason, recent guidelines do not recommend screening of family members of patients with diagnosis of differentiated thyroid cancer (DTC). FNMTC is described as a polygenic disorder associated with multiple low- to moderate-penetrance susceptibility genes and incomplete penetrance. At the moment, the genetic factors contributing to the development of FNMTC remain poorly understood, though many putative genes have been proposed in the recent years. Purpose: Based on current literature and our experience with FNMTC, in this review, we critically discussed the most relevant controversies, including its definition, the genetic background and some clinical aspects as screening and treatment

The presence of immunoreactive cyclooxygenases in the ductuli efferentes and epididymis of prepubertal and adult alpaca (Lama pacos)

In this study, we report the cell specific expression of cyclooxygenase (COX) enzymes, COX1 and COX2, in the ductuli efferentes and epididymis of prepubertal and adult alpaca. COX1 weakly stained the cytoplasm of epithelial cells lining the ductuli efferentes and the epididymal corpus, whereas these cells were immunonegative in the epididymal caput and cauda. In adults, we observed an increase in the immunsignals for COX1 in the cytoplasm of epithelial cells lining the ductuli efferentes and all the epididymal regions. In prepubertal alpaca, immunoreactivity for COX2 was not revealed in the epithelial cells lining the ductuli efferentes and epididymal regions, whereas it was evidenced in adult animals. The apical rich mithocondria cells immunoreacted only with COX1 in the epididymis of prepubertal animals, whereas they expressed both COX1 and -2 in the adult alpaca. Our results suggest that COXs may play a role in the pubertal development of the excurrent duct system of the alpaca

Autosomal dominant familial neurohypophyseal diabetes insipidus caused by a novel missense mutation in AVP gene in a large Italian kindred

Purpose Familial neurohypophysial diabetes insipidus (FNDI), commonly caused by autosomal dominant arginine vasopressin (AVP) mutations, is a rare condition in which vasopressin fails in regulating body's level of water with final polyuria and polydipsia. Genetic testing in familial cases of FNDI should be carry out to ensure adequate treatments and avoid disease manifestations especially in infants. Methods In this study, we investigated three-generations of a large Italian family with clinical diagnosis of familial central diabetes insipidus for the presence of potential pathogenic mutations in the AVP gene. Results We identified a heterozygous missense mutation (c.154 T &gt; A; p.C52S) in AVP gene in all affected members studied of a large Italian family. In silico tools were used to investigate the pathogenic role of the mutation and three-dimensional protein structure predicted that the p.C52S impairs disulfide bridges formation resulting in misfolding of the protein. Conclusions This is the first study that identified a novel missense p.C52S mutation as causative of central diabetes insipidus in a large Italian pedigree. © 2021, The Author(s)

Aprendizaje colaborativo para la integración: un proyecto en el contexto de la formación profesional para compartir tecnologías educativas entre pares

La integración formativa de los estudiantes con discapacidad ha sido aprobado recientemente por una convención internacional: el 13 de deciembre 2006 la Asamblea General de la ONU adoptó formalmente la Convención acerca de los derechos de las personas con discapacidad. Este es un logro importante de la comunidad internacional, ya que, la Convención es el primer tratado de derechos humanos que ha sido adoptado en el siglo XXI. La Convención refleja los esfuerzos más amplios de la UE para construir, en 2020, una Europa sin barreras para los ciudadanos con discapacidad - cerca de 80 millones - según lo establecido en la estrategia de la Comisión Europea en materia de discapacidad. En este marco normativo para la integración de los alumnos con disabilidad se mueve la experiencia proyectiva aprobada dentro de un centro de formación profesional de Roma, EL ENDOFAP Lazio. El proyecto denominado "Aprendizaje Colaborativo para la integración", en el ámbito del aviso público regional por la educación y la integración formativa de los alumnos con dificultad de aprendizaje e/o de origen migratorio. La Región Lazio, con ese intervención se ha puesto el objetivo de reforzar las acciones de sensibilización finalizadas a la integración formativa de los alumnos con disabilidad