RESUMEN
The identification of multilocus imprinting disturbances (MLID) appears fundamental to uncover molecular pathways underlying imprinting disorders (IDs) and to complete clinical diagnosis of patients. However, MLID genetic associated mechanisms remain largely unknown. To characterize MLID in Beckwith-Wiedemann (BWS) and Silver-Russell (SRS) syndromes, we profiled by MassARRAY the methylation of 12 imprinted differentially methylated regions (iDMRs) in 21 BWS and 7 SRS patients with chromosome 11p15.5 epimutations. MLID was identified in 50% of BWS and 29% of SRS patients as a maternal hypomethylation syndrome. By next-generation sequencing, we searched for putative MLID-causative mutations in genes involved in methylation establishment/maintenance and found two novel missense mutations possibly causative of MLID: one in NLRP2, affecting ADP binding and protein activity, and one in ZFP42, likely leading to loss of DNA binding specificity. Both variants were paternally inherited. In silico protein modelling allowed to define the functional effect of these mutations. We found that MLID is very frequent in BWS/SRS. In addition, since MLID-BWS patients in our cohort show a peculiar pattern of BWS-associated clinical signs, MLID test could be important for a comprehensive clinical assessment. Finally, we highlighted the possible involvement of ZFP42 variants in MLID development and confirmed NLRP2 as causative locus in BWS-MLID.
Asunto(s)
Síndrome de Beckwith-Wiedemann/genética , Cromosomas Humanos Par 15/genética , Metilación de ADN , Impresión Genómica , Síndrome de Silver-Russell/genética , Proteínas Adaptadoras Transductoras de Señales/química , Proteínas Adaptadoras Transductoras de Señales/genética , Adolescente , Proteínas Reguladoras de la Apoptosis , Niño , Preescolar , Femenino , Humanos , Lactante , Factores de Transcripción de Tipo Kruppel/química , Factores de Transcripción de Tipo Kruppel/genética , Masculino , Mutación Missense , Adulto JovenRESUMEN
The current work is the presentation of a new project at the IRCSS San Donato Milanese University hospital, in the sphere of Psychocardiology. Hospitalised children and adolescents often face psychosocial difficulties and the psychological condition of their parents frequently has an impact on their wellbeing. A strong need to take care, beyond the mere cure, is necessary in the hospital settings - that is a need to pay attention also to psychological aspects apart from the medical ones. Art therapy could be an answer for this need: the literature has outlined its efficacy in hospital, also due to the higher inclination of children and adolescents toward creativity. By providing and analysing the drawings of 10 young patients with congenital heart disease (CHD), this study outlines how the art therapy program gives these patients the opportunity to freely and directly express fears and anxieties about medical procedures and their disease. Moreover, through the creation of a tangible product, psychologists can better evaluate the psychological troubles of young patients and provide them and their parents with more focused and personalized support. This study also focuses on the perception of the utility that parents have of this new therapeutic intervention, offered at the Department of Paediatric Cardiac Surgery, confirming that art therapy is perceived as being effective and is definitely a good instrument in helping to "take care" of children and adolescents suffering from CHD.
Asunto(s)
Arteterapia , Cardiopatías Congénitas/psicología , Cardiopatías Congénitas/terapia , Hospitalización , Adolescente , Niño , Hospitales , Humanos , Italia , Encuestas y CuestionariosRESUMEN
The influence of airborne pollution on mortality rates has been examined since the well known severe pollution episodes of Pennsylvania (1948) and London (1952). Three main epidemiological approaches are available: transversal studies, time series studies, prospective studies. The most frequently used method is the time series analysis, which retrospectively determines daily mortality rates as compared to daily pollution levels in a defined period. The vast majority of studies applying this approach confirm the existence of a positive correlation between mortality and airborne pollution. The relative risk of death during the most severely polluted days as compared to the least polluted days ranges between 1.02 and 1.13. Airborne pollution affects mortality as related to cardiovascular and chronic obstructive pulmonary diseases mainly in subjects previously affected by these pathologies. The dose-response mortality-pollution curve shows linear increments of mortality at low pollution levels, weak increments at high pollution levels. This phenomenon is attributed to the existence of subjects highly susceptible to pollution induced adverse health effects. These subjects, dying at low pollution levels, are not available to increase mortality rates at high pollution levels. Mortality is mainly related to the concentration of single pollutants, such as suspended particle matter, sulfur oxides, nitric oxides and ozone. Elderly are highly susceptible to pollution-induced mortality increases. Therefore, the study of mortality-pollution correlation is of particular interest in cities characterized by a relative prevalence of the elderly in the population. The latency period between pollution increases and related mortality increases falls in the 1-3 days interval range. The pollution-mortality relationship is influenced by many factors, such as the occurrence of exceedingly high or low environmental temperatures, influenza epidemics, etc. Many hypotheses has been raised to support the causality of the mortality-pollution association, including a direct effect of pollutants on cardiovascular and respiratory apparatus, and the release of inflammatory mediators affecting blood viscosity and pneumocytes homeostasis. On the whole, available data suggest that pollution is able to increase mortality only if associated to other risk factors determining an increased susceptibility in the exposed population.
Asunto(s)
Contaminantes Atmosféricos/efectos adversos , Enfermedades Cardiovasculares/etiología , Enfermedades Pulmonares Obstructivas/etiología , Mortalidad , Enfermedades Cardiovasculares/mortalidad , Humanos , Italia/epidemiología , Enfermedades Pulmonares Obstructivas/mortalidadRESUMEN
The above illustrates the fact that a physician interested in consulting the PDQ database must dedicate a certain amount of time to an analytical review of the database. It is difficult to determine how much time is required to acquire a sufficient level of control because there are many variables affecting the learning time: experience in using computerized systems, cultural background, personal inclination, etc. However, a certain amount of caution and humility should be exercised whenever a physician approaches a database of this type for the first time, in order to avoid the mistake of dangerously underestimating the nature of the problem. On the other hand, the physician's specific competence and professionalism will not be questioned at all, since they are fundamental to obtain productive search results. If, indeed, the above discussion focussed heavily on the most closely documental aspect of the problem, it should not be forgotten that the contents of the database can be fully understood only by experts who are used to encountering certain terms and procedures on a daily basis. In fact, when a physician turns to a documentation center for a PDQ research, the physician's assistance is always requested in order pair clinical and documental competence. It is this second skill that the physician must acquire to become totally independent.