RESUMO
PURPOSE OF REVIEW: This review aims to summarize the current knowledge on the genetic background of dilated cardiomyopathy (DCM), with particular attention to the genotype-phenotype correlations and the possible implications for clinical management. RECENT FINDINGS: Next generation sequencing (NGS) has led to the identification of an increasing number of genes and mutations responsible for DCM. This genetic variability is probably related to the extreme heterogeneity of disease manifestation. Important findings have associated mutations of Lamin A/C (LMNA) and Filamin C (FLNC) to poor prognosis and the propensity to cause an arrhythmic phenotype, respectively. However, a deeper understanding of the genotype-phenotype correlation is necessary, because it could have several implications for the clinical management of the patients. Furthermore, the correct interpretation of pathogenicity of mutations and the clinical impact of genetic testing in DCM patients still represent important fields to be implemented. A pathogenic gene mutation can be identified in almost 40% of DCM patients. The recent discoveries and future research in the field of genotype-phenotype correlation may lead to a more personalized management of the mutation carriers towards the application of precision medicine in DCM.
Assuntos
Cardiomiopatia Dilatada/genética , Mutação , Arritmias Cardíacas/genética , Arritmias Cardíacas/mortalidade , Cardiomiopatia Dilatada/cirurgia , Morte Súbita Cardíaca/etiologia , Estudos de Associação Genética , Marcadores Genéticos , Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Prognóstico , Medição de Risco , Fatores de RiscoRESUMO
TRAF and TNF receptor-associated protein (TTRAP) is a multifunctional protein that can act in the nucleus as a 5'-tyrosyl DNA phosphodiesterase and in the cytoplasm as a regulator of cell signaling. In this paper we show that in response to proteasome inhibition TTRAP accumulates in nucleolar cavities in a promyelocytic leukemia protein-dependent manner. In the nucleolus, TTRAP contributes to control levels of ribosomal RNA precursor and processing intermediates, and this phenotype is independent from its 5'-tyrosyl DNA phosphodiesterase activity. Our findings suggest a previously unidentified function for TTRAP and nucleolar cavities in ribosome biogenesis under stress.
Assuntos
Nucléolo Celular/metabolismo , Proteínas Nucleares/metabolismo , Inibidores de Proteassoma , Processamento Pós-Transcricional do RNA/fisiologia , RNA Ribossômico/metabolismo , Ribossomos/metabolismo , Transdução de Sinais/fisiologia , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Linhagem Celular Tumoral , Nucléolo Celular/genética , Proteínas de Ligação a DNA , Células HEK293 , Humanos , Proteínas Nucleares/genética , Diester Fosfórico Hidrolases , Proteína da Leucemia Promielocítica , Complexo de Endopeptidases do Proteassoma/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , RNA Ribossômico/genética , Ribossomos/genética , Estresse Fisiológico/fisiologia , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genéticaRESUMO
Strict guidelines for selection, monitoring and treatment of Potential Organ Donors (POD) in Neurosurgical Intensive Care Units (ICUs) are mandatory since patients with Acute Brain Injuries (ABI) are more frequently admitted on these specialized ICUs. We report the guidelines accepted in the Neurosurgical ICU of Treviso City Hospital (TVH) and the results obtained in the last three years (1988-1990). All patients with unfavourable neurological outcome were considered POD if absolute or relative contraindications to organ procurement were absent. They were treated with a multisystemic approach, according to standard protocols, including: ECG monitoring, water and electrolyte balance restoration, pharmacological cardiocirculatory support, prophylaxis and treatment of infections, control of hormonal disturbances. Our data demonstrate an increase of POD from TVH due to the centralization of patients with ABI in the Neurosurgical ICU and show an increase of the rate of POD from Neurosurgical ICU vs General ICU of TVH. The increase of POD in the Neurosurgical ICUs involves medical, legal, organizing and psychological problems, related to this clinical condition. The attention to severe protocols, that must be periodically reviewed, makes more easy the management of POD and ameliorates the outcome of these patients.
Assuntos
Cuidados Críticos , Neurocirurgia , Doadores de Tecidos/estatística & dados numéricos , Humanos , Monitorização Fisiológica , Resultado do TratamentoRESUMO
In the period June 1987-March 1988, 80 patients classifiable according to ASPEN criteria were submitted to Total Parenteral Nutrition (TPN) using a single package nutrient mixing technique. The problems relating to the compatibility and stability of the solution are analysed and a protocol is proposed for the preparation of packages and the management of the central venous catheter compatible with the needs of a general surgery department. Personal experience has enabled us to observe the undoubted advantages of this technique: reduction of the time necessary for nursing the TPN patient, greater reliability in controlling speed of infusion and infectious complications, greater comfort for the patient.
