La influencia de la institucionalización sobre la percepción de la autonomía y la calidad de vida en ancianos

Objetivo Evaluar la influencia de la institucionalización en la autonomía y la calidad de vida percibida entre ancianos institucionalizados. Método Estudio casi-experimental (serie temporal interrumpida) y longitudinal. La muestra estuvo compuesta de 104 añosos de tres centros residenciales de Santander, España. A fin de evaluar la calidad de vida y la dependencia fueron utilizadas dos escalas: el Índice de Barthel y el Índice de Lawton. Resultados Se observó una relación significativa entre la autonomía y la independencia y su declinio en virtud de la institucionalización, como los aspectos físicos y sociales. Conclusión La dependencia de las personas mayores es un fenómeno complejo, que demanda distintos tipos de intervención, incluyéndose las acciones de apoyo común, que tienden a cubrir la ausencia de autonomía en la vida cuotidiana, sin recurrir a la institucionalización.Objective To evaluate the influence exercised by institutionalization on the autonomy and perception of quality of life among the institutionalized elderly. Method The study is quasi-experimental (interrupted time series) and longitudinal. The sample is composed for 104 elderly people who went into a three nursing home in Santander, Spain. To assess the quality of life and dependence two scales were used: the Barthel Index and Lawton Index. Results There was an important relationship between autonomy and independence and their deterioration due to their institutionalisation, such as the physical and social aspects. Conclusion It´s important to point out that the dependence of the elderly is a complex phenomenon, which admits many types of intervention, including the customary ones referring to more classic welfare actions which tend to supplant the absence of autonomy in everyday life by facilitating services and attention to make up for this need, without having to resort to institutionalization.Objetivo Avaliar a influência da institucionalização na autonomia e na qualidade de vida percebida entre idosos institucionalizados. Método Estudo quase-experimental (série temporal interrompida) e longitudinal. A amostra foi composta de 104 idosos de três centros residenciais de Santander na Espanha. Para avaliar a qualidade de vida e a dependência foram utilizadas duas escalas: o Índice de Barthel e o Índice de Lawton. Resultados Observou-se uma relação significativa entre autonomia e independência e seu declínio devido à institucionalização, como os aspectos físicos e sociais. Conclusão A dependência dos idosos é um fenômeno complexo, que demanda vários tipos de intervenção, incluindo as ações de apoio comum, que tendem a cobrir a ausência de autonomia na vida cotidiana, sem recorrer a institucionalização

Deciduous Teeth as an Alternative DNA Source for Postmortem Genetic Testing

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Diagnostic yield of targeted next generation sequencing in 2002 Dutch cardiomyopathy patients

BACKGROUND: Next-generation sequencing (NGS) is increasingly used for clinical evaluation of cardiomyopathy patients as it allows for simultaneous screening of multiple cardiomyopathy-associated genes. Adding copy number variant (CNV) analysis of NGS data is not routine yet and may contribute to the diagnostic yield. OBJECTIVES: Determine the diagnostic yield of our targeted NGS gene panel in routine clinical diagnostics of Dutch cardiomyopathy patients and explore the impact of exon CNVs on diagnostic yield. METHODS: Patients (N = 2002) referred for clinical genetic analysis underwent diagnostic testing of 55-61 genes associated with cardiomyopathies. Samples were analyzed and evaluated for single nucleotide variants (SNVs), indels and CNVs. CNVs identified in the NGS data and suspected of being pathogenic based on type, size and location were confirmed by additional molecular tests. RESULTS: A (likely) pathogenic (L)P variant was detected in 22.7% of patients, including 3 with CNVs and 25 where a variant was identified in a gene currently not associated with the patient's cardiomyopathy subtype. Only 15 out of 2002 patients (0.8%) were found to carry two (L)P variants. CONCLUSION: The yield of routine clinical diagnostics of cardiomyopathies was relatively low when compared to literature. This is likely due to the fact that our study reports the outcome of patients in daily routine diagnostics, therefore also including patients not fully fulfilling (subtype specific) cardiomyopathy criteria. This may also explain why (L)P variants were identified in genes not associated with the reported subtype. The added value of CNV analysis was shown to be limited but not negligible

Functional investigation of two simultaneous or separately segregating DSP variants within a single family support the theory of a dose-dependent disease severity

Desmoplakin (DP) is an important component of desmosomes, essential in cell-cell connecting structures in stress-bearing tissues. Over many hundreds of pathogenic variants in DSP have been associated with different cutaneous and cardiac phenotypes or a combination, known as a cardiocutaneous syndrome. Of less than 5% of the reported DSP variants, the effect on the protein has been investigated. Here, we describe and have performed RNA, protein and tissue analysis in a large family where DSPc.273+5G>A/c.6687delA segregated with palmoplantar keratoderma (PPK), woolly hair and lethal cardiomyopathy, while DSPWT/c.6687delA segregated with PPK and milder cardiomyopathy. hiPSC-derived cardiomyocytes and primary keratinocytes from carriers were obtained for analysis. Unlike the previously reported nonsense variants in the last exon of DSP that bypassed the nonsense-mediated mRNA surveillance system leading to protein truncation, variant c.6687delA was shown to cause loss of protein expression. Patients carrying both variants and having a considerably more severe phenotype were shown to have 70% DP protein reduction, while patients carrying only c.6687delA had 50% protein reduction and a milder phenotype. Analysis of RNA from patient cells did not show any splicing effect of the c.273+5G>A variant. However, a minigene splicing assay clearly showed alternative spliced transcripts originating from this variant. This study shows the importance of RNA and protein analyses to pinpoint the exact effect of DSP variants instead of solely relying on predictions. In addition, the particular pattern of inheritance, with simultaneous or separately segregating DSP variants within the same family, strongly supports the theory of a dose-dependent disease severity

Three female patients with Danon disease presenting with predominant cardiac phenotype:a case series

Background: Danon disease is a rare X-linked multisystemic disorder that has primarily been described in male patients. Case summary: We present three female patients with Danon disease with a predominantly cardiac phenotype in whom disease onset and expression was very different from that of male patients. Case 1 was first admitted for acute heart failure and then readmitted a few months later for cardiac shock, necessitating mechanical support, and heart transplantation. Case 2 had complex arrhythmias for which many antiarrhythmic drugs were tried with only limited success. Her disease accelerated after her first pregnancy, and she showed reduced left ventricular function and dilated cardiomyopathy. Case 3 was referred for near syncope and ablated for an accessory pathway; she had extensive left ventricular hypertrophy. In all three cases, a final diagnosis of Danon disease was only made after genetic testing that identified a causal variant in the lysosome-associated membrane protein 2 gene. Discussion: Danon disease in female patients is a challenging diagnosis that may not be identified until genetic testing has been performed

Cardiac b-myosin heavy chain defects in two families with non-compaction cardiomyopathy: linking non-compaction to hypertrophic, restrictive, and dilated cardiomyopathies

Cardiomyopathies are classified according to distinct morphological characteristics. They occur relatively frequent and are an important cause of mortality and morbidity. Isolated ventricular noncompaction or non-compaction cardiomyopathy (NCCM) is characterized by an excessively thickened endocardial layer with deep intertrabecular recesses, reminiscent of the myocardium during early embryogenesis. Aims Autosomal-dominant as well as X-linked inheritance for NCCM has been described and several loci have been associated with the disease. Nevertheless, a major genetic cause for familial NCCM remains to be identified. Methods and Results We describe, in two separate autosomal-dominant NCCM families, the identification of mutations in the sarcomeric cardiac b-myosin heavy chain gene (MYH7), known to be associated with hypertrophic cardiomyopathy (HCM), restricted cardiomyopathy (RCM), and dilated cardiomyopathy (DCM). Conclusion These results confirm the genetic heterogeneity of NCCM and suggest that the molecular classification of cardiomyopathies includes an MYH7-associated spectrum of NCCM with HCM, RCM, and DCM

Коррекция двигательных и поведенческих функций в лечении и реабилитации больных шизотипическим расстройством

На основании особенностей невербального поведения больных шизотипическим расстройством разработаны поведенческие методы, применение которых в их комплексной терапии позволяет добиться более полной редукции психопатологической симптоматики.Behavioral methods were worked out basing of the peculiarities of non−verbal behavior of the patients with schizotypical disorders. The use of the methods in complex therapy allows to achieve more complete reduction in psychopathological signs

A mutation update for the FLNC gene in myopathies and cardiomyopathies

Filamin C (FLNC) variants are associated with cardiac and muscular phenotypes. Originally, FLNC variants were described in myofibrillar myopathy (MFM) patients. Later, high-throughput screening in cardiomyopathy cohorts determined a prominent role for FLNC in isolated hypertrophic and dilated cardiomyopathies (HCM and DCM). FLNC variants are now among the more prevalent causes of genetic DCM. FLNC-associated DCM is associated with a malignant clinical course and a high risk of sudden cardiac death. The clinical spectrum of FLNC suggests different pathomechanisms related to variant types and their location in the gene. The appropriate functioning of FLNC is crucial for structural integrity and cell signaling of the sarcomere. The secondary protein structure of FLNC is critical to ensure this function. Truncating variants with subsequent haploinsufficiency are associated with DCM and cardiac arrhythmias. Interference with the dimerization and folding of the protein leads to aggregate formation detrimental for muscle function, as found in HCM and MFM. Variants associated with HCM are predominantly missense variants, which cluster in the ROD2 domain. This domain is important for binding to the sarcomere and to ensure appropriate cell signaling. We here review FLNC genotype–phenotype correlations based on available evidence

The arrhythmogenic cardiomyopathy phenotype associated with PKP2 c.1211dup variant

Background: The arrhythmogenic cardiomyopathy (ACM) phenotype, with life-threatening ventricular arrhythmias and heart failure, varies according to genetic aetiology. We aimed to characterise the phenotype associated with the variant c.1211dup (p.Val406Serfs*4) in the plakophilin‑2 gene (PKP2) and compare it with previously reported Dutch PKP2 founder variants. Methods: Clinical data were collected retrospectively from medical records of 106 PKP2 c.1211dup heterozygous carriers. Using data from the Netherlands ACM Registry, c.1211dup was compared with 3 other truncating PKP2 variants (c.235C &gt; T (p.Arg79*), c.397C &gt; T (p.Gln133*) and c.2489+1G &gt; A (p.?)). Results: Of the 106 carriers, 47 (44%) were diagnosed with ACM, at a mean age of 41 years. By the end of follow-up, 29 (27%) had experienced sustained ventricular arrhythmias and 12 (11%) had developed heart failure, with male carriers showing significantly higher risks than females on these endpoints (p &lt; 0.05). Based on available cardiac magnetic resonance imaging and echocardiographic data, 46% of the carriers showed either right ventricular dilatation and/or dysfunction, whereas a substantial minority (37%) had some form of left ventricular involvement. Both geographical distribution of carriers and haplotype analysis suggested PKP2 c.1211dup to be a founder variant originating from the South-Western coast of the Netherlands. Finally, a Cox proportional hazards model suggested significant differences in ventricular arrhythmia–free survival between 4 PKP2 founder variants, including c.1211dup. Conclusions: The PKP2 c.1211dup variant is a Dutch founder variant associated with a typical right-dominant ACM phenotype, but also left ventricular involvement, and a possibly more severe phenotype than other Dutch PKP2 founder variants.</p