Mutant mitochondrial elongation factor G1 and combined oxidative phosphorylation deficiency

Although most components of the mitochondrial translation apparatus are encoded by nuclear genes, all known molecular defects associated with impaired mitochondrial translation are due to mutations in mitochondrial DNA. We investigated two siblings with a severe defect in mitochondrial translation, reduced levels of oxidative phosphorylation complexes containing mitochondrial DNA (mtDNA)–encoded subunits, and progressive hepatoencephalopathy. We mapped the defective gene to a region on chromosome 3q containing elongation factor G1 (EFG1), which encodes a mitochondrial translation factor. Sequencing of EFG1 revealed a mutation affecting a conserved residue of the guanosine triphosphate (GTP)–binding domain. These results define a new class of gene defects underlying disorders of oxidative phosphorylation

Risk stratification and subclinical phenotyping of dilated and/or arrhythmogenic cardiomyopathy mutation-positive relatives: CVON eDETECT consortium

In relatives of index patients with dilated cardiomyopathy and arrhythmogenic cardiomyopathy, early detection of disease onset is essential to prevent sudden cardiac death and facilitate early treatment of heart failure. However, the optimal screening interval and combination of diagnostic techniques are unknown. The clinical course of disease in index patients and their relatives is variable due to incomplete and age-dependent penetrance. Several biomarkers, electrocardiographic and imaging (echocardiographic deformation imaging and cardiac magnetic resonance imaging) techniques are promising non-invasive methods for detection of subclinical cardiomyopathy. However, these techniques need optimisation and integration into clinical practice. Furthermore, determining the optimal interval and intensity of cascade screening may require a personalised approach. To address this, the CVON-eDETECT (early detection of disease in cardiomyopathy mutation carriers) consortium aims to integrate electronic health record data from long-term follow-up, diagnostic data sets, tissue and plasma samples in a multidisciplinary biobank environment to provide personalised risk stratification for heart failure and sudden cardiac death. Adequate risk stratification may lead to personalised screening, treatment and optimal timing of implantable cardioverter defibrillator implantation. In this article, we describe non-invasive diagnostic techniques used for detection of subclinical disease in relatives of index patients with dilated cardiomyopathy and arrhythmogenic cardiomyopathy

Complement factor H serum levels determine resistance to pneumococcal invasive disease

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Interventions to prevent disability in frail community-dwelling elderly: a systematic review

<p>Abstract</p> <p>Background</p> <p>There is an interest for intervention studies aiming at the prevention of disability in community-dwelling physically frail older persons, though an overview on their content, methodological quality and effectiveness is lacking.</p> <p>Methods</p> <p>A search for clinical trials involved databases PubMed, CINAHL and Cochrane Central Register of Controlled Trials and manually hand searching. Trials that included community-dwelling frail older persons based on physical frailty indicators and used disability measures for outcome evaluation were included. The selection of papers and data-extraction was performed by two independent reviewers. Out of 4602 titles, 10 papers remained that met the inclusion criteria. Of these, 9 were of sufficient methodological quality and concerned 2 nutritional interventions and 8 physical exercise interventions.</p> <p>Results</p> <p>No evidence was found for the effect of nutritional interventions on disability measures. The physical exercise interventions involved 2 single-component programs focusing on lower extremity strength and 6 multi-component programs addressing a variety of physical parameters. Out of 8 physical exercise interventions, three reported positive outcomes for disability. There was no evidence for the effect of single lower extremity strength training on disability. Differences between the multi-component interventions in e.g. individualization, duration, intensity and setting hamper the interpretation of the elements that consistently produced successful outcomes.</p> <p>Conclusion</p> <p>There is an indication that relatively long-lasting and high-intensive multicomponent exercise programs have a positive effect on ADL and IADL disability for community-living moderate physically frail older persons. Future research into disability prevention in physical frail older persons could be directed to more individualized and comprehensive programs.</p

The psychometric properties of three self-report screening instruments for identifying frail older people in the community

Background: Frailty is highly prevalent in older people. Its serious adverse consequences, such as disability, are considered to be a public health problem. Therefore, disability prevention in community-dwelling frail older people is considered to be a priority for research and clinical practice in geriatric care. With regard to disability prevention, valid screening instruments are needed to identify frail older people in time. The aim of this study was to evaluate and compare the psychometric properties of three screening instruments: the Groningen Frailty Indicator (GFI), the Tilburg Frailty Indicator (TFI) and the Sherbrooke Postal Questionnaire (SPQ). For validation purposes the Groningen Activity Restriction Scale (GARS) was added. Methods: A questionnaire was sent to 687 community-dwelling older people (>= 70 years). Agreement between instruments, internal consistency, and construct validity of instruments were evaluated and compared. Results: The response rate was 77%. Prevalence estimates of frailty ranged from 40% to 59%. The highest agreement was found between the GFI and the TFI (Cohen's kappa = 0.74). Cronbach's alpha for the GFI, the TFI and the SPQ was 0.73, 0.79 and 0.26, respectively. Scores on the three instruments correlated significantly with each other (GFI - TFI, r = 0.87; GFI - SPQ, r = 0.47; TFI - SPQ, r = 0.42) and with the GARS (GFI - GARS, r = 0.57; TFI - GARS, r = 0.61; SPQ - GARS, r = 0.46). The GFI and the TFI scores were, as expected, significantly related to age, sex, education and income. Conclusions: The GFI and the TFI showed high internal consistency and construct validity in contrast to the SPQ. Based on these findings it is not yet possible to conclude whether the GFI or the TFI should be preferred; data on the predictive values of both instruments are needed. The SPQ seems less appropriate for postal screening of frailty among community-dwelling older peopl

The predictive validity of three self-report screening instruments for identifying frail older people in the community

Background: If brief and easy to use self report screening tools are available to identify frail elderly, this may avoid costs and unnecessary assessment of healthy people. This study investigates the predictive validity of three self-report instruments for identifying community-dwelling frail elderly. Methods: This is a prospective study with 1-year follow-up among community-dwelling elderly aged 70 or older (n = 430) to test sensitivity, specificity, and positive and negative predicted values of the Groningen Frailty Indicator, Tilburg Frailty Indicator and Sherbrooke Postal Questionnaire on development of disabilities, hospital admission and mortality. Odds ratios were calculated to compare frail versus non-frail groups for their risk for the adverse outcomes. Results: Adjusted odds ratios show that those identified as frail have more than twice the risk (GFI, 2.62; TFI, 2.00; SPQ, 2,49) for developing disabilities compared to the non-frail group; those identified as frail by the TFI and SPQ have more than twice the risk of being admitted to a hospital. Sensitivity and specificity for development of disabilities are 71% and 63% (GFI), 62% and 71% (TFI) and 83% and 48% (SPQ). Regarding mortality, sensitivity for all tools are about 70% and specificity between 41% and 61%. For hospital admission, SPQ scores the highest for sensitivity (76%). Conclusion: All three instruments do have potential to identify older persons at risk, but their predictive power is not sufficient yet. Further research on these and other instruments is needed to improve targeting frail elderly

Factor structure and construct validity of the Adult Social Care Outcomes Toolkit for Carers (ASCOT-Carer)

Background: The ASCOT-Carer is a self-report instrument designed to measure social care-related quality of life (SCRQoL). This article presents the psychometric testing and validation of the ASCOT-Carer four response-level interview (INT4) in a sample of unpaid carers of adults who receive publicly-funded social care services in England. Methods: Unpaid carers were identified through a survey of users of publicly-funded social care services in England. 387 carers completed a face-to-face or telephone interview. Data on variables hypothesised to be related to SCRQoL (for example, characteristics of the carer, cared-for person and care situation) and measures of carer experience, strain, health-related quality of life and overall QoL were collected. Relationships between these variables and overall SCRQoL score were evaluated through correlation, ANOVA and regression analysis to test the construct validity of the scale. Internal reliability was assessed using Cronbach’s alpha and feasibility by the number of missing responses. Results: The construct validity was supported by statistically significant relationships between SCRQoL and scores on instruments of related constructs, as well as with characteristics of the carer and care recipient in univariate and multivariate analyses. A Cronbach’s alpha of 0.87 (7 items) indicates that the internal reliability of the instrument is satisfactory and a low number of missing responses (<1%) indicates a high level of acceptance. Conclusions: The results provide evidence to support the construct validity, factor structure, internal reliability and feasibility of the ASCOT-Carer INT4 as an instrument for measuring social care-related quality of life of unpaid carers who care for adults with a variety of long-term conditions, disability or problems related to old age

Prospective research on musculoskeletal disorders in office workers (PROMO): study protocol

BACKGROUND: This article describes the background and study design of the PROMO study (Prospective Research on Musculoskeletal disorders in Office workers). Few longitudinal studies have been performed to investigate the risk factors responsible for the incidence of hand, arm, shoulder and neck symptoms among office workers, given the observation that a large group of office workers might be at risk worldwide. Therefore, the PROMO study was designed. The main aim is to quantify the contribution of exposure to occupational computer use to the incidence of hand, arm, shoulder and neck symptoms. The results of this study might lead to more effective and/or cost-efficient preventive interventions among office workers. METHODS/DESIGN: A prospective cohort study is conducted, with a follow-up of 24 months. In total, 1821 participants filled out the first questionnaire (response rate of 74%). Data on exposure and outcome is collected using web-based self-reports. Outcome assessment takes place every three months during the follow-up period. Data on computer use are collected at baseline and continuously during follow-up using a software program. DISCUSSION: The advantages of the PROMO study include the long follow-up period, the repeated measurement of both exposure and outcome, and the objective measurement of the duration of computer use. In the PROMO study, hypotheses stemming from lab-based and field-based research will be investigated

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure