Determinants of multidimensional mental wellbeing in the oldest old: a rapid review

Purpose

Improved life expectancy imposes new challenges for policy-makers. The growing oldest-old age group (defined as 80 and over) is often characterised by increased support needs. Greater attention to wellbeing in this population group is necessary, and may well require a shift in social policy focus. The current review seeks to explore current research on determinants of mental wellbeing for the oldest old.

Methods

An iterative rapid review approach was used to review existing literature in line with four dimensions of mental wellbeing defined by the European Welfare Models and Mental Wellbeing in Final Years of Life (EMMY) study; functional, social, personal and environmental. A specific focus on articles employing multidimensional definitions of mental wellbeing was adopted.

Results

Multidimensional indicators reflect the multifaceted and multidirectional dynamics of wellbeing in very old age. Considerable variety in both measures and terminology was found within the literature making precise comparison difficult. The current review takes steps towards comparability by focusing on studies implementing multiple measures of mental wellbeing including evaluative, hedonistic and eudaimonic factors. Clearly defined and multifaceted measures of mental wellbeing are needed to sharpen evidence used in policy development, appraisal and evaluation in light of the considerable diversity of health and functional states experienced in later life.

Conclusions

Previous studies appear to line up the four main dimensions of mental wellbeing identified in the EMMY study. Actively improving opportunities for older adults to produce benefits to society can be done via a stronger focus on resources such as mental wellbeing.

     

Membrane recruitment of nNOSµ in microdystrophin gene transfer to enhance durability

Several gene transfer clinical trials are currently ongoing with the common aim of delivering a shortened version of dystrophin, termed a microdystrophin, for the treatment of Duchenne muscular dystrophy (DMD). However, one of the main differences between these trials is the microdystrophin protein produced following treatment. Each gene transfer product is based on different selections of dystrophin domain combinations to assemble microdystrophin transgenes that maintain functional dystrophin domains and fit within the packaging limits of an adeno-associated virus (AAV) vector. While domains involved in mechanical function, such as the actin-binding domain and β-dystroglycan binding domain, have been identified for many years and included in microdystrophin constructs, more recently the neuronal nitric oxide synthase (nNOS) domain has also been identified due to its role in enhancing nNOS membrane localization. As nNOS membrane localization has been established as an important requirement for prevention of functional ischemia in skeletal muscle, inclusion of the nNOS domain into a microdystrophin construct represents an important consideration. The aim of this mini review is to highlight what is currently known about the nNOS domain of dystrophin and to describe potential implications of this domain in a microdystrophin gene transfer clinical trial.     

Dissecting the neurological phenotype in children with callosal agenesis,interhemispheric cysts and malformations of cortical development

Journal of Neurology - To describe the neurological phenotype of children with prenatal diagnosis of agenesis of corpus callosum (ACC) and interhemispheric cysts associated with malformations of...     

SWATH label-free proteomics for cystic fibrosis research

BackgroundLabel-free proteomics is a powerful tool for biological investigation. The SWATH protocol, relying on the Pan Human ion library, currently represents the state-of-the-art methodology for this kind of analysis. We recently discovered that this tool is not perfectly suitable for proteomics research in the CF field, as it lacks assays for several proteins crucial for the CF biology, including CFTR.MethodsWe extensively investigated the proteome of a very popular model for in vitro research on CF, CFBE41o-, and we used the corresponding data to improve the power of SWATH proteomics for CF investigation. We then used this improved tool to explore in depth the proteome of primary bronchial epithelial (BE) cells deriving from four CF individuals compared with that of four corresponding non-CF controls. By means of advanced bioinformatics tools, we outlined the presence of a number of protein networks being significantly altered by CF.ResultsOur analysis on patients' BE cells identified 154 proteins dysregulated by the CF pathology (94 upregulated and 60 downregulated). Some known CFTR interactors are present among them, but our analysis also revealed the alteration of other proteins not previously known to be related with CF.ConclusionsThe present work outlines the power of SWATH label free proteomics applied to CF research.     

Silicosis in Artificial Quartz Conglomerate Workers

IntroductionSilicosis is a chronic progressive disease caused by inhalation of crystalline silica. Most cases develop in underground mine workers and in subjects involved in the extraction of natural stone (slate and granite). In view of the progressive emergence of new cases of silicosis in artificial quartz conglomerate workers, we performed a study to analyze the characteristics of silicosis produced by this new agent in Spain.MethodsThe study consisted of a series of 96 cases of silicosis diagnosed according to international criteria during the period 2010–2017. We analyzed clinical, radiological, pathological and functional characteristics.ResultsMean age of participants was 45 years; 55% had simple silicosis and 45% had complicated silicosis. Ten patients were diagnosed with accelerated silicosis, with a mean age of 33 years. Mean time of exposure to conglomerates was 15 years, and 77% had not used appropriate protection measures. Half of the patients were asymptomatic and presented different classic forms on chest X-ray and chest high-resolution computed tomography, along with ground-glass images. No lung function changes were recorded.ConclusionsSilicosis in artificial quartz conglomerate workers occurs in a young, actively employed population, a considerable percentage of whom present an accelerated form. They have few symptoms and no functional limitations. Protection measures are scarce. It is important to characterize these features to provide early diagnosis and implement the necessary preventive measures.     

Inflammatory biomarkers,vascular procedures of lower limbs,and wound healing

Abnormal, persistent inflammation after bypass surgery could prevent healing of an ischaemic foot lesion. In 37 patients with peripheral arterial disease (PAD) (Rutherford Grade III Category 5) who underwent infrapopliteal vein graft and midfoot amputation, plasma levels of fibrinogen, C‐reactive protein (CRP), interleukin‐1 (IL‐1), interleukin‐6 (IL‐6), tumour necrosis factor‐α (TNF‐α), and matrix metalloproteinase‐2 and ‐9 (MMP‐2 and MMP‐9) were determined preoperatively and during the follow up. Nine patients without clinical and Doppler evidence of arterial disease, who underwent post‐traumatic midfoot primary amputation, were included in the experiment group, and 15 age‐matched healthy volunteers served as control. In patients who had midfoot amputation for trauma, all wounds healed. Seven (19%) wounds in patients with an occluded graft healed, and five (13%) required major amputation because of a non‐healing wound. Time required for complete healing of the lesion was similar between trauma and PAD patients (8 ± 2 months vs 11 ± 6, respectively, P = NS). Univariate analysis demonstrated that, in PAD patients, the postoperative high levels of TNF‐α, IL‐6, and MMP‐2 and ‐9 were predictive for wound healing failure at 3, 6, and 9 months (P < 0.05), respectively. Furthermore, the subgroup of patients who experienced occlusion of the vein graft during follow up had a significant increase of MMP‐2, ‐9, IL‐6, and TNF‐α at 3, 6, and 9 months (P < 0.05), respectively. Monitoring inflammatory markers allows the determination of patients at risk of healing failure of midfoot amputation after distal revascularisation and might predict the fate of the vein graft.