The discrepancy between social isolation and loneliness as a clinically meaningful metric: findings from the Irish and English longitudinal studies of ageing (TILDA and ELSA)

OBJECTIVE: Scant evidence is available on the discordance between loneliness and social isolation among older adults. We aimed to investigate this discordance and any health implications that it may have. METHOD: Using nationally representative datasets from ageing cohorts in Ireland (TILDA) and England (ELSA), we created a metric of discordance between loneliness and social isolation, to which we refer as Social Asymmetry. This metric was the categorised difference between standardised scores on a scale of loneliness and a scale of social isolation, giving categories of: Concordantly Lonely and Isolated, Discordant: Robust to Loneliness, or Discordant: Susceptible to Loneliness. We used regression and multilevel modelling to identify potential relationships between Social Asymmetry and cognitive outcomes. RESULTS: Social Asymmetry predicted cognitive outcomes cross-sectionally and at a two-year follow-up, such that Discordant: Robust to Loneliness individuals were superior performers, but we failed to find evidence for Social Asymmetry as a predictor of cognitive trajectory over time. CONCLUSIONS: We present a new metric and preliminary evidence of a relationship with clinical outcomes. Further research validating this metric in different populations, and evaluating its relationship with other outcomes, is warranted. Copyright © 2016 John Wiley & Sons, Ltd

Loneliness and social engagement in older adults: A bivariate dual change score analysis

Few longitudinal studies have explored the impact of loneliness on social engagement. We investigated whether loneliness would result in decreased social engagement over time among older adults and also whether the converse, that low levels of social engagement would predict increases in loneliness, held. Additionally, we explored potential mechanisms (specifically, memory and depressive symptomatology as mediators) in the bidirectional relationship(s) between loneliness and social engagement. Data from 4,714 adults over 50 years of age, participating in Waves 3, 4, and 5 of the English Longitudinal Study of Ageing (between 2006 and 2011), were analyzed using bivariate dual change scores within structural equation models. Higher levels of loneliness were inversely associated with social engagement over time, and high levels of social engagement were inversely associated with loneliness over time. To address the 2nd aim, we used structural equation modeling to evaluate potential mediators of the bidirectional relationships between loneliness and changes in social engagement. Depressive symptomatology, semantic memory, and episodic memory were found to partially mediate the relationship between loneliness measured at baseline and social engagement 4 years later. In addition, these variables also partially mediated the relationship between social engagement at baseline and loneliness 4 years later. A comparison of the 2 models revealed that the model proposing a pathway from loneliness to social engagement (as mediated by depressive symptoms and memory) provided a better fit to the data. Implications for theories of loneliness are discussed. (PsycINFO Database Recor

Functional disability and death wishes in older Europeans: results from the EURODEP concerted action

Functional disability was independently associated with death wishes in older adults. Results can help inform clinicians who care for older persons with functional impairment.</p

Primary Care Staff's Views and Experiences Related to Routinely Advising Patients about Physical Activity. A Questionnaire Survey

Background: United Kingdom public health policy has recently re-emphasised the role of primary health care professionals in tackling increasing levels of physical inactivity within the general population. However, little is known about the impact that this has had in practice. This study explores Scottish primary care staff's knowledge, attitudes and experiences associated with advising patients about physical activity during routine consultations. Methods: A cross-sectional questionnaire survey of general practitioners (or family physicians), practice nurses and health visitors based in four health regions was conducted during 2004. The main outcome measures included: i) health professionals' knowledge of the current physical activity recommendations; (ii) practice related to routine physical activity advising; and (iii) associated attitudes. Results: Questionnaires were returned by 757 primary care staff (response rate 54%). Confidence and enthusiasm for giving advice was generally high, but knowledge of current physical activity recommendations was low. In general, respondents indicated that they routinely discuss and advise patients about physical activity regardless of the presenting condition. Health visitors and practice nurses were more likely than general practitioners to offer routine advice. Lack of time and resources were more likely to be reported as barriers to routine advising by general practitioners than other professional groups. However, health visitors and practice nurses were also more likely than general practitioners to believe that patients would follow their physical activity advice giving. Conclusion: If primary health care staff are to be fully motivated and effective in encouraging and supporting the general population to become more physically active, policymakers and health professionals need to engage in efforts to: (1) improve knowledge of current physical activity recommendations and population trends amongst frontline primary care staff; and (2) consider the development of tools to support individual assessment and advice giving to suit individual circumstances. Despite the fact that this study found that system barriers to routine advising were less of a problem than other previous research has indicated, this issue still remains a challenge

Metabolomics demonstrates divergent responses of two Eucalyptus species to water stress

Past studies of water stress in Eucalyptus spp. generally highlighted the role of fewer than five “important” metabolites, whereas recent metabolomic studies on other genera have shown tens of compounds are affected. There are currently no metabolite profiling data for responses of stress-tolerant species to water stress. We used GC–MS metabolite profiling to examine the response of leaf metabolites to a long (2 month) and severe (Ψpredawn < −2 MPa) water stress in two species of the perennial tree genus Eucalyptus (the mesic Eucalyptus pauciflora and the semi-arid Eucalyptus dumosa). Polar metabolites in leaves were analysed by GC–MS and inorganic ions by capillary electrophoresis. Pressure–volume curves and metabolite measurements showed that water stress led to more negative osmotic potential and increased total osmotically active solutes in leaves of both species. Water stress affected around 30–40% of measured metabolites in E. dumosa and 10–15% in E. pauciflora. There were many metabolites that were affected in E. dumosa but not E. pauciflora, and some that had opposite responses in the two species. For example, in E. dumosa there were increases in five acyclic sugar alcohols and four low-abundance carbohydrates that were unaffected by water stress in E. pauciflora. Re-watering increased osmotic potential and decreased total osmotically active solutes in E. pauciflora, whereas in E. dumosa re-watering led to further decreases in osmotic potential and increases in total osmotically active solutes. This experiment has added several extra dimensions to previous targeted analyses of water stress responses in Eucalyptus, and highlights that even species that are closely related (e.g. congeners) may respond differently to water stress and re-waterin

Evidence for anti-angiogenic and pro-survival functions of the cerebral cavernous malformation protein 3

Mutations in CCM1, CCM2, or CCM3 lead to cerebral cavernous malformations, one of the most common hereditary vascular diseases of the brain. Endothelial cells within these lesions are the main disease compartments. Here, we show that adenoviral CCM3 expression inhibits endothelial cell migration, proliferation, and tube formation while downregulation of endogenous CCM3 results in increased formation of tube-like structures. Adenoviral CCM3 expression does not induce apoptosis under normal endothelial cell culture conditions but protects endothelial cells from staurosporine-induced cell death. Tyrosine kinase activity profiling suggests that CCM3 supports PDPK-1/Akt-mediated endothelial cell quiescence and survival

Small-molecule targeting of brachyury transcription factor addiction in chordoma.

Chordoma is a primary bone cancer with no approved therapy1. The identification of therapeutic targets in this disease has been challenging due to the infrequent occurrence of clinically actionable somatic mutations in chordoma tumors2,3. Here we describe the discovery of therapeutically targetable chordoma dependencies via genome-scale CRISPR-Cas9 screening and focused small-molecule sensitivity profiling. These systematic approaches reveal that the developmental transcription factor T (brachyury; TBXT) is the top selectively essential gene in chordoma, and that transcriptional cyclin-dependent kinase (CDK) inhibitors targeting CDK7/12/13 and CDK9 potently suppress chordoma cell proliferation. In other cancer types, transcriptional CDK inhibitors have been observed to downregulate highly expressed, enhancer-associated oncogenic transcription factors4,5. In chordoma, we find that T is associated with a 1.5-Mb region containing 'super-enhancers' and is the most highly expressed super-enhancer-associated transcription factor. Notably, transcriptional CDK inhibition leads to preferential and concentration-dependent downregulation of cellular brachyury protein levels in all models tested. In vivo, CDK7/12/13-inhibitor treatment substantially reduces tumor growth. Together, these data demonstrate small-molecule targeting of brachyury transcription factor addiction in chordoma, identify a mechanism of T gene regulation that underlies this therapeutic strategy, and provide a blueprint for applying systematic genetic and chemical screening approaches to discover vulnerabilities in genomically quiet cancers

Design of the New Life(style) study: a randomised controlled trial to optimise maternal weight development during pregnancy. [ISRCTN85313483]

BACKGROUND: Preventing excessive weight gain during pregnancy is potentially important in the prevention of overweight and obesity among women of childbearing age. However, few intervention studies aiming at weight management during pregnancy have been performed and most of these interventions were not as successful as expected. In this paper the design of the New Life(style) study is described as well as the content of the individually tailored intervention program, which focuses on controlling weight development during pregnancy. METHODS: The effectiveness of the New Life(style) intervention program versus usual care by midwives is evaluated in a randomised controlled trial. Women who expect their first child and visit one of the participating midwifery practices are included. The intervention is standardised in a protocol and executed by trained counsellors with the women who are randomised in the intervention group. During 5 sessions – at 18, 22, 30 and 36 weeks of pregnancy and at 8 weeks postpartum – individual weight gain is discussed in relation to weight gain guidelines for pregnant women of the American Institute of Medicine. Counsellors coach the women to maintain or optimise a healthy lifestyle, in a period of drastic physical and mental changes. Data is collected at 15, 25, 35 weeks of pregnancy and at 6, 26, and 52 weeks after delivery. Primary outcome measures are body weight, BMI, and skinfold thickness. Secondary outcome measures include physical activity, nutrition and blood levels of factors that are associated with energy homeostasis. DISCUSSION: Results of the current RCT will improve the knowledge of determinants of weight gain during pregnancy, weight retention after childbirth and of the effectiveness of the intervention program that is described. Caregivers and researchers in the field of health promotion are offered more insight in specific elements of the New Life(style) intervention program