Should prevention of falls start earlier? Co-ordinated analyses of harmonised data on falls in middle-aged adults across four population-based cohort studies

© 2018 Peeters et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The prevalence of risk factors for falls increases during middle-age, but the prevalence of falls in this age-range is often overlooked and understudied. The aim was to calculate the prevalence of falls in middle-aged adults (aged 40–64 years) from four countries. Data were from four population-based cohort studies from Australia (Australian Longitudinal Study on Women’s Health, n = 10556, 100% women, 51–58 years in 2004), Ireland (The Irish Longitudinal Study on Ageing, n = 4968, 57.5% women, 40–64 years in 2010), the Netherlands (Longitudinal Aging Study Amsterdam, n = 862, 51.6% women, 55–64 years in 2012–13) and Great Britain (MRC National Survey of Health and Development, n = 2821, 50.9% women, 53 years in 1999). In each study, falls assessment was based on recall of any falls in the past year. The prevalence of falls was calculated for the total group, for each country, for men and women separately, and for 5-year age-bands. The prevalence was higher in Australia (27.8%, women only) and the Netherlands (25.1%) than in Ireland (17.6%) and Great Britain (17.8%, p<0.001). Women (27.0%) had higher prevalences than men (15.2%, p<0.001). The prevalence increased from 8.7% in 40–44 year olds to 29.9% in 60–64 year olds in women, and from 14.7% in 45–49 year olds to 15.7% in 60–64 year olds in men. Even within 5-year age-bands, there was substantial variation in prevalence between the four cohorts. Weighting for age, sex and education changed the prevalence estimates by less than 2 percentage points. The sharp increase in prevalence of falls in middle-age, particularly among women supports the notion that falls are not just a problem of old age, and that middle-age may be a critical life stage for preventive interventions

A comprehensive assessment of risk factors for falls in middle-aged adults: co-ordinated analyses of cohort studies in four countries

© 2019, International Osteoporosis Foundation and National Osteoporosis Foundation. Summary: We identified demographic, health and lifestyle factors associated with falls in adults aged 50–64 years from Australia, The Netherlands, Great Britain and Ireland. Nearly all factors were associated with falls, but there were differences between countries and between men and women. Existing falls prevention programs may also benefit middle-aged adults. Introduction: Between ages 40–44 and 60–64 years, the annual prevalence of falls triples suggesting that middle age may be a critical life stage for preventive interventions. We aimed to identify demographic, health and lifestyle factors associated with falls in adults aged 50–64 years. Methods: Harmonised data were used from four population-based cohort studies based in Australia (Australian Longitudinal Study on Women’s Health, n = 10,641, 51–58 years in 2004), Ireland (The Irish Longitudinal Study on Ageing, n = 4663, 40–64 years in 2010), the Netherlands (Longitudinal Ageing Study Amsterdam, n = 862, 55–64 years in 2012–13) and Great Britain (MRC National Survey of Health and Development, n = 2987, 53 years in 1999). Cross-sectional and prospective associations of 42 potential risk factors with self-reported falls in the past year were examined separately by cohort and gender using logistic regression. In the absence of differences between cohorts, estimates were pooled using meta-analysis. Results: In cross-sectional models, nearly all risk factors were associated with fall risk in at least one cohort. Poor mobility (pooled OR = 1.71, CI = 1.34–2.07) and urinary incontinence (OR range = 1.53–2.09) were consistently associated with falls in all cohorts. Findings from prospective models were consistent. Statistically significant interactions with cohort and sex were found for some of the risk factors. Conclusion: Risk factors known to be associated with falls in older adults were also associated with falls in middle age. Compared with findings from previous studies of older adults, there is a suggestion that specific risk factors, for example musculoskeletal conditions, may be more important in middle age. These findings suggest that available preventive interventions for falls in older adults may also benefit middle-aged adults, but tailoring by age, sex and country is required

Analysis of obstetric complications and uterine connective tissue in tenascin-X-deficient humans and mice

Tenascin-X (TNX) is a large, multi-domain, extracellular matrix glycoprotein. Complete deficiency of TNX in humans leads to a recessive form of Ehlers-Danlos syndrome (EDS), and TNX haploinsufficiency is a cause of hypermobility type EDS. EDS patients appear to have a higher risk of several complications during pregnancy, such as pelvic instability, premature rupture of membranes, and postpartum hemorrhage. Here, we present a study of genitourinary and obstetric complications in TNX-deficient women of reproductive age. We have found complications, such as uterus prolapses, that are in agreement with previous findings in other EDS types. In TNX knockout (KO) mice, we have observed mild pregnancy-related abnormalities. Morphological and immunohistological analysis of uterine tissues has not revealed obvious quantitative or spatial differences between TNX KO and wildtype mice with respect to collagen types I, III, V, and XII or elastic fibers. We conclude that TNX-deficient women are at risk of obstetric complications, but that TNX KO mice show only a mild phenotype. Furthermore, we show that TNX is involved in the stability of elastic fibers rather than in their initial deposition

Prevention of fall incidents in patients with a high risk of falling: design of a randomised controlled trial with an economic evaluation of the effect of multidisciplinary transmural care

Background. Annually, about 30% of the persons of 65 years and older falls at least once and 15% falls at least twice. Falls often result in serious injuries, such as fractures. Therefore, the prevention of accidental falls is necessary. The aim is to describe the design of a study that evaluates the efficacy and cost-effectiveness of a multidisciplinary assessment and treatment of multiple fall risk factors in independently living older persons with a high risk of falling. Methods/Design. The study is designed as a randomised controlled trial (RCT) with an economic evaluation. Independently living persons of 65 years and older who recently experienced a fall are interviewed in their homes and screened for risk of recurrent falling using a validated fall risk profile. Persons at low risk of recurrent falling are excluded from the RCT. Persons who have a high risk of recurrent falling are blindly randomised into an intervention (n = 100) or usual care (n = 100) group. The intervention consists of a multidisciplinary assessment and treatment of multifactorial fall risk factors. The transmural multidisciplinary appraoch entails close cooperation between geriatrician, primary care phys

Chronic Stress Induces Sex-Specific Alterations in Methylation and Expression of Corticotropin-Releasing Factor Gene in the Rat

Contains fulltext : 91627.pdf (publisher's version ) (Open Access

The Origin and Evolutionary History of HIV-1 Subtype C in Senegal

Background: The classification of HIV-1 strains in subtypes and Circulating Recombinant Forms (CRFs) has helped in tracking the course of the HIV pandemic. In Senegal, which is located at the tip of West Africa, CRF02_AG predominates in the general population and Female Sex Workers (FSWs). In contrast, 40% of Men having Sex with Men (MSM) in Senegal are infected with subtype C. In this study we analyzed the geographical origins and introduction dates of HIV-1 C in Senegal in order to better understand the evolutionary history of this subtype, which predominates today in the MSM population Methodology/Principal Findings: We used a combination of phylogenetic analyses and a Bayesian coalescent-based approach, to study the phylogenetic relationships in pol of 56 subtype C isolates from Senegal with 3,025 subtype C strains that were sampled worldwide. Our analysis shows a significantly well supported cluster which contains all subtype C strains that circulate among MSM in Senegal. The MSM cluster and other strains from Senegal are widely dispersed among the different subclusters of African HIV-1 C strains, suggesting multiple introductions of subtype C in Senegal from many different southern and east African countries. More detailed analyses show that HIV-1 C strains from MSM are more closely related to those from southern Africa. The estimated date of the MRCA of subtype C in the MSM population in Senegal is estimated to be in the early 80's. Conclusions/Significance: Our evolutionary reconstructions suggest that multiple subtype C viruses with a common ancestor originating in the early 1970s entered Senegal. There was only one efficient spread in the MSM population, which most likely resulted from a single introduction, underlining the importance of high-risk behavior in spread of viruses

A systematic review of physiological methods in rodent pharmacological MRI studies

Rationale: Pharmacological magnetic resonance imaging (phMRI) provides an approach to study effects of drug challenges on brain processes. Elucidating mechanisms of drug action helps us to better understand the workings of neurotransmitter systems, map brain function or facilitate drug development. phMRI is increasingly used in preclinical research employing rodent models; however, data interpretation and integration are complicated by the use of different experimental approaches between laboratories. In particular, the effects of different anaesthetic regimes upon neuronal and haemodynamic processes and baseline physiology could be problematic. Objectives: This paper investigates how differences in phMRI research methodologies are manifested and considers associated implications, placing particular emphasis on choice of anaesthetic regimes. Methods: A systematic review of rodent phMRI studies was conducted. Factors such as those describing anaesthetic regimes (e.g. agent, dosage) and parameters relating to physiological maintenance (e.g. ventilatory gases) and MRI method were recorded. Results: We identified 126 eligible studies and found that the volatile agents isoflurane (43.7 %) and halothane (33.3 %) were most commonly used for anaesthesia, but dosage and mixture of ventilatory gases varied substantially between laboratories. Relevant physiological parameters were usually recorded, although 32 % of studies did not provide cardiovascular measures. Conclusions: Anaesthesia and animal preparation can influence phMRI data profoundly. The variation of anaesthetic type, dosage regime and ventilatory gases makes consolidation of research findings (e.g. within a specific neurotransmitter system) difficult. Standardisation of a small(er) number of preclinical phMRI research methodologies and/or increased consideration of approaches that do not require anaesthesia is necessary to address these challenges

Characterization of the Single Stranded DNA Binding Protein SsbB Encoded in the Gonoccocal Genetic Island

Background: Most strains of Neisseria gonorrhoeae carry a Gonococcal Genetic Island which encodes a type IV secretion system involved in the secretion of ssDNA. We characterize the GGI-encoded ssDNA binding protein, SsbB. Close homologs of SsbB are located within a conserved genetic cluster found in genetic islands of different proteobacteria. This cluster encodes DNA-processing enzymes such as the ParA and ParB partitioning proteins, the TopB topoisomerase, and four conserved hypothetical proteins. The SsbB homologs found in these clusters form a family separated from other ssDNA binding proteins. Methodology/Principal Findings: In contrast to most other SSBs, SsbB did not complement the Escherichia coli ssb deletion mutant. Purified SsbB forms a stable tetramer. Electrophoretic mobility shift assays and fluorescence titration assays, as well as atomic force microscopy demonstrate that SsbB binds ssDNA specifically with high affinity. SsbB binds single-stranded DNA with minimal binding frames for one or two SsbB tetramers of 15 and 70 nucleotides. The binding mode was independent of increasing Mg 2+ or NaCl concentrations. No role of SsbB in ssDNA secretion or DNA uptake could be identified, but SsbB strongly stimulated Topoisomerase I activity

In vitro epithelial-to-mesenchymal transformation in human adult epicardial cells is regulated by TGFβ-signaling and WT1

Adult epicardial cells are required for endogenous cardiac repair. After myocardial injury, they are reactivated, undergo epithelial-to-mesenchymal transformation (EMT) and migrate into the injured myocardium where they generate various cell types, including coronary smooth muscle cells and cardiac interstitial fibroblasts, which contribute to cardiac repair. To understand what drives epicardial EMT, we used an in vitro model for human adult epicardial cells. These cells have an epithelium-like morphology and markedly express the cell surface marker vascular cell adhesion marker (VCAM-1). In culture, epicardial cells spontaneously undergo EMT after which the spindle-shaped cells now express endoglin. Both epicardial cells before and after EMT express the epicardial marker, Wilms tumor 1 (WT1). Adding transforming growth factor beta (TGFβ) induces loss of epithelial character and initiates the onset of mesenchymal differentiation in human adult epicardial cells. In this study, we show that TGFβ-induced EMT is dependent on type-1 TGFβ receptor activity and can be inhibited by soluble VCAM-1. We also show that epicardial-specific knockdown of Wilms tumor-1 (WT1) induces the process of EMT in human adult epicardial cells, through transcriptional regulation of platelet-derived growth factor receptor alpha (Pdgfrα), Snai1 and VCAM-1. These data provide new insights into the process of EMT in human adult epicardial cells, which might provide opportunities to develop new strategies for endogenous cell-based cardiac repair