Falls, Depression and Antidepressants in Later Life: A Large Primary Care Appraisal

BACKGROUND: Depression and falls are common and co-exist for older people. Safe management of each of these conditions is important to quality of life. METHODS: A cross-sectional survey was used to examine medication use associated with injurious and non-injurious falls in 21,900 community-dwelling adults, aged 60 years or over from 383 Australian general practices recruited for the DEPS-GP Project. Falls and injury from falls, medication use, depressive symptoms (Primary Health Questionnaire (PHQ-9)), clinical morbidity, suicidal ideation and intent, health status (SF-12 Health Survey), demographic and lifestyle information was reported in a standardised survey. FINDINGS: Respondents were 71.8 years (sd 7.7) of age and 58.4% were women. 24% 11% and 8% reported falls, fall related injury, and sought medical attention respectively. Antidepressant use (odds ratio, OR: 1.46; 95% confidence interval, 95%CI: 1.25, 1.70), questionable depression (5-14 on PHQ OR: 1.32, 95%CI: 1.13, 1.53) and clinically significant symptoms of depression (15 or more on PHQ OR: 1.70, 95%CI: 1.14, 1.50) were independently associated with multiple falls. SSRI use was associated with the highest risk of multiple falls (OR: 1.66, 95%CI: 1.36, 2.02) amongst all psychotropic medications. Similar associations were observed for injurious falls. Over 60% of those with four accumulated risk factors had multiple falls in the previous year (OR: 3.40, 95%CI: 1.79, 6.45); adjusted for other demographic and health factors. INTERPRETATION: Antidepressant use (particularly SSRIs) was strongly associated with falls regardless of presence of depressive symptoms. Strategies to prevent falls should become a routine part of the management of older people with depression

Sequence Features and Transcriptional Stalling within Centromere DNA Promote Establishment of CENP-A Chromatin

Centromere sequences are not conserved between species, and there is compelling evidence for epigenetic regulation of centromere identity, with location being dictated by the presence of chromatin containing the histone H3 variant CENP-A. Paradoxically, in most organisms CENP-A chromatin generally occurs on particular sequences. To investigate the contribution of primary DNA sequence to establishment of CENP-A chromatin in vivo, we utilised the fission yeast Schizosaccharomyces pombe. CENP-ACnp1 chromatin is normally assembled on ∼10 kb of central domain DNA within these regional centromeres. We demonstrate that overproduction of S. pombe CENP-ACnp1 bypasses the usual requirement for adjacent heterochromatin in establishing CENP-ACnp1 chromatin, and show that central domain DNA is a preferred substrate for de novo establishment of CENP-ACnp1 chromatin. When multimerised, a 2 kb sub-region can establish CENP-ACnp1 chromatin and form functional centromeres. Randomization of the 2 kb sequence to generate a sequence that maintains AT content and predicted nucleosome positioning is unable to establish CENP-ACnp1 chromatin. These analyses indicate that central domain DNA from fission yeast centromeres contains specific information that promotes CENP-ACnp1 incorporation into chromatin. Numerous transcriptional start sites were detected on the forward and reverse strands within the functional 2 kb sub-region and active promoters were identified. RNAPII is enriched on central domain DNA in wild-type cells, but only low levels of transcripts are detected, consistent with RNAPII stalling during transcription of centromeric DNA. Cells lacking factors involved in restarting transcription-TFIIS and Ubp3-assemble CENP-ACnp1 on central domain DNA when CENP-ACnp1 is at wild-type levels, suggesting that persistent stalling of RNAPII on centromere DNA triggers chromatin remodelling events that deposit CENP-ACnp1. Thus, sequence-encoded features of centromeric DNA create an environment of pervasive low quality RNAPII transcription that is an important determinant of CENP-ACnp1 assembly. These observations emphasise roles for both genetic and epigenetic processes in centromere establishment

Three pillars of sustainability: in search of conceptual origins

The three-pillar conception of (social, economic and environmental) sustainability, commonly represented by three intersecting circles with overall sustainability at the centre, has become ubiquitous. With a view of identifying the genesis and theoretical foundations of this conception, this paper reviews and discusses relevant historical sustainability literature. From this we find that there is no single point of origin of this three-pillar conception, but rather a gradual emergence from various critiques in the early academic literature of the economic status quo from both social and ecological perspectives on the one hand, and the quest to reconcile economic growth as a solution to social and ecological problems on the part of the United Nations on the other. The popular three circles diagram appears to have been first presented by Barbier (Environ Conserv 14:101, doi: 10.1017/s0376892900011449, 1987), albeit purposed towards developing nations with foci which differ from modern interpretations. The conceptualisation of three pillars seems to predate this, however. Nowhere have we found a theoretically rigorous description of the three pillars. This is thought to be in part due to the nature of the sustainability discourse arising from broadly different schools of thought historically. The absence of such a theoretically solid conception frustrates approaches towards a theoretically rigorous operationalisation of ‘sustainability’

Lipase-Catalyzed Dynamic Combinatorial Resolution and the Synthesis of Heteroaromatic Cyanohydrin Ester Enantiomers

Five structurally related thiophene-based aldehydes, acetone cyanohydrin, a base, a lipase enzyme and isopropenyl acetate have been mixed in one-pot, leading to the dynamic combinatorial resolution of a cyanohydrin library. The process is applied in optimizing synthetic conditions for the cyanohydrin acetate library obtained in terms of reactivity and enantiopurity. Anhydrous Na2CO3 and lipase PS-D (Burkholderia cepacia lipase) or Novozym 435 (Candida antarctica lipase B) preparations are shown to be the best catalyst combinations for the DCR of the substrate series in toluene. The justification of the optimized process is confirmed by preparing the thiophene -based (R)-cyanohydrin acetates with 68-99% isolated yields and 82-91 % ee using the traditional dynamic kinetic resolution of each substrate

Lipase-catalyzed asymmetric acylation in the chemoenzymatic synthesis of furan-based alcohols

Eight racemic 1-(furan-2-yl)ethanols were prepared from the corresponding carbonyl compounds for enantioselective acylation studies, and seven of them were used in preparative-scale kinetic resolutions with Candida antarctica lipase B (Novozym 435) and vinyl acetate in dried diisopropyl ether. Mechanism-based competition between the (R)-acetate (enzymatic acylation product), vinyl acetate (added acylating reagent), and acetic acid (enzymatic hydrolysis product) toward CAL-B, together with the residual water of the lipase were shown to be potential reasons for side reactions, which affected the course of the kinetic resolution of 1-[5-(2-chlorophenyl) and (4-bromophenyl)furan-2-yl]ethanols. Clear effects were not observed with the other alcoholic substrates. Alcoholysis of the enantiomerically enriched (R)-acetates with methanol and CAL-B in diisopropyl ether was shown to be a potential method for the deprotection of the (R)-acetates and the formation of (R)-alcohols. (C) 2012 Elsevier Ltd. All rights reserved

Prevalência de quedas em idosos asilados do município de Rio Grande, RS Prevalence of falls in institutionalized elderly in Rio Grande, Southern Brazil

OBJETIVO: O aumento da expectativa de vida nos países em desenvolvimento tem provocado preocupação com a qualidade de vida e o bem-estar dos idosos, principalmente a ocorrência de quedas. Nesse sentido, o objetivo do estudo foi descrever a prevalência de quedas em idosos que vivem em asilos e fatores associados. MÉTODOS: Estudo de delineamento transversal na cidade de Rio Grande (RS), em 2007. Participaram 180 indivíduos idosos (65 anos ou mais) residentes em asilos para acolhimento. Em entrevista, os idosos responderam a questões de instrumento pré-testado sobre a ocorrência de quedas. Além de análise bivariada (Wald), foi realizada análise por regressão de Poisson com cálculo de razões de prevalência e intervalos de confiança de 95%, ajustada para as variáveis de confusão. RESULTADOS: A prevalência de quedas entre os idosos asilados estudados foi de 38,3%. As quedas foram mais comuns no ambiente do asilo (62,3%), sendo o quarto o ambiente onde ocorreu o maior número de quedas (23%). Na análise ajustada, as quedas se mantiveram associadas com cor da pele branca, com os idosos separados e divorciados, com depressão, e maior quantidade referida de medicamentos para uso contínuo. CONCLUSÕES: O estudo mostra que a prevalência de quedas entre idosos asilados é alta. Embora alguns dos possíveis fatores associados sejam passíveis de prevenção, ainda ocorrem quedas em locais que deveriam ser considerados seguros, como o quarto do idoso.<br>OBJETIVO: El aumento de la expectativa de vida en los países en desarrollo ha provocado preocupación con la calidad de vida y el bienestar de los ancianos, principalmente la ocurrencia de caídas. En ese sentido, el objetivo del estudio fue describir la prevalencia de caídas en ancianos que viven en asilos y factores asociados. MÉTODOS: Se realizó estudio de delineamiento transversal en la ciudad de Rio Grande (Sur de Brasil), en 2007. Participaron 180 individuos ancianos (65 años o mas) residentes en asilos para protección. En entrevista, los ancianos respondieron las preguntas de instrumento pre-evaluado sobre la ocurrencia de caídas. Además de un análisis bivariado (Wald), se realizó un análisis por regresión de Poisson con cálculo de razones de prevalencia e intervalos de confianza de 95% ajustada para las variables de confusión. RESULTADOS: La prevalencia de caídas entre los ancianos asilados estudiados fue de 38,3%. Las caídas fueron más comunes en el ambiente del asilo (62,3%), siendo el cuarto el ambiente donde ocurrió el mayor número de caídas (23,0%). En el análisis ajustado, las caídas se mantuvieron asociadas con el color blanco de la piel, con los ancianos separados y divorciados, con la depresión, y mayor cantidad referida de medicamentos para uso continuo. CONCLUSIONES: El estudio muestra que la prevalencia de caídas entre los ancianos asilados es alta. A pesar de que algunos de los posibles factores asociados sean pasibles de prevención, aún ocurren caídas en lugares que deberían ser considerados seguros, como el cuarto del anciano.<br>OBJECTIVE: The increase of life expectancy in developing countries has been a source of concern about quality of life and well-being of elderly people, especially regarding falls. The objective of the study was to assess the prevalence of falls in institutionalized elderly and to describe factors associated. METHODS: Cross-sectional study carried out in the city of Rio Grande (Southern Brazil). A total of 180 elderly (65 years old or more), living in institutions were included in the study. The elderly were interviewed and a pre-tested instrument with questions on falls was administered. In addition to a bivariate analysis (Wald), Poisson's regression analysis was conducted and prevalence ratios and 95% confidence intervals (95% CI) adjusted for confounders were estimated. RESULTS: The prevalence of falls among institutionalized elderly was 38.3%. Falls were most frequently seen at the home premises (62.3%) and mostly in the bedroom (23%). In the adjusted analysis, falls remained associated to white color skin, separated and divorced elderly, depression, and higher continuous use of medications. CONCLUSIONS: The study showed that the prevalence of falls among institutionalized elderly is high and that they can be disabling to this population. Although some of the associated factors are preventable, accidental falls still occur in settings that should be safe, such as the elderly's bedroom