STOPP/START criteria for potentially inappropriate prescribing in older people: version 2

PURPOSE: screening tool of older people's prescriptions (STOPP) and screening tool to alert to right treatment (START) criteria were first published in 2008. Due to an expanding therapeutics evidence base, updating of the criteria was required.

METHODS: we reviewed the 2008 STOPP/START criteria to add new evidence-based criteria and remove any obsolete criteria. A thorough literature review was performed to reassess the evidence base of the 2008 criteria and the proposed new criteria. Nineteen experts from 13 European countries reviewed a new draft of STOPP & START criteria including proposed new criteria. These experts were also asked to propose additional criteria they considered important to include in the revised STOPP & START criteria and to highlight any criteria from the 2008 list they considered less important or lacking an evidence base. The revised list of criteria was then validated using the Delphi consensus methodology.

RESULTS: the expert panel agreed a final list of 114 criteria after two Delphi validation rounds, i.e. 80 STOPP criteria and 34 START criteria. This represents an overall 31% increase in STOPP/START criteria compared with version 1. Several new STOPP categories were created in version 2, namely antiplatelet/anticoagulant drugs, drugs affecting, or affected by, renal function and drugs that increase anticholinergic burden; new START categories include urogenital system drugs, analgesics and vaccines.

CONCLUSION: STOPP/START version 2 criteria have been expanded and updated for the purpose of minimizing inappropriate prescribing in older people. These criteria are based on an up-to-date literature review and consensus validation among a European panel of experts.

Defining the role of common variation in the genomic and biological architecture of adult human height

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated 1/42,000, 1/43,700 and 1/49,500 SNPs explained 1/421%, 1/424% and 1/429% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/I 2-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Manganese Superoxide Dismutase Is a Promising Target for Enhancing Chemosensitivity of Basal-Like Breast Carcinoma

AIMS: Although earlier reports highlighted a tumor suppressor role for manganese superoxide dismutase (MnSOD), recent evidence indicates increased expression in a variety of human cancers including aggressive breast carcinoma. In the present article, we hypothesized that MnSOD expression is significantly amplified in the aggressive breast carcinoma basal subtype, and targeting MnSOD could be an attractive strategy for enhancing chemosensitivity of this highly aggressive breast cancer subtype.

RESULTS: Using MDA-MB-231 and BT549 as a model of basal breast cancer cell lines, we show that knockdown of MnSOD decreased the colony-forming ability and sensitized the cells to drug-induced cell death, while drug resistance was associated with increased MnSOD expression. In an attempt to develop a clinically relevant approach to down-regulate MnSOD expression in patients with basal breast carcinoma, we employed activation of the peroxisome proliferator-activated receptor gamma (PPARγ) to repress MnSOD expression; PPARγ activation significantly reduced MnSOD expression, increased chemosensitivity, and inhibited tumor growth. Moreover, as a proof of concept for the clinical use of PPARγ agonists to decrease MnSOD expression, biopsies derived from breast cancer patients who had received synthetic PPARγ ligands as anti-diabetic therapy had significantly reduced MnSOD expression. Finally, we provide evidence to implicate peroxynitrite as the mechanism involved in the increased sensitivity to chemotherapy induced by MnSOD repression.

INNOVATION AND CONCLUSION: These data provide evidence to link increased MnSOD expression with the aggressive basal breast cancer, and underscore the judicious use of PPARγ ligands for specifically down-regulating MnSOD to increase the chemosensitivity of this subtype of breast carcinoma.

Depicting Characters and danced Narratives: Handel, 'The Italian troupe', and Marie Sallé

Handel’s London career afforded opportunities for responding to dancers working in distinct styles of movement—most notably the Italian troupe resident at the King’s Theatre in 1726-27, and Marie Sallé at Covent Garden in 1734-35. By studying the dances from Admeto (1727) and Ariodante (1735), this paper will explore Handel's response to the serious and grotesque styles, as well as to the character and narrative modes.

Exercise training protects the LDLI subfraction from oxidation susceptibility in an aged human population

Background Exercise training is considered an effective strategy to improve metabolic disease. Despite this, less is known regarding exercise training in the prevention and susceptibility of LDL subfraction oxidation, particularly in an aged population. 
Methods Eleven aged (55 ± 4 yrs) and twelve young (21 ± 2 yrs) participants were randomly separated into an experimental or control group as follows: young exercise (n = 6); young control (n = 6); aged exercise (n = 6) and aged control (n = 5). The participants assigned to the exercise groups performed 12 weeks of moderate intensity (55–65% VO2max) exercise training. Venous blood was extracted at baseline, and 48 h following 12 weeks of exercise and assayed for a range of metabolites associated with lipid composition and lipoprotein susceptibility to oxidation. 
Results Although there was no difference in the oxidation potential (time ½ max) of LDL I, II or III between groups at baseline (p > 0.05), there was an increase in time ½ max for LDL I following exercise within the aged exercise group (p < 0.05). Moreover, α-tocopherol concentration was selectively lower in the aged exercise group, compared to the young exercise at baseline. The lipid composition of LDL I, LDL II, LDL III, VLDL, HDL2, HDL3 and serum lipid hydroperoxides remained unchanged as a function of exercise training and ageing (p > 0.05). 
Conclusion The primary finding of this study demonstrates that adaptations in LDL resistance to oxidation occur following 12 weeks of exercise training in the aged, and this may be of clinical significance, as oxidation of LDL has been implicated in atherosclerosis.

A relação terapêutica como pacto de cuidados (Perspectiva de Paul Ricoeur)

O capítulo é dedicado à reflexão, partindo de Ricoeur, sobre alguns aspectos que podem fornecer alicerce à tematização dos problemas do cuidar da Pessoa em vários níveis da Enfermagem. Importa-nos, acima de tudo, que, na procura da racionalidade própria da vida humana, as questões éticas da decisão do agir não fiquem soterradas por normas ou preceitos deontológicos adoptados acrítica e mecanicamente. Julgamos, então, necessário um esforço reflexivo práxico, pois sem reflexão orientada para a acção sairá malogrado o ideal de cuidar, que é, ao mesmo tempo, ideal de compreender, de respeitar e de servir responsavelmente o Outro, através do cultivo de relações interpessoais competentes, em termos científicos, técnicos e éticos.

Análise custo benefício de gestões alternativas do paúl de Lagos pelo método dos preços hedónicos/contigenciais com recursos a análise ANOVA sic: valorização do paul de Lagos

Dissertação mest., Gestão e Conservação da Natureza, Universidade do Algarve, 2009

Configurações músico-literárias na obra de Paul Bowles : música, violência e política

Tese de doutoramento, Estudos de Literatura e de Cultura (Estudos Americanos), Universidade de Lisboa, Faculdade de Letras, 2014

A Tradução reinventada em The Invention of Solitude de Paul Auster

A leitura da obra de Paul Auster, desde os primeiros poemas e ensaios até à mais recente ficção, revela uma constante reflexão metalinguística e metaficcional sobre o trabalho da escrita. Auster equaciona o problema da escrita enquanto acto, permitindo ao leitor acompanhar e participar desse processo de construção. A narrativa e a linguagem intelectualizam-se, tornam-se conscientes, o que possibilita uma aproximação privilegiada ao ensino da tradução de textos literários através da própria literatura. The Invention of Solitude é como uma arte poética inspirada na experiência efectiva do sujeito, enquanto escritor e tradutor. Podemos considerá-lo um romance-manifesto em duas partes (Portrait of an Invisible Man e The Book of Memory), com especial incidência na exploração analítica da cena da escrita, utilizando a personagem-escritor e suas vivências como cobaia neste processo de auto e heteroconhecimento. A partir da análise aplicada de The Invention of Solitude, este artigo irá remeter também para os ensaios de Ernest Gellner sobre Wittgenstein em Language and Solitude, entre outros escritores que se debruçaram igualmente sobre questões ligadas à tradução literária, como Dryden, Goethe, Nietzsche, Benjamin, Ortega y Gasset e Octávio Paz.