The A-kinase anchoring protein (AKAP)-Lbc-signaling complex mediates alpha1 adrenergic receptor-induced cardiomyocyte hypertrophy.

In response to various pathological stresses, the heart undergoes a pathological remodeling process that is associated with cardiomyocyte hypertrophy. Because cardiac hypertrophy can progress to heart failure, a major cause of lethality worldwide, the intracellular signaling pathways that control cardiomyocyte growth have been the subject of intensive investigation. It has been known for more than a decade that the small molecular weight GTPase RhoA is involved in the signaling pathways leading to cardiomyocyte hypertrophy. Although some of the hypertrophic pathways activated by RhoA have now been identified, the identity of the exchange factors that modulate its activity in cardiomyocytes is currently unknown. In this study, we show that AKAP-Lbc, an A-kinase anchoring protein (AKAP) with an intrinsic Rho-specific guanine nucleotide exchange factor activity, is critical for activating RhoA and transducing hypertrophic signals downstream of alpha1-adrenergic receptors (ARs). In particular, our results indicate that suppression of AKAP-Lbc expression by infecting rat neonatal ventricular cardiomyocytes with lentiviruses encoding AKAP-Lbc-specific short hairpin RNAs strongly reduces both alpha1-AR-mediated RhoA activation and hypertrophic responses. Interestingly, alpha1-ARs promote AKAP-Lbc activation via a pathway that requires the alpha subunit of the heterotrimeric G protein G12. These findings identify AKAP-Lbc as the first Rho-guanine nucleotide exchange factor (GEF) involved in the signaling pathways leading to cardiomyocytes hypertrophy.

Idosos com alteração cognitiva em contexto de pobreza: estudando a rede de apoio social

O objetivo deste trabalho foi analisar a estrutura e função das redes de apoio social de idosos com alterações cognitivas, residentes em contexto de alta e muito alta vulnerabilidade social, além de identificar associações entre as características das redes e a capacidade funcional. Os sujeitos estudados foram 38 idosos, residentes em contexto de alta e muito alta vulnerabilidade social, que apresentaram resultado no Mini Exame do Estado Mental abaixo da nota de corte. Todos os cuidados éticos foram observados. Aplicaram-se o Mini Exame do Estado Mental, o Diagrama de Escolta, o Índice de Katz e o Questionário de Pfeffer. Os resultados demonstraram que os idosos avaliados possuem rede social grande, com predomínio de integrantes no círculo interno, porém poucos integrantes desempenham papéis funcionais. Observou-se correlação entre a variável sexo e o número de integrantes das redes sociais. Não foi observada correlação significativa entre as características das redes e a capacidade funcional dos idosos.

Derivats financers al mercat espanyol: el Model de Black-Scholes i corbes de volatilitat per opcions sobre l'índex niniIBEX-35

El nostre treball es centrarà en conèixer i aprendre les nocions bàsiques del mercat financer espanyol, primer; i aplicar uns coneixements per veure si es verifica unahipòtesi plantejada, després. La incògnita que volem resoldre és la següent: comprovarsi tots els supòsits i resultats que faciliten els models teòrics emprats en l’estudi dels mercats financers a l’hora de la veritat es compleixen.D’entre els múltiples conceptes que ens proporcionen els estudis de mercatsfinancers ens centrarem sobretot en el model de Black-Scholes i els somriures devolatilitat per desenvolupar el nostre treball. Després de cercar les dades necessàries a través de la web del M.E.F.F., entrevistar-nos amb professionals del sector i fer un seguiment d’aproximadament dos mesos dels moviments de les opcions sobre l’Índex Mini-Íbex 35, amb l’ajuda d’un programa informàtic en llenguatge C, hem calculat les corbes de volatilitat de les opcions sobre l’Índex Mini-Íbex 35.Les conclusions més importants que hem extret són que el Model de Black-Scholes, malgrat va revolucionar el món dels mercats financers, està basat en 2 supòsits que no es compleixen a la realitat: la distribució lognormal del preu de les accions i unavolatilitat constant. Tal i com hem pogut comprovar, la corba de volatilitat de lesopcions sobre l’Índex Mini-Íbex 35 és decreixent amb el preu d’exercici i laMoneyness, tal i com sostenen les teories dels somriures de volatilitat; per tant, no és constant. A més, hem comprovat que a mesura que s’apropa el venciment d’una opció,el preu acordat de l’actiu subjacent a l’opció s’apropa al preu de mercat.

Sobrecarga dos cuidadores de idosos com acidente vascular cerebral

O objetivo deste estudo foi avaliar a sobrecarga dos cuidadores de idosos com acidente vascular cerebral (AVC), assim como correlacioná-la com as horas de cuidado, a idade e a independência funcional dos idosos. Trata-se de estudo transversal feito com 62 idosos com AVC e seus cuidadores. O instrumento continha variáveis sociodemográficas e econômicas, Mini-Exame do Estado Mental, Medida da Independência Funcional (MIF) e a Escala de Zarit. A possível correlação entre os escores da escala de Zarit e as outras variáveis foi avaliada por meio do Coeficiente de Correlação de Pearson. A maioria dos cuidadores era adultos, filhos, casados e do sexo feminino. A média do escore de Zarit foi 34,92 (15,8). A MIF apresentou correlação negativa com a sobrecarga do cuidador, porém, não houve correlação com a idade e as horas de cuidado. A sobrecarga da maioria dos cuidadores variou de moderada a severa e parece estar relacionada ao nível de independência funcional dos idosos.

SMP-paalu

Tämä insinöörityö on suomenkielinen työ Skanska Mini Pilestä ja laadittiin Skanska Tekra Oy:n toimeksiannosta. Skanska Tekra Oy oli tuomassa Suomeen uutta paalutusmenetelmää, eikä tämän pohjaksi ollut olemassa yhtenäistä koottua suomenkielistä teosta paalutusmenetelmästä. Tästä syystä yhtenäisen selvityksen laatiminen taustatiedoksi osoittautui tarpeelliseksi. Työn tarkoituksena oli koota tietoa Skanska Mini Pilesta sekä selvittää sen etuja ja haittoja muihin paalutusmenetelmiin nähden. Työssä selvitettiin lähinnä puupaaluperustusten saneerauksessa käytettäviä paalutusmenetelmiä. Esimerkkikohteen avulla verrattiin Skanska Mini Pilea muihin paalutusmenetelmiin. Työn avulla pyrittiin selvittämään, paalutusmenetelmän etuja ja haittoja sekä kirjoittamaan ensimmäinen suomenkielinen selvitys paalutusmenetelmästä. Tulevaisuudessa Skanska Mini Pilen toivotaan olevan varteenotettava paalutusmenetelmä Suomessa ja että sillä pystyttäisiin saamaan lisää uusia paalutuskohteita. Tämä työ kokonaisuudessaan toimii pohjana Skanska Mini Pilen tunnettavuuden tekijänä Suomessa. Selvityksen toivotaan auttavan paalutusmenetelmän tunnettavuuden edistäjänä Suomessa ja näin ollen edesauttaen uusien kohteiden saamisessa.

Associação entre sintomas de insônia e artrite reumatóide em idosos

Esse estudo objetivou avaliar sintomas de insônia em idosos residentes na comunidade e sua associação com a artrite reumatóide. Estudo descritivo, de corte transversal, recorte do projeto multicêntrico Fragilidade em Idosos Brasileiros . Foram avaliados 689 idosos (68,9% mulheres, média de idade 72,2 anos) utilizando-se questionário sociodemográfico e sobre condições clínicas, questões sobre sintomas de insônia (Perfil de Saúde de Nottingham) e teste de rastreio para alterações cognitivas (Mini-exame do Estado Mental). Utilizou-se análise descritiva e análise de regressão logística múltipla, com nível de significância de 5%. A associação entre sintomas de insônia e artrite reumatóide manteve-se significativa na análise multivariada; outros fatores associados foram avaliação subjetiva da saúde muito ruim, não ser aposentado e apresentar depressão. Os profissionais da área da saúde devem investigar cuidadosamente a qualidade do sono noturno dos idosos acometidos por artrite reumatóide, dada sua elevada prevalência nessa população.

Feasibility of transapical aortic valve replacement through a left ventricular apical diverticulum.

ABSTRACT: Transapical aortic valve replacement is an established technique performed in high-risk patients with symptomatic aortic valve stenosis and vascular disease contraindicating trans-vascular and trans-aortic procedures. The presence of a left ventricular apical diverticulum is a rare event and the treatment depends on dimensions and estimated risk of embolisation, rupture, or onset of ventricular arrhythmias. The diagnosis is based on standard cardiac imaging and symptoms are very rare. In this case report we illustrate our experience with a 81 years old female patient suffering from symptomatic aortic valve stenosis, respiratory disease, chronic renal failure and severe peripheral vascular disease (logistic euroscore: 42%), who successfully underwent a transapical 23 mm balloon-expandable stent-valve implantation through an apical diverticulum of the left ventricle. Intra-luminal thrombi were absent and during the same procedure were able to treat the valve disease and to successfully exclude the apical diverticulum without complications and through a mini thoracotomy. To the best of our knowledge, this is the first time that a transapical procedure is successfully performed through an apical diverticulum.

Pain intensity among institutionalized elderly: a comparison between numerical scales and verbal descriptors

AbstractOBJECTIVECorrelating two unidimensional scales for measurement of self-reported pain intensity for elderly and identifying a preference for one of the scales.METHODA study conducted with 101 elderly people living in Nursing Home who reported any pain and reached ( 13 the scores on the Mini-Mental State Examination. A Numeric Rating Scale - (NRS) of 11 points and a Verbal Descriptor Scale (VDS) of five points were compared in three evaluations: overall, at rest and during movement.RESULTSWomen were more representative (61.4%) and the average age was 77.0±9.1 years. NRS was completed by 94.8% of the elderly while VDS by 100%. The association between the mean scores of NRS with the categories of VDS was significant, indicating convergent validity and a similar metric between the scales.CONCLUSIONPain measurements among institutionalized elderly can be made by NRS and VDS; however, the preferred scale for the elderly was the VDS, regardless of gender.

Enhanced generation of specific tumor-reactive CTL in vitro by selected Melan-A/MART-1 immunodominant peptide analogues.

The Melan-A/MART-1 gene, which is expressed by normal melanocytes as well as by most fresh melanoma samples and melanoma cell lines, codes for Ags recognized by tumor-reactive CTL. HLA-A*0201-restricted Melan-A-specific CTL recognize primarily the Melan-A(27-35) (AAGIGILTV) and the Melan-A(26-35) (EAAGIGILTV) peptides. The sequences of these two peptides are not necessarily optimal as far as binding to HLA-A*0201 is concerned, since both lack one of the dominant anchor amino acid residues (leucine or methionine) at position 2. In this study we introduced single amino acid substitutions in either one of the two natural peptide sequences with the aim of improving peptide binding to HLA-A*0201 and/or recognition by specific CTL. Surprisingly, analogues of the Melan-A(27-35) peptide, which bound more efficiently than the natural nonapeptide to HLA-A*0201, were poorly recognized by tumor-reactive CTL. In contrast, among the Melan-A(26-35) peptide analogues tested, the peptide ELAGIGILTV was not only able to display stable binding to HLA-A2.1 but was also recognized more efficiently than the natural peptide by two short-term cultured tumor-infiltrated lymph node cell cultures as well as by five of five tumor-reactive CTL clones. Moreover, in vitro generation of tumor-reactive CTL by stimulation of PBMC from HLA-A*0201 melanoma patients with this particular peptide analogue was much more efficient than that observed with either one of the two natural peptides. These results suggest that the Melan-A(26-35) peptide analogue ELAGIGILTV may be more immunogenic than the natural peptides in HLA-A*0201 melanoma patients and should thus be considered as a candidate for future peptide-based vaccine trials.

GESTÃO E AVALIAÇÃODE DESEMPENHO NA SHELL CABO VERDE, SARL

Cabo Verde foi alcandorado a PDM recentemente o que traz novos e grandes desafios para o seu processo de desenvolvimento. O país que tem as suas vulnerabilidades decorrentes do seu frágil tecido produtivo e da sua reduzida dimensão, para além da escassez de recursos naturais, enfrenta ainda o desafio da insularidade. Assim terá que ancorar-se em primeiro lugar nos seus recursos humanos, para enfrentar esses desafios. A questão da gestão de desempenho e recompensa começa a emergir-se no sector empresarial quer privado quer estatal, como um processo fundamental para se alcançar a excelência operacional, fundamental para enfrentar a competição nos dias de hoje. O presente estudo focou o sistema de avaliação de desempenho na Shell Cabo Verde uma filial do Grupo Shell, que é uma multinacional com uma história rica e com forte experiência no mercado Global. Procurou-se, através de um estudo de caso, fazer o levantamento e o enquadramento teórico do sistema e analisar até que ponto o mesmo tem potenciado a melhoria do desempenho organizacional através do alinhamento dos objectivos individuais e da organização. Cape Verde has recently been upgraded to a Medium Development Country condition which brings along new great challenges to its development process. The country has already its vulnerabilities due to its week productive tissue and its small dimension and beyond the lack of natural resources it has to deal with the challenge of insularity. Thus it has to anchor itself firstly in its human resources to face the challenges. The performance and reward management starts to emerge in both private’s and State’s entrepreneur sector, as a fundamental process to achieve the operational excellence in order to face the competitiveness now-a-days. This study focused the performance evaluation used in Shell Cape Verde, a company that belongs to the multinational Shell with a rich global market experience. We tried, through a case study, to understand the theoric contents of the system and analyze at what point it has enhanced the improvement of the organizational performance through the alignment of individual objectives and organizational objectives.

Drug use and suicide attempts: the role of personality factors.

This study on suicide attempts is part of a large research project on dependent behavior in adolescents and young adults. 228 subjects aged 14-25 (107 "drug abusers," 121 controls) from the French speaking part of Switzerland were evaluated on the basis of a semi-structured interview (Mini International Neuropsychiatric Interview), enabling a DSM-IV diagnosis, and self-reports (SSS by Zuckermann, MMPI-2, IDI by Hirschfeld). 31.5% of "drug abuser" males and 41.2% of "drug abuser" females committed one or more suicide attempts. The results of a logistic regression show that the significant factor explaining suicide attempts in drug users is emotional reliance for males and experience-seeking for females.

Résistances thérapeutiques dans les mouvements anormaux [Resistance to treatment in movement disorders].

Therapeutic strategies for essential tremor (ET) and Parkinson's disease (PD) can be divided into two successive steps, one based on oral medications and the other, more invasive, using pumps or functional neurosurgery. When ET becomes refractory to propranolol, primidone and other, second-choice compounds, deep brain stimulation of the VIM nucleus of the thalamus can be considered. When PD becomes resistant to dopamine replacement therapy using various combinations of dopaminergic agents, then three options can be discussed: first, a subcutaneous apomorphine mini-pump, second, a jejunal levodopa-delivery system by means of percutaneous gastrostomy, and third, bilateral deep brain stimulation of the subthalamic nucleus. The above interventions are successful in about 80% of cases.

Monetary policy in the Euro area: Lessons from 5 years of ECB and implications for Turkey

We examine monetary policy in the Euro area from both theoretical and empirical perspectives. We discuss what theory tells us the strategy of Central banks should be and contrasts it with the one employed by the ECB. We review accomplishments (and failures) of monetary policy in the Euro area and suggest changes that would increase the correlation between words and actions; streamline the understanding that markets have of the policy process; and anchor expectation formation more strongly. We examine the transmission of monetary policy shocks in the Euro area and in some potential member countries and try to infer the likely effects occurring when Turkey joins the EU first and the Euro area later. Much of the analysis here warns against having too high expectations of the economic gains that membership to the EU and Euro club will produce.

Variedades de Mandioca Tolerantes ao Vírus do Mosaico Africano

Até 1988 a produção de mandioca era baseada em variedades locais cultivadas essencialmente em regime de sequeiro nas zonas húmidas e sub húmidas . Nos finais de 1988, surge a doença causada pelo “Vírus do Mosaico Africano” (ACMV) na Ilha de Santiago, comprometendo 30-85% do cultivo da mandioca. O aumento da incidência do vírus e as fracas precipitações ocorridas ao longo dos anos 90 levam a um recuo na produção e à substituição duma parte de mandioca no sequeiro pela batata-doce e/ou a sua transferência para o regadio. Perante este cenário o INIA (atual INIDA) inicia um programa de introdução de variedades a partir de instituições internacionais. Entre 1989 e 1999 , com a colaboração de projetos da FAO “Multiplicação rápida de batata-doce e mandioca “ e “Desenvolvimento de setor hortícola”, foram introduzidas do Brasil e do IITA - Nigéria várias coleções de acessos a partir de material in vitro , sementes botânicas e mini estacas. O programa tem por objetivo identificar clones com alto potencial de rendimento, tolerantes ao ACMV, maturidade precoce, ampla adaptabilidade e boas qualidades culinárias. Uma vez identificados, estes são liberados aos agricultores.

Identification of an agrin mutation that causes congenital myasthenia and affects synapse function.

We report the case of a congenital myasthenic syndrome due to a mutation in AGRN, the gene encoding agrin, an extracellular matrix molecule released by the nerve and critical for formation of the neuromuscular junction. Gene analysis identified a homozygous missense mutation, c.5125G>C, leading to the p.Gly1709Arg variant. The muscle-biopsy specimen showed a major disorganization of the neuromuscular junction, including changes in the nerve-terminal cytoskeleton and fragmentation of the synaptic gutters. Experiments performed in nonmuscle cells or in cultured C2C12 myotubes and using recombinant mini-agrin for the mutated and the wild-type forms showed that the mutated form did not impair the activation of MuSK or change the total number of induced acetylcholine receptor aggregates. A solid-phase assay using the dystrophin glycoprotein complex showed that the mutation did not affect the binding of agrin to alpha-dystroglycan. Injection of wild-type or mutated agrin into rat soleus muscle induced the formation of nonsynaptic acetylcholine receptor clusters, but the mutant protein specifically destabilized the endogenous neuromuscular junctions. Importantly, the changes observed in rat muscle injected with mutant agrin recapitulated the pre- and post-synaptic modifications observed in the patient. These results indicate that the mutation does not interfere with the ability of agrin to induce postsynaptic structures but that it dramatically perturbs the maintenance of the neuromuscular junction.