Effect of a calcium-channel blocker (verapamil) on the morphology, cytoskeleton and collagenase activity of human skin fibroblasts

The effects of verapamil modulating collagen biosynthesis have prompted us to study the role of this drug in cultured fibroblasts. In this article, we describe the effects of verapamil on fibroblast behaviour, with special emphasis to phenotypic modifications, reorganisation of actin filaments and secretion of MMP1. Human dermal fibroblasts treated with 50-mu M verapamil changed their normal spindle-shaped morphology to stellate. Treated cells showed discrete reorganisation of actin filaments, as revealed by fluorescein isothiocyanate (FITC)-phalloidin staining and confocal microscopy. We hypothesised that these effects would be associated to lower levels of cytosolic Ca(2+). Indeed, short time loading with calcium green confirmed that verapamil-treated fibroblasts exhibited lower intracellular calcium levels compared to controls. We also observed that verapamil increases the secretion of MMP1 in cultured fibroblasts, as demonstrated by zymography, specific substrate assays and immunoblot. The morphological alterations induced by verapamil are neither cytotoxic nor associated with other dramatic cytoskeleton alterations. Thus we may conclude that this drug enhances collagenase secretion and does not disrupt the major tracks necessary to deliver these enzymes in the extracellular space. The present results suggested that verapamil could be used at physiological levels to enhance collagen I breakdown, and maybe considered a potential candidate for intralesional therapy of wound healing and fibrocontractive diseases. (C) 2010 Elsevier Ltd and ISBI. All rights reserved.

Kvinnors sexualitet och kroppsuppfattning efter gynekologisk cancer.

Inledning: Kvinnors sexualitet och kroppsuppfattning efter gynekologisk cancer förändras. Som barnmorskor är det viktigt att i tidigt skede medverka till och förebygga de komplikationer som dessa kvinnor drabbas av. Syfte: Syftet med studien var att göra en jämförande, detaljerad beskrivning av attraktion och sexuell lust hos kvinnor som blivit strålbehandlade mot gynekologisk cancer. Metod: En prospektiv kohortstudie med kvantitativ ansats med enkätformulär. Två kohorter har jämförts där 616 kvinnor behandlats för gynekologisk cancer samt 344 kvinnor som inte behandlats. Resultat: Kvinnorna upplever sig mindre attraktiva och att deras partner även tycker det. De hade mindre längtan efter sex och hade sex mer sällan. Flertalet talade inte med någon om sin brist på lust till sex eller om de sexuellt relaterade biverkningarna. De kände sig mindre upphetsade i en sexuell situation där tillfredsställelsen och avspänningen i samband med orgasm förändrats. Kvinnornas välbefinnande påverkades negativt och problem med avföring och gasläckage förekom. Slutsats: Upprepad information och återkoppling före, under och efter behandling mellan kvinnorna och patientansvarig barnmorska/läkare är nödvändigt. Kvinnornas upplevelse av att vara attraktiva, tankar på, längtan och lust efter sex samt ofrivillig gasavgång och avföringsträngningar är de viktigaste faktorerna att belysa för kvinnorna för att kunna förbereda och förebygga komplikationer efter gynekologisk cancer.

Renal transplantation in patients with primary immunoglobulin A nephropathy

Background. Opinions on the clinical course and outcome of renal transplantation in patients with primary immunoglobulin A nephropathy (IgAN) have been controversial.
Methods. We conducted a retrospective single-centre study on 542 kidney transplant recipients over the period 1984–2001. Long-term outcome and factors affecting recurrence in recipients with primary IgAN were analysed.
Results. Seventy-five patients (13.8%) had biopsy-proven IgAN as the cause of renal failure, and their mean duration of follow-up after transplantation was 100 ± 5.8 months. Fourteen (18.7%) of the 75 patients had biopsy-proven recurrent IgAN, diagnosed at 67.7 ± 11 months after transplantation. The risk of recurrence was not associated with HLA DR4 or B35. Graft failure occurred in five (35.7%) of the 14 patients: three due to IgAN and two due to chronic rejection. Three (4.9%) of the 61 patients without recurrent IgAN had graft failure, all due to chronic rejection. Graft survival was similar between living-related and cadaveric/living-unrelated patients (12-year graft survival, 88 and 72%, respectively, P = 0.616). Renal allograft survival within the first 12 years was better in patients with primary IgAN compared with those with other primary diseases (80 vs 51%, P = 0.001). Thereafter, IgAN patients showed an inferior graft survival (74 vs 97% in non-IgAN patients, P = 0.001).
Conclusions. Our data suggested that around one-fifth of patients with primary IgAN developed recurrence by 5 years after transplantation. Recurrent IgA nephropathy in allografts runs an indolent course with favourable outcome in the first 12 years. However, the contribution of recurrent disease to graft loss becomes more significant on long-term follow up.

Indigenous performing arts and the problem of judging 'excellence': A discussion paper

In this paper we look at the persistent debate over notions of access and excellence and intrinsic and instrumentalist rationales for arts practice within cultural policy discussion. Recent research into the Indigenous performing arts in Australia underlines the particular difficulties faced by the sector in balancing the demands of community participation, social inclusion and high-quality aesthetic outcomes. The balancing act has proven unsustainable for some Indigenous performing arts companies and their viability is now in doubt. This suggests that a re-consideration of the question of the purpose and value of the Indigenous performing arts is timely.

The population burden of fractures originates in women with osteopenia, not osteoporosis

Introduction : Osteoporosis is associated with increased risk for fracture. However, most postmenopausal women have bone mineral density (BMD) within the normal or osteopenic range. The aim of this study was to determine the proportion of the population burden of fragility fractures arising from women at modest risk for fracture.

Methods : We measured baseline BMD in a population-based random sample of 616 postmenopausal women aged 60–94 years and followed these individuals for a median of 5.6 years (IQR 3.9–6.5) to determine the incidence of fractures according to age, BMD and the presence of a prior fracture.

Results : Based on WHO criteria, 37.6% of the women had normal total hip BMD, 48.0% had osteopenia and 14.5% had osteoporosis. The incidence of fracture during follow-up was highest in women with osteoporosis, but only 26.9% of all fractures arose from this group; 73.1% occurred in women without osteoporosis (56.5% in women with osteopenia, 16.6% in women with normal BMD). Decreasing BMD, increasing age and prior fracture contributed independently to increased fracture risk; in a multivariate model, the relative risk for fracture increased 65% for each SD decrease in BMD (RR=1.65, 95%CI 1.32–2.05), increased 3% for every year of age (RR=1.03, 95%CI 1.01–1.06) and doubled with prevalent fracture (RR=2.01, 95% CI 1.40–2.88). A prevalent fracture increased the risk for fractures such that women with osteopenia and prevalent fracture had the same, if not greater, risk as women with osteoporosis alone.

Does moral cleansing moderate the effect of evolutionary altruism on helping intention? An exploratory study

There is strong evidence for social evolutionary motivations for helping (e.g., reciprocal altruism) and also growing support for the influence of the social cognitive theory of moral cleansing on prosociality. Where the former motivation is interpersonal, the latter is intrapersonal. This experimental study hypothesized that, in addition to main effects of evolutionary altruism and moral cleansing on helping intention, an interaction would occur between these theoretical motivations. Using three situational helping scenarios as dependent measures, the effect of participants’ morally-valenced recalled behavior (moral/immoral/achievement/failure) and the effect of their social proximity to a helping target (cousin/colleague/stranger) on helping intention was determined. Overall, 616 Australian participants (90.1% female) completed the online experiment. Two-way ANOVA demonstrated a consistent main effect of social proximity on helping intention across all three helping scenarios, supporting evolutionary social psychological explanations for helping. However, instead of moral self-regulation effects, moral identity consistency effects were induced by the moral behavior recall manipulation. A main effect of behaviour recall on helping intention occurred, with moral recall increasing helping intention. The problem of theoretical ambiguity regarding moral identity consistency and moral self-regulation is discussed, as is the useful role of null result publications in informing effective experimental design.

Review of 'Promoting Justice through Clinical Legal Education' by Jeff Giddings, Justice Press, 2013

Review of 'Promoting Justice through Clinical Legal Education' by Jeff Giddings, Justice Press, 2013, 448 pages

TMS stimulus-response asymmetry in left- and right handed individuals

There have been inconsistencies in the literature regarding asymmetrical neural control and results of experiments using TMS techniques. Therefore, the aim of this study was to further our understanding of the neural relationships that may underlie performance asymmetry with respect to the distal muscles of the hand using a TMS stimulus–response curve technique. Twenty-four male subjects (12 right handed, 12 left handed) participated in a TMS stimulus–response (S–R) curve trial. Focal TMS was applied over the motor cortex to find the optimal position for the first dorsal interossei muscle and to determine rest threshold (RTh). Seven TMS intensities ranging from 90 to 150 % of RTh were delivered in 10 % increments. One single TMS block consisted of 16 stimuli at each intensity. Peak-to-peak amplitudes were measured and the S–R curve generated. In right-handed subjects, the mean difference in slopes between the right and left hand was −0.011 ± 0.03, while the mean difference between hands in left-handed subjects was −0.049 ± 0.08. Left-handed normalized data in right handers displayed a mean of 1.616 ± 1.019 (two-tailed t test p < 0.05). The left-handed group showed a significant change in the normalized slope as indicated by a mean of 1.693 ± 0.149 (two-tailed t test p < 0.00006). The results found in this study reinforce previous work which suggests that there is an asymmetry in neural drive that exists in both left- and right-handed individuals. However, the results show that the non-dominant motor hemisphere displays a greater amount of excitability than the dominant, which goes against the conventional dogma. This asymmetry indicates that the non-dominant hemisphere may have a higher level of excitation or a lower level of inhibition for both groups of participants.

Economic evaluation of a group-based exercise program for falls prevention among the older community-dwelling population

BACKGROUND: Falls among older people are of growing concern globally. Implementing cost-effective strategies for their prevention is of utmost importance given the ageing population and associated potential for increased costs of fall-related injury over the next decades. The purpose of this study was to undertake a cost-utility analysis and secondary cost-effectiveness analysis from a healthcare system perspective, of a group-based exercise program compared to routine care for falls prevention in an older community-dwelling population.

METHODS: A decision analysis using a decision tree model was based on the results of a previously published randomised controlled trial with a community-dwelling population aged over 70. Measures of falls, fall-related injuries and resource use were directly obtained from trial data and supplemented by literature-based utility measures. A sub-group analysis was performed of women only. Cost estimates are reported in 2010 British Pound Sterling (GBP).

RESULTS: The ICER of GBP£51,483 per QALY for the base case analysis was well above the accepted cost-effectiveness threshold of GBP£20,000 to £30,000 per QALY, but in a sensitivity analysis with minimised program implementation the incremental cost reached GBP£25,678 per QALY. The ICER value at 95% confidence in the base case analysis was GBP£99,664 per QALY and GBP£50,549 per QALY in the lower cost analysis. Males had a 44% lower injury rate if they fell, compared to females resulting in a more favourable ICER for the women only analysis. For women only the ICER was GBP£22,986 per QALY in the base case and was below the cost-effectiveness threshold for all other variations of program implementation. The ICER value at 95% confidence was GBP£48,212 in the women only base case analysis and GBP£23,645 in the lower cost analysis. The base case incremental cost per fall averted was GBP£652 (GBP£616 for women only). A threshold analysis indicates that this exercise program cannot realistically break even.

CONCLUSIONS: The results suggest that this exercise program is cost-effective for women only. There is no evidence to support its cost-effectiveness in a group of mixed gender unless the costs of program implementation are minimal. Conservative assumptions may have underestimated the true cost-effectiveness of the program.

Alimentos e a responsabilidade civil da genitora em decorrência da negativa de paternidade

O presente trabalho teve como ponto de partida o estudo dos alimentos e da obrigação alimentar. Em seguida, realizou-se um breve estudo sobre o direito à filiação, o qual é assegurado pelo Código Civil de 2002 nos artigos 1.596 e seguintes; artigo 227, parágrafo 6º da Constituição Federal e algumas leis complementares, tais como o Estatuto da Criança e do Adolescente. Também foi abordado o tema da investigação de paternidade e seu ônus probatório, enfatizando a ação negatória de paternidade, a qual isenta o réu da obrigação alimentar. Por fim, um estudo sucinto da responsabilidade civil da genitora que, sabendo não ser o réu o pai do seu filho, ajuíza ação pleiteando alimentos, bem como o dano e sua relação com os alimentos pagos ao menor hipossuficiente.

First-price auction symmetric equilibria with a general distribution

In this paper I obtain the mixed strategy symmetric equilibria of the first-price auction for any distribution. The equilibrium is unique. The solution turns out to be a combination of absolutely continuous distributions case and the discrete distributions case.

Divisia indexes, money and welfare

We suggest the use of a particular Divisia index for measuring welfare losses due to interest rate wedges and in‡ation. Compared to the existing options in the literature: i) when the demands for the monetary assets are known, closed-form solutions for the welfare measures can be obtained at a relatively lower algebraic cost; ii) less demanding integrability conditions allow for the recovery of welfare measures from a larger class of demand systems and; iii) when the demand speci…cations are not known, using an index number entitles the researcher to rank di¤erent vectors of opportunity costs directly from market observations. We use two examples to illustrate the method.

Escala de coping religioso-espiritual (escala CRE) : tradução, adaptação e validação da escala rcope, abordando relações com saúde e qualidade de vida

OBJETIVOS: A importância do coping religioso espiritual (CRE) nas áreas da saúde e qualidade de vida (QV), e a falta de instrumentos brasileiros para avalia-lo são apontadas pela literatura científica. Este estudo objetivou realizar a versão brasileira da RCOPE Scale, gerando a Escala de Coping Religioso Espiritual (Escala CRE), e examinar a relação entre CRE, saúde e QV. MÉTODO: A primeira fase deste estudo compreendeu: tradução por especialistas da RCOPE, adaptação à cultura brasileira, teste piloto com 50 estudantes de nível médio e superior. A segunda abrangeu teste de campo e processo de validação. Os 616 participantes [65% mulheres, 13-DQRV p=18,44)], foram acessados em um dos seguintes locais que freqüentavam: instituições religiosas ou grupos espirituais (74,4%), universidades (13,5%), clínicas para tratamento de saúde (9,1%) e Web Mail (2,9%). Eles completaram vários instrumentos: Consentimento Livre/Esclarecido, Questionário Geral (questões demográficas, socioeconômicas, religiosas, de saúde), Escala CRE, Escala de Atitude Religiosa e WHOQOL-bref. RESULTADOS: Análises fatoriais geraram uma Escala CRE com duas dimensões: CRE Positivo (CREP) (8 fatores, 66 itens) e CRE Negativo (CREN) (4 fatores, 21 itens). Foram criados quatro índices principais para avaliar os respondentes: as médias CREP e CREN, os escores de CRE TOTAL e Razão CREN/CREP. A Escala CRE demonstrou validade de construto, critério, conteúdo e bons níveis de fidedignidade. Testes Qui-quadrado para Classificação Subjetiva de Saúde (7categorias) mostraram problemas de saúde (PS) físicos relacionados a altos escores de CRE TOTAL e baixos de Razão CREN/CREP; PS emocionais, acrescidos ou não de PS físicos, mostraram resultado inverso. Ainda, QV e CRE TOTAL estiveram positiva e significativamente correlacionados. O CREN esteve negativamente correlacionado à QV em grau maior do que o CREP esteve positivamente correlacionado com QV. Usando Testes t de Student, aqueles que tiveram altos escores de CRE TOTAL mostraram maiores níveis de QV em todos os domínios do WHOQOL-bref, além de maior Classificação Objetiva de Saúde (Likert 5-pontos). Ademais, aqueles que tiveram altos níveis de QV demonstraram maior uso de CREP e menor de CREN. CONCLUSÕES: A Escala CRE é válida e fidedigna, permite aplicação clínica e em pesquisas em locais para tratamento de saúde públicos ou privados. PS físicos podem ser motivadores e educadores do uso do CRE. PS emocionais podem dificultar um melhor uso do CRE, sugerindo que intervenções psicológicas poderiam facilitar o processo. Além disso, CRE e QV são construtos correlacionados. Uma proporção mínima de 2CREP:1CREN (Razão CREN/CREP menor/igual 0,5) foi proposta para se obter um efeito benéfico geral do CRE na QV. Evidências sugerem que intervenções focadas no processo de CRE poderiam ser benéficas e efetivas para agentes de saúde pública pelo seu potencial de reduzir custos de intervenções e pelo seu impacto significante na saúde e QV da população. Os próximos passos seriam: utilização de metodologias experimentais longitudinais para melhor avaliar os efeitos do CRE na saúde e na QV, elaboração de uma Escala CRE Abreviada, investigação aprofundada da influência da variável idade na relação CRE-Saúde e testes de proporção e causais, para verificar a direção da correlação, entre CRE e QV.