PlGF-1 and VEGFR-1 pathway regulation of the external epithelial hemato-ocular barrier. A model for retinal edema.

VEGF is considered as an important factor in the pathogenesis of macular edema. VEGF induces the rupture of the blood retinal barrier and may also influence the retinal pigment epithelial (RPE) outer retinal barrier. The aim of this work was to analyze the influence of the VEGF receptor pathways in the modulation of the RPE barrier breakdown in vitro and in vivo. The ARPE19 human junctions in culture are modulated by VEGF through VEGFR-1 but not through VEGFR-2. PlGF-1, that is a pure agonist of VEGFR-1, is produced in ARPE-19 cells under hypoxic conditions and mimics VEGF effects on the external retinal barrier as measured by TER and inulin flux. In vivo, the intravitreous injection of PlGF-1 induces a rupture of the external retinal barrier together with a retinal edema. This effect is reversible within 4 days. VEGF-E, that is a pure agonist of VEGFR-2, does not induce any acute effect on the RPE barrier. These results demonstrate that PlGF-1 can reproduce alterations of the RPE barrier occurring during diabetic retinopathy.

Altered expression of the transcription factor Mef2c during retinal degeneration in Rpe65-/- mice.

Purpose. To investigate the role of the myocyte enhancer factor 2 (Mef2) transcription factor family in retinal diseases, Mef2c expression was assessed during retinal degeneration in the Rpe65(-/-) mouse model of Leber's congenital amaurosis (LCA). Mef2c-dependent expression of photoreceptor-specific genes was further addressed. Methods. Expression of Mef2 members was analyzed by oligonucleotide microarray, quantitative PCR (qPCR) and in situ hybridization. Mef2c-dependent transcriptional activity was assayed by luciferase assay in HEK293T cells. Results. Mef2c was the only Mef2 member markedly downregulated during retinal degeneration in Rpe65(-/-) mice. Mef2c mRNA level was decreased by more than 2 fold at 2 and 4 months and by 3.5 fold at 6 months in retinas of Rpe65(-/-) mice. Downregulation of Mef2c at the protein level was confirmed in Rpe65(-/-) retinas. The decrease in Mef2c mRNA levels in the developing Rpe65(-/-) retinas, from post-natal day (P)13 onward, was concomitant with the decreased expression of the rod-specific transcription factors Nrl and Nr2e3. Nrl was further shown to drive Mef2c transcriptional activity, supporting a physiological role for Mef2c in the retina. In addition, Mef2c appeared to act as a transcriptional repressor of its own expression, as well as those of the retina-specific retinal G-protein coupled receptor (Rgr), rhodopsin and M-opsin genes. Conclusions. These findings highlight the early altered regulation of the rod-specific transcriptional network in Rpe65-related disease. They further indicate that Mef2c may act as a novel transcription factor involved in the development and the maintenance of photoreceptor cells.

Establishment of a reliable laser-Induced Choroidal Neovascularization Animal Model

Purpose: Pathologic choroidal neovascularizations (CNV) are implicated in the wet form of age-related macular degeneration (ARMD). Abnormal vessel growth is also observed in disease when hypoxia and/or inflammation occur. Our goal is to establish a standard protocol of laser-induced CNV in mice that have different levels of pigmentation to identify the most reliable animal model.Methods: CNV was induced by 4 burns around the optic disk, using a green argon laser (100μm diameter spot size; 0,05 sec. duration) in C57/Bl6, DBA/1 and Balb/c to ascertain the efficacy of the method in function of retina pigmentation. Five different intensities were tested and Bruch's membrane disruption was identified by the appearance of a bubble at the site of photocoagulation. Fluorescein angiographies (FA) were undertaken 14 days post lesion and CNV area was quantified by immunohistochemistry on cryosections.Results: CNV retina area was related to spot intensity after laser injury. While 180mW and 200mW do not induce reliable CNV (respectively 27.85±0.35% and 29±1.67% of the retina surface), 260mW is required to induce 51,07±8.52% of CNV in C57/Bl6 mice. For the DBA/1 strain, less pigmented, 200mW was sufficient to induce 49.35±3.9% of CNV, indicating that lower intensity are required to induce CNV. Furthermore, an intensity of 180mW induced greater CNV (35.55±6.01%) than in C57/Bl6 mice. Nevertheless, laser did not induce reproducible 50% CNV in Balb/c albino mice for all intensities tested. Isolectin-B4 and GFAP stainings revealed neovessel formation and photoreceptor (PR) degeneration at the impact site. The presence of glia was observed throughout all the retinal layers and angiograms showed fluorescein leakage in pigmented mice.Conclusions: The establishment of a standard protocol to induce CNV and subsequent PR degeneration is of prime importance for the use of the laser-induced CNV model and will allow to evaluate the therapeutic potency of agents to prevent CNV and retinal degeneration.

The use of the quality model of Parasuraman, Zeithaml and Berry in health services

This is an article about the theoretical model for assessing quality in health services proposed by Parasuraman, Zheitaml and Berry, in order to measure the degree of satisfaction of users. This model is based on the analysis of expectations and perceptions of users of health services, by means of five dimensions: tangibility, reliability, responsiveness, assurance and empathy. From the difference between what is expected by the user and the service offered, gaps or shortcomings are derived that may be the main obstacle for users to perceive the provision of such services with quality. It was observed that the use of the psychometric scale called Service Quality (SERVQUAL) in some studies about satisfaction, obtained very favorable results in the institutions in which it was employed. The analysis revealed the need to improve the existing models of evaluation, as well as the importance of measuring user satisfaction in health institutions.

Effects of rat anti-VEGF antibody in a rat model of corneal graft rejection by topical and subconjunctival routes.

PURPOSE: To compare the effect of a rat anti-VEGF antibody, administered either by topical or subconjunctival (SC) routes, on a rat model of corneal transplant rejection.METHODS: Twenty-four rats underwent corneal transplantation and were randomized into four treatment groups (n=6 in each group). G1 and G2 received six SC injections (0.02 ml 10 µg/ml) of denatured (G1) or active (G2) anti-VEGF from Day 0 to Day 21 every third day. G3 and G4 were instilled three times a day with denatured (G3) or active (G4) anti-VEGF drops (10 µg/ml) from Day 0 to Day 21. Corneal mean clinical scores (MCSs) of edema (E), transparency (T), and neovessels (nv) were recorded at Days 3, 9, 15, and 21. Quantification of neovessels was performed after lectin staining of vessels on flat mounted corneas.RESULTS: Twenty-one days after surgery, MCSs differed significantly between G1 and G2, but not between G3 and G4, and the rejection rate was significantly reduced in rats receiving active antibodies regardless of the route of administration (G2=50%, G4=66.65% versus G1 and G3=100%; p<0.05). The mean surfaces of neovessels were significantly reduced in groups treated with active anti-VEGF (G2, G4). However, anti-VEGF therapy did not completely suppress corneal neovessels.CONCLUSIONS: Specific rat anti-VEGF antibodies significantly reduced neovascularization and subsequent corneal graft rejection. The SC administration of the anti-VEGF antibody was more effective than topical instillation.

Polymorphisms of the " macrophage migration inhibitory factor " gene in infectious diseases

Summary The proinflammatory cytokine macrophage migration inhibitory factor (MIF) has emerged as a central mediator of inflammation and innate immune defense against infections. MIF has been shown to play an important role in the pathogenesis of infectious diseases like sepsis, tuberculosis and autoimmune inflammatory diseases, such as arthritis, inflammatory bowel disease and asthma. Two functional polymorphisms of the MIF gene promoter, a five to eight CATT repeat microsatellite at position -794 and a G/C SNP at position -173, have been associated with increased susceptibility to or severity of autoimmune inflammatory diseases like arthritis, colitis and atopy. The aim of this thesis was to define whether, and if so by which mechanisms, MIF gene polymorphisms influence the susceptibility to or the outcome of one of the most severe and one of the most prevalent infectious diseases: meningococcal sepsis and tuberculosis, respectively. The results of the comparison between 1106 patients suffering from severe meningococcal infections and 434 healthy volunteers showed that carriers of the CATT5-5 genotype were protected from meningococcemia. A transmission disequilibrium test involving 106 families confirmed this association. At baseline and after stimulation with Neisseria meningitidis, the CATT5 MIF promoter drove lower transcriptional activity than the CATT6 or CATT7 alleles in human monocytic cells and whole blood of CATT5-5 healthy individuals tended to produce less MIF than whole blood of CATT6-6 individuals. Beyond, we describe several new MIF gene polymorphisms in Africans. Genotyping the CATT microsatellite and the -173*G/C SNP revealed great genetic diversity in six African ethnic groups. Comparing 471 African tuberculosis cases and 932 matched healthy controls, we observed ethnicity dependent associations of the -173*G/C and the CATT5-8 with susceptibility to or severity of tuberculosis, but confirmation in larger cohorts ìs needed. In conclusion, we report that homozygous carriage of a low expression allele of the MIF gene protects from meningococcal disease. These results support the concept that analyses of MIF genotypes in patients with sepsis may help to classify patients into risk categories and to identify those patients who may benefit from anti-MIF therapeutic strategies.

Gender and attachment representations in the preschool years: comparisons between five countries

Bowlby proposed that the individual's social experiences, as early as in infancy, contribute to the construction of Internal Working Models (IWMs) of attachment, which will later guide the individual's expectations and behaviors in close relationships all along his or her life. The qualitative, individual characteristics of these models reflect the specificity of the individual's early experiences with attachment figures. The attachment literature globally shows that the qualities of IWMs are neither gender specific nor cultural specific. Procedures to evaluate IWMs in adulthood have been well established, based on narrative accounts of childhood experiences. Narrative procedures at earlier ages (e.g., in the preschool years) have been proposed, such as Bretherton's Attachment Story Completion Task (ASCT), to evaluate attachment representations. More than 500 ASCT narratives of preschoolers, coming from five different countries, have been collected, in the perspective of examining possible interactions between gender and culture regarding attachment representations. A specific Q-Sort coding procedure (CCH) has been used to evaluate several dimensions of the narratives. Girls' narratives appeared as systematically more secure than those of same-age boys, whatever their culture. The magnitude of gender differences, however, varied between countries. Taylor's model of gender-specific responses to stress and Harwood's and Posada's hypothesis on inter-cultural differences regarding caregiving are evoked to understand the differences across gender and countries.

Coaching como factor de Diferenciação nas Organizações

O mundo empresarial tem sido alvo de mudanças impulsionadas pela globalização. Neste sentido, as empresas que pretendem sobreviver e atingir um bom nível de competitividade devem focalizar-se na capacitação, no desenvolvimento e na motivação constante dos seus colaboradores. Devido à importância dos recursos humanos como diferencial competitivo, o processo de coaching como modelo de gestão da mudança, tem vindo a merecer muita importância no contexto organizacional. O processo de coaching em consonância com programas de desenvolvimento da liderança no contexto organizacional/empresarial visa ajudar os colaboradores a desenvolverem novas atitudes e competências ao alcance das metas organizacionais. O intuito deste trabalho é apresentar esclarecimentos acerca do termo, abordando os aspectos mais relevantes e o seu respectivo impacto no contexto organizacional. Realizou-se um Estudo de Caso baseado numa empresa de produção e prestação de serviços em São Vicente, com a finalidade de avaliar a motivação dos seus colaboradores, através da aplicação de um questionário aos mesmos. Na sequência da análise dos resultados sugeriu-se um modelo que mais se adapta à realidade da empresa. The business world has been challenged by several changes driven by globalization. Considering the present situation, companies that intend to survive and achieve a somewhat good level of competiveness should focus on their employee’s constant capacity building, development and motivation. Considering the Human Resources importance as a competitive differential, the coaching process as a change management module has been a very importance on the organizational context. The coaching process together with the leadership development programmes on the organizational/entrepreneurial context enables the employees to develop new attitudes and skills aiming for organizational goals. This paper purpose is to enlighten the reader on the subject, addressing the most relevant issues and its impact on the organizational context. We’ve conducted a Case Study, of a production and service company on S. Vicente Island, aiming to assess the employee’s motivation, through the application of a questionnaire. Following the results analysis, a model was proposed to better fit the company’s reality.

MRI visualized neo-intimal dissection and co-localization of novel apoptotic markers apolipoprotein C-1, ceramide and caspase-3 in a Watanabe hyperlipidemic rabbit model

PURPOSE: Apoptotic arterial wall vascular smooth muscle cell death is known to contribute to plaque vulnerability and rupture. Novel apoptotic markers like apolipoprotein C-I have been implicated in apoptotic human vascular smooth muscle cell death via recruiting a neutral sphingomyelinase (N-SMase)-ceramide pathway. In vivo relevance of these observations in an animal model of plaque rupture has not been shown. METHODS AND RESULTS: Using Watanabe rabbits, we investigated three different groups (group 1, three normal Watanabe rabbits; group 2, six Watanabe rabbits fed with high cholesterol diet for 3 months; group 3, five Watanabe rabbits with similar diet but additional endothelial denudation). We followed progression of atherosclerosis to pharmacologically induced plaque rupture non-invasively using novel 3D magnetic resonance Fast-Field-Echo angiography (TR=7.2, TE=3.6 ms, matrix=512 x 512) and Fast-Spin-Echo vessel wall imaging methods (TR=3 heart beats, TE=10.5 ms, matrix=304 x 304) on 1.5 T MRI. MRI provided excellent image quality with good MRI versus histology vessel wall thickness correlation (r=0.8). In six animals of group 2/3 MRI detected neo-intimal dissection in the abdominal aorta which was accompanied by immuno-histochemical demonstration of concomitant aforementioned novel apoptotic markers, previously implicated in the apoptotic smooth muscle cell death in vitro. CONCLUSIONS: Our studies suggest a potential role for the signal transduction pathway involving apolipoprotein C-I for in vivo apoptosis and atherosclerotic plaque rupture visualized by MRI.

LSTA Five Year Plan 2003-2007, 2007

The Iowa Commission of Libraries, the State Library’s governing board, convened the Library Services Task Force in August 2000. This group consisted of 46 Iowans from across the state, including librarians from all types of libraries, library trustees, legislators, members of Iowa Regional Library system (now called Library Service Areas) and Area Education Agencies, and citizens. Their mission was to make recommendations to the Commission on positioning libraries to effectively and efficiently meet the future needs of Iowans. Needs and expectations of Iowa Library customers and funding authorities were identified and examined by the Task Force, and are reflected in its recommendations. The Commission received the Task Force recommendations in December 2000, carefully studied them, solicited input from the Iowa library community, and with a few changes, forwarded the recommendations to the Governor and the Iowa General Assembly. These recommendations are now known as Iowa Commission of Libraries priorities and serve as a blueprint for future development of the Iowa library system. A second need assessment was conducted in 2001 as part of the process to formulate the joint Library Service Area – State Library Plan of Service 2003-2005. Biennial development of this plan is mandated by the Code of Iowa. In 2001, Library Service Area and Library Development staff from the State Library chose to completely revamp this plan, and used the process outlined in the The New Planning for Results by Sandra Nelson (the Public Library Association planning model) to do so. The group conducted a strengths/weaknesses/opportunities/threat analysis of the Iowa library situation, identified needs and put them in priority order, and identified service responses. Needs identified by the Library Services Task Force were similar to those identified by the Library Service Area and Library Development staff group. These needs were further analyzed and documented by State Library staff during the development of the LSTA plan. Sources consulted are identified in the text of the LSTA plan and/or listed at the close of this document. The text of the Library Services Task Force report and the documents created during the development of the Plan of Service 2003-2005 are cited in the appendix to this document.

Determinants of linear judgment: A meta-analysis of lens model studies

The mathematical representation of Brunswik s lens model has been usedextensively to study human judgment and provides a unique opportunity to conduct ameta-analysis of studies that covers roughly five decades. Specifically, we analyzestatistics of the lens model equation (Tucker, 1964) associated with 259 different taskenvironments obtained from 78 papers. In short, we find on average fairly high levelsof judgmental achievement and note that people can achieve similar levels of cognitiveperformance in both noisy and predictable environments. Although overall performancevaries little between laboratory and field studies, both differ in terms of components ofperformance and types of environments (numbers of cues and redundancy). An analysisof learning studies reveals that the most effective form of feedback is information aboutthe task. We also analyze empirically when bootstrapping is more likely to occur. Weconclude by indicating shortcomings of the kinds of studies conducted to date, limitationsin the lens model methodology, and possibilities for future research.

Expression of neutral endopeptidase, endothelin-1, and nuclear factor kappa B in prostate cancer: interrelations and associations with prostate-specific antigen recurrence after radical prostatectomy.

Objective. To study the impact of the neutral endopeptidase (NEP)/neuropeptides (NPs) axis and nuclear factor kappa B (NFκB) as predictors of prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP). Patients and Methods. 70 patients with early-stage PC were treated with RP and their tumor samples were evaluated for expression of NEP, endothelin-1 (ET-1) and NFκB (p65). Time to PSA recurrence was correlated with the examined parameters and combined with preoperative PSA level, Gleason score, pathological TNM (pT) stage, and surgical margin (SM) assessment. Results and Limitations. Membranous expression of NEP (P < 0.001), cytoplasmic ET-1 (P = 0.002), and cytoplasmic NFκB (P < 0.001) were correlated with time to PSA relapse. NEP was associated with ET-1 (P < 0.001) and NFκB (P < 0.001). ET-1 was also correlated with NFκB (P < 0.001). NEP expression (P = 0.017), pT stage (P = 0.013), and SMs (P = 0.036) were independent predictors of time to PSA recurrence. Conclusions. There seems to be a clinical model of NEP/NPs and NFκB pathways interconnection, with their constituents following inverse patterns of expression in accordance with their biological roles and molecular interrelations.

Turismo Rural na Ilha de Santo Antão como factor de Desenvolvimento das Aldeias de Fontaínhas, Corvo e Formiguinhas

Santo Antão é uma ilha onde a oferta turística passa pelo turismo de natureza, e pretendese criar um projecto ligado ao Turismo Rural nas aldeias de Fontaínhas, Corvo e Formiguinhas. As aldeias são rurais e enfrentam vários constrangimentos e é necessário implementar um leque de infra-estruturas como alojamento, estradas, postos de saúde, saneamento para o suporto do Turismo e optar por uma alternativa do desenvolvimento local. O objectivo é criar uma proposta de desenvolvimento do Turismo Rural que seja viável para estas aldeias. Numa segunda fase pretende-se também envolver as famílias rurais no desenvolvimento do turismo. As aldeias em questão reúnem condições naturais para o Turismo Rural, mas pretende apostar na valorização cultura, história e nos produtos locais. Having in mind that Santo Antão is an island where the offer is almost mandatory for nature tourism, it intends to develop a project connected to the Rural Tourism in the following villages of “Fontaínhas,” “Corvo” and “Formiguinhas”. These villages are rural and face various constraints, so it is necessary to implement a range of infrastructures to support Tourism and opt for an alternative that promotes local development. The aim is to create a model of development of Rural Tourism practicable to these villages. We also intend to involve local families in rural tourism development. The villages in question have natural conditions for Rural Tourism, but we want to focus on enhancing products like cultural and historical sites.

Improving generalized regression analysis for the spatial prediction of forest communities

Aim This study used data from temperate forest communities to assess: (1) five different stepwise selection methods with generalized additive models, (2) the effect of weighting absences to ensure a prevalence of 0.5, (3) the effect of limiting absences beyond the environmental envelope defined by presences, (4) four different methods for incorporating spatial autocorrelation, and (5) the effect of integrating an interaction factor defined by a regression tree on the residuals of an initial environmental model. Location State of Vaud, western Switzerland. Methods Generalized additive models (GAMs) were fitted using the grasp package (generalized regression analysis and spatial predictions, http://www.cscf.ch/grasp). Results Model selection based on cross-validation appeared to be the best compromise between model stability and performance (parsimony) among the five methods tested. Weighting absences returned models that perform better than models fitted with the original sample prevalence. This appeared to be mainly due to the impact of very low prevalence values on evaluation statistics. Removing zeroes beyond the range of presences on main environmental gradients changed the set of selected predictors, and potentially their response curve shape. Moreover, removing zeroes slightly improved model performance and stability when compared with the baseline model on the same data set. Incorporating a spatial trend predictor improved model performance and stability significantly. Even better models were obtained when including local spatial autocorrelation. A novel approach to include interactions proved to be an efficient way to account for interactions between all predictors at once. Main conclusions Models and spatial predictions of 18 forest communities were significantly improved by using either: (1) cross-validation as a model selection method, (2) weighted absences, (3) limited absences, (4) predictors accounting for spatial autocorrelation, or (5) a factor variable accounting for interactions between all predictors. The final choice of model strategy should depend on the nature of the available data and the specific study aims. Statistical evaluation is useful in searching for the best modelling practice. However, one should not neglect to consider the shapes and interpretability of response curves, as well as the resulting spatial predictions in the final assessment.

Keeping up with the Joneses: An international asset pricing model

We derive an international asset pricing model that assumes local investorshave preferences of the type "keeping up with the Joneses." In aninternational setting investors compare their current wealth with that oftheir peers who live in the same country. In the process of inferring thecountry's average wealth, investors incorporate information from the domesticmarket portfolio. In equilibrium, this gives rise to a multifactor CAPMwhere, together with the world market price of risk, there existscountry-speciffic prices of risk associated with deviations from thecountry's average wealth level. The model performs signifficantly better, interms of explaining cross-section of returns, than the international CAPM.Moreover, the results are robust, both for conditional and unconditionaltests, to the inclusion of currency risk, macroeconomic sources of risk andthe Fama and French HML factor.