Use of a short hPDE6b promoter for rod gene transfer in a model of severe retinal cystrophy, the Rd10 mouse

Purpose: Gene therapy of severe retinal dystrophies directly affecting photoreceptor is still a challenge in terms of clinical application. One of the main hurdles is to generate high transgene expression specifically in rods or cones. In the present study, we are investigating the possibility to drive hPDE6b expression in the Rd10 mouse retina using a specific sequence of the human PDE6b promoter. Methods: Two 5' flanking fragments of the human PDE6b gene: (-93 to +53 (146 bp) and -297 to +53 (350 bp, see Di Polo and Farber, 1995) were cloned in different plasmids in order to check their expression in vitro and in vivo. These elements drove the activity of either luciferase (pGL3 plasmids) or EGFP (AAV2/8 backbone). Then, an AAV2/8 vector carrying the PDE6b cDNA was tested with subretinal injections at P9 in the Rd10 eyes. Eye fundus, OCT, ERG recordings and histological investigations were performed to assess the efficacy of the gene transfer. Results: The short PDE6b promoter containing 146bp (-93 to +53) showed the highest activity in the Y-79 cells, as described previously (Di Polo and Farber, 1995). Subretinal administrations of AAV2/8-PDE6bpromoter-EGFP allowed a rapid expression specifically in rods and not in cones. The expression is faster than a vector containing the CMV promoter. The AAV2/8-PDE6bpromoter-PDE6b and the control vector were injected at P9 in the Rd10 mouse retina and investigated 5 weeks post-injection. Out of 14 eyes, 6 presented an increased rod sensitivity of about 300 fold, and increased a- and b-wave responses in ERG recordings. Flicker stimulations revealed that cones are also functional. OCT images and histological analyses revealed an increased ONL size in the injected area. The retina treated with the therapeutic vector presented 4-6 rows of photoreceptors with outersegments containing PDE6b. In the control eyes, only 2-4 rows of photoreceptors with almost no OS were observed . Conclusions: The 146 bp promoter sequence (-93 to + 53) is the shortest regulatory element described to date which allows to obtain efficient rod-specific expression in the context of somatic gene transfer. This first result is of great interest for AAV vector design in general allowing more space for the accommodation of transgenes of interest and good expression in rods. Moreover we showed the proof of principle of the efficacy of AAV2/8-PDE6bp-PDE6b vector in the Rd10 mouse model of severe photoreceptor degeneration without using neither AAV mutated capsids, nor self-complementary vectors.

Self-reported social class in adolescents: validity and relationship with gradients in self-reported health

Background: Analyzing social differences in the health of adolescents is a challenge. The accuracy of adolescent's report on familial socio-economic position is unknown. The aims of the study were to examine the validity of measuring occupational social class and family level of education reported by adolescents aged 12 to 18, and the relationship between social position and self-reported health.Methods: A sample of 1453 Spanish adolescents 12 to 18 years old from urban and rural areas completed a self-administered questionnaire including the Child Health and Illness Profile-Adolescent Edition (CHIP-AE), and data on parental occupational social class (OSC) and level of education (LE). The responsible person for a sub-sample of teenagers (n = 91) were interviewed by phone. Kappa coefficients were estimated to analyze agreement between adolescents and proxy-respondents, and logistic regression models were adjusted to analyze factors associated with missing answers and disagreements. Effect size (ES) was calculated to analyze the relationship between OSC, LE and the CHIP-AE domain scores.Results: Missing answers were higher for father's (24.2%) and mother's (45.7%) occupational status than for parental education (8.4%, and 8.1% respectively), and belonging to a non-standard family was associated with more incomplete reporting of social position (OR = 4,98; 95%CI = 1,3–18,8) as was agreement between a parent and the adolescent. There were significant social class gradients, most notably for aspects of health related to resilience to threats to illness.ConclusionAdolescents can acceptably self-report on family occupation and level of education. Social class gradients are present in important aspects of health in adolescents.

Gerência do cuidado de enfermagem em cenários hospitalares: a construção de um conceito

Este estudo teve como objetivo construir e apresentar a definição teórica do conceito de gerência do cuidado de enfermagem em cenários hospitalares, a partir de base literária específica. Optou-se pela utilização das estratégias para construção de conceitos da Análise de Conceito, as regras de formação de conceito da Análise Arqueológica e a Análise Lexical como referencial teórico-metodológico. A operacionalização das estratégias e das regras de formação de conceito possibilitou a construção do conceito gerência do cuidado de enfermagem em cenários hospitalares. O conceito construído apresentou, em sua natureza, a capacidade de integrar dialeticamente os aspectos relativos ao saber-fazer do cuidar e gerenciar. A definição teórica do conceito Gerência do Cuidado de Enfermagem em Cenários Hospitalares deu significado ao termo, no contexto inicial de construção de uma teoria, a Gerência do Cuidado de Enfermagem em Serviços de Saúde.

Avaliação do nível de esperança de vida de idosos renais crônicos em hemodiálise

O presente estudo teve por objetivo avaliar o nível de esperança dos idosos renais crônicos em hemodiálise, por meio da Escala de Esperança de Herth (EEH). Trata-se de um estudo descritivo transversal, realizado em uma Unidade de Terapia Renal Substitutiva do interior do estado de São Paulo. A amostra foi composta por 50 idosos em tratamento hemodialítico. Após o consentimento em participar da pesquisa, realizou-se entrevistas individuais com os referidos idosos aplicando-se um instrumento de caracterização e a Escala de Esperança de Herth. Todos os preceitos éticos foram respeitados (protocolo 512/2009). Quanto aos resultados, houve predomínio do sexo masculino (60%) e idade média de 70,20 (±6,1) anos. O escore médio obtido com a aplicação da Escala de Esperança de Herth foi de 36,20 (±2,90). Conclui-se que em comparação com o estudo brasileiro de validação da Escala de Esperança de Herth, o nível de esperança dos sujeitos do presente estudo foi mais baixo, indicando a necessidade de intervenção sobre esse sentimento.

Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers.

We previously used a single nucleotide polymorphism (SNP) in the CHRNA5-A3-B4 gene cluster associated with heaviness of smoking within smokers to confirm the causal effect of smoking in reducing body mass index (BMI) in a Mendelian randomisation analysis. While seeking to extend these findings in a larger sample we found that this SNP is associated with 0.74% lower body mass index (BMI) per minor allele in current smokers (95% CI -0.97 to -0.51, P = 2.00 × 10(-10)), but also unexpectedly found that it was associated with 0.35% higher BMI in never smokers (95% CI +0.18 to +0.52, P = 6.38 × 10(-5)). An interaction test confirmed that these estimates differed from each other (P = 4.95 × 10(-13)). This difference in effects suggests the variant influences BMI both via pathways unrelated to smoking, and via the weight-reducing effects of smoking. It would therefore be essentially undetectable in an unstratified genome-wide association study of BMI, given the opposite association with BMI in never and current smokers. This demonstrates that novel associations may be obscured by hidden population sub-structure. Stratification on well-characterized environmental factors known to impact on health outcomes may therefore reveal novel genetic associations.

Pilot licensing after aortic valve surgery.

Background and aim of the study: Bicuspid aortic valve is the most common congenital heart malformation, and a high percentage of patients with this condition will develop complications over time. It is rare that pilots undergo aortic valve surgery, and the confirmation of flight-licensing requirements after aortic valve replacement (AVR) is a challenge for the patient's cardiac surgeon and, particularly, for the Aeromedical Examiner (AME). Only AMEs are able to determine the flight status of pilots. Furthermore, in military and in civil aviation (e.g., Red Bull Air Race), the high G-load environment experienced by pilots is an exceptional physiological parameter, which must be considered postoperatively. Methods: A review was conducted of the aeronautical, surgical and medical literature, and of European pilot-licensing regulations. Case studies are also reported for two Swiss Air Force pilots. Results: According to European legislation, pilots can return to flight duty from the sixth postoperative month, with the following limitations: that an aortic bioprosthesis presents no restrictions in cardiac function, requires no cardioactive medications, yet requires a flight operation with co-pilot, the avoidance of accelerations over +3 Gz and, in military aviation, restricts the pilot to non-ejection-seat aircraft. The patient follow up must include both echocardiographic and rhythm assessments every six months. Mechanical prostheses cannot be certified because the required anticoagulation therapy is a disqualifying condition for pilot licensing. Conclusion: Pilot licensing after aortic valve surgery is possible, but with restrictions. The +Gz exposition is of concern in both military and civilian aviation (aerobatics). The choice of bioprosthesis type and size is determinant. Pericardial and stentless valves seem to show better flow characteristics under high-output conditions. Repetitive cardiological controls are mandatory for the early assessment of structural valve disease and rhythm disturbances. A pre-emptive timing is recommended when reoperation is indicated, without waiting for clinical manifestations of structural valve disease.

Internações por Condições Sensíveis à Atenção Primária em uma metrópole brasileira

Este estudo tem como objetivo descrever o perfil das Internações por Condições Sensíveis à Atenção Primária (ICSAP) no município de Curitiba no período de 2005 a 2007. Foi realizado um estudo ecológico, com dados obtidos no Sistema de Informações Hospitalares. Para análise, foi utilizada a estatística descritiva. Observou-se que em Curitiba as ICSAP seguem tendência de estabilização, sendo as causas mais frequentes a angina e a insuficiência cardíaca, maior frequência para o sexo feminino e a faixa etária ≥ 65 anos. Os resultados observados assemelham-se aos de outros estudos e foram, quase na totalidade, altamente significativos do ponto de vista estatístico. Entretanto, devem ser vistos com cuidado, pois se se trata de um indicador que apresenta algumas limitações, dentre as quais a própria confiabilidade do diagnóstico e o uso de dados secundários.

Duration of smoking cessation for the prevention of surgical wound healing complications

The study aimed to find scientific evidence about the duration of preoperative smoking cessation required to reduce surgical wound healing complications. An integrative review was performed in the databases, Latin American and Caribbean Literature on Health Sciences (LILACS) and Medical Literature Analysis and Retrieval System Online (MEDLINE), from 08/17/2012 to 09/17/2012, using the keywords: tobacco use cessation and wound healing; tobacco use cessation and preoperative period; tobacco use cessation and perioperative period (LILACS) and tobacco use cessation and perioperative period; tobacco use cessation and wound healing (MEDLINE). Out of the 81 eligible studies, 12 were included. The duration of smoking cessation needed to reduce healing complications was at least four weeks (four studies with level of evidence I, three studies with level of evidence II, two studies with level of evidence IV, and one study with level of evidence VII).

Blood pressure and low-density lipoprotein-cholesterol lowering for prevention of strokes and cognitive decline: a review of available trial evidence.

BACKGROUND AND OBJECTIVES: It is well established by a large number of randomized controlled trials that lowering blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) by drugs are powerful means to reduce stroke incidence, but the optimal BP and LDL-C levels to be achieved are largely uncertain. Concerning BP targets, two hypotheses are being confronted: first, the lower the BP, the better the treatment outcome, and second, the hypothesis that too low BP values are accompanied by a lower benefit and even higher risk. It is also unknown whether BP lowering and LDL-C lowering have additive beneficial effects for the primary and secondary prevention of stroke, and whether these treatments can prevent cognitive decline after stroke. RESULTS: A review of existing data from randomized controlled trials confirms that solid evidence on optimal BP and LDL-C targets is missing, possible interactions between BP and LDL-C lowering treatments have never been directly investigated, and evidence in favour of a beneficial effect of BP or LDL-C lowering on cognitive decline is, at best, very weak. CONCLUSION: A new, large randomized controlled trial is needed to determine the optimal level of BP and LDL-C for the prevention of recurrent stroke and cognitive decline.

Relatório sobre a Situação da População Mundial 2011

Como nos tornamos tão numerosos? Qual a quantidade de pessoas que a Terra pode sustentar? Essas são questões importantes, mas, talvez, não as mais adequadas para nossos tempos. Quando nos centramos apenas nas enormes quantidades, corremos o risco de sermos subjugados e perdermos a visão das novas oportunidades de tornar a vida melhor para todas e todos no futuro. Assim, ao invés de indagar questões como “Somos uma população grande demais?” deveríamos perguntar: “O que posso fazer para melhorar o mundo em que vivemos?” ou “Como podemos transformar nossas cidades em constante crescimento em forças a favor da sustentabilidade?” Deveríamos também perguntar-nos o que cada um de nós pode fazer para empoderar as pessoas mais idosas, de forma que possam atuar mais ativamente em suas comunidades. O que podemos fazer para soltar a criatividade e o potencial da maior população de jovens que a humanidade jamais viu? E o que podemos fazer para remover as barreiras que impedem a igualdade entre mulheres e homens de maneira que todas e todos tenham o pleno poder de tomar suas próprias decisões e realizar seu pleno potencial? O relatório sobre a Situação da População Mundial 2011 examina as tendências – as dinâmicas – que estão definindo nosso mundo de 7 bilhões de habitantes e mostra o que as pessoas em países e circunstâncias muito diferentes estão realizando em suas próprias comunidades para extrair o melhor deste mundo. Algumas tendências são notáveis: Hoje, existem 893 milhões de pessoas acima de 60 anos em todo o mundo. Na metade deste século, esse número subirá para 2,4 bilhões. Cerca de uma em cada duas pessoas vive em cidades e, em aproximadamente 35 anos, duas entre três o farão. As pessoas com menos de 25 anos j�� compõem 43% da população mundial, chegando a 60% em alguns países.

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.

Supplemental nursing staff´s experiences at a Spanish hospital: Qualitative phenomenology research

The objective of this study was to describe the Supplemental Nursing Staff´s experiences at different hospital units. A qualitative phenomenological approach was conducted; a purposeful and theoretical sampling was implemented with supplemental nursing staff at Santa Barbara Hospital of Soria (Spain), to gain a more in-depth understanding of the Supplemental Nursing Staff ´s experience. Data were collected by in-depth interviews and through a field notebook. Data were analyzed using the Giorgi proposal. Twenty-one nurses with a mean age of 46 years were included. Three main topics emerged from the data analysis: building the first contact, carving out a niche and establishing interprofessional/interpersonal relationships. We conclude that the experience of hosting the supplemental nursing staff in changing clinical environments is conditioned by various factors. It is necessary for nurses and hospital managers to establish clear objectives with regard to the supplemental nursing staff´s role in the units.