Effect of Gene Therapy on Visual Function in Leber's Congenital Amaurosis

Early-onset, severe retinal dystrophy caused by mutations in the gene encoding retinal pigment epithelium–specific 65-kD protein (RPE65) is associated with poor vision at birth and complete loss of vision in early adulthood. We administered to three young adult patients subretinal injections of recombinant adeno-associated virus vector 2/2 expressing RPE65 complementary DNA (cDNA) under the control of a human RPE65 promoter. There were no serious adverse events. There was no clinically significant change in visual acuity or in peripheral visual fields on Goldmann perimetry in any of the three patients. We detected no change in retinal responses on electroretinography. One patient had significant improvement in visual function on microperimetry and on dark-adapted perimetry. This patient also showed improvement in a subjective test of visual mobility. These findings provide support for further clinical studies of this experimental approach in other patients with mutant RPE65. (ClinicalTrials.gov number, NCT00643747.)Supported by grants from the U.K. Department of Health, the British Retinitis Pigmentosa Society, and the Special Trustees of Moorfields Eye Hospital, and by the Sir Jules Thorn Charitable Trust, the Wellcome Trust, the European Union (EVI-Genoret and Clinigene programs), the Medical Research Council, Foundation Fighting Blindness, Fight for Sight, the Ulverscroft Foundation, Fighting Blindness (Ireland), Moorfields Eye Hospital, and Institute of Ophthalmology Biomedical Research Centre for Ophthalmology, University College London

A História da Alimentação: balizas historiográficas

Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema

Recent UK retirees’ views about the work-related factors which influenced their decision to retire: a qualitative study within the Health and Employment After Fifty (HEAF) cohort

BackgroundLower birth rates and increasing longevity have resulted in ageing populations in European countries. These demographic changes place challenges on pension provision as numbers of those who are economically inactive and retired increase relative to those in paid work. Therefore, governments need workers to postpone retirement and work to older ages. Whilst health and wealth are important in retirement decision-making, considerably less is known about the effects of workplace factors. The aim of this study was to explore the views of recent UK retirees about the role that work-related factors played in their decision to retire.MethodsThis qualitative study was nested within the Health and Employment After Fifty (HEAF) cohort. People who had retired 3-6 years previously (not for health reasons) were purposively sampled to obtain the views of men and women from a range of socio-economic backgrounds and jobs. Semi-structured interviews were carried out by telephone using a pre-defined topic guide. Interviews were audio-recorded, transcribed and analysed thematically.ResultsSeventeen interviews were conducted. Thematic analysis showed that retirement decisions were complex and multi-factorial but that work-related factors contributed to decision-making in two main ways. First, some work factors pushed participants towards retirement. These were perceptions that: workplace change had affected the way they were valued or increased pressure on them; work demands, including commuting, had intruded excessively on personal time, effects that were exacerbated by modern technology; work was draining, isolating or under-appreciated; and /or that work was causing physical strain or discomfort relative to their perception of their capacity. In contrast, work factors could also cause participants to pull back towards work, particularly: autonomy; supportive work colleagues; a sense of being appreciated; and perceived job flexibility.ConclusionsRecent retirees explained that their decision to retire was multi-factorial but work-related factors contributed importantly. Potentially, employers could: review workers’ perceptions about their work; their capacity in relation to job demands; increase flexibility; and facilitate a supportive work community to encourage longer working lives

Incorporating cardiopulmonary resuscitation training into a cardiac rehabilitation programme: A feasibility study

The European Society of Cardiology 2017. Background: Patients with a cardiac history are at future risk of cardiac events, including out-of-hospital cardiac arrest. Targeting cardiopulmonary resuscitation (CPR) training to family members of cardiac patients has long been advocated, but is an area in need of contemporary research evidence. An environment yet to be investigated for targeted training is cardiac rehabilitation. Aim: To evaluate the feasibility of providing CPR training in a cardiac rehabilitation programme among patients, their family members and staff. Methods: A prospective before and after study design was used. CPR training was delivered using video self-instruction CPR training kits, facilitated by a cardiac nurse. Data was collected pre-training, post-training and at one month. Results: Cardiac patient participation rates in CPR classes were high (n = 56, 72.7% of eligible patients) with a further 27 family members attending training. Patients were predominantly male (60.2%), family members were predominantly female (81.5%), both with a mean age of 65 years. Confidence to perform CPR and willingness to use skills significantly increased post-training (both p < 0.001). Post training participants demonstrated a mean compression rate of 112 beats/min and a mean depth of 48 mm. Training reach was doubled as participants shared the video self-instruction kit with a further 87 people. Patients, family members and cardiac rehabilitation staff had positive feedback about the training. Conclusions: We demonstrated that cardiac rehabilitation is an effective and feasible environment to provide CPR training. Using video self-instruction CPR training kits enabled further training reach to the target population

Long-term survival of photoreceptors transplanted into the adult murine neural retina requires immune modulation

Stem cell therapy presents an opportunity to replace photoreceptors that are lost as a result of inherited and age-related degenerative disease. We have previously shown that murine postmitotic rod photoreceptor precursor cells, identified by expression of the rod-specific transcription factor Nrl, are able to migrate into and integrate within the adult murine neural retina. However, their long-term survival has yet to be determined. Here, we found that integrated Nrl.gfp(+ve) photoreceptors were present up to 12 months post-transplantation, albeit in significantly reduced numbers. Surviving cells had rod-like morphology, including inner/outer segments and spherule synapses. In a minority of eyes, we observed an early, marked reduction in integrated photoreceptors within 1 month post-transplantation, which correlated with increased numbers of amoeboid macrophages, indicating acute loss of transplanted cells due to an inflammatory response. In the majority of transplants, similar numbers of integrated cells were observed between 1 and 2 months post-transplantation. By 4 months, however, we observed a significant decrease in integrated cell survival. Macrophages and T cells were present around the transplantation site, indicating a chronic immune response. Immune suppression of recipients significantly increased transplanted photoreceptor survival, indicating that the loss observed in unsuppressed recipients resulted from T cell-mediated host immune responses. Thus, if immune responses are modulated, correctly integrated transplanted photoreceptors can survive for extended periods of time in hosts with partially mismatched H-2 haplotypes. These findings suggest that autologous donor cells are optimal for therapeutic approaches to repair the neural retina, though with immune suppression nonautologous donors may be effective

‘I should be disease free, healthy and be happy in whatever I do’: a cross-country analysis of drivers of adolescent diet and physical activity in different low- and middle-income contexts

Objective:To explore perceptions of how context shapes adolescent diet and physical activity in eight low- and middle-income (LMIC) sites at different stages of societal and economic transition.Design:Novel qualitative secondary analysis of eight data sets generated as part of the international Transforming Adolescent Lives through Nutrition (TALENT) collaboration.Setting:Diverse sites in India and Sub-Saharan Africa.Participants:Fifty-two focus group discussions with 491 participants (303 adolescents aged 10–17 years; 188 caregivers).Results:Analysis of pooled qualitative data identified three themes: (1) transitions in generational nutrition education and knowledge; (2) transition in caregiver–adolescent power balance and (3) the implications of societal and economic transition for diet and physical activity. Adolescents in urban and peri-urban areas could readily access ‘junk’ food. Diets in rural settings were determined by tradition, seasonality and affordability. Physical activity was inhibited by site-specific factors including lack of space and crime in urban settings, and the prioritisation of academic performance. Gender influenced physical activity across all sites, with girls afforded fewer opportunities.Conclusions:Interventions to improve adolescent diet and physical activity in LMIC need to be complex, context-specific and responsive to transitions at the individual, economic and societal levels. Moreover, solutions need to acknowledge gender inequalities in different contexts, as well as structural and cultural influences on diet and physical activity in resource-limited settings. Programmes need to be effective in engaging and reconciling adolescents’ and caregivers’ perspectives. Consequently, there is a need for action at both the community-household level and also through policy