An investigation of herpes simplex virus promoter activity compatible with latency establishment reveals VP16-independent activation of immediate-early promoters in sensory neurones

Herpes simplex virus (HSV) type-1 establishes lifelong latency in sensory neurones and it is widely assumed that latency is the consequence of a failure to initiate virus immediate-early (IE) gene expression. However, using a Ore reporter mouse system in conjunction with Ore-expressing HSV-1 recombinants we have previously shown that activation of the IE ICPO promoter can precede latency establishment in at least 30 % of latently infected cells. During productive infection of non-neuronal cells, IE promoter activation is largely dependent on the transactivator VP16 a late structural component of the virion. Of significance, VP16 has recently been shown to exhibit altered regulation in neurones; where its de novo synthesis is necessary for IE gene expression during both lytic infection and reactivation from latency. In the current study, we utilized the Ore reporter mouse model system to characterize the full extent of viral promoter activity compatible with cell survival and latency establishment. In contrast to the high frequency activation of representative IE promoters prior to latency establishment, cell marking using a virus recombinant expressing Ore under VP16 promoter control was very inefficient. Furthermore, infection of neuronal cultures with VP16 mutants reveals a strong VP16 requirement for IE promoter activity in non-neuronal cells, but not sensory neurones. We conclude that only IE promoter activation can efficiently precede latency establishment and that this activation is likely to occur through a VP16-independent mechanism

Decision Support Intervention for people with advanced dementia residing in a nursing home: A study protocol for an International advance care planning intervention (mySupport study)

Background Where it has been determined that a resident in a nursing home living with dementia loses decisional capacity, nursing home staff must deliver care that is in the person's best interests. Ideally, decisions should be made involving those close to the person, typically a family carer and health and social care providers. The aim of the Family Carer Decisional Support intervention is to inform family carers on end-of-life care options for a person living with advanced dementia and enable them to contribute to advance care planning. This implementation study proposes to; 1) adopt and apply the intervention internationally; and, 2) train nursing home staff to deliver the family carer decision support intervention. Methods This study will employ a multiple case study design to allow an understanding of the implementation process and to identify the factors which determine how well the intervention will work as intended. We will enrol nursing homes from each country (Canada n = 2 Republic of Ireland = 2, three regions in the UK n = 2 each, The Netherlands n = 2, Italy n = 2 and the Czech Republic n = 2) to reflect the range of characteristics in each national and local context. The RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework will guide the evaluation of implementation of the training and information resources. Our mixed methods study design has three phases to (1) establish knowledge about the context of implementation, (2) participant baseline information and measures and (3) follow up evaluation. Discussion The use of a multiple case study design will enable evaluation of the intervention in different national, regional, cultural, clinical, social and organisational contexts, and we anticipate collecting rich and in-depth data. While it is hoped that the intervention resources will impact on policy and practice in the nursing homes that are recruited to the study, the development of implementation guidelines will ensure impact on wider national policy and practice. It is our aim that the resources will be sustainable beyond the duration of the study and this will enable the resources to have a longstanding relevance for future advance care planning practice for staff, family carers and residents with advanced dementia

The impact of the mySupport advance care planning intervention on family caregivers' perceptions of decision-making and care for nursing home residents with dementia: pretest-posttest study in six countries

Background the mySupport advance care planning intervention was originally developed and evaluated in Northern Ireland (UK). Family caregivers of nursing home residents with dementia received an educational booklet and a family care conference with a trained facilitator to discuss their relative's future care. Objectives to investigate whether upscaling the intervention adapted to local context and complemented by a question prompt list impacts family caregivers' uncertainty in decision-making and their satisfaction with care across six countries. Second, to investigate whether mySupport affects residents' hospitalisations and documented advance decisions. Design a pretest-posttest design. Setting in Canada, the Czech Republic, Ireland, Italy, the Netherlands and the UK, two nursing homes participated. Participants in total, 88 family caregivers completed baseline, intervention and follow-up assessments. Methods family caregivers' scores on the Decisional Conflict Scale and Family Perceptions of Care Scale before and after the intervention were compared with linear mixed models. The number of documented advance decisions and residents' hospitalisations was obtained via chart review or reported by nursing home staff and compared between baseline and follow-up with McNemar tests. Results family caregivers reported less decision-making uncertainty (-9.6, 95% confidence interval: -13.3, -6.0, P < 0.001) and more positive perceptions of care (+11.4, 95% confidence interval: 7.8, 15.0; P < 0.001) after the intervention. The number of advance decisions to refuse treatment was significantly higher after the intervention (21 vs 16); the number of other advance decisions or hospitalisations was unchanged. Conclusions the mySupport intervention may be impactful in countries beyond the original setting.Public Health and primary careGeriatrics in primary car

Urban indicators for UK butterflies

Most people live in urban environments and there is a need to produce abundance indices to assist policy and management of urban greenspaces and gardens. While regional indices are produced, with the exception of birds, studies of the differences between urban and rural areas are rare. We explore these differences for UK butterflies, with the intention to describe changes that are relevant to people living in urban areas, in order to better connect people with nature in support of conservation, provide a measure relevant to human well-being, and assess the biodiversity status of the urban environment. Transects walked under the UK Butterfly Monitoring Scheme are classified as urban or rural, using a classification for urban morphological zones. We use models from the Generalised Abundance Index family to produce urban and rural indices of relative abundance for UK butterfly species. Composite indices are constructed for various subsets of species. For univoltine and bivoltine species, where we are able to fit phenomenological models, we estimate measures of phenology and identify urban/rural differences. Trends in relative abundance over the period 1995–2014 are more negative in urban areas compared to rural areas for 25 out of 28 species. For the composite indices, all trends are negative, and they are significantly more negative for urban areas than for rural areas. Analysis of phenological parameters shows butterflies tend to emerge earlier in urban than in rural areas. In addition, some fly longer in urban than in rural areas, whereas in other cases the opposite is the case, and hypotheses are proposed to account for these features. Investigating new urban/rural indicators has revealed national declines that are stronger for urban areas. For continued monitoring, there is a need for an urban butterfly indicator, and for this to be evaluated and reported annually. We explain how this may be interpreted, and the relevance for other monitoring schemes. The results of this paper, including the phenological findings, shed new light on the potentially deleterious effects of urbanisation and climate change, which require suitable monitoring and reporting to support policy and management, for example of urban greenspaces and gardens

Hypoxic Pulmonary Vasoconstriction in Humans:Tale or Myth

Hypoxic Pulmonary vasoconstriction (HPV) describes the physiological adaptive process of lungs to preserves systemic oxygenation. It has clinical implications in the development of pulmonary hypertension which impacts on outcomes of patients undergoing cardiothoracic surgery. This review examines both acute and chronic hypoxic vasoconstriction focusing on the distinct clinical implications and highlights the role of calcium and mitochondria in acute versus the role of reactive oxygen species and Rho GTPases in chronic HPV. Furthermore it identifies gaps of knowledge and need for further research in humans to clearly define this phenomenon and the underlying mechanism