Beyond obesity - thermogenic adipocytes and cardiometabolic health

The global prevalence of obesity and related cardiometabolic disease continues to increase through the 21st century. Whilst multi-factorial, obesity is ultimately caused by chronic caloric excess. However, despite numerous interventions focussing on reducing caloric intake these either fail or only elicit short-term changes in body mass. There is now a focus on increasing energy expenditure instead which has stemmed from the recent ‘re-discovery’ of cold-activated brown adipose tissue (BAT) in adult humans and inducible ‘beige’ adipocytes. Through the unique mitochondrial uncoupling protein (UCP1), these thermogenic adipocytes are capable of combusting large amounts of chemical energy as heat and in animal models can prevent obesity and cardiometabolic disease. At present, human data does not point to a role for thermogenic adipocytes in regulating body weight or fat mass but points to a pivotal role in regulating metabolic health by improving insulin resistance as well as glucose and lipid homeostasis. This review will therefore focus on the metabolic benefits of BAT activation and the mechanisms and signalling pathways by which these could occur including improvements in insulin signalling in peripheral tissues, systemic lipid and cholesterol metabolism and cardiac and vascular function

Transition of young people from children’s into adults’ services: what works for whom and in what circumstances – protocol for a realist synthesis

Introduction The process of transitioning young people from children’s or adolescents’ health services into adults’ services is a crucial time in the lives and health of young people and has been reported to be disjointed rather than a process of preparation in which they are involved. Such transitions not only fail to meet the needs of young people and families at this time of significant change, but they may also result in a deterioration in health, or disengagement with services, which can have deleterious long-term consequences. Despite the wealth of literature on this topic, there has yet to be a focus on what works for whom, in what circumstances, how and why, in relation to all young people transitioning from children’s into adults’ services, which this realist synthesis aims to address. Methods and analysis This realist synthesis will be undertaken in six stages: (1) the scope of the review will be defined; (2) initial programme theories (IPTs) developed; (3) evidence searched; (4) selection and appraisal; (5) data extraction and synthesis; and (6) finally, refine/confirm programme theory. A theory-driven, iterative approach using the ‘On Your Own Feet Ahead’ theoretical framework, will be combined with an evidence search including a review of national transition policy documents, supplemented by citation tracking, snowballing and stakeholder feedback to develop IPTs. Searches of EMBASE, EMCARE, Medline, CINAHL, Cochrane Library, Web of Science, Scopus, APA PsycINFO and AMED will be conducted from 2014 to present, supplemented with grey literature, free-text searching (title, abstract and keywords) and citation tracking. Data selection will be based on relevance and rigour and extracted and synthesised iteratively with the aim of identifying and exploring causal links between contexts, mechanisms and outcomes. Results will be reported according to the Realist And Meta-narrative Evidence Syntheses: Evolving Standards Quality and Publication Standards. Ethics and dissemination This realist synthesis forms part of the National Transition Evaluation Study, which has received ethical and regulatory approval (IRAS ID: 313576). Results will be disseminated through peer-review publication, conference presentations and working with healthcare organisations, stakeholder groups and charities

Housing temperature modulates the impact of diet-induced rise in fat mass on adipose tissue before and during pregnancy in rats

Aim: To investigate whether housing temperature influences rat adiposity, and the extent it is modified by diet and/or pregnancy. Housing temperature impacts on brown adipose tissue, that possess a unique uncoupling protein (UCP) 1, which, when activated by reduced ambient temperature, enables rapid heat generation. Methods: We, therefore, examined whether the effects of dietary induced rise in fat mass on interscapular brown fat in female rats were dependent on housing temperature, and whether pregnancy further modulates the response. Four week old rats were either maintained at thermoneutrality (27°C) or at a “standard” cool temperature (20°C), and fed either a control or obesogenic (high in fat and sugar) diet until 10 weeks old. They were then either tissue sampled or mated with a male maintained under the same conditions. The remaining dams were tissue sampled at either 10 or 19 days gestation. Results: Diet had the greatest effect on fat mass at thermoneutrality although, by 19 days gestation, fat weight was similar between groups. Prior to mating, the abundance of UCP1 was higher at 20°C, but was similar between groups during pregnancy. UCP1 mRNA followed a similar pattern, with expression declining to a greater extent in the animals maintained at 20°C. Conclusion: Housing temperature has a marked influence on the effect of dietary induced rise in fat deposition that was modified through gestation. This maybe mediated by the reduction in UCP1 with housing at thermoneutrality prior to pregnancy and could subsequently impact on growth and development of the offspring

Housing Temperature Modulates the Impact of Diet-Induced Rise in Fat Mass on Adipose Tissue Before and During Pregnancy in Rats

Aim: To investigate whether housing temperature influences rat adiposity, and the extent it is modified by diet and/or pregnancy. Housing temperature impacts on brown adipose tissue, that possess a unique uncoupling protein (UCP) 1, which, when activated by reduced ambient temperature, enables rapid heat generation.Methods: We, therefore, examined whether the effects of dietary induced rise in fat mass on interscapular brown fat in female rats were dependent on housing temperature, and whether pregnancy further modulates the response. Four week old rats were either maintained at thermoneutrality (27°C) or at a “standard” cool temperature (20°C), and fed either a control or obesogenic (high in fat and sugar) diet until 10 weeks old. They were then either tissue sampled or mated with a male maintained under the same conditions. The remaining dams were tissue sampled at either 10 or 19 days gestation.Results: Diet had the greatest effect on fat mass at thermoneutrality although, by 19 days gestation, fat weight was similar between groups. Prior to mating, the abundance of UCP1 was higher at 20°C, but was similar between groups during pregnancy. UCP1 mRNA followed a similar pattern, with expression declining to a greater extent in the animals maintained at 20°C.Conclusion: Housing temperature has a marked influence on the effect of dietary induced rise in fat deposition that was modified through gestation. This maybe mediated by the reduction in UCP1 with housing at thermoneutrality prior to pregnancy and could subsequently impact on growth and development of the offspring

Derivation of lowland riparian wetland deposit architecture using geophysical image analysis and interface detection

For groundwater-surface water interactions to be understood in complex wetland settings, the architecture of the underlying deposits requires investigation at a spatial resolution sufficient to characterize significant hydraulic pathways. Discrete intrusive sampling using conventional approaches provides insufficient sample density and can be difficult to deploy on soft ground. Here a noninvasive geophysical imaging approach combining three-dimensional electrical resistivity tomography (ERT) and the novel application of gradient and isosurface-based edge detectors is considered as a means of illuminating wetland deposit architecture. The performance of three edge detectors were compared and evaluated against ground truth data, using a lowland riparian wetland demonstration site. Isosurface-based methods correlated well with intrusive data and were useful for defining the geometries of key geological interfaces (i.e., peat/gravels and gravels/Chalk). The use of gradient detectors approach was unsuccessful, indicating that the assumption that the steepest resistivity gradient coincides with the associated geological interface can be incorrect. These findings are relevant to the application of this approach in settings with a broadly layered geology with strata of contrasting resistivities. In addition, ERT revealed substantial structures in the gravels related to the depositional environment (i.e., braided fluvial system) and a complex distribution of low-permeability putty Chalk at the bedrock surface—with implications for preferential flow and variable exchange between river and groundwater systems. These results demonstrate that a combined approach using ERT and edge detectors can provide valuable information to support targeted monitoring and inform hydrological modeling of wetlands

Transition from children's to adult services for adolescents/young adults with life-limiting conditions : developing realist programme theory through an international comparison

Abstract Background Managing transition of adolescents/young adults with life-limiting conditions from children’s to adult services has become a global health and social care issue. Suboptimal transitions from children’s to adult services can lead to measurable adverse outcomes. Interventions are emerging but there is little theory to guide service developments aimed at improving transition. The Transition to Adult Services for Young Adults with Life-limiting conditions (TAYSL study) included development of the TASYL Transition Theory, which describes eight interventions which can help prepare services and adolescents/young adults with life-limiting conditions for a successful transition. We aimed to assess the usefulness of the TASYL Transition Theory in a Canadian context to identify interventions, mechanisms and contextual factors associated with a successful transition from children’s to adult services for adolescents/young adults; and to discover new theoretical elements that might modify the TASYL Theory. Methods A cross-sectional survey focused on organisational approaches to transition was distributed to three organisations providing services to adolescents with life-limiting conditions in Toronto, Canada. This data was mapped to the TASYL Transition Theory to identify corresponding and new theoretical elements. Results Invitations were sent to 411 potentially eligible health care professionals with 56 responses from across the three participating sites. The results validated three of the eight interventions: early start to the transition process; developing adolescent/young adult autonomy; and the role of parents/carers; with partial support for the remaining five. One new intervention was identified: effective communication between healthcare professionals and the adolescent/young adult and their parents/carers. There was also support for contextual factors including those related to staff knowledge and attitudes, and a lack of time to provide transition services centred on the adolescent/young adult. Some mechanisms were supported, including the adolescent/young adult gaining confidence in relationships with service providers and in decision-making. Conclusions The Transition Theory travelled well between Ireland and Toronto, indicating its potential to guide both service development and research in different contexts. Future research could include studies with adult service providers; qualitative work to further explicate mechanisms and contextual factors; and use the theory prospectively to develop and test new or modified interventions to improve transition

Monsters: interdisciplinary explorations in monstrosity

There is a continued fascination with all things monster. This is partly due to the popular reception of Mary Shelley’s Monster, termed a “new species” by its overreaching but admiringly determined maker Victor Frankenstein in the eponymous novel first published in 1818. The enduring impact of Shelley’s novel, which spans a plethora of subjects and genres in imagery and themes, raises questions of origin and identity, death, birth and family relationships as well as the contradictory qualities of the monster. Monsters serve as metaphors for anxieties of aberration and innovation. Stephen Asma (2009) notes that monsters represent evil or moral transgression and each epoch, to speak with Michel Foucault, evidences a “particular type of monster” (2003, 66). Academic debates tend to explore how social and cultural threats come to be embodied in the figure of a monster and their actions literalize our deepest fears. Monsters in contemporary culture, however, have become are more humane than ever before. Monsters are strong, resilient, creative and sly creatures. Through their playful and invigorating energy they can be seen to disrupt and unsettle. They still cater to the appetite for horror, but they also encourage us to feel empathy. The encounter with a monster can enable us to stop, wonder and change our attitudes towards technology and our body and each other. This commentary article considers the use of the concepts of ‘monsters’ or ‘monstrosity’ in literature, contemporary research, culture and teaching contexts at the intersection of the Humanities and the Social Sciences

Post-supereruption recovery at Toba Caldera

Large calderas, or supervolcanoes, are sites of the most catastrophic and hazardous events on Earth, yet the temporal details of post-supereruption activity, or resurgence, remain largely unknown, limiting our ability to understand how supervolcanoes work and address their hazards. Toba Caldera, Indonesia, caused the greatest volcanic catastrophe of the last 100 kyr, climactically erupting ~74 ka. Since the supereruption, Toba has been in a state of resurgence but its magmatic and uplift history has remained unclear. Here we reveal that new 14 C, zircon U-Th crystallization and (U-Th)/He ages show resurgence commenced at 69.7±4.5 ka and continued until at least ~2.7 ka, progressing westward across the caldera, as reflected by post-caldera effusive lava eruptions and uplifted lake sediment. The major stratovolcano north of Toba, Sinabung, shows strong geochemical kinship with Toba, and zircons from recent eruption products suggest Toba's climactic magma reservoir extends beneath Sinabung and is being tapped during eruptions

‘Browning’ the cardiac and peri-vascular adipose tissues to modulate cardiovascular risk

Excess visceral adiposity, in particular that located adjacent to the heart and coronary arteries is associated with increased cardiovascular risk. In the pathophysiological state, dysfunctional adipose tissue secretes an array of factors modulating vascular function and driving atherogenesis. Conversely, brown and beige adipose tissues utilise glucose and lipids to generate heat and are associated with improved cardiometabolic health. The cardiac and thoracic perivascular adipose tissues are now understood to be composed of brown adipose tissue in the healthy state and undergo a brown-to-white transition i.e. during obesity which may be a driving factor of cardiovascular disease. In this review we discuss the risks of excess cardiac and vascular adiposity and potential mechanisms by which restoring the brown phenotype i.e. “re-browning” could potentially be achieved in clinically relevant populations