Long-term ambient air pollution and coronary atherosclerosis: Results from the Swedish SCAPIS study.

BACKGROUND AND AIMS: Despite firm evidence for an association between long-term ambient air pollution exposure and cardiovascular morbidity and mortality, results from epidemiological studies on the association between air pollution exposure and atherosclerosis have not been consistent. We investigated associations between long-term low-level air pollution exposure and coronary atherosclerosis. METHODS: We performed a cross-sectional analysis in the large Swedish CArdioPulmonary bioImaging Study (SCAPIS, n = 30 154), a random general population sample. Concentrations of total and locally emitted particulate matter <2.5 µm (PM2.5), <10 µm (PM10), and nitrogen oxides (NOx) at the residential address were modelled using high-resolution dispersion models. We estimated associations between air pollution exposures and segment involvement score (SIS), coronary artery calcification score (CACS), number of non-calcified plaques (NCP), and number of significant stenoses, using ordinal regression models extensively adjusted for potential confounders. RESULTS: Median 10-year average PM2.5 exposure was 6.2 µg/m3 (range 3.5-13.4 µg/m3). 51 % of participants were women and 51 % were never-smokers. None of the assessed pollutants were associated with a higher SIS or CACS. Exposure to PM2.5 was associated with NCP (adjusted OR 1.34, 95 % CI 1.13, 1.58, per 2.05 µg/m3). Associations with significant stenoses were inconsistent. CONCLUSIONS: In this large, middle-aged general population sample with low exposure levels, air pollution was not associated with measures of total burden of coronary atherosclerosis. However, PM2.5 appeared to be associated with a higher prevalence of non-calcified plaques. The results suggest that increased risk of early-stage atherosclerosis or rupture, but not increased total atherosclerotic burden, may be a pathway for long-term air pollution effects on cardiovascular disease.

Mixtures of long-term exposure to ambient air pollution, built environment and temperature and stroke incidence across Europe.

INTRODUCTION: The complex interplay of multiple environmental factors and cardiovascular has scarcely been studied. Within the EXPANSE project, we evaluated the association between long-term exposure to multiple environmental indices and stroke incidence across Europe. METHODS: Participants from three traditional adult cohorts (Germany, Netherlands and Sweden) and four administrative cohorts (Catalonia [region Spain], Rome [city-wide], Greece and Sweden [nationwide]) were followed until incident stroke, death, migration, loss of follow-up or study end. We estimated exposures at residential addresses from different exposure domains: air pollution (nitrogen dioxide (NO2), particulate matter < 2.5 µm (PM2.5), black carbon (BC), ozone), built environment (green/blue spaces, impervious surfaces) and meteorology (seasonal mean and standard deviation of temperatures). Associations between environmental exposures and stroke were estimated in single and multiple-exposure Cox proportional hazard models, and Principal Component (PC) Analyses derived prototypes for specific exposures domains. We carried out random effects meta-analyses by cohort type. RESULTS: In over 15 million participants, increased levels of NO2 and BC were associated with increased higher stroke incidence in both cohort types. Increased Normalized Difference Vegetation Index (NDVI) was associated with a lower stroke incidence in both cohort types, whereas an increase in impervious surface was associated with an increase in stroke incidence. The first PC of the air pollution domain (PM2.5, NO2 and BC) was associated with an increase in stroke incidence. For the built environment, higher levels of NDVI and lower levels of impervious surfaces were associated with a protective effect [%change in HR per 1 unit = -2.0 (95 %CI, -5.9;2.0) and -1.1(95 %CI, -2.0; -0.3) for traditional adult and administrative cohorts, respectively]. No clear patterns were observed for distance to blue spaces or temperature parameters. CONCLUSIONS: We observed increased HRs for stroke with exposure to PM2.5, NO2 and BC, lower levels of greenness and higher impervious surface in single and combined exposure models.

Effect of residential relocation on environmental exposures in European cohorts: An exposome-wide approach.

Residential relocation is increasingly used as a natural experiment in epidemiological studies to assess the health impact of changes in environmental exposures. Since the likelihood of relocation can be influenced by individual characteristics that also influence health, studies may be biased if the predictors of relocation are not appropriately accounted for. Using data from Swedish and Dutch adults (SDPP, AMIGO), and birth cohorts (BAMSE, PIAMA), we investigated factors associated with relocation and changes in multiple environmental exposures across life stages. We used logistic regression to identify baseline predictors of moving, including sociodemographic and household characteristics, health behaviors and health. We identified exposure clusters reflecting three domains of the urban exposome (air pollution, grey surface, and socioeconomic deprivation) and conducted multinomial logistic regression to identify predictors of exposome trajectories among movers. On average, 7 % of the participants relocated each year. Before relocating, movers were consistently exposed to higher levels of air pollution than non-movers. Predictors of moving differed between the adult and birth cohorts, highlighting the importance of life stages. In the adult cohorts, moving was associated with younger age, smoking, and lower education and was independent of cardio-respiratory health indicators (hypertension, BMI, asthma, COPD). Contrary to adult cohorts, higher parental education and household socioeconomic position were associated with a higher probability of relocation in birth cohorts, alongside being the first child and living in a multi-unit dwelling. Among movers in all cohorts, those with a higher socioeconomic position at baseline were more likely to move towards healthier levels of the urban exposome. We provide new insights into predictors of relocation and subsequent changes in multiple aspects of the urban exposome in four cohorts covering different life stages in Sweden and the Netherlands. These results inform strategies to limit bias due to residential self-selection in epidemiological studies using relocation as a natural experiment.

Air pollution exposure impairs lung function in infants.

AIM: To assess associations between air pollution exposure and infant lung function. METHODS: Healthy infants from Stockholm were recruited to two cohorts (n = 99 and n = 78). Infant spirometry included plethysmography and raised volume forced expiratory flows. In pooled analyses, lung function at ~6 months of age was related to time-weighted average air pollution levels at residential addresses from birth until the lung function test. The pollutants included particulate matter with an aerodynamic diameter < 10 µm (PM10 ) or <2.5 µm and nitrogen dioxide. RESULTS: There were significant inverse relations between air pollution exposure during infancy and forced expiratory volume at 0.5 s (FEV0.5 ) as well as forced vital capacity (FVC) for all pollutants. For example, the decline was 10.1 ml (95% confidence interval 1.3-18.8) and 10.3 ml (0.5-20.1) in FEV0.5 and FVC, respectively, for an interquartile increment of 5.3 µg/m3 in PM10 . Corresponding associations for minute ventilation and functional residual capacity were 43.3 ml/min (-9.75-96.3) and 0.84 ml (-4.14-5.82). CONCLUSIONS: Air pollution exposure was associated with impaired infant lung function measures related to airway calibre and lung volume, suggesting that comparatively low levels of air pollution negatively affect lung function in early life.

Production of a monolithic fuel cell stack with high power density.

The transportation sector is undergoing a technology shift from internal combustion engines to electric motors powered by secondary Li-based batteries. However, the limited range and long charging times of Li-ion batteries still hinder widespread adoption. This aspect is particularly true in the case of heavy freight and long-range transportation, where solid oxide fuel cells (SOFCs) offer an attractive alternative as they can provide high-efficiency and flexible fuel choices. However, the SOFC technology is mainly used for stationary applications owing to the high operating temperature, low volumetric power density and specific power, and poor robustness towards thermal cycling and mechanical vibrations of conventional ceramic-based cells. Here, we present a metal-based monolithic fuel cell design to overcome these issues. Cost-effective and scalable manufacturing processes are employed for fabrication, and only a single heat treatment is required, as opposed to multiple thermal treatments in conventional SOFC production. The design is optimised through three-dimensional multiphysics modelling, nanoparticle infiltration, and corrosion-mitigating treatments. The monolithic fuel cell stack shows a power density of 5.6 kW/L, thus, demonstrating the potential of SOFC technology for transport applications.

Ambient air pollution and cardiovascular diseases: An umbrella review of systematic reviews and meta-analyses.

The available evidence on the effects of ambient air pollution on cardiovascular diseases (CVDs) has increased substantially. In this umbrella review, we summarized the current epidemiological evidence from systematic reviews and meta-analyses linking ambient air pollution and CVDs, with a focus on geographical differences and vulnerable subpopulations. We performed a search strategy through multiple databases including articles between 2010 and 31 January 2021. We performed a quality assessment and evaluated the strength of evidence. Of the 56 included reviews, the most studied outcomes were stroke (22 reviews), all-cause CVD mortality, and morbidity (19). The strongest evidence was found between higher short- and long-term ambient air pollution exposure and all-cause CVD mortality and morbidity, stroke, blood pressure, and ischemic heart diseases (IHD). Short-term exposures to particulate matter <2.5 µm (PM2.5 ), <10 µm (PM10 ), and nitrogen oxides (NOx ) were consistently associated with increased risks of hypertension and triggering of myocardial infarction (MI), and stroke (fatal and nonfatal). Long-term exposures of PM2.5 were largely associated with increased risk of atherosclerosis, incident MI, hypertension, and incident stroke and stroke mortality. Few reviews evaluated other CVD outcomes including arrhythmias, atrial fibrillation, or heart failure but they generally reported positive statistical associations. Stronger associations were found in Asian countries and vulnerable subpopulations, especially among the elderly, cardiac patients, and people with higher weight status. Consistent with experimental data, this comprehensive umbrella review found strong evidence that higher levels of ambient air pollution increase the risk of CVDs, especially all-cause CVD mortality, stroke, and IHD. These results emphasize the importance of reducing the alarming levels of air pollution across the globe, especially in Asia, and among vulnerable subpopulations.

Living with a Severe Allergy: Lived Perspectives from Swedish Adolescents and their Parents.

BACKGROUND: During adolescence, the young person should gradually develop independence from his or her parents. However, having a chronic disease like a severe allergy may add stress and challenges beyond normal development and involves a struggle between adapting socially, feeling healthy, and managing the disease. OBJECTIVE: To describe experiences of living with a severe allergy from the perspective of adolescents and their parents. METHOD: A qualitative study with six focus group interviews were performed, two with adolescents and four with their parents (10 adolescents, 10-16 years old and 21 parents). The transcribed data were analyzed using systematic text condensation. RESULT: Four themes emerged: Feeling different (adolescents and parents), shift in responsibility (adolescents and parents), the importance of parents (only adolescents) and the importance of healthcare providers (only parents). The adolescents relied on their parents, while also taking responsibility for managing their disease. The parents expressed a need to protect their children; but they did not seem to be aware of the responsibility their children took. The parents highlighted the importance of support from healthcare providers but this was not mentioned by the adolescents. CONCLUSION: This study showed that both the adolescents and their parents stated that they took responsibility for managing the disease, but in different ways. For healthcare providers, this needs to be taken into account in order to support both adolescents and parents for self-management and shift in responsibilities which begins during adolescents.

Is moving to a greener or less green area followed by changes in physical activity?

Green areas might provide an inviting setting and thereby promote physical activity. The objective of this study was to determine whether moving to different green area surroundings was followed by changes of physical activity. Data from a large population-based cohort of adults in Stockholm County responding to surveys in 2010 and 2014 were analysed (n = 42611). Information about walking/cycling and exercise were self-reported and living area greenness data were satellite-derived (NDVI, Normalized Difference Vegetation Index). Multinomial logistic regression analyses were performed separately for changes in levels of walking/cycling and exercise (decrease, stable, increase). Greenness was defined as a change in NDVI quartile to less green, same, or greener. Odds ratio's (OR) with 95% confidence intervals (CI) were presented adjusted for gender, age, education and area-based income. Contrary to what we hypothesized, those moving to a greener area were more likely to decrease their levels of walking/cycling (OR = 1.42, CI = 1.28-1.58), whereas those moving to a less green area were more likely to increase their walking/cycling (OR = 1.26, CI = 1.13-1.41). Exercise behaviour showed another pattern, with people being more likely to decrease exercise both when moving to a greener (OR = 1.25, CI = 1.22-1.38) and to a less green area (OR = 1.22, CI = 1.09-1.36). Studying subpopulations based on sociodemographic characteristics did not aid to clarify our results. This cohort study with repeated measurements did not support the currently available cross-sectional studies showing a strong positive relation between greenness and physical activity. Nevertheless, our findings have shown spatial patterns related to green areas and physical activity which imply a need for place-specific health policies.

Global climate adaptation governance: Why is it not legally binding?

In the last decade, the United Nations Framework Convention on Climate Change has moved from a strong focus on mitigation to increasingly address adaptation. Climate change is no longer simply about reducing emissions, but also about enabling countries to deal with its impacts. Yet, most studies of the climate regime have focused on the evolution of mitigation governance and overlooked the increasing number of adaptation-related decisions and initiatives. In this article, we identify the body of rules and commitments on adaptation and suggest that there are more attempts to govern adaptation than many mitigation-focused accounts of the international climate regime would suggest. We then ask: to what degree are adaptation rules and commitments legalized in the United Nations Framework Convention on Climate Change? We examine the degree of precision and obligation of relevant decisions through an extensive analysis of primary United Nations Framework Convention on Climate Change documents, secondary literature on adaptation initiatives and institutions, interviews with climate change experts and negotiators, and participant observation at climate negotiations. Our analysis finds that adaptation governance is low in precision and obligation. We suggest that this is partly because adaptation is a contested global public good and because 'package deals' are made with mitigation commitments. This article makes a vital contribution to the global environmental politics literature given that adaptation governance is under-studied and poorly understood. It also contributes to the legalization literature by highlighting how contested global public goods may be governed globally, but with low obligation and precision.

"Healthcare seems to vary a lot": A focus group study among parents of children with severe allergy.

BACKGROUND: Living with an allergic disease has consequences for both affected children and their families. The aim of this qualitative study was to gain deeper knowledge of what life is like for families of children with severe allergic disease, in order to improve care and thereby reduce the consequences of living with a chronic disease. METHODS: Four focus group interviews were performed with Swedish parents of children, aged 6-11 and 12-16 years, with severe allergic disease (from one or more allergic conditions, such as food allergy/eczema/hay fever/asthma). The participants were attending a family support weekend. Interviews were analyzed with a qualitative method. RESULTS: Based on parental experiences, the following themes were presented in the analysis: limitations, control, injustices, and fear and anxiety. It was evident that the families lived isolated lives and experienced different kinds of limitations. Parents felt a need to have control of their child's everyday life and described a feeling of constantly being on guard. They also suggested that understanding of the child's allergies was lacking in preschool/school and that healthcare did not provide adequate support. They felt that the same care should be offered to children and families, no matter where they lived. CONCLUSIONS: Based on parental experiences, having a child with severe allergic disease implies a need to constantly be on guard. In order to improve the care of children with severe allergy and their families, a more person- and family-centered approach is needed.

Radixin inhibition decreases adult neural progenitor cell migration and proliferation in vitro and in vivo.

Neuronal progenitors capable of long distance migration are produced throughout life in the subventricular zone (SVZ). Migration from the SVZ is carried out along a well-defined pathway called the rostral migratory stream (RMS). Our recent finding of the specific expression of the cytoskeleton linker protein radixin in neuroblasts suggests a functional role for radixin in RMS migration. The ezrin-radixin-moesin (ERM) family of proteins is capable of regulating migration through interaction with the actin cytoskeleton and transmembrane proteins. The ERM proteins are differentially expressed in the RMS with radixin and moesin localized to neuroblasts, and ezrin expression confined to astrocytes of the glial tubes. Here, we inhibited radixin function using the quinocarmycin analog DX52-1 which resulted in reduced neuroblast migration in vitro, while glial migration remained unaltered. Furthermore, the morphology of neuroblasts was distorted resulting in a rounded shape with no or short polysialylated neural cell adhesion molecule positive processes. Intracerebroventricular infusion of the radixin inhibitor resulted in accumulation of neuroblasts in the anterior SVZ. Neuroblast chains were short and intermittently interrupted in the SVZ and considerably disorganized in the RMS. Moreover, we studied the proliferation activity in the RMS after radixin inhibition, since concentrated radixin expression has been demonstrated in the cleavage furrow of dividing cells, which indicates a role of radixin in cell division. Radixin inhibition decreased neuroblast proliferation, whereas the proliferation of other cells in the RMS was not affected. Our results demonstrate a significant role for radixin in neuroblast proliferation and migration.

Radixin expression in microglia after cortical stroke lesion.

Stroke induces extensive tissue remodeling, resulting in the activation of several cell types in the brain as well as recruitment of blood-borne leucocytes. Radixin is part of a cytoskeleton linker protein family with the ability to connect transmembrane proteins to the actin cytoskeleton, promoting cell functions involving a dynamic cytoskeleton such as morphological changes, cell division and migration which are common events of different cell types after stroke. In the healthy adult brain radixin is expressed in Olig2(+) cells throughout the brain and in neural progenitor cells in the subventricular zone. In the current study, we detected a 2.5 fold increase in the number of radixin positive cells in the peri-infarct cortex two weeks after the induction of cortical stroke by photothrombosis. Similarly, the number of Olig2(+) cells increased in the peri-infarct area after stroke; however, the number of radixin(+)/Olig2(+) cells was unchanged. Neural progenitor cells maintained radixin expression on their route to the infarct. More surprising however, was the expression of radixin in activated microglia in the peri-infarct cortex. Seventy percent of Iba1(+) cells expressed radixin after stroke, a population which was not present in the control brain. Furthermore, activation of radixin was predominantly detected in the peri-infarct region of oligodendrocyte progenitors and microglia. The specific location of radixin(+) cells in the peri-infarct region and in microglia suggests a role for radixin in microglial activation after stroke.

EGF-induced expansion of migratory cells in the rostral migratory stream.

The presence of neural stem cells in the adult brain is currently widely accepted and efforts are made to harness the regenerative potential of these cells. The dentate gyrus of the hippocampal formation, and the subventricular zone (SVZ) of the anterior lateral ventricles, are considered the main loci of adult neurogenesis. The rostral migratory stream (RMS) is the structure funneling SVZ progenitor cells through the forebrain to their final destination in the olfactory bulb. Moreover, extensive proliferation occurs in the RMS. Some evidence suggest the presence of stem cells in the RMS, but these cells are few and possibly of limited differentiation potential. We have recently demonstrated the specific expression of the cytoskeleton linker protein radixin in neuroblasts in the RMS and in oligodendrocyte progenitors throughout the brain. These cell populations are greatly altered after intracerebroventricular infusion of epidermal growth factor (EGF). In the current study we investigate the effect of EGF infusion on the rat RMS. We describe a specific increase of radixin(+)/Olig2(+) cells in the RMS. Negative for NG2 and CNPase, these radixin(+)/Olig2(+) cells are distinct from typical oligodendrocyte progenitors. The expanded Olig2(+) population responds rapidly to EGF and proliferates after only 24 hours along the entire RMS, suggesting local activation by EGF throughout the RMS rather than migration from the SVZ. In addition, the radixin(+)/Olig2(+) progenitors assemble in chains in vivo and migrate in chains in explant cultures, suggesting that they possess migratory properties within the RMS. In summary, these results provide insight into the adaptive capacity of the RMS and point to an additional stem cell source for future brain repair strategies.

Reconnecting to the biosphere.

Humanity has emerged as a major force in the operation of the biosphere, with a significant imprint on the Earth System, challenging social-ecological resilience. This new situation calls for a fundamental shift in perspectives, world views, and institutions. Human development and progress must be reconnected to the capacity of the biosphere and essential ecosystem services to be sustained. Governance challenges include a highly interconnected and faster world, cascading social-ecological interactions and planetary boundaries that create vulnerabilities but also opportunities for social-ecological change and transformation. Tipping points and thresholds highlight the importance of understanding and managing resilience. New modes of flexible governance are emerging. A central challenge is to reconnect these efforts to the changing preconditions for societal development as active stewards of the Earth System. We suggest that the Millennium Development Goals need to be reframed in such a planetary stewardship context combined with a call for a new social contract on global sustainability. The ongoing mind shift in human relations with Earth and its boundaries provides exciting opportunities for societal development in collaboration with the biosphere--a global sustainability agenda for humanity.

The anthropocene: from global change to planetary stewardship.

Over the past century, the total material wealth of humanity has been enhanced. However, in the twenty-first century, we face scarcity in critical resources, the degradation of ecosystem services, and the erosion of the planet's capability to absorb our wastes. Equity issues remain stubbornly difficult to solve. This situation is novel in its speed, its global scale and its threat to the resilience of the Earth System. The advent of the Anthropence, the time interval in which human activities now rival global geophysical processes, suggests that we need to fundamentally alter our relationship with the planet we inhabit. Many approaches could be adopted, ranging from geoengineering solutions that purposefully manipulate parts of the Earth System to becoming active stewards of our own life support system. The Anthropocene is a reminder that the Holocene, during which complex human societies have developed, has been a stable, accommodating environment and is the only state of the Earth System that we know for sure can support contemporary society. The need to achieve effective planetary stewardship is urgent. As we go further into the Anthropocene, we risk driving the Earth System onto a trajectory toward more hostile states from which we cannot easily return.

Effect of levetiracetam on hippocampal protein expression and cell proliferation in rats.

PURPOSE: Levetiracetam (LEV) is a broad-spectrum antiepileptic drug (AED) with possibly also antiepileptogenic properties. LEV has a specific binding site in the central nervous system and reduces brain excitability; however, the precise mechanism of action (MOA) of LEV remains unclear. To further unravel the potential MOA pathways of LEV we investigated altered protein expression and cell proliferation in rat hippocampal tissue during LEV administration. METHODS: On day 1 of the experiment, rats were randomly assigned to a treatment group (LEV, 600 mg/kg/day, n=10) and a control group (saline, n=10). On days 2 and 3 rats were injected with bromodeoxyuridine (50 mg/kg, i.p., BID). After 7 days of treatment rats were killed and their brains removed. The right hemisphere was processed for histochemistry. The left hippocampus was dissected and frozen for proteomic analysis. Proteins were extracted from the tissue and two-dimensional gel electrophoresis was performed. RESULTS: Treatment with LEV did not influence hippocampal cell proliferation. Multivariate analysis of differential protein expression, determined by proteomic analysis, revealed a significant clustering of control and treatment groups. The proteins which most contribute to the difference between groups were identified with mass spectrometry. The identified proteins were either involved in cytoskeleton, energy metabolism, neurotransmission, signal transduction, myelinization or stress response. DISCUSSION: LEV does not affect hippocampal cell proliferation but has significant effects on the expression of proteins involved in a variety of physiological processes involved in physiological processes that play an important role in the currently identified MOAs of AEDs such as neurotransmission and signal transduction.

Interplaying factors for the formation of photoswitchable beta-hairpins: the advantage of a flexible switch.

A series of peptidomimetics intended to promote the beta-hairpin motif have been studied. Structural variations include a turn region with and without a photoswitchable chromophore, and strands with amino acid side chains supporting various degrees of interstrand interactions for hairpin stabilisation. The propensity of the compounds to form beta-hairpins was evaluated experimentally by NMR spectroscopy, translational self-diffusion studies and CD spectroscopy. In the presence of hairpin stabilising interstrand interactions, the structurally flexible stilbene chromophore appeared to be well compatible with the imposed secondary structure.

Chemistry and folding of photomodulable peptides--stilbene and thioaurone-type candidates for conformational switches.

Optimized synthetic strategies for the preparation of photoswitchable molecular scaffolds based on stilbene or on thioaurone chromophores and their conformationally directing properties, as studied by computations and by NMR spectroscopy, are addressed. For the stilbene peptidomimetics 1, 2 and 3, the length of connecting linkers between the chromophore and the peptide strands was varied, resulting in photochromic dipeptidomimetics with various flexibility. Building blocks of higher rigidity, based on para-substituted thioaurone (4 and 6) and meta-substituted thioaurone chromophores (5 and 7) are shown to have a stronger conformationally directing effect. Design, synthesis, theoretical and experimental conformational analyses are presented.