Population growth, urbanisation and climate change represent significant pressures on urban water resources, requiring water managers to consider a wider array of management options that account for ...economic, social and environmental factors. The Dynamic Urban Water Simulation Model (DUWSiM) developed in this study links urban water balance concepts with the land use dynamics model MOLAND and the climate model LARS-WG, providing a platform for long term planning of urban water supply and water demand by analysing the effects of urbanisation scenarios and climatic changes on the urban water cycle. Based on potential urbanisation scenarios and their effects on a city's water cycle, DUWSiM provides the functionality for assessing the feasibility of centralised and decentralised water supply and water demand management options based on forecasted water demand, stormwater and wastewater generation, whole life cost and energy and potential for water recycling. DUWSiM has been tested using data from Dublin, the capital of Ireland, and it has been shown that the model is able to satisfactorily predict water demand and stormwater runoff.
Display omitted
•An urban water balance model linked to a land use dynamics model is detailed.•DUWSiM is applied to Dublin, Ireland.•DUWSiM can satisfactorily predict water demand and stormwater runoff.
The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) regulates metabolic genes in skeletal muscle and contributes to the response of muscle to ...exercise. Muscle PGC-1α transgenic expression and exercise both increase the expression of thermogenic genes within white adipose. How the PGC-1α-mediated response to exercise in muscle conveys signals to other tissues remains incompletely defined. We employed a metabolomic approach to examine metabolites secreted from myocytes with forced expression of PGC-1α, and identified β-aminoisobutyric acid (BAIBA) as a small molecule myokine. BAIBA increases the expression of brown adipocyte-specific genes in white adipocytes and β-oxidation in hepatocytes both in vitro and in vivo through a PPARα-mediated mechanism, induces a brown adipose-like phenotype in human pluripotent stem cells, and improves glucose homeostasis in mice. In humans, plasma BAIBA concentrations are increased with exercise and inversely associated with metabolic risk factors. BAIBA may thus contribute to exercise-induced protection from metabolic diseases.
Display omitted
•β-aminoisobutyric acid (BAIBA) is secreted from PGC-1α-expressing myocytes•BAIBA activates the thermogenic program in white adipocytes via PPARα•Circulating BAIBA levels in mice and humans are increased with exercise•BAIBA is inversely correlated with cardiometabolic risk factors in humans
Roberts et al. use metabolic profiling to identify β-aminoisobutyric acid (BAIBA) as a PGC-1α-responsive small molecule myokine that induces β-oxidation in hepatocytes and the browning of white adipose tissue. In humans, plasma BAIBA concentrations are increased with exercise and inversely associated with metabolic risk factors.
Summary
Sleep and circadian alterations are amongst the very first symptoms experienced in Parkinson's disease, and sleep alterations are present in the majority of patients with overt clinical ...manifestation of Parkinson's disease. However, the magnitude of sleep and circadian dysfunction in Parkinson's disease, and its influence on the pathophysiology of Parkinson's disease remains often unclear and a matter of debate. In particular, the confounding influences of dopaminergic therapy on sleep and circadian dysfunction are a major challenge, and need to be more carefully addressed in clinical studies. The scope of this narrative review is to summarise the current knowledge around both sleep and circadian alterations in Parkinson's disease. We provide an overview on the frequency of excessive daytime sleepiness, insomnia, restless legs, obstructive apnea and nocturia in Parkinson's disease, as well as addressing sleep structure, rapid eye movement sleep behaviour disorder and circadian features in Parkinson's disease. Sleep and circadian disorders have been linked to pathological conditions that are often co‐morbid in Parkinson's disease, including cognitive decline, memory impairment and neurodegeneration. Therefore, targeting sleep and circadian alterations could be one of the earliest and most promising opportunities to slow disease progression. We hope that this review will contribute to advance the discussion and inform new research efforts to progress our knowledge in this field.
Abstract
Aims
To examine the metabolic adaptation to an 80-day exercise intervention in healthy young male adults where lifestyle factors such as diet, sleep, and physical activities are controlled.
...Methods and results
This study involved cross-sectional analysis before and after an 80-day aerobic and strength exercise intervention in 52 young, adult, male, newly enlisted soldiers in 2015. Plasma metabolomic analyses were performed using liquid chromatography, tandem mass spectrometry. Data analyses were performed between March and August 2019. We analysed changes in metabolomic profiles at the end of an 80-day exercise intervention compared to baseline, and the association of metabolite changes with changes in clinical parameters. Global metabolism was dramatically shifted after the exercise training programme. Fatty acids and ketone body substrates, key fuels used by exercising muscle, were dramatically decreased in plasma in response to increased aerobic fitness. There were highly significant changes across many classes of metabolic substrates including lipids, ketone bodies, arginine metabolites, endocannabinoids, nucleotides, markers of proteolysis, products of fatty acid oxidation, microbiome-derived metabolites, markers of redox stress, and substrates of coagulation. For statistical analyses, a paired t-test was used and Bonferroni-adjusted P-value of <0.0004 was considered to be statistically significant. The metabolite dimethylguanidino valeric acid (DMGV) (recently shown to predict lack of metabolic response to exercise) tracked maladaptive metabolic changes to exercise; those with increases in DMGV levels had increases in several cardiovascular risk factors; changes in DMGV levels were significantly positively correlated with increases in body fat (P = 0.049), total and LDL cholesterol (P = 0.003 and P = 0.007), and systolic blood pressure (P = 0.006). This study was approved by the Departments of Defence and Veterans’ Affairs Human Research Ethics Committee and written informed consent was obtained from each subject.
Conclusion
For the first time, the true magnitude and extent of metabolic adaptation to chronic exercise training are revealed in this carefully designed study, which can be leveraged for novel therapeutic strategies in cardiometabolic disease. Extending the recent report of DMGV’s predictive utility in sedentary, overweight individuals, we found that it is also a useful marker of poor metabolic response to exercise in young, healthy, fit males.
•T90 of infectious SARS-CoV-2 at 4°C was 3.8 and 2.2 days in river and seawater•T90 of infectious SARS-CoV-2 at 20°C was 2.3 and 1.1 days in river and seawater•SARS-CoV-2 RNA is more stable than the ...infectious particle in river and seawater•Infectious MS2 persisted longer than infectious SARS-CoV-2 in aquatic environments•The decay rate of MS2 and PMMoV RNA differed from the decay rate of SARS-CoV-2 RNA
The introduction of SARS-CoV-2 containing human stool and sewage into water bodies may raise public health concerns. However, assessment of public health risks by faecally contaminated water is limited by a lack of knowledge regarding the persistence of infectious SARS-CoV-2 in water. In the present study the decay rates of viable infectious SARS-CoV-2 and SARS-CoV-2 RNA were determined in river and seawater at 4 and 20°C. These decay rates were compared to S. typhimurium bacteriophage MS2 and pepper mild mottle virus (PMMoV). Persistence of viable SARS-CoV-2 was temperature dependent, remaining infectious for significantly longer periods of time in both freshwater and seawater at 4°C than at 20°C. T90 for infectious SARS-CoV-2 in river water was 2.3 days and 3.8 days at 20°C and 4°C, respectively. The T90 values were 1.1 days and 2.2 days in seawater at 20°C and 4°C, respectively. In contrast to the rapid inactivation of infectious SARS-CoV-2 in river and sea water, viral RNA was relatively stable. The RNA decay rates were increased in non-sterilised river and seawater, presumably due to the presence of microbiota. The decay rates of infectious MS2, MS2 RNA and PMMoV RNA differed significantly from the decay rate of SARS-CoV-2 RNA, suggesting that their use as surrogate markers for the persistence of SARS-CoV-2 in the environment is limited.
Display omitted
Aims
Identification and management of the Standard Modifiable Cardiovascular Risk Factors (SMuRFs; hypercholesterolaemia, hypertension, diabetes and smoking) has substantially improved cardiovascular ...disease outcomes. However, cardiovascular disease remains the leading cause of death worldwide. Suspecting an evolving pattern of risk factor profiles in the ST elevation myocardial infarction (STEMI) population with the improvements in primary care, we hypothesized that the proportion of ‘SMuRFless’ STEMI patients may have increased.
Methods/results
We performed a single centre retrospective study of consecutive STEMI patients presenting from January 2006 to December 2014. Over the study period 132/695 (25%) STEMI patients had 0 SMuRFs, a proportion that did not significantly change with age, gender or family history. The proportion of STEMI patients who were SMuRFless in 2006 was 11%, which increased to 27% by 2014 (odds ratio 1.12 per year, 95% confidence interval: 1.04–1.22). The proportion of patients with hypercholesterolaemia decreased (odds ratio 0.92, 95% confidence interval 0.86–0.98), as did the proportion of current smokers (odds ratio 0.93, 95% confidence interval 0.86–0.99), with no significant change in the proportion of patients with diabetes and hypertension. SMuRF status was not associated with extent of coronary disease; in-hospital outcomes, or discharge prescribing patterns.
Conclusion
The proportion of STEMI patients with STEMI poorly explained by SMuRFs is high, and is significantly increasing. This highlights the need for bold approaches to discover new mechanisms and markers for early identification of these patients, as well as to understand the outcomes and develop new targeted therapies.
Cerebrovascular disease can complicate head and neck radiotherapy and result in transient ischemic attack and ischemic stroke. Although the incidence of radiation vasculopathy is predicted to rise ...with improvements in median cancer survival, the pathogenesis, natural history, and management of the disease are ill defined.
We examined studies on the epidemiology, imaging, pathogenesis, and management of medium- and large-artery intra- and extra-cranial disease after head and neck radiotherapy. Controlled prospective trials and larger retrospective trials from the last 30 years were prioritized.
The relative risk of transient ischemic attack or ischemic stroke is at least doubled by head and neck radiotherapy. Chronic radiation vasculopathy affecting medium and large intra- and extra-cranial arteries is characterized by increasing rates of hemodynamically significant stenosis with time from radiotherapy. Disease expression is the likely consequence of the combined radiation insult to the intima-media (accelerating atherosclerosis) and to the adventitia (injuring the vasa vasorum). Optimal medical treatment is not established. Carotid endarterectomy is confounded by the need to operate across scarred tissue planes, whereas carotid stenting procedures have resulted in high restenosis rates.
Head and neck radiotherapy significantly increases the risk of transient ischemic attack and ischemic stroke. Evidence-based guidelines for the management of asymptomatic and symptomatic (medium- and large-artery) radiation vasculopathy are lacking. Long-term prospective studies remain a priority, as the incidence of the problem is anticipated to rise with improvements in postradiotherapy patient survival.
Genome-wide association studies (GWAS) have highlighted a large number of genetic variants with potential disease association, but functional analysis remains a challenge. Here we describe an ...approach to functionally validate identified variants through differentiation of induced pluripotent stem cells (iPSCs) to study cellular pathophysiology. We collected peripheral blood cells from Framingham Heart Study participants and reprogrammed them to iPSCs. We then differentiated 68 iPSC lines into hepatocytes and adipocytes to investigate the effect of the 1p13 rs12740374 variant on cardiometabolic disease phenotypes via transcriptomics and metabolomic signatures. We observed a clear association between rs12740374 and lipid accumulation and gene expression in differentiated hepatocytes, in particular, expression of SORT1, CELSR2, and PSRC1, consistent with previous analyses of this variant using other approaches. Initial investigation of additional SNPs also highlighted correlations with gene expression. These findings suggest that iPSC-based population studies hold promise as tools for the functional validation of GWAS variants.
Display omitted
•Peripheral blood cells from study participants were reprogrammed to iPSCs•iPSC lines differentiated into white adipocytes and hepatocyte-like cells•Transcriptomic and metabolomic profiling highlights cellular phenotypes•Differentiated cells reproduce expression of variation-associated loci
As part of the NHLBI NextGen consortium, Warren et al. show that analyzing the cellular pathophysiology of cells differentiated from multiple lines of an iPSC library is a promising complementary approach in the functional analysis of GWAS variants.
Natural biostimulants, such as seaweed extracts, can stimulate plant growth and development in both model and crop plants. Due to the increasing demands for their use in agriculture, it is crucial to ...ensure the sustainability of the sources from which they are produced. Furthermore, some seaweed extracts were recently shown to prime and protect from adverse environmental factors such as drought, salinity and extreme temperatures, as well as from oxidative stress. The molecular mode of action of these biostimulants has still not been fully elucidated, but there has been significant progress in this direction in the last years. Firstly, this review examines the sustainability aspects of harvesting seaweed resources as raw materials for manufacturing biostimulants and provides an overview of the regulatory landscape pertaining to seaweed-based biostimulants. The review then summarises the recent advances in determining the genetic and molecular mechanisms activated by seaweed-based biostimulants, their influence on transcriptome reconfiguration, metabolite adjustment, and ultimately stress protection, improved nutrient uptake, and plant growth and performance. This knowledge is important for deciphering the intricate stress signalling network modulated by seaweed-based biostimulants and can aid in designing molecular priming technologies for crop improvement.
PDF
