Stable isotope food-web analysis and mercury biomagnification in polar bears ( Ursus maritimus )

Mercury (Hg) biomagnification occurs in many ecosystems, resulting in a greater potential for toxicological effects in higher-level trophic feeders. However, Hg transport pathways through different food-web channels are not well known, particularly in high-latitude systems affected by the atmospheric Hg deposition associated with snow and ice. Here, we report on stable carbon and nitrogen isotope ratios, and Hg concentrations, determined for 26, late 19th and early 20th century, polar bear ( Ursus maritimus ) hair specimens, collected from catalogued museum collections. These data elucidate relationships between the high-latitude marine food-web structure and Hg concentrations in polar bears. The carbon isotope compositions of polar bear hairs suggest that polar bears derive nutrition from coupled food-web channels, based in pelagic and sympagic primary producers, whereas the nitrogen isotope compositions indicate that polar bears occupy > fourth-level trophic positions. Our results show a positive correlation between polar bear hair Hg concentrations and δ 15 N. Interpretation of the stable isotope data in combination with Hg concentrations tentatively suggests that polar bears participating in predominantly pelagic food webs exhibit higher mercury concentrations than polar bears participating in predominantly sympagic food webs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73930/1/j.1751-8369.2009.00114.x.pd

Psychology and aggression

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68264/2/10.1177_002200275900300301.pd

Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation.

Thyroid dysfunction is an important public health problem, which affects 10% of the general population and increases the risk of cardiovascular morbidity and mortality. Many aspects of thyroid hormone regulation have only partly been elucidated, including its transport, metabolism, and genetic determinants. Here we report a large meta-analysis of genome-wide association studies for thyroid function and dysfunction, testing 8 million genetic variants in up to 72,167 individuals. One-hundred-and-nine independent genetic variants are associated with these traits. A genetic risk score, calculated to assess their combined effects on clinical end points, shows significant associations with increased risk of both overt (Graves' disease) and subclinical thyroid disease, as well as clinical complications. By functional follow-up on selected signals, we identify a novel thyroid hormone transporter (SLC17A4) and a metabolizing enzyme (AADAT). Together, these results provide new knowledge about thyroid hormone physiology and disease, opening new possibilities for therapeutic targets

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Research priorities in prehabilitation for patients undergoing cancer surgery: an international Delphi study

Background Recently, the number of prehabilitation trials has increased significantly. The identification of key research priorities is vital in guiding future research directions. Thus, the aim of this collaborative study was to define key research priorities in prehabilitation for patients undergoing cancer surgery. Methods The Delphi methodology was implemented over three rounds of surveys distributed to prehabilitation experts from across multiple specialties, tumour streams and countries via a secure online platform. In the first round, participants were asked to provide baseline demographics and to identify five top prehabilitation research priorities. In successive rounds, participants were asked to rank research priorities on a 5-point Likert scale. Consensus was considered if > 70% of participants indicated agreement on each research priority. Results A total of 165 prehabilitation experts participated, including medical doctors, physiotherapists, dieticians, nurses, and academics across four continents. The first round identified 446 research priorities, collated within 75 unique research questions. Over two successive rounds, a list of 10 research priorities reached international consensus of importance. These included the efficacy of prehabilitation on varied postoperative outcomes, benefit to specific patient groups, ideal programme composition, cost efficacy, enhancing compliance and adherence, effect during neoadjuvant therapies, and modes of delivery. Conclusions This collaborative international study identified the top 10 research priorities in prehabilitation for patients undergoing cancer surgery. The identified priorities inform research strategies, provide future directions for prehabilitation research, support resource allocation and enhance the prehabilitation evidence base in cancer patients undergoing surgery

Vascular Remodeling in Health and Disease

The term vascular remodeling is commonly used to define the structural changes in blood vessel geometry that occur in response to long-term physiologic alterations in blood flow or in response to vessel wall injury brought about by trauma or underlying cardiovascular diseases.1, 2, 3, 4 The process of remodeling, which begins as an adaptive response to long-term hemodynamic alterations such as elevated shear stress or increased intravascular pressure, may eventually become maladaptive, leading to impaired vascular function. The vascular endothelium, owing to its location lining the lumen of blood vessels, plays a pivotal role in regulation of all aspects of vascular function and homeostasis.5 Thus, not surprisingly, endothelial dysfunction has been recognized as the harbinger of all major cardiovascular diseases such as hypertension, atherosclerosis, and diabetes.6, 7, 8 The endothelium elaborates a variety of substances that influence vascular tone and protect the vessel wall against inflammatory cell adhesion, thrombus formation, and vascular cell proliferation.8, 9, 10 Among the primary biologic mediators emanating from the endothelium is nitric oxide (NO) and the arachidonic acid metabolite prostacyclin [prostaglandin I2 (PGI2)], which exert powerful vasodilatory, antiadhesive, and antiproliferative effects in the vessel wall

INTRAMYOCELLULAR LIPID CONTENT IN FAMILIAL LONGEVITY: THE LEIDEN LONGEVITY STUDY

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

A critical appraisal of existing concepts for the grouping of nanomaterials

AbstractThe grouping of substances serves to streamline testing for regulatory purposes. General grouping approaches for chemicals have been implemented in, e.g., the EU chemicals regulation. While specific regulatory frameworks for the grouping of nanomaterials are unavailable, this topic is addressed in different publications, and preliminary guidance is provided in the context of substance-related legislation or the occupational setting. The European Centre for Ecotoxicology and Toxicology of Chemicals Task Force on the Grouping of Nanomaterials reviewed available concepts for the grouping of nanomaterials for human health risk assessment. In their broad conceptual design, the evaluated approaches are consistent or complement each other. All go beyond the determination of mere structure–activity relationships and are founded on different aspects of the nanomaterial life cycle. These include the NM’s material properties and biophysical interactions, specific types of use and exposure, uptake and kinetics, and possible early and apical biological effects. None of the evaluated grouping concepts fully take into account all of these aspects. Subsequent work of the Task Force will aim at combining the available concepts into a comprehensive ‘multiple perspective’ framework for the grouping of nanomaterials that will address all of the mentioned aspects of their life cycles