LXRα phosphorylation in cardiometabolic disease: insight from mouse models

Posttranslational modifications, such as phosphorylation, are a powerful means by which the activity and function of nuclear receptors such as LXRα can be altered. However, despite the established importance of nuclear receptors in maintaining metabolic homeostasis, our understanding of how phosphorylation affects metabolic diseases is limited. The physiological consequences of LXRα phosphorylation have, until recently, been studied only in vitro or nonspecifically in animal models by pharmacologically or genetically altering the enzymes enhancing or inhibiting these modifications. Here we review recent reports on the physiological consequences of modifying LXRα phosphorylation at serine 196 (S196) in cardiometabolic disease, including nonalcoholic fatty liver disease, atherosclerosis, and obesity. A unifying theme from these studies is that LXRα S196 phosphorylation rewires the LXR-modulated transcriptome, which in turn alters physiological response to environmental signals, and that this is largely distinct from the LXR-ligand–dependent action

A global perspective on the challenges and opportunities in learning about rheumatic and musculoskeletal diseases in undergraduate medical education : White paper by the World Forum on Rheumatic and Musculoskeletal Diseases (WFRMD).

Rheumatic and musculoskeletal diseases (RMDs) encompass a spectrum of degenerative, inflammatory conditions predominantly affecting the joints. They are a leading cause of disability worldwide and an enormous socioeconomic burden. However, worldwide deficiencies in adult and paediatric RMD knowledge among medical school graduates and primary care physicians (PCPs) persist. In October 2017, the World Forum on Rheumatic and Musculoskeletal Diseases (WFRMD), an international think tank of RMD and related experts, met to discuss key challenges and opportunities in undergraduate RMD education. Topics included needs analysis, curriculum content, interprofessional education, teaching and learning methods, implementation, assessment and course evaluation and professional formation/career development, which formed a framework for this white paper. We highlight a need for all medical graduates to attain a basic level of RMD knowledge and competency to enable them to confidently diagnose, treat/manage or refer patients. The importance of attracting more medical students to a career in rheumatology, and the indisputable value of integrated, multidisciplinary and multiprofessional care are also discussed. We conclude that RMD teaching for the future will need to address what is being taught, but also where, why and to whom, to ensure that healthcare providers deliver the best patient care possible in their local settin

Individualization as driving force of clustering phenomena in humans

One of the most intriguing dynamics in biological systems is the emergence of clustering, the self-organization into separated agglomerations of individuals. Several theories have been developed to explain clustering in, for instance, multi-cellular organisms, ant colonies, bee hives, flocks of birds, schools of fish, and animal herds. A persistent puzzle, however, is clustering of opinions in human populations. The puzzle is particularly pressing if opinions vary continuously, such as the degree to which citizens are in favor of or against a vaccination program. Existing opinion formation models suggest that "monoculture" is unavoidable in the long run, unless subsets of the population are perfectly separated from each other. Yet, social diversity is a robust empirical phenomenon, although perfect separation is hardly possible in an increasingly connected world. Considering randomness did not overcome the theoretical shortcomings so far. Small perturbations of individual opinions trigger social influence cascades that inevitably lead to monoculture, while larger noise disrupts opinion clusters and results in rampant individualism without any social structure. Our solution of the puzzle builds on recent empirical research, combining the integrative tendencies of social influence with the disintegrative effects of individualization. A key element of the new computational model is an adaptive kind of noise. We conduct simulation experiments to demonstrate that with this kind of noise, a third phase besides individualism and monoculture becomes possible, characterized by the formation of metastable clusters with diversity between and consensus within clusters. When clusters are small, individualization tendencies are too weak to prohibit a fusion of clusters. When clusters grow too large, however, individualization increases in strength, which promotes their splitting.Comment: 12 pages, 4 figure

Efficacy of tranexamic acid in reducing blood loss in posterior lumbar spine surgery for degenerative spinal stenosis with instability: a retrospective case control study

<p>Abstract</p> <p>Background</p> <p>Degenerative spinal stenosis and instability requiring multilevel spine surgery has been associated with large blood losses. Factors that affect perioperative blood loss include time of surgery, surgical procedure, patient height, combined anterior/posterior approaches, number of levels fused, blood salvage techniques, and the use of anti-fibrinolytic medications. This study was done to evaluate the efficacy of tranexamic acid in reducing blood loss in spine surgery.</p> <p>Methods</p> <p>This retrospective case control study includes 97 patients who had to undergo surgery because of degenerative lumbar spinal stenosis and instability. All operations included spinal decompression, interbody fusion and posterior instrumentation (4-5 segments). Forty-six patients received 1 g tranexamic acid intravenous, preoperative and six hours and twelve hours postoperative; 51 patients without tranexamic acid administration were evaluated as a control group. Based on the records, the intra- and postoperative blood losses were measured by evaluating the drainage and cell saver systems 6, 12 and 24 hours post operation. Additionally, hemoglobin concentration and platelet concentration were reviewed. Furthermore, the number of red cell transfusions given and complications associated with tranexamic acid were assessed.</p> <p>Results</p> <p>The postoperative hemoglobin concentration demonstrated a statistically significant difference with a p value of 0.0130 showing superiority for tranexamic acid use (tranexamic acid group: 11.08 g/dl, SD: 1.68; control group: 10.29 g/dl, SD: 1.39). The intraoperative cell saver volume and drainage volume after 24 h demonstrated a significant difference as well, which indicates a less blood loss in the tranexamic acid group than the control group. The postoperative drainage volume at12 hours showed no significant differences; nor did the platelet concentration Allogenic blood transfusion (two red cell units) was needed for eight patients in the tranexamic acid group and nine in the control group because of postoperative anemia. Complications associated with the administration of tranexamic acid, e.g. renal failure, deep vein thrombosis or pulmonary embolism did not occur.</p> <p>Conclusions</p> <p>This study suggests a less blood loss when administering tranexamic acid in posterior lumbar spine surgery as demonstrated by the higher postoperative hemoglobin concentration and the less blood loss. But given the relatively small volume of blood loss in the patients of this study it is underpowered to show a difference in transfusion rates.</p

SPECULOOS exoplanet search and its prototype on TRAPPIST

One of the most significant goals of modern science is establishing whether life exists around other suns. The most direct path towards its achievement is the detection and atmospheric characterization of terrestrial exoplanets with potentially habitable surface conditions. The nearest ultracool dwarfs (UCDs), i.e. very-low-mass stars and brown dwarfs with effective temperatures lower than 2700 K, represent a unique opportunity to reach this goal within the next decade. The potential of the transit method for detecting potentially habitable Earth-sized planets around these objects is drastically increased compared to Earth-Sun analogs. Furthermore, only a terrestrial planet transiting a nearby UCD would be amenable for a thorough atmospheric characterization, including the search for possible biosignatures, with near-future facilities such as the James Webb Space Telescope. In this chapter, we first describe the physical properties of UCDs as well as the unique potential they offer for the detection of potentially habitable Earth-sized planets suitable for atmospheric characterization. Then, we present the SPECULOOS ground-based transit survey, that will search for Earth-sized planets transiting the nearest UCDs, as well as its prototype survey on the TRAPPIST telescopes. We conclude by discussing the prospects offered by the recent detection by this prototype survey of a system of seven temperate Earth-sized planets transiting a nearby UCD, TRAPPIST-1.Comment: Submitted as a chapter in the "Handbook of Exoplanets" (editors: H. Deeg & J.A. Belmonte; Section Editor: N. Narita). 16 pages, 4 figure

Anti-fouling graphene-based membranes for effective water desalination

© 2018 The Author(s). The inability of membranes to handle a wide spectrum of pollutants is an important unsolved problem for water treatment. Here we demonstrate water desalination via a membrane distillation process using a graphene membrane where water permeation is enabled by nanochannels of multilayer, mismatched, partially overlapping graphene grains. Graphene films derived from renewable oil exhibit significantly superior retention of water vapour flux and salt rejection rates, and a superior antifouling capability under a mixture of saline water containing contaminants such as oils and surfactants, compared to commercial distillation membranes. Moreover, real-world applicability of our membrane is demonstrated by processing sea water from Sydney Harbour over 72 h with macroscale membrane size of 4 cm 2 , processing ~0.5 L per day. Numerical simulations show that the channels between the mismatched grains serve as an effective water permeation route. Our research will pave the way for large-scale graphene-based antifouling membranes for diverse water treatment applications

Testing in the incremental design and development of complex products

Testing is an important aspect of design and development which consumes significant time and resource in many companies. However, it has received less research attention than many other activities in product development, and especially, very few publications report empirical studies of engineering testing. Such studies are needed to establish the importance of testing and inform the development of pragmatic support methods. This paper combines insights from literature study with findings from three empirical studies of testing. The case studies concern incrementally developed complex products in the automotive domain. A description of testing practice as observed in these studies is provided, confirming that testing activities are used for multiple purposes depending on the context, and are intertwined with design from start to finish of the development process, not done after it as many models depict. Descriptive process models are developed to indicate some of the key insights, and opportunities for further research are suggested

Plasma coenzyme Q10 status is impaired in selected genetic conditions.

Identifying diseases displaying chronic low plasma Coenzyme Q10 (CoQ) values may be important to prevent possible cardiovascular dysfunction. The aim of this study was to retrospectively evaluate plasma CoQ concentrations in a large cohort of pediatric and young adult patients. We evaluated plasma CoQ values in 597 individuals (age range 1 month to 43 years, average 11 years), studied during the period 2005-2016. Patients were classified into 6 different groups: control group of healthy participants, phenylketonuric patients (PKU), patients with mucopolysaccharidoses (MPS), patients with other inborn errors of metabolism (IEM), patients with neurogenetic diseases, and individuals with neurological diseases with no genetic diagnosis. Plasma total CoQ was measured by reverse-phase high-performance liquid chromatography with electrochemical detection and ultraviolet detection at 275 nm. ANOVA with Bonferroni correction showed that plasma CoQ values were significantly lower in the PKU and MPS groups than in controls and neurological patients. The IEM group showed intermediate values that were not significantly different from those of the controls. In PKU patients, the Chi-Square test showed a significant association between having low plasma CoQ values and being classic PKU patients. The percentage of neurogenetic and other neurological patients with low CoQ values was low (below 8%). In conclusión, plasma CoQ monitoring in selected groups of patients with different IEM (especially in PKU and MPS patients, but also in IEM under protein-restricted diets) seems advisable to prevent the possibility of a chronic blood CoQ suboptimal status in such groups of patients

Inter-hemispheric EEG coherence analysis in Parkinson's disease : Assessing brain activity during emotion processing

Parkinson’s disease (PD) is not only characterized by its prominent motor symptoms but also associated with disturbances in cognitive and emotional functioning. The objective of the present study was to investigate the influence of emotion processing on inter-hemispheric electroencephalography (EEG) coherence in PD. Multimodal emotional stimuli (happiness, sadness, fear, anger, surprise, and disgust) were presented to 20 PD patients and 30 age-, education level-, and gender-matched healthy controls (HC) while EEG was recorded. Inter-hemispheric coherence was computed from seven homologous EEG electrode pairs (AF3–AF4, F7–F8, F3–F4, FC5–FC6, T7–T8, P7–P8, and O1–O2) for delta, theta, alpha, beta, and gamma frequency bands. In addition, subjective ratings were obtained for a representative of emotional stimuli. Interhemispherically, PD patients showed significantly lower coherence in theta, alpha, beta, and gamma frequency bands than HC during emotion processing. No significant changes were found in the delta frequency band coherence. We also found that PD patients were more impaired in recognizing negative emotions (sadness, fear, anger, and disgust) than relatively positive emotions (happiness and surprise). Behaviorally, PD patients did not show impairment in emotion recognition as measured by subjective ratings. These findings suggest that PD patients may have an impairment of inter-hemispheric functional connectivity (i.e., a decline in cortical connectivity) during emotion processing. This study may increase the awareness of EEG emotional response studies in clinical practice to uncover potential neurophysiologic abnormalities