Abstract
Aims
Low levels of HDL cholesterol have been associated with increased risk of infectious disease morbidity and mortality. Nuclear magnetic resonance (NMR) spectroscopy permits the ...measurement of HDL particle count and allows further subclassification according to particle size. We tested the hypothesis that low number of different HDL subfractions is associated with increased infectious disease morbidity and mortality.
Methods and results
HDL particle counts were measured using NMR spectroscopy in 30 195 individuals aged 22–99 years from the Copenhagen General Population Study. Using multiple-event Cox regression and cause-specific hazard models, we assessed risk of hospitalizations due to infection and infectious disease-related death, from 2003 through 2018. During follow-up, 9303 individuals had one or more infectious disease events, and 1558 experienced infectious disease-related death. In multifactorial adjusted analyses, low number of small and medium HDL particles was associated with increased risk of any infection and infectious disease-related death, whereas low number of large and extra-large HDL particles was not. A very high number of small and medium HDL particles was also associated with increased risk of any infection, but not with infectious disease-related death. For small and medium HDL particles and compared to individuals in the 91–95th percentile, hazard ratios (HRs) in individuals in the lowest percentile were 2.31 (95% confidence interval: 1.75, 3.05) for any infection and 3.23 (2.08, 5.02) for infectious disease-related death. For the highest percentile, corresponding HRs were 1.36 (1.07, 1.74) and 1.06 (0.57, 1.98), respectively. Individuals in the lowest percentile had increased risk of pneumonia (HR: 1.86; 95% confidence interval: 1.30, 2.65), sepsis (2.17; 1.37, 3.35), urinary tract infection (1.76; 1.17, 2.63), skin infection (1.87; 1.24, 2.81), gastroenteritis (1.78; 1.01, 3.16), and other infections (2.57; 1.28, 5.16).
Conclusion
Low number of the small HDL particles was associated with increased infectious disease morbidity and mortality.
Graphical Abstract
Graphical abstract
Motivation for high-fat food is thought to contribute to excess caloric intake in obese individuals. A novel regulator of motivation for food may be neuromedin U (NMU), a highly-conserved ...neuropeptide that influences food intake. Although these effects of NMU have primarily been attributed to signaling in the paraventricular nucleus of the hypothalamus (PVN), NMU has also been found in other brain regions involved in both feeding behavior and motivation. We investigate the effects of NMU on motivation for food and food intake, and identify the brain regions mediating these effects.
The motivational state for a particular reinforcer (e.g., high-fat food) can be assessed using a progressive-ratio schedule of reinforcement under which an increasing number of lever presses are required to obtain subsequent reinforcers. Here, we have used a progressive-ratio operant responding paradigm in combination with an assessment of cumulative food intake to evaluate the effects of NMU administration in rats, and identify the brain regions mediating these effects.
We found that peripheral administration of NMU decreases operant responding for high-fat food in rats. Evaluation of Fos-like immunoreactivity in response to peripheral NMU indicated the PVN and dorsal raphe nucleus (DRN) as sites of action for NMU. NMU infusion into either region mimics the effects of peripheral NMU on food intake and operant responding for food. NMU-containing projections from the lateral hypothalamus (LH) to the PVN and DRN were identified as an endogenous source of NMU.
These results identify the DRN as a site of action for NMU, demonstrate that the LH provides endogenous NMU to the PVN and DRN and implicate NMU signaling in the PVN and DRN as a novel regulator of motivation for high-fat foods.
Election campaigns are more than simple competitions for votes; they also represent an opportunity for voters to become politically knowledgeable and engaged. Using a large-scale Web panel (N ≈ ...5,000), we track the development of political knowledge, internal efficacy, and external efficacy among voters during the 2011 Danish parliamentary election campaign. Over the course of the campaign, the electorate's political knowledge increases, and these gains are found across genders, generations, and educational groups, narrowing the knowledge gap within the electorate. Furthermore, internal and external efficacy increase over the course of the campaign, with gains found across different demographic groups, particularly narrowing the gaps in internal efficacy. The news media play a crucial role, as increased knowledge and efficacy are partly driven by media use, although tabloids actually decrease external efficacy. The findings suggest that positive campaign effects are universal across various media and party systems.
Research into entrepreneurship education has explored content, audience and pedagogy but much is still to be studied when it comes to the spatial dimensions of learning - that is, where ...entrepreneurship is taught, how this matters for pedagogies used, and the implications for learning. We seek to strengthen a theoretical foundation for understanding learning spaces and the spatial dimensions in entrepreneurship education (EE). We extend the teaching model framework by Fayolle and Gailly, to develop a conceptual model that relates place and pedagogy into learning spaces in EE, informed by recent pedagogical trends in experiential learning and design pedagogy. The model concerns the where-how, the topopraxis, of two types of learning spaces in team-based EE that are grounded in theory on the spatial dimensions of social interaction pertaining to team 'territory', and stakeholder proximity. The model proposes that topopraxis in EE programmes will impact learning processes and outcomes in the form of team relationship building, conceptual development , and student identity formation. To illustrate the applicability of the model, we analyse two cases of EE programmes, both conducted in studio environments, but differing in topopraxes and learning outcomes. Finally, we offer implications for EE research, and for the design of entrepreneurship programmes.
Objectives
Technical assessment of SHINKEI pulse sequence and conventional 3DIRTSE for LS plexus MR neurography.
Methods
Twenty-one MR neurography examinations of the LS plexus were performed at 3 T, ...using 1.5-mm isotropic 3DIRTSE and SHINKEI sequences. Images were evaluated for motion and pulsation artefacts, nerve signal-to-noise ratio, contrast-to-noise ratio, nerve-to-fat ratio, muscle-to-fat ratio, fat suppression homogeneity and depiction of LS plexus branches. Paired Student
t
test was used to assess differences in nerve conspicuity (
p
< 0.05 was considered statistically significant). ICC correlation was obtained for intraobserver performance.
Results
Four examinations were excluded due to prior spine surgery. Bowel motion artefacts, pulsation artefacts, heterogeneous fat saturation and patient motion were seen in 16/17, 0/17, 17/17, 2/17 on 3DIRTSE and 0/17, 0/17, 0/17, 1/17 on SHINKEI. SHINKEI performed better (
p
< 0.01) for nerve signal-to-noise, contrast-to-noise, nerve-to-fat and muscle-to-fat ratios. 3DIRTSE and SHINKEI showed all LS plexus nerve roots, sciatic and femoral nerves. Smaller branches including obturator, lateral femoral cutaneous and iliohypogastric nerves were seen in 10/17, 5/17, 1/17 on 3DIRTSE and 17/17, 16/17, 7/17 on SHINKEI. Intraobserver reliability was excellent.
Conclusion
SHINKEI MRN demonstrates homogeneous and superior fat suppression with increased nerve signal- and contrast-to-noise ratios resulting in better conspicuity of smaller LS plexus branches.
Key Points
• SHINKEI provides homogeneous and superior fat suppression, shown by higher nerve and muscle-to-fat ratios.
• SHINKEI shows better nerve signal-to-noise and contrast-to-noise ratios than 3DIRTSE.
• SHINKEI enables nerve-selective images with increased conspicuity of smaller LS plexus branches.
• SHINKEI should be considered in routine MR neurography of the LS plexus.
Aims/hypothesis
Elevated remnant cholesterol is observationally and causally associated with increased risk of atherosclerotic cardiovascular disease (ASCVD) in the general population. This ...association is not well studied in individuals with diabetes, who are often included in clinical trials of remnant cholesterol-lowering therapy. We tested the hypothesis that elevated remnant cholesterol is associated with increased risk of ASCVD in individuals with diabetes. We also explored the fraction of excess risk conferred by diabetes which can be explained by elevated remnant cholesterol.
Methods
We included 4569 white Danish individuals with diabetes (58% statin users) nested within the Copenhagen General Population Study (2003–2015). The ASCVDs peripheral artery disease, myocardial infarction and ischaemic stroke were extracted from national Danish health registries without losses to follow-up. Remnant cholesterol was calculated from a standard lipid profile.
Results
During up to 15 years of follow-up, 236 individuals were diagnosed with peripheral artery disease, 234 with myocardial infarction, 226 with ischaemic stroke and 498 with any ASCVD. Multivariable adjusted HR (95% CI) per doubling of remnant cholesterol was 1.6 (1.1, 2.3;
p
=0.01) for peripheral artery disease, 1.8 (1.2, 2.5;
p
=0.002) for myocardial infarction, 1.5 (1.0, 2.1;
p
=0.04) for ischaemic stroke, and 1.6 (1.2, 2.0;
p
=0.0003) for any ASCVD. Excess risk conferred by diabetes was 2.5-fold for peripheral artery disease, 1.6-fold for myocardial infarction, 1.4-fold for ischaemic stroke and 1.6-fold for any ASCVD. Excess risk explained by elevated remnant cholesterol and low-grade inflammation was 14% and 8% for peripheral artery disease, 26% and 16% for myocardial infarction, 34% and 34% for ischaemic stroke, and 24% and 18% for any ASCVD, respectively. LDL-cholesterol did not explain excess risk, as it was not higher in individuals with diabetes. We also explored the fraction of excess risk conferred by diabetes which can be explained by elevated remnant cholesterol.
Conclusions/interpretation
Elevated remnant cholesterol was associated with increased risk of ASCVD in individuals with diabetes. Remnant cholesterol and low-grade inflammation explained substantial excess risk of ASCVD conferred by diabetes. Whether remnant cholesterol should be used as a treatment target remains to be determined in randomised controlled trials.
Graphical Abstract
Healthy tissues harbour a surprisingly high number of cells that carry well‐known cancer‐causing mutations without impacting their physiological function. In recent years, strong evidence accumulated ...that the immediate environment of mutant cells profoundly impact their prospect of malignant progression. In this review, focusing on the skin, we investigate potential key mechanisms that ensure tissue homeostasis despite the presence of mutant cells, as well as critical factors that may nudge the balance from homeostasis to tumour formation. Functional in vivo studies and single‐cell transcriptome analyses have revealed a tremendous cellular heterogeneity and plasticity within epidermal (stem) cells and their respective niches, revealing for example wild‐type epithelial cells, fibroblasts or immune‐cell subsets as critical in preventing cancer formation and malignant progression. It’s the same cells, however, that can drive carcinogenesis. Therefore, understanding the abundance and molecular variation of cell types in health and disease, and how they interact and modulate the local signalling environment will thus be key for new therapeutic avenues in our battle against cancer.
Content List ‐ 16th Key symposium: “The origin of cancer”
Controlling the reciprocity between chemical reactivity and supramolecular structure is a topic of great interest in the emergence of molecular complexity. In this work, we investigate the effect of ...a covalent reaction as a trigger to depolymerize a supramolecular assembly. We focus on the impact of an
in situ
thiol-ene reaction on the (co)polymerization of three derivatives of benzene-1,3,5-tricarboxamide (BTA) monomers functionalized with cysteine, hexylcysteine, and alkyl side chains:
Cys-BTA
,
HexCys-BTA
, and
a-BTA
. Long supramolecular polymers of
Cys-BTA
can be depolymerized into short dimeric aggregates of
HexCys-BTA
via
the
in situ
thiol-ene reaction. Analysis of the system by time-resolved spectroscopy and light scattering unravels the fast dynamicity of the structures and the mechanism of depolymerization. Moreover, by intercalating the reactive
Cys-BTA
monomer into an unreactive inert polymer, the
in situ
thiol-ene reaction transforms the intercalator into a sequestrator and induces the depolymerization of the unreactive polymer. This work shows that the implementation of reactivity into supramolecular assemblies enables temporal control of depolymerization processes, which can bring us one step closer to understanding the interplay between non-covalent and covalent chemistry.
We report on the controlled depolymerization of supramolecular 1D polymers into well-defined dimers triggered by a covalent reaction on the side chains of the monomer.
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