The time is now: Achieving FH paediatric screening across Europe – The Prague Declaration

ReviewFamilial Hypercholesterolaemia (FH) is severely under-recognized, under-diagnosed and under-treated in Europe, leading to a significantly higher risk of premature cardiovascular diseases in those affected. FH stands for inherited, very high cholesterol and affects 1:300 individuals regardless of their age, race, sex, and lifestyle, making it the most common inherited metabolic disorder and a non-modifiable cardiovascular disease risk factor in the world..info:eu-repo/semantics/publishedVersio

HYGIENE – CAN A TOOL FROM OUR PAST HELP SAVE THE FUTURE?

Infectious diseases will continue to disrupt modern societies if we do not establish better hygiene literacy to enable a systems approach to hygienical design and planning, wider population access to and uptake of practices, and a strategically better use of cleaning and hygiene as trusted methods to reduce infections. The article introduces the concept of hygiene literacy and outlines how this concept is linked to policies for public health, urban planning, education, research, data collection, and more. Further, it outlines how such a new strategy for Europe could help address infections and epidemics

HYGIENE – CAN A TOOL FROM OUR PAST HELP SAVE THE FUTURE?

Infectious diseases will continue to disrupt modern societies if we do not establish better hygiene literacy to enable a systems approach to hygienical design and planning, wider population access to and uptake of practices, and a strategically better use of cleaning and hygiene as trusted methods to reduce infections. The article introduces the concept of hygiene literacy and outlines how this concept is linked to policies for public health, urban planning, education, research, data collection, and more. Further, it outlines how such a new strategy for Europe could help address infections and epidemics.publishedVersio

Unexpected effects of fasting on murine lipid homeostasis - Transcriptomic and lipid profiling

Background & Aims: Starvation induces massive perturbations in metabolic pathways involved in energy metabolism, but its effect on the metabolism of lipids, particularly cholesterol, is little understood. Methods: A comparative genomic analysis of the gut and the liver in response to fasting was performed, with intestinal perfusion and lipid profiling of the plasma, bile, liver, intestinal tissue, perfusate, and faeces in FVB mice. Results: The expression profiles suggested increased cholesterol trafficking in the liver and decreased trafficking in the small intestine. Plasma cholesterol concentrations significantly increased, and triglycerides decreased in fasting. Surprisingly, in prolonged fasting, the biliary bile salt and lipid output rates increased, with increased hepatic and intestinal lipid turnover, and enhanced trans-intestinal cholesterol excretion. In contrast, faecal sterol loss declined sharply. To investigate whether the increased biliary phospholipid secretion could nourish the intestinal epithelium, we studied the histology of the small intestines upon fasting in multidrug resistant protein 2 deficient mice with scarce biliary phospholipids. Their adaptive biliary response to fasting was lost, while the shortage of biliary phospholipids strongly induced apoptosis and proliferation in the small intestine and increased the number of mucin-producing cells. Conclusion: Even with no dietary fat, lipid levels remain remarkably constant in the murine liver and intestines during prolonged fasting. The biliary system, always assumed to be coupled to the postprandial response, shows a paradoxical increase in activity. We hypothesise that biliary lipids are mobilised to supply the enterocytes with luminal fuel and to stabilise transport systems in the intestine for ensuring a rapid recovery when the food supply resumes. (C) 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved

LIM-only protein FHL2 is a positive regulator of liver X receptors in smooth muscle cells involved in lipid homeostasis

The LIM-only protein FHL2 is expressed in smooth muscle cells (SMCs) and inhibits SMC-rich-lesion formation. To further elucidate the role of FHL2 in SMCs, we compared the transcriptomes of SMCs derived from wild-type (WT) and FHL2 knockout (KO) mice. This revealed that in addition to the previously recognized involvement of FHL2 in SMC proliferation, the cholesterol synthesis and liver X receptor (LXR) pathways are altered in the absence of FHL2. Using coimmunoprecipitation experiments, we found that FHL2 interacts with the two LXR isoforms, LXRα and LXRβ. Furthermore, FHL2 strongly enhances transcriptional activity of LXR element (LXRE)-containing reporter constructs. Chromatin immunoprecipitation (ChIP) experiments on the ABCG1 promoter revealed that FHL2 enhances the association of LXRβ with DNA. In line with these observations, we observed reduced basal transcriptional LXR activity in FHL2-KO SMCs compared to WT SMCs. This was also reflected in reduced expression of LXR target genes in intact aorta and aortic SMCs of FHL2-KO mice. Functionally, the absence of FHL2 resulted in attenuated cholesterol efflux to both ApoA-1 and high-density lipoprotein (HDL), in agreement with reduced LXR signaling. Collectively, our findings demonstrate that FHL2 is a transcriptional coactivator of LXRs and points toward FHL2 being an important determinant of cholesterol metabolism in SMCs

LIM-Only Protein FHL2 Is a Positive Regulator of Liver X Receptors in Smooth Muscle Cells Involved in Lipid Homeostasis

The LIM-only protein FHL2 is expressed in smooth muscle cells (SMCs) and inhibits SMC-rich-lesion formation. To further elucidate the role of FHL2 in SMCs, we compared the transcriptomes of SMCs derived from wild-type (WT) and FHL2 knockout (KO) mice. This revealed that in addition to the previously recognized involvement of FHL2 in SMC proliferation, the cholesterol synthesis and liver X receptor (LXR) pathways are altered in the absence of FHL2. Using coimmunoprecipitation experiments, we found that FHL2 interacts with the two LXR isoforms, LXR alpha and LXR beta. Furthermore, FHL2 strongly enhances transcriptional activity of LXR element (LXRE)-containing reporter constructs. Chromatin immunoprecipitation (ChIP) experiments on the ABCG1 promoter revealed that FHL2 enhances the association of LXR beta with DNA. In line with these observations, we observed reduced basal transcriptional LXR activity in FHL2-KO SMCs compared to WT SMCs. This was also reflected in reduced expression of LXR target genes in intact aorta and aortic SMCs of FHL2-KO mice. Functionally, the absence of FHL2 resulted in attenuated cholesterol efflux to both ApoA-1 and high-density lipoprotein (HDL), in agreement with reduced LXR signaling. Collectively, our findings demonstrate that FHL2 is a transcriptional coactivator of LXRs and points toward FHL2 being an important determinant of cholesterol metabolism in SMC

Effect of Hyperglycemia on Gene Expression during Early Organogenesis in Mice

Cardiovascular and neural malformations are common sequels of diabetic pregnancies, but the underlying molecular mechanisms remain unknown. We hypothesized that maternal hyperglycemia would affect the embryos most shortly after the glucose-sensitive time window at embryonic day (ED) 7.5 in mice. Mice were made diabetic with streptozotocin, treated with slow-release insulin implants and mated. Pregnancy aggravated hyperglycemia. Gene expression profiles were determined in ED8.5 and ED9.5 embryos from diabetic and control mice using Serial Analysis of Gene Expression and deep sequencing. Maternal hyperglycemia induced differential regulation of 1,024 and 2,148 unique functional genes on ED8.5 and ED9.5, respectively, mostly in downward direction. Pathway analysis showed that ED8.5 embryos suffered mainly from impaired cell proliferation, and ED9.5 embryos from impaired cytoskeletal remodeling and oxidative phosphorylation (all P ≤ E-5). A query of the Mouse Genome Database showed that 20-25% of the differentially expressed genes were caused by cardiovascular and/or neural malformations, if deficient. Despite high glucose levels in embryos with maternal hyperglycemia and a ~150-fold higher rate of ATP production from glycolysis than from oxidative phosphorylation on ED9.5, ATP production from both glycolysis and oxidative phosphorylation was reduced to ~70% of controls, implying a shortage of energy production in hyperglycemic embryos. Maternal hyperglycemia suppressed cell proliferation during gastrulation and cytoskeletal remodeling during early organogenesis. 20-25% of the genes that were differentially regulated by hyperglycemia were associated with relevant congenital malformations. Unexpectedly, maternal hyperglycemia also endangered the energy supply of the embryo by suppressing its glycolytic capacit

Food-Based Dietary Guidelines - development of a conceptual framework for future food-based dietary guidelines in Europe:Report of a Federation of European Nutrition Societies Task-Force Workshop in Copenhagen, 12-13 March 2018

Identifying a need for developing a conceptual framework for the future development of Food-Based Dietary Guidelines (FBDG) in Europe, The Federation of European Nutrition Sciences established a Task Force for this purpose. A workshop was held with the specific objective to discuss the various dimensions considered as particularly relevant. Existing frameworks for FBDG were discussed, and presentations from various countries illustrated not only several commonalities but also a high degree of heterogeneity in the guidelines from different countries. Environmental aspects were considered in several countries, and dimensions like food safety, dietary habits and preparation were included in others. The workshop provided an overview of the use of FBDG - both in developing front-of-pack nutrition labels and for reformulation and innovation. The European FBDG dimensions were described with examples from the close connection between FBDG and European Union (EU) policies and activities and from the compilation of a database of national FBDG. Also, the challenges with communication of FBDG were discussed. Considering the current scientific basis and the experiences from several countries, the Task Force discussed the various dimensions of developing FBDG and concluded that environmental aspects should be included in the future conceptual framework for FBDG. A change in terminology to sustainable FDBG (SFBDG) could reflect this. The Task Force concluded that further work needs to be done exploring current practice, existing methodologies and the future prospects for incorporating other relevant dimensions into a future Federation of European Nutrition Societies conceptual framework for SFBDG in Europe and working groups were formed to address that