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Diacylglycerol kinase (DGK) isoforms catalyze an enzymatic reaction that removes diacylglycerol (DAG) and thereby terminates protein kinase C signaling by converting DAG to phosphatidic acid. DGKδ (type II isozyme) downregulation causes insulin resistance, metabolic inflexibility, and obesity. Here we determined whether DGKδ overexpression prevents these metabolic impairments. We generated a transgenic mouse model overexpressing human DGKδ2 under the myosin light chain promoter (DGKδ TG). We performed deep metabolic phenotyping of DGKδ TG mice and wild-type littermates fed chow or high-fat diet (HFD). Mice were also provided free access to running wheels to examine the effects of DGKδ overexpression on exercise-induced metabolic outcomes. DGKδ TG mice were leaner than wild-type littermates, with improved glucose tolerance and increased skeletal muscle glycogen content. DGKδ TG mice were protected against HFD-induced glucose intolerance and obesity. DGKδ TG mice had reduced epididymal fat and enhanced lipolysis. Strikingly, DGKδ overexpression recapitulated the beneficial effects of exercise on metabolic outcomes. DGKδ overexpression and exercise had a synergistic effect on body weight reduction. Microarray analysis of skeletal muscle revealed common gene ontology signatures of exercise and DGKδ overexpression that were related to lipid storage, extracellular matrix, and glycerophospholipids biosynthesis pathways. Overexpression of DGKδ induces adaptive changes in both skeletal muscle and adipose tissue, resulting in protection against HFD-induced obesity. DGKδ overexpression recapitulates exercise-induced adaptations on energy homeostasis and skeletal muscle gene expression profiles. • DGKδ overexpression protects against diet-induced glucose intolerance and obesity • DGKδ overexpression recapitulates exercise-induced improvements in energy homeostasis • Exercise and DGKδ overexpression have synergistic effects on body weight reduction and share similar skeletal muscle gene signatures • Lipid storage, extracellular matrix, and glycerophospholipids biosynthesis pathways are altered • DGKδ2 agonists may enhance energy homeostasis and exercise adaptations [ABSTRACT FROM AUTHOR]

Human milk is, without question, the best source of nutrition for infants containing the optimal balance of fats, carbohydrates and proteins for developing babies. Breastfeeding provides a range of benefits for growth, immunity and development building a powerful bond between mother and her child. Recognition of the manifold benefits of breast milk has led to the adoption of breast-feeding policies by numerous health and professional organizations such as the World Health Organization and American Academy of Pediatrics. In industrially developed as well as in developing nations, human milk contamination by toxic chemicals such as heavy metals, dioxins and organohalogen compounds, however, is widespread and is the consequence of decades of inadequately controlled pollution. Through breastfeeding, the mother may transfer to the suckling infant potentially toxic chemicals to which the mother has previously been exposed. In the present review, environmental exposure, acquisition and current levels of old and emerging classes of breast milk pollutants are systematically presented. Although scientific evidences indicated that the advantages of breast-feeding outweigh any risks from contaminants, it is important to identify contaminant trends, to locate disproportionately exposed populations, and to take public health measures to improve chemical BM pollution as possible.

Chemometrics is a chemical discipline in which mathematical and statistical techniques are applied to design experiments or to analyze chemical data. An important part of chemometrics is modeling, in which one tries to relate two or more characteristics in such a way that the obtained model represents reality as closely as possible. In this article some less known but useful regression methods such as orthogonal least squares, inverse and robust regression are introduced and compared with the well-known classical least squares regression method. Genetic algorithms are described as a means of carrying out feature selection for multivariate regression. Regression methods such as principal component regression and partial least squares are introduced as well as the use of N-way principal components.

Introduction: Frailty is a complex syndrome that can is characterized by the loss of physical functional capacity. The effects of multicomponent exercise training on frailty and correlated biomarkers are not yet fully explored in the scientific literature. Objective: Based on the available literature data, our first endpoint in this systematic review was to present the current knowledge on the influence of multicomponent exercise training in older persons diagnosed with the frailty syndrome. In addition, a second endpoint was to identify not only the most evaluated and responsive biochemical markers in this population, but also how they responded to multicomponent exercise training. Methods: The electronic databases PubMed, SciELO, LILACS, and Science Direct, were accessed. The search was conducted in the English language using MeSH keywords in order to verify which biochemical markers were investigated in the studies that associated frail older persons and multicomponent physical exercise. This systematic review was registered under the reference CRD42018089912. Results: Six randomized controlled trial studies met our inclusion criteria and were used to perform this review. In response to our endpoints, these studies reported that multicomponent exercise training was able to decrease or reverse frailty by improving functional fitness, muscle strength, speed and agility. In addition, this type of exercise training was associated with alteration in several biomarkers, namely C-reactive protein (CRP), interleukin (IL-6), Tumour Necrosis Factor (TNF-Ą), insulin-like growth factor (IGF-1), haemoglobin (HbA), albumin, oxidation products, antioxidants, Vitamin D, and serum/plasma/saliva hormone levels of dehydroepiandrosterone (DHEA), testosterone and parathyroid hormone (PTH). Conclusion: Multicomponent exercise training is a powerful tool to prevent or even revert frailty development in older persons, namely through its mediating action in several metabolic, hormone and pro-inflammatory markers. [ABSTRACT FROM AUTHOR]

Abstract Background Carotid intima-media thickness (IMT), indices of large artery stiffness and measures of endothelium function may be used as markers of early atherosclerosis in type 1 diabetes mellitus (T1DM). The aim of the present study was to compare the indices of large artery structure and function as well as endothelial function and regenerating capacity between adolescents with T1DM and healthy control of similar age. In addition, the associations of different vascular measures with endothelial progenitor cells (EPCs), glyco-metabolic control and serum levels of advanced glycation endproducts (AGEs), soluble receptors for AGEs (sRAGE) and adiponectin were evaluated. Methods Sixteen uncomplicated young T1DM patients (mean age 18 ± 2 years, history of disease 11 ± 5 years, HbA1c 7.7 ± 1.1%) and 26 controls (mean age 19 ± 2 years) were studied. A radiofrequency-based ultrasound system (Esaote MyLab 70) was used to measure carotid IMT and wave speed (WS, index of local stiffness), applanation tonometry (PulsePen) was applied to obtain central pulse pressure (PP) and augmentation index (AIx), and carotid-femoral pulse wave velocity (PWV, Complior) was used as index of aortic stiffness. Peripheral endothelium-dependent vasodilation was determined as reactive hyperemia index (RHI, EndoPAT). Circulating EPCs, glycometabolic profile, AGEs (autofluorescence method), sRAGE and adiponectin were also measured. Results After adjusting for age, sex and blood pressure, T1DM adolescents had significantly higher carotid IMT (456 ± 7 vs. 395 ± 63 μm, p < 0.005), carotid WS (p < 0.005), PWV (p = 0.01), AIx (p < 0.0001) and central PP (p < 0.01) and lower EPCs (p = 0.02) as compared to controls. RHI was reduced only in diabetic patients with HbA1c ≥7.5% (p < 0.05). In the overall population, EPCs were an independent determinant of carotid IMT (together with adiponectin), while fasting plasma glucose was an independent determinant of carotid WS, AIx and central PP. Conclusions Our findings suggest that young subjects with relatively long-lasting T1DM have a generalized preclinical involvement of large artery structure and function, as well as a blunted endothelium regenerating capacity. Hyperglycemia and suboptimal chronic glycemic control seem to deteriorate the functional arterial characteristics, such as large arteries stiffness, wave reflection and peripheral endothelium-dependent vasodilation, whereas an impaired endothelium regenerating capacity and adiponectin levels seem to influence arterial structure.

Abstract Background In order to address the challenges of an ageing population the Belgian government decided to allocate resources to the creation of geriatric day hospitals (GDHs). Although GDHs are meant to be a strategy to support general practitioners (GPs) caring for the frail elderly, few Belgian GPs seem to refer to a GDH. This study aims to explore the barriers and facilitating factors of GPs' referral to GDHs. Methods A qualitative study using focus group discussions (FGDs) was conducted. Fifteen FGDs were organized in the different Belgian regions (Flanders, Wallonia, Brussels). Results Contextual factors such as the unsatisfactory cooperation between hospital and GPs and organizational barriers such as the lack of communication on referral procedures between hospital and primary health care (PHC) were identified. Lack of basic knowledge about the concept or the local organization of GDH seemed to be a problem. Unclear task descriptions, responsibilities and activities of a GDH formed prominent points of discussion in all FGDs. Nevertheless a lot of possible advantages and disadvantages of GDHs for the patient and for the GP were mentioned. Conclusions In the case of poor referral to GDHs, focusing on improving overall collaboration between primary and secondary health care is essential. This can be achieved by actively delivering adequate information, permanent communication and more involvement of PHC in the organization and functioning of GDHs. The absence of a transparent health care system with delineated role definitions, seems to hinder the integration of new initiatives like GDHs in the care process. Strategies to enhance referral to GDHs should use a comprehensive approach.

Abstract Background Skeletal characteristics such as height (Ht), bone mineral density (BMD) or bone turnover markers are strongly inherited. Common variants in the genes encoding for estrogen receptor alpha (ESR1) and beta (ESR2) are proposed as candidates for influencing bone phenotypes at the population level. Methods We studied 641 healthy premenopausal women aged 20–50 years (yrs) participating into the BONTURNO study. Exclusion criteria were irregular cyclic menses, low trauma fracture, metabolic bone or chronic diseases. Serum C-telopeptide of type I collagen (CTX), osteocalcin (OC), and N-terminal propeptide of type I procollagen (P1NP) were measured in all enrolled subjects, who underwent to lumbar spine (LS), total hip (TH) and femoral neck (FN) BMD evaluation by DXA. Five hundred seventy Caucasian women were genotyped for ESR1 rs2234693 and rs9340799 and ESR2 rs4986938 polymorphisms. Results Although no genotype differences were found in body parameters, subjects with combined ESR1 CCGG plus ESR2 AA-AG genotype were taller than those with opposite genotype (P = 0.044). Moreover, ESR1 rs2234693 genotypes correlated with family history of osteoporosis (FHO) and hip fracture (FHF) (P < 0.01), while ESR2 AA-AC genotypes were strongly associated with FHF (OR 2.387, 95% CI 1.432–3.977; P < 0.001). When clustered by age, 20–30 yrs old subjects, having at least one ESR1 rs2234693 C allele presented lower LS- (P = 0.008) and TH-BMD (P = 0.047) than TT genotypes. In 41–50 yrs age, lower FN-BMD was associated with ESR2 AA (P = 0.0180) subjects than in those with the opposite genotype. ESR1 rs2234693 and rs9340799 and ESR2 rs4986938 polymorphisms did not correlate with age-adjusted values of OC, CTX and P1NP. Conclusion These findings support the presence of age-specific effects of ESR1 and ESR2 polymorphisms on various skeletal traits in healthy fertile women.

The Resilience of Democracy in the midst of the COVID-19 Pandemic: Since January 2020, European countries have implemented a wide range of restrictions to contain the COVID-19 pandemic. Yet governments have also implemented democratic compensators in order to offset the negative impacts of restrictions. This article aims to account for the variation of their use between Belgium, the Netherlands and France. We analyse three drivers: the strength of counterpowers, the ruling parties' ideological leanings and political support. Building on an original data set, our results distinguish between embedded and ad hoc compensators. We find that ad hoc compensators are championed mainly by counterpowers, but also by ideology of the ruling coalitions in Belgium and the Netherlands and used strategically to maintain political support in France. Evidence on the link between embedded compensators and counterpowers is more ambiguous. [ABSTRACT FROM AUTHOR]

Abstract Background There is increasing evidence that reproductive abnormalities are increasing in frequency in both human population and among wild fauna. This increase is probably related to exposure to toxic contaminants in the environment. The use of sentinel species to raise alarms relating to human reproductive health has been strongly recommended. However, no simultaneous studies at the same site have been carried out in recent decades to evaluate the utility of wild animals for monitoring human reproductive disorders. We carried out a joint study in Guadeloupe assessing the reproductive function of workers exposed to pesticides in banana plantations and of male wild rats living in these plantations. Methods A cross-sectional study was performed to assess semen quality and reproductive hormones in banana workers and in men working in non-agricultural sectors. These reproductive parameters were also assessed in wild rats captured in the plantations and were compared with those in rats from areas not directly polluted by humans. Results No significant difference in sperm characteristics and/or hormones was found between workers exposed and not exposed to pesticide. By contrast, rats captured in the banana plantations had lower testosterone levels and gonadosomatic indices than control rats. Conclusion Wild rats seem to be more sensitive than humans to the effects of pesticide exposure on reproductive health. We conclude that the concept of sentinel species must be carefully validated as the actual nature of exposure may varies between human and wild species as well as the vulnerable time period of exposure and various ecological factors.

Left: P KA values stratified per BMI classes for CA (1) and PCI (2) procedures. Right: Comparison of the Fluoroscopy Time per range of Complexity Index (CI) for the PCI procedures. Number of cases and median values are reported. One-Sentence Summary: Dose references levels for P KA and Fluoroscopy Time in interventional cardiology should be defined in function of BMI classes and Complexity Index. These could provide an additional tool for refining a facility's quality assurance and optimization processes. • Total air kerma area product (P KA) and fluoroscopy time (FT) increase with BMI and procedure complexity index (CI). • Significant P KA variability was observed among cardiologists for CA (p<0.001) but not for PCI procedures. • Dose references levels for P KA and FT in interventional cardiology should be defined in function of CI and BMI class. • These findings could provide an additional tool for refining a facility's quality assurance and optimization processes. The aim of this study was to assess patient exposure data and operator dose in coronary interventional procedures, when considering patient body-mass index and procedure complexity. Total air kerma area product (P KA), Air-Kerma (AK), Fluoroscopy time (FT), operator dose and patient body-mass index (BMI) from 97 patients' procedures (62 coronary angiography (CA) and 35 Percutaneous Coronary Intervention (PCI) were collected for one year. For PCI procedures, also the complexity index-CI was collected. Continuous variables for each of the 2 groups procedures (CA and PCI) were compared as medians with interquartile range and using Mann-Whitney U test. Multiple group data were compared using Kruskal-Wallis test (significance: p < 0.05). Median P KA was 63 and 125 Gy cm2 for CA and PCI respectively (p < 0.001); FT was 3 and 14 min, respectively (p < 0.001). P KA and FT significantly increased (p < 0.05) with BMI class for CA procedures. P KA and FT also increased in function of CI class for PCI, thought significantly only for FT (p < 0.001), possibly because of the low number of PCI procedures included; cine mode contributed most to P KA. Significant dose variability was observed among cardiologists for CA procedures (p < 0.001). Dose references levels for P KA and FT in interventional cardiology should be defined - on a sufficient number of procedures- in function of CI and BMI classes. These could provide an additional tool for refining a facility's quality assurance and optimization processes. Dose variability associated with cardiologists underlines the importance of continuous training. [ABSTRACT FROM AUTHOR]