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•Residue behavior/processing factors of chlordecone assessed on four cooking processes.•ID-HPLC-MS/MS or LC-HRMS/MS used for target, suspect screening or untargeted approaches.•A ...significant decrease of CLD in bovine meat observed after microwave cooking process.•Traces of 5b-hydro-CLD and mono-hydro-CLD found in the uncooked liver.•No degradation by-product of CLD observed in the cooked liver.
Chlordecone (CLD) is a toxic organochlorine pesticide frequently used in the French West Indies until 1993, resulting in a contamination of soil and food. This study assessed the behaviour of CLD residues and CLD processing factors (PFs) during four home cooking processes: cooking in a conventional oven (“oven”), frying (“pan”), cooking in a microwave oven (“microwave”) and grilling (“grill”). These four processes were applied to six types of naturally contaminated beef (kidney, liver, rib, chuck, top-sirloin and sirloin). Targeted analyses with isotopic dilution were carried out by ID-HPLC-MS/MS to determine CLD concentrations before and after each cooking process and the corresponding processing factors. HPLC-HRMS/MS was used to find potential organochlorine degradation by-products and/or CLD metabolites present in samples by target, suspect and non-target screening. Cooking processes and especially microwave cooking led to a significant decrease in the CLD contained in beef (2% < PF < 17%). Traces of 5b-hydro-CLD and of another mono-hydro-CLD were found in the uncooked liver but no CLD degradation by-product was observed in the cooked liver.
Summary Dementia is receiving increasing attention from governments and politicians. Epidemiological research based on western European populations done 20 years ago provided key initial evidence for ...dementia policy making, but these estimates are now out of date because of changes in life expectancy, living conditions, and health profiles. To assess whether dementia occurrence has changed during the past 20–30 years, investigators of five different studies done in western Europe (Sweden Stockholm and Gothenburg, the Netherlands Rotterdam, the UK England, and Spain Zaragoza) have compared dementia occurrence using consistent research methods between two timepoints in well-defined geographical areas. Findings from four of the five studies showed non-significant changes in overall dementia occurrence. The only significant reduction in overall prevalence was found in the study done in the UK, powered and designed explicitly from its outset to detect change across generations (decrease in prevalence of 22%; p=0·003). Findings from the study done in Zaragoza (Spain) showed a significant reduction in dementia prevalence in men (43%; p=0·0002). The studies estimating incidence done in Stockholm and Rotterdam reported non-significant reductions. Such reductions could be the outcomes from earlier population-level investments such as improved education and living conditions, and better prevention and treatment of vascular and chronic conditions. This evidence suggests that attention to optimum health early in life might benefit cognitive health late in life. Policy planning and future research should be balanced across primary (policies reducing risk and increasing cognitive reserve), secondary (early detection and screening), and tertiary (once dementia is present) prevention. Each has their place, but upstream primary prevention has the largest effect on reduction of later dementia occurrence and disability.
Dementia is an increasing focus for policymakers, civil organizations and multidisciplinary researchers. The most recent descriptive epidemiological research into dementia is enabling investigation ...into how the prevalence and incidence are changing over time. To establish clear trends, such comparisons need to be founded on population-based studies that use similar diagnostic and research methods consistently over time. This narrative Review synthesizes the findings from 14 studies that investigated trends in dementia prevalence (nine studies) and incidence (five studies) from Sweden, Spain, the UK, the Netherlands, France, the USA, Japan and Nigeria. Besides the Japanese study, these studies indicate stable or declining prevalence and incidence of dementia, and some provide evidence of sex-specific changes. No single risk or protective factor has been identified that fully explains the observed trends, but major societal changes and improvements in living conditions, education and healthcare might have favourably influenced physical, mental and cognitive health throughout an individual's life course, and could be responsible for a reduced risk of dementia in later life. Analytical epidemiological approaches combined with translational neuroscientific research could provide a unique opportunity to explore the neuropathology that underlies changing occurrence of dementia in the general population.
Background
Enhanced Recovery After Surgery (ERAS) is widely accepted in current surgical practice due to its positive impact on patient outcomes. The successful implementation of ERAS is challenging ...and compliance with protocols varies widely. Continual staff education is essential for successful ERAS programmes. Teaching modalities exist, but there remains no agreement regarding the optimal training curriculum or how its effectiveness is assessed. We aimed to draw consensus from an expert panel regarding the successful training and implementation of ERAS.
Methods
A modified Delphi technique was used; three rounds of questionnaires were sent to 58 selected international experts from 11 countries across multiple ERAS specialities and multidisciplinary teams (MDT) between January 2016 and February 2017. We interrogated opinion regarding four topics: (1) the components of a training curriculum and the structure of training courses; (2) the optimal framework for successful implementation and audit of ERAS including a guide for data collection; (3) a framework to assess the effectiveness of training; (4) criteria to define ERAS training centres of excellence.
Results
An ERAS training course must cover the evidence-based principles of ERAS with team-oriented training. Successful implementation requires strong leadership, an ERAS facilitator and an effective MDT. Effectiveness of training can be measured by improved compliance. A training centre of excellence should show a willingness to teach and demonstrable team working.
Conclusions
We propose an international expert consensus providing an ERAS training curriculum, a framework for successful implementation, methods for assessing effectiveness of training and a definition of ERAS training centres of excellence.
Diverse bone pathologies are observed in patients with psoriatic arthritis (PsA). Uncoupling of bone remodeling with disordered osteoclastogenesis has been implicated in the pathogenesis of PsA. The ...aim of this study was to examine the role of soluble mediators of bone remodeling within the circulation of patients with PsA.
Patients with PsA (n = 38), with psoriasis (n = 10), and healthy controls (n = 12) were studied. Serum was obtained for testing of Dikkopf-1 (Dkk-1), macrophage-colony stimulating factor (M-CSF), osteoprotegerin (OPG), and receptor activator of nuclear factor-κB ligand (RANKL) with ELISA. Patients with PsA also had bone densitometry, plain radiographs of the hands and feet, and assessment of peripheral blood osteoclast precursors. Radiographs were scored for erosion, joint-space narrowing, osteolysis, and new bone formation.
Compared with those with psoriasis and healthy controls, patients with PsA had higher circulating concentrations of Dkk-1 and M-CSF. In patients with PsA, M-CSF and RANKL, but not Dkk-1, concentrations positively correlated with radiographic erosion, joint-space narrowing, and osteolysis scores. Mediators of bone remodeling did not correlate with the number of joints with new bone formation or with total hip-bone mineral density. Peripheral blood CD14+/CD11b+ cells, and the number of osteoclast-like cells and resorptive pits after culture with RANKL and M-CSF also correlated with radiographic damage scores. Circulating M-CSF concentrations correlated with the percentage of peripheral blood CD14+/CD11b+ cells.
Systemic expression of soluble factors that promote osteoclastogenesis is disordered in patients with PsA and may contribute to periarticular bone loss in this disease.
Epigenetic mechanisms, such as histone modifications, regulate responsiveness to drugs of abuse, such as cocaine, but relatively little is known about the regulation of addictive-like behaviors by ...DNA methylation. To investigate the influence of DNA methylation on the locomotor-activating effects of cocaine and on drug-seeking behavior, rats receiving methyl supplementation via chronic l-methionine (MET) underwent either a sensitization regimen of intermittent cocaine injections or intravenous self-administration of cocaine, followed by cue-induced and drug-primed reinstatement. MET blocked sensitization to the locomotor-activating effects of cocaine and attenuated drug-primed reinstatement, with no effect on cue-induced reinstatement or sucrose self-administration and reinstatement. Furthermore, upregulation of DNA methyltransferase 3a and 3b and global DNA hypomethylation were observed in the nucleus accumbens core (NAc), but not in the medial prefrontal cortex (mPFC), of cocaine-pretreated rats. Glutamatergic projections from the mPFC to the NAc are critically involved in the regulation of cocaine-primed reinstatement, and activation of both brain regions is seen in human addicts when reexposed to the drug. When compared with vehicle-pretreated rats, the immediate early gene c-Fos (a marker of neuronal activation) was upregulated in the NAc and mPFC of cocaine-pretreated rats after cocaine-primed reinstatement, and chronic MET treatment blocked its induction in both regions. Cocaine-induced c-Fos expression in the NAc was associated with reduced methylation at CpG dinucleotides in the c-Fos gene promoter, effects reversed by MET treatment. Overall, these data suggest that drug-seeking behaviors are, in part, attributable to a DNA methylation-dependent process, likely occurring at specific gene loci (e.g., c-Fos) in the reward pathway.
Non-alcoholic steatohepatitis (NASH) is characterized by a robust pro-inflammatory component at both hepatic and systemic levels together with a disease-specific gut microbiome signature. Protein ...tyrosine phosphatase 1 B (PTP1B) plays distinct roles in non-immune and immune cells, in the latter inhibiting pro-inflammatory signaling cascades. In this study, we have explored the role of PTP1B in the composition of gut microbiota and gut barrier dynamics in methionine and choline-deficient (MCD) diet-induced NASH in mice.
Gut features and barrier permeability were characterized in wild-type (PTP1B WT) and PTP1B-deficient knockout (PTP1B KO) mice fed a chow or methionine/choline-deficient (MCD) diet for 4 weeks. The impact of inflammation was studied in intestinal epithelial and enteroendocrine cells. The secretion of GLP-1 was evaluated in primary colonic cultures and plasma of mice.
We found that a shift in the gut microbiota shape, disruption of gut barrier function, higher levels of serum bile acids, and decreased circulating glucagon-like peptide (GLP)-1 are features during NASH. Surprisingly, despite the pro-inflammatory phenotype of global PTP1B-deficient mice, they were partly protected against the alterations in gut microbiota composition during NASH and presented better gut barrier integrity and less permeability under this pathological condition. These effects concurred with higher colonic mucosal inflammation, decreased serum bile acids, and protection against the decrease in circulating GLP-1 levels during NASH compared with their WT counterparts together with increased expression of GLP-2-sensitive genes in the gut. At the molecular level, stimulation of enteroendocrine STC-1 cells with a pro-inflammatory conditioned medium (CM) from lipopolysaccharide (LPS)-stimulated macrophages triggered pro-inflammatory signaling cascades that were further exacerbated by a PTP1B inhibitor. Likewise, the pro-inflammatory CM induced GLP-1 secretion in primary colonic cultures, an effect augmented by PTP1B inhibition.
Altogether our results have unraveled a potential role of PTP1B in the gut–liver axis during NASH, likely mediated by increased sensitivity to GLPs, with potential therapeutic value.
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•MCD diet induces a different shift of gut microbiota in PTP1BWT and PTP1B KO mice.•PTP1B KO mice present higher colonic mucosal inflammation under NASH conditions.•Gut barrier permeability was decreased in PTP1B KO mice with NASH.•PTP1B inhibition increases GLP-1 secretion in colonic cultures exposed to inflammatory stimulus.
In recent years, a rapidly increasing collection of investigative methods in addition to changes in diagnostic criteria for dementia have followed “high-tech” trends in medicine, with the aim to ...better define the dementia syndrome and its biological substrates, mainly in order to predict risk prior to clinical expression. These approaches are not without challenge. A set of guidelines have been developed by a group of European experts in population-based cohort research through a series of workshops, funded by the Joint Program for Neurodegenerative Disorders (JPND). The aims of the guidelines are to assist policy makers and researchers to understand (1) What population studies for ageing populations should encompass and (2) How to interpret the findings from population studies. Such studies are essential to provide evidence relevant to the understanding of healthy and frail brain ageing, including the dementia syndrome for contemporary and future societies by drawing on the past.
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