Synthetic glucocorticoids are potent anti-inflammatory drugs but show dose-dependent metabolic side effects such as the development of insulin resistance and obesity. The precise mechanisms involved in these glucocorticoid-induced side effects, and especially the participation of adipose tissue in this are not completely understood. We used a combination of transcriptomics, antibody arrays and bioinformatics approaches to characterize prednisolone-induced alterations in gene expression and adipokine secretion, which could underlie metabolic dysfunction in 3T3-L1 adipocytes. Several pathways, including cytokine signalling, Akt signalling, and Wnt signalling were found to be regulated at multiple levels, showing that these processes are targeted by prednisolone. These results suggest that mechanisms by which prednisolone induce insulin resistance include dysregulation of wnt signalling and immune response processes. These pathways may provide interesting targets for the development of improved glucocorticoids.
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The thoracic and peritoneal cavities are lined by serous membranes and are home of the serosal immune system. This immune system fuses innate and adaptive immunity, to maintain local homeostasis and repair local tissue damage, and to cooperate closely with the mucosal immune system. Innate lymphoid cells (ILCs) are found abundantly in the thoracic and peritoneal cavities, and they are crucial in first defense against pathogenic viruses and bacteria. Nanomaterials (NMs) can enter the cavities intentionally for medical purposes, or unintentionally following environmental exposure; subsequent serosal inflammation and cancer (mesothelioma) has gained significant interest. However, reports on adverse effects of NMon ILCs and other components of the serosal immune systemare scarce or even lacking. As ILCs are crucial in the first defense against pathogenic viruses and bacteria, it is possible that serosal exposure to NMmay lead to a reduced resistance against pathogens. Additionally, affected serosal lymphoid tissues and cells may disturb adipose tissue homeostasis. This review aims to provide insight into key effects of NMon the serosal immune system.
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Whitepaper van het project ConsuBETER, waarin cijfers,oorzaak en gevolg, eiwitbehoefte en -inname en mogelijke oplossingsrichtingen worden besproken.
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Abstract: Hypertension is both a health problem and a financial one globally. It affects nearly 30 % of the general population. Elderly people, aged ≥65 years, are a special group of hypertensive patients. In this group, the overall prevalence of the disease reaches 60 %, rising to 70 % in those aged ≥80 years. In the elderly population, isolated systolic hypertension is quite common. High systolic blood pressure is associated with an increased risk of cardiovascular disease, cerebrovascular disease, peripheral artery disease, cognitive impairment and kidney disease. Considering the physiological changes resulting from ageing alongside multiple comorbidities, treatment of hypertension in elderly patients poses a significant challenge to treatment teams. Progressive disability with regard to the activities of daily life, more frequent hospitalisations and low quality of life are often seen in elderly patients. There is discussion in the literature regarding frailty syndrome associated with old age. Frailty is understood to involve decreased resistance to stressors, depleted adaptive and physiological reserves of a number of organs, endocrine dysregulation and immune dysfunction. The primary dilemma concerning frailty is whether it should only be defined on the basis of physical factors, or whether psychological and social factors should also be included. Proper nutrition and motor rehabilitation should be prioritised in care for frail patients. The risk of orthostatic hypotension is a significant issue in elderly patients. It results from an autonomic nervous system dysfunction and involves maladjustment of the cardiovascular system to sudden changes in the position of the body. Other significant issues in elderly patients include polypharmacy, increased risk of falls and cognitive impairment. Chronic diseases, including hypertension, deteriorate baroreceptor function and result in irreversible changes in cerebral and coronary circulation. Concurrent frailty or other components of geriatric syndrome in elderly patients are associated with a worse perception of health, an increased number of comorbidities and social isolation of the patient. It may also interfere with treatment adherence. Identifying causes of non-adherence to pharmaceutical treatment is a key factor in planning therapeutic interventions aimed at increasing control, preventing complications, and improving long-term outcomes and any adverse effects of treatment. Diagnosis of frailty and awareness of the associated difficulties in adhering to treatment may allow targeting of those elderly patients who have a poorer prognosis or may be at risk of complications from untreated or undertreated hypertension, and for the planning of interventions to improve hypertension control.
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Hoofdstuk 2 gaat over peer en professionele online support voor ouders bij het opvoeden. In totaal bevat het boek 31 hoofdstukken over sociaal netwerken, geschreven door tientallen onderzoekers wereldwijd.
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What is known in scientific literature at this point in time about the effects of the measures against the transmission of the coronavirus and what is the meaning of this for the organisers of events?
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Abstract Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has challenged healthcare globally. An acute increase in the number of hospitalized patients has neces‑ sitated a rigorous reorganization of hospital care, thereby creating circumstances that previously have been identifed as facilitating prescribing errors (PEs), e.g. a demanding work environment, a high turnover of doctors, and prescrib‑ ing beyond expertise. Hospitalized COVID-19 patients may be at risk of PEs, potentially resulting in patient harm. We determined the prevalence, severity, and risk factors for PEs in post–COVID-19 patients, hospitalized during the frst wave of COVID-19 in the Netherlands, 3months after discharge. Methods: This prospective observational cohort study recruited patients who visited a post-COVID-19 outpatient clinic of an academic hospital in the Netherlands, 3months after COVID-19 hospitalization, between June 1 and October 1 2020. All patients with appointments were eligible for inclusion. The prevalence and severity of PEs were assessed in a multidisciplinary consensus meeting. Odds ratios (ORs) were calculated by univariate and multivariate analysis to identify independent risk factors for PEs. Results: Ninety-eight patients were included, of whom 92% had ≥1 PE and 8% experienced medication-related harm requiring an immediate change in medication therapy to prevent detoriation. Overall, 68% of all identifed PEs were made during or after the COVID-19 related hospitalization. Multivariate analyses identifed ICU admission (OR 6.08, 95% CI 2.16–17.09) and a medical history of COPD / asthma (OR 5.36, 95% CI 1.34–21.5) as independent risk fac‑ tors for PEs. Conclusions: PEs occurred frequently during the SARS-CoV-2 pandemic. Patients admitted to an ICU during COVID19 hospitalization or who had a medical history of COPD / asthma were at risk of PEs. These risk factors can be used to identify high-risk patients and to implement targeted interventions. Awareness of prescribing safely is crucial to prevent harm in this new patient population.
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From the publisher: "Background: The introduction of whole new foods in a population may lead to sensitization and food allergy. This constitutes a potential public health problem and a challenge to risk assessors and managers as the existing understanding of the pathophysiological processes and the currently available biological tools for prediction of the risk for food allergy development and the severity of the reaction are not sufficient. There is a substantial body of in vivo and in vitro data describing molecular and cellular events potentially involved in food sensitization. However, these events have not been organized in a sequence of related events that is plausible to result in sensitization, and useful to challenge current hypotheses. The aim of this manuscript was to collect and structure the current mechanistic understanding of sensitization induction to food proteins by applying the concept of adverse outcome pathway (AOP). Main body: The proposed AOP for food sensitization is based on information on molecular and cellular mechanisms and pathways evidenced to be involved in sensitization by food and food proteins and uses the AOPs for chemical skin sensitization and respiratory sensitization induction as templates. Available mechanistic data on protein respiratory sensitization were included to fill out gaps in the understanding of how proteins may affect cells, cell-cell interactions and tissue homeostasis. Analysis revealed several key events (KE) and biomarkers that may have potential use in testing and assessment of proteins for their sensitizing potential. Conclusion: The application of the AOP concept to structure mechanistic in vivo and in vitro knowledge has made it possible to identify a number of methods, each addressing a specific KE, that provide information about the food allergenic potential of new proteins. When applied in the context of an integrated strategy these methods may reduce, if not replace, current animal testing approaches. The proposed AOP will be shared at the www.aopwiki.org platform to expand the mechanistic data, improve the confidence in each of the proposed KE and key event relations (KERs), and allow for the identification of new, or refinement of established KE and KERs." Authors: Jolanda H. M. van BilsenEmail author, Edyta Sienkiewicz-Szłapka, Daniel Lozano-Ojalvo, Linette E. M. Willemsen, Celia M. Antunes, Elena Molina, Joost J. Smit, Barbara Wróblewska, Harry J. Wichers, Edward F. Knol, Gregory S. Ladics, Raymond H. H. Pieters, Sandra Denery-Papini, Yvonne M. Vissers, Simona L. Bavaro, Colette Larré, Kitty C. M. Verhoeckx and Erwin L. Roggen
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Wat is er op dit moment (medio augustus 2020) in de wetenschappelijke literatuur bekend over (de effecten van maatregelen tegen) de verspreiding van het coronavirus en wat is de betekenis daarvan voor organisatoren van evenementen?
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From PLoS website: In general, dietary antigens are tolerated by the gut associated immune system. Impairment of this so-called oral tolerance is a serious health risk. We have previously shown that activation of the ligand-dependent transcription factor aryl hydrocarbon receptor (AhR) by the environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects both oral tolerance and food allergy. In this study, we determine whether a common plant-derived, dietary AhR-ligand modulates oral tolerance as well. We therefore fed mice with indole-3-carbinole (I3C), an AhR ligand that is abundant in cruciferous plants. We show that several I3C metabolites were detectable in the serum after feeding, including the high-affinity ligand 3,3´-diindolylmethane (DIM). I3C feeding robustly induced the AhR-target gene CYP4501A1 in the intestine; I3C feeding also induced the aldh1 gene, whose product catalyzes the formation of retinoic acid (RA), an inducer of regulatory T cells. We then measured parameters indicating oral tolerance and severity of peanut-induced food allergy. In contrast to the tolerance-breaking effect of TCDD, feeding mice with chow containing 2 g/kg I3C lowered the serum anti-ovalbumin IgG1 response in an experimental oral tolerance protocol. Moreover, I3C feeding attenuated symptoms of peanut allergy. In conclusion, the dietary compound I3C can positively influence a vital immune function of the gut.
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