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- Bischoff, Stephan C, et al.
(författare)
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Towards a multidisciplinary approach to understand and manage obesity and related diseases
- 2017
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Ingår i: Clinical Nutrition. - : Elsevier BV. - 0261-5614 .- 1532-1983. ; 36:4, s. 917-938
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Forskningsöversikt (refereegranskat)abstract
- Overnutrition and sedentary lifestyle result in overweight or obesity defined as abnormal or excessive fat accumulation that may impair health. According to the WHO, the worldwide prevalence of obesity nearly doubled between 1980 and 2008. In 2008, over 50% of both men and women in the WHO European Region were overweight, and approximately 23% of women and 20% of men were obese. Comprehensive diagnostic and therapeutic approaches should include nutritional treatment to favor the best metabolic and nutritional outcome, as well as to induce potential disease-specific benefits from selected nutritional regimens. Obesity is usually accompanied by an increased muscle mass. This might explain why obesity, under particular circumstances such as cancer or high age, might have protective effects, a phenomenon named the 'obesity paradox'. However, loss of muscle mass or function can also occur, which is associated with poor prognosis and termed 'sarcopenic obesity'. Therefore, treatment recommendations may need to be individualized and adapted to co-morbidities. Since obesity is a chronic systemic disease it requires a multidisciplinary approach, both at the level of prevention and therapy including weight loss and maintenance. In the present personal review and position paper, authors from different disciplines including endocrinology, gastroenterology, nephrology, pediatrics, surgery, geriatrics, intensive care medicine, psychology and psychiatry, sports medicine and rheumatology, both at the basic science and clinical level, present their view on the topic and underline the necessity to provide a multidisciplinary approach, to address this epidemic.
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- Cederholm, Tommy, et al.
(författare)
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ESPEN guidelines on definitions and terminology of clinical nutrition
- 2017
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Ingår i: Clinical Nutrition. - 0261-5614 .- 1532-1983. ; 36:1, s. 49-64
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundA lack of agreement on definitions and terminology used for nutrition-related concepts and procedures limits the development of clinical nutrition practice and research.ObjectiveThis initiative aimed to reach a consensus for terminology for core nutritional concepts and procedures.MethodsThe European Society of Clinical Nutrition and Metabolism (ESPEN) appointed a consensus group of clinical scientists to perform a modified Delphi process that encompassed e-mail communication, face-to-face meetings, in-group ballots and an electronic ESPEN membership Delphi round.ResultsFive key areas related to clinical nutrition were identified: concepts; procedures; organisation; delivery; and products. One core concept of clinical nutrition is malnutrition/undernutrition, which includes disease-related malnutrition (DRM) with (eq. cachexia) and without inflammation, and malnutrition/undernutrition without disease, e.g. hunger-related malnutrition. Over-nutrition (overweight and obesity) is another core concept. Sarcopenia and frailty were agreed to be separate conditions often associated with malnutrition. Examples of nutritional procedures identified include screening for subjects at nutritional risk followed by a complete nutritional assessment. Hospital and care facility catering are the basic organizational forms for providing nutrition. Oral nutritional supplementation is the preferred way of nutrition therapy but if inadequate then other forms of medical nutrition therapy, i.e. enteral tube feeding and parenteral (intravenous) nutrition, becomes the major way of nutrient delivery.ConclusionAn agreement of basic nutritional terminology to be used in clinical practice, research, and the ESPEN guideline developments has been established. This terminology consensus may help to support future global consensus efforts and updates of classification systems such as the International Classification of Disease (ICD). The continuous growth of knowledge in all areas addressed in this statement will provide the foundation for future revisions.
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- Barazzoni, Rocco, et al.
(författare)
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Nutritional management of individuals with obesity and COVID-19 : ESPEN expert statements and practical guidance
- 2022
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Ingår i: Clinical Nutrition. - : Elsevier. - 0261-5614 .- 1532-1983. ; 41:12, s. 2869-2886
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Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemics has created unprecedented challenges and threats to patients and healthcare systems worldwide. Acute respiratory complications that require intensive care unit (ICU) management are a major cause of morbidity and mortality in COVID-19 patients. Among other important risk factors for severe COVID-19 outcomes, obesity has emerged along with undernutrition-malnutrition as a strong predictor of disease risk and severity. Obesity-related excessive body fat may lead to respiratory, metabolic and immune derangements potentially favoring the onset of COVID-19 complications. In addition, patients with obesity may be at risk for loss of skeletal muscle mass, reflecting a state of hidden malnutrition with a strong negative health impact in all clinical settings. Also importantly, obesity is commonly associated with micronutrient deficiencies that directly influence immune function and infection risk. Finally, the pandemic-related lockdown, deleterious lifestyle changes and other numerous psychosocial consequences may worsen eating behaviors, sedentarity, body weight regulation, ultimately leading to further increments of obesity-associated metabolic complications with loss of skeletal muscle mass and higher non-communicable disease risk. Therefore, prevention, diagnosis and treatment of malnutrition and micronutrient deficiencies should be routinely included in the management of COVID-19 patients in the presence of obesity; lockdown-induced health risks should also be specifically monitored and prevented in this population. In the current document, the European Society for Clinical Nutrition and Metabolism (ESPEN) aims at providing clinical practice guidance for nutritional management of COVID-19 patients with obesity in various clinical settings.
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4. |
- Bischoff, Stephan C, et al.
(författare)
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Standard operating procedures for ESPEN guidelines and consensus papers
- 2015
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Ingår i: Clinical Nutrition. - : Elsevier BV. - 0261-5614 .- 1532-1983. ; 34:6, s. 1043-1051
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Tidskriftsartikel (refereegranskat)abstract
- The ESPEN Guideline standard operating procedures (SOP) is based on the methodology provided by the Association of Scientific Medical Societies of Germany (AWMF), the Scottish Intercollegiate Guidelines Network (SIGN), and the Centre for Evidence-based Medicine at the University of Oxford. The SOP is valid and obligatory for all future ESPEN-sponsored guideline projects aiming to generate high-quality guidelines on a regular basis. The SOP aims to facilitate the preparation of guideline projects, to streamline the consensus process, to ensure quality and transparency, and to facilitate the dissemination and publication of ESPEN guidelines. To achieve this goal, the ESPEN Guidelines Editorial board (GEB) has been established headed by two chairmen. The GEB will support and supervise the guideline processes and is responsible for the strategic planning of ESPEN guideline activities. Key elements of the SOP are the generation of well-built clinical questions according to the PICO system, a systemic literature search, a classification of the selected literature according to the SIGN evidence levels providing an evidence table, and a clear and straight-forward consensus procedure consisting of online voting's and a consensus conference. Only experts who meet the obligation to disclosure any potential conflict of interests and who are not employed by the Industry can participate in the guideline process. All recommendations will be graded according to the SIGN grading and novel outcome models besides biomedical endpoints. This approach will further extent the leadership of ESPEN in creating up-to-date and suitable for implementation guidelines and in sharing knowledge on malnutrition and clinical nutrition.
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5. |
- Blondelle, Jordan, et al.
(författare)
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Cullin-3-dependent deregulation of ACTN1 represents a pathogenic mechanism in nemaline myopathy
- 2019
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Ingår i: JCI Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 4:10
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Tidskriftsartikel (refereegranskat)abstract
- Nemaline myopathy is a congenital neuromuscular disorder characterized by muscle weakness, fiber atrophy, and presence of nemaline bodies within myofibers. However, understanding of the underlying pathomechanisms is lacking. Recently, mutations in KBTBD13, KLHL40, and KLHL41, three substrate adaptors for the E3 ubiquitin ligase Cullin-3, have been associated with early-onset nemaline myopathies. We hypothesized that deregulation of Cullin-3 and its muscle protein substrates may be responsible for disease development. Using Cullin-3-knockout mice, we identified accumulation of non-muscle α-actinins (ACTN1 and ACTN4) in muscles of these mice, which we also observed in patients with mutations in KBTBD13. Our data reveal that proper regulation of Cullin-3 activity and ACTN1 levels is essential for normal muscle and neuromuscular junction development. While ACTN1 is naturally downregulated during myogenesis, its overexpression in C2C12 myoblasts triggered defects in fusion, myogenesis, and acetylcholine receptor clustering - features that we characterized in Cullin-3-deficient mice. Taken together, our data highlight the importance of Cullin-3-mediated degradation of ACTN1 for muscle development, and indicate what is to our knowledge new pathomechanism for the etiology of myopathies seen in Cullin-3-knockout mice and patients with nemaline myopathy.
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7. |
- Javaheri, Anahita, et al.
(författare)
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Helicobacter pylori adhesin HopQ engages in a virulence-enhancing interaction with human CEACAMs
- 2017
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Ingår i: Nature Microbiology. - : NATURE PUBLISHING GROUP. - 2058-5276. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori specifically colonizes the human gastric epithelium and is the major causative agent for ulcer disease and gastric cancer development. Here, we identify members of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family as receptors of H. pylori and show that HopQ is the surface-exposed adhesin that specifically binds human CEACAM1, CEACAM3, CEACAM5 and CEACAM6. HopQ-CEACAM binding is glycan-independent and targeted to the N-domain. H. pylori binding induces CEACAM1-mediated signalling, and the HopQ-CEACAM1 interaction enables translocation of the virulence factor CagA into host cells and enhances the release of pro-inflammatory mediators such as interleukin-8. Based on the crystal structure of HopQ, we found that a beta-hairpin insertion (HopQ-ID) in HopQ's extracellular 3+4 helix bundle domain is important for CEACAM binding. A peptide derived from this domain competitively inhibits HopQ-mediated activation of the Cag virulence pathway, as genetic or antibody-mediated abrogation of the HopQ function shows. Together, our data suggest the HopQ-CEACAM1 interaction to be a potentially promising novel therapeutic target to combat H. pylori-associated diseases.
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8. |
- Kasliwal, M. M., et al.
(författare)
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Illuminating gravitational waves : A concordant picture of photons from a neutron star merger
- 2017
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 358:6370, s. 1559-
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Tidskriftsartikel (refereegranskat)abstract
- Merging neutron stars offer an excellent laboratory for simultaneously studying strong-field gravity and matter in extreme environments. We establish the physical association of an electromagnetic counterpart (EM170817) with gravitational waves (GW170817) detected from merging neutron stars. By synthesizing a panchromatic data set, we demonstrate that merging neutron stars are a long-sought production site forging heavy elements by r-process nucleosynthesis. The weak gamma rays seen in EM170817 are dissimilar to classical short gamma-ray bursts with ultrarelativistic jets. Instead, we suggest that breakout of a wide-angle, mildly relativistic cocoon engulfing the jet explains the low-luminosity gamma rays, the high-luminosity ultraviolet-optical-infrared, and the delayed radio and x-ray emission. We posit that all neutron star mergers may lead to a wide-angle cocoon breakout, sometimes accompanied by a successful jet and sometimes by a choked jet.
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10. |
- Nuernberger, Vincent, et al.
(författare)
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Hormonally Induced Hepatocellular Carcinoma in Diabetic Wild Type and Carbohydrate Responsive Element Binding Protein Knockout Mice
- 2021
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Ingår i: Cells. - : MDPI. - 2073-4409. ; 10:10
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Tidskriftsartikel (refereegranskat)abstract
- Objective: In the rat, the pancreatic islet transplantation model is an established method to induce hepatocellular carcinomas (HCC), due to insulin-mediated metabolic and molecular alterations like increased glycolysis and de novo lipogenesis and the oncogenic AKT/mTOR pathway including upregulation of the transcription factor Carbohydrate-response element-binding protein (ChREBP). ChREBP could therefore represent an essential oncogenic co-factor during hormonally induced hepatocarcinogenesis.Methods: Pancreatic islet transplantation was implemented in diabetic C57Bl/6J (wild type, WT) and ChREBP-knockout (KO) mice for 6 and 12 months. Liver tissue was examined using histology, immunohistochemistry, electron microscopy and Western blot analysis. Finally, we performed NGS-based transcriptome analysis between WT and KO liver tumor tissues.Results: Three hepatocellular carcinomas were detectable after 6 and 12 months in diabetic transplanted WT mice, but only one in a KO mouse after 12 months. Pre-neoplastic clear cell foci (CCF) were also present in liver acini downstream of the islets in WT and KO mice. In KO tumors, glycolysis, de novo lipogenesis and AKT/mTOR signalling were strongly downregulated compared to WT lesions. Extrafocal liver tissue of diabetic, transplanted KO mice revealed less glycogen storage and proliferative activity than WT mice. From transcriptome analysis, we identified a set of transcripts pertaining to metabolic, oncogenic and immunogenic pathways that are differentially expressed between tumors of WT and KO mice. Of 315 metabolism-associated genes, we observed 199 genes that displayed upregulation in the tumor of WT mice, whereas 116 transcripts showed their downregulated expression in KO mice tumor.Conclusions: The pancreatic islet transplantation model is a suitable method to study hormonally induced hepatocarcinogenesis also in mice, allowing combination with gene knockout models. Our data indicate that deletion of ChREBP delays insulin-induced hepatocarcinogenesis, suggesting a combined oncogenic and lipogenic function of ChREBP along AKT/mTOR-mediated proliferation of hepatocytes and induction of hepatocellular carcinoma.
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