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BackgroundThe Q705K polymorphism in NLRP3 has been implicated in several chronic inflammatory diseases. In this study we determine the functional role of this commonly occurring polymorphism using an in-vitro system.Principal FindingsNLRP3-WT and NLRP3-Q705K were retrovirally transduced into the human monocytic cell line THP-1, followed by the assessment of IL-1β and IL-18 levels in the cell culture supernatant. THP-1 cells expressing the above NLRP3 variants were sorted based upon Green Fluorescent Protein (GFP) expression. Cytokine response to alum (one of the most widely used adjuvants in vaccines) in the cells stably expressing NLRP3-WT and NLRP3-Q705K were determined. IL-1β and IL-18 levels were found to be elevated in THP-1 cells transduced with NLRP3-Q705K compared to the NLRP3-WT. Upon exposure to alum, THP-1 cells stably expressing NLRP3-Q705K displayed an increased release of IL-1β, IL-18 and TNF-α, in a caspase-1 and IL-1 receptor-dependent manner.ConclusionsCollectively, these findings show that the Q705K polymorphism in NLRP3 is a gain-of-function alteration leading to an overactive NLRP3 inflammasome. The option of IL-1β blockade may be considered in patients with chronic inflammatory disorders that are unresponsive to conventional treatments.

BackgroundCell fusion is a natural process in normal development and tissue regeneration. Fusion between cancer cells and macrophages generates metastatic hybrids with genetic and phenotypic characteristics from both maternal cells. However, there are no clinical markers for detecting cell fusion in clinical context. Macrophage-specific antigen CD163 expression in tumor cells is reported in breast and colorectal cancers and proposed being caused by macrophages-cancer cell fusion in tumor stroma. The purpose of this study is to examine the cell fusion process as a biological explanation for macrophage phenotype in breast.MethodsMonocytes, harvested from male blood donor, were activated to M2 macrophages and co-cultured in ThinCert transwell system with GFP-labeled MCF-7 cancer cells. MCF7/macrophage hybrids were generated by spontaneous cell fusion, isolated by fluorescence-activated cell sorting and confirmed by fluorescence microscopy, short tandem repeats analysis and flow cytometry. CD163 expression was evaluated in breast tumor samples material from 127 women by immunohistochemistry.ResultsMCF-7/macrophage hybrids were generated spontaneously at average rate of 2 % and showed phenotypic and genetic traits from both maternal cells. CD163 expression in MCF-7 cells could not be induced by paracrine interaction with M2-activated macrophages. CD163 positive cancer cells in tumor sections grew in clonal collection and a cutoff point >25 % of positive cancer cells was significantly correlated to disease free and overall survival.ConclusionsIn conclusion, macrophage traits in breast cancer might be caused by cell fusion rather than explained by paracrine cellular interaction. These data provide new insights into the role of cell fusion in breast cancer and contributes to the development of clinical markers to identify cell fusion.

Patients with carcinoma of the stomach who underwent curative resection were randomized to total gastrectomy (n = 49), total gastrectomy and an S-shaped gastric substitute (n = 28) or subtotal gastrectomy (n = 12); all had a Roux-en-Y reconstruction. The gastric substitute and gastric remnant allowed a volume of 400-500 ml to be installed without increments in basal pressures. The corresponding volume in the Roux limb was 100 ml. Energy intake was approximately 120 kJ/kg preoperative weight per day 3 months after operation, and then remained constant. Patients who had subtotal gastrectomy ate less (91.7 kJ/kg preoperative weight) 3 months after operation, but thereafter increased their intake. Patients allocated to have a gastric pouch or subtotal gastrectomy complained more frequently of adverse postprandial symptoms (P < 0.03) as a major cause of reduced calorie intake. The construction of a gastric reservoir did not improve nutritional adaptation after surgery for gastric carcinoma.

The current view of dietary carbohydrates as simply providing us with energy is outdated. Because of their varied chemistry and physical form the rate and extent to which the different types are digested in and absorbed from the small intestine varies. This in turn leads to affects on satiety, blood glucose and insulin, protein glycosylation, lipids and bile acids. Some carbohydrates reach the colon where they are fermented and affect many aspects of large bowel function, colonocyte and hepatic metabolism.A new framework for classifying and measuring food carbohydrates is needed to allow a greater understanding of the role of individual species in health and to inform the public of their importance. A classi®cation based primarily on molecular size (degree of polymerisation) into sugars, oligosaccharides and polysaccharides, is suggested, with sub-groups identi®ed by the nature of the monosaccharides. Greater knowledge of the chemical and physical properties of carbohydrates allow a more precise relation with physiology and health to be drawn.The Carbohydrate Group met in Paris in December 1995 at the invitation of Gerard Pascal, Director of CNERNA. Financial support for the meeting was provided by CNERNA.

To elucidate mechanisms involved in weight development after gastrectomy we have prospectively determined changes in body composition during the first year after similar operations. A total of 75 patients were enrolled who had a "curative operation" for gastric carcinoma; 42 were randomized to have a total gastrectomy, 23 total gastrectomy with a gastric substitute, and 10 subtotal gastrectomy. All reconstructions were done with a Roux-en-Y loop of the jejunum. Body composition was assessed preoperatively and at 6 and 12 months after gastrectomy by determining total body potassium and total body water. From these estimates, body cell mass, extracellular water, fat-free extracellular solids, and body fat were calculated with knowledge of the actual body weight and length. Triceps skinfold, arm muscle circumference, and grip strength were also measured. Weight loss (10% of preoperative weight) occurred early after the operations, after which body weight stabilized. Body cell mass remained essentially unchanged over the entire study period in contrast to body fat, which decreased by 40% during the first 6 months after gastrectomy. In accordance with the selective loss of body fat, we recorded a significant decrease in triceps skinfold figures and only a minor decrease of arm muscle circumference without obvious deterioration in hand grip strength. Weight loss after gastrectomy seems to be characterized by selective loss of body fat in contrast to other known clinical situations associated with impaired nutritional intake. Our observations form a basis for future clinical research aimed at preventing weight loss after these operations.

The addition of RBF containing RS(2) to the diet of ileostomy subjects did not interfere with small-bowel absorption of nutrients or total sterols, except for a small increase in iron excretion. The ileostomy model seems to give reliable results for in vivo measurement of RS.

Clinical reasoning is the process of gathering and understanding information conducted by clinicians in the emergency medical services (EMS) so as to make informed decisions. Research on clinical reasoning spans several disciplines, but a comprehensive view of the process is lacking. To our knowledge, no review of clinical reasoning in the EMS has been conducted. Aim The aim was to investigate the nature, deployment, and factors influencing EMS clinicians’ clinical reasoning by means of a review. Method Data was collected through searches in electronic databases, networking among research teams, colleagues and friends, “grey literature,” and through ancestry searches. A total of 38 articles were deemed eligible for inclusion and were analyzed using descriptive thematic analysis. The analysis resulted in an overarching finding - namely, the importance for EMS clinicians to adjust for perceived control in unpredictable situations. Within this finding, 3 themes emerged in terms of EMS clinicians’ clinical reasoning: (1) maintaining a holistic view of the patient; (2) keeping an open mind; and (3) improving through criticism. Seven subthemes subsequently emerged from these three themes. Results This review showed that EMS clinicians’ clinical reasoning begins with the information that they are given about a patient. Based on this information, clinicians calculate the best route to the patient and which equipment to use, and they also assess potential risks. They need to be constantly aware of what is happening on the scene and with the patient and strive to control the situation. This striving also enables EMS clinicians to work safely and effectively in relation to the patient, their relatives, other clinicians, associated organizations, and the wider community. A lack of contextually appropriate guidelines results in the need for creativity and forces EMS clinicians to use “workarounds” to solve issues beyond the scope of the guidelines available. In addition, they often lack organizational support and fear repercussions such as litigation, unemployment, or blame by their EMS or healthcare organization or by patients and relatives. Conclusion Clinical reasoning is influenced by several factors. Further research is needed to determine which influencing factors can be addressed through interventions to minimize their impact on patient outcomes. Electronic supplementary material The online version of this article (10.1186/s13049-019-0646-y) contains supplementary material, which is available to authorized users.