There is overwhelming evidence that functional gastrointestinal disorders(FGIDs) are associated with specific mechanisms that constitute important targets for personalized treatment. There are specific mechanisms in p...There is overwhelming evidence that functional gastrointestinal disorders(FGIDs) are associated with specific mechanisms that constitute important targets for personalized treatment. There are specific mechanisms in patients presenting with functional upper gastrointestinal symptoms(UGI Sx). Among patients with UGI Sx, approximately equal proportions(25%) of patients have delayed gastric emptying(GE), reduced gastric accommodation(GA), both impaired GE and GA,or neither, presumably due to increased gastric or duodenal sensitivity.Treatments targeted to the underlying pathophysiology utilize prokinetics,gastric relaxants, or central neuromodulators. Similarly, specific mechanisms in patients presenting with functional lower gastrointestinal symptoms, especially with diarrhea or constipation, are recognized, including at least 30% of patients with functional constipation pelvic floor dyssynergia and 5% has colonic inertia(with neural or interstitial cells of Cajal loss in myenteric plexus); 25% of patients with diarrhea-predominant irritable bowel syndrome(IBSD) has evidence of bile acid diarrhea; and, depending on ethnicity, a varying proportion of patients has disaccharidase deficiency, and less often sucrose-isomaltase deficiency. Among patients with predominant pain or bloating, the role of fermentable oligosaccharides, disaccharides, monosaccharides and polyols should be considered. Personalization is applied through pharmacogenomics related to drug pharmacokinetics, specifically the role of CYP2 D6, 2 C19 and 3 A4 in the use of drugs for treatment of patients with FGIDs. Single mutations or multiple genetic variants are relatively rare, with limited impact to date on the understanding or treatment of FGIDs. The role of mucosal gene expression in FGIDs, particularly in IBS-D, is the subject of ongoing research. In summary, the time for personalization of FGIDs, based on deep phenotyping, is here;pharmacogenomics is relevant in the use of central neuromodulators. There is still unclear impact of the role of genetics in the management of FGIDs.展开更多
The worldwide rise in the prevalence of obesity supports the need for an increased interaction between ongoing clinical research in the allied fields of gastrointestinal medicine/surgery and diabetes mellitus. There h...The worldwide rise in the prevalence of obesity supports the need for an increased interaction between ongoing clinical research in the allied fields of gastrointestinal medicine/surgery and diabetes mellitus. There have been a number of clinically-relevant advances in diabetes, obesity, and metabolic syndrome emanating from gastroenterological research. Gastric emptying is a significant factor in the development of upper gastrointestinal symptoms. However, it is not the only mechanism whereby such symptoms occur in patients with diabetes. Disorders of intrinsic pacing are involved in the control of stomach motility in patients with gastroparesis; on the other hand, there is limited impact of glycemic control on gastric emptying in patients with established diabetic gastroparesis. Upper gastrointestinal functions related to emptying and satiations are significantly associated with weight gain in obesity. Medications used in the treatment of diabetes or metabolic syndrome, particularly those related to pancreatic hormones and incretins affect upper gastrointestinal tract function and reduce hyperglycemia and facilitate weight loss. The degree of gastric emptying delay is significantly correlated with the weight loss in response to liraglutide, a glucagonlike peptide-1 analog. Network meta-analysis shows that liraglutide is one of the two most efficacious medical treatments of obesity, the other being the combination treatment phentermine-topiramate. Interventional therapies for the joint management of obesity and diabetes mellitus include newer endoscopic procedures, which require long-term follow-up and bariatric surgical procedure for which long-term follow up shows advantages for individuals with diabetes. Newer bariatric procedures are presently undergoing clinical evaluation. On the horizon, combination therapies, in part directed at gastrointestinal functions, appear promising for these indications. Ongoing and future gastroenterological research when translated to care of individuals with diabetes mellitus should provide additional options to improve their clinical outcomes.展开更多
Coal seams with high CO_2 gas contents can be difficult to drain gas for outburst management. Coal has a high affinity for CO_2 with adsorption capacities typically twice that of CH_4. This paper presents an analysis ...Coal seams with high CO_2 gas contents can be difficult to drain gas for outburst management. Coal has a high affinity for CO_2 with adsorption capacities typically twice that of CH_4. This paper presents an analysis of nitrogen injection into coal to enhance drainage of high CO_2 gas contents. Core flooding experiments were conducted where nitrogen was injected into coal core samples from two Australian coal mining basins with initial CO_2 gas contents and pressures that could be encountered during underground mining. Nitrogen effectively displaced the CO_2 with mass balance analysis finding there was only approximately 6%–7% of the original CO_2 gas content residual at the end of the core flood. Using a modified version of the SIMED II reservoir simulator, the core flooding experiments were history matched to determine the nitrogen and methane sorption times. It was found that a triple porosity model(a simple extension of the Warren and Root dual porosity model) was required to accurately describe the core flood observations. The estimated model properties were then used in reservoir simulation studies comparing enhanced drainage with conventional drainage with underground in seam boreholes. For the cases considered, underground in seam boreholes were found to provide shorter drainage lead times than enhanced drainage to meet a safe gas content for outburst management.展开更多
文摘There is overwhelming evidence that functional gastrointestinal disorders(FGIDs) are associated with specific mechanisms that constitute important targets for personalized treatment. There are specific mechanisms in patients presenting with functional upper gastrointestinal symptoms(UGI Sx). Among patients with UGI Sx, approximately equal proportions(25%) of patients have delayed gastric emptying(GE), reduced gastric accommodation(GA), both impaired GE and GA,or neither, presumably due to increased gastric or duodenal sensitivity.Treatments targeted to the underlying pathophysiology utilize prokinetics,gastric relaxants, or central neuromodulators. Similarly, specific mechanisms in patients presenting with functional lower gastrointestinal symptoms, especially with diarrhea or constipation, are recognized, including at least 30% of patients with functional constipation pelvic floor dyssynergia and 5% has colonic inertia(with neural or interstitial cells of Cajal loss in myenteric plexus); 25% of patients with diarrhea-predominant irritable bowel syndrome(IBSD) has evidence of bile acid diarrhea; and, depending on ethnicity, a varying proportion of patients has disaccharidase deficiency, and less often sucrose-isomaltase deficiency. Among patients with predominant pain or bloating, the role of fermentable oligosaccharides, disaccharides, monosaccharides and polyols should be considered. Personalization is applied through pharmacogenomics related to drug pharmacokinetics, specifically the role of CYP2 D6, 2 C19 and 3 A4 in the use of drugs for treatment of patients with FGIDs. Single mutations or multiple genetic variants are relatively rare, with limited impact to date on the understanding or treatment of FGIDs. The role of mucosal gene expression in FGIDs, particularly in IBS-D, is the subject of ongoing research. In summary, the time for personalization of FGIDs, based on deep phenotyping, is here;pharmacogenomics is relevant in the use of central neuromodulators. There is still unclear impact of the role of genetics in the management of FGIDs.
基金Supported by the grant from National Institutes of Health,No.R01-DK67071
文摘The worldwide rise in the prevalence of obesity supports the need for an increased interaction between ongoing clinical research in the allied fields of gastrointestinal medicine/surgery and diabetes mellitus. There have been a number of clinically-relevant advances in diabetes, obesity, and metabolic syndrome emanating from gastroenterological research. Gastric emptying is a significant factor in the development of upper gastrointestinal symptoms. However, it is not the only mechanism whereby such symptoms occur in patients with diabetes. Disorders of intrinsic pacing are involved in the control of stomach motility in patients with gastroparesis; on the other hand, there is limited impact of glycemic control on gastric emptying in patients with established diabetic gastroparesis. Upper gastrointestinal functions related to emptying and satiations are significantly associated with weight gain in obesity. Medications used in the treatment of diabetes or metabolic syndrome, particularly those related to pancreatic hormones and incretins affect upper gastrointestinal tract function and reduce hyperglycemia and facilitate weight loss. The degree of gastric emptying delay is significantly correlated with the weight loss in response to liraglutide, a glucagonlike peptide-1 analog. Network meta-analysis shows that liraglutide is one of the two most efficacious medical treatments of obesity, the other being the combination treatment phentermine-topiramate. Interventional therapies for the joint management of obesity and diabetes mellitus include newer endoscopic procedures, which require long-term follow-up and bariatric surgical procedure for which long-term follow up shows advantages for individuals with diabetes. Newer bariatric procedures are presently undergoing clinical evaluation. On the horizon, combination therapies, in part directed at gastrointestinal functions, appear promising for these indications. Ongoing and future gastroenterological research when translated to care of individuals with diabetes mellitus should provide additional options to improve their clinical outcomes.
文摘Coal seams with high CO_2 gas contents can be difficult to drain gas for outburst management. Coal has a high affinity for CO_2 with adsorption capacities typically twice that of CH_4. This paper presents an analysis of nitrogen injection into coal to enhance drainage of high CO_2 gas contents. Core flooding experiments were conducted where nitrogen was injected into coal core samples from two Australian coal mining basins with initial CO_2 gas contents and pressures that could be encountered during underground mining. Nitrogen effectively displaced the CO_2 with mass balance analysis finding there was only approximately 6%–7% of the original CO_2 gas content residual at the end of the core flood. Using a modified version of the SIMED II reservoir simulator, the core flooding experiments were history matched to determine the nitrogen and methane sorption times. It was found that a triple porosity model(a simple extension of the Warren and Root dual porosity model) was required to accurately describe the core flood observations. The estimated model properties were then used in reservoir simulation studies comparing enhanced drainage with conventional drainage with underground in seam boreholes. For the cases considered, underground in seam boreholes were found to provide shorter drainage lead times than enhanced drainage to meet a safe gas content for outburst management.
