The proton pump inhibitors (PPIs) as a class are remarkably safe and effective for persons with peptic ulcer disorders. Serious adverse events are extremely rare for PPIs, with case reports of interstitial nephritis w...The proton pump inhibitors (PPIs) as a class are remarkably safe and effective for persons with peptic ulcer disorders. Serious adverse events are extremely rare for PPIs, with case reports of interstitial nephritis with omeprazole, hepatitis with omeprazole and lansoprazole, and disputed visual disturbances with pantoprazole and omeprazole. PPI use is associated with the development of fundic gland polyps (FGP); stopping PPIs is associated with regression of FGP. In the absence of Helicobacter pylori infection, the long-term use of PPIs has not been convincingly proven to cause or be associated with the progression of pre-existing chronic gastritis or gastric atrophy or intestinal metaplasia. Mild/modest hypergastrinemia is a physiological response to the reduction in gastric acid secretion due to any cause. The long-term use of PPIs has not been convincingly proven to cause enterochromaff in-like cell hyperplasia or carcinoid tumors. PPIs increase the risk of community acquired pneumonia, but not of hospital acquired (nosocomial) pneumonia. There is no data to support particular care in prescribing PPI therapy due to concerns about risk of hip fracture with the long-termuse of PPIs. Long-term use of PPIs does not lead to vitamin B12 def iciencies, except possibly in the elderly, or in persons with Zollinger-Ellison Syndrome who are on high doses of PPI for prolonged periods of time. There is no convincingly proven data that PPIs increase the risk of Clostridium difficile-associated diarrhea in persons in the community. The discontinuation of PPIs may result in rebound symptoms requiring further and even continuous PPI use for suppression of symptoms. As with all medications, the key is to use PPIs only when clearly indicated, and to reassess continued use so that long-term therapy is used judiciously. Thus, in summary, the PPIs are a safe class of medications to use longterm in persons in whom there is a clear need for the maintenance of extensive acid inhibition.展开更多
Necrotizing enterocolitis is an inflammatory bowel disease of neonates with significant morbidity and mortality in preterm infants. Due to the multifactorial nature o the disease and limitations in disease models, ear...Necrotizing enterocolitis is an inflammatory bowel disease of neonates with significant morbidity and mortality in preterm infants. Due to the multifactorial nature o the disease and limitations in disease models, early diagnosis remains challenging and the pathogenesis elusive. Although preterm birth, hypoxic-ischemic events formula feeding, and abnormal bacteria colonization are established risk factors, the role of genetics and vasoactive/inflammatory mediators is unclear Consequently, treatments do not target the specific underlying disease processes and are symptomatic and surgically invasive. Breast-feeding is the most effective preventative measure. Recent advances in the prevention of necrotizing enterocolitis have focused on bioactive nutrients and trophic factors in human milk. Developmen of new disease models including the aspect of prematurity that consistently predisposes neonates to the disease with multiple risk factors will improve our understanding of the pathogenesis and lead to discovery of innovative therapeutics.展开更多
Celiac disease(CD) is one of the most common diseases,resulting from both environmental(gluten) and genetic factors [human leukocyte antigen(HLA) and nonHLA genes].The prevalence of CD has been estimated to approximat...Celiac disease(CD) is one of the most common diseases,resulting from both environmental(gluten) and genetic factors [human leukocyte antigen(HLA) and nonHLA genes].The prevalence of CD has been estimated to approximate 0.5%-1% in different parts of the world.However,the population with diabetes,autoimmune disorder or relatives of CD individuals have even higher risk for the development of CD,at least in part,because of shared HLA typing.Gliadin gains access to the basal surface of the epithelium,and interact directly with the immune system,via both trans-and para-cellular routes.From a diagnostic perspective,symptoms may be viewed as either "typical" or "atypical".In both positive serological screening results suggestive of CD,should lead to small bowel biopsy followed by a favourable clinical and serological response to the gluten-free diet(GFD) to confirm the diagnosis.Positive anti-tissue transglutaminase antibody or antiendomysial antibody during the clinical course helps to confirm the diagnosis of CD because of their over 99% specificities when small bowel villous atrophy is present on biopsy.Currently,the only treatment available for CD individuals is a strict life-long GFD.A greater understanding of the pathogenesis of CD allows alternative future CD treatments to hydrolyse toxic gliadin peptide,prevent toxic gliadin peptide absorption,blockage of selective deamidation of specific glutamine residues by tissue,restore immune tolerance towards gluten,modulation of immune response to dietary gliadin,and restoration of intestinal architecture.展开更多
Since the first report of use of endoscopy in children in the 1970 s, there has seen an exponential growthin published experience and innovation in the field. In this review article we focus on modern age therapeutic ...Since the first report of use of endoscopy in children in the 1970 s, there has seen an exponential growthin published experience and innovation in the field. In this review article we focus on modern age therapeutic endoscopy practice, explaining use of traditional as well as new and innovative techniques, for diagnosis and treatment of diseases in the paediatric upper gastrointestinal tract.展开更多
Carbohydrates are an important component of the diet. The carbohydrates that we ingest range from simple monosaccharides （glucose, fructose and galactose） to disaccharides （lactose, sucrose） to complex polysacchar...Carbohydrates are an important component of the diet. The carbohydrates that we ingest range from simple monosaccharides （glucose, fructose and galactose） to disaccharides （lactose, sucrose） to complex polysaccharides. Most carbohydrates are digested by salivary and pancreatic amylases, and are further broken down into monosaccharides by enzymes in the brush border membrane （BBM） of enterocytes. For example, lactase-phloridzin hydrolase and sucraseisomaltase are two disaccharidases involved in the hydrolysis of nutritionally important disaccharides. Once monosaccharides are presented to the BBM, mature enterocytes expressing nutrient transporters transport the sugars into the enterocytes. This paper reviews the early studies that contributed to the development of a working model of intestinal sugar transport, and details the recent advances made in understanding the process by which sugars are absorbed in the intestine.展开更多
AIM:To assess the feasibility and utility of double balloon enteroscopy(DBE)in the management of small bowel diseases in children. METHODS:Fourteen patients(10 males)with a median age of 12.9 years(range 8.1-16.7)unde...AIM:To assess the feasibility and utility of double balloon enteroscopy(DBE)in the management of small bowel diseases in children. METHODS:Fourteen patients(10 males)with a median age of 12.9 years(range 8.1-16.7)underwent DBE; 5 for Peutz-Jeghers syndrome(PJ syndrome),2 for chronic abdominal pain,4 for obscure gastrointestinal (GI)bleeding,2 with angiomatous malformations(1 blue rubber bleb nevus syndrome)having persistent GI bleeding,and 1 with Cowden's syndrome with multiple polyps and previous intussusception.Eleven procedures were performed under general anesthesia and 3 with deep sedation. RESULTS:The entire small bowel was examined in 6 patients,and a length between 200 cm and 320 cm distal to pylorus in the remaining 8.Seven patients had both antegrade(trans-oral)and retrograde(transanal and via ileostomy)examinations.One patient underwent DBE with planned laparoscopic assistance.The remaining 6 had trans-oral examination only.The median examination time was 118 min(range 95-195). No complications were encountered.Polyps were detected and successfully removed in all 5 patients with PJ syndrome,in a patient with tubulo-villous adenoma of the duodenum,in a patient with significant anemia and occult bleeding,and in a patient with Cowden's syndrome.A diagnosis was made in a patient with multiple angiomata not amenable to endotherapy,and in 1 with a discrete angioma which was treated with argon plasma coagulation.The source of bleeding was identified in a further patient with varices.DBE was normal or revealed minor mucosal friability in the remaining 3 patients.Hence a diagnostic yield of 11/14 with therapeutic success in 9/14 was achieved. CONCLUSION:Double balloon enteroscopy can be a useful diagnostic and therapeutic tool for small bowel disease in children,allowing endo-therapeutic intervention beyond the reach of the conventional endoscope.展开更多
Phototropins （phot1 and phot2） are blue-light receptor kinases controlling a range of responses that optimize the photosynthetic efficiency of plants. Light sensing is mediated by two flavin-binding motifs, known as...Phototropins （phot1 and phot2） are blue-light receptor kinases controlling a range of responses that optimize the photosynthetic efficiency of plants. Light sensing is mediated by two flavin-binding motifs, known as LOVl and LOV2, located within the N-terminal region of the protein. Photoexcitation via LOV2 leads to activation of the C-terminal kinase domain and consequently receptor autophosphorylation. However, knowledge of the in-vivo phosphorylation sites for Arabidopsis phototropins is lacking and has impeded progress in elucidating the functional significance of receptor phos- phorylation. We have purified photl from Arabidopsis and identified the in-vivo sites of receptor phosphorylation by liquid chromatography tandem mass spectrometry. Arabidopsis-derived photl binds flavin mononucleotide as chromophore and is phosphorylated at four major sites located upstream of LOV2 （Ser^58, Ser^85, Ser^350, and Ser^410）, three of which are induced by blue light. Nevertheless, structure-function analysis indicates that the biological activity of photl can be attributed to a modular unit comprising the LOV2-kinase region of the protein. Thus, peptide regions upstream of LOV2, including the sites of receptor phosphorylation identified here, do not appear to be important for receptor signaling. By contrast, these regions may be necessary for maximizing stomatal performance and possibly light-induced relocalization of photl.展开更多
To determine the clinical characteristics of children with gastrointestinal bleeding (GIB) who died during the course of their admission.METHODSWe interrogated the Pediatric Hospital Information System database, inclu...To determine the clinical characteristics of children with gastrointestinal bleeding (GIB) who died during the course of their admission.METHODSWe interrogated the Pediatric Hospital Information System database, including International Classification of Diseases, Current Procedural Terminology and Clinical Transaction Classification coding from 47 pediatric tertiary centers extracting the population of patients (1-21 years of age) admitted (inpatient or observation) with acute, upper or indeterminate GIB (1/2007-9/2015). Descriptive statistics, unadjusted univariate and adjusted multivariate analysis of the associations between patient characteristics and treatment course with mortality was performed with mortality as primary and endoscopy a secondary outcome of interest. All analyses were performed using the R statistical package, v.3.2.3.RESULTSThe population with GIB was 19528; 54.6% were male, overall mortality was 2.07%; (0.37% in patients with the principal diagnosis of GIB). When considering only the mortalities in which GIB was the principal diagnosis, 48% (12 of 25 principal diagnosis GIB mortalities) died within the first 3 d of admission, whereas 19.8% of secondary diagnosis GIB patients died with 3 d of admission. Patients who died were more likely to have received octreotide (19.8% c.f. 4.04%) but tended to have not received proton pump inhibitor therapy in the first 48 h, and far less likely to have undergone endoscopy during their admission (OR = 0.489, P < 0.0001). Chronic liver disease associated with a greater likelihood of endoscopy. Mortalities were significantly more likely to have multiple complex chronic conditions.CONCLUSIONGIB associated mortality in children is highest within 7 d of admission. Multiple comorbidities are a risk factor whereas early endoscopy during the admission is protective.展开更多
Nutrient deficiencies are common in patients with inflammatory bowel disease （IBD）. Both total parenteral and enteral nutrition provide important supportive therapy for IBD patients, but in adults these are not usef...Nutrient deficiencies are common in patients with inflammatory bowel disease （IBD）. Both total parenteral and enteral nutrition provide important supportive therapy for IBD patients, but in adults these are not useful for primary therapy. Dietary intervention with omega-3 polyunsaturated fatty acids contained in fish oil may be useful for the care of IBD patients, and recent studies have slyessed the role of PPAR on NFKB activity on the potential beneficial effect of dietary lipids on intestinal function.展开更多
Psychiatric disorders arc highly heritable, and in many individuals likely arise from the combined effects of genes and the environment. A substantial body of evidence points toward D1SCI being one of the genes that i...Psychiatric disorders arc highly heritable, and in many individuals likely arise from the combined effects of genes and the environment. A substantial body of evidence points toward D1SCI being one of the genes that influence risk of schizophrenia, bipolar disorder and depression, and functional studies of DISC1 consequently have the potential to reveal much about the pathways that lead to major mental illness. Here, we review the evidence that DISC1 influences disease risk through effects upon multiple critical pathways in the developing and adult brain.展开更多
As is the case in all parts of gastroenterology and hepatology,there have been many advances in our knowledge and understanding of small intestinal diseases.Over 1000 publications were reviewed for 2008 and 2009,and t...As is the case in all parts of gastroenterology and hepatology,there have been many advances in our knowledge and understanding of small intestinal diseases.Over 1000 publications were reviewed for 2008 and 2009,and the important advances in basic science as well as clinical applications were considered.In Part Ⅰ of this Editorial Review,seven topics are considered:intestinal development;proliferation and repair;intestinal permeability;microbiotica,infectious diarrhea and probiotics;diarrhea;salt and water absorption;necrotizing enterocolitis;and immunology/allergy.These topics were chosen because of their importance to the practicing physician.展开更多
In many metazoan species, germ cell formation requires the germ plasm, a specialized cytoplasm which often con-tains electron dense structures. Genes required for germ cell formation in Drosophila have been isolated p...In many metazoan species, germ cell formation requires the germ plasm, a specialized cytoplasm which often con-tains electron dense structures. Genes required for germ cell formation in Drosophila have been isolated predominantlyin screens for maternal-effect mutations. One such gene is tudor (tud); without proper tud function germ cell formationdoes not occur. Unlike other genes involved in Drosophila germ cell specification tud is dispensable for other somaticfunctions such as abdominal patterning. It is not known how TUD contributes at a molecular level to germ cell forma-tion but in tud mutants, polar granule formation is severely compromised, and mitochondrially encoded ribosomal RNAsdo not localize to the polar granule. TUD is composed of 11 repeats of the protein motif called the Tudor domain. Thereare similar proteins to TUD in the germ line of other metazoan species including mice. Probable vertebrate orthologuesof Drosophila genes involved in germ cell specification will be discussed.展开更多
Throughout our lifetime,the intestine changes.Some alterations in its form and function may be genetically determined,and some are the result of adaptation to diet,temperature,or stress.The critical period programming...Throughout our lifetime,the intestine changes.Some alterations in its form and function may be genetically determined,and some are the result of adaptation to diet,temperature,or stress.The critical period programming of the intestine can be modified,such as from subtle differences in the types and ratios of n3:m6 fatty acids in the diet of the pregnant mother,or in the diet of the weanlings.This early forced adaptation may persist in later life,such as the unwanted increased intestinal absorption of sugars,fatty acids and cholesterol.Thus,the ontogeny,early growth and development of the intestine is important for the adult gastroenterologist to appreciate,because of the potential for these early life events to affect the responsiveness of the intestine to physiological or pathological challenges in later life.展开更多
The coaxial compound helicopter has two possible strategies for heading control: collective differential and rudder deflection. A flight dynamics model is developed to assess the effect of different heading control st...The coaxial compound helicopter has two possible strategies for heading control: collective differential and rudder deflection. A flight dynamics model is developed to assess the effect of different heading control strategies. This includes the trim characteristics, steady flight performance,controllability, and manoeuvrability. The trim study demonstrates that heading control strategies are less influential on trim results, and the steady flight performance is also not significantly affected by the heading control strategy adopted. The controllability analysis shows although heading bandwidth and phase delay results at various speeds with different heading control strategies are all satisfied, the control derivative of the collective differential decreases as speed increases, and its heading aggressive agility is degraded into Level 3 in high-speed flight. In addition, using collective differential would lead to severe heading-rolling coupling as forward speed increases. On the contrary, the control derivative and aggressive agility of the rudder deflection is improved with forward speed, and there is no evidence of heading-rolling coupling. Finally, the transient turn MissionTask-Element(MTE) is utilized to investigate the heading manoeuvre characteristics in different heading control strategies, which indicates that the collective differential would add the amplitude of control input and the power consumption during this MTE.展开更多
Background:Arthrofibrosis is a joint disorder characterized by excessive scar formation in the joint tissues.Vitamin E is an antioxidant with potential anti-fibroblastic effect.The aim of this study was to establish a...Background:Arthrofibrosis is a joint disorder characterized by excessive scar formation in the joint tissues.Vitamin E is an antioxidant with potential anti-fibroblastic effect.The aim of this study was to establish an arthrofibrosis rat model after joint replacement and assess the effects of vitamin E supplementation on joint fibrosis.Methods:We simulated knee replacement in 16 male Sprague–Dawley rats.We immobilized the surgical leg with a suture in full flexion.The control groups were killed at 2 and 12 weeks(n=5 per group),and the test group was supplemented daily with vitamin E(0.2 mg/mL)in their drinking water for 12 weeks(n=6).We performed histological staining to investigate the presence and severity of arthrofibrosis.Immunofluorescent staining andα2-macroglobulin(α2M)enzyme-linked immunosorbent assay(ELISA)were used to assess local and systemic inflammation.Static weight bearing(total internal reflection)and range of motion(ROM)were collected for functional assessment.Results:The ROM and weight-bearing symmetry decreased after the procedure and recovered slowly with still significant deficit at the end of the study for both groups.Histological analysis confirmed fibrosis in both lateral and posterior periarticular tissue.Vitamin E supplementation showed a moderate anti-inflammatory effect on the local and systemic levels.The vitamin E group exhibited significant improvement in ROM and weight-bearing symmetry at day 84 compared to the control group.Conclusions:This model is viable for simulating arthrofibrosis after joint replacement.Vitamin E may benefit postsurgical arthrofibrosis,and further studies are needed for dosing requirements.展开更多
文摘The proton pump inhibitors (PPIs) as a class are remarkably safe and effective for persons with peptic ulcer disorders. Serious adverse events are extremely rare for PPIs, with case reports of interstitial nephritis with omeprazole, hepatitis with omeprazole and lansoprazole, and disputed visual disturbances with pantoprazole and omeprazole. PPI use is associated with the development of fundic gland polyps (FGP); stopping PPIs is associated with regression of FGP. In the absence of Helicobacter pylori infection, the long-term use of PPIs has not been convincingly proven to cause or be associated with the progression of pre-existing chronic gastritis or gastric atrophy or intestinal metaplasia. Mild/modest hypergastrinemia is a physiological response to the reduction in gastric acid secretion due to any cause. The long-term use of PPIs has not been convincingly proven to cause enterochromaff in-like cell hyperplasia or carcinoid tumors. PPIs increase the risk of community acquired pneumonia, but not of hospital acquired (nosocomial) pneumonia. There is no data to support particular care in prescribing PPI therapy due to concerns about risk of hip fracture with the long-termuse of PPIs. Long-term use of PPIs does not lead to vitamin B12 def iciencies, except possibly in the elderly, or in persons with Zollinger-Ellison Syndrome who are on high doses of PPI for prolonged periods of time. There is no convincingly proven data that PPIs increase the risk of Clostridium difficile-associated diarrhea in persons in the community. The discontinuation of PPIs may result in rebound symptoms requiring further and even continuous PPI use for suppression of symptoms. As with all medications, the key is to use PPIs only when clearly indicated, and to reassess continued use so that long-term therapy is used judiciously. Thus, in summary, the PPIs are a safe class of medications to use longterm in persons in whom there is a clear need for the maintenance of extensive acid inhibition.
基金Canadian Institute of Health research grant, No. 143315,a National Sciences and Engineering Research Council scholarship
文摘Necrotizing enterocolitis is an inflammatory bowel disease of neonates with significant morbidity and mortality in preterm infants. Due to the multifactorial nature o the disease and limitations in disease models, early diagnosis remains challenging and the pathogenesis elusive. Although preterm birth, hypoxic-ischemic events formula feeding, and abnormal bacteria colonization are established risk factors, the role of genetics and vasoactive/inflammatory mediators is unclear Consequently, treatments do not target the specific underlying disease processes and are symptomatic and surgically invasive. Breast-feeding is the most effective preventative measure. Recent advances in the prevention of necrotizing enterocolitis have focused on bioactive nutrients and trophic factors in human milk. Developmen of new disease models including the aspect of prematurity that consistently predisposes neonates to the disease with multiple risk factors will improve our understanding of the pathogenesis and lead to discovery of innovative therapeutics.
文摘Celiac disease(CD) is one of the most common diseases,resulting from both environmental(gluten) and genetic factors [human leukocyte antigen(HLA) and nonHLA genes].The prevalence of CD has been estimated to approximate 0.5%-1% in different parts of the world.However,the population with diabetes,autoimmune disorder or relatives of CD individuals have even higher risk for the development of CD,at least in part,because of shared HLA typing.Gliadin gains access to the basal surface of the epithelium,and interact directly with the immune system,via both trans-and para-cellular routes.From a diagnostic perspective,symptoms may be viewed as either "typical" or "atypical".In both positive serological screening results suggestive of CD,should lead to small bowel biopsy followed by a favourable clinical and serological response to the gluten-free diet(GFD) to confirm the diagnosis.Positive anti-tissue transglutaminase antibody or antiendomysial antibody during the clinical course helps to confirm the diagnosis of CD because of their over 99% specificities when small bowel villous atrophy is present on biopsy.Currently,the only treatment available for CD individuals is a strict life-long GFD.A greater understanding of the pathogenesis of CD allows alternative future CD treatments to hydrolyse toxic gliadin peptide,prevent toxic gliadin peptide absorption,blockage of selective deamidation of specific glutamine residues by tissue,restore immune tolerance towards gluten,modulation of immune response to dietary gliadin,and restoration of intestinal architecture.
文摘Since the first report of use of endoscopy in children in the 1970 s, there has seen an exponential growthin published experience and innovation in the field. In this review article we focus on modern age therapeutic endoscopy practice, explaining use of traditional as well as new and innovative techniques, for diagnosis and treatment of diseases in the paediatric upper gastrointestinal tract.
文摘Carbohydrates are an important component of the diet. The carbohydrates that we ingest range from simple monosaccharides （glucose, fructose and galactose） to disaccharides （lactose, sucrose） to complex polysaccharides. Most carbohydrates are digested by salivary and pancreatic amylases, and are further broken down into monosaccharides by enzymes in the brush border membrane （BBM） of enterocytes. For example, lactase-phloridzin hydrolase and sucraseisomaltase are two disaccharidases involved in the hydrolysis of nutritionally important disaccharides. Once monosaccharides are presented to the BBM, mature enterocytes expressing nutrient transporters transport the sugars into the enterocytes. This paper reviews the early studies that contributed to the development of a working model of intestinal sugar transport, and details the recent advances made in understanding the process by which sugars are absorbed in the intestine.
文摘AIM:To assess the feasibility and utility of double balloon enteroscopy(DBE)in the management of small bowel diseases in children. METHODS:Fourteen patients(10 males)with a median age of 12.9 years(range 8.1-16.7)underwent DBE; 5 for Peutz-Jeghers syndrome(PJ syndrome),2 for chronic abdominal pain,4 for obscure gastrointestinal (GI)bleeding,2 with angiomatous malformations(1 blue rubber bleb nevus syndrome)having persistent GI bleeding,and 1 with Cowden's syndrome with multiple polyps and previous intussusception.Eleven procedures were performed under general anesthesia and 3 with deep sedation. RESULTS:The entire small bowel was examined in 6 patients,and a length between 200 cm and 320 cm distal to pylorus in the remaining 8.Seven patients had both antegrade(trans-oral)and retrograde(transanal and via ileostomy)examinations.One patient underwent DBE with planned laparoscopic assistance.The remaining 6 had trans-oral examination only.The median examination time was 118 min(range 95-195). No complications were encountered.Polyps were detected and successfully removed in all 5 patients with PJ syndrome,in a patient with tubulo-villous adenoma of the duodenum,in a patient with significant anemia and occult bleeding,and in a patient with Cowden's syndrome.A diagnosis was made in a patient with multiple angiomata not amenable to endotherapy,and in 1 with a discrete angioma which was treated with argon plasma coagulation.The source of bleeding was identified in a further patient with varices.DBE was normal or revealed minor mucosal friability in the remaining 3 patients.Hence a diagnostic yield of 11/14 with therapeutic success in 9/14 was achieved. CONCLUSION:Double balloon enteroscopy can be a useful diagnostic and therapeutic tool for small bowel disease in children,allowing endo-therapeutic intervention beyond the reach of the conventional endoscope.
文摘Phototropins （phot1 and phot2） are blue-light receptor kinases controlling a range of responses that optimize the photosynthetic efficiency of plants. Light sensing is mediated by two flavin-binding motifs, known as LOVl and LOV2, located within the N-terminal region of the protein. Photoexcitation via LOV2 leads to activation of the C-terminal kinase domain and consequently receptor autophosphorylation. However, knowledge of the in-vivo phosphorylation sites for Arabidopsis phototropins is lacking and has impeded progress in elucidating the functional significance of receptor phos- phorylation. We have purified photl from Arabidopsis and identified the in-vivo sites of receptor phosphorylation by liquid chromatography tandem mass spectrometry. Arabidopsis-derived photl binds flavin mononucleotide as chromophore and is phosphorylated at four major sites located upstream of LOV2 （Ser^58, Ser^85, Ser^350, and Ser^410）, three of which are induced by blue light. Nevertheless, structure-function analysis indicates that the biological activity of photl can be attributed to a modular unit comprising the LOV2-kinase region of the protein. Thus, peptide regions upstream of LOV2, including the sites of receptor phosphorylation identified here, do not appear to be important for receptor signaling. By contrast, these regions may be necessary for maximizing stomatal performance and possibly light-induced relocalization of photl.
文摘To determine the clinical characteristics of children with gastrointestinal bleeding (GIB) who died during the course of their admission.METHODSWe interrogated the Pediatric Hospital Information System database, including International Classification of Diseases, Current Procedural Terminology and Clinical Transaction Classification coding from 47 pediatric tertiary centers extracting the population of patients (1-21 years of age) admitted (inpatient or observation) with acute, upper or indeterminate GIB (1/2007-9/2015). Descriptive statistics, unadjusted univariate and adjusted multivariate analysis of the associations between patient characteristics and treatment course with mortality was performed with mortality as primary and endoscopy a secondary outcome of interest. All analyses were performed using the R statistical package, v.3.2.3.RESULTSThe population with GIB was 19528; 54.6% were male, overall mortality was 2.07%; (0.37% in patients with the principal diagnosis of GIB). When considering only the mortalities in which GIB was the principal diagnosis, 48% (12 of 25 principal diagnosis GIB mortalities) died within the first 3 d of admission, whereas 19.8% of secondary diagnosis GIB patients died with 3 d of admission. Patients who died were more likely to have received octreotide (19.8% c.f. 4.04%) but tended to have not received proton pump inhibitor therapy in the first 48 h, and far less likely to have undergone endoscopy during their admission (OR = 0.489, P < 0.0001). Chronic liver disease associated with a greater likelihood of endoscopy. Mortalities were significantly more likely to have multiple complex chronic conditions.CONCLUSIONGIB associated mortality in children is highest within 7 d of admission. Multiple comorbidities are a risk factor whereas early endoscopy during the admission is protective.
文摘Nutrient deficiencies are common in patients with inflammatory bowel disease （IBD）. Both total parenteral and enteral nutrition provide important supportive therapy for IBD patients, but in adults these are not useful for primary therapy. Dietary intervention with omega-3 polyunsaturated fatty acids contained in fish oil may be useful for the care of IBD patients, and recent studies have slyessed the role of PPAR on NFKB activity on the potential beneficial effect of dietary lipids on intestinal function.
文摘Psychiatric disorders arc highly heritable, and in many individuals likely arise from the combined effects of genes and the environment. A substantial body of evidence points toward D1SCI being one of the genes that influence risk of schizophrenia, bipolar disorder and depression, and functional studies of DISC1 consequently have the potential to reveal much about the pathways that lead to major mental illness. Here, we review the evidence that DISC1 influences disease risk through effects upon multiple critical pathways in the developing and adult brain.
文摘As is the case in all parts of gastroenterology and hepatology,there have been many advances in our knowledge and understanding of small intestinal diseases.Over 1000 publications were reviewed for 2008 and 2009,and the important advances in basic science as well as clinical applications were considered.In Part Ⅰ of this Editorial Review,seven topics are considered:intestinal development;proliferation and repair;intestinal permeability;microbiotica,infectious diarrhea and probiotics;diarrhea;salt and water absorption;necrotizing enterocolitis;and immunology/allergy.These topics were chosen because of their importance to the practicing physician.
文摘In many metazoan species, germ cell formation requires the germ plasm, a specialized cytoplasm which often con-tains electron dense structures. Genes required for germ cell formation in Drosophila have been isolated predominantlyin screens for maternal-effect mutations. One such gene is tudor (tud); without proper tud function germ cell formationdoes not occur. Unlike other genes involved in Drosophila germ cell specification tud is dispensable for other somaticfunctions such as abdominal patterning. It is not known how TUD contributes at a molecular level to germ cell forma-tion but in tud mutants, polar granule formation is severely compromised, and mitochondrially encoded ribosomal RNAsdo not localize to the polar granule. TUD is composed of 11 repeats of the protein motif called the Tudor domain. Thereare similar proteins to TUD in the germ line of other metazoan species including mice. Probable vertebrate orthologuesof Drosophila genes involved in germ cell specification will be discussed.
文摘Throughout our lifetime,the intestine changes.Some alterations in its form and function may be genetically determined,and some are the result of adaptation to diet,temperature,or stress.The critical period programming of the intestine can be modified,such as from subtle differences in the types and ratios of n3:m6 fatty acids in the diet of the pregnant mother,or in the diet of the weanlings.This early forced adaptation may persist in later life,such as the unwanted increased intestinal absorption of sugars,fatty acids and cholesterol.Thus,the ontogeny,early growth and development of the intestine is important for the adult gastroenterologist to appreciate,because of the potential for these early life events to affect the responsiveness of the intestine to physiological or pathological challenges in later life.
基金supported by the Priority Academic Program Development of Jiangsu Higher Education Institutions of China, the program of China Scholarships Council (No. 201706830016)the National Natural Science Foundation of China (No. 11672128)
文摘The coaxial compound helicopter has two possible strategies for heading control: collective differential and rudder deflection. A flight dynamics model is developed to assess the effect of different heading control strategies. This includes the trim characteristics, steady flight performance,controllability, and manoeuvrability. The trim study demonstrates that heading control strategies are less influential on trim results, and the steady flight performance is also not significantly affected by the heading control strategy adopted. The controllability analysis shows although heading bandwidth and phase delay results at various speeds with different heading control strategies are all satisfied, the control derivative of the collective differential decreases as speed increases, and its heading aggressive agility is degraded into Level 3 in high-speed flight. In addition, using collective differential would lead to severe heading-rolling coupling as forward speed increases. On the contrary, the control derivative and aggressive agility of the rudder deflection is improved with forward speed, and there is no evidence of heading-rolling coupling. Finally, the transient turn MissionTask-Element(MTE) is utilized to investigate the heading manoeuvre characteristics in different heading control strategies, which indicates that the collective differential would add the amplitude of control input and the power consumption during this MTE.
基金supported in part by the Ruth Jackson Orthopedic Society and the Harris Orthopedic Laboratoryapproved by the Institutional Care and Use Committee of Massachusetts General Hospital(2020N000081)。
文摘Background:Arthrofibrosis is a joint disorder characterized by excessive scar formation in the joint tissues.Vitamin E is an antioxidant with potential anti-fibroblastic effect.The aim of this study was to establish an arthrofibrosis rat model after joint replacement and assess the effects of vitamin E supplementation on joint fibrosis.Methods:We simulated knee replacement in 16 male Sprague–Dawley rats.We immobilized the surgical leg with a suture in full flexion.The control groups were killed at 2 and 12 weeks(n=5 per group),and the test group was supplemented daily with vitamin E(0.2 mg/mL)in their drinking water for 12 weeks(n=6).We performed histological staining to investigate the presence and severity of arthrofibrosis.Immunofluorescent staining andα2-macroglobulin(α2M)enzyme-linked immunosorbent assay(ELISA)were used to assess local and systemic inflammation.Static weight bearing(total internal reflection)and range of motion(ROM)were collected for functional assessment.Results:The ROM and weight-bearing symmetry decreased after the procedure and recovered slowly with still significant deficit at the end of the study for both groups.Histological analysis confirmed fibrosis in both lateral and posterior periarticular tissue.Vitamin E supplementation showed a moderate anti-inflammatory effect on the local and systemic levels.The vitamin E group exhibited significant improvement in ROM and weight-bearing symmetry at day 84 compared to the control group.Conclusions:This model is viable for simulating arthrofibrosis after joint replacement.Vitamin E may benefit postsurgical arthrofibrosis,and further studies are needed for dosing requirements.
