completion. Linking evidence to action Teaching and learning in an online cohort model created a community of inquiry and facilitated experiential learning. The active engagement of students with their practice-based stakeholders promoted change in clinical settings and enhanced students' professional development to lead change.Aim MRP2 is an intestinal ABC transporter that prevents the absorption of dietary xenobiotics. The aims of this work were (1) to evaluate whether a short-term regulation of intestinal MRP2 barrier function takes place in vivo after luminal incorporation of nutrients and (2) to explore the underlying mechanism. Methods MRP2 activity and localization were assessed in an in vivo rat model with preserved irrigation and innervation. Nutrients were administered into distal jejunum. After 30-minutes treatments, MRP2 activity was assessed in proximal jejunum by quantifying the transport of the model substrate 2,4-dinitrophenyl-S-glutathione. MRP2 localization was determined by quantitative confocal microscopy. Participation of extracellular mediators was evaluated using selective inhibitors and by immunoneutralization. Intracellular pathways were explored in differentiated Caco-2 cells. Results Oleic acid, administered intraluminally at dietary levels, acutely stimulated MRP2 insertion into brush border membrane. This was associated with increased efflux activity and, consequently, enhanced barrier function. Immunoneutralization of the gut hormone glucagon-like peptide-2 (GLP-2) prevented oleic acid effect on MRP2, demonstrating the participation of this trophic factor as a main mediator. Further experiments using selective inhibitors demonstrated that extracellular adenosine synthesis and its subsequent binding to enterocytic A2B adenosine receptor (A2BAR) take place downstream GLP-2. Finally, studies in intestinal Caco-2 cells revealed the participation of A2BAR/cAMP/PKA intracellular pathway, ultimately leading to increased MRP2 localization in apical domains. Conclusion These findings reveal an on-demand, acute regulation of MRP2-associated barrier function, constituting a novel physiological mechanism of protection against the absorption of dietary xenobiotics in response to food intake.Aim To determine the glucose-independent effect of the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin versus the sulphonylurea glimepiride on systemic haemodynamics in the fasting and postprandial state in patients with type 2 diabetes (T2D). Materials and methods In this prespecified secondary analysis of a phase IV, double-blind trial, 46 metformin-treated, overweight patients with T2D were included and randomly assigned (11) to once-daily linagliptin (5 mg) or glimepiride (1 mg) for 8 weeks. In a sub-study involving 26 patients, systemic haemodynamics were also assessed following a standardized liquid meal (Nutridrink Yoghurt style). Systemic haemodynamics (oscillometric device and finger photoplethysmography), arterial stiffness (applanation tonometry) and cardiac sympathovagal balance (heart rate variability [HRV]) were measured in the fasting state and repetitively following the meal. Ewing tests were performed in the fasting state. Results From baseline to week 8, linagliptin compared with glimepiride did not affect systemic haemodynamics, arterial stiffness or HRV in the fasting state. Linagliptin increased parasympathetic nervous activity, as measured by the Valsalva manoeuvre (P = .021) and deep breathing test (P = .027) compared with glimepiride. Postprandially, systolic blood pressure (SBP) dropped an average of 7.6 ± 1.6 mmHg. Linagliptin reduced this decrease to 0.7 ± 2.3 mmHg, which was significant to glimepiride (P = .010). Conclusions When compared with glimepiride, linagliptin does not affect fasting blood pressure. However, linagliptin blunted the postprandial drop in SBP, which could benefit patients with postprandial hypotension.Aim To assess the efficacy and safety of combination therapy with a glucagon-like peptide 1 receptor agonist (GLP-1 RA) and a sodium glucose co-transporter 2 inhibitor (SGLT2i) in patients with type 2 diabetes. Methods We searched Medline, Embase, the Cochrane Library, and grey literature sources until December 2, 2019 for randomized controlled trials in adults with type 2 diabetes assessing the combination of GLP-1 RA and SGLT2i, either as co-initiation therapy or as add-on to each other, against placebo or an active comparator. The primary outcome was change in HbA1c . Secondary outcomes included change in body weight, blood pressure, and eGFR, and incidence of severe hypoglycemia, all-cause mortality, cardiovascular mortality, myocardial infarction, stroke and hospitalization for heart failure. We pooled data using random effects meta-analyses. Results Seven trials (1913 patients) were eligible. Compared to GLP-1 RA, GLP-1 RA/SGLT2i combination therapy was associated with greater reduction in HbA1c (weightlong-term effectiveness or effect on cardiovascular outcomes. This article is protected by copyright. All rights reserved.Preventing obesity is of utmost public health importance. This paper systematically reviews associations between eating behaviors and peripartum weight change. This knowledge is crucial in the development of interventions that reduce long-term obesity, often triggered and boosted in the peripartum. Through MEDLINE, EMBASE, and Web of Science, we identified 20 studies that fulfilled inclusion criteria studies on food cravings, disinhibition, restrained, external, emotional, uncontrolled, intuitive, or mindful eating in relation to gestational or postpartum weight among adult women. Higher gestational weight gain was associated with lower intuitive eating (in 3/3 studies) and higher restrained eating (in 4/11 studies), external eating (in 2/2 studies), emotional eating (in 3/4 studies), food cravings (in 3/3 studies), and disinhibition (in 1/3 studies). No association with uncontrolled eating was found (in one study). No studies on mindful eating and gestational weight were identified. Higher postpartum weight loss was associated with higher restrained (in 2/4 studies) and intuitive eating (in 1/1 study). No associations between postpartum weight and food cravings, disinhibition, and mindful eating were found. No studies on external, emotional and uncontrolled eating, and postpartum weight were identified. https://www.selleckchem.com/products/jnj-42756493-erdafitinib.html Concluding, certain eating behaviors might be related to peripartum weight change.
completion. Linking evidence to action Teaching and learning in an online cohort model created a community of inquiry and facilitated experiential learning. The active engagement of students with their practice-based stakeholders promoted change in clinical settings and enhanced students' professional development to lead change.Aim MRP2 is an intestinal ABC transporter that prevents the absorption of dietary xenobiotics. The aims of this work were (1) to evaluate whether a short-term regulation of intestinal MRP2 barrier function takes place in vivo after luminal incorporation of nutrients and (2) to explore the underlying mechanism. Methods MRP2 activity and localization were assessed in an in vivo rat model with preserved irrigation and innervation. Nutrients were administered into distal jejunum. After 30-minutes treatments, MRP2 activity was assessed in proximal jejunum by quantifying the transport of the model substrate 2,4-dinitrophenyl-S-glutathione. MRP2 localization was determined by quantitative confocal microscopy. Participation of extracellular mediators was evaluated using selective inhibitors and by immunoneutralization. Intracellular pathways were explored in differentiated Caco-2 cells. Results Oleic acid, administered intraluminally at dietary levels, acutely stimulated MRP2 insertion into brush border membrane. This was associated with increased efflux activity and, consequently, enhanced barrier function. Immunoneutralization of the gut hormone glucagon-like peptide-2 (GLP-2) prevented oleic acid effect on MRP2, demonstrating the participation of this trophic factor as a main mediator. Further experiments using selective inhibitors demonstrated that extracellular adenosine synthesis and its subsequent binding to enterocytic A2B adenosine receptor (A2BAR) take place downstream GLP-2. Finally, studies in intestinal Caco-2 cells revealed the participation of A2BAR/cAMP/PKA intracellular pathway, ultimately leading to increased MRP2 localization in apical domains. Conclusion These findings reveal an on-demand, acute regulation of MRP2-associated barrier function, constituting a novel physiological mechanism of protection against the absorption of dietary xenobiotics in response to food intake.Aim To determine the glucose-independent effect of the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin versus the sulphonylurea glimepiride on systemic haemodynamics in the fasting and postprandial state in patients with type 2 diabetes (T2D). Materials and methods In this prespecified secondary analysis of a phase IV, double-blind trial, 46 metformin-treated, overweight patients with T2D were included and randomly assigned (11) to once-daily linagliptin (5 mg) or glimepiride (1 mg) for 8 weeks. In a sub-study involving 26 patients, systemic haemodynamics were also assessed following a standardized liquid meal (Nutridrink Yoghurt style). Systemic haemodynamics (oscillometric device and finger photoplethysmography), arterial stiffness (applanation tonometry) and cardiac sympathovagal balance (heart rate variability [HRV]) were measured in the fasting state and repetitively following the meal. Ewing tests were performed in the fasting state. Results From baseline to week 8, linagliptin compared with glimepiride did not affect systemic haemodynamics, arterial stiffness or HRV in the fasting state. Linagliptin increased parasympathetic nervous activity, as measured by the Valsalva manoeuvre (P = .021) and deep breathing test (P = .027) compared with glimepiride. Postprandially, systolic blood pressure (SBP) dropped an average of 7.6 ± 1.6 mmHg. Linagliptin reduced this decrease to 0.7 ± 2.3 mmHg, which was significant to glimepiride (P = .010). Conclusions When compared with glimepiride, linagliptin does not affect fasting blood pressure. However, linagliptin blunted the postprandial drop in SBP, which could benefit patients with postprandial hypotension.Aim To assess the efficacy and safety of combination therapy with a glucagon-like peptide 1 receptor agonist (GLP-1 RA) and a sodium glucose co-transporter 2 inhibitor (SGLT2i) in patients with type 2 diabetes. Methods We searched Medline, Embase, the Cochrane Library, and grey literature sources until December 2, 2019 for randomized controlled trials in adults with type 2 diabetes assessing the combination of GLP-1 RA and SGLT2i, either as co-initiation therapy or as add-on to each other, against placebo or an active comparator. The primary outcome was change in HbA1c . Secondary outcomes included change in body weight, blood pressure, and eGFR, and incidence of severe hypoglycemia, all-cause mortality, cardiovascular mortality, myocardial infarction, stroke and hospitalization for heart failure. We pooled data using random effects meta-analyses. Results Seven trials (1913 patients) were eligible. Compared to GLP-1 RA, GLP-1 RA/SGLT2i combination therapy was associated with greater reduction in HbA1c (weightlong-term effectiveness or effect on cardiovascular outcomes. This article is protected by copyright. All rights reserved.Preventing obesity is of utmost public health importance. This paper systematically reviews associations between eating behaviors and peripartum weight change. This knowledge is crucial in the development of interventions that reduce long-term obesity, often triggered and boosted in the peripartum. Through MEDLINE, EMBASE, and Web of Science, we identified 20 studies that fulfilled inclusion criteria studies on food cravings, disinhibition, restrained, external, emotional, uncontrolled, intuitive, or mindful eating in relation to gestational or postpartum weight among adult women. Higher gestational weight gain was associated with lower intuitive eating (in 3/3 studies) and higher restrained eating (in 4/11 studies), external eating (in 2/2 studies), emotional eating (in 3/4 studies), food cravings (in 3/3 studies), and disinhibition (in 1/3 studies). No association with uncontrolled eating was found (in one study). No studies on mindful eating and gestational weight were identified. Higher postpartum weight loss was associated with higher restrained (in 2/4 studies) and intuitive eating (in 1/1 study). No associations between postpartum weight and food cravings, disinhibition, and mindful eating were found. No studies on external, emotional and uncontrolled eating, and postpartum weight were identified. https://www.selleckchem.com/products/jnj-42756493-erdafitinib.html Concluding, certain eating behaviors might be related to peripartum weight change.
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