Developmental changes in mesenteric artery reactivity in embryonic and newly hatched chicks

At birth, the intestine becomes the sole site for nutrient absorption requiring a dramatic increase in blood flow. The vascular changes accompanying this transition have been partly characterized in mammals. We investigated, using wire myography, the developmental changes in chick mesenteric artery (MA) reactivity. Rings of the MA from 15-day (E15) and 19-day (E19) chicken embryos (total incubation 21 days) as well as non-fed 0–3-h-old (NH3h) and first-fed 1-day-old (NH1d) newly hatched chicks contracted in response to KCl, norepinephrine (NE), U46619, and endothelin (ET)-1 and relaxed in response to acetylcholine (ACh), sodium nitroprusside (SNP), and forskolin indicating the presence of electro- and pharmaco-mechanical coupling as well as cGMP- and cAMP-mediated relaxation. In ovo development and transition to ex ovo life was accompanied by alterations in the response of the MAs, but a different developmental trajectory was observed for each reactivity pathway tested. Thus, the contractile efficacy of KCl underwent a linear increase (E15 < E19 < NH3h < NH1d). The efficacy of NE and U46619 increased in ovo, but not ex ovo (E15 < E19 = NH3h = NH1d) and the efficacy of ET-1 peaked at E19 (E15 < E19 > NH3h = NH1d). The relaxations elicited by ACh (endothelium-dependent), SNP, and forskolin did not undergo significant developmental changes. In conclusion, the ability of chick MAs to constrict in response to pharmacological stimuli increases during the embryonic period, but no dramatic changes are induced by hatching or the first feeding. Maturation of vasodilator mechanisms precedes that of vasoconstrictor mechanisms. Alterations of the delicate balance between vasoconstrictors and vasodilators may play an important role in perinatal intestinal diseases

Performance and reward practices of multinational corporations operating in Australia

This paper examines the performance management and reward practices of multinational corporations operating in Australia. Drawing on a representative sample of 211 multinational corporations, we examine the uptake and determinants of performance management and reward practices used by multinational corporations in Australia. We investigate the influence of established contextual and organisational factors on performance management and rewards and explore the use of such practices amongst managers relative to the largest occupational group. Our findings suggest that overall multinational corporations operating in Australia use a wide range of performance management and reward practices. Findings indicate that multinational corporations are higher users of such practices for managers relative to the largest occupational group. Logistic regression results demonstrate that multinational corporations with higher use of human resource-shared services and global human resource integration are more likely to use the measured performance management and reward practices for both the largest occupational group and managers, suggesting some level of global integration around human resource activities. There is also greater likelihood of the use of these practices where there is low union recognition for the purpose of collective bargaining for the largest occupational group. The implications of these findings are discussed

Packed red cell transfusions alter mesenteric arterial reactivity and nitric oxide pathway in preterm lambs

BACKGROUND: Cases of necrotizing enterocolitis occurring within 48 h of packed red blood cell (PRBC) transfusions are increasingly being described in observational studies. Transfusion-associated gut injury is speculated to result from an abnormal mesenteric vascular response to transfusion. However, the mechanism of disruption of the balance between mesenteric vasoconstriction and relaxation following transfusion is not known. METHODS: Preterm lambs (n = 16, 134 d gestation; term: 145–147 d) were delivered and ventilated for 24 h. All the lambs received orogastric feeds with colostrum. In addition, 10 of these lambs received PRBC transfusions. Vasoreactivity was evaluated in isolated mesenteric arterial rings using norepinephrine and endothelin-1 as vasoconstrictors. Endothelium-dependent (A23187, a calcium ionophore) and endothelium-independent (SNAP) nitric oxide (NO) donors were used as vasorelaxants. Mesenteric arterial endothelial NO synthase (eNOS), soluble guanylyl cyclase (sGC), and phosphodiesterase 5 (PDE5) mRNA analyses and protein assays were performed. RESULTS: Transfusion with PRBC significantly increased mesenteric vasoconstriction to norepinephrine and endothelin-1 and impaired relaxation to A23187 and SNAP. Mesenteric arterial eNOS protein decreased following PRBC transfusion. No significant changes were noted in sGC and PDE5 mRNA or protein assays. CONCLUSION: PRBC transfusion in enterally fed preterm lambs promotes mesenteric vasoconstriction and impairs vasorelaxation by reducing mesenteric arterial eNOS

Fetal and postnatal ovine mesenteric vascular reactivity

BACKGROUND: Intestinal circulation and mesenteric arterial (MA) reactivity may play a role in preparing the fetus for enteral nutrition. We hypothesized that MA vasoreactivity changes with gestation and vasodilator pathways predominate in the postnatal period. METHODS: Small distal MA rings (0.5-mm diameter) were isolated from fetal (116-d, 128-d, 134-d, and 141-d gestation, term ~ 147 d) and postnatal lambs. Vasoreactivity was evaluated using vasoconstrictors (norepinephrine (NE) after pretreatment with propranolol and endothelin-1(ET-1)) and vasodilators (NO donors A23187 and s-nitrosopenicillamine (SNAP)). Protein and mRNA assays for receptors and enzymes (endothelin receptor A, alpha-adrenergic receptor 1A (ADRA1A), endothelial NO synthase (eNOS), soluble guanylyl cyclase (sGC), and phosphodiesterase5 (PDE5)) were performed in mesenteric arteries. RESULTS: MA constriction to NE and ET-1 peaked at 134 d. Relaxation to A23187 and SNAP was maximal after birth. Basal eNOS activity was low at 134 d. ADRA1A mRNA and protein increasedsignificantlyat134danddecreasedpostnatally.sGC and PDE5 protein increased from 134 to 141 d. CONCLUSION: Mesenteric vasoconstriction predominates in late-preterm gestation (134 d; the postconceptional age with the highest incidence of necrotizing enterocolitis (NEC)) followed by a conversion to vasodilatory influences near the time of full-term birth. Perturbations in this ontogenic mechanism, including preterm birth, may be a risk factor for NEC

Prognostic models versus single risk factor approach in first‐trimester selective screening for gestational diabetes mellitus: a prospective population‐based multicentre cohort study

Objectives: To evaluate whether (1) first-trimester prognostic models for gestational diabetes mellitus (GDM) outperform the currently used single risk factor approach, and (2) a first-trimester random venous glucose measurement improves model performance. Design: Prospective population-based multicentre cohort. Setting: Thirty-one independent midwifery practices and six hospitals in the Netherlands. Population: Women recruited before 14 weeks of gestation without pre-existing diabetes. Methods: The single risk factor approach (presence of at least one risk factor: BMI ≥30 kg/m2, previous macrosomia, history of GDM, positive first-degree family history of diabetes, non-western ethnicity) was compared with the four best performing models in our previously published external validation study (Gabbay-Benziv 2014, Nanda 2011, Teede 2011, van Leeuwen 2010) with and without the addition of glucose. Main outcome measures: Discrimination was assessed by c-statistics, calibration by calibration plots, added value of glucose by the likelihood ratio chi-square test, net benefit by decision curve analysis and reclassification by reclassification plots. Results: Of the 3723 women included, a total of 181 (4.9%) developed GDM. The c-statistics of the prognostic models were higher, ranging from 0.74 to 0.78 without glucose and from 0.78 to 0.80 with glucose, compared with the single risk factor approach (0.72). Models showed adequate calibration, and yielded a higher net benefit than the single risk factor approach for most threshold probabilities. Teede 2011 performed best in the reclassification analysis. Conclusions: First-trimester prognostic models seem to outperform the currently used single risk factor approach in screening for GDM, particularly when glucose was added as a predictor. Tweetable abstract: Prognostic models seem to outperform the currently used single risk factor approach in screening for gestational diabetes