ATG16L1 and NOD2 polymorphisms enhance phagocytosis in monocytes of Crohn’s disease patients

AIM:To investigate if the presence of relevant genetic polymorphisms has effect on the effectual clearance of bacteria by monocytes and granulocytes in patients with Crohn’s disease(CD).METHODS:In this study,we assessed the differential responses in phagocytosis by measuring the phagocytic activity and the percentage of active phagocytic monocytes and granulocytes in inflammatory bowel disease patients as well as healthy controls.As both autophagy related like 1(ATG16L1)and immunityrelated guanosine triphosphatase gene are autophagy genes associated with CD and more recently nucleo-tide-binding ligomerization domain-containing protein2(NOD2)has been identified as a potent inducer of autophagy we genotyped the patients for these variants and correlated this to the phagocytic reaction.The genotyping was done with restriction fragment length polymorphisms analysis and the phagocytosis was determined with the pHrodo?Escherichia coli Bioparticles Phagocytosis kit for flowcytometry.RESULTS:In this study,we demonstrate that analysis of the monocyte and granulocyte populations of patients with CD and ulcerative colitis showed a comparable phagocytic activity(ratio of mean fluorescence intensity)between the patient groups and the healthy controls.CD patients show a significantly higher phagocytic capacity(ratio mean percentage of phagocytic cells)compared to healthy controls(51.91%±2.85%vs 37.67%±7.06%,P=0.05).The extend of disease was not of influence.However,variants of ATG16L1(WT:2.03±0.19 vs homozygoot variant:4.38±0.37,P<0.009)as well as NOD2(C-ins)(heterozygous variant:42.08±2.94 vs homozygous variant:75.58±4.34(P=0.05)are associated with the phagocytic activity in patients with CD.CONCLUSION:Monocytes of CD patients show enhanced phagocytosis associated with the presence of ATG16L1 and NOD2 variants.This could be part of the pathophysiological mechanism resulting in the disease.     

Recruitment and retention in academic medicine--what junior faculty and trainees want department chairs to know

Attracting and retaining bright and motivated physicians remains a high priority for academia. Historically, the recruitment of trainees into academia and the retention of junior faculty have been suboptimal. To learn more about the perceived obstacles that discourage the pursuit of academic careers, a Workshop on Academic Career Pathways was conducted during the 2011 Southern Regional Meetings held in New Orleans. The audience included mainly residents and fellows as well as junior and senior faculties. Speakers described career options in academic medicine focusing on the clinician-investigator and the clinician-educator tracks. Afterward, the audience was asked to identify perceived obstacles to recruitment and retention in academic medicine. The group identified 10 major obstacles in 3 categories: financial challenges, personal mentoring and academic skills acquisition. This article summarizes the workshop proceedings and ends with recommendations to chairs and department leaders for improving recruitment and retention in academic medicine based on the discussion.     

Childhood Primary Care Services in Wyoming

Provision of childhood primary care services and differences between types of providers (family practice physicians, pediatricians, nurse practitioners, and physicians' assistants) were explored in this study. A mail survey was conducted in Wyoming using a questionnaire based on the recommendations from the U. S. Preventive Service Task Force. Sixty-one percent of the providers returned questionnaires. While some areas of assessment, screening, and treatment/counseling services were provided at high levels, many were not. Gaps exist particularly in the areas of behavioral and lifestyle assessment and treatment/counseling. Only small differences existed between types of providers. However, nurse practitioners and pediatricians were more likely to report that they followed recommendations, while physicians' assistants were least likely to report that they followed recommendations.     

Validation of the Defining Characteristics of the Nursing Diagnosis Ineffective Airway Clearance

The investigators designed this validation study to determine the defining characteristics of the nursing diagnosis ineffective airway clearance. Using Fehring's Diagnostic Content Validity Model, 546 nurses who care for respiratory clients validated one major and 19 minor defining characteristics. Nine characteristics previously described in the literature were eliminated. Clarification of the defining characteristics of this diagnosis improves communication in practice, education and research.     

Book Review

Performance Breakthroughs for Adolescents With Learning Disabilities or ADD. G. Markel & J. Greenbaum.     

Characterization of the effects of cultured vascular cells on the activation of blood coagulation

The coagulant properties of intact bovine vascular cells (aortic endothelial and smooth muscle cells) and human vascular cells (cutaneous and foreskin microvascular cells, umbilical venous endothelium) grown in vitro were studied. Compared to nonvascular cells (fibroblasts, corneal endothelial cells, fetal lung or intestinal mucosal cells), vascular cells had little procoagulant activity. Radioimmunologic measurement of thrombin in recalcified plasma demonstrated markedly lower concentrations of thrombin in the presence of vascular endothelial and smooth muscle cells compared to corneal endothelial and fetal lung cells. The low thrombin concentrations were not a consequence of thrombin binding to the vascular cells nor were they due to accelerated thrombin inactivation by antithrombin-III or alpha 2-macroglobulin. Neither vascular cells nor the nonvascular cells promoted contact activation of plasma as measured by a sensitive specific assay for kallikrein. Studies with intact cell monolayers and purified factors VIIa and X indicated that while nonvascular cells express tissue factor activity, vascular cells do not exhibit this property. These data suggest that the nonthrombogenic nature of intact vascular cells is due to their failure to initiate contact activation and to express tissue factor activity. In addition, the primary difference in coagulant potential between vascular cells and nonvascular cells is the lack of tissue factor expression by the vascular cells.