Canonical Wnt signals combined with suppressed TGFß/BMP pathways promote renewal of the native human colonic epithelium.

BACKGROUND: A defining characteristic of the human intestinal epithelium is that it is the most rapidly renewing tissue in the body. However, the processes underlying tissue renewal and the mechanisms that govern their coordination have proved difficult to study in the human gut. OBJECTIVE: To investigate the regulation of stem cell-driven tissue renewal by canonical Wnt and TGFß/bone morphogenetic protein (BMP) pathways in the native human colonic epithelium. DESIGN: Intact human colonic crypts were isolated from mucosal tissue samples and placed into 3D culture conditions optimised for steady-state tissue renewal. High affinity mRNA in situ hybridisation and immunohistochemistry were complemented by functional genomic and bioimaging techniques. The effects of signalling pathway modulators on the status of intestinal stem cell biology, crypt cell proliferation, migration, differentiation and shedding were determined. RESULTS: Native human colonic crypts exhibited distinct activation profiles for canonical Wnt, TGFß and BMP pathways. A population of intestinal LGR5/OLFM4-positive stem/progenitor cells were interspersed between goblet-like cells within the crypt-base. Exogenous and crypt cell-autonomous canonical Wnt signals supported homeostatic intestinal stem/progenitor cell proliferation and were antagonised by TGFß or BMP pathway activation. Reduced Wnt stimulation impeded crypt cell proliferation, but crypt cell migration and shedding from the crypt surface were unaffected and resulted in diminished crypts. CONCLUSIONS: Steady-state tissue renewal in the native human colonic epithelium is dependent on canonical Wnt signals combined with suppressed TGFß/BMP pathways. Stem/progenitor cell proliferation is uncoupled from crypt cell migration and shedding, and is required to constantly replenish the crypt cell population.

Job satisfaction of physicians in Russia.

PURPOSE: The purpose of this paper is to determine the relationship between job characteristics and job satisfaction amongst physicians in Russia. DESIGN/METHODOLOGY/APPROACH: Overall satisfaction and relative satisfaction on the bases of facility and gender were measured. Approaches included the perception vs expectation paradigm, and statistical techniques using chi-square, independent samples t-tests, and logistic regression. FINDINGS: The study finds that, overall, male doctors report higher levels of satisfaction than female doctors, while those who work in polyclinics are more satisfied than those employed by hospitals. Female physicians are more satisfied in their relations with patients and colleagues than their male counterparts. The majority of physicians are dissatisfied with administration and time constraints. PRACTICAL IMPLICATIONS: This paper provides practical advice to hospital and polyclinic managers in Russia as attempts at reforming and restructuring the healthcare system gather momentum. ORIGINALITY/VALUE: There is scant empirical data on the job satisfaction of physicians in Russia. This paper found that job characteristic variables such as clinical autonomy, resources, time, and administration moderate physician satisfaction relationships in Russia, just as they do in the West.