In summary, the endocannabinoid system is induced in murine ileitis but is downregulated in chronic murine and human intestinal inflammation, and CB2R activation attenuates murine ileitis, establishing an anti-inflammatory role of the endocannabinoid system.
Pro-inflammatory cytokine TNFα antagonizes regulatory T cell (Treg) suppressive function with a measurable reduction of IL-10 protein secretion. Tregs are critical to suppress excessive immune activation, particularly within the intestine where high antigenic loads elicit chronic subclinical immune activation. Employing a TNFα-driven murine inflammatory bowel disease (IBD) model (TNF
ΔARE/+
), which mirrors the Treg expansion and transmural ileitis seen in Crohn’s disease, we demonstrate that the TNFα-mediated loss of Treg suppressive function coincides with induction of a specific miRNA, miR-106a in both humans and mice, via NFκB promoter binding to suppress post-transcriptional regulation of IL-10 release. Elevation of miR-106a and impaired Treg function in this model recapitulate clinical data from IBD patients. MiR-106a deficiency promotes Treg induction, suppressive function and IL-10 production
in vitro
. MiR-106a knockout attenuated chronic murine ileitis, whereas T cell restricted deficiency of miR106a attenuated adoptive transfer colitis. In both models, attenuated inflammation coincided with suppression of both Th1 and Th17 cell subset expansion within the intestinal lamina propria. Collectively, our data demonstrate impaired Treg suppressive function in a murine IBD model consistent with human disease and support the potential for inhibition of miR-106a as a future therapeutic approach to treat chronic inflammatory conditions including IBD.
Our study using interviews of readmitted Medicaid and uninsured patients revealed complex illnesses complicated by social instability and health system failures. Improved patient-provider trust and shared decision-making, while addressing social determinants and expanding care coordination with community partners, provide opportunity to better meet patients' needs and decrease hospital readmission in high-risk patients.
Plaster checks I write in response to the review of plaster checks by G. Riding, M. Edgell and M. James.' Stated another way, 76% of their plasters were not altered and 16% of patients described the return visit as 'inconvenient'.A recent editorial noted successes with telephone follow-up consultations subject to certain safeguards.2 Perhaps the authors could run their plaster checks along these lines for a trial period.Suitable patients treated with a plaster are given written advice on care of the cast and occasions on which they should return to the department. The next planned follow-up in the department is for removal of plaster. Unless the patient re-presents personally with problems, the 'plaster check' takes place over the telephone. These figures again underline the obvious: that the overwhelming majority of head injured patients admitted for observation are subsequently discharged following uneventful recovery. The implication of Brown et al.1 is that, strictly speaking, the admission of head injured patients to an observation ward is an unnecessary luxury. What they completely ignore, in our opinion, is firstly that many patients who are head injured are intoxicated or confused or both, and an integral A&E department observation ward can provide an invaluable option for procrastination for hard pressed clinical staff confronted by such patients. The oft described stress associated with emergency medicine is greatly tempered when a ward where clinical issues can crystallize or dematerialize with time is readily available. Second, an integral observation ward not only allows the identification of acute complications close to resuscitation facilities and staff but it also offers the potential for reducing the considerable neuropsychiatric morbidity attending many head injuries. Economic and neuroscientific constraints have historically directed the 160
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