TGFβ is a crucial immune regulator and attractive therapeutic target but needs to be activated to function. Kelly et al. show that human monocytes and macrophages activate TGFβ via expression of an integrin, αvβ8, which dampens pro-inflammatory cytokine production and is disrupted in inflammatory bowel disease.
Regulation of intestinal T-cell responses is crucial for immune homeostasis and prevention of inflammatory bowel disease (IBD). A vital cytokine in regulating intestinal Tcells is transforming growth factor-β (TGFβ), which is secreted by cells as a latent complex that requires activation to function. However, how TGFβ activation is regulated in the human intestine, and how such pathways are altered in IBD is completely unknown. Here we show that a key activator of TGFβ, integrin αvβ8, is highly expressed on human intestinal dendritic cells (DCs), specifically on the CD1c+ but not the CD141+ intestinal DC subset. Expression was significantly upregulated on intestinal DC from IBD patients, indicating that inflammatory signals may upregulate expression of this key TGFβ-activating molecule. Indeed, we found that the Toll-like receptor 4 ligand lipopolysaccharide upregulates integrin αvβ8 expression and TGFβ activation by human DC. We also show that DC expression of integrin αvβ8 enhanced induction of FOXP3 in CD4+ Tcells, suggesting functional importance of integrin αvβ8 expression by human DC. These results show that microbial signals enhance the TGFβ-activating ability of human DC via regulation of integrin αvβ8 expression, and that intestinal inflammation may drive this pathway in patients with IBD.
Lymphopenia is common among IBD patients treated with AZA. However, it did not seem to be associated with a higher risk of opportunistic infections and spontaneously resolved in the majority of cases.
A smoking reduction and cessation program was implemented with registered nurses in 3 Canadian provinces. Nurses (n = 117) participated in either an 8-week group or self-directed program using a resource specifically designed for nurses. Questionnaires were administered prior to and at the end of the 8-week interventions and at 6 and 12 months postintervention. Statistically significant changes at 8 weeks in nurses' smoking practices were found on the number of nurses continuing to smoke, mean number of cigarettes smoked, and movement in the stage of behavioral change. Attrition and variation in patterns of quitting over the 12-month study period made assessing participants' longer term outcomes difficult. This study highlights the complexity of assisting nurses to quit smoking and of implementing and evaluating a program based on accepted community health models of practice.
A smoking reduction and cessation program was implemented with registered nurses in 3 Canadian provinces. Nurses (n = 117) participated in either an 8-week group or self-directed program using a resource specifically designed for nurses. Questionnaires were administered prior to and at the end of the 8-week interventions and at 6 and 12 months postintervention. Statistically significant changes at 8 weeks in nurses' smoking practices were found on the number of nurses continuing to smoke, mean number of cigarettes smoked, and movement in the stage of behavioral change. Attrition and variation in patterns of quitting over the 12-month study period made assessing participants' longer term outcomes difficult. This study highlights the complexity of assisting nurses to quit smoking and of implementing and evaluating a program based on accepted community health models of practice.
Anorexia nervosa is a psychiatric disorder with potential life-threatening medical sequelae. This article reviews the principal medical complications associated with anorexia nervosa, highlights associated diagnostic pitfalls and emphasizes the importance of a multidisciplinary approach to management.
A 19 year old male presented with a deliberate overdose of colchicine (50mg). He had no other significant medical history. 36 hours following admission he developed widespread surgical emphysema. An urgent CT scan of his chest and abdomen demonstrated mediastinal gas of lung origin. He also developed bone marrow suppression and disseminated intravascular coagulopathy. He was treated supportively with intravenous fluids, high flow oxygen and intravenous antibiotics and made a full recovery. Colchicine toxicity is a rare, but important presentation with high levels of morbidity and mortality. Pneumomediastinum is a potentially important complication. It may be appropriate to monitor patients in the later stages of the condition through an ambulatory setting.
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