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Paneth cells (PCs), a specialized secretory cell type in the small intestine, are increasingly recognized as having an essential role in host responses to microbiome and environmental stresses. Whether and how commensal and pathogenic microbes modify PC composition to modulate inflammation remain unclear. Using newly developed PC-reporter mice under conventional and gnotobiotic conditions, we determined PC transcriptomic heterogeneity in response to commensal and invasive microbes at single cell level. Infection expands the pool of CD74+ PCs, whose number correlates with auto or allogeneic inflammatory disease progressions in mice. Similar correlation was found in human inflammatory disease tissues. Infection-stimulated cytokines increase production of reactive oxygen species (ROS) and expression of a PC-specific mucosal pentraxin (Mptx2) in activated PCs. A PC-specific ablation of MyD88 reduced CD74+ PC population, thus ameliorating pathogen-induced systemic disease. A similar phenotype was also observed in mice lacking Mptx2. Thus, infection stimulates expansion of a PC subset that influences disease progression.

BackgroundDespite the association of physical activity with improved cardiovascular outcomes and the association of high coronary artery calcification (CAC) scores with poor prognosis, elite endurance athletes have increased CAC. Yet, they nevertheless have better cardiovascular survival. We hypothesized that exercise may transform vascular calcium deposits to a more stable morphology.MethodsTo test this, hyperlipidemic mice (Apoe-/-) with baseline aortic calcification were separated into 2 groups (n = 9/group) with control mice allowed to move ad-lib while the exercise group underwent a progressive treadmill regimen for 9 weeks. All mice underwent blood collections and in vivo 18F-NaF μPET/μCT imaging both at the start and end of the exercise regimen. At euthanasia, aortic root specimens were obtained for histomorphometry.ResultsResults showed that, while aortic calcification progressed similarly in both groups based on µCT, the fold change in 18F-NaF density was significantly less in the exercise group. Histomorphometric analysis of the aortic root calcium deposits showed that the exercised mice had a lower mineral surface area index than the control group. The exercise regimen also raised serum PTH levels twofold.ConclusionThese findings suggest that weeks-long progressive exercise alters the microarchitecture of atherosclerotic calcium deposits by reducing mineral surface growth, potentially favoring plaque stability.

Paneth cells (PCs), a specialized secretory cell type in the small intestine, are increasingly recognized as having an essential role in host responses to microbiome and environmental stresses. Whether and how commensal and pathogenic microbes modify PC composition to modulate inflammation remain unclear. Using newly developed PC‐reporter mice under conventional and gnotobiotic conditions, we determined PC transcriptomic heterogeneity in response to commensal and invasive microbes at single cell level. Infection expands the pool of CD74+ PCs, whose number correlates with auto or allogeneic inflammatory disease progressions in mice. Similar correlation was found in human inflammatory disease tissues. Infection‐stimulated cytokines increase production of reactive oxygen species (ROS) and expression of a PC‐specific mucosal pentraxin (Mptx2) in activated PCs. A PC‐specific ablation of MyD88 reduced CD74+ PC population, thus ameliorating pathogen‐induced systemic disease. A similar phenotype was also observed in mice lacking Mptx2. Thus, infection stimulates expansion of a PC subset that influences disease progression. Synopsis: Changes in Paneth cell (PC) gene expression and function have been linked to various inflammatory intestinal diseases, such as Crohn's disease. Here, a single‐cell transcriptomic analysis of PC heterogeneity in mice identifies a CD74+ PC subset that is expanded upon inflammation or infection to secrete innate immune response molecules. Single‐cell transcriptome analysis reveals that PC heterogeneity can be modified by microbiota colonization in germ‐free mice.A CD74+ PC subset is expanded upon mouse infection with invasive pathogens, in mouse models of ileitis, and in inflammatory bowel disease–patient biopsies.Paneth cell‐specific ablation of MyD88 pathway dampens the expansion and secretory function of CD74+ PCs upon infection.Deletion of Mptx2, a mucosal pentraxin that is enriched in CD74+ PCs, reduces complement activation and inflammation upon infection. [ABSTRACT FROM AUTHOR]

Background: Despite the association of physical activity with improved cardiovascular outcomes and the association of high coronary artery calcification (CAC) scores with poor prognosis, elite endurance athletes have increased CAC. Yet, they nevertheless have better cardiovascular survival. We hypothesized that exercise may transform vascular calcium deposits to a more stable morphology.Methods: To test this, hyperlipidemic mice (Apoe-/-) with baseline aortic calcification were separated into 2 groups (n = 9/group) with control mice allowed to move ad-lib while the exercise group underwent a progressive treadmill regimen for 9 weeks. All mice underwent blood collections and in vivo 18F-NaF μPET/μCT imaging both at the start and end of the exercise regimen. At euthanasia, aortic root specimens were obtained for histomorphometry.Results: Results showed that, while aortic calcification progressed similarly in both groups based on µCT, the fold change in 18F-NaF density was significantly less in the exercise group. Histomorphometric analysis of the aortic root calcium deposits showed that the exercised mice had a lower mineral surface area index than the control group. The exercise regimen also raised serum PTH levels twofold.Conclusion: These findings suggest that weeks-long progressive exercise alters the microarchitecture of atherosclerotic calcium deposits by reducing mineral surface growth, potentially favoring plaque stability. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the impact of an interprofessional Transitions of Care (TOC) service on 30-day hospital reutilization inclusive of hospital readmissions and ED visits. This was a retrospective cohort study including patients discharged from an academic medical center between September 2013 and October 2014. Patients scheduled for a hospital follow-up visit in the post-acute care clinic (PACC) were included in the intervention group and patients without a post-discharge interprofessional TOC service were included in the comparison group. The intervention included a hospital follow-up visit with an interprofessional healthcare team. The primary composite outcome was hospital reutilization, defined as a hospital readmission or ED visit within 30 days of the discharge date. Overall, 330 patients were included in each group. In the intention-to-treat analysis, the primary composite outcome was not significantly different between groups (16.97% vs. 19.39%, P = 0.4195) whereas in the per-protocol analysis (all patients who showed to their PACC appointment), the primary outcome was significantly different in favor of the intervention group (9.28% vs. 19.39%, P = 0.0009). When components were analyzed separately, there was a statistically significant difference in favor of intervention group for hospital readmissions, but there was no difference for ED visits. This study demonstrates that an outpatient interprofessional TOC service with patient engagement from a team of nurses, pharmacists, physicians, and social workers may reduce 30-day hospital readmissions but may not impact 30-day ED visits. [ABSTRACT FROM AUTHOR]