NOD2 is an intracellular sensor that contributes to immune defense and inflammation. Here we investigated whether NOD2 mediates its effects through control of microRNAs (miRNAs). miR-29 expression was upregulated in human dendritic cells (DCs) in response to NOD2 signals, and miR-29 regulated the expression of multiple immune mediators. In particular, miR-29 downregulated interleukin-23 (IL-23) by targeting IL-12p40 directly and IL-23p19 indirectly, likely via reduction of ATF2. DSS-induced colitis was worse in miR-29-deficient mice and was associated with elevated IL-23 and T helper 17 signature cytokines in the intestinal mucosa. Crohn's disease (CD) patient DCs expressing NOD2 polymorphisms failed to induce miR-29 upon pattern recognition receptor stimulation and showed enhanced release of IL-12p40 on exposure to adherent invasive E. coli. Therefore, we suggest that loss of miR-29-mediated immunoregulation in CD DCs might contribute to elevated IL-23 in this disease.

A PDP might reduce the risk of CRC. Conversely, a WDP is associated with a higher risk of disease.

The pharmaceutical care approach serves as a model for medication review, involving collaboration between GPs, pharmacists, patients, and carers. Its use is advocated with older patients who are typically prescribed several drugs. However, it has yet to be thoroughly evaluated. AimTo estimate the effectiveness of pharmaceutical care for older people, shared between GPs and community pharmacists in the UK, relative to usual care. Design of studyMultiple interrupted time-series design in five primary care trusts which implemented pharmaceutical care at 2-month intervals in random order. Patients acted as their own controls, and were followed over 3 years including their 12 months' participation in pharmaceutical care. SettingIn 2002, 760 patients, aged ≥75 years, were recruited from 24 general practices in East and North Yorkshire. Sixty-two community pharmacies also took part. A total of 551 participants completed the study. MethodPharmaceutical care was undertaken by community pharmacists who interviewed patients, developed and implemented pharmaceutical care plans together with patients' GPs, and thereafter undertook monthly medication reviews. Pharmacists and GPs attended training before the intervention. Outcome measures were the UK Medication Appropriateness Index, the Short Form-36 Health Survey (SF-36), and serious adverse events. ResultsThe intervention did not lead to any statistically significant change in the appropriateness of prescribing or health outcomes. Although the mental component of the SF-36 decreased as study participants become older, this trend was not affected by pharmaceutical care. ConclusionThe RESPECT model of pharmaceutical care (Randomised Evaluation of Shared Prescribing for Elderly people in the Community over Time) shared between community pharmacists and GPs did not significantly change the appropriateness of prescribing or quality of life in older patients. Keywordshealth services for the aged; medication therapy management; pharmaceutical care; polypharmacy; randomised controlled trial.