Objective To assess whether a multifaceted intervention can reduce the number of prescriptions for antimicrobials for suspected urinary tract infections in residents of nursing homes. Design Cluster randomised controlled trial. Setting 24 nursing homes in Ontario, Canada, and Idaho, United States. Participants 12 nursing homes allocated to a multifaceted intervention and 12 allocated to usual care. Outcomes were measured in 4217 residents. Interventions Diagnostic and treatment algorithm for urinary tract infections implemented at the nursing home level using a multifaceted approach-small group interactive sessions for nurses, videotapes, written material, outreach visits, and one on one interviews with physicians. Main outcome measures Number of antimicrobials prescribed for suspected urinary tract infections, total use of antimicrobials, admissions to hospital, and deaths. Results Fewer courses of antimicrobials for suspected urinary tract infections per 1000 resident days were prescribed in the intervention nursing homes than in the usual care homes (1.17 v 1.59 courses; weighted mean difference − 0.49, 95% confidence intervals − 0.93 to − 0.06). Antimicrobials for suspected urinary tract infection represented 28.4% of all courses of drugs prescribed in the intervention nursing homes compared with 38.6% prescribed in the usual care homes (weighted mean difference − 9.6%, − 16.9% to -2.4%). The difference in total antimicrobial use per 1000 resident days between intervention and usual care groups was not significantly different (3.52 v 3.93; weighted mean difference − 0.37, -1.17 to 0.44). No significant difference was found in admissions to hospital or mortality between the study arms. Conclusion A multifaceted intervention using algorithms can reduce the number of antimicrobial prescriptions for suspected urinary tract infections in residents of nursing homes.

Dysregulation of microRNA (miRNA) expression in various cancers and their role in cancer progression is well documented. The purpose of this study was to investigate the biological role of miR‐372 in human pancreatic adenocarcinoma (HPAC). We collected 20 pairs of HPAC tissues and adjacent non‐cancerous tissues to detect miR‐372 expression levels. We transfected BXPC‐3 and PANC‐1 cells with miR‐372 inhibitor/mimics to study their effect on cell proliferation, apoptosis, invasion, migration and autophagy. In addition, miR‐372 mimics and a tumor protein UNC51‐like kinase 1 (ULK1) siRNA were co‐transfected into BXPC‐3 and PANC‐1 cells to explore the mechanism of miR‐372 and ULK1 on HPAC tumorigenesis. We found that the expression of miR‐372 was markedly downregulated in HPAC cells compared to adjacent normal tissues. Furthermore, functional assays showed that miR‐372 inhibited cell proliferation, invasion, migration and autophagy in BXPC‐3 and PANC‐1 cells. An inverse correlation between miR‐372 expression and ULK1 expression was observed in HPAC tissues. Downregulation of ULK1 inhibited the overexpression effects of miR‐372, and upregulation of ULK1 reversed the effects of overexpressed miR‐372. Finally, we found that silencing ULK1 or inhibiting autophagy partly rescued the effects of miR‐372 knockdown in HPAC cells, which may explain the influence of miR‐372/ULK1 in HPAC development. Taken together, these results revealed a significant role of the miR‐372/ULK1 axis in suppressing HPAC cell proliferation, migration, invasion and autophagy.

Abstract. Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, mainly due to its high rates of postoperative recurrence and metastasis. Moreover, there is no widely accepted prognostic marker of recurrence. Therefore, the aim of the present study was to determine whether such a marker could be provided by a microRNA (miRNA), since recent evidence indicates that miRNAs are important contributors to the metastatic phenotype. In the present study, we showed that miR-99b was expressed at high levels in tissues of patients with HCC and in cell lines derived from HCCs. Elevated levels of miR-99b predicted poor overall survival as well as disease-free survival of patients with HCC. Moreover, miR-99b expression levels correlated with capsule formation and microvascular invasion, which are required for postoperative recurrence. Overexpression or knockdown of miR-99b expression increased or inhibited, respectively, the metastasis of HCC cells in vitro. Furthermore, using a dual-luciferase assay, we demonstrated that miR-99b inhibited the expression of claudin 11 (CLDN11), a component of tight junction strands by directly targeting the 3'-untranslated region of CLDN11 mRNA. In addition, CLDN11 expression was increased or decreased when miR-99b expression was inhibited or elevated in the HCC cells, respectively. Moreover, the expression of miR-99b was inversely correlated with CLDN11 mRNA or CLDN11 levels in the HCC tissues. These findings suggest that a high level of miR-99b expression is an independent prognostic factor and correlates with poor survival of patients with HCC. Therefore, inhibition of miR-99b expression may serve as a therapeutic approach for inhibiting the metastatic phenotype of HCC. IntroductionHepatocellular carcinoma (HCC) is the fifth most common malignant disease worldwide and is the second leading cause of cancer-related deaths (~700,000 annually) (1-3). Although some patients will benefit from surgery (4), the long-term survival of most is unsatisfactory due to the high incidence of postoperative recurrence and metastasis (5). Unfortunately, effective measures to predict or prevent recurrence and metastasis of HCC are unavailable, mainly since the detailed mechanisms of postoperative metastasis and relapse remain to be determined.Due to the absence of widely accepted nucleic acid and protein markers for predicting the prognosis of HCC, we focused our research on microRNAs (miRNAs), which are highly conserved RNAs, comprised of ~19-22 nucleotides. miRNAs inhibit gene expression at the posttranscriptional level by binding to the 3' untranslated region (3'UTR) of target mRNAs (6). Different miRNAs are involved in the regulation of diverse physiological processes or contribute to pathological processes. Among these miRNAs, more than 50% are encoded by cancer-associated genomic regions or fragile sites (7), indicating that dysregulation of miRNA expression plays important roles in oncogenesis.The epithelial-mesenchymal transition (EMT), which is implicated in pathologies ...

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