Maturation of the 3′end of almost all eukaryotic messenger RNAs(m RNAs)requires cleavage and polyadenylation.Most mammalian m RNAs are polyadenylated at different sites within the last exon,generating alternative pol...Maturation of the 3′end of almost all eukaryotic messenger RNAs(m RNAs)requires cleavage and polyadenylation.Most mammalian m RNAs are polyadenylated at different sites within the last exon,generating alternative polyadenylation(APA)isoforms that have the same coding region but distinct 3′untranslated regions(UTRs).The 3′UTR contains motifs that regulate m RNA metabolism;thus,changing the 3′UTR length via APA can significantly affect gene expression.Endochondral ossification is a central process in bone healing,but the impact of APA on gene expression during this process is unknown.Here,we report the widespread occurrence of APA,which impacts multiple pathways that are known to participate in bone healing.Importantly,the progression of endochondral ossification involves global 3′UTR shortening,which is coupled with an increased abundance of shortened transcripts relative to other transcripts;these results highlight the role of APA in promoting gene expression during endochondral bone formation.Our mechanistic studies of transcripts that undergo APA in the fracture callus revealed an intricate regulatory network in which APA enhances the expression of the collagen,type I,alpha 1(Col1a1)and Col1a2 genes,which encode the 2 subunits of the abundantly expressed protein collagen 1.APA exerts this effect by shortening the 3′UTRs of the Col1a1 and Col1a2 m RNAs,thus removing the binding sites of mi R-29a-3p,which would otherwise strongly promote the degradation of both transcripts.Taken together,our study is the first to characterize the crucial roles of APA in regulating the 3′UTR landscape and modulating gene expression during fracture healing.展开更多
Introduction:The In-patient Medication Order Entry System (IPMOE) was first implemented in the medical ward of Princess Margaret Hospital,Hong Kong.It was a local developed close-loop system including prescription,dis...Introduction:The In-patient Medication Order Entry System (IPMOE) was first implemented in the medical ward of Princess Margaret Hospital,Hong Kong.It was a local developed close-loop system including prescription,dispensing and administration modules.Evaluation on its impact on nursing tasks would be important for practice improvement and subsequent system enhancement.Objective:The study was conducted to quantify the nursing times across medication-associated tasks for paper-based MAR and computer-based IPMOE,including change in the tasks and time patterns before and after IPMOE implementation.Methods:This was a prospective observation study in medical wards before (Jan 2014-Jun 2014) and after (Mar 2015-Jun 2015) the implementation of IPMOE.We conducted 8-hr observation studies of individual nurses with a customized application to time various pre-categorized nursing tasks.Statistical inferences and interrupted time series analysis was performed to identify the change in the intercept and trends over time after implementation.Result:The average number of medication-related tasks was significantly reduced from 61.07 to 29.81,a reduction of 31.26 episodes per duty (P < 0.001,95% CI 22.9-39.63).The time for the medication-related tasks was reduced from 32 min (SD =21.57) to 26.57 min (SD =11.35) and the medication administration time increased from 37.93 min (SD-14.78) to 44.37 min (SD 19.45),but there was no overall significant difference in the time spent on each duty (P =0.315) between the two groups.An improving trend in the delayed effect was observed (P =0.03),which indicated a run-in period for new application was needed in clinical setting.Conclusion:Our study had shown the time motion observation could be applied to measure the impact of the IPMOE in a busy clinical setting.Through classification of activities,validation,objective measurement and longitudinal evaluation,the method could be applied in various systems as well as different clinical settings in measure efficiency.展开更多
基金National Institutes of Health(NIH)R01 DK121327 to R.A.E。
文摘Maturation of the 3′end of almost all eukaryotic messenger RNAs(m RNAs)requires cleavage and polyadenylation.Most mammalian m RNAs are polyadenylated at different sites within the last exon,generating alternative polyadenylation(APA)isoforms that have the same coding region but distinct 3′untranslated regions(UTRs).The 3′UTR contains motifs that regulate m RNA metabolism;thus,changing the 3′UTR length via APA can significantly affect gene expression.Endochondral ossification is a central process in bone healing,but the impact of APA on gene expression during this process is unknown.Here,we report the widespread occurrence of APA,which impacts multiple pathways that are known to participate in bone healing.Importantly,the progression of endochondral ossification involves global 3′UTR shortening,which is coupled with an increased abundance of shortened transcripts relative to other transcripts;these results highlight the role of APA in promoting gene expression during endochondral bone formation.Our mechanistic studies of transcripts that undergo APA in the fracture callus revealed an intricate regulatory network in which APA enhances the expression of the collagen,type I,alpha 1(Col1a1)and Col1a2 genes,which encode the 2 subunits of the abundantly expressed protein collagen 1.APA exerts this effect by shortening the 3′UTRs of the Col1a1 and Col1a2 m RNAs,thus removing the binding sites of mi R-29a-3p,which would otherwise strongly promote the degradation of both transcripts.Taken together,our study is the first to characterize the crucial roles of APA in regulating the 3′UTR landscape and modulating gene expression during fracture healing.
文摘Introduction:The In-patient Medication Order Entry System (IPMOE) was first implemented in the medical ward of Princess Margaret Hospital,Hong Kong.It was a local developed close-loop system including prescription,dispensing and administration modules.Evaluation on its impact on nursing tasks would be important for practice improvement and subsequent system enhancement.Objective:The study was conducted to quantify the nursing times across medication-associated tasks for paper-based MAR and computer-based IPMOE,including change in the tasks and time patterns before and after IPMOE implementation.Methods:This was a prospective observation study in medical wards before (Jan 2014-Jun 2014) and after (Mar 2015-Jun 2015) the implementation of IPMOE.We conducted 8-hr observation studies of individual nurses with a customized application to time various pre-categorized nursing tasks.Statistical inferences and interrupted time series analysis was performed to identify the change in the intercept and trends over time after implementation.Result:The average number of medication-related tasks was significantly reduced from 61.07 to 29.81,a reduction of 31.26 episodes per duty (P < 0.001,95% CI 22.9-39.63).The time for the medication-related tasks was reduced from 32 min (SD =21.57) to 26.57 min (SD =11.35) and the medication administration time increased from 37.93 min (SD-14.78) to 44.37 min (SD 19.45),but there was no overall significant difference in the time spent on each duty (P =0.315) between the two groups.An improving trend in the delayed effect was observed (P =0.03),which indicated a run-in period for new application was needed in clinical setting.Conclusion:Our study had shown the time motion observation could be applied to measure the impact of the IPMOE in a busy clinical setting.Through classification of activities,validation,objective measurement and longitudinal evaluation,the method could be applied in various systems as well as different clinical settings in measure efficiency.
