Introducing the Canadian Thoracic Society Framework for Guideline Dissemination and Implementation,with Concurrent Evaluation

The Canadian Thoracic Society (CTS) is leveraging its strengths in guideline production to enable respiratory guideline implementation in Canada. The authors describe the new CTS Framework for Guideline Dissemination and Implementation, with Concurrent Evaluation, which has three spheres of action: guideline production, implementation infrastructure and knowledge translation (KT) methodological support. The Canadian Institutes of Health Research ‘Knowledge-to-Action’ process was adopted as the model of choice for conceptualizing KT interventions. Within the framework, new evidence for formatting guideline recommendations to enhance the intrinsic implementability of future guidelines were applied. Clinical assemblies will consider implementability early in the guideline production cycle when selecting clinical questions, and new practice guidelines will include a section dedicated to KT. The framework describes the development of a web-based repository and communication forum to inventory existing KT resources and to facilitate collaboration and communication among implementation stakeholders through an online discussion board. A national forum for presentation and peer-review of proposed KT projects is described. The framework outlines expert methodological support for KT planning, development and evaluation including a practical guide for implementers and a novel ‘Clinical Assembly – KT Action Team’, and in-kind logistical support and assistance in securing peer-reviewed funding.     

Heterogeneous ribonucleoprotein R regulates arylalkylamine N‐acetyltransferase synthesis via internal ribosomal entry site‐mediated translation in a circadian manner

Rhythmic arylalkylamine N‐acetyltransferase (AANAT) synthesis is a prominent circadian‐controlled response that occurs in most mammals. AANAT is the core enzyme in melatonin production; because melatonin participates in many physiological processes, the regulation of AANAT is an important research topic. In this study, we focused on the role of heterogeneous ribonucleoprotein R (hnRNP R) in the translation of AANAT. A novel RNA‐binding protein hnRNP R widely interacted with the 5′ untranslated region (UTR) of AANAT mRNA and contributed to translation through an internal ribosomal entry site (IRES). Fine‐tuning of AANAT protein synthesis occurred in response to knockdown and overexpression of hnRNP R. Nocturnal elevation of AANAT protein was dependent on the rhythmic changes of hnRNP R, whose levels are elevated in the pineal gland during nighttime. Increases in hnRNP R additionally improved AANAT production in rat pinealocytes under norepinephrine (NE) treatment. These results suggest that cap‐independent translation of AANAT mRNA plays a role in the rhythmic synthesis of melatonin through the recruitment of translational machinery to hnRNP R‐bound AANAT mRNA.     

A Novel Translational Assay of Response Inhibition and Impulsivity: Effects of Prefrontal Cortex Lesions,Drugs Used in ADHD,and Serotonin 2C Receptor Antagonism

Animal models are making an increasing contribution to our understanding of the psychology and brain mechanisms underlying behavioral inhibition and impulsivity. The aim here was to develop, for the first time, a mouse analog of the stop-signal reaction time task with high translational validity in order to be able to exploit this species in genetic and molecular investigations of impulsive behaviors. Cohorts of mice were trained to nose-poke to presentations of visual stimuli. Control of responding was manipulated by altering the onset of an auditory ‘stop-signal'' during the go response. The anticipated systematic changes in action cancellation were observed as stopping was made more difficult by placing the stop-signal closer to the execution of the action. Excitotoxic lesions of medial prefrontal cortex resulted in impaired stopping, while the clinically effective drugs methylphenidate and atomoxetine enhanced stopping abilities. The specific 5-HT_2C receptor antagonist SB242084 also led to enhanced response control in this task. We conclude that stop-signal reaction time task performance can be successfully modeled in mice and is sensitive to prefrontal cortex dysfunction and drug treatments in a qualitatively similar manner to humans and previous rat models. Additionally, using this model we show novel and highly discrete effects of 5-HT_2C receptor antagonism that suggest manipulation of 5-HT_2C receptor function may be of use in correcting maladaptive impulsive behaviors and provide further evidence for dissociable contributions of serotonergic transmission to response control.     

Public Health Understandings of Policy and Power: Lessons from INSITE

Drug addiction is a major public health problem, one that is most acutely felt in major cities around the globe. Harm reduction and safe injection sites are an attempt to address this problem and are at the cutting edge of public health policy and practice. One of the most studied safe injection sites is INSITE located in Vancouver, British Columbia. Using INSITE as a case study, this paper argues that knowledge translation offers a limited framework for understanding the development of public health policy. This paper also argues that the experience of INSITE suggests that science and social justice, the meta-ideas that lie at the core of the public health enterprise, are an inadequate basis for a theory of public health policy making. However, on a more positive note, INSITE also shows the value of concepts drawn from the ways in which political science analyzes the policy process.     

French translation and validation of the “Anterior Knee Pain Scale” (AKPS)

Purpose: To linguistically and cross-culturally translate the Anterior Knee Pain Scale into French and to evaluate the reliability and validity of this translated version of the questionnaire.

Methods: The translation part was performed in six stages, according to international guidelines: (i) two initial translations from English to French; (ii) synthesis of the two translations; (iii) backward translations into the original language; (iv) expert committee to compare the backward translations with the original questionnaire; (v) pre-final version testing and (VI) expert committee appraisal. To validate the French version of the Anterior Knee Pain Scale, we assessed its validity, reliability and floor/ceiling effects. To do this, volunteer patients from the French part of Belgium and from France, with patellofemoral pain were asked to answer the French version of the Anterior Knee Pain Scale at baseline and after 7?days, as well as the generic SF-36 questionnaire.

Results: The Anterior Knee Pain Scale was translated without any major difficulties. A total of 101 subjects aged 34.5?±?11.4?years (58.4% of women) were included in this study. Results indicated an excellent test-retest reliability (Intra-class correlation coefficient (ICC)?=?0.97, 95%CI: 0.96–0.98), a high internal consistency (Cronbach’s alpha = 0.87), a consistent construct validity (high correlations with the SF-36 questionnaire were found with domains related to physical function (r?=?0.80), physical role (r?=?0.70) and pain (r?=?0.64)) and low or moderate correlations with domains related to mental health (r?=?0.26), vitality (r?=?0.32) and social function (r?=?0.41). Moreover, no floor/ceiling effects have been found.

Conclusions: A valid French version of the Anterior Knee Pain Scale is now available and can be used with confidence to better assess the disease burden associated with patellofemoral pain. It was successfully cross-culturally adapted into French.

• Implications for rehabilitation

• The results on psychometric properties of the French Anterior Knee Pain Scale are comparable with six validated versions obtained for the Finnish, the Turkish, the Chinese, the Dutch, the Thai and the Persian populations.

• The French translated version of the Anterior Knee Pain Scale is a reliable and valid instrument for assessing the functional limitations associated with patellofemoral pain.

• The test–retest reliability of the French Anterior Knee Pain Scale was excellent, the internal consistency was high and the construct validity was consistent. There were no floor/ceiling effects.

     

Cultural adaptation and translation of measures: An integrated method

Differences in the conceptualization and operationalization of health‐related concepts may exist across cultures. Such differences underscore the importance of examining conceptual equivalence when adapting and translating instruments. In this article, we describe an integrated method for exploring conceptual equivalence within the process of adapting and translating measures. The integrated method involves five phases including selection of instruments for cultural adaptation and translation; assessment of conceptual equivalence, leading to the generation of a set of items deemed to be culturally and linguistically appropriate to assess the concept of interest in the target community; forward translation; back translation (optional); and pre‐testing of the set of items. Strengths and limitations of the proposed integrated method are discussed. © 2010 Wiley Periodicals, Inc. Res Nurs Health 33:133–143, 2010     

浅谈方剂名称英译中的异化策略

异化是翻译中处理文化因素的一个重要翻译策略。本文简要分析了方剂名称中的文化因素,从具体的英译实践中,探讨实现异化策略的具体翻译方法,有音译法,直译法,音译或直译加注释法。最后指出采用异化策略处理方剂名称中的文化因素,有助于中医传统文化的保留。     

Novel proteomic approach (PUNCH-P) reveals cell cycle-specific fluctuations in mRNA translation

Monitoring protein synthesis is essential to our understanding of gene expression regulation, as protein abundance is thought to be predominantly controlled at the level of translation. Mass-spectrometric and RNA sequencing methods have been recently developed for investigating mRNA translation at a global level, but these still involve technical limitations and are not widely applicable. In this study, we describe a novel system-wide proteomic approach for direct monitoring of translation, termed puromycin-associated nascent chain proteomics (PUNCH-P), which is based on incorporation of biotinylated puromycin into newly synthesized proteins under cell-free conditions followed by streptavidin affinity purification and liquid chromatography-tandem mass spectrometry analysis. Using PUNCH-P, we measured cell cycle-specific fluctuations in synthesis for >5000 proteins in mammalian cells, identified proteins not previously implicated in cell cycle processes, and generated the first translational profile of a whole mouse brain. This simple and economical technique is broadly applicable to any cell type and tissue, enabling the identification and quantification of rapid proteome responses under various biological conditions.