Translation controlled

A report of the meeting 'Translational Control', Cold Spring Harbor, USA, 3-7 September 2008

Change in Nutritional Status Modulates the Abundance of Critical Pre-initiation Intermediate Complexes During Translation Initiation \u3cem\u3ein Vivo\u3c/em\u3e

In eukaryotic translation initiation, eIF2∙GTP–Met-tRNAiMet ternary complex (TC) interacts with eIF3–eIF1–eIF5 complex to form the multifactor complex (MFC), while eIF2∙GDP associates with eIF2B for guanine nucleotide exchange. Gcn2p phosphorylates eIF2 to inhibit eIF2B. Here we evaluate the abundance of eIFs and their pre-initiation intermediate complexes in gcn2 deletion mutant grown under different conditions. We show that ribosomes are three times as abundant as eIF1, eIF2 and eIF5, while eIF3 is half as abundant as the latter three and hence, the limiting component in MFC formation. By quantitative immunoprecipitation, we estimate that ∼ 15% of the cellular eIF2 is found in TC during rapid growth in a complex rich medium. Most of the TC is found in MFC, and important, ∼ 40% of the total eIF2 is associated with eIF5 but lacks tRNAiMet. When the gcn2Δ mutant grows less rapidly in a defined complete medium, TC abundance increases threefold without altering the abundance of each individual factor. Interestingly, the TC increase is suppressed by eIF5 overexpression and Gcn2p expression. Thus, eIF2B-catalyzed TC formation appears to be fine-tuned by eIF2 phosphorylation and the novel eIF2/eIF5 complex lacking tRNAiMet

Cognitive function and oral health among ageing adults

Objectives: There is inconclusive evidence that cognitive function is associated with oral health in older adults. This study investigated the association between cognitive function and oral health among older adults in England. Methods: This longitudinal cohort study included 4416 dentate participants aged 50 years or older in the English Longitudinal Study of Ageing during 2002‐2014. Cognitive function was assessed at baseline in 2002/2003 using a battery of cognitive function tests. The self‐reported number of teeth remaining and self‐rated general oral health status was reported in 2014/2015. Ordinal logistic regression was applied to model the association between cognitive function at baseline and tooth loss or self‐rated oral health. Results: Cognitive function at baseline was negatively associated with the risk of tooth loss (per each 1 standard deviation lower in cognitive function score, OR: 1.13, 95% CI: 1.05‐1.21). When cognitive function score was categorized into quintiles, there was a clear gradient association between cognitive function and tooth loss (P‐trend = 0.003); people in the lowest quintile of cognitive function had higher risk of tooth loss than those in the highest quintile (OR: 1.39, 95% CI: 1.12‐1.74). A similar magnitude and direction of association were evident between cognitive function and self‐rated oral health. Conclusion: This longitudinal study in an English ageing population has demonstrated that poor cognitive function at early stage was associated with poorer oral health and higher risk of tooth loss in later life. The gradient relationship suggests that an improvement in cognitive function could potentially improve oral health and reduce the risk of tooth loss in the ageing population

Identification and appraisal of outcome measures used to evaluate hypodontia care: A systematic review

Introduction: Identification and appraisal of the outcome measures that have been used to evaluate hypodontia treatment and deliver services are essential for improving care. A lack of alignment between outcomes and patient values can limit the scope for patient-centered care. Our objectives were to identify and appraise the outcomes selected to evaluate hypodontia care. Methods: Data sources included 10 electronic databases and grey literature, searched using terms for hypodontia and its treatment methods. Study eligibility included mixed study designs to ensure comprehensive identification of outcomes, excluding case reports and case series with fewer than 10 participants and nonsystematic reviews. Participants and interventions involved people with hypodontia receiving any dental treatment to manage their hypodontia. Simulated treatment, purely laboratory-based interventions, and future treatments still in development were excluded. Research outcomes were identified and synthesised into 4 categories: clinical indicators, and patient-reported, clinician-reported, and lay-reported outcomes. No synthesis of efficacy data was planned, and consequently no methodologic quality appraisal of the studies was undertaken. Results: The search identified 497 abstracts, from which 106 eligible articles were retrieved in full. Fifty-six studies and 8 quality-improvement reports were included. Clinical indicators were reported in 49 studies (88%) including appearance, function, dental health, treatment longevity, treatment success and service delivery. Patient-reported outcomes were given in 22 studies (39%) including oral health-related quality of life, appearance, function, symptoms of temporomandibular dysfunction, and patient experience. Clinician-reported outcomes were limited to appearance. Variability was seen in the tools used for measuring outcomes. Conclusions: There is a lack of rationale and consistency in the selection of outcome measures used to evaluate hypodontia care. Outcomes are largely clinician and researcher-driven with little evidence of their relevance to patients. There was a paucity of outcomes measuring access to care, quality of care, and cost. Evidence from hypodontia research is clinician-focused and likely to have limited value to support patients during decision making. Attempts to synthesise the evidence base for translation into practice will be challenging. There is a need for a core outcomes set with a patient-centric approach to drive improvements in health services

A Comparison of U. S. and European University-Industry Relations in the Life Sciences

We draw on diverse data sets to compare the institutional organization of upstream life science research across the United States and Europe. Understanding cross-national differences in the organization of innovative labor in the life sciences requires attention to the structure and evolution of biomedical networks involving public research organizations (universities, government laboratories, nonprofit research institutes, and research hospitals), science-based biotechnology firms, and multinational pharmaceutical corporations. We use network visualization methods and correspondence analyses to demonstrate that innovative research in biomedicine has its origins in regional clusters in the United States and in European nations. But the scientific and organizational composition of these regions varies in consequential ways. In the United States, public research organizations and small firms conduct R&D across multiple therapeutic areas and stages of the development process. Ties within and across these regions link small firms and diverse public institutions, contributing to the development of a robust national network. In contrast, the European story is one of regional specialization with a less diverse group of public research organizations working in a smaller number of therapeutic areas. European institutes develop local connections to small firms working on similar scientific problems, while cross-national linkages of European regional clusters typically involve large pharmaceutical corporations. We show that the roles of large and small firms differ in the United States and Europe, arguing that the greater heterogeneity of the U. S. system is based on much closer integration of basic science and clinical development

CANCER RISK IN MULTIPLE SCLEROSIS PATIENTS TAKING CLADRIBINE

J Neurol Neurosurg Psychiatry 2014;85(10):A1–A5

Eliciting preferences in dentistry with multiattribute stated preference methods: A systematic review

Background: Preference experiments are used to understand how patients and stakeholders value aspects of health care. These methods are gaining popularity in dentistry, but quality and breadth of use have not been evaluated. Objectives: To describe multiattribute stated preference experiment use in dentistry through illustration and critique of existing studies. Data Sources: Systematic literature search of PubMed, Econlit and Ovid for Medline, Embase, PsychINFO, PsychARTICLES, and All EBM Reviews, as well as gray literature. Study Eligibility: Multiattribute stated preference experiments eliciting preferences for dental service delivery, treatments, and oral health states from the perspective of patients, the public, and dental professionals. Outcomes of interest were preference weights and marginal rates of substitution. Study selection was independently performed by 2 reviewers. Appraisal: Ten-point checklist published by the International Society of Pharmacoeconomics and Outcomes Research was used for quality assessment. Synthesis: Descriptive analysis. Results: Searches identified 12 records published between 1999 and 2015, mostly in nondental academic journals. Studies were undertaken in high-income countries in Europe and the United States. The studies aimed to elicit preference for service delivery, treatment, or oral health states from the perspective of the patients, dentists, or the public via discrete choice experiment methods. The quality scores for the studies ranged from 53% to 100%. Limitations: A detailed description and critique of stated preference methods are provided, but it was not possible to provide synthesized preference data. Conclusions: Multiattribute stated preference experiments are increasingly popular, but understanding the methods and outputs is essential for designing and interpreting preference studies to improve patient care. Patient preferences highlight important considerations for decision making during treatment planning. Valuation of health states and estimation of willingness-to-pay are important for resource planning and allocation and economic evaluation. Preference estimates and relative value of attributes for interventions and service delivery inform development and selection of treatments and service