Tryptophan-Mediated Interactions between Tristetraprolin and the CNOT9 Subunit Are Required for CCR4-NOT Deadenylase Complex Recruitment.

The zinc-finger protein tristetraprolin (TTP) binds to AU-rich elements present in the 3' untranslated regions of transcripts that mainly encode proteins of the inflammatory response. TTP-bound mRNAs are targeted for destruction via recruitment of the eight-subunit deadenylase complex "carbon catabolite repressor protein 4 (CCR4)-negative on TATA-less (NOT)," which catalyzes the removal of mRNA poly-(A) tails, the first obligatory step in mRNA decay. Here we show that a novel interaction between TTP and the CCR4-NOT subunit, CNOT9, is required for recruitment of the deadenylase complex. In addition to CNOT1, CNOT9 is now included in the identified CCR4-NOT subunits shown to interact with TTP. We find that both the N- and C-terminal domains of TTP are involved in an interaction with CNOT9. Through a combination of SPOT peptide array, site-directed mutagenesis, and bio-layer interferometry, we identified several conserved tryptophan residues in TTP that serve as major sites of interaction with two tryptophan-binding pockets of CNOT9, previously found to interact with another modulator GW182. We further demonstrate that these interactions are also required for recruitment of the CCR4-NOT complex and TTP-directed decay of an mRNA containing an AU-rich element in its 3'-untranslated region. Together the results reveal new molecular details for the TTP-CNOT interaction that shape an emerging mechanism whereby TTP targets inflammatory mRNAs for deadenylation and decay.

Evidence based medicine in clinical practice: how to advise patients on the influence of age on the outcome of surgical anterior cruciate ligament reconstruction: a review of the literature.

OBJECTIVE: To determine, using a literature search, whether patient age influences the outcome of surgical reconstruction of a torn anterior cruciate ligament. METHODS: Medline (1966 to present) was searched using the PubMed interface, Embase (1974 to present) using the Datastar system, and the Cochrane Library at the Update Software web site. Papers retrieved from the three databases were independently assessed by two reviewers using preliminary inclusion criteria. Reference lists of papers satisfying the preliminary criteria were then scanned and appropriate papers reviewed. Any new papers in turn had their reference lists scanned, this process continuing until no new papers were identified. Final inclusion criteria were then applied to all papers satisfying the preliminary inclusion criteria. RESULTS: The initial search identified 661 papers. Exclusion of duplicates produced 536 unique papers. Medline contained 445, Embase 185, and the Cochrane Library 31. Of the 536, 523 were assessed by abstract and 12 by full text; one paper was not retrieved. Application of the preliminary inclusion criteria produced 33 papers. Their reference lists contained 950 references. Scanning of these added six new papers to the dataset. These six had their reference lists assessed; no new papers were identified. Four of the 39 papers in the completed dataset satisfied the final inclusion criteria. There was wide variation in the total number of subjects in the four studies, ranging from 22 to 203 patients. The total number of different outcome measures was 17; only one measure was used by all four studies. None of the objective outcome measures showed any significant difference between age groups, and the subjective measures, which did show differences, were contradictory. A total of 108 interlibrary loans were requested, by a full time researcher, at a total cost of 432.00 Irish pounds over a 10 week period. CONCLUSIONS: When advising patients on the outcome of anterior cruciate ligament reconstruction, age should not be considered in isolation. In the absence of relevant guidelines, meta-analyses, or systematic reviews, the application of evidence based medicine to clinical practice has significant resource implications.

The accuracy of MEDLINE and Journal contents pages for papers published in Clinical Otolaryngology.

MEDLINE is widely used as a source for identifying and reviewing medical journal literature. Its accuracy is generally taken for granted, as is that of the contents pages published by the journals themselves. In this study of citation accuracy we examined the articles published in Clinical Otolaryngology and Allied Sciences from 1976 to 1998. The entries in MEDLINE were compared with the entries in the Journal's contents pages, and with the actual articles. Of 1651 articles published in the journal, one was omitted from MEDLINE and 25 (1.5%) were incorrectly cited, while 88 (5.3%) were incorrectly cited in the contents pages. Twenty-one (84%) of the errors in MEDLINE involved names of authors. Apart from incomplete retrieval of information for practice and research, errors could result in an author not getting credit for publications.

A national census of ambulance response times to emergency calls in Ireland.

BACKGROUND: Equity of access to appropriate pre-hospital emergency care is a core principle underlying an effective ambulance service. Care must be provided within a timeframe in which it is likely to be effective. A national census of response times to emergency and urgent calls in statutory ambulance services in Ireland was undertaken to assess current service provision. METHODS: A prospective census of response times to all emergency and urgent calls was carried out in the nine ambulance services in the country over a period of one week. The times for call receipt, activation, arrival at and departure from scene and arrival at hospital were analysed. Crew type, location of call and distance from ambulance base were detailed. The type of incident leading to the call was recorded but no further clinical information was gathered. Results-2426 emergency calls were received by the services during the week. Fourteen per cent took five minutes or longer to activate (range 5-33%). Thirty eight per cent of emergencies received a response within nine minutes (range 10-47%). Only 4.5% of emergency calls originating greater than five miles from an ambulance station were responded to within nine minutes (range 0-10%). Median patient care times for "on call" crews were three times longer than "on duty" crews. CONCLUSION: Without prioritized use of available resources, inappropriately delayed responses to critical incidents will continue. Recommendations are made to improve the effectiveness of emergency medical service utilisation.

The accuracy of citation and quotation in otolaryngology/head and neck surgery journals.

A high rate of errors of citation and quotation has been reported in the publications of many medical specialties. The aim of this study was to determine the prevalence of citation and quotation errors in otolaryngology/head and neck surgery journals. A retrospective analysis was performed based on the first issue for 1997 of each of four journals: Laryngoscope; Annals of Otology, Rhinology and Laryngology; Clinical Otolaryngyology; and Journal of Laryngology and Otology. A sample of 50 references from each journal was randomly selected and each was checked for accuracy against the original referenced paper. Citation errors were categorized as major, intermediate or minor and quotation errors as major or minor. Citation errors occurred in 37.5% of the references, 11.9% of which were considered major errors. Quotation errors occurred in 17%, with 11.1% major errors. This prevalence is similar to the established error rate in medical literature.

Characteristics of attenders and their attendances at an urban accident and emergency department over a one year period.

OBJECTIVES: To describe (1) the characteristics of attenders to an urban accident and emergency (A&E) department over a one year period according to the frequency of their attendance and (2) the features of their attendances according to the frequency which the patient attended the department during the study period. METHODS: A dataset containing information on all new attendances to an urban A&E department in 1995 was formed. For each attendance the following information was recorded: day of the week, hour of attendance, referral source, triage category, and disposal. A second dataset, consisting of the individuals ("attenders") who made the A&E visits ("attendances") during 1995 was also produced. For each attender the following information was recorded: age, sex, postal code of residence, socioeconomic status, marital status, and number of attendances during 1995. A methodology reviewing the trends of frequency of attendance was utilised, as opposed to the use of an arbitrary cut off point. RESULTS: 34,908 patients made 46,735 visits in 1995. Increasing frequency of attendance was significantly associated with increasing age (Kruskal-Wallis < 0.001), being male (chi 2 for linear trend 14.06, p < 0.001), having a local postal address (chi 2 279.79, p < 0.0001), general medical services eligibility (chi 2 781.67, p < 0.0001), and inversely associated with being married (chi 2 33.91, p < 0.0001). Increasing frequency of attendance was significantly associated with attendance between the hours of 1700 and 0900 (chi 2 295.62, p < 0.001), being triaged as a non-emergency (chi 2 1254.33, p < 0.0001), and self referral (chi 2 141.4, p < 0.0001). CONCLUSIONS: A small group of A&E attenders accounts for a disproportionately large percentage of the total number of departmental attendances. The characteristics of frequent A&E attenders suggest that they may represent a vulnerable group of patients. A follow up study of the utilisation of all primary care services by such patients is suggested.

Searching for the evidence in pre-hospital care: a review of randomised controlled trials. On behalf of the Ambulance Response Time Sub-Group of the National Ambulance Advisory Committee.

OBJECTIVES: To identify randomised controlled trials (RCTs) which evaluate aspects of pre-hospital care; to perform categorisation by theme; to compare the sensitivity and precision of the search databases. DATA SOURCES: August 1997 updates of MEDLINE and EMBASE databases, using the Datastar online system. Papers published in 1987 or later were included, with no language restrictions. STUDY SELECTION: A trial was eligible for inclusion if it was judged, by two independent and blinded assessors, that participants followed up in the trial were definitely or possibly assigned prospectively to one of two or more alternative forms of healthcare with random allocation or a quasi-random method of allocation. RESULTS: The literature search retrieved 849 papers, of which 569 (67%) were in MEDLINE and 486 (57%) in EMBASE. Forty one (5%) were confirmed as reports of RCTs or quasi-RCTs, and the total number of individual trials was 38. Ten of these trials dealt with thrombolytic drugs; 14 were concerned with other drugs, 12 with equipment, and two with other interventions. Four trials were based on a sample size of more than 1000, and seven reported a statistically significant effect on mortality. All 41 papers were in EMBASE, and all but one were also in MEDLINE. CONCLUSIONS: Evidence based policy making with respect to the organisation of pre-hospital services cannot depend on RCTs. In the current relative absence of such evidence, practitioners and decision makers must use alternative information sources. A future review could examine a broader range of literature and be based on a wider search of published and unpublished material.

Making the most of MEDLINE.

The MEDLINE database is firmly established as an essential tool in medical research and practice, and all doctors should develop MEDLINE search skills. This article reviews key elements of the database, looking particularly at areas of common error, and the options available when fine-tuning a search. A better understanding of MEDLINE should lead to more effective use of this invaluable resource.

Writing a research abstract: structure, style and content.

The communication of ideas is fundamental to the development of all professions. Producing an abstract is an essential part of this process and it requires careful planning if it is to fulfil its purpose correctly. This article explains how to compose and use the abstract of a research paper to its full potential.

Selecting a database for literature searches in nursing: MEDLINE or CINAHL?

This study compares the usefulness of the MEDLINE and CINAHL databases for students on post-registration nursing courses. We searched for nine topics, using title words only. Identical searches of the two databases retrieved 1162 references, of which 88% were in MEDLINE, 33% in CINAHL and 20% in both sources. The relevance of the references was assessed by student reviewers. The positive predictive value of CINAHL (70%) was higher than that of MEDLINE (54%), but MEDLINE produced more than twice as many relevant references as CINAHL. The sensitivity of MEDLINE was 85% (95% CI 82-88%), and that of CINAHL was 41% (95% CI 37-45%). To assess the ease of obtaining the references, we developed an index of accessibility, based on the holdings of a number of Irish and British libraries. Overall, 47% of relevant references were available in the students' own library, and 64% could be obtained within 48 hours. There was no difference between the two databases overall, but when two topics relating specifically to the organization of nursing were excluded, references found in MEDLINE were significantly more accessible. We recommend that MEDLINE should be regarded as the first choice of bibliographic database for any subject other than one related strictly to the organization of nursing.

Library use and academic achievement among medical students.

Many factors play a part in determining the performance of students in examinations, but the extent to which students use library facilities does not appear to have been recently considered as a factor, in medicine or in any other academic subject. In this study, the number of books borrowed from the library by undergraduate medical students was used as a simple measure of library use, and significant differences in book-borrowing levels were found between students in different years of the medical course, students from different regions of the world, and men and women students. In the first year of the course, students who borrowed most also performed best in their end-of-year examinations, and this association was only partly explained by regional differences. No such association was found among final-year students, suggesting different study habits and different assessment criteria in the clinical years of the course.

Information on marketed drugs for doctors and patients. Experience in six European countries.

This article describes a project that looked at the availability of information on marketed pharmaceutical products to doctors and patients in six European countries. It examines the legal status of the drug compendia published in each country and reports on the implementation of EC Directive 92/27/EEC on labeling and packaging. A small survey showed that it is hard to compare patient information because it is difficult to obtain copies of pack inserts available in each country. However, a limited analysis revealed some differences in the content and presentation of data for doctors and patients.