Sry delivery to the adrenal medulla increases blood pressure and adrenal medullary tyrosine hydroxylase of normotensive WKY rats

BACKGROUND: Our laboratory has shown that a locus on the SHR Y chromosome increases blood pressure (BP) in the SHR rat and in WKY rats that had the SHR Y chromosome locus crossed into their genome (SHR/y rat). A potential candidate for this Y chromosome hypertension locus is Sry, a gene that encodes a transcription factor that is responsible for testes development and the Sry protein may affect other target genes. METHODS: The following study examined if exogenous Sry would elevate adrenal Th, adrenal catecholamines, plasma catecholamines and blood pressure. We delivered 10 μg of either the expression construct, Sry1/pcDNA 3.1, or control vector into the adrenal medulla of WKY rats by electroporation. Blood pressure was measured by the tail cuff technique and Th and catecholamines by HPLC with electrochemical detection. RESULTS: In the animals receiving Sry there were significant increases after 3 weeks in resting plasma NE (57%) and adrenal Th content (49%) compared to vector controls. BP was 30 mmHg higher in Sry injected animals (160 mmHg, p < .05) compared to vector controls (130 mmHg) after 2–3 weeks. Histological analysis showed that the electroporation procedure did not produce morphological damage. CONCLUSION: These results provide continued support that Sry is a candidate gene for hypertension. Also, these results are consistent with a role for Sry in increasing BP by directly or indirectly activating sympathetic nervous system activity

Analysis of clinical uncertainties by health professionals and patients: an example from mental health

<p>Abstract</p> <p>Background</p> <p>The first step in practising Evidence Based Medicine (EBM) has been described as translating clinical uncertainty into a structured and focused clinical question that can be used to search the literature to ascertain or refute that uncertainty. In this study we focus on questions about treatments for schizophrenia posed by mental health professionals and patients to gain a deeper understanding about types of questions asked naturally, and whether they can be reformulated into structured and focused clinical questions.</p> <p>Methods</p> <p>From a survey of uncertainties about the treatment of schizophrenia we describe, categorise and analyse the type of questions asked by mental health professionals and patients about treatment uncertainties for schizophrenia. We explore the value of mapping from an unstructured to a structured framework, test inter-rater reliability for this task, develop a linguistic taxonomy, and cross tabulate that taxonomy with elements of a well structured clinical question.</p> <p>Results</p> <p>Few of the 78 Patients and 161 clinicians spontaneously asked well structured queries about treatment uncertainties for schizophrenia. Uncertainties were most commonly about drug treatments (45.3% of clinicians and 41% of patients), psychological therapies (19.9% of clinicians and 9% of patients) or were unclassifiable.(11.8% of clinicians and 16.7% of patients). Few naturally asked questions could be classified using the well structured and focused clinical question format (i.e. PICO format). A simple linguistic taxonomy better described the types of questions people naturally ask.</p> <p>Conclusion</p> <p>People do not spontaneously ask well structured clinical questions. Other taxonomies may better capture the nature of questions. However, access to EBM resources is greatly facilitated by framing enquiries in the language of EBM, such as posing queries in PICO format. People do not naturally do this. It may be preferable to identify a way of searching the literature that more closely matches the way people naturally ask questions if access to information about treatments are to be made more broadly available.</p

Technology mediator: a new role for the reference librarian?

The Arizona Health Sciences Library has collaborated with clinical faculty to develop a federated search engine that is useful for meeting real-time clinical information needs. This article proposes a technology mediation role for the reference librarian that was inspired by the project, and describes the collaborative model used for developing technology-mediated services for targeted users

Teaching clinical informatics to third-year medical students: negative results from two controlled trials

BACKGROUND: Prior educational interventions to increase seeking evidence by medical students have been unsuccessful. METHODS: We report two quasirandomized controlled trials to increase seeking of medical evidence by third-year medical students. In the first trial (1997–1998), we placed computers in clinical locations and taught their use in a 6-hour course. Based on negative results, we created SUMSearch(TM), an Internet site that automates searching for medical evidence by simultaneous meta-searching of MEDLINE and other sites. In the second trial (1999–2000), we taught SUMSearch's use in a 5½-hour course. Both courses were taught during the medicine clerkship. For each trial, we surveyed the entire third-year class at 6 months, after half of the students had taken the course (intervention group). The students who had not received the intervention were the control group. We measured self-report of search frequency and satisfaction with search quality and speed. RESULTS: The proportion of all students who reported searching at least weekly for medical evidence significantly increased from 19% (1997–1998) to 42% (1999–2000). The proportion of all students who were satisfied with their search results increased significantly between study years. However, in neither study year did the interventions increase searching or satisfaction with results. Satisfaction with the speed of searching was 27% in 1999–2000. This did not increase between studies years and was not changed by the interventions. CONCLUSION: None of our interventions affected searching habits. Even with automated searching, students report low satisfaction with search speed. We are concerned that students using current strategies for seeking medical evidence will be less likely to seek and appraise original studies when they enter medical practice and have less time

EMBASE search strategies for identifying methodologically sound diagnostic studies for use by clinicians and researchers

BACKGROUND: Accurate diagnosis by clinicians is the cornerstone of decision making for recommending clinical interventions. The current best evidence from research concerning diagnostic tests changes unpredictably as science advances. Both clinicians and researchers need dependable access to published evidence concerning diagnostic accuracy. Bibliographic databases such as EMBASE provide the most widely available entrée to this literature. The objective of this study was to develop search strategies that optimize the retrieval of methodologically sound diagnostic studies from EMBASE for use by clinicians. METHODS: An analytic survey was conducted, comparing hand searches of 55 journals with retrievals from EMBASE for 4,843 candidate search terms and 6,574 combinations. All articles were rated using purpose and quality indicators, and clinically relevant diagnostic accuracy articles were categorized as 'pass' or 'fail' according to explicit criteria for scientific merit. Candidate search strategies were run in EMBASE, the retrievals being compared with the hand search data. The proposed search strategies were treated as "diagnostic tests" for sound studies and the manual review of the literature was treated as the "gold standard." The sensitivity, specificity, precision and accuracy of the search strategies were calculated. RESULTS: Of the 433 articles about diagnostic tests, 97 (22.4%) met basic criteria for scientific merit. Combinations of search terms reached peak sensitivities of 100% with specificity at 70.4%. Compared with best single terms, best multiple terms increased sensitivity for sound studies by 8.2% (absolute increase), but decreased specificity (absolute decrease 6%) when sensitivity was maximized. When terms were combined to maximize specificity, the single term "specificity.tw." (specificity of 98.2%) outperformed combinations of terms. CONCLUSION: Empirically derived search strategies combining indexing terms and textwords can achieve high sensitivity and specificity for retrieving sound diagnostic studies from EMBASE. These search filters will enhance the searching efforts of clinicians

Just-in-Time Information Improved Decision-Making in Primary Care: A Randomized Controlled Trial

BACKGROUND: The "Just-in-time Information" (JIT) librarian consultation service was designed to provide rapid information to answer primary care clinical questions during patient hours. This study evaluated whether information provided by librarians to answer clinical questions positively impacted time, decision-making, cost savings and satisfaction. METHODS AND FINDING: A randomized controlled trial (RCT) was conducted between October 2005 and April 2006. A total of 1,889 questions were sent to the service by 88 participants. The object of the randomization was a clinical question. Each participant had clinical questions randomly allocated to both intervention (librarian information) and control (no librarian information) groups. Participants were trained to send clinical questions via a hand-held device. The impact of the information provided by the service (or not provided by the service), additional resources and time required for both groups was assessed using a survey sent 24 hours after a question was submitted. The average time for JIT librarians to respond to all questions was 13.68 minutes/question (95% CI, 13.38 to 13.98). The average time for participants to respond their control questions was 20.29 minutes/question (95% CI, 18.72 to 21.86). Using an impact assessment scale rating cognitive impact, participants rated 62.9% of information provided to intervention group questions as having a highly positive cognitive impact. They rated 14.8% of their own answers to control question as having a highly positive cognitive impact, 44.9% has having a negative cognitive impact, and 24.8% with no cognitive impact at all. In an exit survey measuring satisfaction, 86% (62/72 responses) of participants scored the service as having a positive impact on care and 72% (52/72) indicated that they would use the service frequently if it were continued. CONCLUSIONS: In this study, providing timely information to clinical questions had a highly positive impact on decision-making and a high approval rating from participants. Using a librarian to respond to clinical questions may allow primary care professionals to have more time in their day, thus potentially increasing patient access to care. Such services may reduce costs through decreasing the need for referrals, further tests, and other courses of action. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN96823810

Rapid Reactivation of Extralymphoid CD4 T Cells during Secondary Infection

After infection, extralymphoid tissues are enriched with effector and memory T cells of a highly activated phenotype. The capacity for rapid effector cytokine response from extralymphoid tissue-memory T cells suggests these cells may perform a ‘sentinel’ function in the tissue. While it has been demonstrated that extralymphoid CD4+ T cells can directly respond to secondary infection, little is known about how rapidly this response is initiated, and how early activation of T cells in the tissue may affect the innate response to infection. Here we use a mouse model of secondary heterosubtypic influenza infection to show that CD4+ T cells in the lung airways are reactivated within 24 hours of secondary challenge. Airway CD4+ T cells initiate an inflammatory cytokine and chemokine program that both alters the composition of the early innate response and contributes to the reduction of viral titers in the lung. These results show that, unlike a primary infection, extralymphoid tissue-memory CD4+ T cells respond alongside the innate response during secondary infection, thereby shaping the overall immune profile in the airways. These data provide new insights into the role of extralymphoid CD4+ T cells during secondary immune responses

“Excellence R Us”: university research and the fetishisation of excellence

The rhetoric of “excellence” is pervasive across the academy. It is used to refer to research outputs as well as researchers, theory and education, individuals and organisations, from art history to zoology. But does “excellence” actually mean anything? Does this pervasive narrative of “excellence” do any good? Drawing on a range of sources we interrogate “excellence” as a concept and find that it has no intrinsic meaning in academia. Rather it functions as a linguistic interchange mechanism. To investigate whether this linguistic function is useful we examine how the rhetoric of excellence combines with narratives of scarcity and competition to show that the hypercompetition that arises from the performance of “excellence” is completely at odds with the qualities of good research. We trace the roots of issues in reproducibility, fraud, and homophily to this rhetoric. But we also show that this rhetoric is an internal, and not primarily an external, imposition. We conclude by proposing an alternative rhetoric based on soundness and capacity-building. In the final analysis, it turns out that that “excellence” is not excellent. Used in its current unqualified form it is a pernicious and dangerous rhetoric that undermines the very foundations of good research and scholarship