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A catalog for transcripts in the venom gland of the Agkistrodon acutus: identification of the toxins potentially involved in coagulopathy.

Agkistrodon acutus is a special agkistrodon halys, only distributed in Southern China, with a few exceptions in Vietnam. It is a cherished element used in traditional Chinese medicine. In order to produce a global panorama of gene expression in the Agkistrodon acutus venom gland, a non-normalized cDNA library was constructed, and 8696 high quality 5' end expressed sequenced tags (ESTs) were sequenced and analyzed. The initial sequences were assembled into 2855 clusters. Of these clusters, only 45.60% clusters matched known sequence and 54.40% had no match to any known sequence in GenBank. Except for putative cellular proteins (1184 clusters), the remaining 118 clusters (40.16% of all ESTs) corresponded to sequences associated with diverse toxin function. According to expression abundance, the major toxin components were metalloproteinases (32.08%) and C-type lectin (5.22%), and other components including bradykinin-potentiating peptide (0.90%), serine proteases (0.51%), nucleotidase and nuclease (0.41%), phospholipase A2 (0.30%), disintegrin (0.05%), cytokine-like molecules (0.06%), and other proteins (0.63%). The majority of these components are thought to be responsible for coagulopathy after A. acutus bites. We have therefore generated a comprehensive catalog of the A. acutus venom gland described so far. Gene expression from the very specialized secretory tissue, especially for those involved in coagulopathy, can be surveyed and provide important information in finding novel toxins.

Agkistrodon↗

The increasing globalization of health librarianship: a brief survey of international trends and activities.

BACKGROUND AND PURPOSE: Throughout his career, Leslie Morton was interested in international developments in health librarianship. In memory of the work he did in this field, the authors examine current developments in international health librarianship and describe some current themes. PROCEDURES: The authors draw from their combined experience in international activities and the published information available from selected library associations and related organizations. FINDINGS: Although many of the major health library associations around the world are tackling agendas specific to their own country, issues of international concern are emerging in common. These are grouped around globalization, partnerships and co-operation, electronic access, especially open access, and working with the developing world in a number of different ways. Of course, the basis of all of these initiatives is to improve the health of the population by providing the best possible access to materials. CONCLUSIONS: Professional associations can provide a useful institutional infrastructure for addressing issues of international interest. Librarians should encourage their associations to develop these international initiatives and to seek out new and innovative ways to work together across international boundaries.

Australia↗

Characterization and genetic mapping of simple repeat sequences in the tomato genome.

Tomato genomic libraries were screened for the presence of simple sequence repeats (SSRs) with seventeen synthetic oligonucleotide probes, consisting of 2- to 5-basepair motifs repeated in tandem. GAn and GTn sequences were found to occur most frequently in the tomato genome (every 1.2 Mb), followed by ATTn and GCCn (every 1.4 Mb and 1.5 Mb, respectively). In contrast, only ATn and GAn microsatellites (n > 7) were found to be frequent in the GenBank database, suggesting that other motifs may be preferentially located away from genes. Polymorphism of microstellites was measured by PCR amplification of individual loci of by Southern hybridization, using a set of ten tomato cultivars. Surprisingly, only two of the nine microsatellite clones surveyed (five GTn, three GAn and one ATTn), showed length variation among these accessions. Polymorphism was also very limited between Lycopersicon esculentum and L. pennelli, two distant species. Southern analysis using the seventeen oligonucleotide probes identified GATAn and GAAAn as useful motifs for the detection of multiple polymorphic fragments among tomato cultivars. To determine the structure of microsatellite loci, a GAn probe was used for hybridization at low stringency on a small insert genomic library, and randomly selected clones were analyzed. GAn based motifs of increasing complexity were found, indicating that simple dinucleotide sequences may have evolved into larger tandem repeats such as minisatellites as a result of basepair substitution, replication slippage, and possibly unequal crossing-over. Finally, we genetically mapped loci corresponding to two amplified microsatellites, as well as nine large hypervariable fragments detected by Southern hybridization with a GATA8 probe. All loci are located around putative tomato centromeres. This may contribute to understanding of the structure of centromeric regions in tomato.

Base Sequence↗

Axillary recurrence after a negative sentinel node biopsy for breast cancer: incidence and clinical significance.

BACKGROUND: Sentinel lymph node biopsy (SLNB) carries the inherent risk of approximately 5% false-negative sampling. Undetected tumor-positive nodes of clinical importance are those that lead to axillary recurrence. This survey aims at clarifying the extent of this problem in current practice and literature. METHODS: In a regional teaching hospital, 696 consecutive breast cancer patients underwent SLNB between January 1998 and July 2003, and data were entered in a prospective database. PubMed and the Cochrane library were searched for a systematic review of the literature. Thirteen studies dealt with the follow-up of a cohort of sentinel lymph node (SLN)-negative patients or presented a case report. RESULTS: The SLN identification rate was 97.1%. The SLN was tumor free in 439 (65%) of the 676 patients. After a median follow-up of 26 months, axillary recurrence was detected in 2 of 439 patients 4 and 27 months after the SLNB. The incidence of clinically apparent false-negative SLNB is .46%. The systematic review resulted in 3184 SLNB-negative patients with a median follow-up of 25 months. Axillary recurrence occurred in eight patients after a median of 21 months. The axillary recurrence rate in the literature is .25%. One third of these patients present with synchronous systemic metastases. CONCLUSIONS: Axillary recurrences after a negative SLNB occur, but at a much lower rate than would be expected on the basis of historical figures and the false-negative SLN findings. The natural history of axillary relapse after negative SLNB resembles the locoregional recurrence of breast cancer.

Adult↗

Simultaneous and combinatorial chemical synthesis techniques for the generation and screening of molecular diversity.

By skillful 'mixing and sorting', thousand millions of different compounds, so-called molecular repertoires or molecular libraries, can be produced and screened for biological activity in a very short time. Today, both sophisticated as well as surprisingly simple procedures for simultaneous and combinatorial chemical synthesis open fascinating new perspectives for basic research, biotechnology and drug development. This contribution will give a brief survey of current strategies in the chemical synthesis of oligonucleotide and peptide repertoires with special emphasis on techniques employing membrane-type solid supports developed in this laboratory.

Amino Acid Sequence↗

Public endorsement of restrictions on three aspects of free expression by homosexuals: socio-demographic and trends analysis 1973-1988.

The willingness of the public to endorse proposals to remove gay-positive books from library shelves, to dismiss college teachers who are homosexuals, and to prohibit public speaking by homosexuals was examined. A socio-demographic analysis aggregating the entire period 1973 through 1988, and an analysis of trends over the period, were undertaken using data from the General Social Surveys. Responses to survey questions concerning homosexuals were compared with responses to similar questions concerning other unpopular groups, and to questions which called upon the respondent to make a moral judgment concerning homosexual relations. A significant decline over the period was found in the public's willingness to endorse restrictions on homosexuals, and on each of the other unpopular groups used for comparison. Level of education appeared to be a strong indicator of a more tolerant attitude. Paradoxically, negative moral attitudes toward homosexual relations did not decline. Bias in the wording of the General Social Surveys' questions concerning the moral dimension of homosexuality may have distorted these results, however. The public's moral attitude toward homosexual behavior does appear to be quite labile from year to year, suggesting that concerted efforts to educate the public on this subject can have an important and rapid effect.

Adult↗

[Consensus-based guidelines on prostate biopsy].

OBJECTIVE: To develop evidence-based and consensus-based guidelines, helping physicians to take decisions about diagnostic procedures for men wishing to undergo examination for detection of prostate cancer. MATERIAL AND METHODS: A panel of multidisciplinary Italian experts in urology, medical oncology, laboratory medicine, radiotherapy, pathology and methodologists for clinical trial (Mario Negri Institution) grouped together in 2002 to address specific questions relating to clinical controversies in prostate cancer diagnosis. A practitioners feedback survey by means of a questionnaire of 49 items was also conducted in 2003 to assess the great variability in all the aspects relating a prostate biopsy (PB). Experts reviewed relevant evidence, using CeVEAS scale, of the literature from 1966 to December 2004 (Medline, Embase, Cochrane library) before offering the discussion panel proposed guidelines for a given subset of questions. The discussion panel, which consisted of presenters and representatives from medical oncology, forensic medicine, radiotherapy, ethics, biochemistry and family practice medicine, took place on February 12, 2005 in Bologna. The panel deliberated to reach consensus on suggested guidelines. When evidence was insufficient, suggested guidelines represent the opinion of a cross-section of the presenters and discussion panel. RESULTS: Consensus was achieved regarding all the aspects relating PB. The final paper was approved by the jury, the panel of experts and the audience. A standardized guideline, containing a short version for physicians and a standardized patient information booklet, for nation-wide use was developed. In the final document it has been reported as following: Prostatic biopsy (PB) is recommended in all patients with a PSA> = 4.0 ng/ml (2,5 ng/ml in patients with positive family history), abnormal DRE and %FPSA < 10%. PSAD and PSAV are considered controversial predictive factors. Antibiotic prophylaxis with a fluoroquinolone, which can be omitted in cases of transperineal (TP) PB, is mandatory when using a transrectal (TR) approach. It is necessary to start the prophylaxis the day before and continued for 2-3 days after the procedure. Anaesthesia is mandatory in case of TP biopsy and strongly recommended in cases of TR PB (10 cc of periprostatic lidocaine injection rather than intrarectal lidocaine gel). The optimal PB scheme should include more than 6 cores (preferably 10-12 cores) weighted more laterally and apically. PB directed only to the hypoechoic lesion or standard sextant biopsy (Hodge's scheme) are considered obsolete. PB of the transition zone are mandatory only in cases of re-biopsy. A tru-cut needle with a diameter of 18 Fr. is recommended and a sandwich technique for core fixation informalin is considered the optimal approach. A PB should be repeated within 6-12 months in the following cases:1) First biopsy is inadequate (less than 6 cores, absence of prostatic cells on the cores), 2) in presence of HGPIN, ASAP or both on first PB, 3) in cases with persistently high levels of PSA (PSA > 10 ng/ml or PSA velocity > 0,75 ng/ml/year). PB after radiotherapy is not routinely indicated as well as biopsy of the vesico-urethral anastomosis after radical prostatectomy in patients with PSA failure. CONCLUSIONS: The suggested guidelines represent a reasonable diagnostic approach in patients to be submitted to PB, with the understanding that new data, subsequent findings, or other methodological considerations may lead to future modifications.

Biopsy↗

Comparing and using assessments of the value of information to clinical decision-making.

This paper discusses the Value project, which assessed the value to clinical decision-making of information supplied by National Health Service (NHS) library and information services. The project not only showed how health libraries in the United Kingdom help clinicians in decision-making but also provided quality assurance guidelines for these libraries to help make their information services more effective. The paper reviews methods and results used in previous studies of the value of health libraries, noting that methodological differences appear to affect the results. The paper also discusses aspects of user involvement, categories of clinical decision-making, the value of information to present and future clinical decisions, and the combination of quantitative and qualitative assessments of value, as applied to the Value project and the studies reviewed. The Value project also demonstrated that the value placed on information depends in part on the career stage of the physician. The paper outlines the structure of the quality assurance tool kit, which is based on the findings and methods used in the Value project.

Cost Savings↗

Promoting health and improving health care in a cost-effective manner through a military digital library.

OBJECTIVE: The Virtual Naval Hospital (VNH) is a digital library designed to meet the information needs of U.S. Navy medical professionals. The goal of this study was to determine whether the VNH promoted health and improved patient care in a cost-effective manner. DESIGN AND MEASUREMENTS: An economic analysis determining the costs and benefits from the perspective of the U.S. Navy was conducted. As part of this analysis, medical professionals were surveyed from February to August 2000. RESULTS: Respondents used the VNH for a variety of professional activities (average, 8.2 h/wk). Respondents (70%) thought that VNH usage improved patient care. Medical providers thought it improved their diagnosis (70%) and treatment (60%). Respondents stated that the VNH affected 81 medical evacuations and 668 sick-in-quarter days. Overall content satisfaction was 94%. The VNH had a net savings of $143,848/yr and a cost/benefit ratio of 55.9%. CONCLUSIONS: The VNH has a beneficial impact on the Navy's health care system by improving health promotion and patient care and by being economically cost-effective.

Cost-Benefit Analysis↗

Genome-wide protein interaction maps using two-hybrid systems.

Automated sequence technology has rendered functional biology amenable to genomic scale analysis. Among genome-wide exploratory approaches, the two-hybrid system in yeast (Y2H) has outranked other techniques because it is the system of choice to detect protein-protein interactions. Deciphering the cascade of binding events in a whole cell helps define signal transduction and metabolic pathways or enzymatic complexes. The function of proteins is eventually attributed through whole cell protein interaction maps where totally unknown proteins are partnered with fully annotated proteins belonging to the same functional category. Since its first description in the late 1980's, several versions of the Y2H have been developed in order to overcome the major limitations of the system, namely false positives and false negatives. Optimized versions have been recently applied at multi-molecular and genomic scale. These genome-wide surveys can be methodologically divided into two types of approaches: one either tests combinations of predefined polypeptides (the so-called matrix approach) using various short-cuts to speed up the process, or one screens with a given polypeptide (bait) for potential partners (preys) present in complex libraries of genomic or complementary DNA (library screening). In the former strategy, one tests what one knows, for example pair-wise interactions between full-length open reading frames from recently sequenced and annotated genomes. Although based on a one-by-one scheme, this method is reported to be amenable to large-scale genomics thanks to multicloning strategies and to the use of small robotics workstations. In the latter, highly complex cDNA or genomic libraries of protein domains can be screened to saturation with high-throughput screening systems allowing the discovery of yet unidentified proteins. Both approaches have strengths and drawbacks that will be discussed here. None yields a full proteome-wide screening since certain proteins (e.g. some transcription factors) are not usable in Y2H. Novel two-hybrid assays have been recently described in bacteria. Applications of these time- and cost-effective assays to genomic screening will be discussed and compared to the Y2H technology.

Animals↗

Teachers in general practice: a comparative study.

Thirty-nine randomly selected general practitioners in the Cambridgeshire Health Area were surveyed in an attempt to determine whether there were prior differences between those practitioners who choose to become involved with undergraduate medical students and those who choose not to. Teachers were found to have graduated more recently, subscribe to more journals and were more likely to use medical libraries than non-teachers. All the solo practitioners in the study and two of the four practitioners in two-man groups belonged to a subgroup of non-teachers who had never had students and did not want students in the future. This subfroup also subscribed to fewer journals than the other groups, bought fewer textbooks and used medical libraries less. The only prior differences between teachers and non-teacher that have been demonstrated are year of graduation and type of practice. Other differences could well be attributed to the influence of the students themselves. Studies are needed to clarify this issue, especially as it realates to continuing medical education.

Education, Medical, Continuing↗

Evaluation of the KA24 (Knowledge Access 24) service for health- and social-care staff in London and the south-east of England. Part 1: quantitative.

AIMS AND OBJECTIVES: This two-part paper aims to identify the main transferable lessons learned from both the quantitative and qualitative evaluations of the Knowledge Access 24 (KA24) service of online databases and selected full-text journals for health and social care staff in London and the south-east of England. The quantitative evaluation analysed usage rates and user registration with the objective of measuring uptake by previously disadvantaged staff, and to inform the subsequent qualitative survey. METHODS: User and usage data were analysed by type of NHS Trust, by type of user, and by what was being used. The evaluation assessed development in user registration and usage of both databases and journals over a 2-year period. Data were aggregated and analysed both monthly and quarterly. RESULTS: Usage levels increased, but uptake in both the mental health and primary care sectors was comparatively slow. Nurses and allied professionals used the service more than doctors. The increase in usage of full-text journals over the usage of databases was marked. CONCLUSIONS: Previously disadvantaged staff used electronic resources. A qualitative survey was needed to identify the main enablers and barriers to uptake.

Community Health Services↗

Systematic review of patient and nurse attitudes to depot antipsychotic medication.

BACKGROUND: Depot antipsychotic medication is used widely in the treatment and prophylaxis of severe mental illness. AIMS: To review the literature on patient and nurse satisfaction with, and attitudes towards, depots. METHOD: A systematic search of Medline, Embase, PsycINFO, CINAHL and The Cochrane Library was undertaken, along with citation searches. Studies were selected if satisfaction/attitude data were described in the title or abstract and original data were included. Study quality was rated. RESULTS: The search produced 1374 articles; 22 articles met the inclusion criteria, 18 of which were cross-sectional surveys. Of the 12 studies with relevant data, 10 conveyed a positive opinion of depot medication. Five out of six studies comparing depot with oral medication showed patient preference for depot. CONCLUSIONS: High-quality data examining patient and nurse attitudes regarding depot antipsychotics are sparse. What data there are show a positive attitude to depots from patients. Future randomised controlled trials should include satisfaction as an outcome.

Administration, Oral↗

[Hospital Information Systems and their application in public health].

The objective of this study was to survey the scientific production of applications for data from the Hospital Information System of Brazil's Unified National System (SUS) in analyses of relevant Public Health issues. To find articles published in scientific journals from 1984 to 2003, the authors consulted the SciELO, MEDLINE, and Virtual Public Health Library databases. To locate monographs, theses, and dissertations, the authors consulted the websites of institutions providing Master's and doctoral courses in Public Health. A total of 76 articles were identified for the reference period, and they were classified into five categories with different analytical approaches. Although the Hospital Information System in the SUS has incomplete coverage and there are uncertainties about the reliability of its data, the range of studies showed internal consistency with current knowledge, reinforcing the system's importance and the need to understand its strengths and weaknesses.

Bibliometrics↗

Multi-file searching: a review of the current situation.

This paper investigates the problems of multi-file searching, which have arisen from the recent expansion of data-bases. The papers presented on this theme at the recent European MEDLINE Workshop are summarized. Special emphasis is placed on the specificity of searching NLM files on ELHILL, based on a survey of their actual use among the French network of associate centres. Recommendations for improving multi-file searching in ELHILL are also listed.

Humans↗

Dual pricing of health sciences periodicals: a survey.

A survey of dual pricing practices among publishers of health-related journals identified 281 periodicals with an average price differential of over 100% between individual and institutional subscription rates. Both the practice itself and the amount of the differential are increasing, indicating that journal subscriptions of health sciences libraries increasingly provide the financial support necessary for the publication of health sciences journals. Dual pricing is also correlated with copyright royalties. The problems that dual pricing creates for health sciences libraries' budgets are due in part to uncritical purchasing by libraries. Increased consumerism on the part of health science librarians is recommended.

Cost Allocation↗

Continuing Medical Education in Clinical Pharmacology and Therapeutics: report of a questionnaire survey.

AIMS: To seek the views of medically qualified members of the Clinical Section of the British Pharmacological Society (BPS) on their perceived needs for Continuing Medical Education (CME); on how and by whom these needs should be addressed; and on how the outcome of any educational intervention might best be assessed. METHODS: A structured questionnaire. RESULTS: Of 233 recipients, 140 (60%) responded, but only 123 of these fulfilled the criteria for analysis. A large majority of respondents were clinicians, most of whom devoted at least 25% of their working week to their NHS commitment. There was widespread reliance on textbooks and journals as sources of CME, supplemented by discussions with specialist peers at national and international meetings. Many felt that fulfilling even this agenda was stretching their commitment to the limit, and their greatest need was for protected time in which to learn. There was a desire among 49% of all respondents for the BPS Clinical Section to take some responsibilty for addressing the future needs of its members, and 75% took the view that academic departments should contribute to the development and updating of materials. There was no clear agreement about what these should comprise, but around half of all respondents favoured web-based, journal-based or computer-assisted educational material offering self-assessment opportunities; and CME symposia or workshops at BPS meetings. Almost half (46%) felt that assessment of CME should be integrated with a well-organized appraisal system and the use of portfolios. Six out of 10 respondents were already, or were about to be, regularly appraised at their place of work. CONCLUSIONS: The questionnaire survey revealed a broad canvas of views and little evidence of consensus except for a general plea for more time in which to learn. The aim of the Clinical Section should be to facilitate and help its members to organize their learning, in a way that is consistent with national trends in Continuing Professional Development. The Clinical Section should co-ordinate the setting up of an electronic library of appropriate published material, compiled by academic and industrial sources, that would guide members seeking up-to-date knowledge of Clinical Pharmacology and Therapeutics. The British Journal of Clinical Pharmacology (BJCP) should commission review articles on recent developments where no suitable published material exists. Academic departments should also be invited to identify or develop self-assessment material that members could use to reinforce their learning, and demonstrate their knowledge to relevant professional bodies. The Clinical Section should organize Symposia and Workshops at which contentious issues in Clinical Pharmacology and Therapeutics can be discussed and resolved.

Education, Medical, Continuing↗

Are data from different gene expression microarray platforms comparable?

Many commercial and custom-made microarray formats are routinely used for large-scale gene expression surveys. Here, we sought to determine the level of concordance between microarray platforms by analyzing breast cancer cell lines with in situ synthesized oligonucleotide arrays (Affymetrix HG-U95v2), commercial cDNA microarrays (Agilent Human 1 cDNA), and custom-made cDNA microarrays from a sequence-validated 13K cDNA library. Gene expression data from the commercial platforms showed good correlations across the experiments (r = 0.78-0.86), whereas the correlations between the custom-made and either of the two commercial platforms were lower (r = 0.62-0.76). Discrepant findings were due to clone errors on the custom-made microarrays, old annotations, or unknown causes. Even within platform, there can be several ways to analyze data that may influence the correlation between platforms. Our results indicate that combining data from different microarray platforms is not straightforward. Variability of the data represents a challenge for developing future diagnostic applications of microarrays.

Cell Line, Tumor↗