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Bringing a virtual library to a small group classroom.

A small group case discussion class would seem to be the ideal setting for a virtual library. Two courses at the Albert Einstein College of Medicine were observed. One hour of observation was of groups with no computer available, one hour of groups with a computer available "incidentally", and two hours of groups with computer integrated case material. Across all groups, at least one student was using a reference source (paper or computer) 55% of the time. In a room with no computer, paper references were used 59% of the time. In a room with a computer, references were used 53% of the time (18% computer only, 13% paper only, 22% both). While the amount of data is insufficient for detecting statistically significant difference, this study does provide important baseline data not previously available concerning reference use behavior for electronic and paper sources.

Databases as Topic↗

Molecular pharmacology of aromatase and its regulation by endogenous and exogenous agents.

Aromatase (estrogen synthase) is the cytochrome P450 enzyme complex that converts C19 androgens to C18 estrogens. Aromatase activity has been demonstrated in breast tissue in vitro, and expression of aromatase is highest in or near breast tumor sites. Thus, local regulation of aromatase by both endogenous factors as well as exogenous medicinal agents will influence the levels of estrogen available for breast cancer growth. The prostaglandin E2 (PGE2) increases intracellular cAMP levels and stimulates estrogen biosynthesis, and our recent studies have shown a strong linear association between CYP19 expression and the sum of COX-1 and COX-2 expression in breast cancer specimens. PGE2 can bind to four receptor subtypes, EP1-EP4, which are coupled to different intracellular signaling pathways. In primary human breast stromal cell cultures, aromatase activity was significantly induced by PGE2, dexamethasone, and agonists for the EP1 and EP2 receptor subtypes. An EP1 antagonist, SC-19220, inhibited the induction of enzyme activity by PGE2 or 17-phenyltrinor-PGE2, an EP1 agonist. Sulprostone, an EP3 agonist, did not alter aromatase activity levels. Investigations are also underway on the regulation of aromatase by exogenous medicinal agents. Selective steroidal and nonsteroidal agents are effective in inhibiting breast tissue aromatase. The benzopyranone ring system is a molecular scaffold of considerable interest, and this scaffold is found in certain flavonoid natural products that have weak aromatase inhibitory activity. Our novel synthetic route for benzopyranones utilizes readily available salicylic acids and terminal alkynes as starting materials. The synthesis of flavones with diversity on the benzopyranone moiety and at the C-2 position occurs with good to excellent yields using these reaction conditions, resulting in an initial benzopyranone library of thirty compounds exhibiting enhanced and differential aromatase inhibition. Current medicinal chemistry efforts focus on diversifying the benzopyranone scaffold and utilizing combinatorial chemistry approaches to construct small benzopyranone libraries as potential aromatase inhibitors.

Aromatase↗

Cloning and characterization of glutamate dehydrogenase (GDH) from the gut of Haemonchus contortus.

Vaccination of lambs with the membrane-bound (S3) thiol-Sepharose binding protein (TSBP) fraction derived from the gut of Haemonchus contortus confers significant protection against homologous challenge. The S3 TSBP peptide profile is dominated by a major protein of ca. 60 kDa which is strongly recognized by antisera from sheep demonstrably protected following immunization with S3 TSBP. In an attempt to identify this protein, sera from protected lambs were employed to screen a lambda gt11 cDNA library of the adult parasite and resulted in the isolation of numerous clones encoding a homologue of the mitochondrial enzyme, glutamate dehydrogenase (GDH). GDH enzyme activity was readily demonstrable in S3 TSBP material and immunolocalization studies showed that the enzyme was localized to the cytoplasm of the parasite's gut. Furthermore, the enzyme appeared to be developmentally regulated, with both GDH mRNA and protein expressed almost exclusively during the blood-feeding parasitic stages.

Amino Acid Sequence↗

Identification of environmental stress-regulated genes in Helicobacter pylori by a lacZ reporter gene fusion system.

BACKGROUND: Helicobacter pylori persists in the human stomach for decades. This requires an efficient adaptation of H. pylori to the gastric niche and involves the regulation of bacterial genes in response to environmental stress. Efficient molecular tools to identify regulated H. pylori genes are scarce, therefore we developed a genomic lacZ reporter gene fusion system in H. pylori to screen for stress-regulated genes. MATERIALS AND METHODS: The integration vector pBW was constructed and used to generate random genomic lacZ fusions in H. pylori. Two-hundred-and-fifty H. pylori transformants were selected from this library, replica-plated and screened for differential lacZ expression after exposure to two environmental stress conditions: increased temperature (42 degrees C), and iron-limitation. RESULTS: From a library of H. pylori transformants with random genomic transcriptional lacZ fusions, two stress-regulated H. pylori loci were identified. The transcription of a gene of unknown function (designated hsp12) was increased by incubation at 42 degrees C. The transcription of a locus, consisting of the three fumarate reductase subunit genes (frdCAB) and the HP0190 gene from H. pylori strain 26695, was decreased under iron-limitation. CONCLUSIONS: This is the first time that a genomic transcriptional lacZ reporter gene H. pylori library has been used as a tool for the fast and efficient identification of environmental stress-regulated H. pylori genes.

Bacterial Proteins↗

Probabilistic representation of gene regulatory networks.

MOTIVATION: Recent experiments have established unambiguously that biological systems can have significant cell-to-cell variations in gene expression levels even in isogenic populations. Computational approaches to studying gene expression in cellular systems should capture such biological variations for a more realistic representation. RESULTS: In this paper, we present a new fully probabilistic approach to the modeling of gene regulatory networks that allows for fluctuations in the gene expression levels. The new algorithm uses a very simple representation for the genes, and accounts for the repression or induction of the genes and for the biological variations among isogenic populations simultaneously. Because of its simplicity, introduced algorithm is a very promising approach to model large-scale gene regulatory networks. We have tested the new algorithm on the synthetic gene network library bioengineered recently. The good agreement between the computed and the experimental results for this library of networks, and additional tests, demonstrate that the new algorithm is robust and very successful in explaining the experimental data. AVAILABILITY: The simulation software is available upon request. SUPPLEMENTARY INFORMATION: Supplementary material will be made available on the OUP server.

Algorithms↗

Organizing the present, looking to the future: an online knowledge repository to facilitate collaboration.

BACKGROUND: Comprehensive data available in the Canadian province of Manitoba since 1970 have aided study of the interaction between population health, health care utilization, and structural features of the health care system. Given a complex linked database and many ongoing projects, better organization of available epidemiological, institutional, and technical information was needed. OBJECTIVE: The Manitoba Centre for Health Policy and Evaluation wished to develop a knowledge repository to handle data, document research Methods, and facilitate both internal communication and collaboration with other sites. METHODS: This evolving knowledge repository consists of both public and internal (restricted access) pages on the World Wide Web (WWW). Information can be accessed using an indexed logical format or queried to allow entry at user-defined points. The main topics are: Concept Dictionary, Research Definitions, Meta-Index, and Glossary. The Concept Dictionary operationalizes concepts used in health research using administrative data, outlining the creation of complex variables. Research Definitions specify the codes for common surgical procedures, tests, and diagnoses. The Meta-Index organizes concepts and definitions according to the Medical Sub-Heading (MeSH) system developed by the National Library of Medicine. The Glossary facilitates navigation through the research terms and abbreviations in the knowledge repository. An Education Resources heading presents a web-based graduate course using substantial amounts of material in the Concept Dictionary, a lecture in the Epidemiology Supercourse, and material for Manitoba's Regional Health Authorities. Confidential information (including Data Dictionaries) is available on the Centre's internal website. RESULTS: Use of the public pages has increased dramatically since January 1998, with almost 6,000 page hits from 250 different hosts in May 1999. More recently, the number of page hits has averaged around 4,000 per month, while the number of unique hosts has climbed to around 400. CONCLUSIONS: This knowledge repository promotes standardization and increases efficiency by placing concepts and associated programming in the Centre's collective memory. Collaboration and project management are facilitated.

Databases as Topic↗

The reporting of randomized controlled trials in prosthodontics.

PURPOSE: This article evaluates the reporting of randomized controlled trials (RCT) in prosthodontics, excluding endosseous implant-based prosthetics. MATERIALS AND METHODS: Reports of RCTs published to the end of 2000 in any language were identified using a multilayered search strategy. The Cochrane Oral Health Group specialized register, Medline, and personal libraries were searched. Three researchers appraised the articles independently using guidelines following Jadad and CONSORT, complemented with an evaluation of the appropriateness of the reported statistics. RESULTS: Ninety-two reports of RCTs were evaluated, covering a wide spectrum of study hypotheses, topics, and issues within various prosthodontic domains. The interrater agreements on appraisal criteria were relatively high, with median kappa values ranging between 0.65 and 0.79. The reports were in general of poor methodologic quality. Randomization and procedures for concealment allocation were not described in 70% of the articles. The methods used to generate the random allocation sequence were not mentioned in 82%. The methods used to implement the random allocation sequence, clarifying whether it was concealed until all interventions were assigned, was not mentioned in 94%. Reporting who generated allocation sequence, who enrolled patients, and who assigned participants to groups was not reported in 7%. Reasons for withdrawals were not given in 23% of the reports. No attempt at blinding was reported in 72%. Statistical analysis was not described in 6% of the papers, while these analyses were assessed as appropriate for 75%, unclear in 12%, and inappropriate in 7%. CONCLUSION: Few RCTs in prosthodontics are reported in accordance with contemporary guidelines for adequate reporting of trials.

Adhesives↗

[Postnatal care in a cross-cultural and historical perspective].

BACKGROUND: In most societies, birth and the immediate postpartum period are considered a time of vulnerability for mother and child. Rituals for major changes in the life cycle are common in most societies. The aim of this study was to present some examples of postpartum customs in a cross-cultural and historical perspective. We also present research on associations between postnatal care and mental health. MATERIAL AND METHODS: A systematic search was performed in Medline and the Science Citation Index Expanded (ISI) from 1966 until March 2003. Reference lists in books about pregnancy and birth from the library of the University of Oslo were used to get additional information. RESULTS: The postnatal period is defined as approximately 40 days in most cultures; most societies have special postnatal customs that include special diet, isolation, rest and help in the household. The resemblance between different cultures is striking. Many postnatal customs from rural societies that were common before 1950 have disappeared. The focus on rest and help in the household for the mother after delivery has been reduced. INTERPRETATION: We need more knowledge about the impact of different kinds of postnatal care on the mother's wellbeing.

Anthropology↗

Computer-assisted instruction in surgery.

Computer-assisted instruction (CAI) is an educational medium which provides a highly interactive, adaptive, and individualized learning experience for the student or physician. A CAI system has benn developed to prepare a curriculum in general surgery. The surgical seminars written on this system have been used enthusiastically by students, residents, and interns for the past 18 months. Using a computer terminal (printer or television screen) connected by telephone to a minicomputer, the user participates in simulated seminars with the authors, viewing information and answering questions based on the material presented. The student responds by typing the answer in his own words, and the computer (author) responds with further information designed specifically for that answer. This response may support or contest what the student said, may branch the student to material covered previously, or instead may lead the student through as much remedial material as he needs. A more sophisticated student will progress rapidly through the seminar. Twenty-five surgeon/authors (at 15 medical schools) are preparing seminars, and it is planned that a complete library in general surgery will be available to departments of surgery nationally by September, 1978, via the Health Education Network.

Computer-Assisted Instruction↗

Information needs of rural health care practitioners in Hawaii.

Rural health care workers need a wide range of specialized information but have difficulties locating and accessing information resources. The information needs of Hawaii's rural health care practitioners and their methods of accessing information were studied through interviews and mailed questionnaires. The following barriers to information access were identified: lack of funds, inadequate hardware, infrastructure problems, and insufficient knowledge about information sources and how to use them. Although many (85%) reported having computers, only a minority (30%) have modems, and even fewer use online resources or the free electronic databases at public and university libraries. Most reported that journal articles were the information source that best met their needs and that personal files or a colleague's collection were the most common places for accessing needed materials. Recommendations for solving some of the information problems include development of a State of Hawaii rural health information clearinghouse; better identification, training, and use of available services; and, most importantly, the establishment of rural health care information agents (modeled on agriculture extension agents) on each major island.

Hawaii↗

Small changes in the polymer structure influence the adsorption behavior of fibrinogen on polymer surfaces: validation of a new rapid screening technique.

Numerous studies conclude that the selective adsorption of plasma proteins on materials contacting blood or tissue affects all subsequent interactions related to the biocompatibility of artificial surfaces. However, there are only a few studies available, which clearly demonstrate that there is a correlation between surface chemistry and selective protein adsorption. Detailed knowledge of such correlations would facilitate the design of biocompatible materials. In this study, a rapid, fluorescence-based, screening technique using a 384-well format for polymer-protein interactions was developed. The screening assay was used to measure the adsorption of human fibrinogen on 46 test polymers (44 polyarylates selected from a combinatorial library of tyrosine-derived polyarylates, and two lactide-based polymers). In this library of polyarylates, structural changes are generated by variations in either the polymer backbone or the polymer pendent chain. Although no overall trend between polymer hydrophobicity and fibrinogen adsorption could be identified using the entire set of test polymers (R(2) = 0.43), fibrinogen adsorption was clearly correlated with variations in the pendent chain structure. Thus, when the test polymers were grouped by backbone composition, increased hydrophobicity of the pendent chain was significantly correlated with reduced fibrinogen adsorption. The following R(2) coefficients within the polymer backbone groups were determined: 0.87 (diglycolates); 0.98 (glutarates); 0.73 (adipates); 0.87 (suberates); 0.67 (3-methyl-adipates). Our results demonstrate that it is possible to screen for protein-material interactions in a cost-effective fashion using a miniaturized immunofluorescence technique. Further, we demonstrate that small changes in chemical composition can significantly influence the adsorption of human fibrinogen on polymer surfaces. The lactide-based polymers were among those polymers exhibiting the highest tendency to adsorb fibrinogen. This information may be useful when polymers have to be selected for specific biomaterial applications.

Adsorption↗

Searching the databases: a quick look at Amazon and two other online catalogues.

The Amazon Online Catalogue was compared with the Library of Congress Catalogue and the British Library Catalogue, both also available online, by searching on both neutral (Gay, Lesbian, Homosexual) and pejorative (Perversion, Sex Crime) subject terms, and also by searches using Boolean logic in an attempt to identify Lesbian Fiction items and religion-based anti-gay material. Amazon was much more likely to be the first port of call for non-academic enquiries. Although excluding much material necessary for academic research, it carried more information about the individual books and less historical homophobic baggage in its terminology than the great national catalogues. Its back catalogue of second-hand books outnumbered those in print. Current attitudes may partially be gauged by the relative numbers of titles published under each heading--e.g., there may be an inverse relationship between concern about child sex abuse and homophobia, more noticeable in U.S. because of the activities of the religious right.

Bibliometrics↗

Portable software tools for 3D radiation therapy planning.

PURPOSE: Produce a collection of software tools (computer programs) that support three-dimensional (3D) radiation therapy planning. The tools are not a complete 3D planning system. Instead, they work with any 3D planning system that meets certain minimal specifications. The tools assist in deriving anatomic data from images, generating target volume contours, evaluating treatment plans, and verifying accurate treatment delivery. The tools are portable: they can run without source code changes in any computing environment that provides a library of functions and data definitions called the Foundation. The Foundation couples the portable tools to the (usually nonportable) file system and dose calculation associated with a particular 3D planning system. METHODS AND MATERIALS: Tools were written at three different (geographically separated) institutions. Software developers from all three sites specified the Foundation. The programmers' interface to the Foundation is portable, but a Foundation implementation need not be portable. Each group implemented a Foundation adapted to the (different) 3D planning system used at their site. RESULTS: All tools run at all three sites without source code changes. Each Foundation was implemented in a few person-months of programming effort. The program text and documentation for the tools have been placed in the public domain. CONCLUSIONS: It is practical and economical to produce portable radiotherapy treatment planning tools. Providers of 3D planning programs should offer Foundations for their systems, so they can be used with tools. Researchers considering new computer programs should write them as tools, so they can work with any 3D planning system.

Costs and Cost Analysis↗

Clinical and molecular evaluation of four patients with partial duplications of the long arm of chromosome 18.

Four individuals with partial duplications of the long arm of chromosome 18 were analyzed at the clinical, cytogenetic, and molecular levels. Two of the individuals had duplications of the long arm from 18q21.1-qter because of inheritance of an unbalanced translocation. Both of these individuals displayed the clinical phenotype characteristic of Edwards syndrome. Two other patients had de novo interstitial duplications of 18q but did not have a clinical diagnosis of Edwards syndrome. The extent of the duplicated material in each patient was determined initially by using cytogenetic analysis and subsequently with more detailed comparisons of the duplicated regions by using molecular probes derived from a chromosome 18-specific lambda phage library. The results demonstrated that one of the de novo interstitial duplications that did not result in the Edwards syndrome phenotype had a more proximal breakpoint than that of the partial duplications of the two patients with features of Edwards syndrome. These results suggest that a single critical region for Edwards syndrome in the proximal portion of 18q is unlikely.

Adolescent↗

Male pelvic anatomy reconstructed from the visible human data set.

PURPOSE: To improve understanding of the male pelvic anatomy pertinent to urological surgery we performed computer generated, 3-dimensional reconstruction of the male pelvis from the Visible Human data set. MATERIALS AND METHODS: A total of 18 discrete anatomical structures, including the prostate, bladder, urethra, rectum and pelvic musculature, was segmented from the Visible Human cross-sectional data obtained from the National Library of Medicine. Using high speed computing and rendering software, 3-dimensional models of each structure were generated and assembled into composite figures. RESULTS: These reconstructions offer a revised view of pelvic anatomy as it has been traditionally depicted. The lateral surfaces of the levator ani muscle are oriented vertically in the pelvis and directly applied to the entire lateral surface of the prostate. The bladder rests primarily anterior to the prostate rather than directly above it, as has been commonly depicted. In the cross-sectional data and reconstructions the trigone and anterior fibromuscular stroma of the prostate appear as a single unit in continuity, which may have functional implications for understanding the mechanisms of continence at the bladder neck. The striated urethral sphincter appears circular with abundant tissue posteriorly. This sphincteric muscle has greater length anteriorly than posteriorly. CONCLUSIONS: These 3-dimensional reconstructions provide unique insights into male pelvic anatomy. They are a useful teaching tool for investigation and virtual reality modeling of the male pelvis.

Adult↗

Generation and characterization of a human chromosome 9 cosmid library.

A cosmid library has been constructed from the hamster-human hybrid cell line PK-87-9, which contains chromosome 9 as its sole known human component. Ten thousand colonies were produced, of which approximately 200, or 2%, contain human material. Fifty of these 200 were regionally mapped by an Alu-primed PCR product hybridization procedure. These cosmids were localized to all regions of chromosome 9, but were especially concentrated in the distal portion of 9q. The map location derived by the Alu-primed PCR product hybridization procedure was compared to the map location derived by fluorescent in situ hybridization. Assignment of chromosomal location by the two methods was correspondent in all but a few cases. The presumptive presence of HTF islands was investigated for 130 cosmids by digestion with the restriction enzyme NotI. Twenty percent of cosmids contained at least one NotI site. A number of simple sequence repeat polymorphisms identified from the cosmid set were characterized and will provide a link between the genetic and physical maps for this chromosome.

Animals↗

Detection of Chlamydia psittaci in free-ranging koalas (Phascolarctos cinereus): DNA hybridization and immuno-slot blot analyses.

DNA-slot hybridization and immuno-slot blot analyses were compared for the detection of Chlamydia psittaci in crude swab material from free-ranging koalas. Immuno-slot blot analysis detected chlamydiae in 43 out of 68 koalas, with the sensitivity of the assay varying from 52 to 73% depending on the site of infection. Gene probe analysis was also used employing a genus-specific probe pCKO-10 isolated from a koala chlamydial gene library (ocular strain) and a plasmid probe pCKU cloned from a urogenital strain. The sensitivity of these two assays was comparable and they were considerably more efficient than the immuno-slot blot method for the detection of chlamydiae. Comparison of these data with a cell-culture method of detection, previously used with the same samples, demonstrated that gene probe analysis detected more positives than observed with cell culture. However, this appears to reflect more on the condition of the swab material rather than the sensitivity of the method.

Animals↗

Changes in bacterial community during fermentative hydrogen and acid production from organic waste by thermophilic anaerobic microflora.

AIMS: Changes in fermentation pattern during the treatment of organic wastes containing solid materials by thermophilic anaerobic microflora were investigated with respect to product formation and bacterial community structure during hydrogen production. METHODS AND RESULTS: Anaerobic microflora enriched from sludge compost was cultivated using artificial garbage slurry in a continuous flow-stirred tank reactor. Product formation varied depending on pH and hydraulic retention time (HRT) applied. Community analysis by terminal restriction fragment length polymorphism and clone library analysis of polymerase chain reaction-amplified bacterial 16S rDNA indicated that difference in the fermentative product distribution could be caused by different populations of micro-organisms in the microflora. CONCLUSION: Hydrogen fermentation with acetate/butyrate formation was optimized at <1.0 d HRT at pH 5.0 and 6.0. Thermoanaerobacterium thermosaccharolyticum was the dominant hydrogen-producing micro-organism. Conversely, unidentified organisms became dominant after 4.0 d HRT at pH 7.0 and 8.0, where relatively high-solubilization efficiency of solid materials was observed with no production of hydrogen. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report describing product formation in the fermentation of solid organic wastes by a mixed population of micro-organisms. Various fermentation patterns including hydrogen fermentation were characterized and evaluated from engineering and microbial aspects.

Acids↗