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[The primary study on a novel protein binding to the death domain of the death receptor 4].

OBJECTIVE: To clone and identify novel proteins binding to the death domain of the death receptor 4 (DR4). METHODS: The yeast two-hybrid system was used for this study. Automatic sequencing was carried out for DNA sequencing. The sequence homology and the functional domains were analyzed by BLAST and the ScanProsite Tool softwares, respectively. Co-immunoprecipitate method was used to confirm human formyl peptide receptor-like 1 (FPRL1) binding specifically with DR4CD (the cytoplasmic domain of DR4) in HEK293T cells. RESULTS: Two positive clones, named as pADB1 and pADB2, were obtained. BLAST searching showed that the homology of the insert sequence of pADB1 with the mRNA of FPRL1 was 97%. The insert of pADB2 shared no homology with any known peptides in GeneBank. Co-immunoprecipitate analysis further confirmed that FPRL1 could bind to DR4CD in vivo specifically. CONCLUSIONS: FPRL1 may associate with DR4CD in vivo specifically. The functional studies of FPRL1 in signaling pathway mediated by TNF-related apoptosis inducing ligand (TRAIL) are in active progress in our laboratory.

Amino Acid Sequence↗

Managing the tensions between national standardization vs. regional localization of clinical content and templates.

The deployment of sophisticated software tools and electronic health records offers many new opportunities and challenges to support care delivery. One of the key opportunities is to enhance the quality of care with evidence-based medicine (EBM). One of the key challenges is to embed EBM in tools that directly facilitate the process of documentation and care delivery. Since clinicians typically have the option of using free text for most of their documentation, the tools that provide embedded EBM must be at least as efficient as free text. There are many requirements that must be met in order to effectively embed EBM within clinical content tools and enhance both the usability and the actual use of such tools and clinical content: (1) Facilitate the documentation process; (2) Facilitate the care delivery process, e.g. make order entry faster; (3) Contain recommendations that are highly relevant to the clinical context of an encounter; (4) Aid in the capture of discrete coded data. Support for local variation is often key to meeting these objectives and becomes a central factor in helping clinicians shift from unstructured free text, to the use of these tools, which support the delivery of EBM. This document describes the central tension between the objective of national standardization and delivery of EBM and the need for regional localization of clinical content. This tension must be thoughtfully managed to maximize the quality of care delivery and associated workflow practices. The key elements of legitimate local variation that must be recognized in order to achieve these goals are described in this document, and the key principles for managing the tensions between generalization and localization are identified.

Decision Support Systems, Clinical↗

Realistic Virtual Endoscopy of the ventricle system and haptic-based surgical simulator of hydrocefalus treatment.

New methods and software tools for automatic extraction of the ventricle system from magnetic resonance imagery (MRI) data, ventricle part classification, and realistic texturing are proposed to support Virtual Endoscopy (VE). Volume- and surface-based medical atlases are intensively used as templates in the methods. The processed ventricle-related surfaces are then utilized in a haptic-based system, which provides a surgeon with several basic functions simulating "virtual treatment" of hydrocephalus.

Cerebral Ventricles↗

Step-by-step mark-up of medical guideline documents.

The quality of document-centric formalisation of medical guidelines can be improved using a decomposition of the whole process into several explicit steps. We present a methodology and a software tool supporting the step-by-step formalisation process. The knowledge elements can be marked up in the text with increasing level of detail, rearranged into an XML knowledge base and exported into the operational representation. Semi-automated transitions can be specified by means of rules. The approach has been tested in a hypertension application.

Czech Republic↗

Atlas-based recognition of anatomical structures and landmarks and the automatic computation of orthopedic parameters.

OBJECTIVE: This paper describes methods for the automatic atlas-based segmentation of bone structures of the hip, the automatic detection of anatomical point landmarks and the computation of orthopedic parameters to avoid the interactive, time-consuming pre-processing steps for the virtual planning of hip operations. METHODS: Based on the CT data of the Visible Human Data Sets, two three-dimensional atlases of the human pelvis have been built. The atlases consist of labeled CT data sets, 3D surface models of the separated structures and associated anatomical point landmarks. The atlas information is transferred to the patient data by a non-linear gray value-based registration algorithm. A surface-based registration algorithm was developed to detect the anatomical landmarks on the patient's bone structures. Furthermore, a software tool for the automatic computation of orthopedic parameters is presented. Finally, methods for an evaluation of the atlas-based segmentation and the atlas-based landmark detection are explained. RESULTS: A first evaluation of the presented atlas-based segmentation method shows the correct labeling of 98.5% of the bony voxels. The presented landmark detection algorithm enables the precise and reliable localization of orthopedic landmarks. The accuracy of the landmark detection is below 2.5 mm. CONCLUSION: The atlas-based segmentation of bone structures, the atlas-based landmark detection and the automatic computation of orthopedic measures are suitable to essentially reduce the time-consuming user interaction during the pre-processing of the CT data for the virtual three-dimensional planning of hip operations.

Algorithms↗

Analysis of transcriptional regulation of the small leucine rich proteoglycans.

PURPOSE: Small leucine rich proteoglycans (SLRPs) constitute a family of secreted proteoglycans that are important for collagen fibrillogenesis, cellular growth, differentiation, and migration. Ten of the 13 known members of the SLRP gene family are arranged in tandem clusters on human chromosomes 1, 9, and 12. Their syntenic equivalents are on mouse chromosomes 1, 13, and 10, and rat chromosomes 13, 17, and 7. The purpose of this study was to determine whether there is evidence for control elements, which could regulate the expression of these clusters coordinately. METHODS: Promoters were identified using a comparative genomics approach and Genomatix software tools. For each gene a set of human, mouse, and rat orthologous promoters was extracted from genomic sequences. Transcription factor (TF) binding site analysis combined with a literature search was performed using MatInspector and Genomatix' BiblioSphere. Inspection for the presence of interspecies conserved scaffold/matrix attachment regions (S/MARs) was performed using ElDorado annotation lists. DNAseI hypersensitivity assay, chromatin immunoprecipitation (ChIP), and transient transfection experiments were used to validate the results from bioinformatics analysis. RESULTS: Transcription factor binding site analysis combined with a literature search revealed co-citations between several SLRPs and TFs Runx2 and IRF1, indicating that these TFs have potential roles in transcriptional regulation of the SLRP family members. We therefore inspected all of the SLRP promoter sets for matches to IRF factors and Runx factors. Positionally conserved binding sites for the Runt domain TFs were detected in the proximal promoters of chondroadherin (CHAD) and osteomodulin (OMD) genes. Two significant models (two or more transcription factor binding sites arranged in a defined order and orientation within a defined distance range) were derived from these initial promoter sets, the HOX-Runx (homeodomain-Runt domain), and the ETS-FKHD-STAT (erythroblast transformation specific-forkhead-signal transducers and activators of transcription) models. These models were used to scan the genomic sequences of all 13 SLRP genes. The HOX-Runx model was found within the proximal promoter, exon 1, or intron 1 sequences of 11 of the 13 SLRP genes. The ETS-FKHD-STAT model was found in only 5 of these genes. Transient transfections of MG-63 cells and bovine corneal keratocytes with Runx2 isoforms confirmed the relevance of these TFs to expression of several SLRP genes. Distribution of the HOX-Runx and ETS-FKHD-STAT models within 200 kb of genomic sequence on human chromosome 9 and 500 kb sequence on chromosome 12 also were analyzed. Two regions with 3 HOX-Runx matches within a 1,000 bp window were identified on human chromosome 9; one located between OMD and osteoglycin (OGN)/mimecan genes, and the second located upstream of the putative extracellular matrix protein 2 (ECM2) promoter. The intergenic region between OMD and mimecan was shown to coincide with different patterns of DNAse I hypersensitivity sites in MG-63 and U937 cells. ChiP analysis revealed that this region binds Runx2 in U937 cells (mimecan transcript note detectable), but binds Pitx3 in MG-63 cells (expressing high level of mimecan), thereby demonstrating its functional association with mimecan expression. Upon comparing the predictions of S/MARs on the relevant chromosomal context of human chromosomes 9 and 12 and their rodent equivalents, no convincing evidence was found that the tandemly arranged genes build a chromosomal loop. CONCLUSIONS: Twelve of 13 known SLRP genes have at least one HOX-Runx module match in their promoter, exon 1, intron 1, or intergenic region. Although these genes are located in different clusters on different chromosomes, the common HOX-Runx module could be the basis for co-regulated expression.

Animals↗

[The effects of body posture on upper airway in OSAHS patients].

OBJECTIVE: To explore the effects of body posture on upper airway shapes in OSAHS patients. METHOD: Thirty-one male OSAHS patients were included in the study. The fibre endoscopic photos were taken on palate and lingua region upper airway at normal breath at supine with 30 degree neck flexion, supine and right lateral recumbent position, respectively. The cross section area and the dimensions of palate and lingua region upper airway were studied by running image tools software in computer. RESULT: In OSAHS patients, there were obviously difference in the area and arrowy dimension of palate airway among three posture, and so to in area, arrowy and coronary dimension of lingua airway. CONCLUSION: The study suggests that the body posture changes have obviously influence on upper airway, and the influence is the base of apnea increasing at special posture.

Adult↗

Comparative evaluation of phenobarbital-induced CYP3A and CYP2H1 gene expression by quantitative RT-PCR in Bantam, Bantamized White Leghorn and White Leghorn chicks.

The present work was to study induction of cytochrome P450 (CYP)3A and CYP2H1 gene by reverse transcriptase polymerase chain reaction (RT-PCR) and quantitative RTPCR in Bantam, Bantamized White Leghorn and White Leghorn chicks. Out of 18 chicks total 3 from each group (Bantam, Bantamized White Leghorn and White Leghorn) were treated intraperitoneal with phenobarbital at the dose rate of 12 mg/100 g (body weight) while the control group was treated with the saline. Total RNA was extracted from the liver samples using Tri Reagent based method. First strand cDNA was synthesized using one step RT-PCR kit. The PCR was performed and the product was subjected to agarose gel electrophoresis. Quantitative RT-PCR was conducted to quantify gene expression level of CYP3A and CYP2H1 genes. Relative expression ratio of CYP3A and CYP2H1 genes was calculated using relative expression software tool (REST). It was found that CYP3A is up regulated by factor of 1.34, 14.51 and 1.00 in Bantam, Bantamized White Leghorn and White Leghorn chicks, respectively. In Bantam and Bantamized White Leghorn chicks CYP2H1 gene was up regulated by factor 1.50 and 80.87, respectively but down regulated by a factor of 1.97 in White Leghorn chicks. The PCR efficiency ranged from 1.30 to 1.70, 0.86 to 1.70 and 0.91 to 1.58 for CYP3A, CYP2H1 and beta-actin, respectively in Bantam, Bantamized White Leghorn and White Leghorn chicks.

Animals↗

Reification of abstract concepts to improve comprehension using interactive virtual environments and a knowledge-based design: a renal physiology model.

Several abstract concepts in medical education are difficult to teach and comprehend. In order to address this challenge, we have been applying the approach of reification of abstract concepts using interactive virtual environments and a knowledge-based design. Reification is the process of making abstract concepts and events, beyond the realm of direct human experience, concrete and accessible to teachers and learners. Entering virtual worlds and simulations not otherwise easily accessible provides an opportunity to create, study, and evaluate the emergence of knowledge and comprehension from the direct interaction of learners with otherwise complex abstract ideas and principles by bringing them to life. Using a knowledge-based design process and appropriate subject matter experts, knowledge structure methods are applied in order to prioritize, characterize important relationships, and create a concept map that can be integrated into the reified models that are subsequently developed. Applying these principles, our interdisciplinary team has been developing a reified model of the nephron into which important physiologic functions can be integrated and rendered into a three dimensional virtual environment called Flatland, a virtual environments development software tool, within which a learners can interact using off-the-shelf hardware. The nephron model can be driven dynamically by a rules-based artificial intelligence engine, applying the rules and concepts developed in conjunction with the subject matter experts. In the future, the nephron model can be used to interactively demonstrate a number of physiologic principles or a variety of pathological processes that may be difficult to teach and understand. In addition, this approach to reification can be applied to a host of other physiologic and pathological concepts in other systems. These methods will require further evaluation to determine their impact and role in learning.

Comprehension↗

[Application of virtual instrumentation technique in toxicological studies].

Research investigations require frequently direct connection of measuring equipment to the computer. Virtual instrumentation technique considerably facilitates programming of sophisticated acquisition-and-analysis procedures. In standard approach these two steps are performed subsequently with separate software tools. The acquired data are transfered with export / import procedures of particular program to the another one which executes next step of analysis. The described procedure is cumbersome, time consuming and may be potential source of the errors. In 1987 National Instruments Corporation introduced LabVIEW language based on the concept of graphical programming. Contrary to conventional textual languages it allows the researcher to concentrate on the resolved problem and omit all syntactical rules. Programs developed in LabVIEW are called as virtual instruments (VI) and are portable among different computer platforms as PCs, Macintoshes, Sun SPARCstations, Concurrent PowerMAX stations, HP PA/RISK workstations. This flexibility warrants that the programs prepared for one particular platform would be also appropriate to another one. In presented paper basic principles of connection of research equipment to computer systems were described.

Humans↗

Sanitary and phytosanitary measures and food safety: challenges and opportunities for developing countries.

Because of fast-growing demand, export markets can absorb high value added products and offer high returns; for many developing countries export market development is thus a key requirement for rural income generation and rural growth. Although developing countries face increasingly strict sanitary and phytosanitary standards in their export markets, they can maintain and improve market access--and improve domestic food safety and agricultural productivity--by adopting a strategic approach to food safety, agricultural health and trade. High-income countries should increase development flows to help developing countries build the capacity to plan and execute the necessary strategies. The first proposal in this paper is to make two existing sets of guidelines widely available to interested parties, in particular through the World Bank and the World Organisation for Animal Health (OIE). The first covers the broad process of problem assessment, strategy development and action plan formulation; the second set deals with institutional analysis and training of staff of the official sanitary control services. The second proposal is that interested countries and donors should speed up the ongoing development of guidelines, computer software tools and training material to help countries quantify the importance and impact of food safety issues. The focus here is on a 'multipurpose agricultural data analysis and modelization system'. The third proposal is to carry out a case study to help demonstrate that a number of animal health issues related to food safety should be treated as relating to 'global public goods' and thus require intervention on a global scale. Possible candidates are foot and mouth disease and highly pathogenic avian influenza.

Agriculture↗

Development of a system supporting patient supervision and treatment in contemporary home-care: status report.

The emerging amalgamation of informatics, communication technologies, and entertainment electronics in the field of Biomedical Technology combined to, first, the increase in length of the mean life expectancy, and, second, the hospitalization cost avalanche, will facilitate gradually the development of a new Hi-Tec home-care environment. We have developed a home-computer based system, addressing crucial aspects of the development of contemporary home-care that comprises of: First, the employment of low-cost commercially available components, supporting home-care patient's well-being observation, including eventually vital-signs monitoring. Second, software means for the processing, the evaluation, and the targeted transmission of the acquired health-data. Third, software tools for the planning, the documentation, and the management of the corresponding home-care case. The present paper constitutes a progress report of the ongoing development efforts.

Greece↗

Management of data quality--development of a computer-mediated guideline.

Appropriate data quality is a crucial issue in the use of electronically available health data. As source data verification (SDV) and feedback are two standard procedures for measuring and improving data quality it would be worthwhile to adapt these procedures to a current level of quality in order to reduce costs in data management. This project aims to develop a guideline for the management of data quality with special emphasis on this adaptation against the backdrop of research networks in Germany, which operate registers and conduct epidemiological studies. The first step in guideline development was a thorough literature review. The literature offers many measurements as candidates for quality indicators, however, systematic assessments and concepts of SDV and feedback are missing. We assigned possible quality indicators to the levels plausibility, organization, and trueness. Each indicator must be operationally defined to allow automatical calculation. The SDV sample size calculation leads to lower numbers for sites providing data of good quality and larger numbers for sites with poor data quality. The guideline's implementation in a software tool combines two cycles, one for the adaptation of recommendations to a given study/register, the other for the improvement of data quality in a PDCA-like approach. The recommendations will address needs common to medical documentation in daily health care, clinical, epidemiological, and observational studies as well as in surveillance data bases and registers. Further work will have to supplement other aspects of data management.

Feedback↗

Process frame instances for integrating strategic, tactical and operational information management in hospitals.

An approach to reduce the complexity of information management is to distinguish it into strategic, tactical and operational management with each of the levels using its own software tools. In practice, the management levels are tightly connected and interact closely. The most evident information that has to be interchanged between the management levels is the information about finished, cancelled, running and planned activities or projects, respectively. We claim that the levels of information management should share information about the work done, and propose their integration by means of a network of so-called process frame instances. Process frame instances hold information about the activities of different information management levels in a structured and reusable way.

Germany↗

The CAREPLAN knowledge base. A prototype expert system for postpartum nursing care.

With the growth of scientific knowledge in the health care disciplines, it has become increasingly difficult for practicing health care professionals to store and manipulate the information required to make clinical decisions. Where the decision making process can be defined and validated, expert systems will be able to assist beginning professionals to learn appropriate patterns of decision making. This article discusses the rationale for utilization of expert systems in a nursing environment. A prototype expert system called CAREPLAN, developed for use in an obstetrical environment, was built using Personal Consultant Plus, a software tool based on the LISP language. The project demonstrates that it is feasible to develop and validate an expert system for a specialized clinical environment in a relatively short period of time in comparison to traditional development methods. Graphics were used to enhance textual information and to increase user appeal. Strategies for future implementation and evaluation are outlined.

Expert Systems↗

A microcomputer-based system for mapping microvascular networks.

A new method has been developed for mapping microvascular networks using an IBM-AT microcomputer and a video-microscope. After recording a vascular network on video tape, it can be reconstructed off-line using frame by frame analysis. A software tool, developed for mapping and editing networks, is used to prepare a montage of the network using a video cursor and mouse. Vessel lengths and diameters can also be measured from the video image using the same methodology. When the analysis is completed, the vessel network, together with a tabulation of lengths and diameters of individual vessels, can be displayed on a TV monitor or reduced to hard copy. This system provides a simple method for quantitative studies of arteriolar, venular and capillary networks.

Animals↗

Knowledge-based automation.

Future technologic advances in microcomputer hardware will allow us to build complex interactive information systems that go far beyond conventional laboratory management functions to address the needs of laboratorians as well as physicians in patient care activities. These systems will use a "local-area network to transmit not only text but also images to workstations throughout a hospital. Unlike current systems driven from a central computer, future systems will decentralize much of the memory and processing to individual workstations." The expansion of software tools for modeling the decision-making process coupled with the development and testing of useful systems in relatively narrow problem domains will help the laboratory construct the necessary knowledge bases for future applications. Such systems will present complex medical data in a useful, informative manner, leading to a more rapid, consistent, and, it is hoped, cost effective decision making process. Utilizing these techniques, laboratory medicine can play a crucial role in fostering the appropriate and logical use of the laboratory.

Artificial Intelligence↗

Computerized medical records--new opportunities.

The new generation of computer hardware and software is providing many new opportunities for physicians to use computerized medical records in their practices. A substantial number of new commercial systems have been introduced within the past few years, and many more will likely become available soon. In addition, there are opportunities for physicians to create their own customized systems using new software tools now available.

Forms and Records Control↗