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PubMed2004

[Application of the WHO chronic respiratory diseases programme in Sub-Saharian Africa: problems in Senegal].

INTRODUCTION: To prevent and control chronic respiratory diseases, the WHO has outlined a programme to be applied in all the countries. In Sub-Saharan countries like Senegal, its application faces many barriers. METHODS: This work is a detailed analysis of the main areas of the programme based on the socio-economic, cultural and medical realities present in Sub-Saharan Africa countries, and particularly in Senegal. RESULTS: There is a lack of political engagement resulting from the precarious socio-economical situation. The demand for care is impaired because of the prevalence of illiteracy and the practice of traditional healing methods which is the first recourse for patients. The inaccessibility and lack of adequate health structures, technical equipment and qualified medical staff, and the high cost of medications for the majority of the population is the cause of this weakness of the healthcare system. These international recommendations are both not compatible with the local realities and not known to the majority of health providers. CONCLUSIONS: The mobilisation of international and national human and financial resources, the involvement of community-based structures, the adaptation and revision of the recommendations, the introduction of medications advocated by the Bamako Initiative, the training of health providers, the adaptation of regional and continental initiatives against tobacco and the creation of smoking cessation centres are needed if this chronic respiratory diseases programme is to be efficiently implemented.

Asthma↗

PubMed2004

TOPS: an enhanced database of protein structural topology.

The TOPS database holds topological descriptions of protein structures. These compact and highly abstract descriptions reduce the protein fold to a sequence of Secondary Structure Elements (SSEs) and three sets of pairwise relationships between them, hydrogen bonds relating parallel and anti- parallel beta strands, spatial adjacencies relating neighbouring SSEs, and the chiralities of selected supersecondary structures, including connections in betaalphabeta units and between parallel alpha helices. The database is used as a resource for visualizing folding topologies, fast topological pattern searching and structure comparison. Here, significant enhancements to the TOPS database are described. The topological description has been enhanced to include packing relationships between helices, which significantly improves the description of protein folds with little beta strand content. Further, the topological description has been annotated with sequence information. The query interfaces to the database have been improved and the new version can be found at http://www.tops.leeds.ac.uk/.

Animals↗

PubMed2005

PDB-Ligand: a ligand database based on PDB for the automated and customized classification of ligand-binding structures.

PDB-Ligand (http://www.idrtech.com/PDB-Ligand/) is a three-dimensional structure database of small molecular ligands that are bound to larger biomolecules deposited in the Protein Data Bank (PDB). It is also a database tool that allows one to browse, classify, superimpose and visualize these structures. As of May 2004, there are about 4870 types of small molecular ligands, experimentally determined as a complex with protein or DNA in the PDB. The proteins that a given ligand binds are often homologous and present the same binding structure to the ligand. However, there are also many instances wherein a given ligand binds to two or more unrelated proteins, or to the same or homologous protein in different binding environments. PDB-Ligand serves as an interactive structural analysis and clustering tool for all the ligand-binding structures in the PDB. PDB-Ligand also provides an easier way to obtain a number of different structure alignments of many related ligand-binding structures based on a simple and flexible ligand clustering method. PDB-Ligand will be a good resource for both a better interpretation of ligand-binding structures and the development of better scoring functions to be used in many drug discovery applications.

Adenosine Triphosphate↗

PubMed2002

ASTRAL compendium enhancements.

The ASTRAL compendium provides several databases and tools to aid in the analysis of protein structures, particularly through the use of their sequences. It is partially derived from the SCOP database of protein domains, and it includes sequences for each domain as well as other resources useful for studying these sequences and domain structures. Several major improvements have been made to the ASTRAL compendium since its initial release 2 years ago. The number of protein domain sequences included has doubled from 15 190 to 30 867, and additional databases have been added. The Rapid Access Format (RAF) database contains manually curated mappings linking the biological amino acid sequences described in the SEQRES records of PDB entries to the amino acid sequences structurally observed (provided in the ATOM records) in a format designed for rapid access by automated tools. This information is used to derive sequences for protein domains in the SCOP database. In cases where a SCOP domain spans several protein chains, all of which can be traced back to a single genetic source, a 'genetic domain' sequence is created by concatenating the sequences of each chain in the order found in the original gene sequence. Both the original-style library of SCOP sequences and a new library including genetic domain sequences are available. Selected representative subsets of each of these libraries, based on multiple criteria and degrees of similarity, are also included. ASTRAL may be accessed at http://astral.stanford.edu/.

Amino Acid Sequence↗

PubMed2002

Multiple sclerosis in Stockholm County. A pilot study of utilization of health-care resources, patient satisfaction with care and impact on family caregivers.

Multiple sclerosis (MS) is a progressive, incurable neurological disease with a large impact on the person/people with MS (PwMS), the family of the PwMS, medical resources and the community. We have explored the feasibility of calculating utilization of health-care resources within Stockholm County and evaluated methods for interviewing PwMS and family caregivers in their homes. Home visits were made to 26 PwMS with different levels of disability, both in ordinary and sheltered living. Questionnaires assessing patient satisfaction, the use of technical aids and home adaptations, help from municipal and family caregivers, and health-related quality of life were administered in the form of structured interviews. Utilization of health-care resources was evaluated with the help of an available computerized register. The study shows that the chosen methods are feasible for PwMS, irrespective of level of disability or form of living. They are well accepted by both PwMS and family caregivers and need only minor modifications in order to be suitable for a population-based study.

Adult↗

PubMed2004

The Digital Cytocochleogram.

The Mouse Cochlea Database (MCD) is a collection of resources that include digital images and bibliographic information on the mouse cochlea and is available at: http://mousecochlea.ccgb.umn.edu. The purpose of this communication is to report on the development of one MCD resource: the Digital Cytocochleogram. A cytocochleogram is a graphic representation of the anatomical state of the hair cells along the complete width and length of the organ of Corti. The Digital Cytocochleogram provides Internet users with a complete collection of digital images of one or more surface preparations of the mouse organ of Corti from which morphometric information can be obtained. By moving a mouse driven, screen cursor over a digital image, the location and approximate frequency region of the anatomical structure is displayed. Users can also measure the straight-line distance between any two structures on the image. The Digital Cytocochleogram resource uses two software programs, the Coordinate Finder and Viewer, which are written as CGI scripts. The Coordinate Finder program maps each digital image to an X,Y coordinate system. The total length of the organ of Corti from all tissue segments is computed using an arc-distance approximation formula, with the lateral border of the inner pillar cell headplates serving as a trace line or reference location. After all of the digital images of the tissue segments are mapped, they are placed on the MCD Website where users can use the Viewer program to view and morphometrically assess structures using a web browser. A single, complete surface preparation from a normal mouse is presently available on the MCD website. As the MCD grows, additional images of surface preparations at different magnifications from normal, mutant, and experimentally altered mouse cochleas will become available.

Animals↗

PubMed2002

Effect of centre-, patient- and procedure-related factors on intensive care resource utilisation after cardiac surgery.

OBJECTIVE: To determine associations between intensive care resource utilisation and centre-, patient- and procedure-related factors. DESIGN: Prospective multicentre cohort study. SETTING: Twenty-one European intensive care units. PATIENTS AND PARTICIPANTS: Four thousand four hundred adult patients who had undergone cardiac or thoracic aortic surgery in 21 centres. INTERVENTION: None (observational study). MEASUREMENTS AND RESULTS: Primary outcomes were duration of artificial ventilation and intensive care unit (ICU) length of stay. Exposures were centres and patient- and procedure-related factors. Both outcomes varied fourfold among centres. Median time to extubation varied from 5 to 19 h and ICU length of stay varied from 22 to 91 h. Cox regression analysis was performed to adjust risks of prolonged ventilation and ICU length of stay for patient-, procedure- and centre-related factors. Patient- and procedure-related factors were the main risk factors among individual patients, accounting for nearly two thirds of the risk of prolonged ventilation and ICU length of stay. Centre-related variation accounted for the remaining risk. CONCLUSIONS: In European ICUs resource utilisation is highly variable after cardiac surgery. Up to two thirds more patients could be treated with current ICU resources if the most efficient strategies and structures were applied across all centres.

Adolescent↗

PubMed1997

Event-related-potential (ERP) reflections of mental resources: a review and synthesis.

In this review studies are evaluated that have utilized middle-latency and late components of the event-related potential (ERP) as indices of the activation of processing resources. Processing resources are defined as energetical systems that modulate cognitive processes or data processing systems. An essential element of the resource conceptualization is the idea that processing structures receive not only information input but also input from these energetical systems. It is argued further that the principal role of these systems is to provide the 'gain' for the data processing systems. In reviewing these studies special attention is paid to factors affecting the amplitude of ERP components in single- and dual-task studies, and to the inferences that can be drawn about which particular types of processing resources are reflected in these changes in component amplitudes. Finally, a working model is presented relating middle-latency and late ERP components to specific perceptual, perceptual-central and central processing resources.

Attention↗

PubMed1998

Implications of resource-ratio theory for oral microbial ecology.

The ability to compete for the limited nutrients available to the microorganisms of dental plaque is a strong ecological determinant of the structure of the subgingival ecosystem. This paper introduces a new concept from the field of ecology, resource-ratio theory, and applies it to the dynamics of microbial dental plaque with emphasis on the putative periodontal pathogens. Resource-ratio theory is a mechanistic theory of resource competition that utilizes pairs of growth-limiting nutrients in a stoichiometric fashion to predict zones of competitive dominance, exclusion, and coexistence for organisms competing for these resources. Once these resource pairs are identified for plaque organisms, resource-ratio theory may provide predictions of changes in the microbial community structure of plaque based on directional changes in their resource supply ratios.

Bacteria↗

PubMed2006

An event-related fMRI investigation of phonological-lexical competition.

This study explored the neural correlates of phonological-lexical competition and frequency on word recognition. An event-related fMRI experiment was conducted using an auditory lexical decision task in which word and nonword stimuli varied in terms of neighborhood density (high and low). Word stimuli also varied in terms of frequency (high and low). Behavioral results were similar to those of Luce and Pisoni [Luce, P. A., & Pisoni, D. B. (1998). Recognizing spoken words: The neighborhood activation model. Ear and Hearing, 19, 1-36], with the reaction time data showing a main effect of word frequency and density as well as a significant interaction effect between these two factors. fMRI results revealed an overall greater neural response for high-density compared to low-density words in the left supramarginal gyrus, consistent with the view that there are greater demands on phonological processing under conditions of increased phonological-lexical competition. The comparison between high and low frequency words revealed greater activation for high frequency words in both anterior and posterior left middle temporal gyrus. A significant interaction between density and frequency was found in lateral and medial frontal structures. This frontal activation may reflect the greater computational resources required in integrating frequency and density information in order to access a word. Overall, these findings demonstrate the sensitivity of neural structures to different properties of the lexicon.

Acoustic Stimulation↗

PubMed2004

Early prediction of drug metabolism and toxicity: systems biology approach and modeling.

Many of the drug candidates that fail in clinical trials are withdrawn because of unforeseen effects of human metabolism, such as toxicity and unfavorable pharmacokinetic profiles. Early pre-clinical elimination of such compounds is important but not yet possible. An ideal system would enable researchers to make a confident elimination decision based purely on the structure of a new compound, and incorporate and use multiple pre-clinical experimental data to support such a decision. Currently available resources can be split into three categories: (i). structure-activity relationships (SAR) computational models based on compound structure; (ii). 'pattern' databases of tissue or organ response to drugs, compiled from high-throughput experiments; and (iii). 'systems biology' databases of metabolic pathways, genes and regulatory networks. In this review, we outline the advantages and drawbacks of each of these systems and suggest directions for their integration.

Animals↗

PubMed2006

SuperHapten: a comprehensive database for small immunogenic compounds.

The immune system protects organisms from foreign proteins, peptide epitopes and a multitude of chemical compounds. Among these, haptens are small molecules, eliciting an immune response when conjugated with carrier molecules. Known haptens are xenobiotics or natural compounds, which can induce a number of autoimmune diseases like contact dermatitis or asthma. Furthermore, haptens are utilized in the development of biosensors, immunomodulators and new vaccines. Although hapten-induced allergies account for 6-10% of all adverse drug effects, the understanding of the correlation between structural and haptenic properties is rather fragmentary. We have developed a manually curated hapten database, SuperHapten, integrating information from literature and web resources. The current version of the database compiles 2D/3D structures, physicochemical properties and references for about 7500 haptens and 25,000 synonyms. The commercial availability is documented for about 6300 haptens and 450 related antibodies, enabling experimental approaches on cross-reactivity. The haptens are classified regarding their origin: pesticides, herbicides, insecticides, drugs, natural compounds, etc. Queries allow identification of haptens and associated antibodies according to functional class, carrier protein, chemical scaffold, composition or structural similarity. SuperHapten is available online at http://bioinformatics.charite.de/superhapten.

Cross Reactions↗

PubMed2001

A Short Copper-Copper Distance in a (µ-1,2-Peroxo)dicopper(II) Complex Having a 1,8-Naphthyridine Unit as an Additional Bridge This work was supported by grants from the National Science Foundation and the National Institutes of Health. We thank A. M. Barrios for help in acquiring resonance Raman spectra. X-ray absorption spectroscopic data were measured at SSRL. SSRL is funded by the Department of Energy, Office of Basic Energy Science. The SSRL Structural Molecular Biology Program is supported by the National Institute of Health, National Center for Research Resources, Biomedical Technology Program, and by the Department of Energy, Office of Biological and Environmental Research.

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Journal Article↗

PubMed1994

The ageing of elderly people.

OBJECTIVE: To assess the performance of activities of daily living, social resources and incidence of dementia in a cohort of elderly Chinese. DESIGN: This was a longitudinal study which measured changes in a five-year interval. SETTING: The study was conducted in the Henderson district of Singapore at the subjects' homes and at a day centre. SUBJECTS: A random sample of elderly Chinese was selected in 1985 from the electoral roll of the Henderson constituency and reassessed after 5 years. OUTCOME MEASURES: A semi-structured questionnaire adapted from the Older American Resources and Services, and the computerised mental state programme, GMS-AGECAT. RESULTS: There was no apparent change in social resources after 5 years and the majority of the elderly (80.3%) were still living with their families. On activities of daily living, there was a significant decline especially after the age of 75. The incidence of dementia was 2.01%--the rate of Alzheimer's disease was 0.67% and multi-infarct dementia 1.34%. CONCLUSION: The change in performance of activities of daily living after the age of 75 and the low incidence of dementia were similar to studies in Europe and the United States.

Activities of Daily Living↗

PubMed2003

Bioinformatics Resources for In Silico Proteome Analysis.

In the growing field of proteomics, tools for the in silico analysis of proteins and even of whole proteomes are of crucial importance to make best use of the accumulating amount of data. To utilise this data for healthcare and drug development, first the characteristics of proteomes of entire species-mainly the human-have to be understood, before secondly differentiation between individuals can be surveyed. Specialised databases about nucleic acid sequences, protein sequences, protein tertiary structure, genome analysis, and proteome analysis represent useful resources for analysis, characterisation, and classification of protein sequences. Different from most proteomics tools focusing on similarity searches, structure analysis and prediction, detection of specific regions, alignments, data mining, 2D PAGE analysis, or protein modelling, respectively, comprehensive databases like the proteome analysis database benefit from the information stored in different databases and make use of different protein analysis tools to provide computational analysis of whole proteomes.

Journal Article↗

PubMed2006

Integrating protein structures and precomputed genealogies in the Magnum database: examples with cellular retinoid binding proteins.

BACKGROUND: When accurate models for the divergent evolution of protein sequences are integrated with complementary biological information, such as folded protein structures, analyses of the combined data often lead to new hypotheses about molecular physiology. This represents an excellent example of how bioinformatics can be used to guide experimental research. However, progress in this direction has been slowed by the lack of a publicly available resource suitable for general use. RESULTS: The precomputed Magnum database offers a solution to this problem for ca. 1,800 full-length protein families with at least one crystal structure. The Magnum deliverables include 1) multiple sequence alignments, 2) mapping of alignment sites to crystal structure sites, 3) phylogenetic trees, 4) inferred ancestral sequences at internal tree nodes, and 5) amino acid replacements along tree branches. Comprehensive evaluations revealed that the automated procedures used to construct Magnum produced accurate models of how proteins divergently evolve, or genealogies, and correctly integrated these with the structural data. To demonstrate Magnum's capabilities, we asked for amino acid replacements requiring three nucleotide substitutions, located at internal protein structure sites, and occurring on short phylogenetic tree branches. In the cellular retinoid binding protein family a site that potentially modulates ligand binding affinity was discovered. Recruitment of cellular retinol binding protein to function as a lens crystallin in the diurnal gecko afforded another opportunity to showcase the predictive value of a browsable database containing branch replacement patterns integrated with protein structures. CONCLUSION: We integrated two areas of protein science, evolution and structure, on a large scale and created a precomputed database, known as Magnum, which is the first freely available resource of its kind. Magnum provides evolutionary and structural bioinformatics resources that are useful for identifying experimentally testable hypotheses about the molecular basis of protein behaviors and functions, as illustrated with the examples from the cellular retinoid binding proteins.

Amino Acid Sequence↗

PubMed2003

Social support and quality of life.

Social support is a broad term, which includes the supportive ways that different people behave in the social environment. Structural measures of the environment deal with the mere existence of social relationships. Functional measures refer to the resources that people within an individual's social network provide. Structural support shows a linear relation to quality of life; the functional aspects of support demonstrate the stress-buffering hypothesis. One of the main focuses of this article is to help researchers determine what aspects of social relationships or what types of support need to be measured and to consider the mechanisms by which support might influence quality of life. Also addressed is how to translate the correlational research on social support and quality of life into the field of support interventions, taking into account individual and situational differences.

Adaptation, Psychological↗

PubMed1991

Long-term care and federal policy.

A major deficiency of national health care policy is the lack of a structured and comprehensive system of long-term care. A review of existing federal programs reveals that substantial resources are being expended to care for the elderly. Program structures and requirements, however, are frequently skewed toward institutional care to the exclusion of more appropriate home- and community-based services. A recent federal study highlighted the dimensions of the long-term-care problem and proposed a compelling remedy, but a consensus continues to elude policymakers, and the prospects for fundamental reform are uncertain.

Aged↗