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PubMed1995

Procedures for the detection of chemically induced aneuploidy: recommendations of a UK Environmental Mutagen Society working group.

The development of assays to detect numerical chromosome aberrations has not kept pace with that for assays used to detect other genotoxicity endpoints such as gene mutations and structural chromosome aberrations, even though the importance of aneuploidy in relation to heritable defects in germ cells and to carcinogenesis in somatic cells is acknowledged. Regulatory bodies at present have no formal requirements concerning aneuploidy detection and decisions are made on a case-by-case basis. The aim of this review is to indicate which assays are available for the detection of chemically induced aneuploidy and what aspects should be taken into account when testing for chemically induced aneuploidy using in vitro, in vivo somatic and in vivo germ cell assays without dictating exact protocols. Our recommendations concentrate on systems that, to date, have been most extensively used and we indicate where future developments may lie. It is important that the currently available and future tests for chemically induced aneuploidy should be adequately validated before being implemented into screening strategies or regulatory guidelines. This requirement has not yet been met and is confounded by the lack of a well defined reference database of animal and human chemical aneugens.

Aneuploidy↗

PubMed2006

RegulonDB (version 5.0): Escherichia coli K-12 transcriptional regulatory network, operon organization, and growth conditions.

RegulonDB is the internationally recognized reference database of Escherichia coli K-12 offering curated knowledge of the regulatory network and operon organization. It is currently the largest electronically-encoded database of the regulatory network of any free-living organism. We present here the recently launched RegulonDB version 5.0 radically different in content, interface design and capabilities. Continuous curation of original scientific literature provides the evidence behind every single object and feature. This knowledge is complemented with comprehensive computational predictions across the complete genome. Literature-based and predicted data are clearly distinguished in the database. Starting with this version, RegulonDB public releases are synchronized with those of EcoCyc since our curation supports both databases. The complex biology of regulation is simplified in a navigation scheme based on three major streams: genes, operons and regulons. Regulatory knowledge is directly available in every navigation step. Displays combine graphic and textual information and are organized allowing different levels of detail and biological context. This knowledge is the backbone of an integrated system for the graphic display of the network, graphic and tabular microarray comparisons with curated and predicted objects, as well as predictions across bacterial genomes, and predicted networks of functionally related gene products. Access RegulonDB at http://regulondb.ccg.unam.mx.

Databases, Genetic↗

PubMed2005

Dose-reducing H2 receptor antagonists in the presence of low glomerular filtration rate: a systematic review of the evidence.

BACKGROUND: While it is recommended that H2 receptor antagonists (H2RAs) be dose reduced in the presence of low glomerular filtration rate (GFR), in practice such adjustments often do not occur. We reviewed the evidence for this recommendation. METHODS: We searched multiple medical reference databases for relevant cohort studies and randomized clinical trials. Studies that enrolled five or more participants with low GFR who also received at least one unadjusted dose of an H2RA, and who were compared with controls were included. Data were abstracted on study and participant characteristics and drug-related adverse effects. Pharmacokinetic measures were pooled using meta-analysis. RESULTS: A total of 22 articles were included, comprising 19 unique cohort studies. With declining GFR, there was a significant increase in the area under the curve (AUC) and elimination half-life (t(1/2)) of the serum drug concentration of H2RAs (P < 0.001). Compared with a GFR >80 ml/min/1.73 m2, drug AUC increased by 200% when the GFR was 30 ml/min/1.73 m2, and by 300% when the GFR was 20 ml/min/1.73 m2. In hospitalized patients with low GFR, reducing the interval dose of intravenous H2RA was associated with fewer adverse reactions. The gastro-protective effects of H2RAs were similar with reduced and unadjusted doses. CONCLUSIONS: Reducing the dose of H2RAs in persons with low GFR will decrease drug expenditure and may prevent adverse events, without a change in efficacy. Quality assurance programmes, which improve deficiencies in H2RAs prescribing, appear justified.

Dose-Response Relationship, Drug↗

PubMed2006

Effects of bisphosphonates on bone loss in the first year after renal transplantation--a meta-analysis of randomized controlled trials.

BACKGROUND: Bone loss remains a serious problem after kidney transplantation and is most pronounced during the first months after engraftment. Bisphosphonates are frequently used to treat post-transplant osteodystrophy, but data of large randomized controlled trials (RCTs) are missing. METHODS: We, therefore, conducted this systematic review of the literature, searching electronic databases, reference lists and abstracts from scientific meetings to identify RCTs in all languages. The primary outcome assessed was the change in bone mineral density (BMD) during the early post-transplantation period. Based on the mean BMD change presented in the identified publications, the authors were asked for the individual BMD results of all randomized patients, determined at lumbar spine and femoral neck before and after bisphosphonate therapy. Data were pooled for summary estimates by using weighted mean differences of absolute change in BMD. An analysis of covariance was performed, adjusted for individual baseline values, treatment arm and individual trial. RESULTS: Five studies involving 180 participants were included in our meta-analysis. Treatment with bisphosphonates showed a substantial effect in preventing post-transplant osteodystrophy. BMD decline at the lumbar spine within 6-12 months after transplantation was significantly reduced by 0.06 g/cm(2) in patients treated with bisphosphonates (95% CI 0.05-0.08 g/cm(2)). At the femoral neck, the loss of BMD was reduced by 0.05 g/cm(2) during this period (95% CI 0.0-0.11 g/cm(2)), reaching just non-statistical significance. This benefit of bone loss prevention could be reached without major side effects. CONCLUSION: Bisphosphonates are effective in preventing bone loss in the early post-transplant period.

Bone Density↗

PubMed2005

Outcome following onset of juvenile idiopathic inflammatory arthritis: II. predictors of outcome in juvenile arthritis.

OBJECTIVE: To assess the relative contributions of demographic, clinical and laboratory variables in predicting outcome in juvenile idiopathic inflammatory arthritis (JIA), based on a review of the existing literature. METHODS: Electronic reference database searches for the previous 10 yr were conducted and studies examining the role of major potential predictors of main outcomes were identified. Where possible, subjects were grouped by JIA disease subtype. In addition to demographic variables, the following disease-related predictors were assessed: nature of joint involvement, acute-phase response, and presence of autoantibodies. These were then analysed for three main outcomes of interest: remission as assessed by disease activity; functional impairment; and structural damage as assessed by radiological joint erosions. RESULTS: In general, female gender, polyarticular and symmetrical joint involvement, elevated inflammatory markers and rheumatoid factor positivity were the most consistent predictors of a poor outcome, although the studies were frequently inconsistent in both the direction and the magnitude of the effects. CONCLUSIONS: These data are too variable to accurately identify those predictors associated with poor outcome following the onset of JIA. Although some of this variation may be the result of true differences between study populations, the vast majority of inconsistencies are explainable by the absence of standardized classification systems, outcome definitions, therapeutic approach and research tools. More comprehensive prospective evaluation is required before robust prediction models can be generated.

Acute-Phase Reaction↗

PubMed2004

Radon mapping in south Tyrol: comparison between two different procedures.

In this paper two different procedures for radon mapping have been compared on the same database referring to indoor radon records of South Tyrol. The first procedure is based on descriptive statistics applied to administrative units while the second one implies a more complicated statistical analysis applied to a regular grid: it involves floor level normalization of radon data, filling and smoothing algorithms for the territory cells.

Air Pollutants, Radioactive↗

PubMed1997

Testing linkage equilibrium on allelic data between VNTR loci.

We extend Geisser and Johnson's methods and propose simple tests for linkage equilibrium of fragment lengths between VNTR loci. The tests are shown to have asymptomatically normal or chi-square null distributions. They are applied to the reference databases of Asian populations, including the Hong Kong Chinese, Singapore Chinese, Singapore Malays, and Singapore Indians. It seems that there is little linkage disequilibrium in the data.

Alleles↗

PubMed1995

Prediction of movement using bispectral electroencephalographic analysis during propofol/alfentanil or isoflurane/alfentanil anesthesia.

Conventional electroencephalographic (EEG) analysis techniques do not use the phase information from the Fourier analysis. This study used a new technique of EEG analysis, bispectral analysis, which measures interfrequency phase relationships in the EEG. Using a reference database, and a process of multivariate discriminant analysis, we developed a univariate bispectral variable, the bispectral index (BIS). This study was designed to test the efficacy of BIS in predicting movement to incision during either an isoflurane/alfentanil anesthetic or a propofol/alfentanil anesthetic technique. Fifty consenting patients were randomized to two groups; one received isoflurane/alfentanil and the other, propofol/alfentanil for anesthesia. EEG was recorded using a microcomputer system and the data were analyzed off-line. Hemodynamic variables were also recorded. After skin incision, each patient was observed carefully for 2 min to detect purposeful movement. A significant difference was found between the BIS values for movers versus nonmovers within each of the two treatment groups (P < or = 0.002). However, isoflurane/alfentanil nonmovers could not be distinguished from propofol/alfentanil movers (P < or = 0.180), suggesting a treatment group effect independent of response classification. Preincision hemodynamic variables did not predict patient movement in response to skin incision. These findings suggest the possibility that different anesthetics have different effects on BIS, and thus BIS may not be independent of the anesthetic. Interfrequency phase coupling, a nonlinear feature of the EEG which is measured with bispectral analysis, may contain clinically useful information for the assessment of anesthetic adequacy. In this study, BIS was a better predictor of patient response than other currently available variables including hemodynamic status.

Adult↗

PubMedDate not supplied

Gender differences in joint biomechanics during walking: normative study in young adults.

The effect of gender on specific joint biomechanics during gait has been largely unexplored. Given the perceived, subjective, and temporal differences in walking between genders, we hypothesized that quantitative analysis would reveal specific gender differences in joint biomechanics as well. Sagittal kinematic (joint motion) and kinetic (joint torque and power) data from the lower limbs during walking were collected and analyzed in 99 young adult subjects (49 females), aged 20 to 40 years, using an optoelectronic motion analysis and force platform system. Kinetic data were normalized for both height and weight. Female and male data were compared graphically and statistically to assess differences in all major peak joint kinematic and kinetic values. Females had significantly greater hip flexion and less knee extension before initial contact, greater knee flexion moment in pre-swing, and greater peak mechanical joint power absorption at the knee in pre-swing (P < 0.0019 for each parameter). Other differences were noted (P < 0.05) that were not statistically significant when accounting for multiple comparisons. These gender differences may provide new insights into walking dynamics and may be important for both clinical and research studies in motivating the development of separate biomechanical reference databases for males and females.

Absorption↗

PubMed2003

Advice nursing practice: on the quality of the evidence.

OBJECTIVE: The primary objective was to review the research regarding advice nursing practice to determine the content areas investigated and the quality of the evidence. METHODS: A systematic review of advice nursing research was done in electronic databases, reference lists, and the literature identified by experts (N = 527). After deletion of duplicates and clinical and theoretical articles, full text reviews were done on 62 studies. RESULTS: Eight thematic content areas were identified: delivery and continuity of care to populations, appropriateness of advice given, patient/provider satisfaction, disposition/utilization after calls, reason for calling, cost analysis, process of decision-making, and documentation. The most frequently investigated subject was delivery/continuity of care (n = 16). IMPLICATIONS: For certain chronic disease populations, interventions using telephone advice for social support, education, and symptom management improve clinical outcomes. Availability and use of protocols and guidelines do not guarantee standardized care or ensure that appropriate advice will be given. Consumer satisfaction with advice nursing is high, and appears to be related to the intervention component of the nursing process. The priority for future research should be given to those studies that describe the character and suitable dose of the nursing intervention that is advice nursing.

Chronic Disease↗

PubMed2001

Multidisciplinary biopsychosocial rehabilitation for subacute low back pain in working-age adults: a systematic review within the framework of the Cochrane Collaboration Back Review Group.

STUDY DESIGN: A systematic review of randomized controlled trials was performed. OBJECTIVE: To evaluate the effectiveness of multidisciplinary biopsychosocial rehabilitation for subacute low back pain among working-age adults. SUMMARY OF BACKGROUND DATA: Multidisciplinary biopsychosocial rehabilitation programs are widely applied for patients with chronic low back pain. The multidisciplinary biopsychosocial approach for prolonged low back pain could be considered to prevent chronicity. Work site visits and a close relationship with occupational health care might produce results in terms of patients working ability. METHODS: Reviewed randomized controlled trials as well as controlled trials were identified from electronic bibliographic databases, reference checking, and consultation with experts in the rehabilitation field. Four blinded reviewers selected the trials. Two rehabilitation specialists evaluated the clinical relevance. Two other blinded reviewers extracted the data and assessed the main results along with the methodologic quality of the studies. A qualitative analysis was performed to evaluate the level evidence. RESULTS: Of 1808 references, only 2 relevant studies were included. Both were considered to be methodologically low-quality randomized controlled trials. The clinical relevance of the studies was sufficient. The level of scientific evidence was moderate, showing that multidisciplinary rehabilitation involving work site visit or more comprehensive occupational health care intervention helps patients return to work faster, makes sick leaves less, and alleviates subjective disability. CONCLUSIONS: There is moderate evidence showing that multidisciplinary rehabilitation for subacute low back pain is effective, and that work site visit increases the effectiveness, but because the analyzed studies had some methodologic shortcomings, an obvious need still exists for high-quality trials in this field.

Humans↗

PubMed2005

Progestational agents to prevent preterm birth: a meta-analysis of randomized controlled trials.

OBJECTIVE: To perform an updated systematic review with meta-analysis to further elucidate the efficacy of progestational agents for the prevention of preterm births in patients at elevated risk. DATA SOURCES: Computerized databases, references in published studies, and textbook chapters in all languages were used to identify randomized controlled trials (RCTs) evaluating the use of progestational agents for the prevention of preterm births in women at elevated risk. METHODS OF STUDY SELECTION: We identified RCTs that compared progestational agents with placebo for patients at risk for preterm birth and evaluated at least one of the following: delivery before 37 weeks of gestation, birth weight less than 2,500 g, threatened preterm labor, respiratory distress syndrome, and perinatal mortality. The primary outcomes assessed were preterm delivery and perinatal mortality. TABULATION, INTEGRATION, AND RESULTS: Ten studies met inclusion criteria for this review. For each study with binary outcomes, an odds ratio (OR) with 95% confidence intervals (CIs) was calculated for selected outcomes. Homogeneity was tested across the studies. Compared with women allocated to receive placebo, those who received progestational agents had lower rates of preterm delivery (26.2% versus 35.9%; OR 0.45, 95% CI 0.25-0.80). Similar results were noted when comparing patients who were specifically treated with 17alpha-hydroxyprogesterone caproate (29.3% versus 40.9%; OR 0.45, 95% CI 0.22-0.93). Additionally, subjects allocated to receive 17alpha-hydroxyprogesterone caproate had lower rates of birth weights less than 2,500 g (OR 0.50, 95% CI 0.36-0.71). No differences in rates of hospital admissions for threatened preterm labor or perinatal mortality were noted for subjects receiving progestational agents in general or for those receiving only 17alpha-hydroxyprogesterone caproate specifically. CONCLUSION: The use of progestational agents and 17alpha-hydroxyprogesterone caproate reduced the incidence of preterm birth and low birth weight newborns.

17 alpha-Hydroxyprogesterone Caproate↗

PubMed2005

The University of Michigan Student Health Physics Society's Radiation and Health Physics World Wide Web Site.

The University of Michigan Student Health Physics Society's (UMSHPS) Radiation and Health Physics World Wide Web Site is an informative database of radiation and health physics related topics. With over 1,000 visitors each day, the UMSHPS web site provides professionals and the general public with a valuable resource for information and research. Users of this site can either search for information by topic or submit questions directly to the qualified members the national Health Physics Society. During the past year, progress has been made in replacing the site's older, less versatile framework with new search engines and refined submittal forms, as well as a "Frequently Asked Questions" section. Within the database, references will include brief summaries of the site's available information and target audience. Although these changes have been beneficial for the site, the UMSHPS continuously seeks professional opinions and ideas to further the services that this online resource can provide to the profession and to the general public.

Health Physics↗

PubMed2004

Interleukin 2 receptor antagonists for renal transplant recipients: a meta-analysis of randomized trials.

BACKGROUND: Interleukin 2 receptor antagonists (IL-2Ra) are increasingly used to treat renal transplant recipients. This study aims to systematically identify and summarize the effects of using IL-2Ra as induction immunosuppression, as an addition to standard therapy, or as an alternative to other antibody therapy. METHODS: Databases, reference lists, and abstracts of conference proceedings were searched extensively to identify relevant randomized controlled trials in all languages. Data were synthesized using the random effects model. Results are expressed as relative risk (RR), with 95% confidence intervals (CI). RESULTS: A total of 117 reports from 38 trials involving 4,893 participants were included. When IL-2Ra were compared with placebo (17 trials; 2,786 patients), graft loss was not significantly different at 1 year (14 trials: RR 0.84; CI 0.64-1.10) or 3 years (4 trials: RR 1.08; CI 0.71-1.64). Acute rejection was significantly reduced at 6 months (12 trials: RR 0.66; CI 0.59-0.74) and at 1 year (10 trials: RR 0.67; CI 0.60-0.75). At 1 year, cytomegalovirus infection (7 trials: RR 0.82; CI 0.65-1.03) and malignancy (9 trials: RR 0.67; CI 0.33-1.36) were not significantly different. When IL-2Ra were compared with other antibody therapy, no significant differences in treatment effects were demonstrated, but IL-2Ra had significantly fewer side effects. CONCLUSIONS: Given a 40% risk of rejection, seven patients would need treatment with IL-2Ra in addition to standard therapy, to prevent one patient from undergoing rejection, with no definite improvement in graft or patient survival. There is no apparent difference between basiliximab and daclizumab.

Graft Survival↗

PubMed2000

Restriction endonuclease analysis using Hhal and Hpall to discriminate among group B Pasteurella multocida associated with haemorrhagic septicaemia.

The purpose of this study was to improve and standardise restriction endonuclease analysis (REA) for discriminating isolates of serogroup B Pasteurella multocida associated with haemorrhagic septicaemia in wild and domestic animals and to create a reference database that can be used for epidemiological studies. Two techniques for extraction and isolation of chromosomal DNA were compared, a DNAzol method and an enzymic lysis followed by a two-phase partition method. No differences were observed between DNA fingerprint profiles with either technique; however, the former technique was faster and easier to perform. P. multocida isolated from different animals in different countries representing serotypes B:2, B:3, B:3,4 and B:4 were subjected to REA with HhaI and HpaII endonucleases. Forty-eight fingerprint profiles were distinguished among 222 isolates when only HhaI was used. By combining the data from REA with HhaI and HpaII used separately, 88 different groups could be distinguished among the same isolates. Following digestion with HhaI and electrophoresis, the DNA of all serotype B:2 isolates produced fingerprint profiles characterised by two trailing bands at approximately 8.4-7.1 kb which have not been observed in any other serotypes of P. multocida. Passage of three serotype B:2 isolates on laboratory media or two serotype B:2 isolates through mice did not result in a change of DNA fingerprint profile detectable by REA. The findings with 59 isolates from Sri Lanka showed that REA was highly discriminative in determining the genetic diversity of serotype B:2 P. multocida in an area where haemorrhagic septicaemia is endemic.

Animals↗

PubMed2001

Prediction of protein functional domains from sequences using artificial neural networks.

An artificial neural network (ANN) solution is described for the recognition of domains in protein sequences. A query sequence is first compared to a reference database of domain sequences by use of and the output data, encoded in the form of six parameters, are forwarded to feed-forward artificial neural networks with six input and six hidden units with sigmoidal transfer function. The recognition is based on the distribution of scores precomputed for the known domain groups in a database versus database comparison. Applications to the prediction of function are discussed.

Computational Biology↗

PubMed2004

The Arabidopsis root transcriptome by serial analysis of gene expression. Gene identification using the genome sequence.

Large-scale identification of genes expressed in roots of the model plant Arabidopsis was performed by serial analysis of gene expression (SAGE), on a total of 144,083 sequenced tags, representing at least 15,964 different mRNAs. For tag to gene assignment, we developed a computational approach based on 26,620 genes annotated from the complete sequence of the genome. The procedure selected warrants the identification of the genes corresponding to the majority of the tags found experimentally, with a high level of reliability, and provides a reference database for SAGE studies in Arabidopsis. This new resource allowed us to characterize the expression of more than 3,000 genes, for which there is no expressed sequence tag (EST) or cDNA in the databases. Moreover, 85% of the tags were specific for one gene. To illustrate this advantage of SAGE for functional genomics, we show that our data allow an unambiguous analysis of most of the individual genes belonging to 12 different ion transporter multigene families. These results indicate that, compared with EST-based tag to gene assignment, the use of the annotated genome sequence greatly improves gene identification in SAGE studies. However, more than 6,000 different tags remained with no gene match, suggesting that a significant proportion of transcripts present in the roots originate from yet unknown or wrongly annotated genes. The root transcriptome characterized in this study markedly differs from those obtained in other organs, and provides a unique resource for investigating the functional specificities of the root system. As an example of the use of SAGE for transcript profiling in Arabidopsis, we report here the identification of 270 genes differentially expressed between roots of plants grown either with NO3- or NH4NO3 as N source.

Arabidopsis↗

PubMed2026

Combining Annotation Software to Identify Orthologous Genes (CASIO) Provides a New Dataset of Orthologous Genes for Swallowtail Butterflies.

With the massive increase in genomic resources, it is becoming increasingly popular to analyse thousands of loci across many species. However, many of the available genomes are not annotated, which hinders an efficient search for orthologous protein-coding genes. Here, we aim to develop a semi-automated pipeline and compare four genomic annotation methods (BRAKER2, BUSCO, Miniprot and Scipio). Our results highlight the importance of integrating multiple annotation tools to optimise ortholog detection and improve genomic studies. Each annotation method showed different strengths. BRAKER2 annotated a substantial number of genes. BUSCO, despite limitations inherent to its reference database, identified a higher number of orthologs. Miniprot exhibited notable flexibility in accommodating diverse protein datasets, whereas Scipio successfully recovered a considerable set of genes that were not detected by the other tools. The combination of these tools allowed for more comprehensive ortholog detection. Taking advantage of this pipeline, we developed a comprehensive dataset of orthologous genes for swallowtail butterflies (Lepidoptera: Papilionidae), called Papilionidae_odb, which will facilitate future studies, especially for a non-model group with abundant genomic data and few transcriptomic resources. We tested Papilionidae_odb by inferring a robust phylogenetic framework for Leptocircini using 142 complete genomes, which improved branch support for some phylogenetic relationships, although challenges remained in resolving relationships within certain species groups, likely due to rapid radiations. Our results highlight the complementary nature of the annotation methods and suggest that combining these tools can yield more accurate results in genomic research. This approach was implemented in a Snakemake workflow called CASIO (Combining Annotation Software to Identify Orthologous genes) and can easily be applied to other non-model groups to improve genomic datasets in diverse taxa where transcriptomic resources are still limited.

Animals↗