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PubMed2006

Telephone follow-up, initiated by a hospital-based health professional, for postdischarge problems in patients discharged from hospital to home.

BACKGROUND: It is known that many patients encounter a variety of problems in the first weeks after they have been discharged from hospital to home. In recent years many projects have addressed discharge planning, with the aim of reducing problems after discharge. Telephone follow-up (TFU) is seen as a good means of exchanging information, providing health education and advice, managing symptoms, recognising complications early, giving reassurance and providing quality aftercare service. Some research has shown that telephone follow-up is feasible, and that patients appreciate such calls. However, at present it is not clear whether TFU is also effective in reducing postdischarge problems. OBJECTIVES: To assess the effects of follow-up telephone calls in the first month post discharge, initiated by hospital-based health professionals, to patients discharged from hospital to home. SEARCH STRATEGY: We searched the following databases from their start date to July 2003, without limits as to date of publication or language: the Cochrane Consumers and Communication Review Group's Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), PubMed, EMBASE (OVID), BiomedCentral, CINAHL, ERIC (OVID), INVERT (Dutch nursing literature index), LILACS, Picarta (Dutch library system), PsycINFO/PsycLIT (OVID), the Combined Social and Science Citation Index Expanded (SCI-E), SOCIOFILE. We searched for ongoing research in the following databases: National Research Register (http://www.update-software.com/nrr/); Controlled Clinical Trials (http://www.controlled-trials.com/); and Clinical Trials (http://clinicaltrials.gov/). We searched the reference lists of included studies and contacted researchers active in this area. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of TFU initiated by a hospital-based health professional, for patients discharged home from an acute hospital setting. The intervention was delivered within the first month after discharge; outcomes were measured within 3 months after discharge, and either the TFU was the only intervention, or its effect could be analysed separately. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion and for methodological quality. The methodological quality of included studies was assessed using the criteria from the Cochrane Effective Practice and Organisation of Care Review Group. The data-extraction form was based on the template developed by the Cochrane Consumers and Communication Review Group. Data was extracted by one review author and checked by a second author. For as far it was considered that there was enough clinical homogeneity with regard to patient groups and measured outcomes, statistical pooling was planned using a random effects model and standardised mean differences for continuous scales and relative risks for dichotomous data, and tests for statistical heterogeneity were performed. MAIN RESULTS: We included 33 studies involving 5110 patients. Predominantly, the studies were of low methodological quality. TFU has been applied in many patient groups. There is a large variety in the ways the TFU was performed (the health professionals who undertook the TFU, frequency, structure, duration, etc.). Many different outcomes have been measured, but only a few were measured across more than one study. Effects are not constant across studies, nor within patient groups. Due to methodological and clinical diversity, quantitative pooling could only be performed for a few outcomes. Of the eight meta-analyses in this review, five showed considerable statistical heterogeneity. Overall, there was inconclusive evidence about the effects of TFU. AUTHORS' CONCLUSIONS: The low methodological quality of the included studies means that results must be considered with caution. No adverse effects were reported. Nevertheless, although some studies find that the intervention had favourable effects for some outcomes, overall the studies show clinically-equivalent results between TFU and control groups. In summary, we cannot conclude that TFU is an effective intervention.

Aftercare↗
PubMed2006

Shedding genomic light on Aristotle's lantern.

Sea urchins have proved fascinating to biologists since the time of Aristotle who compared the appearance of their bony mouth structure to a lantern in The History of Animals. Throughout modern times it has been a model system for research in developmental biology. Now, the genome of the sea urchin Strongylocentrotus purpuratus is the first echinoderm genome to be sequenced. A high quality draft sequence assembly was produced using the Atlas assembler to combine whole genome shotgun sequences with sequences from a collection of BACs selected to form a minimal tiling path along the genome. A formidable challenge was presented by the high degree of heterozygosity between the two haplotypes of the selected male representative of this marine organism. This was overcome by use of the BAC tiling path backbone, in which each BAC represents a single haplotype, as well as by improvements in the Atlas software. Another innovation introduced in this project was the sequencing of pools of tiling path BACs rather than individual BAC sequencing. The Clone-Array Pooled Shotgun Strategy greatly reduced the cost and time devoted to preparing shotgun libraries from BAC clones. The genome sequence was analyzed with several gene prediction methods to produce a comprehensive gene list that was then manually refined and annotated by a volunteer team of sea urchin experts. This latter annotation community edited over 9000 gene models and uncovered many unexpected aspects of the sea urchin genetic content impacting transcriptional regulation, immunology, sensory perception, and an organism's development. Analysis of the basic deuterostome genetic complement supports the sea urchin's role as a model system for deuterostome and, by extension, chordate development.

Animals↗
PubMed1999

Identification of a novel zinc finger gene, zf5-3, as a potential mediator of neuroblastoma differentiation.

We established a unique parental neuroblastoma cell line, NUB-7, which mimics the bipotentiality of neuroblastoma in vivo along neuronal and Schwann cell lineages following dibutyryl cAMP and retinoic acid treatments, respectively. Differential display identified a putative novel zinc finger gene as a potential differentiation-responsive gene coincident with retinoic acid treatment of NUB-7. This cDNA clone, now designated zf5-3, was mapped to chromosome 19 using somatic cell hybrids, and a larger cDNA clone further localized this gene to band 13.1-13.2 by fluorescent in situ hybridization. zf5-3 possesses 4 characteristic zinc finger DNA-binding motifs as determined by its nucleic acid and proposed amino acid sequence. Expression of zf5-3 is restricted to fetal neuronal, hepatic and renal tissues and their tumor-derived cell lines, including 8/9 neuroblastomas and 2/2 malignant rhabdoid tumors of kidney. The restricted expression in the kidney of zf5-3 to collecting tubules and ureter epithelium is suggestive of an ectodermal histogenesis of malignant rhabdoid tumors of kidney. During development of the fetal human brain, high levels of zf5-3 mRNA are restricted to the mitotically active, undifferentiated neuroblasts. Morphological evidence of overt differentiation was generally accompanied by a marked loss in zf5-3 expression. Therefore, the neuronal tissue expression profile and the down-regulation coincident with retinoic acid-induced neuroblastoma maturation implicate zf5-3 as a potential mediator of their differentiation.

Amino Acid Sequence↗
PubMed2005

Family therapy for attention-deficit disorder or attention-deficit/hyperactivity disorder in children and adolescents.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is diagnosed in between 3% and 7% of school-age children and consists of the core symptoms of inattention, impulsivity and hyperactivity. Children are often treated with medication, usually stimulant medication such as methylphenidate. Stimulant medication has been found to be effective for alleviating ADHD symptoms, at least in the short term. ADHD is also treated with a variety of psychosocial and psychoeducational interventions for parents, children, and with multicomponent interventions combined with medication management. However, many patients (10 to 13% of patients) cannot or prefer not to take medication. Family therapy without medication may help to develop structure in the family, help to manage children's behaviour, and may help families cope with distress from the presence of the disorder. OBJECTIVES: This review seeks to address the question of whether family therapy without medication can reduce the core symptoms of ADHD as compared to no treatment or standard treatment. SEARCH STRATEGY: The following electronic databases were searched using a specific search strategy: The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2004), MEDLINE (1966 to April 2004), PsycINFO (1872 to April 2004), CINAHL (1982 to April 2004), Biosis (Biological Abstracts) (1985 to March 2004), Dissertation Abstracts (1980 to April 2004), and Sociological Abstracts (Sociofile) (1963 to April 2004). Hand searches of relevant journals and bibliographies were also conducted and experts in the field were contacted for further information. SELECTION CRITERIA: Included studies were randomised controlled trials investigating the efficacy of behavioural family therapy, cognitive behavioural family therapy, or functional family therapy for children with ADHD or ADD (Attention Deficit Disorder). DATA COLLECTION AND ANALYSIS: Studies were evaluated for methodological quality and to determine whether they met the inclusion criteria. MAIN RESULTS: This assessment yielded two studies. Data were extracted for both studies. The findings from Jensen 1999 (N=579) indicate that no difference can be detected between the efficacy of behavioural family therapy and treatment as usual in the community. The finding from the available data from Horn 1991 slightly favours treatment over medication placebo. AUTHORS' CONCLUSIONS: Further research examining the effectiveness of family therapy versus a no-treatment control condition is needed to determine whether family therapy is an effective intervention for children with ADHD. There were no results available from studies investigating forms of family therapy other than behavioural family therapy.

Adolescent↗
PubMed2005

Investigation of changes in global gene expression in the frontal cortex of early-weaned and socially isolated piglets using microarray and quantitative real-time RT-PCR.

We hypothesize that early-weaned piglets experience aberrant expression of stress-responsive genes in the frontal cortex, a key brain area involved in cognitive function and behavior organization. To test this hypothesis, female early-weaned piglets (EW; n = 6) were weaned 10 days after birth, while non-weaned piglets (NW; n = 6) were left with their dams. Half of EW (n = 3) and NW (n = 3) animals were socially isolated (SI) for 15 min at 12 days of age, when all animals (n = 12) were euthanized and tissue collected. The effects of EW and SI were examined by gene expression profiling using cDNA microarray hybridizations, generated from a porcine brain cDNA library. A total of 103 genes were differentially expressed (P < 0.05, fold change >1.25) among four direct comparisons. Forty-two genes had known functions, from which 24 showed relevant brain-related functions. Quantitative real-time polymerase chain reaction (Q-RT-PCR) was used to confirm regulation of expression of a subset of 6 genes with important brain functions, selected from the microarray outcomes. In non-weaned animals, a significant suppression of mRNA abundance for carboxypeptidase E, 14-3-3 protein and phosphoprotein enriched in astrocytes 15 kDa was observed in response to SI. Also, in early-weaned animals, diazepam binding inhibitor and actin-related protein 2/3 complex mRNA levels were suppressed in response to SI. Results suggest that social isolation of non- and early-weaned piglets may impact expression of genes involved in regulation of neuronal function, development, and protection in the frontal cortex of young pigs.

Animals↗
PubMed2004

Evaluation of HIV/AIDS prevention resources in Liberia: strategy and implications.

The purpose of this preliminary study was to assess the HIV/AIDS prevention needs, services, and resources in Liberia, including the readiness of local providers to conduct HIV/AIDS-related prevention programs based on a set of six key dimensions (prevention needs, knowledge, leadership, environment, risky behaviors, and resources). A valid self-administered qualitative-based health survey, based on a community readiness model, was utilized as the primary data collection source. A cross-sectional design that utilized a convenient sample of key informants such as health coordinators, program directors, and health administrator from both public and private HIV/AIDS-based organizations was used. Furthermore, an extensive review of the National Library of Medicine database of published articles from mid-1980 to 2002 was simultaneously conducted to gauge the extent of scientific publications on HIV/AIDS-related prevention services in Liberia. The findings from this study strongly suggest that Liberia is in a stage of vague awareness, as defined by the Tri-Ethnic Center community readiness framework, regarding HIV/AIDS-related activities, including a significant lack of HIV/AIDS-related resources and scientific publications. Accordingly, there is a critical need to acquire adequate resources and build capacity to implement effective HIV/AIDS-related prevention programming services in order to avert the negative public health consequences associated with HIV/AIDS, including the implementation of relevant evaluation and dissemination strategies. Most importantly, this model has the potential to be utilized in other resource-constraint settings, especially in the developing world, to assess prevention-related resources and programmatic readiness. This is the first published study to evaluate Liberia's HIV/AIDS prevention resources and to systematically document the extent and magnitude of the HIV/AIDS crises in the country.

HIV Infections↗
PubMed2002

Analysis of differential gene expression by ligation specificity-based transcript profiling.

An open architecture mRNA profiling technology, LEAD (Ligation specificity-based Expression Analysis Display), was developed for studying differential gene expression. This method utilizes restriction enzymes with N(m) degeneracy in their recognition/cleavage sequences to fractionate cDNA population (N represents any one of the four possible bases; while m > or = 1, represents the number of degenerate bases). The fractionated cDNAs are subpooled by selective ligation with specific adapters, and then amplified and labeled by PCR. Fluorescent-labeled cDNA fingerprints are separated by electrophoresis as distinct bands with unique size and sequence, and quantified electronically by using the LEAD Finder program. The specificity of ligation and the uniform efficiency of PCR reaction allow precise quantification of differential gene expression among samples. Transcripts of low abundance (1/100,000 copies) can be detected, allowing the status of nearly all mRNA to be monitored. Because of its sequence independence, this technology can be used to monitor gene expression in both model and nonmodel systems lacking whole genome information. It can also be applied to separate and collect different cDNA species fingerprints to build a nonredundant EST library for microarray and other applications.

Animals↗
PubMed1999

Making sense of the electronic resource marketplace: trends in health-related electronic resources.

Changes in the practice of medicine and technological developments offer librarians unprecedented opportunities to select and organize electronic resources, use the Web to deliver content throughout the organization, and improve knowledge at the point of need. The confusing array of available products, access routes, and pricing plans makes it difficult to anticipate the needs of users, identify the top resources, budget effectively, make sound collection management decisions, and organize the resources effectively and seamlessly. The electronic resource marketplace requires much vigilance, considerable patience, and continuous evaluation. There are several strategies that librarians can employ to stay ahead of the electronic resource curve, including taking advantage of free trials from publishers; marketing free trials and involving users in evaluating new products; watching and testing products marketed to the clientele; agreeing to beta test new products and services; working with aggregators or republishers; joining vendor advisory boards; benchmarking institutional resources against five to eight competitors; and forming or joining a consortium for group negotiating and purchasing. This article provides a brief snapshot of leading biomedical resources; showcases several libraries that have excelled in identifying, acquiring, and organizing electronic resources; and discusses strategies and trends of potential interest to biomedical librarians, especially those working in hospital settings.

Computer Communication Networks↗
PubMed2005

Glucocorticosteroids for primary biliary cirrhosis.

BACKGROUND: Primary biliary cirrhosis is a chronic progressive cholestatic liver disease of presumed autoimmune etiology, characterised by the destruction of small intrahepatic bile ducts and the eventual development of cirrhosis and liver failure. Its progression may be influenced by immunosuppression. Glucocorticosteroids are potent immunosuppressive agents, but they are associated with significant adverse effects, including osteoporosis. OBJECTIVES: To systematically evaluate the beneficial and harmful effects of glucocorticosteroids versus placebo or no intervention for patients with primary biliary cirrhosis. SEARCH STRATEGY: The Cochrane Hepato-Biliary Controlled Trials Register,The Cochrane Library, MEDLINE, EMBASE, and the full text of the identified studies were searched until June 2004. The search strategy included terms for primary biliary cirrhosis and glucocorticosteroids (including the names of frequently used preparations). Previous research groups and manufacturers were contacted for additional references. No language restrictions were applied. SELECTION CRITERIA: Double-blind, single-blind, or unblinded randomised clinical trials evaluating any preparation of glucocorticosteroids versus placebo or no intervention in patients with primary biliary cirrhosis diagnosed by abnormal liver function tests and either anti-mitochondrial antibodies or histology were included. Additional agents were allowed if they were administered to both groups equally. DATA COLLECTION AND ANALYSIS: The quality of the randomised clinical trials was evaluated by methodology components (generation of allocation sequence; allocation concealment; blinding; follow up). Analyses were performed according to the intention-to-treat method with missing data being accounted for by imputation. MAIN RESULTS: Only two underpowered trials (reporting 36 and 40 patients) were identified. These differed markedly in their inclusion criteria and treatment protocols. Both stated that they used placebo. However, allocation concealment was unclear. Only one trial reported any patient deaths. No significant improvement in mortality was identified (odds ratio (OR) 0.42, 95% confidence interval (CI) 0.10 to 1.76). Improvements in serum markers of liver inflammation and liver histology were identified. Potentially prognostically linked markers such as bilirubin and albumin were incompletely reported. Bone mineral density (weighted mean difference -2.84%, 95% CI -4.16 to -1.53) and the number of patients with any adverse event (OR 8.99, 95% CI 2.15 to 37.58) were significantly increased in the glucocorticosteroid group. AUTHORS' CONCLUSIONS: There is insufficient data to support or reject the use of glucocorticosteroids for patients with primary biliary cirrhosis. It may be appropriate to consider a large prospective randomised clinical trial on this topic.

Budesonide↗
PubMed1996

The identification of transposon-tagged mutations in essential genes that affect cell morphology in Saccharomyces cerevisiae.

The yeast Saccharomyces cerevisiae reproduces by budding, and many genes are required for proper bud development. Mutations in some of these genes cause cells to die with an unusual terminal morphology-elongated or otherwise aberrantly shaped buds. To gain insight into bud development, we set out to identify novel genes that encode proteins required for proper bud morphogenesis. Previous studies screened collections of conditional mutations to identify genes required for essential functions, including bud formation. However, genes that are not susceptible to the generation of mutations that cause a conditional phenotype will not be identified in such screens. To identify a more comprehensive collection of mutants, we used transposon mutagenesis to generate a large collection of lethal disruption mutations. This collection was used to identify 209 mutants with disruptions that cause an aberrant terminal bud morphology. The disruption mutations in 33 of these mutants identify three previously uncharacterized genes as essential, and the mutant phenotypes suggest roles for their products in bud morphogenesis.

Amino Acid Sequence↗
PubMed2003

Pentoxifylline for neonatal sepsis.

BACKGROUND: Although the overall incidence of neonatal sepsis has declined over the past decade, mortality remains high in the pre term infant. The high level of mortality and morbidity from sepsis despite the use of potent anti-microbial agents, and the global emergence of antibiotic resistance, have led to the search for new modalities to boost new born host defences. Pentoxifylline, a xanthine derivative and a phosphodiesterase inhibitor, has been shown to possess a broad spectrum of activity modulating inflammation. OBJECTIVES: The primary objective was to assess the effect on mortality and the safety of intravenous pentoxifylline as an adjunct to antibiotic therapy in neonates with suspected or confirmed sepsis. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2002), MEDLINE, EMBASE and CINAHL were searched in October 2002 and again in March 2003. Science Citation Index for articles referencing Lauterbach 1996 and Lauterbach 1999 was searched as well as proceedings of the Pediatric Academic Societies which were published in Pediatric Research from 1980. Doctoral dissertations and theses were searched from 1980. The reference lists of identified RCTs, and personal files were searched. No language restriction was applied. SELECTION CRITERIA: Studies were included if they were randomised or quasi-randomised trials, assessing the efficacy of pentoxifylline compared to placebo or no intervention as an adjunct to antibiotic therapy of suspected or confirmed sepsis in newborn infants less than 28 days old. Eligible trials were required to report treatment effects on at least one of the following outcomes: all cause mortality during initial hospital stay, neurological development at two years of age or later, length of hospital stay, duration of ventilation via endotracheal intubation, chronic lung disease in survivors, periventricular leukomalacia, necrotising enterocolitis, or adverse events. DATA COLLECTION AND ANALYSIS: Two reviewers independently abstracted information for the outcomes of interest. Any differences were resolved by mutual discussion. Typical Relative Risk (RR) and Risk Difference (RD) with 95% confidence intervals (CI) using fixed effects model are reported for dichotomous outcomes. NNT was calculated for outcomes for which there was a statistically significant reduction in RD. MAIN RESULTS: Two RCTs enrolled a total of 140 preterm (< 36 weeks) neonates with suspected late onset (> 7 days) sepsis to evaluate the effect of pentoxifylline on neonatal outcomes. However, the two studies reported outcomes of only the 107 randomised patients with confirmed sepsis. The results showed a reduction in 'all cause mortality during hospital stay' following pentoxifylline treatment [typical RR 0.14 (95% CI 0.03, 0.76), RD -0.16 (95% CI -0.27, - 0.04), NNT 6 (95% CI 4, 25)]. No adverse effects due to pentoxifylline were observed in the two included trials. No other outcomes of interest were reported. REVIEWER'S CONCLUSIONS: Current evidence suggests that the use of pentoxifylline as an adjunct to antibiotics in neonatal sepsis reduces mortality without any adverse effects. But the number of neonates studied is small and considerable methodological weaknesses exist in the included trials. Hence these results should be interpreted with caution. Researchers are encouraged to undertake large well-designed trials to confirm or refute the effectiveness of pentoxifylline to reduce mortality and adverse outcomes in neonates with suspected or confirmed neonatal sepsis. Researchers might also compare pentoxifylline with other adjuncts to antibiotics which modulate inflammation (e.g. intravenous immunoglobulins, haematopoetic colony stimulating factors among others) in reducing mortality and morbidity due to neonatal sepsis.

Anti-Bacterial Agents↗
PubMed2006

Interventions for stimulus deprivation amblyopia.

BACKGROUND: Stimulus deprivation amblyopia (SDA) develops due to an obstruction to the clear passage of light, preventing clear formation of an image on the retina for example, cataract, ptosis (droopy eyelid). It is particularly severe and can be resistant to treatment and the visual prognosis is often poor. Stimulus deprivation amblyopia is rare and precise estimates of prevalence difficult to come by; it probably constitutes less than 3% of all cases of amblyopia. In developed countries most patients present under the age of one; in less developed parts of the world presentation is likely to be significantly later than this.The mainstay of treatment is patching of the better-seeing eye but regimes vary, treatment is difficult to execute and results are often disappointing. OBJECTIVES: The objectives of this review were to evaluate the effectiveness of occlusion treatment for SDA, determine the optimum treatment regime and factors that may affect outcome. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials - CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) on The Cochrane Library (2006, Issue 1), MEDLINE (1996 to April 2006), EMBASE (1980 to April 2006) and LILACS (Latin American and Caribbean Literature on Health Sciences) (to November 2004). There were no date or language restrictions. SELECTION CRITERIA: We aimed to include randomised and quasi-randomised controlled trials of subjects with unilateral SDA defined as worse than 0.2 LogMAR or equivalent. There were no restrictions with respect to age, gender, ethnicity, co-morbidities, medication use, and the number of participants. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study abstracts identified by the electronic searches. MAIN RESULTS: No trials were identified that met the inclusion criteria. AUTHORS' CONCLUSIONS: It is not possible to conclude how effective treatment for SDA is or which treatment regime produces the best results. There is a need for further study in this area.

Amblyopia↗
PubMed2004

A unigene catalogue of 5700 expressed genes in cassava.

Two economically important characters, starch content and cassava bacterial blight resistance, were targeted to generate a large collection of cassava ESTs. Two libraries were constructed from cassava root tissues of varieties with high and low starch contents. Other libraries were constructed from plant tissues challenged by the pathogen Xanthomonas axonopodis pv.manihotis. We report here the single pass sequencing of 11,954 cDNA clones from the 5' ends, including 111 from the 3' ends. Cluster analysis permitted the identification of a unigene set of 5,700 sequences. Sequence analyses permitted the assignment of a putative functional category for 37% of sequences whereas approximately 16% sequences did not show any significant similarity with other proteins present in the database and therefore can be considered as cassava specific genes. A group of genes belonging to a large multigene family was identified. We characterize a set of genes detected only in infected libraries putatively involved in the defense response to pathogen infection. By comparing two libraries obtained from cultivars contrasting in their starch content a group of genes associated to starch biosynthesis and differentially expressed was identified. This is the first large cassava EST resource developed today and publicly available thus making a significant contribution to genomic knowledge of cassava.

Cluster Analysis↗
PubMed2002

Microbial technologies for the discovery of novel bioactive metabolites.

Soil microbes represent an important source of biologically active compounds. These molecules present original and unexpected structure and are selective inhibitors of their molecular targets. At Biosearch Italia, discovery of new bioactive molecules is mostly carried out through the exploitation of a proprietary strain collection of over 50000 strains, mostly unusual genera of actinomycetes and uncommon filamentous fungi. A critical element in a drug discovery based on microbial extracts is the isolation of unexploited groups of microorganisms that are at the same time good producers of secondary metabolites. Molecular genetics can assist in these efforts. We will review the development and application of molecular methods for the detection of uncommon genera of actinomycetes in soil DNA and for the rapid dereplication of actinomycete isolates. The results indicate a substantial presence in many soils of the uncommon genera and a large diversity of isolated actinomycetes. However, while uncommon actinomycete strains may provide an increased chance of yielding novel structures, their genetics and physiology are poorly understood. To speed up their manipulation, we have developed vectors capable of stably maintaining large segments of actinomycete DNA in Escherichia coli and of integrating site specifically in the Streptomyces genome. These vectors are suitable for the reconstruction of gene clusters from smaller segment of cloned DNA, the preparation of large-insert libraries from unusual actinomycete strains and the construction of environmental libraries.

Actinobacteria↗
PubMed1999

Substance abuse studies and prevention efforts among Arabs in the 1990s in Israel, Jordan and the Palestinian Authority--a literature review.

This paper is the result of a collaborative project of Israeli, Jordanian and Palestinian scientists gathered to reveal the current extent of substance abuse and efforts at prevention among Arabs in Israel, Jordan and the Palestinian Authority territories, in order to identify needs and suggest future collaborative activities and directions for regional cooperation. The article provides data and covers the current state of substance abuse prevention and research among Moslems, Christians and Druze in the trilateral region in the 1990s by reviewing prevention materials and studies published in the professional literature, as well as in reports and Doctoral and Master's theses in Arabic, which have been located in academic libraries and other institutions, in the framework of a comprehensive search. This manuscript is the first to summarize Jordanian and Palestinian findings in the substance abuse domain. The review shows that most of the Israeli research in the Arab sector deals with alcohol use among youth, that the majority of Jordanian studies focus on illicit drug use, that the research among Palestinians is in its infancy, and that comprehensive prevention programs are lacking in the trilateral region. It describes the key results of most of the 12 Israeli studies among Arabs, 11 Jordanian studies and four Palestinian studies. It reveals that drug abuse among Israeli Arab students is probably more prevalent than among Jewish adolescents, that the typical Jordanian drug addict has a higher level of education than the typical Palestinian drug addict, and that the Palestinian is more likely to be a multiple drug user. Recommendations for future activities include organization of a regional collaborative workshop in order to establish data collection systems for basic statistics relevant to drug abuse and development of comprehensive prevention programs, as well as studies in the substance abuse domain concerning knowledge, attitudes and behavior among the general Arab population.

Arabs↗
PubMed2004

Model based on GRID-derived descriptors for estimating CYP3A4 enzyme stability of potential drug candidates.

A number of computational approaches are being proposed for an early optimization of ADME (absorption, distribution, metabolism and excretion) properties to increase the success rate in drug discovery. The present study describes the development of an in silico model able to estimate, from the three-dimensional structure of a molecule, the stability of a compound with respect to the human cytochrome P450 (CYP) 3A4 enzyme activity. Stability data were obtained by measuring the amount of unchanged compound remaining after a standardized incubation with human cDNA-expressed CYP3A4. The computational method transforms the three-dimensional molecular interaction fields (MIFs) generated from the molecular structure into descriptors (VolSurf and Almond procedures). The descriptors were correlated to the experimental metabolic stability classes by a partial least squares discriminant procedure. The model was trained using a set of 1800 compounds from the Pharmacia collection and was validated using two test sets: the first one including 825 compounds from the Pharmacia collection and the second one consisting of 20 known drugs. This model correctly predicted 75% of the first and 85% of the second test set and showed a precision above 86% to correctly select metabolically stable compounds. The model appears a valuable tool in the design of virtual libraries to bias the selection toward more stable compounds.

Cytochrome P-450 CYP3A↗
PubMed1994

Ethical issues involved in establishing a registry for familial Alzheimer's disease.

In January 1992, the IMAGE Project extended the establishment of its registry of familial Alzheimer cases to all areas of the province of Quebec, for collection of epidemiological and clinical data, as well as biological samples. The aim is to study genetic transmission patterns of Alzheimer's disease (AD) and to provide a sampling framework for further etiologic and risk factor studies. The IMAGE registry already includes data of a population-based study in the Saguenay-Lac-St-Jean area; the project to collect data on familial AD (FAD) cases across the province of Quebec is known as the ALGENE Initiative. The registry is thus a collection of "AD families" for both familial and sporadic cases. The establishment of the registry involves several steps in the field work: recruitment and selection of families; collection of information on family medical history; selection of informative families and genetic testing for AD/FAD by linkage analysis. As AD is not homogeneous in its etiology and since we do not know if, in the event that genetics is involved in AD whether or not penetrance of the gene(s) is high, we must be aware of the "genetic horizons" of AD in collecting and conserving data on families of cases, and in the genetic testing for AD/FAD by linkage analysis. Families who choose genetic testing must be aware of the implications of our undertaking, assured of the confidentiality of the test and, at the same time, they must understand its limitations. The experimental nature of our research project raises ethical dilemmas. This article examines these initial considerations of the field work involved in developing a registry pertaining to genetic testing for AD/FAD by linkage analysis and offers some preliminary observations on the experience of the first year of this project.

Aged↗
PubMed2005

Introducing DOTUR, a computer program for defining operational taxonomic units and estimating species richness.

Although copious qualitative information describes the members of the diverse microbial communities on Earth, statistical approaches for quantifying and comparing the numbers and compositions of lineages in communities are lacking. We present a method that addresses the challenge of assigning sequences to operational taxonomic units (OTUs) based on the genetic distances between sequences. We developed a computer program, DOTUR, which assigns sequences to OTUs by using either the furthest, average, or nearest neighbor algorithm for each distance level. DOTUR uses the frequency at which each OTU is observed to construct rarefaction and collector's curves for various measures of richness and diversity. We analyzed 16S rRNA gene libraries derived from Scottish and Amazonian soils and the Sargasso Sea with DOTUR, which assigned sequences to OTUs rapidly and reliably based on the genetic distances between sequences and identified previous inconsistencies and errors in assigning sequences to OTUs. An analysis of the two 16S rRNA gene libraries from soil demonstrated that they do not contain enough sequences to support a claim that they contain different numbers of bacterial lineages with statistical confidence (P > 0.05), nor do they contain enough sequences to provide a robust estimate of species richness when an OTU is defined as containing sequences that are no more than 3% different from each other. In contrast, the richness of OTUs at the 3% level in the Sargasso Sea collection began to plateau after the sampling of 690 sequences. We anticipate that an equivalent extent of sampling for soil would require sampling more than 10,000 sequences, almost 100 times the size of typical sequence collections obtained from soil.

Algorithms↗