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Cysticercosis: towards the design of a diagnostic kit based on synthetic peptides.

Cysticercosis caused by Taenia solium is a very common disease in developing countries that seriously affects human health. Diagnosis can only be confirmed with the aid of computerized tomography or nuclear magnetic resonance (NMR) creating obvious difficulties for epidemiological studies. Reliable immunoassays employing cerebrospinal fluid (CSF) have been developed, based on the use of cysticercal antigens. However, the reliance on parasite material is restrictive. Herein, we report the advances in the design of a diagnostic kit based on immunodominant synthetic peptides, targeting four candidate epitopes KETc1, KETc12, 410 and 413 which were identified from three different clones (KETc1, 12 and 4) selected from a cDNA library of Taenia crassiceps. CSF antibodies against T. solium cysticercal antigens (TCA) as well as the four peptides were determined by enzyme-linked immunoabsorbent assays (ELISA) using two panels of CSF from patients with confirmed neurocysticercosis and other neurological diseases. In the first CSF panel which included patients with high level of antibodies against TCA, KETc12 exhibited almost the same sensitivity (87.5%) as TCA (93.7%) and 100% specificity. In the second panel of 110 CSF collected at random, two peptides (KETc1 and KETc12) exhibited sensitivities of 40 and 36% respectively, and were 100% specific.

Animals↗

Epitope mapping of factor VIII inhibitor antibodies of Chinese origin.

Epitopes recognized by factor VIII (FVIII) inhibitors of Chinese origin were analysed by immunoblotting with full-length recombinant FVIII (rFVIII), thrombin-activated FVIII (FVIIIa) and 16 FVIII fusion proteins synthesized by bacteria. Twenty-eight patients, 12 with haemophilia A and 16 with autoimmune diseases, were recruited. Antibodies from 22 patients showed reactivity with rFVIII, 20 with FVIIIa, and one reacted only with FVIII fusion proteins. Of these 22 cases, most were reactive with A2-a2 and A3-C1-C2 of FVIII(a). Of the nine cases that depicted binding to the fusion proteins, three were reactive with the A domains, three with only the B domain, and the other three with both the A and B (or C) domains. An epitope for a neutralizing antibody of a haemophilia A patient, designated TWN-112, was localized to residues 323-390, specified by FVIII fusion proteins. The same epitope also appeared on an FVIII-expression phage library screening. Immunoabsorption of antibodies from TWN-112 with the epitope reduced the neutralizing activity of the inhibitor by 33%. The incidence of a1 of FVIII is higher, and that of a3 is lower, than previously reported. Two novel epitopes, reported for the first time in this paper, were localized on the 8B2 (amino acid residues 1022-1204) and 8A2(V) (residues 673-740) fusion proteins. These two epitopes were able to reduce inhibitory antibody activity by 24% and 25% respectively. Changes of FVIII fragment specificity were also observed in one of six patients for whom multiple samples, collected at different times, were available. Our initial finding showed that the FVIII inhibitors in these Chinese patients shared epitopes with those of patients from very different genetic backgrounds, suggesting a common mechanism for the development of FVIII inhibitors.

Adolescent↗

Comprehensive transposon mutant library of Pseudomonas aeruginosa.

We have developed technologies for creating saturating libraries of sequence-defined transposon insertion mutants in which each strain is maintained. Phenotypic analysis of such libraries should provide a virtually complete identification of nonessential genes required for any process for which a suitable screen can be devised. The approach was applied to Pseudomonas aeruginosa, an opportunistic pathogen with a 6.3-Mbp genome. The library that was generated consists of 30,100 sequence-defined mutants, corresponding to an average of five insertions per gene. About 12% of the predicted genes of this organism lacked insertions; many of these genes are likely to be essential for growth on rich media. Based on statistical analyses and bioinformatic comparison to known essential genes in E. coli, we estimate that the actual number of essential genes is 300-400. Screening the collection for strains defective in two defined multigenic processes (twitching motility and prototrophic growth) identified mutants corresponding to nearly all genes expected from earlier studies. Thus, phenotypic analysis of the collection may produce essentially complete lists of genes required for diverse biological activities. The transposons used to generate the mutant collection have added features that should facilitate downstream studies of gene expression, protein localization, epistasis, and chromosome engineering.

Escherichia coli↗

Characterization and quantification of ammonia-oxidizing bacteria in eutrophic coastal marine sediments using polyphasic molecular approaches and immunofluorescence staining.

Tokyo Bay, a eutrophic bay in Japan, receives nutrients from wastewater plants and other urban diffuse sources via river input. A transect was conducted along a line from the Arakawa River into Tokyo Bay to investigate the ecological relationship between the river outflow and the distribution, abundance and population structure of ammonia-oxidizing bacteria (AOB). Five surficial marine sediments were collected and analysed with polyphasic approaches. Heterogeneity and genetic diversity of beta-AOB populations were examined using restriction fragment length polymorphism (RFLP) analysis of 16S rRNA and amoA genes. A shift of the microbial community was detected in samples along the transect. Both 16S rRNA and amoA genes generated polymorphisms in the restriction profiles that were distinguishable at each sampling site. Two 16S rRNA gene libraries were constructed using the reverse transcription polymerase chain reaction (RT-PCR) method to determine the major ammonia oxidizers maintaining high cellular rRNA content. Two major groups were observed in the Nitrosomonas lineage; no Nitrosospira were detected. The effort to isolate novel AOB was successful; the isolate dominated in the gene libraries. For quantitative analysis, a real-time PCR assay targeting the 16S rRNA gene was developed. The population sizes of beta-AOB ranged from 1.6 x 10(7) to 3.0 x 10(8) cells g(-1) in dry sediments, which corresponded to 0.1-1.1% of the total bacterial population. An immunofluorescence staining using anti-hydroxylamine oxidoreductase (HAO) antibody was also tested to obtain complementary data. The population sizes of ammonia oxidizers ranged between 2.4 x 10(8) and 1.2 x 10(9) cells g(-1) of dry sediments, which corresponded to 1.2-4.3% of the total bacterial fraction. Ammonia-oxidizing bacteria cell numbers deduced by the two methods were correlated (R = 0.79, P < 0.01). In both methods, the number of AOB increased with the distance from the river mouth; ammonia-oxidizing bacteria were most numerous at B30, where the ammonium concentration in the porewater was markedly lower and the nitrite concentration was slightly higher than nearby sites. These results reveal spatial distribution and shifts in the population structure of AOB corresponding to nutrients and organic inputs from the river run-off and phytoplankton bloom.

Ammonia↗

Functional genomics of the social amoebae, Dictyostelium discoideum.

Dictyostelium discoideum is one of the simplest organisms to form a multicellular structure, and it offers several advantages as a model. In order to understand the genetic basis of the multicellular development, a comprehensive analysis of cDNAs is being performed. To date, about 75,000 ESTs have been collected at different stages of development. They have been assembled into about 6,400 independent sequences that represent 70-80% of all of the expected genes in D. discoideum. The results are available on the Internet. In addition to structural analyses, functional analyses of the temporal and spatial expression patterns and gene targeting are being carried out. Furthermore, there are plans to combine the information that is obtained from the cDNA, Genome, and Proteome Projects, as well as the published results, into an integrated database, DictyBase.

Animals↗

Alpha-1 proteinase inhibitor (a1PI) for preventing chronic lung disease in preterm infants.

BACKGROUND: Inflammation of the pulmonary parenchyma is one of the important mechanisms implicated in development of chronic lung disease (CLD) in preterm neonates. Release of enzymes and other anti - oxidants following cell damage is considered to be responsible for the damage to lung tissue. Various strategies have been attempted to counteract enzymatic damage to pulmonary parenchyma and to prevent CLD. OBJECTIVES: This review examines the effectiveness of alpha 1 proteinase inhibitor (a1PI) for the prevention of CLD defined as requirement of supplemental oxygen at 36 weeks post menstrual age (PMA) in preterm neonates. SEARCH STRATEGY: A literature search was performed using the following databases: MEDLINE (1966 - February 2001), EMBASE (1980 -February 2001), CINAHL (1982 - February 2001), Cochrane Controlled Trials Register (Issue 1, 2001 of Cochrane Library) and abstracts from the annual meetings of the Society of Pediatric Research, American Pediatric Society and Pediatric Academic Societies published in Pediatric Research (1991-2000). No language restrictions were applied. SELECTION CRITERIA: Selection criteria applied to the clinical trials were: 1. The population had to be preterm neonates 2. The intervention had to be administration of a1PI compared to placebo or no treatment within the first week of life 3. The eligible studies had to include any of the following outcomes: a. prevention of CLD b. reduction in duration of assisted ventilation c. reduction in the duration of oxygen requirement d. reduction in the need for systemic antiinflammatory therapy e. reduction in mortality or f. reduction in long term adverse neurological sequelae. 4. The trial had to be randomized or quasi-randomized. DATA COLLECTION AND ANALYSIS: The methodological quality of the trials was assessed using the information provided in the studies and by personal communication with the authors. Data on relevant outcomes were extracted and the effect size was estimated and reported as pooled relative risk (RR), risk difference (RD) and weighted mean difference (WMD) as appropriate. Two strategies were used for analysis : 1. Comparison of 60 mg/kg/dose of a1PI administered for 4 days in first 2 weeks after birth, versus placebo and 2. Comparison of any dose of a1PI administered in first 2 weeks after birth, versus placebo. MAIN RESULTS: Two eligible studies were identified. The methodological qualities of identified studies were good. One study randomized infants to either placebo, or a1PI 60 mg/kg/dose for four doses while in the second study the same investigators explored the efficacy of different dose regimens of a1PI compared to placebo. There was no statistically significant difference in the development of CLD at 36 weeks PMA amongst all randomized infants. For 60 mg/kg/dose for four doses of a1PI compared to placebo the pooled RR was 0.64 [95% CI 0.35, 1.18] and RD was -0.10 [95% CI -0.23, 0.03] while for any doses of a1PI the pooled RR was 0.79 [95% CI 0.44, 1.41], RD was -0.05 [95% CI -0.17, 0.06]. There was a trend towards reduced risk of development of oxygen dependency at 28 days postnatal age, pooled RR 0.81 [95% CI 0.64, 1.01], RD -0.14 [95% CI -0.29, 0.00] for 60 mg/kg/dose for four doses of a1PI compared to placebo. The pooled RR was statistically significant, RR 0.80 [95% CI 0.65, 0.98], RD -0.15 (95 % CI -0.29, -0.01) when any doses of a1PI were combined. The number of patients needed to treat (NNT) with a1PI to prevent one infant developing oxygen dependency at 28 weeks was 7. The benefits of short-term outcomes did not remain for long-term outcomes such as CLD and/or death at 36 weeks post menstrual age (pooled RR 0.84 [95% CI 0.53, 1.34], RD -0.06 [95% CI -0.20, 0.09] for 60 mg/kg/dose and pooled RR 0.95 [95% CI 0.61, 1.49], RD -0.02 [95% CI -0.15, 0.12] for any dose) or risk of development of long term neurodevelopmental abnormalities (pooled RR 1.29 [95% CI 0.43, 3.90], RD 0.03 [95% CI -0.11, 0.18]). In addition, no statistically significant difference was noted in other respiratory parameters such as duration of oxygen requirement or respiratory support. REVIEWER'S CONCLUSIONS: Prophylactic administration of a1PI did not reduce the risk of CLD at 36 weeks or long term adverse developmental outcomes in preterm neonates.

Chronic Disease↗

A third Ig light chain gene isotype in Xenopus laevis consists of six distinct VL families and is related to mammalian lambda genes.

Xenopus laevis is a unique model for studying the ontogenetic development of immune functions. A short primer PCR amplification method was employed to amplify fragments from Xenopus genomic DNA that are related to Ig light chains and TCR. One fragment was identified that appeared to represent a novel type of light chain and was used as a probe to recover the corresponding cDNA from a spleen cDNA library. We designate these light chains type III. Using an iterative screening procedure, six families of VL genes, two distinct JL and two distinct CL sequences, were identified. In a comparison of phylogenetically diverse light chains, the type III genes align with higher vertebrate lambda genes. Southern blot hybridization analyses with genomic DNA from different animals showed the VL and CL sequences to be both diverse and polymorphic. Intrafamily sequence comparisons of VL genes revealed additional diversity. Collectively, these studies confirm the existence of a third type of light chain gene in Xenopus, establish a high degree of genetic variation in the sequences encoding the light chain V regions, and provide the most significant evidence to date for the presence of a lambda-like light chain gene at the phylogenetic level of the amphibians.

Amino Acid Sequence↗

Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for apnea of prematurity.

BACKGROUND: Apnea of prematurity is almost universal in infants who are born before 34 weeks gestation. Previous randomised trials and systematic reviews have found methylxanthines to be effective in preventing apnea of prematurity. However, recent concerns about potential long term side effects of methylxanthines on the neurodevelopment of low birth weight infants have led to an increased interest in alternate methods of treating apnea of prematurity. Nasal continuous positive airway pressure (NCPAP) is a useful method of respiratory support which reduces the incidence of obstructive or mixed apnea. However, apneic infants managed with NCPAP, with or without methylxanthines, sometimes require endotracheal intubation with its attendant morbidity and cost. Nasal intermittent positive pressure ventilation (NIPPV) is a simple, effective mode of respiratory support for older children and adults. It has been used to treat apnea in preterm infants but case reports of gastrointestinal perforations have limited its widespread use. OBJECTIVES: In preterm infants with recurrent apnea, does treatment with NIPPV lead to a greater reduction in apnea and need for intubation and mechanical ventilation, as compared with treatment with NCPAP? Does NIPPV increase the incidence of gastrointestinal complications, i.e. gastric distension leading to cessation of feeds, or perforation? SEARCH STRATEGY: Medline was searched (1966-2000) using the MeSH terms: infant, newborn (exp) and positive-pressure respiration (exp). Other sources included the Cochrane Controlled Trials Register and CINAHL (search terms: infant, newborn and intermittent positive pressure ventilation); also used were expert informants, previous reviews including cross-references, and conference and symposia proceedings. SELECTION CRITERIA: All randomised and quasi-randomised trials were included. Participants included unventilated preterm infants experiencing apnea of prematurity. Interventions compared were intermittent positive pressure ventilation administered via the nasal route, either by short nasal prongs or nasopharyngeal tube, and nasal CPAP delivered by the same methods. Types of outcome measures: - failure of therapy as defined by apnea that is frequent or severe requiring additional ventilatory support - rates of endotracheal intubation - rates of apnea and bradycardia expressed as events per hour - gastrointestinal complications i.e. abdominal distension requiring cessation of feeds, or GI perforation DATA COLLECTION AND ANALYSIS: Data were extracted independently by the three reviewers. The trials were analysed using relative risk (RR), risk difference (RD) and number needed to treat (NNT) for dichotomous data; means and weighted mean difference (WMD) were used for continuous data. MAIN RESULTS: Two trials, enrolling 54 infants in total, fulfilled the inclusion criteria. Both reported only the short term results (4 to 6 hours) of the interventions. Only one infant (randomised to NCPAP) required intubation during this period. Ryan (1989), in a cross over study of 20 infants, showed no significant difference in rates of apnea (events/hr) between the 2 interventions (WMD -0.10 (-0.53,0. 33)). Lin (1998) randomised 34 infants and demonstrated a greater reduction in frequency of apneas (events/hr) with NIPPV compared to NCPAP (WMD -1.19 (-2.31,-0.07)). Meta-analysis of both trials showed no difference in pCO2 (mmHg) at the end of the 4-6 hour study period (WMD 0.95 (-3.05,4.94)). No data were reported on gastrointestinal complications. REVIEWER'S CONCLUSIONS IMPLICATIONS FOR PRACTICE: NIPPV may be a useful method of augmenting the beneficial effects of NCPAP in preterm infants with apnea that is frequent or severe. Its use appears to reduce the frequency of apneas more effectively than NCPAP. Additional safety and efficacy data are required before recommending NIPPV as standard therapy for apnea. IMPLICATIONS FOR RESEARCH: Future trials with sufficient power should assess the efficacy (reduction in failure of therapy) and safety (GI complications) of NIPPV. Outcomes should be assessed throughout the entire period during which the infant requires assisted ventilation. The recent ability to synchronise NIPPV with an infant's spontaneous respirations is a promising development requiring further assessment.

Apnea↗

Penicillin for secondary prevention of rheumatic fever.

BACKGROUND: People with a history of rheumatic fever are at high risk of recurrent attacks of rheumatic fever and developing rheumatic heart disease following a streptococcal throat infection. Giving penicillin to these people can prevent recurrent attacks of rheumatic fever and subsequent rheumatic heart disease. However, there is no agreement on the most effective method of giving penicillin. OBJECTIVES: To assess the effects of penicillin compared to placebo and the effects of different penicillin regimens and formulations for preventing streptococcal infection and rheumatic fever recurrence. SEARCH STRATEGY: We searched the Controlled Trials Register (Cochrane Library Issue 2, 2001), MEDLINE (1997 to July 2000), EMBASE (1998 to July 2000), reference lists of articles and we contacted experts in the field. SELECTION CRITERIA: Randomised and quasi-randomised studies comparing (i) penicillin with control, (ii) oral with intramuscular penicillin (iii) 2- or 3-weekly with 4-weekly intramuscular penicillin in patients with previous rheumatic fever. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. MAIN RESULTS: Nine studies were included (n=3008). Data were not pooled because of heterogeneity. Overall, the methodological quality of included studies was poor. Three trials (n= 1301) compared penicillin with control. Only one of three studies showed that penicillin reduced rheumatic fever recurrence (RR 0.45, 95% CI 0.22 to 0.92) and streptococcal throat infection (RR 0.84, 95% CI 0.72 to 0.97). Four trials (n=1098) compared intramuscular with oral penicillin and all showed that intramuscular penicillin reduced rheumatic fever recurrence and streptococcal throat infections compared to oral penicillin. One trial (n= 360) compared 2-weekly with 4-weekly intramuscular penicillin. Penicillin given every two-weeks was better at reducing rheumatic fever recurrence (RR 0.52, 95% CI 0.33 to 0.83) and streptococcal throat infections (RR 0.60, 95% CI 0.42 to 0.85). One trial (n= 249) showed 3-weekly intramuscular penicillin injections reduced streptococcal throat infections (RR 0.67, 95% CI 0.48 to 0.92) compared to 4-weekly intramuscular penicillin. REVIEWER'S CONCLUSIONS: Intramuscular penicillin seemed to be more effective than oral penicillin in preventing rheumatic fever recurrence and streptococcal throat infections. Two-weekly or 3-weekly injections appeared to be more effective than 4-weekly injections. However, the evidence is based on poor quality of trials.

Administration, Oral↗

Generation of multipurpose alleles for the functional analysis of the mouse genome.

A novel generation of retroviral gene-trap vectors has been developed with the ability to induce conditional mutations in most genes expressed in mouse embryonic stem (ES) cells. The vectors rely on directional site-specific recombination systems, which can repair and re-induce the gene-trap mutations when activated in succession. After the gene-trap insertions are passaged into mice, this system enables the induction of temporally and spatially restricted mutations in somatic cells. In addition to their conditional features, the vectors create multipurpose alleles amenable to a wide range of post-insertional modifications. These vectors have been used to assemble the largest library of ES cell lines with conditional mutations in single genes, presently totalling 1724 unique genes. Due to their efficiency, the vectors are part of the core technologies to be used by EUCOMM for establishing a complete collection of conditional null mutations in mice.

Alleles↗

Genetic expression by fetal chorionic villi during the first trimester of human gestation.

OBJECTIVE: The growth and differentiation of the embryo and the contiguous placental structures are fundamental to human reproduction and survival. Little is known, however, about the genetic control of these processes during early human development. Normal placentation is the result of a well-orchestrated sequence of events that consists of cellular adhesion and limited invasion controlled by relatively unknown genetic processes. We hypothesized that genes expressed by first-trimester chorionic villi constitute critical regulators of placentation and hence of early human development. Our objective was therefore to isolate and characterize genes, both known and unknown, expressed by the human placenta during the first trimester. STUDY DESIGN: Tissues collected consisted of placental material collected during first-trimester elective pregnancy terminations. Fetal chorionic villi were separated grossly from maternal decidual and quickly frozen in liquid nitrogen for ribonucleic acid preservation. Tissues from different gestational ages were kept separate. Total ribonucleic acid was extracted, messenger ribonucleic acid was isolated, and complementary deoxyribonucleic acid was synthesized. Complementary deoxyribonucleic acid was cloned into the ZAP Express lambda vector (Stratagene, La Jolla, Calif). Automated sequencing of random plaques was done. Sequence homology was searched for with the Basic Local Assignment Search Tool to search the Genbank database (National Center for Biotechnology Institute, Bethesda, Md). In the event that a known gene sequence was derived, no further workup was undertaken. If no homology was identified, the complete complementary deoxyribonucleic acid insert was sequenced in its entirety. Novel genes were further characterized by tissue-specific patterns, cellular localization, and chromosomal location. Expression by fetal villi was confirmed by reverse transcriptase polymerase chain reaction. RESULTS: We isolated a number of genes known to be expressed at the maternal-fetal interface. Seventeen of 186 random clones were >1 kilobase in length and did not display homology with known genes, and these may therefore constitute novel genes critical for placentation. One of the clones from a human chorionic villi complementary deoxyribonucleic acid library at 12 weeks' gestation is a 7-kilobase gene that is also abundantly expressed in human fetal brain, lung, liver, and kidney. In situ hybridization localized the transcript to the fetal renal glomerulus. CONCLUSIONS: Our findings indicate that the placenta serves as a rich source for potential novel gene expression. Seventeen clones were >1 kilobase in length and are potential novel genes involved in early first-trimester placentation. One of these 17 potential novel genes is expressed in abundance in several fetal tissues, which suggests a role in early human fetal development. Other potential novel genes are currently being characterized. The powerful molecular techniques that we used to isolate genes expressed by early fetal chorionic villi will lead us to a better understanding of the genetic control of normal human reproduction. They also may be used to study obstetric and other human disease.

Adult↗

Radiofrequency thermal ablation versus other interventions for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant diseases worldwide. The only possibly curative therapeutic option is surgical resection. Due to impaired liver function and/or anatomical reasons only a low percentage of patients can be treated surgically. For the remainder, several non-surgical treatment approaches have been developed. In addition to percutaneous ethanol injection, transarterial interventions, and several medical interventions, radiofrequency thermal ablation has been investigated in coagulating HCC lesions. OBJECTIVES: To evaluate the effects of radiofrequency thermal ablation in HCC patients with respect to clinically relevant outcomes (mortality, rate of recurrences, adverse events, quality of life, and duration of hospital stay). SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Trials Register, The Cochrane Controlled Trials Register on The Cochrane Library, MEDLINE, Current Contents, EMBASE, and CancerLit until June 2001 and further handsearch was conducted. Reference lists of the identified articles were checked for further trials. SELECTION CRITERIA: All randomised or quasi-randomised clinical trials investigating radiofrequency thermal ablation versus placebo, no intervention, or any other therapeutic approach were considered for inclusion, regardless of blinding, language, and publication status. DATA COLLECTION AND ANALYSIS: Trial inclusion, quality assessment, and data extraction were performed independently by two reviewers. Principal investigators were contacted for further information. MAIN RESULTS: One randomised trial which is still ongoing and only published as an interim analysis was identified. This trial compared radiofrequency thermal ablation versus percutaneous ethanol injection in 102 patients with small HCC. With respect to mortality the trial showed no significant difference between the two treatments (relative risk = 0.19, 95% confidence interval 0.02 to 1.59). Concerning the recurrence free survival the trial demonstrated no significant superiority of radiofrequency thermal ablation versus percutaneous ethanol injection (relative risk = 0.70, 95% confidence interval 0.46 -1.04). REVIEWER'S CONCLUSIONS: At present, radiofrequency thermal ablation is an insufficiently studied intervention for HCC.

Carcinoma, Hepatocellular↗

Status and opportunities for genomics research with rainbow trout.

The rainbow trout (Oncorhynchus mykiss) is one of the most widely studied of model fish species. Extensive basic biological information has been collected for this species, which because of their large size relative to other model fish species are particularly suitable for studies requiring ample quantities of specific cells and tissue types. Rainbow trout have been widely utilized for research in carcinogenesis, toxicology, comparative immunology, disease ecology, physiology and nutrition. They are distinctive in having evolved from a relatively recent tetraploid event, resulting in a high incidence of duplicated genes. Natural populations are available and have been well characterized for chromosomal, protein, molecular and quantitative genetic variation. Their ease of culture, and experimental and aquacultural significance has led to the development of clonal lines and the widespread application of transgenic technology to this species. Numerous microsatellites have been isolated and two relatively detailed genetic maps have been developed. Extensive sequencing of expressed sequence tags has begun and four BAC libraries have been developed. The development and analysis of additional genomic sequence data will provide distinctive opportunities to address problems in areas such as evolution of the immune system and duplicate genes.

Animals↗

Genome resource banking for wildlife research, management, and conservation.

Cryobiology offers an important opportunity to assist in the management and study of wildlife, including endangered species. The benefits of developing genome resource banks for wildlife are profound, perhaps more so than for traditional uses in terms of livestock and human fertility. In addition to preserving heterozygosity and assisting in the genetic management of rare populations held in captivity, frozen repositories help insure wild populations against natural and human-induced catastrophes. Such banks also are an invaluable source of new knowledge (for basic and applied research) from thousands of species that have yet to be studied. However, it is crucial that genome resource banks for wildlife species be developed in a coordinated fashion that first benefits the conservation of biodiversity. Spurious collections will be of no advantage to genuine conservation. The Conservation Breeding Specialist Group (CBSG; of the International Union for the Conservation of Nature and Natural Resources' Species Survival Commission) has promoted international dialogue on this topic. CBSG working groups have recognized that such repositories be developed according to specific, scientific guidelines consistent with an international standard that ensures practicality, high-quality ethics, and cost-effectiveness. Areas requiring priority attention also are reviewed, including the need for more basic research, advocacy, and support for developing organized repositories of biomaterials representing the world's diverse biota.

Animals↗

Mapping the literature of physical therapy.

Physical therapy is a fast growing profession because of the aging population, medical advances, and the public's interest in health promotion. This study is part of the Medical Library Association (MLA) Nursing and Allied Health Resources Section's project to map the allied health literature. It identifies the core journals in physical therapy by analyzing the cited references of articles in two established physical therapy journals, Physical Therapy and Archives of Physical Medicine and Rehabilitation, during the period 1991 through 1993. This bibliometric analysis also determines the extent to which these journals are covered by the primary indexing sources, Allied and Alternative Medicine (AMED), the Cumulative Index to Nursing and Allied Health Literature, EMBASE, and MEDLINE. In this study, fourteen journals were found to supply one-third of all references studied. Ninety-five journals provided an additional third of the references. MEDLINE rated the highest as the indexing tool of choice for these 109 journals. The study results can assist in collection development decisions, advise physical therapists as to the best access to their core literature, and influence database producers to increase their coverage of the literature important to physical therapy.

Abstracting and Indexing↗

Methods of consumer involvement in developing healthcare policy and research, clinical practice guidelines and patient information material.

BACKGROUND: The importance of consumer involvement in health care is widely recognised. Consumers can be involved in developing healthcare policy and research, clinical practice guidelines and patient information material, through consultations to elicit their views or through collaborative processes. Consultations can be single events, or repeated events, large or small scale. They can involve individuals or groups of consumers to allow debate; the groups may be convened especially for the consultation or be established consumer organisations. They can be organised in different forums and through different media. We anticipated finding few comparative evaluations that reliably evaluated the effects of consumer involvement. OBJECTIVES: To assess the effects of consumer involvement and compare different methods of involvement in developing healthcare policy and research, clinical practice guidelines, and patient information material. SEARCH STRATEGY: We searched: the Cochrane Consumers and Communication Review Group's Specialised Register (4 May 2006); the Cochrane Controlled Trials Register (CENTRAL) (The Cochrane Library, Issue 1 2006), MEDLINE (1966 to January Week 2 2006); EMBASE (1980 to Week 03 2006); CINAHL (1982 to December Week 2 2005), PsycINFO (1806 to January Week 3 2006); Sociological Abstracts (1952 to 24 January 2006); and SIGLE (System for Information on Grey Literature in Europe) (1980 to 2003/1). We scanned reference lists from relevant articles and contacted authors. SELECTION CRITERIA: Randomised and quasi-randomised trials, interrupted time series analyses, and controlled before-after studies assessing methods for involving consumers in developing healthcare policy and research, clinical practice guidelines or patient information material. The outcome measures were: participation or response rates of consumers; consumer views elicited; consumer influence on decisions, healthcare outcomes or resource utilisation; consumers' or professionals' satisfaction with the involvement process or resulting products; impact on the participating consumers; costs. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, assessed their quality and extracted data. We contacted study authors for clarification and to seek missing data. We presented results in a narrative summary and pooled data as appropriate. MAIN RESULTS: Five randomised controlled trials of moderate or low methodological quality involving 1031 participants were included. There is moderate quality evidence that involving consumers in the development of patient information material results in material that is more relevant, readable and understandable to patients, without affecting their anxiety. This 'consumer-informed' material can also improve patients' knowledge. There is low quality evidence that using consumer interviewers instead of staff interviewers in satisfaction surveys can have a small influence on the survey results. There is very low quality evidence of telephone discussions and face-to-face group meetings engaging consumers better than mailed surveys in order to set priorities for community health goals, and resulting in different priorities being set for these goals. AUTHORS' CONCLUSIONS: There is little evidence from comparative studies of the effects of consumer involvement in healthcare decisions at the population level. The studies included in this review demonstrate that randomised controlled trials are feasible for providing evidence about the effects of consulting consumers to inform these decisions.

Community Participation↗

Interventions to improve water quality for preventing diarrhoea.

BACKGROUND: Diarrhoeal diseases are a leading cause of mortality and morbidity, especially among young children in developing countries. While many of the infectious agents associated with diarrhoeal disease are potentially waterborne, the evidence for reducing diarrhoea in settings where it is endemic by improving the microbiological quality of drinking water has been equivocal. OBJECTIVES: To assess the effectiveness of interventions to improve water quality for preventing diarrhoea. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (December 2005), CENTRAL (The Cochrane Library 2005, Issue 4), MEDLINE (December 2005), EMBASE (December 2005), and LILACS (December 2005). We also handsearched relevant conference proceedings, contacted researchers and organizations working in the field, and checked references from identified studies. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing interventions aimed at improving the microbiological quality of drinking water with no intervention in children and adults living in settings where diarrhoeal disease is endemic. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We used meta-analyses to estimate pooled measures of effect, where appropriate, and investigated potential sources of heterogeneity using subgroup analyses. MAIN RESULTS: Thirty trials (including 38 independent comparisons) covering over 53,000 participants met the inclusion criteria. Differences between the trials limited the comparability of results and pooling by meta-analysis. In general, the evidence suggests that interventions to improve the microbiological quality of drinking water are effective in preventing diarrhoea both for populations of all ages and children less than five years old. Subgroup analyses suggest that household interventions are more effective in preventing diarrhoea than interventions at the water source. Effectiveness was positively associated with compliance. Effectiveness was not conditioned on the presence of improved water supplies or sanitation in the study setting, and was not enhanced by combining the intervention to improve water quality with other common environmental interventions intended to prevent diarrhoea. AUTHORS' CONCLUSIONS: Interventions to improve water quality are generally effective in preventing diarrhoea, and interventions to improve water quality at the household level are more effective than those at the source. Significant heterogeneity among the trials suggests that the actual level of effectiveness may depend on a variety of conditions that research to date cannot fully explain. Rigorous, blinded, multi-arm randomized controlled trials conducted over a longer duration in a variety if settings may help clarify the potential effectiveness.

Adult↗

A personal reference retrieval system for medium sized computers allowing automatic data entry from ONLINE databases.

A series of programs has been developed for the storage and retrieval of bibliographic references, which allow automatic cross-referencing of the stored entries. Reference retrieval becomes successively faster as more searches are performed and references are automatically sub-grouped under indexed terms allow complete sub-sets to be scanned independently. The indexing allows complete sub-collections of references to be printed, e.g. for a review, with no further searching requirements. This style of retrieval is conceptually similar to card systems in use by many scientists and should enable a rapid familiarization with the retrieval system. The editing features of the programs provide for the direct collection of references from large ONLINE databases (e.g. MEDLINE) and the automatic entering of the references into the personal data collection. The programs provide reliable storage of references for individual scientists, so that their collections from library databases, or from manual input may be updated and searched quickly.

Abstracting and Indexing↗