Toxic effects of chlorinated and brominated alkanoic acids on pseudomonas-putida PP3 : selction at high-frequencies of mutations in genes encoding dehalogenases

Mutant strains of Pseudomonas putida PP3 capable of utilizing monochloroacetate (MCA) and dichloroacetate (DCA) as the sole sources of carbon and energy were isolated from chemostat cultures. The mutants differed from the parent strain in that they could grow on products of MCA and DCA dehalogenation (catalyzed by inducible dehalogenases I and II) and were resistant to growth inhibition by the two substrates. The growth inhibition of strain PP3 by MCA, DCA, and other halogenated alkanoic acids was studied. Sensitivity to dehalogenase substrates was related to the expression of the dehalogenase genes. For example, mutants producing elevated levels of one or both of the dehalogenases were sensitive to 2-monochloropropionate and 2-monochlorobutanoate at concentrations which did not affect the growth of strain PP3. P. putida PP1, the parent of strain PP3, was resistant to the inhibitory effects of MCA and DCA. Spontaneous mutants of strain PP3, also resistant to MCA and DCA, were selected at high frequency, and four different classes of these strains were distinguished on the basis of dehalogenase phenotype. All dehalogenase-producing mutants were inducible; no constitutive mutant has yet been isolated. Most of the resistant mutants examined did not produce one or both of the dehalogenase, and over half of those tested failed to revert back to the parental (strain PP3) phenotype, indicating that the observed mutations involved high-frequency deletion of DNA base sequences affecting expression of genes encoding dehalogenases and associated permease(s)

Performance on the balloon analogue risk task and anticipatory response inhibition task is associated with severity of impulse control behaviours in people with Parkinson's disease

Dopamine agonist medication is one of the largest risk factors for development of problematic impulse control behaviours (ICBs) in people with Parkinson’s disease. The present study investigated the potential of dopamine gene profiling and individual performance on impulse control tasks to explain ICB severity. Clinical, genetic and task performance data were entered into a mixed-effects linear regression model for people with Parkinson’s disease taking (n = 50) or not taking (n = 25) dopamine agonist medication. Severity of ICBs was captured via the Questionnaire for Impulsive-compulsive disorders in Parkinson’s disease Rating Scale. A cumulative dopamine genetic risk score (DGRS) was calculated for each participant from variance in five dopamine-regulating genes. Objective measures of impulsive action and impulsive choice were measured on the Anticipatory Response Inhibition Task and Balloon Analogue Risk Task, respectively. For participants on dopamine agonist medication, task performance reflecting greater impulsive choice (p = 0.014), and to a trend level greater impulsive action (p = 0.056), as well as a longer history of DA medication (p < 0.001) all predicted increased ICB severity. DGRS however, did not predict ICB severity (p = 0.708). No variables could explain ICB severity in the non-agonist group. Our task-derived measures of impulse control have the potential to predict ICB severity in people with Parkinson’s and warrant further investigation to determine whether they can be used to monitor ICB changes over time. The DGRS appears better suited to predicting the incidence, rather than severity, of ICBs on agonist medication.publishedVersio

Musculoskeletal care pathways for adults

Background: Musculoskeletal (MSK) conditions are the most frequently reported chronic conditions and one of the biggest causes of disability in the UK. Given the ageing population and the impact of these problems, the demand for MSK treatment will rise. Despite reduced waiting times, MSK pathways have remained variable and inconsistent and need to be improved to meet patient needs. The aim of this systematic review is to understand the evidence for the effectiveness of current models of service delivery and care pathways for adult hip/knee pain patients accessing secondary care for specialist opinions. Methods: MEDLINE, MEDLINE In-Process, CINAHL, Embase, PEDro, PubMed, Web of Science, Cochrane Central and HMIC databases will be searched without language restrictions for papers published from 1990 onward. Websites will be reviewed for grey literature including care pathways, policy documents and unpublished MSK research. Additionally, reference lists will be checked and citations tracked for included studies. Discussion: The following evidence will be included: research considering care pathways at the intersection between primary and secondary care for adults with hip and/or knee pain in countries with an established clinical pathway. Studies considering generalised inflammatory arthropathy and post-surgical care pathways will be excluded. Screening for included data will be conducted independently by two reviewers. After benchmarking, quality assessment and data extraction will be conducted by one reviewer and checked by a second. A mixed method analysis will be conducted. This systematic review will be used as part of a programme of research to identify best practice for MSK hip and knee pain care pathways. It will provide recommendations for pathway re-design to meet patient needs and ensure efficient streamlining of the patient journey. The review will combine a wide range of information sources including patient and clinician opinion, clinical guidelines, health service delivery research and stakeholder requirements. This should result in a pathway that provides better patient experience and outcomes, whilst meeting the demands placed on the NHS for high-quality evidence-based interventions with efficient use of resources

The value and impact of information provided through library services for patient care: a systematic review

Objective: An updated systematic review was carried out of research studies looking at the value and impact of library services on health outcomes for patients and time saved by health professionals. Methods: A comprehensive systematic search was undertaken of the published literature to September 2003 in ERIC, LISA, Medline, PreMedline, Embase, the Cochrane Controlled Trials Register and Google. Some handsearching was carried out, reference lists were scanned and experts in the field were contacted. 28 research studies of professionally led libraries for healthcare staff, including clinical librarian projects, met the inclusion criterion of at least one health or 'time saved' outcome. Papers were critically appraised using internationally accepted criteria. Data were extracted and results were summarised using a narrative format since the studies were heterogeneous and precluded a statistical analysis. Results: There is evidence of impact from both traditional and clinical librarian services. The higher quality studies of traditional services measured impacts of 37-97% on general patient care, 10-31% on diagnosis, 20-51% on choice of tests, 27-45% on choice of therapy and 10-19% on reduced length of stay. Four studies of clinical librarian projects suggested that professionals saved time as a result of clinical librarian input, and two of these studies showed evidence of cost-effectiveness. However, the clinical librarian studies were generally smaller, with poorer quality standards. Conclusions: Research studies suggest that professionally-led library services have an impact on health outcomes for patients and may lead to time savings for health care professionals. The available studies vary greatly in quality but the better quality studies also suggest positive impacts. Good practice can be gathered from these studies to guide the development of a pragmatic survey for library services that includes the direct effects for patients among the outcome measures

Suicide prevention: update of the summary of evidence

This document has been produced by the Vulnerable Groups Team of the Public Health Wales NHS Trust in conjunction with the Support Unit for Research Evidence at Cardiff University. It updates the document originally published by the National Public Health Service for Wales in 2007. This document brings together evidence relevant to the prevention of suicide and self harm. It adopts a public health approach to prevention and the evidence is presented at four levels. The document is primarily to support the health boards in developing suicide prevention plans but will be of relevance to other agencies and individuals with an interest in suicide and self harm preventio

Searching for research studies in children's social care: some techniques and tools

This report looks at five techniques that may help with a search for research studies in children’s social care