291 research outputs found

    Smc5/6: a link between DNA repair and unidirectional replication?

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    Of the three structural maintenance of chromosome (SMC) complexes, two directly regulate chromosome dynamics. The third, Smc5/6, functions mainly in homologous recombination and in completing DNA replication. The literature suggests that Smc5/6 coordinates DNA repair, in part through post-translational modification of uncharacterized target proteins that can dictate their subcellular localization, and that Smc5/6 also functions to establish DNA-damage-dependent cohesion. A nucleolar-specific Smc5/6 function has been proposed because Smc5/6 yeast mutants display penetrant phenotypes of ribosomal DNA (rDNA) instability. rDNA repeats are replicated unidirectionally. Here, we propose that unidirectional replication, combined with global Smc5/6 functions, can explain the apparent rDNA specificity

    Prevalence of pain-free weeks in chiropractic subjects with low back pain - a longitudinal study using data gathered with text messages

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    <p>Abstract</p> <p>Introduction</p> <p>The use of automated text messages has made it possible to identify different courses of low back pain (LBP), and it has been observed that pain often fluctuates and that absolute recovery is rather rare. The purpose of this study was to describe the prevalence of pain-free weeks and pain-free periods in subjects with non-specific LBP treated by chiropractors, and to compare subjects from two different countries in these aspects.</p> <p>Methods</p> <p>Data were obtained from two practice-based multicentre prospective outcome studies, one Danish and one Swedish, involving subjects being treated by chiropractors for non-specific LBP. Over 18 weeks, subjects answered a weekly automated text message question on the number of days in the past week that they had experienced bothersome LBP, i.e. a number between 0 and 7. The number of weeks in a row without any LBP at all ("zero weeks") as well as the maximum number of zero weeks in a row was determined for each individual. Comparisons were made between the two study samples. Estimates are presented as percentages with 95% confidence intervals.</p> <p>Results</p> <p>In the Danish and the Swedish populations respectively, 93/110 (85%) and 233/262 (89%) of the subjects were eligible for analysis. In both groups, zero weeks were rather rare and were most commonly (in 40% of the zero weeks) reported as a single isolated week. The prevalence of pain free periods, i.e. reporting a maximum of 0, 1 or 2, or 3-6 zero weeks in a row, were similar in the two populations (20-31%). Smaller percentages were reported for ≥ 7 zero weeks in a row. There were no significant differences between the two study groups.</p> <p>Conclusion</p> <p>It was uncommon that chiropractic subjects treated for non-specific LBP experienced an entire week without any LBP at all over 18 weeks. When this occurred, it was most commonly reported for brief periods only. Hence, recovery in the sense that patients become absolutely pain free is rare, even in a primary care population.</p

    Study protocol of cost-effectiveness and cost-utility of a biopsychosocial multidisciplinary intervention in the evolution of non-specific sub-acute low back pain in the working population: cluster randomised trial.

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    This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain (LBP), with high incidence and prevalence rate, is one of the most common reasons to consult the health system and is responsible for a significant amount of sick leave, leading to high health and social costs. The objective of the study is to assess the cost-effectiveness and cost-utility analysis of a multidisciplinary biopsychosocial educational group intervention (MBEGI) of non-specific sub-acute LBP in comparison with the usual care in the working population recruited in primary healthcare centres. Methods/design: The study design is a cost-effectiveness and cost-utility analysis of a MBEGI in comparison with the usual care of non-specific sub-acute LBP.Measures on effectiveness and costs of both interventions will be obtained from a cluster randomised controlled clinical trial carried out in 38 Catalan primary health care centres, enrolling 932 patients between 18 and 65 years old with a diagnosis of non-specific sub-acute LBP. Effectiveness measures are: pharmaceutical treatments, work sick leave (% and duration in days), Roland Morris disability, McGill pain intensity, Fear Avoidance Beliefs (FAB) and Golberg Questionnaires. Utility measures will be calculated from the SF-12. The analysis will be performed from a social perspective. The temporal horizon is at 3 months (change to chronic LBP) and 12 months (evaluate the outcomes at long term. Assessment of outcomes will be blinded and will follow the intention-to-treat principle. Discussion: We hope to demonstrate the cost-effectiveness and cost-utility of MBEGI, see an improvement in the patients' quality of life, achieve a reduction in the duration of episodes and the chronicity of non-specific low back pain, and be able to report a decrease in the social costs. If the intervention is cost-effectiveness and cost-utility, it could be applied to Primary Health Care Centres. Trial registration: ISRCTN: ISRCTN5871969

    The quality of different types of child care at 10 and 18 months. A comparison between types and factors related to quality.

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    The quality of care offered in four different types of non-parental child care to 307 infants at 10 months old and 331 infants at 18 months old was compared and factors associated with higher quality were identified. Observed quality was lowest in nurseries at each age point, except that at 18 months they offered more learning activities. There were few differences in the observed quality of care by child-minders, grandparents and nannies, although grandparents had somewhat lower safety and health scores and offered children fewer activities. Cost was largely unrelated to quality of care except in child-minding, where higher cost was associated with higher quality. Observed ratios of children to adults had a significant impact on quality of nursery care; the more infants or toddlers each adult had to care for, the lower the quality of the care she gave them. Mothers' overall satisfaction with their child's care was positively associated with its quality for home-based care but not for nursery settings

    Hepatitis B Seroprevalence in the U.S. Military and its Impact on Potential Screening Strategies

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    INTRODUCTION: Knowledge of the contemporary epidemiology of hepatitis B virus (HBV) infection among military personnel can inform potential Department of Defense (DoD) screening policy and infection and disease control strategies. MATERIALS AND METHODS: HBV infection status at accession and following deployment was determined by evaluating reposed serum from 10,000 service members recently deployed to combat operations in Iraq and Afghanistan in the period from 2007 to 2010. A cost model was developed from the perspective of the Department of Defense for a program to integrate HBV infection screening of applicants for military service into the existing screening program of screening new accessions for vaccine-preventable infections. RESULTS: The prevalence of chronic HBV infection at accession was 2.3/1,000 (95% CI: 1.4, 3.2); most cases (16/21, 76%) identified after deployment were present at accession. There were 110 military service-related HBV infections identified. Screening accessions who are identified as HBV susceptible with HBV surface antigen followed by HBV surface antigen neutralization for confirmation offered no cost advantage over not screening and resulted in a net annual increase in cost of $5.78 million. However, screening would exclude as many as 514 HBV cases each year from accession. CONCLUSIONS: Screening for HBV infection at service entry would potentially reduce chronic HBV infection in the force, decrease the threat of transfusion-transmitted HBV infection in the battlefield blood supply, and lead to earlier diagnosis and linkage to care; however, applicant screening is not cost saving. Service-related incident infections indicate a durable threat, the need for improved laboratory-based surveillance tools, and mandate review of immunization policy and practice

    Costs and Consequences: Hepatitis C Seroprevalence in the Military and Its Impact on Potential Screening Strategies

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    UNLABELLED: Knowledge of the contemporary epidemiology of hepatitis C viral (HCV) infection among military personnel can inform potential Department of Defense screening policy. HCV infection status at the time of accession and following deployment was determined by evaluating reposed serum from 10,000 service members recently deployed to combat operations in Iraq and Afghanistan in the period 2007-2010. A cost model was developed from the perspective of the Department of Defense for a military applicant screening program. Return on investment was based on comparison between screening program costs and potential treatment costs avoided. The prevalence of HCV antibody-positive and chronic HCV infection at accession among younger recently deployed military personnel born after 1965 was 0.98/1000 (95% confidence interval 0.45-1.85) and 0.43/1000 (95% confidence interval 0.12-1.11), respectively. Among these, service-related incidence was low; 64% of infections were present at the time of accession. With no screening, the cost to the Department of Defense of treating the estimated 93 cases of chronic HCV cases from a single year\u27s accession cohort was 9.3million.ScreeningwiththeHCVantibodytestfollowedbythenucleicacidtestforconfirmationyieldedanetannualsavingsanda9.3 million. Screening with the HCV antibody test followed by the nucleic acid test for confirmation yielded a net annual savings and a 3.1 million dollar advantage over not screening. CONCLUSIONS: Applicant screening will reduce chronic HCV infection in the force, result in a small system costs savings, and decrease the threat of transfusion-transmitted HCV infection in the battlefield blood supply and may lead to earlier diagnosis and linkage to care; initiation of an applicant screening program will require ongoing evaluation that considers changes in the treatment cost and practice landscape, screening options, and the epidemiology of HCV in the applicant/accession and overall force populations

    Target Site Recognition by a Diversity-Generating Retroelement

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    Diversity-generating retroelements (DGRs) are in vivo sequence diversification machines that are widely distributed in bacterial, phage, and plasmid genomes. They function to introduce vast amounts of targeted diversity into protein-encoding DNA sequences via mutagenic homing. Adenine residues are converted to random nucleotides in a retrotransposition process from a donor template repeat (TR) to a recipient variable repeat (VR). Using the Bordetella bacteriophage BPP-1 element as a prototype, we have characterized requirements for DGR target site function. Although sequences upstream of VR are dispensable, a 24 bp sequence immediately downstream of VR, which contains short inverted repeats, is required for efficient retrohoming. The inverted repeats form a hairpin or cruciform structure and mutational analysis demonstrated that, while the structure of the stem is important, its sequence can vary. In contrast, the loop has a sequence-dependent function. Structure-specific nuclease digestion confirmed the existence of a DNA hairpin/cruciform, and marker coconversion assays demonstrated that it influences the efficiency, but not the site of cDNA integration. Comparisons with other phage DGRs suggested that similar structures are a conserved feature of target sequences. Using a kanamycin resistance determinant as a reporter, we found that transplantation of the IMH and hairpin/cruciform-forming region was sufficient to target the DGR diversification machinery to a heterologous gene. In addition to furthering our understanding of DGR retrohoming, our results suggest that DGRs may provide unique tools for directed protein evolution via in vivo DNA diversification
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