365 research outputs found

    Ultra-brief intervention for problem drinkers: research protocol

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    Background: Helping the large number of problem drinkers who will never seek treatment is a challenging issue. Public health initiatives employing educational materials or mass media campaigns have met with mixed success. However, clinical research has developed effective brief interventions to help problem drinkers. This project will employ an intervention that has been validated in clinical settings and then modified into an ultra-brief format suitable for use as a public health intervention. The major objective of this study is to conduct a randomized controlled trial to establish the effectiveness of an ultra-brief, personalized feedback intervention for problem drinkers. Methods/design: Problem drinkers recruited on a baseline population telephone survey conducted in a major metropolitan city in Canada will be randomized to one of three conditions - a personalized feedback pamphlet condition, a control pamphlet condition, or a no intervention control condition. In the week after the baseline survey, households in the two pamphlet conditions will be sent their respective pamphlets. Changes in drinking will be assessed post intervention at three-month and six-month follow-ups. Drinking outcomes will be compared between experimental conditions using Structural Equation Modeling. The primary hypothesis is that problem drinkers from households who receive the personalized feedback pamphlet intervention will display significantly improved drinking outcomes at three and six-month follow-ups as compared to problem drinkers from households in the no intervention control condition. Secondary hypotheses will test the impact of the intervention on help seeking, and explore the mediating or moderating role of perceived drinking norms, perceived alcohol risks and the problem drinker's social reasons for drinking. Discussion: This trial will provide information on the effectiveness of a pamphlet-based personalized feedback intervention for problem drinkers in a community setting. Trial registration: ClinicalTrials.gov registration #NCT00688584.This study is funded by the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Grant #R01 AA015680-01A2

    Subdivisions of the Auditory Midbrain (N. Mesencephalicus Lateralis, pars dorsalis) in Zebra Finches Using Calcium-Binding Protein Immunocytochemistry

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    The midbrain nucleus mesencephalicus lateralis pars dorsalis (MLd) is thought to be the avian homologue of the central nucleus of the mammalian inferior colliculus. As such, it is a major relay in the ascending auditory pathway of all birds and in songbirds mediates the auditory feedback necessary for the learning and maintenance of song. To clarify the organization of MLd, we applied three calcium binding protein antibodies to tissue sections from the brains of adult male and female zebra finches. The staining patterns resulting from the application of parvalbumin, calbindin and calretinin antibodies differed from each other and in different parts of the nucleus. Parvalbumin-like immunoreactivity was distributed throughout the whole nucleus, as defined by the totality of the terminations of brainstem auditory afferents; in other words parvalbumin-like immunoreactivity defines the boundaries of MLd. Staining patterns of parvalbumin, calbindin and calretinin defined two regions of MLd: inner (MLd.I) and outer (MLd.O). MLd.O largely surrounds MLd.I and is distinct from the surrounding intercollicular nucleus. Unlike the case in some non-songbirds, however, the two MLd regions do not correspond to the terminal zones of the projections of the brainstem auditory nuclei angularis and laminaris, which have been found to overlap substantially throughout the nucleus in zebra finches

    Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

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    Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

    Interferon-Alpha Mediates Restriction of Human Immunodeficiency Virus Type-1 Replication in Primary Human Macrophages at an Early Stage of Replication

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    Type I interferons (IFNα and β) are induced directly in response to viral infection, resulting in an antiviral state for the cell. In vitro studies have shown that IFNα is a potent inhibitor of viral replication; however, its role in HIV-1 infection is incompletely understood. In this study we describe the ability of IFNα to restrict HIV-1 infection in primary human macrophages in contrast to peripheral blood mononuclear cells and monocyte-derived dendritic cells. Inhibition to HIV-1 replication in cells pretreated with IFNα occurred at an early stage in the virus life cycle. Late viral events such as budding and subsequent rounds of infection were not affected by IFNα treatment. Analysis of early and late HIV-1 reverse transcripts and integrated proviral DNA confirmed an early post entry role for IFNα. First strand cDNA synthesis was slightly reduced but late and integrated products were severely depleted, suggesting that initiation or the nucleic acid intermediates of reverse transcription are targeted. The depletion of integrated provirus is disproportionally greater than that of viral cDNA synthesis suggesting the possibility of a least an additional later target. A role for either cellular protein APOBEC3G or tetherin in this IFNα mediated restriction has been excluded. Vpu, previously shown by others to rescue a viral budding restriction by tetherin, could not overcome this IFNα induced effect. Determining both the viral determinants and cellular proteins involved may lead to novel therapeutic approaches. Our results add to the understanding of HIV-1 restriction by IFNα

    Kinetic and stoichiometric characterization of anoxic sulfideoxidation by SO-NR mixed cultures from anoxic biotrickling filters.

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    Monitoring the biological activity in biotrickling filters is difficult since it implies estimating biomass concentration and its growth yield, which can hardly be measured in immobilized biomass systems. In this study, the characterization of a sulfide-oxidizing nitrate-reducing biomass obtained from an anoxic biotrickling filter was performed through the application of respirometric and titrimetric techniques. Previously, the biomass was maintained in a continuous stirred tank reactor under steady-state conditions resulting in a growth yield of 0.328±0.045 g VSS/g S. To properly assess biological activity in respirometric tests, abiotic assays were conducted to characterize the stripping of CO2 and sulfide. The global mass transfer coefficient for both processes was estimated. Subsequently, different respirometric tests were performed: (1) to solve the stoichiometry related to the autotrophic denitrification of sulfide using either nitrate or nitrite as electron acceptors, (2) to evaluate the inhibition caused by nitrite and sulfide on sulfide oxidation, and (3) to propose, calibrate, and validate a kinetic model considering both electron acceptors in the overall anoxic biodesulfurization process. The kinetic model considered a Haldane-type equation to describe sulfide and nitrite inhibitions, a non-competitive inhibition to reflect the effect of sulfide on the elemental sulfur oxidation besides single-step denitrification since no nitrite was produced during the biological assays

    A study of a couple with type 2 diabetes: dyadic adjustment and psychological morbidity

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    Objective: this study assessed dyadic adjustment and psychological morbidity in type 2 diabetic patients and their partners, focusing on the role of gender. Methods: 214 diabetic patients and their partners participated in the cross-sectional study and were assessed on psychological morbidity (HADS) and marital adjustment (RDAS). Data was analyzed using dyadic analysis, a statistical process that studies the patient/partner dyads simultaneously. Results: results revealed that the negative relationship between dyadic adjustment and psychological morbidity in female patients was stronger than in male diabetic patients or in partners of male diabetic patients. On the other hand, the relationship between dyadic adjustment and psychological morbidity in partners of diabetic men was stronger than the same relationship in partners of diabetic women. Conclusion: since gender is a moderator, it is important to attend to the different needs of female and male patients and the education of diabetic patients should be centered on the patient/partner dyad.Fundação para a Ciência e a Tecnologia (FCT

    Reliability and Validity of the Dutch Version of the Brief Infant-Toddler Social and Emotional Assessment (BITSEA)

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    Background: The Brief Infant-Toddler Social and Emotional Assessment (BITSEA) is a relatively new and short (42-item) questionnaire that measures psychosocial problems in toddlers and consists of a Problem and a Competence scale. In this study the reliability and validity of the Dutch version of the BITSEA were examined for the whole group and for gender and ethnicity subgroups. Methods: Parents of 7140 two-year-old children were invited in the study, of which 3170 (44.4%) parents completed the BITSEA. For evaluation of the score distribution, the presence of floor/ceiling effects was determined. The internal consistency (Cronbach's alpha) was evaluated and in subsamples the test-retest, parent-childcare provider interrater reliability and concurrent validity with regard to the Child Behavioral Checklist (CBCL). Discriminative validity was evaluated by comparing scores of parents that worry and parents that do not worry about their child's development. Results: The BITSEA showed no floor or ceiling effects. Psychometric properties of the BITSEA Problem and Competence scale were respectively: Cronbach's alphas were 0.76 and 0.63. Test-retest correlations were 0.75 and 0.61. Interrater reliability correlations were 0.30 and 0.17. Concurrent validity was as hypothesised. The BITSEA was able to discriminate between parents that worry about their child and parents that do not worry. The psychometric properties of the BITSEA were comparable across gender and ethnic background. Conclusion: The results in this large-scale study of a diverse sample support the reliability and validity of the BITSEA Problem scale. The BITSEA Competence scale needs further study. The performance of the BITSEA appears to be similar in subgroups by gender and ethnic background

    KCND3 potassium channel gene variant confers susceptibility to electrocardiographic early repolarization pattern.

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    BACKGROUNDThe presence of an early repolarization pattern (ERP) on the surface ECG is associated with risk of ventricular fibrillation and sudden cardiac death. Family studies have shown that ERP is a highly heritable trait, but molecular genetic determinants are unknown.METHODSTo identify genetic susceptibility loci for ERP, we performed a GWAS and meta-analysis in 2,181 cases and 23,641 controls of European ancestry.RESULTSWe identified a genome-wide significant (P < 5 × 10-8) locus in the potassium voltage-gated channel subfamily D member 3 (KCND3) gene that was successfully replicated in additional 1,124 cases and 12,510 controls. A subsequent joint meta-analysis of the discovery and replication cohorts identified rs1545300 as the lead SNP at the KCND3 locus (OR 0.82 per minor T allele, P = 7.7 × 10-12) but did not reveal additional loci. Colocalization analyses indicate causal effects of KCND3 gene expression levels on ERP in both cardiac left ventricle and tibial artery.CONCLUSIONSIn this study, we identified for the first time to our knowledge a genome-wide significant association of a genetic variant with ERP. Our findings of a locus in the KCND3 gene provide insights not only into the genetic determinants but also into the pathophysiological mechanism of ERP, discovering a promising candidate for functional studies.FUNDINGThis project was funded by the German Center for Cardiovascular Research (DZHK Shared Expertise SE081 - STATS). For detailed funding information per study, see the Supplemental Acknowledgments
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