The GCC repeat length in the 5'UTR of MRP1 gene is polymorphic: a functional characterization of its relevance for cystic fibrosis

BACKGROUND: Among the members of the ATP binding cassette transporter superfamily, MRPs share the closest homology with the CFTR protein, which is defective in CF disease. MRP1 has been proposed as a potential modifier gene and/or as novel target for pharmacotherapy of CF to explain the clinical benefits observed in some CF patients treated with the macrolide AZM. The 5'UTR of the MRP1 gene contains a GCC triplet repeat that could represent a polymorphic site and affect the activity of the promoter. METHODS: The MRP1 5' flanking region was amplified by PCR from 36 CF patients and 100 non-CF subjects and the number of GCC triplets of each allele was determined by sequence and electrophoretic analysis. We performed gene reporter studies in CF airway epithelial cells 16HBE14o-AS3, in basal conditions and in the presence of AZM. RESULTS: We found that the GCC repeat is polymorphic, ranging from 7 to 14 triplets either in CF or in non-CF subjects. Our data are preliminary and have to be confirmed on a larger population of CF subjects. The transcriptional activity of the proximal MRP1 5' regulatory region revealed no statistically significant correlations between the number of repeats and treatment with AZM. CONCLUSION: We identified a novel polymorphism in the 5'UTR of MRP1 gene that provides multiple alleles in a gene relevant for multidrug resistance as well as for CF, determining that this region is transcriptionally active and that this activity does not appear to be influenced by AZM treatment

Predictors of binge drinking in adolescents: ultimate and distal factors - a representative study

<p>Abstract</p> <p>Background</p> <p>As epidemiological surveys have shown, binge drinking is a constant and wide-spread problem behavior in adolescents. It is not rare to find that more than half of all adolescents engage in this behavior when assessing only the last 4 weeks of time independent of the urbanity of the region they live in. There have been several reviews on predictors of substance consumption in adolescents in general, but there has been less high quality research on predictors of binge drinking, and most studies have not been theoretically based. The current study aimed to analyze the ultimate and distal factors predicting substance consumption according to Petraitis' theory of triadic influence. We assessed the predictive value of these factors with respect to binge drinking in German adolescents, including the identification of influence direction.</p> <p>Methods</p> <p>In the years 2007/2008, a representative written survey of N = 44,610 students in the 9^thgrade of different school types in Germany was carried out (net sample). The return rate of questionnaires was 88% regarding all students whose teachers or school directors had agreed to participate in the study. In this survey, prevalence of binge drinking was investigated as well as potential predictors from the social/interpersonal, the attitudinal/environmental, and the intrapersonal fields (3 factors of Petraitis). In a multivariate logistic regression analysis, these variables were included after testing for multicollinearity in order to assess their ability to predict binge drinking.</p> <p>Results</p> <p>Prevalence of binge drinking in the last 30 days was 52.3% for the surveyed adolescents with a higher prevalence for boys (56.9%) than for girls (47.5%). The two most influential factors found to protect against binge drinking with <it>p </it>< .001 were low economic status and importance of religion. The four most relevant risk factors for binge drinking (<it>p </it>< .001) were life-time prevalence of school absenteeism/truancy, academic failure, suicidal thoughts, and violence at school in the form of aggressive behavior of teachers. The model of Petraitis was partly confirmed for Binge Drinking in German adolescents and the direction of influence factors was clarified.</p> <p>Conclusions</p> <p>Whereas some of the risk and protective factors for binge drinking are not surprising since they are known for substance abuse in general, there are two points that could be targeted in interventions that do not focus on adolescents alone: (a) training teachers in positive, reassuring behavior and constructive criticism and (b) a focus on high risk adolescents either because they have a lack of coping strategies when in a negative mood or because of their low academic achievement in combination with absenteeism from school.</p

Community planning and urban design in contested places. Some insights from Belfast

Although social conflict due to the presence of different groups divided by cultural, religious or ethnic issues plagues many contemporary cities, community and participatory planning methods still pay little attention to segregation in contested spaces as a specific matter of concern. This paper aims to contribute to filling this gap through the development of a novel tool to be implemented during community planning processes in contested cities, particularly in (visual) mapping processes. The pilot area for developing the lexicon has been selected within the city of Belfast, which has been struggling for years with problems related to inter-religious sectarian conflicts. The material effects on the urban structure of the long process of defensive planning during the socalled Troubles and within the post-conflicts peace programmes have been investigated by analysing urban artefacts including edges, borders, barriers, doors, visual control points. The paper suggests that a simple, recognizable lexicon may contribute to honing community planning methods in contested places by integrating the traditional methodology of visual mapping with a tailored taxonomy of elements of urban conflict, which may be used at many stages of the planning process, including developing a visual map, design and planning, and developing and implementing an action plan

Global wealth disparities drive adherence to COVID-safe pathways in head and neck cancer surgery

Peer reviewe

"Delirium Day": A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 \ub1 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys

Non linear ciruit model of a polymer electrolyte membrane fuel cell

A nonlinear circuit model of a polymer electrolyte membrane (PEM) fuel cell stack is presented. The model considers the time dimension, allowing the simulation of both steady-state and dynamic behaviour of the stack. The circuit parameters can be obtained by means of simple experimental tests and calculations. The PEM stack is modeled as seen from the power conditioning system side, without requiring parameters necessary for complex mathematical models and not easily obtainable by the majority of users. A procedure of parameter determination is developed and a comparison between the simulated and experimental results for both steady-state and dynamic behaviour of the PEM stack is shown

Nonlinear circuit model of a polymer electrolyte membrane fuel cell

A nonlinear circuit model of a polymer electrolyte membrane (PEM) fuel cell stack is presented. The model considers the time dimension, allowing the simulation of both steady-state and dynamic behaviour of the stack. The circuit parameters can be obtained by means of simple experimental tests and calculations. The PEM stack is modeled as seen from the power conditioning system side, without requiring parameters necessary for complex mathematical models and not easily obtainable by the majority of users. A procedure of parameter determination is developed and a comparison between the simulated and experimental results for both steady-state and dynamic behaviour of the PEM stack is shown