Functional constraints on the constitutive androstane receptor inferred from human sequence variation and cross-species comparisons

<p>Abstract</p> <p>Members of the NR1I subfamily of nuclear receptors play a role in the transcriptional activation of genes involved in drug metabolism and transport. NR1I3, the constitutive androstane receptor (CAR), mediates the induction of several genes involved in drug response, including members of the <it>CYP3A</it>, <it>CYP2B </it>and <it>UGT1A </it>subfamilies. Large inter-individual variation in drug clearance has been reported for many drug metabolising enzyme genes. Sequence variation at the <it>CAR </it>locus could potentially contribute to variation in downstream targets, as well as to the substantial variation in expression level reported. We used a comparative genomics-based approach to select resequencing segments in 70 subjects from three populations. We identified 21 polymorphic sites, one of which results in an amino acid substitution. Our study reveals a common haplotype shared by all three populations which is remarkably similar to the ancestral sequence, confirming that CAR is under strong functional constraints. The level and pattern of sequence variation is approximately similar across populations, suggesting that interethnic differences in drug metabolism are not likely to be due to genetic variation at the <it>CAR </it>locus. We also identify several common non-coding variants that occur at highly conserved sites across four major branches of the mammalian phylogeny, suggesting that they may affect <it>CAR </it>expression and, ultimately, the activity of its downstream targets.</p

Electrical studies and plasma characterization of an atmospheric pressure plasma jet operated at low frequency

Low-temperature, high-pressure plasma jets have an extensive use in medical and biological applications. Much work has been devoted to study these applications while comparatively fewer studies appear to be directed to the discharge itself. In this work, in order to better understand the kind of electrical discharge and the plasma states existing in those devices, a study of the electrical characteristics of a typical plasma jet, operated at atmospheric pressure, using either air or argon, is reported. It is found that the experimentally determined electrical characteristics are consistent with the model of a thermal arc discharge, with a highly collisional cathode sheet. The only exception is the case of argon at the smallest electrode separation studied, around 1 mm in which case the discharge is better modeled as either a non-thermal arc or a high-pressure glow. Also, variations of the electrical behavior at different gas flow rates are interpreted, consistently with the arc model, in terms of the development of fluid turbulence in the external jet.Fil: Giuliani, Leandro Estanislao. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; ArgentinaFil: Xaubet Brea, Magalí Noel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; ArgentinaFil: Grondona, Diana Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; ArgentinaFil: Minotti, Fernando Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; ArgentinaFil: Kelly, Hector Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; Argentin

Antibiotic susceptibility of Neochlamydia hartmanellae and Parachlamydia acanthamoebae in amoebae.

Parachlamydia acanthamoebae and Neochlamydia hartmanellae are Chlamydia-related bacteria naturally infecting free-living amoebae. These strict intracellular bacteria might represent emerging pathogens. Recent studies report an association with lower respiratory tract infections, especially with pneumonia where they have been identified as a potential causative agent in 1-2% of cases. In this study, we defined the antibiotic susceptibility of N. hartmanellae, two strains of P. acanthamoebae and two yet unclassified Parachlamydiaceae strains using a quantitative approach. We confirmed the results obtained earlier for P. acanthamoebae strain Bn9 in an observational study. Macrolides (MICs &lt; 0.06-0.5 μg/ml), rifampicin (MICs 0.25-2) and doxycycline (2-4 μg/ml) were active against P. acanthamoebae strains and Neochlamydia. All strains were resistant to amoxicillin, ceftriaxone and imipenem (MIC ≥32 μg/ml). Similarly to other Chlamydia-related bacteria, all investigated Parachlamydiaceae were resistant to quinolones (MICs ≥ 16 μg/ml). Therefore, we recommend a treatment with macrolides for Parachlamydia-associated pneumonia

Evaluation of a web-based app to assist home-hazard modification in falls prevention

Given the impact falls can have on older people and their families, many health and social care services are focused on preventing falls and implementing interventions to reduce future falls. FallCheck is a web app that supports identification of home-hazards and directs users towards self-management strategies to reduce risk of falling. Method: A survey by clinical experts of a beta version of FallCheck was conducted, producing quantitative and qualitative data including issues and attributes identified by respondents. Thirty-six individuals signed up to take part in the study, and 27 respondents took part in the final evaluation survey. Findings: Testing by health and social care professionals found there is scope for using the app as a digital self-assessment tool by people at risk of falls. It has further potential as an effective tool to support environmental/behavioural change to reduce risk of falls. Conclusion: FallCheck was developed from a sound evidence-base to support home-hazard modification as an effective intervention component within a multifactorial intervention to prevent falls. Health and social care professionals found it had good acceptability for use in practice, justifying further testing of the usability and effectiveness of the app in supporting behavioural changes and environmental modifications with people at risk of falling and carers

Addressing Inequities in Urban Health: Do Decision-Makers Have the Data They Need? Report from the Urban Health Data Special Session at International Conference on Urban Health Dhaka 2015

Rapid and uncontrolled urbanisation across low and middle-income countries is leading to ever expanding numbers of urban poor, defined here as slum dwellers and the homeless. It is estimated that 828 million people are currently living in slum conditions. If governments, donors and NGOs are to respond to these growing inequities they need data that adequately represents the needs of the urban poorest as well as others across the socio-economic spectrum. We report on the findings of a special session held at the International Conference on Urban Health, Dhaka 2015. We present an overview of the need for data on urban health for planning and allocating resources to address urban inequities. Such data needs to provide information on differences between urban and rural areas nationally, between and within urban communities. We discuss the limitations of data most commonly available to national and municipality level government, donor and NGO staff. In particular we assess, with reference to the WHO’s Urban HEART tool, the challenges in the design of household surveys in understanding urban health inequities. We then present two novel approaches aimed at improving the information on the health of the urban poorest. The first uses gridded population sampling techniques within the design and implementation of household surveys and the second adapts Urban HEART into a participatory approach which enables slum residents to assess indicators whilst simultaneously planning the response. We argue that if progress is to be made towards inclusive, safe, resilient and sustainable cities, as articulated in Sustainable Development Goal 11, then understanding urban health inequities is a vital pre-requisite to an effective response by governments, donors, NGOs and communities

Internet-based medical education: a realist review of what works, for whom and in what circumstances

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Patient information leaflets (PILs) for UK randomised controlled trials : a feasibility study exploring whether they contain information to support decision making about trial participation

Peer reviewedPublisher PD

Seizures and Brain Tumor in Neurologically Intact Adult Patients: Role of Computerized Tomography (CT Scan)

CT scan of 13 patients with adult onset of seizures who were neurologically intact and otherwise asymptomatic revealed a supratentorial mass in all. Significant EEG abnormalities were recorded in five, and the isotope brain scan was positive in eight. In three patients, both studies were normal. Angiograms confirmed the location of tumor, and histology was established following craniotomy. The value of the CT scan as a screening test for detecting brain tumor in this group of seizure patients is evident

Quantitative image analysis for the characterization of microbial aggregates in biological wastewater treatment : a review

Quantitative image analysis techniques have gained an undeniable role in several fields of research during the last decade. In the field of biological wastewater treatment (WWT) processes, several computer applications have been developed for monitoring microbial entities, either as individual cells or in different types of aggregates. New descriptors have been defined that are more reliable, objective, and useful than the subjective and time-consuming parameters classically used to monitor biological WWT processes. Examples of this application include the objective prediction of filamentous bulking, known to be one of the most problematic phenomena occurring in activated sludge technology. It also demonstrated its usefulness in classifying protozoa and metazoa populations. In high-rate anaerobic processes, based on granular sludge, aggregation times and fragmentation phenomena could be detected during critical events, e.g., toxic and organic overloads. Currently, the major efforts and needs are in the development of quantitative image analysis techniques focusing on its application coupled with stained samples, either by classical or fluorescent-based techniques. The use of quantitative morphological parameters in process control and online applications is also being investigated. This work reviews the major advances of quantitative image analysis applied to biological WWT processes.The authors acknowledge the financial support to the project PTDC/EBB-EBI/103147/2008 and the grant SFRH/BPD/48962/2008 provided by Fundacao para a Ciencia e Tecnologia (Portugal)