27,538 research outputs found

    Smoking and health-related quality of life in English general population: Implications for economic evaluations

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    Copyright @ 2012 Vogl et al; licensee BioMed Central Ltd. 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.This article has been made available through the Brunel Open Access Publishing Fund.Background: Little is known as to how health-related quality of life (HRQoL) when measured by generic instruments such as EQ-5D differ across smokers, ex-smokers and never-smokers in the general population; whether the overall pattern of this difference remain consistent in each domain of HRQoL; and what implications this variation, if any, would have for economic evaluations of tobacco control interventions. Methods: Using the 2006 round of Health Survey for England data (n = 13,241), this paper aims to examine the impact of smoking status on health-related quality of life in English population. Depending upon the nature of the EQ-5D data (i.e. tariff or domains), linear or logistic regression models were fitted to control for biology, clinical conditions, socio-economic background and lifestyle factors that an individual may have regardless of their smoking status. Age- and gender-specific predicted values according to smoking status are offered as the potential 'utility' values to be used in future economic evaluation models. Results: The observed difference of 0.1100 in EQ-5D scores between never-smokers (0.8839) and heavy-smokers (0.7739) reduced to 0.0516 after adjusting for biological, clinical, lifestyle and socioeconomic conditions. Heavy-smokers, when compared with never-smokers, were significantly more likely to report some/severe problems in all five domains - mobility (67%), self-care (70%), usual activity (42%), pain/discomfort (46%) and anxiety/depression (86%) -. 'Utility' values by age and gender for each category of smoking are provided to be used in the future economic evaluations. Conclusion: Smoking is significantly and negatively associated with health-related quality of life in English general population and the magnitude of this association is determined by the number of cigarettes smoked. The varying degree of this association, captured through instruments such as EQ-5D, may need to be fed into the design of future economic evaluations where the intervention being evaluated affects (e.g. tobacco control) or is affected (e.g. treatment for lung cancer) by individual's (or patients') smoking status

    Molecular mechanisms of autoimmunity triggered by microbial infection

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    Autoimmunity can be triggered by microbial infection. In this context, the discovery of Toll-like receptors (TLRs) provides new insights and research perspectives. TLRs induce innate and adaptive antimicrobial immune responses upon exposure to common pathogen-associated molecules, including lipopeptides, lipopolysaccharides, and nucleic acids. They also have the potential, however, to trigger autoimmune disease, as has been revealed by an increasing number of experimental reports. This review summarizes important facts about TLR biology, available data on their role in autoimmunity, and potential consequences for the management of patients with autoimmune disease

    Intra- and interspecies interactions between prion proteins and effects of mutations and polymorphisms

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    Recently, crystallization of the prion protein in a dimeric form was reported. Here we show that native soluble homogenous FLAG-tagged prion proteins from hamster, man and cattle expressed in the baculovirus system are predominantly dimeric. The PrP/PrP interaction was confirmed in Semliki Forest virus-RNA transfected BHK cells co-expressing FLAG- and oligohistidine-tagged human PrP. The yeast two-hybrid system identified the octarepeat region and the C-terminal structured domain (aa90-aa230) of PrP as PrP/PrP interaction domains. Additional octarepeats identified in patients suffering from fCJD reduced (wtPrP versus PrP+90R) and completely abolished (PrP+90R versus PrP+90R) the PrP/PrP interaction in the yeast two-hybrid system. In contrast, the Met/Val polymorphism (aa129), the GSS mutation Pro102Leu and the FFI mutation Asp178Asn did not affect PrP/PrP interactions. Proof of interactions between human or sheep and bovine PrP, and sheep and human PrP, as well as lack of interactions between human or bovine PrP and hamster PrP suggest that interspecies PrP interaction studies in the yeast two-hybrid system may serve as a rapid pre-assay to investigate species barriers in prion diseases

    Highlight: Molecular machines

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    Development of a test system to analyze different hip fracture osteosyntheses under simulated walking

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    The mechanical complications of osteosyntheses after hip fractures are previously investigated by mostly static or dynamic uniaxial loading test systems. However, the physiologic loading of the hip joint during a normal gait is a multiplanar, dynamic movement. Therefore, we constructed a system to test osteosyntheses for hip fractures under physiologic multiplanar loading representative of normal gait. To evaluate the testing system, 12 femora pairs were tested under 25,000 cycles with two standard osteosyntheses (Proximal Femoral Nail Antirotation/Gamma3 Nail). For angular movement, the varus collapse to cut out (proportional to(CO)) (proportional to(CO) = 4.8 degrees +/- 2.1 degrees for blade and proportional to(CO) = 7.8 degrees +/- 3.8 degrees for screw) was the dominant failure mode, and only slight rotational angle shifts (proportional to(Rot)) (proportional to(Rot) = 1.7 degrees +/- 0.4 degrees for blade and proportional to(Rot) = 2.4 degrees +/- 0.3 degrees for screw) of the femoral head around the implant axis were observed. Angular displacements in varus direction and rotation were higher in specimens reinforced with screws. Hence, the cut out model and the migration directions showed a distinction between helical blade and hip screw. However, there were no significant differences between the different implants. The new setup is able to create clinical failures and allows to give evidence about the anchorage stability of different implant types under dynamic gait motion pattern

    Fever-like temperature modification differentially affects in vitro signaling of bradykinin B-1 and B-2 receptors

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    The bradykinin (BK) B-2 and B-1 receptors (B2R, B1R) belong to the rhodopsin-like G protein-coupled receptors (GPCRs) and are involved in (patho)physiological processes such as blood pressure regulation or inflammation. They mediate the effects of the pro-inflammatory peptides bradykinin/kallidin and desArg(9)-BK/desArg(10)-kallidin, respectively. Whereas the B2R is constitutively expressed and gets internalized upon activation, the B1R is especially induced by inflammatory mediators and responds to stimulation with increased surface receptor numbers. Stimulation of both receptors activates phospholipase C beta (PLC beta) and mitogen activated protein kinase (MAPK) signaling. Because inflammatory processes are characterized by heat (fever), we analyzed the effect of increased temperature (41 degrees C vs. 37 degrees C) on B1R and B2R signaling in HEK 293 and IMR 90 cells. Our results show that signaling of both receptors is temperature-sensitive, however to a different extent and with regard to the investigated pathways. Comparing PLCb activity and Ca2+-regulated signals, a temperature-dependent increase was only observed for B1R but not for B2R activation, whereas MAPK activities were doubled at 41 degrees C for both receptors. Taken together, our findings suggest that the observed temperature sensitivity of B1R-induced PLCb activation is B1R-specific. In contrast, the enhanced stimulation of MAPK activity under hyperthermic conditions appears to be a common phenomenon for GPCRs

    Finiteness and children with specific language impairment: an exploratory study

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    Children with specific language impairment (SLI) are well known for their difficulties in mastering the inflectional paradigms; in the case of learning German they also have problems with the appropriate verb position, in particular with the verb in second position. This paper explores the possibilities of applying a broader concept of finiteness to data from children with SLI in order to put their deficits, or rather their skills, into a wider perspective. The concept, as developed by Klein (1998, 2000), suggests that finiteness is tied to the assertion that a certain state of affairs is valid with regard to some topic time; that is, finiteness relates the propositional content to the topic component. Its realization involves the interaction of various grammatical devices and, possibly, lexical means like temporal adverbs. Furthermore, in the acquisition of finiteness it has been found that scope particles play a major role in both first- and second-language learning. The purpose of this paper is to analyze to what extent three German-learning children with SLI have mastered these grammatical and lexical means and to pinpoint the phase in the development of finiteness they have reached. The data to be examined are mostly narrative and taken from conversations and experiments. It will be shown that each child chooses a different developmental path to come to grips with the interaction of these devices

    Decreasing resistance in the maternal uterine and peripheral arterial system is apparently unrelated to plasma and urinary levels of nitrite/nitrate and cyclic-guanosinmonophosohate during the course of normal pregnancies

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    Aims: The aim of the presented study was to clarify the relationship between the pulsatility index of the uterine arteries and the maternal cubital artery and peripheral concentrations of the metabolites of nitric oxide (NO) and its second messenger cyclic guanosinmonophophate (cGMP) during the normal course of pregnancy and postpartum. Methods: 49 uncomplicated pregnancies were investigated every 46 weeks until delivery, 29 of them were additionally investigated postpartum. Paralleling each Doppler sonografic investigation maternal blood and urine samples were taken. The measurements of nitrite/ nitrate and cGMP were performed with a colorimetric and radio immuno assay. We demonstrate a significant decrease of the PI of the uterine arteries and of the cubital artery with inverse correlation to advancing gestational age. Results: The concentrations of nitrite/nitrate and cGMP remain stable during gestation and do not correlate to the PI of the uterine and cubital artery. Postpartum a reincrease in the uterine and peripheral resistance can be shown. The concentrations of urinary cGMP and nitrite/ nitrate as well as plasma cGMP remain unchanged, whereas plasma nitrite/nitrate decreases postpartum. Conclusions: The status of NO biosyntheses in normal pregnancy remains controversial. We hypothesize further systemically acting mediators which contribute to the decreasing vascular resistance

    Liquid chromatography-tandem mass spectrometry - Application in the clinical laboratory

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    This review provides a concise survey of liquid chromatography tandem mass spectrometry (LCTMS) as an emerging technology in clinical chemistry. The combination of two mass spectrometers with an interposed collision cell characterizes LCTMS as an analytical technology on its own and not just as a more specific detector for HPLC compared with conventional techniques. In LCTMS, liquid chromatography is rather used for sample preparation but not for complete resolution of compounds of interest. The instrument technology of LCTMS is complex and comparatively expensive; however, in routine use, methods are far more rugged compared to conventional chromatographic techniques and enable highthroughput analyses with very limited manual handling steps. Moreover, compared to both gas chromatographymass spectrometry (GCMS) and conventional HPLC techniques, LCTMS is substantially more versatile with respect to the spectrum of analyzable compounds. For these reasons it is likely that LCTMS will gain far more widespread use in the clinical laboratory than HPLC and GCMS ever did. In this article, the key features of LCTMS are described, method development is explained, typical fields of application are discussed, and personal experiences are related
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