7,668 research outputs found

    Use of scanned detection in optical position encoders

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    The physiological expression of inducible nitric oxide synthase (iNOS) in the human colon

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    Inducible nitric oxide synthase (iNOS) is expressed in the colonic epithelium in both inflammatory bowel disease and colorectal cancer. Nitric oxide (NO), the product of this enzyme, has been implicated in the pathogenesis of both conditions. However, there are conflicting data on whether iNOS is expressed in the normal, uninflamed human colon. To evaluate the expression of iNOS in histologically normal, non-inflamed human colonic mucosa. Reverse transcription polymerase chain reaction (RT-PCR), immunoblotting, and immunohistochemistry were used to investigate the expression of iNOS in 17 histologically normal specimens obtained at colectomy performed for colorectal neoplasia. In addition, 16 endoscopic mucosal biopsies, taken from normal individuals, were also evaluated. Eleven surgical specimens and 16 endoscopic biopsies from patients with refractory ulcerative colitis were used as inflammatory controls. All types of specimens expressed iNOS mRNA. Immunoblotting revealed a protein of approximately 130 kDa consistent with iNOS in mucosal extracts of 77% of normal individuals, and 85% of diseased controls. Immunolabelling localised this protein to the surface epithelium in most of the normal specimens and also to the crypt epithelium and inflammatory cells in the diseased controls. These findings provide evidence that iNOS is often expressed in the surface epithelium of non-inflamed human colon, suggesting that it is induced by local luminal factors, such as bacterial lipopolysaccharide (endotoxin). The resultant NO produced at this site might act as an oxidative barrier, reducing bacterial translocation and providing a means of defence against pathogenic microorganisms

    Pharmacokinetics of adrenaline autoinjectors.

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    Anaphylaxis is a medical emergency with adrenaline acknowledged as the first line therapy. It is therefore important that patients have access to self-injectable adrenaline in the community. Manufacturers have been requested by European Medicine Regulators to generate pharmacokinetic data for these autoinjector devices. For the first time, these data provide an insight into how individual devices work in different populations, and how they compare. We undertook a thorough literature search and also accessed grey literature, using searches of medicine regulators' websites and freedom of information requests. The data demonstrate that it takes at least 5-10 minutes to achieve early peak plasma concentration for most devices. The specific autoinjector device seems to be the most important determinant of pharmacokinetics, with different devices giving rise to different plasma adrenaline profiles. Needle length does not seem to be the most important factor; rather, the force and speed of injection (which varies from one device to another) is likely to be of greater importance. In general, peak plasma adrenaline concentration is lower and time-to-peak concentration longer with increased skin-to-muscle depth. However, it is difficult to draw conclusions with the current available data, due to a lack of head-to-head comparisons, small numbers of study participants, and the failure to acknowledge the biphasic nature of intramuscular adrenaline absorption for analysis purposes

    Identification of differentially distributed gene expression and distinct sets of cancer-related genes identified by changes in mean and variability.

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    There is increasing evidence that changes in the variability or overall distribution of gene expression are important both in normal biology and in diseases, particularly cancer. Genes whose expression differs in variability or distribution without a difference in mean are ignored by traditional differential expression-based analyses. Using a Bayesian hierarchical model that provides tests for both differential variability and differential distribution for bulk RNA-seq data, we report here an investigation into differential variability and distribution in cancer. Analysis of eight paired tumour-normal datasets from The Cancer Genome Atlas confirms that differential variability and distribution analyses are able to identify cancer-related genes. We further demonstrate that differential variability identifies cancer-related genes that are missed by differential expression analysis, and that differential expression and differential variability identify functionally distinct sets of potentially cancer-related genes. These results suggest that differential variability analysis may provide insights into genetic aspects of cancer that would not be revealed by differential expression, and that differential distribution analysis may allow for more comprehensive identification of cancer-related genes than analyses based on changes in mean or variability alone

    Why lose weight? Reasons for seeking weight loss by overweight but otherwise healthy men

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    OBJECTIVE: To identify the reasons for seeking weight loss in overweight or obese but otherwise healthy men. DESIGN: Interviews, prior to intervention, with subjects who had volunteered to participate in a work-site-based weight loss study. SUBJECTS: Ninety-one overweight=obese male workers. Mean age 41, range 18 – 55 y, mean body mass index (BMI) 31.0, range 26.2 – 41.6 kg=m2. MEASUREMENTS: Anthropometric measurements; body weight and height. Body mass index calculated. A short interview using open questions to determine the individuals reason for seeking weight loss. RESULTS: The message that weight loss is beneficial to health for the overweight was recognized by all subjects regardless of BMI, and was reported as the main factor for attempting weight loss. Improved fitness and effects on appearance and well-being were reported half as often as the primary reason for weight loss. CONCLUSION: Overweight lay members of the public have accepted the health education message that weight loss can improve health. Overweight but otherwise healthy men who responded, of their own accord, to an electronic mail message offering help to lose weight did not regard obesity and overweight as primarily a cosmetic issue. This is still, however, important, especially to younger people

    Preparing pharmacists to deliver a targeted service in hypertension management: Evaluation of an interprofessional training program

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    © 2015 Bajorek et al. Background: Non-adherence to medicines by patients and suboptimal prescribing by clinicians underpin poor blood pressure (BP) control in hypertension. In this study, a training program was designed to enable community pharmacists to deliver a service in hypertension management targeting therapeutic adjustments and medication adherence. A comprehensive evaluation of the training program was undertaken. Methods: Tailored training comprising a self-directed pre-work manual, practical workshop (using real patients), and practice scenarios, was developed and delivered by an inter-professional team (pharmacists, GPs). Supported by practical and written assessment, the training focused on the principles of BP management, BP measurement skills, and adherence strategies. Pharmacists' experience of the training (expectations, content, format, relevance) was evaluated quantitatively and qualitatively. Immediate feedback was obtained via a questionnaire comprising Likert scales (1∈=∈"very well" to 7∈=∈"poor") and open-ended questions. Further in-depth qualitative evaluation was undertaken via semi-structured interviews several months post-training (and post service implementation). Results: Seventeen pharmacists were recruited, trained and assessed as competent. All were highly satisfied with the training; other than the 'amount of information provided' (median score∈=∈5, "just right"), all aspects of training attained the most positive score of '1'. Pharmacists most valued the integrated team-based approach, GP involvement, and inclusion of real patients, as well as the pre-reading manual, BP measurement workshop, and case studies (simulation). Post-implementation the interviews highlighted that comprehensive training increased pharmacists' confidence in providing the service, however, training of other pharmacy staff and patient recruitment strategies were highlighted as a need in future. Conclusions: Structured, multi-modal training involving simulated and inter-professional learning is effective in preparing selected community pharmacists for the implementation of new services in the context of hypertension management. This training could be further enhanced to prepare pharmacists for the challenges encountered in implementing and evaluating services in practice

    TetAB46, a predicted heterodimeric ABC transporter conferring tetracycline resistance in Streptococcus australis isolated from the oral cavity.

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    OBJECTIVES: To identify the genes responsible for tetracycline resistance in a strain of Streptococcus australis isolated from pooled saliva from healthy volunteers in France. S. australis is a viridans Streptococcus, originally isolated from the oral cavity of children in Australia, and subsequently reported in the lungs of cystic fibrosis patients and as a cause of invasive disease in an elderly patient. METHODS: Agar containing 2 mg/L tetracycline was used for the isolation of tetracycline-resistant organisms. A genomic library in Escherichia coli was used to isolate the tetracycline resistance determinant. In-frame deletions and chromosomal repair were used to confirm function. Antibiotic susceptibility was determined by agar dilution and disc diffusion assay. RESULTS: The tetracycline resistance determinant from S. australis FRStet12 was isolated from a genomic library in E. coli and DNA sequencing showed two open reading frames predicted to encode proteins with similarity to multidrug resistance-type ABC transporters. Both genes were required for tetracycline resistance (to both the naturally occurring and semi-synthetic tetracyclines) and they were designated tetAB(46). CONCLUSIONS: This is the first report of a predicted ABC transporter conferring tetracycline resistance in a member of the oral microbiota
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