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Selected AbstractsExpression of the porcine adrenergic receptor beta 2 gene in longissimus dorsi muscle is affected by cis -regulatory DNA variationANIMAL GENETICS, Issue 1 2009E. Muráni Summary The beta-2 adrenergic receptor (AR) mediates metabolic actions of catecholamines, including glycogenolysis, lipolysis and proteolysis, in muscle and adipose tissue. Factors influencing the density of beta-2 ARs thus might affect carcass composition and meat quality. One such factor might represent cis -regulatory DNA variation affecting mRNA expression of the adrenergic receptor beta 2 (ADRB2) gene in relevant tissues. To identify potential cis -regulatory DNA variation of porcine ADRB2, we comparatively sequenced part of the 5, flanking region and identified 10 single nucleotide polymorphisms (SNPs). The SNP at position g.673C>T (AF000134) resides in an evolutionarily conserved region (ECR) in an in silico predicted androgen response element. Quantification of total transcript levels and allelic expression imbalance (AEI) revealed significant variability in mRNA expression of ADRB2 in longissimus dorsi muscle of slaughter pigs, partly attributable to cis -regulatory DNA variation. However, the g.673C>T SNP has, in the given temporo-spatial context, no significant effect but is apparently in linkage disequilibrium with the causal cis -regulatory DNA variant. We used the g.673C>T SNP as a marker to study the association of ADRB2 variation with carcass and meat quality in four commercial lines. We found association with the pH of loin at 45 min and 24 h postmortem (p.m.) and with the pH of ham at 24 h p.m. Supporting evidence for ADRB2 as a candidate gene for pork quality is provided by our assignment of the gene to the telomeric end of the q arm of porcine chromosome 2, where several quantitative trait loci for meat quality were reported. [source] REALISE-ing their potential?: implementing local library projects to support evidence-based health careHEALTH INFORMATION & LIBRARIES JOURNAL, Issue 2 2001Louise Falzon Librarian involvement in Evidence-based Health Care provides many opportunities at a local level. Unfortunately, the potential for innovative projects to inform future developments is generally lost by a failure to ,pass the baton',to identify lessons learnt and transferable principles. The ,Library Support for Evidence-based Health Care' Project, funded by the NHS Executive Northern and Yorkshire, resulted in the implementation of locally responsive packages of hardware and software in six of the Region's libraries. The opportunity to evaluate the collective experience of these sites, and to synthesize principles of good practice, was provided by a separately funded post-hoc evaluation, the Research Evaluation to Audit Library and Information Support for EBHC (REALISE). This paper reports on how this evaluation was conducted, documents the strengths and weaknesses of the Project itself, and attempts to provide a checklist for use in similar projects. The paper concludes by outlining the relevance of the findings to the introduction of planned organizational approaches to quality (clinical governance) and the development of local implementation strategies across the UK, required by the NHS Information Strategy, Information for Health. [source] The impact of pharmacy computerised clinical decision support on prescribing, clinical and patient outcomes: a systematic review of the literatureINTERNATIONAL JOURNAL OF PHARMACY PRACTICE, Issue 2 2010Jane Robertson Abstract Objectives Computerised clinical decision support systems (CDSSs) are being used increasingly to support evidence-based decision-making by health care professionals. This systematic review evaluated the impact of CDSSs targeting pharmacists on physician prescribing, clinical and patient outcomes. We compared the impact of CDSSs addressing safety concerns (drug interactions, contraindications, dose monitoring and adjustment) and those focusing on medicines use in line with guideline recommendations (hereafter referred to as Quality Use of Medicines, or QUM). We also examined the influence of clinical setting (institutional versus ambulatory care), system- or user-initiation of CDSS, prescribing versus clinical outcomes reported and use of multi-faceted versus single interventions on system effectiveness. Methods We searched Medline, Embase, CINAHL and PsycINFO (1990,2009) for methodologically adequate studies (experiments and strong quasi-experiments) comparing a CDSS with usual pharmacy care. Individual study results are reported as positive trends or statistically significant results in the direction of the intentions of the CDSS being tested. Studies are aggregated and compared as the proportions of studies showing the effectiveness of the CDSS on the majority (, 50%) of outcomes reported in the individual study. Key findings Of 21 eligible studies, 11 addressed safety and 10 QUM issues. CDSSs addressing safety issues were more effective than CDSSs focusing on QUM (10/11 versus 4/10 studies reporting statistically significant improvements in favour of CDSSs on , 50% of all outcomes reported; P= 0.01). A number of QUM studies noted the limited contact between pharmacists and physicians relating to QUM treatment recommendations. More studies demonstrated CDSS benefits on prescribing outcomes than clinical outcomes (10/10 versus 0/3 studies; P= 0.002). There were too few studies to assess the impact of system- versus user-initiated CDSS, the influence of setting or multi-faceted interventions on CDSS effectiveness. Conclusions Our study demonstrated greater effectiveness of safety-focused compared with QUM-focused CDSSs. Medicine safety issues are traditional areas of pharmacy activity. Without good communication between pharmacists and physicians, the full benefits of QUM-focused CDSSs may not be realised. Developments in pharmacy-based CDSSs need to consider these inter-professional relationships as well as computer-system enhancements. [source] Systematic reviews to support evidence-based psychiatry: what about schizophrenia?JOURNAL OF EVALUATION IN CLINICAL PRACTICE, Issue 6 2009Massimo Morlino MD Abstract Objective, To assess whether systematic reviews (SRs), the gold standard for scientific research, can offer valuable support in evidence-based psychiatry in the treatment of schizophrenia. Methods, We used three database services (Ovid, PubMed and Cochrane) to identify SRs related to schizophrenia, found 163 reviews and grouped them by topic. We then evaluated each study's conclusions and divided them into three groups based on results (ranging from certain to null conclusions). Results, SRs of pharmacological treatments represented 59% of the studies sampled, only 23% of which had reached certain conclusions. Other clinical topics were less frequently represented and had achieved lower degrees of certainty. Conclusions, Only 40 SRs (22 studies investigating pharmacological treatment) provided clear-cut answers to clinical questions examined. Results therefore showed that SRs provide a certain but rather limited contribution to scientific evidence in the field of schizophrenia. [source] Preference Conditioning in Healthy Individuals: Correlates With Hazardous DrinkingALCOHOLISM, Issue 6 2010Iris M. Balodis Background:, Conditioned reward is a classic measure of drug-induced brain changes in animal models of addiction. The process can be examined in humans using the Conditioned Pattern Preference (CPP) task, in which participants associate nonverbal cues with reward but demonstrate low awareness of this conditioning. Previously, we reported that alcohol intoxication does not affect CPP acquisition in humans, but our data indicated that prior drug use may impact conditioning scores. Methods:, To test this possibility, the current study examined the relationship between self-reported alcohol use and preference conditioning in the CPP task. Working memory was assessed during conditioning by asking participants to count the cues that appeared at each location on a computer screen. Participants (69 female and 23 male undergraduate students) completed the Alcohol Use Disorders Identification Test (AUDIT) and the Rutgers Alcohol Problem Index (RAPI) as measures of hazardous drinking. Results:, Self-reported hazardous drinking was significantly correlated with preference conditioning in that individuals who scored higher on these scales exhibited an increased preference for the reward-paired cues. In contrast, hazardous drinking did not affect working memory errors on the CPP task. Conclusions:, These findings support evidence that repeated drug use sensitizes neural pathways mediating conditioned reward and point to a neurocognitive disposition linking substance misuse and responses to reward-paired stimuli. The relationship between hazardous drinking and conditioned reward is independent of changes in cognitive function, such as working memory. [source] Total body exposure to ultraviolet radiation does not influence plasma levels of immunoreactive ,-endorphin in manPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 6 2001Marjolein Wintzen Background/Aims: A growing number of reports support evidence of proopiomelanocortin (POMC)-derived peptides in human skin cells, although not consistently. Also the effect of ultraviolet radiation (UVR) on cutaneous and plasma levels of these POMC peptides has not been established unequivocally. We hypothesized that production of ,-endorphin (,E) may explain the sense of well-being many people experience when sun-bathing. The aim of the present study was to investigate whether exposure of the skin to UVR elevates plasma ,E. Method: Healthy volunteers (n=26) received a single, weighted dose of 15 J/cm2 of UVA. Several times during the hour following irradiation, plasma ,E- immunoreactivity (,E-IR) was determined by radioimmunoassay. The effect of repeated exposure wasassessed in 35 patients treated with UVB, UVA, or UVA-1. Plasma ACTH-IR was monitored in parallel. Results: Overall, plasma levels of ,E-IR and ACTH-IR showed no significant changes during the experiment, indicating that these peptides are not influenced by single or repeated exposures to UVR of different wavelengths. Conclusion: On the basis of these results, the skin does not appear to contribute significantly to the levels of circulating ,E or ACTH. These data offer no support for the hypothesis that exposure to UVR leads to an increased concentration of circulating ,E, which could contribute to the feeling of well-being that often accompanies sun-bathing. [source] Effects of two novel cationic staphylococcal proteins (NP-taseand p70) and enterotoxin B on IgE synthesis and interleukin-4 and interferon-, production in patients with atopic dermatitisBRITISH JOURNAL OF DERMATOLOGY, Issue 4 2000A. Jahreis We have characterized the cell-mediated and humoral immune response of patients with atopic dermatitis (AD) and healthy controls in response to two novel staphylococcal antigens (NP-tase, p70) and the superantigen staphylococcal enterotoxin B (SEB). The parameters studied were IgE, interleukin (IL)-4 and interferon (IFN)-, synthesis by peripheral blood mononuclear cells (PBMC) after stimulation with NP-tase, p70 and SEB in vitro. Both antigens, as well as SEB, induced IL-4 and IFN-, secretion in patients and controls. However, patients with AD showed a significantly diminished IFN-, production in response to NP-tase or SEB. Furthermore, we demonstrated a good correlation between antigen-stimulated IgE production and the IL-4/IFN-, ratio in vitro. A distinct subgroup of PBMC showed impaired IFN-, synthesis and enhanced IL-4 secretion after incubation with p70 or NP-tase. These data support evidence that a subgroup of patients with AD, synthesizing low levels of IFN-, after stimulation with staphylococcal antigens, may have impaired abilities to clear Staphylococcus aureus colonization. Persistent staphylococcal antigens could then be responsible for inflammatory and allergic skin reactions in patients with AD. We therefore conclude that, besides superantigens, staphylococcal antigens may also play a part in the pathogenesis of AD. [source] Detection of muscarinic receptor subtypes in human urinary bladder mucosa: Age and gender-dependent modifications,,§NEUROUROLOGY AND URODYNAMICS, Issue 5 2008Nicola Arrighi Abstract Aims Muscarinic receptor subtypes expressed in the human urinary bladder mucosa were characterized, investigating whether there were gender-dependent differences and if aging could induce changes in their expression. Methods The study was carried out on 34 subjects, 22 men and 12 women, divided in four groups, based on gender and age. Gene expression was evaluated by quantitative RT-PCR. The Western blot was performed using the 4,12% NuPAGE Bis,Tris Gel System. Results The molecular expression of each subtype of the M1 receptor family was observed and it was not influenced either by gender or age. M2 receptor family transcripts revealed that both M2 and M4 were detected and that the M2 transcripts were modified by both gender and age. Indeed, M2 mRNA was lower in old rather than adult men (P,<,0.05), but higher in rather old than adult women (P,<,0.05). Further, adult men expressed more M2 mRNA than adult women (P,<,0.05), while the opposite was detected in old age (P,<,0.05). The Western blot followed by quantification confirmed that the mRNAs were translated into proteins, and that the M2 subtype showed similar modifications found at molecular level. Discussion The selective modification of M2 receptors observed at the urinary bladder mucosa levels indicates that this anatomical structure could play an active role in the pathophysiology of micturition and supports evidence suggesting an effect of antimuscarinic drugs at this level. Whether these results may influence the age-dependent development of micturition disorders remains to be determined. Neurourol. Urodynam. 27:421,428, 2008. © 2007 Wiley-Liss, Inc. [source] |