New Hits as Antagonists of GPR103 Identified by HTS

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Community pharmacies automation: any impact on counselling duration and job satisfaction?

Background One key indicator of the quality of health practitioners–patient interaction is the encounters’ duration. Automation have been presented as beneficial to pharmacy staff work with patients and thus with a potential impact on pharmacists’ and technicians’ job satisfaction. Objective To compare the interaction length between pharmacy staff and patients, as well as their job satisfaction, in community pharmacies with and without automation. Setting Portuguese community pharmacies with and without automation. Methods This cross-sectional study followed a quasi-experimental design, divided in two phases. In the first, paired community pharmacies with and without automation were purposively selected for a non-participant overt observation. The second phase comprised a job satisfaction questionnaire of both pharmacists and technical staff. Practitioners and patients demographic and interactional data, as well as job satisfaction, were statistically compared across automation. Main outcome measure Interaction length and job satisfaction. Results Sixty-eight practitioners from 10 automated and non-automated pharmacies produced 721 registered interaction episodes. Automation had no significant influence in interaction duration, controlling for gender and professional categories, being significantly longer with older patients (p = 0.017). On average, staff working at the pharmacy counter had 45 % of free time from direct patient contact. The mean overall satisfaction in this sample was 5.52 (SD = 0.98) out of a maximum score of seven, with no significant differences with automation as well as between professional categories, only with a significant lower job satisfaction for younger pharmacists. Conclusion As with previous studies in other settings, duration of the interactions was not influenced by pharmacy automation, as well as practitioners’ job satisfaction, while practitioners’ time constrains seem to be a subjective perception.     

The prospects of single-cell analysis in autoimmunity

In the last decade, there has been a tremendous development of technologies focused on analysing various molecular attributes in single cells, with an ever-increasing number of parameters becoming available at the DNA, RNA and protein levels. Much of this progress has involved cells in suspension, but also in situ analysis of tissues has taken great leaps. Paralleling the development in the laboratory, and because of increasing complexity, the analysis of single-cell data is also constantly being updated with new algorithms and analysis platforms. Our immune system shares this complexity, and immunologists have therefore been in the forefront of this technological development. These technologies clearly open new avenues for immunology research, maybe particularly within autoimmunity where the interaction between the faulty immune system and the thymus or the target organ is important. However, the technologies currently available can seem overwhelming and daunting. The aim of this review is to remedy this by giving a balanced overview of the prospects of using single-cell analysis in basal and clinical autoimmunity research, with an emphasis on endocrine autoimmunity.     

The Osteogenic Effect of Erythropoietin on Human Mesenchymal Stromal Cells is Dose-Dependent and Involves Non-Hematopoietic Receptors and Multiple Intracellular Signaling Pathways

Erythropoietin (EPO) is a pleiotropic growth factor. Of interest for skeletal tissue engineering, the non-hematopoietic capabilities of EPO include its osteogenic and angiogenic potencies. The main aim of this study was to investigate the dose–response relationship and determine the lowest effective dose of EPO that reliably increases the osteogenic differentiation of human mesenchymal stromal cells (hMSCs). Additional aims were to elucidate the surface receptors and to investigate the role of the intracellular signaling pathways by blocking the mammalian target of rapamycin (mTOR), Jak-2 protein tyrosine kinase (JAK2), and phosphoinositide 3-kinases (PI3K). The primary outcome measures were two mineralization assays, Arsenazo III and alizarin red, applied after 10, 14, and 21 days. Moreover, alkaline phosphatase activity, cell number, and cell viability were determined after 2 and 7 days. A proportional dose–response relationship was observed. In vivo, the lowest effective dose of 20 IU/ml should be used for further research to accommodate safety concerns about adverse effects. Ex vivo, the most effective dose of 100 IU/ml could facilitate vascularization and bone ingrowth in cell-based scaffolds. The expression of non-hematopoietic receptors EPOR and CD131 was documented, and EPO triggered all three examined intracellular pathways. Future studies of the efficacy of EPO in cell-based tissue engineering can benefit from our findings.     

Post-cesarean surgical site infections according to CDC standards: rates and risk factors. A prospective cohort study

OBJECTIVES: The aim of this study was to document the true incidence of post-cesarean surgical site infections (SSI), according to the definition of the US Centers for Disease Control and Prevention (CDC), and to identify independent risk factors for infection. DESIGN: Prospective population-based cohort study in Norway. Setting. Sykehuset Asker og Baerum HF, a secondary community hospital, associated with the University of Oslo (UiO), Norway, accounting for 2,000 deliveries per year. Participants. All cesarean deliveries during a 12-month period from September 2003. Main outcome measures. Rate and risk factors for SSI. RESULTS: The total rate of SSI was 8.9%, with an observation period of 30 days post-operatively, compared to 1.8% registered at hospital discharge. The total response rate was 100%. There was no significant difference in SSI rate in elective or emergency cesarean section (CS), respectively. All SSI were superficial. We found 2 significant independent risk factors: operating time > or =38 min and body mass index (BMI) >30. CONCLUSION: The rate of SSI is underestimated if the observation time is limited to the hospital stay. Operating time exceeding 38 min substantially increases the risk of SSI. The finding of no significant difference in SSI rate between elective and emergency CS should lead to a different approach concerning the use of antibiotics: subgroup at risk (operating time > or =38 min and BMI >30) may benefit from antibiotics in relation to the operation, whether the CS is an emergency or elective operation.     

Regulation of actin dynamics by protein kinase R control of gelsolin enforces basal innate immune defense

Primary resistance to pathogens is reliant on both basal and inducible immune defenses. To date, research has focused upon inducible innate immune responses. In contrast to resistance via cytokine induction, basal defense mechanisms are less evident. Here we showed that the antiviral protein kinase R (PKR) inhibited the key actin-modifying protein gelsolin to regulate actin dynamics and control cytoskeletal cellular functions under homeostatic conditions. Through this mechanism, PKR controlled fundamental innate immune, actin-dependent processes that included membrane ruffling and particle engulfment. Accordingly, PKR counteracted viral entry into the cell. These findings identify a layer of host resistance, showing that the regulation of actin-modifying proteins during the innate immune response bolsters first-line defense against intracellular pathogens and has a sustained effect on virus production. Moreover, these data provide proof of principle for a concept in which the cell cytoskeleton could be targeted to elicit broad antiviral protection.