Heparin and Heparan Sulfate: Analyzing Structure and Microheterogeneity [chapter]

available in PMC 2013 August 28The structural microheterogeneity of heparin and heparan sulfate is one of the major reasons for the multifunctionality exhibited by this class of molecules. In a physiological context, these molecules primarily exert their effects extracellularly by mediating key processes of cellular cross-talk and signaling leading to the modulation of a number of different biological activities including development, cell proliferation, and inflammation. This structural diversity is biosynthetically imprinted in a nontemplate-driven manner and may also be dynamically remodeled as cellular function changes. Understanding the structural information encoded in these molecules forms the basis for attempting to understand the complex biology they mediate. This chapter provides an overview of the origin of the structural microheterogeneity observed in heparin and heparan sulfate, and the orthogonal analytical methodologies that are required to help decipher this information

The worldwide NORM production and a fully automated gamma-ray spectrometer for their characterization

Materials containing radionuclides of natural origin, which is modified by human made processes and being subject to regulation because of their radioactivity are known as NORM. We present a brief review of the main categories of non-nuclear industries together with the levels of activity concentration in feed raw materials, products and waste, including mechanisms of radioisotope enrichments. The global management of NORM shows a high level of complexity, mainly due to different degrees of radioactivity enhancement and the huge amount of worldwide waste production. The future tendency of guidelines concerning environmental protection will require both a systematic monitoring based on the ever-increasing sampling and high performance of gamma ray spectroscopy. On the ground of these requirements a new low background fully automated high-resolution gamma-ray spectrometer MCA_Rad has been developed. The design of Pb and Cu shielding allowed to reach a background reduction of two order of magnitude with respect to laboratory radioactivity. A severe lowering of manpower cost is obtained through a fully automation system, which enables up to 24 samples to be measured without any human attendance. Two coupled HPGe detectors increase the detection efficiency, performing accurate measurements on sample volume (180 cc) with a reduction of sample transport cost of material. Details of the instrument calibration method are presented. MCA_Rad system can measure in less than one hour a typical NORM sample enriched in U and Th with some hundreds of Bq/kg, with an overall uncertainty less than 5%. Quality control of this method has been tested. Measurements of certified reference materials RGK-1, RGU-2 and RGTh-1 containing concentrations of K, U and Th comparable to NORM have been performed, resulting an overall relative discrepancy of 5% among central values within the reported uncertainty.Comment: 21 pages, 4 figures, 6 table

Efficacy of a training intervention on the quality of practitioners' decision support for patients deciding about place of care at the end of life: A randomized control trial: Study protocol

<p>Abstract</p> <p>Background</p> <p>Most people prefer home palliation but die in an institution. Some experience decisional conflict when weighing options regarding place of care. Clinicians can identify patients' decisional needs and provide decision support, yet generally lack skills and confidence in doing so. This study aims to determine whether the quality of clinicians' decision support can be improved with a brief, theory-based, skills-building intervention.</p> <p>Theory</p> <p>The Ottawa Decision Support Framework (ODSF) guides an evidence based, practical approach to assist clinicians in providing high-quality decision support. The ODSF proposes that decisional needs [personal uncertainty, knowledge, values clarity, support, personal characteristics] strongly influence the quality of decisions patients make. Clinicians can improve decision quality by providing decision support to address decisional needs [clarify decisional needs, provide facts and probabilities, clarify values, support/guide deliberation, monitor/facilitate progress].</p> <p>Methods/Design</p> <p>The efficacy of a brief education intervention will be assessed in a two-phase study. In phase one a focused needs assessment will be conducted with key informants. Phase two is a randomized control trial where clinicians will be randomly allocated to an intervention or control group. The intervention, informed by the needs assessment, knowledge transfer best practices and the ODSF, comprises an online tutorial; an interactive skills building workshop; a decision support protocol; performance feedback, and educational outreach. Participants will be assessed: a) at baseline (quality of decision support); b) after the tutorial (knowledge); and c) four weeks after the other interventions (quality of decision support, intention to incorporate decision support into practice and perceived usefulness of intervention components). Between group differences in the primary outcome (quality of decision support scores) will be analyzed using ANOVA.</p> <p>Discussion</p> <p>Few studies have investigated the efficacy of an evidence-based, theory guided intervention aimed at assisting clinicians to strengthen their patient decision support skills. Expanding our understanding of how clinicians can best support palliative patients' decision-making will help to inform best practices in patient-centered palliative care. There is potential transferability of lessons learned to other care situations such as chronic condition management, advance directives and anticipatory care planning. Should the efficacy evaluation reveal clear improvements in the quality of decision support provided by clinicians who received the intervention, a larger scale implementation and effectiveness trial will be considered.</p> <p>Trial registration</p> <p>This study is registered as NCT00614003</p

Pro-inflammatory profile of preeclamptic placental mesenchymal stromal cells: new insights into the etiopathogenesis of preeclampsia.

The objective of the present study was to evaluate whether placental mesenchymal stromal cells (PDMSCs) derived from normal and preeclamptic (PE) chorionic villous tissue presented differences in their cytokines expression profiles. Moreover, we investigated the effects of conditioned media from normal and PE-PDMSCs on the expression of pro-inflammatory Macrophage migration Inhibitory Factor (MIF), Vascular Endothelial Growth Factor (VEGF), soluble FMS-like tyrosine kinase-1 (sFlt-1) and free β-human Chorionic Gonadotropin (βhCG) by normal term villous explants. This information will help to understand whether anomalies in PE-PDMSCs could cause or contribute to the anomalies typical of preeclampsia. METHODS: Chorionic villous PDMSCs were isolated from severe preeclamptic (n = 12) and physiological control term (n = 12) placentae. Control and PE-PDMSCs’s cytokines expression profiles were determined by Cytokine Array. Control and PE-PDMSCs were plated for 72 h and conditioned media (CM) was collected. Physiological villous explants (n = 48) were treated with control or PE-PDMSCs CM for 72 h and processed for mRNA and protein isolation. MIF, VEGF and sFlt-1 mRNA and protein expression were analyzed by Real Time PCR and Western Blot respectively. Free βhCG was assessed by immunofluorescent. RESULTS: Cytokine array showed increased release of pro-inflammatory cytokines by PE relative to control PDMSCs. Physiological explants treated with PE-PDMSCs CM showed significantly increased MIF and sFlt-1 expression relative to untreated and control PDMSCs CM explants. Interestingly, both control and PE-PDMSCs media induced VEGF mRNA increase while only normal PDMSCs media promoted VEGF protein accumulation. PE-PDMSCs CM explants released significantly increased amounts of free βhCG relative to normal PDMSCs CM ones. CONCLUSIONS: Herein, we reported elevated production of pro-inflammatory cytokines by PE-PDMSCs. Importantly, PE PDMSCs induced a PE-like phenotype in physiological villous explants. Our data clearly depict chorionic mesenchymal stromal cells as central players in placental physiopathology, thus opening to new intriguing perspectives for the treatment of human placental-related disorders as preeclampsia

Instruments to assess the perception of physicians in the decision-making process of specific clinical encounters: a systematic review

<p>Abstract</p> <p>Background</p> <p>The measurement of processes and outcomes that reflect the complexity of the decision-making process within specific clinical encounters is an important area of research to pursue. A systematic review was conducted to identify instruments that assess the perception physicians have of the decision-making process within specific clinical encounters.</p> <p>Methods</p> <p>For every year available up until April 2007, PubMed, PsycINFO, Current Contents, Dissertation Abstracts and Sociological Abstracts were searched for original studies in English or French. Reference lists from retrieved studies were also consulted. Studies were included if they reported a self-administered instrument evaluating physicians' perceptions of the decision-making process within specific clinical encounters, contained sufficient description to permit critical appraisal and presented quantitative results based on administering the instrument. Two individuals independently assessed the eligibility of the instruments and abstracted information on their conceptual underpinnings, main evaluation domain, development, format, reliability, validity and responsiveness. They also assessed the quality of the studies that reported on the development of the instruments with a modified version of STARD.</p> <p>Results</p> <p>Out of 3431 records identified and screened for evaluation, 26 potentially relevant instruments were assessed; 11 met the inclusion criteria. Five instruments were published before 1995. Among those published after 1995, five offered a corresponding patient version. Overall, the main evaluation domains were: satisfaction with the clinical encounter (n = 2), mutual understanding between health professional and patient (n = 2), mental workload (n = 1), frustration with the clinical encounter (n = 1), nurse-physician collaboration (n = 1), perceptions of communication competence (n = 2), degree of comfort with a decision (n = 1) and information on medication (n = 1). For most instruments (n = 10), some reliability and validity criteria were reported in French or English. Overall, the mean number of items on the modified version of STARD was 12.4 (range: 2 to 18).</p> <p>Conclusion</p> <p>This systematic review provides a critical appraisal and repository of instruments that assess the perception physicians have of the decision-making process within specific clinical encounters. More research is needed to pursue the validation of the existing instruments and the development of patient versions. This will help researchers capture the complexity of the decision-making process within specific clinical encounters.</p

Social comparison, self-stereotyping, and gender differences in self-construals

Four studies examined gender differences in self-construals and the role of social comparison in generating these differences. Consistent with previous research, Study 1 (N = 461) showed that women define themselves as higher in relational interdependence than men, and men define themselves as higher in independence/agency than women. Study 2 (N = 301) showed that within-gender social comparison decreases gender differences in self-construals relative to a control condition, whereas between-genders comparison increases gender differences on both relational interdependence and independence/agency. Studies 3 (N = 169) and 4 (N = 278) confirmed these findings and showed that changing self-construal changes gender differences in social dominance orientation. Across the 4 studies, strong evidence for the role of in-group stereotyping as mediator of the effect of gender on self-construal was observed on the relational dimension but not on the agentic dimension