Assessing satisfaction in simulation among nursing students: psychometric properties of the Satisfaction with Simulation Experience - Italian Version scale.

BACKGROUND: The Satisfaction with Simulation Experience scale is a 5-point Likert scale that measures students' satisfaction in medium and high-fidelity simulation scenarios. This study aims at investigating the psychometric properties of the Satisfaction with Simulation Experience - Italian Version scale. METHODS: A multi-centre cross-sectional study was conducted. The scale was administered to a sample of 266 undergraduate nursing students from two Italian universities after attending a medium- and high-fidelity simulation session in November 2022 and March 2023. Cronbach's alpha coefficient and item-total correlation were sorted out to assess internal consistency and reliability. The test-retest method was used as a measure of scale stability over time as well as the confirmatory factor analysis to verify construct validity. RESULTS: The Cronbach's alpha value was 0.94 for the overall scale, indicating excellent reliability, and it was 0.84 or higher for each subscales, indicating good reliability. A large correlation coefficient of 0.60 or higher was found between each item and its subscale and between each item and the overall scale score. A medium test-retest correlation coefficient was found for most items (r > 0.30). The confirmatory factor analysis confirmed the factorial structure found in the original study. CONCLUSIONS: Satisfaction is an important teaching and learning quality indicator along with the achievement of learning outcomes in simulation. The Satisfaction with Simulation Experience - Italian Version scale showed good reliability and validity; therefore, it could be a useful tool to assess simulation impact in Italian nursing students. The extensive utilization of the Satisfaction with Simulation Experience scale, along with its various validated versions, could facilitate assessing satisfaction in simulation across diverse contexts and enable comparisons of findings across studies in different countries.

Learning to teach with patients and caregivers: a focused ethnography.

BACKGROUND: Little is known about what happens when patients and caregivers are involved in an academic setting as co-teachers and how healthcare professionals approach a new model of partnership-based teaching. This study aimed to explore the learning and behavioural patterns of a group of healthcare professionals who were learning to teach with patients and caregivers as co-teachers in a post-graduate course. METHODS: A focused ethnographic study involving 11 health professionals was conducted. Data were collected through participatory observation during the course, individual semi-structured interviews, and a follow-up focus group. Taxonomic analysis was performed. RESULTS: Three categories were identified: 'group', 'role of narration' and 'applying co-teaching with patients and caregivers '. Specifically, heterogeneity, absence of hierarchies, and balanced relationships characterised the group dynamic and promoted partnership. Narration played a key role both in learning and in healthcare professionals' relationship with patients and caregivers and promoted emotional skills and self-awareness. Project planning and lessons simulations were essential aspects of the implementation process. CONCLUSIONS: This focused ethnography helped further understanding of the context of a specific project involving patients and caregivers as co-teachers in healthcare professional education. The development of emotional skills and self-awareness are the main learning patterns of co-teaching, and interprofessionalism and balanced relationships are the basis of the behavioural patterns. These patterns facilitated the involvement of patients and caregivers in health education.

Effectiveness of patients' involvement in a medical and nursing pain education programme: a protocol for an open-label randomised controlled trial including qualitative data.

INTRODUCTION: Pain is a multidimensional experience that varies among individuals and has a significant impact on their health. A biopsychosocial approach is recommended for effective pain management; however, health professionals' education is weak on this issue. Patient involvement is a promising didactic methodology in developing a more holistic perspective, however there is a lack of reliable evidence on this topic. The aim of the present study is to evaluate the effectiveness of patient involvement in pain education in undergraduate medicine and nursing students. METHODS AND ANALYSIS: An open-label randomised controlled trial including qualitative data will be conducted. After an introductory lesson, each student will be randomly assigned to the intervention group, which includes an educational session conducted by a patient-partner along with an educator, or to the control group in which the session is exclusively conducted by an educator. Both sessions will be carried out according to the Case-Based Learning approach. Primary outcomes will be students' knowledge, attitudes, opinions and beliefs about pain management, whereas the secondary outcome will be students' satisfaction. The Pain Knowledge and Attitudes (PAK) and Chronic Pain Myth Scale (CPMS) will be administered preintervention and postintervention to measure primary outcomes. Students' satisfaction will be measured by a questionnaire at the end of the session. Two focus groups will be conducted to evaluate non-quantifiable aspects of learning. ETHICS AND DISSEMINATION: The protocol of this study was approved by the independent Area Vasta Emilia Nord ethics committee.Adherence to The Declaration of Helsinki and Good Clinical Practice will ensure that the rights, safety and well-being of the participants in the study are safeguarded, as well as data reliability. The results will be disseminated through scientific publications and used to improve the educational offer. A version of the anonymised data set will be released for public access. TRIAL REGISTRATION: Trial was not registered on ClinicalTrials.gov as the interventions being compared only concern educational programmes and the outcomes considered do not refer to any clinical dimension.

Nursing students' evaluation of clinical learning environment and supervision models before and during the COVID-19 pandemic: a comparative study.

BACKGROUND AND AIM: The COVID-19 pandemic has required a rapid reorganization of clinical training and supervision models for nursing education. The aim of this study was to compare students' levels of perception of the quality of the Clinical Learning Environment (CLE) using two different clinical supervision models. METHODS: A comparative design was implemented. A convenience sample of second and third-year undergraduate nursing students (n=127) in clinical training in the 2018/2019 Academic Year (AY) received the usual nursing staff supervision model, while during the COVID-19 pandemic in the following year, they (n=69) received an individualized supervision model. Data were collected using three instruments: the Clinical Learning Environmental Quality Evaluation Index (CLEQI); the Clinical Learning Environment, Supervision and Nurse Teacher Scale (CLES+T); and a socio-demographic tool. RESULTS: The mean total scores of both scales had increased in the second survey (CLEQI: M=57.88±11.8 vs. M=60.88±9.3, p=0.035; CLES+T: M=148.4±23.3 vs. M=154.5±21.9, p=0.037). The nursing students reported high levels of CLE quality with both supervision models, even though the individualized supervision model was rated significantly higher by the students than the staff supervision model. CONCLUSIONS: Students supported by a personal supervisor during clinical training had a more positive experience and rated the quality of the tutorial strategies, learning opportunities, safety and nursing care, leadership style of the ward manager and overall CLE more highly.

Evaluation of an interprofessional education intervention in partnership with patient educators.

BACKGROUND AND AIM: Patient involvement in interprofessional education is a novel approach to building collaborative and empathic skills in students. However, this area of teaching is lacking in rigorous studies. The project aimed to evaluate whether an interprofessional education intervention in partnership with patient educators (IPE-PE) would increase readiness for interprofessional learning and empathy in health sciences students. METHODS: This is the report of a didactic innovation project. Participants included 310 undergraduate health sciences students who took part in an IPE-PE intervention. Data were collected before and after the training, using the Readiness for Interprofessional Learning Scale (RIPLS) and the Jefferson Scale of Empathy-Health Professions Student version (JSE-HPS). Only at the end of the intervention, a data collection form was administered to explore the value of the patient educator in the training and to investigate the socio-demographic variables. RESULTS: The mean age of participants was 21±3.2 SD years and 76% were female. A paired t-test showed significant changes from before to after the IPE-PE in the mean total RIPLS score (42.7±5.8 SD vs 44.62±5.9 SD, P<0.001) and the mean total JSE-HPS score (112.7±12.5 SD vs 116.03±12.8 SD, P<0.001).            Conclusions: Our students reported that IPE-PE had helped them to become more effective healthcare team members, to think positively about other professionals, and to gain empathic understanding of the perspective of the person being cared for. The results of the project confirm that the intervention promoted the development of empathy, fostering a better understanding of the patient-centred perspective.

The patient involvement in nursing education: A mixed-methods systematic review.

OBJECTIVE: To evaluate the effects patient involvement in nursing education has on students, patients and academic staff using a specific theoretical framework. DESIGN: Mixed-methods systematic review based on Joanna Briggs Institute methodology (Prospero no. CRD42022327158). DATA SOURCES: Seven databases (PubMed, Cochrane Library, Cinahl, PsychINFO, Scopus, ERIC, Embase), Google Scholar and reference lists were searched. REVIEW METHODS: Qualitative, quantitative and mixed-method studies published from 2012 to 2022 were included. Two reviewers independently assessed the studies for eligibility and quality; any disagreement was discussed with a third reviewer. Data were extracted and analysed according to the Joanna Briggs Institute converged integrated approach. RESULTS: Twenty-one qualitative, one quantitative and five mixed-methods studies met the inclusion criteria. Data were provided from three points of view: students, patients and academic staff. Student integrated findings included: (i) students' reactions towards patient involvement in education; (ii) students' views on the learning process and (iii) on ethical issue. From the patient point of view, the integrated findings addressed (i) patients' goals and effects on students' learning; (ii) how patients teach and get involved with students; (iii) how patients perceived their role; the patients' views on facilitators (iv) and barriers (v) in education; (vi) the perceived effects of being involved in education. Four integrated findings were derived from the academic staff's point of view: (i) academics' perceptions on patient vulnerability; (ii) perceived barriers to the efficacy of patient involvement in education; (iii) effects of patient involvement in nursing education; and (iv) methodological aspects of patient involvement in university curriculum. CONCLUSIONS: This systematic review provides useful information from all stakeholders' perspectives on the effects of patient involvement in nursing education. It offers a broader view of the implications for implementation and for developing theoretical frameworks and hypotheses for future research.

Lymphomatoid papulosis associated with myeloid neoplasm with eosinophilia and FIP1L1::PDGFRA rearrangement: Successful imatinib treatment in two cases.

Lymphomatoid papulosis (LyP) is a benign condition, listed among primary cutaneous CD30+ lymphoproliferative disorders. Its typical picture consists of relapsing-remitting papular lesions and it can be encountered in the course of a hematologic disease, at times representing its first manifestation. Hypereosinophilic syndromes are a heterogeneous group of disorders characterized by persistent peripheral blood hypereosinophilia that may lead to life-threatening organ damage. Among eosinophilic disorders, the subtype identified as myeloid/lymphoid neoplasm with eosinophilia and tyrosine kinase gene fusions has aroused particular interest due to its excellent response to tyrosine kinase inhibitors, including imatinib. Here, we described the case of two 33-year-old men presenting with LyP and myeloid neoplasm with eosinophilia and FIP1L1::PDGFRA rearrangement who achieved complete clinical and molecular remission of both conditions a few months after starting imatinib.

The effects of online Team-Based Learning on undergraduate nursing students' performance, attitudes and accountability during COVID-19 pandemic.

BACKGROUND AND AIM: The COVID-19 pandemic forced many institutions to move Team-Based Learning to an online format. The primary aim of this study is to examine the performance of undergraduate nursing students on tRAT and iRAT during online TBL. The secondary aims are to evaluate the students' attitudes and their accountability, preferences and satisfaction with online TBL. METHODS: The study employed a one-group pretest-posttest quasi-experimental design. The primary outcome was evaluated by comparing the students' average scores in the tRAT versus the iRAT in each online TBL session. The secondary outcomes were evaluated through the questionnaire designed by Parmelee et al. (2009) and the Team-Based Learning Student Assessment Instrument (TBL-SAI) (Mennenga, 2012). RESULTS: A statistically significant improvement was identified between tRAT and iRAT performances in all online TBL sessions (p<0.001). Students' satisfaction with team experience showed a statistically significant increase (p=0.003). Participants considered the peer evaluation to be fair (p<0.001), although it didn't encourage them to study more (p=0.028). Finally, students felt they were able to make the right decisions (p<0.001). The mean scores for accountability (m=30±3.7) and preferences for TBL (m=51.8±6.3) were higher than their neutral values (n=24; n=48). Students' satisfaction was neutral (m=27.8±5, n=27). CONCLUSIONS: In online TBL, teamwork has improved individual performances and has been appreciated by the participants. The online TBL had a positive effect on the accountability of students who preferred it to frontal lectures.

Pain Management in a Prehospital Emergency Setting: A Retrospective Observational Study.

Purpose: Acute pain is a prevalent symptomatology in prehospital emergency care. Although inadequate assessment and treatment of acute pain are associated with various complications, about 43% of adults suffering from pain are undertreated. This phenomenon is poorly studied, and limited data are available in the literature. The objective was to investigate the pain management in a prehospital emergency health-care setting, verifying pain assessment, pharmacological treatment adherence and the effectiveness of pain relief therapy. Patients and Methods: A retrospective observational study was conducted in a sample including all adults treated by the professionals of nurse-staffed ambulances and medical cars in an Italian Emergency Medical Services (EMS) from 1 January 2019 to 31 May 2019. We collected both demographic information and Numeric Rating Scale scores, which evaluated presence and intensity of pain, from the EMS paper forms. All analyses were performed using SPSS, version 27. Results: The study sample was composed of 629 people: 310 males (49%) and 319 females (51%), with an average age of 64.2±22 years (range 18-108). Pain information was collected in 75.5% (n = 475) of our sample; among them 222 patients (46.7%) suffered from pain. We recorded that 79.7% (n = 177) of the subjects with pain received no pharmacological treatment, and in almost all of the treated cases they did not adhere to the analgesia algorithm in use. Among those who were pharmacologically treated, pain statistically significantly decreased in intensity, from before to after, in both emergency vehicles (nurse-staffed ambulances pre m = 8.36±0.9 vs post m = 4.18±2.2, p<0.001; medical cars pre m = 7.25±1.7 vs post m = 3.50±2.6, p<0.001). Subsequently, pain was only re-ascertained in 24.3% of subjects. Conclusion: Our findings confirm that pain is a prevalent symptom in prehospital patients, especially in the younger age range, but that it remains an underrecognized, underestimated, and undertreated symptom with the risk of causing worse health outcomes.

The effectiveness of team-based learning in nursing education: A systematic review.

AIM: Team-Based Learning (TBL) is an active teaching methodology, recently implemented also in the field of nursing education. The main objective of this study was to identify, appraise and summarize primary studies on the effectiveness of TBL in achieving learning outcomes in undergraduate nursing students. The secondary objective was to explore the generic competencies the students developed, and their reactions and attitudes. STUDY DESIGN: A systematic review of experimental and quasi-experimental studies. DATABASES SOURCES: Cochrane Library, Pubmed/Medline, Cinahl, PsycINFO, and Eric; Google Scholar was used to search for grey literature and the reference lists of the retrieved papers. REVIEW METHODS: A research protocol was developed according to the PRISMA-P guidelines. Two reviewers conducted the selection process. The "JBI Critical Appraisal Checklist" was used to check the quality of the selected studies. RESULTS: We included 12 studies: 2 monocentric randomized controlled trials and 10 quasi-experimental studies. Nine out of 12 studies produced significant results in favour of TBL in terms of academic performance and skills development, however results were divergent when TBL was compared with other teaching methods. The results of 7 studies highlighted the effectiveness of TBL in improving the development of communication skills, interprofessional learning, and self-directed learning. Divergent results were obtained with regard to problem solving and critical thinking skills. TBL promoted classroom engagement, however it did not seem to be associated with better learning outcomes. CONCLUSIONS: Overall, TBL was found to be effective in achieving undergraduate nursing students' learning outcomes, but evidence was not sufficiently strong to warrant that it is more effective than other teaching methods. The results of this review are in favour of the implementation of TBL in nursing education, however studies with more rigorous methods and with a mixed method design are required to improve the transferability of results.

The antiplatelet agent revacept prevents the increase of systemic thromboxane A2 biosynthesis and neointima hyperplasia.

Neointima hyperplasia is a crucial component of restenosis after coronary angioplasty. We have hypothesized that enhanced generation of platelet-derived thromboxane (TX)A2 in response to vascular damage plays a critical role in neointimal hyperplasia and that antiplatelet agents may mitigate it. In cocultures of human platelets and coronary artery smooth muscle cells (CASMC), we found that platelets induced morphologic changes and enhanced the migration of CASMC. The exposure of platelets to Aspirin [an inhibitor of cyclooxygenase (COX)-1] reduced the generation of TXA2 and prevented the morphological and functional changes induced by platelets in CASMC. Platelet-derived TXA2 induced COX-2 and enhanced prostaglandin (PG)E2 biosynthesis in CASMC, a known mechanism promoting neointimal hyperplasia. COX-2 induction was prevented by different antiplatelet agents, i.e., Aspirin, the TP antagonist SQ29,548, or Revacept (a dimeric soluble GPVI-Fc fusion protein). The administration of the novel antiplatelet agent Revacept to C57BL/6 mice, beginning three days before femoral artery denudation, and continuing up to seven days after injury, prevented the increase of the systemic biosynthesis di TXA2 and reduced femoral artery intima-to-media area and the levels of markers of cell proliferation and macrophage infiltration. Revacept might serve as a therapeutic agent for percutaneous coronary angioplasty and stent implantation.

Platelet-Specific Deletion of Cyclooxygenase-1 Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice.

Inflammatory bowel disease (IBD) is associated with an increased risk for thromboembolism, platelet activation, and abnormalities in platelet number and size. In colitis, platelets can extravasate into the colonic interstitium. We generated a mouse with a specific deletion of cyclooxygenase (COX)-1 in megakaryocytes/platelets [(COX-1 conditional knockout (cKO)] to clarify the role of platelet activation in the development of inflammation and fibrosis in dextran sodium sulfate (DSS)-induced colitis. The disease activity index was assessed, and colonic specimens were evaluated for histologic features of epithelial barrier damage, inflammation, and fibrosis. Cocultures of platelets and myofibroblasts were performed. We found that the specific deletion of COX-1 in platelets, which recapitulated the human pharmacodynamics of low-dose aspirin, that is, suppression of platelet thromboxane (TX)A2 production associated with substantial sparing of the systemic production of prostacyclin, resulted in milder symptoms of colitis, in the acute phase, and almost complete recovery from the disease after DSS withdrawal. Reduced colonic accumulation of macrophages and myofibroblasts and collagen deposition was found. Platelet-derived TXA2 enhanced the ability of myofibroblasts to proliferate and migrate in vitro, and these effects were prevented by platelet COX-1 inhibition or antagonism of the TXA2 receptor. Our findings allow a significant advance in the knowledge of the role of platelet-derived TXA2 in the development of colitis and fibrosis in response to intestinal damage and provide the rationale to investigate the potential efficacy of the antiplatelet agent low-dose aspirin in limiting the inflammatory response and fibrosis associated with IBD. SIGNIFICANCE STATEMENT: Inflammatory bowel disease (IBD) is characterized by the development of a chronic inflammatory response, which can lead to intestinal fibrosis for which currently there is no medical treatment. Through the generation of a mouse with specific deletion of cyclooxygenase-1 in megakaryocytes/platelets, which recapitulates the human pharmacodynamics of low-dose aspirin, we demonstrate the important role of platelet-derived thromboxane A2 in the development of experimental colitis and fibrosis, thus providing the rationale to investigate the potential efficacy of low-dose aspirin in limiting the inflammation and tissue damage associated with IBD.

[The effective educational interventions in the promotion of self-care in people with heart failure: a literature review]. / Gli interventi educativi efficaci nella promozione del self-care nelle persone con scompenso cardiaco: una revisione della letteratura.

INTRODUCTION: Self-care in people with heart failure is subject of recent middle-range and short-range nursing theories and its promotion is recognized as a sensitive nursing outcome, achievable through various strategies including education. PURPOSE: To identify educational interventions that are effective in the promotion of self-care in adults and elderly people with heart failure, evaluating educational methods and tools used and their effectiveness in the medium-long term period. METHOD: We conducted a literature review, beginning with a search of secondary studies consulting Cochrane Library and than searching for the most recent primary studies in these scientific databases: PubMed, CINAHL, Scopus, and PsycINFO. RESULTS: The information meeting, focused on cognitive learning method, is the most frequently used and it shows a good and heterogeneous effectiveness in the promotion of self- care. The best statically significant results were obtained from the integration of this method with patients' training and counseling, relating respectively to the psycho-motor and psycho- affective learning. In support of the hetero-directed interventions were useful informational tools, self-monitoring tools and facilitating tools. The education was effective in promoting self-care until 12 months in most of the studies. CONCLUSIONS: The selected literature shows that is difficult to identify the best method or educational tool and that a single intervention is often not enough to promote self-care. Heal- thcare providers need to think about education as a continuous and dynamic process that includes multiple sessions and encourages the participation of the patient, turning the meeting into a discussion time where any provided is useful to answer to specific situations through activities and relationships.

Induced beliefs about a fictive energy drink influences 200-m sprint performance.

Placebo and nocebo effects occur in response to subjective expectations and their subsequent neural actions. Research shows that information shapes expectations that, consequently, influence people's behaviour. In this study, we examined the effects of a fictive and inert green colour energy drink provided for three groups (n = 20/group) with different information. The first group was led to expect that the drink augments running performance (positive information), the second group was led to expect that the drink may or may not improve performance (partial-positive information), while the third group was told that earlier research could not demonstrate that the drink improves performance (neutral/control). At baseline, the three groups did not differ in their 200-m sprint performance (p > .05). One week later, 20-min immediately after ingesting the drink, all participants again ran 200 m. The positive information group increased its performance by 2.41 s, which was statistically significant (p < .001) and also perceived its sprint-time shorter (p < .05) than the other two groups. A better performance (0.97 s) that approached but did not reach statistical significance was also noted in the partial-positive information group, and a lesser change (0.72 s) that was statistically not significant was noted in the neutral information control group. These results reveal that drinking an inert liquid, primed with positive information, changes both the actual and the self-perceived time on a 200-m sprint. The current findings also suggest that the level of certainty of the information might be linked to the magnitude of change in performance.

Aspirin prevents colorectal cancer metastasis in mice by splitting the crosstalk between platelets and tumor cells.

We investigated whether platelets prime colon cancer cells for metastasis and whether pharmacological inhibition of platelet function may prevent it. Coculturing HT29 human colon carcinoma cells with human platelets led to the induction of mesenchymal-like cancer cells characterized by downregulation of E-cadherin and upregulation of Twist1, enhanced cell mobility and a proaggregatory action on platelets. These changes were prevented by different antiplatelet agents, aspirin[an inhibitor of cyclooxygenase(COX)-1], DG-041[an antagonist of prostaglandin(PG)E2 EP3 receptor] and ticagrelor (a P2Y12 receptor antagonist). The injection of HT29 cells, exposed to platelets in vitro, into the tail vein of humanized immunodeficient mice led to higher incidence of lung metastasis compared to the injection of untreated HT29 cells. This effect was associated with enhanced systemic biosynthesis of thromboxane(TX)A2 and PGE2in vivo. Platelet COX-1 inhibition by aspirin administration to mice prevented the increased rate of metastasis as well as the enhanced production of TXA2 and PGE2 induced by the in vitro priming of HT29 cells by platelets. In conclusion, targeting platelet COX-1 with low-dose aspirin exerts an antimetastatic action by averting the stem cell mimicry of cancer cells associated with enhanced proaggregatory effects induced by platelet-tumor cell interactions. These effects may be shared by other antiplatelet drugs.

Novel insights into the regulation of cyclooxygenase-2 expression by platelet-cancer cell cross-talk.

Platelets are activated by the interaction with cancer cells and release enhanced levels of lipid mediators [such as thromboxane (TX)A2 and prostaglandin (PG)E2, generated from arachidonic acid (AA) by the activity of cyclooxygenase (COX)-1], granule content, including ADP and growth factors, chemokines, proteases and Wnt proteins. Moreover, activated platelets shed different vesicles, such as microparticles (MPs) and exosomes (rich in genetic material such as mRNAs and miRNAs). These platelet-derived products induce several phenotypic changes in cancer cells which confer high metastatic capacity. A central event involves an aberrant expression of COX-2 which influences cell-cycle progression and contribute to the acquisition of a cell migratory phenotype through the induction of epithelial mesenchymal transition genes and down-regulation of E-cadherin expression. The identification of novel molecular determinants involved in the cross-talk between platelets and cancer cells has led to identify novel targets for anti-cancer drug development.

Dysregulated post-transcriptional control of COX-2 gene expression in gestational diabetic endothelial cells.

BACKGROUND AND PURPOSE: Hyperglycaemic memory describes the progression of diabetic complications during subsequent periods of improved glycaemia. We addressed the hypothesis that transient hyperglycaemia causes aberrant COX-2 expression in HUVEC in response to IL-1ß through the induction of long-lasting epigenetic changes involving microRNA-16 (miR-16), a post-transcriptional modulator of COX-2 expression. EXPERIMENTAL APPROACH: Studies were performed on HUVEC collected from women with gestational diabetes mellitus (GDM) (dHUVEC) and normal women (nHUVEC). KEY RESULTS: In dHUVEC treated with IL-1ß, the expression of COX-2 mRNA and protein was enhanced and generation of prostanoids increased (the most abundant was the promitogenic PGF2α ). COX-2 mRNA was more stable in dHUVEC and this was associated with miR-16 down-regulation and c-Myc induction (a suppressor of miR expression). dHUVEC showed increased proliferation in response to IL-1ß, which was prevented by a COX-2 inhibitor and PGF2α receptor antagonist. Comparable changes in COX-2 mRNA, miR-16 and c-Myc detected in dHUVEC were produced in nHUVEC exposed to transient high glucose and then stimulated with IL-1ß under physiological glucose levels; superoxide anion production was enhanced under these experimental conditions. CONCLUSIONS AND IMPLICATIONS: Our results describe a possible mechanism operating in GDM that links the enhanced superoxide anion production and epigenetic changes, associated with hyperglycaemic memory, to endothelial dysfunction through dysregulated post-transcriptional control of COX-2 gene expression in response to inflammatory stimuli. The association of conventional therapy for glycaemic control with agents affecting inflammatory responses and oxidative stress might lead to a more effective prevention of the complications associated with GDM.

Rare SNP rs12731181 in the miR-590-3p Target Site of the Prostaglandin F2α Receptor Gene Confers Risk for Essential Hypertension in the Han Chinese Population.

OBJECTIVE: To investigate whether rs12731181 (A→G) interrupted miR-590-3p-mediated suppression of the prostaglandin F2α receptor (FP) and whether it is associated with essential hypertension in the Chinese population. APPROACH AND RESULTS: We found that miR-590-3p regulates human FP gene expression by binding to its 3'-untranslated region. rs12731181 (A→G) altered the binding affinity between miR-590-3p and its FP 3'-untranslated region target, thus reducing the suppression of FP expression, which, in turn, enhanced FP receptor-mediated contractility of vascular smooth muscle cells. Overexpression of FP augmented vascular tone and elevated blood pressure in mice. An association study was performed to analyze the relationship between the FP gene and essential hypertension in the Han Chinese population. The results indicated that the rs12731181 G allele was associated with susceptibility to essential hypertension. Carriers of the AG genotype exhibited significantly higher blood pressure than those of the AA genotype. FP gene expression was significantly higher in human peripheral leukocytes from individuals with the AG genotype than that in leukocytes from individuals with the AA genotype. CONCLUSIONS: rs12731181 in the seed region of the miR-590-3p target site is associated with increased risk of essential hypertension and represents a new paradigm for FP involvement in blood pressure regulation.

EP3 receptor deficiency attenuates pulmonary hypertension through suppression of Rho/TGF-ß1 signaling.

Pulmonary arterial hypertension (PAH) is commonly associated with chronic hypoxemia in disorders such as chronic obstructive pulmonary disease (COPD). Prostacyclin analogs are widely used in the management of PAH patients; however, clinical efficacy and long-term tolerability of some prostacyclin analogs may be compromised by concomitant activation of the E-prostanoid 3 (EP3) receptor. Here, we found that EP3 expression is upregulated in pulmonary arterial smooth muscle cells (PASMCs) and human distal pulmonary arteries (PAs) in response to hypoxia. Either pharmacological inhibition of EP3 or Ep3 deletion attenuated both hypoxia and monocrotaline-induced pulmonary hypertension and restrained extracellular matrix accumulation in PAs in rodent models. In a murine PAH model, Ep3 deletion in SMCs, but not endothelial cells, retarded PA medial thickness. Knockdown of EP3α and EP3ß, but not EP3γ, isoforms diminished hypoxia-induced TGF-ß1 activation. Expression of either EP3α or EP3ß in EP3-deficient PASMCs restored TGF-ß1 activation in response to hypoxia. EP3α/ß activation in PASMCs increased RhoA-dependent membrane type 1 extracellular matrix metalloproteinase (MMP) translocation to the cell surface, subsequently activating pro-MMP-2 and promoting TGF-ß1 signaling. Activation or disruption of EP3 did not influence PASMC proliferation. Together, our results indicate that EP3 activation facilitates hypoxia-induced vascular remodeling and pulmonary hypertension in mice and suggest EP3 inhibition as a potential therapeutic strategy for pulmonary hypertension.

Platelets, cyclooxygenases, and colon cancer.

A growing body of evidence supports the central role of platelets in early events of tumorigenesis and metastasis. Activated platelets, in response to tissue damage, induce a proinflammatory program involving the aberrant expression of cyclooxygenase (COX)-2, which leads to increased tissue concentrations of the proinflammatory and protumorigenic prostaglandin E2. The central role of platelet activation in cancer development is sustained by the analysis of clinical studies with aspirin showing an anti-cancer efficacy by the drug, even at the low doses used for the prevention of atherothrombosis. Low-dose aspirin acts as an antiplatelet agent by causing an irreversible inactivation of platelet COX-1 activity and the synthesis of thromboxane A2. Further experimental and clinical studies are ongoing to confirm the central role of platelets in the development of inflammation and cancer. The corroboration of this hypothesis will open new opportunities for the prevention and treatment of cancer. In addition to the possible use of traditional antithrombotic agents, the recent identification of novel molecular determinants involved in the cross-talk between platelets and other cellular player of tumorigenesis and metastasis has led to the suggestion of novel therapeutic strategies in oncology.