Background Pulmonary hypertension is a common and serious complication of chronic obstructive pulmonary disease (COPD). Studies suggest that cigarette smoke can initiate pulmonary vascular remodelling by stimulating cell proliferation; however, the underlying cause, particularly the role of vasoactive prostanoids, is unclear. We hypothesize that cigarette smoke extract (CSE) can induce imbalanced vasoactive prostanoid release by differentially modulating the expression of respective synthase genes in human pulmonary artery smooth muscle cells (PASMCs) and endothelial cells (PAECs), thereby contributing to cell proliferation. Methods Aqueous CSE was prepared from 3R4F research-grade cigarettes. Human PASMCs and PAECs were treated with or without CSE. Quantitative real-time RT-PCR and Western blotting were used to analyse the mRNA and protein expression of vasoactive prostanoid syhthases. Prostanoid concentration in the medium was measured using ELISA kits. Cell proliferation was assessed using the cell proliferation reagent WST-1. Results We demonstrated that CSE induced the expression of cyclooxygenase-2 (COX-2), the rate-limiting enzyme in prostanoid synthesis, in both cell types. In PASMCs, CSE reduced the downstream prostaglandin (PG) I synthase (PGIS) mRNA and protein expression and PGI2 production, whereas in PAECs, CSE downregulated PGIS mRNA expression, but PGIS protein was undetectable and CSE had no effect on PGI2 production. CSE increased thromboxane (TX) A synthase (TXAS) mRNA expression and TXA2 production, despite undetectable TXAS protein in both cell types. CSE also reduced microsomal PGE synthase-1 (mPGES-1) protein expression and PGE2 production in PASMCs, but increased PGE2 production despite unchanged mPGES-1 protein expression in PAECs. Furthermore, CSE stimulated proliferation of both cell types, which was significantly inhibited by the selective COX-2 inhibitor celecoxib, the PGI2 analogue beraprost and the TXA2 receptor antagonist daltroban. Conclusions These findings provide the first evidence that cigarette smoke can induce imbalanced prostanoid mediator release characterized by the reduced PGI2/TXA2 ratio and contribute to pulmonary vascular remodelling and suggest that TXA2 may represent a novel therapeutic target for pulmonary hypertension in COPD.

IntroductionWithin the UK, chest pain is one of the most common reasons for emergency (999) ambulance calls and the most common reason for emergency hospital admission. Diagnosing acute coronary syndromes (ACS) in a patient with chest pain in the prehospital setting by a paramedic is challenging. The Troponin-only Manchester Acute Coronary Syndromes (T-MACS) decision rule is a validated tool used in the emergency department (ED) to stratify patients with suspected ACS following a single blood test.We are seeking to evaluate the diagnostic accuracy of the T-MACS decision aid algorithm to ‘rule out’ ACS when used in the prehospital environment with point-of-care troponin assays. If successful, this could allow paramedics to immediately rule out ACS for patients in the ‘very low risk’ group and avoid the need for transport to the ED, while also risk stratifying other patients using a single blood sample taken in the prehospital setting.Methods and analysisWe will recruit patients who call emergency (999) ambulance services where the responding paramedic suspects cardiac chest pain. The data required to apply T-MACS will be prospectively recorded by paramedics who are responding to each patient. Paramedics will be required to draw a venous blood sample at the time of arrival to the patient. Blood samples will later be tested in batches for cardiac troponin, using commercially available troponin assays. The primary outcome will be a diagnosis of acute myocardial infarction, established at the time of initial hospital admission. The secondary outcomes will include any major adverse cardiac events within 30 days of enrolment.Ethics and disseminationThe study obtained approval from the National Research Ethics Service (reference: 18/ES/0101) and the Health Research Authority. We will publish our findings in a high impact general medical journal.Trial registration numberRegistration number: ClinicalTrials.gov, study ID: NCT03561051

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Background Physically active individuals are susceptible to sports injuries, one of which is anterior cruciate ligament (ACL) injury. ACL injury can be managed conservatively or by surgical reconstruction. Returning to sport (RTS) after ACL injury is one of the main goals of ACL reconstruction (ACLR). However, rates of return vary and can be affected by several factors. The objectives of this study were to estimate the rate of return and to identify the factors that might affect RTS after ACLR. Methods This was a cross-sectional study, including individuals who had an ACLR. Participants were sent an online survey included questions about their injury, sport participation, International Knee Documentation Committee form (IKDC), and the Tampa Scale for Kinesiophobia (TSK-11). Participants who had their surgery in the period between January 2011 to December 2018 and participated in sports regularly were included. Descriptive statistics were performed. Chisquare and student t-tests were performed to explore the differences between participants who returned and the ones that did not.

ObjectivePoint-of-care (POC) cardiac troponin (cTn) assays have a rapid turnaround time but are generally less sensitive than laboratory-based assays. Previous research found that the Abbott i-Stat cardiac troponin I (cTnI) assay has good diagnostic accuracy when used with the Troponin-only Manchester Acute Coronary Syndromes (T-MACS) decision aid and serial sampling over 3 hours. Accuracy of other assays may differ. We therefore evaluated the diagnostic accuracy of a different POC cTnI assay with serial sampling over 3 hours, both with T-MACS and when used alone.MethodsIn a prospective diagnostic accuracy study at eight EDs in England (July 2015–October 2017), we collected clinical data from consenting adults with suspected ACS at the time of assessment in the ED. Blood samples were drawn on arrival and 3 hours later for POC cTnI (Cardio 3 Triage, Alere). The target condition was an adjudicated diagnosis of acute myocardial infarction (AMI), based on reference standard serial laboratory-based cTn testing. We calculated test characteristics for POC cTnI using the limit of detection (LoD, 0.01 µg/L) and the T-MACS decision aid.ResultsOf 347 participants, 59 (14.9%) had AMI. With serial POC cTnI testing over 3 hours, POC cTnI at the LoD cut-off ruled out AMI in 193 (55.6%) patients with 98.1% sensitivity (95% CI 89.9% to 100.0%) and 99.5% negative predictive value (NPV, 95% CI 96.5% to 99.9%). T-MACS ruled out AMI in 117 (33.7%) patients with 98.1% sensitivity (95% CI 89.9% to 100%) and 99.2% NPV (95% CI 94.3% to 99.9%). T-MACS ruled in AMI with 97.9% specificity (95% CI 95.8% to 99.5%) and 83.7% positive predictive value (95% CI 70.6% to 91.7%).ConclusionsWith serial sampling over 3 hours, the Alere Cardio 3 Triage cTnI assay has relatively high NPV for AMI using either the LoD cut-off alone or the T-MACS decision aid. However, wide CIs around the measures of diagnostic accuracy mean that further prospective testing of this strategy is required before clinical implementation.Trial registration numberUKCRN 18000.

Abstract Introduction: Chest pain is one of the most common reasons for 999 calls and transfers to the emergency department (ED). In these patients, acute myocardial infarction (AMI) is often the diagnosis that clinicians are seeking to exclude. However, only a minority of those patients have AMI, causing a substantial financial burden to health services. Cardiac troponin (cTn) is the reference standard biomarker for the diagnosis of AMI. Several commercially available point-of-care (POC) cTn assays are portable and could feasibly be used in an ambulance. The aim of this paper is to systematically review existing evidence for the use of POC cTn assays in the prehospital setting to rule out AMI. Methods: A systematic search was conducted on EMBASE, MEDLINE, and CINAHL Plus databases, reference lists, and relevant grey literature, including combinations of the relevant terms. Papers published in English language since the year 2000 were eligible for inclusion. A narrative synthesis of the evidence was then undertaken. Results: The initial search and cross-referencing revealed a total of 350 papers, of which 243 were excluded. Seven papers were included in the systematic literature review. Conclusion: Current evidence does not support the use of POC troponin assays to exclude AMI due to issues with diagnostic accuracy and insufficient high-quality evidence.

Commiphora gileadensis (CG) is a small tree distributed throughout the Middle East. It was traditionally used in perfumes in countries in this area. In Saudi Arabia, it was used to treat wounds burns and as an antidote to scorpion stings. This study aimed to evaluate the antimicrobial activity and cutaneous wound healing efficiency of the CG extracts using microbiological tests, rate of wound contraction and histopathological changes. CG pants were extracted using the methanol extraction technique; then, the methanolic extract was characterized using liquid chromatography coupled with mass spectrometry (LC–MS). Afterwards, a six-millimetre (mm) excision wound was induced in 60 male Balb/c mice. Mice were classified into two classes; each class consisted of three groups of 10 mice. In the non-infected wound class, the group I was assigned as control and received normal saline. Group II received gentamicin treatment, and group III treated with CG-methanolic extract. In the Staphylococcus aureus-infected class, group IV received normal saline, and groups V and VI were treated with gentamicin and CG-methanolic extract, respectively. The colonization of infected wounds was determined using colony-forming units (CFUs), and the percentage of wound contraction was measured in all groups. Finally, the histopathologic semi-quantitative determination of wound healing was evaluated by inflammatory cell infiltration, the presence of collagen fibres and granulation tissue, and the grade of re-epithelization. Composition analysis of the methanolic extract confirmed the presence of a high amount of ceramide (69%) and, to a lesser extent, hexosylceramide (18%) and phosphatidylethanolamine (7%) of the total amount. Additionally, there was a statistically significant difference between the percentage of wound contraction in the CG-treated and control groups in both Staphylococcus aureus-infected and non-infected wounds (p < 0.01). The colonization of the infected wounds was lower in the group treated with CG than in the control group (p < 0.01). In both non-infected and infected wounds, the CG-treated group showed significant statistical differences in inflammatory cell infiltration, collagen fibres, re-epithelization and granulation tissue formation compared with the control group (p < 0.01). The CG extract possesses antibacterial and anti-inflammatory properties that induce wound healing.

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