115 research outputs found

    Novel modified Peyton's approach for knowledge retention on newborn life support training in medical students

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    Aim We sought to improve retention of neonatal resuscitation skills by modifying step 3 through additional functional verbalisation in Peyton's four‐step approach (P4S). Methods Newborn life support (NLS) training was performed in a simulation‐based setting. In contrast to the traditional approach, students taught with the modified approach were requested to explain every step of their performance in Peyton's step 3. A total of 123 students were allocated into both experimental groups. Students were then assessed by megacode on day four (initial assessment) and 6 months (follow‐up assessment). Results Both groups showed similar scorings in the initial, follow‐up assessment and in mean change. On initial megacode, time to start with initial inflation and post‐resuscitation care was significantly faster in the control group. All showed a significant loss of performance irrespective of modification in step 3 in the follow‐up assessment. Only time until start with post‐resuscitation care shows a significant group difference in mean change between initial and follow‐up with increasing time in the control and decreasing time span in intervention group. Conclusion Both methods showed equal levels of knowledge acquisition and long‐term decline in NLS performances. Verbalisation in step 3 influenced speed of applied NLS performance

    Profiling of Phenolic Compounds and Antioxidant Activity of Dry Extracts from the Selected Sorbus Species

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    The antioxidant efficiency of dry extracts from inflorescences and/or leaves of seven Sorbus species was studied using four in vitro tests of SET (single electron transfer) and HAT-type (hydrogen atom transfer) mechanisms. The 70% methanol extracts and its diethyl ether, ethyl acetate, n-butanol and water fractions were tested in parallel with the phenolic standards, e.g., caffeic acid, quercetin, BHA, BHT, and TroloxÒ. The SET-type activity of the extracts depended primarily on the extraction solvent. The most valuable extracts were n-butanol and ethyl acetate ones, which activity was high in the DPPH (EC50 = 3.2–5.2 ÎŒg/mL), TEAC (2.8–4.0 mmol TroloxÂź/g), and FRAP (9.8–13.7 mmol Fe2+/g) tests, and strongly correlated with the total phenolic levels (39.6–58.2% of gallic acid equivalents). The HPLC-PDA analysis of the extracts led to the identification of chlorogenic acid, isoquercitrin, hyperoside, rutin, quercetin 3-O-sophoroside, and sexangularetin 3-O-b-D-glucopyranoside as the main components. Apart from flavonoids and hydroxycinnamic acids, proanthocyanidins have also a significant impact on the SET-type activity. The HAT-reactivity of the extracts in the linoleic acid peroxidation test (IC50 = 36.9–228.3 ÎŒg/mL) depended more strongly on the plant tissue than on the extraction solvent, and its correlation with the phenolic content was weak. Both SET and HAT-type activity of the most potent Sorbus extracts was comparable with the activity of the standards, indicating their great potential as effective sources for health products

    The Empirical Landscape of Trade Policy

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    This chapter surveys empirically the broad features of trade policy in goods for 31 major economies that collectively represented 83 percent of the world's population and 91 percent of the world's GDP in 2013. We address five questions: Do some countries have more liberal trading regimes than others? Within countries, which industries receive the most import protection? How do trade policies change over time? Do countries discriminate among their trading partners when setting trade policy? Finally, how liberalized is world trade? Our analysis documents the extent of cross-sectional heterogeneity in applied commercial policy across countries, their economic sectors, and their trading partners, over time. We conclude that substantial trade policy barriers remain as an important feature of the world economy.antidumpin

    Circulating serum miR-362-3p and miR-6721-5p as potential biomarkers for classification patients with adult-type diffuse glioma

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    According to the fifth edition of the WHO Classification of Tumours of the Central Nervous System (CNS) published in 2021, grade 4 gliomas classification includes IDH-mutant astrocytomas and wild-type IDH glioblastomas. Unfortunately, despite precision oncology development, the prognosis for patients with grade 4 glioma remains poor, indicating an urgent need for better diagnostic and therapeutic strategies. Circulating miRNAs besides being important regulators of cancer development could serve as promising diagnostic biomarkers for patients with grade 4 glioma. Here, we propose a two-miRNA miR-362-3p and miR-6721-5p screening signature for serum for non-invasive classification of identified glioma cases into the highest-grade 4 and lower-grade gliomas. A total of 102 samples were included in this study, comprising 78 grade 4 glioma cases and 24 grade 2–3 glioma subjects. Using the NanoString platform, seven miRNAs were identified as differentially expressed (DE), which was subsequently confirmed via RT-qPCR analysis. Next, numerous combinations of DE miRNAs were employed to develop classification models. The dual panel of miR-362-3p and miR-6721-5p displayed the highest diagnostic value to differentiate grade 4 patients and lower grade cases with an AUC of 0.867. Additionally, this signature also had a high AUC = 0.854 in the verification cohorts by RT-qPCR and an AUC = 0.842 using external data from the GEO public database. The functional annotation analyses of predicted DE miRNA target genes showed their primary involvement in the STAT3 and HIF-1 signalling pathways and the signalling pathway of pluripotency of stem cells and glioblastoma-related pathways. For additional exploration of miRNA expression patterns correlated with glioma, we performed the Weighted Gene-Co Expression Network Analysis (WGCNA). We showed that the modules most associated with glioma grade contained as many as six DE miRNAs. In conclusion, this study presents the first evidence of serum miRNA expression profiling in adult-type diffuse glioma using a classification based on the WHO 2021 guidelines. We expect that the discovered dual miR-362-3p and miR-6721-5p signatures have the potential to be utilised for grading gliomas in clinical applications

    Characterisation of volatile organic compounds in hospital indoor air and exposure health risk determination

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    Several volatile organic compounds (VOCs) have impacts on human health, but little is known about the concentrations of VOCs in the hospital environment. This study characterised VOCs present in clinical assessment rooms. More than 600 samples of air were collected over 31 months (2017–2020) at two hospital sites in Leicester, United Kingdom, and analysed by comprehensive two-dimensional gas chromatography, making this the largest hospital environment database worldwide on VOCs and first such UK study. The most abundant VOCs found were 2-propanol, ethyl chloride, acetone and hexane, with respective mean concentrations of 696.6 ÎŒgm−3, 436.5 ÎŒgm−3, 83.9 ÎŒgm−3 and 58.5 ÎŒgm−3. Acetone, 2-propanol and hexane concentrations were 4, 9 and 30-fold higher respectively compared to similar studies performed in other hospitals. Our results showed that the most frequently detected VOCs, with the highest concentrations, were most likely released by healthcare activities, or related to ingress of vehicle emissions. Hazard quotient (HQ) and cancer risk (CR) were calculated to identify the potential risk of VOCs exposure to the health of healthcare workers. No HQs were measured above 1, compared to inhaled US EPA and OEHHA health guidelines for non-cancer chemicals. For both hospitals, trichloroethylene CR were calculated above 1E-06 by using inhaled US EPA cancer risk values, leading to possible risks to healthcare workers with long-term exposure. More studies of this type, including measurements of VOCs such as formaldehyde that we were unable to include in this study, are needed to better characterise exposures and risks, both to healthcare workers and patients

    CLDN6-specific CAR-T cells plus amplifying RNA vaccine in relapsed or refractory solid tumors:the phase 1 BNT211-01 trial

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    The oncofetal antigen Claudin 6 (CLDN6) is highly and specifically expressed in many solid tumors, and could be a promising treatment target. We report dose escalation results from the ongoing phase 1/2 BNT211-01 trial evaluating the safety and feasibility of chimeric antigen receptor (CAR) T cells targeting the CLDN6 with or without a CAR-T cell-amplifying RNA vaccine (CARVac) at two dose levels (DLs) in relapsed/refractory CLDN6-positive solid tumors. The primary endpoints were safety and tolerability, maximum tolerated dose and recommended phase 2 dose (RP2D). Secondary endpoints included objective response rate (ORR) and disease control rate. We observed manageable toxicity, with 10 out of 22 patients (46%) experiencing cytokine release syndrome including one grade 3 event and 1 out of 22 (5%) with grade 1 immune effector cell-associated neurotoxicity syndrome. Dose-limiting toxicities occurred in two patients at the higher DL, resolving without sequelae. CAR-T cell engraftment was robust, and the addition of CARVac was well tolerated. The unconfirmed ORR in 21 evaluable patients was 33% (7 of 21), including one complete response. The disease control rate was 67% (14 of 21), with stable disease in seven patients. Patients with germ cell tumors treated at the higher DL exhibited the highest response rate (ORR 57% (4 of 7)). The maximum tolerated dose and RP2D were not established as the trial has been amended to utilize an automated manufacturing process. A repeat of the dose escalation is ongoing and will identify a RP2D for pivotal trials. ClinicalTrials.gov Identifier: NCT04503278 .</p

    Development of Core Outcome Measures sets for paediatric and adult Severe Asthma (COMSA)

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    BACKGROUND: Effectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe Asthma) working group sought to develop Core Outcome Measures (COM) sets to facilitate better synthesis of data and appraisal of biologics in paediatric and adult asthma clinical studies.METHODS: COMSA utilised a multi-stakeholder consensus process among patients with severe asthma, adult, and paediatric clinicians, pharmaceutical representatives and health regulators from across Europe. Evidence included a systematic review of development, validity, and reliability of selected outcome measures plus a narrative review and a pan-European survey to better understand patients' and carers' views about outcome measures. It was discussed using a modified GRADE Evidence to Decision framework. Anonymous voting was conducted using predefined consensus criteria.RESULTS: Both adult and paediatric COM sets include forced expiratory volume in 1 s (FEV1) as z scores, annual frequency of severe exacerbations and maintenance oral corticosteroid use. Additionally, the paediatric COM set includes the Paediatric Asthma Quality of Life Questionnaire, and Asthma Control Test (ACT) or Childhood-ACT while the adult COM includes the Severe Asthma Questionnaire and the Asthma Control Questionnaire-6 (symptoms and rescue medication use reported separately).CONCLUSIONS: This patient-centred collaboration has produced two COM sets for paediatric and adult severe asthma. It is expected that they will inform the methodology of future clinical trials, enhance comparability of efficacy and effectiveness of biological therapies, and help assess their socioeconomic value. COMSA will inform definitions of non-response and response to biological therapy for severe asthma.</p
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