An activity-guided isolation study on the EtOH extract prepared from the bulbs of Prospero autumnale yielded four new phenolic compounds, including a new stilbenoid (1), a new homoisoflavonoid derivative (8), a new homoisoflavonoid dimer (9), and an unprecedented homoisoflavone-stilbene heterodimer (10), together with six known (2-7) analogs. Their chemical structures were elucidated by spectroscopic analysis and theoretical NMR and ECD calculations. Compounds 9 and 10 are unique in their scaffolds. The in vitro cytotoxic activity of purified compounds was evaluated against eight tumor cell lines (HCT116, LoVo, DU145, PC3, HEP3B, HEPG2, MCF7, and MDA-MB-231) and one nontumor cell line (L929) by the MTS assay. Compounds 1, 2, 4, and 10 exhibited inhibition with IC50 values ranging from 8.2 to 37.6 μM. Cytotoxic cell death mechanisms were further investigated, indicating variability in apoptosis, necrosis, or cell cycle arrest.
- MeSH
- Apoptosis drug effects MeSH
- Antineoplastic Agents, Phytogenic * pharmacology chemistry MeSH
- Isoflavones pharmacology chemistry isolation & purification MeSH
- Plant Roots chemistry MeSH
- Humans MeSH
- Molecular Structure MeSH
- Cell Line, Tumor MeSH
- Drug Screening Assays, Antitumor MeSH
- Stilbenes * pharmacology chemistry MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
The novel diiron amine complexes [Fe2Cp2(CO)(NH2R')(μ-CO){μ-CN(Me)(Cy)}]CF3SO3 [R' = H, 3; Cy, 4; CH2CH2NH2, 5; CH2CH2NMe2, 6; CH2CH2(4-C6H4OMe), 7; CH2CH2(4-C6H4OH), 8; Cp = η5-C5H5, Cy = C6H11 = cyclohexyl] were synthesized in 49-92 % yields from [Fe2Cp2(CO)2(μ-CO){μ-CN(Me)(Cy)}]CF3SO3, 1a, using a straightforward two-step procedure. They were characterized by IR and multinuclear NMR spectroscopy, and the structure of 7 was confirmed through X-ray diffraction analysis. Complexes 3-8 and the acetonitrile adducts [Fe2Cp2(CO)(NCMe)(μ-CO){μ-CN(Me)(R)}]CF3SO3 (R = Cy, 2a; Me, 2b; Xyl = 2,6-C6H3Me2, 2c) were assessed for their water solubility, octanol-water partition coefficient and stability in physiological-like solutions. The in vitro antiproliferative activity of 2a-c and 3-8 was tested on seven human cancer cell lines (A2780, A2780R, PC3, A549, MCF7, HOS and HT-29), while the selectivity was evaluated using normal MRC-5 cells. Overall, the complexes exhibited variable cytotoxicity, with IC50 values reaching the low micromolar range for 3, 7 and 8 in A2780 and A2780R cells, along with significant selectivity. Targeted experiments covered cell cycle modification, induction of cell death, mitochondrial membrane potential, ROS production and interaction with DNA and bovine serum albumin (BSA) as a model protein. The interaction of 3 with BSA was further investigated through computational studies. Results showed a negligible increase in intracellular ROS levels (except for 2b) and insignificant changes in mitochondrial membrane potential.
- MeSH
- Amines chemistry pharmacology MeSH
- Coordination Complexes chemistry pharmacology chemical synthesis MeSH
- Humans MeSH
- Ligands MeSH
- Molecular Structure MeSH
- Cell Line, Tumor MeSH
- Cell Proliferation * drug effects MeSH
- Antineoplastic Agents * pharmacology chemistry chemical synthesis MeSH
- Drug Screening Assays, Antitumor * MeSH
- Dose-Response Relationship, Drug MeSH
- Structure-Activity Relationship MeSH
- Iron chemistry MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Using the perspective of the recent COVID-19 pandemic, which represents a public health challenge that also affects education and the psychological well-being of students, this paper aims to assess the vulnerability to anxiety and stress of the Romanian students from the Faculty of Administration and Business of the University of Bucharest pursuing their degrees in administration and business. METHODS: Our study is based on the results of the survey that was administered to a sample of 422 students (39.6% females and 60.4% males) selected from the pool of 2000 recruited respondents. We employed the ANOVA/linear Dependent Dirichlet Process mixture model to explain the causes of stress and anxiety after various grouping variables represented by gender, specialisation, as well as labour market status. RESULTS: Our results revealed that more than 80% of the students in the sample yielded medium and high vulnerability to stress, while 64% of the respondents were affected by severe anxiety (high frequency of psychological, social, and physical problems that were difficult for them to control). The most important stressors were the fear of getting infected and social distancing, while self-control was considered the most effective coping strategy by 62.6% of employed students. CONCLUSIONS: These results allow us to provide practical recommendations for effectively coping with stress and anxiety among students in Romania and beyond and to help stakeholders and policymakers design strategies for strengthening students' resilience, mental health, and well-being in case of future pandemics or other extreme contexts.
- MeSH
- Adaptation, Psychological * MeSH
- Coping Skills MeSH
- COVID-19 * epidemiology psychology MeSH
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Pandemics MeSH
- Surveys and Questionnaires MeSH
- Stress, Psychological * epidemiology psychology MeSH
- SARS-CoV-2 MeSH
- Students * psychology statistics & numerical data MeSH
- Universities MeSH
- Anxiety * epidemiology psychology MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Romania MeSH
A newly identified subtype of hereditary axonal motor neuropathy, characterized by early proximal limb involvement, has been discovered in a cohort of 34 individuals with biallelic variants in von Willebrand factor A domain-containing 1 (VWA1). This study further delineates the disease characteristics in a cohort of 20 individuals diagnosed through genome or exome sequencing, incorporating neurophysiological, laboratory and imaging data, along with data from previously reported cases across three different studies. Newly reported clinical features include hypermobility/hyperlaxity, axial weakness, dysmorphic signs, asymmetric presentation, dystonic features and, notably, upper motor neuron signs. Foot drop, foot deformities and distal leg weakness followed by early proximal leg weakness are confirmed to be initial manifestations. Additionally, this study identified 11 novel VWA1 variants, reaffirming the 10 bp insertion-induced p.Gly25ArgfsTer74 as the most prevalent disease-causing allele, with a carrier frequency of ∼1 in 441 in the UK and Western European population. Importantly, VWA1-related pathology may mimic various neuromuscular conditions, advocating for its inclusion in diverse gene panels spanning hereditary neuropathies to muscular dystrophies. The study highlights the potential of lower quality control filters in exome analysis to enhance diagnostic yield of VWA1 disease that may account for up to 1% of unexplained hereditary neuropathies.
- Publication type
- Journal Article MeSH
BACKGROUND: The outcomes after prolonged treatment in the intensive care unit (ICU) after surgery for Stanford type A aortic dissection (TAAD) have not been previously investigated. METHODS: This analysis included 3538 patients from a multicenter study who underwent surgery for acute TAAD and were admitted to the cardiac surgical ICU. RESULTS: The mean length of stay in the cardiac surgical ICU was 9.9±9.5 days. The mean overall costs of treatment in the cardiac surgical ICU 24086±32084 €. In-hospital mortality was 14.8% and 5-year mortality was 30.5%. Adjusted analyses showed that prolonged ICU stay was associated with significantly lower risk of in-hospital mortality (adjusted OR 0.971, 95%CI 0.959-0.982), and of five-year mortality (adjusted OR 0.970, 95%CI 0.962-0.977), respectively. Propensity score matching analysis yielded 870 pairs of patients with short ICU stay (2-5 days) and long ICU stay (>5 days) with balanced baseline, operative and postoperative variables. Patients with prolonged ICU stay (>5 days) had significantly lower in-hospital mortality (8.9% vs. 17.4%, <0.001) and 5-year mortality (28.2% vs. 30.7%, P=0.007) compared to patients with short ICU-stay (2-5 days). CONCLUSIONS: Prolonged ICU stay was common after surgery for acute TAAD. However, when adjusted for multiple baseline and operative variables as well as adverse postoperative events and the cluster effect of hospitals, it was associated with favorable survival up to 5 years after surgery.
- MeSH
- Aortic Aneurysm surgery economics mortality MeSH
- Length of Stay * economics MeSH
- Aortic Dissection * surgery economics mortality MeSH
- Intensive Care Units * economics MeSH
- Middle Aged MeSH
- Humans MeSH
- Hospital Mortality * MeSH
- Prognosis MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND AND OBJECTIVES: The relevance of the use of intra-aortic balloon pump (IABP) in cardiogenic shock (CS) has been discussed over the past years. The aim of this study is to describe a single-centre 10-year experience with IABP and analyse the risk factors for 30-day mortality. METHODS: The data for this single-centre, observational, retrospective study were drawn from records dated from January 2012 to May 2022 pertaining to patients presenting with CS, treated with IABP and hospitalised at the Department of Acute Cardiology, Institute for Clinical and Experimental Medicine, Prague. RESULTS: Among the patients included in the study, 87% patients presented with newly developed heart failure. The leading cause of CS was acute myocardial infarction accounting for 86% of cases. Hospital mortality was recorded at 39% and the 30-day mortality reached 43%. Upon multi-variable analysis, only the vasoactive inotropic score on day 5 emerged as a statistically significant predictor for 30-day mortality (p=0.0055). Cox regression analysis revealed that the presence of mechanical complications was the only variable identified as yielding a statistically significant impact on the 30-day survival (Log-rank p=0.014, HR 2.19, 95% CI: 1.15‒4.15). There was no statistically significant difference in the 30-day mortality across the SCAI classes. CONCLUSION: The main cause of CS was a newly developed acute heart failure secondary to acute myocardial infarction. Despite the implementation of mechanical circulatory support, both in-hospital and 30-day mortality rates remained high. Increased vasoactive inotropic score and presence of mechanical complications were identified as significant predictors the 30-day survival (Tab. 6, Fig. 1, Ref. 36). Text in PDF www.elis.sk Keywords: cardiogenic shock, IABP, risk factors, mortality, Czech Republic, AMICS.
- MeSH
- Myocardial Infarction complications mortality MeSH
- Intra-Aortic Balloon Pumping * MeSH
- Shock, Cardiogenic * mortality therapy etiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Hospital Mortality * MeSH
- Retrospective Studies MeSH
- Risk Factors MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Heart Failure mortality therapy complications MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Observational Study MeSH
- Geographicals
- Czech Republic MeSH
BACKGROUND: Medication non-adherence is a common issue in chronic illness. The World Health Organization has recognized a need for a valid and reliable method of measuring adherence to understand and mitigate non-adherence. This study aimed to psychometrically evaluate the English version of the Adelphi Adherence Questionnaire (ADAQ©), a questionnaire designed to assess patient-reported medication adherence across multiple therapy areas, in patients with Osteoarthritis (OA). METHODOLOGY: Data from the Adelphi OA Disease Specific ProgrammeTM, a survey of physicians and their consulting adult patients with OA conducted in the United States, November 2020 to March 2021, was used to assess the psychometric properties of the ADAQ. Patients completed the ADAQ, Adherence to Refills and Medication Scale (ARMS), Western Ontario and McMaster Universities Arthritis Index (WOMAC), and EQ-5D-3L. The measurement model of the 13-item ADAQ was assessed and refined using latent variable modelling (Multiple Indicator Multiple Cause, confirmatory and exploratory factor analyses, item response theory, Mokken scaling, and bifactor analyses). Correlational analyses (Spearman's rank and polyserial as appropriate) with ARMS, WOMAC, and EQ-5D-3L scores assessed construct validity. Anchor- and distribution-based analyses were performed to estimate between-group clinically important differences (CID). RESULTS: Overall, 723 patients were included in this analysis (54.5% female, 69.0% aged ≥ 60). Latent variable modelling indicated a unidimensional reflective model was appropriate, with a bifactor model confirming an 11-item essentially unidimensional score. Items 12 and 13 were excluded from scoring as they measured a different concept. The ADAQ had high internal reliability with omega hierarchical and Cronbach's alpha coefficients of 0.89 and 0.97, respectively. Convergent validity was supported by moderate correlations with items of the ARMS, and physician-reported adherence and compliance. Mean differences in ADAQ score between high and low adherence groups yielded CID estimates between 0.49 and 1.05 points, with a correlation-weighted average of 0.81 points. CONCLUSION: This scoring model showed strong construct validity and internal consistency reliability when assessing medication adherence in OA. Future work should focus on confirming validity across a range of disease areas.
- MeSH
- Medication Adherence * psychology MeSH
- Adult MeSH
- Assessment of Medication Adherence * MeSH
- Middle Aged MeSH
- Humans MeSH
- Osteoarthritis * drug therapy psychology MeSH
- Surveys and Questionnaires MeSH
- Psychometrics * methods MeSH
- Reproducibility of Results MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- United States MeSH
BACKGROUND: Faecal microbiota transplantation (FMT) is a developing therapy for disorders related to gut dysbiosis. Despite its growing application, standardised protocols for FMT filtrate preparation and quality assessment remain undeveloped. The viability of bacteria in the filtrate is crucial for FMT's efficacy and for validating protocol execution. We compared two methods-in vitro cultivation and membrane integrity assessment-for their accuracy, reproducibility and clinical applicability in measuring bacterial viability in frozen FMT stool filtrate. METHODS: Bacterial viability in stool filtrate was evaluated using (i) membrane integrity through fluorescent DNA staining with SYTO9 and propidium iodide, followed by flow cytometry and (ii) culturable bacteria counts (colony-forming units, CFU) under aerobic or anaerobic conditions. RESULTS: Using different types of samples (pure bacterial culture, stool of germ-free and conventionally bred mice, native and heat-treated human stool), we refined the bacterial DNA staining protocol integrated with flow cytometry for assessment of bacterial viability in frozen human stool samples. Both the membrane integrity-based and cultivation-based methods exhibited significant variability in bacterial viability across different FMT filtrates, without correlation. The cultivation-based method showed a mean coefficient of variance of 30.3%, ranging from 7.4% to 60.1%. Conversely, the membrane integrity approach yielded more reproducible results, with a mean coefficient of variance for viable cells of 6.4% ranging from 0.2% to 18.2%. CONCLUSION: Bacterial viability assessment in stool filtrate using the membrane integrity method offers robust and precise data, making it a suitable option for faecal material evaluation in FMT. In contrast, the cultivation-dependent methods produce inconsistent outcomes.
- MeSH
- Bacteria isolation & purification MeSH
- Feces * microbiology MeSH
- Fecal Microbiota Transplantation * methods MeSH
- Humans MeSH
- Microbial Viability * MeSH
- Mice MeSH
- Flow Cytometry * methods MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Comparative Study MeSH
Aim: To measure the level of emotional intelligence in medical-surgical nursing specialist nurses. Design: A quantitative descriptive cross-sectional study. Methods: Data were collected through a digital form comprising a questionnaire divided into two sections: first - sociodemographic and professional characterization; second - a Portuguese version of the Schutte Emotional Intelligence Scale. The internal consistency of the instrument, measured by Cronbach's alpha (unidimensional), was 0.878. Data were collected between 27 January and 16 March 2023. A non-probability convenience sampling technique was used to enroll the participants. Results: The final sample consisted of 168 medical-surgical nursing specialist nurses. Their mean emotional intelligence score was 105.28 points, with a standard deviation of 10.56 points. The variables academic degree (p = 0.002) and gender (p = 0.035) showed a statistically significant association with the total emotional intelligence score. Conclusion: This study allowed to measure the level of emotional intelligence in medical-surgical nursing specialist nurses, yielding high mean scores. Nevertheless, it is essential to invest in strategies for the acquisition of emotional intelligence skills by professionals with low mean scores.
Cognitive decline represents a severe non-motor symptom of Parkinson's disease (PD) that can significantly reduce the benefits of subthalamic deep brain stimulation (STN DBS). Here, we aimed to describe post-surgery cognitive decline and identify pre-surgery cognitive profile associated with faster decline in STN DBS-treated PD patients. A retrospective observational study of 126 PD patients treated by STN DBS combined with oral dopaminergic therapy followed for 3.54 years on average (SD = 2.32) with repeated assessments of cognition was conducted. Pre-surgery cognitive profile was obtained via a comprehensive neuropsychological examination and data analysed using exploratory factor analysis and Bayesian generalized linear mixed models. On the whole, we observed a mild annual cognitive decline of 0.90 points from a total of 144 points in the Mattis Dementia Rating Scale (95% posterior probability interval [-1.19, -0.62]) with high inter-individual variability. However, true score changes did not reach previously reported reliable change cut-offs. Executive deficit was the only pre-surgery cognitive variable to reliably predict the rate of post-surgery cognitive decline. On the other hand, exploratory analysis of electrode localization did not yield any statistically clear results. Overall, our data and models imply mild gradual average annual post-surgery cognitive decline with high inter-individual variability in STN DBS-treated PD patients. Nonetheless, patients with worse long-term cognitive prognosis can be reliably identified via pre-surgery examination of executive functions. To further increase the utility of our results, we demonstrate how our models can help with disentangling true score changes from measurement error in future studies of post-surgery cognitive changes.
- MeSH
- Deep Brain Stimulation * methods MeSH
- Cognition physiology MeSH
- Cognitive Dysfunction * etiology therapy physiopathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Neuropsychological Tests MeSH
- Subthalamic Nucleus * MeSH
- Parkinson Disease * therapy physiopathology MeSH
- Retrospective Studies MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Observational Study MeSH