Chloroquine and cinchonine affect rat vascular smooth muscle tonus through calcium channels - in silico and in vitro approaches.

BACKGROUND: In the present study, two structurally similar alkaloids from trees of Cinchona genus, chloroquine and cinchonine, were examined for their vasorelaxant effects in a model of phenylephrine-induced smooth muscle contractions. METHODS: Potential mechanisms of action associated with endothelial vasorelaxant compounds, voltage-gated Ca2+ channels (LTCCs), and inositol triphosphate receptors were examined in isolated rat aortic rings. Also, an in silico approach was used to predict the activity of the two test compounds. RESULTS: Experimental results revealed that both chloroquine and cinchonine significantly decrease phenylephrine-induced smooth muscle contractions, although to a different extent. Evaluated mechanisms of action indicate that endothelium is not involved in the vasorelaxant action of the two tested alkaloids. On the other hand, voltage-gated Ca2+ channels were found to be the dominant way of action associated with the vasorelaxant action of chloroquine and cinchonine. Finally, IP3R is found to have only a small impact on the observed activity of the tested compounds. CONCLUSION: Molecular docking studies predicted that chloroquine possesses a significant activity toward a suitable model of LTCCs, while cinchonine does not. The results of the present study point to the fact that great caution should be paid while administering chloroquine to vulnerable patients, especially those with cardiovascular disorders (Tab. 3, Fig. 3, Ref. 28).

Coping with Symptoms of Mental Health Disorders among University Students during the COVID-19 Pandemic in Relation to Their Lifestyle Habits.

Background and Objectives: The time of the pandemic brought great difficulties, both in state and interstate systems, industry, trade, and with individuals themselves. In addition, numerous studies have shown a drastic increase in mental disorders in people around the world. Therefore, the basic idea of our study was to investigate these disorders in university students in relation to their different lifestyles. Materials and Methods: The cross-sectional study was carried out at the University of Nis (Serbia) from December 2021 to February 2022. All of the participants were assessed by using appropriate questionnaires. The study included 1400 randomly selected students (692 females and 708 males). The statistical analysis of the data included the application of multiple regression analyses and correlation tests. Results: Statistical analysis indicates that extremely severe levels of depression symptoms were reported by 232 students (16.6%). Severe and extremely severe anxiety symptoms were reported by 480 students (34.3%). Multiple linear regression analysis found that for the increased depressive symptoms, the "most deserving" parameters were related to the consumption of alcoholic beverages and psychoactive substances (ß = 0.10, and 0.11, respectively), compared to the period before the COVID-19 pandemic. For anxiety symptoms, the main role was played by alcohol consumption (ß = 0.11) but also by the use of social networks as an adequate substitute for deprived content during the pandemic (ß = 0.13). Alcohol consumption was the most "responsible" for elevated stress levels compared to the period before the pandemic (ß = 0.19). Conclusions: Due to the COVID-19 pandemic, symptoms of depression, anxiety, and stress were drastically increased in the university students. There was significantly more frequent consumption of alcoholic beverages and psychoactive substances among them. That is why social support from a close environment is the most important strategy in coping with mental health issues during emergency situations.

A longitudinal study of the association between depression, anxiety and stress symptoms of university students in Serbia with excessive social media use before and during COVID-19 pandemic.

Background: Besides the well known good side of social media, it cannot be denied some of its negative effects. This two-phase study aimed to find out whether the usage of social media during the COVID-19 pandemic showed some significant association with depression and anxiety symptoms, and levels of stress. Methods: The study was based on the survey of 1,476 randomly selected students at the initial phase (December 2019 to February 2020), and 1,400 students of the same cohort at the follow up phase (December 2021-February 2022). The collected data included socio-demographics, social media usage aspects, and the ones concerning levels of depression, stress and anxiety symptoms. Standardized questionnaires - the Bergen Social Media Addiction Scale (BSMAS) was applied to measure the levels of social media addiction, and the Depression Anxiety Stress Scale (DASS 42) was administered to evaluate the symptoms of depression, anxiety and stress. Results: The comparison of responses regarding the six components of online social media addiction, which constitute the BSMAS, between the two phases of the study showed significant difference (p < 0.01) in favor of the follow up phase in the raised scores of all but one component. The probable severe or extremely severe symptoms of depression, anxiety, and stress were notably enhanced during the peak of pandemic, and all three of them were positively correlated with all 6 BSMAS components (p < 0.01). The results also indicate that students, who consumed alcohol beverages and psychoactive substances more frequently in the pandemic, exhibited more noticeable symptoms of depression (p < 0.01, for both associations). Higher levels of anxiety symptoms in students were found to be associated with longer sleep during the night (p < 0.01), increased alcoholic beverages consumption (p < 0.01). Stress levels had the strongest correlations with consuming alcoholic beverages during the pandemic (r = 0.16, p < 0.01). Conclusion: The comparison between two phases of this follow-up study revealed significant changes in the Internet usage characteristics, which may have had an essential influence on the investigated symptoms of depression, anxiety, and stress. However, other factors that may have influenced student's mental health during the COVID-19 pandemic should also be considered.

Supporting Tourism by Assessing the Predictors of COVID-19 Vaccination for Travel Reasons.

The persistence of the SARS-CoV-2 virus imposed vaccination passports for traveling in most countries. We investigated psychological factors that predict the intention to vaccinate for travel. In a cross-sectional study, we examined how demographic variables, vaccination status, perceived risk of infection and severity of disease contracted at travel destination, safety and effectiveness of vaccines against contracting COVID-19 during travel, and conspiracy beliefs are related to intention to vaccinate for travel. Further analyses involved differences between vaccinated and unvaccinated individuals in a Romanian sample regarding conspiracy beliefs, attitudes about vaccines, and self-efficacy of controlling COVID-19 infection. Results showed that the intention to vaccinate for travel reasons is best predicted by vaccination status and perceptions of safety and efficacy of vaccines against COVID-19. Thus, vaccinated individuals believing that vaccines are safe and effective most probably will take another vaccine booster if it will allow them to travel. Positive relationships of the intention to vaccinate for travel reasons were found with age, vaccination status, conspiracy beliefs, perceptions of safety and effectiveness of vaccines, intention to travel, and a more cautious approach to travel. No significant relationships were found between perceptions of risk for self or for transmitting the disease to others, severity of disease, and the intention to vaccinate for travel. We also found significant differences between vaccinated and unvaccinated participants, as unvaccinated participants showed higher levels of conspiracy beliefs and less trust in the safety and efficacy of vaccines. We conclude that campaigns focused on promoting information on the safety and efficacy of vaccines is the most important direction for promoting vaccination in young travelers.

Predictors of Changes in Travel Behavior during the COVID-19 Pandemic: The Role of Tourists' Personalities.

This study investigates travel behavior and psychosocial factors that influence it during the COVID-19 pandemic. In a cross-sectional study, using an online survey, we examined changes in travel behavior and preferences after lifting travel restrictions, and how these changes were influenced by exposure to COVID-19, COVID-19 travel-related risk and severity, personality, fear of travel, coping, and self-efficacy appraisals in the Romanian population. Our results showed that participants traveled less in the pandemic year than the year before-especially group and foreign travel-yet more participants reported individual traveling in their home county during the pandemic period. Distinct types of exposure to COVID-19 risk, as well as cognitive and affective factors, were related to travel behavior and preferences. However, fun-seeking personality was the only major predictor of travel intention, while fear of travel was the only predictor of travel avoidance. Instead, people traveled more cautiously when they perceived more risk of infection at the destination, and had higher levels of fear of travel, but also a high sense of efficacy in controlling the infection and problem-solving capacity. The results suggest that specific information about COVID-19, coping mechanisms, fear of travel, and neuropsychological personality traits may affect travel behavior in the pandemic period.

Prothrombin 3'end Gene Variants in Patients With Sporadic Colon Adenocarcinoma.

BACKGROUND/AIM: Thrombin plays significant roles in various types of cancer. However, the expression levels of prothrombin, the thrombin precursor, in cancer remain unclear. Variants of the 3'end of the prothrombin gene lead to increased prothrombin expression. This study aimed to analyze prothrombin 3'end gene variants in colon tumor and adjacent normal tissue samples. MATERIALS AND METHODS: The study group consisted of 93 patients suffering from colon adenocarcinoma. The 3'end of the prothrombin gene was analyzed by DNA sequencing. RESULTS: Three variants, all previously associated with increased prothrombin expression were detected. Frequency of the FII 19911G allele was 46.77% and 47.85% in tumor and normal tissue, respectively. For the FII 20210A allele, the detected frequencies were 2.15% and 1.61%, respectively. The frequency of the FII c.1824T allele was 0.54% in both tissues. Four patients showed different genotypes in tumor and normal tissue. CONCLUSION: Prothrombin 3' end gene variants may play a role in colorectal cancer.

Management of Anaesthesia.

Surgical treatment of the craniovertebral junction (CVJ) requires excellent management by the anaesthetist. Patients undergoing this type of surgery have a wide range of concomitant diseases. Therefore, before proceeding to CVJ surgery, it is recommended to analyse the clinical aspects of the patient that could complicate the outcome of the surgical procedure.In this paper we aim to establish what constitutes the best surgical and anaesthesia management of these patients. We consider airway management, trying to identify the gold standard for the patient. We also consider the most appropriate intraoperative approach to guarantee the best management of the patient.

When the heart gets the flu: Fulminant influenza B myocarditis: A case-series report and review of the literature.

PURPOSE: To describe patients with refractory cardiogenic shock related to influenza B virus myocarditis rescued by venoarterial Extracorporeal Membrane Oxygenation (VA-ECMO). MATERIAL AND METHODS: Consecutive patients hospitalized in our unit for influenza-associated myocarditis were prospectively included. We also conducted a systematic MEDLINE database literature review through the PubMed search engine, between 1946 and 2017. RESULTS: We report the cases of 4 young patients with fulminant myocarditis requiring VA-ECMO for 6 [5-8] days. Influenza B virus was detected in all patients, either in nasopharyngeal sampling or bronchoalveolar lavage fluid. The 4 patients received oseltamivir. Heart function recovery allowed ECMO device removal without cardiac sequelae in all 4 patients. Systematic review retrieved 184 cases of influenza-associated myocarditis, most cases associated with H1N1 type-A infection during the 2009 pandemic. Forty eight cases of influenza myocarditis-associated cardiogenic shock requiring mechanical circulatory support including 3 cases due to influenza B virus were described. Mean duration of mechanical circulatory support was 8.5 ±â€¯6 days and mortality rate was 33%. CONCLUSIONS: Influenza myocarditis is a rare but reversible cause of cardiogenic shock amenable to VA-ECMO rescue. Early antiviral therapy and ECMO support should be considered for patients with fulminant myocarditis during an influenza epidemic.

Brain injury during venovenous extracorporeal membrane oxygenation.

PURPOSE: The frequency of neurological events and their impact on patients receiving venovenous extracorporeal membrane oxygenation (VV-ECMO) are unknown. We therefore study the epidemiology, risk factors, and impact of cerebral complications occurring in VV-ECMO patients. METHODS: Observational study conducted in a tertiary referral center (2006-2012) on patients developing a neurological complication (ischemic stroke or intracranial bleeding) while on VV-ECMO versus those who did not, and a systematic review on this topic. RESULTS: Among 135 consecutive patients who had received VV-ECMO, 18 (15 assessable) developed cerebral complications on ECMO: cerebral bleeding in 10 (7.5 %), ischemic stroke in 3 (2 %), or diffuse microbleeds in 2 (2 %), occurring after respective medians (IQR) of 3 (1-11), 21 (10-26), and 36 (8-63) days post-ECMO onset. Intracranial bleeding was independently associated with renal failure at intensive care unit admission and rapid PaCO2 decrease at ECMO initiation, but not with age, comorbidities, or hemostasis disorders. Seven (70 %) patients with intracranial bleeding and one (33 %) with ischemic stroke died versus 40 % of patients without neurological event. A systematic review found comparable intracranial bleeding rates (5 %). CONCLUSIONS: Neurological events occurred frequently in patients on VV-ECMO. Intracranial bleeding, the most frequent, occurred early and was associated with higher mortality. Because it was independently associated with rapid hypercapnia decrease, the latter should be avoided at ECMO onset, but its exact role remains to be determined. These findings may have major implications for the care of patients requiring VV-ECMO.

Gabexate mesylate as treatment in the course of ANCA-negative microscopic polyangiitis.

Patients with small vessel vasculitis present fluctuating antineutrophil cytoplasmic antibodies (ANCA) levels to the point that positive ANCA may be missed even if only up to 10% of patients with microscopic polyangiitis (MPA) are ANCA-negative. The first-line treatment of MPA is the association of steroids and cyclophosphamide, especially in the presence of a rapidly progressive glomerulonephritis. Plasmapheresis, intravenous immunoglobulins, and tumor necrosis factor inhibitors have been proposed as alternative to standard therapy. Disseminated intravascular coagulation (DIC) is a possible event in the course of small vessel vasculitis. Gabexate mesylate is a protease inhibitor able to suppress endothelial cell injury, and it may be administered to treat DIC related to different diseases. In ANCA-associated vasculitis, cytokines play a key role in promoting endothelial damage. DIC-related thrombocytopenia may be misinterpreted as drug-induced because of the immunosuppressive properties of cyclophosphamide. Two cases of ANCA-positive MPA associated with DIC and treated with gabexate are reported in the literature with improvement of both hematological disorder and renal function. Our patient presented a rapidly progressive glomerulonephritis, and the renal biopsy showed MPA, in the absence of ANCA. After two weeks of steroid treatment, our patient developed a DIC. This case represents the first report of ANCA-negative MPA managed with gabexate, which showed improvement of coagulation disorders and kidney function. In conclusion, the anti-inflammatory properties of gabexate could be helpful in MPA at increased bleeding risk when immunosuppressive treatment is contraindicated, even in ANCA-negative vasculitis.