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Red blood cells were used to detect possible membrane perturbations as effects of rats total body exposure to 1800 MHz radiofrequency electromagnetic radiation (RFEMR) using 2 different schemes of irradiation: 2-hour single and fractional exposure during 4 consecutive days for 0.5 hour daily. The following characteristic indices of erythrocyte membrane functional indices were analyzed: total permeability for K+ ions, activity of specific Ca2+-activated K+-channels, as well as membrane potential and lipid peroxidation intensity. Our research revealed a biological response of erythrocyte membrane to 1800 MHz frequency RF-EMR at both schemes of irradiation manifested as alterations in functional properties after animal whole body exposure. Moreover, long-lasting character of these effects was revealed. [ABSTRACT FROM AUTHOR]

The study of incidence (frequency of occurrence) of hereditary thrombophilias and their structure among reproductive-aged women both with fetal loss syndrome and uncomplicated obstetric anamnesis was performed on the clinical basis of the RA Republican Institute of Reproductive Health, Perinatology, Obstetrics and Gynecology. There were 80 women involved in the studies: 60 with complicated obstetric anamnesis (fetal loss syndrome), the other 20 - clinically healthy. To diagnose the hereditary thrombophilias the genetic polymorphism PAI-1, F5 Leiden (G1691A), F2 (G20210A), MTHFR (C677T) were detected by PCR method. The research results proved the positive correlation between thrombophilias, caused by gene mutations, and fetal loss syndrome, especially at the presence of PAI-1, MTHFR (C677T) homozygous gene mutations. In case of fetal loss syndrome the inherited predisposition to thrombophilias caused by gene mutations made up over 60%. [ABSTRACT FROM AUTHOR]

The study of physiological anticoagulative system deficiency among reproductive-aged women with fetal loss syndrome and clinically healthy ones were performed on the clinical basis of the RA Republican Institute of Reproductive Health, Perinatology, Obstetrics and Gynecology. The research involved 40 women: 25 women – with fetal loss syndrome in medical history and 15 – clinically healthy. From the physiological anticoagulants there were studied AT III, PC and PS ones. The activity of AT III was determined by kinetic colorimetric method, and for PC and PS the immunoenzyme assay method was used. The investigations proved the positive correlation between the physiological anticoagulative system deficiency and fetal loss syndrome. [ABSTRACT FROM AUTHOR]

Objectives: Patent foramen ovale (PFO) closure is recommended for patients who experience a cryptogenic stroke attributable to PFO. Although few randomized control trials (RCTs) have captured long-term effectiveness of PFO closure, observational data has been abundant. This is the first systematic review of observational studies determining incidence of long-term adverse outcomes in adults who underwent transcatheter PFO closure, with comparisons to findings from RCTs., Methods: Medline, Cochrane, and Embase databases were searched from inception to October 2023. Only observational studies with ≥4 years of mean or median follow-up were included. A meta-analysis was conducted to calculate the incidence of recurrent stroke after PFO closure., Results: After reviewing 2,432 records, 13 prospective and 12 retrospective cohort studies were included. Average follow-up lengths ranged from 4 to 12.3 years, and sample sizes from 75 to 1,533 participants. The average age ranged between 43.5-63.0, and 24.0-72.8% patients had an atrial septal aneurysm. The incidence of stroke was 0.34 per 100 person-years (I 2 = 67%). This was similar to rates from four RCTs that were used for comparison (0.35 per 100 person-years, I 2 = 51%). There was a significant improvement in heterogeneity once the study with one of the largest follow-up was removed., Conclusions: Real-world PFO closure studies with long-term follow-up report similar outcomes as RCTs which is important considering the exclusion of several important populations from trials. Future observational studies should include more rigorous reporting of follow-up strategies and explore different long-term adverse outcomes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Eric Horlick reports a relationship with Abbott Cardiovascular that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

The Fontan circuit is associated with chronically elevated systemic venous pressures and decreased cardiac output, often leading to circuit failure. Managing Fontan circuit failure is complex and requires multiple therapeutic options. Transcatheter interventions have emerged as a reliable approach. They can alleviate obstructions and improve cyanosis by enhancing pulmonary blood flow and oxygen saturation. These procedures can also increase cardiac output and reduce systemic venous pressure, contributing to patient stabilization. In addition, they help mitigate volume overload and decrease the risk of bleeding during heart or combined heart and liver transplants. In recent years, percutaneous interventions have rapidly evolved and become a key therapeutic option for addressing various aspects of Fontan circuit failure. These interventions should be considered integral to the management strategy for this specific patient population., Competing Interests: None.

Background: Evidence from trials suggests that patent foramen ovale closure is superior to medical therapy alone in reducing stroke recurrence in men but not in women. Evidence from real-world data on the impact of sex on outcomes after patent foramen ovale closure, however, remains scarce. Therefore, the present study aimed to assess sex-based differences in long-term outcomes after transcatheter closure of patent foramen ovale., Methods: This was a single-center, retrospective cohort study enrolling patients who underwent transcatheter patent foramen ovale closure to prevent recurrent cerebrovascular events. Detailed information from medical charts was entered into a clinical registry, which has been linked to population-based administrative health databases in Ontario. Procedural, short, and long-term outcomes have been compared by sex., Results: Of the 783 patients included in the sample, 349 (44.5%) were women and 434 (55.5%) were men. Women were younger and had a higher rate of migraine, while men had a higher prevalence of cardiovascular risk factors. No differences were observed in procedural and 30-day outcomes by sex. At a median follow-up of 14 years, the event rates of recurrent cerebrovascular events, survival, and new-onset atrial fibrillation were not different by sex. In adjusted analysis, men experienced higher rates of pacemaker implantation (hazard ratio, 5.62 [95% CI, 1.57-20.1])., Conclusions: No sex-based differences in recurrent cerebrovascular events, survival, or new-onset atrial fibrillation were observed in this study, suggesting equal benefits for both sexes. Future studies should report outcomes by sex to enhance the reproducibility of our findings and help support guideline development., Competing Interests: Dr Horlick is a consultant for Abbott, Edwards, and Medtronic. He received research grants from Abbott and Occlutech for other projects. The Structural Heart Disease Program at the University Health Network receives educational support from Abbott, Edwards, and Medtronic. Abbott, Edwards, and Medtronic were not involved in the planning or execution of this study and have not seen or reviewed this article. Dr Lee is the Ted Rogers Chair in Heart Function Outcomes, a joint Hospital-University Chair of the University Health Network and the University of Toronto. The other authors report no conflicts.

The last 60 years have seen the emergence of several zoonotic viruses, some of which originate from bats. Among these are Nipah virus, Marburg virus and Ebola viruses, which have high case fatality rates, and pose significant public health risks. In 2012, another zoonotic paramyxovirus from bats, known as Sosuga Virus (SOSV), was discovered in a hospitalized biologist who had returned from a trip to Africa. Given the potential public health threats of the SOSV, investigating its pathogenesis, epidemiology and developing antiviral strategies are crucial to control possible future outbreaks. Thus, in this review, we explore the latest advancements in understanding SOSV since its discovery, focusing on its pathogenesis, animal models and the development of antiviral strategies. By examining the current literature, this review aims to provide a comprehensive overview to guide future studies and help public health efforts in better mitigating potential SOSV outbreaks., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Markarian and Abrahamyan.)

The ongoing Coronavirus Disease 19 (COVID-19) pandemic has had a profound impact on the global healthcare system. As the SARS-CoV-2 virus, responsible for this pandemic, continues to spread and develop mutations in its genetic material, new variants of interest (VOIs) and variants of concern (VOCs) are emerging. These outbreaks lead to a decrease in the efficacy of existing treatments such as vaccines or drugs, highlighting the urgency of new therapies for COVID-19. Therefore, in this study, we aimed to identify potential SARS-CoV-2 antivirals using a virtual screening protocol and molecular dynamics simulations. These techniques allowed us to predict the binding affinity of a database of compounds with the virus M pro protein. This in silico approach enabled us to identify twenty-two chemical structures from a public database (QSAR Toolbox Ver 4.5 ) and ten promising molecules from our in-house database. The latter molecules possess advantageous qualities, such as two-step synthesis, cost-effectiveness, and long-lasting physical and chemical stability. Consequently, these molecules can be considered as promising alternatives to combat emerging SARS-CoV-2 variants.

Background: Chronic kidney disease (CKD) is a risk factor for embolic stroke, and many nonvalvular atrial fibrillation (NVAF) patients have concomitant CKD. Anticoagulation therapy can be challenging in CKD due to increased bleeding risk, and left atrial appendage occlusion (LAAO) may be a promising alternative., Objective: This systematic review aimed to consolidate current evidence on the safety and effectiveness of transcatheter LAAO in patients with CKD and end-stage renal disease (ESRD)., Methods: Medline, Cochrane, and Embase databases were searched from inception to September 2, 2022. We conducted a meta-analysis if an outcome was evaluated in at least two similar studies., Results: We included 15 studies with 77,780 total patients. Of the 15 studies, 11 had a cohort design (five prospective and six retrospective), and four were case series. Patients with CKD were older and had a higher prevalence of comorbidities than non-CKD patients. The two groups did not differ in procedural failure rate, vascular complications, or pericardial tamponade. CKD patients exhibited higher odds of in-hospital acute kidney injury (AKI) and bleeding, longer-term bleeding, and mortality than those without CKD. The risk of in-hospital and longer-term cardioembolic events was similar between CKD and non-CKD populations (odds ratio = 1.01 [95% CI 0.70-1.15] and 1.05 [95% CI 0.55-2.00], respectively). Patients with ESRD had higher odds of in-hospital mortality and cardioembolic events than non-ESRD patients, with no differences in risk of pericardial tamponade., Conclusions: Based on observational studies, LAAO may be an effective option to prevent cardioembolic events in CKD. However, CKD patients may have higher odds of AKI and in-hospital and long-term bleeding and mortality. The adverse clinical outcomes observed in CKD patients may be attributed to this population's high burden of comorbidities, especially among those with ERSD, rather than the LAAO procedure itself. To ensure maximum clinical benefit, careful patient selection, management, and surveillance involving multidisciplinary teams are essential for CKD patients undergoing LAAO., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Introduction: Some aspects of gender differences in patients with schizophrenia spectrum disorders (SSD) have been studied, especially in cross-sectional designs and with a short-term follow-up. However, only a few studies have considered the evolution during the follow-up of SSD patients according to their gender. In this study, we explore gender differences from the time of entry in an early intervention program for psychosis, up to three years follow-up., Methods: We conducted a prospective study including a cohort of 474 patients treated at the Treatment and Early Intervention in Psychosis (TIPP) program, 319 men and 155 women, having presented a first episode of psychosis (FEP). Data regarding premorbid and baseline sociodemographic, psychopathological and patient functioning, were collected. These data were reassessed longitudinally after 2, 6, 12, 18, 24, 30 and 36 months after entry in TIPP., Results: Regarding premorbid and baseline characteristics, woman developed threshold symptoms of a FEP 1 year later than men on average. Women were more likely to be married, men were more likely to live in pension or care home facility or to be homeless. Women displayed a higher rate of history of suicide attempts and exposure to childhood trauma, while men were more likely to have a forensic history, a history of abuse of alcohol and cannabis as well as a dependency to cannabis at the time of entry in TIPP. Regarding evolution, men were more prone to violent acts and were less likely to decrease their usage of substances. The longitudinal analysis highlighted that men displayed greater negative symptoms over the entire treatment period, lower functioning after 6 months and on all assessment points after. Both genders displayed similar rate of improvement in these 3 dimensions over time., Conclusion: Our study confirms that there are some gender differences in the early phase of psychosis that may require differentiation of assessment and treatment to improve recovery., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Limited data are available on transcatheter patent foramen ovale (PFO) closure outcomes in the elderly., Aims: Through this study, we aimed to determine the incidence and predictors of adverse events (recurrent cerebrovascular events [CVE] and atrial fibrillation [AF]) post-PFO closure in older patients with cryptogenic events., Methods: This multicentre international study included patients over 60 years undergoing PFO closure for cryptogenic thromboembolic events. A dedicated database compiled baseline, procedural, and follow-up data. Competing risk and adjusted outcome predictor analyses were conducted., Results: A total of 689 patients were included (median age 65 years, 41.2% female, mean Risk of Paradoxical Embolism [RoPE] score 4.5). The procedural success rate was 99.4%. After a median follow-up of 2 (interquartile range 1-5) years, 66 patients (9.6%) had died. CVE and stroke rates were 1.21 and 0.55 per 100 patient-years, respectively. Diabetes (hazard ratio [HR] 3.89, 95% confidence interval [CI]: 1.67-9.07; p=0.002) and atrial septal aneurysm (ASA; HR 5.25, 95% CI: 1.56-17.62; p=0.007) increased the CVE risk. New-onset AF occurred at a rate of 3.30 per 100 patient-years, with 51.3% within one month post-procedure. Older age (HR 1.05 per year, 95% CI: 1.00-1.09; p=0.023) and the absence of hypertension (HR 2.04, 95% CI: 1.19-3.57; p=0.010) were associated with an increased risk of AF., Conclusions: Older patients undergoing PFO closure had a relatively low rate of CVE and new-onset AF after a median follow-up of 2 years. The presence of diabetes, ASA, and a more advanced age determined an increased risk of adverse clinical events. These factors may be considered in the clinical decision-making process regarding PFO closure in this challenging population.

Background & Aims: Biochemical response to ursodeoxycholic acid (UDCA) therapy is associated with good prognosis in people living with primary biliary cholangitis (PBC). Biochemical response is typically assessed early in disease and it is not known what proportion of patients lose previously attained biochemical response, nor whether this impacts long-term liver transplant (LT)-free survival., Methods: We identified all UDCA-treated patients with PBC from the Canadian Network for Autoimmune Liver disease with biochemical measurements at 1 year, and evaluated their liver biochemistry over time. Inadequate biochemical response was defined as serum alkaline phosphatase ≥1.67x the upper limit of normal or abnormal serum total bilirubin at 1 year of UDCA therapy and all time points thereafter. Multistate Markov models were used to estimate transition rates between biochemical response states and from each state to LT or death. Results were validated in an external cohort (GLOBAL PBC registry)., Results: A total of 823 patients from eight centers were included. Mean age at diagnosis was 53 years, 91% were female, 33% had inadequate biochemical response to UDCA at 1 year (n = 269). Patients who retained initial adequate response had lower rates of LT or death compared to patients who subsequently lost response (relative rate 0.102, 95% CI 0.047-0.223). Patients who regained adequate response had lower rates than patients who did not (0.016, 95% CI 0.001-0.568), and patients who lost response once more (0.010, 95% CI 0.001-0.340). Patients who regained adequate response for a third time also had lower rates than patients who did not (0.151, 95% CI 0.040-0.566). Analyses in the GLOBAL PBC registry (n = 2,237) validated these results., Conclusion: Loss of biochemical response at any time is associated with heightened risks of LT or death in people living with PBC. Achievement of biochemical response is an important goal throughout follow-up, regardless of biochemical response profile early in therapy., Impact and Implications: Early biochemical response to ursodeoxycholic acid is associated with good prognosis in patients with primary biliary cholangitis (PBC). Our work demonstrates that patients with PBC transition between biochemical response states over time, and that these transitions correspond with changes in risk of liver transplantation or death. Clinicians should re-evaluate risk and optimize treatment decisions for patients with PBC throughout follow-up, regardless of early biochemical response to therapy., (© 2024 The Author(s).)

Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease. Palliative procedures, either surgical or transcatheter, aim to improve oxygen saturation, affording definitive procedures at a later stage. Transcatheter interventions have been used before and after surgical palliative or definitive repair in children and adults. This review aims to provide an overview of the different catheter-based interventions for TOF across all age groups, with an emphasis on palliative interventions, such as patent arterial duct stenting, right ventricular outflow tract stenting, or balloon pulmonary valvuloplasty in infants and children and transcatheter pulmonary valve replacement in adults with repaired TOF, including the available options for a large, dilated native right ventricular outflow tract., Competing Interests: Funding Support and Author Disclosures Dr Horlick is supported by the Peter Munk Chair in Structural Heart Disease Intervention. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Congenital tricuspid valve stenosis is extremely rare. We describe 2 cases of patients with adult congenital heart disease with hypoplastic tricuspid valve annulus who were symptomatic from annular- and leaflet-level tricuspid stenosis. The patients underwent transcatheter balloon valvuloplasty with good clinical outcomes. An extensive literature review and analysis of various procedural strategies suggests that percutaneous balloon valvuloplasty may be a reasonable therapeutic choice as a first-line therapy or when open surgical repair is associated with prohibitively high mortality. This procedure can be performed either as a destination therapy or as a bridge to valve replacement.

Purpose: Geriatric assessment (GA) is a guideline-recommended approach to optimize cancer management in older adults. We conducted a cost-utility analysis alongside the 5C randomized controlled trial to compare GA and management (GAM) plus usual care (UC) against UC alone in older adults with cancer., Methods: The economic evaluation, conducted from societal and health care payer perspectives, used a 12-month time horizon. The Canadian 5C study randomly assigned patients to receive GAM or UC. Quality-adjusted life-years (QALYs) were measured using the EuroQol five dimension-5L questionnaire and health care utilization using cost diaries and chart reviews. We evaluated the incremental net monetary benefit (INMB) for the full sample and preselected subgroups., Results: A total of 350 patients were included, of whom 173 received GAM and 177 UC. At 12 months, the average QALYs per patient were 0.728 and 0.751 for GAM and UC, respectively (ΔQALY, -0.023 [95% CI, -0.076 to 0.028]). Considering a societal perspective, the total average costs (in 2021 Canadian dollars) per patient were $46,739 and $45,177 for GAM and UC, respectively (ΔCost, $1,563 [95% CI, -$6,583 to $10,403]). At a cost-effectiveness threshold of $50,000/QALY, GAM was not cost-effective compared with UC (INMB, -$2,713 [95% CI, -$11,767 to $5,801]). The INMB was positive ($2,984 [95% CI, -$7,050 to $14,179]; probability of being cost-effective, 72%) for patients treated with curative intent, but remained negative for patients treated with palliative intent (INMB, -$9,909 [95% CI, -$24,436 to $4,153]). Findings were similar considering a health care payer perspective., Conclusion: To our knowledge, this is the first cost-utility analysis of GAM in cancer. GAM was cost-effective for patients with cancer treated with curative but not with palliative intent. The study provides further considerations for future adoption of GAM in practice.

Background: Frailty and multimorbidity among older cancer patients affect treatment tolerance and efficacy. Comprehensive geriatric assessment and management is recommended to optimize cancer treatment, but its effect on various outcomes remains uncertain., Objective: Our objective was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) and cost-effectiveness studies comparing comprehensive geriatric assessment (with or without implementation of recommendations) to usual care in older cancer patients., Methods: We searched MEDLINE, EMBASE, CINAHL, and Cochrane trials from inception to January 27, 2023, for RCTs and cost-effectiveness studies. Pooled estimates for outcomes were calculated using random-effects models., Results: A total of 19 full-text articles representing 17 RCTs were included. Average participant age was 72-80 years, and 31%-62% were female. Comprehensive geriatric assessment type, mode of delivery, and evaluated outcomes varied across studies. Meta-analysis revealed no difference in risk of mortality (risk ratio [RR] = 1.08. 95% confidence interval [CI] = 0.91 to 1.29), hospitalization (RR = 0.92, 95% CI = 0.77 to 1.10), early treatment discontinuation (RR = 0.89, 95% CI = 0.67 to 1.19), initial dose reduction (RR = 0.99, 95% CI = 0.99 to 1.26), and subsequent dose reduction (RR = 0.87, 95% CI = 0.70 to 1.09). However, the risk of treatment toxicity was statistically significantly lower in the comprehensive geriatric assessment group (RR = 0.78, 95% CI = 0.70 to 0.86). No cost-effectiveness studies were identified., Conclusion: Compared with usual care, comprehensive geriatric assessment was not associated with a difference in risk of mortality, hospitalization, treatment discontinuation, and dose reduction but was associated with a lower risk of treatment toxicity indicating its potential to optimize cancer treatment in this population. Further research is needed to evaluate cost-effectiveness., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Different methodologies have been used to assess the role of AV calcification (AVC) on TAVI outcomes. This systematic review aims to describe the burden of AVC, synthesize the different methods of calcium score quantification, and evaluate the impact of AVC on outcomes after TAVI. We included studies of TAVI patients who had reported AV calcium scoring by contrast-enhanced multidetector CT and the Agatston method. The impact of calcification on TAVI outcomes without restrictions on follow-up time or outcome type was evaluated. Results were reported descriptively, and a meta-analysis was conducted when feasible. Sixty-eight articles were included, with sample sizes ranging from 23 to 1425 patients. Contrast-enhanced calcium scoring was reported in 30 studies, calcium volume score in 28 studies, and unique scoring methods in two. All studies with calcium volume scores had variable protocols, but most utilized a modified Agatston method with variable attenuation threshold values of 300-850 HU. Eight studies used the Agatston method, with the overall mean AV calcium score in studies published from 2010 to 2012 of 3342.9 AU [95%CI: 3150.4; 3535.4, I2 ​= ​0%]. The overall mean score was lower and heterogenous in studies published from 2014 to 2020 (2658.9 AU [95% CI: 2517.3; 2800.5, I2 ​= ​79%]. Most studies reported a positive association between calcium burden and increased risk of adverse outcomes, including implantation of permanent pacemaker (7/8 studies), paravalvular leak (13/13 studies), and risk of aortic rupture (2/2 studies). AVC quantification methodology with contrast-enhanced CT is still variable. AVC negatively impacts TAVI outcomes independently of the quantification method., (Copyright © 2023. Published by Elsevier Inc.)