A Conscious Porcine Model for Sudden Cardiac Death

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Gene Duplication and Gain in the Trematode Atriophallophorus winterbourni Contributes to Adaptation to Parasitism.

Gene duplications and novel genes have been shown to play a major role in helminth adaptation to a parasitic lifestyle because they provide the novelty necessary for adaptation to a changing environment, such as living in multiple hosts. Here we present the de novo sequenced and annotated genome of the parasitic trematode Atriophallophorus winterbourni and its comparative genomic analysis to other major parasitic trematodes. First, we reconstructed the species phylogeny, and dated the split of A. winterbourni from the Opisthorchiata suborder to approximately 237.4 Ma (±120.4 Myr). We then addressed the question of which expanded gene families and gained genes are potentially involved in adaptation to parasitism. To do this, we used hierarchical orthologous groups to reconstruct three ancestral genomes on the phylogeny leading to A. winterbourni and performed a GO (Gene Ontology) enrichment analysis of the gene composition of each ancestral genome, allowing us to characterize the subsequent genomic changes. Out of the 11,499 genes in the A. winterbourni genome, as much as 24% have arisen through duplication events since the speciation of A. winterbourni from the Opisthorchiata, and as much as 31.9% appear to be novel, that is, newly acquired. We found 13 gene families in A. winterbourni to have had more than ten genes arising through these recent duplications; all of which have functions potentially relating to host behavioral manipulation, host tissue penetration, and hiding from host immunity through antigen presentation. We identified several families with genes evolving under positive selection. Our results provide a valuable resource for future studies on the genomic basis of adaptation to parasitism and point to specific candidate genes putatively involved in antagonistic host-parasite adaptation

In vivo genotoxicity and inflammatory effects of uncoated and coated CeO2 NPs in mice

P17-045 Ceria nanoparticles (CeO2 NPs) have several industrial applications and pharmacological potential due to their antioxidant properties. However, toxicity data on CeO2 NPs are scarce and show contradictory results. In the present study, uncoated, polyethylene glycol- and citrate-coated CeO2 NPs (4-8 nm) were administrated to C57Bl/6 mice by repeated dose (3×) pharyngeal aspiration using four different doses of each type of NPs (corresponding to 4.4, 8.8, 17.6 and 35.2 µg Ce2+/mouse/aspiration), and sampled 1 and 28 days after the last administration. DNA damage was assessed by the comet assay locally in bronchoalveolar lavage (BAL) and lung cells, and systemically in liver cells. Micronuclei, a biomarker of chromosome damage, were analysed in bone marrow and peripheral blood erythrocytes. Immunotoxicity was evaluated by BAL cell counting. Furthermore, histopathological effects on the lungs and biodistribution of the NPs (analysis of Ce2+ in several organs) were assessed. At 24-h, a significant increase in DNA damage was induced at the highest doses by uncoated and citrate-coated NPs in BAL cells. For these NPs a significant, but non-dose-dependent, effect was observed in lung and liver cells at 28-d. No systemic genotoxic effects were observed with any of the NPs. A dose-dependent accumulation of macrophages and activated lymphocytes was seen in the lungs for all the NPs, although a milder reaction was elicited by the coated NPs. Our findings show that short-term exposure of mice to CeO2 NPs induces pulmonary inflammation, and non-dose-dependent DNA damage, but no systemic genotoxicity. (Funded by the EU FP-7 GUIDEnano, Grant Agreement No.604387)

Preoperative paroxysmal atrial fibrillation predicts high cardiovascular mortality in patients undergoing surgical aortic valve replacement with a bioprosthesis: CAREAVR study

Background Preoperative permanent atrial fibrillation (AF) is associated with impaired outcome after surgical aortic valve replacement (SAVR). The impact of preoperative paroxysmal AF, however, has remained elusive. Purpose We assessed the impact of preoperative paroxysmal AF on outcome in patients undergoing SAVR with bioprosthesis. Methods A total of 666 patients undergoing isolated AVR with a bioprosthesis were included. Survival data was obtained from the national registry Statistics Finland. Patients were divided into three groups according to the preoperative rhythm: sinus rhythm (n = 502), paroxysmal AF (n = 90), and permanent AF (n = 74). Results Patients in the sinus rhythm and paroxysmal AF groups did not differ with respect to age (P = .484), gender (P = .402) or CHA(2)DS(2)-VASc score (P = .333). At 12-month follow-up, AF was present in 6.2% of sinus rhythm patients and in 42.4% of paroxysmal AF patients (P <.001). During follow-up, incidence of fatal strokes in the paroxysmal AF group was higher compared to sinus rhythm group (1.9 vs 0.4 per 100 patient-years, HR 4.4 95% Cl 1.8-11.0, P = .001). Cardiovascular mortality was higher in the paroxysmal AF group than in the sinus rhythm group (5.0 vs 3.0 per 100 patient-years, HR 1.70 95% CI 1.05-2.76, P = .03) and equal to patients in the permanent AF (5.0 per 100 patient-years). Conclusion Patients undergoing SAVR with bioprosthesis and history of paroxysmal AF had higher risk of developing permanent AF, cardiovascular mortality and incidence of fatal strokes compared to patients with preoperative sinus rhythm. Life-long anticoagulation should be considered in patients with a history of preoperative paroxysmal AF.Peer reviewe

Adverse events and survival with postpericardiotomy syndrome after surgical aortic valve replacement

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Late incidence and recurrence of new-onset atrial fibrillation after isolated surgical aortic valve replacement

Publisher Copyright: © 2021 The AuthorsObjectives: Atrial fibrillation (AF) is a common complication after cardiac surgery. More knowledge is needed about long-term AF recurrence and adverse outcomes related to new-onset AF (NOAF) during the index hospitalization. Methods: A total of 1073 patients underwent isolated surgical aortic valve replacement at the 4 participating hospitals (2002-2014). After the exclusion of patients with a history of any preoperative AF, the final study population included 529 patients in the bioprosthetic and 253 patients in the mechanical valve prosthesis cohort. Median follow-up time was 5.4 (interquartile range, 3.4-8.2) years in the combined cohort. Results: Altogether 333 (42.6%) patients had in-hospital NOAF and 250 (32.0%) AF after hospital discharge. In the mechanical cohort, 64 (25.3%) experienced in-hospital NOAF and 74 (29.2%) AF after hospital discharge, whereas in the bioprosthetic cohort, 269 (50.9%) patients had in-hospital NOAF and 176 (33.3%) AF after hospital discharge. Patients with NOAF during the index hospital stay had a multifold risk of AF after hospital discharge in the combined cohort (hazard ratio [HR], 3.68; 95% confidence interval [CI], 2.82-4.81; P <.0001) as well as in both cohorts separately (bioprosthetic: HR, 4.35; 95% CI, 3.05-6.22; P <.001; mechanical: HR, 2.54; 95% CI, 1.59-4.03; P <.001). Patients with an in-hospital NOAF also had a significantly higher adjusted risk of death during the follow-up in the mechanical (HR, 2.05; 95% CI, 1.10-3.82; P =.025) and bioprosthetic (HR, 1.63; 95% CI, 1.17-2.28; P =.004) valve prosthesis cohorts. Conclusions: NOAF during the index hospitalization is associated with a 2- to 4-fold risk of later AF and 1.6- to 2.0-fold risk of all-cause mortality after mechanical and bioprosthetic surgical aortic valve replacement.Peer reviewe

Mental health conditions and adherence to direct oral anticoagulants in patients with incident atrial fibrillation : A nationwide cohort study

Objective: Medication adherence is essential for effective stroke prevention in patients with atrial fibrillation (AF). We aimed to assess whether adherence to direct oral anticoagulants (DOACs) in AF patients is affected by the presence of mental health conditions (MHCs). Methods: The nationwide FinACAF cohort covered 74,222 AF patients from all levels of care receiving DOACs during 2011-2018 in Finland. Medication possession ratio (MPR) was used to quantify adherence. Patients with MPR >= 0.90 were defined adherent. MHCs of interest were depression, bipolar disorder, anxiety disorder and schizophrenia. Results: The patients' (mean age 75.4 +/- 9.5 years, 50.8% female) mean MPR was 0.84 (SD 0.22), and 59.5% had MPR >= 0.90. Compared to patients without MHC, the adjusted ORs (95% CI) for adherent DOAC use emerged slightly lower in patients with depression (0.92 (0.84-0.99)) and bipolar disorder (0.77 (0.61-0.97)) and unsignificant in patients with anxiety disorder (1.08 (0.96-1.21)) and schizophrenia (1.13 (0.90-1.43)). However, when only persistent DOAC therapy was analyzed, no MHC was associated with poor adherence, and instead anxiety disorder was associated with adherent DOAC use (1.18 (1.04-1.34)). Conclusion: Adherence to DOACs in AF patients in Finland was relatively high, and no meaningful differences between patients with and without MHCs were observed.Peer reviewe

Mental Health Conditions and Nonpersistence of Direct Oral Anticoagulant Use in Patients With Incident Atrial Fibrillation : A Nationwide Cohort Study

BACKGROUND: Mental health conditions (MHCs) are associated with poor outcomes in patients with atrial fibrillation. However, persistence of oral anticoagulation therapy in patients with atrial fibrillation and MHCs is unknown. We aimed to evaluate the effect of MHCs on the persistence of direct oral anticoagulant (DOAC) use in patients with atrial fibrillation based on a nationwide cohort. METHODS AND RESULTS: The nationwide registry-based FinACAF (Finnish Anticoagulation in Atrial Fibrillation) cohort included 67 503 patients with incident atrial fibrillation and indication for permanent oral anticoagulation (CHA(2)DS(2)-VASc score >1 in men and >2 in women) starting DOAC therapy between 2011 and 2018. MHCs of interest were depression, bipolar disorder, anxiety disorder, schizophrenia, and composite of any MHC. The main outcome was nonpersistence of DOAC use, defined as the first 120-day period without DOAC purchases after drug initiation. The mean age of the patients was 75.3 +/- 8.9 years, 53.6% were women, and the prevalence of any MHC was 17.8%. Persistence after 1 year from DOAC initiation was 79.3% in patients without MHCs and 77.2% in patients with any MHC, and after 2 years were 64.4% and 60.6%, respectively (P CONCLUSIONS: MHCs are associated with nonpersistence of DOAC use.Peer reviewe

Socioeconomic factors and bleeding events in patients with incident atrial fibrillation : A Finnish nationwide cohort study

Background: Low socioeconomic status has been associated with higher risk of ischemic stroke and death in patients with atrial fibrillation (AF). However, whether socioeconomic status affects risk of bleeding events is unknown. We assessed the hypothesis that low income and educational attainment are associated with higher risk of bleeding in patients with AF.Methods: The registry-based FinACAF study covers all patients with AF in Finland during 2007-2018. Patients were divided into income quartiles and three categories based on their educational attainment. Outcomes of interest were the first-ever gastrointestinal (GI), intracranial (IC) and any bleeding.Results: We identified 205 019 patients (50.9 % female; mean age 72.3 (SD 13.4) years) with incident AF without prior bleeding. Mean follow-up time was 4.0 (SD 3.2) years, during which 25 013 (12.2 %) patients experienced first-ever any bleeding (incidence rate 3.07 (95 % CI 3.03-3.10) /100 patient-years). Low income was inde-pendently associated with hazard of any bleeding as well as GI and IC bleeding (adjusted hazard ratios (HRs) comparing lowest vs highest income quartile: 1.13 (1.08-1.17), 1.32 (1.23-1.41) and 1.15 (1.06-1.24), respectively). Income-related bleeding disparities were larger among younger patients under 65 years and among men. Education-related bleeding disparities were smaller than income related-disparities (adjusted HRs comparing lowest vs highest educational category: any bleeding 1.06 (1.02-1.11), GI bleeding 1.16 (1.08-1.24), IC bleeding 1.10 (0.93-1.09))Conclusions: Patients with AF and low income are at higher risk of bleeding, especially GI bleeding.Peer reviewe

Mental health conditions and bleeding events in patients with incident atrial fibrillation : A Finnish nationwide cohort study

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