Structural and functional properties of subsidiary atrial pacemakers in a goat model of sinus node disease

Background: The sinoatrial/sinus node (SAN) is the primary pacemaker of the heart. In humans, SAN is surrounded by the paranodal area (PNA). Although the PNA function remains debated, it is thought to act as a subsidiary atrial pacemaker (SAP) tissue and become the dominant pacemaker in the setting of sinus node disease (SND). Large animal models of SND allow characterization of SAP, which might be a target for novel treatment strategies for SAN diseases.Methods: A goat model of SND was developed (n = 10) by epicardially ablating the SAN and validated by mapping of emergent SAP locations through an ablation catheter and surface electrocardiogram (ECG). Structural characterization of the goat SAN and SAP was assessed by histology and immunofluorescence techniques.Results: When the SAN was ablated, SAPs featured a shortened atrioventricular conduction, consistent with the location in proximity of atrioventricular junction. SAP recovery time showed significant prolongation compared to the SAN recovery time, followed by a decrease over a follow-up of 4 weeks. Like the SAN tissue, the SAP expressed the main isoform of pacemaker hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) and Na+/Ca2+ exchanger 1 (NCX1) and no high conductance connexin 43 (Cx43). Structural characterization of the right atrium (RA) revealed that the SAN was located at the earliest activation [i.e., at the junction of the superior vena cava (SVC) with the RA] and was surrounded by the paranodal-like tissue, extending down to the inferior vena cava (IVC). Emerged SAPs were localized close to the IVC and within the thick band of the atrial muscle known as the crista terminalis (CT).Conclusions: SAN ablation resulted in the generation of chronic SAP activity in 60% of treated animals. SAP displayed development over time and was located within the previously discovered PNA in humans, suggesting its role as dominant pacemaker in SND. Therefore, SAP in goat constitutes a promising stable target for electrophysiological modification to construct a fully functioning pacemaker

The safety of early pharmacological venous thromboembolism prophylaxis in patients with traumatic intracranial haemorrhage: a systematic review and meta-analysis

In patients with traumatic intracranial haemorrhage (tICH) there is significant risk of both venous thromboembolism (VTE) and haemorrhage progression. There is a paucity of literature to inform the timing of pharmacological thromboprophylaxis (PTP) initiation. This meta-analysis aims to summarise the current literature on the timing of PTP initiation in tICH. This meta-analysis followed the Methodological Expectations of Cochrane Intervention Reviews checklist and the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Following the literature search, studies were matched against the criteria for inclusion. Data from included studies was pooled, analysed using random-effect analysis and presented as forest plots of risk ratios, except one result reported as difference of means. The ROBINS-I tool was used to assess the risk of bias in the studies. The GRADE approach was taken to assess the quality of included studies. Heterogeneity of studies was assessed using Tau∧2. Funnel plots were generated and used in conjunction with Harbord’s test and Rucker’s arcsine to assess for small-study effect including publication bias. A total of 9927 ICH patients who received PTP were included from 15 retrospective observational cohort studies, 4807 patients received early PTP, the remaining 5120 received late PTP. The definition of early was dependent on the study but no more than 72-hours after admission. The mean age of the included cohort was 45.3 (std dev ±9.5) years, and the proportion of males was 71%. Meta-analysis indicated that there was a significant difference between early and late groups for the rate of VTE (RR, 0.544; p = 0.000), pulmonary embolus (RR, 0.538; p = 0.004), deep vein thrombosis (RR, 0.484; p = 0.000) and the intensive care unit length of stay (difference of means, −2.021; 95% CI, −2.250, −1.792; p = 0.000; Tau∧2 = 0.000), favouring the early group. However, the meta-analysis showed no significant difference between the groups for the rate of mortality (RR, 1.008; p = 0.936), tICH progression (RR, 0.853; p = 0.157), and neurosurgical intervention (RR, 0.870; p = 0.480). These findings indicated that early PTP appears to be safe and effective in patients with tICH.</p

The Oral Microbiome Profile of Water Polo Players Aged 16–20

Objectives: Chlorine has a strong antibacterial property and is the disinfectant most frequently used in swimming pools. Therefore, the microbiota community in the oral cavity of those who practice water sports is assumed to be special due to their regular immersion in water. Adverse changes in the composition of oral cavity microbiota may have serious health consequences. We aimed to compare the oral microbiome between water polo players and non-athletes. We hypothesized that the oral cavity microbiota community differed between water polo players and non-athletes. Materials and Methods: Altogether, 124 water polo players (62 males and 62 females, aged between 9 and 20 years) and 16 non-athlete youths (control group, eight males and eight females, aged between 16 and 20 years, mean age + SD = 17.1 + 1.4 years) who participated in body structure examinations voluntarily agreed to participate in the study. In a randomly selected subsample of water polo players (n: 29, aged between 16 and 20 years, mean age + SD = 17.3 + 1.0 years), saliva samples were also collected. Saliva samples were collected from all non-athlete youths (n: 16, aged between 16 and 20 years). The oral microbiome was determined from a saliva sample, and DNA was isolated using the QIAmp DNA Blood Mini Kit. The 16S rRNA gene amplicon sequencing method was used to analyze the microbiome community. PCR primers were trimmed from the sequence reads with Cutadapt. R library DADA2 was used to process reads in the abundance analysis. Results: In general, Streptococcus, Veilonella, and Prevotella genera constituted more than 50% of the oral microbiome community in the two participant groups combined (n = 45). The oral microbial profile had significant sexual dimorphism and differed between water polo players and the non-athletes. Compared to females, males had a higher (p Atopobium (medium effect size) and Pravotella_7 (very large effect size) genera and a lower (p Fusobacterium (large effect size), Gemella (large effect size), and Streptococcus (large effect size) genera. Compared to non-athletes, water polo players had higher (p Veillonella and lower (p < 0.05, large effect size) relative abundance of the genus Gemella. Conclusions: The results suggest that regular water training can unfavorably alter the composition of the oral microbial community

Impact of COVID-19 on patients awaiting ablation for atrial fibrillation

ObjectiveAtrial fibrillation (AF) ablation services were significantly affected by the COVID-19 pandemic. We aimed to evaluate a symptom-based clinician prioritisation scheme for waiting list management compared with patient-completed quality of life (QoL) scores. We also sought to understand factors influencing QoL, particularly the impact of COVID-19, on patients awaiting AF ablation, via a bespoke questionnaire.MethodsPatients awaiting AF ablation were sent two QoL questionnaires (Atrial Fibrillation Effect on QualiTy of Life (AFEQT) and EuroQol 5D (EQ5D-5L)) and the bespoke questionnaire. At a separate time point, patients were categorised as C1-urgent, C2-priority or C3-routine by their cardiologist based on review of clinic letters.ResultsThere were 118 patients included with priority categorisation available for 86 patients. Median AFEQT scores were lower in C2 (30.4; 17.2-51.9) vs C3 patients (56.5; 32.1-74.1; pConclusionThe QoL of patients awaiting AF ablation is impaired and AFEQT helps to identify patients at risk of admission, over and above physician assessment. COVID-19 influenced patients seeking medical attention with symptomatic AF when they normally would. Regular exercise is associated with better QoL in patients awaiting AF ablation