microRNA and the Post-Transcriptional Response to Oxidative Stress during Neuronal Differentiation: Implications for Neurodevelopmental and Psychiatric Disorders.

Oxidative stress is one of the most important environmental exposures associated with psychiatric disorders, but the underlying molecular mechanisms remain to be elucidated. In a previous study, we observed a substantial alteration of the gene expression landscape in neuron-like cells that were differentiated from SH-SY5Y cells after or during exposure to oxidative stress, with a subset of dysregulated genes being enriched for neurodevelopmental processes. To further explore the regulatory mechanisms that might account for such profound perturbations, we have now applied small RNA-sequencing to investigate changes in the expression of miRNAs. These molecules are known to play crucial roles in brain development and response to stress through their capacity to suppress gene expression and influence complex biological networks. Through these analyses, we observed more than a hundred differentially expressed miRNAs, including 80 previously reported to be dysregulated in psychiatric disorders. The seven most influential miRNAs associated with pre-treatment exposure, including miR-138-5p, miR-96-5p, miR-34c-5p, miR-1287-5p, miR-497-5p, miR-195-5p, and miR-16-5p, supported by at least 10 negatively correlated mRNA connections, formed hubs in the interaction network with 134 genes enriched with neurobiological function, whereas in the co-treatment condition, miRNA-mRNA interaction pairs were enriched in cardiovascular and immunity-related disease ontologies. Interestingly, 12 differentially expressed miRNAs originated from the DLK1-DIO3 location, which encodes a schizophrenia-associated miRNA signature. Collectively, our findings suggest that early exposure to oxidative stress, before and during prenatal neuronal differentiation, might increase the risk of mental illnesses in adulthood by disturbing the expression of miRNAs that regulate neurodevelopmentally significant genes and networks.

DOxy: A Dissolved Oxygen Monitoring System.

Dissolved Oxygen (DO) in water enables marine life. Measuring the prevalence of DO in a body of water is an important part of sustainability efforts because low oxygen levels are a primary indicator of contamination and distress in bodies of water. Therefore, aquariums and aquaculture of all types are in need of near real-time dissolved oxygen monitoring and spend a lot of money on purchasing and maintaining DO meters that are either expensive, inefficient, or manually operated-in which case they also need to ensure that manual readings are taken frequently which is time consuming. Hence a cost-effective and sustainable automated Internet of Things (IoT) system for this task is necessary and long overdue. DOxy, is such an IoT system under research and development at Santa Clara University's Ethical, Pragmatic, and Intelligent Computing (EPIC) Laboratory which utilizes cost-effective, accessible, and sustainable Sensing Units (SUs) for measuring the dissolved oxygen levels present in bodies of water which send their readings to a web based cloud infrastructure for storage, analysis, and visualization. DOxy's SUs are equipped with a High-sensitivity Pulse Oximeter meant for measuring dissolved oxygen levels in human blood, not water. Hence a number of parallel readings of water samples were gathered by both the High-sensitivity Pulse Oximeter and a standard dissolved oxygen meter. Then, two approaches for relating the readings were investigated. In the first, various machine learning models were trained and tested to produce a dynamic mapping of sensor readings to actual DO values. In the second, curve-fitting models were used to produce a successful conversion formula usable in the DOxy SUs offline. Both proved successful in producing accurate results.

Delivering a sleep intervention across a youth mental health service using non-expert practitioners: A service evaluation.

AIMS: Poor sleep is highly prevalent in young people and increases risk of mental health difficulties, yet access to sleep interventions remains limited. This paper evaluates the use of a sleep intervention delivered by non-expert practitioners in a secondary care youth mental health service. METHOD: Assistant psychologists were trained to deliver a six-session 1:1 cognitive-behavioural sleep intervention adapted for use with young people with mental health difficulties. A within-subject design assessed clinical outcomes relating to sleep (Insomnia Severity Index), psychological distress and personal goals (Goal Based Outcome Measures) at four time points. RESULTS: High referral, intervention take-up (82.82%) and completion (70%) rates were reported, together with high baseline levels of insomnia (Insomnia Severity Index mean 20.47, SD 3.68) and poor sleep efficiency (56.36%, SD 17.23). Fifty-six young people (average age 19.2 years, SD 3.25) were included in the outcome analysis. Statistically and clinically significant improvements were seen across all outcome measures, with 68% no longer meeting clinical threshold (ISI ≥15) for insomnia at endpoint. CONCLUSIONS: This study demonstrates exceptionally high levels of clinical need and engagement with a sleep intervention adapted specifically for young people with mental health difficulties. Whilst limited by the uncontrolled design, large improvements in insomnia and psychological distress support its effectiveness and utility in clinical settings. More robust implementation and evaluation is warranted in broader youth mental health services to promote earlier access.

A randomized sham-controlled study of pulmonary vein isolation in symptomatic atrial fibrillation (The SHAM-PVI study): Study design and rationale.

INTRODUCTION: Pulmonary vein (PV) isolation has been shown to reduce atrial fibrillation (AF) burden and symptoms in patients. However, to date previous studies have been unblinded raising the possibility of a placebo effect to account for differences in outcomes. HYPOTHESIS & METHODS: The objective of this study is to compare PV isolation to a sham procedure in patients with symptomatic AF. The SHAM-PVI study is a double blind randomized controlled clinical trial. 140 patients with symptomatic paroxysmal or persistent AF will be randomized to either PV isolation (with cryoballoon ablation) or a sham procedure (with phrenic nerve pacing). All patients will receive an implantable loop recorder. The primary outcome is total AF burden at 6 months postrandomisation (excluding the 3 month blanking period). Key secondary outcomes include (1) time to symptomatic and asymptomatic atrial tachyarrhythmia (2) total atrial tachyarrhythmia episodes and (3) patient reported outcome measures. RESULTS: Enrollment was initiated in January 2020. Through April 2023 119 patients have been recruited. Results are expected to be disseminated in 2024. CONCLUSION: This study compares PV isolation using cryoablation to a sham procedure. The study will estimate the effect of PV isolation on AF burden.

Nonspherical ultrasound microbubbles.

Surface tension provides microbubbles (MB) with a perfect spherical shape. Here, we demonstrate that MB can be engineered to be nonspherical, endowing them with unique features for biomedical applications. Anisotropic MB were generated via one-dimensionally stretching spherical poly(butyl cyanoacrylate) MB above their glass transition temperature. Compared to their spherical counterparts, nonspherical polymeric MB displayed superior performance in multiple ways, including i) increased margination behavior in blood vessel-like flow chambers, ii) reduced macrophage uptake in vitro, iii) prolonged circulation time in vivo, and iv) enhanced blood-brain barrier (BBB) permeation in vivo upon combination with transcranial focused ultrasound (FUS). Our studies identify shape as a design parameter in the MB landscape, and they provide a rational and robust framework for further exploring the application of anisotropic MB for ultrasound-enhanced drug delivery and imaging applications.

Variations of wet-bulb globe temperature across high school athletics in South Carolina.

The purpose was to describe wet bulb globe temperature (WBGT) throughout a high school fall athletic season (August to November) after a state-wide mandate requiring schools to use a WBGT-guided activity modification table with categories (AMTC). A cross-sectional research design utilized 30 South Carolina high schools. The independent variables were region (upstate, midlands, and coastal), sport (football, tennis, cross-country), month, start times (7-10 am, 10 am-3 pm, 3-6 pm, and 6-9 pm), and event type (practice, competition). Dependent variables were event frequency, average WBGT, and AMTC. Practice WBGT was 78.7 ± 8.2 °F (range: 34.7 to 99.0 °F). A significant difference for WBGT across month (F6, 904.7 = 385.07, P < 0.001) existed, with early September hotter than all other months (84.8 °F ± 3.8, P < 0.001). Every month had practices in each AMTC, until early November. Most events (64.6%, n = 1986) did not change AMTC; however, 9.1% (n = 281) changed to a hotter category. The 10 am-3 pm start time was significantly hotter than all other time frames (83.0 °F ± 7.2, P < 0.05). Tennis experienced hotter practices (79.9 °F ± 6.9) than football (78.4 °F ± 8.5; P < 0.001) and cross country (78.2 °F ± 8.8, P < 0.001). Schools in the Midlands experienced hotter practices (80.1 °F ± 7.8) than upstate (P < 0.001) and coastal schools (P = 0.005). Competition WBGT was significantly cooler than practices (72.3 ± 10.5 °F, t = 12.04, P < 0.001) and differed across sports (F2, 20.78 = 18.39, P < .001). Both cross-country (P = 0.003) and tennis (P < 0.001) were hotter than football. Schools should continuously monitor WBGT throughout practices and until November to optimize AMTC use. Risk mitigation strategies are needed for sports other than football to decrease the risk of exertional heat illnesses.

Controlled Delivery of Corticosteroids Using Tunable Tough Adhesives.

Hydrogel-based drug delivery systems typically aim to release drugs locally to tissue in an extended manner. Tissue adhesive alginate-polyacrylamide tough hydrogels are recently demonstrated to serve as an extended-release system for the corticosteroid triamcinolone acetonide. Here, the stimuli-responsive controlled release of triamcinolone acetonide from the alginate-polyacrylamide tough hydrogel drug delivery systems (TADDS) and evolving new approaches to combine alginate-polyacrylamide tough hydrogel with drug-loaded nano and microparticles, generating composite TADDS is described. Stimulation with ultrasound pulses or temperature changes is demonstrated to control the release of triamcinolone acetonide from the TADDS. The incorporation of laponite nanoparticles or PLGA microparticles into the tough hydrogel is shown to further enhance the versatility to control and modulate the release of triamcinolone acetonide. A first technical exploration of a TADDS shelf-life concept is performed using lyophilization, where lyophilized TADDS are physically stable and the bioactive integrity of released triamcinolone acetonide is demonstrated. Given the tunability of properties, the TADDS are a suggested technology platform for controlled drug delivery.

Xylem conduit deformation across vascular plants: an evolutionary spandrel or protective valve?

The hydraulic system of vascular plants and its integrity is essential for plant survival. To transport water under tension, the walls of xylem conduits must approximate rigid pipes. Against this expectation, conduit deformation has been reported in the leaves of a few species and hypothesized to function as a 'circuit breaker' against embolism. Experimental evidence is lacking, and its generality is unknown. We demonstrated the role of conduit deformation in protecting the upstream xylem from embolism through experiments on three species and surveyed a diverse selection of vascular plants for conduit deformation in leaves. Conduit deformation in minor veins occurred before embolism during slow dehydration. When leaves were exposed to transient increases in transpiration, conduit deformation was accompanied by large water potential differences from leaf to stem and minimal embolism in the upstream xylem. In the three species tested, collapsible vein endings provided clear protection of upstream xylem from embolism during transient increases in transpiration. We found conduit deformation in diverse vascular plants, including 11 eudicots, ginkgo, a cycad, a fern, a bamboo, and a grass species, but not in two bamboo and a palm species, demonstrating that the potential for 'circuit breaker' functionality may be widespread across vascular plants.

ECG-I phenotyping of persistent AF based on driver burden and distribution to predict response to pulmonary vein isolation (PHENOTYPE-AF).

BACKGROUND: This prospective trial sought to phenotype persistent atrial fibrillation (AF) based on AF mechanisms using electrocardiographic imaging (ECGI) mapping to determine whether this would predict long-term freedom from arrhythmia after pulmonary vein isolation (PVI). METHODS: Patients with persistent AF of <2 years duration underwent cryoballoon PVI. ECGI mapping was performed before PVI to determine potential drivers (PDs) defined as rotational activations completing ≥1.5 revolutions or focal activations. The coprimary endpoint was the association between (1) PD burden (defined as the number of PD occurrences) and (2) PD distribution (defined as the number of segments on an 18-segment model of the atria harboring PDs) with freedom from arrhythmia at 1-year follow up. RESULTS: Of 100 patients, 97 completed follow up and 52 (53.6%) remained in sinus rhythm off antiarrhythmic drugs. Neither PD burden nor PD distribution predicted freedom from arrhythmia (hazard ratio [HR]: 1.01, 95% confidence interval [CI]: 0.99-1.03, p = .164; and HR: 1.04, 95% CI: 0.91-1.17, p = .591, respectively). Otherwise, the burden of rotational PDs, rotational stability, and the burden of PDs occurring at the pulmonary veins and posterior wall all failed to predict arrhythmia recurrence (all p > .10). CONCLUSIONS: AF mechanisms as determined using ECGI mapping do not predict outcomes after PVI for persistent AF. Further studies using different methodologies to characterize AF mechanisms are warranted (NCT03394404).

Contemporary Practice and Optimising Referral Pathways for Implantable Cardiac Monitoring for Atrial Fibrillation after Cryptogenic Stroke.

OBJECTIVES: Diagnosing atrial fibrillation (AF) in patients following Cryptogenic stroke (CS) has therapeutic implications that can reduce the risk of further strokes. However, it's indolent and paroxysmal nature makes this challenging. Prolonged rhythm monitoring using implantable loop recorders (ILRs) can significantly increase the AF detection rate in the clinical trial paradigm. Whether this can be translated to real-world practice is unknown. An evaluation of referral pathways, workload and real-world efficacy may help select patients and inform service development. MATERIALS AND METHODS: Retrospective review of all patients with CS referred to a tertiary electrophysiology referral hospital for ILR implantation between February 2017 and October 2020 for AF detection was conducted. The electronic health record was used to determine demographic and mortality data. Remote monitoring was used to identify AF occurrence. RESULTS: 107 patients were included. The average time from stroke to ILR implantation was 10.5 (5.9-18.6) months. The average monitoring duration was 18.1 ± 11.2 months with 15 (14.0%) patients diagnosed with AF and commenced on anticoagulation. One diagnosis were made in the first 30 days whereas 11 (73%) were made within 12 months. Paroxysmal AF episodes ranged from 6 min to 13 h. Patients with CHA2DS2-VASc >3 were more likely to have AF (20.3% vs 4.7%, p = 0.02). Age was independently associated with AF detection after multi-variate regression. 352 ± 1171 unique events were recorded per patient, 75% of which were for suspected AF. External manufacturer-led triage of transmissions reduced transmission volume by 33%. CONCLUSIONS: ILR-based AF detection rate was high among referred CS patients, despite implantation occurring relatively late. Older patients may be less likely to be referred despite positive correlation between age and AF detection. Although recording algorithms and external triage reduced transmission volume, specialist analysis was required to manage the ILR event burden.

Assessing Noninvasive Delineation of Low-Voltage Zones Using ECG Imaging in Patients With Structural Heart Disease.

OBJECTIVES: This study sought to assess the association between electrocardiographic imaging (ECGI) parameters and voltage from simultaneous electroanatomic mapping (EAM). BACKGROUND: ECGI offers noninvasive assessment of electrophysiologic features relevant for mapping ventricular arrhythmia and its substrate, but the accuracy of ECGI in the delineation of scar is unclear. METHODS: Sixteen patients with structural heart disease underwent simultaneous ECGI (CardioInsight, Medtronic) and contact EAM (CARTO, Biosense-Webster) during ventricular tachycardia catheter ablation, with 7 mapped epicardially. ECGI and EAM geometries were coregistered using anatomic landmarks. ECGI points were paired to the closest site on the EAM within 10 mm. The association between EAM voltage and ECGI features from reconstructed epicardial unipolar electrograms was assessed by mixed-effects regression models. The classification of low-voltage regions was performed using receiver-operating characteristic analysis. RESULTS: A total of 9,541 ECGI points (median: 596; interquartile range: 377-737 across patients) were paired to an EAM site. Epicardial EAM voltage was associated with ECGI features of signal fractionation and local repolarization dispersion (N = 7; P < 0.05), but they poorly classified sites with bipolar voltage of <1.5 mV or <0.5 mV thresholds (median area under the curve across patients: 0.50-0.62). No association was found between bipolar EAM voltage and low-amplitude reconstructed epicardial unipolar electrograms or ECGI-derived bipolar electrograms. Similar results were found in the combined cohort (n = 16), including endocardial EAM voltage compared to epicardial ECGI features (n = 9). CONCLUSIONS: Despite a statistically significant association between ECGI features and EAM voltage, the accuracy of the delineation of low-voltage zones was modest. This may limit ECGI use for pr-procedural substrate analysis in ventricular tachycardia ablation, but it could provide value in risk assessment for ventricular arrhythmias.

Long-term Outcomes of Catheter Ablation for Ventricular Arrhythmias in Post-Myocarditis Patients: Insights from a Meta-Analysis of Current Data.

BACKGROUND: In the past decade, catheter ablation (CA) has become a rapidly expanding treatment option for ventricular tachycardia (VT); however it is not commonly utilised for patients with post-myocarditis VT. We aimed to systematically review up-to-date evidence regarding feasibility, effectiveness, and safety of CA, with a specific focus on long-term relapse rate and procedural complications. METHODS: A structured electronic database search (PubMed, Embase, Cochrane) of the scientific literature was performed according to PRISMA guidelines for studies describing outcomes at up to 7.3 years after CA. The primary outcome measured was VT recurrence post-ablation. Procedural success was defined as freedom of ventricular arrhythmias (at the end of follow-up after an ablation procedure). The secondary outcome was significant procedural complications which included procedural death, stroke, cardiac tamponade, acute myocardial infarction, major vascular complications, and major bleeding, assessed on a study-by-study basis. RESULTS: A total of 186 patients were included in analysis with most patients (88%) being male. Over the follow-up period, there was a 18% relapse rate (n = 34) (confidence interval (CI); 0.12-0.24, I 2≈0, p = 0.77) with the majority of patients remaining VT free for the duration of follow-up. The overall procedural complication rate was 3.0% (n = 7) (CI; 0.01-0.07, I 2≈0, p = 0.44), and of note, there were no peri-procedural deaths or heart transplant surgeries reported. However, a single study reported a mortality of 10% (n = 2) during the follow-up period. CONCLUSIONS: CA is an effective and durable long-term therapeutic strategy for post-myocarditis VT patients with limited relapse rate and very low complication rates based on these non-randomised data. Larger randomised-controlled trials with standardised treatment and long follow-up are required to compare CA versus conventional treatment in the post-acute myocardial phase. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42399-022-01137-w.

Detailed Assessment of Low-Voltage Zones Localization by Cardiac MRI in Patients With Implantable Devices.

OBJECTIVES: The purpose of this study was to assess the performance and limitations of low-voltage zones (LVZ) localization by optimized late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) scar imaging in patients with cardiac implantable electronic devices (CIEDs). BACKGROUND: Scar evaluation by LGE-CMR can assist ventricular tachycardia (VT) ablation, but challenges with electroanatomical maps coregistration and presence of imaging artefacts from CIED limit accuracy. METHODS: A total of 10 patients underwent VT ablation and preprocedural LGE-CMR using wideband imaging. Scar was segmented from CMR pixel signal intensity maps using commercial software (ADAS-VT, Galgo Medical) with bespoke tools and compared with detailed electroanatomical maps (CARTO). Coregistration of EP and imaging-derived scar was performed using the aorta as a fiducial marker, and the impact of coregistration was determined by assessing intraobserver/interobserver variability and using computer simulations. Spatial smoothing was applied to assess correlation at different spatial resolutions and to reduce noise. RESULTS: Pixel signal intensity maps localized low-voltage zones (V <1.5 mV) with area under the receiver-operating characteristic curve: 0.82 (interquartile range [IQR]: 0.76-0.83), sensitivity 74% (IQR: 71%-77%), and specificity 78% (IQR: 73%-83%) and correlated with bipolar voltage (r = -0.57 [IQR: -0.68 to -0.42]) across patients. In simulations, small random shifts and rotations worsened LVZ localization in at least some cases. The use of the full aortic geometry ensured high reproducibility of LVZ localization (r >0.86 for area under the receiver-operating characteristic curve). Spatial smoothing improved localization of LVZ. Results for LVZ with V <0.5 mV were similar. CONCLUSIONS: In patients with CIEDs, novel wideband CMR sequences and personalized coregistration strategies can localize LVZ with good accuracy and may assist VT ablation procedures.

Driver characteristics associated with structurally and electrically remodeled atria in persistent atrial fibrillation.

Background: Recent studies suggest persistent atrial fibrillation (AF) is maintained by localized focal or rotational electrical activations termed drivers. Objective: The purpose of this study was to evaluate how left atrial (LA) dilation and time in AF impact persistent AF mechanisms. Methods: Patients with persistent AF <2 years underwent electrocardiographic image mapping. Potential drivers (PDs) were defined as rotational wavefront activity ≥1.5 revolutions or focal activations. Distribution of PDs was recorded using an 18-segment model. Results: One hundred patients were enrolled (age 61.3 ± 12.1 years). Of these patients, 47 were hypertensive, 14 had diabetes mellitus, and 10 had ischemic heart disease. AF duration was 8 [5-15] months. Median LA diameter was 39 [33-43] mm. Although LA dimensions did not correlate with overall PD burden or distribution, there was a modest correlation between increasing LA area (r = 0.235; P = .024) and LA volume (r = 0.216; P = .039) with proportion of PDs that were rotational. Although time in AF did not correlate with overall PD burden or distribution, there was a correlation between time in AF and the number of focal PDs (r = 0.203; P = .044). Female gender, increasing age, and hypertension also were associated with an increase in focal PDs. Conclusion: This is the first study to demonstrate different AF mechanisms in patient subgroups. Greater understanding of patient-specific AF mechanisms may facilitate a tailored approach to AF mapping and ablation.

The Use of Electrocardiographic Imaging in Localising the Origin of Arrhythmias During Catheter Ablation of Ventricular Tachycardia.

Non-invasive electrocardiographic imaging (ECGI) is a novel clinical tool for mapping ventricular arrhythmia. Using multiple body surface electrodes to collect unipolar electrograms and conventional medical imaging of the heart, an epicardial shell can be created to display calculated electrograms. This calculation is achieved by solving the inverse problem and allows activation times to be calculated from a single beat. The technology was initially pioneered in the US using an experimental torso-shaped tank. Accuracy from studies in humans has varied. Early data was promising, with more recent work suggesting only moderate accuracy when reproducing cardiac activation. Despite these limitations, the system has been successfully used in pioneering work with non-invasive cardiac radioablation to treat ventricular arrhythmia. This suggests that the resolution may be sufficient for treatment of large target areas. Although untested in a well conducted clinical study it is likely that it would not be accurate enough to guide more discreet radiofrequency ablation.

Examining Correlates of Suicidal Ideation between those with and without Psychosis in a Psychiatric Inpatient Sample.

BACKGROUND: The present study explored group differences in suicide-related variables between those with and without psychosis within the context of a psychiatric inpatient sample that included a range of affective disorder diagnoses. METHODS: 54 individuals with psychosis and 103 individuals without psychosis (but experiencing other severe and acute mental health issues) were compared, and analyses of indirect effects were conducted to test specificity of thwarted belongingness, perceived burdensomeness, capability for suicide, agitation, and insomnia as accounting for group differences in suicidal ideation. RESULTS: Patients without psychosis experienced higher levels of suicidal ideation, perceived burdensomeness, thwarted belongingness, agitation, and insomnia than patients with psychosis. Additionally, perceived burdensomeness and agitation emerged as robust explanatory factors for the relationship between psychosis status and suicidal ideation. LIMITATIONS: Future work should include longitudinal analyses to understand temporal relationships between study variables. Additionally, stability of patients' psychotic symptoms was required and therefore may not reflect those at greatest acuity. CONCLUSIONS: Although several studies have investigated suicide-related variables among those with psychosis as compared to the general population, the present study is novel in that the severity of these symptoms in those with psychosis is compared to that of those in other acutely ill populations (e.g., major depression, substance use).

Impact of adenosine on mechanisms sustaining persistent atrial fibrillation: Analysis of contact electrograms and non-invasive ECGI mapping data.

BACKGROUND: We evaluated the effect of adenosine upon mechanisms sustaining persistent AF through analysis of contact electrograms and ECGI mapping. METHODS: Persistent AF patients undergoing catheter ablation were included. ECGI maps and cycle length (CL) measurements were recorded in the left and right atrial appendages and repeated following boluses of 18 mg of intravenous adenosine. Potential drivers (PDs) were defined as focal or rotational activations completing ≥ 1.5 revolutions. Distribution of PDs was assessed using an 18 segment biatrial model. RESULTS: 46 patients were enrolled. Mean age was 63.4 ± 9.8 years with 33 (72%) being male. There was no significant difference in the number of PDs recorded at baseline compared to adenosine (42.1 ± 15.2 vs 40.4 ± 13.0; p = 0.417), nor in the number of segments harbouring PDs, (13 (11-14) vs 12 (10-14); p = 0.169). There was a significantly higher percentage of PDs that were focal in the adenosine maps (36.2 ± 15.2 vs 32.2 ± 14.4; p < 0.001). There was a significant shortening of CL in the adenosine maps compared to baseline which was more marked in the right atrium than left atrium (176.7 ± 34.7 vs 149.9 ± 27.7 ms; p < 0.001 and 165.6 ± 31.7 vs 148.3 ± 28.4 ms; p = 0.003). CONCLUSION: Adenosine led to a small but significant shortening of CL which was more marked in the right than left atrium and may relate to shortening of refractory periods rather than an increase in driver burden or distribution. Registered on Clinicaltrials.gov: NCT03394404.

A Primary Prevention Clinical Risk Score Model for Patients With Brugada Syndrome (BRUGADA-RISK).

OBJECTIVES: The goal of this study was to develop a risk score model for patients with Brugada syndrome (BrS). BACKGROUND: Risk stratification in BrS is a significant challenge due to the low event rates and conflicting evidence. METHODS: A multicenter international cohort of patients with BrS and no previous cardiac arrest was used to evaluate the role of 16 proposed clinical or electrocardiogram (ECG) markers in predicting ventricular arrhythmias (VAs)/sudden cardiac death (SCD) during follow-up. Predictive markers were incorporated into a risk score model, and this model was validated by using out-of-sample cross-validation. RESULTS: A total of 1,110 patients with BrS from 16 centers in 8 countries were included (mean age 51.8 ± 13.6 years; 71.8% male). Median follow-up was 5.33 years; 114 patients had VA/SCD (10.3%) with an annual event rate of 1.5%. Of the 16 proposed risk factors, probable arrhythmia-related syncope (hazard ratio [HR]: 3.71; p < 0.001), spontaneous type 1 ECG (HR: 3.80; p < 0.001), early repolarization (HR: 3.42; p < 0.001), and a type 1 Brugada ECG pattern in peripheral leads (HR: 2.33; p < 0.001) were associated with a higher risk of VA/SCD. A risk score model incorporating these factors revealed a sensitivity of 71.2% (95% confidence interval: 61.5% to 84.6%) and a specificity of 80.2% (95% confidence interval: 75.7% to 82.3%) in predicting VA/SCD at 5 years. Calibration plots showed a mean prediction error of 1.2%. The model was effectively validated by using out-of-sample cross-validation according to country. CONCLUSIONS: This multicenter study identified 4 risk factors for VA/SCD in a primary prevention BrS population. A risk score model was generated to quantify risk of VA/SCD in BrS and inform implantable cardioverter-defibrillator prescription.

Post-operative cardiac implantable electronic devices in patients undergoing cardiac surgery: a contemporary experience.

AIMS: Optimum timing of pacemaker implantation following cardiac surgery is a clinical challenge. European and American guidelines recommend observation, to assess recovery of atrioventricular block (AVB) (up to 7 days) and sinus node (5 days to weeks) after cardiac surgery. This study aims to determine rates of cardiac implantable electronic devices (CIEDs) implants post-surgery at a high-volume tertiary centre over 3 years. Implant timing, patient characteristics and outcomes at 6 months including pacemaker utilization were assessed. METHODS AND RESULTS: All cardiac operations (n = 5950) were screened for CIED implantation following surgery, during the same admission, from 2015 to 2018. Data collection included patient, operative, and device characteristics; pacing utilization and complications at 6 months. A total of 250 (4.2%) implants occurred; 232 (3.9%) for bradycardia. Advanced age, infective endocarditis, left ventricle systolic impairment, and valve surgery were independent predictors for CIED implants (P < 0.0001). Relative risk (RR) of CIED implants and proportion of AVB increased with valve numbers operated (single-triple) vs. non-valve surgery: RR 5.4 (95% CI 3.9-7.6)-21.0 (11.4-38.9) CIEDs. Follow-up pacing utilization data were available in 91%. Significant utilization occurred in 82% and underutilization (<1% A and V paced) in 18%. There were no significant differences comparing utilization rates in early (≤day 5 post-operatively) vs. late implants (P = 0.55). CONCLUSION: Multi-valve surgery has a particularly high incidence of CIED implants (14.9% double, 25.6% triple valve). Age, left ventricle systolic impairment, endocarditis, and valve surgery were independent predictors of CIED implants. Device underutilization was infrequent and uninfluenced by implant timing. Early implantation (≤5 days) should be considered in AVB post-multi-valve surgery.

Size, shape, and flexibility influence nanoparticle transport across brain endothelium under flow.

Nanoparticle-based therapeutic formulations are being increasingly explored for the treatment of various ailments. Despite numerous advances, the success of nanoparticle-based technologies in treating brain diseases has been limited. Translational hurdles of nanoparticle therapies are attributed primarily to their limited ability to cross the blood-brain barrier (BBB), which is one of the body's most exclusive barriers. Several efforts have been focused on developing affinity-based agents and using them to increase nanoparticle accumulation at the brain endothelium. Very little is known about the role of fundamental physical parameters of nanoparticles such as size, shape, and flexibility in determining their interactions with and penetration across the BBB. Using a three-dimensional human BBB microfluidic model (µHuB), we investigate the impact of these physical parameters on nanoparticle penetration across the BBB. To gain insights into the dependence of transport on nanoparticle properties, two separate parameters were measured: the number of nanoparticles that fully cross the BBB and the number that remain associated with the endothelium. Association of nanoparticles with the brain endothelium was substantially impacted by their physical characteristics. Hard particles associate more with the endothelium compared to soft particles, as do small particles compared to large particles, and spherical particles compared to rod-shaped particles. Transport across the BBB also exhibited a dependence on nanoparticle properties. A nonmonotonic dependence on size was observed, where 200 nm particles exhibited higher BBB transport compared to 100 and 500 nm spheres. Rod-shaped particles exhibited higher BBB transport when normalized by endothelial association and soft particles exhibited comparable transport to hard particles when normalized by endothelial association. Tuning nanoparticles' physical parameters could potentially enhance their ability to cross the BBB for therapeutic applications.