Arrhythmogenic Potential of Myocardial Edema: The Interstitial Osmolality Induces Spiral Waves and Multiple Excitation Wavelets.

Myocardial edema is a common symptom of pathological processes in the heart, causing aggravation of cardiovascular diseases and leading to irreversible myocardial remodeling. Patient-based studies show that myocardial edema is associated with arrhythmias. Currently, there are no studies that have examined how edema may influence changes in calcium dynamics in the functional syncytium. We performed optical mapping of calcium dynamics on a monolayer of neonatal rat cardiomyocytes with Fluo-4. The osmolality of the solutions was adjusted using the NaCl content. The initial Tyrode solution contained 140 mM NaCl (1T) and the hypoosmotic solutions contained 105 (0.75T) and 70 mM NaCl (0.5T). This study demonstrated a sharp decrease in the calcium wave propagation speed with a decrease in the solution osmolality. The successive decrease in osmolality also showed a transition from a normal wavefront to spiral wave and multiple wavelets of excitation with wave break. Our study demonstrated that, in a cellular model, hypoosmolality and, as a consequence, myocardial edema, could potentially lead to fatal ventricular arrhythmias, which to our knowledge has not been studied before. At 0.75T spiral waves appeared, whereas multiple wavelets of excitation occurred in 0.5T, which had not been recorded previously in a two-dimensional monolayer under conditions of cell edema without changes in the pacing protocol.

Re-entry in models of cardiac ventricular tissue with scar represented as a Gaussian random field.

Introduction: Fibrotic scar in the heart is known to act as a substrate for arrhythmias. Regions of fibrotic scar are associated with slowed or blocked conduction of the action potential, but the detailed mechanisms of arrhythmia formation are not well characterised and this can limit the effective diagnosis and treatment of scar in patients. The aim of this computational study was to evaluate different representations of fibrotic scar in models of 2D 10 × 10 cm ventricular tissue, where the region of scar was defined by sampling a Gaussian random field with an adjustable length scale of between 1.25 and 10.0 mm. Methods: Cellular electrophysiology was represented by the Ten Tusscher 2006 model for human ventricular cells. Fibrotic scar was represented as a spatially varying diffusion, with different models of the boundary between normal and fibrotic tissue. Dispersion of activation time and action potential duration (APD) dispersion was assessed in each sample by pacing at an S1 cycle length of 400 ms followed by a premature S2 beat with a coupling interval of 323 ms. Vulnerability to reentry was assessed with an aggressive pacing protocol. In all models, simulated fibrosis acted to delay activation, to increase the dispersion of APD, and to generate re-entry. Results: A higher incidence of re-entry was observed in models with simulated fibrotic scar at shorter length scale, but the type of model used to represent fibrotic scar had a much bigger influence on the incidence of reentry. Discussion: This study shows that in computational models of fibrotic scar the effects that lead to either block or propagation of the action potential are strongly influenced by the way that fibrotic scar is represented in the model, and so the results of computational studies involving fibrotic scar should be interpreted carefully.

Optimal timing of staged percutaneous coronary intervention after subintimal tracking and re-entry: Rationale and design of the subintimal tracking and re-entry with deferred stenting study.

BACKGROUND: Ten to fifteen percent of chronic total occlusion (CTO) percutaneous coronary interventions (PCIs) are unsuccessful in contemporary practice. Subintimal tracking and re-entry (STAR) (one form of "investment procedure") with staged reattempt and stenting may further increase the ultimate success and safety of CTO as a bailout strategy. The optimal timing for staged stenting after STAR is unknown. METHODS AND RESULTS: We designed a six-center, prospective randomized trial with a planned enrollment of 150 patients where STAR is utilized in case of impending failure. The primary aim is to evaluate the optimal timing of the staged PCI after STAR by randomizing the timing to earlier (5-7 weeks) versus later (12-14 weeks) staged PCI. The primary endpoint of the study is the technical success rate of the staged procedure. The secondary endpoints include: (1) the rate of thrombolysis in myocardial infarction 3 flow at the start of staged intervention, (2) rate of partial technical and procedural success of the staged procedure, (3) rate of in-hospital and 12-month major cardiac and cerebrovascular adverse events, and (4) change in patient-reported quality at 30 days, 6 months, and 12 months assessed by Seattle Angina Questionnaire. CONCLUSION: This study will ascertain the optimal timing of staged stenting after bail-out STAR approach in contemporary CTO PCI (ClinicalTrials.gov NCT05089864).

Antegrade techniques for chronic total occlusion percutaneous coronary intervention.

Antegrade techniques are the foundation of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). Antegrade wiring with the intent to achieve an intraplaque guidewire tracking is not always feasible, and crossing into the extraplaque space with subsequent reentry (antegrade dissection and reentry), might be needed, particularly in more complex occlusions. The present article reviews in detail the antegrade approaches to CTO PCI, focusing on equipment, techniques, and overcoming challenges.

Cinnamaldehyde protects SH-SY5Y cells against advanced glycation end-products induced ectopic cell cycle re-entry.

Accumulation of advanced glycation end-products (AGEs) in the brain contributes significantly to cognitive impairment in patients with diabetes by disrupting the post-mitotic state of neuronal cells, thereby triggering ectopic cell cycle re-entry (CCR) and subsequent neuronal apoptosis. Cinnamaldehyde (CINA), a potential mitigator of cognitive impairment due to its blood glucose-lowering properties, warrants exploration for its role in counteracting diabetes-related neurological damage. In this study, we examined the neuroprotective effect of CINA on AGE-damaged SH-SY5Y human neuroblastoma cells differentiated in vitro. We investigated the impact of CINA on AGE-induced neuronal CCR and apoptosis, finding that it substantially suppressed aberrant DNA replication, precluded cells from entering the mitotic preparatory phase, and diminished apoptosis. Additionally, CINA inhibited the expression of eIF4E without altering S6K1 phosphorylation. These findings indicate that CINA safeguards neuronal cells from AGE-related damage by preventing abnormal CCR, preserving the post-mitotic state of neuronal cells, and reducing AGE-induced apoptosis, potentially through the inhibition of eIF4E-controlled cell proliferation. Our results highlight the prospective utility of CINA in managing diabetic neuropathy.

Challenges, experiences, and potential supports for East and Southeast Asian mothers in the workforce: a systematic review.

OBJECTIVE: To examine the challenges faced by Asian working mothers with a focus on re-entry to the workplace. In addition, we highlight potential supports that retain women in the workforce. DESIGN: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations and registered with PROSPERO database (CRD42022341130). METHODS: Three independent reviewers were involved in the study selection to screen the search results sequentially by title, abstract, and full text using predefined inclusion and exclusion criteria. The methodological quality of each article was assessed via the Critical Appraisal Skills Programme (CASP) tool. RESULTS: We analysed a total of 36 studies conducted across different regions: 30 from the East and 6 from Southeast Asia. Among these studies, 20 were quantitative in nature, 15 were qualitative, and one intervention. The 36 studies cover five themes: 1) policies, 2) external support sources, 3) external pressure, 4) breastfeeding and 5) health status. Within each theme the same factor can have a positive or negative impact on the mother depending on her having a pro-career or pro-family mindset. Companies can take various initiatives to support working mothers, such as providing facilities for expressing breast milk at the workplace, educating staff to promote breastfeeding and accommodate childcare needs, and extending maternity leaves. However, there is a lack of literature that directly addresses the barriers and concrete support available to working mothers in Asia, beyond the scope of breastfeeding. CONCLUSIONS: Our findings underscore several obstacles that can impede a woman's seamless return to work. Pro-family and pro-career mothers have differing needs that cannot be addressed at the same time. There is a lack of comprehensive understanding regarding effective strategies or interventions that can support a positive reintegration into the workforce.

Dislodgeable Foliar Residue Measurements and Assessment of Dermal Exposure to Captan for Workers in Apple Orchards.

Captan dislodgeable foliar residues (DFRs) were determined by following the applications of this fungicide in an apple orchard. The study comprised an investigation of the variability of captan DFR values and 14 days of DFR monitoring to assess kinetic modeling. A method combining solid-phase microextraction (SPME) gas chromatography and high-resolution mass spectrometry (GC-QTOF-MS) was developed for the quantification of captan residues from DFR aqueous extracts. The results evidenced that (1) sampling parameters such as the position of the tree in a row and the height of foliar significantly influenced captan DFR levels (247-1450 ng·cm-2), highlighting the need to implement a comprehensive sampling strategy; (2) the DFR captan dissipation kinetic model best matched with a biphasic one, with half-lives of DFRcaptan of 3.4 and 12.8 days, respectively, for the initial rapid phase 1 decline (day 0-5) and the slower phase 2 decline phase (day 6-14). Furthermore, through DFR measurements, the potential dermal exposure (PDE) of workers was assessed using transfer coefficients (TCs) from the literature. Compared to the acceptable operator exposure levels (AOELs), the results showed that the re-entry interval for captan may not sufficiently protect workers whose arms, hands, and legs are not covered.

Demonstration of Arrhythmia Substrate-Associated Dispersion of Repolarization by Epicardial Unipolar Mapping in Brugada Syndrome.

BACKGROUND: Epicardial unipolar mapping has not been thoroughly investigated in Brugada syndrome (BrS). OBJECTIVES: This study aims to examine the characteristics of epicardial unipolar potentials in BrS and investigate the differences from overt cardiomyopathy. METHODS: Epicardial mapping was performed in 8 patients with BrS and 6 patients with cardiomyopathy. We investigated the J-wave amplitudes using unipolar recordings at delayed potential (DP) sites via bipolar recordings. The repolarization time (RT) at and around the DP recording sites was measured, and maximum dispersion of the RT divided by the distance was defined as the RT dispersion index. RESULTS: Epicardial mapping at baseline revealed significantly higher J-wave amplitude with bipolar DP in patients with BrS than in patients with cardiomyopathy. J-wave amplitude ≥0.42 mV had 99.1% sensitivity and 100% specificity for diagnosing BrS. The RT dispersion index was significantly higher in patients with BrS than in patients with cardiomyopathy at baseline. In all patients with BrS, coved-type unipolar electrograms without negative T waves (short RT) appeared close to coved-type electrograms with negative T waves (long RT) at the DP recording sites after pilsicainide administration. Thus, a steep RT dispersion was observed in this region, and ventricular arrhythmias emerged from this shorter RT area in all 3 patients with BrS in whom ventricular arrhythmias were induced. CONCLUSIONS: Bipolar DP-related prominent unipolar J waves and steep repolarization gradients may be more specific for characterizing BrS than for overt cardiomyopathy. Ventricular arrhythmias in BrS are associated with a steep repolarization gradient, indicating phase 2 re-entry as a possible cause.

Observations of substance use treatment engagement during the period of community re-entry following residential treatment.

BACKGROUND: The period of community re-entry following residential substance use treatment is associated with elevated risk for return to substance use. Although continuity of care is best practice, many individuals do not engage in follow-up treatment, struggle to engage in follow-up treatment, or continue to use substances while participating in follow-up treatment. There is a need to both characterize treatment engagement during community re-entry following residential substance use treatment as well as understand how treatment impacts substance use during this high-risk period. METHOD: This observational study used retrospective self-report to examine treatment engagement and substance use among individuals who had exited residential substance use treatment. Participants completed a Timeline Follow-back interview reporting substance use and treatment engagement in the 30 days following residential treatment. RESULTS: Most participants (83.1 %) reported engaging in substance use treatment following discharge. The most common treatments were Alcoholics Anonymous/Narcotics Anonymous (61.1 %), medication for addiction treatment (40 %), and outpatient therapy (29.2 %). Participants were less likely to use substances on a day in which they engaged in outpatient therapy (OR = 0.32, 95 % CI [0.12, 0.90], p = 0.030) and more likely on days they engaged in medication treatment (OR = 21.49, 95 % CI [1.46, 316.74], p = 0.025). CONCLUSION: Findings characterize engagement in substance use treatment in the month following residential treatment. Treatment engagement was common during community re-entry; however, only outpatient therapy was found to reduce substance use during this high-risk period. Findings may inform intervention efforts during the high-risk period of community re-entry.

Case report of a double-wave re-entry atrial flutter in a patient with atrial cardiomyopathy.

Background: Double-wave macrore-entry is a rare mechanism of atrial tachycardia with limited documentation in the literature. We present a three-dimensional documentation of a double-wave 'typical' atrial flutter in a patient with extensive atrial cardiomyopathy. Case summary: A 78-year-old female with a history of atrial cardiomyopathy and dual-chamber pacemaker for sinus node disease presented with palpitations and incessant atrial flutter. Electrophysiological study revealed a regular tachycardia with a cycle length (TCL) of 230 ms, with proximal to distal coronary sinus (CS) activation. Three-dimensional mapping identified two independent wavefronts circulating the cavotricuspid isthmus (CTI), each with a TCL of 460 ms. Cavotricuspid isthmus ablation resulted in conversion into a distinct tachycardia with left atrial roof origin. Linear ablation in this location slowed the TCL to 435 ms with concentric CS activation and another CTI dependent atrial flutter was mapped, this time with only one wavefront of activation. Further ablation with a second, more lateral, line in the CTI led to tachycardia interruption. Given the extensive atrial scarring and high arrhythmic recurrence risk, atrioventricular node ablation was performed. Discussion: Double-wave re-entrant tachycardias were primarily observed in experimental models, precipitating acceleration of ventricular and supraventricular tachycardias via extrastimulation. In our case, there is documentation of a spontaneous double-wave of activation around the CTI, representing the first documented double-wave 'typical' atrial flutter. Unlike other cases in the literature, the two wavefronts were equidistant, which resulted in a regular tachycardia with TCL that was half of the single-wave cycle length. Three-dimensional propagation mapping was essential to visualize the two distinct wavefronts.

Anatomical and Electrophysiological Characteristics of Dual-Loop Re-Entry in Atypical Atrial Flutter: Implications for Mapping and Catheter Ablation.

Background: Atypical atrial flutter (AFL) can be challenging to ablate, especially when involving dual-loop re-entry. We sought to assess the electroanatomical characteristics of single- and dual-loop AFLs in patients undergoing catheter ablation. Methods: We analyzed 25 non-cavotricuspid isthmus-dependent macro-re-entrant AFL in 19 consecutive patients. Three-dimensional high-density activation mapping was performed, and active re-entry loops were confirmed by entrainment mapping. Results: Of 25 AFLs (24 left, 1 right atrial), 13 (52%) exhibited dual-loop re-entry. The most common circuits included, in 6/13 (46% of dual loops), a perimitral re-entry with a second loop around the right/left pulmonary veins (PV) and, in 6/13 (46%), involved a right PV ostium with a second loop around either a functional conduction block or another PV. Ablation at the common isthmus of dual-loop AFLs and at the critical isthmus of single-loop AFLs terminated the arrhythmia more frequently than ablation at a secondary isthmus of dual-loop AFLs (5/6 (83%) and 8/11 (73%) versus 1/8 (13%), respectively, p = 0.013). Conclusions: More than half of AFLs exhibited a dual-loop re-entrant mechanism. Most critical isthmuses were found at the mitral isthmus, the left atrial roof or right PV ostia. Ablation targeting the common isthmus resulted in a higher termination rate.

The effects of aftercare/resettlement services on crime and violence in children and youth: A systematic review.

Background: High rates of youth re-offending indicate that young custody-leavers face challenges when reintegrating into their communities. Aftercare and resettlement programs can occur pre-, during, and post-release and generally provide multiple forms of support services to address youths' transitional needs. Objectives: The present review examines (1) the impact of youth aftercare/resettlement programs on crime-related outcomes, (2) how treatment effect is moderated by participant, program, and study characteristics, (3) whether some types of interventions are more effective than others, (4) barriers/facilitators to effective program implementation, (5) the theory of change underlying resettlement interventions, and (6) available research on intervention cost. Search Methods: A comprehensive set of keywords and synonyms was combined in a Boolean search across 26 electronic databases. Multiple gray literature sources were also searched, including 23 journals, 4 meeting archives, 11 organization websites, 3 open access journal websites, and the CVs of 8 well-known researchers in the field. The search was completed in January 2023. Selection Criteria: For objectives 1-3, studies were included if they utilized a randomized controlled design or quasi-experimental comparison group design in which participants were matched on at least some baseline variables and included at least one quantitative individual-measure of crime. For objective 4, included studies presented process evaluations of aftercare/reentry programs, clearly stated their research goals, and used qualitative methods in an appropriate way to answer the stated research question. For objectives 5 and 6, no specific methods were required; any study meeting the criteria for objectives 1-4 which presented findings on theory of change or cost data were included. For all outcomes, only studies conducted in a westernized country, and published after 1991 in English, French, or German were considered. Data Collection and Analysis: Two coders conducted primary data extraction for the included studies. Data were entered into a Microsoft Excel database. After data extraction, the two coders validated the coding by cross-checking the database with each research report. Discrepancies between coders were discussed until consensus was reached. Where consensus could not be reached, a third coder was consulted. Study risk of bias was addressed using the ROBINS-I (Sterne et al., 2016), ROB-2 (Higgins et al., 2019), and the critical appraisal skills programme (CASP, 2018). Objectives 1-3 were addressed by synthesizing quantitative outcomes from rigorous impact evaluations of aftercare interventions using random effects models and meta-regression. Thematic and narrative analysis was conducted to address objectives 4-6. Results: The search resulted in 15 impact studies, representing 4,718 participants across 21 program sites, and 35 effect sizes. The 21 impact evaluations were rated as having either low/moderate bias (k = 11) or serious bias (k = 10). The synthesis of 15 impact studies found no significant effects for arrest (k = 14; OR = 1.044, 95% prediction interval [0.527, 2.075], t = 0.335) or incarceration (k = 8, OR = 0.806, 95% prediction interval [2.203, 1.433], t = -1.674). A significant pooled effect was found for conviction (k = 13, OR = 1.209, 95% prediction interval [1.000, 1.462], t = 2.256), but results were highly sensitive to the inclusion of specific studies. No meaningful pattern of results emerged in moderator analyses with respect to study, sample, program component, or program delivery characteristics. The 19 process studies were rated as either high quality (k = 12) or moderate quality (k = 7). Thematic synthesis of the process evaluations revealed 15 themes related to the strengths/challenges of program implementation. The assessment of program cost (k = 7) determined a lack of data within the literature, preventing any summative analysis. Authors' Conclusions: Current evidence is promising with respect to conviction outcomes but overall does not find that aftercare/resettlement interventions have a reliably positive impact on crime-related outcomes for young people who have offended. High variability across outcomes and reported data resulted in small sample sizes per outcome and limited moderator analyses. Multiple challenges for program implementation exist; additional rigorous research is sorely needed to further investigate the nuances of the program effects.

Bipolar radiofrequency ablation for re-entrant ventricular tachycardia of right bundle branch block and left bundle branch block morphologies with the common slow conduction zone at the left ventricular summit: a case report.

Background: The left ventricular (LV) summit has anatomical limitations, so the detailed mapping is difficult. Therefore, the mechanism of ventricular tachycardia (VT) originating from the LV summit is not well understood. Case summary: A 70-year-old man had VTs with right bundle branch block (VT1 and VT3) and left bundle branch block (VT2) morphologies originating from the left ventricular summit (LV summit). During the VT2 and VT3, fragmented potentials, which occurred earlier than the QRS onset, were recorded from bipolar electrodes of a catheter at the anterior intraventricular vein (AIV). By pacing from right ventricular apex, constant and progressive fusion were observed. During the entrainment pacing, the fragmented potentials in the AIV catheter were activated orthodromically and those in the His bundle were activated antidromically. In addition, there were two components of the ventricular electrogram at the LV summit area with the interval of more than 100 ms during the VTs. We performed bipolar radiofrequency ablation between the LV endocardium and AIV, and the VTs became non-inducible. Discussion: Non-sustained VT/premature ventricular contraction originating from LV summit is generally considered to occur due to abnormal automaticity or triggered activity. In contrast, using entrainment technique, we demonstrated that the VTs with multiple morphologies were sustained with a re-entrant mechanism. Fragmentated potentials recorded in the AIV catheter were activated orthodromically with the entrainment pacing, indicating the slowly conducting isthmus. The intramural VT substrate was also suggested with a prolonged conduction time between the two ventricular components during the VTs.

Tip Detection-Antegrade Dissection and Re-Entry With New Puncture Wire in CTO Intervention: Revolution Through 3D-Wiring.

Background: The authors devised the tip detection (TD) method and developed AnteOwl WR intravascular ultrasound to standardize intravascular ultrasound-based 3-dimensional wiring for intraplaque tracking in chronic total occlusion (CTO)-percutaneous coronary intervention (PCI). The TD method also allowed antegrade dissection and re-entry (ADR). Combining TD-ADR with Conquest Pro 12 Sharpened Tip (CP12ST) wire, a new ADR wire with the strongest penetration force developed to date, enabled re-entry anywhere except calcification sites. Objectives: This study investigated the efficacy and feasibility of TD-ADR by comparison of procedural outcomes with Stingray-ADR in CTO-PCI. Methods: Twenty-seven consecutive CTO cases treated by TD-ADR with CP12ST wire between August 2021 and April 2023 and 27 consecutive CTO cases treated by Stingray-ADR with Conquest 8-20 (CP20) wire between March 2018 and July 2021 were retrospectively enrolled as the TD-ADR by CP12ST wire group and Stingray-ADR by CP20 wire group, respectively, from 4 facilities that could share technical information on these procedures. Results: The success rate of the ADR procedure was significantly improved (27 of 27 cases [100%] vs 18 of 27 cases [67%], respectively; P = 0.002) and total procedural time was significantly reduced (median procedural time: 145.0 [Q1-Q3: 118.0-240.0] minutes vs 185.0 [Q1-Q3: 159.5-248.0] minutes, respectively; P = 0.028) in the TD-ADR by CP12ST wire group compared to the Stingray-ADR by CP20 wire group. There were few in-hospital major adverse cardiac and cerebrovascular events or no complications in either group. Conclusions: TD-ADR by CP12ST wire can standardize highly accurate ADR in CTO-PCI.

Simulation and analysis of chest loads on crews during Lunar-Earth re-entry returns.

The safety of crews is the primary concern in the manned lunar landing project, particularly during re-entry as the manned spacecraft returns from a direct Lunar-Earth trajectory. This paper analyzed the crew's chest biomechanical response to assess potential injuries caused by acceleration loads during the re-entry phase. Initially, a sophisticated finite element model of the chest was constructed, whose effectiveness was verified by experiments involving vertebral range of motion, rib lateral rupture, and chest frontal impact. The model was then subjected to the return re-entry loads simulating the Apollo and Chang'e 5 T1 (CE-5T1) test returner to specifically analyze the correlation between the acceleration load and the injury of the crew's chest tissues and organs. The results indicate that the biomechanical response of crew chest bone tissue under the two return missions is within the threshold value and will not directly cause damage. Compared to the Apollo mission, the CE-5T1 mission's load poses a higher risk to internal organs. These findings can enhance the crew's safety and provide reliable assurance for future space exploration.

High-density "APLE" Mapping-Activation, Propagation, Low Voltage, and Electrogram Evaluation with the HD Grid for Atrioventricular Nodal Re-entry Tachycardia Ablation.

This is the first case series to evaluate high-density mapping of the triangle of Koch (TOK) using the HD Grid to guide slow-pathway ablation integrating activation, propagation (with wave collision), low-voltage signals, and atrial electrogram appearance. We will describe our technique and the results in this case series. Using three-dimensional mapping and the HD Grid, patients underwent high-density voltage mapping of the TOK. Ablation site selection was based on properties during sinus rhythm with late activation, at or above the propagation wave collision, over low voltage, and with appropriate electrogram appearance. Five patients underwent mapping of the slow pathway using the HD Grid. Their median age was 14 years, their median weight was 54.1 kg, and their median height was 161.5 cm. The TOK was mapped with the HD Grid for a median of 3 min. The procedure was successful in all patients using this technique. The median lesion number to the site of success was 3, with a median total number of cryotherapy lesions of 11. No radiation was used. There were no recurrences. Using activation, propagation wave, low voltage, and electrogram appearance when mapping for slow-pathway localization and ablation with the HD Grid can be successful, results in high-density maps, and is relatively faster.