Neuromuscular electrical stimulation at submaximal intensity combined with motor imagery increases corticospinal excitability.

PURPOSE: There is sparse evidence in the literature that the combination of neuromuscular electrical stimulation (NMES) and motor imagery (MI) can increase corticospinal excitability more that the application of one or the other modality alone. However, the NMES intensity usually employed was below or at motor threshold, not allowing a proper activation of the whole neuromuscular system. This questions the effect of combined MI + NMES with higher intensities, closer to those used in clinical settings. The purpose here was to assess corticospinal excitability during either MI, NMES or a combination of both at different evoked forces. METHODS: Seventeen healthy participants were enrolled in one session consisting of 6 conditions targeting flexor carpi radialis muscle (FCR): rest, MI, NMES at 5% and 20% of maximal voluntary contraction (MVC) and MI and NMES performed simultaneously (MI + NMES). During each condition, corticospinal excitability was assessed by evoking MEP of FCR by using transcranial magnetic stimulation. Maximal M-wave (Mmax) was measured by using the stimulation of the median nerve. RESULTS: MEPs during MI were greater as compared to rest (P = 0.005). MEPs during MI were significantly lower than during MI + NMES at 5% (P = 0.02) and 20% (P = 0.001). Then, MEPs during NMES 5% was significantly lower than during MI + NMES 20% (P < 0.005). CONCLUSION: The present study showed that MI + NMES increased corticospinal excitability more than MI alone. However, corticospinal excitability was not higher as the intensity increase during MI + NMES. Therefore, MI + NMES targeting FCR may not significantly increase the corticospinal excitability between different low-submaximal contractions intensities.

[Contractive function of mesenteric lymph nodes in obese rats].

Over the past 50 years, the prevalence of obesity around the world has increased several times and has become a pandemic. The effect of obesity on the lymphatic system, which plays a key role in the regulation of fluid homeostasis, immune cell migration, antigen presentation, and resolution of inflammatory responses, is poorly understood, and there is no data on the contractile activity of the lymph nodes in obesity. The purpose of the research was to investigate the parameters and mechanisms of dysfunction of the contractile function of the mesenteric lymph nodes of rats in obesity caused by the feeding with the high-fat diet (HFD). Material and methods. The study was conducted on 50 male Sprague-Dawley rats. Rats aged 6 weeks were randomly divided into groups: a control group (n=10) fed a standard diet and a group of rats (n=40) kept on HFD (60% fat content by calorie value). Rats received food and water ad libitum for 16 weeks. Before the end of the experiment, four groups of HFD rats were formed: obesity resistant animals (HFD-OR, n=11), without additional interventions (HFD, n=10), rats which were administered dexamethasone three days before the study (HFD+Dexa, n=9), HFD followed by 8-week diet restriction (HFD+DR, n=9). At the end of the experiment, mesenteric lymph nodes (LNs) were taken from rats under anesthesia and their contractile function was studied in a myograph using 1400W, dynastat and Tempol. Results. LNs of control rats had a high level of tone and generated spontaneous high-amplitude phasic contractions. The LNs of HFD rats had a low initial tone, and rare low-amplitude phasic contractions were recorded in them. The parameters of contractile activity of the LNs of rats in HFD-OR and HFD+Dexa groups differed slightly from the corresponding parameters of the LNs of rats in the control group. Calorie restriction for 8 weeks in obese rats (HFD+DR) resulted in an increase in tone, frequency and amplitude of phasic contractions of the LNs compared to those in HFD rats. iNOS inhibition caused a significant increase in the tone, amplitude and frequency of phasic contractions of the LNs in the HFD group. An increase in the frequency of phasic contractions was observed only in the LNs of HFD+Dex and HFD+DR rats. Inhibition of cyclooxygenase 2 did not affect the contractile function of the LNs of rats of all groups, with the exception of animals from the HFD group (increase in the amplitude and frequency of phasic contractions). Tempol significantly increased the tone, frequency and amplitude of phasic contractions of the LNs in rats of the HFD group and increased the frequency of phasic contractions of the LNs of the HFD+DR rats. Conclusion. A high-fat diet leads to impaired contractile function of rat LNs and can create additional obstacles to the movement of lymph, promoting its leakage into surrounding tissues. Obesity is accompanied by the development of inflammation in the LNs and perinodal adipose tissue, which induces the expression of inducible NO synthase, cyclooxygenase-2 and the accumulation of reactive oxygen species (ROS). NO, prostaglandins and ROS have an inhibitory effect on the SMC capsules of the LNs, leading to a decrease in tonic tension and a weakening of spontaneous phasic contractions. The reason for inhibition of LN contractile function is obesity, but not consumption of food high in fat. Transferring obese rats to a calorie-restricted diet results in a decrease in body weight and visceral fat mass and an improvement in LN contractile function.

Premature ventricular contraction patterns associated with nonsustained ventricular tachycardia.

BACKGROUND: Occurrence of nonsustained ventricular tachycardia (NSVT) is associated with negative outcomes. It is not clear whether specific electrocardiographic characteristics of premature ventricular contractions (PVCs) are associated with the occurrence of NSVT. The aim of this study was to identify electrocardiographic patterns associated with the presence of NSVT during 24-h electrocardiographic monitoring in patients with >10 PVCs per hour. METHODS: This was a retrospective, observational, cross-sectional study. We reviewed consecutive patients who received 24-h ECG monitoring performed at a single outpatient cardiology center. Patients who received 24-h electrocardiographic monitoring, with a PVC burden ≥10 PVCs/h were included. Occurrence of NSVT during 24-h electrocardiographic monitoring was the main outcome. RESULTS: A total of 343 patients were analyzed (mean [SD] age, 69.7 [12.5] years; 177 men [51.6 %]). NSVT occurred in 72 patients who were compared with 271 patients without NSVT. The novel term "premature beat ratio", which aims to correlate the coupling interval and compensatory pause, was introduced; a value >0.5 was independently associated with NSVT according to the multivariate model (OR = 3.73, 95 % CI = 1.57-8.82; P = 0.002). PVC burden (OR = 1.09, 95 % CI = 1.02-1.17; P = 0.006), and triplets (OR = 18.19, 95 % CI = 7.32-45.18 P = 0.0) were also associated with NSVT in the multivariate model. CONCLUSION: These findings suggest that patients with a high PVC burden, triplets, and a premature beat ratio greater than 0.5 have an increased probability of presenting with NSVT and may benefit from more rigorous follow-up.

Enhanced labor pain monitoring using machine learning and ECG waveform analysis for uterine contraction-induced pain.

OBJECTIVES: This study aims to develop an innovative approach for monitoring and assessing labor pain through ECG waveform analysis, utilizing machine learning techniques to monitor pain resulting from uterine contractions. METHODS: The study was conducted at National Taiwan University Hospital between January and July 2020. We collected a dataset of 6010 ECG samples from women preparing for natural spontaneous delivery (NSD). The ECG data was used to develop an ECG waveform-based Nociception Monitoring Index (NoM). The dataset was divided into training (80%) and validation (20%) sets. Multiple machine learning models, including LightGBM, XGBoost, SnapLogisticRegression, and SnapDecisionTree, were developed and evaluated. Hyperparameter optimization was performed using grid search and five-fold cross-validation to enhance model performance. RESULTS: The LightGBM model demonstrated superior performance with an AUC of 0.96 and an accuracy of 90%, making it the optimal model for monitoring labor pain based on ECG data. Other models, such as XGBoost and SnapLogisticRegression, also showed strong performance, with AUC values ranging from 0.88 to 0.95. CONCLUSIONS: This study demonstrates that the integration of machine learning algorithms with ECG data significantly enhances the accuracy and reliability of labor pain monitoring. Specifically, the LightGBM model exhibits exceptional precision and robustness in continuous pain monitoring during labor, with potential applicability extending to broader healthcare settings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04461704.

The Efficacy of Ischemic Preconditioning on Handgrip Strength and Strength Endurance in Para-Athletes With Spinal-Cord Injury: A Pilot Study.

PURPOSE: This pilot study investigated the functional outcomes after ischemic preconditioning (IPC) in high-level para-athletes with spinal-cord injury. METHODS: Nine athletes completed 2 handgrip exercise trials (an isometric hold to failure at 60% maximal voluntary contraction [ISO] and a progressive, intermittent handgrip to failure [INT]), preceded by either IPC (220 mm Hg) or sham (20 mm Hg) for six 5-minute periods, in a repeated-measures, crossover design. RESULTS: Although small performance improvements in time to task failure were observed in the ISO (∼5%) and INT (∼8%) IPC conditions, which are similar to those reported elsewhere, no statistical influence was observed (ISO-IPC, 74.2 [32.6] s; SHAM, 70.7 [27.2] s; P = .73; INT-IPC, 426.0 [80.1] s; SHAM, 392.2 [42.5] s; P = .35). Fatigue was evident in the forearm muscle force (maximal voluntary contraction) ISO (mean decline of 178.1 [76.0] N [95% CI, -10.4 to 366.7 N]; P < .05) and INT (mean decline of 182.2 [72.5] N [95% CI, 34.5-329.8 N]; P < .05) trials but not different between treatments (P > .95). CONCLUSIONS: Although small performance improvements in time to task failure were observed, the findings of the present data set suggest that acute bouts of IPC do not meaningfully influence fatigue during handgrip exercise in para-athletes with spinal-cord injury.

Pulsed electromagnetic fields attenuate human musculocutaneous nerve damage induced by biceps eccentric contractions.

Pulsed electromagnetic field (PEMF) therapy, a noninvasive treatment, has shown promise in mitigating nerve damage. However, unaccustomed exercises, such as eccentric contractions (ECCs), can damage both muscle and nerve tissue. This study investigated whether magnetic stimulation (MS) with PEMF could aid in nerve recovery after ECCs in the elbow flexors. Twenty participants were randomly assigned to either a control (CNT) or an MS group. Following ECCs, we measured the latency of the M-wave in the musculocutaneous nerve as an indicator of nerve function. Additionally, isometric torque, range of motion, and muscle pain were assessed for muscle function. Interestingly, only the CNT group exhibited a significant increase in latency on Day 2 (p < 0.05). The MS group, on the other hand, displayed an earlier recovery trend in isometric torque, range of motion, and muscle soreness. Notably, muscle soreness significantly decreased immediately after MS treatment compared to pretreatment levels. These findings suggest that MS treatment can effectively attenuate nerve damage induced by ECCs exercise.

Myocardial work in idiopathic premature ventricular contractions: Assessing left ventricular function and prognosis.

BACKGROUND: Premature ventricular contractions (PVCs) can lead to impairment of left ventricular function. The noninvasive myocardial work technique, which incorporates left ventricular afterload, represents a new method for assessing left ventricular functional. AIM: The aim of this study is to explore the value of noninvasive myocardial work technique in assessing left ventricular systolic function in patients with PVCs. METHODS: Compare the clinical data, two-dimensional echocardiography parameters, and myocardial work parameters of 66 patients with PVCs and 35 healthy volunteers and explore the relevant risk factors for postoperative recurrence in patients with PVCs. RESULTS: In patients with PVCs compared to the control group, they exhibit enlargement of left atrial diameter (LAD) and left ventricular internal dimension in diastole (LVIDd), as well as thickening of the left ventricular wall. The global work waste (GWW) increases, while the global work efficiency (GWE) decreases. There is a significant negative correlation between the PVC burden and GWE (r = -0.70, p <0.01), and a significant positive correlation between the PVC burden and GWW (r = 0.58, p <0.01). GWE is a sensitive indicator for predicting the recurrence of PVCs after radiofrequency ablation. Patients with GWE <91.5%, global longitudinal strain (GLS) <15.5%, and ejection fraction (EF) <62.5% have a higher postoperative recurrence rate. CONCLUSION: PVCs can cause impairment of left ventricular systolic function. GWE is the most sensitive indicator for predicting postoperative recurrence in patients with PVCs. Patients with GWE <91.5%, GLS <15.5%, and EF <62.5% have a higher postoperative recurrence rate.

Transcriptional and morphological responses following distinct muscle contraction protocols for Snell dwarf (Pit1dw/dw) mice.

The Snell dwarf mouse (Pit1dw/dw), an animal model of congenital combined pituitary hormone deficiency, displays skeletal muscle weakness. While enhanced responsivity to repeated exposures of muscle contractions have been documented for Snell dwarf mice, the response following single exposure to distinct contraction protocols remained uncharacterized. The purpose of this study was to investigate the muscle recovery of Snell dwarf and control littermate mice following a single exposure to two separate protocols-an intermittent slow velocity (30°/s) contraction protocol or a continuous rapid velocity (500°/s) contraction protocol. Following both protocols for control mice, torque values were 30% and 80% of pre-protocol values at 5 min and 3 days, respectively. At 10 days, performance returned to baseline for the 30°/s protocol and were depressed for the 500°/s protocol. For Snell dwarf mice following both protocols, torques were depressed to 5% of pre-protocol values at 5 min and returned to baseline by 3 days. Recovery following the 30°/s protocol for control mice and both protocols for Snell dwarf mice coincided with increased transcriptional output, upregulation of cytokine-mediated signaling genes, and a distribution shift to smaller muscle fibers with reduced area per nucleus. These features represent efficacious remodeling ubiquitous across distinct contraction paradigms in the context of the Pit1 mutation.

Cellular responses following ex vivo lung exposure to the nerve agent VX - Potential for additional treatment targets?

Following inhalation exposure to organophosphorus nerve agents, symptoms rapidly develop and severe respiratory symptoms, such as bronchorrhea and bronchoconstriction are the leading causes of lethality. Nerve agent-induced lung injury is little investigated and the standard treatment for symptomatic relief targets the enzyme acetylcholinesterase and muscarinic acetylcholine and GABAergic receptors. In the present study, cellular responses in lung tissue during the acute (40 min) and extended phase (24 h) following severe exposure to the nerve agent VX have been investigated using an ex vivo rat precision-cut lung slice model including electrostimulation to induce a cholinergic response. Changes in protein amount, cell viability, together with, inflammatory and oxidative stress markers have been determined in both the lung tissue and incubation medium. During the acute phase, VX caused significantly increased airway contraction and decreased airway relaxation. Five micromolar of VX did not affect the sample protein levels and cell viability in lung tissue. Among seven markers of cellular responses investigated in the lung tissue, increased levels of heme oxygenase-1 and matrix metalloproteinase-9 together with decreased levels of glutathione in the incubation medium were observed in the acute phase following VX-exposure compared to electrostimulation only. No difference in cellular response was observed following VX-exposure for 24 h compared to the air control. In comparison, LPS-exposure resulted in time-dependent changes in all markers of inflammation and oxidative response. In conclusion, the present study demonstrated VX-specific patterns of oxidative responses in the lung, as well as, signs of inflammatory response and remodelling of extracellular matrix. These potential mechanisms of tissue injury should be further investigated for their potential as additional therapeutic targets during the acute phase of intoxication.

Cigarette smoke exposure impairs early-stage recovery from lengthening contraction-induced muscle injury in male mice.

The use of tobacco cigarettes produces locomotor muscle weakness and fatigue intolerance. Also, smokers and chronic obstructive pulmonary disease patients have a greater incidence of muscle injury and a deficient myogenic response. However, the effects of smoke exposure on the recovery from eccentric exercise-induced muscle injuries are unknown. Mice were exposed daily to cigarette smoke (CS) or room air (Air) for 4 months; the anterior crural muscles from one limb were injured by a lengthening contractions protocol (LCP) and recovered for 7 days. Lung compliance was greater, and body weights were lower, in CS-exposed than in the Air group. In LCP-subjected limbs, CS exposure lowered tibialis anterior myofiber cross-sectional area, decreased the size of centrally nucleated myofibers, and decreased extensor digitorum longus (EDL) mass, but did not affect EDL force from both limbs. CS exposure upregulated the mRNA levels of several myogenic (Pax7, Myf5, nNOS) genes in the EDL. The combination of CS exposure and LCP decreased Myf5 and nNOS mRNA levels and exacerbated pro-inflammatory mRNA levels. These data suggest that smoke exposure leads to an excessive pro-inflammatory response in regenerating muscle that is associated with a lower muscle mass recovery from a type of injury that often occurs during strenuous exercise.

Relative uteroplacental insufficiency of labor.

Relative uteroplacental insufficiency of labor (RUPI-L) is a clinical condition that refers to alterations in the fetal oxygen "demand-supply" equation caused by the onset of regular uterine activity. The term RUPI-L indicates a condition of "relative" uteroplacental insufficiency which is relative to a specific stressful circumstance, such as the onset of regular uterine activity. RUPI-L may be more prevalent in fetuses in which the ratio between the fetal oxygen supply and demand is already slightly reduced, such as in cases of subclinical placental insufficiency, post-term pregnancies, gestational diabetes, and other similar conditions. Prior to the onset of regular uterine activity, fetuses with a RUPI-L may present with normal features on the cardiotocography. However, with the onset of uterine contractions, these fetuses start to manifest abnormal fetal heart rate patterns which reflect the attempt to maintain adequate perfusion to essential central organs during episodes of transient reduction in oxygenation. If labor is allowed to continue without an appropriate intervention, progressively more frequent, and stronger uterine contractions may result in a rapid deterioration of the fetal oxygenation leading to hypoxia and acidosis. In this Commentary, we introduce the term relative uteroplacental insufficiency of labor and highlight the pathophysiology, as well as the common features observed in the fetal heart rate tracing and clinical implications.

Can the efficacy of a medical treatment be predicted based on the type of idiopathic premature ventricular contraction?

BACKGROUND: Premature ventricular contractions (PVCs) are common arrhythmias with diverse clinical implications. This retrospective study aimed to evaluate the efficacy of medical treatments using various clinical, imaging, and electrocardiographic parameters in patients with idiopathic PVCs. METHODS: A total of 1051 patients with idiopathic PVCs were retrospectively analyzed. Patients were categorized into three groups based on treatment response: beta-blocker (BB) responders (479 patients), calcium-channel blocker (CCB) responders (335 patients), and class 1c antiarrhythmic (AA) responders (237 patients). Clinical, imaging, and electrocardiographic data were collected and analyzed to assess the factors influencing treatment response. RESULTS: Age, left ventricular ejection fraction (LVEF), PVC QRS duration, CI variability, and multiple PVC morphologies were identified as significant factors affecting treatment response. Older age and lower LVEF were associated with better response to BB treatment, whereas CCB responders showed narrower QRS complexes. BB responders also exhibited higher CI variability, possibly linked to automaticity mechanisms. Moreover, the BB responder group had a higher frequency of multiple PVC morphologies. CONCLUSION: These findings emphasize the importance of tailored treatment approaches based on individual patient characteristics.

Effects of detraining on neuromuscular function and structural adaptations following once- or twice-weekly eccentric resistance training in older adults.

BACKGROUND: Eccentric resistance training elicits greater preservation of training-induced muscular adaptations compared with other training modalities, however the detraining profiles of different training dosages remain unknown. AIMS: To examine the detraining effects following once- or twice-weekly eccentric-specific resistance training in older adults. METHODS: Twenty-one older adults (age = 70.5 ± 6.0 year) completed a 12-week detraining period following the 12-week eccentric training programmes with neuromuscular function and muscle structure assessed six (mid-detraining) and 12 (post-detraining) weeks following training cessation. RESULTS: From post-training to post-detraining, no significant regression of the training-induced improvements (collapsed group data reported) occurred in power (0%), strength (eccentric = 0%, isometric = 39%), or explosive strength over numerous epochs (0-32%), resulting in values that remained significantly greater than at pre-training. However, significant regression in the improvements in muscle thickness (91%) and fascicle angle (100%) occurred, resulting in values that were not significantly greater than pre-training. DISCUSSION: The limited regression in neuromuscular function following a 12-week detraining period has important implications for supporting eccentric exercise prescription in older adults who often face periods of inactivity. However, further work is required to develop an effective maintenance dosage strategy that preserves improvements in muscle structure. CONCLUSIONS: Eccentric resistance training elicits improvements in the neuromuscular function of older adults, which are sustained for at least 12 weeks after eccentric training cessation.

Cardiac fibromas in adult patients: a case series focusing on rhythmology and radiographic features.

Background: Fibromas are rare primary benign cardiac tumours that can become symptomatic due to expansive growth, ventricular rhythm disturbances, and sudden cardiac death. Distinguishing fibromas from other (malign) cardiac masses is essential for accurate diagnosis and treatment. While there is some experience in management of cardiac fibromas in children, management of adult patients is unknown. Case summary: We present three cases of cardiac fibroma in adult patients diagnosed by echocardiography, cardiovascular magnetic resonance (CMR), and computed tomography (CT): (1) a 55-year-old male with a left ventricular fibroma leading to reduced left ventricular ejection fraction and mitral regurgitation. He had family history of sudden cardiac death, showed premature ventricular contractions (PVCs), and was treated with a primary preventive subcutaneous implantable cardiac defibrillator (S-ICD); (2) a 39-year-old male with right ventricular fibroma as an incidental finding. He complained of episodes of PVC. Due to a low PVC burden, decision was made against ablation and the patient was planned for follow-up; and (3) an 18-year-old female with left ventricular apex fibroma detected by CMR shortly after birth and confirmed by surgical biopsy. Being asymptomatic, conservative management was pursued and follow-up by CMR planned. Discussion: Cardiac fibromas can show various clinical presentations and hence being detected late in life. Given potential complications of surgical biopsy, diagnosis of cardiac fibromas is primarily based on echocardiography, CT, and CMR. Rhythm disturbances as PVCs are common. Due to association with ventricular arrhythmias and sudden cardiac death, preventive ICD placement might be appropriate on an individual basis.

Clinical utility of ambulatory ECG monitoring and 2D-ventricular strain for evaluation of post-COVID-19 ventricular arrhythmia.

BACKGROUND: A relatively common complication of COVID -19 infection is arrhythmia. There is limited information about myocardial deformation and heart rate variability (HRV) in symptomatic post COVID patients presented by ventricular arrhythmia. AIM OF THE STUDY: Our goal was to assess 2D-ventricular strain and heart rate variability indices (evaluated by ambulatory ECG monitoring) in post-COVID-19 patients suffering from ventricular arrhythmia. METHODS: The current observational case-control study performed on 60 patients one month after they had recovered from the COVID-19 infection. Thirty healthy volunteers served as the control group. Each participant had a full medical history review, blood tests, a 12-lead surface electrocardiogram (ECG), 24-h ambulatory ECG monitoring, and an echo-Doppler examination to evaluate the left ventricular (LV) dimensions, tissue Doppler velocities, and 2D-speckle tracking echocardiography (2D-STE) for both the LV and right ventricular (RV) strain. RESULTS: Symptomatic post-COVID patients with monomorphic premature ventricular contractions (PVCs) showed a substantial impairment of LV/RV systolic and diastolic functions, LV/RV myocardial performance (MPI) with reduced indices of HRV. Patients with higher versus lower ventricular burden had poorer functional status, higher levels of inflammatory biomarkers and reduced parameters of HRV (New York Heart Association (NYHA) class: 2.1 ± 0.9 vs. 1.5 ± 0.6, p < 0.001, C-reactive protein (CRP): 13.3 ± 4.1 vs. 8.3 ± 5.9 mg/L, p < 0.0001, low frequency/high frequency (LF/HF): 3.6 ± 2.4 vs. 2.2 ± 1.2, p < 0.002, the root mean square of the difference between successive normal intervals (rMSSD): 21.8 ± 4.7 vs. 29.3 ± 14.9 ms, p < 0.039 and the standard deviation of the RR interval (SDNN): 69.8 ± 19.1 vs.108.8 ± 37.4 ms, p < 0.0001). The ventricular burden positively correlated with neutrophil/lymphocyte ratio (NLR) (r = 0.33, p < 0.001), CRP (r = 0.60, p < 0.0001), while it negatively correlated with LV-global longitudinal strain (GLS) (r = -0.38, p < 0.0001), and RV-GLS (r = -0.37, p < 0.0001). CONCLUSIONS: Patients with post-COVID symptoms presented by ventricular arrhythmia had poor functional status. Patients with post-COVID symptoms and ventricular arrhythmia had subclinical myocardial damage, evidenced by speckle tracking echocardiography while having apparently preserved LV systolic function. The burden of ventricular arrhythmia in post-COVID patients significantly correlated with increased inflammatory biomarkers and reduced biventricular strain.

Zero-fluoroscopy catheter ablation of premature ventricular contractions: comparative outcomes from the right ventricular outflow tract and other ventricular sites.

BACKGROUND: The three-dimensional electroanatomic mapping (EAM) system allows performing catheter ablation (CA) without fluoroscopy in patients with premature ventricular contractions (PVCs). The right ventricle outflow tract (RVOT) location is favorable for performing zero-fluoroscopy CA. Non-RVOT zero-fluoroscopy CA is a challenging procedure. The study aimed to evaluate the efficacy and safety of zero-fluoroscopy CA using the EAM in patients with PVCs from RVOT and non-RVOT. METHODS: Completely zero-fluoroscopy CA of PVCs guided by EAM was performed in 107 patients with PVCs. 54 patients underwent zero-fluoroscopy RVOT CA. The remaining 53 patients underwent zero-fluoroscopy non-RVOT CA. Demographic and clinical baseline characteristics, procedure parameters, and follow-up were obtained from medical records. Primary outcomes were the acute and the permanent success rate (12-month follow-up), complications, and procedure time. RESULTS: There were no significant differences between groups regarding baseline characteristics. Acute procedural success was achieved in 52 patients (94,44%) in the RVOT zero-fluoroscopy CA group and in 45 patients (86,54%) in the non-RVOT zero-fluoroscopy CA group (ns). A long-term success rate was achieved in 50 patients (90,74%) in the RVOT zero-fluoroscopy CA group and in 44 patients (84,62%) in the non-RVOT zero-fluoroscopy CA group (ns). The median procedure time was 80.5 minutes in the RVOT group and 90 minutes in the non-RVOT group (ns). There were two complications in the non-RVOT group (ns). CONCLUSIONS: There were no differences in procedure time efficacy and safety zero-fluoroscopy ablation between RVOT and non-RVOT locations. Non-fluoroscopy CA of PVCs is a feasible, safe, and efficient procedure.

Titin Cardiomyopathy Associated With Refractory Ventricular Tachycardia: A Case Report.

Cardiomyopathy is defined as structural and functional myocardial abnormality not attributed to ischemic, valvular, hypertensive, or congenital cardiac causes. The main phenotypes of cardiomyopathy include hypertrophic, dilated, non-dilated left ventricular, restrictive, arrhythmogenic right ventricular, Takotsubo, and left ventricular noncompaction cardiomyopathies. A significant proportion of dilated cardiomyopathy (DCM) cases represents patients with genetic mutations, most commonly titin gene truncating variants (TTNtv). It has been shown that TTNtv mutation contributes to the development of certain types of DCM such as alcohol, chemotherapy, and peripartum. We present a case of DCM where genetic workup revealed TTNtv without other contributing factors. The course was complicated by multiple ventricular tachycardias (VTs) refractory to medical management, despite treatment with amiodarone, sotalol, dofetilide, mexiletine, and propranolol. Interestingly, endocardial mapping failed to delineate the substrate of tachycardia. This report underscores the importance of genetic testing in DCM and highlights the potential association of titin cardiomyopathy with refractory VTs, possibly of epicardial origin.

Spontaneous enteric nervous system activity generates contractile patterns prior to maturation of gastrointestinal motility.

BACKGROUND: Spontaneous neuronal network activity is essential to the functional maturation of central and peripheral circuits, yet whether this is a feature of enteric nervous system development has yet to be established. Although enteric neurons are known exhibit electrophysiological properties early in embryonic development, no connection has been drawn between this neuronal activity and the development of gastrointestinal (GI) motility patterns. METHODS: We use ex vivo GI motility assays with newly developed unbiased computational analyses to identify GI motility patterns across mouse embryonic development. KEY RESULTS: We find a previously unknown pattern of neurogenic contractions termed "clustered ripples" that arises spontaneously at embryonic day 16.5, an age earlier than any identified mature GI motility patterns. We further show that these contractions are driven by nicotinic cholinergic signaling. CONCLUSIONS & INFERENCES: Clustered ripples are neurogenic contractile activity that arise from spontaneous ENS activity and precede all known forms of neurogenic GI motility. This earliest motility pattern requires nicotinic cholinergic signaling, which may inform pharmacology for enhancing GI motility in preterm infants.

Total Synthesis of (±)-Baphicacanthcusine A Enabled by Sequential Ring Contractions.

Reported herein is the first total synthesis of the poly-pseudoindoxyl natural product baphicacanthcusine A. The synthesis leverages the oxidative rearrangement of indoles to pseudoindoxyls to install vicinal pseudoindoxyl heterocycles in a diastereoselective manner. Key steps include an acid-mediated cyclization/indole transposition, two diastereoselective oxidative ring contractions, and a site-selective C-H oxygenation. The synthesis of the oxidation precursors was guided by recognition of an element of hidden symmetry. This work provides a foundation for the chemical synthesis of other poly-pseudoindoxyl alkaloids.