Repetitive transcranial magnetic stimulation (rTMS) system is an important therapeutic tool used in non-invasive brain stimulation. The electric field induced by the time-varying magnetic field in a ...stimulating coil could activate nerve fibers in the brain, resulting in depolarization or hyperpolarization of the neurons. However, the potential adverse effects of rTMS on heart rhythm have not been extensively investigated. This study aims to develop an optimized design of rTMS system to evaluate the potential adverse effects of rTMS on mouse heart rhythm via vagus nerve modulation for pre-clinical application. The rTMS-induced electric field in the vagus nerve of brain produced by the strong rate of current change of 1.04 × 10 8 A/s in a stimulating coil, which was directly determined by circuit design in charging voltage of the capacitor bank and inductance value of a stimulating coil. A finite element method (FEM) mathematical simulation indicated that the maximum eddy current was 25.4 μA/mm 2 , which was greatly exceeded the vagus nerve activation threshold of 5.6 μA/mm 2 . The animal experiment results also verify that the induced electric field activates the RR-interval prolonging effect might be attributed to vagus nerve stimulation (VNS) from rTMS, and the most pronounced heart rhythm prolonging effect at 20 Hz magnetic field treatment, causing the average heart rate decreased to 58.65% of that before rTMS in 10 mice. In conclusion, above-threshold rTMS at 20 Hz could produce maximum adverse effect on heart rhythm through direct vagus nerve activation for pre-clinical applications such as safety screening.
Pacemaker cells can be differentiated from stem cells or transdifferentiated from quiescent mature cardiac cells via genetic manipulation. Here we show that the exposure of rat quiescent ventricular ...cardiomyocytes to a silk-fibroin hydrogel activates the direct conversion of the quiescent cardiomyocytes to pacemaker cardiomyocytes by inducing the ectopic expression of the vascular endothelial cell-adhesion glycoprotein cadherin. The silk-fibroin-induced pacemaker cells exhibited functional and morphological features of genuine sinoatrial-node cardiomyocytes in vitro, and pacemaker cells generated via the injection of silk fibroin in the left ventricles of rats functioned as a surrogate in situ sinoatrial node. Biomaterials with suitable surface structure, mechanics and biochemistry could facilitate the scalable production of biological pacemakers for human use.
Chronic heavy alcohol use is associated with lethal arrhythmias. Whether common East Asian-specific aldehyde dehydrogenase deficiency (ALDH2*2) contributes to arrhythmogenesis caused by low level ...alcohol use remains unclear. Here we show 59 habitual alcohol users carrying ALDH2 rs671 have longer QT interval (corrected) and higher ventricular tachyarrhythmia events compared with 137 ALDH2 wild-type (Wt) habitual alcohol users and 57 alcohol non-users. Notably, we observe QT prolongation and a higher risk of premature ventricular contractions among human ALDH2 variants showing habitual light-to-moderate alcohol consumption. We recapitulate a human electrophysiological QT prolongation phenotype using a mouse ALDH2*2 knock-in (KI) model treated with 4% ethanol, which shows markedly reduced total amount of connexin43 albeit increased lateralization accompanied by markedly downregulated sarcolemmal Nav1.5, Kv1.4 and Kv4.2 expressions compared to EtOH-treated Wt mice. Whole-cell patch-clamps reveal a more pronounced action potential prolongation in EtOH-treated ALDH2*2 KI mice. By programmed electrical stimulation, rotors are only provokable in EtOH-treated ALDH2*2 KI mice along with higher number and duration of ventricular arrhythmia episodes. The present research helps formulate safe alcohol drinking guideline for ALDH2 deficient population and develop novel protective agents for these subjects.
The impact of the new International Association for the Study of Lung Cancer pathology committee grading system for advanced lung adenocarcinoma (LADC) on survival is unclear, especially in Asian ...populations. In this study, we reviewed the prognostic outcomes of patients with late-stage disease according to the new grading system. We reviewed 136 LADC cases who underwent a small biopsy from 2007 to 2018. Tumors were classified according to the new grading system for LADC. Baseline characteristics (age, sex, smoking status, body mass index, and driver gene mutations) were analyzed. Kaplan–Meier and Cox regression analyses were used to determine correlations with the new grading system and prognosis. Patients with poorly differentiated adenocarcinoma were significantly correlated with a poor progression-free survival (PFS) (p = 0.013) but not overall survival (OS) (p = 0.154). Subgroup analysis showed that wild-type EGFR patients with poorly differentiated adenocarcinoma treated with chemotherapy had significantly worse PFS (p = 0.011). There was no significant difference in survival among the patients with epidermal growth factor receptor mutations who were treated with tyrosine kinase inhibitors. Patients aged >70 years and those with a BMI ≤ 25 kg/m2 and wild-type patients had significantly worse OS in both univariate (HR = 1.822, p = 0.006; HR = 2.250, p = 0.004; HR = 1.537, p = 0.046, respectively) and multivariate analyses (HR = 1.984, p = 0.002; HR = 2.383, p = 0.002; HR = 1.632, p = 0.028, respectively). Despite therapy, patients with poorly differentiated tumors still fared worse than those with better differentiated tumors. No differences were found among the EGFR mutations treated with TKI. Our findings highlight that the therapeutic regimen should be adjusted for EGFR Wild-type patients with poorly differentiated adenocarcinoma treated with chemotherapy to provide better outcomes.
Newly-diagnosed or relapses of immunoglobulin A nephropathy (IgAN) have been associated with COVID-19 vaccination in the literature. Most reported cases were mild clinical diseases characterized by ...microscopic haematuria and do not require dialysis treatment. This current case report describes a 55-year-old male patient that presented to the emergency department with acute kidney injury after receiving the first dose of the mRNA-1273 COVID-19 vaccine. After admission, his renal function deteriorated rapidly, and then he developed uraemic encephalopathy. He underwent emergency haemodialysis with a rapid improvement in his mental status. Renal biopsy showed newly-diagnosed IgA nephropathy along with markedly elevated plasma level of galactose-deficient-IgA 1 (Gd-IgA 1 ) antibody. The patient did not receive immunosuppressive treatment and is now dialysis-free. Immune activation is considered an essential factor in developing or exacerbating IgAN following COVID-19 vaccination. This current case report demonstrates that elevated Gd-IgA 1 antibody may be the potential mechanistic link between COVID-19 vaccination and IgAN.
Ischemic stroke (IS) is a catastrophic complication of hypertrophic cardiomyopathy (HCM) with aging. We investigated the incidence of IS in HCM patients without atrial fibrillation (AF) and compared ...the relative risk of IS with matched general population with AF. This study identified 17,371 HCM patients without AF and utilized propensity-score-matching to identify one-to-one matched control of general population with AF receiving oral anti-coagulants (OACs). During a median follow-up of 7.3 years, 847 (4.9%) subjects experienced IS with the incidence of 0.589/100 person-years. The corresponding matched controls experienced 788 (4.5%) events with the incidence of 0.494/100 person-years. Compared with control, HCM patients had similar risk of IS (Hazard ratios HRs 0.965, 95% confidence interval CI 0.854-1.091). HCM patients with age above 65 years had a significantly increased risk of IS (age 65-74 years, HR 1.278, 95% CI 1.070-1.335; age ≥75 years, HR 1.757, 95% CI 1.435-2.152). Stratified by CHA
DS
-VASc score, HCM subjects with score 0, 1 and 2 had significantly increased risk of IS than control while those with score ≥2 had similar risk as control. Compared with general population with AF, HCM patients without AF had similar risk of IS, suggesting OACs might be necessary in HCM patient without AF.
BACKGROUND:Circumferential difference of lymphedematous limbs at designated anatomic distances has been the primary mode for measuring lymphedematous extremities. Computed tomography (CT) imaging ...produces accurate, consistent, hygienic volume measurements and a direct limb representation. This study compares these 2 main modalities and assesses their correlation.
METHODS:CT and circumferential difference measurements, costs, and correlation of patient limbs that received vascularized lymph node transfer were compared.
RESULTS:Mean circumferential difference by tape measurement pre- and postoperatively was 31.4% ± 19.1% and 17.4% ± 8.8% for upper limbs and 43.2% ± 16.1% and 22.4% ± 12% for the lower limbs, respectively. Mean CT volumetric difference pre- and postoperatively were 36.1 ± 4.1% and 27.2 ± 2.8% for the upper limb and 46.2 ± 3.2% and 33.2 ± 2.1% for the lower limbs, respectively. CT volume measurements significantly correlated with their respective circumferential difference with Pearson correlation coefficient of r = +0.7, which was statistically significant (P = 0.03), indicating a strong positive correlation between circumferential difference and actual limb volume changes as determined by CT imaging. Circumferential differences are more cost effective than CT volume assessments in the domains of measurement frequency (P = 0.03), fee (P < 0.01), time (P = 0.03), total cost per year (P < 0.01), and cost/minute (P = 0.03).
CONCLUSIONS:Standardized circumferential differences that are currently used are comparable to unbiased CT volumetric measurements and can be used as a reliable, reproducible, minimally invasive, low cost, and accurate method of measuring the lymphedematous limbs.
Chronic hypertension is a multifactorial disease that is highly associated with cardiovascular disorders. Physical activity, such as long-term exercise, is advocated as a treatment for hypertension, ...but the responses of different age groups to long-term exercise are unknown. We used aged spontaneous hypertensive rats (SHRs, 80 weeks old) to test the hypothesis that long-term exercise compensated for deficient autonomic control and reduced susceptibility to ventricular tachycardia (VT) and ventricular fibrillation (VF) in this animal model. The aged SHRs were divided into control and voluntary exercise groups. Ambulatory electrocardiography was recorded for the heart rate variability (HRV) analysis. Programmed stimulation was applied to exposed hearts to induce ventricular arrhythmia in situ. Then, the hearts were isolated for an optical mapping study. The results showed that increased HRV indices were broadly related to vagal dominance in the high-intensity exercise group. Exercise altered the electrical propagation dynamic properties, such as the action potential duration restitution (APDR). Furthermore, the VF inducibility decreased with increased exercise intensity. Taken together, our results suggest that long-term exercise reduces the risk of arrhythmogenesis in aged SHRs through enhanced vagal control and stabilized electrical dynamics.
•Vagal dominance was noted in the high-intensity exercise group.•Exercise altered the electrical propagation dynamic properties, such as the action potential duration restitution.•Exercise reduced the risk of arrhythmogenesis in aged hypertensive rats.
BACKGROUND:Submental lymph node transfer has proved to be an effective approach for the treatment of lymphedema. This study was to investigate the anatomy and distribution of vascularized submental ...lymph node (VSLN) flap using magnetic resonance imaging (MRI) and their clinical outcome.
METHODS:Fifteen patients who underwent 19 VSLN flap transfers for upper or lower limb lymphedema were retrospectively analyzed. The number of submental lymph nodes was compared among preoperative MRI, preoperative sonography, intraoperative finding, postoperative sonography, and postoperative computed tomography angiography. The outcome was compared between preoperatively and postoperatively.
RESULTS:All 19 VSLN flaps survived. Two hundred fifteen lymph nodes were identified in 30 submandibular regions by MRI. The mean number of submental lymph nodes on preoperative MRI was 7.2 ± 2.4, on preoperative sonography was 3.2 ± 1.1, on intraoperative finding was 3.1 ± 0.6, postoperative sonography was 4.6 ± 1.8, and postoperative CTA was 5.2 ± 1.9. Sixty-one percent of the lymph nodes were located in the central two-quarters of the line drawn from the mental protuberance to the mandibular angle. The actual harvest rate of submental lymph nodes was 72.2%. At a 12-month follow-up, mean episodes of cellulitis were improved from 2.7 ± 0.6 to 0.8 ± 0.2 (P < 0.01); mean of circumferential difference was improved 3.2 ± 0.4 cm (P < 0.03). The overall lymphedema quality-of-life was improved 4.9 ± 0.3 (P < 0.04).
CONCLUSIONS:The preoperative MRI is a useful tool for the detection of mean 7.2 submental lymph nodes. Mean 72.2% of submental lymph nodes can be successfully transferred for extremity lymphedema with optimal functional recovery.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
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