Normal Rhythm Research Articles

Night shift-induced circadian disruption: links to initiation of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and risk of hepatic cancer.

The circadian system plays a crucial role in regulating metabolic homeostasis at both systemic and tissue levels by synchronizing the central and peripheral clocks with exogenous time cues, known as zeitgebers (such as the light/dark cycle). Our body's behavioral rhythms, including sleep-wake cycles and feeding-fasting patterns, align with these extrinsic time cues. The body cannot effectively rest and repair itself when circadian rhythms are frequently disrupted. In many shift workers, the internal rhythms fail to fully synchronize with the end and start times of their shifts. Additionally, exposure to artificial light at night (LAN), irregular eating patterns, and sleep deprivation contribute to circadian disruption and misalignment. Shift work and jet lag disrupt the normal circadian rhythm of liver activity, resulting in a condition known as "circadian disruption". This disturbance adversely affects the metabolism and homeostasis of the liver, contributing to excessive fat accumulation and abnormal liver function. Additionally, extended working hours, such as prolonged night shifts, may worsen the progression of non-alcoholic fatty liver disease (NAFLD) toward non-alcoholic steatohepatitis (NASH) and increase disease severity. Studies have demonstrated a positive correlation between night shift work (NSW) and elevated liver enzymes, indicative of hepatic metabolic dysfunction, potentially increasing the risk of hepatocellular carcinoma (HCC) related to NAFLD. This review consolidates research findings on circadian disruption caused by NSW, late chronotype, jet lag, and social jet lag, drawing insights from studies involving both humans and animal models that investigate the effects of these factors on circadian rhythms in liver metabolism.

Interplay Between the Circadian Clock and Sirtuins.

The circadian clock is an autonomous timekeeping system evolved by organisms to adapt to external changes, regulating a variety of important physiological and behavioral processes. Recent studies have shown that the sirtuin family of histone deacetylases is involved in regulating the expression of clock genes and plays an important role in maintaining the normal rhythm of clock gene expression and behavior. Moreover, sirtuins are regulated directly or indirectly by the circadian clock system. The mutual regulation between the circadian clock and sirtuins is likely involved in a variety of signal transduction and metabolism processes. In this review, we discuss the molecular mechanisms and research progress on the intertwined relationship between the circadian clock and sirtuins, mainly in mammals, highlighting sirtuins as molecular links between metabolic control and circadian rhythms and offering our perspectives on future developments in the field.

Adaptive control of cardiac rhythms

Cardiac rhythms are related to heart electrical activity, being the essential aspect of the cardiovascular physiology. Usually, these rhythms are represented by electrocardiograms (ECGs) that are useful to detect cardiac pathologies. Essentially, the heart activity starts in the sinoatrial node (SA) node, the natural pacemaker, propagating to the atrioventricular node (AV), and finally reaching the His-Purkinje complex (HP). This paper investigates the control of cardiac rhythms in order to induce normal rhythms from pathological responses. A mathematical model that presents close agreement with experimental measurements is employed to represent the heart functioning. The adopted model comprises a network of three nonlinear oscillators that represent each one of the cardiac nodes, connected by delayed couplings. The pathological behavior is induced by an external stimulus in the SA node. An adaptive controller is proposed acting in the SA node considering an strategy based on the signal obtained by the natural pacemaker and its regularization. The incorporation of adaptive compensation in a Lyapunov-based control scheme allows the compensation for the unknown dynamics. The controller ability to deal with interpatient variability is evaluated by assuming that the heart model is not available to the controller design, being used only in the simulator to assess the control performance. Results show that the adaptive term can reduce the control effort by around 3% while reducing the tracking error by 20%, when compared to the conventional feedback approach. Additionally, the controller can avoid abnormal rhythms, turning the ECG closer to the expected normal behavior and preventing critical cardiac responses. Therefore, this work demonstrates that an adaptive controller can be used to regulate the ECG signal without prior information about the system and disregarding inter- and intrapatient variability.

Evaluation of Awareness, Knowledge, and Attitude Toward Basic Life Support Among the General Population in Saudi Arabia: A Nationwide Survey.

Background Basic life support (BLS) is the key component in changing the outcome from death to survival when cardiac arrest occurs. It involves providing cardiopulmonary resuscitation (CPR) and utilizing an automated external defibrillator (AED) to help restore the normal cardiac rhythm. By equipping more individuals with BLS training, it will enhance community preparedness and public health. Aim This study aimed to evaluate the general population's awareness, knowledge, and attitude toward BLS in Saudi Arabia. Subject and methods This cross-sectional study was conducted among the Saudi general population covering all five main regions in Saudi Arabia (Central, Eastern, Western, Southern, and Northern). A self-administered questionnaire was sent through volunteer data collectors in every area in which they live to the population using a Google (Google, Inc., Mountain View, CA) survey. The questionnaire includes socio-demographic characteristics (i.e., age, gender, region of residence, etc.) to assess the awareness, knowledge, and attitude toward BLS using a 20-item questionnaire based on the American Heart Association (AHA). Results Of the 992 participants, 615 (62%) were females, and 325 were aged between 26 and 35 years (32.8%). Four hundred eleven participants (41.4%) attended training related to BLS. The most common source of training information was a resuscitation society course (51.8%), followed by the university curriculum (24.6%) and school (10.7%). The overall mean knowledge score was 9.64 (SD 2.92) out of 20 points. Among them, 487 (49.1%) had moderate knowledge levels, 466 (47%) were poor, and only 39 (3.9%) had good knowledge. Factors associated with increased knowledge include younger age, living outside Central Region, better education, being a healthcare worker, knowing how to give a cardiac massage, previous participation in BLS training, and witnessed of sudden death. The biggest barrier that would prevent participants from providing a cardiac massage is fear of making a mistake (63.1%). Conclusion The general population's knowledge of BLS was found to be inadequate. However, younger participants who had a better education and worked in a healthcare institution tended to be more knowledgeable about BLS than the rest of the groups. The gaps in the knowledge are evidently seen in this study. Hence, appropriate measures are needed to bridge knowledge gaps. Healthcare authorities should devise a program to deliver necessary information about the basic facts of BLS throughout the community.

MULTI-LEVEL CLASSIFICATION BASED ON DEEP LEARNING FOR ACCURATE RISK STRATIFICATION OF ARRHYTHMIAS

Arrhythmias, also known as irregular heartbeats, are important health problems that must be accurately identified to diagnose and treat cardiovascular disease. Within the scope of this study, a network for classifying arrhythmias, which are important in the diagnosis and treatment of cardiovascular diseases, was proposed by using one-dimensional convolutional neural network (1D CNN), one of the deep learning techniques. With the proposed 1D-CNN architecture, arrhythmia types and normal rhythm ECGs were subjected to a more detailed examination from general to specific according to urgency situations. In the classifications made, first of all, a binary classification was made and an evaluation was made as whether there was a life risk or not. In triple, quadruple and six-fold classification, the detection of arrhythmia status is detailed. More complex classifications have helped to define different types of arrhythmias in more detail. This study proposes a deep learning network for automatic identification and classification of arrhythmias and shows that different arrhythmia conditions can be diagnosed with a single network model by applying the proposed network structure to multi-class arrhythmia disorders.

A Rare Case of Aconite Poisoning in a Tertiary Care Center in Nepal: Clinical Presentation and Management

Introduction: Aconite poisoning, caused by the toxin aconitine in the Aconitum genus (monkshood or wolfsbane), can be severe and requires supportive care as there is no specific antidote. Aconitine inhibits sodium channel inactivation, leading to dangerous cardiovascular and neurological symptoms.  Case Presentation: A 46-year-old male ingested half of a suspected aconite seed, leading to abdominal cramping, persistent vomiting, tingling sensations, and weakness. Upon admission, he exhibited hypotension, tachycardia, and bilateral mydriasis. ECG showed ventricular premature contractions. Treatment included intravenous amiodarone, magnesium sulfate, calcium gluconate, and gastric lavage with activated charcoal. He was admitted to the ICU for intensive monitoring and treatment, including ongoing amiodarone administration. After improvement, he was transferred to the general ward and later discharged.  Discussion: Aconite poisoning involves symptoms from aconitine's effect on sodium channels, including arrhythmias, hypotension, and neurological issues. Management focuses on supportive care, antiemetics, and monitoring. Advanced treatments like flecainide or amiodarone may restore normal heart rhythm, and severe cases might require a cardiac bypass or VA- ECMO.  Conclusion: This case describes a rare aconite poisoning with severe neurological, cardiovascular, and gastrointestinal symptoms after ingestion of a suspected aconite seed. The patient was treated with decontamination, intravenous amiodarone, and ICU care, leading to recovery. Despite its traditional use, aconite poisoning often results from its application without proper regulation, highlighting the need for rapid diagnosis and management.

A brain-body feedback loop driving HPA-axis dysfunction in breast cancer.

Breast cancer patients often exhibit disrupted circadian rhythms in circulating glucocorticoids (GCs), such as cortisol. This disruption correlates with reduced quality of life and higher cancer mortality 1-3 . The exact cause of this phenomenon - whether due to treatments, stress, age, co-morbidities, lifestyle factors, or the cancer itself remains unclear. Here, we demonstrate that primary breast cancer alone blunts host GC rhythms by disinhibiting neurons in the hypothalamus, and that circadian phase-specific neuromodulation of these neurons can attenuate tumor growth by enhancing anti-tumor immunity. We find that mice with mammary tumors exhibit blunted GC rhythms before tumors are palpable, alongside increased activity in paraventricular hypothalamic neurons expressing corticotropin-releasing hormone (i.e., PVN CRH neurons). Tumor-bearing mice have fewer inhibitory synapses contacting PVN CRH neurons and reduced miniature inhibitory post-synaptic current (mIPSC) frequency, leading to net excitation. Tumor-bearing mice experience impaired negative feedback on GC production, but adrenal and pituitary gland functions are largely unaffected, indicating that alterations in PVN CRH neuronal activity are likely a primary cause of hypothalamic-pituitary-adrenal (HPA) axis dysfunction in breast cancer. Using chemogenetics (hM3Dq) to stimulate PVN CRH neurons at different circadian phases, we show that stimulation just before the light-to-dark transition restores normal GC rhythms and reduces tumor progression. These mice have significantly more effector T cells (CD8+) within the tumor than non-stimulated controls, and the anti-tumor effect of PVN CRH neuronal stimulation is absent in mice lacking CD8+ T cells. Our findings demonstrate that breast cancer distally regulates neurons in the hypothalamus that control output of the HPA axis and provide evidence that therapeutic targeting of these neurons could mitigate tumor progression.

Scalable Drug-Mimicking Nanoplasmonic Therapy for Bradyarrhythmia in Cardiomyocytes.

Bradyarrhythmia poses a serious threat to human health, with chronic progression causing heart failure and acute onset leading to sudden death. In this study, we develop a scalable drug-mimicking nanoplasmonic therapeutic strategy by introducing gold nanorod (Au NR) mediated near-infrared (NIR) photothermal effects. An integrated sensing and regulation platform is established for in situ synchronized NIR laser regulation and electrophysiological property recording. The Au NR plasmonic regulation enables the restoration of normal cardiomyocyte rhythm from the bradyarrhythmia. By regulating the aspect ratio and concentration of Au NRs, as well as the intensity and time of NIR irradiation, we precisely optimized the plasmonic photothermal effect to explore effective therapeutic strategies. Furthermore, mRNA sequencing revealed a significant increase in the number of differentially expressed genes (DEGs) involved in the electrophysiological activities of cardiomyocytes following photothermal therapy. Au NR-mediated plasmonic photothermal therapy, as an efficient and noninvasive approach to bradyarrhythmia, holds profound implications for cardiology research.

QMWT: Design of an Improved EEG Classification Model via Q-Learning Based Processing of Multispectral Wave Traits

Electroencephalogram (EEG) signals represent various wave patterns that assist in identification of normal & abnormal brain activities. These wave patterns consist of alpha waves, which indicate relaxation phases, beta waves, that indicate normal brain rhythms & can be disturbed due to cortical & other damages, delta waves, which are dominant in infants during sleep, & theta waves, which represent irregular metabolic & hydrocephalus activities in adults. A combination of these waves is capable of representing multiple brain conditions for both adolescents & adults. Various models have been proposed by researchers to analyze these signals, and most of them work on single or bi-domain features, which limits their classification performance. Most of these models are also static, and do not incorporate continuous feedback & incremental processes. Due to which their precision & recall performance is either constant or reduces w.r.t. newer evaluations. To overcome these limitations, this text proposes design of a novel EEG classification model that uses Q-Learning for classification of multispectral feature sets. The model extracts Mel Frequency Cepstral Coefficients (MFCC), and iVector features from raw EEG data, which assists in multispectral representation of these signals. The extracted features are classified via Q-Learning based Recurrent Neural Network (RNN) classifier, that combines Gated Recurrent Unit (GRU), and Long-Short-Term Memory (LSTM) based feature sets. Due to extraction of MFCC, the GRU & LSTM Models are able to identify power spectral variation, cepstral variations, spectrogram patterns, DCT (Discrete Cosine Transform) variations, etc. While, due to iVector, entropy variations are recognized and processed for better accuracy levels. Thus, both LSTM & GRU Models assist in augmenting extracted features, which improves feature variance for better classification performance. Results of these classifications are feedback into the training set via a correlation-based analysis layer, that assists in continuously improving precision & recall performance for different evaluations. Due to incorporation of this layer, the model is capable of improving precision by 8.5%, recall by 8.3%, and accuracy by 4.9% when compared with various state-of-the-art models. It was also observed that this performance incrementally improves w.r.t. number of evaluations, which assists in deploying the model for real-time applications.

A New Remote Monitoring System: Evaluation of the Efficiency and Accuracy of the Smart Emergency Medical System-Health Internet of Things Device.

The remote medical monitoring system can facilitate monitoring patients with cardiac arrhythmia, and consequently, reduce mortality and complications in individuals requiring emergency interventions. Hence, it is necessary to evaluate new telemedicine devices and compare them with standard devices. Therefore, this study aimed to evaluate and compare the new remote monitoring system, Smart Emergency Medical System-Health Internet of Things (SEMS-HIOT) developed by the Health Technology Development Centre of Babol University of Medical Sciences on patients with different cardiac arrhythmias and compare it with the standard device. In this case-control study, 60 patients were divided into the six most common arrhythmia groups (n=10 per each group and equal gender) as atrial fibrillation, ventricular tachycardia, paroxysmal supraventricular tachycardia, premature ventricular contractions, atrial tachycardia, and premature atrial contractions. Also, 20 healthy individuals (including 10 men and 10 women) without any arrhythmia (normal rhythm) were considered as the control group. Three similar SEMS-HIOT devices were used as test devices and a standard cardiac monitoring device as the control device. The clinical parameters, including heart rate, pulse rate, oxygen saturation, body temperature, and cardiac electrical activity via electrocardiogram (ECG) lead-II were recorded. Findings showed that the performance of the SEMS-HIOT test device was similar and in the same range for all indices in each group and there were no significant differences compared to the performance of the control device (P0.05). Also, the ECG records measured with SEMS-HIOT and standard device indicate no significant differences (P0.05). Our study showed that the cardiac indices as well as ECG findings, which were measured with SEMS-HIOT and common standard devices confirmed the accuracy and reliability of the new telematics device for monitoring patients with cardiac diseases.

Evaluation of Changes in Cardiac Troponin I Levels After Direct Current Cardioversion in Patients With Atrial Fibrillation.

Direct current cardioversion (DCCV) of atrial fibrillation (AF) is a procedure used to restore normal heart rhythm. Cardiac biomarkers, such as cardiac troponin I (cTnI), are elevated in situations where injury-myocardial cell necrosis is induced. The aim of the present study was to investigate the change in cTnIlevels, i.e., whether a myocardial injury is present, in patients with AF whose elective treatment was synchronized DCCV via a biphasic defibrillator. The study sample included 59 patientswho underwent synchronized DCCV for AF reversion. Measurement of cTnI before and after DCCV (one, three, and six hours) was performed by blood sampling and subsequent assay. It was observed that the value of cTnI did not change (<0.1 ng/mL) after DCCV at the measurement time points (one, three, and six hours). In addition, the value of cTnI remained constant (<0.1 ng/mL) in relation to the energy delivered, before DCCV and after DCCV (one, three, and six hours). However, it was found that there was a correlation between the outcome (AF reversion or not) and the energy used (joules). Synchronized DCCV with a biphasic defibrillator did not cause myocardial injury in any of the patients, as there was no change in cTnI values before and after DCCV.

Patient Driven EKG Device Performance in Adults with Fontan Palliation.

The aim of this study was to evaluate the accuracy of the KardiaMobile (KM) device in adults with a Fontan palliation, and to assess the KM function as a screening tool for atrial arrhythmias. While patient driven electrocardiogram (EKG) devices are becoming a validated way to evaluate cardiac arrhythmias, their role for patients with congenital heart disease is less clear. Patients with single ventricle Fontan palliation have a high prevalence of atrial arrhythmias and represent a unique cohort that could benefit from early detection of atrial arrhythmias. This single center prospective study enrolled adult patients with Fontan palliation to use the KM heart rhythm monitoring device for both symptomatic episodes and asymptomatic weekly screening over a 1-year period. Accuracy was assessed by comparing the automatic KM interpretation (KM-auto) to an electrophysiologist overread (KM-EP) and traditional EKG. Fifty patients were enrolled and 510 follow-up transmissions were received. The sensitivity and specificity of enrollment KM-auto compared to EKG was 65% and 100%, respectively. The sensitivity and specificity of enrollment KM-auto compared to the KM-EP was 75% and 96%, respectively. In the adult Fontan palliation, the accuracy of the KM device to detect a normal rhythm was reliable and best with a physician overread. Abnormal or uninterpretable KM-auto device interpretations, symptomatic transmissions, and any transmissions with a high heart rate compared to a patient's normal baseline should warrant further review.

Circadian rhythm sleep loss impairs motor inhibition more than motor execution in continuous action

Under total sleep deprivation, both inhibitory and motor control are impaired. However, how circadian rhythm sleep loss caused by irregular sleep pattern affects motor inhibition and execution in continuous actions remains unknown. This study utilized a pointing task to investigate the question over 30 days. During regular trials, participants were instructed to tap on a specified location, while in countermanding trials, they were required to countermand their current action. Additionally, there was a control group performed the same task following a normal 24-h rhythm. The results indicated that the decrease in accuracy and the increase in movement time in countermanding trials were more prominent in the shift work group. In contrast, there was no significant difference in reaction time between the two groups. Notably, the shift work group outperformed the control group in terms of movement time in regular trials and radial displacement in countermanding trials. Overall, these results show that circadian rhythm sleep loss predominantly affects inhibitory control, rather than motor control, underscoring the nuanced impacts of sleep disruption on differential aspects of cognitive and motor functions.

Investigating the cardiotoxicity of N-n-butyl haloperidol iodide: Inhibition mechanisms on hERG channels

The human Ether-à-go-go-Related Gene (hERG) encodes a protein responsible for forming the alpha subunit of the IKr channel, which plays a crucial role in cardiac repolarization. The proper functioning of hERG channels is paramount in maintaining a normal cardiac rhythm. Inhibition of these channels can result in the prolongation of the QT interval and potentially life-threatening arrhythmias. Cardiotoxicity is a primary concern in the field of drug development. N-n-Butyl haloperidol iodide (F2), a derivative of haloperidol, has been investigated for its therapeutic potential. However, the impact of this compound on cardiac toxicity, specifically on hERG channels, remains uncertain. This study employs computational and experimental methodologies to examine the inhibitory mechanisms of F2 on hERG channels. Molecular docking and molecular dynamics simulations commonly used techniques in computational biology to predict protein-ligand complexes' binding interactions and stability. In the context of the F2-hERG complex, these methods can provide valuable insights into the potential binding modes and strength of interaction between F2 and the hERG protein. On the other hand, electrophysiological assays are experimental techniques used to characterize the extent and nature of hERG channel inhibition caused by various compounds. By measuring the electrical activity of the hERG channel in response to different stimuli, these assays can provide important information about the functional effects of ligand binding to the channel. The study's key findings indicate that F2 interacts with the hERG channel by forming hydrogen bonding, π-cation interactions, and hydrophobic forces. This interaction leads to the inhibition of hERG currents in a concentration-dependent manner, with an IC50 of 3.75 μM. The results presented in this study demonstrate the potential cardiotoxicity of F2 and underscore the significance of considering hERG channel interactions during its clinical development. This study aims to provide comprehensive insights into the interaction between F2 and hERG, which will may guid us in the safe use of F2 and in the development of new derivatives with high efficiency while low toxicity.

In situ assembly of an injectable cardiac stimulator

Without intervention, cardiac arrhythmias pose a risk of fatality. However, timely intervention can be challenging in environments where transporting a large, heavy defibrillator is impractical, or emergency surgery to implant cardiac stimulation devices is not feasible. Here, we introduce an injectable cardiac stimulator, a syringe loaded with a nanoparticle solution comprising a conductive polymer and a monomer that, upon injection, forms a conductive structure around the heart for cardiac stimulation. Following treatment, the electrode is cleared from the body, eliminating the need for surgical extraction. The mixture adheres to the beating heart in vivo without disrupting its normal rhythm. The electrofunctionalized injectable cardiac stimulator demonstrates a tissue-compatible Young’s modulus of 21 kPa and a high conductivity of 55 S/cm. The injected electrode facilitates electrocardiogram measurements, regulates heartbeat in vivo, and rectifies arrhythmia. Conductive functionality is maintained for five consecutive days, and no toxicity is observed at the organism, organ, or cellular levels.

Evaluation of fibromyalgia in on-call healthcare workers

Introduction: Fibromyalgia (FM) is a non-articular, chronic rheumatic disease with unknown etiology, characterized by widespread musculoskeletal pain, sleep disorder, fatigue, and the presence of numerous tender points. Working with the shift work and night shift system contradicts the normal biological rhythm of the body and negatively affects the person in many ways. The complaint of sleep disorder is widespread in patients with FM; close to 100% prevalence has been reported in some studies. This study aimed to investigate the relationship between fibromyalgia and shift working order in our hospital staff. Methods: This cross-sectional study was conducted in our university hospital. 120 people who met the inclusion criteria were included in the study, and 80 were accepted. As a control group, 95 people were reached, 80 of whom agreed to participate in the study. The Fibromyalgia Impact Scale (FES) was questioned in cases with fibromyalgia. The SF-36 quality of life questionnaire was applied to all the cases in which the study was conducted. 1990 ACR Fibromyalgia Diagnostic Criteria were used for diagnosis. The Fibromyalgia Impact Scale (FES) was questioned in cases with FM. Results: The average score of all SF-36 quality of life questionnaire sub-field groups was significantly higher in the control group than in the group who stand duty (p &amp;lt;0.05). There is a difference between the study group and the control group in terms of "physical function" (p&amp;lt;0.001). The "physical function" score is higher in the control group. A significant difference was found in SF-36 subgroups in cases with FM (N:39) compared to cases with non-FM (N:141) (p&amp;lt;0.05). General health status was more negatively affected in the cases with FM. There is a weakly positive linear relationship (borderline significant) between FES1.2 (laundry) and "social function" (r=0.349, p=0.054). There is a moderately negative linear relationship between FES1.3 (preparing meals) and “general health” (r=- 0.420, p=0.019) Conclusion: As a result, fibromyalgia is more common in health workers who are working night shifts and have at least four night shifts a month. This situation negatively affects health workers' quality of life and general health. the number and intensity of night shifts per person should be minimized as much as possible to reduce the potential negative impact of night shifts on workers, especially in the lines of work where a shift work order negatively affects the human biological clock.

An unusual cause of inappropriate shocks delivered by an implantable cardioverter defibrillator

IntroductionCardiac implantable electronic device (CIED) complications present significant challenges in clinical practice, especially in elderly patients with multiple comorbidities. Common adverse events include infection, lead malfunction, and device migration. Twiddler’s Syndrome, a rare but serious CIED complication characterised by patient manipulation causing lead displacement and device malfunction, is often underreported. The literature consists mainly of case reports and small series, providing limited guidance on prevention and management. As CIEDs are critical for managing cardiac arrhythmias and heart failure, understanding and addressing Twiddler’s Syndrome is essential. This case report aims to contribute to the literature by detailing a case of Twiddler’s Syndrome, emphasising the importance of a multidisciplinary approach for optimal management.Case PresentationA 59-year-old male presented with discomfort around his implantable cardioverter defibrillator (ICD) site and the sternal area over the past two days. He denied pain, dyspnoea, or dizziness. Clinical examination revealed a normal heart rhythm and no peripheral pulse deficit. Ultrasound revealed a reduced left ventricular ejection fraction. The atrial lead was not visible, and the shock coil was misplaced. ICD interrogation showed inappropriate shocks due to sensing artifacts and exit block in both leads, with no arrhythmias detected. An X-ray confirmed lead dislodgement and significant entanglement in the pocket. The patient was diagnosed with Twiddler’s Syndrome and scheduled for surgical revision.Discussion/ConclusionsDilated cardiomyopathy (DCM), characterised by left ventricular dilatation and dysfunction, accounts for a significant proportion of systolic heart failure cases. Despite advancements in heart failure management, DCM patients remain at high risk for sudden cardiac death (SCD), making ICD implantation crucial. However, CIED placement carries risks of complications, including Twiddler’s Syndrome. This condition can lead to lead dislodgement and device malfunction, resulting in inappropriate shocks and potential patient harm. In this case, a single-session extraction and re-implantation were successfully performed using a multidisciplinary approach, emphasising the importance of comprehensive management strategies to address such complications effectively. Regular follow-up showed no adverse events, highlighting the procedure’s success and the potential benefits of using advanced antimicrobial adjuncts to prevent infections. This case underscores the need for awareness and standardised protocols for managing Twiddler’s Syndrome to improve patient outcomes in the growing population of CIED recipients.

Circadian rhythm disruption upregulating Per1 in mandibular condylar chondrocytes mediating temporomandibular joint osteoarthritis via GSK3β/β-CATENIN pathway

BackgroundTemporomandibular joint osteoarthritis (TMJOA) has a high incidence rate, but its pathogenesis remains unclear. Circadian rhythm is an important oscillation in the human body and influences various biological activities. However, it is still unclear whether circadian rhythm affects the onset and development of TMJOA.MethodsWe disrupted the normal rhythm of rats and examined the expression of core clock genes in the mandibular condylar cartilage of the jaw and histological changes in condyles. After isolating rat mandibular condylar chondrocytes, we upregulated or downregulated the clock gene Per1, examined the expression of cartilage matrix-degrading enzymes, tested the activation of the GSK3β/β-CATENIN pathway and verified it using agonists and inhibitors. Finally, after downregulating the expression of Per1 in the mandibular condylar cartilage of rats with jet lag, we examined the expression of cartilage matrix-degrading enzymes and histological changes in condyles.ResultsJet lag led to TMJOA-like lesions in the rat mandibular condyles, and the expression of the clock gene Per1 and cartilage matrix-degrading enzymes increased in the condylar cartilage of rats. When Per1 was downregulated or upregulated in mandibular condylar chondrocytes, the GSK3β/β-CATENIN pathway was inhibited or activated, and the expression of cartilage matrix-degrading enzymes decreased or increased, which can be rescued by activator and inhibitor of the GSK3β/β-CATENIN pathway. Moreover, after down-regulation of Per1 in mandibular condylar cartilage in vivo, significant alleviation of cartilage degradation, cartilage loss, subchondral bone loss induced by jet lag, and inhibition of the GSK3β/β-CATENIN signaling pathway were observed. Circadian rhythm disruption can lead to TMJOA. The clock gene Per1 can promote the occurrence of TMJOA by activating the GSK3β/β-CATENIN pathway and promoting the expression of cartilage matrix-degrading enzymes. The clock gene Per1 is a target for the prevention and treatment of TMJOA.

The importance and use of defibrillation in pediatric surgery

Pediatric surgery is a delicate and complex process. Anatomical and physiological characteristics of pediatric patients are different compared to adults and this may increase the risk for some complications during surgical interventions. Complications that may occur during surgical procedures may include sudden cardiac events and cardiac arrest. These situations are among the emergencies that require rapid intervention and one of the most effective tools of this is defibrillation. Defibrillation is a procedure that is used to correct the life-threatening arrhythmia (ventricular fibrillation and pulseless ventricular tachycardia). This procedure aims to restore normal rhythm through electric shock to the heart. In children, defibrillation requires great care in terms of correct timing and using appropriate energy levels. Since incorrect practices may cause serious harm, correct use of defibrillation is vital in the management of possible complications during pediatric surgery.

Leadwise clustering multi-branch network for multi-label ECG classification

The 12-lead electrocardiogram (ECG) is widely used for diagnosing cardiovascular diseases in clinical practice. Recently, deep learning methods have become increasingly effective for automatically classifying ECG signals. However, most current research simply combines the 12-lead ECG signals into a matrix without fully considering the intrinsic relationships between the leads and the heart's structure. To better utilize medical domain knowledge, we propose a multi-branch network for multi-label ECG classification and introduce an intuitive and effective lead grouping strategy. Correspondingly, we design multi-branch networks where each branch employs a multi-scale convolutional network structure to extract more comprehensive features, with each branch corresponding to a lead combination. To better integrate features from different leads, we propose a feature weighting fusion module. We evaluate our method on the PTB-XL dataset for classifying 4 arrhythmia types and normal rhythm, and on the China Physiological Signal Challenge 2018 (CPSC2018) database for classifying 8 arrhythmia types and normal rhythm. Experimental results on multiple multi-label datasets demonstrate that our proposed multi-branch network outperforms state-of-the-art networks in multi-label classification tasks