The Role of Endoplasmic Reticulum Stress in Metabolic Diseases.

The endoplasmic reticulum (ER), the center of protein folding, also controls the cell's life-and-death signaling mechanisms. ER stress caused by unfolded or misfolded proteins leads to the activation of the unfolded protein response (UPR) in the cell. The UPR utilizes three main signaling pathways to restore disrupted ER homeostasis. These signaling pathways are protein kinase R-like endoplasmic reticulum kinase, inositol-requiring enzyme 1, and activating transcription factor 6. Studies have reported that ER stress (ERS) plays a role in the pathogenesis of metabolic disorders such as diabetes, obesity, atherosclerosis, and nonalcoholic liver disease. This review will briefly discuss the ERS response in these metabolic diseases.

Investigation the effects of bee venom and H-dental-derived mesenchymal stem cells on non-small cell lung cancer cells (A549).

BACKGROUND: Lung cancer, one of the most common oncological diseases worldwide, continues to be the leading cause of cancer-related deaths. The development of new approaches for lung cancer, which still has a low survival rate despite medical advances, is of great importance. METHODS AND RESULTS: In this study, bee venom (BV), conditioned medium of MSCs isolated from dental follicles (MSC-CM) and cisplatin were applied at different doses and their effects on A549 cell line were evaluated. Dental follicles were used as a source of MSCs source and differentiation kits, and characterization studies (flow cytometry) were performed. Cell viability was measured by the MTT method and apoptosis was measured by an Annexin V-FITC/PI kit on flow cytometer. IC50 dose values were determined according to the 24th hour and were determined as 15.8 µg/mL for BV, 10.78% for MSC-CM and 5.77 µg/mL for cisplatin. IC50 values found for BV and MSC-CM were also given in combination and the effects were observed. It was found that the applied substances caused BV to decrease in cell viability and induced apoptosis in cells. In addition to the induction of apoptosis in BV, MSC-CM, and combined use, all three applications led to an increase in Bax protein expression and a decrease in Bcl-2 protein expression. The molecular mechanism of anticancer activity through inhibition of Bax and Bcl-2 proteins and the NF-κB signaling pathway may be suggested. CONCLUSION: Isolated MSCs in our study showed anticancer activity and BV and MSC-CM showed synergistic antiproliferative and apoptotic effects.

Unmasking the uncommon: bidirectional ventricular tachycardia in two rare paediatric cardiomyopathies.

We present two exceptional cases of 14-year-old girls diagnosed with rare cardiomyopathies (left ventricular non-compaction, and arrhythmogenic right ventricular cardiomyopathy), both presenting with the unusual finding of bidirectional ventricular tachycardia.

From cyanosis to diagnosis: A case report on right atrial fibroma in a pediatric patient.

A 3-year-old female patient presented with symptoms of cyanosis and intermittent eyelid edema, leading to the discovery of a lobulated mass in the right atrium, obstructing the superior vena cava. Despite the inability to entirely remove the mass due to its origins in the right atrium myocardium and its extension towards the sinoatrial node, successful surgical intervention and subsequent histopathological evaluation identified the mass as a fibroma, and postoperative symptoms were significantly alleviated.

Effects of Systolic Dysfunction on Clinical and Diagnostic Parameters in Pediatric Patients with Isolated Left Ventricular Non-compaction.

OBJECTIVE: Left ventricular non-compaction is a rare cardiomyopathy following an early arrest in endomyocardial morphogenesis. This study aimed to present the clinical and electrocardiographic characteristics, diagnostic features, treatment strategies, effects of systolic dysfunction on clinical and diagnostic parameters, and follow-up of pediatric patients diagnosed with left ventricular non-compaction. METHODS: We retrospectively reviewed children with isolated left ventricular non-compaction at Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital from January 2010 to June 2020. RESULTS: Fifty-five children were diagnosed with left ventricular non-compaction. Thirty-two patients (58.2%) were male, and the median age of presentation was 8.5 years (1 month-17.9 years). The median follow-up of the study was 19 months (1-121 months). Fourteen (25.5%) presented with systolic dysfunction (ejection fraction < 45%), and 2 presented with resuscitated/aborted cardiac arrest. Electrocardiographic abnormalities were present in 78.2%. Fragmented QRS was observed in 6 patients, and QTc duration was 450 milliseconds and above in 17 patients (30.9%). Electrocardiographic abnormalities, low QRS voltage, fragmented QRS, and thrombus were common in patients with ejection fraction < 45% group. Atrial and ventricular arrhythmias (including ventricular fibrillation-VF) were found with similar frequency in both ejection fraction < 45% and ≥45% groups. One patient with a complete atrioventricular block and 1 with long QT syndrome and severe bradycardia underwent permanent pacemaker implantation. Five (9.1%) patients died. CONCLUSIONS: Left ventricular non-compaction has heterogeneous clinical findings in childhood. It is essential to follow-up with the patients closely for the development of ventricular dysfunction or arrhythmias due to the progressive course of the disease. Further studies are needed since life-threatening ventricular arrhythmias can be seen, even in patients with preserved ejection fraction.

High-density Mapping Catheter (Advisor™ HD Grid) Usage for Intra-atrial Reentrant Tachycardia Ablation in Children and Young Adult Patients with Congenital Heart Disease.

BACKGROUND: We aimed to share our experience of intra-atrial reentrant tachycardia mapping and ablation with a new grid-style multielectrode high-density mapping catheter (Advisor™ HD Grid) in pediatric and young adult patients with operated congenital heart disease. METHODS: All patients with operated congenital heart disease and intra-atrial reentrant tachycardia mapping with the new grid-style catheter between October 2019 and December 2022 were included (group 1), and the results were compared to those patients who operated with conventional catheter methods before this period (group 2). All procedures were performed using the EnSite Precision 3D mapping system (Abbott Laboratories, Abbott Park, Ill, USA) with a limited fluoroscopy approach. Data were evaluated retrospectively. RESULTS: In group 1 (n = 16; 9 male), the median age was 21 years (10-36), compared to 19 years (9-27) in group 2 (n = 10; 5 male). While irrigated radiofrequency ablation was pre-ferred in all patients, the median number of 15 lesions (8-38) in group 1 was significantly less than the median of 30 lesions (8-71) in group 2 (P =.027). The median procedure duration of 159 minutes (110-233) in group 1 was significantly shorter compared to 280 minutes (180-370) in group 2 (P <.05). Acute procedural success was achieved in all patients (16/16; 100%) in group 1 compared to 8/10 patients (80%) in group 2. During the median follow-up of 27 months (11-36), there was only 1 intra-atrial reentrant tachycardia recurrence in group 1 (1/16; 6.2%) and 2 recurrences (2/8; 25%) in group 2 during the median follow-up of 110 months (56-151). No complications related to the mapping catheter itself occurred. CONCLUSION: In the intra-atrial reentrant tachycardia ablation of children with congenital heart disease to increase procedural success and shorten the mapping duration, the utility of Advisor™ HD Grid mapping catheter seems to be a feasible alternative.

Online in-class vs. out-of-class flipped learning models in English as foreign language writing classes.

Flipped learning models are considered as important elements of English as a foreign language (EFL) writing courses in order to advance the EFL learners' writing skills. Significantly, studies examining the efficacy of in-class and out-of-class writing models in flipped classroom settings when teaching online EFL writing courses are still of focus in the Turkish Cypriot context. This investigation aimed to examine the most efficient flipped learning model among the in-class vs. out-of-class writing models for the purpose of helping instructors to advance their EFL learners' writing achievement in an online writing setting. In addition, this study sorted to reveal the EFL learners' perceptions toward learning writing through in-class and out-of-class flipped learning writing models. A mixed methods research design was applied to achieve the aforementioned aims. Twenty-eight EFL learners studying at a private university's English Language Teaching department constituted the participants of this study. As the findings pointed out, the EFL learners in group A who wrote their essays in-class outperformed those in group B, who wrote their essays out-of-class. Moreover, it was found that the majority of the participants had more positive perceptions toward the in-class flipped classroom writing model. This study highlights that, better learner performances are achieved when the learners write during the class session online with the support of the instructor when implementing a flipped classroom model to teach EFL writing.

Surgical treatment of Ebstein anomaly in pediatric patients: A 10-year single-center study.

OBJECTIVE: We report the early and long-term results of the strategies and surgical methods used in our center to treat pediatric patients who underwent surgical intervention to correct Ebstein anomaly (EA) in our center. MATERIALS AND METHODS: In our study, a consecutive sample of 29 patients who underwent surgery for EA between February 2011 and February 2020 in our center were evaluated retrospectively. RESULTS: The 29 patients underwent a total of 40 operations. Univentricular repair was performed in 5 (17.2%), 1.5 ventricular repair in 5 (17.2%), and biventricular repair in the remaining 19 (65.5%) patients. Cone reconstruction (CR) was performed in eight (27.5%), non-Cone tricuspid valve (TV) repair technique in five (17.2%), ring annuloplasty in two (6.9%), and TV replacement in two patients (6.9%) who had undergone biventricular repair. In two patients (6.9%), only close an atrial septal defect. Two (6.9%) patients underwent a second operation for advanced tricuspid regurgitation (TR) in the early period. None of the 15 patients who underwent CR and TV plasty had moderate or advanced TR before discharge. Early mortality was seen in 1 (3.4%) patient. The mean follow-up period of the patients was 48.4±27.6 months. Three (10.7%) of the patients who were discharged after their first operation later underwent a second operation for TV regurgitation in the long term. No mortality was observed in any patient during long-term follow-up. CONCLUSION: Surgical treatment of EA is difficult, but its overall results are good. The anatomical repair rate is lower in neonatal and infant patients requiring surgery, but most of these patients underwent biventricular repair. Our long-term results demonstrated an acceptable survival rate, low mortality in the early postoperative period, and low incidence of re-intervention and morbidity.

Clinical spectrum and long-term course of sustained ventricular tachycardia in pediatric patients: 10 years of experience.

OBJECTIVE: Pediatric ventricular tachycardias (VTs) have heterogeneous etiology and different clinical features. This study aimed to evaluate the clinical spectrum and long-term course of pediatric sustained VTs. METHODS: Patients diagnosed as having sustained VT between 2010 and 2020 were evaluated retrospectively. RESULTS: A total of 129 patients with VT were evaluated; 74 patients were male, and the median age was 12.5 years (0.25-18 years). Patients were grouped as having idiopathic VT (IVT) [n=85 (65.9%)], cardiomyopathy-associated VT (CMP-VT) [n=24 (18.6%)], catecholaminergic polymorphic VT [n=17 (13.2%)], and myocarditis-associated VT [n=3, (2.3%)]. Palpitations (n=61) and syncope (n=24) were the most common symptoms. VT originated from the right ventricle in 53.6% of the patients. Half of the patients underwent electrophysiological study, 64 patients received radiofrequency ablation therapy, and 29 patients had implantable cardiac defibrillators. During the follow-up, 70.4% of all patients had complete resolution, whereas 19 patients had a partial resolution and 23 patients (19.5%) had stable disease. Monomorphic VTs and VTs with left bundle bunch block were more thriving controlled (p=0.02 vs. p=0.04). In terms of long-term results, no statistical difference was found among the VT groups (p=0.39). Deaths were observed only in IVT (n=1) and CMP-VT (n=8) groups (p<0.001), and the overall mortality rate of pediatric sustained VT was observed at 6.9% in this study. CONCLUSION: VTs, which can cause sudden cardiac arrest, are potentially life-threatening arrhythmias. Identifying the heterogeneity of this VT and its peculiar characteristics would facilitate appropriate diagnosis and therapy.

Cardiac resynchronization therapy in paediatric patients with congenital heart disease: single centre with 10 years of experience.

OBJECTIVES: In recent years, cardiac resynchronization therapy (CRT) has also started to be performed in the paediatric and CHD population. This study aimed to evaluate the efficacy of CRT in children with CHD. PATIENTS AND METHODS: Patients with CHD who underwent CRT treatment in our paediatric cardiology clinic between January, 2010 and January, 2020 were included in the study. Demographic findings, 12-lead electrocardiograms, echocardiograms, clinical characteristics, management strategies, and outcomes were reviewed systematically. RESULTS: The study population consisted of 18 CHD patients who had been treated with CRT for 10 years in our institution. The median age was 11 years (2.2-18 years) and the median weight was 39 kg (10-81 kg). Systemic ventricle was left ventricle in 13 patients, right ventricle in 4 patients, and 1 patient had single-ventricle physiology. CRT implantation indications were as follows: dysfunction after permanent pacemaker in 11 patients, dysfunction after left bundle branch block in 4 patients, and systemic ventricular dysfunction in 3 patients. CRT implantation techniques were epicardial (n = 13), hybrid (n = 4), and transvenous (n = 1) methods. QRS duration significantly decreased after CRT implantation (160 versus 124 m/second, p < 0.05). Median systemic ventricle ejection fraction (EF) significantly increased after the procedure (30 versus 50%, p < 0.05). Fourteen patients (78%) were responders, two patients (11%) were superresponders, and two patients (11%) were non-responders after the CRT treatment. One patient deceased during follow-up. Median follow-up duration was 40 months (6-117 months). CONCLUSION: When electromechanical dyssynchrony occurs in paediatric cases with CHD and developing heart failure, patients should be evaluated in terms of CRT to improve ventricular function. Alternative CRT therapy will be beneficial in these cases that do not improve clinically despite optimal medical treatment.

Mesenchymal stem cell therapy for COVID-19.

The coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) started in December 2019 and affected the whole world in a short time. The course of the disease depends on the person's immune system, physical properties, health status, etc. as it varies according to its characteristics while it is asymptomatic in some people, it causes fatal processes that start with flu-like symptoms such as cough, fever, respiratory distress in some people and progress to acute respiratory distress syndrome (ARDS), severe pneumonia and multi-organ dysfunction, and the basic mechanism underlying these effects known as a cytokine storm. There is no specific effective antiviral drug or vaccine in treatment yet. Supportive/alternative treatment methods are needed as both the desired effect cannot be achieved and undesirable side effects are seen with the current treatments used in the clinic. Mesenchymal stem cells (MSCs) are frequently preferred recently from basic studies to clinical studies and are effective and safe in immune-mediated inflammatory diseases such as Systemic Lupus Erythematosus, Graft-versus-Host disease. MSCs can secrete many types of cytokines through paracrine secretion or directly interact with immune cells leading to immunomodulation. According to the results of the completed studies; it has been stated that the cytokine storm caused by the overstimulation of the immune system decreases and even damage of the cytokine storm on organs decreases, respiratory distress is relieved and contributes to the healing process by repairing damaged tissues. In this review, clinical trials completed/ongoing on MSCs recommended for treating COVID-19, a global problem, are reviewed and the review is prepared to specify the existence of such a route to clinicians.

Clinical characteristics of hypertrophic cardiomyopathy in children: An 8-year single center experience.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the second most common pediatric cardiomyopathy. Although there is a large body of literature about HCM in adults, there is limited information on HCM in childhood. We evaluated various aspects of pediatric HCM patients treated at our center. METHODS: We identified 152 pediatric patients with HCM between October 2011 and October 2019. Clinical history, invasive (ICD, pacemaker, electrophysiologic study, catheter ablation therapy) and non-invasive (ECG, holter moniterization, echocardiography, cardiac MR, genetic study, medicam treatment) data were collected and evaluated. RESULTS: The mean ± standard deviation age of patients was 8.9 ± 5.7 years (1 month-18 years) and 67.8% were male. The most frequent clinical symptoms were murmur and palpitations. Three cases (2%) had aborted sudden death as the first manifestation of HCM. Of these patients, 120 (78.9%) had non-syndromic HCM and 32 (27.2%) had syndromic HCM. Asymmetric septal hypertrophy was common (48.3%) in the non-syndromic group, whereas concentric hypertrophy was common (56.2%) in syndromic group. Left ventricular outflow tract obstruction (LVOTO) occurred in 39 (25.6%) patients. Nine (5.9%) patients underwent electrophysiologic study and/or ablation and 16 patients underwent surgical intervention. Implantable cardioverter defibrillator (ICD) insertion was performed in 38 patients (26 transvenous, 12 epicardial). ICDs were inserted in three (7.9%) patients for secondary prevention; in the remaining patients (92.1%) the devices were placed for primary prevention. Mean SD follow-up time was 27.1 ± 22 months. Five (3.3%) patients died during the follow-up. No patient had heart transplantation or a long-term assistive device. CONCLUSION: The etiology of HCM is heterogeneous and present at any age. It is important to determine the timing of surgery and potential risks for sudden cardiac arrest. As most cases of HCM are familial, evaluation of family members at risk should be a routine component of clinical management.