Cardiac Innervation and Sudden Cardiac Death

The heart is extensively innervated and its performance is tightly controlled by the nervous system. Cardiac innervation density varies in diseased hearts leading to unbalanced neural activation and lethal arrhythmia. Diabetic sensory neuropathy causes silent myocardial ischemia, characterized by loss of pain perception during myocardial ischemia, which is a major cause of sudden cardiac death in diabetes mellitus (DM). Despite its clinical importance, the mechanisms underlying the control and regulation of cardiac innervation remain poorly understood

Cardiac Complications in Immune Checkpoint Inhibition Therapy

Immune checkpoint inhibitors (ICIs) have changed the treatment landscape of advanced cancers. Unfortunately, these agents can induce a wide spectrum of immune-related adverse events (irAEs) through activation of immune responses in non-target organs, including the heart. As the clinical use of ICI therapy increases rapidly, management of irAEs is becoming extremely important. The most commonly presented cardiac irAE is myocarditis. Histopathologically, T-cell (with a predominance of CD8+ cells) and macrophage infiltration in the myocardium is typically observed in ICI-associated myocarditis. Other presentations of cardiac irAEs include congestive heart failure, Takotsubo cardiomyopathy, pericardial disease, arrhythmias, and conduction disease. Although cardiac irAEs are relatively rare, they can be life-threatening. Hence, cardiologists and oncologists should be vigilant for these presentations

Direct Cardiac Reprogramming: A Novel Approach for Heart Regeneration

Cardiac diseases are among the most common causes of death globally. Cardiac muscle has limited proliferative capacity, and regenerative therapies are highly in demand as a new treatment strategy. Although pluripotent reprogramming has been developed, it has obstacles, such as a potential risk of tumor formation, poor survival of the transplanted cells, and high cost. We previously reported that fibroblasts can be directly reprogrammed to cardiomyocytes by overexpressing a combination of three cardiac-specific transcription factors (Gata4, Mef2c, Tbx5 (together, GMT)). We and other groups have promoted cardiac reprogramming by the addition of certain miRNAs, cytokines, and epigenetic factors, and unraveled new molecular mechanisms of cardiac reprogramming. More recently, we discovered that Sendai virus (SeV) vector expressing GMT could efficiently and rapidly reprogram fibroblasts into integration-free cardiomyocytes in vitro via robust transgene expression. Gene delivery of SeV-GMT also improves cardiac function and reduces fibrosis after myocardial infarction in mice. Through direct cardiac reprogramming, new cardiomyocytes can be generated and scar tissue reduced to restore cardiac function, and, thus, direct cardiac reprogramming may serve as a powerful strategy for cardiac regeneration. Here, we provide an overview of the previous reports and current challenges in this field. View Full-Tex

Cardiac Complications in Immune Checkpoint Inhibition Therapy

Immune checkpoint inhibitors (ICIs) have changed the treatment landscape of advanced cancers. Unfortunately, these agents can induce a wide spectrum of immune-related adverse events (irAEs) through activation of immune responses in non-target organs, including the heart. As the clinical use of ICI therapy increases rapidly, management of irAEs is becoming extremely important. The most commonly presented cardiac irAE is myocarditis. Histopathologically, T-cell (with a predominance of CD8+ cells) and macrophage infiltration in the myocardium is typically observed in ICI-associated myocarditis. Other presentations of cardiac irAEs include congestive heart failure, Takotsubo cardiomyopathy, pericardial disease, arrhythmias, and conduction disease. Although cardiac irAEs are relatively rare, they can be life-threatening. Hence, cardiologists and oncologists should be vigilant for these presentations

Clinical outcomes of takotsubo syndrome in patients with cancer: a systematic review and meta-analysis

BackgroundRecent studies suggested a relationship between Takotsubo syndrome (TTS) and malignancy. However, clinical outcomes of TTS associated with cancer have not been assessed completely. This study was aimed to investigate the outcomes of patients with TTS and cancer.MethodsWe performed a systematic review and meta-analysis to evaluate the clinical outcomes of TTS in patients with and without malignancy. We systematically reviewed and analyzed 14 studies (189,210 patients) published in PubMed and Cochrane Library databases until December 2022. The primary outcome was all-cause mortality at the longest follow-up.ResultsThe prevalence of current or previous malignancy in patients with TTS was 8.7% (16,461 patients). Patients with TTS and malignancy demonstrated a higher risk of mortality at the longest follow-up than those with TTS alone (odds ratio [OR], 2.41; 95% confidence interval [CI]; 1.95–2.98; P < 0.001). Moreover, cancer was significantly associated with an increased risk of in-hospital or 30-day mortality (OR 2.36; 95% CI, 1.67–3.33; P < 0.001), shock (OR 1.42; 95% CI, 1.30–1.55; P < 0.001), mechanical respiratory support (OR 1.68; 95% CI, 1.59–1.77; P < 0.001), arrhythmia (OR 1.27; 95% CI, 1.21–1.34; P < 0.001), and major adverse cardiac events (OR 1.69; 95% CI, 1.18–2.442; P < 0.001).ConclusionsThis study revealed significant associations between previous or active cancer and an increased risk of all-cause mortality and in-hospital adverse events in patients with TTS

Clinical Applications of Natriuretic Peptides in Heart Failure and Atrial Fibrillation

Natriuretic peptides (NPs) have become important diagnostic and prognostic biomarkers in cardiovascular diseases, particularly in heart failure (HF). Diagnosis and management of coronary artery disease and atrial fibrillation (AF) can also be guided by NP levels. When interpreting NP levels, however, the caveat is that age, sex, body mass index, renal dysfunction, and race affect the clearance of NPs, resulting in different cut-off values in clinical practice. In AF, NP levels have been associated with incident AF in the general population, recurrences after catheter ablation, prediction of clinical prognosis, and the risk of stroke. In this article, we first review and summarize the current evidence and the roles of B-type NP and atrial NP in HF and coronary artery disease and then focus on the increasing utility of NPs in the diagnosis and management of and the research into AF

Role of cyclooxygenase-2-mediated prostaglandin E2-prostaglandin E receptor 4 signaling in cardiac reprogramming

Direct cardiac reprogramming from fibroblasts can be a promising approach for disease modeling, drug screening, and cardiac regeneration in pediatric and adult patients. However, postnatal and adult fibroblasts are less efficient for reprogramming compared with embryonic fibroblasts, and barriers to cardiac reprogramming associated with aging remain undetermined. In this study, we screened 8400 chemical compounds and found that diclofenac sodium (diclofenac), a non-steroidal anti-inflammatory drug, greatly enhanced cardiac reprogramming in combination with Gata4, Mef2c, and Tbx5 (GMT) or GMT plus Hand2. Intriguingly, diclofenac promoted cardiac reprogramming in mouse postnatal and adult tail-tip fibroblasts (TTFs), but not in mouse embryonic fibroblasts (MEFs). Mechanistically, diclofenac enhanced cardiac reprogramming by inhibiting cyclooxygenase-2, prostaglandin E2/prostaglandin E receptor 4, cyclic AMP/protein kinase A, and interleukin 1β signaling and by silencing inflammatory and fibroblast programs, which were activated in postnatal and adult TTFs. Thus, anti-inflammation represents a new target for cardiac reprogramming associated with aging

大阪教育大学附属池田小学校 (仮校舎) の防犯体制

In June 2001 a middle-aged man murdered several children at Ikeda Elementary School associated with Osaka University of Education. After the murder case, a temporary school was constructed at a place near the original site. In the temporary school facilities and equipment were carefully designed to protect children against crimes of offenders intruding into school. A security guard at the school gate, observation video cameras on school sites, a teachers\u27 room looking onto the playground, checking guests at the front desk, emergency buttons in classrooms, safety rules and manuals, and other measures were considered to be extremely important for protection against crimes

A Study on "Dashing-out" Behavior of Children

In the present study it is attempted to measure the safety behavior of the children in the situation where "dashing-out" is likely to occur. The "dashing-out" situations were simulated in the playground of a nursery, a kindergarten and an elementary school, and the behavior of each child in the situation was recorded by video tape recorders. Subjects were the children at the age from 3 to 10. The main components of the measurement procedure were as follows: 1. Two screens (3.6m by 1.8m) are set in a line with 1.0m space in between. 2. A motorcycle runs behind the screens. 3. In front of the screens a child with his or her back to the screens plays catch with the experimenter. Before playing catch, the experimenter warns the child that a motorcycle is running behind the screens. 4. After the motorcycle has stopped running, the experimenter throws the ball high above the child as if he misthrew. 5. The ball goes through the space between the screens and child goes through that space to take the ball. The child\u27s behavior at that time is recorded. The main results were as follows: 1. When the definition of safety behavior is that the child decreases the running (or walking) speed at the space and looks at the right and/or left side there, the rates of children who showed safety behavior increased in proportion to the age level. 2. There was no significant difference between the rates of the boys and the girls who showed safety behavior at almost all the age levels