Ryanodine receptors (RyR) are intracellular calcium (Ca²⁺) release channels on the sarcoplasmic reticulum of skeletal and cardiac muscles that play a central role in excitation-contraction coupling. Genetic mutations or posttranslational modifications of RyR causes hyperactivation of the channel, leading to various skeletal muscle and heart diseases. Currently, no specific treatments exist for most RyR-associated diseases. Recently, high-throughput screening (HTS) assays have been developed to identify potential candidates for treating RyR-related muscle diseases. These assays have successfully identified several compounds as novel RyR inhibitors, which are effective in animal models. In this review, we will focus on recent progress in HTS assays and discuss future perspectives of these promising approaches.

Aeromonas species are Gram-negative rods known to cause infections such as gastroenteritis, bacteremia and wound infections. Colistin is one of few treatments for multidrug-resistant Gram-negative bacteria. However, colistin-resistant bacteria carrying the mobilized colistin resistance (mcr) gene are a threat in healthcare settings worldwide. In recent years, colistin-resistant Aeromonas species have been detected in environmental and clinical samples. We analyzed the genomic characteristics of one highly colistin-resistant A. jandaei isolated from a blood sample in Nepal, which harbored four novel mcr-like genes on its chromosome. Our study strongly suggests that A. jandaei is a reservoir of colistin-resistant genes. Inappropriate use of drugs in medicine and food production should be reduced and continued global surveillance for colistin-resistant bacteria is necessary.

The numbers of coronavirus (COVID-19) infections have exploded in Japan since mid-March 2020, making it difficult for outpatients to visit our hospital (Juntendo Hospital in Tokyo). For this reason, the hospital expanded the use of online medical care in May 2020 to ensure uninterrupted medication treatment for outpatients who could not attend in person. Although the number of outpatient visits in person was reduced, patients were still able to consult our clinic and receive their medication through online medical care via audio–video systems. This paper discusses the background to this situation, as well as the guidelines, the medical fee system, and the advantages and disadvantages of online medical care in Japan.

Objectives Septal myectomy confers survival benefits on patients with hypertrophic cardiomyopathy. However, its role in the treatment of severe aortic stenosis (sAS) with left ventricular outflow tract obstruction (LVOTO) remains under investigation. Another challenging question in the era of transcatheter aortic valve replacement is who would benefit more from traditional surgical aortic valve replacement (SAVR) with myectomy. Therefore, this study aimed to investigate myectomy cases at our hospital in Japan.

Methods A total of 740 patients who underwent SAVR for sAS between 2012 and 2019 were identified. The demographics and baseline echocardiographic findings were retrospectively compared between patients who underwent concomitant myectomy and those who did not. The myectomy group was further assessed for factors predisposing to LVOTO, operative details, echocardiographic changes, and prognosis. The resected septa were histopathologically analyzed.

Results The myectomy group mostly comprised elderly females with a small hypercontractile heart. Myectomy with SAVR led to statistically significant improvements in concentric left ventricular hypertrophy and LVOTO parameters. Survival was comparable with that reported in previous reports, even in the elderly subset (≥ 75 years). The septa showed mild fibrosis.

Conclusions Myectomy can be safely performed with SAVR for sAS with LVOTO, even in the elderly, and it effectively improves LVOTO. Special attention should be paid to elderly females with relatively more severe AS and a small yet extra-hypertrophic and extra-hypercontractile heart. Such patients warrant comprehensive assessment of LVOTO, and despite its invasiveness, SAVR may be potentially more beneficial by allowing direct observation of LVOTO and ancillary myectomy.

Objective We retrospectively investigated the degree of completion of the checklist during or immediately after diving accident, who were transported by a physician-staffed helicopter emergency medical service (HEMS).

Method From May 2016 to December 2020, we conducted a retrospective the diving accident checklist review of all patients with diving accident, who were transported by HEMS. If all questions of the diving accident checklist were answered, full marks were 40 points. Subjects were divided into two groups: the Arrest group, which included subjects who became cardiac arrest in prehospital setting, and the Control group.

Results A total of 86 patients with diving accident were transported by the HEMS. Among these patients, there were 16 subjects in the Arrest group and 70 in the Control group. Average total score in the Arrest group were significantly smaller than those in the Control group.

Conclusion Degree of completion of the diving accident checklist in cases with cardiac arrest was low in comparison with cases without cardiac arrest. To improve this, further approach based on several remedies will be required in the future.

Objectives The purpose of this study was to develop and validate a machine learning prediction model for the prognosis of non-cardiogenic out-of-hospital cardiac arrest (OHCA) with an initial non-shockable rhythm.

Design Data were obtained from a nationwide OHCA registry in Japan. Overall, 222,056 patients with OHCA and an initial non-shockable rhythm were identified from the registry in 2016 and 2017. Patients aged <18 years and OHCA caused by cardiogenic origin, cancer, and external factors were excluded. Finally, 58,854 participants were included.

Methods Patients were classified into the training dataset (n=29,304, data from 2016) and the test dataset (n=29,550, data from 2017). The training dataset was used to train and develop the machine learning model, and the test dataset was used for internal validation. We selected XGBoost as the machine learning classifier. The primary outcome was the poor prognosis defined as cerebral performance category of 3-5 at 1 month. Eleven prehospital variables were selected as outcome predictors.

Results In validation, the machine learning model predicted the primary outcome with an accuracy of 90.8% [95% confidence interval (CI): 90.5-91.2], a sensitivity of 91.4% [CI: 90.7-91.4], a specificity of 74.1% [CI: 69.2-78.6], and an area under the receiver operating characteristic value of 0.89 [0.87-0.92]. The important features for model development were the prehospital return of spontaneous circulation, prehospital adrenaline administration, and initial electrical rhythm.

Conclusions We developed a favorable machine learning model to predict the prognosis of non-cardiogenic OHCA with an initial non-shockable rhythm in the early stage of resuscitation.

Objectives Atherosclerosis is a chronic inflammatory disease characterized by lipid accumulation and local inflammation, which are regulated by the immune system. The immunological aspects of this disease are unclear. Immunoglobulin A regulates many cell responses through interactions with Fcα receptor type I (FcαRI). Anti-FcαRI antibody inhibits activating receptors by inducing an inhibitory immunoreceptor tyrosine-based activation motif configuration. However, the role of FcαRI in atherosclerosis development is unclear. Here, we investigated the utility of FcαRI targeting to induce inhibitory immunoreceptor tyrosine-based activation motif signaling in atherosclerosis treatment.

Materials ApoE^-/- transgenic mice expressing the FcαRIR209L/FcRγ chimeric protein (FcαRIR209L/FcRγApoE^-/- mice) were generated. We prepared an FcαRIR209L/FcRγ transfectant (I3D) from a mouse macrophage cell line (RAW264.7).

Methods Anti-FcαRI or control antibody was used to investigate a high-fat-diet-induced FcαRIR209L/FcRγApoE^-/- mouse model of atherosclerosis. The antibody was also used to assess macrophage foam cell formation via Oil Red O staining and mitogen-activated protein kinase signaling via immunoblotting in the FcαRIR209L/FcRγ-expressing RAW264.7 macrophage cell line I3D.

Results Targeting of monovalent FcαRI induced inhibitory effects in the FcαRIR209L/FcRγApoE^-/- mouse model of atherosclerosis by inhibiting macrophage infiltration. FcαRI targeting using the anti-FcαRI antibody also reduced mitogen-activated protein kinase signaling and foam cell formation, leading to decreased interleukin (IL)-1b and monocyte chemoattractant protein (MCP)-1.

Conclusions We demonstrated that targeting monovalent FcαRI suppresses atherosclerosis development. These findings can support the future clinical exploration of FcαRI targeting for atherosclerosis treatment.

Background Platelet-rich plasma (PRP) is a biological product obtained from autologous blood that contains growth factors, promoting the healing and regeneration of human tissues. Several oral diseases require surgical intervention, producing residual wounds that undergo a healing process, accompanied by pain, swelling, superinfections, and bone remodeling. This protocol study aims to evaluate the safety of PRP use for the following dental procedures: post-extraction socket healing, periodontal tissue regeneration, maxillary sinus floor elevation, tooth transplantation, and intentional tooth replantation.

Methods Ten patients will be enrolled and subjected to the required treatment with the addition of PRP, after appropriate hematological and biochemical evaluations. The participants will then be subjected to an observation period of 4 weeks to monitor adverse events through clinical observation. Secondary outcomes will regard pain, and clinical evolution of the treated site. Among these, presence of infection, swelling, wound healing, stability of the transplanted tooth.

Discussion Safety of medical procedures represents the first requirement for their introduction in routine practice. A careful evaluation of clinical response during follow-up period and registration of adverse effects is fundamental for safety confirmation and subsequent use of PRP for the proposed dental procedures.

Trial registration Japan Registry of Clinical Trials (https://jrct.niph.go.jp/, registry number: jRCTc030190273, jRCTc030190274, jRCTc030190275, jRCTc030190276, jRCTc030190277; Date of registration: 31 March 2020).

In recent years, the outcomes of the Fontan procedure have been good, but Fontan-associated liver disease (FALD), which causes congestive hepatopathy due to elevated central venous pressure (CVP), has become a serious problem when considering patients’ long-term prognosis. A 28-year-old woman with Emanuel syndrome was admitted to our hospital for the treatment of hepatocellular carcinoma (HCC). She was diagnosed with pulmonary atresia and underwent a bidirectional pulmonary artery shunt at the age of 1 year and 10 months and the Fontan procedure at 4 years of age. Blood tests showed an increase in γ-glutamyltransferase in her early 20s and a marked increase in alfa-fetoprotein levels at age 27 years. She was diagnosed as having HCC in the S7 region by contrast-enhanced computed tomography and underwent hepatectomy. There were no serious adverse events, and the patient has survived 18 months after surgery without recurrence. In this report, the optimal time for the transition from the pediatrics department to adult healthcare units is also discussed, along with the management system for FALD in our hospital.