A let-7 microRNA-RALB axis links the immune properties of iPSC-derived megakaryocytes with platelet producibility.

We recently achieved the first-in-human transfusion of induced pluripotent stem cell-derived platelets (iPSC-PLTs) as an alternative to standard transfusions, which are dependent on donors and therefore variable in supply. However, heterogeneity characterized by thrombopoiesis-biased or immune-biased megakaryocytes (MKs) continues to pose a bottleneck against the standardization of iPSC-PLT manufacturing. To address this problem, here we employ microRNA (miRNA) switch biotechnology to distinguish subpopulations of imMKCLs, the MK cell lines producing iPSC-PLTs. Upon miRNA switch-based screening, we find imMKCLs with lower let-7 activity exhibit an immune-skewed transcriptional signature. Notably, the low activity of let-7a-5p results in the upregulation of RAS like proto-oncogene B (RALB) expression, which is crucial for the lineage determination of immune-biased imMKCL subpopulations and leads to the activation of interferon-dependent signaling. The dysregulation of immune properties/subpopulations, along with the secretion of inflammatory cytokines, contributes to a decline in the quality of the whole imMKCL population.

[Left Ventricular Outflow Tract Obstruction After Transcatheter Aortic Valve Replacement due to Pannus Formation].

We experienced a case of surgical aortic valve re-replacement due to structural valve deterioration caused by pannus formation 4 years after transcatheter aortic valve replacement( TAVR). The patient underwent surgery because the mean transvalvular pressure gradient increased to 48 mmHg on echocardiography. Contrast-enhanced computed tomography (CT) was useful for predicting the site of adhesion to surrounding tissue preoperatively and exploring the presence of the pannus. Intraoperative findings showed the TAVR valve was covered with neointima except around the origins of the left and right coronary arteries and was firmly adhered to the surrounding tissues. As residual pannus was present in the subvalvular tissues, it was carefully removed. The explanted TAVR valve functioned well with good opening and closure. The postoperative course was uneventful. Pannus formation can result from mechanical stress. TAVR valves put significantly greater stress on the left ventricular outflow tract than surgical valves and may be more likely to cause pannus formation.

Remimazolam in perioperative management of Eisenmenger syndrome: a case report.

BACKGROUND: Eisenmenger syndrome (ES) is characterized by severe and irreversible pulmonary hypertension stemming from an uncorrected intracardiac shunt of significant size. The imbalance between systemic and pulmonary artery pressures predisposes patients with ES to the risk of cardiac arrest. Remimazolam has caused less circulatory depression, which may be advantageous for ES. However, no studies reported the use of remimazolam in perioperative ES management. CASE PRESENTATION: A 45-year-old female patient with ES derived from a ventricular septal defect was scheduled to undergo bilateral adnexectomy for an ovarian tumor. Her oxygen saturation was 80% with 3 L/min oxygen at rest, and her pulmonary and systemic flow ratio was 0.53. She underwent general anesthesia with remimazolam, and intraoperative hemodynamics was stable without hypotension or reduced oxygen saturation. CONCLUSIONS: Our successful management of ovarian tumor surgery in a patient with ES using remimazolam reveals its potential effectiveness in perioperative care.

[Surgical Explantation of a Bioprosthesis Nine Months After Transcatheter Aortic Valve Implantation].

CASE: 82-year-old female. In October 2020, the patient underwent transcatheter aortic valve implantation( TAVI)[Evolut PRO R 23 mm] via left subclavian artery approach for severe aortic valve stenosis. The patient was discharged home without any issues. However, nine months after surgery, the patient was hospitalized at another hospital for a right upper arm fracture and developed a fever. The patient was transferred to our hospital and was diagnosed with Enterococcal bacteremia while receiving antibiotic treatment. Echocardiography revealed leaflet thickening and cord-like structure on the artificial valve, and a diagnosis of prosthetic valve endocarditis (PVE) was made. The patient then underwent surgical removal of the valve. The patient had a good postoperative course and completed 4 weeks of antibiotic treatment before being transferred back to the referring hospital 31 days after surgery. TAVI made unprecendented revolution in the treatment of aortic valve stenosis. TAVI is often used for elderly patients with comorbidities because of high perioperative risk is for surgical aortic valve replacement. Although TAVI is widely promoted for its benefits, it is not without limitations. In cases with more than one year of follow-up, there are many complications and the risk of surgery is high. There have been few reports of cases from Japan requiring surgical removal of TAVI valve. In this case, PVE was diagnosed nine months after TAVI and the patient had a good outcome.

Effect of steroids on increased permeability of blood vessels of the stria vascularis after auditory ossicle vibration by a drill in otologic surgery.

OBJECTIVES: The vibration caused by drills used for middle ear surgery is considered one of the causes of postoperative sensorineural deafness. Seki et al reported that when drill-induced damage was created in the auditory ossicles of guinea pigs, permeability across the capillary vessels in the stria vascularis increased significantly with the duration of drill-induced vibration. The present study was undertaken to examine changes in permeability across the stria vascularis capillaries following vibration in experimental animals pretreated with steroids, with the goal of developing a method of preventing a vibration-induced increase in permeability across these capillaries. METHODS: After an intravenous dose of hydrocortisone and horseradish peroxidase, the auditory ossicles of guinea pigs were vibrated with a drill for 60 seconds. RESULTS: Intravenous steroid administration before vibration reduced the leakage of horseradish peroxidase from the stria vascularis capillaries after vibration. CONCLUSIONS: The findings suggested that steroids suppress the increase in permeability across the stria vascularis capillaries that results from drill-induced vibration.

Caged gene-inducer spatially and temporally controls gene expression and plant development in transgenic Arabidopsis plant.

Two new types of caged gene-inducers, caged 17beta-estradiol and caged dexamethazone, were synthesized. Caged gene-inducers were applied to transgenic Arabidopsis plants carrying a steroid hormone-inducible transactivation system. Light uncaged caged gene-inducers and controlled spatial and temporal expression of transgene in the transgenic plant. Furthermore, caged gene-inducers enabled the control of root development by light.

A case of fatal respiratory failure after surgery for advanced supraglottic laryngeal carcinoma.

Pulmonary lymphangitic carcinomatosis (PLC) is an uncommon type of pulmonary metastasis from laryngeal carcinoma. We encountered a case of fatal respiratory failure after surgery for supraglottic laryngeal carcinoma with multiple cervical lymph node metastases. On day 25 postoperatively, the patient suddenly developed fever and noted slowly progressive difficulty in breathing. Laboratory data, radiological findings, and the clinical course of this patient were strongly suggestive of PLC. The patient refused fiberoptic bronchoscopy and glucocorticoid therapy, leading to rapid deterioration due to increasing respiratory distress, and died of respiratory failure on postoperative day 32. PLC should be considered a possible presentation of pulmonary metastasis associated with head and neck carcinoma. Chest CT may be needed to detect subclinical PLC, especially in cases of advanced head and neck carcinomas.

[A case of advanced lateral wall oropharyngeal carcinoma showing complete response to chemotherapy with TS-1].

We report a recent case of squamous cell carcinoma originating in the right tonsil, with metastasis to the right superior cervical lymph nodes (T3N2bM0: stage IVA). Chemo-radiotherapy was administered as first-line therapy; and adjuvant chemotherapy with TS-1 was applied during the subsequent 4-week period for the treatment of the residual tumor in the neck. In this patient (female, 61 years old), the primary tonsillar tumor showed a complete response to the first-line therapy, however, the metastatic lesions in the cervical lymph nodes persisted, although the nodes also decreased markedly in size. Subsequent chemotherapy with TS-1 (80 mg/day) given for a 4-week period resulted in complete disappearance of the residual malignancy (CR), as determined by palpation and diagnostic imaging. No serious adverse events occurred during the therapy. Surgical treatment in patients with advanced head and neck cancer often results in a diminished quality of life. Although further accumulation of cases is necessary, TS-1, which allows oral chemotherapy on an outpatient basis, would seem to be a useful drug for adjuvant chemotherapy following radical irradiation in patients with advanced head and neck cancer.