The Cytoplasm of mammalian oocytes contains enormous amounts of mitochondria/mitochondrial DNA (mtDNA), which is important for mammalian fertilization and subsequent early embryonic development. MtDNA inheritance is exclusively maternal and only passes from mother to child through eggs. Owing to this unique feature of mitochondrial inheritance, it is feasible to replace mitochondria/mtDNA via innovate technology, which is called mitochondrial replacement therapy1). We developed the maternal spindle transfer (MST) using primate mature MII oocytes and demonstrated efficient replacement of mitochondria/mtDNA. Furthermore, we demonstrated that mtDNA can also be efficiently replaced in humans. With the advent of reliable and safer technologies, several MRT techniques, including MST, are now considered for germline gene therapy for inherited mitochondrial diseases. Recently, several clinical trials are underway. In this review, the utilization of MRT for germline gene therapy of inherited mitochondrial diseases, as well as its potential applications in standard ART practice, are described.

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Objective: It has been reported that repetitive transcranial magnetic stimulation (rTMS) over the motor cortex is useful for the recovery of motor function in poststroke patients. We recorded motor evoked potentials (MEP) evoked by TMS and compared the results of motor recovery obtained by rTMS with those of rehabilitation between patients with MEP and patients lacking MEP. Methods: The subjects were 40 poststroke patients with motor weakness at the upper extremity with Brunnstrome Recovery Stage (BRS) of II to V. We started rTMS at least 1 month after the onset of stroke. The rTMS was applied via the MagPro R30 and a figure-8 coil. One thousand pulses per day were delivered to the hand area of the motor cortex in the affected hemisphere (10 trains of 10 Hz for 10 seconds with a 15-second intertrain interval), and this treatment continued for 4 weeks with rehabilitation. Results: Not only in patients with MEP but also in patients lacking MEP, the FMA score increased significantly after rTMS and rehabilitation, and the recovery amount of FMA was significantly greater in patients with MEP than in patients lacking MEP. Conclusions: rTMS with rehabilitation is useful for the recovery of FMA in poststroke patients with motor weakness, and MEP recording is useful for predicting the recovery amount of FMA obtained by rTMS with rehabilitation.

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A 75-year-old woman was admitted to our hospital with a diagnosis of congestive heart failure, and in the course of a close examination of the cause, pseudoaneurysm of the mitral-aortic intervalvular fibrosa (P-MAIVF) was revealed. She had a history of aortic valve replacement for infective endocarditis at age 40. P-MAIVF is a rare disease that is often associated with aortic valve surgery or infective endocarditis. In this case, transthoracic echocardiography revealed a pulsatile mass-like structure with systolic expansion from the posterior aortic sinus to the annulus of the aortic valve, and a pseudoaneurysm of the annulus was initially suspected. Additional transesophageal echocardiography revealed the diagnosis of P-MAIVF. When structural abnormalities are noted via transthoracic echocardiography, it is important to add detailed observation with transesophageal echocardiography, and transesophageal echocardiography is very useful in the diagnosis of P-MAIVF.

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(Case) A 57-year-old female. (present history) A few days prior, she noticed an enlargement of the left nipple area and a difference between the right and left sides. Breast ultrasonography revealed a hypoechoic area with a point-like hyperechoic area of approximately 31 × 7 mm in the left BD region and a hypoechoic area of approximately 10 mm in the AC region. The patient underwent surgery with a diagnosis of cTisN0M0 stage 0 disease. She had a pacemaker implanted in the left anterior chest for complete atrioventricular block due to cardiac sarcoidosis. pT1mi N0 M0 Stage I ER+, PgR+̇ , HER2: 3+, Ki67: 40%. (Discussion) Problems with the treatment strategy for breast cancer arising on the side of pacemaker implantation include damage to the device by electrocautery, lead amputation, and electromagnetic induction failure. In this case, the resection was limited to the suprapectoral region without any desire for radiation therapy or reconstructive surgery in the postoperative period, so the operation could be performed safely with subpectoral replacement.

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A 71-year-old male presented at our hospital with progressive dyspnea (mMRC Grade 2), cough, and sputum persisting for six months. Examination revealed fine crackles in both lungs but no hypoxemia (PaO2 81 torr). A chest CT scan displayed a non-segmental reticular shadow predominantly in the bilateral lower lungs. Based on these findings, we diagnosed unclassifiable interstitial pneumonia, even though his KL-6 level was 490 U/ml. All autoantibodies, including MPO-ANCA, were negative, leading us to decide on a therapeutic strategy without medications. Two years later, there was a worsening of radiological findings and the MPO-ANCA turned positive. We then diagnosed the patient with interstitial pneumonia associated with lung lesion-preceding ANCA-associated vasculitis (AAV). Bronchoalveolar lavage fluid analysis revealed an increase in inflammatory cells. We considered steroid treatment, but the patient did not consent, so we continued follow-up without medication. Over four years, his radiological findings gradually worsened. Six years after the initial presentation, his interstitial pneumonia began to improve spontaneously, although he became PR3-ANCA positive. After seven years, there was further improvement in his radiological findings. This case exemplifies interstitial pneumonia associated with lung lesion-preceding AAV, which progressed gradually and involved renal dysfunction. Remarkably, the patient improved over a sevenyear period without treatment.

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