The application of tetanic stimulation of the unilateral tibial nerve before transcranial stimulation can augment the amplitudes of myogenic motor-evoked potentials from the muscles in the bilateral upper and lower limbs.

BACKGROUND: Recently, we reported a new technique to augment motor-evoked potentials (MEPs) under general anesthesia, posttetanic MEP (p-MEP), in which tetanic stimulation of the peripheral nerve before transcranial stimulation enlarged amplitudes of MEPs from the muscle innervated by the nerve subjected to tetanic stimulation. In the present study, we tested whether tetanic stimulation of the left tibial nerve can also augment amplitudes of MEPs from the muscles which are not innervated by the nerve subjected to tetanic stimulation. METHODS: Thirty patients undergoing spinal surgery under propofol-fentanyl anesthesia with partial neuromuscular blockade were examined. For conventional MEP (c-MEP) recording, transcranial stimulation with train-of-five pulses was delivered to C3-4, and the compound muscle action potentials were bilaterally recorded from the abductor pollicis brevis, abductor hallucis (AH), tibialis anterior, and soleus muscles. For p-MEP recording, tetanic stimulation (50 Hz, 50 mA of stimulus intensity) with a duration of 5 s was applied to the left tibial nerve at the ankle 1 s before transcranial stimulation. Transcranial stimulation and recording of compound muscle action potentials were performed in the same manner as c-MEP recording. Amplitudes of c-MEP and p-MEP were compared using Wilcoxon's signed rank test. RESULTS: Amplitudes of p-MEPs from the left AH muscle innervated by the left tibial nerve with tetanic stimulation were significantly larger compared with those of c-MEPs. Amplitudes of p-MEPs from the bilateral abductor pollicis brevis and soleus muscles and right AH and tibialis anterior muscles, which were not innervated by the left tibial nerve with tetanic stimulation, were also significantly larger compared with those of c-MEPs. CONCLUSION: In patients under propofol and fentanyl anesthesia with partial neuromuscular blockade, the application of tetanic stimulation to the left tibial nerve augmented the amplitudes of MEPs from the muscles without tetanic nerve stimulation and those with stimulation.博士（医学）・乙第1317号・平成25年7月22

Bilateral coronary ostial stenosis and aortic regurgitation in a patient with cardiovascular syphilis

AbstractCardiovascular syphilis is associated with the tertiary stage of syphilis infection; it involves the ascending aorta and can cause aortic aneurysm, aortic regurgitation, and coronary ostial stenosis. We report a surgical case of bilateral coronary ostial lesion and aortic regurgitation due to syphilitic aortitis.<Learning objective: Syphilitic aortitis involves the ascending aorta, resulting in aortic aneurysm, aortic regurgitation, and coronary ostial stenosis. Unlike atherosclerosis, coronary ostial stenosis is caused by aortic wall thickening, and coronary lesions distal to the ostia occur only rarely. After surgery, long-term follow up is mandatory as a result of aortic dilatation involving the sinuses of Valsalva, occurrence of prosthetic valve dehiscence, or graft failure caused by continuous infection of the aortic wall.

Autonomic function measurements for evaluating fatigue and quality of life in patients with breast cancer undergoing radiation therapy: a prospective longitudinal study

Background: Fatigue during radiation therapy in women with breast cancer can decrease quality of life (QOL), yet it is often underestimated and needs to be evaluated objectively. This longitudinal study aimed to evaluate fatigue and QOL of women with breast cancer undergoing radiotherapy with a simple autonomic function measurement. Methods: Women with breast cancer who underwent postoperative radiotherapy in eight cancer care hospitals in Chubu and Kinki regions in Japan were recruited between October 2021 and June 2022. The women underwent a self-administered questionnaire that included the Cancer Fatigue Scale (CFS) and the Short Form-8 Health Survey (SF-8) and an autonomic nervous function measurement using a simple, non-invasive device before (T0, baseline), mid (T1), and at the end (T2) of treatment. Results: The 57 women showed similar trends, with CFS scores and log LF/HF ratio being the highest at T0 and significantly decreasing at T1 (both p < 0.05). The log LF/HF trends differed between those with high and low baseline log LF/HF values. Women with mental component summary (MCS) score improvement (T0 to T2) had the highest log LF/HF ratio at T0 and had significantly lower log LF/HF values at T1 and T2 than at T0 (p < 0.01 and p < 0.05, respectively). The change of (⊿) MCS from T0 to T1 was negatively correlated with ⊿log LF/HF from T0 to T1 (r = − 0.36, p < 0.01). Conclusions: Measurement of autonomic nerve function with a simple device is useful for objective fatigue assessment during radiotherapy. Psychological support is important as improvement in mental health helps improve autonomic nerve function and, in turn, fatigue.Aoki M., Kuratsune H., Yamamoto S., et al. Autonomic function measurements for evaluating fatigue and quality of life in patients with breast cancer undergoing radiation therapy: a prospective longitudinal study. Radiation Oncology 18, 171 (2023); https://doi.org/10.1186/S13014-023-02362-W

A selective PIKfyve inhibitor blocks PtdIns(3,5)P2 production and disrupts endomembrane transport and retroviral budding

Phosphoinositides have crucial roles in cellular controls, many of which have been established through the use of small-molecule inhibitors. Here, we describe YM201636, a potent inhibitor of the mammalian class III phosphatidylinositol phosphate kinase PIKfyve, which synthesizes phosphatidylinositol 3,5-bisphosphate. Acute treatment of cells with YM201636 shows that the PIKfyve pathway is involved in the sorting of endosomal transport, with inhibition leading to the accumulation of a late endosomal compartment and blockade of retroviral exit. Inhibitor specificity is shown by the use of short interfering RNA against the target, as well as by rescue with the drug-resistant yeast orthologue Fab1. We concluded that the phosphatidylinositol 3,5-bisphosphate pathway is integral to endosome formation, determining morphology and cargo flux

Inhibitory Effects of Dopamine Receptor D1 Agonist on Mammary Tumor and Bone Metastasis

Dopaminergic signaling plays a critical role in the nervous system, but little is known about its potential role in breast cancer and bone metabolism. A screening of ~1,000 biologically active compounds revealed that a selective agonist of dopamine receptor D1 (DRD1), A77636, inhibited proliferation of 4T1.2 mammary tumor cells as well as MDA-MB-231 breast cancer cells. Herein, we examined the effect of A77636 on bone quality using a mouse model of bone metastasis from mammary tumor. A77636 inhibited migration of cancer cells in a DRD1-dependent fashion and suppressed development of bone-resorbing osteoclasts by downregulating NFATc1 through the elevation of phosphorylation of eIF2α. In the mouse model of bone metastasis, A77636 reduced osteolytic lesions and prevented mechanical weakening of the femur and tibia. Collectively, we expect that dopaminergic signaling might provide a novel therapeutic target for breast cancer and bone metastasis

Management strategy for acute pancreatitis in the JPN Guidelines

The diagnosis of acute pancreatitis is based on the following findings: (1) acute attacks of abdominal pain and tenderness in the epigastric region, (2) elevated blood levels of pancreatic enzymes, and (3) abnormal diagnostic imaging findings in the pancreas associated with acute pancreatitis. In Japan, in accordance with criteria established by the Japanese Ministry of Health, Labour, and Welfare, the severity of acute pancreatitis is assessed based on the clinical signs, hematological findings, and imaging findings, including abdominal contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI). Severity must be re-evaluated, especially in the period 24 to 48 h after the onset of acute pancreatitis, because even cases diagnosed as mild or moderate in the early stage may rapidly progress to severe. Management is selected according to the severity of acute pancreatitis, but it is imperative that an adequate infusion volume, vital-sign monitoring, and pain relief be instituted immediately after diagnosis in every patient. Patients with severe cases are treated with broad-spectrum antimicrobial agents, a continuous high-dose protease inhibitor, and continuous intraarterial infusion of protease inhibitors and antimicrobial agents; continuous hemodiafiltration may also be used to manage patients with severe cases. Whenever possible, transjejunal enteral nutrition should be administered, even in patients with severe cases, because it seems to decrease morbidity. Necrosectomy is performed when necrotizing pancreatitis is complicated by infection. In this case, continuous closed lavage or open drainage (planned necrosectomy) should be the selected procedure. Pancreatic abscesses are treated by surgical or percutaneous drainage. Emergency endoscopic procedures are given priority over other methods of management in patients with acute gallstone-associated pancreatitis, patients suspected of having bile duct obstruction, and patients with acute gallstone pancreatitis complicated by cholangitis. These strategies for the management of acute pancreatitis are shown in the algorithm in this article