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Cell replacement therapy is expected as a new and more radical treatment against brain damage. We previously reported that transplanted human cerebral organoids extend their axons along the corticospinal tract in rodent brains. The axons reached the spinal cord but were still sparse. Therefore, this study optimized the host brain environment by the adeno-associated virus (AAV)-mediated expression of axon guidance proteins in mouse brain. Among netrin-1, SEMA3, and L1CAM, only L1CAM significantly promoted the axonal extension of mouse embryonic brain tissue-derived grafts. L1CAM was also expressed by donor neurons, and this promotion was exerted in a haptotactic manner by their homophilic binding. Primary cortical neurons cocultured on L1CAM-expressing HEK-293 cells supported this mechanism. These results suggest that optimizing the host environment by the AAV-mediated expression of axon guidance molecules enhances the effect of cell replacement therapy., 遺伝子治療によるホスト脳の環境最適化が細胞移植効果を高める --ホスト脳へのL1CAMの強制発現によるマウス胎仔脳移植片の軸索伸長促進効果--. 京都大学プレスリリース. 2023-03-24., Combining cell transplantation and gene therapy to enhance axonal outgrowth in the central nervous system. 京都大学プレスリリース. 2023-04-06.

Cavernous internal carotid artery (ICA) aneurysm complicated by simultaneous and spontaneous formation of thromboses in the aneurysm and the parent artery is a rare clinical condition. Although the majority of patients have good outcomes, some patients experience severe ischemic stroke. Here, we report a case of symptomatic large cavernous ICA aneurysm complicated by rapid growth of an intra-aneurysmal thrombosis with simultaneous parent artery thrombosis. A 68-year-old female presented with sudden-onset diplopia, right ptosis, right conjunctival hyperemia, and paresthesia of the right face. Magnetic resonance imaging (MRI) and digital subtract angiography (DSA) revealed the presence of a large partially thrombosed aneurysm in the cavernous portion of the right ICA. We planned endovascular embolization using a flow-diverting (FD) stent. Dual-antiplatelet therapy (DAPT) with aspirin and clopidogrel was started 2 weeks prior to treatment. Although the neurological state was stable, DSA conducted on the day of the endovascular treatment showed rapid growth of an intra-aneurysmal thrombosis and de novo thrombosis in the parent artery. Direct aspiration was performed via a distal support catheter with proximal blood flow arrest using a balloon-guide catheter, and the FD stent was successfully deployed. The patient’s symptoms improved postoperatively and DSA obtained 12 months after the procedure confirmed complete occlusion of the aneurysm. Although the exact mechanism of simultaneous thrombosis formation of the aneurysm and its parent artery remains unclear, it is important to recognize that rapid growth of the thrombosis increases the risk of ischemic stroke.

Endovascular treatment of unruptured intracranial aneurysms may increase cerebral microbleeds (CMBs) in postprocedural T2*-weighted MRIs, which may be a risk for future intracerebral hemorrhage. This study examined the characteristics of postprocedural CMBs and the factors that cause their increase. The patients who underwent endovascular treatment for unruptured intracranial aneurysms from April 2016 to February 2018 were retrospectively analyzed. Treatment techniques for endovascular treatment included simple coiling, balloon-assisted coiling, stent-assisted coiling, or flow diverter placement. To evaluate the increase in CMBs, a head MRI including diffusion-weighted imaging and T2*-weighted MRIs was performed on the preprocedural day; the first postprocedural day; and at 1, 3, and 6 months after the procedure. Among the 101 aneurysms that were analyzed, 38 (37.6%) showed the appearance of new CMBs. In the multivariate analysis examining the causes of the CMB increases, chronic kidney disease, a higher number of preprocedural CMBs, and a higher number of diffusion-weighted imaging–positive lesions on the first postprocedural day were independent risk factors. Furthermore, a greater portion of the increased CMBs was found in cortical and subcortical lesions of the treated vascular perfusion area within 1 month after the procedure. In endovascular treatment for unruptured intracranial aneurysms, CMBs tended to increase in patients with small vessel disease before the procedure, and it was also implicated in hemorrhagic changes after periprocedural microinfarction.

The long-term outcomes of patients with intraprocedural aneurysm rupture (IPR) during endovascular coiling of unruptured intracranial aneurysms (UIAs) remain unclear. We investigated the long-term outcomes and predictors of neurological outcomes in patients who sustained IPR during coil embolization of UIAs.We retrospectively analyzed the medical record of 312 untreated UIAs in 284 patients who underwent endovascular coiling between April 2013 and July 2018.The mean follow-up period for the entire cohort was 25.6 months. Twelve patients (3.8%) experienced IPR. The mean aneurysm size in the IPR cohort was significantly smaller than that in the no-IPR cohort (P = 0.045). The IPR cohort had a higher percentage of earlier subarachnoid hemorrhage from another aneurysm (P = 0.019), anterior communicating artery (AComA) aneurysm (P0.001), and basilar artery (BA) aneurysm (P = 0.022) than the no-IPR cohort. Neurologic deterioration was observed in 3 patients. The morbidity and mortality rates of the IPR cohort were 25% and 8.3%, respectively. Patients with IPR during coil embolization for AComA aneurysm did not develop neurological deterioration. Two of the 3 patients (66.7%) with a BA aneurysm had neurological deterioration. The proportion of patients with an mRS score of 0-2 at the last follow-up did not differ between the 2 cohorts (P = 0.608).The proportion of functionally independent patients did not differ between patients with and without IPR. Patients with BA aneurysms who developed an IPR tended to exhibit more unfavorable clinical courses than patients with AcomA aneurysms.

The origin and pathogenesis of perineurial cysts remain unclear. Here, we report a rare case of multiple sacral perineurial cysts presented symptoms triggered by nonaneurysmal perimesencephalic subarachnoid hemorrhage (SAH). A 48-year-old male presented with a severe headache of sudden onset. Brain computed tomography revealed a SAH in the basal cistern; however, no abnormal vascular lesion was detected. Four days after the onset of the SAH, he suffered from left buttock pain, followed by urinary dysfunction and paresthesia in the left S2 and S3 dermatomes. Magnetic resonance (MR) imaging demonstrated multiple cystic lesions at the left S1 and bilateral S2 sacral roots. The two cysts at the S2 level exhibited high signal intensity on both T1- and T2-weighted images, suggesting the content of the cysts included a hematoma. He was treated with intravenous injections of steroids, and the symptoms recovered completely within 2 months. Follow-up MR imaging revealed remarkable shrinkage of the cysts. Sacral perineurial cysts should be listed in the differential diagnosis if the patient suffers from low back pain or sacral radiculopathy after the onset of SAH.

Background Various radiologic patterns of posterior reversible encephalopathy syndrome (PRES) have been reported. Among them, PRES involving brainstem, thalamus, or deep white matter and lacking parieto-occipital edema is rare. Although PRES in general has a benign course, PRES-related intracranial hemorrhage has been associated with a poor prognosis. We report a case of variant type of PRES associated with deep brain hemorrhage and discuss the characteristics of PRES-related intracranial hemorrhage via a literature review. Case Description A woman aged 41 years with a history of untreated hypertension presented to our hospital complaining of severe headache and with an elevated blood pressure of 237/142 mmHg. Computed tomography revealed a hemorrhage in the left thalamus and basal ganglia. Magnetic resonance imaging revealed remarkable hyperintensity in the left cerebellum, pons, bilateral temporal lobes, bilateral basal ganglia, and bilateral cerebral white matter on fluid-attenuated inversion recovery imaging, which represented vasogenic edema. The parieto-occipital regions were unremarkable. Given this clinical presentation, PRES associated with deep brain hemorrhage was suspected. The patient received strict blood pressure control treatment, which resulted in gradual symptom improvement. Magnetic resonance images obtained 1 month after admission demonstrated an almost complete resolution of the edema. Conclusions Although hemorrhage in the thalamus, basal ganglia, or brainstem is uncommon in patients with PRES, it may occur in patients with variant type of PRES involving these lesions. It is important to recognize the presence of variant patterns of clinical features and radiologic findings of PRES to allow for early identification and appropriate treatment.

Background Antiplatelet agents are typically administered before and after treatment using flow-diverter stents (FDS) to prevent thrombotic complications, but the effects of anticoagulants are unclear. We present a patient with a giant aneurysm treated with an FDS. The thrombus within the aneurysm was dissolved when a direct factor Xa inhibitor was administered to treat lower limb venous thrombosis that occurred secondary to steroid use. Case Description A 60-year-old woman with a 30-mm giant thrombosed aneurysm in the cavernous segment of the right internal carotid artery presenting with headache and right abducens nerve palsy was treated by placing an FDS. Diplopia and increased pain in her right eye appeared on postoperative day 7, and both were alleviated by continuous oral administration of prednisolone. Angiography 3 months postoperatively revealed that the aneurysm thrombosis had progressed, and there were signs of healing. However, at the same time, lower limb venous thrombosis occurred, which was treated by continuous edoxaban. Six months after surgery, her headaches worsened and angiography showed that the aneurysm was again contrast enhanced and that the thrombus within the aneurysm had dissolved. After discontinuing edoxaban 9 months after surgery, the aneurysmal thrombosis had again rapidly progressed. Conclusions Administration of a direct factor Xa inhibitor during healing after placing an FDS may cause dissolution of an existing thrombus; therefore factor Xa inhibitors must be used with caution.

The epidemiology of patients with traumatic brain injury (TBI) has changed dramatically over recent decades as a result of rapid advances in aging societies. We assessed the influence of age on outcomes of patients with TBI and sought to identify prognostic factors for in-hospital mortality of TBI among elderly patients.Using a nationwide database, we analyzed data from 5651 patients with TBI. Univariate analysis was conducted to compare patient demographics, neurologic status on admission, radiologic findings, systemic complication rates, length of hospital stay, in-hospital mortality, and home discharge rates between elderly and nonelderly groups. Multivariable analysis was conducted to determine prognostic factors for in-hospital mortality among elderly patients.Overall in-hospital mortality was significantly higher in elderly patients (12.8% vs. 19.3%; P0.001). In-hospital mortality of elderly patients with mild TBI increased significantly at7 days after admission, whereas that of elderly patients with moderate or severe TBI was significantly higher immediately after admission. Age (odds ratio [OR], 1.62; P = 0.024), male sex (OR, 1.30; P = 0.004), Japan Coma Scale score on admission (OR, 5.95, P0.001), and incidence of acute subdural hematoma (OR, 1.89; P0.001) were associated with in-hospital mortality in elderly patients with TBI.Elderly patients with TBI showed significantly higher in-hospital mortality. Delayed increases in in-hospital mortality were observed among elderly patients with mild TBI. Level of consciousness on admission was the strongest predictor of in-hospital mortality among elderly patients.

Introduction: Intraprocedural rupture(IPR) is one of the most severe complications during coil embolization of intracranial aneurysms. The incidence of IPR during endovascular coiling has been estimated to be 1-8.7%; however, few studies have focused exclusively on unruptured aneurysms. The aim of the present study is to evaluate the predisposing factors for IPR during coil embolization of unruptured intracranial aneurysms. Methods: This study included 254 consecutive patients with 281 unruptured intracranial aneurysms treated with endovascular coiling between April 2013 to March 2018 at our institution (mean age 61.7, range 26-88). Dissecting aneurysms and repeated endovascular procedures in recurrent aneurysms were excluded. The medical records were reviewed retrospectively and the following data were collected: age; gender; medical history; smoking habit; family history of intracranial aneurysm; presence or absence of multiple aneurysms; history of earlier subarachnoid hemorrhage from another aneurysm; aneurysm location, size and morphology; and procedural details. The mechanisms of IPR were also investigated. Univariate and multivariate analyses were conducted to determine independent predictors of IPR. Results: The incidence of IPR was 4.2%(12 of 281 endovascular procedures). The most common mechanism of IPR was perforation by coils. In the univariate analysis, IPR was associated with aneurysm size(less than 5mm)[odds ratio(OR) 4.8, 95% confidence interval(CI) 1.44-15.88, p=0.005], aneurysms of the anterior communicating artery(OR 4.6, CI 1.39-15.35, p=0.007), aneurysms of the basilar artery(OR 4.4, CI 1.10-17.56, p=0.024) and history of earlier subarachnoid hemorrhage from another aneurysm(OR 5.8, CI 1.10-30.30, p=0.020). There was no significant association between IPR and treatment modality. Multivariate logistic regression analysis proved that the size of aneurysm(less than 5mm) was an independent factor associated with IPR(OR 6.9, CI 1.24-38.52, p=0.027). Conclusion: This study suggests the association of the size of aneurysm with incidence of IPR during coil embolization for unruptured intracranial aneurysms. Small aneurysms less than 5mm are associated with increased risk of IPR during coil embolization.

Objectives: Brain infarction is a critical complication after lung resection using video-assisted thoracoscopic surgery. Recent reports have described its association with thrombosis in the pulmonary vein (PV) stump. However, the optimal management of this complication remains controversial. We describe serial 3 cases of brain infarctions associated with thrombosis in the PV stumps, which were successfully treated with the oral Xa inhibitor rivaroxaban. Methods and Results: We retrospectively reviewed medical records of 3 patients. The first case was a 72-year-old man who underwent left upper lobectomy for treatment of lung adenocarcinoma. The second case was a 55-year-old man who underwent right lower segmentectomy for treatment of metastatic tumor from Barrett's esophageal carcinoma. The third case was a 73-year-old man who underwent left upper lobectomy for treatment of metastatic tumor from colon adenocarcinoma. In the first case, a large cerebellar infarction was developed and a decompressive craniotomy was performed on postoperative day 4. In the second and the third case, cerebral infarctions in the territories of right middle cerebral arteries occurred on postoperative day 2. In all cases, contrast-enhanced computed tomography demonstrated the thrombi in the stumps of the PVs. They were treated with oral administration of rivaroxaban without adverse effect, and the thrombi in the PVs disappeared within 1 month. Discussion: Blood flow stasis in the long PV stump after lung resection might contribute to thrombosis development. Oral Xa inhibitor rivaroxaban appeared to be safe and useful for the management of ischemic stroke associated with PV thrombosis after lung resection.

Introduction: Type 2 diabetes mellitus (T2DM) is a well-known risk factor for atherosclerosis. A previous carotid ultrasound study found diabetic patients had more echolucent plaques compared with nondiabetic patients. Another MRI-based carotid plaque imaging study revealed diabetes was associated with development of vulnerable plaques. Therefore diabetes is considered as a predictor for the presence of unstable plaques. The aim of this study is to investigate the association between vulnerability of carotid plaques and clinical characteristics in patients with T2DM. Methods: This study included type 2 diabetic patients with moderate to severe carotid artery stenosis (n=38, mean age 67.8, range 40-83). Using black-blood MRI of carotid arteries, the signal intensity of carotid plaques were measured in all patients. Univariable and multivariable analysis was conducted to examine the association between signal intensity of carotid plaques and clinical characteristics. Results: Vulnerable plaques (VP) , defined as plaques presenting more than one and a half times higher signal intensity than that of ipsilateral sternocleidomastoid muscle, were found in 8 patients. The rates of symptomatic lesions were significantly higher in patients with VP compared to patients without VP [odds ratio (OR) 17.4, 95% confidence interval (CI) 1.495-202.470, p=0.024]. In univariable analysis, VP was associated with age (p=0.0016) and ischemic heart disease (OD 10.5, 95% CI 1.142-96.576, p=0.0422). The association between other factors (sex, hypertension, hyperlipidemia, smoking habit, HbA1c, diabetic retinopathy, diabetic nephropathy) and VP was not significant. Multivariate logistic regression analysis proved that age was an independent factor associated with VP (OD 1.319, 95% CI 1.072-1.939, p=0.0455). Conclusion: This study suggests that there is a significant correlation between presence of VP detected by carotid MRI and ischemic symptoms, and that aging contributes to vulnerability of carotid plaques in patients with T2DM.

Recent reports on superconductivity in parent compounds T ′ - RE 2 CuO 4 [RE = Pr, Nd, Sm, Eu, Gd] prepared by metal-organic decomposition (MOD) shed new light on the electronic and magnetic phase diagram of electron-doped cuprates. A thorough reduction process is the key to inducing superconductivity in square-planar coordinated cuprates. In this work, Pr2CuO4 films were grown epitaxially by molecular beam epitaxy (MBE) on (001)SrTiO3, (110)GdScO3 and (110)DyScO3 substrates. A modified two-step reduction process is required in order to obtain single-phase superconducting samples. The optimized superconducting properties are T c zero = 26 K , while the room-temperature resistivity is about 400 μ Ω cm . Hence, we show that even amorphous Pr2CuOy films deposited on (110)DyScO3 become superconducting after the application of the two-step annealing process. These results indicate that superconductivity is induced to Pr2CuO4 by systematic optimization of the reduction conditions, irrespective of the synthesis route.

In many of today's most interesting materials, strong interactions prevail upon the magnetic moments, the electrons and the crystal lattice, forming strong links between these different aspects of the system. Particularly, in two-dimensional cuprates, where copper is either five- or six-fold coordinated, superconductivity is commonly induced by chemical doping which is deemed to be mandatory by destruction of long-range antiferromagnetic order of 3d9 Cu2+ moments. Here we show that superconductivity can be induced in Pr2CuO4, where copper is four-fold coordinated. We induced this novel quantum state of Pr2CuO4 by realizing pristine square-planar coordinated copper in the copper-oxygen planes, thus, resulting in critical superconducting temperatures even higher than by chemical doping. Our results demonstrate new degrees of freedom, i.e., coordination of copper, for the manipulation of magnetic and superconducting order parameters in quantum materials.

A 70-year-old man who had undergone esophagectomy with reconstructive surgery using a portion of the stomach 5 years earlier for esophageal cancer was admitted to our hospital after a routine endoscopy and histological examination of a biopsy specimen revealed poorly differentiated adenocarcinoma in the stomach. A gastrectomy and intrathoracic esophagojejunostomy was performed on January 20, 1993; however, the patient suffered a cerebral infarction and died of septic shock on April 9, 1993. At autopsy, metastatic tumors were macroscopically observed in various organs, including a bone tumor measuring 1.0 cm in diameter in the L4 vertebra. To clarify the origin of the bone tumor, we conducted histological and immunohistochemical examinations. Histological examination revealed a mixture of osteoclast-like giant cells (OGCs) and poorly differentiated adenocarcinoma cells, although no histologic features of OGCs were observed either in a primary site or in any of the multiple metastatic lesions. On immunohistochemistry, adenocarcinoma cells in the bone stained positively for the carcinoembryonic antigen (CEA), whereas no staining for CEA was observed in the OGCs which demonstrated negative staining for all the antigens of epithelial markers. These findings led us to conclude that this bone tumor had metastasized from the stomach cancer and that the OGCs may have originated from mesenchymal cells reacting to the adenocarcinoma cells.

The structure of a ZnSnAs2 thin film epitaxially grown on an InP substrate was evaluated using x-ray fluorescence holography. The reconstructed three-dimensional atomic images clearly show that the crystal structure of the ZnSnAs2 thin film is mainly of the sphalerite type, in contrast to the bulk form. A large disordering of the As layers is observed, whereas the positions of the Zn/Sn atoms are relatively stable. The analysis of the data indicates that the As layers serve as a buffer and relax the strain caused by the random occupation of Zn and Sn atoms. These results provide further understanding and a means of controlling the growth of Mn-doped ZnSnAs2, a high- Tc diluted magnetic semiconductor.

It is commonly believed that the parent compounds of high-Tc cupratres are, universally, charge transfer insulators and triggered by Mott physics. In our experiments using metal-organic decomposition (MOD), however, accumulating evidences show that the parent compounds of “electron-doped” superconductors, RE2-xCexCuO4 [RE = rare earth ion] with x = 0, are not Mott insulators but superconductors [1-5]. They have a Tc of 30 K and crystallize in the Nd2CuO4 (T’) structure. Most likely, the sharp contradiction between our results and commonly achieved data originates from the complicated oxygen chemistry in these materials. The as-synthesized specimens contain a fair amount of impurity interstitial oxygen. Throughout the reduction process it is required to remove exclusively impurity oxygen while preserving regular oxygen site occupied in order to obtain superconductivity. With decreasing x the constraints of the reduction process are getting more tight. In this study, we systematically investigated the post-annealing process using MBE-grown T’-Pr2CuO4 films. The MBE films were reduced ex-situ in a tubular furnace following a specially designed 2-step process, as in the case of MOD films. The films were annealed at Ta = 700 - 850°C in a reducing atmosphere (PO2 = 2 x 10−5 − 2 x 10−3 atm) and finally reduced at a lower temperature Tred = 450 – 700°C under vacuum (< 10−4 Torr). The film properties systematically changed with Ta, PO2, and Tred. The optimized Tred varies from 475°C to 650°C mainly depending on Ta, since the microstructure and grain size of the films are determined by Ta. Optimal superconducting properties are Tc of 26 K, while ρ(300 K) = 250 μΩcm, and RRR ~ 10. We believe the combination of thin-film synthesis and specially designed post-reduction process enabled us to obtain nearly intact CuO2 planes. Samples prepared by above-mentioned method unveiled the intrinsic properties of the parent compounds, which are not triggered by Mott physics. This result also agrees with the recent calculation result indicating the parent compounds with T’ structure are not charge transfer insulators [6-8].

穿刺細胞診・組織診で確診できた肺クリプトコッカス症の2例を報告した. 症例1は75歳の女性. 特発性浮腫の加療中に偶然胸部結節状陰影を指摘された. 気管支内視鏡下肺穿刺細胞診および組織診で黄膜を有する酵母型真菌を貧食した組織球を認め, 肺クリプトコッカス症と診断できた. 内科的治療で結節状陰影は消失した. 症例2は46歳女性. 職場検診で肺の空洞性陰影を指摘された. 透視下経皮的肺穿刺細胞診・組織診でPAS反応陽性の萸膜を有する酵母型真菌を証明し, 肺クリプトコッカス症と診断した. その後, 肺の外科的切除が行われ, 線維乾酪性肉芽腫性病変内にクリプトコッカスの存在を確認した. 自験2例ともに臨床的に肺癌との鑑別が問題となったが, 穿刺細胞診および組織診が確定診断に有効であった.