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Studies the association between the candidate gene, DUSP6 and 12q23 gene using fluorescence resonance energy transfer-based curve analysis on the LightCycler apparatus. Emphasis on intracellular signalling pathways; Pathogenesis of affective disorders; Methods for genotyping of single nucleotide polymorphisms.

Background: Spinal cord diffuse midline glioma (DMG) is a relatively rare disease with a poor prognosis and no effective treatment., Observations: A 45-year-old man presented with rapidly progressive paraplegia in both lower extremities, along with bladder and bowel disturbance. Spinal magnetic resonance imaging (MRI) showed a heterogeneously contrast-enhanced mass at the T1-4 levels. A biopsy via T1-4 decompressive laminectomy with expansive duraplasty was performed. The histopathological diagnosis was DMG, H3K27-altered, World Health Organization grade 4. Radiation plus concomitant temozolomide was started; however, follow-up MRI showed tumor progression. Additional hypofractionated radiotherapy (HFRT; 24 Gy/5 fractions) was performed, with bevacizumab (BEV) plus low-dose ifosfamide-carboplatin-etoposide (ICE) as second-line treatment. One month later, MRI showed tumor regression with significant improvement in the peritumoral edema. The chemotherapy regimen was repeated every 4-6 weeks, and the patient remained stable. After 13 courses of chemotherapy, the size of the spinal DMG increased markedly, with dissemination to the temporal lobe. The patient died approximately 21 months after the initial diagnosis., Lessons: Spinal DMG is a malignant tumor with a poor prognosis. However, treatment with additional HFRT combined with BEV plus low-dose ICE may inhibit tumor progression to prolong the progression-free period and survival. https://thejns.org/doi/10.3171/CASE2464.

Background: The prognosis for cancer patients has been improved because of the development of molecularly targeted drugs. Treatment of intracranial tumors must be personalized while prioritizing the treatment of comorbid cancers., Observations: A 38-year-old man presented with bloody sputum, bilateral multiple nodules, and a mass in the lower lobe of his right lung. Bronchoscopy revealed stage IV lung adenocarcinoma with an epidermal growth factor receptor (EGFR) mutation. Screening head magnetic resonance imaging revealed a 38-mm-diameter mass in the left petroclival area. Because the patient was neurologically intact, the treatment of lung adenocarcinoma was prioritized, and the third-generation EGFR-tyrosine kinase inhibitor osimertinib was used. Although nodules in the lung began to shrink, the intracranial lesion expanded and caused hydrocephalus, necessitating a ventriculoperitoneal shunt. The tumor also caused diplopia, dysarthria, and gait abnormalities. A left anterior transpetrosal approach was used to remove the tumor derived from the trochlear nerve. The pathological examination revealed schwannoma. Neurological symptoms improved following surgery. Osimertinib was continued during the perioperative period., Lessons: Osimertinib was effective for lung adenocarcinoma but not for trochlear nerve schwannoma, which required surgical intervention. It is necessary to tailor the treatment of benign brain tumors in patients with concurrent malignant cancers. https://thejns.org/doi/10.3171/CASE24144.

The spread of coronavirus disease 2019(COVID-19)is a concern as it may delay the detection of malignant tumors due to delayed medical checkups. We examined changes in the treatment of metastatic brain tumors before and after COVID- 19. A retrospective review of 211 patients with metastatic brain tumors who underwent initial gamma knife radiosurgery between July 2019 and December 2021 was conducted. Data collected include patient age, gender, the Karnofsky performance status(KPS), primary tumor control, number, total volume, and outcome during the COVID-19 emergency declaration period and outside of it. The patient number was 164 outside of the emergency period and 47 during the period. Symptomatic cases(KPS<90)and poor control of the primary site increased during the COVID-19 period. The treatment number and volume of brain metastasis did not change. Metastatic control after 4 months of treatment also showed no difference. The number of symptomatic patients increased during the emergency declaration period, suggesting that COVID- 19 may have reduced the rate of asymptomatic patients being seen. However, these were not enough to affect the prognosis at 4 months. Overall, the COVID-19 pandemic had a small impact on the provision of stereotactic radiotherapy for metastatic brain tumors.

Background and Purpose: Radiation-induced changes can occur after stereotactic radiosurgery for brain AVMs, potentially causing symptomatic complications. We evaluated the incidence of such changes and the efficacy of repeat gamma knife radiosurgery for incompletely obliterated AVMs., Materials and Methods: We retrospectively evaluated 150 patients who underwent gamma knife radiosurgery for AVMs between 2002 and 2020; twenty-five underwent further radiosurgical procedures for incompletely obliterated AVMs. We recorded the median margin doses at the first (median, 20 Gy; range, 12-23 Gy; AVM volume, 0.026-31.3 mL) and subsequent procedures (median, 18 Gy; range, 12-23 Gy; AVM volume, 0.048-9.2 mL)., Results: After the first treatment, radiologic radiation-induced changes developed in 48 (32%) patients, eight of whom had symptomatic changes. After repeat gamma knife radiosurgery, 16 of 25 patients achieved complete AVM obliteration (64%). The development of radiation-induced changes after the first treatment was significantly associated with successful obliteration by subsequent radiosurgery (OR = 24.0, 95% CI 1.20-483, P  = .007). Radiation-induced changes occurred in only 5 (20%) patients who underwent a second gamma knife radiosurgery, one of whom experienced transient neurologic deficits. Between the first and repeat gamma knife radiosurgery procedures, there was no significant difference in radiologic and symptomatic radiation-induced changes ( P  = .35 and P  = 1.0, respectively)., Conclusions: Radiation-induced changes after the first gamma knife radiosurgery were associated with AVM obliteration after a repeat procedure. The risk of symptomatic radiation-induced changes did not increase with retreatment. When the first procedure fails to achieve complete AVM obliteration, a favorable outcome can be achieved by a repeat gamma knife radiosurgery, even if radiation-induced changes occur after the first treatment., (© 2023 by American Journal of Neuroradiology.)

The number of awake craniotomies is increasing because of its beneficial features. However, not enough information is available regarding the current status of awake craniotomy in Japan. To evaluate the current status of awake craniotomy in institutes, a nationwide questionnaire survey was conducted. From June to August 2019, we conducted a questionnaire survey on awake craniotomy in the neurosurgery department of 45 institutes that perform awake craniotomies in Japan. Responses were obtained from 39 institutes (response rate, 86.7%). The main methods of awake craniotomy were almost the same in all institutes. Twenty-six institutes (66.7%) had fewer than 10 awake craniotomies (low-volume institutes) per year, and 13 high-volume institutes (33.3%) performed more than 10 awake craniotomies annually. Some institutes experienced a relatively high frequency of adverse events. In 11 institutes (28.2%), the frequency of intraoperative seizures was more than 10%. An intraoperative seizure frequency of 1%-9%, 10%-29%, and over 30% was identified in 12 (92%), 0 (0%), and 1 (8%) of the high-volume institutes, which was significantly less than in 16 (62%), 10 (38%), and 0 (0%) of the low-volume institutes (p = 0.0059). The routine usage of preoperative antiepileptic drugs was not different between them, but the old type was used more often in the low-volume institutes (p = 0.0022). Taken together, the annual number of awake craniotomies was less than 10 in over two-thirds of the institutes. Fewer intraoperative seizures were reported in the high-volume institutes, which tend not to preoperatively use the old type of antiepileptic drugs.

Introduction: Brachiocephalic artery stenosis rarely causes right hemispheric infarction with associated left hemiparesis. To date, there have been no reported cases of stroke associated with brachiocephalic artery stenosis that were successfully treated with recombinant tissue-type plasminogen activator (rt-PA), alteplase. Case Report: An 80-year-old woman presented with left hemiparesis. Brain computed tomography showed no hemorrhage, and computed tomography angiography demonstrated brachiocephalic artery stenosis. Alteplase was administered based on a diagnosis of ischemic stroke. Brain magnetic resonance imaging showed multiple acute infarctions. Thereafter, the blood pressure of the right arm was found to be lower than that of the left arm. The patient's neurological deficits gradually improved; she was eventually able to walk again and was thus discharged home. Conclusion: While the combination of left hemiparesis and a decrease in blood pressure in the right arm are well known in patients with stroke associated with Stanford type A aortic dissections, it may also occur in patients with stroke due to brachiocephalic artery stenosis. Unlike stroke associated with Stanford type A aortic dissections, stroke due to brachiocephalic artery stenosis may be treated with alteplase., Competing Interests: The authors report no disclosures relevant to the manuscript., (©2021 The Japanese Association of Rural Medicine.)

Most viruses inhibit the innate immune system and/or the RNA degradation processes of host cells to construct an advantageous intracellular environment for their survival. Characteristic RNA sequences within RNA virus genomes or RNAs transcribed from DNA virus genomes contribute toward this inhibition. In this study, we developed a method called "Fate-seq" to comprehensively identify the RNA sequences derived from RNA and DNA viruses, contributing RNA stability in the cells. We examined the stabilization activity of 5,924 RNA fragments derived from 26 different viruses (16 RNA viruses and 10 DNA viruses) using next-generation sequencing of these RNAs fused 3' downstream of GFP reporter RNA. With the Fate-seq approach, we detected multiple virus-derived RNA sequences that stabilized GFP reporter RNA, including sequences derived from severe acute respiratory syndrome-related coronavirus (SARS-CoV). Comparative genomic analysis revealed that these RNA sequences and their predicted secondary structures are highly conserved between SARS-CoV and the novel coronavirus, SARS-CoV-2, which is responsible for the global outbreak of the coronavirus-associated disease that emerged in December 2019 (COVID-19). These sequences have the potential to enhance the stability of viral RNA genomes, thereby augmenting viral replication efficiency and virulence., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Pain and discomfort during the awake phase in awake craniotomy should be relieved to facilitate brain mapping. Although some anaesthesiologists use low-dose (0.01-0.05 µg/kg/min) remifentanil infusion to provide analgesia during this phase, its efficacy and side effects have never been evaluated. Therefore, this study primarily aimed to investigate the effects of low-dose remifentanil infusion on the need for antiemetic treatment during brain mapping and secondarily aimed to determine its effects on the need for additional analgesic treatment., Methods: This retrospective study included 218 patients who underwent awake craniotomy at our centre from 2008 to 2018. The relationship between low-dose remifentanil infusion during the awake phase and the requirement for analgesic or antiemetic treatment was examined. A multivariable competing risk regression analysis was performed to adjust for patient and operative variables., Results: Sixty-six patients (30.3%) received low-dose (median rate: 0.01 µg/kg/min) remifentanil infusion during the awake phase. Forty-nine patients (22.5%) received an antiemetic and 99 (45.4%) received additional analgesic treatment. The difference in additional analgesic treatment was not significant between patients who received low-dose remifentanil infusion and those who did not (adjusted hazard ratio: 1.13; 95% confidence interval: 0.75-1.70; P = .570); however, the use of antiemetics significantly increased in patients who received remifentanil (adjusted hazard ratio: 1.78; 95% confidence interval: 1.01-3.15; P = .047)., Conclusion: Low-dose remifentanil infusion during the awake phase in awake craniotomy significantly increased the need for antiemetics but did not decrease the need for additional analgesic treatment., (© 2020 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Alpha-linolenic acid (ALA), a polyunsaturated fatty acid, is involved in bioregulatory functions. In recent years, the health-promoting effects of vegetable-derived edible oils rich in ALA have attracted attention. ALA has a variety of physiological effects such as anti-arteriosclerotic and antiallergic properties, but is prone to oxidation. Therefore, safety concerns exist with regard to adverse effects on humans induced by its oxides. However, the effects on neuronal cells induced by oxidized ALA-rich oils, such as perilla and linseed oils, have not been fully investigated. This information is very important from the viewpoint of food safety. In this study, we investigated the effects of oxidized perilla and linseed oils, which are rich in ALA, on the toxicity of neuronal SH-SY5Y cells. Perilla and linseed oils were significantly oxidized compared with other edible vegetable oils. These oxidized oils induce neuronal cell death and apoptosis via caspase-dependent and -independent pathways through reactive oxygen species (ROS) generation. Furthermore, they suppressed neurite outgrowth. These results suggest that oxidized perilla and linseed oils have the potential to cause neuronal loss and ROS-mediated apoptosis, and thus may affect the onset and progression of neurodegenerative disorders and other diseases.

Objectives: The aim of this study was to investigate the impact of intensively lowered low-density lipoprotein cholesterol (LDL-C) level on the deferred lesion prognosis after revascularization deferral based on fractional flow reserve (FFR)., Background: Lowering LDL-C is associated with lower cardiovascular event rate, but its benefit on the deferred lesion prognosis has not been well evaluated., Methods: This retrospective, single-center, observational study analyzed 192 deferred lesions with FFR value >0.80 in 192 patients with stable coronary artery disease. According to the first follow-up LDL-C level, they were assigned to the LOW group (<70 mg/dL) or the HIGH group (≥70 mg/dL). Deferred lesion failure (DLF) was defined as the composite of deferred lesion revascularization and deferred vessel myocardial infarction., Results: Of all participants, 61 and 131 patients were assigned to the LOW and the HIGH group, respectively. During the median follow-up of 2.8 years, DLF occurred in 1 and 14 patients in the LOW group and the HIGH group (1.6% and 10.7%, log-rank p = .043), respectively. The incidence of any unplanned revascularization was also significantly lower in the LOW group than in the HIGH group (3.3% vs. 14.5%, log-rank p = .032)., Conclusions: The incidence of DLF was significantly lower in the patients with LDL-C < 70 mg/dL than in those with LDL-C ≥ 70 mg/dL at the first follow-up after FFR-based deferral of revascularization., (© 2019 Wiley Periodicals, Inc.)

Background: Malignant peripheral nerve sheath tumors (MPNSTs) are a rare subtype of soft-tissue sarcoma, derived from a peripheral branch or the sheath of the sciatic nerve, brachial plexus, or sacral plexus. The clinical outcomes for MPNST patients with unresectable or metastatic tumors are dismal, and novel therapeutic strategies are required. Although patient-derived cancer cell lines are vital for basic research and preclinical studies, few MPNST cell lines are available from public cell banks. Therefore, the aim of this study was to establish cancer cell lines derived from MPNST patients., Methods: We used tumor tissues from five patients with MPNSTs, including one derived from a rare bone tissue MPNST. The tumor tissues were obtained at the time of surgery and were immediately processed to establish cell lines. A patient-derived xenograft was also established when a sufficient amount of tumor tissue was available. The characterization of established cells was performed with respect to cell proliferation, spheroid formation, and invasion. The mutation status of actionable genes was monitored by NCC Oncopanel, by which the mutation of 114 genes was assessed by next-generation sequencing. The response to anti-cancer agents, including anti-cancer drugs approved for the treatment of other malignancies was investigated in the established cell lines., Results: We established five cell lines (NCC-MPNST1-C1, NCC-MPNST2-C1, NCC-MPNST3-C1, NCC-MPNST4-C1, and NCC-MPNST5-C1) from the original tumors, and also established patient-derived xenografts (PDXs) from which one cell line (NCC-MPNST3-X2-C1) was produced. The established MPNST cell lines proliferated continuously and formed spheroids while exhibiting distinct invasion abilities. The cell lines had typical mutations in the actionable genes, and the mutation profiles differed among the cell lines. The responsiveness to examined anti-cancer agents differed among cell lines; while the presence of an actionable gene mutation did not correspond with the response to the anticipated anti-cancer agents., Conclusion: The established cell lines exhibit various characteristics, including proliferation and invasion potential. In addition, they had different mutation profiles and response to the anti-cancer agents. These observations suggest that the established cell lines will be useful for future research on MPNSTs., Competing Interests: Competing interestsThe authors declare that they have no competing interests. The funders had no role in the design of the study, collection, analyses, or interpretation of data, writing of the manuscript, or in the decision to publish the results., (© The Author(s) 2020.)

Extraskeletal osteosarcoma (ESOS) is a rare mesenchymal malignancy producing osteoid and bone in soft tissue without skeletal attachment. ESOS exhibits chemoresistance and poor prognosis, and is distinct from osseous osteosarcoma. The biological characteristics of ESOS are not fully understood, and patient-derived cell lines of ESOS are not available from public cell banks. Here, we established a novel cell line of ESOS and characterized its genetic and biological characteristics as well as examined its response to anti-cancer reagents. The cell line was established using tumor tissue from a 58-year-old female patient with ESOS, and named as NCC-ESOS1-C1. Phenotypes relevant to malignancy such as proliferation and invasion were examined in vitro, and genetic features were evaluated using the NCC Oncopanel assay. The response to inhibitors was monitored by screening of an anti-cancer reagent library. The cells constantly proliferated, showing spheroid formation and invasion capabilities. The NCC Oncopanel revealed the presence of actionable mutations in PIK3CA. Library screening revealed the presence of anti-cancer reagents with significant anti-proliferative effects on NCC-ESOS1-C1 at a low concentration. In conclusion, we established and characterized a novel ESOS cell line, NCC-ESOS1-C1. This cell line will be a useful resource for basic research and preclinical studies.

Background: The recent development of wearable devices has enabled easy and continuous measurement of heart rate (HR). Exercise intensity can be calculated from HR with indices such as percent HR reserve (%HRR); however, this requires an accurate measurement of resting HR, which can be time-consuming. The use of HR during sleep may be a substitute that considers the calibration-less measurement of %HRR. This study examined the validity of %HRR on resting HR during sleep in comparison to percent oxygen consumption reserve (%VO 2 R) as a gold standard. Additionally, a 24/7%HRR measurement using this method is demonstrated., Methods: Twelve healthy adults aged 29 ± 5 years underwent treadmill testing using the Bruce protocol and a 6-min walk test (6MWT). The %VO 2 R during each test was calculated according to a standard protocol. The %HRR during each exercise test was calculated either from resting HR in a sitting position (%HRR sitting ), when lying awake (%HRR lying ), or during sleep (%HRR sleeping ). Differences between %VO 2 R and %HRR values were examined using Bland-Altman plots. A 180-day, 24/7%HRR measurement with three healthy adults was also conducted. The %HRR values during working days and holidays were compared., Results: In the treadmill testing, the mean difference between %VO 2 R and %HRR sleeping was 1.7% (95% confidence interval [CI], - 0.2 to 3.6%). The %HRR sitting and %HRR lying values were 10.8% (95% CI, 8.8 to 12.7%) and 7.7% (95% CI, 5.4 to 9.9%), respectively. In the 6MWT, mean differences between %VO 2 R and %HRR sitting , %HRR lying and %HRR sleeping were 12.7% (95% CI, 10.0 to 15.5%), 7.0% (95% CI, 4.0 to 10.0%) and - 2.9% (95% CI, - 5.0% to - 0.7%), respectively. The 180-day, 24/7%HRR measurement presented significant differences in %HRR patterns between working days and holidays in all three participants., Conclusions: The results suggest %HRR sleeping is valid in comparison to %VO 2 R. The results may encourage a calibration-less, 24/7 measurement model of exercise intensity using wearable devices., Trial Registration: UMIN000034967.Registered 21 November 2018 (retrospectively registered)., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2019.)

Purpose: The purpose is to examine whether patient-derived sarcoma models recapitulate the spectrum of sarcoma heterogeneity seen in patients., Experimental Design: To characterize patient-derived models for functional studies, proteomic comparisons with originating sarcomas representative of three intrinsic subtypes by MS are performed., Results: Human protein profiling is found to be retained with high fidelity in patient-derived models. The protein profiles of patient sarcoma tumors and mouse stroma are characterized by species-specific quantitative proteomics. Protein-expression levels in mouse stroma are affected by the primary human tumor. The levels of stromal proteins derived from tumors are lower in PDXs and cell lines, and some human stromal proteins are replaced by the corresponding mouse proteins in PDXs., Conclusions and Clinical Relevance: These findings suggest that the effects of the microenvironment on drug responses may not reflect those in the primary tumor. This cross-species proteomic analysis in PDXs can potentially improve preclinical evaluation of treatment modalities and enhance the ability to predict clinical trial responses., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Surgical intervention in a case of internal carotid artery stenosis with moyamoya vessels has not been well described. We present a case with detailed description of the surgical procedure and perioperative management., Case Description: A 58-year-old man with symptomatic internal carotid artery stenosis had concurrent moyamoya vessels intracranially. He had motor weakness and numbness in the left upper extremity. Magnetic resonance imaging showed an ischemic lesion in the right frontal lobe and right chronic subdural hematoma. On day 18 after surgery for subdural hematoma, carotid artery stenting was performed under proximal balloon protection and distal filter protection. After carotid artery stenting, systolic blood pressure was maintained at <120 mm Hg. Hyperperfusion syndrome or hemorrhagic complication did not occur. The patient was discharged without any neurologic deficits., Conclusions: In our patient with internal carotid artery stenosis with moyamoya vessels, strict control of blood pressure likely contributed to prevention of hyperperfusion syndrome or hemorrhagic complications., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Sarcomas are rare mesenchymal malignant tumors with unique biological and clinical features. Given their diversity, heterogeneity, complexity, and rarity, the clinical management of sarcomas is quite challenging. Cell lines have been used as indispensable tools for both basic research and pre-clinical studies. However, empirically, sarcoma cell lines are not readily available. To understand the present status of sarcoma cell lines and identify their current challenges, we systematically reviewed reports on sarcoma cell lines. We searched the cell line database, Cellosaurus, and categorized the sarcoma cell lines according to the WHO classification. We identified the number and availability of sarcoma cell lines with a specific histology. We found 844 sarcoma cell lines in the Cellosaurus database, and 819 of them were named according to the WHO classification. Among the 819 cell lines, 36 multiple and nine single cell lines are available for histology. No cell lines were reported for 133 of the histological subtypes. Among the 844 cell lines, 148 are currently available in public cell banks, with 692 already published. We conclude that there needs to be a larger number of cell lines, with various histological subtypes, to better benefit sarcoma research.

Objective: Molecularly targeted therapy has been adopted to treat a number of cancers. Bevacizumab, a recombinant humanized monoclonal antibody against vascular endothelial growth factor, is a representative agent used in molecularly targeted therapeutic regimens. However, the therapeutic effect of bevacizumab for the treatment of brain metastases remains unknown. We report the clinical effects of low dose bevacizumab(≤2.5mg/kg/week)to treat recurrent brain metastases., Methods: We retrospectively analyzed patients with brain metastases who had been treated with bevacizumab between 2012 and 2016 at our institution. We identified clinical characteristics, including age, gender, primary tumor site, dose of bevacizumab, therapeutic and adverse effects, and magnetic resonance imaging results. The lesions were assessed with the RECIST criteria based on gadolinium-enhanced T1-weighted, T2-weighted, and FLAIR images. Statistical analysis was performed using t-test and Fisher's exact test., Results: The cohort comprised 26 patients(8 men, 18 women)with a median age of 61 years(range 39-82 years). There were no significant clinical differences between the low dose and non-low dose groups. Patients in the low dose group did not report any adverse effects from bevacizumab. Three patients with brain metastases from colon cancer are illustrated to report the clinical course of low dose bevacizumab., Conclusion: Low dose bevacizumab may be a safe and effective therapeutic option to treat recurrent brain metastases from bevacizumab-sensitive cancers.

We report a case in which strict anticoagulant therapy management was useful for a recurrent in-stent thrombosis after carotid artery stenting (CAS). An 84-year-old man presented with cognitive decline that progressed rapidly over two months. Head magnetic resonance imaging showed an acute-stage infarct occurring frequently in the right cerebral hemisphere, and he underwent hospitalization and treatment. On neck magnetic resonance angiography (MRA), severe stenosis was found at the origin of the right internal carotid artery. Since he took aspirin, clopidogrel, and a statin after placement of an indwelling coronary stent, we treated him by adding argatroban and edaravone drip therapy to his existing medication. CAS was performed on day 15 of the hospitalization. A small in-stent thrombosis with plaque protrusion was observed on a carotid sonogram performed at the second day after CAS, and re-examination at the seventh day confirmed enlargement of the lesion and an increase in peak systolic velocity; thus, a second CAS procedure was performed on the same day. After the second CAS, oral cilostazol was added for triple antiplatelet therapy (TAPT), but as the in-stent thrombosis increased further, we started a continuous infusion of heparin with the goal of an activated partial thromboplastin time (APTT) of 50 to 65 seconds. After starting heparin, the lesion did not progress; after 14 days of continuous heparin infusion, the patient was switched to TAPT, and regression of the plaque was confirmed. This case demonstrated to us that controlled anticoagulation therapy can be an effective treatment for cases in which a thrombus recurs within a stent after CAS.

The horizontal stenting technique facilitates endovascular treatment of wide-necked bifurcation intracranial aneurysms. Previous literature shows, however, that subsequent coil embolization at initial treatment results in incomplete obliteration in many cases. The authors present two consecutive cases of wide-necked large bifurcation aneurysms to describe an additional coil embolization technique following horizontal stenting. The patients were a 53-year-old female with an unruptured internal carotid artery terminus aneurysm and a 57-year-old female with a recurrent basilar artery tip aneurysm. Both patients underwent endovascular treatment with horizontal stenting followed by coil embolization with jailed double-microcatheters. Immediate complete obliteration was achieved with no complications, and no recanalization was observed at the one-year follow-up in both cases. Coil embolization with jailed double-microcatheter technique following horizontal stenting is a safe and effective strategy for wide-necked bifurcation aneurysms.

Cerebral aneurysm rupture is a serious complication that can occur after flow diverter (FD) placement, but the underlying mechanisms remain unclear. We encountered a case in which direct stress on the aneurysm wall caused by residual blood flow at the inflow zone near the neck during the process of thrombosis after FD placement appeared associated with aneurysm rupture. The patient was a 67-year-old woman with progressive optic nerve compression symptoms caused by a large intracranial paraclinoid internal carotid aneurysm. The patient had undergone treatment with a Pipeline embolization device (PED) with satisfactory adherence between the PED and vessel wall. Surgery was completed without complications, and optic nerve compression symptoms improved immediately after treatment. Postoperative clinical course was satisfactory, but the patient suddenly died 34 days postoperatively. Autopsy confirmed the presence of subarachnoid hemorrhage caused by rupture of the internal carotid aneurysm that had been treated with PED. Although the majority of the aneurysm lumen including the outflow zone was thrombosed, a non-thrombosed area was observed at the inflow zone. Perforation was evident in the aneurysm wall at the inflow zone near the neck, and this particular area of aneurysm wall was not covered in thrombus. Macrophage infiltration was not seen on immunohistochemical studies of the aneurysm wall near the perforation. A hemodynamically unstable period during the process of complete thrombosis of the aneurysm lumen after FD placement may be suggested, and blood pressure management and appropriate management with antiplatelet therapy may be important., (© The Author(s) 2015.)

There is consistent data from European cohorts suggesting a genetic contribution from the major histocompatibility complex (MHC) to the pathogenesis of schizophrenia. However, the genomic complexity and ethnicity-specific diversity found in the MHC cause difficulties in identifying causal variants or genes, and there is a need for studies encompassing the entire MHC region in multiple ethnic populations. Here, we report on association signals in the MHC region, with schizophrenia in the Japanese population. We genotyped and imputed a total of 10,131 single nucleotide polymorphisms (SNPs), spanning the entire MHC interval. The analysis included 3302 participants (1518 schizophrenics and 1784 healthy controls) from the Japanese population. In this study, we present evidence for association at rs494620, located in the SLC44A4 gene. The association survived after correction for multiple testing (unadjusted P=7.78×10(-5), empirical P=0.0357). The imputation results detected the highest association at rs707937 in the MSH5-SAPCD1 gene (imputed P=8.40×10(-5)). In expression analysis using postmortem brains from schizophrenia and control samples, MSH5-SAPCD1 showed marginally significant expression differences in Brodmann's area 46 (P=0.044 by unpaired t test with Welch's correction, P=0.099 by Mann-Whitney U test). Our study further strengthens evidence for the involvement of the MHC in schizophrenia across populations, and provides insight into population-specific mechanisms for the MHC region in schizophrenia susceptibility., (Copyright © 2015 Elsevier B.V. All rights reserved.)

In contrast to mammals, higher plants have evolved to express diverse protein phosphatase 2Cs (PP2Cs). Of all Arabidopsis thaliana PP2Cs, members of PP2C subfamily A, including ABI1, have been shown to be key negative regulators of abscisic acid (ABA) signalling pathways, which regulate plant growth and development as well as tolerance to adverse environmental conditions. However, little is known about the enzymatic and signalling roles of other PP2C subfamilies. Here, we report a novel Arabidopsis subfamily E PP2C gene, At3g05640, designated AtPP2CF1. AtPP2CF1 was dramatically expressed in response to exogenous ABA and was expressed in vascular tissues and guard cells, similar to most subfamily A PP2C genes. In vitro enzymatic activity assays showed that AtPP2CF1 possessed functional PP2C activity. However, yeast two-hybrid analysis revealed that AtPP2CF1 did not interact with PYR/PYL/RCAR receptors or three SnRK2 kinases, which are ABI1-interacting proteins. This was supported by homology-based structural modelling demonstrating that the putative active- and substrate-binding site of AtPP2CF1 differed from that of ABI1. Furthermore, while overexpression of ABI1 in plants induced an ABA-insensitive phenotype, Arabidopsis plants overexpressing AtPP2CF1 (AtPP2CF1oe) were weakly hypersensitive to ABA during seed germination and drought stress. Unexpectedly, AtPP2CF1oe plants also exhibited increased biomass yield, mainly due to accelerated growth of inflorescence stems through the activation of cell proliferation and expansion. Our results provide new insights into the physiological significance of AtPP2CF1 as a candidate gene for plant growth production and for potential application in the sustainable supply of plant biomass., (© The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)