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We report the case of a 70-year-old woman with metastatic brain tumors who underwent surgical removal of the tumor and radiation necrosis. The patient had a history of colon cancer and had undergone surgical removal of a left occipital tumor. Histopathological evaluation revealed a metastatic brain tumor. The tumor recurred six months after surgical removal, followed by whole-brain radiotherapy, and the patient underwent stereotactic radiosurgery. Six months later, the perifocal edema had increased, and the patient became symptomatic. The diagnosis was radiation necrosis and corticosteroids were initially effective. However, radiation necrosis became uncontrollable, and the patient underwent removal of necrotic tissue two years after stereotactic radiosurgery. Pathological findings predominantly showed necrotic tissue with some tumor cells. Since the vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) were expressed around the necrotic tissue, the main cause of the edema was determined as radiation necrosis. Differences in the expression levels and distribution of HIF-1α and VEGF were observed between treatment-naïve and recurrent tumor tissue and radiation necrosis. This difference suggests the possibility of different mechanisms for edema formation due to the tumor itself and radiation necrosis. Although distinguishing radiation necrosis from recurrent tumors using MRI remains challenging, the pathophysiological mechanism of perifocal edema might be crucial for differentiating radiation necrosis from recurrent tumors.
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Two-thiouridine (s2U) at position 54 of transfer RNA (tRNA) is a posttranscriptional modification that enables thermophilic bacteria to survive in high-temperature environments. s2U is produced by the combined action of two proteins, 2-thiouridine synthetase TtuA and 2-thiouridine synthesis sulfur carrier protein TtuB, which act as a sulfur (S) transfer enzyme and a ubiquitin-like S donor, respectively. Despite the accumulation of biochemical data in vivo, the enzymatic activity by TtuA/TtuB has rarely been observed in vitro, which has hindered examination of the molecular mechanism of S transfer. Here we demonstrate by spectroscopic, biochemical, and crystal structure analyses that TtuA requires oxygen-labile [4Fe-4S]-type iron (Fe)-S clusters for its enzymatic activity, which explains the previously observed inactivation of this enzyme in vitro. The [4Fe-4S] cluster was coordinated by three highly conserved cysteine residues, and one of the Fe atoms was exposed to the active site. Furthermore, the crystal structure of the TtuA-TtuB complex was determined at a resolution of 2.5 Å, which clearly shows the S transfer of TtuB to tRNA using its C-terminal thiocarboxylate group. The active site of TtuA is connected to the outside by two channels, one occupied by TtuB and the other used for tRNA binding. Based on these observations, we propose a molecular mechanism of S transfer by TtuA using the ubiquitin-like S donor and the [4Fe-4S] cluster.
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Proteínas de Bactérias , Proteínas Ferro-Enxofre , Ligases , Thermus thermophilus , Tiouridina/análogos & derivados , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Catálise , Cristalografia por Raios X , Proteínas Ferro-Enxofre/química , Proteínas Ferro-Enxofre/metabolismo , Ligases/química , Ligases/metabolismo , RNA Bacteriano/química , RNA Bacteriano/metabolismo , RNA de Transferência/química , RNA de Transferência/metabolismo , Thermus thermophilus/química , Thermus thermophilus/metabolismo , Tiouridina/química , Tiouridina/metabolismoRESUMO
PURPOSE: In assisted reproductive technology, normal zygotes are bipronuclear (2PN) during fertilization confirmation; however, sometimes, nonpronuclear zygotes (0PN) and monopronuclear zygotes (1PN) are found during routine observations. METHODS: To elucidate the clinical usefulness of in vitro-fertilized embryos, we investigated the rates of clinical pregnancy, live birth, miscarriage, and congenital abnormality after transfer of frozen-thawed 1PN- and 0PN-derived single blastocysts at Denentoshi Ladies Clinic, Kanagawa, Japan. RESULTS: The rates of pregnancy and live birth for 1PN-derived blastocysts obtained by conventional in vitro fertilization were 37.5% and 27.1%, respectively, which was not significantly different from those for 2PN-derived blastocysts; however, the rates for 0PN-derived blastocysts were significantly lower. The pregnancy and live birth rates for 0PN-derived embryos obtained by intracytoplasmic sperm injection (ICSI) were 45.7% and 34.8%, respectively, which was not significantly different from those for 2PN-derived blastocysts; however, the rates for 1PN-derived blastocysts were significantly lower (4.0% for both) than those for 2PN- and 0PN-derived blastocysts. No congenital abnormalities were found in infants resulting from transfer of 0PN- or 1PN-derived blastocysts. CONCLUSIONS: Both 1PN- and 0PN-derived blastocysts can be used for embryo transfer; however, care should be taken in making decisions about 1PN-derived blastocysts, especially if they are obtained by ICSI.
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BACKGROUND: Preoperative embolization for meningiomas is controversial regarding its effectiveness in reducing intraoperative blood loss and operative time. In contrast, some reports have documented improved surgical outcomes in large meningiomas. In this study, we retrospectively compared the outcomes of craniotomy for meningiomas with/without preoperative embolization with diluted N-butyl-2-cyanoacrylate (NBCA) primarily in a single institution. METHODS: Data (World Health Organization grade, Simpson grade, maximum tumor diameter, intraoperative bleeding, operative time, history of hypertension, and time from embolization to craniotomy) of patients with initial intracranial meningiomas were compared with or without preoperative embolization from January 2015 to April 2022. RESULTS: The embolization group consisted of 56 patients and the nonembolization group included 76 patients. Diluted NBCA (13% concentration for all patients) was used in 51 of 56 patients (91.1%) who underwent transarterial embolization. Permanent neurological complications occurred in 2 (3.6%) patients. Intraoperative bleeding was significantly lower in the embolization group for a maximum tumor diameter ≥40â¯mm (155 vs. 305â¯ml, respectively, p < 0.01). In the nonembolization group, for a maximum tumor diameter ≥30â¯mm, patients with hypertension had more intraoperative bleeding than non-hypertensive ones. CONCLUSIONS: Despite its limitations, the present results showed that, under certain conditions, preoperative embolization for intracranial meningiomas caused less intraoperative bleeding. The safety of treatment was comparable with that reported in the Japan Registry of NeuroEndovascular Therapy 3 (JR-NET3) with a complication rate of 3.7% for preoperative embolization of meningiomas, despite the treatment focused on the liquid embolization material.
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Embolização Terapêutica , Embucrilato , Hipertensão , Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/diagnóstico por imagem , Meningioma/cirurgia , Embucrilato/uso terapêutico , Neoplasias Meníngeas/cirurgia , Neoplasias Meníngeas/patologia , Estudos Retrospectivos , Resultado do Tratamento , Embolização Terapêutica/métodos , Hipertensão/etiologiaRESUMO
Airway complications that occur after anterior cervical spine surgery pose a life-threatening risk, which encompasses complications including prolonged intubation, unplanned reintubation, and/or necessity of tracheostomy. The present study aimed to identify the surgical risks associated with postoperative airway complications in neurosurgical training institutes. A retrospective, multicenter, observational review of data from 365 patients, who underwent anterior cervical spine surgery between 2018 and 2022, at three such institutes was carried out. Postoperative airway complication was defined as either the need for prolonged intubation on the day of surgery or the need for unplanned reintubation. The perioperative medical information was obtained from their medical records. The average age of the cohort was over 60 years, with males comprising approximately 70%. Almost all surgeries predominantly involved anterior cervical discectomy and fusion or anterior cervical corpectomy and fusion, with most surgeries occurring at the level of C5/6. In total, 363 of 365 patients (99.5%) were extubated immediately after surgery, and the remaining two patients were kept under intubation because of the risk of airway complications. Of the 363 patients who underwent extubation immediately after surgery, two (0.55%) required reintubation because of postoperative airway complications. Patients who experienced airway complications were notably older and exhibited a significantly lower body mass index. The results of this study suggested that older and frailer individuals are at an elevated risk for postoperative airway complications, with immediate postoperative extubation generally being safe but requiring careful judgment in specific cases.
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Manuseio das Vias Aéreas , Vértebras Cervicais , Complicações Pós-Operatórias , Humanos , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Vértebras Cervicais/cirurgia , Feminino , Complicações Pós-Operatórias/etiologia , Idoso , Fusão Vertebral/efeitos adversos , Adulto , Procedimentos Neurocirúrgicos/efeitos adversos , Intubação Intratraqueal/efeitos adversos , Discotomia/efeitos adversos , Idoso de 80 Anos ou maisRESUMO
OBJECTIVE: The term "weekend effect" refers to an increase in the mortality rate for hospitalizations occurring on weekends versus weekdays. In this study, we investigated whether such an effect exists in patients undergoing mechanical thrombectomy for acute ischemic stroke with large vessel occlusion (currently the standard treatment for this condition) at a single center in Japan. METHODS: We surveyed 151 patients who underwent mechanical thrombectomy for acute ischemic stroke with large vessel occlusion (75 and 76 patients were treated during daytime and nighttime, respectively) from January 2019 to June 2021. The items evaluated in this analysis were the rate of modified Rankin Scale ≤2 or prestroke scale, mortality, and procedural treatment time. RESULTS: The rates of modified Rankin Scale ≤2 or prestroke scale and mortality at 90 days after treatment did not differ significantly between daytime and nighttime (41.3% vs. 29.0%, p=0.11; 14.7% vs. 11.8%, p=0.61, respectively). The door-to-groin time tended to be shorter during daytime versus nighttime (57 [IQR: 42.5-70] min vs. 70 [IQR: 55-82]) min, p=0.0507). CONCLUSIONS: This study did not reveal differences in treatment outcome between daytime and nighttime in patients undergoing mechanical thrombectomy for acute ischemic stroke with large vessel occlusion. Therefore, the "weekend effect" was not observed in our institution.
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Background: Neuronavigation systems have become essential tools in image-guided neurosurgery that aid in the accurate resection of brain tumors. Recent advancements to these devices can indicate the precise location of lesions but can also project an augmented reality (AR) image on the microscope eyepiece to facilitate a successful surgical operation. Although the transcortical approach is a very popular method in neurosurgery, it can lead to disorientation and can cause unnecessary brain damage when the distance from the brain surface to the lesion is long. Herein, we report on an actual case in which a virtual line from AR images was used to assist the transcortical approach. Methods: A virtual line connecting the entry point and the target point, which were set as the navigation route, was created using Stealth station S7® (Medtronic, Minneapolis, USA). This line was projected as an AR image on the microscope eyepiece. It was possible to reach the target point by proceeding through the white matter along the displayed virtual line. Results: The lesion was reached within a short duration using virtual line without disorientation. Conclusion: Setting a virtual line as an AR image using neuronavigation is a simple and accurate method that can effectively support the conventional transcortical approach.
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Background: In the cervical nerve sheath tumor (NST) surgery with dumbbell extension of Eden type 2 or 3, selection of anterior, posterior, or combined approach remains controversial. Objectives: This technical note aimed to propose possible advantages of the posterior unilateral approach (PUA). Methods: Six patients who underwent the surgical treatment of cervical NSTs with dumbbell extension of Eden type 2 or 3 were included. The critical surgical steps included (1) complete separation of extradural and intradural procedures, (2) careful peeling of the neural membranes (epineurium and perineurium) from the tumor surface in the extradural procedure, (3) complete removal of the extradural tumor within the neural membranes, (4) intradural disconnection of tumor origin, and (5) intentional tumor removal up to the vertebral artery (VA), i.e., the VA line. Results: The tumor location of dumbbell extension was Eden types 2 and 3 in two and four patients. Gross total resection was achieved in two patients and intentional posterior removal of the tumor to the VA line was achieved in the remaining four patients. No vascular or neural injuries associated with surgical procedures occurred. Postoperative neurological assessment revealed no symptomatic aggravation in all patients. No secondary surgery was performed during the study period. Conclusion: PUA was safe and less invasive for functional recovery and tumor resection, if the anatomical relationship between the tumor and VA is clearly understood. The VA line is an important anatomical landmark to limit the extent of tumor resection.
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OBJECTIVE: The objective of this study was to verify that spine surgery for late-stage elderly (LSE) (age 65-74 years) is as safe as that for early-stage elderly (ESE) (age 65-74 years). METHODS: This retrospective multicenter study included elderly patients aged ≥65 years who underwent spine surgery between 2018 and 2021. The medical information for individual patients was obtained from medical records. Activities of daily living (ADL) were estimated using a 5-grade scale based on the Eastern Cooperative Oncology Group performance status. Good outcome was defined as ADL grade 0 or 1 at discharge; poor outcome was defined as ADL grade 2 to 4 at discharge. The postoperative complications were listed with reference to the Common Terminology Criteria for Adverse Events v5.0. RESULTS: There were 311 patients in the ESE group and 395 patients in the LSE group. Reoperation during hospitalization was significantly higher in the LSE group (4.6%) than in the ESE group (1.6%). The total number of days of hospitalization was significantly longer in the LSE group than in the ESE group. However, there was no significant difference in the postoperative complications or ADL at discharge between the 2 groups. In the statistical analysis, preoperative American Society of Anesthesiologists physical status class 3-6, underlying heart or renal disease, and cervical or thoracic spine level of surgical procedures were significantly associated with poor ADL outcomes at discharge. CONCLUSIONS: Spine surgery even for LSE can be safely done, if perioperative risk factors are appropriately managed.
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Atividades Cotidianas , Coluna Vertebral , Idoso , Humanos , Coluna Vertebral/cirurgia , Hospitalização , Complicações Pós-Operatórias/epidemiologia , Alta do Paciente , Estudos RetrospectivosRESUMO
BACKGROUND: Cancer cells with stem cell-like features are generally more resistant to chemotherapy and radiotherapy than differentiated tumor cells. Thus, these cells tend to increase the propensity for tumor recurrence and metastasis. This study investigated the efficacy of 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) in destructing glioma stem cells (GSCs), including the mesenchymal subtype (MES-GSCs) demonstrated to have the lowest radio- and chemosensitivity. METHODS: Five high-grade glioma (HGG) GSC lines and derived differentiated glioma cell (DGC) lines were examined for protoporphyrin-IX (PpIX) expression using fluorescence-activated cell sorting (FACS) and then assessed for ALA-PDT sensitivity using cell viability assays. MES-GSCs surviving ALA-PDT were then isolated and evaluated for stem cell and mesenchymal marker expression levels (CD44, ALDH1A3, KLF4, nestin) by qRT-PCR. The ability of these surviving cells to form tumors was then examined using colony forming and by xenograft tumor assays in athymic mice. Finally, the relationship between PpIX expression level (high versus low) and ALA-PDT sensitivity was examined by FACS and colony forming assays. RESULTS: ALA-PDT was effective against all GSC lines including MES-GSCs. MES-GSC lines exhibited higher PpIX expression than derived DGCs. Surviving MES-GSCs demonstrated lower stem cell marker expression and tumor forming potential than naive MES-GSCs. Higher PpIX production capacity by MES-GSCs was associated with greater colony forming ability, and ALA-PDT was more effective against MES-GSCs with greater PpIX accumulation. CONCLUSION: ALA-PDT may be clinically effective against HGG by targeting GSCs, including MES-GSCs.
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Glioma , Fotoquimioterapia , Camundongos , Animais , Humanos , Ácido Aminolevulínico/farmacologia , Ácido Aminolevulínico/uso terapêutico , Ácido Aminolevulínico/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fotoquimioterapia/métodos , Linhagem Celular Tumoral , Recidiva Local de Neoplasia/tratamento farmacológico , Glioma/tratamento farmacológico , Glioma/patologia , Células-Tronco Neoplásicas , Protoporfirinas/metabolismoRESUMO
Objective: We describe the rare case of a patient who was treated for a ruptured distal posterior inferior cerebellar artery (PICA) aneurysm via an ipsilateral persistent primitive proatlantal artery (PPPA). Case Presentation: An 86-year-old female with a medical history of hypertension presented with headache and nausea. CT showed subarachnoid hemorrhage in the posterior cranial fossa, and CTA revealed an aneurysm at the left-side distal PICA. In the left-sided common carotid angiography, the artery with a branch of the occipital artery from the external carotid artery was described. This artery continued as the V3 segment and entered the dura via the foramen magnum. The artery perfused the territory of the left vertebral artery and PICA. We concluded that the artery, which entered the dura, was a PPPA. We decided to perform endovascular therapy that passed through the PPPA. The aneurysm was located in the cortical segments, beyond the cranial loop. We decided that parent artery occlusion (PAO) would be more effective than selective coil embolization to achieve safe and adequate hemostasis. The patient had a good outcome with PAO not assessing collateral circulation. Conclusion: The emergency endovascular treatment with rare vascular variations requires accurate anatomical knowledge for treatment.
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BACKGROUND: Glioblastoma (GBM) is a high-grade, poor prognosis tumor that is resistant to standard treatment. The presence of a small number of glioma stem cells (GSCs) surviving in the harsh microenvironment is responsible for their refractoriness. This study aimed to investigate the effect of a hypoxic environment on the sensitivity of GSCs to photodynamic therapy with 5-aminolevulinic acid (ALA-PDT). MATERIALS AND METHODS: Six human GSC lines, Mesenchymal types HGG13, HGG30, HGG1123, and Proneural types HGG146, HGG157, HGG528, were divided into two groups: normoxia (O2 21%)-cultured cells (Normoxia-GSCs), and hypoxia (O2 5%)-cultured cells (Hypoxia-GSCs). To compare the effects of different oxygen partial pressures on photoporphyrin â ¨ (Ppâ ¨) biosynthetic activity, Ppâ ¨ biosynthetic enzyme and transporter expression levels were examined by qRT-PCR; the intracellular Ppâ ¨ concentration was determined using flow cytometry. Additionally, the sensitivity of these two groups of cells to ALA-PDT was evaluated in vitro. RESULTS: Hypoxia-GSCs showed higher mRNA levels of FECH (ferrochelatase), which is required for iron synthesis to convert Ppâ ¨ to heme, compared with Normoxia-GSCs. Flow cytometry revealed that the accumulation of Ppâ ¨ in Hypoxia-GSCs reduced upon incubation with ALA. However, Hypoxia-GSCs showed less reduction in sensitivity to ALA-PDT than Normoxia-GSCs. CONCLUSION: Hypoxia-GSCs had lower intracellular Ppâ ¨ accumulation than Normoxia-GSCs due to increased gene expression of FECH, and that their sensitivity to ALA-PDT was reduced less, despite accumulating lower concentrations of Ppâ ¨. ALA-PDT is a potentially effective therapy for hypoxia-tolerant GSCs that exist in hypoxia at 5% oxygen concentration.
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Glioma , Fotoquimioterapia , Humanos , Ácido Aminolevulínico/farmacologia , Ácido Aminolevulínico/uso terapêutico , Ácido Aminolevulínico/metabolismo , Fotoquimioterapia/métodos , Protoporfirinas/metabolismo , Linhagem Celular Tumoral , Glioma/tratamento farmacológico , Glioma/patologia , Hipóxia/tratamento farmacológico , Oxigênio , Fármacos Fotossensibilizantes/farmacologia , Microambiente TumoralRESUMO
OBJECTIVE: Acute mechanical thrombectomy (AMT) in patients with acute ischemic stroke from large vessel occlusion (LVO) is performed without directly identifying the occluded vessels. In this study, we evaluated whether 1.5 T magnetic resonance imaging (MRI) with 3D-fast imaging employing steady-state acquisition (FIESTA) could visualize the occluded intracranial middle cerebral artery (MCA) and internal carotid artery (ICA) before AMT. METHODS: This retrospective study included 21 consecutive patients who underwent time-of-flight magnetic resonance angiography (TOF MRA) and 3D-FIESTA MRI immediately before AMT. The patients also underwent TOF MRA after AMT and achieved TICI 2b or 3 by AMT at our hospital between February 2018 and April 2019. When LVO in the anterior circulation was detected by TOF MRA, 3D-FIESTA MRI was additionally performed. Then, the occluded intracranial MCA and ICA, including their branches, were constructed on the workstation with volume rendering. The obtained images were fused with the TOF MRA images to create combined 3D images. RESULTS: The length and top-to-bottom distance of the affected M1 segment (calculated by the ipsilateral-to-contralateral ratio) were 1.29 and 1.17, respectively, on 3D-FIESTA MRI before AMT and 1.34 and 1.24, respectively, on TOF MRA after AMT. We assessed the number of M2 segments branching from the affected M1/M2 junction and visualized the affected anterior temporal artery. The 3D-FIESTA MRI before AMT and TOF MRA after AMT were consistent in all patients, except for two who moved vigorously during imaging. CONCLUSIONS: Images acquired by 1.5T 3D-FIESTA MRI can visualize to predict the existing path of the occluded MCA and ICA before AMT in patients with LVO of the anterior circulation.
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PURPOSE: As age increases, oxidative stress increases, sperm motility decreases, and DNA fragmentation increases. To date, reports of age-related effects on semen have focused on reactive oxygen species (ROS) or total antioxidant capacity (TAC) as indicators of oxidative stress. However, assessments of ROS and TAC must be considered within a more comprehensive context in order to correctly evaluate oxidative stress and interpret findings. In this regard, the purpose of this study was to investigate the relationship between the static oxidation reduction potential (sORP) and paternal age with the goal of using the sORP as an indicator of semen oxidative stress. MATERIALS AND METHODS: Semen samples from 173 men were analyzed for the following parameters: volume, motility, and beat cross frequency (BCF). The sORP was measured by using the MiOXSYS™ system. The correlation between semen parameters and the sORP level was analyzed as a function of age. The rate of sORP positivity was compared between men <34 and ≥34 years of age, with a positive sORP defined as a level ≥1.38. RESULTS: Volume, motility, and BCF were negatively correlated with age (p<0.001). The semen sORP level was positively correlated with age (p<0.05). The rate of sORP positivity was significantly increased in men ≥34 years of age compared with that in men <34 years of age (33% compared with 12%, respectively; p<0.01). CONCLUSIONS: The sORP may play a role in age-related decreases in semen parameters (volume, motility, and BCF). The rate of sORP positivity increased significantly after 34 years of age.
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Envelhecimento/metabolismo , Estresse Oxidativo , Sêmen/metabolismo , Adulto , Fatores Etários , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Tortuous/abnormal vertebral arteries (VAs) sometimes cause neurovascular compression syndromes (NVCs), such as trigeminal neuralgia, hemifacial spasm, and, rarely, myelopathy/radiculopathy. Abnormalities/tortuosity of the VA at the level of the atlas and axis are of particular note; these may be characterized by a persistent first intersegmental artery (PFIA) and C2 segmental type of VA. Herein, we report a 72-year-old male who presented with cervical myelopathy/radiculopathy due to bilateral tortuosity of the PFIA resulting in spinal cord compression at the craniocervical junction. CASE DESCRIPTION: A 72-year-old male presented with cervical pain when turning his neck and progressive gait disturbance. The neurological examination demonstrated a moderate myeloradicular syndrome (Nurick Grade III). The magnetic resonance revealed compression of the medulla and spinal cord due to tortuosity of both dorsal VA at the C1 vertebral level. The three-dimensional computed tomography angiogram confirmed bilateral PFIA running medially. In addition, the left side of VA forms fenestration. Surgery through a C1 laminectomy and midline small suboccipital craniectomy, both VAs were transposed and tethered to the ipsilateral dura utilizing Aron Alpha and vinyl prostheses. In addition, a large vinyl prosthesis was inserted between both VAs to protect them from contacting the spinal cord. Following this decompressive procedure, the patient's symptoms fully resolved, and he remains asymptomatic 10 years later exhibiting no recurrent vascular pathology. CONCLUSION: Microvascular decompression of anomalous VAs contributing to cord compression at the C1 level was safe and effective in a 72-year-old male.
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Microstructures of electrodeposited Ni were studied from the perspective of growth modes during electrodeposition. The electrodeposited Ni had a heterogeneous microstructure composed of nanocrystalline- and microcrystalline-grains. Electron backscatter diffraction analyses showed that nanocrystalline- and microcrystalline-grains were preferentially oriented to specific planes. Secondary ion mass spectrometry also revealed that coarse-grained regions had higher S content than that of finer-grained regions. Hence, microstructural heterogeneity in electrodeposited Ni is reflected by the overlap of inhibited and free growth modes. Our discussion surrounding microstructural heterogeneity also provides insight into other electrodeposited nanocrystalline systems.
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Bioaccumulation and trophic transfer of cyclic volatile methylsiloxanes (cVMS), specifically octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5), and dodecamethylcyclohexasiloxane (D6), were evaluated in the pelagic marine food web of Tokyo Bay, Japan. Polychlorinated biphenyl (PCB) congeners that are "legacy" chemicals known to bioaccumulate in aquatic organisms and biomagnify across aquatic food webs were used as a benchmark chemical (CB-180) to calibrate the sampled food web and as a reference chemical (CB-153) to validate the results. Trophic magnification factors (TMFs) were calculated from slopes of ordinary least-squares (OLS) regression models and slopes of bootstrap regression models, which were used as robust alternatives to the OLS models. Various regression models were developed that incorporated benchmarking to control bias associated with experimental design, food web dynamics, and trophic level structure. There was no evidence from any of the regression models to suggest biomagnification of cVMS in Tokyo Bay. Rather, the regression models indicated that trophic dilution of cVMS, not trophic magnification, occurred across the sampled food web. Comparison of results for Tokyo Bay to results from other studies indicated that bioaccumulation of cVMS was not related to type of food web (pelagic vs demersal), environment (marine vs freshwater), species composition, or location. Rather, results suggested that differences between study areas was likely related to food web dynamics and variable conditions of exposure resulting from non-uniform patterns of organism movement across spatial concentration gradients.
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Dimetilpolisiloxanos/análise , Monitoramento Ambiental , Cadeia Alimentar , Poluentes Químicos da Água/análise , Animais , Baías , TóquioRESUMO
We report effective treatment with nivolumab of a patient with recurrent primary central nervous system lymphoma (PCNSL) after multiple therapies. A 41-year-old woman with a right parietal PCNSL underwent treatment with high-dose methotrexate and radiotherapy. After recurrence in the left frontal lobe, the patient received several chemotherapies, including methotrexate and rituximab, and underwent surgery. The tumor was refractory to these treatments, and the patient then underwent intensity-modulated radiotherapy (IMRT). Multiple small, new recurrent tumors appeared in the right frontal lobe and the left frontoparietal region 2 months after IMRT. The patient received nivolumab 3 mg/kg with dendritic cell vaccination. Complete remission of the tumors was achieved after six cycles of nivolumab, and remission was maintained for 10 months after the initiation of nivolumab. Nivolumab could be a novel treatment for intractable recurrent PCNSL in the future.
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Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/terapia , Imunoterapia , Linfoma/terapia , Recidiva Local de Neoplasia/terapia , Adulto , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Células Dendríticas/imunologia , Feminino , Humanos , Linfoma/diagnóstico por imagem , Linfoma/patologia , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , NivolumabeRESUMO
The ubiquitin-like protein TtuB is a sulfur carrier for the biosynthesis of 2-thioribothymidine (s2T) at position 54 in some thermophilic bacterial tRNAs. TtuB captures a S atom at its C-terminus as a thiocarboxylate and transfers it to tRNA by the transferase activity of TtuA. TtuB also functions to suppress s2T formation by forming a covalent bond with TtuA. To explore how TtuB interacts with TtuA and switches between these two different functions, high-resolution structure analysis of the TtuA-TtuB complex is required. In this study, the TtuA-TtuB complex from Thermus thermophilus was expressed, purified and crystallized. To mimic the thiocarboxylated TtuB, the C-terminal Gly residue was replaced with Cys (G65C) to obtain crystals of the TtuA-TtuB complex. A Zn-MAD data set was collected to a resolution of 2.5â Å. MAD analysis successfully determined eight Zn sites, and a partial structure model composed of four TtuA-TtuB complexes in the asymmetric unit was constructed.