Multi-regulated GDP-l-galactose phosphorylase calls the tune in ascorbate biosynthesis.

Ascorbate is involved in numerous vital processes, in particular in response to abiotic but also biotic stresses whose frequency and amplitude increase with climate change. Ascorbate levels vary greatly depending on species, tissues, or stages of development, but also in response to stress. Since its discovery, the ascorbate biosynthetic pathway has been intensely studied and it appears that GDP-l-galactose phosphorylase (GGP) is the enzyme with the greatest role in the control of ascorbate biosynthesis. Like other enzymes of this pathway, its expression is induced by various environmental and also developmental factors. Although mRNAs encoding it are among the most abundant in the transcriptome, the protein is only present in very small quantities. In fact, GGP translation is repressed by a negative feedback mechanism involving a small open reading frame located upstream of the coding sequence (uORF). Moreover, its activity is inhibited by a PAS/LOV type photoreceptor, the action of which is counteracted by blue light. Consequently, this multi-level regulation of GGP would allow fine control of ascorbate synthesis. Indeed, experiments varying the expression of GGP have shown that it plays a central role in response to stress. This new understanding will be useful for developing varieties adapted to future environmental conditions.

Effectiveness of Keyhole Clipping of Unruptured Intracranial Aneurysms Detected by "Brain Dock" in Healthy Japanese Adults.

In Japan, brain docking has enhanced the detection of unruptured intracranial aneurysms in healthy adults. At our institution, surgical clipping is the first-line treatment for unruptured intracranial aneurysms (UIA). In this study, the differences in neurological and radiological outcomes, as well as cognitive and psychological results, between standard clipping and keyhole clipping for these aneurysms detected via brain docking were evaluated. The study included 131 aneurysms detected via "brain dock." Of these, 65 were treated with keyhole clipping surgery (keyhole clipping group), and 66 were treated with standard clipping surgery (standard clipping group). Evaluations at 3 months included the National Institutes of Health Stroke Scale, modified Rankin Scale, Mini-Mental State Examination, Hasegawa's Dementia Scale-revised, Beck Depression Inventory, Hamilton Rating Scale for Depression, and radiological abnormalities. The mean operative time and postoperative hospitalization period were significantly shorter in the keyhole clipping group than in the standard clipping group (p < 0.001). Between the groups, no significant differences in postoperative neurological complications or radiological abnormalities were found. The keyhole clipping group demonstrated slightly but significantly better Beck Depression Inventory and Hamilton Rating Scale for Depression scores than the standard clipping group (Beck Depression Inventory, p = 0.046; Hamilton Rating Scale for Depression, p < 0.01). Both the Beck Depression Inventory and Hamilton Rating Scale for Depression scores at 3 months were significantly enhanced (p < 0.001) in the keyhole clipping group. These findings propose that keyhole clipping could be considered a new therapeutic option for small UIA detected via brain docking.

"The microcatheter contrast injection technique": A novel technique to detect the proximal end of a thrombus in mechanical thrombectomy.

Background: An aspiration catheter needs to attach to a thrombus in order to achieve first-pass recanalization by mechanical thrombectomy (MT) for acute ischemic stroke (AIS), particularly that using a direct aspiration first pass technique. The meniscus sign, which is defined as meniscoid contrast opacification indicating the proximal edge of a thrombus, has been suggested to contribute to successful recanalization. In some cases, the meniscus sign is not detected following an injection of contrast medium through a guiding catheter. To precisely identify the location of a thrombus, we use "the microcatheter contrast injection (MCI) technique," which accurately shows the proximal edge of a thrombus. We herein introduce this novel technique and discuss its efficacy in MT. Methods: In cases without the meniscus sign, a microcatheter was advanced to the distal end of contrast opacification, and contrast medium was injected through the microcatheter to detect the meniscus sign. An aspiration catheter was then advanced to the thrombus indicated by the meniscus sign and slowly withdrawn under aspiration. Results: 29 patients underwent MT for AIS using the MCI technique. Even in cases without the meniscus sign on initial angiography, the MCI technique accurately revealed the proximal edge of the thrombus. Moreover, middle cerebral artery occlusion due to atherosclerotic stenosis and displacement of the aspiration catheter and thrombus axis were detected using this technique. Conclusions: The MCI technique may effectively reveal the exact site of a thrombus and increase the success rate of first-pass recanalization.

Melanocortin-4 receptor in macrophages attenuated angiotensin II-induced abdominal aortic aneurysm in mice.

Obesity is recognized as an independent risk factor for abdominal aortic aneurysm (AAA). While mutations in the melanocortin-4 receptor (MC4R) gene is the most common cause of obesity caused by mutations in a single gene, the link between MC4R function and vascular disease has still remained unclear. Here, by using melanocortin-4 receptor (MC4R) deficient mice, we confirmed MC4R deficiency promotes AAA and atherosclerosis. We demonstrated the contribution of two novel factors towards vascular vulnerability in this model: leptin signaling in vascular smooth muscle cells (VSMCs) and loss of MC4R signaling in macrophages. Leptin was shown to promote vascular vulnerability via PI3K-dependent upregulation of Spp1 expression in VSMC. Additionally, Ang II-induced AAA incidence was significantly reduced when MC4R gene expression was myeloid cell-specifically rescued in MC4R deficient (MC4RTB/TB) mice. Ex vivo analysis showed a suppression in NF-κB activity in bone marrow-derived macrophages from LysM(+);MC4RTB/TB mice compared to LysM(-);MC4RTB/TB mice, which exaggerates with endogenous MC4R ligand treatment; α-MSH. These results suggest that MC4R signaling in macrophages attenuates AAA by inhibiting NF-κB activity and subsequent vascular inflammation.

Ischemic stroke patients with low DWI ASPECTS scores require puncture to recanalization within 30 min for large vessel occlusion.

BACKGROUND: The clinical benefits of faster recanalization in acute large vessel occlusion are well recognized, but the optimal procedure time remains uncertain. The aim of this study was to identify patient characteristics that necessitate puncture-to-recanalization (P-R) time within 30 min to achieve favorable outcome. METHODS: We evaluated the patients from a prospective, multicenter, observational registry of acute ischemic stroke patients. The study included patients who underwent endovascular therapy for ICA or MCA M1 occlusion and achieved successful recanalization. Patients were categorized into subgroups based on pre-treatment characteristics and the frequency of favorable outcomes was compared between P-R time < 30 min and ≥ 30 min. Interaction terms were incorporated into the models to assess the correlation between each patient characteristic and P-R time. RESULTS: A total of 1053 patients were included in the study. Univariate analysis within each subgroup revealed a significant association between P-R < 30 min and favorable outcomes in patients with DWI ASPECTS ≤6, age > 85 and NIHSS ≥16. In the multivariable analysis, NIHSS, age, time from symptom recognition to puncture, and DWI ASPECTS were significant independent predictors of favorable outcomes. Notably, only DWI ASPECTS exhibited interaction terms with P-R < 30 min. The multivariable analysis indicated that P-R < 30 min was an independent predictor for favorable outcome in DWI ASPECTS ≤6 group, whereas not in DWI ≥7. CONCLUSIONS: P-R time < 30 min is predictive of favorable outcomes; however, the effect depends on DWI ASPECTS. Target P-R time < 30 min is appropriate for patients with DWI ASPECTS ≤6.

Validation of Efficacy and Safety of TachoSil ® Tissue Sealant for Vessel Transposition in Microvascular Decompression.

BACKGROUND AND OBJECTIVES: Use of TachoSil ® as the transposition material of microvascular decompression (MVD) for hemifacial spasm (HFS) and trigeminal neuralgia (TN) is easy and safe to perform, but the efficacy and safety of this technique are unknown. This study attempted to validate the efficacy and safety of TachoSil ® as a transposition material of MVD. METHODS: A retrospective study of the surgical results and complications of 63 patients (35 HFS and 28 TN) treated by the TachoSil ® technique between January 2011 and December 2021 was conducted. The efficacy of the treatment was evaluated by Kaplan-Meier survival analysis. Magnetic resonance imaging follow-up study was performed to detect any adverse events including a mass formation. RESULTS: The rate of complete disappearance of HFS was 91.4% at 1 year and estimated to be 85.7% after a 10-year follow-up. The rate of no pain without medication for TN was 85.4% at 1 year and estimated to be 69.0% after a 9-year follow-up. These surgical results are comparable with those previously reported. Flaking of TachoSil ® releasing the offending artery was only recognized in one case (1.6%). Therefore, TachoSil ® can be considered as an effective transposition material for MVD. TachoSil ® did not increase the rate of acute and subacute adverse events such as inflammation and delayed facial palsy. Magnetic resonance imaging follow-up identified no abnormalities including mass that suggested granuloma formation. CONCLUSION: The efficacy of the TachoSil ® technique for HFS and TN and the reliability of TachoSil ® as an adhesive material in MVD were verified. No adverse events associated with TachoSil ® use in MVD were found. We conclude that the TachoSil ® technique has relatively long efficacy and safety for MVD.

Enzyme-based kinetic modelling of ASC-GSH cycle during tomato fruit development reveals the importance of reducing power and ROS availability.

The ascorbate-glutathione (ASC-GSH) cycle is at the heart of redox metabolism, linking the major redox buffers with central metabolism through the processing of reactive oxygen species (ROS) and pyridine nucleotide metabolism. Tomato fruit development is underpinned by changes in redox buffer contents and their associated enzyme capacities, but interactions between them remain unclear. Based on quantitative data obtained for the core redox metabolism, we built an enzyme-based kinetic model to calculate redox metabolite concentrations with their corresponding fluxes and control coefficients. Dynamic and associated regulations of the ASC-GSH cycle throughout the whole fruit development were analysed and pointed to a sequential metabolic control of redox fluxes by ASC synthesis, NAD(P)H and ROS availability depending on the developmental phase. Furthermore, we highlighted that monodehydroascorbate reductase and the availability of reducing power were found to be the main regulators of the redox state of ASC and GSH during fruit growth under optimal conditions. Our kinetic modelling approach indicated that tomato fruit development displayed growth phase-dependent redox metabolism linked with central metabolism via pyridine nucleotides and H2 O2 availability, while providing a new tool to the scientific community to investigate redox metabolism in fruits.

Supraorbital keyhole approach for paraclinoid aneurysms clipping: A case series with literature review.

Background: Paraclinoid aneurysms (PcAs) are challenging aneurysms due to the complexity of their relation to the surrounding bony and neurovascular structures. Although over the past decade, their management strategy has shifted from transcranial to endovascular approaches; here, we try to revolve around a subcategory to which minimal invasive supraorbital keyhole (SOK) surgery is feasible depending on specific radiological criteria with a literature review. Methods: A group of unruptured PcAs was managed surgically, with a subset that was clipped through the SOK approach. They were selected by preoperative simulation images using 3D computed tomography (CT) angiography (CTA). We also conducted an extensive literature review based on a database available on PubMed and Google Scholar, the yielded cases from the literature review plus our cases were analyzed according to six parameters including their size, location, dome direction, need for clinoidectomy and proximal cervical control, and surgical outcome. Results: From February 2009 to August 2022, 49 cases of unruptured PcAs were managed by clipping, and of these, four cases were clipped by the SOK approach, in addition, four cases were yielded through the literature review. The sizes of the PcAs ranged from 3 to 8 mm. Their location fluctuated from anterior to the superomedial wall and their domes pointed superiorly except for one which points posteriorly. Six of eight cases required anterior clinoidectomy, the outcome was uneventful. Conclusion: A subset of unruptured PcAs are amenable to SOK with criteria such as unruptured small aneurysm (<10 mm) and projected superiorly. These characteristics can be determined preoperatively using CTA.

Atlantoaxial Stabilization Using C1 Lateral Mass and C2 Pedicle/Translaminar Screw Fixation by Intraoperative C1- and C2-Direct-Captured Navigation with Preoperative Computed Tomography Images.

In C1-C2 posterior fixation, the C1 lateral mass and C2 pedicle/translaminar screw insertion under spine navigation have been used frequently. To avoid the risk of neurovascular damage in atlantoaxial stabilization, we assessed the safety and effectiveness of a preoperative computed tomography (CT) image-based navigation system with intraoperative independent C1 and C2 vertebral registration. It is ideal when a reference frame can be linked directly to the C1 posterior arch for C1-direct-captured navigation, but there is a mechanical challenge. A new spine clamp-tracker system was implemented recently, which allows reliable C1- and C2- direct-captured navigation in nine patients with traumatic C2 fractures. In this way, there was no misalignment of C1-C2 screws. C1 lateral mass screws were used except for one case, and translaminar screws were primarily used as an anchor for C2. The C1 lateral mass screw locations, which are 19 mm laterally from the C1 posterior arch's center, are taken to be constant. However, there is one unusual circumstance in which using a C1 laminar hook instead of a C1 lateral mass screw appears to be a beneficial substitute. The increase of surgical accuracy for posterior C1-C2 screw fixation without cost constraints is significantly facilitated by intraoperative C1- and C2-direct-captured navigation with preoperative computed CT images.

Blue light promotes ascorbate synthesis by deactivating the PAS/LOV photoreceptor that inhibits GDP-L-galactose phosphorylase.

Ascorbate (vitamin C) is an essential antioxidant in fresh fruits and vegetables. To gain insight into the regulation of ascorbate metabolism in plants, we studied mutant tomato plants (Solanum lycopersicum) that produce ascorbate-enriched fruits. The causal mutation, identified by a mapping-by-sequencing strategy, corresponded to a knock-out recessive mutation in a class of photoreceptor named PAS/LOV protein (PLP), which acts as a negative regulator of ascorbate biosynthesis. This trait was confirmed by CRISPR/Cas9 gene editing and further found in all plant organs, including fruit that accumulated 2 to 3 times more ascorbate than in the WT. The functional characterization revealed that PLP interacted with the 2 isoforms of GDP-L-galactose phosphorylase (GGP), known as the controlling step of the L-galactose pathway of ascorbate synthesis. The interaction with GGP occurred in the cytoplasm and the nucleus, but was abolished when PLP was truncated. These results were confirmed by a synthetic approach using an animal cell system, which additionally demonstrated that blue light modulated the PLP-GGP interaction. Assays performed in vitro with heterologously expressed GGP and PLP showed that PLP is a noncompetitive inhibitor of GGP that is inactivated after blue light exposure. This discovery provides a greater understanding of the light-dependent regulation of ascorbate metabolism in plants.

Traumatic rupture of intracranial dermoid cyst with continuous fat droplet migration.

Background: The intracranial dermoid cyst (ICD) can be complicated by rupture and spilling of its contents with potentially dreadful consequences. Head trauma as a predisposing element for this phenomenon is extremely rare. Few reports address the diagnosis and management of trauma-related rupture of ICD. However, there is a pronounced knowledge gap related to the long-term follow-up and the fate of the leaking contents. Here, we present a unique case of traumatic rupture of ICD complicated by continuous fat particle migration within the subarachnoid space with its surgical implications and outcome. Case Description: A 14-year-old girl had an ICD rupture following a vehicle collision. The cyst was located near the foramen ovale with intra and extradural extensions. Initially, we opted to follow the patient clinically and radiologically as she had no symptoms, and the imaging showed no red flags. Over the next 24 months, the patient remained asymptomatic. However, the sequential brain magnetic resonance imaging revealed significant continuous migration of the fat within the subarachnoid space, with the droplets noticed to increase in the third ventricle. That is considered an alarming sign of potentially serious complications impacting the patient's outcome. Based on the above, the ICD was completely resected through an uncomplicated microsurgical procedure. On follow-up, the patient is well, with no new radiological findings. Conclusion: Trauma-related ruptured ICD may have critical consequences. Persistent migration of dermoid fat can be managed with surgical evacuation as a viable option to prevent those potential complications such as obstructive hydrocephalus, seizures, and meningitis.

Impact of Low Skeletal Muscle Mass on the Prognosis of Patients with Head and Neck Cancer Treated Nonsurgically.

INTRODUCTION: Sarcopenia, characterized by low skeletal muscle mass, and the outcome of cancer therapy are closely related based on recent research. This study aimed to evaluate the correlation between skeletal muscle mass and prognosis in head and neck cancer (HNC) patients. METHODS: In this study, 51 male patients with HNC treated nonsurgically between January 2016 and April 2018 at Shinshu University Hospital were evaluated. Skeletal muscle mass was assessed using bioelectrical impedance analysis, and the skeletal mass index (SMI) was calculated to classify the patients. RESULTS: The low-SMI group had a significantly worse overall survival (OS) than the normal-SMI group (3-year OS: 72.0% vs. 93.0%, p = 0.014), and there was a trend toward worse progression-free survival (PFS) in the low-SMI group (3-year PFS: 49.6% vs. 79.3%, p = 0.064). Multivariate analysis also showed that low SMI (p = 0.04) and severe N stage (p = 0.009) were significantly associated with poorer OS. CONCLUSION: The pretreatment assessment of SMI using bioelectrical impedance analysis is useful for identifying patients with poor prognoses. To improve the treatment outcome in HNC, we need to think of the intervention, such as cancer rehabilitation and nutritional support, during or before treatment, especially for patients with low SMI.

A case of meningioma originating from the lateral wall of the cavernous sinus.

Meningioma originating from the lateral wall of the cavernous sinus is rare with only two reported cases. A 67-year-old man presented with recent memory disturbance and partial seizure. Magnetic resonance imaging revealed a well-demarcated and homogeneously enhanced mass lesion originating from the lateral wall of the left cavernous sinus. Total tumor removal was performed through a combined epi- and intradural approach. Histological diagnosis was transitional meningioma. Postoperative course was uneventful. This combined approach was helpful for cranial nerve preservation, total tumor removal, and bleeding control from the feeder of the tumor.

Mixed pial and dural arteriovenous fistula after craniotomy: case report and literature review.

Dural arteriovenous fistula (AVF) is known to occur after craniotomy, but mixed pial and dural AVF after craniotomy has not been reported. A 45-year-old man who had undergone surgical clipping of an unruptured aneurysm 2 years previously presented with small subcortical hemorrhage from mixed pial and dural AVF. Surgical disconnection could not be cured completely due to the granulomatous tissue around the aneurysm, and the presence of an undetected shunt. Postoperative digital subtraction angiography showed a new pial AVF supplied by the middle cerebral artery pial branches. Many branches were associated with the remnant aneurysm and pial AVF, so we did not try to embolize the fistula. Gamma knife surgery was performed as adjuvant radiotherapy, which achieved angiographically complete occlusion of the shunt points. Multimodal approaches including surgery, endovascular intervention, and radiotherapy are needed for radiological and clinical cure of mixed pial and dural AVF. Long-term follow up is essential.

Primary results of mechanical thrombectomy for acute ischemic stroke: The K-NET registry in the Japanese metropolitan area.

BACKGROUND: Endovascular treatment (EVT) for acute large vessel occlusion has proven to be effective in randomized controlled trials. We conducted a prospective cohort study to evaluate the real-world efficacy of EVT in a metropolitan area with a large number of comprehensive stroke centers and to compare it with the results of other registries and randomized controlled trials (RCTs). METHODS: We analyzed the Kanagawa Intravenous and Endovascular Treatment of Acute Ischemic Stroke registry, a prospective, multicenter observational study of patients treated by EVT and/or intravenous tissue-type plasminogen activator (tPA). Of the 2488 patients enrolled from January 2018 to June 2020, 1764 patients treated with EVT were included. The primary outcome was a good outcome, which was defined as a modified Rankin Scale (mRS) of 0-2 at 90 days. Secondary analysis included predicting a good outcome using multivariate logistic regression analysis. RESULTS: The median age was 77 years, and the median National Institute of Health Stroke Scale (NIHSS) score was 18. Pretreatment mRS score 0-2 was 87%, and direct transport was 92%. The rate of occlusion in anterior circulation was 90.3%. Successful recanalization was observed in 88.7%. The median time from onset to recanalization was 193 min. Good outcomes at 90 days were 43.3% in anterior circulation and 41.9% in posterior circulation. Overall mortality was 12.6%. Significant predictors for a good outcome were as follows: age, male, direct transfer, NIHSS score, Alberta Stroke Program Early Computed Tomography Score, intravenous tPA, and successful recanalization. CONCLUSION: EVT in routine clinical use in a metropolitan area showed comparable good outcomes and lower mortality compared to previous studies, despite the high proportion of patients with older age, pretreatment mRS score of >2, posterior circulation occlusion, and higher NIHSS. Those results may have been associated with more direct transport and faster onset-to-recanalization times.

Angioarchitecture of the hemorrhagic developmental venous anomaly with stenosis of the collecting vein and cavernous malformation: a case report.

We herein report a case of developmental venous anomaly (DVA) with venous congestion caused by stenosis of the collecting vein that presented with intracerebral hemorrhage (ICH). A 74-year-old woman was referred to our hospital a few days after the onset of motor aphasia. Computed tomography (CT) and magnetic resonance imaging (MRI) showed ICH in the left frontal lobe. Angiography revealed DVA in the left frontal lobe in the late venous phase. Stenosis of the collecting vein of DVA at the entrance to the superior sagittal sinus was detected and accompanied by cavernous malformation (CM) beside DVA. Cone-beam CT revealed the absence of the left septal vein and hypoplastic transverse caudate veins. The patient was treated by blood pressure management and no additional neurological symptoms were detected. DVA develops to compensate for the absence of pial or deep venous systems, and generally benign and clinically asymptomatic. However, the outflow restriction of DVA causes chronic venous hypertension and the formation of CM. These abnormalities are considered to occur during post-natal life and may result in ICH. The risk of hemorrhage needs to be considered in cases of DVA with restricted venous outflow or CM.

Glioependymal cyst in the medulla oblongata - A case report.

Background: Glioependymal cysts (GECs) are rare benign lesions that can be found anywhere along the neuroaxis, with most of the reports denoting supratentorial location. Here, we introduce a rare case of successfully treated glioependymal cysts lying in an uncommon location, namely medulla oblongata. Case Description: A 69-year-old lady presented with progressive unsteadiness and swallowing disturbances, and brain magnetic resonance imaging showed a dorsally located lesion within the medulla oblongata; based on the presentation and radiological features, surgical intervention was deemed mandatory. The suboccipital midline approach was used to perform marsupialization of the cyst with shunting through a syringosubarachnoid shunt to prevent future recurrence, and the patient outcome was improved. Conclusion: Medulla Oblongata's location for glioependymal cysts proposed unique diagnostic and operative challenges that may require highlighting for practicing neurosurgeons.

Cerebral Infarction Due to Occlusion of Main Trunk of Middle Cerebral Artery in Patient with Accessory Middle Cerebral Artery.

The existence of an accessory middle cerebral artery (AMCA) usually has no pathological significance. Three patients developed cerebral infarction due to thromboembolic occlusion of the main trunk of the middle cerebral artery (MCA). In these patients, AMCA originating from the anterior cerebral artery was intact, and ran to the lateral side along the main MCA. Emergency endovascular treatment to remove the thrombus in the main MCA was performed, and MCA was recanalized. In one patient, the main MCA re-occluded and cerebral infarction developed on the next day. The diameter of AMCA is commonly smaller than that of the main MCA. Therefore, volume of ischemic region depends on the collateral blood flow to the left MCA territory by AMCA. Once an anomalous MCA is detected in a patient with cerebral infarction involving the MCA territory, close examinations to assess the anatomy of both the main and anomalous MCA are mandatory.