Assessing the usability of aromatic mouthwashes in alleviating physiological stress responses.

Background: Mouthwashes play a pivotal role in oral care, and their efficacy has been explored extensively across various dimensions. As a contribution to the development of novel oral care products, this study aims to investigate the psychophysiological effects of aromatic mouthwashes during the resilience period from a short-term cognitive stressor utilizing biological signals and subjective evaluations. Methods: A within-participant experimental design with 22 healthy females was conducted with four mouthwashes; peppermint (Mint), peppermint + bergamot (MB), peppermint + sweet orange (MO), and peppermint + lavender (ML), and water as the control (Ctl), after a 20-min calculation task. Subjective evaluations and physiological responses including skin conductance level and electrocardiogram were recorded throughout the experiment. Results: Citrus mouthwashes (MO and MB) showed a greater decrease in heart rate and a significant increase in the high-frequency component of heart rate variability. The participants indicated a significant effect in terms of "flavor preference" and "refreshing sensation" for mouthwash use compared to the Ctl. Conclusion: The results suggest that rinsing with citrus-flavored mouthwashes has a positive impact in alleviating the physiological stress response (in terms of cardiac activity). These findings may have implications for the development of innovative, novel oral care products that promote stress reduction and improve oral health.

Combined Endovascular Antegrade and Direct Retrograde Carotid Artery Stenting for Chronic and Long Segment Common Carotid Artery Occlusion: Technical Note and Review of Literature.

Common carotid artery (CCA) occlusion (CCAO) is a rare cause of ischemic stroke and bypass surgery is the common treatment approach. However, safer alternatives should be developed to treat CCAO. A 68-year-old male was diagnosed with left-sided CCAO with decreased left visual acuity due to neck radiation therapy for laryngeal cancer. Recanalization therapy using a pull-through technique was initiated because cerebral blood flow progressively decreased during the follow-up period. First, after a short sheath was inserted into the CCA, the occluded CCA was retrogradely penetrated through the sheath. Second, a micro-guidewire was guided to the aorta from the femoral sheath where it was caught using a snare wire guided from the cervical sheath. Subsequently, the micro-guidewire was gently pulled out from the cervical sheath, penetrated the occluded lesion, and was secured to the femoral and cervical sheaths. Finally, the occluded lesion was dilated using a balloon, and the stent was placed. Five days postprocedure, the patient was discharged uneventfully and exhibited improved left visual acuity. In terms of reliable penetration of obstructive lesions and reduction of embolic and hemorrhagic complications, combined endovascular antegrade and direct retrograde carotid artery stenting is a versatile and minimally invasive treatment option for CCAO.

Scratching and Stretching the Shrunken Cranial Dura for Primary Closure.

BACKGROUND: At craniotomy, the dura shrinks due to the drying effect of illumination and air exposure, rendering its primary closure difficult. When the opening is narrow, it can be patched with autologous grafts. However, tissue harvesting and meticulous suturing take time. As the cost-effectiveness of using dural substitutes is poor, we developed a new technique that involves dural scratching for the primary closure of dural openings. METHODS: We applied our technique because in 53 adults who underwent supratentorial craniotomy we encountered difficulties with the primary closure of a dural opening 5 mm or less in width. With a scalpel, we placed several fine scratches parallel to the edge of the opening on the surface of the dura, taking care not to perforate the deep layer. This relieved dural tension and the tissue was stretched enough to permit closing with sutures. RESULTS: Our technique achieved primary dural closure in 46 of 53 patients (87%) who primarily had undergone narrow supratentorial craniotomies. The other 7 additionally required small autologous grafts to patch narrow residual openings at the intersection of the durotomy. There were no procedure-related complications such as cerebrospinal fluid leakage and persistent headache due to tension of the closed dura. CONCLUSIONS: Dural scratching is simple, safe, requires no special instrumentation, facilitates primary closure of the shrunken dura by stretching, and reduces the need for patch grafting.

Feasibility of Preoperative Magnetic Resonance Angiography/Black-Blood Magnetic Resonance Imaging/Computed Tomography Fusion Imaging Without Contrast Agent for Carotid Endarterectomy.

BACKGROUND: Preoperative identification of the carotid bifurcation (CB) location and plaque and stenosis distal end of the cervical internal carotid artery in relation to bony structures is essential for carotid endarterectomy (CEA). However, for patients with contrast contraindications, cervical 3-dimensional computed tomography angiography (3D-CTA) is unavailable. In this study, we created fusion images of magnetic resonance angiography (MRA), black-blood (BB) magnetic resonance imaging (MRI), and CT to determine if these noncontrast agent images are superior to 3D-CTA for preoperative CEA planning. METHODS: The fusion images showed vascular structures obtained by MRA, plaque observed by BB-MRI, and bone structures shown by CT. Spatial localization accuracy was verified by directly overlaying contrast-enhanced 3D-CTA images on the fusion images. We validated this technique in 50 patients with unilateral ICA stenosis, 28 of whom underwent CEA. The 2D-distance CB MRA-CTA (the 2D distance difference between CB MRA and CB CTA perpendicular to the long axis of the carotid artery) was measured. We also compared the findings of the fusion image regarding the CB location and plaque distal end with the operative findings. RESULTS: The median 2D distance CB MRA-CTA was 1 mm. CB MRA was located distal and proximal to CB CTA in 21and 29 patients, respectively. The CB location and fusion-image plaque were consistent with the intraoperative findings in all CEA patients. CONCLUSIONS: Fusion images created from MRA, BB-MRI, and noncontrast CT were feasible as an alternative to 3D-CTA for patients with contrast contraindications.

Pull-Force Generated by the Revolving High-speed Drill Shaft Results in Unexpected Tissue Wrapping Around the Shaft.

BACKGROUND: Despite holding soft tissue away from high-speed drills during surgery, tissue can unexpectedly wrap around the drill shaft. We performed experiments to examine what precipitates such mishaps. METHODS: In a windless environment, a Signature Drill System (Stryker) featuring a 4-mm diameter coarse diamond or cutting bit was placed parallel to a suspended strip of polypropylene. The distance between the end of the strip and the drill shaft or bits was 4 or 8 mm. In another experiment, we placed the drill horizontally 10 mm above the top of dry-ice fog. The maximum drill speed was 75,000 rpm, and the horizontal motion of the polypropylene strip and the vertical motion of the dry-ice fog were recorded by a video camera. RESULTS: In the experiments, the strip parallel to the vertical shaft and the dry-ice fog were pulled toward the shaft; the higher the revolving drill speed, the faster its motion. On the other hand, in experiments where the end of the strip was next to either bit, no such motion was observed. CONCLUSIONS: The pulling force generated by revolving high-speed drill shafts may result in tissue wraparound even when soft tissue is held away from the shaft.

Comparative Metabolomics of Small Molecules Specifically Expressed in the Dorsal or Ventral Marginal Zones in Vertebrate Gastrula.

Many previous studies have reported the various proteins specifically secreted as inducers in the dorsal or ventral regions in vertebrate gastrula. However, little is known about the effect on cell fate of small molecules below 1000 Da. We therefore tried to identify small molecules specifically expressed in the dorsal marginal zone (DMZ) or ventral marginal zone (VMZ) in vertebrate gastrula. Small intracellular and secreted molecules were detected using explants and supernatant samples. Hydrophilic metabolites were analyzed by capillary ion chromatography-mass spectrometry and liquid chromatography-mass spectrometry, and lipids were analyzed by supercritical fluid chromatography-tandem mass spectrometry. In total, 190 hydrophilic metabolites and 396 lipids were identified. The DMZ was found to have high amounts of glycolysis- and glutathione metabolism-related metabolites in explants, and the VMZ was richer in purine metabolism-related metabolites. We also discovered some hydrophilic metabolites and lipids differentially contained in the DMZ or VMZ. Our research would contribute to a deeper understanding of the cellular physiology that regulates early embryogenesis.

Using a Carpenter's Square to Localize Narrow or Multilayered Chronic Subdural Hematomas Diagnosed on Computed Tomography.

BACKGROUND: Chronic subdural hematomas (CSDHs) with narrow or multilayered hematomas must be accurately localized for burr hole drainage. We present a simple alternative localization method using conventional computed tomography (CT) scans acquired for the initial diagnosis and a commercially available carpenter's square (CS). METHODS: Using our novel method, we localized 77 narrow or multilayered CSDHs. A single burr hole site on the thickest portion of narrow hematomas or on the site allowing access to both the isolated superficial layer and the deep layer of multilayered hematomas was identified on axial CT images; the image was parallel to the orbitomeatal line (OML). On the target CT slice, the level from the OML and from the surface of the forehead to the intended burr hole (sagittal distance) was measured. The OML and the level of the CT target slice were marked using the CS. Then, the CS was placed at the marked target level; the 2 edges of the CS were situated on the frontal and temporal scalp and parallel to the OML and the sagittal line. The sagittal distance was then marked. RESULTS: All burr holes reached the CSDHs. The mean deviation of the burr holes was 4.7 mm inferior and 1.4 mm anterior to the intended site. In 65 instances (84.4%), a deviation within 10 mm was observed in both the superoinferior and the anteroposterior directions. CONCLUSIONS: Our simple and inexpensive method can localize narrow or multilayered CSDHs with acceptable accuracy and increases the efficiency of routine clinical work.

Protocadherin-1 is expressed in the notochord of mouse embryo but is dispensable for its formation.

Notochord is an embryonic midline structure that serves as mechanical support for axis elongation and the signaling center for the surrounding tissues. Precursors of notochord are initially induced in the dorsal most mesoderm region in gastrulating embryo and separate from the surrounding mesoderm/endoderm tissue to form an elongated rod-like structure, suggesting that cell adhesion molecules may play an important role in this step. In Xenopus embryo, axial protocadherin (AXPC), an orthologue of mammalian Protocadherin-1 (PCDH1), is indispensable for the assembly and separation from the surrounding tissue of the notochord cells. However, the role of PCDH1 in mammalian notochord remains unknown. We herein report that PCDH1 is expressed in the notochord of mouse embryo and that PCDH1-deficient mice form notochord normally. First, we examined the temporal expression pattern of pcdh1 and found that pcdh1 mRNA was expressed from embryonic day (E) 7.5, prior to the stage when notochord cells detach from the surrounding endoderm tissue. Second, we found that PCDH1 protein is expressed in the notochord of mouse embryos in addition to the previously reported expression in endothelial cells. To further investigate the role of PCDH1 in embryonic development, we generated PCDH1-deficient mice using the CRISPR-Cas9 system. In PCDH1-deficient embryos, notochord formation and separation from the surrounding tissue were normal. Structure and marker gene expression of notochord were also unaffected by loss of PCDH1. Major vascular patterns in PCDH1-deficient embryo were essentially normal. These results suggest that PCDH1 is dispensable for notochord formation, including the tissue separation process, in mammalian embryos. We successfully identified the evolutionary conserved expression of PCDH1 in notochord, but its function may differ among species.

[Anterior Interosseous Nerve Palsy with Isolated Flexion Palsy of the Thumb or Index Finger as an Initial Symptom:Two Case Reports].

Case 1: A 73-year-old man who had undergone neurolysis for right cubital tunnel syndrome complained of difficulty using chopsticks. Froment's sign test showed that the interphalangeal(IP)joint of the right thumb that had flexed preoperatively was extended. This finding was considered to indicate recovery from ulnar neuropathy, and the patient was closely followed up. One year later, the patient was unable to push a camera shutter button and was unable to flex the IP joint of the thumb and the distal interphalangeal(DIP)joint of the index finger, a characteristic symptom of anterior interosseous nerve(AIN)palsy. Therefore, the patient underwent AIN neurolysis and subsequently reported slight improvement in his condition. Case 2: A 60-year-old woman reported difficulty performing computer mouse clicks with her right hand. As flexing the index finger DIP joint was difficult, a local lesion was suspected, and the patient was closely followed up. One year later, the patient was unable to push the button of a ballpoint pen with her thumb. Extension of the thumb and index finger indicated AIN palsy. The patient refused treatment and was only followed up. The following year, the patient reported that the weakness improved. Simultaneous flexion palsy of the thumb and index finger can lead to a diagnosis of AIN palsy. However, flexion palsy of a single finger in incomplete AIN palsy, as reported here, is often overlooked because of its similarity to the flexor tendon rupture. Awareness regarding this incomplete form of AIN palsy is needed for early and correct diagnosis.

Cortical Neural Damage Associated with Cerebral Hyperperfusion after Reperfusion Therapy for Acute Ischemic Stroke: 123I-iomazenil Single-photon Emission Computed Tomography Findings.

We present an 88-year-old man with cerebral hyperperfusion (CH) after acute reperfusion therapy. He developed acute cerebral ischemia as a result of occluded middle cerebral artery that was subsequently recanalized with endovascular thrombectomy. I-123 N-isopropyl-p-iodoamphetamine single-photon emission computed tomography (SPECT) after reperfusion therapy showed increased cerebral blood flow (CBF) in brain areas that exhibited no abnormal findings on magnetic resonance imaging (MRI). Follow-up MRI did not demonstrate structural brain damage associated with CH. However, later I-123 iomazenil SPECT imaging showed a reduction in benzodiazepine receptor binding potential (BRBP) in these areas, a finding that correlates with cortical neural damage. CH is being increasingly observed after endovascular treatment for acute stroke. However, little is known about CH when not associated with cerebral hemorrhage or infarction. The role of CH after reperfusion therapy in causing brain damage remains unclear. BRBP on I-123 iomazenil SPECT images is useful to evaluate brain neural density: a reduction in cortical BRBP indicates cortical neural damage or loss. Our findings suggest that post-reperfusion hyperperfusion induces cortical neural damage even in the absence of associated brain infarction or hemorrhage on MRI. Early postoperative SPECT is recommended to detect CH after acute reperfusion therapy. CH should be considered when the recovery from stroke is unexpectedly poor for a patient.

Aneurysms Arising from Persistent Arteries in the Vertebrobasilar Paramedian Longitudinal Axis: Two Case Reports.

A 50-year-old man and a 69-year-old woman with consciousness disturbance were diagnosed to have suffered from subarachnoid hemorrhage (SAH) involving the posterior fossa. In both cases, the initial 3D CT angiogram failed to reveal the SAH source in the vertebrobasilar system. Delayed 3D rotational angiography revealed aneurysms on unfamiliar aberrant arteries. One was a dissecting aneurysm located between the proximal part of the posterior inferior cerebellar artery and the distal part of the intracranial vertebral artery. It was trapped and resected; the patient subsequently presented with lateral medullary symptoms. The other aneurysm was between the distal posterior and the distal anterior inferior cerebellar artery. It was successfully embolized; there were no complications. We think that the aberrant aneurysm-harboring vessels encountered in these two patients were primitive arteries on or adjacent to the vertebrobasilar paramedian longitudinal axis and that they persisted past the embryologic stage. Such aneurysms arising from unfamiliar persistent arteries beside the brainstem are extremely rare but must be considered when the SAH source is not detected in the trunk of the vertebrobasilar system.

[Lymphorrhea at the Site of Repeated Fascia Lata Harvesting:A Case Report].

This 74-year-old man had undergone a third re-operation for anaplastic meningioma in the convexity six weeks before he was referred to us. He presented with a bulge on the lateral aspect of the left thigh. We observed a fresh fascia lata harvesting scar that extended peripherally from an old proximal scar. The bulge was colorless. The aspirated subcutaneous fluid(more than 200mL)was watery and yellowish;there was no evidence of abscess or hematoma. Although the bulge shrank after aspiration and the placement of a compression bandage, it recurred in three days. Surgery-associated lymphorrhea was the diagnosis given. Goreisan, a herbal medicine for hydrostatic modulation, was administered. One week later, the bulge diminished in size. Harvesting of the fascia lata in the lateral aspect of the thigh is usually safe. However, additional dissection and peripheral extension due to repeated harvesting risks damaging the superficial lymphatic pathways because of scar formation after earlier surgeries and the hyperdense distribution of the lymphatic pathways in the peripheral part. When subcutaneous fluid collection after fascia lata harvesting is refractory, lymphorrhea must be considered in the differential diagnosis.

Ergonomics-based Positioning of the Operating Handle of Surgical Microscopes.

Handling surgical microscopes with one hand requires force, especially when gripping the operating handle (OH) to swing the optic axis toward the surgeon and when moving it laterally or medially. These physical issues may be attributable to the non-ergonomic handling of the OH. To optimize the ease of OH handling, we applied ergonomic criteria to the positioning of the OH, i.e. holding the OH at as little ulnar deviation as possible and at abduction to strengthen the grip and ease arm rotation. Of eight male surgeons holding the OH of a mechanically counterbalanced surgical microscope, the OPMI Neuro/NC4 (Carl Zeiss AG), in ergonomics-based positions, six experienced reduced fatigue in the upper extremity. All reported that their hold on the microscope was firm when it unexpectedly became unbalanced. Ergonomics-based OH positioning, i.e. placing the involved muscles in the optimal length-tension relationship, may generate sufficient force for moving the microscope efficiently and reduce arm fatigue.

[False Aneurysm Formation at the Origin of the M2 Segment of the Middle Cerebral Artery Following a Blunt Head Trauma:A Case Report].

A 43-year-old man fell from a 1m-high truck loading platform and sustained an injury in the occiput. On admission, he was alert and neurologically intact. Computed tomography(CT)showed hemorrhage in the right sylvian fissure and parenchyma adjacent to the sphenoid wing. Magnetic resonance angiography detected no abnormalities. The course was uneventful for 11 days. However, on the 12th day, he spontaneously manifested with stupor. CT and CT angiography revealed expansion of the hemorrhage and an aneurysm arising from the origin of the M2 segment of the right middle cerebral artery. After superficial temporal artery to middle cerebral artery bypass, the aneurysm, a reddish pulsatile mass, was removed from the origin of the torn M2 segment, and the laceration was sutured. The histological diagnosis was false aneurysm. He recovered and was discharged 4 months after the trauma. Traumatic cerebral aneurysms are rare in the proximal segment of the middle cerebral artery. However, they should be distinguished from nontraumatic true aneurysms in the same region and treated as false aneurysms, which are major and critical traumatic aneurysms, for favorable outcomes.

Angiographic Characterization of the External Carotid Artery: Special Attention to Variations in Branching Patterns.

Knowledge of branching patterns of external carotid artery (ECA) is essential for planning and execution of head and neck surgeries. Digital subtraction angiography (DSA) images of 532 ECAs from 302 consecutive patients were retrospectively evaluated. We classify the branch variants of ECA into three types, simply based on the number of branches arising close together. Type A, Type B, and Type C variants are defined as two, three, and four or more branches of ECAs arising at a common point from the proximal ECA, respectively. In this classification, the distal ECA was counted as one branch. Of 532 ECAs, Type A was found in 344 ECAs (64.6%) of 237 patients (78.5%), Type B in 134 ECAs (25.2%) of 110 patients (36.4%), and Type C in 54 ECAs (10.2%) of 49 patients (16.2%). The distance from the common carotid artery (CCA) bifurcation to the first branch of ECA with Type C was 14.7 ± 6.6 mm; its distance is shorter compared with Type A (21.8 ± 15.6 mm) and Type B (20.6 ± 8.9 mm) (P < 0.05). The position of CCA bifurcation with Type C was detected at the third-fourth junction cervical vertebral level or higher in 52 of 54 ECAs (96.3%), significantly higher than those of the other types (P < 0.05). In conclusion, Type C ECA has aggregated vessels with short distance from CCA and high position of CCA bifurcation. Type C ECA is not uncommon; thus, special consideration should be paid to avoid complications during surgeries.

Half-tied Stay Suture Technique for Cerebrovascular End-to-side Anastomosis: A Technique to Expand the View of the Hidden Ostium.

In cerebrovascular end-to-side anastomosis, thick, hard donor arteries overlying thin recipient arteries impair the view of the ostium, and may result in occlusion of the anastomosis. To improve the intraoperative view, we modified the stay sutures. After performing standard recipient arteriotomy and placing the first stay suture, we half-tied the second stay suture to leave a loop: half-tied stay suture (HSS). The thread of the HSS was secured with a clip to avoid slippage. For suturing side A, the clip pulling on the HSS was gently moved to the opposite side of side A, i.e. to side B, and the donor artery was revolved by several degrees to side B; the first stay suture was used as the fulcrum. Under the expanded view of the ostium, untied interrupted sutures were placed on side A. Then the donor vessel was revolved to the opposite side and side B was sutured in the same manner. At last, the HSS and all other sutures were tied fully. Our HSS method was used in three adults who underwent superficial temporal- to middle cerebral artery anastomosis despite anticipated poor visibility of the ostium. Compared with the conventional method, the view of the ostium was expanded with less manipulation of the vessel walls. There were no complications, and the anastomosis remained patent in all three patients. This simple modification of the stay sutures reduces the risk of anastomotic occlusion due to iatrogenic vascular damage by excessive manipulation under a restricted view.

Axis elongation during Xenopus tail-bud stage is regulated by GABA expressed in the anterior-to-mid neural tube.

The receptors of gamma-aminobutyric acid (GABA), which is a well-known neurotransmitter, are expressed in the anterior-to-mid neural tube at an early stage of Xenopus development, but there has been no report on the role of GABA in the presumptive central nervous system. Therefore, we tried to reveal the function of GABA for Xenopus early embryogenesis. We first confirmed that the region expressing a gene encoding glutamate decarboxylase 1 (gad1), which is an enzyme that catalyzes the decarboxylation of L-glutamate to GABA, overlapped with that of several genes encoding GABA receptors (gabr) in the neural tube. Metabolome analysis of culture medium of dorsal tail-bud explants containing the neural tube region of tail-bud stage embryos also revealed that GABA was expressed at this stage. Then, we examined the treatment of pentylenetetrazole (PTZ) and picrotoxin (PTX), which are known as inhibitors of GABA receptors (GABA-R), on the early stages of Xenopus embryogenesis, and found that axis elongation in the tail-bud was inhibited by both treatments, and these phenotypic effects were rescued by co-treatment with GABA. Moreover, our spatial- and temporal-specific inhibitor treatments revealed that the gabr- and gad1-overlapped region, which presents at the anterior-to-mid neural tube during the tail-bud stages, was much more sensitive to PTZ and thus caused severe inhibition of axis elongation. Taken together, our results indicate that the small ligand molecule GABA functions as a regulator to induce the axis elongation event in the tail-bud during early embryogenesis via direct stimulation of the neural tube and indirect stimulation of the surrounding area.

Rupture of Thrombosed Cerebral Aneurysm During Antithrombotic Therapy for Ischemic Stroke: Case Report and Literature Review.

BACKGROUND: Thrombosed cerebral aneurysm (TCA) can cause cerebral infarction. However, treatment of cerebral infarction due to embolism from TCA is controversial because of the risk of rupture, and no consensus has been established for the treatment of patients with this condition. CASE DESCRIPTION: A 75-year-old woman suffered left hemiparesis. Computed tomography (CT) showed a high-density round mass in the right sylvian fissure, which was suspected to be a nonruptured TCA. Magnetic resonance (MR) angiography and CT angiography demonstrated an aneurysm in the distal part of the right middle cerebral artery with poor opacification of most of the aneurysm, suggesting partial thrombosis. Diffusion-weighted MR imaging revealed high intensity in the right frontal lobe, in a distribution distal to the aneurysm. The diagnosis was cerebral infarction due to embolism from a partially thrombosed aneurysm. She was treated with antithrombotic therapy. On day 4, she suddenly became comatose. CT and CT angiography revealed subarachnoid hemorrhage (SAH) and enlarged opacification in the aneurysm, respectively. She underwent neck clipping of the aneurysm, but her neurologic improvement was poor. TCA causing ischemic stroke followed by SAH is extremely rare, with only 4 previous reported cases. All patients had received antithrombotic therapies, and most aneurysms had ruptured within a few days after starting antithrombotic therapy. The outcomes were extremely poor. CONCLUSIONS: We suggest that antithrombotic therapy might be avoided for these patients. Early surgical treatment without antithrombotic therapy is recommended to prevent aneurysm rupture and recurrent distal embolism from the TCA.

Visual disorders caused by cranial arteriovenous fistula with venous drainage into the superior ophthalmic vein.

BACKGROUND: Although the abnormal venous drainage into the superior ophthalmic vein (SOV) is a well-known entity responsible for ocular symptoms, it remains unclear to what degree it affects the visual function. The purpose of this study was to evaluate the incidence, characteristics and outcomes of the visual disorders in patients with intracranial arteriovenous fistula (AVF) with venous drainage into the SOV. METHODS: This retrospective study involved eight patients diagnosed with intracranial AVFs with abnormal venous drainage into the SOV between January 2014 and December 2016. RESULTS: The most common location of AVF was the cavernous sinus (CS) in five patients, followed by the intraorbit in two patients and superior sagittal sinus (SSS) in one patient. Visual disorders were detected in three patients (two intraorbit and one CS). The visual field contraction was observed in a patient with intraorbital AVF, and the reduction of visual acuity was confirmed in another patient with intraorbital AVF and a patient with CS dural AVF. All patients underwent an interventional treatment consisting of endovascular embolisation, stereotactic radiosurgery or both, which was selected based on their angioarchitecture. Although angiographic cure of AVF was confirmed in all patients, visual function did not fully recover in two patients with intraorbital AVF. CONCLUSIONS: In cases of intraorbital AVF, visual disorders are more frequent and can result in poorer outcomes compared with other dural AVFs with drainage into the SOV. Early diagnosis and treatment are crucial to preserve the visual function of patients with intraorbital AVF.

Cluster of Differentiation 46 Is the Major Receptor in Human Blood-Brain Barrier Endothelial Cells for Uptake of Exosomes Derived from Brain-Metastatic Melanoma Cells (SK-Mel-28).

Brain metastasis is a frequent complication of cancer and may be mediated, at least in part, by the internalization of cancer-cell-derived exosomes into brain capillary endothelial cells. Clarifying the mechanism(s) of this internalization is of interest because it could help us to develop ways to block brain metastasis, as well as affording a potential new route for drug delivery into the brain. Therefore, the purpose of the present study was to address this issue by identifying the receptors involved in the internalization of exosomes derived from a brain-metastatic cancer cell line (SK-Mel-28) into human blood-brain barrier endothelial cells (hCMEC/D3 cells). The combination of sulfo-SBED-based cross-linking and comprehensive proteomics yielded 20 proteins as exosome receptor candidates in hCMEC/D3 cells. The uptake of PKH67-labeled exosomes by hCMEC/D3 cells measured at 37 °C was significantly reduced by 95.6% at 4 °C and by 15.3% in the presence of 1 mM RGD peptide, an integrin ligand. Therefore, we focused on the identified RGD receptors, integrin α5 and integrin αV, and CD46, which is reported to act as an adenovirus receptor, together with integrin αV. A mixture of neutralizing antibodies against integrin α5 and integrin αV significantly decreased the exosome uptake by 11.8%, while application of CD46 siRNA reduced it by 39.0%. Immunohistochemical analysis confirmed the presence of CD46 in human brain capillary endothelial cells. These results suggest that CD46 is a major receptor for the uptake of SK-Mel-28-derived exosomes by human blood-brain barrier endothelial cells (hCMEC/D3 cells).