Genome-Wide Association Study with Three Control Cohorts of Japanese Patients with Esotropia and Exotropia of Comitant Strabismus and Idiopathic Superior Oblique Muscle Palsy.

Esotropia and exotropia in the entity of comitant strabismus are multifactorial diseases with both genetic and environmental backgrounds. Idiopathic superior oblique muscle palsy, as the predominant entity of non-comitant (paralytic) strabismus, also has a genetic background, as evidenced by varying degrees of muscle hypoplasia. A genome-wide association study (GWAS) was conducted of 711 Japanese patients with esotropia (n= 253), exotropia (n = 356), and idiopathic superior oblique muscle palsy (n = 102). The genotypes of single nucleotide polymorphisms (SNPs) were determined by Infinium Asian Screening Array. Three control cohorts from the Japanese population were used: two cohorts from BioBank Japan (BBJ) and the Nagahama Cohort. BBJ (180K) was genotyped by a different array, Illumina Infinium OmniExpressExome or HumanOmniExpress, while BBJ (ASA) and the Nagahama Cohort were genotyped by the same Asian array. After quality control of SNPs and individuals, common SNPs between the case cohort and the control cohort were chosen in the condition of genotyping by different arrays, while all SNPs genotyped by the same array were used for SNP imputation. The SNPs imputed with R-square values ≥ 0.3 were used to compare the case cohort of each entity or the combined entity with the control cohort. In comparison with BBJ (180K), the esotropia group and the exotropia group showed CDCA7 and HLA-F, respectively, as candidate genes at a significant level of p < 5 × 10-8, while the idiopathic superior oblique muscle palsy group showed DAB1 as a candidate gene which is involved in neuronal migration. DAB1 was also detected as a candidate in comparison with BBJ (ASA) and the Nagahama Cohort at a weak level of significance of p < 1 × 10-6. In comparison with BBJ (180K), RARB (retinoic acid receptor-ß) was detected as a candidate at a significant level of p < 5 × 10-8 in the combined group of esotropia, exotropia, and idiopathic superior oblique muscle palsy. In conclusion, a series of GWASs with three different control cohorts would be an effective method with which to search for candidate genes for multifactorial diseases such as strabismus.

A cell competition system with one gene expression from a single-copy gene in one cell.

Even with advanced plasmid and viral vectors, attaining copy numbers of multiple genes among different transfected cells is challenging. We achieved one gene expression from a single-copy gene in one cell using a transgene competition system, a combination of the Kazusa cDNA clones and our dual recombinase-mediated cassette exchange system. All 48 nuclear receptors were simultaneously expressed in one dish at the same expression level in HEK293 using this system, and the cell proliferation rate was compared. Significant differences were observed between cells transfected with CMV- or EF1 promoter-driven expression of the 48 nuclear receptors after 8 weeks. The EF1-NR1I2 cell line, which exhibited the highest increase from 2 to 8 weeks, showed 1.13-fold higher proliferation than the EF1-DsRed line. On the other hand, the EF1-NR4A1 cell line, which showed the maximum decrease at 8 weeks, showed 0.88-fold lower proliferation than the EF1-DsRed line. The results were confirmed in both our transgene competition system and long-term growth experiments. Our transgene competition system offers a wide-range, simple, and accurate cell competition method.

Characterization of carotid plaques using chemical exchange saturation transfer imaging.

PURPOSE: The preoperative assessment of carotid plaques is necessary to render revascularization safe and effective. The aim of this study is to evaluate the usefulness of chemical exchange saturation transfer (CEST)-MRI, particularly amide proton transfer (APT) imaging as a preoperative carotid plaque diagnostic tool. METHODS: We recorded the APT signal intensity on concentration maps of 34 patients scheduled for carotid endarterectomy. Plaques were categorized into group A (APT signal intensity ≥ 1.90 E-04; n = 12) and group B (APT signal intensity < 1.90 E-04; n = 22). Excised plaques were subjected to histopathological assessment and, using the classification promulgated by the American Heart Association, they were classified as intraplaque hemorrhage-positive [type VI-positive (tVI+)] and -negative [no intraplaque hemorrhage (tVI-)]. RESULTS: Of the 34 patients, 22 (64.7%) harbored tVI+- and 12 (35.3%) had tVI- plaques. The median APT signals were significantly higher in tVI+- than tIVI- patients (2.43 E-04 (IQR = 0.98-4.00 E-04) vs 0.54 E-04 (IQR = 0.14-1.09 E-04), p < .001). Histopathologically, the number of patients with tVI+ plaques was significantly greater in group A (100%, n = 12) than group B (45%, n = 22) (p < .01). The number of symptomatic patients or asymptomatic patients with worsening stenosis was also significantly greater in group A than group B (75% vs 36%, p < .01). CONCLUSION: In unstable plaques with intraplaque hemorrhage and in patients with symptoms or progressive stenosis, the ATP signals were significantly elevated. CEST-MRI studies has the potential for the preoperative assessment of the plaques' characteristics.

Transcriptomic Analysis Reveals Sixteen Potential Genes Associated with the Successful Differentiation of Antibody-Secreting Cells through the Utilization of Unfolded Protein Response Mechanisms in Robust Responders to the Influenza Vaccine.

The seasonal influenza vaccine remains one of the vital recommended infection control measures for the elderly with chronic illnesses. We investigated the immunogenicity of a single dose of influenza vaccine in 123 seronegative participants and classified them into four distinct groups, determined by the promptness of vaccine response, the longevity of humoral immunity, and the likelihood of exhibiting cross-reactivity. Subsequently, we used transcriptional profiling and differential gene expression analysis to identify potential genes directly associated with the robust response to the vaccine. The group of exemplary vaccine responders differentially expressed 16 genes, namely: MZB1, MYDGF, TXNDC5, TXNDC11, HSP90B1, FKBP11, PDIA5, PRDX4, CD38, SDC1, TNFRSF17, TNFRSF13B, PAX5, POU2AF1, IRF4, and XBP1. Our findings point out a list of expressed proteins that are related to B cell proliferation, unfolded protein response, and cellular haemostasis, as well as a linkage of these expressions to the survival of long-lived plasma cells.

Nonconvulsive status epilepticus in patients with acute subarachnoid hemorrhage is associated with negative arterial spin labeling on peri-ictal magnetic resonance images.

Purpose: Non-convulsive status epilepticus (NCSE) is characterized by repetitive or continuous seizures without convulsions. Arterial spin labeling (ASL) is useful for assessing hyperperfusion due to neurovascular unit coupling in patients with NCSE; subarachnoid hemorrhage (SAH) impairs the neurovascular unit. We hypothesized that the sensitivity of ASL in detecting NCSE is low in patients with SAH during the acute phase. Methods: Based on ASL findings obtained within 48 h after the clinical suspicion of focal-onset NCSE, we divided 34 patients into ASL-negative (no hyperperfusion; n = 10) and ASL-positive (confirmed hyperperfusion; n = 24) groups. We further divided the two groups according to the NCSE etiology: patients who were diagnosed with NCSE within 14 days after SAH onset (acute SAH, n = 11) and patients with NCSE due to factors other acute SAH (n = 23) and compared their characteristics. Results: In 10 of the 34 patients (29.4 %) the ASL findings were normal. The rate of acute SAH was significantly higher in ASL-negative- (n = 8, 80.0 %) than ASL-positive patients (n = 3, 12.5 %). The rate of patients in aphasic status was significantly lower in ASL-negative patients (n = 1, 10 %) than in ASL-positive patients (n = 12, 50.0 %). Conclusion: Normal ASL findings alone should not be used to exclude a diagnosis of NCSE particularly in patients in the acute phase of SAH with deterioration or no improvement in consciousness.

Coexistence of anterior choroidal artery and posterior cerebral artery retia mirabilia presenting with subarachnoid hemorrhage: illustrative case.

BACKGROUND: A rete mirabile is a rare vascular anomaly, with posterior cerebral artery (PCA) involvement being especially rare. Its pathogenesis has been speculated as a remnant of "distal annexation" between the primitive anterior choroidal artery (AchA) and the PCA at this site, but the exact mechanisms remain unclear. OBSERVATIONS: A 29-year-old man presented with subarachnoid hemorrhage. Arteriovenous malformation in the medial temporal lobe was initially suspected, but an arteriovenous shunt was not detected. First, conservative treatment was administered; however, rebleeding occurred 1 month later. Carotid angiography revealed a network-like cluster of blood vessels at the choroidal point of the AchA, suggesting a rete mirabile; these vessel clusters led to the persistent temporo-occipital branch of the AchA. Furthermore, an aneurysm was detected at the junction between the rete mirabile and the persistent temporo-occipital branch of the AchA. Additionally, vertebral angiography demonstrated a rete mirabile at the P2 segment. These findings suggested the coexistence of AchA and PCA retia mirabilia. Consequently, the aneurysm was clipped using a subtemporal approach to prevent re-rupture, and the postoperative course was uneventful. LESSONS: This first report of coexisting AchA and PCA retia mirabilia supports the remnant of distal annexation between the primitive AchA and the PCA as the reason for rete formation at this site.

Experience of using coronary perfusion balloon catheter for acute middle cerebral artery occlusion.

Background: We present the case of an individual with acute occlusion of the middle cerebral artery caused by atherosclerosis. The patient underwent angioplasty using a coronary perfusion balloon, which resulted in a favorable clinical outcome. Case Description: A 66-year-old male patient presented with an acute onset of right hemiplegia and dysarthria. Magnetic resonance imaging revealed an occlusion of the left middle cerebral artery, and alteplase was administered, followed by a mechanical thrombectomy and intracranial balloon catheter angioplasty. Due to restenosis, a coronary perfusion balloon catheter was used for a 15-minute angioplasty procedure while maintaining the perfusion. This treatment approach led to the recanalization of the artery and favorable clinical outcomes. Conclusion: The coronary perfusion balloon may represent a viable therapeutic alternative for the management of refractory intracranial atherosclerotic large vessel occlusion.

Trivalent inactivated influenza vaccine response and immunogenicity assessment after one week and three months in repeatedly vaccinated adults.

BACKGROUND: The influenza vaccine administrated every year is a recommended infection control procedure for individuals above the age of six months. However, the effectiveness of repeated annual vaccination is still an active research topic. Therefore, we investigated the vaccine immunogenicity in two independent groups: previously vaccinated versus non-vaccinated individuals at three time points; prior vaccination, one week and three months post vaccination. The assessment enabled us to evaluate the elicited immune responses and the durability of the induced protection in both groups. RESEARCH DESIGN AND METHODS: A research study was conducted to assess the immunogenicity of a single dose of Trivalent Inactivated Influenza Vaccine (A/H1N1, A/H3N2, and B) in 278 healthy adults aged between 32 and 66 years. Almost half of the participants, 140 (50·36%), received influenza vaccination at least once precursor to past influenza seasons. One blood sample was taken prior to vaccination for complete blood analysis and baseline immunogenicity assessment. The selected study participants received a single vaccine dose on the first day, and then followed up for three months. Two blood samples were taken after one week and three months post vaccination, respectively, for vaccine immunogenicity assessment. RESULTS: Before vaccination, the seroprotection, defined as a hemagglutination-inhibiting titer of =>1:40, was detected for the three vaccine virus strains in 20 previously vaccinated participants (14·29%) [8·95%, 21·2%]. We compared the overall vaccine response for the three virus strains using a normalized response score calculated from linearly transformed titer measurements; the score before vaccination was 84% higher in the previously vaccinated group and the mean difference between the two groups was statistically significant. Three months post-vaccination, we didn't find a significant difference in vaccine responses; the number of fully seroprotected individuals became 48 (34·29%) [26·48%, 42·77%] in the previously vaccinated group and 59 (42·75%) [34·37%, 51·45%] in the non-vaccinated group. The calculated response score was almost equal in both groups and the mean difference was no longer statistically significant. CONCLUSION: Our findings suggest that a single dose of influenza vaccine is equally protective after three months for annually vaccinated adults and first-time vaccine receivers.

Stent retrieval for free-floating thrombus attached to carotid artery stenosis: A report of two cases.

Background: We report two cases who underwent mechanical thrombectomy using a stent retriever in advance of urgent carotid artery stenting (CAS) for carotid artery stenosis with free-floating thrombus (FFT). Case Description: Two patients showing symptomatic carotid artery stenosis with FFT underwent urgent endovascular surgery due to progressive neurological symptoms. The first case showed an FFT with 70% internal carotid artery (ICA) stenosis. After the completion of the common and external carotid artery balloon and distal ICA filter protection, we deployed a 6-mm-diameter stent retriever in the distal part of the stenosis. The white thrombus was retrieved; the angiographic shadow of the FFT disappeared; and CAS was performed. In the second case, due to a 90% severe stenosis lesion with FFT, balloon angioplasty was performed on the lesion using the push wire of the stent retriever. After angioplasty, the stent retriever was smoothly retrieved, and CAS was performed. Postoperative magnetic resonance imaging showed an increase in cerebral embolism in the first case; however, the patient's neurological symptoms improved. The second case showed in-stent plaque protrusion and required two additional stent placements; the patient showed no worsening of his neurological symptoms. Conclusion: In cases of carotid artery stenosis with FFT, it is technically possible to retrieve a thrombus with a stent retriever. Although thrombus removal may help reduce the risk of ischemic complications in a series of urgent CAS procedures, there are concerns such as mechanical irritation to the carotid artery plaque, and its indications and alternative treatments should be carefully considered.

Internal radiation exposure from 137Cs and its association with the dietary habits of residents from areas affected by the Chernobyl nuclear accident, Ukraine: 2016-2018.

The total annual effective dose has steadily decreased since the fallout of the Chernobyl Nuclear Power Plant. However, chronic internal exposure to 137Cs still persists and fluctuates in a complex and unpredictable manner. Recently, body contamination was found to primarily occur owing to the intake of forest foodstuffs that contain long-lived 137Cs. Forest foodstuffs may have up to 100 times higher concentration of cesium than does local milk and meat. The present study aimed to investigate the recent dietary habits of residents in the Zhytomyr region of Ukraine, and assess the effect of the intake of forest foodstuffs on the increase in internal radioactivity from 137Cs. We screened 1,612 participants, from July 2016 to February 2018 for internal radioactivity, using whole-body counter at Korosten Medical Center and surveyed their background and intake habits. We analyzed the association among food type, intake frequency, and internal exposure dose. The analysis revealed that nearly 90% of the participants regularly consumed one of the forest foodstuffs (mushrooms, berries, fish) or milk. Nearly 80% of the participants indicated that they consumed mushrooms or berries or both. Internal radioactivity was detected in 30% of the participants. The diet that included mushrooms exhibited the highest internal radioactivity. The lowest Bq/kg concentration was observed in the only-berry group, following the no-intake group. There was a significant correlation between the intake frequency and the magnitude of Bq/kg. Radioactivity detected in the mushroom-berry and only-mushroom group were 8.6 and 9.2 Bq/kg, respectively. The lowest and highest intake frequency showed a radioactivity of 2.4 and 7.5 Bq/kg, respectively. Radioactivity in the winter season was significantly higher than that in other seasons. In conclusion, our study revealed that internal radioactivity varies depending on the type of food, intake frequency, and season.

Evaluation of Serial Intra-Arterial Indocyanine Green Videoangiography in the Surgical Treatment of Cranial and Craniocervical Junction Arteriovenous Fistulae: A Case Series.

BACKGROUND AND OBJECTIVES: Intravenous indocyanine green (IV-ICG) videoangiography is commonly performed to detect blood flow in the microscopic view. However, intra-arterial ICG (IA-ICG) videoangiography provides high-contrast imaging, repeatability within a short period of time, and clear-cut separation of the arterial and venous phases compared with IV-ICG. These features are useful for detecting retrograde venous drainage (RVD) and shunt occlusion in arteriovenous fistulae (AVF) surgery. This study aimed to investigate whether IA-ICG videoangiography can be repeatable within a short period of time and be useful for detecting RVD and shunt occlusion in cranial- and craniocervical junction (CCJ)-AVF surgery. METHODS: Between January 2012 and December 2022, 50 patients were treated with endovascular or surgical intervention for cranial- and CCJ-AVF at Tokushima University Hospital. Of these, 5 patients (6 lesions) underwent open surgery with IA-ICG videoangiography in a hybrid operating room. We analyzed the data of these 5 patients (6 lesions). RESULTS: There were 4/patient (median, range 2-12) and 3.5/lesion (median, range 2-10) intraoperative IA-ICG runs. IA-ICG videoangiography detected RVD in all patients. Clearance of IA-ICG-induced fluorescence was achieved within 30 seconds in all patients at each region of interest. After the disconnection of the fistulae, IA-ICG videoangiography and intraoperative digital subtraction angiography (DSA) confirmed the disappearance of RVD in all patients. There were no complications associated with IA-ICG videoangiography. CONCLUSION: This study showed that IA-ICG videoangiography is repeatable within a short period of time before and after obliteration and can be useful for detecting RVD and shunt occlusion in cranial- and CCJ-AVF surgery. IA-ICG videoangiography also allows intraoperative DSA studies in a hybrid operating room. Considering the recent advancements in hybrid operating rooms, combining IA-ICG videoangiography with intraoperative DSA is a useful strategy for cranial- and CCJ-AVF surgery.

Prognostic factors for acute large vessel occlusion with NIHSS 5 or lower.

BACKGROUND: Intravenous recombinant tissue plasminogen activator (IV rt-PA) and endovascular treatment have been performed for severe large vessel occlusion (LVO) and the results have been reported at high levels of evidence. However, acute treatment for LVO with mild symptom remains controversial. We retrospectively examined prognostic factors for LVO with mild symptoms. METHOD: We studied retrospectively the patients within 24 h of onset with large vessel occlusion with NIHSS score ??5. Outcomes were evaluated by modified Rankin Scale (mRS) at 90 days, with 0?2 defined as a good outcome and 3?6 as a poor outcome. Clinical characteristics of each case were examined. RESULT: Participants comprised 76 patients. Of the 76 patients. ICA occlusion showed good outcome in 17?/?19 cases (90%), whereas MCA occlusion showed good outcome in 36?/?54 cases (67%). Among the 14 cases showing positive results for distal intraarterial signal (d-IAS), outcomes were good in 6 cases (43%). On the other hand, the 32 d-IAS-negative cases showed good outcome in 28 cases (88%). Outcomes were thus significantly poorer for d-IAS-positive cases. CONCLUSION: MCA occlusion is associated with poor prognosis, even with NIHSS score ??5, and d-IAS may provide a predictor. J. Med. Invest. 70 : 22-27, February, 2023.

Differences in amyloid-ß and tau/p-tau deposition in blood-injected mouse brains using micro-syringe to mimic traumatic brain microhemorrhages.

BACKGROUND: Cerebral microbleeds (CMBs) due to traumatic brain injuries (TBI) have been shown to lead to cognitive decline and impairment. CMBs caused by TBI may be associated with pathophysiological mechanisms involving inflammation and the accumulation of amyloid-ß (Aß), tau, and phosphorylated tau (p-tau), contributing to cognitive abnormalities. However, their relationships remain unclear. OBJECTIVES: To test our hypothesis that Aß, tau, and p-tau are accumulated and regulated separately in mice with injuries imitating CMBs from TBI, we studied. METHODS: Seven-week-old C57BL/6 male mice were injected with 15 µL of heparinized autologous blood or saline by micro-syringe into the front lobe. Expression profiles and regulation of Aß, tau, and p-tau were assessed immunohistochemically over time. RESULTS: On day 7 after blood injection, Iba-1+ and S100B+ cells in damaged cortex adjacent to the injection site were higher than saline injection group and non-injected sham. On days 3-14, Aß deposition were gradually increased but normalized by day 28. In contrast, tau/p-tau deposition gradually increased during days 14-28 and dispersed along the corticomedullary junction adjacent to hem deposits, indicating different expression profiles from Aß. Deposits of Aß, but not tau/p-tau, were phagocytosed by CD163+ macrophages increased by Gc-protein macrophage-activating factor during days 7-28, suggesting different mechanisms of deposition and regulation between Aß and tau/p-tau. CONCLUSION: Deposition and regulation differ between Aß and tau/p-tau in mice with injuries mimicking CMBs from TBI. Further clarification of relationships between the pathologies of cognitive impairment and their neurodegenerative consequences is needed.

Design and implementation of a hybrid cloud system for large-scale human genomic research.

In the field of genomic medical research, the amount of large-scale information continues to increase due to advances in measurement technologies, such as high-performance sequencing and spatial omics, as well as the progress made in genomic cohort studies involving more than one million individuals. Therefore, researchers require more computational resources to analyze this information. Here, we introduce a hybrid cloud system consisting of an on-premise supercomputer, science cloud, and public cloud at the Kyoto University Center for Genomic Medicine in Japan as a solution. This system can flexibly handle various heterogeneous computational resource-demanding bioinformatics tools while scaling the computational capacity. In the hybrid cloud system, we demonstrate the way to properly perform joint genotyping of whole-genome sequencing data for a large population of 11,238, which can be a bottleneck in sequencing data analysis. This system can be one of the reference implementations when dealing with large amounts of genomic medical data in research centers and organizations.

Long-sheath Introducer-assisted Revascularization (L-SHARE) Technique for Treating Large-vessel Occlusion by a Giant Clot.

Revascularization for common carotid artery (CCA) occlusion might be difficult. We reported our strategy for revascularizing CCA occlusion by giant clots. A 94-year-old woman was transferred to our hospital because of right hemiparesis and aphasia. CCA occlusion and giant clots were detected on ultrasonography. We performed mechanical thrombectomy using a 9-Fr balloon-guiding catheter, stent retriever, and aspiration catheter through a 9-Fr long-sheath introducer [long-sheath introducer-assisted revascularization (L-SHARE) technique]. We successfully recanalized CCA occlusion using this method. The L-SHARE technique might be useful for recanalization of CCA occlusion.

Activation of the NLRP3/IL-1ß/MMP-9 pathway and intracranial aneurysm rupture associated with the depletion of ERα and Sirt1 in oophorectomized rats.

OBJECTIVE: Subarachnoid hemorrhage (SAH) due to intracranial aneurysm (IA) rupture is often a devastating event. Since the incidence of SAH increases especially in menopause, it is crucial to clarify the detailed pathogenesis of these events. The activation of vascular nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasomes has been studied in ischemic stroke and cardiovascular disease. However, the role of NLRP3 in IA rupture still needs to be explained. The authors sought to test their hypothesis that, under estrogen-deficient conditions, activation of NLRP3 inflammasomes via downregulation of the estrogen receptor (ER) facilitates IA rupture. METHODS: Ten-week-old female Sprague Dawley rats with and without oophorectomy were subjected to hemodynamic changes and hypertension (OVX+/HT and OVX-/HT, respectively) and fed a high-salt diet. Separately, using human brain endothelial cells (HBECs) and human brain smooth muscle cells (HBSMCs), the authors tested the effect of NLRP3 under estrogen-free conditions and in the presence of estradiol or of ER agonists. RESULTS: In OVX+/HT rats, the frequency of IA rupture was significantly higher than in OVX-/HT rats (p = 0.03). In the left posterior cerebral artery prone to rupture in OVX+/HT rats, the levels of the mRNAs encoding ERα and Sirt1, but not of that encoding ERß, were decreased, and the levels of the mRNAs encoding NLRP3, interleukin-1ß (IL-1ß), and matrix metalloproteinase 9 (MMP-9) were elevated. Immunohistochemical analysis demonstrated that the expression profiles of these proteins correlated with their mRNA levels. Treatment with an ER modulator, bazedoxifene, normalized the expression profiles of these proteins and improved SAH-free survival. In HBECs and HBSMCs under estrogen-free conditions, the depletion of ERα and Sirt1 and the accumulation of NLRP3 were counteracted by exposure to estradiol or to an ERα agonist but not to an ERß agonist. CONCLUSIONS: To the authors' knowledge, this work represents the first demonstration that, in an aneurysm model under estrogen-deficient conditions, the depletion of ERα and Sirt1 may contribute to activation of the NLRP3/IL-1ß/MMP-9 pathway, facilitating the rupture of IAs in the estrogen-deficient rat IA rupture model.

Efficacy of Utilizing Both 3-Dimensional Multimodal Fusion Image and Intra-Arterial Indocyanine Green Videoangiography in Cerebral Arteriovenous Malformation Surgery.

OBJECTIVE: An understanding of the complex morphology of an arteriovenous malformation (AVM) is important for successful resection. We have previously reported the utility of intra-arterial indocyanine green (ICG) videoangiography for this purpose, but that method cannot detect the angioarchitecture covered by brain tissue. 3-dimensional (3D) multimodal fusion imaging is reportedly useful for this same purpose, but cannot always visualize the exact angioarchitecture due to poor source images and processing techniques. This study examined the results of utilizing both techniques in patients with AVMs. METHODS: Both techniques were applied in 12 patients with AVMs. Both images were compared with surgical views and evaluated by surgeons. RESULTS: Although evaluations for identifying superficial feeders by ICG videoangiography were high in all cases, the more complicated the AVM, the lower the evaluation by 3D multimodal fusion imaging. Conversely, evaluation of the estimated range of the nidus was high in all cases by 3D multimodal fusion imaging, but low in all but one case by ICG videoangiography. Nidus flow reduction was recognized by Flow 800 analysis obtained after ICG videoangiography. CONCLUSIONS: These results showed that utilizing both techniques together was more useful than each modality alone in AVM surgery. This was particularly effective in identifying superficial feeders and estimating the range of the nidus. This technique is expected to offer an optimal tool for AVM surgery.

The association between upper gastrointestinal endoscopic findings and internal radiation exposure in residents living in areas affected by the Chernobyl nuclear accident.

Many people living around the Chernobyl Nuclear Power Plant (CNPP) have been exposed to 137Cs for several decades after the CNPP accident. Although half-life of 137Cs is about 30 years, some wild forest foodstuffs are contaminated by 137Cs even now. We pointed out in a previous report that low-dose internal radiation has been occasionally detected in people's body. Moreover, some doctors in local hospitals have claimed that internal exposure from contaminated foodstuffs may affect the digestive organs and possibly cause gastrointestinal (GI) diseases. Thus, we attempt to assess whether internal radiation exposure affects digestive organs or not, and the possible factors that influence digestive organs. Overall, 1,612 residents were assessed for internal 137Cs concentration using Whole-Body Counter and their digestive organs were screened with upper GI endoscopy from 2016-2018 in the Zhytomyr region, Ukraine. All participants answered to the questionnaire including their background, intake of wild forest foodstuff, intake frequency, smoking habits, and alcohol consumption. We checked the number of upper GI endoscopic diagnosis per person to assess the extent of damage to the upper digestive organs. Next, we statistically analyzed associations between this number and age, sex, level of internal exposure dose, alcohol consumption, wild forest foodstuff intake, and smoking. Consequently, we revealed that the number of GI diagnosis is significantly increased by factors such as sex, intake of wild forest foodstuff, and alcohol consumption. However, the average level of internal exposure of 137Cs and smoking did not relate to the number of GI diagnosis. Thus, the results of multiple regression revealed that alcohol consumption is independently related to the number of GI diagnosis that is most likely accompanied by the intake of wild forest foodstuff. In conclusion, the low-dose internal exposure may not affect the digestive organs of residents living around CNPP.

An imbalance between RAGE/MR/HMGB1 and ATP1α3 is associated with inflammatory changes in rat brain harboring cerebral aneurysms prone to rupture.

BACKGROUND AND PURPOSE: An aneurysmal subarachnoid hemorrhage is a devastating event. To establish an effective therapeutic strategy, its pathogenesis must be clarified, particularly the pathophysiology of brain harboring intracranial aneurysms (IAs). To elucidate the pathology in brain harboring IAs, we examined the significance of the receptor for advanced glycation end-products (RAGE)/mineralocorticoid receptor (MR) pathway and Na+/K+-ATPase (ATP1α3). METHODS: Ten-week-old female rats were subjected to oophorectomy as well as hypertension and hemodynamic changes to induce IAs, and were fed a high-salt diet. Brain damage in these rats was assessed by inflammatory changes in comparison to sham-operated rats fed a standard diet. RESULTS: Six weeks after IA induction (n = 30), irregular morphological changes, i.e., an enlarged vessel diameter and vascular wall, were observed in all of the left posterior cerebral arteries (Lt PCAs) prone to rupture. Approximately 20% of rats had ruptured IAs within 6 weeks. In brain harboring unruptured IAs at the PCA, the mRNA levels of RAGE and MR were higher, and that of ATP1α3 was lower than those in the sham-operated rats (p < 0.05, each). Immunohistochemically, elevated expression of RAGE and MR, and decreased expression of ATP1α3 were observed in the brain parenchyma adjacent to the Lt PCA, resulting in increased Iba-1 and S100B expression that reflected the inflammatory changes. There was no difference between the unruptured and ruptured aneurysm rat groups. Treatment with the MR antagonist esaxerenone abrogated these changes, and led to cerebral and vascular normalization and prolonged subarachnoid hemorrhage-free survival (p < 0.05). CONCLUSIONS: Regulation of the imbalance between the RAGE/MR pathway and ATP1α3 may help attenuate the damage in brain harboring IAs, and further studies are warranted to clarify the significance of the down-regulation of the MR/RAGE pathway and the up-regulation of ATP1α3 for attenuating the pathological changes in brain harboring IAs.