Search

We examined feathers of domestic ducks and geese inoculated with 2 different avian influenza virus (H5N1) genotypes. Together with virus isolation from the skin, the detection of viral antigens and ultrastructural observation of the virions in the feather epidermis raise the possibility of feathers as sources of infection. [ABSTRACT FROM AUTHOR]

CD5 expression is seen in 5%-10% of de novo diffuse large B-cell lymphomas (DLBCLs). Primary large B-cell lymphoma of the central nervous system (PCNS-LBCL) also exhibits CD5 expression in a minority of cases, however, clinicopathological and molecular features remain largely unclarified. Here we present the clinical, molecular, and pathological features of 11 CD5-positive ( + ) PCNS-LBCL cases, occupying 6.7% of all 165 PCNS-LBCLs diagnosed in our institutions. While CD5 + systemic DLBCL has been recognized as a distinctive subgroup showing an aggressive clinical course, no obvious differences were found between CD5 + and CD5-negative subgroups among the present CNS patients clinically. MYD88 p.L265P and CD79B p.Y196 mutations were detected in eight (73%) and seven (64%) cases, respectively, supporting previous reports. Notably, the microenvironmental immune cells were universally PD-L1/CD274-positive, and the higher levels tended to present favorable overall survival, as already evidenced in the PCNS-LBCL series. In contrast, neoplastic PD-L1/CD274 expression was undetectable in all cases. Indeed, no structural variations or copy number alterations involving PD-1 ligands were detected by targeted-capture sequencing and fluorescence in situ hybridization. While further studies are warranted, we may have confirmed similarity between PCNS-LBCLs and intravascular large B-cell lymphomas from a molecular standpoint., (© 2024 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

How do regional brain volume ratios and cerebral blood flow (CBF, mL/min) change with aging, and are there sex differences? This study aimed to comprehensively evaluate the relationships between regional brain volume ratios and CBF in healthy brains. The study participants were healthy volunteers who underwent three-dimensional T1-weighted MRI, time-of-flight MR angiography, and four-dimensional (4D) flow MRI between 2020 and 2022. The brain was automatically segmented into 21 brain subregions from 3D T1-weighted MRI, and CBF in 16 major intracranial arteries were measured by 4D flow MRI. The relationships between segmented brain volume ratios and CBFs around the circle of Willis were comprehensively investigated in each decade and sex. This study included 129 healthy volunteers (mean age ± SD, 48.2 ± 16.8; range, 22-92 years; 43 males and 86 females). The association was strongest between the cortical gray matter volume ratio and total outflow of the intracranial major arteries distal to the circle of Willis (Pearson's correlation coefficient, r: 0.425). In addition, the mean flow of the total inflow and outflow around the circle of Willis were significantly greater in women than men, and significant left-right differences were observed in CBFs even on the peripheral side of the circle of Willis. Moreover, the correlation was strongest between the left cortical gray matter volume ratio and the combined flows of the left anterior and posterior cerebral arteries distal to the circle of Willis (r: 0.486). There was a trend toward greater total intracranial CBF, especially among women in their 40s and younger, who had a larger cortical gray matter volume. This finding may be one of the reasons for the approximately twofold higher incidence of cerebral aneurysms and subarachnoid hemorrhage, and a threefold higher incidence of migraine headaches.

Pathological gait in patients with Hakim's disease (HD, synonymous with idiopathic normal-pressure hydrocephalus; iNPH), Parkinson's disease (PD), and cervical myelopathy (CM) has been subjectively evaluated in this study. We quantified the characteristics of upper and lower limb movements in patients with pathological gait. We analyzed 1491 measurements of 1 m diameter circular walking from 122, 12, and 93 patients with HD, PD, and CM, respectively, and 200 healthy volunteers using the Three-Dimensional Pose Tracker for Gait Test. Upper and lower limb movements of 2D coordinates projected onto body axis sections were derived from estimated 3D relative coordinates. The hip and knee joint angle ranges on the sagittal plane were significantly smaller in the following order: healthy > CM > PD > HD, whereas the shoulder and elbow joint angle ranges were significantly smaller, as follows: healthy > CM > HD > PD. The outward shift of the leg on the axial plane was significantly greater, as follows: healthy < CM < PD < HD, whereas the outward shift of the upper limb followed the order of healthy > CM > HD > PD. The strongest correlation between the upper and lower limb movements was identified in the angle ranges of the hip and elbow joints on the sagittal plane. The lower and upper limb movements during circular walking were correlated. Patients with HD and PD exhibited reduced back-and-forth swings of the upper and lower limbs.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is a major human pathogen and a research priority for developing new antimicrobial agents. CRAB is a causative agent of a variety of infections in different body sites. One of the manifestations is catheter-associated urinary tract infection, which exposes the bacteria to the host's urine, creating a particular environment. Exposure of two CRAB clinical isolates, AB5075 and AMA40, to human urine (HU) resulted in the differential expression levels of 264 and 455 genes, respectively, of which 112 were common to both strains. Genes within this group play roles in metabolic pathways such as phenylacetic acid (PAA) catabolism, the Hut system, the tricarboxylic acid (TCA) cycle, and other processes like quorum sensing and biofilm formation. These results indicate that the presence of HU induces numerous adaptive changes in gene expression of the infecting bacteria. These changes presumably help bacteria establish and thrive in the hostile conditions in the urinary tract. These analyses advance our understanding of CRAB's metabolic adaptations to human fluids, as well as expand knowledge on bacterial responses to distinct human fluids containing different concentrations of human serum albumin (HSA)., (© 2024. The Author(s).)

We investigated the reduction in regional brain volume and cerebral blood flow (CBF) with aging and explored potential sex differences in healthy brains. Three-dimensional (3D) T1-weighted magnetic resonance imaging (MRI), time-of-flight magnetic resonance angiography, and four-dimensional (4D) flow MRI were performed on 129 healthy volunteers aged 22-92 years. The brains of healthy volunteers were segmented into 21 subregions using 3D T1-weighted MRI and CBFs in 16 major intracranial arteries were measured using 4D flow MRI. The cortical gray matter volume decreased linearly with aging, whereas the cerebral white matter volume increased until the 40s and then decreased, and the subcortical gray matter volume changed little with aging. The cortical gray matter volume was significantly associated with the total CBF of the major intracranial arteries distal to the circle of Willis; however, the cerebral white matter and subcortical gray matter volumes were not. Generally, women have higher total CBF than men, particularly in their 40s and younger, despite the smaller intracranial volume and smaller diameters of intracranial arteries than men. This may contribute to the higher incidence of subarachnoid hemorrhage due to cerebral aneurysms and migraine in women., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Hair loss is driven by multiple factors, including genetics. Androgenetic alopecia (AGA) is a condition in which treatments necessitate prolonged compliance with prescribed medications. We have developed IVL3001, a long-acting injectable (LAI) formulation of finasteride encapsulated within poly lactic-co-glycolic acid microspheres, to enhance the efficacy of the finasteride and to achieve consistent positive outcomes in adults. An open-label, sequential, single-dose phase I clinical trial was designed to evaluate the safety, pharmacokinetic (PK), and pharmacodynamic (PD) of IVL3001., Methods: A total of 40 non-smoking, healthy adult males were divided into three cohorts where the IVL3001 group received a single subcutaneous injection of 12-36 mg IVL3001 and 1 mg finasteride (Propecia ® ) once daily for 28 days. The plasma concentrations of finasteride, dihydrotestosterone (DHT), and testosterone were measured using liquid chromatography-tandem mass spectrometry. The tolerability of the injections was assessed, and compartment models were developed to predict the effective dose and assess PK/PD profiles., Results: IVL3001 and finasteride 1 mg tablets were well tolerated. IVL3001 showed consistent plasma concentrations without bursts or fluctuations. Consistent with its mechanism of action, IVL3001 reduced DHT levels. Simulation data showed that the administration of 12-36 mg of IVL3001 every 4 weeks achieved plasma concentrations similar to finasteride, with comparable DHT reduction., Conclusion: The present study represents the first clinical trial to evaluate the safety, pharmacokinetic (PK), pharmacodynamic (PD), and tolerability of finasteride long-acting injectables (LAI) in adults. The rapid onset of action sustained effective drug concentration and the prolonged half-life of IVL3001 suggest that it offers multiple benefits over conventional oral formulations in terms of therapeutic response and compliance., Trial Registration: ClinicalTrials.gov identifier, NCT04945226., (© 2024. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Subependymal giant cell astrocytoma (SEGA) is a low-grade periventricular tumor that is closely associated with tuberous sclerosis complex (TSC). SEGA typically arises during the first two decades of life and rarely arises after the age of 20-25 years. Nevertheless, it has also been reported that glioma histologically resembling SEGA, so-called SEGA-like astrocytoma, can arise in neurofibromatosis type 1 (NF1) patients, even in the elderly. Herein, we report a case of SEGA-like circumscribed astrocytoma arising in the lateral ventricle of a 75-year-old woman. Whole-exome sequencing revealed a somatic variant of NF1. Methylation array analysis led to a diagnosis of "methylation class glioblastoma, IDH-wildtype, mesenchymal-type (GBM, MES)" with a high calibrated score (0.99). EGFR amplification, CDKN2A/B homozygous deletion, chromosomal +7/-10 alterations, and TERT promoter mutation, typical molecular abnormalities usually found in GBM, were also observed. While most reported cases of SEGA-like astrocytoma have arisen in NF1 patients, the patient was neither TSC nor NF1. Near total removal was accomplished with endoscopic cylinder surgery. At the 36-month follow-up, there was no tumor recurrence without adjuvant therapies. This clinical behavior did not match GBM. SEGA-like astrocytoma of the elderly is rare, and this is the oldest case reported so far. In addition, high-grade molecular features found in circumscribed tumor remain unclear. Further investigations among larger series are needed for clarifying the underlying molecular mechanisms., (© 2023 Japanese Society of Neuropathology.)

Background: Bidirectional reciprocal motion of cerebrospinal fluid (CSF) was quantified using four-dimensional (4D) flow magnetic resonance imaging (MRI) and intravoxel incoherent motion (IVIM) MRI. To estimate various CSF motions in the entire intracranial region, we attempted to integrate the flow parameters calculated using the two MRI sequences. To elucidate how CSF dynamics deteriorate in Hakim's disease, an age-dependent chronic hydrocephalus, flow parameters were estimated from the two MRI sequences to assess CSF motion in the entire intracranial region., Methods: This study included 127 healthy volunteers aged ≥ 20 years and 44 patients with Hakim's disease. On 4D flow MRI for measuring CSF motion, velocity encoding was set at 5 cm/s. For the IVIM MRI analysis, the diffusion-weighted sequence was set at six b-values (i.e., 0, 50, 100, 250, 500, and 1000 s/mm 2 ), and the biexponential IVIM fitting method was adapted. The relationships between the fraction of incoherent perfusion (f) on IVIM MRI and 4D flow MRI parameters including velocity amplitude (VA), absolute maximum velocity, stroke volume, net flow volume, and reverse flow rate were comprehensively evaluated in seven locations in the ventricles and subarachnoid spaces. Furthermore, we developed a new parameter for fluid oscillation, the Fluid Oscillation Index (FOI), by integrating these two measurements. In addition, we investigated the relationship between the measurements and indices specific to Hakim's disease and the FOIs in the entire intracranial space., Results: The VA on 4D flow MRI was significantly associated with the mean f-values on IVIM MRI. Therefore, we estimated VA that could not be directly measured on 4D flow MRI from the mean f-values on IVIM MRI in the intracranial CSF space, using the following formula; e 0.2(f-85)  + 0.25. To quantify fluid oscillation using one integrated parameter with weighting, FOI was calculated as VA × 10 + f × 0.02. In addition, the FOIs at the left foramen of Luschka had the strongest correlations with the Evans index (Pearson's correlation coefficient: 0.78). The other indices related with Hakim's disease were significantly associated with the FOIs at the cerebral aqueduct and bilateral foramina of Luschka. FOI at the cerebral aqueduct was also elevated in healthy controls aged ≥ 60 years., Conclusions: We estimated pulsatile CSF movements in the entire intracranial CSF space in healthy individuals and patients with Hakim's disease using FOI integrating VA from 4D flow MRI and f-values from IVIM MRI. FOI is useful for quantifying the CSF oscillation., (© 2024. The Author(s).)

We compared survival outcomes of high-dose concomitant boost radiotherapy (HDCBRT) and conventional dose radiotherapy (CRT) for newly diagnosed glioblastoma (GB). Patients treated with intensity-modulated radiation therapy for newly diagnosed GB were included. In HDCBRT, specific targets received 69, 60, and 51 Gy in 30 fractions, while 60 Gy in 30 fractions was administered with a standard radiotherapy method in CRT. Overall survival (OS) and progression-free survival (PFS) were compared using the Log-rank test, followed by multivariate Cox analysis. The inverse probability of treatment weighting (IPTW) method was also applied to each analysis. Among 102 eligible patients, 45 received HDCBRT and 57 received CRT. With a median follow-up of 16 months, the median survival times of OS and PFS were 21 and 9 months, respectively. No significant differences were observed in OS or PFS in the Kaplan-Meier analyses. In the multivariate analysis, HDCBRT correlated with improved OS (hazard ratio, 0.49; 95% confidence interval, 0.27-0.90; P = 0.021), and this result remained consistent after IPTW adjustments (P = 0.028). Conversely, dose suppression due to the proximity of normal tissues and IMRT field correlated with worse OS and PFS (P = 0.008 and 0.049, respectively). A prospective study with a stricter protocol is warranted to validate the efficacy of HDCBRT for GB., (© 2024. The Author(s).)

Background: Disproportionately enlarged subarachnoid-space hydrocephalus (DESH) is a key feature for Hakim disease (idiopathic normal pressure hydrocephalus: iNPH), but subjectively evaluated. To develop automatic quantitative assessment of DESH with automatic segmentation using combined deep learning models., Methods: This study included 180 participants (42 Hakim patients, 138 healthy volunteers; 78 males, 102 females). Overall, 159 three-dimensional (3D) T1-weighted and 180 T2-weighted MRIs were included. As a semantic segmentation, 3D MRIs were automatically segmented in the total ventricles, total subarachnoid space (SAS), high-convexity SAS, and Sylvian fissure and basal cistern on the 3D U-Net model. As an image classification, DESH, ventricular dilatation (VD), tightened sulci in the high convexities (THC), and Sylvian fissure dilatation (SFD) were automatically assessed on the multimodal convolutional neural network (CNN) model. For both deep learning models, 110 T1- and 130 T2-weighted MRIs were used for training, 30 T1- and 30 T2-weighted MRIs for internal validation, and the remaining 19 T1- and 20 T2-weighted MRIs for external validation. Dice score was calculated as (overlapping area) × 2/total area., Results: Automatic region extraction from 3D T1- and T2-weighted MRI was accurate for the total ventricles (mean Dice scores: 0.85 and 0.83), Sylvian fissure and basal cistern (0.70 and 0.69), and high-convexity SAS (0.68 and 0.60), respectively. Automatic determination of DESH, VD, THC, and SFD from the segmented regions on the multimodal CNN model was sufficiently reliable; all of the mean softmax probability scores were exceeded by 0.95. All of the areas under the receiver-operating characteristic curves of the DESH, Venthi, and Sylhi indexes calculated by the segmented regions for detecting DESH were exceeded by 0.97., Conclusion: Using 3D U-Net and a multimodal CNN, DESH was automatically detected with automatically segmented regions from 3D MRIs. Our developed diagnostic support tool can improve the precision of Hakim disease (iNPH) diagnosis., Competing Interests: SY received speakers’ honoraria from Fujifilm Medical Systems. HI and HM are employed by the FUJIFILM Corporation and made substantial contributions to the development of the applications of the SYNAPSE 3D workstation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yamada, Ito, Matsumasa, Ii, Otani, Tanikawa, Iseki, Watanabe, Wada, Oshima and Mase.)

The zebrafish model has emerged as a reference tool for phenotypic drug screening. An increasing number of molecules have been brought from bench to bedside thanks to zebrafish-based assays over the last decade. The high homology between the zebrafish and the human genomes facilitates the generation of zebrafish lines carrying loss-of-function mutations in disease-relevant genes; nonetheless, even using this alternative model, the establishment of isogenic mutant lines requires a long generation time and an elevated number of animals. In this study, we developed a zebrafish-based high-throughput platform for the generation of F0 knock-out (KO) models and the screening of neuroactive compounds. We show that the simultaneous inactivation of a reporter gene ( tyrosinase ) and a second gene of interest allows the phenotypic selection of F0 somatic mutants (crispants) carrying the highest rates of mutations in both loci. As a proof of principle, we targeted genes associated with neurodevelopmental disorders and we efficiently generated de facto F0 mutants in seven genes involved in childhood epilepsy. We employed a high-throughput multiparametric behavioral analysis to characterize the response of these KO models to an epileptogenic stimulus, making it possible to employ kinematic parameters to identify seizure-like events. The combination of these co-injection, screening and phenotyping methods allowed us to generate crispants recapitulating epilepsy features and to test the efficacy of compounds already during the first days post fertilization. Since the strategy can be applied to a wide range of indications, this study paves the ground for high-throughput drug discovery and promotes the use of zebrafish in personalized medicine and neurotoxicity assessment.

We herein report a case of acute neurological symptoms and a fever initially suspected of being encephalitis but later revealed to be dural arteriovenous fistula (dAVF). An 84-year-old woman had a fever and cerebral edema and was initially treated for encephalitis. A review of her magnetic resonance imaging findings revealed abnormal blood flow signals. After cerebral angiography, the patient was finally diagnosed with left transverse-sigmoid sinus dAVF. The present case showed that dAVF can also present with an acute onset and a fever, mimicking acute encephalitis. Because the treatments for encephalitis and dAVF differ greatly, the possibility of dAVF should also be considered when diagnosing encephalitis.

Background: The efficacy of intermittent cerebrospinal fluid (CSF) drainage compared with that of continuous CSF drainage in patients with subarachnoid hemorrhage (SAH) remains undetermined to date. Therefore, we investigated whether intermittent CSF drainage is effective in reducing secondary chronic hydrocephalus (sCH) after aneurysmal SAH., Methods: Overall, 204 patients (69 men and 135 women) treated for aneurysmal SAH between 2007 and 2022 were included in this study. Following SAH onset, 136 patients were managed with continuous CSF drainage, whereas 68 were managed with intermittent CSF drainage. Logistic regression analyses were used to calculate the age-adjusted and multivariate odds ratios for the development of sCH. The Cox proportional hazards regression model were used to compare the effects of intermittent and continuous CSF drainage on sCH development., Results: Overall, 96 patients developed sCH among the 204 patients with SAH. In total, 74 (54.4%) of the 136 patients managed with continuous CSF drainage developed sCH, whereas 22 (32.4%) of the 68 patients managed with intermittent CSF drainage developed sCH. This demonstrated that the rate of sCH development was significantly lower among patients managed with intermittent CSF drainage. Compared with continuous CSF drainage, intermittent CSF drainage exhibited a multivariate odds ratio (95% confidential interval) of 0.25 (0.11-0.57) for sCH development. Intermittent CSF drainage was more effective (0.20, 0.04-0.95) in patients with severe-grade SAH than in those with mild-grade SAH (0.33, 0.12-0.95). Intermittent CSF drainage was ineffective in patients with acute hydrocephalus (8.37, 0.56-125.2), but it was effective in patients without acute hydrocephalus (0.11, 0.04-0.31)., Conclusions: Compared with continuous CSF drainage, intermittent drainage is more effective in reducing sCH after aneurysmal SAH. Although intermittent drainage was ineffective in cases of co-occurrence of acute hydrocephalus, it was effective in reducing sCH development regardless of the severity of initial symptoms at SAH onset., (© 2023. The Author(s).)

Background and Purpose: Various prophylactic drugs for cerebral vasospasm and delayed cerebral infarction (DCI) after subarachnoid hemorrhage (SAH) have been used in Japan. To investigate the treatment trends for cerebral vasospasm and frequency of DCI after SAH throughout Japan in 2021., Methods: In 2021 we conducted an anonymous questionnaire survey on management for preventing cerebral vasospasm after aneurysmal SAH, and the frequency of DCI. The questionnaire was emailed to 955 certified neurosurgeons at 553 hospitals in Japan. Of them, 162 hospitals (29% response rate) responded to the questionnaire. Of these, 158 were included in this study, while four hospitals that responded insufficiently were excluded. The efficacy of treatments for reducing DCI were examined through a logistic regression analysis., Results: Among 3,093 patients treated with aneurysmal SAH, 281 patients (9.1%) were diagnosed with DCI related to cerebral vasospasm. Coil embolization had significantly lower DCI frequency (6.9%), compared to microsurgical clipping (11.8%, odds ratio, 0.90; 95% confidential intervals, 0.84-0.96; P , 0.007). In addition, cilostazol administration was associated with significantly lower DCI frequency (0.48; 0.27-0.82; 0.026). The efficacy of cilostazol in reducing DCI remained unchanged after adjustment for covariates. The most effective combination of multiple prophylactic drugs in reducing DCI related to cerebral vasospasm was cilostazol, fasudil, and statin (0.38; 0.22-0.67; 0.005)., Conclusions: This study elucidated the trends in prophylactic drugs to prevent cerebral vasospasm and frequency of DCI after aneurysmal SAH in Japan. Coil embolization and cilostazol administration showed effectiveness in reducing DCI related to cerebral vasospasm in 2021., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Nishikawa, Yamada, Uchida, Yamanaka, Hayashi, Katano, Tanikawa, Iwama, Iihara, Morioka and Mase.)

Cerebrospinal fluid (CSF) dynamics has dramatically changed in this century. In the latest concept of CSF dynamics, CSF is thought to be produced mainly from interstitial fluid excreted from the brain parenchyma and is absorbed in the meningeal lymphatics. Moreover, CSF does not always flow from the ventricles to the subarachnoid space unidirectionally through the foramina of Magendie and Luschka. In an environment of increased intracranial CSF in idiopathic normal pressure hydrocephalus, CSF freely moves through the inferior choroidal point of the choroidal fissure, which interfaces between the inferior horn of the lateral ventricles and the ambient cistern and through the velum interpositum between the third ventricle and the quadrigeminal cistern. The structure of the hippocampus adjacent to the inferior part of the choroidal fissure may be important in preventing the accumulation of waste products in the hippocampus. A recent imaging technology for CSF dynamics, such as four-dimensional flow and intravoxel incoherent motion magnetic resonance imaging, can visualize and quantify the pulsatile complex CSF motion in clinical usage. We present the current concepts of CSF dynamics with advanced magnetic resonance imaging techniques, which will be helpful in the management and understanding of the pathogenesis of chronic hydrocephalus in adults., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Trends regarding the locations of hypertensive cerebral hemorrhages are unclear. To clarify hypertensive hemorrhage trends, we investigated intracerebral hemorrhages (ICHs) over an 18-year period, focusing on thalamic hemorrhages compared with other sites of hemorrhages., Methods: We reviewed the cases of patients hospitalized for hypertensive ICH in 2004-2021 at our hospital; 1,320 eligible patients were registered with a primary ICH/intraventricular hemorrhage. After exclusion criteria were applied, we retrospectively analyzed 1,026 hypertensive ICH cases., Results: The proportions of thalamic and subcortical hemorrhages increased over the 18-year period, whereas putaminal hemorrhage decreased. Multivariate logistic regression analyses revealed that for thalamic hemorrhage, ≥200 mmHg systolic blood pressure ( p  = 0.031), bleeding <15 mL ( p  = 0.001), and higher modified Rankin scale (mRS) score ≥ 4 at discharge ( p  = 0.006) were significant variables in the late period (2013-2021) versus the early period (2004-2012), whereas for putaminal hemorrhage, significant factors in the late period were triglyceride <150 mg/dL ( p  = 0.006) and mRS score ≥ 4 at discharge ( p  = 0.002). Among the features of the thalamic hemorrhages in the late period revealed by our group comparison with the putaminal and subcortical hemorrhages, the total and subcortical microbleeds were more notable in the thalamic hemorrhages than in the other two types of hemorrhage, whereas cerebellar microbleeds were more prominent when compared only with subcortical hemorrhages., Discussion: Our findings revealed an increasing trend for thalamic hypertensive hemorrhage and a decreasing trend for putaminal hemorrhage. The thalamic hemorrhage increase was observed in both young and older patients, regardless of gender. The main features of thalamic hemorrhage in the late period versus the early period were decrease in larger hemorrhage (≥15 mL) and an increase in cases with higher systolic blood pressure (at least partially involved a small number of untreated hypertensive patients who developed major bleeding). The total and subcortical microbleeds were more notable in the thalamic hemorrhages of the late period than in the putaminal and subcortical hemorrhages. These results may contribute to a better understanding of the recent trends of hypertensive ICHs and may help guide their appropriate treatments for this condition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher., (Copyright © 2023 Katano, Nishikawa, Uchida, Yamanaka, Hayashi, Yamada, Tanikawa, Yamada and Mase.)

Objective: The presence of tightened sulci in the high-convexities (THC) is a key morphological feature for the diagnosis of idiopathic normal pressure hydrocephalus (iNPH), but the exact localization of THC has yet to be defined. The purpose of this study was to define THC and compare its volume, percentage, and index between iNPH patients and healthy controls., Methods: According to the THC definition, the high-convexity part of the subarachnoid space was segmented and measured the volume and percentage from the 3D T1-weighted and T2-weighted magnetic resonance images in 43 patients with iNPH and 138 healthy controls., Results: THC was defined as a decrease in the high-convexity part of the subarachnoid space located above the body of the lateral ventricles, with anterior end on the coronal plane perpendicular to the anterior commissure-posterior commissure (AC-PC) line passing through the front edge of the genu of corpus callosum, the posterior end in the bilateral posterior parts of the callosomarginal sulci, and the lateral end at 3 cm from the midline on the coronal plane perpendicular to the AC-PC line passing through the midpoint between AC and PC. Compared to the volume and volume percentage, the high-convexity part of the subarachnoid space volume per ventricular volume ratio < 0.6 was the most detectable index of THC on both 3D T1-weighted and T2-weighted magnetic resonance images., Conclusions: To improve the diagnostic accuracy of iNPH, the definition of THC was clarified, and high-convexity part of the subarachnoid space volume per ventricular volume ratio <0.6 proposed as the best index for THC detection in this study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Currently, surgical obliterations are a mainstay for treating dural arteriovenous fistula (DAVF) in the anterior cranial fossa (ACF), which has high risks of hemorrhage and functional disorder. By introducing an endoscope into a high frontal approach and utilizing its advantages, we attempted to establish it as a new surgical procedure that eliminates the drawbacks of various approaches that have been used to date., Methods: By using 30 clinical datasets of venous-phase head computed tomography angiogram, measurements and comparisons on a 3-dimensional workstation were performed to identify the appropriate positioning of keyhole craniotomy for endoscope-controlled high frontal approach (EHFA). Based on these data, a cadaver-based surgery was simulated to verify the feasibility of EHFA and develop an efficient procedure., Results: In EHFA, though raising the position of the keyhole craniotomy made the operative field deeper, significant advantages were obtained in the angle between the operative axis and the medial-anterior cranial base and the amount of bone removal required at the anterior edge of craniotomy. Minimally invasive EHFA, performed through a keyhole craniotomy without opening the frontal sinus, proved to be feasible on 10 sides of 5 cadaver heads. Moreover, 3 patients with DAVF in ACF were successfully treated by clipping the fistula via EHFA., Conclusions: EHFA, which provided a direct corridor to the medial ACF at the level of the foramen cecum and crista galli and the minimum necessary operative field, was found to be a suitable procedure for clipping the fistula of DAVF in ACF., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The Japanese rhinoceros beetle Trypoxylus dichotomus is a giant beetle with distinctive exaggerated horns present on the head and prothoracic regions of the male. T. dichotomus has been used as a research model in various fields such as evolutionary developmental biology, ecology, ethology, biomimetics, and drug discovery. In this study, de novo assembly of 615 Mb, representing 80% of the genome estimated by flow cytometry, was obtained using the 10 × Chromium platform. The scaffold N50 length of the genome assembly was 8.02 Mb, with repetitive elements predicted to comprise 49.5% of the assembly. In total, 23,987 protein-coding genes were predicted in the genome. In addition, de novo assembly of the mitochondrial genome yielded a contig of 20,217 bp. We also analyzed the transcriptome by generating 16 RNA-seq libraries from a variety of tissues of both sexes and developmental stages, which allowed us to identify 13 co-expressed gene modules. We focused on the genes related to horn formation and obtained new insights into the evolution of the gene repertoire and sexual dimorphism as exemplified by the sex-specific splicing pattern of the doublesex gene. This genomic information will be an excellent resource for further functional and evolutionary analyses, including the evolutionary origin and genetic regulation of beetle horns and the molecular mechanisms underlying sexual dimorphism., (© 2023. The Author(s).)

Background: Although there have been some reports on endoscopic glioblastoma surgery, the indication has been limited to deep-seated lesions, and the difficulty of hemostasis has been a concern. In that light, we attempted to establish an endoscopic procedure for excision of glioblastoma which could be applied even to hypervascular or superficial lesions, in combination with pre-operative endovascular tumor embolization., Methods: Medical records of six consecutive glioblastoma patients who received exclusive endoscopic removal between September and November 2020 were analyzed. Preoperative tumor embolization was performed in cases with marked tumor stain and proper feeder arteries having an abnormal shape, for instance, tortuous or dilated, without passing through branches to the normal brain. Endoscopic tumor removal through a key-hole craniotomy was performed by using an inside-out excision for a deep-seated lesion, with the addition of an outside-in extirpation for a shallow portion when needed., Results: Endoscopic removal was successfully performed in all six cases. Before resection, endovascular tumor embolization was performed in four cases with no resulting complications, including ischemia or brain swelling. Gross total resection was achieved in three cases, and near total resection in the other three cases. Intraoperative blood loss exceeded 1,000 ml in only one case, whose tumor showed a prominent tumor stain but no proper feeder artery for embolization. In all patients, a smooth transition to adjuvant therapy was possible with no surgical site infection., Conclusion: Endoscopic removal for glioblastoma was considered to be a promising procedure with minimal invasiveness and a favorable impact on prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sakata, Tanikawa, Yamada, Fujinami, Nishikawa, Yamada and Mase.)

Cerebrospinal fluid (CSF) production and absorption concept significantly changed in the early 2010s from "third circulation theory" and "classical bulk flow theory" to a whole new one as follows: First, CSF is mainly produced from interstitial fluid excreted from the brain parenchyma, and CSF produced from the choroid plexus plays an important role in maintaining brain homeostasis. Second, CSF is not absorbed in the venous sinus via the arachnoid granules, but mainly in the dural lymphatic vessels. Finally, the ventricles and subarachnoid spaces have several compensatory direct CSF pathways at the borders attached to the choroid plexus, e.g., the inferior choroidal point of the choroidal fissure, other than the foramina of Luschka and Magendie. In idiopathic normal pressure hydrocephalus (iNPH), the lateral ventricles and basal cistern are enlarged simultaneously due to the compensatory direct CSF pathways. The average total intracranial CSF volume increased from about 150 mL at 20 years to about 350 mL at 70 years due to the decrease in brain volume with aging and further increased above 400 mL in patients with iNPH. CSF movements are composed of a steady microflow produced by the rhythmic wavy movement of motile cilia on the ventricular surface and dynamic pulsatile flow produced by the brain and cerebral artery pulsation, respiration, and head movement. Pulsatile CSF movements might totally decrease with aging, but it in the ventricles might increase at the foramina of Magendie and Luschka dilation. Aging CSF dynamics are strongly associated with ventricular dilatation in iNPH.

Wild-caught Eurasian tree sparrows ( Passer montanus ) were experimentally inoculated with genotype VII velogenic Newcastle disease virus (NDV) APMV1/chicken/Japan/Fukuoka-1/2004 to investigate the susceptibility and pathogenesis of infected sparrows. Intranasal inoculation of two groups with high or low doses of the virus resulted in the mortality of some birds in both groups on days 7-15 postinoculation. Neurologic signs, ruffled feathers, labored breathing, emaciation, diarrhea, depression, and ataxia were observed in a few birds that eventually succumbed to death. The inoculation of the higher viral load resulted in higher mortality and hemagglutination inhibition antibody detection rates. Tree sparrows that survived the 18-day observation period after inoculation exhibited no apparent clinical signs. Histologic lesions in dead birds were observed in the nasal mucosa, orbital ganglion, and central nervous system, accompanied by NDV antigens detected by immunohistochemistry. Viral inclusion bodies were rarely observed in the cytoplasm of neurons. NDV was isolated from the oral swab and brain of dead birds but not from other organs, including the lung, heart, muscle, colon, and liver. In another experimental group, tree sparrows were intranasally inoculated with the virus and then examined 1-3 days later to examine the early pathogenesis of the disease. Inoculated birds exhibited inflammation of the nasal mucosa with viral antigens, and virus was isolated from some oral swab samples on days 2 and 3 postinoculation. The results of the present study suggest that tree sparrows are susceptible to velogenic NDV, and the infection could be fatal, although some birds can exhibit asymptomatic or mild infection. The unique pathogenesis regarding the neurologic signs and viral neurotropism of velogenic NDV was characteristic in infected tree sparrows.

Background: The Finger Tapping (F-T) test is useful for assessing motor function of the upper limbs in patients with idiopathic normal pressure hydrocephalus (iNPH). However, quantitative evaluation of F-T for iNPH has not yet been established. The purpose of this study was to investigate the usefulness of the quantitative F-T test and optimal measurement conditions as a motor evaluation and screening test for iNPH., Methods: Sixteen age-matched healthy controls (mean age 73 ± 5 years; 7/16 male) and fifteen participants with a diagnosis of definitive iNPH (mean age 76 ± 5 years; 8/15 male) completed the study (mean ± standard deviation). F-T performance of the index finger and thumb was quantified using a magnetic sensing device. The performance of repetitive F-T by participants was recorded in both not timing-regulated and timing-regulated conditions. The mean value of the maximum amplitude of F-T was defined as M-Amplitude, and the mean value of the maximum velocity of closure of F-T was defined as cl-Velocity., Results: Finger Tapping in the iNPH group, with or without timing control, showed a decrease in M-Amplitude and cl-Velocity compared to the control group. We found the only paced F-T with 2.0 Hz auditory stimuli was found to improve both M-Amplitude and cl-Velocity after shunt surgery., Conclusion: The quantitative assessment of F-T with auditory stimuli at the rate of 2.0 Hz may be a useful and potentially supplemental screening method for motor assessment in patients with iNPH., Competing Interests: AK was employed by Hitachi, Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shimizu, Tanikawa, Horiba, Sahashi, Kawashima, Kandori, Yamanaka, Nishikawa, Matsukawa, Ueki and Mase.)

Virulent fowl adenovirus serotype 4 (FAdV-4) causes hydropericardium syndrome (HPS) with high mortality in chickens, leading to significant economic losses to the poultry industry. The development of an effective vaccine is essential for successful disease control. Here, we produced recombinant fiber-1 protein of FAdV-4, isolated from a Japanese HPS outbreak strain, JP/LVP-1/96, using a baculovirus expression system and evaluated its immunogenicity and protective efficacy. Recombinant fiber-1 protein induced high levels of neutralizing antibodies in immunized chickens, which were maintained for a minimum of 10 weeks. After being challenged with the virulent FAdV-4 strain JP/LVP-1/96, the immunized chickens did not exhibit clinical signs of infection or histopathological changes, there was a significant reduction in the viral load in various organs and total serum proteins, and albumin levels did not decline. These results suggest that the recombinant fiber-1 protein produced in this study can serve as a subunit vaccine to control HPS in chickens., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

We report the complete genome sequences of strains JP/Yamanashi/93 and JP/Shimane/98, which are classified in JP-II (GI-7) and JP-III (GI-19), respectively, the major genotypes of infectious bronchitis virus (IBV) in Japan. This information will be useful for the in-depth understanding of the evolution of IBV in Japan.

Modern western dietary habits and low physical activity cause metabolic abnormalities and abnormally elevated levels of metabolites such as low-density lipoprotein, which can lead to immune cell activation, and inflammatory reactions, and atherosclerosis. Appropriate stimulation of vascular endothelial cells can confer protective responses against inflammatory reactions and atherosclerotic conditions. This study aims to determine whether a designed optogenetic approach is capable of affecting functional changes in vascular endothelial cells and to evaluate its potential for therapeutic regulation of vascular inflammatory responses in vitro . We employed a genetically engineered, blue light-activated Ca 2+ channel switch molecule that utilizes an endogenous store-operated calcium entry system and induces intracellular Ca 2+ influx through blue light irradiation and observed an increase in intracellular Ca 2+ in vascular endothelial cells. Ca 2+ -dependent activation of the nuclear factor of activated T cells and nitric oxide production were also detected. Microarray analysis of Ca 2+ -induced changes in vascular endothelial cells explored several genes involved in cellular contractility and inflammatory responses. Indeed, there was an increase in the gene expression of molecules related to anti-inflammatory and vasorelaxant effects. Thus, a combination of human blue light-activated Ca 2+ channel switch 2 (hBACCS2) and blue light possibly attenuates TNFα-induced inflammatory NF-κB activity. We propose that extrinsic cellular Ca 2+ regulation could be a novel approach against vascular inflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yamanaka, Ueki, Mase and Inoue.)

To assess pathological gaits quantitatively, three-dimensional coordinates estimated with a deep learning model were converted into body axis plane projections. First, 15 healthy volunteers performed four gait patterns; that is, normal, shuffling, short-stepped, and wide-based gaits, with the Three-Dimensional Pose Tracker for Gait Test (TDPT-GT) application. Second, gaits of 47 patients with idiopathic normal pressure hydrocephalus (iNPH) and 92 healthy elderly individuals in the Takahata cohort were assessed with the TDPT-GT. Two-dimensional relative coordinates were calculated from the three-dimensional coordinates by projecting the sagittal, coronal, and axial planes. Indices of the two-dimensional relative coordinates associated with a pathological gait were comprehensively explored. The candidate indices for the shuffling gait were the angle range of the hip joint < 30° and relative vertical amplitude of the heel < 0.1 on the sagittal projection plane. For the short-stepped gait, the angle range of the knee joint < 45° on the sagittal projection plane was a candidate index. The candidate index for the wide-based gait was the leg outward shift > 0.1 on the axial projection plane. In conclusion, the two-dimensional coordinates on the body axis projection planes calculated from the 3D relative coordinates estimated by the TDPT-GT application enabled the quantification of pathological gait features.

Progressive stenosis and occlusion of the bilateral internal carotid artery terminals and circle of Willis are typical features of Moyamoya disease. However, aplastic or twig-like middle cerebral artery (Ap/T-MCA)-wherein the unilateral main trunk of the middle cerebral artery (MCA) is not depicted, and a plexiform arterial network is formed-is similar to the findings of Moyamoya disease. Here, we describe a 78-year-old man who presented with mild right paralysis and aphasia. Magnetic resonance angiography (MRA) at admission did not show the bilateral MCAs. The findings were similar to those of Moyamoya disease, and his symptoms worsened after hospitalization. Endovascular treatment was performed, and the left MCA was completely recanalized. Later, paroxysmal atrial fibrillation was detected, and we finally determined that left MCA occlusion had occurred due to embolism. The right MCA was completely occluded at its origin, indicating an Ap/T-MCA. Embolic occlusion of the unilateral MCA and contralateral Ap/T-MCA made this case resemble Moyamoya disease in the acute stage. Even when chronic occlusion is suspected on MRA in acute cerebral infarction, endovascular treatment should be considered. Additionally, a heterotypic R4810K polymorphism was later found in the RNF213 gene. To our knowledge, this is the second report of Ap/T-MCA with the RNF213 gene polymorphism; however, their association remains unclear and requires further analyses.

Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a rare glioneuronal neoplasm newly included in the 2016 World Health Organization Classification of Tumors of the Central Nervous System. Owing to the wide spectrum of its histopathological and radiological features, accurate diagnosis can be challenging. Recently, molecular testing including DNA methylation array has been introduced with the possibility of improving diagnostic accuracy and contributing to the subtyping especially for brain tumors with ambiguous histology. Two molecularly distinct subtypes of DLGNT have been reported: methylation class-1 (MC-1) with an indolent clinical course and MC-2, the latter aggressive. Herein, we report a case of a 14-year-old girl with a conspicuous hypothalamic mass lesion and diffuse leptomeningeal enhancement on magnetic resonance imaging. Biopsy specimens obtained from the hypothalamic lesion endoscopically were mainly composed of oligodendrocyte-like cells. However, it was difficult to make a definite diagnosis from these non-specific histological findings. Thus, DNA methylation array analysis was performed additionally by using formalin-fixed, paraffin-embedded tissue, resulting in a diagnosis of "MC-1 subtype of DLGNT" with a high calibrated score (0.99). Consequently, she was treated conservatively, with neither progression of the tumor nor aggravation of symptoms for the next 12 months. It was concluded that DNA methylation array analysis for DLGNT, a rare glioneuronal tumor, could be a powerful tool not only for accurate diagnosis but also decision-making in selecting the best treatment., (© 2022 Japanese Society of Neuropathology.)

The reduced availability of human donor hearts compared with the needs of patients with advanced heart failure refractory to medical therapy has promoted the search for therapeutic alternatives to cardiac allografts. Porcine heart xenotransplantation represents one of the most promising frontiers in this field today. From the first researches in the 1960s to today, the numerous advances achieved in the field of surgical techniques, genetic engineering and immunosuppression have made it possible at the beginning of 2022 to carry out the first swine-to-human heart transplant, attaining a survival of 2 months after surgery. The main intellectual and experimental stages that have marked the history of xenotransplantation, the latest acquisitions in terms of genetic editing, as well as the improvement of immunosuppressive therapy are discussed analytically in this article in order to illustrate the underlying complexity of this therapeutic model., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)