Computational Fluid Dynamics Analysis of Trigeminal Neuralgia Associated with the Vertebral Artery: A Report of Two Cases.

Trigeminal neuralgia is a nerve disorder that causes unilateral severe facial pain. The clinical features of trigeminal neuralgia are agonizing, paroxysmal, anticipated in one or more divisions of the trigeminal nerve, with repetitive bursts of a few seconds, exacerbated by cutaneous stimuli. Microvascular decompression is proven effective, resulting in a positive outcome. Here, we report two cases of trigeminal neuralgia associated with the vertebral artery, who underwent endoscopic microvascular decompression. This case report aims to show the benefit of computational fluid dynamics evaluation of the neurovascular contact and its effect on change in wall shear stress magnitude of the offending vertebral artery after surgical management with microvascular decompression.

Questionnaire for Dental Practitioners to Screen for Trigeminal Neuralgia.

Objective Trigeminal neuralgia (TN) is a neurological disorder that often presents as severe toothache. The majority of TN patients visit dental clinics first, so TN represents a potential pitfall for dental practitioners. This report describes the development of a trigeminal neuralgia questionnaire (TNQ), assessing 10 characteristics of TN, to assist dentists in screening for TN in dental clinics, and evaluates the effectiveness of TNQ. Materials and Methods Fifty-three patients who visited the TN outpatient department in our institute and completed the TNQ were included in this study. All patients were examined by two neurosurgeons and neuroimaging was performed. Statistical Analysis Patients were classified into a TN group and a non-TN group. TNQ score was retrospectively compared between groups. Furthermore, history and characteristics of TN were investigated in the TN group to clarify the status of the reference situation. Results Thirty-seven cases were assigned to the TN group, and 16 cases to the non-TN group. Mean TNQ score was 8.3 in the TN group and 6.6 in the non-TN group. Setting a TNQ cutoff score of 7 offered 91% sensitivity and 56% specificity for TN. Investigation of the history of the present illness indicated that 39.2% of TN cases were improperly triaged and referred from initial dental clinics, and interdisciplinary practice was insufficient. Conclusion TNQ offers a reliable, convenient method to triage TN patients, and may assist dentists in screening for TN. Multidisciplinary practice is necessary for total management of TN and the TNQ is expected to connect dentists and TN specialists.

10-GHz-clock time-multiplexed non-degenerate optical parametric oscillator network with a variable planar lightwave circuit interferometer.

A coherent XY machine (CXYM) is a physical spin simulator that can simulate the XY model by mapping XY spins onto the continuous phases of non-degenerate optical parametric oscillators (NOPOs). Here, we demonstrated a large-scale CXYM with >47,000 spins by generating 10-GHz-clock time-multiplexed NOPO pulses via four-wave mixing in a highly nonlinear fiber inside a fiber ring cavity. By implementing a unidirectional coupling from the ith pulse to the (i + 1)th pulse with a variable 1-pulse delay planar lightwave circuit interferometer, we successfully controlled the effective temperature of a one-dimensional XY spin network within two orders of magnitude.

C-X-C domain ligand 14-mediated stromal cell-macrophage interaction as a therapeutic target for hand dermal fibrosis.

Dupuytren's contracture, a superficial dermal fibrosis, causes flexion contracture of the affected finger, impairing hand function. Specific single-nucleotide polymorphisms within genes in the Wnt signalling pathway are associated with the disease. However, the precise role of Wnt signalling dysregulation in the onset and progression of Dupuytren's contracture remains unclear. Here, using a fibrosis mouse model and clinical samples of human Dupuytren's contractures, we demonstrate that the activation of Wnt/ß-catenin signalling in Tppp3-positive cells in the dermis of the paw is associated with the development of fibrosis. Fibrosis development and progression via Wnt/ß-catenin signalling are closely related to stromal cell-macrophage interactions, and Wnt/ß-catenin signalling activation in Tppp3-positive stromal cells causes M2 macrophage infiltration via chemokine Cxcl14, resulting in the formation of a TGF-ß-expressing fibrotic niche. Inhibition of Cxcl14 mitigates fibrosis by decreasing macrophage infiltration. These findings suggest that Cxcl14-mediated stromal cell-macrophage interaction is a promising therapeutic target for Wnt/ß-catenin-induced fibrosis.

Detecting partial synchrony in a complex oscillatory network using pseudovortices.

Partial synchronization is an important dynamical process of coupled oscillators on various natural and artificial networks, which can remain undetected due to the system complexity. With an analogy between pairwise asynchrony of oscillators and topological defects, i.e., vortices, in the two-dimensional XY model, we propose a robust and data-driven method to identify the partial synchronization on complex networks. The proposed method is based on an integer matrix whose element is pseudovorticity that discretely quantifies asynchronous phase dynamics in every two oscillators, which results in graphical and entropic representations of partial synchrony. As a first trial, we apply our method to 200 FitzHugh-Nagumo neurons on a complex small-world network. Partially synchronized chimera states are revealed by discriminating synchronized states even with phase lags. Such phase lags also appear in partial synchronization in chimera states. Our topological, graphical, and entropic method is implemented solely with measurable phase dynamics data, which will lead to a straightforward application to general oscillatory networks including neural networks in the brain.

Reprogramming of pancreatic islet cells for regeneration and rejuvenation.

The pancreatic ß cell, which produces insulin, is a terminally differentiated cell type that divides rarely. Consequently, the regenerative ability of ß cells is limited and irreversible diabetes occurs after severe loss of ß-cell function. In view of such poor regenerative capacity, considerable research efforts have been made to promote the expansion of functional insulin-producing cells as a regenerative therapy for diabetes. Here, we discuss recent findings regarding the robust expansion of functional mature islet cells both in vivo and ex vivo through MYCL-mediated reprogramming. We also describe the potential prospects for the application of reprogramming technologies to regenerative therapy and rejuvenation of islet cells.

Preoperative detailed evaluation intracranial artery stenosis using three-dimensional visualization analysis reduces the invasiveness of superficial temporal artery-middle cerebral artery bypass.

Objectives: Superficial temporal artery (STA) to middle cerebral artery (MCA) bypass surgery is a common treatment for preventing cerebral ischemia in patients with intracranial artery stenosis. The aim of this study was to analyze the surgical outcomes of the STA-MCA bypass procedure, particularly with regard to the invasiveness of targeted bypass (TB) with preoperative planning using Amira® software. Methods: Consecutive patients with single STA-MCA bypass performed by a single neurosurgeon from January 2019 to May 2022 were included. The clinical parameters of seven TB patients were compared with those of 11 patients treated with the conventional method (CM). Results: Compared with CM patients, TB using Amira® software patients had a shorter scalp incision (median [interquartile range]=11.2 [9.7-12.7] cm vs. 16.9 [16.0-17.7] cm, respectively; p=0.004], smaller craniotomy size (11.8 [11.5-14.4] cm2 vs. 20.9 [17.1-22.2] cm2, respectively; p=0.01], shorter surgery duration (201 [195-218] min vs. 277 [229-310] min, respectively; p=0.003], and less intraoperative bleeding (10 [10-20] g vs. 23 [20-50] g, respectively; p=0.033]. However, there were no differences in surgical complications between the two groups. Conclusions: Detailed preoperative evaluation using Amira® software can reduce the invasiveness of the STA-MCA bypass procedure.

Exploring the potential of in vivo reprogramming for studying embryonic development, tissue regeneration, and organismal aging.

Forced expression of a specific set of transcription factors can reprogram terminally differentiated cells and convert them into induced pluripotent stem cells that correspond to cells in the inner cell mass of the developing embryo. It is now recognized that the scope of the reprogramming factors extends far beyond the stem cell biology. Studies using mouse models demonstrated that the induction of the reprogramming factors promotes cellular reprogramming in vivo. Closer inspection of these mice has revealed that expression of the reprogramming factors results in unique consequences that are not seen when cells are reprogrammed ex vivo, and can provide insights into development, tissue regeneration, cancer, and aging.

Complementary role of Indocyanine green video angiography, dual-image video angiography and flow-800.

BACKGROUND: Visualization of cerebral vessels, their branches and the surrounding structures are essential during cerebrovascular surgery. Indocyanine green dye-based video angiography is a commonly used technique in cerebrovascular surgery. This paper aims to analyze the real-time imaging of ICG-AG, DIVA, and the use of ICG-VA with Flow 800 to compare their usefulness in surgery. METHODS: Intraoperative real-time identification of vascular and surrounding structures in twenty nine anterior circulation aneurysms and three posterior circulation aneurysm clipping, one STA-MCA bypass, and two carotid endarterectomies were performed in patients using ICG-VA alone, DIVA, ICG-VA with Flow 800 to analyze and compare each of these methods in details. RESULTS: ICG-VA and DIVA couldn't visualize perforators in twenty-three cases of cerebral aneurysms clipping when used alone. Compared to that by adding Flow 800 perforators were easily visualized. In three cases, occlusion of perforators after clip application was visualized by DIVA and solved by repositioning surgical clips. In one STA-MCA bypass surgery, adequate blood flow to cortical branches of MCA (M4) from STA branches was assessed with ICG-VA, DIVA, and the use of ICG-VA with Flow 800 color mapping. ICG-VA, DIVA, and Flow 800 observed the lack of blood flow and fluttering atherosclerotic plaques in carotid endarterectomy. In one case of basilar tip aneurysm, we used ICG-VA with Flow 800; the intensity diagram drawn after determining regions of interest showed that there was no flow within the aneurysm sac after clipping. CONCLUSION: In real-time surgery, a multimodal approach using ICG-VA, DIVA, and ICG-VA with Flow 800 colour mapping can serve as useful tools for better visualization of vascular and surrounding structures. The benefits of flow 800 color mapping, such as determining regions of interest, intensity diagrams, and color-coded images, outweigh the advantages over the ICG-VA and DIVA in the visualization of critical vascular anatomy in humans during surgical procedures.

Contrast-Induced Encephalopathy after Endovascular Treatment: Two Case Reports.

Contrast-induced encephalopathy (CIE) is a rare neurological complication that occurs after the use of contrast medium in various angiographic procedures. Symptoms can be different, from headache to severe neurological deficit and coma. In the articles published to date, symptoms appeared immediately after application of contrast agent or within 24 hours. Here we present two cases of patients in whom CIE developed delayed after endovascular treatment.

Predicting Morphological Changes to Vessel Walls Adjacent to Unruptured Cerebral Aneurysms Using Computational Fluid Dynamics.

Objective This study compared intraoperative findings with preoperative computed tomography angiography (CTA) and computational fluid dynamics (CFD) analysis of perianeurysmal findings for the indication of possible vessel wall thinning. Materials and Methods Participants comprised 38 patients with unruptured middle cerebral artery aneurysms treated by surgical clipping at our hospital between May 2020 and April 2021. We defined parent artery radiation sign (PARS) as the presence of each of the following three findings in CFD analysis based on preoperative CTA: (1) impingement of the stream line on the outer parent vessel wall of the aneurysm; (2) radiation of wall shear stress vectors outwards from the same site; and (3) increased wall pressure compared with the surrounding area. CFD analysis showing PARS was compared with intraoperative findings. Results In all nine cases with PARS, no morphological abnormalities were found in the same area on CTA. However, intraoperative findings showed thinning of the parent artery wall in one of the nine cases and formation of a very small mass in three cases, differing from CTA findings. All nine patients underwent additional clipping and/or wrapping and coating at the site of PARS. Conclusion Detecting thinning of the vessel wall or the presence of a microaneurysm may be difficult in endovascular therapy, which is based on the visualization of the vessel lumen. CFD analysis suggests the necessity of confirming findings for the vessel wall around an aneurysm by direct manipulation, as the presence of PARS may indicate partial thinning of the vessel wall or formation of a microaneurysm.

Efficient simultaneous double DNA knock-in in murine embryonic stem cells by CRISPR/Cas9 ribonucleoprotein-mediated circular plasmid targeting for generating gene-manipulated mice.

Gene targeting of embryonic stem (ES) cells followed by chimera production has been conventionally used for developing gene-manipulated mice. Although direct knock-in (KI) using murine zygote via CRISPR/Cas9-mediated genome editing has been reported, ES cell targeting still has merits, e.g., high throughput work can be performed in vitro. In this study, we first compared the KI efficiency of mouse ES cells with CRISPR/Cas9 expression vector and ribonucleoprotein (RNP), and confirmed that KI efficiency was significantly increased by using RNP. Using CRISPR/Cas9 RNP and circular plasmid with homologous arms as a targeting vector, knock-in within ES cell clones could be obtained efficiently without drug selection, thus potentially shortening the vector construction or cell culture period. Moreover, by incorporating a drug-resistant cassette into the targeting vectors, double DNA KI can be simultaneously achieved at high efficiency by a single electroporation. This technique will help to facilitate the production of genetically modified mouse models that are fundamental for exploring topics related to human and mammalian biology.

Coexistence of neurovascular compression syndrome and unruptured cerebral aneurysm.

Unruptured cerebral aneurysms (UCAs) are usually asymptomatic and detected incidentally by intracranial examinations. The coexistence of neurovascular compression syndrome (NVCS) and UCAs has not been well described. The aim of this study was to clarify the characteristics of UCAs with the NVCS. A total of 103 cases that underwent microvascular decompression (MVD) for trigeminal neuralgia (TN) or hemifacial spasm (HFS) were assigned to the NVCS group. The prevalence of UCAs in the NVCS group was compared retrospectively to that in 110 control cases (a control group) by neuro-imaging. Overall treatment courses for NVCS and UCAs were investigated in the NVCS group. Sixteen (15.3%; TN 11 cases, HFS 5 cases) of 103 MVD cases had 19 UCAs, a significantly higher prevalence than the 3.6% in the control group. Binomial logistic regression showed that NVCS is a significant factor for predicting the presence of UCAs, with an odds ratio of 4.80. In the NVCS group, 18 UCAs (94.7%) were supratentorial aneurysms, and 17 UCAs (89.5%) were less than 5 mm in size. Nine UCAs were surgically treated with clipping or coiling. Of the surgical cases, 2 UCAs were treated before MVD for NVCS, whereas the other 7 UCAs were treated after MVD. No aneurysms ruptured during the treatment course. The NVCS occurred with UCAs at a significantly higher rate than in the control group. Most UCAs with the NVCS were supratentorial, small aneurysms that did not affect the surgical treatment of NVCS.

Depiction of Cerebral Aneurysm Wall by Computational Fluid Dynamics (CFD) and Preoperative Illustration.

Introduction Preoperative illustration is a part of an important exercise to study the configuration, direction, and presence of any perforations, and is the weakest point in the wall of the cerebral aneurysm. The same illustration is used to study the surrounding brain structures to decide the best and safe surgical approach prior to any surgical procedure. With the evolution of the aneurysm wall study and study of flow dynamic within the involved artery and its aneurysm wall using computational fluid dynamics (CFD), a better surgical plan can be formulated to improve the flow dynamics. As one of the clinical applications of CFD, we propose a study using a composite image that combines preoperative illustration and CFD, which is traditionally widely used in neurosurgery. Methods and Materials We study the use of illustrations of the unruptured cerebral aneurysm of internal carotid-posterior communicating (ICPC) artery and anterior communicating artery (AcomA) treated at our hospital. The combinations of both preoperative illustrations and CFD images by using "ipad Pro" were used. Result and Conclusion Medical illustration in the preoperative study of unruptured cerebral aneurysm with combinations of CFD and surrounding brain structures is helpful to decide the surgical approaches and successful surgical treatments.

Efficacy of tadalafil on symptom-specific bother in men with lower urinary tract symptoms.

INTRODUCTION: This multicenter and prospective study was performed to evaluate the efficacy of tadalafil on patient-reported bother for each symptom in men with lower urinary tract symptoms (LUTS). METHODS: Men with LUTS received 5 mg of tadalafil daily for 4 weeks. We assessed change in symptom severity using both international prostate symptom score (IPSS), and overactive bladder symptom score (OABSS), as well as patient-reported quality of life (QOL: bother or satisfaction) for each symptoms using IPSS-visual analog scale (IPSS-VAS) and OABSS-VAS. RESULTS: We found significant improvements in total IPSS (P < 0.001), including voiding symptoms (P < 0.001), storage symptoms (P < 0.001), and QOL (P < 0.001). All VAS measures corresponding to symptoms in IPSS and OABSS also significantly improved (P < 0.001). The most bothersome symptoms for each patient at baseline evaluated by VAS measures significantly improved (P < 0.001). Patients whose most bothersome symptoms at baseline included IPSS-Q7 (nocturia) showed significantly smaller improvement of VAS measure after treatment than those without it (P = 0.024). CONCLUSIONS: Daily tadalafil significantly improved not only symptom severity of LUTS but also patient-reported QOL on each symptom.

Preoperative 3D Image Evaluation of EC-IC Bypass by 3D Visualization Analysis Software Amira®.

Background: Careful evaluation of the preoperative imaging for extracranial-intracranial bypass performed for conditions like intracranial stenosis and Moya disease is important. The traditional use of 2D imaging has a significant limitation for neurosurgeons, primarily to determine the optimal location of the recipient artery for performing the surgical bypass. Therefore, many neurosurgeons use 3D angiograms more frequently to overcome these shortcomings. Materials And Methods: We performed the preoperative evaluation of the possibility of performing an anastomosis between the superficial temporal artery and the middle cerebral artery (STA-MCA) bypass by synthesizing images of computerized tomography (CT), magnetic resonance imaging (MRI), and digital subtraction angiography (DSA) using Amira® of 3D visualization analysis software (Thermo Scientific Co.). Results: The 3D images prepared before surgery using this software showed good agreement with the intraoperative findings. Conclusion: Preoperative image processing using tools like Amira provide optimal information for good planning and communication for performing STA-MCA bypass and may become a helpful tool.

YAP1/TAZ activity maintains vascular integrity and organismal survival.

Radiation therapy is one of the major treatment modalities for patients with cancers. However, ionizing radiation (IR) damages not only cancer cells but also the surrounding vascular endothelial cells (ECs). Hippo pathway effector genes Yap1 and Taz are the two transcriptional coactivators that have crucial roles in tissue homeostasis and vascular integrity in various organs. However, their function in adult ECs at the steady state and after IR is poorly understood. Here, we report sex- and context-dependent roles of endothelial YAP1/TAZ in maintaining vascular integrity and organismal survival. EC-specific Yap1/Taz deletion compromised systemic vascular integrity, resulting in lethal circulation failure preferentially in male mice. Furthermore, EC-specific Yap1/Taz deletion induced acute lethality upon sublethal IR that was closely associated with exacerbated systemic vascular dysfunction and circulation failure. Consistent with these findings, RNA-seq analysis revealed downregulation of tight junction genes in Yap1/Taz-deleted ECs. Collectively, our findings highlight the importance of endothelial YAP1/TAZ for maintaining adult vascular function, which may provide clinical implications for preventing organ injury after radiation therapy.

The oncogene-dependent resistance to reprogramming unveils cancer therapeutic targets.

The resistance to transcription factor-mediated reprogramming into pluripotent stem cells is one of the distinctive features of cancer cells. Here we dissect the profiles of reprogramming factor binding and the subsequent transcriptional response in cancer cells to reveal its underlying mechanisms. Using clear cell sarcomas (CCSs), we show that the driver oncogene EWS/ATF1 misdirects the reprogramming factors to cancer-specific enhancers and thereby impairs the transcriptional response toward pluripotency that is otherwise provoked. Sensitization to the reprogramming cue is observed in other cancer types when the corresponding oncogenic signals are pharmacologically inhibited. Exploiting this oncogene dependence of the transcriptional "stiffness," we identify mTOR signaling pathways downstream of EWS/ATF1 and discover that inhibiting mTOR activity substantially attenuates the propagation of CCS cells in vitro and in vivo. Our results demonstrate that the early transcriptional response to cell fate perturbations can be a faithful readout to identify effective therapeutics targets in cancer cells.