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Hands-on training is a crucial part of education in neuroendovascular treatment to ensure safe and rapid acquisition of techniques. However, there is a significant gap between training and actual clinical practice. This study will introduce innovations for more practical thrombus retrieval training that was developed in this process. A Smart Vascular Model 3 in 1 was used. A pink pseudothrombus was inserted into the M1 (horizontal segment of the middle cerebral artery) section of the model. Then, a "red underlay" purchased at a stationery store was placed to cover the proximal part of M1 and beyond so that the pseudothrombus was not visible. The thrombus was retrieved during training by looking for the location of the thrombus based on the behavior and resistance of the tip of the guidewire and deployment of the stent retriever. The participants were required to have detailed observation skills and precise manipulation skills using a red film to prevent the direct visualization of the pseudothrombus. The implementation of this innovation to the previous hands-on training made the training more practical and effective. If the exact thrombus location can be determined by the behavior of the wire tip, the device's capabilities can be maximized, and rapid retrieval can be expected. It could also reduce complications, as unnecessary peripheral guidance of the device could be avoided.

Objective  In neuroendovascular treatment, there are many opportunities to guide multiple catheters into the intracranial blood vessels. We report the relationship between two microcatheters according to the guiding order with experimental in vitro studies. Materials and Methods  We hypothesize that in a bent blood vessel such as a paraclinoid region of the internal carotid artery, the catheter that was first guided tended to pass through the inside, and the catheter that was guided later tended to pass through the outside. The in vitro verification was performed using a microcatheter and a balloon catheter in a silicone vascular aneurysmal model. Results  As a result, it was found that the two catheters were arranged according to our hypothesis. This finding was also observed during the actual operation of balloon-assisted coil embolization. Conclusion  The positional relationship between the two catheters according to the navigation order is very important, in particular during balloon-assisted coiling and stent-assisted coiling via a jailed microcatheter., Competing Interests: Conflict of Interest Dr. Miyachi and Dr. Ohshima are reported speaker fees from Medtronic., (Asian Congress of Neurological Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Objective  We noticed that the X-ray absorption value of the tip of each microcatheter used for aneurysm treatment varied from product to product. We hypothesized that the differences were caused by variations in the metal's density braid, which could be related to the ability of the tip to retain its shape. Methods  The X-ray absorption value of each microcatheter tip was measured. Next, heat forming was performed using a shaping mandrel at 6 mm and 90 degrees to determine whether there was a correlation between the X-ray absorption value and the forming angle. Next, the optimal mandrel angle for forming each microcatheter at 90 degrees was investigated. We also examined the shape retention after 20 times wire insertions into each microcatheter. Conclusion  It was found that the higher the X-ray absorption value, the harder it was for the microcatheter to be formed. The mandrel angle required to form 90 degrees was determined by the X-ray absorption value. The higher the X-ray absorption value, the higher the shape retention of the tip shape. The heat formation and shape-retention conditions of the microcatheter tip were correlated with the X-ray absorption value of the metal braid. Even for unknown microcatheters, the optimum shaping conditions can be inferred from the X-ray absorption value., Competing Interests: Conflict of Interest S. M. and T. O. have received speaker fees from Medtronic., (Asian Congress of Neurological Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Transarterial embolization using Onyx is a well-established treatment for dural arteriovenous fistulas (DAVFs). However, complications can arise when Onyx migrates into the venous side, impairing the draining veins. We encountered a case where Onyx, injected through the arterial side, strayed into the jugular vein, forming a hairball-like structure. Our study aimed to investigate the underlying mechanism of this unusual phenomenon. We postulated that Onyx precipitates into thread-like shapes when passing through extremely narrow openings. To test this, we extruded Onyx from a syringe through a 27-gauge needle into a silicone tube with flowing water. By varying the flow speed, we observed the hardening behavior of Onyx. Under slow flow, the extruded Onyx quickly solidified at the needle tip, forming a round mass. Conversely, high-speed flow resulted in Onyx being dispersed as small pieces. We successfully replicated the formation of "Onyx threads" under continuous slow flow conditions, similar to our case. This phenomenon occurs when Onyx unexpectedly migrates to the draining vein through a tiny opening during transarterial embolization for arteriovenous shunt diseases. Early recognition and appropriate measures are necessary to prevent occlusive complications in the draining veins and the pulmonary system.

Background: Clinical guidelines recommend antipsychotics for the treatment of delirium; however, there has been no confirmed recommendation regarding their administrating patterns. This study aims to investigate whether different dosing patterns of antipsychotics (single or multiple administrations) influence the outcomes of delirium treatment., Methods: This is a secondary analysis of a prospective observational study involving patients with advanced cancer and delirium receiving antipsychotics. The Delirium Rating Scale Revised-98 was administered at baseline and after 72 h of starting pharmacotherapy. Patients were classified into single administration group (received a single dosage within 24 h before the assessment) and multiple administration group (received more than one dosage)., Results: A total of 555 patients (single administration 492 (88.6%); multiple administration 63 (11.4%)) were subjected to analyses. The patients in the multiple administration group were more likely to be male, in psycho-oncology consulting settings, with lower performance status, with hyperactive delirium and with severer delirium symptoms. In the multivariate analysis, single administration was significantly associated with better improvement of delirium (p < 0.01, 95% confidence interval: 1.83-5.87) even after controlling covariates. There were no significant differences in the mean dosages of antipsychotics per day in chlorpromazine equivalent (single administration 116.8 mg/day, multiple administration 123.5 mg/day) and the incidence of adverse events between the two groups., Conclusions: In this observational study sample, Delirium Rating Scale severity score improvement in single administration was higher than that seen in multiple administration. There was no difference in adverse events between the two groups., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The COVID-19 pandemic has demanded a change in learning modalities, which led us to develop a remote personal training system for clinicians performing neuroendovascular procedures. A portable vascular model designed for practicing catheter navigation guidance, thrombus retrieval, and intracranial aneurysm coil embolisation was established. We created an environment that enabled interactive dialogue and communication across long distances using the Internet. The instructor conducted approximately 2 h of hands-on training with two to four trainees at a time. Despite the restrictions enforced by the Government of Japan due to the COVID-19 pandemic, 17 online hands-on training were successfully conducted throughout Japan over 1 year for a total of 48 trainees. The developed remote training programme, to avoid the aggregation of a large number of trainees at a developed time, proved to be at par with the conventional learning system. The training was well-received since the operation time was longer and the question and answer sessions were more fulfilling compared to the conventional format in which a group of trainees had got a brief opportunity to receive actual hands-on experience.

In the hippocampus, environmental changes elicit rearrangement of active neuronal ensembles or remapping of place cells. However, it remains elusive how the brain ensures a consistent representation of a certain environment itself despite salient events occurring there. Here, we longitudinally tracked calcium dynamics of dorsal hippocampal CA1 neurons in mice subjected to contextual fear conditioning and extinction training. Overall population activities were significantly changed by fear conditioning and were responsive to footshocks and freezing. However, a small subset of neurons, termed environment cells, were consistently active in a specific environment irrespective of experiences. A decoder modeling study showed that these cells, but not place cells, were able to predict the environment to which the mouse was exposed. Environment cells might underlie the constancy of cognition for distinct environments across time and events. Additionally, our study highlights the functional heterogeneity of cells in the hippocampus., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: A method of guiding an intermediate catheter from a new alpha-type guiding catheter placed in the ascending aorta to the carotid artery is evaluated in neuroendovascular treatment in challenging anatomic directions of the guiding catheter, such as the bovine aortic arch and type III aortic arch., Methods: The existing 8-Fr guiding catheter was given a strong bending shape at the tip to make it an alpha type. The total length of the catheter was 85 cm. This guiding catheter was inserted into the ascending aorta to verify whether a 6-Fr intermediate or aspiration catheter could be coaxially guided into the right and left internal carotid arteries. A silicone vascular model was used for evaluation and in actual clinical cases., Results: Creating an alpha shape of the catheter at the aortic arch was very easy. The inner catheter could be easily guided from the brachiocephalic artery to the right common carotid artery by pushing the alpha shape guiding catheter toward the aortic valve. The catheter was easily guided into the left common carotid artery when the α-guide was pulled a little bit backward. The 0.071-inch lumen aspiration catheter reached the bilateral middle cerebral arteries., Conclusions: The 8-Fr alpha shape guiding catheter quickly guides the inner catheter into the bovine and the type III aortic arch by looking up from the ascending aorta., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Context: With global population aging, the number of older patients with cancer is increasing. However, few data are available on palliative care for these patients., Objectives: To evaluate differences in symptom prevalence and the need for medical interventions among patients of different ages in a palliative care unit., Methods: In this retrospective analysis, a consecutive sample of 1032 terminally ill patients with cancer were categorized into the following age ranges: <70, 70-79, 80-89, and ≥90 years. We evaluated symptom prevalence, the need for palliative medicines, opioid dose on the day before death, and the need for palliative sedation. Trend tests were used to examine whether the prevalence of findings increased or decreased with age., Results: As age increased, significant decreasing trends were observed in the prevalence of pain, dyspnea, fatigue, constipation, nausea, drowsiness, difficulty sleeping, anxiety, and dysuria but not in appetite loss, edema, sputum production, or delirium. As age increased, significant decreasing trends were also observed in the need for opioids, benzodiazepines, antiemetics, and anticholinergics. The median opioid doses in the <70, 70-79, 80-89, and ≥90 years age groups were 118, 72, 48, and 48 mg oral morphine equivalents/day, respectively (P < 0.0001). The need for palliative sedation showed a significant decreasing trend as age increased (P < 0.0001)., Conclusion: We found age to be inversely related to symptom prevalence and medical interventions among terminally ill patients with cancer, contributing to the understanding of the experience of older patients with cancer., (Copyright © 2021 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: We investigated the age distribution of cerebral saccular aneurysms in various locations to clarify the differences by location and discuss the mechanism of formation., Materials and Methods: We retrospectively assessed clinical material obtained from 1,252 unruptured aneurysms treated with endovascular embolization between 2004 and 2019. Age, sex, laterality, and size were investigated by the location of aneurysms, classified as cavernous internal carotid artery (ICA), paraclinoid ICA, supraclinoid ICA, anterior communicating artery, anterior cerebral artery, middle cerebral artery, basilar artery complex, and posterior inferior cerebellar artery. Paraclinoid aneurysms were subclassified into 3 patterns according to their projecting direction: S-type, with superior protrusion; M-type, with medial protrusion; and P-type, with posteroinferior protrusion., Results: There was no significant difference by location for sex, laterality, and size. The mean age of patients with paraclinoid aneurysms (56.5 years old) was significantly lower than that of other aneurysm patients (64.3 years old). Notably, 40% of the patients with M-type aneurysms were <50 years old. This percentage was significantly higher than that of aneurysms at other locations (P<0.05)., Conclusion: We found a young female predominance for patients with paraclinoid carotid aneurysms. This study may suggest that congenital factors contribute to paraclinoid aneurysm formation as well acquired factors, such as hemodynamic stress, atherosclerotic wall damage, and local inflammation.

Objectives: For patients with acute ischemic stroke, various endovascular approaches have been reported with high recanalization rates and good clinical outcomes. However, the best technique for the first attempt at mechanical thrombectomy remains a matter of debate. In this study, we evaluated the efficacy of a modified version of a stent-retrieving into an aspiration catheter with a proximal balloon (ASAP) technique., Materials and Methods: Modification 1: After stent deployment, the microcatheter was not removed immediately. Modification 2: After the withdrawal of the stent retriever into an aspirator and its removal from the entire system, we focused on the drainage of fluid into a pump. The aspirator was withdrawn slowly until the fluid appeared to be draining continuously into the pump. Before the removal of the aspirator, we performed angiography through the aspirator. We carried out a retrospective analysis of 30 consecutive patients with acute ischemic stroke caused by occlusion of the anterior circulation who were treated with the modified ASAP technique at our institution., Results: A thrombolysis in cerebral infarction score of 2B or 3 was achieved in 29/30 patients (96.7%). The average number of passes was 1.2 ± 0.5. The mean time from puncture to recanalization was 17.6 ± 6.84 min. Twenty-three (76.7%) patients achieved a modified Rankin Scale score of 0-2 at 3 months after the procedure., Conclusions: We found that the modified ASAP technique yielded fast recanalization, minimal complications, and good clinical outcomes of mechanical thrombectomy in this case series., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Asian Journal of Neurosurgery.)

Objective: Accurately determining the clot position is highly important for immediate recanalization when endovascular mechanical thrombectomy is performed using a stent retriever and aspiration catheter. We describe a new method that facilitates the precise identification of the clot position called pull the trigger sign (PTS)., Case Presentation: Selective angiography was performed through a 0.027-inch microcatheter that penetrated the clot into the distal lumen. Although the contrast media highlighted the occluded artery, it often stagnated in the distal artery. It was washed away at a certain point when a stent clot retriever was deployed over the potential clot site. We hypothesized that this point represented the exact position of the clot's proximal end and used in vitro analyses to assess this hypothesis. Briefly, a circulation-enabled silicone vascular model in which colored water was used to simulate stagnation beyond a fake clot was developed and utilized to investigate PTS six times. The rate of identifying PTS in the vascular model was 100%. As hypothesized, stagnant fluid was washed away when the deployed stent reached the clot's proximal position. The clinical efficacy of PTS was also confirmed., Conclusion: PTS was useful in revealing the precise position of clot's proximal end, which enabled safer contact aspiration when using an aspiration catheter. Thus, PTS led to a higher success rate and faster recanalization in the first attempt than conventional methods., Competing Interests: Drs. Ohshima and Miyachi received rewards, such as lecture fees, from Medtronic Japan Co., Ltd. (Tokyo). The other authors declare no conflict of interest., (©2021 The Japanese Society for Neuroendovascular Therapy.)

Purpose: Parenteral morphine is widely used for dyspnea of imminently dying cancer patients, but the outcomes to expect over time remain largely unknown. We examined outcomes after the administration of parenteral morphine infusion over 48 h in cancer patients with a poor performance status., Methods: This was a multicenter prospective observational study. Inclusion criteria were metastatic/locally advanced cancer, ECOG performance status = 3-4, a dyspnea intensity ≥ 2 on a Support Team Assessment Schedule, Japanese version (STAS-J), and receiving specialized palliative care. After initiating parenteral morphine infusion, we measured dyspnea STAS-J as well as Memorial Delirium Assessment Scale (MDAS), item 9, and Communication Capacity Scale (CCS), item 4, every 6 h over 48 h., Results: We enrolled 167 patients (median survival = 4 days). The mean age was 70 years, 80 patients (48%) had lung cancer, and 109 (65%) had lung metastases. The mean STAS-J scores decreased from 3.1 (95% confidence interval (CI) = 3.0-3.2) at the baseline to 2.1 (95%CI = 1.9-2.2) at 6 h, and remained 1.6-1.8 over 12-48 h. The proportion of patients with dyspnea relief (STAS-J ≤ 1) increased to 39% at 6 h, and ranged between 49 and 61% over 12-48 h. In contrast, up to 6.6 and 20% of patients showed hyperactive delirium (MDAS item 9 ≥ 2) and an inability to communicate (CCS item 4 = 3), respectively, over 48 h., Conclusions: Overall, terminal dyspnea was relatively well controlled with parenteral morphine, though a significant number of patients continued to suffer from dyspnea. Future efforts are needed to improve outcomes following standardized dyspnea treatment using patient-reported outcomes for imminently dying patients.

Background: When endovascular clot retrievals are performed using a stent retriever and/or an aspiration catheter, identifying the accurate position of a clot is extremely important for a successful immediate recanalization. Herein, we report a new technique called microcatheter withdrawing angiography, which facilitates the identification of the precise position of a clot. The negative shadow appearance of the clot on angiography was referred to as the actual crab claw sign., Methods: When a 0.027-inch microcatheter penetrated the clot after inserting a 0.014-inch microwire, selective angiography was conducted using the microcatheter. Simultaneously, the microcatheter was slowly withdrawn with continuous contrast media injection, while the microwire was kept in the distal vessel. The precise position of the clot was found, which was referred to as the actual crab claw sign. Next, we conducted in vitro and in vivo analyses., Results: The actual crab claw sign could be identified in the vascular model and in actual clinical settings. Therefore the sweet spot of the stent retriever could be set over the clot, and an accurate contact aspiration could be performed using an aspirator., Conclusions: Microcatheter withdrawing angiography can help identify the actual crab claw sign. This technique has a higher success rate and faster recanalization than conventional strategy, particularly in challenging cases of unsuccessful recanalization during the first attempt., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Mechanical thrombectomy has been widely used for the treatment of acute ischemic stroke. During this procedure, operators must navigate the microcatheter with a microguidewire (MGW) into vessels that cannot be visualized on fluoroscopy as rapidly as possible. In this study, we developed a modified pigtail-shaped MGW (MPMGW) for security and controllability. Moreover, the efficacy of the MPMGW for the treatment of acute ischemic stroke was assessed. The MPMGW was designed using 0.014 MGW. Because we created four MPMGWs during a clinical evaluation before the launch in the market, these wires were used in four consecutive patients with acute ischemic stroke in the single institution. The occluded arteries were the basilar artery ( n = 1), middle cerebral arteries (M1 and M2, n = 2), and internal carotid artery ( n = 1). All four procedures were conducted without any complications. The procedures included navigating the MGW and passing it through the clot. Complete recanalization was achieved in all cases. The average time between femoral artery puncture and recanalization was 15 min. The use of the preshaped MPMGW in acute thrombectomy was effective in terms of both security of procedure and reduction in recanalization time., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Asian Journal of Neurosurgery.)

Variegatic acid, isolated from Tylopilus ballouii dry fruiting bodies, is an inhibitor of β-hexosaminidase release and tumor necrosis factor (TNF)-α secretion from rat basophilic leukemia (RBL-2H3) cells, with IC 50 values of 10.4 μM and 16.8 μM, respectively. On the other hand, it inhibits PKCβ1 activity with an IC 50 value of 36.2 μM., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Complete and secure occlusion of the entire aneurysmal neck remains a problem despite major advances in the treatment of intracranial aneurysms using endovascular coil embolization. Here, we present our initial clinical experience using a novel strategy for endovascular coil embolization involving a microcatheter tip, known as the "Γ (gamma) tip method," and compare the in vitro results of this technique with those of conventional straight microcatheters. The microcatheters were bent at a right angle starting 1-2 mm from the length of the tip using a catheter-shaping mandrel and a hot air gun. The tiny right-angled tip is the "Γ tip." In aneurysm models, we assessed the efficacy of shaping during coil deployment. The Γ-tipped microcatheters demonstrated better movement and oscillation during insertion of the coil into the aneurysm compared with the straight-tipped catheters. Moreover, the Γ-tipped microcatheter provided less coil protrusion into the parent artery and less microcatheter kickback compared with the straight tip. With the Γ-tipped microcatheter, even if the first coil loop migrated into the parent artery, its subsequent dynamic movement routed it back into the aneurysm. The Γ tip method enabled smooth movement of the microcatheter into the aneurysm, demonstrating the safety and security of coil insertion using the Γ tip compared with the conventional straight tip.

Background: When inserting coils under stent deployment, a jailed microcatheter technique is typically applied as a first line approach. However, the trans cell approach might be required to achieve satisfactory complete occlusion. The trans cell approach occasionally ends in failure because the catheter cannot safely follow a proceeding guidewire into the aneurysm. Here, we report the new wireless trans cell approach (WTA), which allows feasible and safe catheter navigation through the stent strut into the aneurysm, without a proceeding guidewire., Methods: A straight tip microcatheter was used, and the tip was shaped as a very small bend of approximately 45°. The side aspect of the catheter tip exhibited a right angled edge, while the front aspect showed a round curve in the advancing direction. We compared the 45° microcatheter with a straight tip microcatheter using a silicon vascular model and then applied the WTA in a case of an unruptured basilar apex aneurysm., Results: Catheter navigation through the stent strut was smoother with the WTA than the conventional wire assisted approach. Our case of a basilar apex aneurysm was successfully treated with the dual catheter technique, which involved a jailed catheter and navigation using the WTA. After stent deployment from the right posterior cerebral artery to the basilar artery through the 45° microcatheter, the WTA was applied using the same catheter. No stress was detected during catheter navigation through the stent strut into the aneurysm., Conclusions: The WTA is associated with smoother catheter navigation compared with the conventional wire assisted approach in cases of a terminal type aneurysm., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Asian Journal of Neurosurgery.)

Background: Stent clot retrievers can be used to perform mechanical thrombectomies to treat cases of acute major arterial occlusion. This approach is associated with faster recanalization and better outcomes than internal treatments. The function of the stent retrievers is based on a technique known as confront clot scrambling method (CCSM), which usually involves the insertion of two stent retrievers (one from each side) and the simultaneous withdrawal of the retrievers with an equal force. It was determined that a stent used to remove the sham clot possessed a stronger ability for clot retrieval. However, this method involves inherent manipulation bias, and the results may vary due to operator-specific factors. Thus, this approach can be difficult to teach, especially to beginners., Materials and Methods: We evaluated the accuracy of using an equitable automatic withdrawal machine for the CCSM on a model of a sham clot in the middle of a polyvinyl chloride tube., Results: This tool is expected to facilitate thorough and repeated training that is needed to learn the fine maneuvers against invisible vessels associated with actual endovascular clot retrieval, particularly for beginners., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Asian Journal of Neurosurgery.)

Background : Tumor fever and infection are common febrile etiologies among advanced cancer patients. To date, only few studies have been conducted to differentiate between tumor fever and infections. Objective: This study aimed to identify discriminating factors that provide rapid results and are feasible and minimally invasive for discriminating between tumor fever and infection in advanced cancer patients. Methods : This is a retrospective cohort study. Advanced cancer patients with clinically diagnosed tumor fever or infection, who received medical treatment from palliative care specialists in 10 nationwide Japanese hospitals, were consecutively identified during August 2012 and November 2014. The symptoms, physical findings, blood test results at baseline and during fever, imaging findings, and sociodemographic factors of these patients were retrospectively extracted. Results : Thirty-three patients with tumor fever and 72 patients with infection were identified. Their mean age was 68.8 years, 68 (64.8%) were men, and the median palliative performance status (PPS) was 50. Statistically significant factors predicting tumor fever by logistic regression analysis were as follows: deterioration of PPS (odds ratio, 0.078), shaking chills during fever (0.067), and change from baseline data of neutrophil/lymphocyte ratio of ≥5 (0.14). Conclusions : Shaking chills during fever, and changes from baseline of performance status and white blood cell differentiation can be useful to differentiate between tumor fever and infection among advanced cancer patients. Further confirmatory studies are needed.

Background: Gastrointestinal symptoms, including nausea, vomiting, bowel obstruction, ascites, constipation, and anorexia, are common and often refractory in advanced cancer patients. The palliation of gastrointestinal symptoms is important in improving the quality of life of cancer patients, as well as that of their families and caregivers. Currently published clinical guidelines for the management of gastrointestinal symptoms in cancer patients do not comprehensively cover the topics or are not based on a formal process for the development of clinical guidelines. Methods: The Japanese Society for Palliative Medicine (JSPM) developed comprehensive clinical guidelines for the management of gastrointestinal symptoms in cancer patients after a formal guideline development process. Results: This article summarizes the recommendations along with their rationale and a short summary of the development process of the JSPM gastrointestinal symptom management guidelines. We established 31 recommendations, all of which are based on the best available evidence and agreement of expert taskforce members. Discussion: Future clinical studies and continuous guideline updates are required to improve gastrointestinal symptom management in cancer patients.

Background: Persistent primitive trigeminal artery (PPTA) is the most common type of fetal carotid-basilar persisting communication in adulthood; however, carotid-cavernous fistulas (CCFs) associated with PPTA are rare., Case Description: An 84-year-old woman presented with traumatic CCF associated with PPTA manifesting as vascular bruit. Transarterial embolization was performed. Although a detachable coil was deployed at the fistula point, it was easy to migrate into the cavernous sinus because of the high-flow shunt. Therefore, a stent was deployed in the PPTA, and the inner lumen of the stent with a focus on the fistula point was occluded by using coils. Subsequently, the CCF completely disappeared., Conclusions: In-stent coil embolization was effective and reasonable for the high-flow CCF associated with the PPTA. This method reduced the number of coils required and operating time. However, careful preservation of perforators is needed., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: When a shaping mandrel is inserted into the tip of a preshaped microcatheter, the existing curve becomes uncertain because the tip is straightened by the inner mandrel. Therefore, we developed a way to perform microcatheter shaping by means of an external cast, which we named "microcatheter shaping cast.", Techniques: A shaping mandrel attached to a microcatheter was used and coiled 4-5 times around a metallic introducer, which was attached using a microguidewire. Then, a stent-like handmade cast was prepared. After the microcatheter tip was inserted into the cast, it was manually bent according to the aneurysmal shape and size. The tip and cast were heated with a hot air gun. We evaluated the relationship between degrees of bending and heating time to achieve appropriate right-angled shaping memory., Conclusions: The presented microcatheter shaping method should be more useful than conventional internal shaping, especially in cases that require an additional microcatheter shaping or reshaping during aneurysmal coil embolization., Competing Interests: There are no conflicts of interest.

Background: Robotic technology is rapidly developing in the medical field, particularly contributing to support operative intervention using the da Vinci system during endoscopic surgery. Neuroendovascular intervention robot surgery is preferred when aiming to reduce radiation exposure among surgeons., Methods: We developed a prototype of a support robot with 2 independent slaves manipulating both the microcatheter and microguidewire connected with the remote master driver with 2 joysticks. This design simulates usual catheterization with both hands. The slave manipulator has a sufficient output force >1 N to reproduce the exact master intervention without slip and delay. This machine has a unique function that indicates the reaction force of the resistance on wire stuck using the sensor system. We investigated the master-slave response, reliability of the force gauge, and degree of slippage of the slave motion on the table and checked the controllability, safety, and reproducibility of microcatheterization and insertion maneuver into the experimental aneurysm in the in vivo silicone vessel model., Results: We realized the well master-slave response with a stable driving speed of the microguidewire at approximately 1 mm/s and with linear correlation between the output voltage and driving force. Also, we confirmed the well safety function to avoid the overloading to the vascular wall with the slippage of the slave roller on loading >1 N pushing force. Successful microcatheterization and insertion into the aneurysm model was performed in the wet vascular model corresponding to the 3-dimensional handling without excessive stress to the vascular or aneurysmal wall., Conclusions: Neuroendovascular intervention requires delicate power adjustment with fine finger control. Our support robot for neuroendovascular interventions demonstrated the accurate reproducibility of the operator's maneuver and safe operation in the vascular model using the sensor system. This system will realize the neurointervention without human operators in the AngioSuite and may facilitate telesurgery with remote control in the near future., (Copyright © 2019. Published by Elsevier Inc.)

Lumbar cerebrospinal fluid drainage has been widely performed in patients at the bedside; however, technical failure can occasionally occur as a result of blind maneuvering. Herein, we present the use of rotational fluoroscopic unit-guided lumbar drainage for patients with an unsuccessful initial attempt at bedside. In four of the 24 patients with aneurysmal subarachnoid hemorrhage, initial lumbar drainage could not be performed at bedside. Thus, a three-dimensional rotational technology guided by a high-quality fluoroscopic unit was used. After a cone-beam computed tomography scan was performed, an accurate puncture point and a target thecal sac were identified using the software. The fluoroscopic unit helped us to identify the puncture point and trajectory with a laser pointer on the patient. A needle was inserted along the tract until the cerebrospinal fluid was collected. The lumbar drainage tube was successfully inserted with a single puncture in all four patients. Rotational fluoroscopic technology helps to identify a suitable puncture point, trajectory and target site for lumbar spinal drainage. Our technique is considerably useful in an era wherein minimally invasive procedures are preferred.

Background: Sinus pericranii (SP) is a rare abnormal connection between the intracranial and extracranial venous drainage pathways through the osseous channels. Herein we present the case of a patient with growing SP, which was successfully treated using endovascular transvenous embolization through external compression with a plastic cup for preventing glue migration into subcutaneous veins., Case Description: A 9-month-old boy presented with a gradually growing mass on the midline cranial vertex after his birth, for which transvenous embolization was performed. A microcatheter was successfully navigated into the SP from the superior sagittal sinus. Because the subcutaneous drainages were confirmed to be multidirectional, we compressed the drainages through the skin using a plastic cup during the glue injection step for preventing glue migration. Subsequently, the SP was completely obliterated. The postoperative course was uneventful., Conclusions: Manual compression using a plastic cup was useful not only for embolization but also for reducing the physician's exposure to radiation as compared with that in the finger compression method. When a direct puncture is required, a plastic cylinder can also be used., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Stent retrievers (SRs) can be used to perform mechanical thrombectomy for the treatment of acute major arterial occlusion. Recanalization is faster, and outcomes are better with treatment involving these devices than with internal treatment. Although several SRs are available, their clot-capturing abilities are unclear. Therefore in the present study, we numerically evaluated the clot-capturing abilities of SRs in an experimental vascular model., Methods: A sham clot (urethane foam) was fixed with sutures at the middle of a vascular model (polyvinyl chloride tube). One end of the tube was connected to a measuring instrument. From the other end, an SR was inserted and deployed over the sham clot. The delivery wire of the stent was then withdrawn at a constant velocity using an automatic withdrawal machine. The maximum frictional force before the stent left the clot was measured. Five stents (Trevo ProVue [2 sizes], Revive, and Solitaire [2 sizes]) and three stent-deployment techniques (standard, push-and-fluff, and wire-push techniques) were evaluated., Results: The clot-capturing ability (maximum withdrawing force [N: newton]) was greater for large-diameter stents than for small-diameter stents (mean 0.39 ± 0.11 vs. 0.56 ± 0.18). For Trevo and Revive, the clot-capturing ability was highest with the push and fluff technique (mean 0.43 ± 0.05). For Solitaire, the ability was the highest with the simple wire-push technique (mean 0.705 ± 0.16)., Conclusions: We successfully numerically evaluated the clot-capturing abilities of SRs. The clot-capturing ability differed among SRs and among stent-deployment techniques., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Ehlers-Danlos syndrome (EDS) is a rare genetic connective tissue disorders, but the vascular type (type IV) typically poses the greatest risk to patients. We report a case of multiple cranial artery dissection, which was successfully treated with carotid artery stenting., Case Description: A 50-year-old woman presented with recurrent severe headaches caused by bilateral vertebral artery dissections that were treated conservatively at our hospital. However, she developed right cervical pain and dizziness at 3 days after admission, and a magnetic resonance angiogram revealed dissection of the right internal carotid artery. Because the dissected portion of the artery had narrowed, a stent was placed. The pearl and string formations in the bilateral vertebral arteries then improved spontaneously. Subsequently, the patient was diagnosed with EDS type IV via a skin biopsy, and review of her family history revealed that multiple family members had suffered from subarachnoid hemorrhages. No neurologic deficits were observed, and the patient was discharged without further events at 30 days after admission., Conclusions: It is extremely rare for multiple artery dissections to occur at the same time. EDS type IV should be considered as an important differential diagnosis in similar cases, even in adult patients without a known history of connective tissue disease or vascular complications., (Copyright © 2018 Elsevier Inc. All rights reserved.)

We previously reported using a microguidewire with a curved, pigtail-shaped tip as an anchor for navigating a microcatheter. However, we considered that the microcatheter could follow even if the tip of wire did not advance so far distally. The present study assessed the usefulness of a modified version of this pigtail-shaped microguidewire for navigating microcatheters to difficult vasculatures during neurointerventions. The microguidewire was repeatedly evaluated using a silicon tube vascular model. We also employed this method as the first choice for some patients. In both the in vitro tests and clinical use, the round curved tip could be used to position the microguidewire at the entry of a sharply angled vessel or aneurysmal neck, and the following catheter could then be advanced gently and easily. This technique allowed navigation of the microcatheter without inserting the guidewire into the distal vasculature.

Background: Pial arteriovenous fistulas (PAVFs) are rare vascular malformations, especially in neonates. The purpose of this report is to discuss the treatment strategy and its associated challenges. We present a case of prenatal intracranial PAVF treated by endovascular embolization in the neonatal period., Case Description: The patient was born through Cesarean delivery and then treated twice using transarterial embolization with detachable platinum coils and n-butyl cyanoacrylate due to intractable heart failure. Even though angiography findings showed dramatical reduction in the shunt, the patient did not recover from heart failure and died at day 49 after birth., Conclusions: Despite current developments in medical technology and therapies, the effective treatment of critical PAVFs still poses a challenge. Therefore, more indications and effective alternative treatments must be discussed., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To report a novel technique ("paper rail") to facilitate inserting the tail of a microguidewire into the tip of a low-profile device during endovascular procedures., Technique: A sterilized nonwoven fabric tape with a smooth glossy paper backing is used. The tape has several linear folds ideal for a paper rail. Holding each piece of equipment about 5 cm from its respective tip, both the tail of the guidewire and the tip of the catheter are navigated at a 30° angle toward each other in the crease until the guidewire enters the catheter. The paper rail technique was compared with the conventional freehand method under varying luminosities found in an operating room. The paper rail technique was most effective in suboptimal lighting, where the mean time was reduced from 83 seconds with the conventional method to 20 seconds with the paper rail maneuver. The times required to insert the wire with the paper rail method were comparable (~22 seconds) at all light levels., Conclusion: The paper rail method may help improve the speed and accurate insertion of the tail of a microguidewire into the tip of low-profile devices during endovascular procedures. It may be particularly useful for physicians in a low-light environment or trainees.

This report describes a cost-effective experimental method for determining an intrinsically disordered protein (IDP) region in a given protein sample. In this area, the most popular (and conventional) means is using the amide ( 1 H N ) NMR signal chemical shift distributed in the range of 7.5-8.5 ppm. For this study, we applied an additional step: analysis of 1 H N chemical shift temperature coefficients ( 1 H N -CSTCs) of the signals. We measured 1 H- 15 N two-dimensional NMR spectra of model IDP samples and ordered samples at four temperatures (288, 293, 298, and 303 K). We derived the 1 H N -CSTC threshold deviation, which gives the best correlation of ordered and disordered regions among the proteins examined (below -3.6 ppb/K). By combining these criteria with the newly optimized chemical shift range (7.8-8.5 ppm), the ratios of both true positive and true negative were improved by approximately 19% (62-81%) compared with the conventional "chemical shift-only" method., (© 2018 The Protein Society.)

Background: Segmental arterial mediolysis is a rare disease characterized by idiopathic noninflammatory vasculopathy involving small to medium arteries. Here, we report a case of ruptured cerebral and abdominal aneurysms, which were successfully treated using emergency endovascular coil embolization., Case Description: A 45-year-old male suffered subarachnoid hemorrhage caused by the rupture of the right vertebral artery dissecting aneurysm, which was treated using emergency endovascular coiling. Iatrogenic dissection of the left vertebral artery occurred during the procedure. A stent was placed, and antivasospasm therapy was initiated after operation. Eight days after admission, the patient experienced sudden hypovolemic shock because of an abdominal hemorrhage, which was diagnosed as the rupture of an aneurysm in the accessory middle colic artery and treated with urgent coil embolization., Conclusions: It is extremely rare for a subarachnoid and an abdominal hemorrhage to occur simultaneously during hospitalization. Here, owing to the vulnerability of the unaffected vertebral artery during the initial procedure, segmental arterial mediolysis was diagnosed., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background and purpose In our previous study, we established the utility of 8-F balloon guide catheters for anterior circulation aneurysms. This study aims to assess the efficacy of the proximal flow control method using 8-F balloon guide catheters for coil deployment into the aneurysms as a novel adjunctive technique for aneurysmal coil embolisation along with local balloon neck remodeling, stent assist and double catheter techniques. Materials and methods We retrospectively analysed patients who underwent endovascular coiling of anterior circulation aneurysms between August 2013 and December 2017. Results Of 206 patients enrolled in this study, the balloon of the guiding catheter was inflated to assist coil deployment in 43 patients (20.9%). In addition, the proximal flow control method found utility in cases with small aneurysms and relatively narrow-necked internal carotid artery. We observed no intraprocedural complications in this study. Conclusion This technique enabled secure coil deployment without navigating another microcatheter or balloon catheter around the aneurysms.

Olfactory signals, including the scent of urine, are thought to be processed by specific brain regions, such as the medial amygdala (Me), and regulate sexual behavior in a sex-dependent manner. We aimed to reveal the sex-specific neural circuit from the accessory olfactory bulb (AOB) to Me by using a transgenic mouse. We quantified the long-lasting green fluorescent protein (GFP) expression profile, which was controlled by the c-fos promotor in a sex-dependent manner by the scent of urine. Female urine predominantly activated neurons of the posterodorsal medial amygdala (MePD) in male mice and the posteroventral medial amygdala (MePV) in female mice. Male urine, in contrast, generated the opposite pattern of activation in the Me. Secondary, the selective artificial activation of these circuits was used to examine their specific behavioral function, by using a dual Cre-loxP viral infection. AAV-hSyn-FLEX-hM3Dq-EGFP-the designer receptor exclusively activated by a designer drug-was infused into the AOB after infection with trans-synaptic AAV(DJ)-CMV-mCherry-2A-Cre-TTC into either the MePD or the MePV. Double virus-transfected mice were injected with hM 3 Dq activator and their sexual behavior was monitored. However, selective activation of sex-dependent circuits, i.e., the AOB-MePD or AOB-MePV, did not significantly alter mounting or attack behavior in male mice. There were clear sex differences in the pheromone conveying circuits in the AOB-Me of mice. The sex-dependent functional activation of the Me, however, no effect on behavior. This suggests that a diverse number of nuclei and brain areas are likely to function in concert to successfully facilitate sexual and aggressive behaviors., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background and Purpose: We report a secure endovascular approach for the treatment of vascular lesions of the posterior circulation. Even if a large profile guide catheter is wedged in the unilateral vertebral artery (VA), our VA flow reversal method can prevent ischemic complications, including the spinal cord infarction., Case Presentation: The patient was a 64-year-old woman who had been followed up for arteriovenous malformation (AVM) and an unruptured aneurysm of the basilar artery-superior cerebellar artery bifurcation. Endovascular treatment was performed because minor bleeding occurred from the AVM. When a 6-French guide catheter was navigated into the right VA, the guide catheter became completely wedged, and blood flow between the tip of the catheter and the VA union was fully stagnated. Because ischemia of the anterior spinal artery and right posterior inferior cerebellar artery could persist for a few hours during the endovascular procedure, we built a continuous reversal circulation from the guiding catheter tip to the femoral vein. The flow stagnation disappeared immediately. There was no complication during embolization of both the AVM and aneurysm., Conclusions: The VA flow reversal method was secure in this case in which the tip of the guide catheter became wedged in the VA during the endovascular procedure., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: The posterior meningeal artery (PMA) is known as a dura mater-nourishing vessel. We encountered a patient with Wallenberg syndrome during transarterial embolization of the PMA associated with the dural arteriovenous fistula (DAVF)., Methods: After development of Wallenberg syndrome in the patient, we assessed origins of the PMA patterns in 300 cases and divided them into 3 types., Case Presentation: A 63-year-old man was incidentally diagnosed as having transverse-sigmoid sinus DAVF with a cortical venous reflux. During the transarterial embolization, the patient complained of vertigo and numbness of the right extremities. Postoperatively, the patient exhibited Wallenberg syndrome. Diffusion-weighted magnetic resonance imaging showed a high-intensity area on the lateral side of the right medulla., Conclusions: While performing arterial embolization of the PMA that directly originates from the intracranial vertebral artery, the possibility of deficient brainstem nourishment must be considered., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

OBJECTIVE The posterior inferior cerebellar artery (PICA) and the vertebral artery (VA) often exhibit anatomical variations at the craniovertebral junction (CVJ). An example of this is the PICA originating extradurally from the V 3 segment of the VA. To date, some cadaveric investigations have been reported, but the incidence and relationship of this variation to the VA and the atlas as observed on clinical imaging have not been discussed. This study evaluated the prevalence of PICAs originating from the V 3 on CT scanning. Other variations of the atlas and VA were also analyzed. METHODS CT images from a series of 153 patients who underwent 3D CT angiography (CTA) were analyzed, and variations of the PICA, VA, and atlas were investigated. RESULTS A total of 142 patients (284 sides) were analyzed; 11 patients (7.2%) were excluded due to poor image quality. The most common VA variation was the PICA originating from V 3 (9.5% of 284 sides), which was more frequently observed on the nondominant VA than the dominant VA (22.5% vs 6.25%, p = 0.0005). A VA with a PICA end was identified in 4 sides (1.4%), which is the same incidence as observed in the persistent first intersegmental VA (1.4%). VA fenestration was only found in 1 side (0.35%). Regarding the atlas, ponticulus posticus was observed in 24 sides (8.5%). There was no relationship between the incidence of ponticulus posticus and the variations of the VA. CONCLUSIONS A PICA originating from V 3 was the most common VA variation at the CVJ and was more common on the nondominant VA. Three-dimensional CTA is useful for the evaluation of this variance. Surgeons should be mindful of this variation during operations.

Intrinsically disordered proteins (IDPs) are an emerging phenomenon. They may have a high degree of flexibility in their polypeptide chains, which lack a stable 3D structure. Although several biological functions of IDPs have been proposed, their general function is not known. The only finding related to their function is the genetically conserved YSK₂ motif present in plant dehydrins. These proteins were shown to be IDPs with the YSK₂ motif serving as a core region for the dehydrins' cryoprotective activity. Here we examined the cryoprotective activity of randomly selected IDPs toward the model enzyme lactate dehydrogenase (LDH). All five IDPs that were examined were in the range of 35-45 amino acid residues in length and were equally potent at a concentration of 50 μg/mL, whereas folded proteins, the PSD-95/Dlg/ZO-1 (PDZ) domain, and lysozymes had no potency. We further examined their cryoprotective activity toward glutathione S -transferase as an example of the other enzyme, and toward enhanced green fluorescent protein as a non-enzyme protein example. We further examined the lyophilization protective activity of the peptides toward LDH, which revealed that some IDPs showed a higher activity than that of bovine serum albumin (BSA). Based on these observations, we propose that cryoprotection is a general feature of IDPs. Our findings may become a clue to various industrial applications of IDPs in the future., Competing Interests: The authors declare no conflict of interest.

Background: Corticosteroids are often used to treat fatigue and anorexia, but occasionally produce delirium. Information on the predictors of delirium in corticosteroid-treated cancer patients remains limited., Objective: To identify potential factors predicting the development of delirium in corticosteroid-treated cancer patients., Design: An exploratory, multicenter, prospective, observational study., Setting/subjects: Inclusion criteria for this study were patients who had metastatic or locally advanced cancer and a fatigue or anorexia intensity score of 4 or more on a 0-10 Numerical Rating Scale., Measurement: Univariate and multivariable analyses were performed to identify the predictors of delirium diagnosed by the Confusion Assessment Method (CAM) within three days of initiation of corticosteroids., Results: Among 207 patients administered corticosteroids, 35 (17%; 95% confidence interval [CI] 12%-23%) developed at least one episode of delirium diagnosed by the CAM. Factors predictive of the development of delirium were as follows: Palliative Performance Scale ≤20, Eastern Cooperative Oncology Group Performance Status (ECOG PS) = 4, the Support Team Assessment Schedule (STAS) score of drowsiness >1, concurrent opioid use, parenteral hydration volume ≤500 mL, and the absence of lung metastasis. A multivariable analysis identified the independent factors predicting responses as ECOG PS = 4 (odds ratio [OR] 4.0; 95% CI 1.7-9.3), STAS score of drowsiness >1 (OR 3.4; 95% CI 1.4-8.2), and concurrent opioid use (OR 3.7; 95% CI 1.0-13)., Conclusion: Delirium in corticosteroid-treated advanced cancer patients may be predicted by PS, drowsiness, and concurrent opioid use. Larger prospective studies are needed to confirm these results.

Purpose: Although corticosteroids can relieve dyspnea in advanced cancer patients, factors predicting the response remain unknown. We aimed to explore potential factors predicting the response to corticosteroids for dyspnea in advanced cancer patients., Methods: In this preliminary multicenter prospective observational study, we included patients who had metastatic or locally advanced cancer, were receiving specialized palliative care services, and had a dyspnea intensity of ≥3 on a 0-10 Numerical Rating Scale (NRS) (worst during the last 24 h). The primary endpoint was NRS of dyspnea on day 3 after the administration of corticosteroids. Univariate/multivariate analyses were conducted to identify factors predicting ≥1-point reduction in NRS., Results: Of 74 patients who received corticosteroids, 50 (68%) showed ≥1-point reduction in dyspnea NRS. Factors that significantly predicted the response were an age of 70 years or older (82 vs. 53%, p = 0.008), absence of liver metastases (77 vs. 46%, p = 0.001), Palliative Prognostic Index (PPI) ≤ 6 (90 vs. 61%, p = 0.041), presence of pleuritis carcinomatosa with a small collection of pleural effusions (84 vs. 55%, p = 0.011), presence of audible wheezes (94 vs. 60%, p = 0.014), and baseline dyspnea NRS ≥7 (76% vs. 52%, p = 0.041). In a multivariate analysis, factors predicting response included PPI <6 (odds ratio (OR), 36.2; p = 0.021), baseline dyspnea NRS (worst) ≥7 (OR, 6.6; p = 0.036), and absence of liver metastases (OR, 0.19; p = 0.029) or ascites/liver enlargement (OR, 0.13; p = 0.050)., Conclusions: The patient characteristics, etiologies of dyspnea, and clinical manifestations may predict responses to corticosteroids for dyspnea. Larger prospective studies are promising to confirm our findings.

Fear memory extinction has several characteristic behavioral features, such as spontaneous recovery, renewal, and reinstatement, suggesting that extinction training does not erase the original association between the conditioned stimulus (CS) and the unconditioned stimulus (US). However, it is unclear whether reactivation of the original physical record of memory (i.e., memory trace) is sufficient to produce conditioned fear response after extinction. Here, we performed pharmacogenetic neuronal activation using transgenic mice expressing hM3Dq DREADD (designer receptor exclusively activated by designer drug) under the control of the activity-dependent c-fos gene promoter. Neuronal ensembles activated during fear-conditioned learning were tagged with hM3Dq and subsequently reactivated after extinction training. The mice exhibited significant freezing, even when the fear memory was no longer triggered by external CS, indicating that the artificial reactivation of a specific neuronal ensemble was sufficient to evoke the extinguished fear response. This freezing was not observed in non-fear-conditioned mice expressing hM3dq in the same brain areas. These results directly demonstrated that at least part of the original fear memory trace remains after extinction, and such residual plasticity might reflect the persistent memory., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The claustrum, a subcortical structure situated between the insular cortex and striatum, is reciprocally connected with almost all neocortical regions. Based on this connectivity, the claustrum has been postulated to integrate multisensory information and, in turn, coordinate widespread cortical activity. Although studies have identified how sensory information is mapped onto the claustrum, the function of individual topographically arranged claustro-cortical pathways has been little explored. Here, we investigated the organization and function of identified claustro-cortical pathways in mice using multiple anatomical and optogenetic techniques. Retrograde and anterograde tracing demonstrated that the density of anterior claustrum-to-cortical projection differs substantially depending on the target cortical areas. One of the major targets was the medial entorhinal cortex (MEC) and the MEC-projecting claustral neurons were largely segregated from the neurons projecting to primary cortices M1, S1, or V1. Exposure to a novel environment induced c-Fos expression in a substantial number of MEC-projecting claustral neurons and some M1/S1/V1-projecting claustral neurons. Optogenetic silencing of the MEC-projecting claustral neurons during contextual fear conditioning impaired later memory retrieval without affecting basal locomotor activity or anxiety-related behavior. These results suggest that the dense, anterior claustro-MEC pathway that is largely separated from other claustro-cortical pathways is activated by novel context and modulates the MEC function in contextual memory., Significance Statement: The claustrum is a poorly understood subcortical structure reciprocally connected with widespread neocortical regions. We investigated the organization and function of identified claustro-cortical projections in mice using pathway-specific approaches. Anatomical tracing showed that the density of anterior claustrum-to-cortical projection is dependent on the target cortical areas and that the medial entorhinal cortex (MEC) is one of the major projection targets. Novel context exposure activated multiple claustro-cortical pathways and a large fraction of the activated neurons projected to the MEC. Optogenetic silencing of the claustro-MEC pathway during contextual fear learning suppressed subsequent memory retrieval. These results suggest that the dense claustro-MEC pathway is activated by novel context and modulates MEC function in contextual memory., (Copyright © 2017 the authors 0270-6474/17/370269-12$15.00/0.)

Purpose: Although corticosteroids are widely used to relieve anorexia, information regarding the factors predicting responses to corticosteroids remains limited. The purpose of the study is to identify potential factors predicting responses to corticosteroids for anorexia in advanced cancer patients., Methods: Inclusion criteria for this multicenter prospective observational study were patients who had metastatic or locally advanced cancer and had an anorexia intensity score of 4 or more on a 0-10 Numerical Rating Scale (NRS). Univariate and multivariate analyses were conducted to identify the factors predicting ≥2-point reduction in NRS on day 3., Results: Among 180 patients who received corticosteroids, 99 (55 %; 95 % confidence interval [CI], 47-62 %) had a response with ≥2-point reduction. Factors that significantly predicted responses were Palliative Performance Scale (PPS) > 40 and absence of drowsiness. In addition, factors that tended to be associated with ≥2-point reduction in NRS included PS 0-3, absence of diabetes mellitus, absence of peripheral edema, presence of lung metastasis, absence of peritoneal metastasis, baseline anorexia NRS of >6, presence of pain, and presence of constipation. A multivariate analysis showed that the independent factors predicting responses were PPS of >40 (odds ratio = 2.7 [95 % CI = 1.4-5.2]), absence of drowsiness (2.6 [1.3-5.0]), and baseline NRS of >6 (2.4 [1.1-4.8])., Conclusions: Treatment responses to corticosteroids for anorexia may be predicted by PPS, drowsiness, and baseline symptom intensity. Larger prospective studies are needed to confirm these results.

The details of contextual or episodic memories are lost and generalized with the passage of time. Proper generalization may underlie the formation and assimilation of semantic memories and enable animals to adapt to ever-changing environments, whereas overgeneralization of fear memory evokes maladaptive fear responses to harmless stimuli, which is a symptom of anxiety disorders such as post-traumatic stress disorder (PTSD). To understand the neural basis of fear memory generalization, we investigated the patterns of neuronal ensemble reactivation during memory retrieval when contextual fear memory expression is generalized using transgenic mice that allowed us to visualize specific neuronal ensembles activated during memory encoding and retrieval. We found preferential reactivations of neuronal ensembles in the primary somatosensory cortex (SS), when mice were returned to the conditioned context to retrieve their memory 1 day after conditioning. In the hippocampal dentate gyrus (DG), exclusively separated ensemble reactivation was observed when mice were exposed to a novel context. These results suggest that the DG as well as the SS were likely to distinguish the two different contexts at the ensemble activity level when memory is not generalized at the behavioral level. However, 9 days after conditioning when animals exhibited generalized fear, the unique reactivation pattern in the DG, but not in the SS, was lost. Our results suggest that the alternations in the ensemble representation within the DG, or in upstream structures that link the sensory cortex to the hippocampus, may underlie generalized contextual fear memory expression.