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We numerically investigated the aggregation dynamics and resulting network structures of colloidal gels using the slippery diffusion-limited cluster aggregation (DLCA) model. In this model, bonds are irreversibly formed upon the particle contacts, but the angles among them are not fixed, unlike the conventional DLCA. This allows clusters to be deformed in the process of aggregation. By characterizing the aggregation dynamics and using a reduced network scheme, our simulation revealed two distinct branching structure formation routes depending on the particle volume fraction ϕ. In lower volume fraction systems (ϕ ≤ 8%), the deformations of small-size clusters proceed prior to the percolation. When the Maxwell criterion is satisfied and the clusters become mechanically stable, the formation of the branching structure is nearly completed. After forming the branching structures, they aggregate and form a larger percolating network. Then, the aggregation proceeds through the elongation and straightening of the chain parts of the network. In higher volume fraction systems (ϕ > 8%), on the other hand, the clusters percolate, and a fine and homogeneous branching structure is formed at the early stage of the aggregation. In the aging stage, it collapses into a denser and more heterogeneous structure and becomes more stable. Our quantitative analyses of the branching structure will shed light on a new strategy for describing the network formation and elasticity of colloidal gels. [ABSTRACT FROM AUTHOR]

Background: Surveys using questionnaires to collect epidemiologic data may be subject to misclassification. Here, we analyzed a headache questionnaire to evaluate which questions led to a classification other than migraine. Methods: Anonymized surveys coupled with medical claims data from individuals 19–74 years old were obtained from DeSC Healthcare Inc. to examine proportions of patients with primary headache disorders (i.e.; migraine, tension-type headache, cluster headache, and "other headache disorders"). Six criteria that determined migraine were used to explore how people with other headache disorders responded to these questions. Results: Among the 21480 respondents, 7331 (34.0%) reported having headaches. 691 (3.2%) respondents reported migraine, 1441 (6.7%) had tension-type headache, 21 (0.1%) had cluster headache, and 5208 (24.2%) reported other headache disorders. Responses of participants with other headache disorders were analyzed, and the top 3 criteria combined with "Symptoms associated with headache" were "Site of pain" (7.3%), "Headache changes in severity during daily activities" (6.4%), and the 3 criteria combined (8.8%). The symptoms associated with headache were "Stiff shoulders" (13.6%), "Stiff neck" (9.4%), or "Nausea or vomiting" (8.7%), Photophobia" (3.3%) and "Phonophobia" (2.5%). Conclusions: Prevalence of migraine as diagnosed by questionnaire was much lower than expected while the prevalence of "other headache" was higher than expected. We believe the reason for this observation was due to misclassification, and resulted from the failure of the questionnaire to identify some features of migraine that would have been revealed by clinical history taking. Questionnaires should, therefore, be carefully designed, and doctors should be educated, on how to ask questions and record information when conducting semi-structured interviews with patients, to obtain more precise information about their symptoms, including photophobia and phonophobia. Highlights: It is difficult to correctly identify "symptoms associated with headache" in a single response survey. Surveys with questions regarding photophobia and phonophobia should be carefully designed to help headache classification. It is necessary to educate patients to understand the symptoms of photophobia and phonophobia. [ABSTRACT FROM AUTHOR]

This paper proposes a practical algorithm and its implementation of automatic berthing in wind disturbances environments. Berthing operation is one of the most complex tasks for seafarers. Automation of the highly burdensome berthing maneuver can be used to assist seafarers. In this study, we analyze the effect of wind disturbance on path following and propose a new path following control algorithm using a 2-DoF controller that introduces a feed-forward control. We also propose a method to reduce path deviation by introducing a runway in path planning. The effectiveness of the proposed method is verified by numerical simulations and shipboard tests using an experimental ship, and the proposed method shows higher performance under wind disturbance than the previous methods. The algorithm verified in this study is implemented as a PLC system, AutoBerth PLC. A PLC is an industrial computer, stable in operation. Using the AutoBerth PLC, we conducted an experiment of automatic berthing by an actual ship and confirmed that the system can be controlled faster and more stable than when controlled by a laptop. To realize a practical system, an alert function for the ODD, an alert function for fallback response regarding self-diagnosis of PLCs and communication monitoring functions were implemented as required functions in a maritime autonomous surface ship (MASS), and these functions were verified on the experimental ship. [ABSTRACT FROM AUTHOR]

In this study, the accuracy of estimation of the ship's position and the heading angle using simultaneous localization and mapping (SLAM) with a light detection and ranging (LiDAR) at sea was verified. In general, the ship's position and the heading angle are obtained using a global navigation satellite system (GNSS) such as global positioning system (GPS) positioning and a GPS compass. The quasi-zenith satellite system (QZSS) has also emerged in Japan with the centimeter-level positioning augmentation system (CLAS), but it does not always provide the best positioning accuracy, even at sea. In addition, while position information and the heading angle of ship are important for control of maritime autonomous surface ships (MASS), they are conventionally dependent on GNSS-based sensor systems. In considering sensor redundancy for safety of MASS, this study performed SLAM using the LiDAR to create a point cloud map of the coast. The point cloud map was compared with open map data, and it was confirmed that a highly accurate map was obtained. This point cloud map can be used for autonomous navigation such as automatic berthing. In order to evaluate the accuracy of estimating the ship's position and the heading angle using LiDAR SLAM, we used the experimental ship to simultaneously take measurements with the marine GPS compass and the QZSS receiver for comparison, in addition to the IMU and the LiDAR, and compared the measurement accuracy by the three sensors. As a result, the position and the heading angle were estimated with higher accuracy using LiDAR SLAM at μ = 1.4 m ( σ = 1.2 m) for position estimation than the GPS with the QZSS data in the RTK-Fix condition as a reference. [ABSTRACT FROM AUTHOR]

Background: Limited epidemiological data are available for headache disorders in Japan, and no recent studies have reported the impact of several primary headache disorders in Japan. This study aimed to report the up-to-date epidemiological data and impact of primary headaches on daily activities as well as the use of medical care, clinical features, and pain severity/activity impairment using nationwide data in Japan. Methods: We used anonymized online survey data coupled with medical claims data, from individuals aged 19–74 years old, that were provided by DeSC Healthcare Inc. The outcomes included the prevalence of migraine, tension-type headache, cluster headache, and other headache types stratified by age and sex, use of medical care, clinical features, medication use, and severity of pain/activity impairment. All outcomes were examined separately for each headache type. This is the second paper reported concurrently with this research. Results: The study population comprised 691/1,441/21/5,208 individuals with migraine/tension-type headache/cluster headache/other headache types, respectively. The prevalence of migraine and tension-type headache was higher in women than in men but was similar for cluster headache (male vs. female, 1.7% vs. 7.4%, 5.3% vs. 10.8%, and 0.1% vs. 0.1%, respectively). The percentage of individuals with migraine, tension-type headache, cluster headache who had not seen a doctor was 81.0%, 92.0%, 57.1%, respectively. The common headache triggers were fatigue in migraine and tension-type headache, and weather-related phenomena and turning of the seasons in migraine. Common activities refrained from or reduced by headaches were “operating a computer or smartphone”, “drinking alcohol”, and “going to crowded places” in all three headache types and housework-related activities in women. Among individuals taking medicines, 16.8%, 15.8%, 47.6% with migraine, tension-type headache, and cluster headache reported moderate to severe pain, respectively, and 12.6%, 7.7%, 19.0% reported moderate to severe disability, respectively. Conclusions: This study found various triggers of headache attacks, and daily activities refrained from or reduced by headaches. Additionally, this study suggested that the disease burden in people possibly experiencing tension-type headaches, many of whom had not seen a doctor. The study findings are of clinical value for the diagnosis and treatment of primary headaches. [ABSTRACT FROM AUTHOR]

Background: Migraine is a chronic disease characterized by episodic headache attacks. No recent studies have, however been conducted on the epidemiology of migraine or the treatment landscape in Japan. This study was conducted as a fact-finding survey using medical claims data and an online survey on migraine and headaches, conducted among members of health insurance associations with the objective of gaining an understanding of migraine prevalence and the treatment status in Japan. Methods: The study methodology utilized a unique approach of combined data sources. The data sources used in this study are medical claims data and linked online survey data provided by DeSC Healthcare Inc (DeSC). The primary outcomes (from survey responses) were: the overall number and proportion of migraine patients; and the overall prevalence of migraine, stratified by age and sex. The secondary outcomes (from survey responses) were use of medical care; and clinical features/headache symptoms. The analysis population included all individuals who had response data for surveys conducted by DeSC. The online survey data and medical claims data were summarized. Results: The data population comprised 21,480 individuals. On the basis of the survey results, including probable cases, the overall prevalence of migraine was 3.2%. The highest prevalence of migraine was observed in patients aged 30–39 years. The prevalence of migraine in women was 4.4 times higher than in men. The percentage of migraine patients who had not been seen by a doctor was 81.0%. More than 80% of patients were taking over-the-counter drugs and 4.8% took prescription medicines only. Approximately 52.9% of patients considered that the intensity of pain symptoms was severe. Moreover, the majority of patients (72.9%) considered that the impairment of daily life activities was of moderate or severe degree. Conclusions: In Japan, the percentage of people with migraine who did not receive medical attention is as high as 80%. Additionally, the majority of patients tend to endure symptoms and continue with everyday activities. With innovative treatment approaches becoming available it is necessary to disseminate information that migraine is not a simple headache but an illness that requires medical treatment and consultation. [ABSTRACT FROM AUTHOR]

Background: Migraine is a chronic disease characterized by episodic headache attacks. No recent studies have, however been conducted on the epidemiology of migraine or the treatment landscape in Japan. This study was conducted as a fact-finding survey using medical claims data and an online survey on migraine and headaches, conducted among members of health insurance associations with the objective of gaining an understanding of migraine prevalence and the treatment status in Japan. Methods: The study methodology utilized a unique approach of combined data sources. The data sources used in this study are medical claims data and linked online survey data provided by DeSC Healthcare Inc (DeSC). The primary outcomes (from survey responses) were: the overall number and proportion of migraine patients; and the overall prevalence of migraine, stratified by age and sex. The secondary outcomes (from survey responses) were use of medical care; and clinical features/headache symptoms. The analysis population included all individuals who had response data for surveys conducted by DeSC. The online survey data and medical claims data were summarized. Results: The data population comprised 21,480 individuals. On the basis of the survey results, including probable cases, the overall prevalence of migraine was 3.2%. The highest prevalence of migraine was observed in patients aged 30–39 years. The prevalence of migraine in women was 4.4 times higher than in men. The percentage of migraine patients who had not been seen by a doctor was 81.0%. More than 80% of patients were taking over-the-counter drugs and 4.8% took prescription medicines only. Approximately 52.9% of patients considered that the intensity of pain symptoms was severe. Moreover, the majority of patients (72.9%) considered that the impairment of daily life activities was of moderate or severe degree. Conclusions: In Japan, the percentage of people with migraine who did not receive medical attention is as high as 80%. Additionally, the majority of patients tend to endure symptoms and continue with everyday activities. With innovative treatment approaches becoming available it is necessary to disseminate information that migraine is not a simple headache but an illness that requires medical treatment and consultation. [ABSTRACT FROM AUTHOR]

Purpose: In two 24‐week migraine prevention studies in Japan, erenumab was associated with significantly greater reductions in migraine frequency versus placebo over Weeks 13–24 (primary endpoint). This post hoc analysis evaluated the onset of efficacy within the first 4 weeks after the initiation of erenumab from the 24‐week double‐blind periods of these studies. Methods: Placebo‐adjusted differences in least squares mean (LSM) change from baseline in weekly migraine days (WMD) were assessed weekly in each study and by migraine type (episodic (EM]/chronic [CM]) (Study 20170609). Results: A total of 407 patients from Study 20120309 (70 mg: N = 135; 140 mg: N = 136; placebo: N = 136) and 261 patients from Study 20170609 ([EM] 70 mg: N = 78; placebo: N = 81; [CM] 70 mg: N = 52; placebo: N = 50) were included. For Study 20120309, onset of efficacy was observed as early as Week 1 in favor of erenumab versus placebo. Placebo‐adjusted differences in LSM (95% confidence interval [CI]) change from baseline in WMD at Week 1 were −0.38 (−0.71 to −0.05; p =.022) and −0.49 (−0.82 to −0.16; p =.004) in favor of erenumab 70 and 140 mg, respectively. For Study 20170609, significant placebo‐adjusted differences were observed with erenumab 70 mg at Week 1 in patients with EM (LSM [95% CI]: −0.55 [−0.97 to −0.12; p =.012]), and at Week 2 in patients with CM (LSM [95% CI]: −0.81 [−1.53 to −0.09; p =.028]) and for the overall population (LSM [95% CI]: −0.71 [−1.09 to −0.33; p <.001]). Conclusions: Erenumab treatment significantly reduced WMD compared with placebo. Onset of erenumab efficacy occurred as early as Week 1 in patients with migraine. [ABSTRACT FROM AUTHOR]

The ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE study in Japan (OVERCOME [Japan]) aimed to provide an up-to-date assessment of migraine epidemiology in Japan. OVERCOME (Japan) was a cross-sectional, population-based web survey of Japanese adults recruited from consumer panels. People with active migraine (met modified International Classification of Headache Disorders, 3rd edition [ICHD-3] criteria or had a self-reported physician diagnosis of migraine) answered questions about headache features, physician consultation patterns, and migraine medication use. The burden and impact of migraine were assessed using Migraine Disability Assessment (MIDAS) and Work Productivity and Activity Impairment scales. In total, 231,747 respondents accessed the screener, provided consent, and were eligible for the survey. The migraine group included 17,071 respondents (mean ± SD age 40.7 ± 13.0 years; 66.5% female). ICHD-3 migraine criteria were met by 14,033 (82.2%) respondents; 9667 (56.6%) self-reported a physician diagnosis of migraine. The mean number of monthly headache days was 4.5 ± 5.7 and pain severity (0–10 scale) was 5.1 ± 2.2. In the migraine group, 20.7% experienced moderate to severe migraine-related disability (MIDAS score ≥ 11). Work productivity loss was 36.2% of work time missed, including 34.3% presenteeism. Only 57.4% of respondents had ever sought medical care for migraine/severe headache. Most respondents (75.2%) were currently using over-the-counter medications for migraine; 36.7% were using prescription nonsteroidal anti-inflammatory drugs, and only 14.8% were using triptans. Very few (9.2%) used preventive medications. Unmet needs for migraine health care among people with migraine in Japan include low rates of seeking care and suboptimal treatment. [ABSTRACT FROM AUTHOR]

Background: These subgroup analyses of a Phase 3, randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of erenumab 70 mg in Japanese migraine patients with/without prior preventive treatment failure(s) ("failed-yes" and "failed-no" subgroups) and with/without concomitant preventive treatment ("concomitant preventive-yes" and "concomitant preventive-no" subgroups). Methods: Overall, 261 patients were randomized; 130 and 131 patients to erenumab 70 mg and placebo, respectively. Subgroup analyses evaluated the change from baseline to Months 4–6 in mean monthly migraine days (MMD) (primary endpoint), achievement of a ≥50% reduction in mean MMD, and change from baseline in mean monthly acute migraine-specific medication (MSM) treatment days. Treatment-emergent adverse events were also evaluated. Results: Of the 261 patients randomized, 117 (44.8%) and 92 (35.3%) patients were in the failed-yes and concomitant preventive-yes subgroups, respectively. Erenumab 70 mg demonstrated consistent efficacy across all subgroups, with greater reductions from baseline in mean MMD versus placebo at Months 4–6 (treatment difference versus placebo [95% CI], failed-yes: − 1.9 [− 3.3, − 0.4]; failed-no: − 1.4 [− 2.6, − 0.3]; concomitant preventive-yes: − 1.7 [− 3.3, 0.0]; concomitant preventive-no: − 1.6 [− 2.6, − 0.5]). Similar results were seen for achievement of ≥50% reduction in mean MMD and change from baseline in mean monthly acute MSM treatment days. The safety profile of erenumab 70 mg was similar across subgroups, and similar to placebo in each subgroup. Conclusion: Erenumab was associated with clinically relevant improvements in all efficacy endpoints and was well tolerated across all subgroups of Japanese migraine patients with/without prior preventive treatment failure(s) and with/without concomitant preventive treatment. Trial registration: Clinicaltrials.gov. NCT03812224. Registered January 23, 2019. [ABSTRACT FROM AUTHOR]

Objective: Restless legs syndrome (RLS) is a sensorimotor disorder that is characterized by uncomfortable and unpleasant sensations mainly in the legs. Two placebo-controlled studies (Phase II/III and post-marketing) in Japanese patients with RLS failed to demonstrate the efficacy of gabapentin enacarbil (GE) 600 mg in the change from baseline in International Restless Legs Syndrome Rating Scale (IRLS) score at the end of the treatment period. The high response to placebo is thought to be a possible reason why the post-marketing study failed. The objectives of these post hoc analyses were to determine potential predictive factors associated with improvement in IRLS score with GE treatment and to identify subgroups with higher placebo responses.Methods: We combined data from the two Japanese studies and analyzed change from baseline in IRLS score in the pooled population and subgroups defined by several patient characteristics. Moreover, we calculated the variable importance of each factor and performed predictive enrichment analysis to identify an enrichable subpopulation with greater improvement by GE treatment.Results: The post hoc analyses suggested that higher baseline IRLS score (≥21) and higher body mass index (≥25 kg/m2) were associated with higher placebo responses. On the other hand, positive family history of RLS, prior use of dopaminergic receptor agonists, and higher baseline ferritin level (≥50 ng/mL) were associated with higher responses to GE.Conclusions: Our results suggest that patients with typical idiopathic RLS characteristics, including positive family history and no low ferritin level, would be expected to derive the greatest benefits from GE treatment. [ABSTRACT FROM AUTHOR]

Introduction: Migraine attacks notably impact people's daily lives, health-related quality of life (HRQoL), and ability to work. Triptans are widely used as acute medication for a migraine attack but are ineffective, poorly tolerated, or contraindicated in some patients. HRQoL and work productivity are therefore likely to pose particular problems for patients whose migraine attacks do not respond sufficiently to triptan acute treatment. This real-world study aimed to determine whether migraine-related HRQoL, disability, and work productivity differed between triptan insufficient responders (TIRs) and sufficient responders (TSRs) receiving this acute treatment for migraine in Japan. Methods: This was a retrospective analysis of 2017 Adelphi Migraine Disease Specific Programme cross-sectional survey data collected from physicians and their consulting patients with migraine in Japan. Patients had to be receiving a triptan as their sole acute prescribed medication for migraine. TIRs were defined as patients who achieved headache pain freedom within 2 h of taking triptan acute treatment in no more than three of five migraine attacks. Differences in outcomes between TIRs and TSRs were examined in adjusted analyses using a multivariable general linear model. Results: Of 200 patients receiving a triptan as their sole prescribed acute treatment for migraine, 88 (44.0%) were classed as TIRs. Migraine-Specific Quality of Life Questionnaire scores were significantly lower—indicating poorer HRQoL—among TIRs than TSRs, as were mean EuroQol 5-dimension utility and visual analog scale scores (p < 0.05 for comparisons). TIRs also reported significantly (p ≤ 0.003) greater impairment than TSRs across all Work Productivity and Activity Impairment domains, with the exception of work time missed. Migraine disability was higher among TIRs than TSRs. Conclusion: Migraine attacks had a negative impact on the HRQoL, disability, and work productivity of people with migraine in Japan reporting insufficient efficacy with acute triptan treatment, highlighting the need for more effective acute treatment options. [ABSTRACT FROM AUTHOR]

This paper aims to verify a new automatic berthing system using a path following algorithm. Berthing operation is one of the most burdensome tasks for crews among several ship operations. The maneuverability of a ship at low speed during berthing operation deteriorates and becomes more vulnerable to disturbances such as wind. Therefore, it is necessary to support and automate operations that require advanced skills such as berthing operation. Previous studies on automatic berthing have investigated various methods to handle the nonlinearity of ship maneuvering motion and determine the optimal control variable. There is a trade-off between accuracy and real-time performance of berthing control from these studies. The algorithms must have sufficiently real-time performance while maintaining the accuracy of control. For these purposes, we propose the automatic berthing system applied a path following algorithm for a ship with one propeller and one rudder in this paper. We show the mathematical model for numerical simulation of berthing control and carried out system identification of the subject ship. In full-scale experiments, the proposed system performed automatic berthing control in both calm wind conditions around 2 m/s and strong wind conditions around 6 m/s. [ABSTRACT FROM AUTHOR]

Background: Real-world data on sufficient/insufficient response, and predictors of insufficient response, to acute treatments for migraine are limited in Japan. This study aimed to identify factors associated with insufficient response to acute treatment of migraine by exploring significant differences between people with migraine who sufficiently/insufficiently respond to prescribed acute treatment in Japan.Methods: This was a retrospective analysis of 2014 Adelphi Migraine Disease Specific Programme cross-sectional survey data collected from physicians and their consulting adult patients with migraine in Japan. Insufficient responders to prescribed acute treatment were patients who achieved headache pain freedom within 2 h of acute treatment in no more than three of their last five migraine attacks. Factors associated with insufficient response to prescribed acute migraine treatment were identified using backward logistic regression.Results: Overall, 227/538 (42.2%) patients were classified as insufficient responders to prescribed acute migraine treatment. Significantly more insufficient responders than sufficient responders had consulted a neurologist or a migraine/headache specialist, and had chronic migraine or medication-overuse or tension-type headaches (p < 0.05). More insufficient responders than sufficient responders reported taking acute treatment when/after the pain started (77.0 vs. 68.9%) than at first sign of migraine (p < 0.05). Compared with sufficient responders, insufficient responders reported a significantly higher mean ± standard deviation (SD) Migraine Disability Assessment total score (12.7 ± 23.3 vs. 5.8 ± 10.4, p < 0.001) and lower quality of life (EuroQol-5 Dimensions utility score 0.847 ± 0.19 vs. 0.883 ± 0.16, p = 0.024). Factors significantly associated with insufficient response to acute treatment included seeing a neurologist versus an internist (odds ratio [OR] 1.93; 95% confidence interval [CI] 1.29-2.88; p = 0.002), taking acute medication when/after pain started versus at first sign of migraine (OR 1.65; 95% CI 1.05-2.60; p = 0.030), a higher MIDAS total score (OR 1.04; 95% CI 1.02-1.06; p < 0.001), and presence of comorbid cardiovascular disease (OR 0.53; 95% CI 0.28-0.98; p = 0.044).Conclusions: Many people with migraine in Japan struggle to adequately treat migraine attacks with prescribed acute medication and exhibit high levels of unmet need for acute treatment. Optimized management strategies utilizing existing therapeutic options as well as additional effective therapeutic options for migraine are required to improve symptoms and quality of life. [ABSTRACT FROM AUTHOR]

Background: The current status of site-specific cancer registry has not been elucidated, but sufficient system is found in some societies. The purpose of this study was to clear the present condition of site-specific cancer registries in Japan and to suggest for the improvement. Methods: The questionnaire was conducted by the study group of the Ministry of Health, Labor, and Welfare. It consisted of 38 questions, conflicts of interest, clinical research method, informed consent and funding for registry. We distributed this questionnaire to 28 academic societies, which had published the clinical practice guideline(s) assessed under Medical Information Network Distribution Service (MINDS). Results: The concept of the importance in assessment for medical quality by the data of the site-specific cancer registry was in good consensus. But the number of the society with the mature registry was limited. The whole-year registry with the scientific researches in the National Clinical Database (NCD) and in the Translational Research Informatics Center (TRI) might seem to be in success, because assured enhancement may be estimated. Now, academic societies have the structural factors, i.e., the financial limitation in the registry maintenance and the data analysis, and in the difficulty of employment of the researchers with skill and talent. Conclusions: To manage the site-specific cancer registry effectively, the scientific registry system will be essentially important. Each academic society had much experienced highly qualified clinical researches in past. Accordingly, the scientific suggestion and co-operation should be of great importance for the improvement. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "A Study to Investigate the Prevalence of Headache Disorders and Migraine Among People Registered in a Health Insurance Association in Japan" which appeared in the 2022 issue.

Background: The current status and adoption of cancer-related clinical practice guidelines in Japan has not been elucidated yet. The purpose of this study was to propose roles and suggestions to develop future cancer-related clinical guidelines.Methods: A questionnaire consisting of four domains with a total of 17 questions was developed. We distributed the questionnaire to 28 specific academic organizations in Japan which have developed any cancer-related clinical practice guidelines and which were funded by the Ministry of Health, Labor, and Welfare.Results: Most organizations have investigated nationwide dissemination and adoption of clinical practice guidelines. The rate of adoption in clinical practice was estimated at approximately ≥ 70%. However, organizations with smaller budgets reported surveying approximately 60% of the time, whereas the ones with larger budgets reported approximately 100% success in surveying about their guidelines. The presidents of the organizations agreed that a new organization operated directly by the national government was necessary.Conclusion: In Japan, to develop cancer-related clinical practice guidelines, a study of clinical validation is necessary. Sufficient funds must be available to support the project to maintain and revise the guidelines. Furthermore, legal and ethical issues should be solved before establishing any registry system. [ABSTRACT FROM AUTHOR]

The cotton aphid, Aphis gossypii Glover, is one of the most agriculturally important insect pests. Neonicotinoid insecticides and sulfoxaflor have generally shown excellent control of A. gossypii , but these aphids have recently developed resistance against neonicotinoid insecticides. We previously characterized a field-collected A. gossypii Kushima clone that showed higher resistance to nitro-substituted neonicotinoids, such as imidacloprid, than to cyano-substituted neonicotinoids, such as acetamiprid. This Kushima clone harbors the R81T mutation in the nicotinic acetylcholine receptor (nAChR) β1 subunit; this mutation is the source of neonicotinoid insecticide resistance. In the present study, electrophysiological analyses and molecular modeling were employed to investigate the differential effects of the R81T mutation on cyano- and nitro-substituted neonicotinoids and sulfoxaflor. We isolated full-length coding sequences of A. gossypii nAChR α1, α2, and β1 subunits. When co-expressed in Xenopus laevis oocytes with chicken β2 nAChR, A. gossypii α1 evoked inward currents in a concentration-dependent manner in response to acetylcholine (ACh) and showed sensitivity to neonicotinoid and sulfoxaflor. Additionally, the chicken β2 T77R + E79V (equivalent double mutant of R81T) mutation resulted in a lower effect to cyano-substituted neonicotinoids and sulfoxaflor than to nitro-substituted neonicotinoids. Electrophysiological data and nAChR homology modeling analysis suggested that the Kushima clone exhibited different levels of resistance to cyano- and nitro-substituted neonicotinoid insecticides. [ABSTRACT FROM AUTHOR]

Purpose: To understand the current situation of the development and publication of cancer clinical practice guidelines and discuss an ideal structure in future. Methods: A questionnaire survey pertaining to the development and publication of cancer clinical practice guidelines was conducted with funding by a Health and Labour Sciences Research Grant. Respondents included presidents and chairpersons of academic societies developing guidelines and members of the Cancer Guidelines Committee of the Japan Society of Clinical Oncology who were specialists in various cancer sites. Results: Concerning the question of funding for the development and publication of the guidelines, 80.7 % of respondents indicated that partial public funding is required. As for the flow of public funds, 80.4 % of respondents thought that funds should be distributed appropriately to each academic society by a third-party organization. Regarding the question about the publication of the guidelines, 82.5 % of respondents replied that a comprehensive publication site needs to be established. In terms of the choice of organization that would be responsible for setting up and managing this site, the responses varied as follows: 'a newly established organization' (38.3 %); 'Center for Cancer Control and Information Services' (29.8 %); 'Japan Society of Clinical Oncology' (23.4 %); and 'Medical Information Network Distribution Service' (23.4 %) (multiple answers allowed). Conclusion: While the guidelines should be developed voluntarily by each academic society, partial public funding is also considered to be necessary for maintaining the continuous revision process. As for the publication of the guidelines, the establishment of a new comprehensive publication site would improve user convenience. [ABSTRACT FROM AUTHOR]

The voltage-sensitive sodium (Na+) channel (Vssc) is the target site of pyrethroid insecticides. Pest insects develop resistance to this class of insecticide by acquisition of one or multiple amino acid substitution(s) in this channel. In Southeast Asia, two major Vssc types confer pyrethroid resistance in the dengue mosquito vector Aedes aegypti, namely, S989P+V1016G and F1534C. We expressed several types of Vssc in Xenopus oocytes and examined the effect of amino acid substitutions in Vssc on pyrethroid susceptibilities. S989P+V1016G and F1534C haplotypes reduced the channel sensitivity to permethrin by 100- and 25-fold, respectively, while S989P+V1016G+F1534C triple mutations reduced the channel sensitivity to permethrin by 1100-fold. S989P+V1016G and F1534C haplotypes reduced the channel sensitivity to deltamethrin by 10- and 1-fold (no reduction), respectively, but S989P+V1016G+F1534C triple mutations reduced the channel sensitivity to deltamethrin by 90-fold. These results imply that pyrethroid insecticides are highly likely to lose their effectiveness against A. aegypti if such a Vssc haplotype emerges as the result of a single crossing-over event; thus, this may cause failure to control this key mosquito vector. Here, we strongly emphasize the importance of monitoring the occurrence of triple mutations in Vssc in the field population of A. aegypti. Author Summary: Pyrethroids are one of the major classes of insecticides that is widely used to control mosquito vectors. The target site of pyrethroids is found in the voltage-sensitive Na+ channel (Vssc) consisting of about 2100 amino acid residues. In this study we generated several types of Vssc with a single or multiple mutations, expressed in Xenopus oocytes, and examined their electrophysiological properties using two-electrode voltage clamp method. We confirmed that Aedes aegypti Vssc harboring a triple mutations exhibited extremely high levels of resistance to pyrethroid insecticides. This Vssc type can be generated by a single crossing-over event of two resistant Vssc genes that are widely distributed in Southeast Asia, one of the greatest dengue endemic areas. Our results highlight the importance of intensive monitoring for the triple mutations in Vssc in the A. aegypti mosquito. [ABSTRACT FROM AUTHOR]

The voltage-sensitive sodium (Na+) channel (Vssc) is the target site of pyrethroid insecticides. Pest insects develop resistance to this class of insecticide by acquisition of one or multiple amino acid substitution(s) in this channel. In Southeast Asia, two major Vssc types confer pyrethroid resistance in the dengue mosquito vector Aedes aegypti, namely, S989P+V1016G and F1534C. We expressed several types of Vssc in Xenopus oocytes and examined the effect of amino acid substitutions in Vssc on pyrethroid susceptibilities. S989P+V1016G and F1534C haplotypes reduced the channel sensitivity to permethrin by 100- and 25-fold, respectively, while S989P+V1016G+F1534C triple mutations reduced the channel sensitivity to permethrin by 1100-fold. S989P+V1016G and F1534C haplotypes reduced the channel sensitivity to deltamethrin by 10- and 1-fold (no reduction), respectively, but S989P+V1016G+F1534C triple mutations reduced the channel sensitivity to deltamethrin by 90-fold. These results imply that pyrethroid insecticides are highly likely to lose their effectiveness against A. aegypti if such a Vssc haplotype emerges as the result of a single crossing-over event; thus, this may cause failure to control this key mosquito vector. Here, we strongly emphasize the importance of monitoring the occurrence of triple mutations in Vssc in the field population of A. aegypti. [ABSTRACT FROM AUTHOR]

Abstract: The present study aimed to examine the long-term efficacy and safety of rotigotine treatment for restless legs syndrome (RLS), as well as the rate of clinically significant augmentation, in a 1-year open-label study of Japanese subjects. Japanese patients with RLS who had been treated with rotigotine or placebo in a double-blind trial were enrolled in a 1-year, open-label, uncontrolled extension study and treated with rotigotine at a dose of up to 3mg/24h after an 8-week titration phase. Outcomes included International Restless Legs Syndrome Study Group rating scale (IRLS scale), Pittsburgh Sleep Quality Index (PSQI), safety, and investigator-/expert panel-assessed augmentation (including Augmentation Severity Rating Scale). Overall, 185 patients entered the open-label study and 133 completed the study. IRLS and PSQI total scores improved throughout the 52-week treatment period (IRLS, from 23.2±5.1 to 7.8±7.6 and PSQI, from 8.0±3.1 to 5.0±2.9). Treatment-emergent adverse events were mild to moderate in severity, and included application site reactions (52.4%) and nausea (28.6%). Clinically significant augmentation occurred in five patients (2.7%). These results indicate a good long-term efficacy of rotigotine for treating RLS, with a relatively low risk of clinically significant augmentation. [Copyright &y& Elsevier]

Asperparalines produced by Aspergillus japonicus JV-23 induce paralysis in silkworm (Bombyx mori) larvae, but the target underlying insect toxicity remains unknown. In the present study, we have investigated the actions of asperparaline A on ligand-gated ion channels expressed in cultured larval brain neurons of the silkworm using patch-clamp electrophysiology. Bath-application of asperparaline A (10 μM) had no effect on the membrane current, but when delivered for 1 min prior to co-application with 10 μM acetylcholine (ACh), it blocked completely the ACh-induced current that was sensitive to mecamylamine, a nicotinic acetylcholine receptor (nAChR)-selective antaogonist. In contrast, 10 μM asperparaline A was ineffective on the γ-aminobutyric acid- and L-glutamate-induced responses of the Bombyx larval neurons. The fungal alkaloid showed no-use dependency in blocking the ACh-induced response with distinct affinity for the peak and slowlydesensitizing current amplitudes of the response to 10 mM ACh in terms of IC50 values of 20.2 and 39.6 nM, respectively. Asperparaline A (100 nM) reduced the maximum neuron response to ACh with a minimal shift in EC50, suggesting that the alkaloid is non-competitive with ACh. In contrast to showing marked blocking action on the insect nAChRs, it exhibited only a weak blocking action on chicken α3β4, α4β2 and α7 nAChRs expressed in Xenopus laevis oocytes, suggesting a high selectivity for insect over certain vertebrate nAChRs. [ABSTRACT FROM AUTHOR]

Depression, apathy, and anhedonia are often comorbid in patients with Parkinson's disease. Since the morbid states of apathy and anhedonia are complicated, these symptoms are often difficult to diagnose. Several therapeutic methods for apathy and anhedonia are considered effective. However, the validity of these methods has not been established. Similar to depression, apathy and anhedonia clearly affect the quality of life of patients and their families. Therefore, accurate diagnoses of morbid states in the early stage of the disease and corresponding appropriate treatments should be given high priority. [ABSTRACT FROM AUTHOR]

Depression, apathy, and anhedonia are often comorbid in patients with Parkinson's disease. Since the morbid states of apathy and anhedonia are complicated, these symptoms are often difficult to diagnose. Several therapeutic methods for apathy and anhedonia are considered effective. However, the validity of these methods has not been established. Similar to depression, apathy and anhedonia clearly affect the quality of life of patients and their families. Therefore, accurate diagnoses of morbid states in the early stage of the disease and corresponding appropriate treatments should be given high priority. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate the efficacy of pramipexole on polysomnographic measures, patient ratings and a clinical rating in Japanese patients with primary restless legs syndrome (RLS). Methods: Patients with moderate to severe RLS having periodic limb movements in bed index (PLMI)⩾5 were randomly assigned to receive pramipexole or placebo in a 6-week, double-blind, placebo-controlled study with forced titration from 0.125 to 0.75mg/day. Both polysomnography (PSG) and the suggested immobilization test (SIT) were performed at baseline and 6weeks after starting treatment. Results: The analysis of covariance of log-transformed PLMI showed that the adjusted means at the end of study were significantly smaller in the pramipexole group than in the placebo group (p =0.0019). In all patients, variables on SIT did not show any differences between the two groups, whereas a significant improvement was shown in the pramipexole group compared with the placebo group for patients with a SIT-PLM index at baseline⩾15. Pramipexole group showed a significant reduction in the International Restless Legs Syndrome Study Group rating scale (IRLS; p =0.0005), a significant improvement in both Patient Global Impression (PGI; p <0.0001) and Clinical Global Impressions (CGI-I; p =0.0488), and a significantly greater mean reduction in the Pittsburgh Sleep Quality Index (PSQI; p =0.0016), when compared with those of placebo group at week 6. Conclusions: Pramipexole is highly efficacious in the reduction of PLMI and in the improvement of subjective severity of RLS and subjective sleep disturbance caused by the disorder. [Copyright &y& Elsevier]

Abstract: Neonicotinoid insecticides target nicotinic acetylcholine receptors (nAChRs), which, in both vertebrates and invertebrates, mediate fast-acting synaptic neurotransmission in the nervous system. Recently, Kagabu et al. synthesized bis-neonicotinoids. The neural activities of bis-neonicotinoids have been evaluated on the central nerve cord of American cockroaches. However, the action of bis-neonicotinoids on nAChRs expressed by dissociated insect neurons has not yet been studied. Thus, the actions of several alkylene-tethered bis-neonicotinoids on the terminal abdominal ganglion neurons of the American cockroach, Periplaneta americana, were investigated using whole-cell patch-clamp electrophysiology. All of the ligands tested did not induce membrane currents, but reduced the responses to ACh when bath applied prior to co-application with ACh. Of the compounds tested, HK-13, which possesses two imidacloprid units linked with a hexamethylene bridge, had the highest antagonist potency. The antagonist action was reduced, not only by elongating, but also by shortening the linker. [Copyright &y& Elsevier]

Abstract: Prodrugs of imidacloprid and the thiazolylmethyl analog masked with oxodioxolylmethyl group on the N3 site were prepared. The prodrugs decomposed in a buffer solution of pH 8.3 and in a physiological salt solution with half-lives of 10–15h, releasing the parent insecticides. Being consistent with this, an inward current was evoked in dissociated cockroach neurons treated with the masked compound solutions, which were maintained for 24h after preparation, as measured using patch–clamp electrophysiology, whereas no response was observed in neurons when the solutions were challenged immediately after preparation. The insecticidal test on the American cockroach showed that the minimum lethal dose for each compound at 24h after injection was 6.4×10−8 mol, which was similar to that for imidacloprid and the thiazolyl derivative. This result strongly suggested a regeneration of the active ingredients in vivo. [Copyright &y& Elsevier]

Background: In Japan the annual incidence of pancreatic cancer has increased over the last decade, but no advancement has been made in the long-term prognosis after resection. The significant differences in the surgical procedures between Western countries and Japan have been discussed. Therefore, an adequate comparison and analysis of the data from Japan, Europe and the USA is required. This review evaluates many important published reports from Japan which influence surgical procedure. Methods: Several important highlights and controversies regarding the concept of surgical treatment and surgical procedure are discussed comparing the results in Japan with those in Western countries. Results: No significant difference in diagnostic strategy using various imaging methods was observed between Japan and Europe. The stage classification for pancreatic cancer by the Japanese Pancreatic Society (JPS) seems to be superior to others, because the results on long-term prognosis after pancreatectomy of cases with pancreatic head cancer, diagnosed as tubular adenocarcinoma, has been arranged logically. Pancreatectomy with extended radical dissection is recommended in Japan, but several clinical studies from Europe and the USA suggest that this is ineffective. The basic concepts of this controversy have recently come closer altogether. Scientific clinical trials for instance on the necessity of adjuvant treatment, etc., are now on-going. Conclusion: The characteristics on diagnosis and treatment of pancreatic cancer in Japan are described. The JPS registration system for pancreatic cancer can provide much more information, i.e. dependency on diagnostic methods, highly frequent sites of lymph node and of distant metastases, the prognosis of small pancreatic cancers, etc. The indication for any surgical treatments should be limited to cases with the possibility of cancer free margins. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Cranial neuropathy is clinically uncommon in patients with chronic inflammatory demyelinating polyneuropathy (CIDP), but there is little information on the neurophysiological examination of cranial nerve involvement. To determine the incidence of trigeminal and facial nerve involvement in patients with CIDP, the direct response of the orbicularis oculi muscle to percutaneous electric stimulation of the facial nerve and the blink reflex (induced by stimulation of the supraorbital nerve) were examined in 20 CIDP patients. The latency of the direct response was increased in 12 patients (60%) and an abnormal blink reflex was observed in 17 patients (85%). There was no correlation between electrophysiological findings and the latencies of the direct and R1 responses and disease duration or clinical grade in CIDP patients. Nevertheless, the prevalence of subclinical trigeminal and facial neuropathy is extremely high in patients with CIDP when examined by neurophysiological tests. Muscle Nerve 2006 [ABSTRACT FROM AUTHOR]

Abstract: The best-known developments of a regular tetrahedron are an equilateral triangle and a parallelogram. Are there any other convex developments of a regular tetrahedron? In this paper we will show that there are convex developments of a regular tetrahedron having the following shapes: an equilateral triangle, an isosceles triangle, a right-angled triangle, scalene triangles, rectangles, parallelograms, trapezoids, quadrilaterals which are not trapezoids, pentagons and hexagons, and furthermore these cases exhaust all the possibilities of convex developments with sides . And we will show that there are no convex n-gons which are developments of a regular tetrahedron when . Here, we mean by a development of a polyhedron a connected plane figure, from which one can construct the polyhedron by folding it without getting overlap or gap. In so folding we do not require that the sides of the development should end up as the edges of the polyhedron. [Copyright &y& Elsevier]

Poststroke depression (PSD) has an important impact on the quality of life of patients with stroke. We studied 100 stroke patients (mean age ± SD: 64.6 ± 11.6, range: 32–85 years) in the subacute phase (2–5 weeks after onset) and investigated the prevalence and clinical correlates of PSD in the subacute phase. The prevalences of PSD and major depression in the subacute phase evaluated by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, were 20.0 and 5.0%, respectively. These values were lower than those reported in Caucasian studies. The Zung Self-Rating Depression Scale (SDS) did not underestimate the presence of PSD and was thus considered valuable for the initial screening of PSD. However, SDS may overestimate PSD especially in patients with anxiety disorders or somatoform disorders and vice versa. Apathy was observed in 40.2% of patients; however, it was widely distributed and observed even in patients without serious depression. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Laparoscopic procedures for pancreatic surgery have been significantly improved recently; however, the number of successful laparoscopic or laparoscopy-assisted pancreaticoduodenectomies (PDs) has been limited. The limitations could be attributed to the complexity of the reconstruction procedures under laparoscopic observations and the high incidence of critical morbidity with PDs. To overcome the shortcomings, we developed the first hand-assisted laparoscopic pylorus-preserving PD and, in this report, present the case of a patient with a low-grade malignant tumor on the pancreas head. [Copyright &y& Elsevier]

Small hepatocytes (SH), which are hepatic progenitor cells, were isolated from an adult rat liver. SH in a colony sometimes change their shape from small to large and from flat to rising/piled-up. The morphological changes of SH may be correlated with hepatic maturation. Cytochrome P450s (CYP) are drug-metabolizing enzymes and the expression is one of hepatic differentiated functions. However, it is well known that the re-expression and maintenance of CYP activity are very difficult in cultured hepatocytes. We investigated the expression of CYP and the enzymatic activities in long-term cultured SH.SH were isolated from adult rat livers and SH colonies were collected, replated on new dishes, and then cultured. CYP1A1/2, CYP2B1, CYP3A2, CYP4A1, and CYP2E1 were induced by the addition of 3-methylcholanthrene, phenobarbital, pregnenolone-16α-carbonitrile, clofibric acid, and ethanol, respectively. Immunocytochemistry, immunoblots, and enzyme activities were examined.SH could differentiate into mature hepatocytes by the addition of Matrigel and re-express constitutive CYPs. The expression of CYP1A1/2, CYP2B1, CYP3A2, and CYP4A1 dose-dependently increased and the amounts gradually increased with time in culture, especially in the cells treated with Matrigel. Activities of CYP1A, CYP2B, CYP3A and CYP2E in SH treated with Matrigel induced by each of the inducers were approximately 120-fold, 2.8-fold, 6.4-fold and 0.8-fold higher than in the control.The matured SH could re-express the constitutive CYP and recover inducibility, not only of protein expression but also of enzyme activities. [ABSTRACT FROM AUTHOR]

We investigated the efficacy of the levodopa (l-dopa) on cognitive function in patients with de novo Parkinson''s disease (PD) using the event-related potential (ERP) measure and neuropsychological test batteries. We studied 20 PD patients who had never received anti-Parkinson medications. The ERP with auditory oddball P3 paradigm and neuropsychological tests such as Mini-Mental State Examination (MMSE), New Modified Wisconsin Card Sorting Test (WCST) and Trail Making Test were repeated in the patients before and after administration of levodopa plus benserazide daily 300 mg. For the ERP''s components, reference-independent measures of global field power (GFP) were determined, and P3 GFP peak, peak latency and topography were assessed. After administration of levodopa, the patients revealed significant increase of the achieved categories and decrease of preservation errors in the WSCT, shortening of time in Trail Making Test although MMSE score showed no significant difference. The P3 GFP peak attenuated although there were no differences in peak latency or on scalp topography. These findings suggest that levodopa affect on the neural circuit connects frontal cortex with the striatum and normalizes its function, and it causes decrease of P3 GFP peak reflecting appropriate resource allocation. In addition, P3 GFP might be a more appropriate indicator than psychological tests. [Copyright &y& Elsevier]

The clinical significance of serum apolipoprotein A-1 levels as an indicator of hepatic protein synthesis after hepatectomy was investigated. A total of 50 patients who had undergone hepatectomy at our department from 1997 to 1999 were selected for this study. The serum levels of apolipoprotein A-1, indocyanine green dye retention at 15 minutes, lectin-cholesterol acyltransferase, prealbumin, and high-density lipoprotein cholesterol were measured in these patients preoperatively and on postoperative days 7 and 14. The type of hepatic resection conducted was partial resection in 13 cases, subsegmentectomy in 13 cases, segmentectomy in five cases, and bisegmentectomy in 19 cases. All the patients tolerated the operation, and none of the cases had any severe complications, such as liver failure. In most cases, the serum apolipoprotein A-1 levels decreased on postoperative day 7 and recovered by day 14. There were no significant differences in the changes in apolipoprotein A-1 levels between patients with the individual types of operative procedures. The serum apolipoprotein A-1 levels showed significant correlations with the serum high-density lipoprotein cholesterol, lectin-cholesterol acyltransferase and prealbumin levels on postoperative days 7 and 14; however, there was no significant correlation with the indocyanine green retention test. When the cases were divided into three groups according to the serum level of apolipoprotein A-1 on postoperative day 7 (group A: over 81 mg/dl, group B: 61–80 mg/dl, group C: under 60 mg/dl), the serum indocyanine green retention, prealbumin, lectin-cholesterol acyltransferase and high-density lipoprotein cholesterol levels in group C were significantly lower than those in group A on postoperative day 7. On the basis of these results, it is suggested that the pattern of changes in the serum apolipoprotein A-1 levels may be a good indicator of the hepatic protein synthetic ability during the perioperative period after... [ABSTRACT FROM AUTHOR]

It is well known that the angle-dependent disturbance in a servo motor caused by nonuniformity of field windings, armature cogging, rotor imbalance, nonuniform load and so on, may influence the speed control performance greatly. This often leads to large speed fluctuations which are undesired in practical situations. Therefore speed fluctuation reduction techniques in the presence of angle-dependent disturbances are strongly required and have been studied by many researchers. In this paper, the authors propose a new approach to this problem via adaptive control with the aid of a radial basis function (RBF) network composed of Gaussian basis functions. The angle-dependent disturbance, viewed as a periodic non-linear function with a period of 2π radians in the angular domain, is approximated by an RBF network in (0, 2π) radians. Then an adaptive linearization control system employing the RBF network which compensates for the disturbance is proposed. The RBF network has the advantage that it is linear in the parameters and hence parameter adaption is very fast and easy to implement. It is proved through theoretical analysis that the stability of adaptive control is guaranteed by Lyapunov stability theory. Finally, simulation and experimental results are included in the paper to show the excellent performance of the proposed method. © 1997 Scripta Technica, Inc. Electr Eng Jpn, 119(4): 77–86, 1997 [ABSTRACT FROM AUTHOR]

Background: Anti-calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) have greatly changed migraine treatment options. In Japan, although CGRPmAb guidelines (≥ 4 monthly migraine days (MMDs) and ≥ 1 previous preventive failure) are well-acknowledged, the actual use of CGRPmAbs and the circumstances of the related headache care are unknown. Methods: We conducted an online survey of Japanese Headache Society members, inquiring about the physicians' experience with CGRPmAbs and how they make decisions related to their use. Results: Of the 397 respondents, 320 had prescribed CGRPmAbs. The threshold number of previous preventive failures for recommending a CGRPmAb was two for the majority of the respondents (n = 170, 54.5%), followed by one (n = 64, 20.5%). The MMD threshold was ≥ 4 for 71 respondents (22.8%), ≥ 6 for 68 (21.8%), ≥ 8 for 76 (24.4%), and ≥ 10 for 81 (26.0%). The respondents tended to assess treatment efficacy after 3 months (episodic migraine: n = 217, 69.6%, chronic migraine: n = 188, 60.3%). The cost of CGRPmAbs was described by many respondents in two questions: (i) any request for a CGRPmAb (27.7%), and (ii) the most frequently reported reason for responders to discontinue CGRPmAbs (24.4%). Conclusions: Most of the respondents recommended CGRPmAbs to patients with ≥ 2 preventive failures, followed by ≥ 1. The MMD threshold ranged mostly from ≥ 4 to ≥ 10. The concern for costs was raised as a major limiting factor for prescribing CGRPmAbs. [ABSTRACT FROM AUTHOR]

Introduction: The impacts of migraine on daily life, including daily activities and fundamental health indicators (sleep and mental health), have not been described in detail for people with migraine in Japan. Methods: The cross-sectional ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE (OVERCOME [Japan]) study was conducted between July and September 2020. Impacts of migraine on housework, family/social/leisure activities, driving, and sleep were assessed using questions from the Migraine Disability Assessment (MIDAS), Migraine-Specific Quality-of-Life Questionnaire, and Impact of Migraine on Partners and Adolescent Children scales and questions developed for OVERCOME (Japan). The Migraine Interictal Burden Scale (MIBS-4) evaluated burden on days without headaches. Depression and anxiety were assessed with the Patient Health Questionnaire (PHQ-8) and Generalized Anxiety Disorder (GAD-7) scales, respectively. Impacts on daily life were also described across MIDAS/MIBS-4 categories. Results: Among 17,071 respondents with migraine, 24.8% required assistance with housework at least sometimes. Migraine interfered with relationships, leisure, and social activities at least sometimes for 31.8%, 41.6%, and 18.0% of respondents, respectively. Between headache days, 26.8% of respondents worried about planning social/leisure activities at least sometimes. Among respondents living with family (N = 13,548), migraine also had impacts on participation in and enjoyment of family activities. Among respondents who drove (N = 10,921), 43.9% reported that symptoms interfered with driving at least sometimes. Migraine interfered with sleep and mood at least sometimes for 52.7% and 70.7% of respondents, respectively. PHQ-8 and GAD-7 thresholds for clinical depression and anxiety were met by 28.6% and 22.0% of respondents, respectively. Impact of migraine on daily life increased with increasing severity of MIDAS/MIBS-4 categories. Conclusion: The burden of migraine on daily activities, sleep, and mental health is substantial for people with migraine in Japan. In clinical practice, it is important to evaluate the impact of migraine on daily life in addition to migraine symptoms. [ABSTRACT FROM AUTHOR]

• Efficiencies of attentional networks and their interactions in PD were investigated. • The executive control efficiency was reduced in both PDS and PDnS. • Higher alerting efficiency and lower orienting efficiency were found in PDS. • Largely changed attentional network interactions and correlation were found in PDS. Attention is composed of three distinct attentional networks: alerting, orienting, and executive control. Previous studies have confirmed that Parkinson's disease (PD) is associated with executive control deficits; however, the interactions among the three attentional networks and the influence of sleep disturbance in PD patients have not been investigated. Herein, the efficiencies for the three attentional networks and their interactions were evaluated using the revised attention network test. The results showed a significantly slower response and lower accuracy in the PD group than in the normal control group and a significantly slower response and lower accuracy in PD patients with sleep disturbance (PDS) than in PD patients without sleep disturbance (PDnS), which indicates a response deficit in PD and worsening in PDS. Additionally, the executive control efficiency was reduced in both PDS and PDnS, and significantly higher alerting efficiency and lower orienting efficiency were found in PDS. Furthermore, largely changed interactions and correlation patterns of attentional networks were found in PDS but not in PDnS. These results suggested that attentional networks were impaired in PD patients, particularly in those affected by sleep disturbances, and that PDS might establish special connections between attentional networks to compensate for cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Recently, calcitonin gene‐related peptide (CGRP) monoclonal antibodies (mAbs) have become available as a prophylactic treatment for migraine and have shown high efficacy and safety in clinical practice. CGRP mAbs have been reported to be effective not only for migraine but also for other comorbidities, such as psychiatric complications in patients with migraine. However, there are no reports examining the effect of CGRP mAbs on dystonia. We treated a patient with comorbid migraine and focal task‐specific dystonia (writer's cramp) with a CGRP mAb (erenumab) because of an increase in monthly migraine days despite the addition of migraine prophylaxis. In this patient, erenumab treatment for 3 months led to improvements in symptoms of both focal dystonia and migraine, suggesting a role for CGRP in the pathophysiology of both conditions. [ABSTRACT FROM AUTHOR]

Objectives: Erenumab is a human anti‐calcitonin gene‐related peptide receptor monoclonal antibody approved for migraine prevention. Global studies have demonstrated its efficacy in chronic and episodic migraine (EM). Here we report the outcomes from a Phase 3 study of erenumab in Japanese patients with chronic migraine (CM) or EM. Methods: Japanese patients with EM (<15 headache days/month, including ≥4 migraine days/month) or CM (≥15 headache days/month, including ≥8 migraine days/month) were randomized 1:1 to placebo or erenumab 70 mg once monthly for a 24‐week double‐blind treatment phase (DBTP). The primary endpoint of change from baseline in mean monthly migraine days (MMD) over months 4, 5, and 6 of the DBTP was compared between erenumab and placebo groups. Secondary efficacy and safety endpoints were also assessed. Results: A total of 261 patients were randomized to placebo (n = 131) or erenumab 70 mg (n = 130); all patients were included in the efficacy and safety analyses. The mean (standard deviation) MMD at baseline was 11.84 (5.70) for the placebo group and 12.40 (5.99) for erenumab 70 mg. The mean (standard error) change in MMD was –1.98 (0.38) for the placebo group (n = 131) and –3.60 (0.38) for erenumab 70 mg (n = 130). The difference in MMD reduction between groups was −1.67 (95% CI: –2.56, –0.78, p < 0.001) for EM and –1.57 (95% CI: –3.39, 0.24, p = 0.089) for CM. Adverse events (AEs) were consistent with earlier studies. The most frequent AEs (placebo, erenumab) were nasopharyngitis (28.2% and 26.9%, respectively), back pain (4.6% and 5.4%), and constipation (0.8% and 4.6%). Conclusion: Treatment with erenumab 70 mg once monthly demonstrated favorable efficacy and safety findings in Japanese patients with EM or CM. [ABSTRACT FROM AUTHOR]

Ovarian resection as a treatment for hysteria, called 'Battey's operation' or 'normal ovariotomy', was performed in the nineteenth century. Battey later reported that the resected ovaries appeared to have 'cystic degeneration'. Currently, patients with acute neuropsychiatric symptoms are screened for teratomas for the differential diagnosis of anti-NMDA receptor encephalitis. There is now a hypothesis that ovarian lesions resulting in paraneoplastic encephalitis were among the patients who underwent Battey's operation. We identified 94 published cases of Battey's operation for neuropsychiatric symptoms in the late nineteenth century. Among 36 cases with detailed descriptions, we found 3 patients who showed acute onset neuropsychiatric symptoms with macropathological ovarian findings that were compatible with teratoma. They showed favourable prognoses after surgery and might have motivated the surgeons to perform the operation. [ABSTRACT FROM AUTHOR]

Background: In real-world studies, it is unclear whether galcanezumab has a significant effect in the first week after administration. Methods: We retrospectively assessed 55 high-frequency episodic migraine (HFEM) and chronic migraine patients who received three galcanezumab doses. Mean changes in the numbers of weekly migraine days (WMDs) during month 1 and migraine days per month (MMDs) after 1–3 months of treatment were obtained. Clinical factors related to a ≥ 50% response rate (RR) at month 3 were analyzed. The prediction of ≥ 50% responders at month 3 using different weekly RRs at week 1 (W1) was evaluated. The RR at W1 was calculated with the following formula: RR (%) = 100 − [(WMDs at W1/baseline WMD) × 100]. Results: The number of MMDs significantly improved from baseline to 1, 2 and 3 months. The ≥ 50% RR was 50.9% at 3 months. The number of WMDs decreased significantly from baseline to week 1 (− 1.6 ± 1.7 days), week 2 (− 1.2 ± 1.6 days), week 3 (− 1.0 ± 1.3 days), and week 4 (− 1.1 ± 1.6 days) during month 1. The RR at W1 was largest (44.6 ± 42.2%). The ≥ 30%, ≥ 50% and ≥ 75% RRs at W1 were significantly predictive of a ≥ 50% RR at 3 months. Logistic regression analysis predicting a ≥ 50% RR at month 3 showed that the RR at W1 was the sole contributing factor. Conclusion: In our study, galcanezumab showed a significant effect in the first week after administration, and the RR at W1 could predict the RR at 3 months. [ABSTRACT FROM AUTHOR]

Abstract: IgG anti-GQ1b antibodies are associated with Fisher syndrome (FS) as well as with its more and less extensive variants, Bickerstaff brainstem encephalitis and acute ophthalmoparesis. Passive transfer experiments provide evidence that anti-ganglioside antibodies and complement are pathogenic in the development of FS. In the current in vitro study, we could not demonstrate the association of complement activation with disease extension. [Copyright &y& Elsevier]

A letter to the editor is presented in response to the article related to ocular myasthenia that appeared in the previous issue.

Abstract The computer-ordering system (COS) database was used to investigate hypnotic prescriptions issued to outpatients at various medical departments at the Dokkyo University School of Medicine. Hypnotics were prescribed for 3428 patients (1613 men, 1815 women), with a mean age of 56 years (range 8–91 years). The number of prescriptions was 3.5% of the total number of prescriptions (123 518). Although hypnotics were prescribed most often to patients in their 60s, generally, the incidence was higher for younger-aged patients. Physicians in all specialty areas tended to prescribe short-acting benzodiazepine hypnotics. The issuance of hypnotic prescriptions should be investigated to determine the prevalence of insomnia in various medical specialties. [ABSTRACT FROM AUTHOR]