Scalp Nerve Block Alleviates Headaches Associated With Sonication During Transcranial Magnetic Resonance-Guided Focused Ultrasound.

BACKGROUND AND OBJECTIVES: In magnetic resonance-guided focused ultrasound (MRgFUS) procedures, headache is a frequent symptom and cause of treatment discontinuation. Herein, we assessed the efficacy of scalp nerve block (SNB) for alleviating headache during MRgFUS procedures. METHODS: The effect of SNB on intraprocedural headache was examined by retrospectively comparing 2 patient cohorts at a single institution. During the study period from April 2020 to February 2022, an SNB protocol for all patients with a skull density ratio ≤0.55 was instituted on October 6, 2021. The number of patients with a skull density ratio ≤0.55 was 34 before the protocol and 36 afterward. Headache intensity was evaluated using a numerical rating scale (NRS) after each sonication. To evaluate the effect of SNB on headache intensity, multiple regression analysis was performed per patient and per sonication. In the per-patient analysis, the effect of SNB was evaluated using the maximum NRS, mean NRS, and NRS at the first ultrasound exposure that reached 52.5°C. In the per-sonication analysis, the effect of SNB was evaluated not only for the entire sonication but also for sonications classified into ≤9999 J, 10 000 to 29 999 J, and ≥30 000 J energy doses. RESULTS: With SNB, headache alleviation was observed in the NRS after the first sonication that reached 52.5°C in each patient (ß = -2.40, 95% CI -4.05 to -0.758, P = .00499), in the NRS when all sonications were evaluated (ß = -0.647, 95% CI -1.19 to -0.106, P = .0201), and in the NRS when all sonications were classified into 10 000 to 29 999 J (ß = -1.83, 95% CI -3.17 to -0.485, P = .00889). CONCLUSION: SNB significantly reduced headache intensity during MRgFUS, especially that caused by sonication with a moderate-energy dose. These findings suggest that scalp nerves play a role in headache mechanisms during MRgFUS.

Erythema and Induration of Bacillus Calmette-Guérin Scar Associated With Multisystem Inflammatory Syndrome in Children in Japan: A Case Report.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare febrile disorder with multisystem organ involvement temporally associated with coronavirus 2019 infection (COVID-19) and frequently exhibits features mimicking Kawasaki disease (KD), another febrile disorder in children. The pathogenesis and the full clinical spectrum of MIS-C is poorly understood: It is still unclear whether MIS-C and KD are different syndromes or represent a common spectrum. The erythema and induration of Bacillus Calmette-Guérin (BCG) scar is one of the characteristic findings of KD, and is useful for the diagnosis in countries where BCG vaccination is mandated in infancy. Furthermore, such findings in BCG scar were also reported after SARS-CoV-2 vaccination, which may be related to molecular mimicry. However, there are no reports of changes at the BCG scar in MIS-C cases. Here, we report a case of MIS-C in a 3-year-old Hispanic boy in Japan, with erythema and induration at the BCG scar. The patient received BCG vaccination at 16 months of age in Japan. Four weeks before the onset, he had positive polymerase chain reaction (PCR) results for SARS-CoV-2 following household outbreak, although he was asymptomatic. He presented with fever and gastrointestinal symptoms, followed by the appearance of all six principal findings of complete KD. He exhibited congestive heart failure, following intravenous immunoglobulin (IVIG) therapy. He was diagnosed with MIS-C based on characteristic mucocutaneous and gastrointestinal symptoms, decreased cardiac function, and coagulopathy, in addition to laboratory data consistent with MIS-C. The BCG finding was present from the early stage of the disease. The patient was refractory to two doses of IVIGs, and the third IVIG plus prednisolone resulted in defervescence and improvement in heart failure. No coronary involvement was observed. This is the first case of erythema and induration at the BCG scar associated with MIS-C accompanied by KD features, which may give clinical and mechanistic insights in the understanding of the disease. Since the full spectrum of MIS-C is still evolving and both of them are syndromes with overlapped clinical features, further studies are warranted for deep phenotyping of MIS-C with KD features relative to KD in countries with mandatory BCG programs in infancy.

Increased anteroventral striatal dopamine transporter and motor recovery after subthalamic deep brain stimulation in Parkinson's disease.

OBJECTIVE: Subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease is effective; however, its mechanism is unclear. To investigate the degree of neuronal terminal survival after STN-DBS, the authors examined the striatal dopamine transporter levels before and after treatment in association with clinical improvement using PET with [11C]2ß-carbomethoxy-3ß-(4-fluorophenyl)tropane ([11C]CFT). METHODS: Ten patients with Parkinson's disease who had undergone bilateral STN-DBS were scanned twice with [11C]CFT PET just before and 1 year after surgery. Correlation analysis was conducted between [11C]CFT binding and off-period Unified Parkinson's Disease Rating Scale (UPDRS) scores assessed preoperatively and postoperatively. RESULTS: [11C]CFT uptake reduced significantly in the posterodorsal putamen contralateral to the parkinsonism-dominant side after 1 year; however, an increase was noted in the contralateral anteroventral putamen and ipsilateral ventral caudate postoperatively (p < 0.05). The percentage increase in [11C]CFT binding was inversely correlated with the preoperative binding level in the bilateral anteroventral putamen, ipsilateral ventral caudate, contralateral anterodorsal putamen, contralateral posteroventral putamen, and contralateral nucleus accumbens. The percentage reduction in UPDRS-II score was significantly correlated with the percentage increase in [11C]CFT binding in the ipsilateral anteroventral putamen (p < 0.05). The percentage reduction in UPDRS-III score was significantly correlated with the percentage increase in [11C]CFT binding in the ipsilateral anteroventral putamen, ventral caudate, and nucleus accumbens (p < 0.05). CONCLUSIONS: STN-DBS increases dopamine transporter levels in the anteroventral striatum, which is correlated with the motor recovery and possibly suggests the neuromodulatory effect of STN-DBS on dopaminergic terminals in Parkinson's disease patients. A preoperative level of anterior striatal dopamine transporter may predict reserve capacity of STN-DBS on motor recovery.

A boy with biallelic frameshift variants in TTC5 and brain malformation resembling tubulinopathies.

Brain malformations have heterogeneous genetic backgrounds. Tubulinopathies are a wide range of brain malformations caused by variants in tubulin and microtubules-associated genes. Recently biallelic variants in TTC5, also known as stress responsive activator of p300, have been reported in 11 patients from seven families with developmental delay, intellectual disability, and brain malformations. Here, we report compound heterozygous frameshift variants in TTC5 in a Japanese boy who showed severe psychomotor developmental delay and pseudobulbar palsy with growth failure. Brain magnetic resonance imaging showed a simplified gyral pattern and undetectable anterior limb of the internal capsule, suggesting tubulinopathies. Immunoblotting using lymphoblastoid cells derived from the patient showed undetectable TTC5 protein. Ttc5 silencing by RNA interference in Neuro2a cells reduced Tubulin ß3 protein level and caused abnormal cell cycle. Our report suggests a possible link between TTC5-related brain malformation and tubulinopathies.

Application of Deep Brain Stimulation for Treatment-resistant Obsessive Compulsive Disorder: Current Status and Future Perspectives in Japan.

As in many Western countries, deep brain stimulation (DBS) is already being used daily in Japan to clinically treat neurological diseases such as Parkinson's disease, essential tremor, and dystonia. Additionally, in both Europe and the United States, numerous case reports as well as multicenter randomized controlled trials have examined its use for treatment-refractory mental illnesses such as obsessive compulsive disorder (OCD) and major depressive disorder. Based on a number of the reports, the European Union (EU) and the USA Food and Drug Administration (FDA) granted limited approval of DBS for treatment-resistant OCD in 2009. Furthermore, a systematic review and meta-analysis in 2015 showed that DBS therapy for patients with treatment-resistant OCD had efficacy and was safe. Unlike the EU and the USA, DBS is not used to treat OCD or other psychiatric disorders in Japan, even though people with treatment-resistant OCD and their physicians and families urgently need additional treatments. This situation results from the "Resolution of total denial for psychosurgery," which the Japanese Society of Psychiatry and Neurology adopted in 1975. We believe that the appropriateness of using DBS for treating psychiatric disorders including OCD should be considered after thorough discussion and consideration based on accurate and objective understanding. Currently, the field of psychiatry in Japan seems to lack scientific consideration as well as scientific understanding in this area. Under these circumstances, we hope that this review article will help psychiatrists and other relevant parties in Japan to gain an accurate and scientific understanding of DBS.

Development of a novel gripping test for the evaluation of the finger fine motor ability in MPTP-treated monkeys.

Assessing the finger fine motor ability is extremely important. However, conventional behavioral tests in monkeys are complicated and costly. We attempted to develop a new task to assess the precise finger grip in Parkinson's disease monkeys based on the principles of objectification, multipurpose, and simplification. This study involved seven adult male cynomolgus monkeys. A gripping test based on the previous food reaching test was developed. Parallel experiments of food reaching test and gripping test affected by the treatments of levodopa and deep brain stimulation of the subthalamic nucleus were performed to verify the utility of the gripping test. We found that gross motor ability (measured by food reaching test) could be significantly improved by both the subthalamic nucleus and levodopa administration, which reproduced the results of our previous study. The finger fine motor ability (measured by the gripping test) could be significantly improved by levodopa administration, but not by the subthalamic nucleus. Our results verified the utility and reliability of the gripping test, which is a simple, convenient, and objective task for evaluating the finger fine motor skill in Parkinson's disease monkeys. Mechanisms of the efficacy of deep brain stimulation on fine motor ability require further investigation.

A randomized controlled trial of 5 daily sessions and continuous trial of 4 weekly sessions of repetitive transcranial magnetic stimulation for neuropathic pain.

We conducted a multicenter, randomized, patient- and assessor-blinded, sham-controlled trial to investigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) in patients with neuropathic pain (NP). Patients were randomly assigned to receive 5 daily sessions of active or sham rTMS of M1 corresponding to the part of the body experiencing the worst pain (500 pulses per session at 5 Hz). Responders were invited to enroll in an open-label continuous trial involving 4 weekly sessions of active rTMS. The primary outcome was a mean decrease in a visual analogue scale of pain intensity (scaled 0-100 mm) measured daily during the daily sessions in an intention-to-treat population. Secondary outcomes were other pain scores, quality-of-life measures, and depression score. One hundred forty-four patients were assigned to the active or sham stimulation groups. The primary outcome, mean visual analogue scale decreases, was not significantly different (P = 0.58) between the active stimulation group (mean, 8.0) and the sham group (9.2) during the daily sessions. The secondary outcomes were not significantly different between 2 groups. The patients enrolled in the continuous weekly rTMS achieved more pain relief in the active stimulation group compared with the sham (P < 0.01). No serious adverse events were observed. Five daily sessions of rTMS with stimulus conditions used in this trial were ineffective in short-term pain relief in the whole study population with various NP. Long-term administration to the responders should be investigated for the clinical use of rTMS on NP in the future trials.

Fluid-Blood Level and Hematoma Expansion in a Cerebral Amyloid Angiopathy-Associated Intracerebral Hematoma.

BACKGROUND Cerebral amyloid angiopathy (CAA) results from progressive deposition of amyloid-ß in the walls of cortical and leptomeningeal vessels, leading to CAA-associated intracerebral hemorrhage (ICH). Hematoma expansion is a common early complication of spontaneous ICH, and is a strong independent predictor of poor outcome. However, there are limited reports of hematoma expansion related to CAA-associated ICH. Herein, we describe a novel case of hematoma expansion with a fluid-blood level in the cystic cavity of CAA-associated ICH. CASE REPORT A 76-year-old male was initially diagnosed with probable CAA according to the modified Boston criteria, and presented with lobar ICH in the left frontal lobe 4 months later. Admission computed tomography scans showed an ICH including a high-density hematoma within a cystic cavity, revealing a clearly lower-density fluid component. Serial computed tomography scans showed no evidence of an expansion of the high-density clot, but obvious expansion of the fluid component containing a fluid-blood level. We recognized a bleeding site with no enhancement on preoperative magnetic resonance imaging. Left frontal craniotomy revealed a liquefied hematoma, which was removed by suction. We subsequently evacuated the blood clot extending into the left frontal sulcus, and confirmed and cauterized the bleeding site, leading to successful hemostasis. CONCLUSIONS We report a CAA-associated ICH case showing hematoma expansion with a fluid-blood level. Intraparenchymal fluid-blood level suggests extravasation of blood into pre-existing cystic cavities because of hematoma liquefaction. Thus, fluid-blood levels are an important finding of hematoma expansion in acute CAA-associated ICH, and early treatment should be considered.

Can the Latest Computerized Technologies Revolutionize Conventional Assessment Tools and Therapies for a Neurological Disease? The Example of Parkinson's Disease.

Dramatic breakthroughs in the treatment and assessment of neurological diseases are lacking. We believe that conventional methods have several limitations. Computerized technologies, including virtual reality, augmented reality, and robot assistant systems, are advancing at a rapid pace. In this study, we used Parkinson's disease (PD) as an example to elucidate how the latest computerized technologies can improve the diagnosis and treatment of neurological diseases. Dopaminergic medication and deep brain stimulation remain the most effective interventions for treating PD. Subjective scales, such as the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr stage, are still the most widely used assessments. Wearable sensors, virtual reality, augmented reality, and robot assistant systems are increasingly being used for evaluation of patients with PD. The use of such computerized technologies can result in safe, objective, real-time behavioral assessments. Our experiences and understanding of PD have led us to believe that such technologies can provide real-time assessment, which will revolutionize the traditional assessment and treatment of PD. New technologies are desired that can revolutionize PD treatment and facilitate real-time adjustment of treatment based on motor fluctuations, such as telediagnosis systems and "smart treatment systems." The use of these technologies will substantially improve both the assessment and the treatment of neurological diseases before next-generation treatments, such as stem cell and genetic therapy, and next-generation assessments, can be clinically practiced, although the current level of artificial intelligence cannot replace the role of clinicians.

An Application of Photoactivatable Substrate for the Evaluation of Epithelial-mesenchymal Transition Inhibitors.

Epithelial-mesenchymal transition (EMT), phenotypic changes in cell adhesion and migration, is involved in cancer invasion and metastasis, hence becoming a target for anti-cancer drugs. In this study, we report a method for the evaluation of EMT inhibitors by using a photoactivatable gold substrate, which changes from non-cell-adhesive to cell-adhesive in response to light. The method is based on the geometrical confinement of cell clusters and the subsequent migration induction by controlled photoirradiation of the substrate. As a proof-of-concept experiment, a known EMT inhibitor was successfully evaluated in terms of the changes in cluster area or leader cell appearance, in response to biochemically and mechanically induced EMT. Furthermore, an application of the present method for microbial secondary metabolites identified nanaomycin H as an EMT inhibitor, potentially killing EMTed cells in disseminated conditions. These results demonstrate the potential of the present method for screening new EMT inhibitors.

Deep Brain Stimulation for Intractable Obsessive-compulsive Disorder: The International and Japanese Situation/Scenario.

Deep brain stimulation (DBS) is used to treat symptoms by modulating the cortico-striato-thalamo-cortical (CSTC) loop in the central nervous system (CNS), and attempts to research loop circuit disorders have been globally initiated among the intractable neurological and psychiatric disorders. DBS treatment has been evaluated for all these newly found CNS loop circuit disorders. In 2011, neurosurgical treatments for psychiatric disorders were renamed from "psychosurgery" to "neurosurgery for psychiatric disorders (NPD)" by the World Society for Stereotactic and Functional Neurosurgery (WSSFN). Moreover, in 2014, "Consensus on guidelines for stereotactic neurosurgery for psychiatric disorders" was published by the WSSFN to address the differences in correspondence of stereotactic NPD. Globally, two multicenter prospective randomized control trials regarding DBS of the subcallosal cingulated gyrus and ventral anterior internal capsule/ventral striatum for intractable depression have been terminated after futility analysis. However, DBS for intractable obsessive-compulsive disorder (OCD), unlike for intractable depression, is showing steady development. In Japan, NPDs have not been performed since 1975 following the adoption of "Resolution of total denial for psychosurgery" by the Japanese Society of Psychiatry and Neurology. Nevertheless, a trend to adopt new neuro-modulation techniques for psychiatric disorders, including DBS, are emerging. We have created a clinical research protocol for the use of DBS in intractable OCD, which has been approved by the ethical committee of Hamamatsu University School of Medicine, with the hope of commencing DBS treatment for intractable OCD patients in the near future.

Current behavioral assessments of movement disorders in children.

Pediatric movement disorders (PMDs) are common and have recently received increasing attention. As these disorders have special clinical features, the selection of appropriate behavioral assessment tools that can clearly distinguish movement disorders from other diseases (eg, epilepsy and neuromuscular disorders) is crucial for achieving an accurate diagnosis and treatment. However, few studies have focused on behavioral assessments in children. The present report attempts to provide a critical review of the available subjective and objective assessment tests for common PMDs. We believe that the principles of objectification, multi-purpose use, and simplification are also applicable to the selection and development of satisfactory pediatric behavioral assessment tools. We expect that the development of wearable sensors, virtual reality, and augmented reality will lead to the establishment of more reliable and simple tests. In addition, more rigorous randomized controlled trials that have been specifically designed to evaluate behavioral testing in children are also expected in the future.

Effect of Subthalamic Deep Brain Stimulation on Upper Limb Dexterity in Patients with Parkinson Disease.

OBJECTIVE: The efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on dexterity remains controversial despite its recognition as an effective strategy for Parkinson disease. The present study investigated the efficacy of STN-DBS for ameliorating bradykinesia and dexterity compared with dopaminergic medications. METHODS: Part III of the Unified Parkinson's Disease Rating Scale was used for the evaluation of bradykinesia, whereas the Purdue Pegboard Test and the Box and Block test were selected for dexterity. RESULTS: Our findings indicate that bradykinesia is significantly improved with both DBS and dopaminergic medication, whereas dexterity is improved only with DBS. Dopaminergic medication did not show a satisfactory efficacy on dexterity, and there was little synergistic effect of dopaminergic medication and STN-DBS for improving dexterity associated with Parkinson disease. CONCLUSIONS: Our results suggest that DBS is potentially more effective than dopaminergic medications for improving dexterity. The disparities in efficacy for bradykinesia and dexterity between DBS and dopaminergic medication hint at the potential mechanisms of STN-DBS. We speculate that DBS follows at least 2 different mechanisms for improving parkinsonian symptoms: 1) the dopaminergic system, primarily for the improvement of bradykinesia and 2) the nondopaminergic system, for the improvement of dexterity. This hypothesis requires further verification and investigation.

Multifaceted interventions for improving spontaneous reporting of adverse drug reactions in a general hospital in China.

BACKGROUND: The present study investigates changes in spontaneous reporting (SR) compliance and ADR patterns following adoption of a new hospital SR system, and multiple interventions designed for its improvement use under modified drug administration guidelines. METHODS: In total, 1389 ADR cases were reviewed. Cases were divided into two groups, cases from period 1 (n = 557, from January 2006 to June 2011) under the old SR system and cases in period 2 (n = 832, from July 2011 to December 2016) under the new SR system with multiple interventions to improve physician SR compliance. General information, drug information, and clinical manifestations were investigated and compared between periods. RESULTS: Interventions for improved clinician training, education on knowledge, attitudes, and practices (KAP), and economic incentives substantially improved SR adherence. We also found that changing drug usage patterns (based on the new drug administration guidelines) greatly influenced ADR occurrence and type. CONCLUSIONS: We found the SR compliance can be improved by multifaceted interventions. Drug usage patterns also influence ADR occurrence, so programs tailored for rational use are essential. These results could lead to further improvements in the SR system for ADRs in China, and provide guidance for establishing better methods of pharmacovigilance.

Psychometric evaluation of the Chinese version of the revised American Pain Society Patient Outcome Questionnaire concerning pain management in Chinese orthopedic patients.

The present study tested the clinical efficiency (item grouping, internal consistency of the subscales, construct validity, and clinical feasibility) of a widely used pain assessment system, the Mandarin version of the American Pain Society Patient Outcome Questionnaire (APS-POQ-R-C), in Chinese patients. We also attempted to investigate the current quality of pain management provided in orthopedic inpatient units in China and provide baseline data. First, we investigated the test-retest reliability of APS-POQ-R-C. In total, 236 orthopedic patients were evaluated. Our results showed that APS-POQ-R-C has satisfactory internal consistency and construct validity, although some items are not appropriate for orthopedic patients. Test-retest reliability outcomes indicated that APS-POQ-R-C is a satisfactory battery with acceptable validity and reliability, and is therefore recommended for pain management in future studies.

Human behavioral assessments in current research of Parkinson's disease.

Parkinson's disease (PD) is traditionally classified as a movement disorder because patients mainly complain about motor symptoms. Recently, non-motor symptoms of PD have been recognized by clinicians and scientists as early signs of PD, and they are detrimental factors in the quality of life in advanced PD patients. It is crucial to comprehensively understand the essence of behavioral assessments, from the simplest measurement of certain symptoms to complex neuropsychological tasks. We have recently reviewed behavioral assessments in PD research with animal models (Asakawa et al., 2016). As a companion volume, this article will systematically review the behavioral assessments of motor and non-motor PD symptoms of human patients in current research. The major aims of this article are: (1) promoting a comparative understanding of various behavioral assessments in terms of the principle and measuring indexes; (2) addressing the major strengths and weaknesses of these behavioral assessments for a better selection of tasks/tests in order to avoid biased conclusions due to inappropriate assessments; and (3) presenting new concepts regarding the development of wearable devices and mobile internet in future assessments. In conclusion we emphasize the importance of improving the assessments for non-motor symptoms because of their complex and unique mechanisms in human PD brains.

Supratentorial subdural hematoma following microvascular decompression: a report of four cases.

INTRODUCTION: Microvascular decompression has become an accepted surgical technique for the treatment of trigeminal neuralgia, hemifacial spasm, and other cranial nerve rhizopathies. However, critical complications still exist, and postoperative hemorrhage is one of the most life threatening complications following microvascular decompression. Most of the hemorrhages occur in the infratentorial region, and we found only four reports of supratentorial acute hemorrhages following microvascular decompression. Here, we report four cases of such hematomas and discuss the potential underlying mechanisms. Moreover, we discuss methods for handling such complications. CASE DESCRIPTION: Between 2004 and 2015, four patients developed postoperative hemorrhages, all of which were supratentorial subdural hematomas. The hematomas occurred ipsilaterally in two cases and contralaterally in two cases. All of the patients were treated conservatively and discharged without clinical symptoms. DISCUSSION AND EVALUATION: Although several intracranial hematomas have been reported distant from the craniotomy site, few reports of remote subdural hematomas after microvascular decompression exist. Draining large amounts of intraoperative cerebrospinal fluid may induce brain shifts and tearing of the small bridging veins. Of our four cases, two were ipsilateral and two were contralateral, and the side of the hemorrhage may suggest possible mechanisms of remote subdural hematomas in microvascular decompression. Although a lateral position for microvascular decompression mainly extends ipsilateral bridging veins, a postoperative supine position can extend bilateral veins equally. Therefore, we assumed that, supratentorial subdural hematomas occurred when the patients were returned to the supine position at the end of the microvascular decompression surgery. We may be able to prevent supratentorial subdural hematomas with the application of sufficient amounts of artificial cerebrospinal fluid immediately after a microvascular decompression. CONCLUSION: We suggest that it is important to avoid excessive CSF aspiration and to compensate for the cerebrospinal fluid loss with artificial cerebrospinal fluid adequately in order to avoid subdural hematomas after microvascular decompression. In addition, immediate postoperative CT scan is recommended even if the MVD has performed uneventfully.

Animal behavioral assessments in current research of Parkinson's disease.

Parkinson's disease (PD), a neurodegenerative disorder, is traditionally classified as a movement disorder. Patients typically suffer from many motor dysfunctions. Presently, clinicians and scientists recognize that many non-motor symptoms are associated with PD. There is an increasing interest in both motor and non-motor symptoms in clinical studies on PD patients and laboratory research on animal models that imitate the pathophysiologic features and symptoms of PD patients. Therefore, appropriate behavioral assessments are extremely crucial for correctly understanding the mechanisms of PD and accurately evaluating the efficacy and safety of novel therapies. This article systematically reviews the behavioral assessments, for both motor and non-motor symptoms, in various animal models involved in current PD research. We addressed the strengths and weaknesses of these behavioral tests and their appropriate applications. Moreover, we discussed potential mechanisms behind these behavioral tests and cautioned readers against potential experimental bias. Since most of the behavioral assessments currently used for non-motor symptoms are not particularly designed for animals with PD, it is of the utmost importance to greatly improve experimental design and evaluation in PD research with animal models. Indeed, it is essential to develop specific assessments for non-motor symptoms in PD animals based on their characteristics. We concluded with a prospective view for behavioral assessments with real-time assessment with mobile internet and wearable device in future PD research.

pp32 and APRIL are host cell-derived regulators of influenza virus RNA synthesis from cRNA.

Replication of influenza viral genomic RNA (vRNA) is catalyzed by viral RNA-dependent RNA polymerase (vRdRP). Complementary RNA (cRNA) is first copied from vRNA, and progeny vRNAs are then amplified from the cRNA. Although vRdRP and viral RNA are minimal requirements, efficient cell-free replication could not be reproduced using only these viral factors. Using a biochemical complementation assay system, we found a novel activity in the nuclear extracts of uninfected cells, designated IREF-2, that allows robust unprimed vRNA synthesis from a cRNA template. IREF-2 was shown to consist of host-derived proteins, pp32 and APRIL. IREF-2 interacts with a free form of vRdRP and preferentially upregulates vRNA synthesis rather than cRNA synthesis. Knockdown experiments indicated that IREF-2 is involved in in vivo viral replication. On the basis of these results and those of previous studies, a plausible role(s) for IREF-2 during the initiation processes of vRNA replication is discussed.