Sex differences in the characteristics of stimulant offenders with a history of substance use disorder treatment.

We analyzed the results of a nationwide questionnaire administered to 699 stimulant offenders and examined sex differences in the association between various psychosocial problems and treatment history for substance use disorder. Based on their attributes, we predominantly evaluated the treatment and support provided to women with substance use disorder. The rates of childhood (before the age of 18) traumatic experiences (physical, psychological, and sexual abuse and neglect) and lifetime intimate partner violence were significantly higher in women than in men. The history of treatment for substance use disorder was also significantly higher in women than in men, at 15.8% for men and 42.4% for women [χ2 (1) = 41.223, p < 0.001]. Logistic regression analysis was performed using the treatment history of substance use disorder as the dependent variable. The results showed that treatment history was significantly associated with the total drug abuse screening test-20 score and suicidal ideation in men and with survivors of child abuse and eating disorders in women. A comprehensive assessment is required for several issues, such as child abuse, domestic violence, trauma symptoms, eating disorders, and drug problems. Moreover, an integrated treatment for substance use disorder, trauma, and eating disorders is required for female stimulant offenders.

Differentiating between Laryngopharyngeal Dysesthesia and Hypersensitivity Reactions to Oxaliplatin and Addressing Dyspnea: 2 Case Reports.

Oxaliplatin is a key drug for colorectal cancer and causes peripheral neuropathy. Oxaliplatin-induced laryngopharyngeal dysesthesia is an acute peripheral neuropathy similar to a hypersensitivity reaction. Hypersensitivity reactions to oxaliplatin do not require immediate discontinuation, but re-challenge and desensitization therapy can be very burdensome for patients. We encountered 2 cases in which laryngopharyngeal dysesthesia could be differentiated from hypersensitivity reactions to oxaliplatin, and treatment could continue. The first case was that of a 58-year-old woman who developed dyspnea during the first course of combination therapy with capecitabine and oxaliplatin as the primary treatment for advanced rectal cancer. After laryngopharyngeal dysesthesia was differentiated from hypersensitivity reaction based on these typical symptoms, she was considered to have grade 3 (Common Terminology Criteria for Adverse Events [CTCAE] ver. 5) laryngopharyngeal dysesthesia. The second course of oxaliplatin was extended from 2 to 4 h, but symptoms recurred. The third course was performed with a reduced dose of oxaliplatin from 130 mg/m2 to 100 mg/m2, and the patient could complete the treatment without symptom recurrence. The second case involved a 76-year-old woman who developed grade 3 laryngopharyngeal dysesthesia during the first course of combination therapy with capecitabine and oxaliplatin as the primary treatment for localized colon cancer. Based on the experience of the first case, we reduced the oxaliplatin dose from 130 mg/m2 to 100 mg/m2 for the second course, and the patient completed the treatment without symptoms. This dose reduction was effective for grade 3 laryngopharyngeal dysesthesia caused by oxaliplatin without reducing therapeutic efficacy.

Efficacy and safety of crisaborole ointment in Chinese and Japanese patients aged ≥2 years with mild-to-moderate atopic dermatitis.

Atopic dermatitis is a chronic inflammatory skin disease with a significant impact on the overall wellbeing of patients and their families. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor approved for the treatment of mild-to-moderate atopic dermatitis in multiple countries. However, in the key pivotal trials, a low proportion of the overall patient population was Asian, therefore the safety and efficacy of crisaborole in the Asian population with atopic dermatitis remains unclear. CrisADe CLEAR was a multicenter, randomized, double-blind, vehicle-controlled, phase 3 study (NCT04360187) to assess the efficacy and safety of crisaborole ointment in Chinese and Japanese patients aged ≥2 years with mild-to-moderate atopic dermatitis involving ≥5% treatable body surface area. Patients were randomly assigned 2:1 to receive crisaborole or vehicle twice daily for 28 days. The primary endpoint was percentage change from baseline in the Eczema Area and Severity Index total score at day 29. Additional endpoints were improvement and success per Investigator's Static Global Assessment score at day 29 and change from baseline on the Peak Pruritus Numerical Rating Scale at week 4. Safety was assessed using rates of treatment emergent adverse events, serious adverse events, and clinically significant changes in vital signs and clinical laboratory parameters. Crisaborole-treated patients showed a significantly greater reduction versus vehicle in percentage change from baseline in Eczema Area and Severity Index total score at day 29 (P = 0.0002). Response rates for achievement of Investigator's Static Global Assessment improvement and success at day 29 were significantly higher for patients treated with crisaborole versus vehicle (P = 0.0124 and P = 0.0078, respectively). Crisaborole-treated patients showed a significantly greater reduction versus vehicle in change from baseline on the Peak Pruritus Numerical Rating Scale at week 4 (P = 0.0009). No new safety signals were identified. Treatment with crisaborole was effective and well tolerated in Chinese and Japanese patients with mild-to-moderate atopic dermatitis.

A Case of Contained Rupture of the Common Iliac Artery with Idiopathic Retroperitoneal Fibrosis: Efficacy of Surgical Treatment and Immunosuppressive Therapy at 2-Year Follow-Up.

Rupture of inflammatory aortic aneurysm associated with retroperitoneal fibrosis (RF) is rare. We report a 62-year-old man with an inflammatory abdominal aortic aneurysm (IAAA) complicated with idiopathic RF, resulting in a contained rupture of the common iliac artery. The patient also presented with mild renal insufficiency due to urethral obstruction and left hydronephrosis. Surgical procedures including graft replacement and ureterolysis relieved the symptoms. Postoperative immunosuppressive treatment using corticosteroid and methotrexate successfully maintained clinical remission without signs of recurrence of RF and IAAA at the 2-year follow-up.

Methods of Cleaning Taps to Prevent Hospital-Associated Infections: An Environmental Survey-Based Study.

In hospitals, outbreaks can occur due to pathogens accumulating in the areas around the wards' washbasins. Carbapenem-resistant Enterobacterales (CRE) was detected in an environmental survey in the high-care unit of a university hospital in Isehara, Japan, and effective cleaning methods were investigated. This study investigated methods of cleaning taps using commonly used detergents and disinfectants, and it assessed their effectiveness in removing hard scale and pathogens, including CRE. The taps were cleaned using various methods and cleaning agents, including environmentally neutral detergent, citric acid, baking soda, cleanser, 80% ethanol, 0.1% sodium hypochlorite, and a phosphoric acid-based environmental detergent (Space Shot). The cleaning effect was assessed based on the agent's effectiveness at removing hard scale from taps. Biofilms and scale were identified on taps, and several bacterial species were cultured. Only phosphoric acid-based detergent was effective at removing hard scale. After cleaning with the phosphoric acid-based detergent, the bacterial count decreased, and no CRE or other pathogens were detected. These results provide a reference for other facilities considering introducing this cleaning method.

Prevalence of adverse childhood experiences and their association with suicidal ideation and non-suicidal self-injury among incarcerated methamphetamine users in Japan.

BACKGROUND: Adverse childhood experiences (ACEs) are distressing and/or traumatic events that occur during childhood that increase the risk of negative health outcomes in adulthood. OBJECTIVE: This study estimated the prevalence of ACEs in a nationwide sample of Japanese methamphetamine users in prison and examined associations among ACEs, suicidal ideation, and non-suicidal self-injury. PARTICIPANTS AND SETTING: Participants were 636 inmates (418 male and 218 female) who were newly incarcerated in Japan for Stimulants Control Act violations. METHODS: First, 699 participants completed an anonymous self-report questionnaire. Of these, 636 participants who did not have any missing responses were included in the analysis. After calculating descriptive statistics, the associations between ACEs and suicidal behaviors were assessed using binary logistic regression analyses. RESULTS: Results showed that 76.1 % of the participants reported at least one ACE before the age of 18, and female participants reported a significantly higher number of adversities than their male counterparts. The most common ACEs were parental death or divorce, followed by psychological abuse. Logistic regression analyses revealed that ACE scores significantly increased the risk of suicidal ideation (SI; adjusted odd ratio [AOR] = 1.18, p < .001) and non-suicidal self-injury (NSSI; AOR = 1.18, p < .001) after controlling for possible confounding variables. CONCLUSIONS: Findings suggest the importance of early prevention and intervention for traumatic experiences, and have implications for the recommendation of gender-responsive, trauma-focused interventions, especially for female inmates in the criminal justice system, to break the intergenerational chain of abuse. Future research directions and treatment are discussed.

Gender Differences in the Relationship between Methamphetamine Use and High-risk Sexual Behavior among Prisoners: A Nationwide, Cross-sectional Survey in Japan.

This study aimed to examine the relationship between methamphetamine (MA) use and high-risk sexual behavior among newly incarcerated prisoners in Japan. We conducted a secondary analysis using cross-sectional survey data, which constituted a nationwide prison sample surveyed between July and November 2017. In total, 699 participants (462 male and 237 female prisoners), who completed the self-administered questionnaire during imprisonment were recruited for the study. The prevalence of high-risk sexual behaviors was as follows: inconsistent condom use (78.4% male, 81.7% female), multiple sexual partners (61.3% male, 41.3% female), history of sexually transmitted diseases (14.1% male, 23.6% female), and trading sex for drugs (15.6% male, 17.7% female). A logistic regression analysis showed that MA use during sex increased the likelihood of high-risk sexual behavior in both male (adjusted odds ratio [AOR] = 5.86; 95% confidence interval [CI] = 3.41-10.07) and female prisoners (AOR = 2.58; 95% CI = 1.33-5.00). Additionally, in female prisoners, a history of sharing MA injection (AOR = 1.60; 95% CI = 1.06-2.42) increased high-risk sexual behavior. Our results indicate that harm reduction programs tailored according to the specific necessities of each gender to reduce high-risk sexual behaviors among MA users should be included in Japanese drug policies.

18F-THK5351 Positron Emission Tomography Imaging in Neurodegenerative Tauopathies.

Introduction: We aimed to determine whether in vivo tau deposits and monoamine oxidase B (MAO-B) detection using 18F-THK5351 positron emission tomography (PET) can assist in the differential distribution in patients with corticobasal syndrome (CBS), progressive supranuclear palsy (PSP), and Alzheimer's disease (AD) and whether 18F-THK5351 retention of lesion sites in CBS and PSP can correlate with clinical parameters. Methods: 18F-THK5351 PET was performed in 35 participants, including 7, 9, and 10 patients with CBS, PSP, and AD, respectively, and 9 age-matched normal controls. In CBS and PSP, cognitive and motor functions were assessed using the Montreal Cognitive Assessment, Addenbrooke's Cognitive Examination-Revised, and Frontal Assessment Battery, Unified Parkinson's Disease Rating Scale Motor Score, and PSP Rating Scale. Results: 18F-THK5351 retention was observed in sites susceptible to disease-related pathologies in CBS, PSP, and AD. 18F-THK5351 uptake in the precentral gyrus clearly differentiated patients with CBS from those with PSP and AD. Furthermore, 18F-THK5351 uptake in the inferior temporal gyrus clearly differentiated patients with AD from those with CBS and PSP. Regional 18F-THK5351 retention was associated with the cognitive function in CBS and PSP. Conclusion: Measurement of the tau deposits and MAO-B density in the brain using 18F-THK5351 may be helpful for the differential diagnosis of tauopathies and for understanding disease stages.

Gender Differences in Triggers of Stimulant Use Based on the National Survey of Prisoners in Japan.

BACKGROUND: There are a few studies on gender differences in terms of reasons and motives for methamphetamine use. Purpose/Objectives: To examine gender differences in triggers of methamphetamine use Methods: We provided a questionnaire survey to 699 inmates who were incarcerated because of violation of the Stimulants Control Act. Results: The results of DAST-20 (the severity of drug dependence) moderately correlated with the applicable numbers of the 37 situational triggers and 34 emotional triggers for stimulant use, respectively. Regarding gender differences, items including "when having sex" [46.3% (men) vs. 25.3% (women)], "when I have some money" (39.4% vs. 25.3%), and "after getting paid from work" (22.1% vs. 11.4%) were applicable in a significantly higher proportion in males (p < 0.001 and p = 0.008, respectively), whereas items including "worried about the body shape" (3.5% vs. 31.2%) and "after quarreling with someone" (11.7% vs. 29.1%) were applicable in a significantly higher proportion in females (p < 0.001 for both comparisons). Further, most trigger (emotions) items that exhibited gender differences were significantly higher in females. Many females answered that they had used drugs to relieve discomfort symptoms associated with menstrual periods. Conclusions/Importance: Thus, the awareness of important factors including learning how to deal with negative emotions (e.g. depression), repairing self-image, and recognizing physical and emotional changes associated with the menstrual cycle is helpful in providing proper care and treatment of drug addiction in females.

Optimal beam quality for chest flat panel detector system: realistic phantom study.

OBJECTIVE: To investigate optimal beam quality for chest flat panel detector (FPD) system by semi-quantitatively assessment using a realistic lung phantom. MATERIALS AND METHODS: Chest FPD radiographs were obtained on a realistic lung phantom with simulated lung opacities using various X-ray tube voltage levels (90-140 kV) with/without copper filter. Entrance skin dose was set to maintain identical for all images (0.1 mGy). Three chest radiologists unaware of the exposure settings independently evaluated the image quality of each simulated opacity and normal structure using a 5-point scale (+ 2: clearly superior to the standard; + 1: slightly superior to the standard; 0: equal to the standard; - 1: slightly inferior to the standard; - 2: clearly inferior to the standard). The traditional FPD image obtained at a tube voltage of 120 kV was used as the standard. The scores of image quality were statistically compared using the Wilcoxon rank test with Bonferroni correction. RESULTS: FPD images using 90-kV shot with copper filter were superior to the traditional 120-kV shot without filter with respect to the visibility of vertebra, pulmonary vessels, and nodules overlapping diaphragm and heart (p < 0.05). There was no significant difference with respect to the visibility of all other simulated lung opacities (lung nodules except for overlying diaphragm/heart and honeycomb opacity) between each tube voltage level with/without copper filter and the traditional 120-kV shot without filter. CONCLUSION: Image quality of FPD images using 90 kV with copper filtration is superior to that using standard tube voltage when dose is identical. KEY POINTS: • FPD image quality using 90 kV with filter is superior to that using traditional beam. • Ninety-kilovolt shot with copper filter may be suitable for chest FPD image. • Clinical study dealing with chest FPD beam optimization would be warranted.

Detection of lung carcinoma with predominant ground-glass opacity on CT using temporal subtraction method.

PURPOSE: To evaluate the usefulness of the CT temporal subtraction (TS) method for the detection of the lung cancer with predominant ground-glass opacity (LC-pGGO). MATERIALS AND METHODS: Twenty-five pairs of CT and their TS images in patients with LC-pGGO (31 lesions) and 25 pairs of those in patients without nodules were used for an observer performance study. Eight radiologists participated and the statistical significance of differences with and without the CT-TS was assessed by JAFROC analysis. RESULTS: The average figure-of-merit (FOM) values for all radiologists increased to a statistically significant degree, from 0.861 without CT-TS to 0.912 with CT-TS (p < .001). The average sensitivity for detecting the actionable lesions improved from 73.4 % to 85.9 % using CT-TS. The reading time with CT-TS was not significantly different from that without. CONCLUSION: The use of CT-TS improves the observer performance for the detection of LC-pGGO. KEY POINTS: • CT temporal subtraction can improve the detection accuracy of lung cancer. • Reading time with temporal subtraction is not different from that without. • CT temporal subtraction improves observer performance for ground-glass/subsolid nodule detection.

In vivo visualization of tau deposits in corticobasal syndrome by 18F-THK5351 PET.

OBJECTIVE: To determine whether 18F-THK5351 PET can be used to visualize tau deposits in brain lesions in live patients with corticobasal syndrome (CBS). METHODS: We evaluated the in vitro binding of 3H-THK5351 in postmortem brain tissues from a patient with corticobasal degeneration (CBD). In clinical PET studies, 18F-THK5351 retention in 5 patients with CBS was compared to that in 8 age-matched normal controls and 8 patients with Alzheimer disease (AD). RESULTS: 3H-THK5351 was able to bind to tau deposits in the postmortem brain with CBD. In clinical PET studies, the 5 patients with CBS showed significantly higher 18F-THK5351 retention in the frontal, parietal, and globus pallidus than the 8 age-matched normal controls and patients with AD. Higher 18F-THK5351 retention was observed contralaterally to the side associated with greater cortical dysfunction and parkinsonism. CONCLUSIONS: 18F-THK5351 PET demonstrated high tracer signal in sites susceptible to tau deposition in patients with CBS. 18F-THK5351 should be considered as a promising candidate radiotracer for the in vivo imaging of tau deposits in CBS.

Applicability assessment of ceramic microbeads coated with hydroxyapatite-binding silver/titanium dioxide ceramic composite earthplus™ to the eradication of Legionella in rainwater storage tanks for household use.

Water environments appear to be the habitats of Legionella species. Legionellosis is considered as a preventable illness because bacterial reservoirs can be controlled and removed. Roof-harvested rainwater has attracted significant attention not only as a groundwater recharge but also as a potential alternative source of nonpotable water. We successfully developed ceramic microbeads coated with hydroxyapatite-binding silver/titanium dioxide ceramic composite earthplus™ using the thermal spraying method. The ceramic microbeads were demonstrated to have bactericidal activities against not only Legionella but also coliform and heterotrophic bacteria. Immersing the ceramic microbeads in household rainwater storage tanks was demonstrated to yield the favorable eradication of Legionella organisms. Not only rapid-acting but also long-lasting bactericidal activities of the ceramic microbead were exhibited against Legionella pneumophila. However, time-dependent attenuation of the bactericidal activities against Legionella were also noted in the sustainability appraisal experiment. Therefore, the problems to be overcome surely remain in constantly managing the Legionella-pollution by means of immersing the ceramic microbeads. The results of our investigation apparently indicate that the earthplus™-coated ceramic microbeads would become the favorable tool for Legionella measures in household rainwater storage tanks, which may become the natural reservoir for Legionella species. Our investigation would justify further research and data collection to obtain more reliable procedures to microbiologically regulate the Legionella in rainwater storage tanks.

Retrospective analysis of Guillain-Barré syndrome and Fisher syndrome after the Great East Japan Earthquake.

Guillain-Barré syndrome (GBS) and Fisher syndrome (FS) are immune-mediated peripheral neuropathies, and most of these cases were known to be associated with a preceding infection. Recent reports evidenced an increase in the number of infectious disease cases after the earthquake. The aim of this report is to investigate the incidence and clinical features of GBS and FS after the Great East Japan Earthquake. We found GBS and FS patients had markedly increased in 2011, the year of the earthquake. In regard to an antecedent illness, gastrointestinal infection was significantly increased in GBS patients after the earthquake. These results suggest environmental factors including infectious agents and stress caused by the earthquake might have been involved in the outbreak of the diseases.

Bath water contamination with Legionella and nontuberculous mycobacteria in 24-hour home baths, hot springs, and public bathhouses of Nagano Prefecture, Japan.

Bath water samples were collected from 116 hot springs, 197 public bathhouses, and 38 24-hour home baths in Nagano Prefecture, Japan, during the period of April 2009 to November 2011, for determining the presence and extent of contamination with Legionella and nontuberculous mycobacteria. Cultures positive for Legionella were observed in 123 of the 3,314 bath water samples examined. The distribution and abundance of Legionella and/or combined contamination with Legionella and nontuberculous mycobacteria were investigated to clarify the contamination levels. The abundance of Legionella was demonstrated to correlate considerably with the levels of combined contamination with Legionella and nontuberculous mycobacteria. Legionella spp. were obtained from 61% of the water samples from 24-hour home baths, but only from 3% of the samples from public bathhouses and hot springs. This is despite the fact that a few outbreaks of Legionnaires' disease in Nagano Prefecture as well as other regions of Japan have been traced to bath water contamination. The comparatively higher rate of contamination of the 24-hour home baths is a matter of concern. It is therefore advisable to routinely implement good maintenance of the water basins, particularly of the 24-hour home baths.

Incidence of Legionella and heterotrophic bacteria in household rainwater tanks in Azumino, Nagano prefecture, Japan.

Many administrative agencies in Japan are encouraging installation of household rainwater-storage tanks for more effective use of natural rainwater. Water samples were collected periodically from 43 rainwater tanks from 40 households and tested for the presence of Legionella species and the extent of heterotrophic bacteria in Azumino city, Nagano prefecture, Japan. PCR assays indicated the presence of Legionella spp. in 12 (30%) of the 43 tank water samples. Attempts were made to identify correlations between PCR positive samples, topography, pH, chemical oxygen demand (COD), atmospheric temperature and the numbers of heterotrophic bacteria. Between June and October, 2012, the numbers of heterotrophic bacteria in rainwater tanks and the values of COD positively correlated with the presence of Legionella species. In most of the Legionella-positive cases, heterotrophic bacterial cell counts were >10(4) CFU/mL. Moreover, Legionella species were less frequently detected when the COD value was >5 mg KMnO(4)/L. Therefore, at least in Azumino, Japan between June and October 2012, both heterotrophic bacterial counts and COD values may be considered index parameters for the presence of Legionella cells in rainwater tanks. Much more accumulation of such data is needed to verify the accuracy of these findings.

Hypometabolism in the supplementary and anterior cingulate cortices is related to dysphagia in Parkinson's disease: a cross-sectional and 3-year longitudinal cohort study.

OBJECTIVE: Dysphagia is one of the cardinal symptoms of Parkinson's disease (PD). It is closely related to the quality of life and longevity of PD patients. The aim of the study is to clarify the pathophysiological mechanisms responsible for dysphagia in PD. DESIGN: A cross-sectional and longitudinal comparative study. SETTING: Tohoku University Hospital. PARTICIPANTS: Eight patients with dysphagia, 15 patients without dysphagia and 10 normal control subjects. MAIN OUTCOME MEASURES: The time needed for swallowing initiation and changes in brain glucose metabolism at baseline and after a 3-year follow-up period. RESULTS: The time needed for swallowing initiation was significantly longer in the patients with dysphagia compared with the patients without dysphagia at baseline and after the 3-year follow-up period (p<0.05). The patients with dysphagia exhibited hypometabolism in the supplementary motor area (SMA) and the anterior cingulate cortex (ACC) compared with the 10 normal control subjects at baseline (uncorrected p<0.001). After the 3-year follow-up period, the number of brain areas showing hypometabolism increased, involving not only the SMA and the ACC but also the bilateral medial frontal lobes, middle cingulate cortex, thalamus and right superior, middle, inferior and orbital frontal gyri (uncorrected p<0.001). In contrast, the patients without dysphagia showed virtually no regional hypometabolism at baseline (uncorrected p<0.001) and only a small degree of hypometabolism in the SMA and ACC after the 3-year follow-up period (uncorrected p<0.001). CONCLUSIONS: These results suggest that dysphagia in PD patients is mainly related to a difficulty in swallowing initiation that is based on a combination of poor movement planning due to SMA dysfunction and impaired cognitive processing due to ACC dysfunction.

Percutaneous transhepatic ethanol ablation for postoperative bile leakage after a hepatectomy.

A 68-year-old male underwent a partial hepatectomy for hepatocellular carcinoma located in S5 close to the confluence of the anterior and posterior Glisson's sheath. Thereafter, bile leakage developed from the drain on postoperative day (POD) 2. Endoscopic nasobiliary drainage of the biliary tree and percutaneous drainage of the biloma proved ineffective, and the bile leakage continued at a constant volume of 40 mL per day. A fistulogram on POD 62 demonstrated an enhancement of the isolated bile duct. Ethanol injection into the isolated bile duct was attempted to ablate biliary epithelium but this was unsuccessful because it was impossible to insert the tube into the isolated bile duct. Ethanol was injected into the liver parenchyma surrounding the isolated bile duct via the percutaneous transhepatic approach under sonographic guidance on POD 78 in order to eliminate the production of bile juice by destroying both the biliary epithelium and liver parenchyma. The bile leakage decreased one day following the ethanol injection, although the patient experienced a prolonged fever for a week, and he was discharged on POD 100. This is the first report of ethanol injection into the liver parenchyma by a percutaneous transhepatic approach, instead of into the bile duct, to treat intractable bile leakage.

The AAA-ATPase VPS4 regulates extracellular secretion and lysosomal targeting of α-synuclein.

Many neurodegenerative diseases share a common pathological feature: the deposition of amyloid-like fibrils composed of misfolded proteins. Emerging evidence suggests that these proteins may spread from cell-to-cell and encourage the propagation of neurodegeneration in a prion-like manner. Here, we demonstrated that α-synuclein (αSYN), a principal culprit for Lewy pathology in Parkinson's disease (PD), was present in endosomal compartments and detectably secreted into the extracellular milieu. Unlike prion protein, extracellular αSYN was mainly recovered in the supernatant fraction rather than in exosome-containing pellets from the neuronal culture medium and cerebrospinal fluid. Surprisingly, impaired biogenesis of multivesicular body (MVB), an organelle from which exosomes are derived, by dominant-negative mutant vacuolar protein sorting 4 (VPS4) not only interfered with lysosomal targeting of αSYN but facilitated αSYN secretion. The hypersecretion of αSYN in VPS4-defective cells was efficiently restored by the functional disruption of recycling endosome regulator Rab11a. Furthermore, both brainstem and cortical Lewy bodies in PD were found to be immunoreactive for VPS4. Thus, VPS4, a master regulator of MVB sorting, may serve as a determinant of lysosomal targeting or extracellular secretion of αSYN and thereby contribute to the intercellular propagation of Lewy pathology in PD.