Background: and Purpose Neuropsychiatric symptoms (NPS) are frequent in dementia and mild cognitive impairment (MCI), yet their reported associations with white matter hyperintensities (WMHs) remain inconsistent. We examined item-level associations between WMHs and NPS across Alzheimer’s disease dementia (ADD), dementia with Lewy bodies (DLB), and amnestic MCI (aMCI). Methods: This multicenter retrospective study involved 523 patients: 276 with ADD, 67 with DLB, and 180 with aMCI. Three-dimensional T1-weighted and T2–fluid-attenuated inversion recovery magnetic resonance images were processed with BAAD (Brain Anatomical Analysis using Diffeomorphic Deformation) software to quantify WMH volume (WMHV) and gray matter volume (GMV), normalized to total intracranial volume (TIV). NPS were assessed using the Neuropsychiatric Inventory. Multiple regression analyses were performed within each group, adjusting for GMV/TIV, age, sex, years of education, Clinical Dementia Rating–Sum of Boxes score, and institution. Results: In the aMCI group, higher WMHV/TIV was positively associated with depression, apathy, and disinhibition, and negatively with delusions. Subregional analyses revealed NPSspecific topographic patterns. No significant associations were detected in the ADD or DLB group. GMV/TIV was positively associated with delusions in the ADD group, but negatively associated with hallucinations in the DLB group. Conclusions Associations between WMHs and NPS were evident in the aMCI group but absent in the ADD and DLB groups, suggesting a stage-dependent effect. WMHs may contribute to NPS primarily in prodromal stages, whereas their influence may be overshadowed by neurodegenerative pathology in dementia. Clarifying the mechanisms underlying WMHs is critical for evaluating their potential as intervention targets.

BACKGROUND: Long screen time hours may be associated with behavioral problems in children. To better understand the relationship between children's behavioral problems and screen time, it the associated risk factors must be subdivided based on the purpose underlying screen use. This study examined the relationship between screen time based on intended usage and behavioral problems in Japan. METHODS: This study included 3,332 children aged between 7-17 years from the Hokkaido Study on Environment and Children's Health. From October 2020 to October 2021, the children and their parents answered questionnaires on the children's screen use duration (never used, <30 min, ≥30 min & <1 hour, ≥1 h & <2 h, ≥2 h) based on seven intended usage categories: watching television/video, video gaming, reading books/comics, sending/receiving e-mail/messages, browsing/posting on social networking services, studying for classes/homework, drawing/editing pictures/photos/videos, along with the Strengths and Difficulties Questionnaire (SDQ). Logistic regression was used to analyze the association between screen time, purpose of children's screen use, and behavioral problems across the 13 SDQ total scores. RESULTS: The mean ± standard deviation age of the participants was 12.4 ± 2.4-years-old, 487 (14.6%) children were determined to have behavioral problems, and the duration of screen time increased with their age. The children's primary purposes for screen use were watching television/video, video gaming, sending/receiving e-mail/messages, and browsing/posting on social networking services. Children who reported playing video games for ≥2 hours on weekdays had higher odds of problematic total difficulties scores than never user (Odds Ratio: 2.10, 95% confidence interval: 1.45-3.06). CONCLUSION Long video gaming screen time is associated with behavioral issues, hyperactivity/inattention, and prosocial behaviors in children. Conversely, watching television and videos for 30 min-1 h per day, using e-mail or messaging, and using social networking services were significantly association with reduced odds ratio for peer relationship problems as compared to children who never engaged in these activities. Longitudinal follow-up is needed to further examine screen time and problem behaviors.
Humans ; Screen Time ; Child ; Japan/epidemiology* ; Male ; Female ; Adolescent ; Problem Behavior/psychology* ; Surveys and Questionnaires ; Child Behavior ; Television/statistics & numerical data* ; Video Games/statistics & numerical data*

Objective: Advanced ovarian clear cell carcinoma (OCCC) is associated with poor outcomes owing to chemoresistance. Bevacizumab (Bev) is increasingly being used to treat advanced ovarian cancer; however, its efficacy in OCCC remains unclear. This study evaluated the treatment outcomes of frontline bevacizumab chemotherapy in patients with OCCC. Methods: This retrospective multi-institutional study included patients diagnosed with advanced OCCC at eight institutions in Japan between 2008 and 2018. Patients were categorized into pre and post-market groups based on the Bev approval dates. Progressionfree survival (PFS) and overall survival (OS) were analyzed using univariate and multivariate methods. Additionally, patients were classified into Bev-treated (Bev+) and non-Bev-treated (Bev−) groups, and their prognoses were compared. Results: A total of 96 patients were in the pre-market group and 82 in the post-market group. The post-market group had a significantly higher proportion of patients with poor performance status and patients who underwent interval debulking surgery (p<0.01 and p<0.01, respectively). Univariate analysis demonstrated a better PFS in the post-market group (p=0.041). In multivariate analysis, better PFS (hazard ratio [HR]=0.52; p=0.002) and OS (HR=0.47; p=0.002) were observed in the post-market group than in the pre-market group.Bev+ patients had significantly better PFS and OS than Bev− patients in univariate (p<0.001 and p<0.001, respectively) and multivariate analyses (PFS: HR=0.36; p<0.001 and OS:HR=0.21; p=0.001, respectively). Conclusion Incorporating Bev into frontline chemotherapy may improve outcomes in patients with advanced OCCC.

Background: No consensus exists regarding which anthropometric measurements are related to bone mineral density (BMD), and this relationship may vary according to sex and age. A large Japanese cohort was analyzed to provide an understanding of the relationship between BMD and anthropometry while adjusting for known confounding factors. Methods: Our cohort included 10,827 participants who underwent multiple medical checkups including distal forearm BMD scans. Participants were stratified into four groups according to age (≥50 years or <50 years) and sex. The BMD values were adjusted for confounding factors, after which single and partial correlation analyses were performed. The prevalence of osteopenia was plotted for each weight index (weight or body mass index [BMI]) class. Results: Cross-sectional studies revealed that weight was more favorably correlated than BMI in the older group (R=0.278 and 0.212 in men and R=0.304 and 0.220 in women, respectively), whereas weight and BMI were weakly correlated in the younger age groups. The prevalence of osteopenia exhibited a negative linear relationship with weight among older women ≥50 years of age, and an accelerated increase was observed with decreasing weight in older men weighing <50 kg and younger women weighing <60 kg. When weight was replaced with BMI, the prevalence was low in most subgroups classified by weight. Conclusions Weight, rather than BMI, was the most important indicator of osteopenia but it might not be predictive of future bone loss.

Objective：Only 44 of the 82 university medical schools in Japan have rehabilitation medicine departments, although rehabilitation medicine is one of the 19 basic specialties recognized by the Japanese Medical Specialty Board, and many medical doctors are concerned regarding selecting rehabilitation medicine as a basic specialty without sufficient education in the field. The “Let's Become a Physiatrist” Seminar has been organized since 2017 to eliminate such concerns, and this study aimed to investigate how these results are manifested in the number of majors.Methods：We examined the number of past attendees and tracked how many of them became rehabilitation medicine majors.Results：The number of seminar attendees over a 5-year period was 589. The number of on-demand viewers in FY2020 and FY2021, which were held via the web, was 554. A total of 116 of the 471 physicians who began specialty training in rehabilitation medicine after the seminar was planned attended or web viewed the seminar accounting for 24.63％．This percentage has been increasing each year, with 36.81％ of the majors who applied in 2022 attending the seminar, and the number of multiple attendees also increased. The number of majors has increased significantly doubling to 144 in 2022 compared with 74 in 2018.Conclusion：In many cases, the seminar helped the attendees learn more about physiatrists and develop their thoughts while attending multiple times. Thus, they started their majors. Five years have passed since we started planning this seminar, and we believe that the results are now coming to fruition.

Objective：Only 44 of the 82 university medical schools in Japan have rehabilitation medicine departments, although rehabilitation medicine is one of the 19 basic specialties recognized by the Japanese Medical Specialty Board, and many medical doctors are concerned regarding selecting rehabilitation medicine as a basic specialty without sufficient education in the field. The “Let's Become a Physiatrist” Seminar has been organized since 2017 to eliminate such concerns, and this study aimed to investigate how these results are manifested in the number of majors.Methods：We examined the number of past attendees and tracked how many of them became rehabilitation medicine majors.Results：The number of seminar attendees over a 5-year period was 589. The number of on-demand viewers in FY2020 and FY2021, which were held via the web, was 554. A total of 116 of the 471 physicians who began specialty training in rehabilitation medicine after the seminar was planned attended or web viewed the seminar accounting for 24.63％．This percentage has been increasing each year, with 36.81％ of the majors who applied in 2022 attending the seminar, and the number of multiple attendees also increased. The number of majors has increased significantly doubling to 144 in 2022 compared with 74 in 2018.Conclusion：In many cases, the seminar helped the attendees learn more about physiatrists and develop their thoughts while attending multiple times. Thus, they started their majors. Five years have passed since we started planning this seminar, and we believe that the results are now coming to fruition.

Advances in information and communication technology (ICT)-especially, the spread of social networking services (SNSs)-have facilitated the dissemination of information and an explosion of health information lacking scientific evidence. Therefore, we believe that community pharmacies are the most suitable bases for distributing health information. In 2019, we launched the health support pharmacy “Toyonaka Model” in collaboration with the pharmaceutical association, municipal government, and university. Touch-panel digital signage (DS) was used for real-time distribution of ever-changing information and a rapid grasp of pharmacy users’ responses to various types of information. Between September 2019 and August 2021, one DS was installed in a pharmacy in each of Toyonaka City’s seven areas along with 14 questions on the usefulness of the delivered information. Respondents answered the 14 questions by a tablet or questionnaire; touch logs for DS were collected. When a pharmacy user consulted with a pharmacist about information delivered via DS, the contents were recorded and described by the pharmacist on a 4-point scale (e.g., “inquiry only,” “went through to execution”). From the 850 completed questionnaires and 61,565 touches, 88.7% of the respondents indicated that the information was useful, and 90.0% expressed interest in receiving more health information in the future. Thus, health information provided by DS may be useful to pharmacy users, as demonstrated by 113 cases in which the pharmacist was consulted regarding such information. In 62 of these cases, there were indications that the DS information might have influenced users’ behavior and intended actions.

Objective: Maternal embryonic leucine zipper kinase (MELK) is receiving an attention as a therapeutic target in various types of cancers. In this study, we aimed to evaluate the prognostic significance of MELK expression in ovarian cancer using clinical samples, and assessed the efficacy of a small molecule MELK inhibitor, OTS167, using patient-derived ovarian cancer cells as well as cell lines. Methods: Expression levels of MELK in 11 ovarian cancer cell lines were confirmed by western blotting. Inhibitory concentration of OTS167 was determined by colorimetric assay.MELK messenger RNA (mRNA) expression was evaluated in 228 ovarian cancer patients by quantitative polymerase chain reaction. Growth inhibition of OTS167 was also evaluated using freshly-isolated primary ovarian cancer cells including spheroid formation condition. Results: MELK mRNA expression was significantly higher in ovarian cancer than in normal ovaries (p<0.001), and high MELK mRNA expression was observed in patients with advanced stage, positive ascites cytology and residual tumor size. Patients with high MELK mRNA expression showed shorter progression-free survival (p=0.001). Expression of MELK was also confirmed in 10 of 11 ovarian cancer cell lines tested, and the half maximal inhibitory concentration of MELK inhibitor, OTS167, ranged from 9.3 to 60 nM. Additionally, OTS167 showed significant growth inhibitory effect against patient-derived ovarian cancer cells, regardless of their tumor locations, histologic subtypes and stages. Conclusions We demonstrated MELK as both a prognostic marker and a therapeutic target for ovarian cancer using clinical ovarian cancer samples. MELK inhibition by OTS167 may be an effective approach to treat ovarian cancer patients.

OBJECTIVE: Directional leads are used for deep brain stimulation (DBS). Two of the four contacts of the leads are divided into three parts, enabling controlled stimulation in a circumferential direction. The direction of adverse effects evoked by DBS in the subthalamic nucleus (STN) and stimulation strategies using directional leads were evaluated. METHODS: Directional leads were implanted into the bilateral STN of six parkinsonian patients (1 man, 5 women; mean age 66.2 years). The contact centers were located within the upper border of the STN, and the locations were identified electrically using microrecordings. Adverse effects were evaluated with electrical stimulation (30 μs, 130 Hz, limit 11 mA) using the directional part of each lead after surgery, and the final stimulation direction was investigated. Unified Parkinson's disease rating scale (UPDRS) scores were evaluated before and after DBS. RESULTS: Fifty-six motor and four sensory symptoms were evoked by stimulation; no adverse effect was evoked in 14 contacts. Motor and sensory symptoms were evoked by stimulation in the anterolateral direction and medial to posterolateral direction, respectively. Stimulation in the posteromedial direction produced adverse effects less frequently. The most frequently used contacts were located above the STN (63%), followed by the upper part of the STN (32%). The mean UPDRS part III and dyskinesia scores decreased after DBS from 30.2 ± 11.7 to 7.2 ± 2.9 and 3.3 ± 2.4 to 0.5 ± 0.8, respectively. CONCLUSION: The incidence of adverse effects was low for the posteromedial stimulation of the STN. Placing the directional part of the lead above the STN may facilitate the control of dyskinesia.
Deep Brain Stimulation ; Dyskinesias ; Electric Stimulation ; Female ; Humans ; Incidence ; Parkinson Disease ; Pilot Projects ; Subthalamic Nucleus

OBJECTIVE: Uterine serous carcinoma (USC) is an aggressive type 2 endometrial cancer. Data on prognostic factors for patients with early-stage USC without adjuvant therapy are limited. This study aims to assess the baseline recurrence risk of early-stage USC patients without adjuvant treatment and to identify prognostic factors and patients who need adjuvant therapy. METHODS: Sixty-eight patients with International Federation of Gynecology and Obstetrics (FIGO) stage I–II USC between 1997 and 2016 were included. All the cases did not undergo adjuvant treatment as institutional practice. Clinicopathological features, recurrence patterns, and survival outcomes were analyzed to determine prognostic factors. RESULTS: FIGO stages IA, IB, and II were observed in 42, 7, and 19 cases, respectively. Median follow-up time was 60 months. Five-year disease-free survival (DFS) and overall survival (OS) rates for all cases were 73.9% and 78.0%, respectively. On multivariate analysis, cervical stromal involvement and positive pelvic cytology were significant predictors of DFS and OS, and ≥1/2 myometrial invasion was also a significant predictor of OS. Of 68 patients, 38 patients had no cervical stromal invasion or positive pelvic cytology and showed 88.8% 5-year DFS and 93.6% 5-year OS. CONCLUSION: Cervical stromal invasion and positive pelvic cytology are prognostic factors for stage I–II USC. Patients with stage IA or IB USC showing negative pelvic cytology may have an extremely favorable prognosis and need not receive any adjuvant therapies.
Adenocarcinoma ; Cytodiagnosis ; Disease-Free Survival ; Endometrial Neoplasms ; Female ; Follow-Up Studies ; Gynecology ; Humans ; Institutional Practice ; Multivariate Analysis ; Obstetrics ; Prognosis ; Recurrence