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Summary. Objective: To study the relative rates of progression of early Parkinson's disease (PD) in patients started on a dopamine agonist, ropinirole, or L-dopa. Methods: A double-blind study of 45 early PD patients [mean age 61 ± 9.8 SD and mean symptom duration, 26 ± 16 SD months] randomized 2 : 1 (ropinirole : L-dopa). Supplementary L-dopa was allowed if, during the trial, there was lack of a therapeutic effect. 18F-dopa PET scans were performed at baseline (n = 45) and 2 years (n = 37). Results: At two years, the mean percentage reduction in putamen 18F-dopa uptake (Kio) was not significantly different between the two groups (13% ropinirole, n = 28 versus 18% L-dopa, n = 9). Conclusions: We found no significant overall difference in underlying PD progression, after two years treatment, between patients groups. In summary, 18F-dopa PET can be employed to objectively evaluate the effect of potential neuroprotective agents on dopaminergic function. [ABSTRACT FROM AUTHOR]

METHODS. The prevalence of dementia was investigated in Okinawa Prefecture, Japan. In all, 3524 subjects, > or = 65 years old, were sampled randomly (urban and rural populations 61.1% and 38.9% respectively). Phase 1 of the survey was carried out by specially trained students of the Faculty of Medicine who used the Mini-Mental State (MMS) scale (interview rate: 94.3%) to screen 522 (15.8%) of the 3312 subjects for the phase 2 survey. Phase 2, conducted by psychiatrists using the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) criteria, detected 172 cases of dementia. RESULTS. The estimated prevalence of dementia was 6.7%. For women, the rate increased sharply in the 90-99 year old group, and was 41.4%; for men in the 90-99 year old group prevalence was 21.2%. The ratio of Alzheimer-type dementia to multi-infarct dementia was 1.5:1 (men 1.2:1, women 1.7:1). The breakdown of the severity of dementia in the total cases was: mild 16.9%, moderate 30.8%, and severe 52.3%. The number of severe cases increased with age. [ABSTRACT FROM AUTHOR]

In Japan, the traditional method for measuring plasma aldosterone concentration (PAC) was radioimmunoassay (RIA), which had several challenges, including poor traceability of certified reference materials and reduced detection sensitivity at low concentrations. To overcome these issues, a chemiluminescent enzyme immunoassay (CLEIA) for PAC measurement was introduced in April 2021 and the Japan Endocrine Society published new guidelines for primary aldosteronism (PA). This study aimed to evaluate the impact of the transition from RIA to CLEIA for PAC measurement on PA diagnosis. Data from 190 patients admitted to the Second Department of Internal Medicine, University of the Ryukyus Hospital, between April 2012 and March 2021 were analyzed. Patients who were diagnosed with PA underwent adrenal venous sampling. The PAC measured by RIA (PAC(RIA)) was converted to the estimated PAC measured by CLEIA (ePAC(CLEIA)) using a conversion formula. The present study evaluated the discordance rates in diagnoses based on screening (SC), captopril challenge test (CCT), saline infusion test (SIT), and diagnosis of PA between results judged by PAC(RIA) according to the previous guidelines and those judged by ePAC(CLEIA) according to the new guidelines. The results revealed discordant diagnosis rates of 6.4% for SC and 10.1% for CCT, with no discordance for SIT. The discordant diagnosis rate for PA was 3.7%. Our study reveals the challenges in establishing appropriate diagnostic criteria for PA using PAC(CLEIA) and highlights the demand for further research on provisionally positive categories.

Post-traumatic pituitary stalk transection syndrome (PSTS) is an extremely rare cause of combined pituitary hormone deficiency (CPHD), affecting approximately 9 per 100,000 cases of traumatic brain injury. In contrast, pituitary stalk interruption syndrome (PSIS) is also a rare cause of CPHD. Importantly, these conditions are often confused due to their similar names and resembling findings on magnetic resonance imaging (MRI). PSIS has been thought to be a prenatal developmental event resulting from a couple of genetic aberrations. In typical PSIS, anterior pituitary hormone deficiencies are restricted to growth hormone (GH) and gonadotropin during the pediatric age, gradually and generally progressing to panhypopituitarism in most cases. In contrast, global deficiencies of the anterior pituitary hormones in PSTS are temporally associated with trauma. To the best of our knowledge, no case reports of PSTS combined with acute traumatic spinal cord injury have been reported. A 34-year-old female was transferred to our hospital after jumping from the fourth building floor. She was diagnosed as an acute traumatic spinal cord injury and underwent the operation of elective posterior spinal fusion. On postoperative day 7, the blood tests revealed considerable hyperkalemia, hyponatremia and eosinophilia. Notably, menstruation stopped after falling from a height. Pituitary function tests revealed GH deficiency, hypogonadism, hypothyroidism and hypoadrenocorticism. MRI revealed loss of the pituitary stalk, whilst the hyperintense signal from distal axon of hypothalamus was still identified. Based on these findings, she was diagnosed as PSTS. Our case highlights endocrinological landscape of transection of the pituitary stalk by acute trauma.

Aim: The present cohort study explored whether specific gut microbiota (GM) profile would predict the development of impaired glucose tolerance (IGT) in individuals with normal glucose tolerance (NGT)., Methods: A total of 114 study subjects with NGT in Kumejima island, Japan participated in the present study and underwent 75 g oral glucose tolerance tests at baseline and one year later. We compared the profile of GM at baseline between individuals who consistently maintained NGT (NRN, n = 108) and those who transitioned from NGT to IGT (NTI, n = 6)., Results: Within-individual bacterial richness and evenness as well as inter-individual bacterial composition showed no significant differences between NRN and NTI. Of note, however, partial least squares discriminant analyses revealed distinct compositions of GM between groups, with no overlap in their 95 % confidence interval ellipses. Multi-factor analyses at the genus level demonstrated that the proportions of CF231, Corynebacterium, Succinivibrio, and Geobacillus were significantly elevated in NTI compared to NRN (p < 0.005, FDR < 0.1, respectively) after adjusting for age, sex, HbA1c level, and BMI., Conclusions: Our data suggest that increased proportion of specific GM is linked to the future deterioration of glucose tolerance, thereby serving as a promising predictive marker for type 2 diabetes mellitus., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. The sponsors were not involved in the study design; collection, analyses, or interpretation of the data; the writing of this manuscript; or the decision to submit the manuscript for publication. The authors, their immediate families, and any research foundations with which they are affiliated have not received any financial payment or other benefits from any commercial entity related to the subject of this article., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

We investigated the impact of the Coronavirus disease 2019 (COVID-19) pandemic on the management of endocrine and metabolic disorders in Japan. We conducted a cross-sectional nationwide questionnaire survey targeting board-certified endocrinologists under the auspices of the Japan Endocrine Society. The questionnaire consisted of multiple-choice questions and open-ended responses. Out of approximately 2,700 specialists, 528 (19.5%) opted to participate, suggesting a high level of interest in COVID-19 management among endocrinologists. The study found that almost half of participants had encountered cases of endocrine and metabolic disorders following COVID-19 infection or vaccination. Conditions related to thyroid diseases, glucose metabolism disorders/diabetes, and hypothalamic-pituitary disorders were particularly prevalent. Diabetes and obesity were identified as having high rates of severe cases or fatalities due to COVID-19. The study also highlighted challenges in routine diagnosis and treatment, emphasizing the potential benefits of combining remote consultations with in-person visits to optimize the frequency of examinations and check-ups during infectious disease outbreak which disrupts access to healthcare providers. The insights obtained from this survey are expected to contribute to ensuring appropriate healthcare provision for patients with endocrine and metabolic disorders by using flexible consultation formats, particularly even in the conditions where medical access may be limited due to future outbreaks of emerging or re-emerging infectious diseases.

Aims: This cohort study investigated the association between treatment cessation and incidence/progression of diabetic retinopathy (DR) in Japanese patients with type 2 diabetes mellitus (T2DM)., Materials and Methods: Data were extracted from electronic medical records at the University of the Ryukyu Hospital and the Tomishiro Central Hospital of Okinawa, Japan. We enrolled 417 diabetic patients without DR ( N  = 281) and with nonproliferative DR ( N  = 136) at the baseline. Treatment cessation was defined as failing to attend outpatient clinics for at least twelve months prior to the baseline. After a median follow-up of 7 years, we compared the incidence/progression rate of DR including nonproliferative and proliferative DR between patients with and without treatment cessation and calculated the odds ratio (OR) in the treatment cessation group using a logistic regression model., Results: The overall prevalence of treatment cessation was 13% in patients with T2DM. Characteristics of treatment cessation included relative youth (57 ± 11 years vs. 63 ± 12 years, P  < 0.01). Treatment cessation was tightly associated with the incidence of DR (OR 4.20 [95% confidence interval [CI] 1.46-12.04, P  < 0.01) and also incidence/progression of DR (OR 2.70 [1.28-5.69], P  < 0.01), even after adjusting for age, sex, BMI, duration of T2DM, and HbA1c level., Conclusions: By considering major confounding factors, the present study demonstrates an independent association between treatment cessation and incidence of DR in patients with T2DM, highlighting treatment cessation as an independent risk for DR in T2DM., Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-024-00724-7., Competing Interests: Conflict of interestNone of the authors have any conflicts of interest to disclose., (© The Japan Diabetes Society 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Childhood obesity is rapidly increasing worldwide and is largely the consequence of adoption of unhealthy diets excessive in calories and salt (NaCl) as well as devoid in pivotal micronutrients such as potassium (K) and magnesium (Mg). Education-based programs aiming to encourage healthy food knowledge and behaviors are crucial at a young age, and for this purpose, convenient ways to assess daily dietary intake are warranted. We therefore attempted to evaluate the dietary intake of Okinawan schoolchildren in Japan by analyzing a series of biomarkers in morning spot urine samples and explore whether these biomarkers correlate with body weight and a series of metabolic parameters. We enrolled 98 third-grade elementary schoolchildren in Okinawa, Japan. Morning spot urine samples were collected and analyzed using high-performance liquid chromatography (HPLC) to assess dietary intake. We found that estimated daily NaCl intake was higher in obese/overweight children as compared to healthy-weight children (p = 0.0001). There was also a significant positive correlation between body mass index (BMI) and NaCl intake (Spearman) (ρ = 0.45, p < 0.0001) and a negative correlation between BMI and Mg/Cr (ρ =  -0.27, p = 0.01). Furthermore, Na/K ratio was higher in samples collected on Monday (weekend) as compared to samples collected on Thursday or Friday (weekday) (p < 0.0001)., Conclusion: Via the use of morning spot urine analyses, our results show that NaCl intake was associated with obesity, and Mg excretion negatively correlated with BMI in Japanese schoolchildren, highlighting the potential role of these micronutrients in maintaining a healthy body weight., What Is Known: •Overweight and obesity are largely due to excessive consumption of calories and positively correlated with salt (NaCl) intake. •Spot urine methods are convenient for assessing the nutritional needs and targeting prevention programs in children., What Is New: •Utilizing morning spot urine analyses, estimated NaCl intake is positively correlated and Mg/Cr negatively correlated with BMI in Okinawan schoolchildren. •As estimated via morning spot urine samples, a greater proportion of children likely exceeds the recommended NaCl intake on the weekend as compared to weekday., (© 2022. The Author(s).)

Numerous studies have revealed distinct differences in the profiles of gut microbiota between non-obese and obese individuals. To date, however, little is known if any disparities in the community of gut microbiota exist between metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO) subjects. We therefore aimed to comprehensively characterize the gut microbiota and circulating metabolites in serum from both MHO and MUO residing in the remote island, Kumejima, where the prevalence of obesity is one of the highest in Japan, and explored possible correlations between the gut microbiota profile and markers of metabolic syndrome. Results revealed that MUO showed significantly higher levels of genera such as g&#95;Succinivibrio, g&#95;Granulicatella, g&#95;Brachyspira, g&#95;Oribacterium and g&#95;Atopobium in comparison to MHO. Moreover, abundance of g&#95;Succinivibrio, g&#95;Brachyspira and g&#95;Atopobium were positively correlated with value of fasting insulin, HOMA-R, circulating triglycerides, diastolic blood pressure, BMI, body weight, waist circumference and HbA1c. In addition, MUO compared to MHO showed an imbalance of serum metabolites, with a significant elevation in 2-oxoisovaleric acid, pyruvic acid, 2-hydroxybutyric acid, and creatine. Our data highlight unmet needs in precision approaches for the treatment of obesity, targeting the gut microbiota profile and serum metabolites in a distinct population affected by obesity., (© 2022. The Author(s).)

Accumulating evidence to date suggests that brown rice is superior to white rice in regard to its beneficial impact on a number of risk factors of the metabolic syndrome (MetS). However, little is known about the influence of fermented brown rice beverage on the gut microbiota in humans. We therefore hypothesized that its impact would beneficially alter the gut microbiota composition of patients with MetS. Using a 4-week randomized, single-arm study design, subjects (n = 40) were advised to consume a daily fermented brown rice beverage (BA) or fermented white rice beverage (WA) as a replacement of their main meal. Clinical and anthropometric measurements as well as fecal samples were collected at baseline and immediately after completion of the intervention. Gut microbiota was analyzed using 16S ribosomal RNA sequencing and capillary electrophoresis-time-of-flight mass spectrometry was used to measure plasma short-chain fatty acids. Interestingly, ingestion of BA in contrast to WA resulted in a unique elevation in the abundance of number of beneficial species belonging to the Clostridia class, associated with reduced inflammation, and increased short-chain fatty acid production: Lactobacillales bacterium DJF B280 (P = .005), Butyrate producing bacterium A2 207 (P = .012), and Firmicutes bacterium DJF VP44 (P = .038). This study demonstrates that consumption of BA is effective to beneficially modulate the gut microbiota compared with WA in patients with MetS., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to declare., (Copyright © 2022. Published by Elsevier Inc.)

(1) Background: Evidence has accumulated regarding the etiology of lower urinary tract symptoms associated with obesity and metabolic syndrome. Therefore, the present study aimed to identify which subjectively and objectively measured voiding parameters were associated with obesity in a community-based population. (2) Methods: Voiding parameters on a self-administered questionnaire and a digital self-health monitoring system for urine excretion (s-HMSU) were compared between participants with and without obesity, defined as a body mass index ≥ 25 kg/m2 (n = 30 and 29, respectively), from a community in Okinawa, Japan. Logistic regression analysis was employed to calculate the odds ratios of abnormalities in voiding parameters for the obese group, with the non-obese group serving as a reference. (3) Results: The obese group had odds ratios of 5.17 (95% confidence interval: 1.33−20.0) for shortened hours of undisturbed sleep (<302 min) by s-HMSU and 7.65 (1.88−31.1) for nighttime urinary frequency by a questionnaire after adjusting for age and sex. In addition, the obese group had an adjusted odds ratio of 2.27 (0.76−6.78) for decreased maximum bladder capacity (<212 mL) by s-HMSU. (4) Conclusion: the results of the present study suggest that nocturia and shortened hours of undisturbed sleep are signs of obesity.

Extra-virgin olive oil (EVOO), a popular functional food and major source of fat in the Mediterranean diet, possesses a variety of healthful components, including monounsaturated fatty acids and bioactive phenolic compounds that, individually and collectively, exert beneficial effects on cardiometabolic markers of health and act as neuroprotective agents through their anti-inflammatory and antioxidant activities. The gut microbiota and health of the intestinal environment are now considered important factors in the development of obesity, metabolic disease, and even certain neurodegenerative conditions via the gut-brain axis. Recently, data are emerging which demonstrate that the health-promoting benefits of EVOO may also extend to the gut microbiota. In this review, we aimed to examine findings from recent studies regarding the impact of EVOO on gut microbiota and intestinal health and explore how modulations in composition of gut microbiota, production of microbially produced products, and activity and functioning of the mucosal immune system may lead to favorable outcomes in cardiovascular, metabolic, and cognitive health., (© The Author(s) 2021. Published by Oxford University Press on behalf of the International Life Sciences Institute.)

Purpose: To evaluate the effect of a mobile digital intervention on voiding patterns, we performed 24-h voided volume monitoring in individuals with metabolic disorders., Methods: Participants with metabolic disorders were grouped into either the intervention group (n = 17), who had access to a smartphone app (CARADA), or the non-intervention group (n = 11), who did not. Urine monitoring was conducted for 24 h using a novel digital self-health monitoring system for urine excretion (s-HMSU). Body weight, abdominal circumference, blood pressure, and biomarkers were measured., Results: Physical findings and blood test results at baseline and 6 months indicated no significant between-group differences. Night-time frequency did not change between baseline and 6 months in the intervention group but significantly worsened at 6 months in the non-intervention group, as compared to baseline (1.0 ± 0.7 vs. 1.5 ± 0.5, p < 0.05). The change in night-time frequency over 6 months did not differ between the intervention and non-intervention groups. Furthermore, the change in hours of undisturbed sleep over 6 months did not differ between the two groups. However, compared with baseline, nocturnal polyuria index tended to worsen at 6 months in the non-intervention group., Conclusion: Our study results suggest that mobile digital intervention might be useful for behavioral therapy to improve night-time frequency and urine production and that s-HMSU might be beneficial for confirming the prevention of progress in individuals with metabolic disorders, which can aid in modifying lifestyle., (© 2021. The Author(s).)

Gender differences in risks for macrovascular complications in type 2 diabetes mellitus (T2DM) have been well established. However, the impact of gender differences on diabetic retinopathy (DR) has not been fully elucidated. We therefore retrospectively explored gender-specific determinants for DR in patients with T2DM in a small sized Japanese cohort in Okinawa. There were 214 patients who were diagnosed as no DR (n = 142) and non-proliferative DR (n = 72) in 2009. During the follow-up of median 7 years, 41/142 of incidence, 26/72 of progression, and 67/214 of incidence and progression were observed, respectively. DR was assessed using the modified international clinical DR severity scales. The risks for incidence, progression as well as incidence and progression of DR were comparable between men and women, respectively. Cox proportional hazard models in multivariate analyses demonstrated that the only common determinant in both men and women for DR was the duration of T2DM. Regarding gender-specific determinants, lower level of serum albumin in men as well as higher HbA1c, lower level of estimated glomerular filtration rate, and lower level of serum uric acid in women were extracted, respectively. Although precise mechanisms for such gender-specific determinants of DR still remain unsolved, the present study would highlight a couple of factors associated with gender-specific determinants for DR in a limited numbers of Japanese cohort. Prospective observational studies on gender-specific determinants of DR in a large scale cohort are warranted to further clarify underlying mechanisms.

Purpose: Extra virgin olive oil (EVOO) and flaxseed oil (FO) contain a variety of constituents beneficial for chronic inflammation and cardio-metabolic derangement. However, little is known about the impact of EVOO and FO on dysbiosis of gut microbiota, intestinal immunity, and barrier. We, therefore, aimed to assess the impact of EVOO and FO on gut microbiota, mucosal immunity, barrier integrity, and metabolic health in mice., Methods: C57BL/6 J mice were exposed to a low-fat (LF), lard (HF), high fat-extra virgin olive oil (HF-EVOO), or high fat-flaxseed oil (HF-FO) diet for 10 weeks. Gut microbiota assessment was undertaken using 16S rRNA sequencing. Levels of mRNA for genes involved in intestinal inflammation and barrier maintenance in the intestine and bacterial infiltration in the liver were measured by qPCR., Results: HF-EVOO or HF-FO mice showed greater diversity in gut microbiota as well as a lower abundance of the Firmicutes phylum in comparison with HF mice (P < 0.05). The qPCR analyses revealed that mRNA level of FoxP3, a transcription factor, and IL-10, an inducer of regulatory T cells, was significantly elevated in the intestines of mice-fed HF-EVOO in comparison with mice-fed HF (P < 0.05). The mRNA level of the antimicrobial peptide, RegӀӀӀγ, was markedly elevated in the intestines of HF-EVOO and HF-FO compared with HF group (P < 0.05)., Conclusions: Our data suggest that the consumption of EVOO or FO can beneficially impact gut microbiota, enhance gut immunity, and assist in the preservation of metabolic health in mice.

Background : A recent study revealed that whole-body vibration (WBV) tends to decrease spasticity in stroke-related hemiplegic legs. However, acute changes in cortical activation after WBV are unclear. Objective : To examine whether WBV induces acute changes in sensorimotor cortical activation in patients with stroke-related hemiplegic legs. Methods : Eleven stroke patients (mean age 52.6 [SD 15.4] years; median time after stroke 3 [25 th and 75 th percentiles; 3 and 10.5, respectively] months) participated in a comparative before-and-after intervention trial. Six healthy adults were also studied. WBV at 30 Hz was applied for 5 min to the hamstrings, gastrocnemius, and soleus muscles. Spasticity was assessed according to the modified Ashworth scale (MAS). Active and passive range of motion (A-ROM and P -ROM, respectively) were also measured. Change in Oxy-Hb concentration in bilateral sensorimotor cortex associated with voluntary ankle dorsiflexion of the affected limb was assessed via functional near-infrared spectroscopy (fNIRS) before and immediately after WBV. Results : MAS score, A-ROM, and P -ROM improved immediately after WBV. In the patients, while there was no significant interaction between effects of region (ipsilesional and contralesional sensorimotor cortex) and the WBV intervention (before and immediately after WBV) ( F 1,10  = 0.702, p = .422), there was a significant main effect of the WBV intervention ( F 1,10  = 6.971, p = .025). In the healthy participants, there was no association with the WBV intervention or region. Conclusions : In patients with stroke-related spastic-hemiplegic legs, WBV might result not only in clinical improvement but also in acute increase in sensorimotor cortical activation.

Background: Gait analysis, such as portable gait rhythmogram (PGR), provides objective information that helps in the quantitative evaluation of human locomotion., Objective: The purpose of this study was to assess the reliability of PGR in post-stroke patients., Methods: Two raters (A and B) examined 48 post-stroke patients. To assess intra-rater reliability, rater A tested subjects on three separate occasions (Days 1, 2, and 3). To assess inter-rater reliability, raters A and B independently tested participants on the same occasion (Day 3)., Results: There was no significant systematic bias between test occasions or raters. Intraclass correlation coefficient values were 0.93-0.97 for intra-rater reliability at both the comfortable speed and maximum speed, and 0.97-0.98 (comfortable speed) and 0.97-0.99 (maximum speed) for inter-rater reliability. The standard error was 1.25-1.49 (comfortable speed) and 1.62-1.77 (maximum speed) for intra-rater investigation, and 1.04-1.32 (comfortable speed) and 0.91-1.26 (maximum speed) for inter-rater investigation. At the 90% confidence level, the minimum detectable change ranged from 2.9-4.1%, and the error of an individual's score at a given time point ranged from ±2.1-2.9%., Conclusions: Based on this excellent reliability of the PGR in post-stroke patients, it can be recommended as a simple test of gait analysis in this population.

While we previously detected anti-bornavirus antibodies via radioligand assay in psychiatric patients, we did not examine the viral pathogenicity in these individuals. Herein, we present 2 psychiatric patients who were seropositive for bornavirus and whose treatment-resistant symptoms improved after oral administration of ribavirin, a broad-spectrum antiviral agent. Cerebrospinal fluid analysis indicated that ribavirin affected the central nervous system of these patients. Ribavirin ameliorated intermittent involuntary head shaking, which is reminiscent of a symptom observed in bornavirus-infected animals. Using radioligand assays to examine the serial sera of these patients, we found a relationship between the titers of anti-bornavirus antibodies and the change in the patients' symptoms. Our findings suggest there is a relationship between bornavirus infection and human symptoms and that ribavirin may be useful in suppressing chronic bornavirus infection in some neuropsychiatric patients. However, the possibility remains that some other known or unknown virus other than bornavirus that is sensitive to ribavirin may have caused the symptoms. Additional evidence that directly indicates the causative relationship between bornavirus infection and human symptoms is needed before establishing the pathogenesis and treatment for human bornavirus infection.

Background: Several reports have focused on the effects of whole body vibration (WBV) on spasticity with differing results. Most studies used modified Ashworth scale (MAS) for qualitative measurements, but the effect was small., Objective: To investigate the effect of WBV on spasticity in hemiplegic legs of patients with stroke using F-wave parameters., Methods: Sixteen patients with stroke (mean age, 54.7 ± 13.5 years: time after stroke, 28.0 ± 26.3 months) were enrolled in a comparative before-and-after intervention trial. WBV was applied at 30 Hz (4-8 mm amplitude) for 5 min on the hamstrings, gastrocnemius, and soleus muscles in a sitting position. Spasticity was assessed according to the F-wave parameters, MAS, and active and passive range of motion (A-ROM and P-ROM, respectively). These assessments were obtained before, immediately after, and 20 min after each intervention., Results: The F-wave parameters, MAS score, and P-ROM improved significantly after the WBV and remained below the baseline level, even after 20 min; no such change was noted in the unaffected limb via the F-wave parameters. The WBV also improved volitional movement immediately after intervention, as indicated by the A-ROM., Conclusions: These results confirmed a significant reduction of motor neuron excitability until 20 min after the WBV, as indicated by F-wave parameters.

[Purpose] Gait analysis, such as portable gait rhythmogram (PGR) provides objective information that helps in the quantitative evaluation of human locomotion. The purpose of this study was to assess the reliability of PGR in post-stroke patients. [Subjects and Methods] Two raters (A and B) examined 44 post-stroke patients. To assess intra-rater reliability, rater A tested subjects on three separate occasions (Days 1, 2, and 3). To assess inter-rater reliability, raters A and B independently tested participants on the same occasion (Day 3). [Results] There was no significant systematic bias between test occasions or raters. Intraclass correlation coefficient values were 0.93-0.97 for intra-rater reliability at both the comfortable speed and maximum speed, and 0.97-0.98 (comfortable speed) and 0.87-0.99 (maximum speed) for inter-rater reliability. The standard error was 1.25-1.49 (comfortable speed) and 1.62-1.77 (maximum speed) for intra-rater investigation, and 1.04-1.32 (comfortable speed) and 0.91-1.26 (maximum speed) for inter-rater investigation. At the 90% confidence level, the minimum detectable change ranged from 2.9-4.1%, and the error of an individual's score at a given time point ranged from ±2.1-2.9%. [Conclusion] Based on this excellent reliability of the PGR in post-stroke patients, it can be recommended as a simple test of gait analysis in this population.

[Purpose] This study investigated the short-term effects of a combination therapy consisting of repetitive facilitative exercises and orthotic treatment. [Subjects and Methods] The subjects were chronic post-stroke patients (n=27; 24 males and 3 females; 59.3 ± 12.4 years old; duration after onset: 35.7 ± 28.9 months) with limited mobility and motor function. Each subject received combination therapy consisting of repetitive facilitative exercises for the hemiplegic lower limb and gait training with an ankle-foot orthosis for 4 weeks. The Fugl-Meyer assessment of the lower extremity, the Stroke Impairment Assessment Set as a measure of motor performance, the Timed Up & Go test, and the 10-m walk test as a measure of functional ambulation were evaluated before and after the combination therapy intervention. [Results] The findings of the Fugl-Meyer assessment, Stroke Impairment Assessment Set, Timed Up & Go test, and 10-m walk test significantly improved after the intervention. Moreover, the results of the 10-m walk test at a fast speed reached the minimal detectible change threshold (0.13 m/s). [Conclusion] Short-term physiotherapy combining repetitive facilitative exercises and orthotic treatment may be more effective than the conventional neurofacilitation therapy, to improve the lower-limb motor performance and functional ambulation of chronic post-stroke patients.

Objectives: To date, controlled clinical trials evaluating the efficacy of underwater exercise in improving the lower-extremity function and quality of life (QOL) in post-stroke patients have yet to be conducted. The purpose of the present study was to determine whether repeated underwater exercise enhances the therapeutic effect of conventional therapy for post-stroke patients., Design: This was a pilot controlled clinical trial., Setting: The study took place in a research facility attached to a rehabilitation hospital., Patients: This prospective trial included 120 consecutive post-stroke inpatients with hemiplegic lower limbs (Brunnstrom stage 3-6). Patients were assigned to either an experimental or a control group. Patients in the experimental group received both repeated underwater exercise and conventional rehabilitation therapy., Interventions: The underwater exercise consisted of 30-min training sessions in a pool with a water temperature of 30-31°C in which patients followed the directions and movements of trained staff. Training sessions were conducted once a day on 2 days of the week for a total of 24 times. Patients in the control group received only the conventional therapy., Outcome Measures: The 10-Minute Walk Test (10MWT), the Modified Ashworth Scale, and the 36-Item Short Form Health Survey were the outcome measures used. Lower-extremity function and QOL were assessed before and upon completion of the 12-week program., Results: Improvements in 10MWT results and spasticity parameters were greater in the experimental group than they were in the control group (p < 0.01). Significant differences between the groups were observed in magnitudes of changes of all QOL parameters (p < 0.01)., Conclusions: Combining conventional therapy with repeated underwater exercise may improve both lower-extremity function and QOL in post-stroke patients.

Objective: To investigate the impact of stroke on health status and the effects of repetitive facilitation exercises (RFEs) for convalescent patients after stroke., Methods: The study was a prospective observational study of patients enrolled in an RFE programme. Between April 2008 and March 2012, 468 patients with stroke were enrolled in an intensive, comprehensive RFE programme. Patients participated in this interdisciplinary programme for 12 weeks, for an average of 5 hours per week. Before and immediately after the programme, several measures of rehabilitation outcomes and health-related quality-of-life were evaluated., Results: At baseline, most patients (95.4%) had modified Rankin scale scores of 3-5. Their health-related quality-of-life was significantly impaired, with physical and mental component summary scores on the Short Form 36-item questionnaire (SF-36) of 30.7 and 35.8, respectively. After the RFE programme, all outcome measures improved significantly., Conclusions: The results demonstrate that convalescent patients after stroke may benefit substantially from RFE programmes in stroke rehabilitation centres, even when patients have impaired health status or high levels of healthcare utilization. Thus, an RFE programme is a simple yet highly effective means to improve rehabilitation outcomes and health-related quality-of-life, with a relatively low dropout rate.

Objectives: To investigate whether a footbath inhibits spasticity in the hemiplegic lower limbs of post-stroke patients., Design: Randomized, controlled study., Setting: Rehabilitation education and research hospital., Interventions: Twenty-two post-stroke patients were randomly allocated to control or experimental groups. After relaxing in a supine posture for 30min, the experimental group subject's legs were immersed in 41°C water below the knee joint for 15min, while the control group remained in a resting posture., Main Outcome Measures: Modified Ashworth Scale (MAS) scores of the affected triceps surae muscle and F-wave parameters (i.e., F-wave amplitude, F/M ratio, and F-wave persistence) were recorded before, immediately after, and 30min after each intervention. Physiological parameters were simultaneously monitored to determine the thermo-therapeutic mechanisms and side effects of footbath usage., Results: At the time immediately after the intervention, F-wave amplitudes decreased significantly in the experimental group, compared to the control group (p<0.01, difference: -106.8; 95% CI; -181.58 to -32.09). F-wave amplitudes decreased significantly after 30-min intervention in the experimental group, with a total reduction of 161.2μV being recorded compared to 8.8μV increase in the control group (p<0.01, difference: -170.0; 95% CI; -252.73 to -87.33). There were also significant differences between the experimental and control group for both F/M ratio and F-wave persistence, immediately after and 30min after the intervention. Further, there were significant differences between the experimental and control group for the MAS scores immediately after the intervention (p<0.05, difference: -0.72; 95% CI; -1.262 to -0.193), and 30min after the intervention (p<0.05, difference: -0.73; 95% CI; -1.162 to -0.293)., Conclusion: These findings demonstrate that the use of footbaths is an effective non-pharmacological anti-spastic treatment for use in stroke rehabilitation., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

To examine the feasibility of adapting whole body vibration (WBV) in the hemiplegic legs of post-stroke patients and to investigate the anti-spastic effects, and the improvement of motor function and walking ability. Twenty-five post-stroke patients with lower-limb spasticity were enrolled in the study. Each subject sat with hip joint angles to approximately 90° of flexion, and with knee joint angles to 0° of extension. WBV was applied at 30 Hz (4-8 mm amplitude) for 5 min on hamstrings, gastrocnemius and soleus muscles. The modified Ashworth scale was significantly decreased, active and passive range of motion (A-ROM, P-ROM) for ankle dorsiflexion and straight leg raising increased, and walking speed and cadence both improved during the 5-min intervention. Our proposed therapeutic approach could therefore be a novel neuro-rehabilitation strategy among patients with various severities., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

While examining the acute effects of electroconvulsive therapy (ECT) on regional cerebral blood flow (rCBF), we could compare the changes in rCBF between missed (not generalized) and generalized seizures using H(2)(15)O positron emission tomography in patients with depression under anesthesia. In contrast to missed seizures, rCBF was increased extensively, particularly in the centrencephalic structures in generalized seizures. These results further support the centrencephalic theory of seizure generalization., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Alzheimer disease (AD) is characterized by progressive cognitive decline caused by synaptic dysfunction and neurodegeneration in the brain, and late-onset AD (LOAD), genetically classified as a polygenetic disease, is the major form of dementia in the elderly. It has been shown that beta amyloid, deposited in the AD brain, interacts with dynamin 1 and that the dynamin 2 (DNM2) gene homologous to the dynamin 1 gene is encoded at chromosome 19p13.2 where a susceptibility locus has been detected by linkage analysis. To test the genetic association of LOAD with the DNM2 gene, we performed a case-control study of 429 patients with LOAD and 438 sex- and age-matched control subjects in a Japanese population. We found a significant association of LOAD with single nucleotide polymorphism markers of the DNM2 gene, especially in non-carriers of the apolipoprotein E-epsilon4 allele. Even though subjects with the genotype homozygous for the risk allele at rs892086 showed no mutation in exons of the DNM2 gene, expression of DNM2 mRNA in the hippocampus was decreased in the patients compared to non-demented controls. We propose that the DNM2 gene is a novel susceptibility gene for LOAD.

We scanned throughout chromosome 21 to assess genetic associations with late-onset Alzheimer disease (AD) using 374 Japanese patients and 375 population-based controls, because trisomy 21 is known to be associated with early deposition of beta-amyloid (Abeta) in the brain. Among 417 markers spanning 33 Mb, 22 markers showed associations with either the allele or the genotype frequency (P < 0.05). Logistic regression analysis with age, sex and apolipoprotein E (APOE)-epsilon4 dose supported genetic risk of 17 markers, of which eight markers were linked to the SAMSN1, PRSS7, NCAM2, RUNX1, DYRK1A and KCNJ6 genes. In logistic regression, the DYRK1A (dual-specificity tyrosine-regulated kinase 1A) gene, located in the Down syndrome critical region, showed the highest significance [OR = 2.99 (95% CI: 1.72-5.19), P = 0.001], whereas the RUNX1 gene showed a high odds ratio [OR = 23.3 (95% CI: 2.76-196.5), P = 0.038]. DYRK1A mRNA level in the hippocampus was significantly elevated in patients with AD when compared with pathological controls (P < 0.01). DYRK1A mRNA level was upregulated along with an increase in the Abeta-level in the brain of transgenic mice, overproducing Abeta at 9 months of age. In neuroblastoma cells, Abeta induced an increase in the DYRK1A transcript, which also led to tau phosphorylation at Thr212 under the overexpression of tau. Therefore, the upregulation of DYRK1A transcription results from Abeta loading, further leading to tau phosphorylation. Our result indicates that DYRK1A could be a key molecule bridging between beta-amyloid production and tau phosphorylation in AD.

We sought to clarify the effect of short-acting benzodiazepine hypnotic on the relationship of arterial blood pressure and arterial partial pressure of carbon dioxide (Paco2) to regional cerebral blood flow (rCBF) during human non-rapid-eye-movement (non-REM) sleep. Nine young normal volunteers were treated in a randomized, crossover design with triazolam or placebo and underwent positron emission tomography at night. During wakefulness and stage 2 and slow wave (stages 3 and 4) sleep, we measured mean arterial blood pressure (MAP), Paco2, and absolute CBF. With triazolam compared to placebo, MAP reduced gradually. During stage 2 sleep, Paco2 increased and whole-brain mean CBF decreased. With triazolam, relative rCBF of the left orbital basal forebrain decreased more during stage 2 than slow wave sleep, whereas absolute CBF of the occipital cortex and cerebral white matter remained constant. During triazolam-induced stage 2 sleep, absolute CBF of the cerebral white matter correlated more strongly to both MAP and Paco2 than during placebo sleep and also correlated more strongly to both MAP and Paco2 than absolute CBF of the occipital cortex. In the frontal white matter, during triazolam-induced stage 2 sleep compared to wakefulness, absolute CBF was significantly better correlated to MAP, but not to Paco2. During triazolam-induced stage 2, the cerebral white matter may receive a modulated CBF regulation having the strengthened relationship of Paco2 to CBF and, more locally, the frontal white matter may depend precariously on CBF regulation.

This study aimed to identify brain regions with the least decreased cerebral blood flow (CBF) and their relationship to physiological parameters during human non-rapid eye movement (NREM) sleep. Using [(15)O]H(2)O positron emission tomography, CBF was measured for nine normal young adults during nighttime. As NREM sleep progressed, mean arterial blood pressure and whole brain mean CBF decreased significantly; arterial partial pressure of CO(2) and, selectively, relative CBF of the cerebral white matter increased significantly. Absolute CBF remained constant in the cerebral white matter, registering 25.9 +/- 3.8 during wakefulness, 25.8 +/- 3.3 during light NREM sleep, and 26.9 +/- 3.0 (ml.100 g(-1).min(-1)) during deep NREM sleep (P = 0.592), and in the occipital cortex (P = 0.611). The regression slope of the absolute CBF significantly differed with respect to arterial partial pressure of CO(2) between the cerebral white matter (slope 0.054, R = - 0.04) and frontoparietal association cortex (slope - 0.776, R = - 0.31) (P = 0.005) or thalamus (slope - 1.933, R = - 0.47) (P = 0.004) and between the occipital cortex (slope 0.084, R = 0.06) and frontoparietal association cortex (P = 0.021) or thalamus (P < 0.001), and, with respect to mean arterial blood pressure, between the cerebral white matter (slope - 0.067, R = - 0.10) and thalamus (slope 0.637, R = 0.31) (P = 0.044). The cerebral white matter CBF keeps constant during NREM sleep as well as the occipital cortical CBF, and may be specifically regulated by both CO(2) vasoreactivity and pressure autoregulation.

Objective: The authors' goal was to identify differences in regional brain activity between physiological and benzodiazepine-induced sleep to clarify the brain structures involved in the drug's hypnotic effect., Method: Using positron emission tomography, they compared regional cerebral blood flow during non-REM sleep in nine volunteers treated with placebo or triazolam, a short-acting benzodiazepine, in a double-blind, crossover design., Results: Blood flow in the basal forebrain and amygdaloid complexes was lower during non-REM sleep when subjects were given triazolam than when they were given placebo., Conclusions: The hypnotic effect of the benzodiazepines may be mediated mainly by deactivation of the forebrain control system for wakefulness and also by the anxiolytic effect induced by deactivation of the emotional center.

There is a hypothesis that autoimmune abnormalities in neurotransmitter receptors might cause some psychiatric disorders. Using a sensitive radioligand assay, we detected serum autoantibodies to recombinant human muscarinic cholinergic receptor 1 (CHRM1, 34.4%), mu-opioid receptor (OPRM1, 13.1%), 5-hydroxytryptamine receptor 1A (HTR1A, 7.4%), and dopamine receptor D2 (DRD2, 4.9%) in 122 psychiatric patients. Positive antibodies to CHRM1 were found in 34.1%, 34.9%, 33.3%, and 9.1% of patients with schizophrenic disorders (n=44), mood disorders (n=63), other psychiatric disorders (n=15) and autoimmune diseases (n=33), respectively. All three patients with neuroleptic maliganant syndrome had high activities of autoantibodies to CHRM1, OPRM1, and/or HTR1A. Our data suggest that autoimmunity to neurotransmitter receptors might be associated with the induction of psychiatric symptoms and have some relation to neuroleptic malignant syndrome.

Background: The precise neural mechanisms of propofol anesthesia in humans are still unknown. The authors examined the acute effects of propofol on regional cerebral blood flow (rCBF) using positron emission tomography in patients with severe depression., Methods: In six severely depressed patients (mean age, 55.0 yr) scheduled for electroconvulsive therapy, anesthetic levels were monitored by electroencephalography, and rCBF was serially quantified in the awake, sedated, and anesthetized states. The authors used high-resolution positron emission tomography with 15O-labeled water and statistical parametric mapping 99 for imaging and analysis of the data., Results: Global cerebral blood flow showed sharp decreases from the awake level during the administration of propofol, decreasing 26.8% in the sedated state and 54.4% in the anesthetized state. Moreover, a dose effect was seen in both parietal cortices and the left lateral prefrontal region with larger regions of relative decrease in rCBF at higher propofol doses. At the higher dose, the values of rCBF in the pulvinar nucleus of the thalamus, the pontine tegmentum, and the cerebellar cortex were also affected. Meanwhile, there were few changes of relative rCBF in the basal frontal lobes during both sedated and anesthetized states., Conclusions: As in earlier studies using normal subjects, pronounced suppression in rCBF in the brain stem reticular formation, the thalamus, and the parietal association cortex occurred even in severely depressed patients. However, previously reported decreases in rCBF in the basal frontal lobe were absent in depressed patients.

Neuroimaging studies of autism have shown abnormalities in the limbic system and cerebellar circuits and additional sites. These findings are not, however, specific or consistent enough to build up a coherent theory of the origin and nature of the brain abnormality in autistic patients. Twenty-three children with infantile autism and 26 non-autistic controls matched for IQ and age were examined using brain-perfusion single photon emission computed tomography with technetium-99m ethyl cysteinate dimer. In autistic subjects, we assessed the relationship between regional cerebral blood flow (rCBF) and symptom profiles. Images were anatomically normalized, and voxel-by-voxel analyses were performed. Decreases in rCBF in autistic patients compared with the control group were identified in the bilateral insula, superior temporal gyri and left prefrontal cortices. Analysis of the correlations between syndrome scores and rCBF revealed that each syndrome was associated with a specific pattern of perfusion in the limbic system and the medial prefrontal cortex. The results confirmed the associations of (i) impairments in communication and social interaction that are thought to be related to deficits in the theory of mind (ToM) with altered perfusion in the medial prefrontal cortex and anterior cingulate gyrus, and (ii) the obsessive desire for sameness with altered perfusion in the right medial temporal lobe. The perfusion abnormalities seem to be related to the cognitive dysfunction observed in autism, such as deficits in ToM, abnormal responses to sensory stimuli, and the obsessive desire for sameness. The perfusion patterns suggest possible locations of abnormalities of brain function underlying abnormal behaviour patterns in autistic individuals.

To clarify the neural correlates and brain activity during the progression of human non-rapid eye movement (NREM) sleep, we examined the absolute regional cerebral blood flow (rCBF) during light and deep NREM sleep and during wakefulness in normal humans using positron emission tomography with H(2)(15)O. Relative changes in rCBF during light and deep NREM sleep in comparison to the rCBF during wakefulness were also analyzed. During light NREM sleep, the rCBF in the midbrain, in contrast to that in the pons and thalamic nuclei, did not decrease when compared to that during wakefulness, whereas rCBF decreased in the left medial frontal gyrus, left inferior frontal gyrus, and left inferior parietal gyrus of the neocortex. During deep NREM sleep, the rCBF in the midbrain tegmentum decreased, and there was a marked and bilateral decrease in the rCBF in all neocortical regions except for the perirolandic areas and the occipital lobe. There have been three groups of brain structures, each representing one type of deactivation during the progression of NREM sleep. The activity of the midbrain reticular formation is maintained during light NREM sleep and therefore represents a key distinguishing characteristic between light and deep NREM sleep. Selective deactivation of heteromodal association cortices, including those related to language, occurs with increasingly deep NREM sleep, which supports the recent theory that sleep is not a global, but it is a local process of the brain.