Daily Dietary Supplementation with Steamed Soybean Improves Muscle Volume and Strength in Healthy People Lacking Exercise.

Various dietary protein supplements are used by the elderly and bedridden to maintain their skeletal muscle mass and functions. High-quality proteins act as an anabolic driver and help to improve muscle strength and performance. Previously, we reported that soy protein significantly attenuates denervation-induced loss of muscle mass and myofiber cross sectional area in mice with inhibition of ubiquitination and degradation of IRS-1 in tibialis anterior muscle. It also increased muscle volume and strength in bedridden patients. In the present study, we investigated the effects of dietary soybean supplementation on muscle functions in taxi drivers lacking vigorous physical exercise. We conducted a case-control study on 25 healthy, male taxi drivers between the ages of 36 and 71 y performing minimal physical exercise. They were divided into two dietary groups: the soybean diet group (n=13) who ate daily meals (dinner) supplemented with 50 g of steamed soybean for 30 d and the control diet group (n=12) who received no soybean supplement. Next, we measured the muscle cross-sectional area (CSA) and muscle strength and function in both the groups before and after 30 d of soybean intake. The body weights of both diet groups did not differ significantly over time. However, after 30 d of soybean supplementation, the soybean-fed group developed significantly higher muscle CSA and grip strength compared to the control groups. In conclusion, dietary soybean supplementation improved muscle function in taxi drivers who lacked exercise.

MR spectroscopy and imaging-derived measurements in the supplementary motor area for biomarkers of amyotrophic lateral sclerosis.

The diagnosis of amyotrophic lateral sclerosis (ALS) requires both upper and lower motor neuron signs. However, quite a few patients with ALS lack the upper motor neuron sign during the disease. This study sought to investigate whether metabolites, including glutamate (Glu), N-acetyl aspartate (NAA), and gamma aminobutyric acid (GABA), in the supplementary motor area (SMA) measured by magnetic resonance spectroscopy (MRS), could be a surrogate biomarker for ALS. Twenty-five patients with ALS and 12 controls underwent 3.0-T MR scanning, which measured Glu, NAA, and GABA. Finally, receiver operating characteristic (ROC) curves were created and the area under curve (AUC) was calculated to assess the diagnostic power. Logistic regression analysis revealed the usefulness of both Glu and NAA for the differentiation of ALS from controls (Glu, P = 0.009; NAA, P = 0.033). The ratio of Glu to NAA or GABA was significantly increased in patients with ALS (Glu/NAA, P = 0.027; Glu/GABA, P = 0.003). Both the AUCs were more than 0.7, with high specificity but low sensitivity. The present findings might indicate that both the Glu/NAA and the Glu/GABA ratios in the SMA could be potential biomarkers for the diagnosis of ALS.

MM2-type sporadic Creutzfeldt-Jakob disease: new diagnostic criteria for MM2-cortical type.

OBJECTIVE: To clinically diagnose MM2-cortical (MM2C) and MM2-thalamic (MM2T)-type sporadic Creutzfeldt-Jakob disease (sCJD) at early stage with high sensitivity and specificity. METHODS: We reviewed the results of Creutzfeldt-Jakob disease Surveillance Study in Japan between April 1999 and September 2019, which included 254 patients with pathologically confirmed prion diseases, including 9 with MM2C-type sCJD (MM2C-sCJD) and 10 with MM2T-type sCJD (MM2T-sCJD), and 607 with non-prion diseases. RESULTS: According to the conventional criteria of sCJD, 4 of 9 patients with MM2C- and 7 of 10 patients with MM2T-sCJD could not be diagnosed with probable sCJD until their death. Compared with other types of sCJD, patients with MM2C-sCJD showed slower progression of the disease and cortical distribution of hyperintensity lesions on diffusion-weighted images of brain MRI. Patients with MM2T-sCJD also showed relatively slow progression and negative results for most of currently established investigations for diagnosis of sCJD. To clinically diagnose MM2C-sCJD, we propose the new criteria; diagnostic sensitivity and specificity to distinguish 'probable' MM2C-sCJD from other subtypes of sCJD, genetic or acquired prion diseases and non-prion disease controls were 77.8% and 98.5%, respectively. As for MM2T-sCJD, clinical and laboratory features are not characterised enough to develop its diagnostic criteria. CONCLUSIONS: MM2C-sCJD can be diagnosed at earlier stage using the new criteria with high sensitivity and specificity, although it is still difficult to diagnose MM2T-sCJD clinically.

Development of Quality Indicators of Stroke Centers and Feasibility of Their Measurement Using a Nationwide Insurance Claims Database in Japan　­ J-ASPECT Study ­

BACKGROUND: We aimed to develop quality indicators (QIs) related to primary and comprehensive stroke care and examine the feasibility of their measurement using the existing Diagnosis Procedure Combination (DPC) database. METHODS AND RESULTS: We conducted a systematic review of domestic and international studies using the modified Delphi method. Feasibility of measuring the QI adherence rates was examined using a DPC-based nationwide stroke database (396,350 patients admitted during 2013-2015 to 558 hospitals participating in the J-ASPECT study). Associations between adherence rates of these QIs and hospital characteristics were analyzed using hierarchical logistic regression analysis. We developed 17 and 12 measures as QIs for primary and comprehensive stroke care, respectively. We found that measurement of the adherence rates of the developed QIs using the existing DPC database was feasible for the 6 QIs (primary stroke care: early and discharge antithrombotic drugs, mean 54.6% and 58.7%; discharge anticoagulation for atrial fibrillation, 64.4%; discharge antihypertensive agents, 51.7%; comprehensive stroke care: fasudil hydrochloride or ozagrel sodium for vasospasm prevention, 86.9%; death complications of diagnostic neuroangiography, 0.4%). We found wide inter-hospital variation in QI adherence rates based on hospital characteristics. CONCLUSIONS: We developed QIs for primary and comprehensive stroke care. The DPC database may allow efficient data collection at low cost and decreased burden to evaluate the developed QIs.

Carcinosarcoma of the uterus: MRI findings including diffusion-weighted imaging and MR spectroscopy.

BACKGROUND: Recently carcinosarcoma has become regarded as a subset of endometrial carcinoma. Because the clinical course of carcinosarcoma is aggressive with poor prognosis, it should be differentiated from endometrial carcinomas for the appropriate surgical management and adjuvant therapy. PURPOSE: To clarify the magnetic resonance imaging (MRI) characteristics of uterine carcinosarcoma including diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) measurement and MR spectroscopy (MRS) with quantitative metabolite evaluation. MATERIAL AND METHODS: MRI findings of 12 pathologically diagnosed uterine carcinosarcomas obtained on 3T MRI were retrospectively evaluated. The mean and minimum ADCs, and the lipid and choline concentration levels were compared with those of pathologically diagnosed 38 endometrial carcinomas. RESULTS: The mean and minimum ADCs in carcinosarcomas and endometrial carcinomas were not significantly different. The mean ADC of carcinosarcomas was significantly higher than that of higher grade (G2 and G3) endometrial carcinomas. The choline concentration in carcinosarcomas was significantly lower than that in endometrial carcinomas. High lipid peak was observed in 91% of carcinosarcomas and in 24% of endometrial carcinomas. CONCLUSION: Large, exophytic heterogeneous endometrial mass containing strongly enhanced areas, which may exhibit "tumor delivery", is a suggestive of carcinosarcoma. Relatively high mean ADC and low choline concentration considering its highly malignant nature due to intra-tumoral heterogeneity with necrosis and epithelial cystic components, and the presence of necrosis-associated high lipid peak may be compatible with carcinosarcoma.

The ratio of N-acetyl aspartate to glutamate correlates with disease duration of amyotrophic lateral sclerosis.

Glutamate (Glu)-induced excitotoxicity has been implicated in the neuronal loss of amyotrophic lateral sclerosis. To test the hypothesis that Glu in the primary motor cortex contributes to disease severity and/or duration, the Glu level was investigated using MR spectroscopy. Seventeen patients with amyotrophic lateral sclerosis were diagnosed according to the El Escorial criteria for suspected, possible, probable or definite amyotrophic lateral sclerosis, and enrolled in this cross-sectional study. We measured metabolite concentrations, including N-acetyl aspartate (NAA), creatine, choline, inositol, Glu and glutamine, and performed partial correlation between each metabolite concentration or NAA/Glu ratio and disease severity or duration using age as a covariate. Considering our hypothesis that Glu is associated with neuronal cell death in amyotrophic lateral sclerosis, we investigated the ratio of NAA to Glu, and found a significant correlation between NAA/Glu and disease duration (r=-0.574, p=0.02). The "suspected" amyotrophic lateral sclerosis patients showed the same tendency as possible, probable and definite amyotrophic lateral sclerosis patients in regard to correlation of NAA/Glu ratio with disease duration. The other metabolites showed no significant correlation. Our findings suggested that glutamatergic neurons are less vulnerable compared to other neurons and this may be because inhibitory receptors are mainly located presynaptically, which supports the notion of Glu-induced excitotoxicity.

Non-invasive evaluation of the GABAergic/glutamatergic system in autistic patients observed by MEGA-editing proton MR spectroscopy using a clinical 3 tesla instrument.

Amino acids related to neurotransmitters and the GABAergic/glutamatergic system were measured using a 3 T-MRI instrument in 12 patients with autism and 10 normal controls. All measurements were performed in the frontal lobe (FL) and lenticular nuclei (LN) using a conventional sequence for n-acetyl aspartate (NAA) and glutamate (Glu), and the MEGA-editing method for GABA. The GABA level and [GABA]/[NAA] ratio were significantly lower (p < 0.01) in the FL, but not the LN, in patients with autism compared to normal controls. The [GABA]/[Glu] ratio in the FL was also significantly lower (p < 0.05) in the patients than in the normal controls, thus suggesting a possible abnormality in the regulation between GABA and Glu.

Function of the frontal lobe in autistic individuals: a proton magnetic resonance spectroscopic study.

PURPOSE: In this investigation, we studied differences in chemical metabolites in certain brain regions between autistic patients and normal control subjects. METHODS: Proton magnetic resonance spectroscopy ((1)H-MRS) was used to evaluate functional activity in these regions. Specific regions studied were right and left dorsolateral prefrontal cortex(DLPFC) and the anterior cingulated cortex(ACC). RESULTS: In the ACC, the N-acetylaspartate(NAA)/creatine/phosphocreatine(Cr) ratio in autistic patients (n=31) was significantly lower than that in control subjects (n=28). The decrease in the NAA/Cr ratio for the ACC was much greater in the group with worst social ability. NAA/Cr for the left DLPFC and social ability of autistic patients also correlated well. Furthermore, NAA/Cr for the left DLPFC in the group with intelligence quotient (IQ) below 50 was significantly less than in controls. NAA/Cr for the right DLPFC in autistic patients was not decreased compared to controls, and did not correlate with IQ or social ability. CONCLUSIONS: These findings suggest neuronal dysfunction in the ACC and left DLPFC in autism, and also a relationship between social disability and metabolic dysfunction in these regions. Dysfunction in the ACC and the left DLPFC may contribute to the pathogenesis of autism.

Can Kampo therapy prolong the life of cancer patients?

Our policy regarding the performance of radiotherapy to squamous cell carcinoma of the uterine cervix has not changed since 1969. We have already reported the treatment results which were as good as those from other institutions. Since 1978, Kampo therapy was first introduced in the treatment of cancer patients in dealing with problems such as the side effects of radiotherapy and chemotherapy and various types of general malaise. We analyzed our treatment results in order to re-evaluate the chemo-radiotherapy in combination with Kampo. Survival rates for 5, 10 and 15 years, respectively, were 90.9%, 71.6% and 71.6% for Stage IB, 78.9%, 61.8% and 41.8% for Stage II, 62.3%, 49.1% and 41.2% for Stage III and 53.1%, 36.5% and 16.7% for Stage IV. The Kampo significantly extended the survival of patients with uterine cervical cancer. We intend to perform further research with more patients to explore how this therapy contributes to the prolonging of patients survival.

cDNA cloning and expression analysis of thyroid hormone receptor in the coho salmon Oncorhynchus kisutch during smoltification.

Two types of cDNA clones encoding thyroid hormone receptor (TR) genes, TRalpha and TRbeta, were isolated from the coho salmon Oncorhynchus kisutch. The two genes each consists of multiple isoforms, derived from different loci or by an alternative splicing. RT-PCR revealed a broad localization of the TRalpha and TRbeta transcripts that both expressed in brain, gill, liver, muscle, kidney, ovary, skin and eyeball. During the early stages of the smoltification period, the mRNA level of the TR transcripts showed a large individual variability at the maximum of 10-fold. In contrast, as the plasma thyroid hormone level elevated at the middle of the period, the variation in the expression level became much smaller at 2-fold. After the completion of the smoltification, the mRNA accumulation level of the TR genes rapidly decreased. These findings suggest that the dynamics of the receptor (TR) should be taken account in addition to the availability of the hormone ligands (T3 and T4) to understand the underlying mechanisms of the smoltification causing numerous physiological and morphological changes in salmonids.

[Case of methotrexate encephalopathy: findings on diffusion tensor image and correlation with clinical outcome].

Methotrexate (MTX) is a major cause of treatment-related acute neurotoxicity. We report on clinical and imaging findings of reversibly restricted diffusion in a patient with transient encephalopathy after high dose MTX therapy for osteosarcoma. During the chemotherapy, a 19-year-old man was introduced for the evaluation of consciousness disturbance. Neurological examination revealed confusion, inability of speak at the onset On next day, there were still difficulties in swallowing and phonation, and furthermore deep tendon reflexes were hyperactive in bilateral lower limbs with positive Babinski responses bilaterally. By the 6th day, findings at neurological examination were completely normal. Initial imaging on presentation was performed using MRI. Diffusion weighted MRI clearly indicated areas of restricted diffusion within both centrum semiovale. These abnormalities were confirmed by the diffusion tensor (DT) technique (ADC and FA map). The follow-up MRI examinations using same protocol showed resolution of the ADC and FA abnormalities but increasing T2-signal changes. Neither contrast enhancement nor atrophy was encountered. Early detection of MTX white matter injury by DT image has the potential to alert the oncologist and neurologist to this event and provide a technique by which treatment of neurotoxicity can be monitored.

Proton magnetic resonance spectroscopy reveals an abnormality in the anterior cingulate of a subgroup of obsessive-compulsive disorder patients.

Numerous neuroimaging studies have suggested that obsessive-compulsive disorder (OCD) patients had a neurobiological abnormality in the frontal-subcortical circuits. On the other hand, there are distinct differences in the responses to pharmacological treatment among OCD patients. In the present study, we measured the concentration of N-acetyl aspartate (NAA), a putative marker of neuronal viability, with proton magnetic resonance spectroscopy (MRS) in OCD patients with different pharmacological responses. Participants comprised 20 patients and 26 healthy control subjects. OCD patients were divided into three groups according to the pharmacological response; responders to a selective serotonin reuptake inhibitor (SSRI) (group A: n=7), responders to SSRI with an atypical antipsychotic (group B: n=8) and non-responders to either SSRI or SSRI with an atypical antipsychotic (group C: n=5). Short echo proton MRS was used to measure NAA concentrations in the anterior cingulate, the left basal ganglia and the left prefrontal lobe of subjects. A significantly lower NAA concentration was observed only in group B compared with control subjects in the anterior cingulate. Our results suggest that a subgroup of OCD patients who respond to an SSRI with an atypical antipsychotic have distinct biological abnormalities in the anterior cingulate.

Brain abscess and glioblastoma identified by combined proton magnetic resonance spectroscopy and diffusion-weighted magnetic resonance imaging--two case reports.

The differential diagnosis between brain abscesses and necrotic tumors such as glioblastomas is sometimes difficult to establish by conventional computed tomography and magnetic resonance imaging. Combined proton magnetic resonance spectroscopy (1H-MRS) and diffusion-weighted magnetic resonance imaging (DWI) were used to establish the preoperative diagnosis of brain abscess and glioblastoma. DWI visualized the brain abscess as a homogeneous hyperintense lesion and 1H-MRS revealed the presence of acetate, lactate, and amino acids and the absence of the normal brain components. DWI sometimes shows glioblastoma as a hyperintense lesion, but 1H-MRS reveals markedly increased lactate and decreased N-acetyl-aspartate. Combined DWI and 1H-MRS findings can distinguish brain abscess and glioblastoma.