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Background: Identifying postmenopausal women with a high risk of having osteoporosis and fractures is a current challenge. This study aimed to assess the diagnostic performance of biochemical tests in identifying secondary osteoporosis and the fracture risk assessment tool (FRAX) in identifying fracture risk.Methods: Data from biochemical tests and bone densitometry of postmenopausal women were analyzed. Additionally, the FRAX result was obtained and the patients were classified according to the National Osteoporosis Guideline Group (NOGG).Results: A total of 646 women were evaluated, of whom 201 (31.1%) had osteoporosis or a previous frailty fracture. These women had statistically different parathyroid hormone (PTH) and alkaline phosphatase serum levels (pp=0.02, respectively) than those without osteoporosis or fracture. However, those at high risk had a higher prevalence of hypovitaminosis D (46% vs. 36%) and hypocalciuria (17% vs. 9%). The FRAX showed an area under the curve of 0.757 (pp

Introduction Posterior Circulation (PC) stroke represents one-fifth of all ischemic strokes, with peculiar physiological characteristics. Hemorrhagic Transformation (HT) is a dreaded complication among stroke patients. Many predictive scores of this complication have been proposed, but none is designed specifically for PC stroke patients – therefore, patients who are not eligible to reperfusion therapies (RT) represent about 80% of hospitalized cases. We propose a scoring system to assess the HT risk in PC stroke patients not submitted to RT. Methods We retrospectively evaluated data of patients diagnosed with PC stroke not treated with RT from 5 Comprehensive Stroke Centers (four in Brazil, 1 in the US) from 2015 to 2018. All patients underwent CT scan or MRI at admission and a follow-up neuroimaging within seven days. Independent variables identified in a logistic regression analysis were used to produce a predictive grading score.Results We included 952 patients in the final analysis. The overall incidence of HT was 8.7%. Male gender (1 point), NIH Stroke Scale at admission ≥ 5 points (1), blood glucose at admission ≥ 160mg/dL (1), and cardioembolism (2) were independently associated with HT. The AUC of the grading score (0 to 5 points) was 0.713 (95% CI 0.65-0.78). Subjects with a score ≥ 3 points had an OR of 4.8 (95% CI 2.9-7.9, pConclusions Our score is accurate in identifying patients at higher risk of HT. This score may be useful for evaluating secondary prevention and stratifying patients in the context of even clinical trials.

Aims/Introduction An efficient screening strategy for identification of cognitive dysfunction remains a clinical issue in the management of elderly adults with diabetes. A magnetic resonance imaging voxel‐based specific regional analysis system for Alzheimer’s disease (VSRAD) has been developed as an automated brain morphometry system that includes the hippocampus. We carried out a multicenter retrospective study to evaluate the utility of VSRAD for screening cognitive dysfunction in diabetes outpatient clinics. Materials and Methods We enrolled patients with diabetes aged >65 years who underwent brain magnetic resonance imaging scans for the purpose of a medical checkup between November 2018 and May 2019. Patients who were already suspected or diagnosed with mild cognitive impairment and/or dementia as well as those with a history of cerebrovascular disease were excluded. Results A total of 67 patients were enrolled. Five patients were diagnosed with mild cognitive impairment or dementia (clinical cognitive dysfunction). Patients with clinical cognitive dysfunction showed a significantly higher z‐score in VSRAD analysis (2.57 ± 0.47 vs 1.15 ± 0.55, P, We evaluated the utility of the voxel‐based specific regional analysis system of Alzheimer's disease, an automated brain morphometry system that includes the hippocampus, for screening unrecognized cognitive dysfunction in elderly patients with diabetes. This is the first report to assess the association between hippocampal atrophy and cognitive dysfunction by an automated voxel‐based morphometry system in clinical diabetes practice. The results suggest that the voxel‐based specific regional analysis system of Alzheimer's disease can be useful for early identification of cognitive dysfunction in the elderly with diabetes.

Immune checkpoint inhibitors (ICIs) frequently cause immune-related adverse events (irAEs) that often involve endocrine organs. Pembrolizumab and atezolizumab are currently administered in combination with chemotherapy for several malignancies. Although transient thyrotoxicosis within 6 weeks after the first ICI dose is the typical course of thyroid irAEs with ICI monotherapy, we encountered a unique course of a thyroid irAE in a patient who received combination therapy consisting of pembrolizumab plus pemetrexed and carboplatin. Delayed onset of thyrotoxicosis occurred at 22 weeks after the first dose of pembrolizumab. To understand more about this curious event, we conducted a retrospective cohort study of the following groups: pembrolizumab monotherapy (Pem-mono), pembrolizumab plus chemotherapy (Pem-combi), atezolizumab monotherapy (Atezo-mono), and atezolizumab plus chemotherapy (Atezo-combi). There were no differences in the incidence of overt thyroid irAEs: Pem-mono, 12 of 151 patients (7.9%) versus Pem-combi, 4 of 56 patients (7.1%) (p = 0.85) and Atezo-mono, 5 of 27 patients (18.5%) versus Atezo-combi, 5 of 57 patients (8.8%) (p = 0.20). Through detailed analyses of patients with thyrotoxicosis, we found some patients with delayed-onset thyroid irAE, defined as development at 16 weeks or more after the first ICI dose. Delayed-onset thyroid irAEs were only observed in the combination therapy groups: Pem-combi or Atezo-combi, 3 of 8 patients versus Pem-mono or Atezo-mono, 0 of 10 patients. Our observation that thyroid irAE development can be delayed with ICIs when used in combination with chemotherapy suggests longer monitoring of thyroid function is needed to avoid missing irAEs.

There is limited information available about the physiological content of glyceraldehyde, a precursor of toxic advanced glycation end products. The conventional derivatization method for aldoses using 1-phenyl-3-methyl-5-pyrazolone did not allow reproducible quantification of glyceraldehyde due to the instability of glyceraldehyde compared to other aldoses. We optimized the derivatization condition to achieve high and reproducible recovery of derivatives for liquid chromatography tandem mass spectrometry quantification. Based on the stability of glyceraldehyde during sample preparation and high recovery of spiked standard, the present method provides reproducible quantification of glyceraldehyde in the body. The glyceraldehyde contents in fasting conditions in the rodent liver (mice: 50.0 ± 3.9 nmol/g; rats: 35.5 ± 4.9 nmol/g) were higher than those in plasma (9.4 ± 1.7 and 7.2 ± 1.2 nmol/mL). The liver glyceraldehyde levels significantly increased after food consumption (p < 0.05) but remained constant in the plasma. High fat diet feeding significantly increased plasma glyceraldehyde levels in mice (p < 0.005). In healthy human volunteers, the plasma glyceraldehyde levels remained unchanged after the consumption of steamed rice. In patients with type 2 diabetes, the plasma glyceraldehyde level was positively correlated with the plasma glucose level (r = 0.84; p < 0.0001).

Sarcopenia is an age-related disease with an increased risk of mortality. It is emerging that low serum 25-hydroxyvitamin D [25(OH)D] affects the sarcopenic state in general, but in rheumatoid arthritis (RA), these associations are not understood although the prevalence of vitamin D insufficiency is high in RA. We conducted a cross-sectional study of older female outpatients from our cohort (KURAMA) database. We measured skeletal muscle mass, handgrip strength, and gait-speed to diagnose severe sarcopenia. The serum 25(OH)D concentration was measured using electrochemiluminescence immunoassay. A total of 156 female patients with RA (sarcopenia:44.9%, severe sarcopenia: 29.5%, and without sarcopenia: 25.6%) were enrolled. Classification of vitamin D status at a cutoff point of median 25(OH)D concentration revealed that low 25(OH)D status was associated with a high prevalence of severe sarcopenia and with low measured values of muscle mass, handgrip, and gait speed. Furthermore, multivariable logistic regression analysis identified that low 25(OH)D status was associated with a high prevalence of severe sarcopenia (OR 6.00; 95% CI 1.99–18.08).The same association was observed when the cut-off value was set at 20 ng/ml. In components of sarcopenia, both low physical performance and muscle mass were associated with low 25(OH)D status. In conclusion, vitamin D status was inversely associated with severe sarcopenia, low physical performance, and low skeletal muscle mass. Modification of vitamin D status including vitamin D supplementation should be investigated as a therapeutic strategy for sarcopenic patients with RA.

Objetivo: Analisar as representações sociais da equipe de enfermagem sobre o conhecimento técnico cientí­fico dos protocolos para atendimento de paciente politraumatizados. Método: pesquisa de campo e qualitativa com dados coletados por entrevistas semiestruturadas áudio-gravadas no mês de dezembro de 2019. Resultados: A análise dos dados obtidos permitiram construir seis discursos a partir das expressões-chave, com suas respectivas ideias centrais. Considerações Finais: A equipe de enfermagem apesar de realizar algumas das etapas do protocolo preconizado pela instituição, de forma assistemática, têm dificuldades em reconhecer e o significado de protocolos.

In a patient with variant angina of the proximal left anterior descending coronary artery, myocardial ischemia changed the QRS-ST-T configurations without J-waves into those resembling “lambda” waves at maximal ST-segment elevation, and couplets or triplets of supraventricular extrasystole (SVE) changed the ischemia-induced “lambda” waves into QRS-ST-T configurations resembling a “tombstone” morphology or “monophasic QRS-ST complex.” At the resolution phase of coronary spasm, the QRS-ST-T configurations returned to those without J-waves and were changed by SVE into “lambda” waves. Interestingly, neither ischemia- nor SVE-induced “lambda” waves or SVE-induced “tombstone” morphology or “monophasic QRS-ST complex” were complicated by ventricular tachyarrhythmia.

We characterised the bioavailability, safety, and tolerability of brivaracetam 100 mg intravenous bolus and 15-min infusion versus oral reference tablet in 24 healthy Japanese participants.In this randomised, open-label, three-period crossover study, participants received three 100 mg single doses of brivaracetam, intravenous bolus, infusion, and oral tablets. Maximum plasma concentration (C

A 65-year-old man was presented with infective endocarditis of mitral valve. Echocardiography revealed severe mitral regurgitation and moderate aortic regurgitation. The aortic regurgitant jet directed toward the mitral anterior leaflet, so thickening and perforation of the anterior leaflet of the mitral valve were observed. In addition, Staphylococcus epidermidis was detected in blood culture. After infection control, aortic valve replacement and mitral valve repair was performed. A 17 mm diam-eter perforation of the anterior mitral leaflet were closed directly and longitudinally with 5-0 prolene polypropylene suture and mitral valve regurgitation was controlled. Primary closure was simple and effective for anterior mitral leaflet perforation.

Sodium glucose co-transporter 2 (SGLT2) inhibitors are anti-diabetic drugs for type 2 diabetes that lower blood glucose levels and body weight. It is of special interest that SGLT2 inhibitors also improve liver metabolism and fatty liver. Liver is an important organ in regulation of energy metabolism, but the metabolic action of SGLT inhibitors in liver remains unclear.We investigated the factors associated with the beneficial effects of dapagliflozin, a SGLT2 inhibitor, in the liver after confirming its glucose-lowering and weight loss effects using an obesity and diabetes mouse model. We also performed clinical study of patients with type 2 diabetes to explore candidate biomarkers that reflect the beneficial action of dapagliflozin in the liver.In animal study, dapagliflozin induced autophagy in the liver (LC3-II to LC3-I expression ratio: P 0·05 vs. control), and valine and leucine levels were increased in plasma (P 0·01 vs. control) as well as in liver (P 0·05 vs. control). Thus, increased plasma valine and leucine levels are potential biomarkers for improved liver metabolism. Clinical study found that valine and leucine levels were markedly higher in patients treated with dapagliflozin (valine: P 0·05 vs. control, leucine: P 0·01 vs. control) than those not treated after one week intervention.Dapagliflozin improves liver metabolism via hepatic autophagy, and plasma valine and leucine levels may reflect its metabolic effect.AstraZeneca K.K., Ono Pharmaceutical Co., Ltd., Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan Society for the Promotion of Science (JSPS), Japan Agency for Medical Research and Development (AMED), Novo Nordisk Pharma Ltd., and Japan Foundation for Applied Enzymology, and MSD Life Science Foundation International.

Sarcopenia is an age-related disease with an increased risk of mortality. It is emerging that low serum vitamin D (25(OH)D) affects the sarcopenic state in general, but in rheumatoid arthritis (RA), these associations are not understood although the prevalence of vitamin D insufficiency is high in RA. We conducted a cross-sectional study of older female outpatients from our cohort (KURAMA) database. We measured skeletal muscle mass, handgrip strength, and gait-speed to diagnose severe sarcopenia. The serum 25(OH)D concentration was measured using electrochemiluminescence immunoassay. A total of 156 Patients (sarcopenia:44.9%, severe sarcopenia: 29.5%, and without sarcopenia: 25.6%) were enrolled. Classification of vitamin D status at a cutoff point of median 25(OH)D concentration revealed that low 25(OH)D status was associated with a high prevalence of severe sarcopenia and with low measured values of muscle mass, handgrip, and gait-speed. Furthermore, multiple regression analysis identified that low 25(OH)D status was associated with a high prevalence of severe sarcopenia (OR 6.00; 95% CI 1.99–18.08). In components of sarcopenia, both low physical performance and muscle mass were associated with low 25(OH) status. In conclusion, vitamin D levels are associated with severe sarcopenia and its components, and modification of vitamin D status including vitamin D supplementation may play a role in improving sarcopenia in RA.

Aims/Introduction Recent evidence shows that cultural context can influence the management of diabetes mellitus. The aim of the present study was to examine the relationship between interdependence, which is valued in the Eastern cultural context, and diabetes self‐care behavior in Japanese patients with type 2 diabetes mellitus. Material and Methods We carried out a cross‐sectional survey of 161 Japanese adults with type 2 diabetes mellitus using well‐established questionnaires. The association of an interdependent tendency with diabetes self‐care activities was analyzed using multiple regression analysis. Results Diabetes self‐care activities had a negative correlation with interdependent tendency (r = −0.16, P = 0.047), and they had positive correlations with age (r = 0.42, P

Objective Although mental disorder is one of the most common comorbidities of rheumatoid arthritis (RA) and is known as a critical influence on RA remission rates, there is little knowledge regarding a possible therapeutic strategy for depression or anxiety in a RA population. Most recently, clinical evidence of dietary improvement for depression has emerged in a general population, but the relationship between dietary habits and mental disorder has not been investigated in RA. The purpose of this study is to elucidate clinical associations between mental disorder (depression/anxiety), dietary habits and disease activity/physical function in patients with RA. Methods A cross-sectional study was performed with 267 female outpatients from the KURAMA database. Using the Hospital Anxiety and Depression Scale (HADS), we classified the participants into three groups by depression state, and their characteristics were compared. Using the 20-items on the self-reported food frequency questionnaire, we investigated the relationship between dietary habits and depression or anxiety, adopting a trend test and a multivariate standardized linear regression analysis for the HADS score of depression or that of anxiety as a dependent variable. Results According to the classified stage of depression, current disease activity (DAS28-CRP: 28-Joint RA Disease Activity Score-C-reactive protein) and the health assessment questionnaire disability Index (HAQ-DI) were significantly increased. Trend analyses revealed that the depression score was inversely associated with the consumption of three food (fish, vegetables and fruit) out of twenty as was the anxiety score with only fish intake. Furthermore, multiple linear regression analysis revealed that the depression score was negatively associated with frequent fish intake (≥ 3 times per week) (Estimate -0.53, p = 0.033), HAQ-DI score within normal range (Estimate -0.88, p ≤ 0.001) and MTX use (Estimate -0.60, p ≤ 0.023). For the anxiety score, multivariate analysis showed similar but not significant associations with variables except for HAQ-DI score. Conclusions In a RA population, both depression and anxiety had a significant and negative association with HAQ-DI score, and depression rather than anxiety had negative association with frequent fish intake. Modification of dietary habits such as increased fish consumption may have a beneficial effect on the depression state in RA patients.

Miso, a paste of salted fermented soybean, is a seasoning used extensively in traditional Japanese cuisine. Herein, pyroglutamyl peptides present in miso were identified by a liquid chromatography-tandem mass spectrometry (LC-MS/MS), detecting precursor ions, which generated immonium ion of pyroglutamyl residue. By using this method, 13 pyroglutamyl peptides were identified in four types of miso. Administration of the water extract prepared from 0.6 g soybean miso/kg body weight/day significantly suppressed high fat diet-induced weight gain. A similar effect was exerted by the hydrophobic pyroglutamyl peptide fraction, including pyroglutamyl proline (pEP), pEV, pEI, and pEL. Administration of a mixture of synthetic pEP, pEV, pEI, and pEL in a ratio to that in miso or pEL alone also suppressed the weight gain in a dose dependent manner. These results suggest that the short-chain hydrophobic pyroglutamyl peptides present in miso are effective in suppressing high fat diet-induced obesity.

Background: Excessive salt intake is thought to exacerbate both development of hypertension and autoimmune diseases in animal models, but the clinical impact of excessive salt in rheumatoid arthritis (RA) patients is still unknown. We performed a cross-sectional study to clarify the associations between salt load index (urinary sodium-to-potassium ratio (Na/K ratio)), current disease activity and hypertension in an RA population.Methods: Three hundred thirty-six participants from our cohort database (KURAMA) were enrolled. We used the spot urine Na/K ratio as a simplified index of salt loading, and used the 28-Joint RA Disease Activity Score (DAS28-ESR) as an indicator of current RA disease activity. Using these indicators, we evaluated statistical associations between urinary Na/K ratio, DAS28-ESR and prevalence of hypertension.Results: Urinary Na/K ratio was positively associated with measured systolic and diastolic blood pressure and also with prevalence of hypertension even after covariate adjustment (OR 1.30, p < 0.001). In addition, increased urinary Na/K ratio was significantly and positively correlated with DAS28-ESR in multiple regression analysis (estimate 0.12, p < 0.001), as was also the case in gender-separated and prednisolone-separated sub-analyses.Conclusion: Urinary Na/K ratio was independently associated with current disease activity as well as with prevalence of hypertension in RA patients. Thus, dietary modifications such as salt restriction and potassium supplementation may well attenuate both disease activity and hypertension in RA patients.

Background Excessive salt intake is thought to exacerbate both development of hypertension and autoimmune diseases in animal models, but the clinical impact of excessive salt in rheumatoid arthritis (RA) patients is still unknown. We performed a cross-sectional study to clarify the associations between salt load index (urinary sodium-to-potassium ratio (Na/K ratio)), current disease activity, and hypertension in an RA population. Methods Three hundred thirty-six participants from our cohort database (KURAMA) were enrolled. We used the spot urine Na/K ratio as a simplified index of salt loading and used the 28-Joint RA Disease Activity Score (DAS28-ESR) as an indicator of current RA disease activity. Using these indicators, we evaluated statistical associations between urinary Na/K ratio, DAS28-ESR, and prevalence of hypertension. Results Urinary Na/K ratio was positively associated with measured systolic and diastolic blood pressure and also with prevalence of hypertension even after covariate adjustment (OR 1.34, p p Conclusion Urinary Na/K ratio was independently associated with current disease activity as well as with prevalence of hypertension in RA patients. Thus, dietary modifications such as salt restriction and potassium supplementation should be investigated as a potential candidate for attenuating both disease activity and hypertension in RA patients.

Purpose To determine patients with abnormal sensation in the throat (AST) who would respond to potassium-competitive acid blocker (P-CAB) or serotonin noradrenaline reuptake inhibitor (SNRI) treatment. Methods AST patients were randomly divided into two groups. Thirty-one and 21 patients received P-CAB and SNRI treatment, respectively. GETS-J, the Japanese version of Glasgow Edinburgh Throat Scales (GETS), consisted of three subscales of throat symptoms (globus sensation, pain/swelling of the throat, and dysphagia) and somatic distress due to the disease, Frequency Scale for the Symptoms of Gastro-esophageal reflux disease (FSSG), and Hospital Anxiety and Depression Scale (HADS) were used before and after treatments. Responders to treatments were defined as those who showed 50% or more decrease in symptom scores or somatic distress. Results Pre-treatment GETS-J pain/swelling scores and FSSG acid reflux scores were higher in P-CAB responders and decreased after treatment. Receiver operating characteristic curve for pain/swelling subscale had an area under the curve (AUC) of 0.792 to predict P-CAB responders and a score of 11 provided the best combination of sensitivity (62.5%) and specificity (80%). Somatic distress and HADS anxiety scores, but no other GETS-J symptom scores, decreased after SNRI treatment. Pre-treatment globus scores were lower in SNRI responders. AUC value for globus subscale to predict SNRI responders was 0.741 and a score of 6.5 provided the best combination of sensitivity (70%) and specificity (73%). Conclusions Pain/swelling is a characteristic symptom in AST patients who respond to P-CAB treatment. SNRI treatment would be effective for somatic distress in cases with mild symptoms.

Frailty is a geriatric syndrome characterized by anabolic-catabolic imbalance and multisystem dysregulation resulting in increased adverse health outcomes, and is closely related with dietary habits in the general population. Although chronic inflammatory diseases are thought to accelerate development of frailty, correlations between rheumatoid arthritis (RA), frailty and dietary habits have not been examined. We performed a cross-sectional study using our cohort database (KURAMA cohort), and classified 306 participants into three groups (robust, prefrail and frail) according to the Study of Osteoporotic Fracture (SOF) criteria. Multivariate logistic analysis revealed that the presence of frailty/prefrailty was significantly correlated with the disease activity score (DAS28-ESR) (OR 1.70 (1.30–2.22), p two times a week) was an independent covariate negatively correlated with frailty/prefrailty (OR 0.35 (0.19–0.63), p = 0.00060). In conclusion, habitual fish intake may play a key role in nutritional intervention to prevent progression of frailty and RA.

Objective To clarify the relationship between dietary habit and disease activity of rheumatoid arthritis (RA). Methods This study enrolled RA patients who met the ACR/EULAR 2010 classification criteria from Kyoto University Rheumatoid Arthritis Management Alliance (KURAMA) cohort in 2015. 22-item food frequency questionnaire (FFQ) was taken for the measurement of dietary habit in a single-institution cohort of RA (Kyoto University Rheumatoid Arthritis Management Alliance: KURAMA) in 2015. The disease activities of RA using the Disease Activity Score calculated based on the erythrocyte sedimentation rate (DAS28-ESR), Simplified Disease Activity Index (SDAI), Health Assessment Questionnaire (HAQ), and serum matrix metalloproteinase-3 (MMP-3) level, the use of disease-modifying anti-rheumatic drugs (DMARDs), disease duration, rheumatoid factor, anti-cyclic citrullinated antibody, and body mass index were also examined. All of them were combined and statistically analyzed. Results 441 RA patients (81% women; mean age 65 years; mean disease duration 15 years) were enrolled from the KURAMA cohort. Average Disease Activity Score-28 using the erythrocyte sedimentation rate (DAS28-ESR) was 2.7. Univariate analysis showed that intake frequency of vegetables had a statistically significant negative correlation with disease activity markers, such as DAS28-ESR (ρ = −0.11, p

Key points The primary olfactory (or piriform) cortex is a promising model system for understanding how the cerebral cortex processes sensory information, although an investigation of the piriform cortex is hindered by a lack of detailed information about the intrinsic electrical properties of its component neurons. In the present study, we quantify the properties of voltage-dependent sodium currents and voltage- and calcium-dependent potassium currents in two important classes of excitatory neurons in the main input layer of the piriform cortex. We identify several classes of these currents and show that their properties are similar to those found in better-studied cortical regions. Our detailed quantitative descriptions of these currents will be valuable to computational neuroscientists who aim to build models that explain how the piriform cortex encodes odours. Abstract The primary olfactory cortex (or piriform cortex, PC) is an anatomically simple palaeocortex that is increasingly used as a model system for investigating cortical sensory processing. However, little information is available on the intrinsic electrical conductances in neurons of the PC, hampering efforts to build realistic computational models of this cortex. In the present study, we used nucleated macropatches and whole-cell recordings to rigorously quantify the biophysical properties of voltage-gated sodium (NaV ), voltage-gated potassium (KV ) and calcium-activated potassium (KCa ) conductances in two major classes of glutamatergic neurons in layer 2 of the PC, semilunar (SL) cells and superficial pyramidal (SP) cells. We found that SL and SP cells both express a fast-inactivating NaV current, two types of KV current (A-type and delayed rectifier-type) and three types of KCa current (fast-, medium- and slow-afterhyperpolarization currents). The kinetic and voltage-dependent properties of the NaV and KV conductances were, with some exceptions, identical in SL and SP cells and similar to those found in neocortical pyramidal neurons. The KCa conductances were also similar across the different types of neurons. Our results are summarized in a series of empirical equations that should prove useful to computational neuroscientists seeking to model the PC. More broadly, our findings indicate that, at the level of single-cell electrical properties, this palaeocortex is not so different from the neocortex, vindicating efforts to use the PC as a model of cortical sensory processing in general.

Context International interest in the Japanese diet has grown in recent years. Objective The aim of this systematic review was to evaluate and organize the Japanese diet and dietary characteristics from an epidemiological perspective, mainly focusing on the nutritional and dietary elements. Data sources PubMed, Web of Science, Japan Medical Abstracts Society, JDream III, and CiNii databases were searched. Study selection The eligibility criteria included research with an epidemiological study design that was either cross-sectional, cohort, or case-control-based that defined the dietary patterns of the Japanese diet using dietary pattern analysis. A total of 39 research articles that described the Japanese diet were included. Data extraction The data that were extracted included the following: implementing country, location, study design, participant characteristics, key outcomes, methods used in the analysis of dietary patterns, and descriptions of the Japanese diet. Data synthesis As a result of the systematic review analyzing the descriptions of the Japanese diet from 39 selected articles, we were able to aggregate the descriptions into 16 categories from 33 factors. After performing a content analysis using a further aggregation of categories, we found that the top three applicable categories were soybeans/soybean-derived products, seafood, and vegetables; these were followed by rice and miso soup. Conclusion The Japanese dietary content was found to be diverse based on an examination of epidemiological studies; however, we were able to aggregate the content into 16 categories. The Japanese diet is considered to be a dietary pattern that contains a combination of factors: the dietary staple, side dishes, and soup.

PyroGlu-Leu is present in certain food protein hydrolysates and traditional Japanese fermented foods. Our previous study demonstrated that the oral administration of pyroGlu-Leu (0.1 mg/kg body weight) attenuates dysbiosis in mice with experimental colitis. The objective of this study was to elucidate why such a low dose of pyroGlu-Leu attenuates dysbiosis in different animal models. High fat diet extensively increased the ratio of Firmicutes/Bacteroidetes in feces of rats compared to control diet. Oral administration of pyroGlu-Leu (1 mg/kg body weight) significantly attenuated high fat diet-induced dysbiosis. By focusing on the production of intestinal antimicrobial peptides, we found that pyroGlu-Leu significantly increased the level of 4962 Da peptides, which identified as the propeptide of rattusin or defensin alpha 9, in ileum. We also observed increased tryptic fragment peptides from rattusin in the lumen. Here, we report that orally administered pyroGlu-Leu attenuates dysbiosis by increasing in the host antimicrobial peptide, rattusin.

Background: Moderate-intensity physical activity improves insulin sensitivity and shows beneficial effects for prevention of diabetes. However, it hasn’t been investigated what type of physical activity is more effective in reducing insulin resistance. In the current study, we examined the association between the type of physical activity and insulin resistance in Japanese general population. Methods: We conducted cross-sectional analysis using a community-based cohort, the Nagahama Prospective Cohort for Comprehensive Human Bioscience. In this study, “exercise habits” means the habit of exercise for over 30 min a time, 2 or more times weekly, and “non-exercise activity” means physical activity in daily life equivalent to one-hour or more walking. Multiple linear regression analysis was performed with log HOMA-IR as a dependent variable and exercise habits, non-exercise activity, tobacco smoking, medical history of diabetes, family medical history of diabetes, age, sex and BMI as simultaneous independent variables. Results: A total of 7047 subjects were included in the analysis. Multiple regression analysis showed that log HOMA-IR was determined by exercise habits (β = -0.027, p = 0.011), non-exercise activity (β = -0.025, p = 0.017) and BMI (β = 0.571, p < 0.001). We divided subjects into two groups at the BMI of 23 (kg/m2), which is the cut point to consider diabetes screening for Asian adults (Diabetes Care, 2015). In the lower BMI group, multiple regression analysis showed that exercise habits (β = -0.047, p = 0.002) and BMI (β = 0.356, p < 0.001) were significant determinants of log HOMA-IR. In the higher BMI group, on the other hand, non-exercise activity (β = -0.042, p = 0.033) and BMI (β = 0.369, p < 0.001) were significant determinants of log HOMA-IR. Conclusion: In Japanese people with BMI≧23 (kg/m2), “non-exercise activity” was more strongly associated with reduced insulin resistance, while in those with BMI Disclosure F. Mano: None. K. Ikeda: Research Support; Self; Terumo Medical Corporation. D. Tanaka: Research Support; Self; Merck Sharp & Dohme Corp. N. Inagaki: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Japan Tobacco Inc., Kyowa Hakko Kirin Co., Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Ono Pharmaceutical Co., Ltd., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited.

Small bowel adenocarcinomas are rare. There is no definite consensus as to whether they should be treated in a manner similar to gastric or to colon cancer. We report the case of a young woman with a primary jejunal adenocarcinoma, bilateral ovary metastases, and peritoneal dissemination. First- and second-line chemotherapy for the gastric cancer failed. She was then treated with the immune checkpoint inhibitor nivolumab and had temporary improvement in her condition. To the best of our knowledge, this is the first case wherein nivolumab has been used to treat small bowel adenocarcinoma.

Background/Aims: Direct-acting antiviral agents (DAAs) have increased the sustained viral response rate with minimal adverse effects and short treatment duration. In addition, recent data suggest the possibility that hepatitis C virus (HCV) clearance results in rapid improvement in metabolic pathways. The aim of the present study was to evaluate whether the DAA treatment without ribavirin lowers hemoglobin A1c (HbA1c) at 12 weeks after therapy completion. Methods: We performed an observational study to assess the effect of sofosbuvir and ledipasvir (SOF/LED) treatment on glycemic control. We compared HbA1c levels before and after treatment with SOF/LED, considering that anemia is not a side effect of these drugs. Results: In the 36 patients with HCV eradication, HbA1c levels decreased significantly after treatment (pre-treatment 5.85% vs. post-treatment 5.65%, p < 0.01). Conclusion: This pilot study shows the possibility that HCV eradication by SOF/LED was accompanied by an improvement of glucose metabolism in the population with or without diabetes, and suggests further investigation.

Dietary habits and lifestyles are considered to affect the frequency of epigastric symptoms. In our previous study, we found that three amino acids in Japanese broth promoted gastric emptying. We hypothesized that a higher consumption of miso soup which was mainly composed of Japanese broth and miso paste would be associated with a lower frequency of epigastric symptoms. We conducted a cross-sectional study of the association between frequency of miso soup intake and reflux or dyspepsia symptoms in a general Japanese population. Sixteen items of dietary habits were assessed using a self-reported questionnaire, and epigastric symptoms were evaluated using the Frequency Scale for Symptoms of Gastroesophageal Reflux Disease (FSSG). We fitted generalized linear models to analyze the association between miso soup intake and FSSG, reflux, or dyspepsia scores adjusted by age, sex, body mass index (BMI), another 15 dietary habits, smoking, drinking alcohol, and unfavorable dietary behaviors. A total of 9,364 subjects were included in the analysis. Trend analysis revealed that higher frequency of miso soup intake was associated with lower FSSG scores (p

The purpose of this study was to examine the influence of two kinds of major Japanese staple foods, white rice and white bread, on gut microbiota against the background in which participants eat common side dishes. Seven healthy subjects completed the dietary intervention with two 1-week test periods with a 1-week wash-out period in cross-over design (UMIN registration UMIN000023142). White bread or white rice and 21 frozen prepared side dishes were consumed during the test periods. At baseline and at the end of each period, fasting blood samples, breath samples, and fecal samples were collected. For fecal samples, 16S rRNA gene sequencing was used to analyze the gut microbiota. After the bread period, the abundance of fecal Bifidobacterium genus (19.2 &plusmn, 14.5 vs. 6.2 &plusmn, 6.6 (%), p = 0.03), fasting glucagon-like peptide 1 (GLP-1) (13.6 &plusmn, 2.0 vs. 10.5 &plusmn, 2.9 (pg/mL), p = 0.03), and breath hydrogen (23.4 &plusmn, 9.9 vs. 8.2 &plusmn, 5.5 (ppm), p = 0.02) were significantly higher than those of after the rice period. Plasma SCFAs also tended to be higher after the bread period. White bread contains more dietary fiber than refined short grain rice. These findings suggest that indigestible carbohydrate intake from short grain rice as a staple food may be smaller than that of white bread.

Sodium glucose co-transporter 2 inhibitors (SGLT2i) are antidiabetic drugs for type 2 diabetes that lower blood glucose levels and induce weight loss. However, the efficacy of SGLT2i is known to be affected by dietary factors such as carbohydrate and fat intake. In this study, we compared the effects of the SGLT2i (dapagliflozin) in eight-week-old male KK-Ay mice (a diabetic obese model) pair-fed a normal carbohydrate diet (NCD; carbohydrate 65, protein 23, fat 12%) or a low carbohydrate diet (LCD; carbohydrate 20, protein 45, fat 35%) for 8 weeks with or without dapagliflozin (5 mg/kg p.o.) (n=5-6). Dapagliflozin reduced body weight gain and blood glucose levels in the fed state in NCD and LCD, but reduced fasting blood glucose levels in NCD only. Likewise, dapagliflozin ameliorated glucose intolerance and enhanced hepatic gluconeogenesis in NCD only. Dapagliflozin decreased serum LDL cholesterol levels and subcutaneous fat in both groups, but decreased epidydimal fat (a visceral fat) in NCD only. We then investigated the metabolic effects of dapagliflozin and their underlying mechanisms in liver using transcriptomics (DNA microarray analysis) and metabolomics (Capillary Electrophoresis-Mass Spectrometry: CE-MS and Liquid Chromatography-Mass spectrometry: LC/MS). Dapagliflozin upregulated the expression of genes related to gluconeogenesis and β-oxidation in liver in both groups. In NCD, dapagliflozin increased several kinds of amino acids, and in LCD, it increased ketone bodies. Dapagliflozin upregulated the expression of genes related to bile acid metabolism in NCD only. Both groups showed a reduction in cholesterol ester, a major component of LDL cholesterol, in liver. Our results suggest that the efficacy of SGLT2i is attenuated under LCD, and that differences in liver metabolism between NCD and LCD under dapagliflozin treatment contribute to this outcome. Disclosure F. Furuya: None. Y. Fujita: Research Support; Self; AstraZeneca, Ono Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, MSD K.K., Eli Lilly and Company. N. Matsuo: None. Y. Oguri: None. H. Minamino: None. K. Ikeda: None. S. Harashima: Advisory Panel; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Research Support; Self; AstraZeneca. Speaker's Bureau; Self; Sanofi K.K.. Research Support; Self; Sanofi K.K.. Speaker's Bureau; Self; Tanabe Mitsubishi KK. Advisory Panel; Self; Tanabe Mitsubishi KK. Speaker's Bureau; Self; Novartis Pharma K.K., Eli Lilly and Company, Ono Pharmaceutical Co., Ltd.. Y. Wang: None. Y. Liu: None. N. Inagaki: Research Support; Self; Daiichi Sankyo Company, Limited, AstraZeneca, Ono Pharmaceutical Co., Ltd., Sanofi K.K., Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company Limited, Japan Tobacco Inc., MSD K.K., Sumitomo Dainippon Pharma Co., Ltd., Nippon Boehringer Ingelheim Co. Ltd., Novartis Pharma K.K., Kissei Pharmaceutical Co., Ltd., Novo Nordisk Pharma Ltd., Eli Lilly and Company, Sanwa Chemical Industrial Co., Ltd., Teijin Pharma Limited.

Background Recurrence of glomerulonephritis is an important risk factor for renal graft dysfunction. Cryoglobulinemia is known as a relatively rare cause of renal failure, and doctors are usually hesitant to perform transplantation on a recipient with cryoglobulinemia because of the risk for graft loss. We present a case of renal transplantation on a patient with organ manifestations of type II cryoglobulinemia. Case presentation At the age of 44 years, the patient developed acute kidney injury and purpura on the lower extremities with type II cryoglobulinemia after interferon therapy for hepatitis C virus. Cryoglobulinemic glomerulonephritis was suspected; however, despite immunosuppressive therapy combined with plasmapheresis, she eventually needed hemodialysis treatment. She was referred to us at the age of 49 years for renal transplantation. Cryocrit was 14% and the organ manifestations persisted, including the lower extremity purpura and neurologic symptoms. After monitoring and confirming sufficient suppression of cryoglobulin concentration by immunosuppressive treatment with prednisolone, cyclophosphamide, and rituximab combined with plasmapheresis, the operation was performed. After transplantation, the cryoglobulin concentration was continuously monitored, and plasmapheresis and rituximab infusion were performed as appropriate. Her graft function has remained stable for 2 years and 6 months. Conclusion Our case suggested that a patient with cryoglobulinemia and persistent organ manifestations can receive a renal graft if the cryoglobulin concentration is sufficiently controlled by pretransplant treatment.