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Objective: This study investigated outcomes in community mental health research that were important to caregivers of people with schizophrenia. Using an online survey conducted from August 1–31, 2020, data were collected from caregivers belonging to the LINE Schizophrenia Family Association. Caregivers identified outcomes important in community mental health research. Two researchers categorized caregivers’ statements into research outcomes.Results: A total of 132 caregivers completed the online self-reported questionnaire, and 296 caregiver statements were identified. Qualitative analysis identified 17 outcome categories. The caregivers tended to value having more free time, maintaining an appropriate relationship with people with schizophrenia, and being able to cope with their symptoms. This exploratory study newly demonstrates the outcomes that caregivers of people with schizophrenia consider important in community mental health research. The findings may be useful in selecting outcomes for future studies of caregivers.

Severe hypertension in pregnancy is a hypertensive crisis that requires urgent and intensive care due to its high maternal and fetal mortality. However, there is still a conflict of opinion on the recommendations of antihypertensive therapy. This study aimed to identify the optimal blood pressure (BP) levels to prevent severe hypertension in pregnant women with nonsevere hypertension. Ovid MEDLINE and the Cochrane Library were searched, and only randomized controlled trials (RCTs) were included if they compared the effects of antihypertensive drugs and placebo/no treatment or more intensive and less intensive BP-lowering treatments in nonsevere hypertensive pregnant patients. A random effects model meta-analysis was performed to estimate the pooled risk ratio (RR) for the outcomes. Forty RCTs with 6355 patients were included in the study. BP-lowering treatment significantly prevented severe hypertension (RR, 0.46; 95% CI, 0.37-0.56), preeclampsia (RR, 0.82; 95% CI, 0.69-0.98), severe preeclampsia (RR, 0.38; 95% CI, 0.17-0.84), placental abruption (RR, 0.52; 95% CI, 0.32-0.86), and preterm birth ( 37 weeks; RR, 0.81; 95% CI, 0.71-0.93), while the risk of small for gestational age infants was increased (RR, 1.25; 95% CI, 1.02-1.54). An achieved systolic blood pressure (SBP) of 130 mmHg reduced the risk of severe hypertension to nearly one-third compared with an SBP of ≥ 140 mmHg, with a significant interaction of the BP levels achieved with BP-lowering therapy. There was no significant interaction between the subtypes of hypertensive disorders of pregnancy and BP-lowering treatment, except for placental abruption. BP-lowering treatment aimed at an SBP 130 mmHg and accompanied by the careful monitoring of fetal growth might be recommended to prevent severe hypertension.

Introduction: We have developed an online cognitive test (Brain Assessment [BA]) which exhibits moderate correlations with established neuropsychological tests. We made a short version of the BA that requires only 10 min and investigated correlations with the original version. Participants and Methods: Three hundred and twenty-three subjects (26–82 years old, mean age 41.9 years) were recruited via the internet and performed the original version of the BA online, and, for the analyses of the original and short version, the results of the whole and of the first 2 min were utilized, respectively. Correlations were evaluated between both versions, and 144 subjects agreed to be interviewed about BA utilization. Results: Correlations between the short and original versions of the BA were strong (memory of numbers, r = 0.72: total, r = 0.73) or moderate (memory of words, r = 0.66; visuospatial, r = 0.42; working memory, r = 0.53; judgment, r = 0.54). We found a strong negative correlation between the “memory of words” subtest and age (short version, r = −0.85; original version, r = −0.88). Regarding the interview, most wanted to be assessed by the short version every year. In the case of a concerning score, they would then want to be examined by the original version of the BA and/or more specific neuropsychological tests. Discussion: We found that the short and the original versions of the BA exhibited strong correlations, and the correlation coefficients between age and subtest scores were almost the same between the two versions. Conclusion: The short version of the BA will be useful to perform cognitive assessments in the clinic.

Pituitary apoplexy is an uncommon syndrome that often results in spontaneous hemorrhage or infarction of pituitary tumors or glands. We previously reported pituitary apoplexy occurred most frequently in nonfunctional pituitary adenomas among all types of pituitary incidentalomas. In the present study, we aimed to investigate the characteristics of pituitary apoplexy in patients with incidental nonfunctional pituitary adenomas. 65 patients with pituitary incidentaloma were enrolled. All patients underwent clinical/endocrinological/pathological investigations. As a result, 33 patients were diagnosed with nonfunctional pituitary adenomas. Of these, 12.1% of patients had pituitary apoplexy. There was no difference in tumor diameter, age, or sex between the apoplexy and the non-apoplexy groups. However, the liver enzymes aspartate transaminase and alanine aminotransferase were significantly higher, and plasma sodium and chloride levels were significantly lower in the apoplexy group than in the non-apoplexy group (each P .05). In addition, low-density lipoprotein-cholesterol was significantly higher in the apoplexy group than in the non-apoplexy group (P .05). Besides, thyroid-stimulating hormone, luteinizing hormone, follicle-stimulating hormone, and prolactin deficiencies were significantly more frequent in the apoplexy group than in the non-apoplexy group (each P .05), and growth hormone and adrenocorticotropic hormone deficiencies were more frequent in the apoplexy group than in the non-apoplexy group (P = .09 and.08, respectively). Furthermore, tumor diameter was not associated with pituitary apoplexy, whereas thyroid-stimulating hormone, luteinizing hormone, and follicle-stimulating hormone deficiencies were significantly associated with the apoplexy group (each P .05). Hence, the present study indicated that pituitary apoplexy could not be related to tumor diameter. Moreover, hormonal deficiencies, hepatic dysfunction, hyponatremia or hypochloremia, and dyslipidemia might be indicators of pituitary apoplexy. There could be the possibility the treatment for dyslipidemia prevents pituitary apoplexy.

ObjectivesThe COVID-19 pandemic has had an impact on people’s lifestyles such as causing body weight changes. This study examined associations among lifestyle changes and body weight during the COVID-19 pandemic among the Japanese population.DesignA cross-sectional study.SettingA nationwide survey of the general Japanese population.ParticipantsTotal participants were 2244 men and women, of which 911 young/middle-aged (30–69 years old) and 899 older adults (70 years and older) were analysed separately.OutcomeChanges in lifestyle (physical activity, dietary habits and alcohol intake) and body weight during the first wave of COVID-19 in spring 2020.ResultsUnder the COVID-19 pandemic, 24.1% and 10.1% of Japanese respondents reported weight gain and reduction, respectively. Multivariable-adjusted stepwise logistic regression analyses revealed that the young/middle-aged respondents in the group increased body weight, weight gain was significantly associated with decrease in physical activity (OR 4.01, 95% CI 2.83 to 5.69) and both increase (OR 5.82, 95% CI 3.85 to 8.80) and decrease (OR 2.73, 95% CI 1.52 to 4.93) in eating between meals. In the group that decreased body weight, body weight reduction was significantly associated with increase in physical activity (OR 3.66, 95% CI 1.94 to 6.90), decrease in eating between meals (OR 5.97, 95% CI 3.11 to 11.48) and both increase and decrease in alcohol intake in the young/middle age. For the older adults, body weight gain was higher in women than in men, and significantly associated with higher quartile of regional COVID-19 infection, decrease in physical activity (OR 2.98, 95% CI 1.98 to 4.49), increase in home-cooked meals and increase in eating between meals (OR 4.22, 95% CI 2.55 to 6.99). On the other hand, body weight reduction was significantly associated with decreases in physical activity (OR 2.63, 95% CI 1.62 to 4.27), home-cooked meals and eating between meals (OR 1.95, 95% CI 1.05 to 3.61) in the older adults.ConclusionChanges in physical activity and eating between meals were associated with body weight change under the COVID-19 pandemic among Japanese.

Hypothalamic adrenal insufficiency (AI) is a rare but distinct type of AI. The leading cause of hypothalamic AI is a secondary side-effect of exogenous steroid intake, particularly in large amounts and/or long-term periods. The next cause would be the effect of the tumor in the hypothalamic lesions. We show here 9 cases of hypothalamic AI without any disorder on imagings and a history of steroid administration. All patients had general fatigue; 7 patients (77.8%) had a history of hypoglycemia; 5 patients (55.6%) had a history of hypotension. None of the patients had hyponatremia, hyperkalemia, or eosinophilia. Their morning plasma adrenocorticotropic hormone (ACTH) value was low at 8.5 ± 4.2 pg/mL, and serum cortisol value was low at 4.5 ± 1.3 µg/dL. All patients demonstrated normal responses during the corticotropin-releasing hormone loading (CRH) test but inadequate responses during the insulin tolerance test (ITT). After hydrocortisone replacement therapy, their morning plasma ACTH and serum cortisol values were significantly recovered (P.05). Moreover, more than half of the patients were fine after discontinuing hydrocortisone replacement therapy. These results indicate that this unique type of hypothalamic AI has a curable clinical course making hydrocortisone replacement therapy a novel therapeutic option.

Introduction Both body mass index (BMI) and waist circumference (WC) are associated with diabetes risk, and the difference between them in predictive ability for diabetes is still contentious. We conducted a population-based study to investigate and compare the association of them with diabetes by sex. Methods This study included a total of 4754 subjects aged 40–80 years with no diabetes at baseline between 2008 and 2017. Using multivariate Cox proportional hazards models, we calculated hazard ratios for diabetes according to tertiles of BMI or WC. Harrell's C statistics was applied to assess and compare the predictive ability of the models using BMI and WC. Results Both BMI and WC showed the significant positive trends with diabetes risk. In men, the extreme tertiles (BMI > 25.1 kg/m2 and WC > 88.0 cm) provided 1.58-fold or 2.04-fold higher risk compared with the first tertiles ( 24.4 kg/m2 showed 3.28-fold higher risk than the first tertile (

Introduction: There are several problems with standard in-person neuropsychological assessments, such as habituation, necessity of human resources, and difficulty of in-person assessment under societal conditions during the outbreak of coronavirus disease 2019. Thus, we developed an online cognitive test (the Brain Assessment [BA]). In this study, we investigated the correlation between the results of the BA and those of established neuropsychological tests. Participants and Methods: Seventy-seven elderly persons (mean 71.3 ± 5.1 years old; range 65–86; male:female = 45:32) were recruited through the internet. Correlations were evaluated between the BA and the following widely used neuropsychological tests: the mini-mental state examination (MMSE), the Raven’s colored progressive matrices (RCPM), the logical memory I and II of the Rivermead Behavioral Memory Test, the word fluency (WF) test, and the Trail-Making TestA/B. Results: We found moderate correlations between the total cognitive score of the BA and the total score of the MMSE (r = 0.433, p < 0.001), as well as between the total BA score and the total RCPM score (r = 0.582, p < 0.001) and time to complete the RCPM (r = 0.455, p < 0.001). Moderate correlations were also observed between the cognitive score of the memory of words BA subtest and the LM-I (r = 0.518, p < 0.001), the mental rotation subtest and figure drawing (r = 0.404, p < 0.001), the logical reasoning subtest and total RCPM score (r = 0.491, p < 0.001), and the memory of numbers and words subtests and WF (memory of numbers and total WF: r = 0.456, p < 0.001; memory of words and total WF: r = 0.571, p < 0.001). Discussion: We found that the BA showed moderate correlations between established neuropsychological tests for intellect, memory, visuospatial function, and frontal function. The MMSE and the RCPM reflect Spearman’s s-factor and g-factor, respectively, and thus the BA also covered both factors. Conclusion: The BA is a useful tool for assessing the cognitive function of generally healthy elderly persons.

BackgroundThe number of patients with mental illness living in the community has been increasing in Japan. Treatment goals for mental illness have expanded from hospital discharge and improved functioning to employment, living alone, and personal realization. These changes in treatment goals have also influenced mental health research. Recent studies have addressed the development of core outcome sets focusing on clinical aspects of mental illness such as depression and anxiety. However, a well-developed framework of essential outcomes for people with mental illness (service users) who live in the community is lacking. In addition, recent worldwide trends suggest more patient and public involvement (PPI) and the importance of considering multiple stakeholders’ views in the area of mental health research. Purpose of this study to explore consensus on high-priority outcome domains among multiple stakeholders such as service users, caregivers, service providers, governmental staff, and researchers in community mental health care and relevant fields in Japan. MethodsA three-step approach to developing an outcome list will be used. First, we will develop a long list of outcomes relevant to stakeholders through a literature review of outcomes reported in existing systematic reviews and randomized controlled trials, focus group interviews with key stakeholders, and two online questionnaire surveys of service users and caregivers. Second, the long list will be checked and revised in a two rounds of pilot study. Third, the long list will be shortened to the outcome list through the Delphi methodology with participation from multiple stakeholders. Three rounds of Delphi survey will be conducted and consensus reached if at least 70% of the participants considered at ‘very important’ or ‘important’. Outcome items that were indeterminate will be taken to the next round. All responses of survey will be feedback to participants in the next round.DiscussionIdentifying important common outcome domains through collaboration among service users, caregivers, and other stakeholders appears to contribute to the development of evidence for community mental health research in Japan. In addition, the study process itself may help promote PPI in education, practice, and research in the field of community mental health.

Recent advances in imaging technology resulted in an increase in pituitary incidentalomas (PIs) detection. PIs were reported to be present in 1.6% persons with magnetic resonance imaging of the brain. Whereas, there were few studies about PIs with detailed investigation. We aimed to investigate the clinical and endocrinological characteristics of PIs. We evaluated 65 patients diagnosed with PIs who underwent detailed clinical and endocrinological evaluations. Of the 65 patients, 33 (50.8%) had non-functional pituitary adenomas (NFPAs), 11 (16.9%) had Rathke's cleft cysts (RCCs), 7 (10.8%) had functional pituitary adenomas (FPAs), 6 (9.2%) had benign extra-pituitary tumors (BEPTs), and 8 (12.3%) had malignant tumors (MTs). Compared with patients with NFPAs, those with MTs were significantly younger and had a significantly lower body mass index, lower prevalence of hypertension, and lower prevalence of dyslipidemia. Patients with MTs had significantly higher prevalence of central diabetes insipidus than those with NFPAs. In addition, patients with NFPAs had significantly higher prevalence of pituitary apoplexy than those with FPAs, BEPTs, and MTs. In conclusion, our study demonstrated clinical and endocrinological characteristics of PIs. Highly detailed clinical and endocrinological investigations should be performed for PIs. In addition, MTs should be considered in the differential diagnosis for young and lean patients with central diabetes insipidus.

White matter hyperintensity (WMH), defined as abnormal signals on magnetic resonance imaging (MRI), is an important clinical indicator of aging and dementia. Although MRI image analysis software can automatically detect WMH, the quantitative accuracy of periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH) is unknown.This study was a sub-analysis of MRI data from an ongoing hospital-based prospective cohort study (the Gimlet study). Between March 2016 and March 2017, we enrolled patients who visited our memory clinic and agreed to undergo medical assessments of cognitive function and fecal examination to study the gut microbiome. Participants with a history of stroke were excluded. WMH was independently quantitatively analyzed using two MRI imaging analysis software modalities: SNIPER and FUSION. Intraclass correlation coefficients and the mean difference in volume were calculated and compared between modalities.The data of 87 patients (49 women, mean age 74.8 ± 7.9 years) were analyzed. Both total WMH and DWMH volumes obtained using FUSION were greater (p0.001), and PVH volume was smaller (p0.001) than those obtained using SNIPER. Intraclass correlation coefficients for the lesion measurements of WMH, PVH, and DWMH between the different software were 0.726 (p0.001), 0.673 (p0.001), and 0.048 (p = 0.231), respectively.There were significant differences in the quantitative data of WMH between the two MRI imaging analysis software modalities. Thus, care should be taken for quantitative assessments of WMH.

The induction of a high blood pressure due to diabetic nephropathy depends on the increase in renin secretion from juxtaglomerular cells, but many aspects of how juxtaglomerular cells sense blood pressure changes in the afferent arteriole and consequently react remain unclear. In this study, we detected the juxtaglomerular cell-specific phosphorylation of the threonine-788/789 site of β1-integrin, and its expression was negatively correlated with renin production. This relationship was also observed in a culture system of a juxtaglomerular cell line, suggesting that β1-integrin is deeply involved in the regulation of renin production. The knockdown of β1-integrin in the culture system increased renin production, but the degree of the increase was comparable to the increase in renin production by knockdown of connexin-40, which is considered to be an important molecule that plays a role in the pressure sensing mechanism of juxtaglomerular cells. This suggests that the mechanism underlying the regulation of renin production by β1-integrin in juxtaglomerular cells may contribute to the pressure-sensing function of juxtaglomerular cells themselves. Threonine-788/789 phosphorylation of β1-integrin may be involved in the regulation of this pressoreceptor function. (176 words)

Sodium glucose transporter 2 inhibitors (SGLT2is), new antidiabetic agents, were reported to improve not only glycemic parameters but also metabolic and circulatory parameters. Whereas, several adverse events caused by SGLT2is were also reported. We aimed to investigate the changes of glycemic, metabolic, and circulatory parameters as well as safety with low-dose administration of two SGLT2is, canagliflozin and ipragliflozin, and also the difference between the two agents. 25 individuals with type-2 diabetes mellitus (T2DM) were recruited and administered with low-dose SGLT2is, canagliflozin (n = 10, 50 mg/day) and ipragliflozin (n = 15, 25 mg/day). We examined glycemic, metabolic, and circulatory parameters at baseline and 24 weeks after administration. All patients completed the study without complications. Compared with baseline, levels of glycated hemoglobin, fasting plasma glucose, and homeostasis model assessment of β-cell function improved significantly at 24 weeks after administration (p < 0.05). Levels of body weight, low-density lipoproteincholesterol, aspartate transaminase, γ-glutamyl transferase, and urinary excretion of albumin also improved significantly (p < 0.05). Moreover, systolic/diastolic blood pressure and levels of brain natriuretic peptide improved significantly (p < 0.05). The comparison of improvement ratio (values of improvement/values of basement) of each agent revealed that there was a significant difference between low-dose canagliflozin and low-dose ipragliflozin for brain natriuretic peptide (0.4404 vs. 0.0970, p = 0.0275). Hence, low-dose SGLT2is could be useful for patients of T2DM not only for hyperglycemia but also for metabolic and circulatory disorders without eliciting adverse events. In addition, with regard to the efficacy upon cardiovascular function, canagliflozin could be more suitable than ipragliflozin.

// Makiko Abe 1, 2, 3 , Nitin Shivappa 4, 5, 6 , Hidemi Ito 3, 7 , Isao Oze 3 , Tetsuya Abe 8 , Yasuhiro Shimizu 8 , Yasuhisa Hasegawa 9 , Chikako Kiyohara 1 , Masatoshi Nomura 10 , Yoshihiro Ogawa 2, 11 , James R. Hebert 4, 5, 6 and Keitaro Matsuo 3, 7 1 Department of Preventive Medicine, Kyushu University Faculty of Medical Sciences, Fukuoka, 812-8582, Japan 2 Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Fukuoka, 812-8582, Japan 3 Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, Nagoya, 464-8681, Japan 4 Cancer Prevention and Control Program, University of South Carolina, Columbia, SC, 29208, USA 5 Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, 29208, USA 6 Connecting Health Innovations LLC, Columbia, SC, 29201, USA 7 Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan 8 Department of Gastrointestinal Surgery, Aichi Cancer Center Hospital, Nagoya, 464-8681, Japan 9 Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, 464-8681, Japan 10 Department of Endocrinology and Metabolism, Kurume University School of Medicine, Kurume, 830-0011, Japan 11 Department of Molecular and Cellular Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan Correspondence to: Keitaro Matsuo, email: kmatsuo@aichi-cc.jp Keywords: upper aerodigestive tract cancer; dietary inflammatory index; Japanese adults; persistent infection; case-control study Received: November 26, 2017 Accepted: April 13, 2018 Published: May 08, 2018 ABSTRACT Background: The inflammatory potential of diet that has been shown to be associated with cancer risk. We examined the association between dietary inflammatory potential as measured by the dietary inflammatory index (DII ® ) and risk of upper aerodigestive tract cancers in a Japanese case-control study. Results: A positive association was observed between increasing DII scores and overall upper aerodigestive tract cancers, and across anatomic subsites. For upper aerodigestive tract cancers, the OR Q4vsQ1 = 1.73 (95% CI: 1.37–2.20); head and neck cancer, the OR Q4vsQ1 was 1.92 (95% CI: 1.42–2.59); and for esophageal cancer, the OR Q4vsQ1 was1.71 (95% CI: 1.54–1.90). Risks for hypopharyngeal and nasopharyngeal cancers were greatly elevated: (OR Q4vsQ1 = 4.05 (95% CI: 1.24–13.25) for hypopharyngeal cancer and OR Q4vsQ1 = 4.99 (95% CI: 1.14–21.79) for nasopharyngeal cancer. Conclusion: A more pro-inflammatory diet was associated with an elevated risk of upper aerodigestive tract cancers after accounting for important confounders. All anatomic subsites, except larynx, showed the consistently elevated risk with increasing DII score. Those subsites with known etiological associations with persistent infection showed the largest elevation in risk. These results warrant further evaluation in future studies. Materials and Methods: This is a case-control study of 1,028 cases and 3,081 age- and sex-matched non-cancer controls recruited at Aichi Cancer Center. DII scores were computed based on estimates of macro- and micro-nutrients from a self-administered food frequency questionnaire. Scores were further categorized into quartiles (based on the distribution in controls). Conditional logistic regression models were fit to estimate odds ratio (OR) and 95% confidence intervals (CIs) adjusted for smoking, ethanol consumption, alcohol flushing, number of teeth, and occupation group.

Background/Aims: The missing fundamental phenomenon (MFP) is a universal pitch perception illusion that occurs in animals and humans. In this study, we aimed to determine whether the MFP is impaired in patients with Alzheimer’s disease (AD) using an auditory pitch perception experiment. We further examined anatomical correlates of the MFP in patients with AD by measuring gray matter volume (GMV) on magnetic resonance images via voxel-based morphometric analysis. Methods: We prospectively enrolled 29 patients with AD and 20 healthy older adults. Auditory stimuli included 12 melodies of Japanese nursery songs that were expected to be familiar to participants. We constructed the melodies using pure and missing fundamental tones (MFTs). Results: Patients with AD exhibited significantly poorer performance on the MFT task than healthy controls. MFT scores were positively correlated with GMV in the bilateral insula and temporal poles, left inferior frontal gyrus, right entorhinal cortex, and right cerebellum. Conclusions: These results suggest that impairments in the MFP represent a manifestation of the degeneration of auditory-related brain regions in AD. Further studies are required to more fully elucidate the neural mechanisms underlying auditory impairments in patients with AD and related dementia disorders.

Little is known about the difference of genetic predisposition for CRC between ethnicities; however, many genetic traits common to colorectal cancer have been identified. This study investigated whether more SNPs identified in GWAS in East Asian population could improve the risk prediction of Japanese and explored possible application of genetic risk groups as an instrument of the risk communication. 558 Patients histologically verified colorectal cancer and 1116 first-visit outpatients were included for derivation study, and 547 cases and 547 controls were for replication study. Among each population, we evaluated prediction models for the risk of CRC that combined the genetic risk group based on SNPs from GWASs in European-population and a similarly developed model adding SNPs from GWASs in East Asian-population. We examined whether adding East Asian-specific SNPs would improve the discrimination. Six SNPs (rs6983267, rs4779584, rs4444235, rs9929218, rs10936599, rs16969681) from 23 SNPs by European-based GWAS and five SNPs (rs704017, rs11196172, rs10774214, rs647161, rs2423279) among ten SNPs by Asian-based GWAS were selected in CRC risk prediction model. Compared with a 6-SNP-based model, an 11-SNP model including Asian GWAS-SNPs showed improved discrimination capacity in Receiver operator characteristic analysis. A model with 11 SNPs resulted in statistically significant improvement in both derivation (P = 0.0039) and replication studies (P = 0.0018) compared with six SNP model. We estimated cumulative risk of CRC by using genetic risk group based on 11 SNPs and found that the cumulative risk at age 80 is approximately 13% in the high-risk group while 6% in the low-risk group. We constructed a more efficient CRC risk prediction model with 11 SNPs including newly identified East Asian-based GWAS SNPs (rs704017, rs11196172, rs10774214, rs647161, rs2423279). Risk grouping based on 11 SNPs depicted lifetime difference of CRC risk. This might be useful for effective individualized prevention for East Asian.

Glucose intolerance is often observed in patients with pheochromocytoma. However, it remains controversial issue that glucose intolerance on pheochromocytoma is caused by impaired insulin secretion and/or by increased insulin resistance. We aimed to reveal the mechanism of glucose intolerance on pheochromocytoma with regard to the type and amount of catecholamines released. We evaluated 12 individuals diagnosed with pheochromocytoma and who underwent surgery to remove it. We examined glycemic parameters before and after surgery and investigated the association between the change of parameters of insulin secretion (homeostasis model assessment of β-cell function (HOMA-β)), insulin resistance (homeostasis model assessment of insulin resistance (HOMA-IR)) and that of urinary levels of metanephrine/normetanephrine before and after surgery. Overall, fasting plasma glucose, glycated hemoglobin (HbA1c), HOMA-β, and HOMA-IR were improved significantly after surgery. Regression analysis showed that the improvement in HOMA-β from before to after surgery was significantly positively associated with an improvement in urinary levels of metanephrine from before to after surgery and showed a significantly negative association with improvement in urinary levels of normetanephrine from before to after surgery. The improvement in HOMA-IR from before to after surgery was significantly positively associated with an improvement in urinary levels of normetanephrine from before to after surgery. Our results showed that pheochromocytoma extirpation improved glycemic parameters. Furthermore, the different effects elicited by excess amounts of adrenaline and noradrenaline on glucose intolerance were demonstrated.

A 63-year-old, right-handed professional chorus conductor developed right putaminal hemorrhage, and became unable to experience emotion while listening to music. Two years later, neurological examination revealed slight left hemiparesis. Neuromusicological assessments revealed impaired judgment of "musical sense," and the inability to discriminate the sound of chords in pure intervals from those in equal temperament. Brain MRI and tractography identified the old hemorrhagic lesion in the right putamen and impaired fiber connectivity between the right insula and superior temporal lobe. These findings suggest that musical anhedonia might be caused by a disconnection between the insula and auditory cortex.

Osteoporosis is a complication of type 2 diabetes mellitus (T2DM). Blockade of receptor activator of nuclear factor kappa-B ligand (RANKL) improves osteoporosis, but might also improve glucose tolerance through reduction of hepatic insulin resistance. However, the effect of denosumab (a human monoclonal antibody of RANKL) upon glycemic and metabolic parameters is controversial. We revealed the effect of denosumab upon glycemic and metabolic parameters for 52 weeks. We evaluated 20 individuals diagnosed with both osteoporosis (male and female: postmenopausal) and T2DM. We measured glycemic and metabolic parameters before and 26/52 weeks after administration of denosumab (60 mg per 26 weeks) without changing any other medication each patient was taking. All patients completed the study without complications and the T-score (lumbar spine and femoral neck) improved significantly from baseline to 52 weeks after denosumab administration (P < .001, .001, respectively). None of the glycemic parameters changed significantly from baseline to 26 weeks after denosumab administration, but levels of glycated hemoglobin and homeostasis model assessment of insulin resistance improved significantly from baseline to 52 weeks after administration (P = .019, .008, respectively). The levels of liver enzymes did not change significantly from baseline to 26 weeks after denosumab administration, but levels of aspartate transaminase and alanine aminotransferase improved significantly from baseline to 52 weeks after administration (P = .014, .004, respectively). None of the markers of lipid metabolism and body mass index changed significantly from baseline to 26/52 weeks after denosumab administration. These data demonstrated that denosumab is useful for T2DM patients with osteoporosis for glycemic control via improvement of insulin resistance. Also, the effect of denosumab might be due to improvement of hepatic function.

Objective To evaluate the effects of six-month liraglutide treatment on body weight, visceral and subcutaneous fat and related markers in Japanese type 2 diabetic patients. Methods A total of 59 patients with type 2 diabetes were treated with liraglutide (0.3 mg/day for ≥1 week and then 0.6 mg/day for ≥1 week, gradually increasing the dose to 0.9 mg/day) for six months. Changes in body weight, body mass index (BMI), HbA1c, the fasting blood glucose level, visceral and subcutaneous fat areas, hepatic and renal CT values and the associated markers proinsulin, adiponectin and pentraxin (PTX) 3 were measured. Results The study included one treatment-naive patient, 10 patients who were switched from oral antidiabetic drugs and 35 patients who were switched from insulin therapy. At six months after treatment, the preprandial blood glucose levels were higher (148.8±40.5 mg/dL) than the baseline values (130.8±36.7, p

Background Tubulointerstitial fibrosis (TIF) is seen as the final stage of progressive nephropathy, and the degree of TIF is reported to be a major determinant in renal outcomes. In recent years, epithelial-mesenchymal transition (EMT) and the zinc-finger transcription factor snail homolog 1 (Snai1) have each been implicated in the mechanism of TIF. The relationship between EMT and these transcription factors is unclear, however, so in this study we attempted to elucidate the correlation between the expression of Snai1 and clinical markers. Methods We performed immunohistochemical staining on human renal tissue obtained from patients with diabetic nephropathy (DN), IgA nephropathy (IgAN), minimal change disease (MCD) and minor glomerular abnormality (MGA) using anti-Snai1 and anti-vimentin antibodies. We counted Snai1-positive and Snai1/vimentin double positive tubular epithelial cells. Results Snai1 protein was mainly observed in the nuclei of flattened, damaged tubular epithelial cells, especially in IgAN and DN, and positive cell numbers were significantly higher in IgAN than in MGA, MCD or DN. Snai1/vimentin double staining showed that some vimentin-positive tubular epithelial cells also contained Snai1-positive nuclei, and double positive cell numbers were increased in IgAN and DN. Statistical analysis revealed positive correlations between Snai1/vimentin double positive cell numbers and proteinuria and creatinine in IgAN. Positive correlations were also seen between Snai1/vimentin double positive cell numbers and the severity of proteinuria in DN. Conclusions The results of this study indicate that Snai1 plays an important role in TIF in patients with progressive nephropathy.

Objective Diabetic nephropathy (DN) is a common cause of end-stage renal disease. However, the precise mechanism of DN, which involves the role of lipid, is still not fully understood. Lectin-like oxidized LDL receptor-1 (LOX-1) is a type II single-transmembrane protein that binds oxidized low density lipoprotein (Ox-LDL). This study examined the expression of LOX-1 mRNA in renal tissues from type 2 diabetes patients with DN using in situ hybridization (ISH). Patients and Methods Renal tissues were obtained from 15 type 2 patients with DN and 5 minimal change nephrotic syndrome (MCNS), membranous nephropathy (MN) and normal human kidney (NHK). Glomerular and tubulointerstitial LOX-1 mRNA expression was evaluated by ISH. Results The cells positive for LOX-1 mRNA were identified in the glomeruli of DN, MCNS, MN and NHK, however, there was no positive signal in the tubulointerstitial area in MCNS and NHK. Some cells positive for LOX-1 mRNA were detectable in the tubulointerstitial area in DN and MN. In the results of glomerular staining, there was no significant difference between them. There was a significant correlation between the tubulointerstitial LOX-1 expression and the degree of the tubulointerstitial damage and urinary protein in DN. Conclusion Increased expression of LOX-1 mRNA in the tubulointerstitial area may be closely linked to the development and progression of human DN, and in particular the tubulointerstitial damage.

Objective The loss of podocytes has been reported to have a role in the onset and progression of diabetic nephropathy (DN). Although structural changes such as podocyte hypertrophy are considered to be associated with podocyte loss, the relationship has not been thoroughly investigated using human DN renal tissues. Methods The subjects were 17 patients with DN diagnosed histopathologically by renal biopsy. Immunostaining was performed with antibodies for Wilm's tumor 1 (WT1) and synaptopodin (SPD), which are markers of podocytes, to determine the number of podocytes and assess podocyte hypertrophy. Results The number of podocytes was decreased in DN patients compared with the controls. An inverse correlation was observed between the number of podocytes and both the urinary protein excretion and the extent of mesangial expansion. Podocyte hypertrophy was also more marked in DN patients compared with controls. Conclusion Based on these results, podocyte loss and hypertrophy were suggested to be involved in the development and progression of human DN.

A 75-year-old woman who had been healthy except for mild glycemia and lipidemia discovered three and a half months before admission experienced severe dysphagia secondary to oral and esophageal candidiasis. She eventually developed diabetic hyperosmolar syndrome and ketoacidosis. Since anti-GAD antibody was negative and her diabetes was controlled with a moderate dose of insulin, we made a diagnosis of type 2 diabetes. Her only risk factors for candidiasis were hyperglycemia, age, and continuous denture use. The fact that her diabetes developed in association with oral candidiasis supports the hypothesis that there is a bidirectional interrelationship between diabetes and oral infection.