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This study aimed to determine independent factors for developing postoperative hypertension using 4 biomarkers in patients receiving oral and maxillofacial surgery under general anesthesia. Brain natriuretic peptide (BNP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity myocardial troponin T (hs-TnT), and high-sensitivity myocardial troponin I (hs-TnI) were measured and preoperative echocardiograms were examined. Episodes of systolic blood pressure (SBP) ≥ 170 mmHg or diastolic blood pressure ≥ 100 mmHg within 1 week after surgery were considered postoperative hypertension. We analyzed 213 (130 men; 83 women) patients, who were divided into a postoperative hypertension group (HT group, n = 32) and a normal group (N group, n = 181). The HT group showed a higher LVMI (113.5 versus 100.1), higher E/e' of the lateral wall (9.1 versus 7.7), and higher BNP (39.2 versus 22.9 pg/mL), NT-proBNP (400.1 versus 143.9 pg/mL), and hs-TnT (15.6 versus 10.3 ng/L) concentrations compared to the N group. NT-proBNP and hs-TnT concentrations positively associated with E/e', but BNP and hs-TnI did not. NT-proBNP (AUC = 0.64, cutoff value: 117.0 pg/mL) and hs-TnT (AUC = 0.61, cutoff value: 11.0 ng/L) concentrations were effective for discriminating E/e' ≥ 12. Multivariate logistic regression analyses showed that risk factors responsible for developing postoperative hypertension were NT-proBNP and hs-TnT using biomarkers and E/e' as independent variables, and NT-proBNP and SBP at admission using biomarkers and SBP at admission as independent variables. These findings suggest that NT-proBNP and hs-TnT concentrations, and SBP at admission, are useful to predict postoperative hypertension after minor to moderate surgery, and that left ventricular filling pressure is a primary factor associated with postoperative hypertension.

Arteriosclerosis leads to various serious diseases that substantially reduce the quality of life. When treating hypertension, it is important to evaluate the degree of arteriosclerosis. In recent years, the cardio-ankle vascular index and augmentation index have been frequently used as indicators of arterial wall sclerosis. However, the superiority of either the cardio-ankle vascular index or the augmentation index as an index of arteriosclerosis remains unclear. Therefore, the present study compared the usefulness of these two indices as an index of arteriosclerosis. Associations between the cardio-ankle vascular index or augmentation index and risk factors for arteriosclerosis and other indices of arteriosclerosis in 535 consecutive patients with essential hypertension were evaluated. The cardio-ankle vascular index was significantly correlated with age, hemoglobin A1c, brain natriuretic peptide, and estimated glomerular filtration rate. In contrast, the augmentation index showed significant correlations only with age, brain natriuretic peptide, and estimated glomerular filtration rate. In addition, these correlations with the augmentation index were generally weaker than those with the cardio-ankle vascular index. The cardio-ankle vascular index, but not the augmentation index, was significantly correlated with flow-mediated dilation, an index of vascular endothelial function, and carotid intima-media thickness, an index of carotid atherosclerosis. Similar results were observed in subgroups stratified by sex and age. These data indicate that the cardio-ankle vascular index is more closely associated with risk factors for arteriosclerosis and other indices of arteriosclerosis than the augmentation index, suggesting that the cardio-ankle vascular index may be superior to the augmentation index as an index of arteriosclerosis.

Background Identifying predictive factors of fetal congenital heart block (CHB) in pregnant women with positive anti-SS-A antibodies is important to manage the cases properly. Methods We retrospectively reviewed the medical records of 59 anti-SS-A antibody-positive women undergoing perinatal management at our hospital from January 2011 to November 2021. Univariate and multivariate analyses were performed to investigate predictive factors for the development of fetal CHB. Results Of 59 women with positive anti-SS-A antibodies, 9 had fetal CHB. In univariate analysis, fetal CHB was associated with diagnosing connective tissue disease (OR 0.109, p = .009) and positive anti-SS-A antibodies after conception (OR 31.333, p = .0002). In multivariate analysis, diagnosing connective tissue disease was a protective factor (OR 0.049, p = .025), and positive anti-SS-A antibody after conception was a risk factor (OR 41.738, p = .004). However, other maternal clinical characteristics did not influence the development of fetal CHB. Conclusions In pregnancies of anti-SS-A antibody-positive women, diagnosing connective tissue disease was an independent protective factor for fetal CHB, and positive anti-SS-A antibody after conception was an independent risk factor.

Although the life expectancy of women is over 80 years in many countries, oral sensation has scarcely been compared between adults ≥ 80 years and younger age groups. The purpose of this study was to clarify age-related changes in oral sensation throughout adulthood. After exclusion of individuals with factors that might have confounded somatosensory performance, 123 female participants were divided into four age groups: 20–39 years, 40–59 years, 60–79 years, and 80–96 years. Perceptions of tactile and thermal sensations were examined at points on the anterior and posterior palate, anterior and posterior tongue, lower labial-attached gingiva, lower lip, and buccal mucosa; two-point discrimination was examined only on the tongue. The tactile and two-point discrimination thresholds for the anterior and posterior tongue were significantly higher in the 80–96-year-old group than in any other age group (p

Background Growth hormone (GH) deficiency, a common endocrine deficit in non-functioning pituitary tumors, causes visceral obesity and fatty liver and increases cardiovascular event risks. High-sensitivity C-reactive protein (hs-CRP) has been used as a useful marker to estimate cardiovascular event risks. Because GH supplementation therapy was reported to decrease serum hs-CRP levels in GH deficient patients, inflammatory processes might be activated in GH deficient state, however, the underlying mechanism has been still unknown. Patients and Methods We retrospectively reviewed charts of 134 patients with non-functioning pituitary adenoma and Rathke's cysts who underwent preoperative GH-releasing peptide-2 (GHRP-2) tests and investigated the association between serum hs-CRP levels and background characteristics. Patients who had a history of pituitary surgery, severe renal insufficiency or active inflammatory diseases or received GH supplementation therapy were excluded. GH secretion was determined by GHRP-2 tests. Results Among 134 patients (94 NFPA and 40 Rathke's cysts), 46 (34%) presented severe GH deficiency, as diagnosed using GHRP-2 tests. Serum hs-CRP levels were significantly higher in the patients with severe GH deficiency than in those without severe GH deficiency (723 [299-1285] vs 278 [124-561] ng/mL, P < 0. 001). Serum hs-CRP levels were significantly higher in men (P = 0. 003) and in patients with diabetes mellitus (P = 0. 040) and were significantly correlated with age (r s = 0.19, P = 0. 039), body mass index (r s = 0.37, P < 0. 001), serum levels ofgamma-glutamyl transpeptidase(r s = 0.28, P = 0. 001), creatinine (r s = 0.30, P < 0. 001), low-density lipoprotein cholesterol (r s = 0.21, P = 0. 013), triglyceride (r s = 0.38, P < 0. 001) and free thyroxine (r s = -0.30, P= 0. 001), blood hemoglobin A1c levels (r s = 0.20, P = 0. 018), peak GH response to GHRP-2 (r s = -0.47, P < 0. 001) and IGF-1 SD score (r s = -0.18, P = 0. 040). In the multiple regression analysis, peak GH response to GHRP-2 was a significant variable for determining serum hs-CRP levels (β = -0.340, P = 0. 003) after adjustment with age, sex, BMI, smoking, alcohol consumption, hypertension, diabetes mellitus, serum levels ofgamma-glutamyl transpeptidase, creatinine,triglyceride and free thyroxine and adrenal function. Conclusion We observed a significant association between GH deficiency and increased serum hs-CRP levels independent to BMI and liver dysfunction. GH deficient state might cause inflammation independent to development of visceral obesity and fatty liver. Presentation: No date and time listed

During pregnancy, there is no established treatment for idiopathic hyperaldosteronism (IHA), the most common form of primary aldosteronism due to bilateral adrenal hyperplasia. Here, we report the case of a pregnant patient with IHA who was successfully treated with esaxerenone, a nonsteroidal mineralocorticoid receptor (MR) antagonist. A 39-year-old woman was diagnosed with IHA and commenced on nifedipine 20 mg daily because she desired to be pregnant. After 1 year, she became pregnant. Her blood pressure was well controlled until 34 weeks of gestation when her home blood pressure became elevated up to 140/90 mmHg. Although the dose of nifedipine was increased to 80 mg daily, her blood pressure increased to 151/97 mmHg, and urinary test showed proteinuria of 2+ in 35 weeks of gestation. She was diagnosed with superimposed preeclampsia (SPE) and additionally treated with esaxerenone. Her blood pressure decreased to 120-140/98-100 mmHg and the proteinuria improved to ±. A successful cesarean section at 37 weeks resulted in the delivery of a healthy baby boy. Her blood pressure was well controlled although esaxerenone was discontinued 2 weeks after the delivery. This is the first case of a pregnant woman who was safely treated with esaxerenone despite being a female at advanced maternal age who had been diagnosed with IHA and developed SPE. Further studies are needed to investigate the efficacy and safety of nonsteroidal selective MR antagonist in similar pregnant patients with IHA to establish better treatment strategy for these patients.

The saline infusion test (SIT) is widely used to confirm PA, but some patients may not tolerate the standard loading volume of 2 L saline over 4 h. The shortened SIT, loading only 1 L saline over 2 h, is suggested to be useful and would be more acceptable if the diagnostic utility of the shortened SIT is comparable to that of the standard SIT. We compared the diagnostic values of the plasma aldosterone concentration after 2 h of 1 L saline loading (2 h PAC) and that after 4 h of 2 L saline loading (4 h PAC) for the prediction of unilateral aldosterone hypersecretion and postoperative outcome. This retrospective, single-center study involved 555 PA-suspected patients who underwent SIT, 153 patients with adrenal vein sampling (AVS) results, and 37 patients with a 1-year postoperative evaluation. To detect the Japanese cutoff of 4 h PAC > 60 pg/mL, a 2-h PAC Youden Index at 66 pg/mL showed 91% sensitivity and 75% specificity. For unilateral aldosterone hypersecretion, the sensitivity and specificity of 2 h PAC were not inferior to those of 4 h PAC by Markov chain Monte Carlo (MCMC) methods. The sensitivity and specificity of 2 h PAC for postoperative reduction of anti-hypertensive drugs were also not inferior to those of 4 h PAC. Although using the 2 h PAC > 66 pg/mL cutoff may increase false positives for PA diagnosis, the shortened SIT, possibly using a cutoff value higher than 66 pg/mL, may be as useful as the standard SIT for selecting PA patients for AVS and to predict postoperative outcomes with reduced burden on patients.

Dental anxiety about extraction of impacted mandibular third molars changes the activity of the autonomic nervous system. Thus, to provide safe dental treatment, it is important that a surgeon be aware of a patient's pretreatment anxiety and autonomic nervous system state. Therefore, we analyzed how a scheduled treatment to extract mandibular third molars affects the pretreatment electroencephalogram (EEG), autonomic nervous system, and psychological state of patients. We compared their findings with those of volunteers not scheduled to undergo dental treatment.The study enrolled 30 patients who were scheduled to undergo impacted mandibular third molar extraction (ie, pretreatment group) and 30 volunteers who were not (ie, control group). Heart rate variability and an EEG were recorded during the experiment. The State Anxiety Inventory-State Anxiety scale (STAI-S) scores were recorded before the procedure. For the statistical analysis, P .05 was deemed statistically significant.High-frequency (HF) variability was significantly decreased and the STAI-S score was significantly increased in the pretreatment group compared with the control group (P .01 for both). The low frequency (LF)/HF ratio and alpha-wave activity showed a significant negative correlation on both sides in the control group (P .01); however, no correlation existed in the pretreatment group. The LF/HF ratio and STAI-S score showed a significant positive correlation in the pretreatment group (P .05); however, no correlation existed in the control group.Predicting a patient's autonomic nervous system state before dental treatment based on the EEG was difficult. The STAI-S psychological test was a useful method.

Plasma aldosterone concentration increases in proportion to the severity of heart failure, even during treatment with renin-angiotensin system inhibitors. This study investigated alternative regulatory mechanisms of aldosterone production that are significant in heart failure. Dahl salt-sensitive rats on a high-salt diet, a rat model of heart failure with cardio-renal syndrome, had high plasma aldosterone levels and elevated β3-adrenergic receptor expression in hypoxic zona glomerulosa cells. In H295R cells (a human adrenocortical cell line), hypoxia-induced β3-adrenergic receptor expression. Hypoxia-mediated β3-adrenergic receptor expression augmented aldosterone production by facilitating hydrolysis of lipid droplets though ERK-mediated phosphorylation of hormone-sensitive lipase, also known as cholesteryl ester hydrolase. Hypoxia also accelerated the synthesis of cholesterol esters by acyl-CoA:cholesterol acyltransferase, thereby increasing the cholesterol ester content in lipid droplets. Thus, hypoxia enhanced aldosterone production by zona glomerulosa cells via promotion of the accumulation and hydrolysis of cholesterol ester in lipid droplets. In conclusion, hypoxic zona glomerulosa cells with heart failure show enhanced aldosterone production via increased catecholamine responsiveness and activation of cholesterol trafficking, irrespective of the renin-angiotensin system.

For understanding the factors affecting bovine viral diarrhea virus (BVDV) transmission, this study investigated the distribution of BVDV and the epidemiological features of persistently infected (PI) cattle in Ibaraki Prefecture of Japan, and identified farm-level risk factors associated with BVDV infection, with a focus on within-farm transmission and PI animal detection. Among all 377 dairy farms, forty-four PI cattle were identified on 22 farms. Thirty-eight and six PI cattle were born on their current farms or purchased, respectively. Twenty-six PI cattle were born from pregnancies on their current farms, seven from pregnancies in summer pastures, and eight from pregnancies on other farms. The within-farm seroprevalence on farms with PI animals was significantly higher than that on farms without PI cattle. Of 333 farms holding homebred cattle without movement records, antibody-positivity in homebred cattle was observed on 194 farms; these cattle were likely infected by within-farm transmission. Herd size, summer pasturing, and BVDV infection status of the nearest dairy farm were risk factors associated with within-farm transmission. Likewise, herd size, summer pasturing, and the proportion of purchased cattle were related to PI animal occurrence. This study shows the risk of within-farm transmission and occurrence of PI animals after the introduction of BVDV via purchasing and summer pasturing, and illustrates the significant role of PI cattle in circulating BVDV. More effective measures for screening BVDV infection and PI animals, including intensive tests targeting moved cattle and newborn calves, and bulk milk surveillance, are required to control the spread of BVDV in Japan.

Langerhans cell histiocytosis (LCH) is a multi-organ disorder that rarely involves the hypothalamic-pituitary region (HPR). HPR-LCH presents with severe progressive pituitary dysfunction and its prognosis is poor. The definitive diagnosis of LCH is considerably difficult and complicated owing to the occurrence of several diseases with similar manifestations in the HPR and its location in the deepest portion of the anterior skull base, in close proximity to important normal structures, severely limiting the size of the biopsy specimen. Chemotherapy is the established treatment modality for LCH; hence, timely and accurate diagnosis of LCH is essential for early therapeutic intervention. We retrospectively reviewed clinical features and biopsy procedures in four patients with HPR-LCH (all female, 28-44 years old) from 2009 to 2020. Maximum diameter of supra-sellar lesions was 23-35 mm and 2 cases had skip lesions. All patients demonstrated central diabetes insipidus, hyper-prolactinemia, and severe anterior pituitary dysfunction. Two of the patients had progressive disease. Furthermore, four patients presented body weight gain, two visual disturbance, and two impaired consciousness. The duration from onset to diagnosis of LCH was 3 to 10 (average 7.25) years. In total, eight operations were performed until final diagnosis. The percentage of correct diagnosis by biopsy was 50% (4/8). Clinical features of HPR-LCH are very similar to those of other HPR diseases, and their symptoms are progressive and irreversible. Clinicians should consider repeated biopsy with a more aggressive approach if the lesion is refractory to steroid therapy, in order to ensure accurate diagnosis and appropriate treatment.

Primary aldosteronism is characterized by inappropriate overproduction of aldosterone by adrenal lesions and leads to hypertension. Excess aldosterone causes organ damage; therefore, finding a biomarker for organ damage risk is vital. The (pro)renin receptor regulates the tissue renin-angiotensin-aldosterone system. The blood soluble (pro)renin receptor concentration is a candidate biomarker that reflects the activity of the tissue renin-angiotensin-aldosterone system. This study investigated the relationships between serum soluble (pro)renin receptor concentrations and indices of organ damage in patients with primary aldosteronism. We examined plasma aldosterone and serum soluble (pro)renin receptor concentrations in patients with primary aldosteronism and evaluated the relationships between these values and organ damage indices, such as the cardio-ankle vascular index, urinary albumin excretion, estimated glomerular filtration rate, and high-sensitivity C-reactive protein levels. We enrolled 121 patients with primary aldosteronism (46 males, 54.9 ± 12.2 years of age). Serum soluble (pro)renin receptor concentrations were significantly positively correlated with the cardio-ankle vascular index, urinary albumin excretion, and high-sensitivity C-reactive protein levels and negatively associated with estimated glomerular filtration rates, independent of other factors. Plasma aldosterone concentrations showed no significant relationships with these indices. In patients with primary aldosteronism, serum soluble (pro)renin receptor concentrations, but not plasma aldosterone concentrations, showed significant associations with organ damage, suggesting that the serum soluble (pro)renin receptor level could be a high-risk biomarker of organ damage.

Background The fatty acid (FA) composition of membrane phospholipid reflects at least in part dietary fat composition. Saturated FA (SFA) suppress Sirt1 activity, while monounsaturated FA (MUFA) counteract this effect. Objective We explored a role of Sirt1 in homeostatic control of the fatty acid composition of membrane phospholipid in the presence of SFA overload. Methods and results Sirt1 deficiency in cardiomyocytes decreased the expression levels of liver X receptor (LXR)-target genes, particularly stearoyl-CoA desaturase-1 (Scd1), a rate-limiting enzyme in the cellular synthesis of MUFA from SFA, increased membrane SFA/MUFA ratio, and worsened left ventricular (LV) diastolic function in mice fed an SFA-rich high fat diet. In cultured cardiomyocytes, Sirt1 knockdown (KD) exacerbated the palmitate overload-induced increase in membrane SFA/MUFA ratio, which was associated with decrease in the expression of LXR-target genes, including Scd1. Forced overexpression of Scd1 in palmitate-overloaded Sirt1KD cardiomyocytes lowered the SFA/MUFA ratio. Nicotinamide mononucleotide (NMN) increased Sirt1 activity and Scd1 expression, thereby lowering membrane SFA/MUFA ratio in palmitate-overloaded cardiomyocytes. These effects of NMN were not observed for Scd1KD cardiomyocytes. LXRα/βKD exacerbated palmitate overload-induced increase in membrane SFA/MUFA ratio, while LXR agonist T0901317 alleviated it. NMN failed to rescue Scd1 protein expression and membrane SFA/MUFA ratio in palmitate-overloaded LXRα/βKD cardiomyocytes. The administration of NMN or T0901317 showed a dramatic reversal in membrane SFA/MUFA ratio and LV diastolic function in SFA-rich HFD-fed mice. Conclusion Cardiac Sirt1 counteracted SFA overload-induced decrease in membrane phospholipid unsaturation and diastolic dysfunction via regulating LXR-mediated transcription of the Scd1 gene.

Aim: A close association between primary aldosteronism (PA) and atherosclerosis has been well established. We aimed to determine the association between plasma renin activity (PRA) and aldosterone levels (PAC) as well as their ratios (PAC-to-PRA ratio: ARR) with urinary albumin excretion (UAE) in type 2 diabetic patients who did not fulfill PA confirmatory criteria. Methods: The subjects were 70 type2 diabetic patients (age: 53.3±11.0 years, male: 51, female: 19) with UAE ≤100 mg/gCr. They did not take ACE inhibitors, angiotensin receptor blockers (ARB) or diuretic agents. Patients were selected for this study based on various criteria: PRA level ˂10 ng/ml/hr, PAC ˂20 ng/dl, and ARR ˂20 (ng/dl per ng/ml/hr). They were divided into three groups according to UAE levels: NL group (N=33) ˂ 10mg/gCr, N group (N=22) 10-29 mg/gCr, and M group (N=15) 30-100 mg/gCr. Results: There were no significant differences in age, BMI, HbA1c, and eGFR levels among the three groups. The systolic blood pressure in the M group was significantly higher than those in the NL and N groups. The ARR in the M group was 10.1±4.6, which was significantly higher than those in NL (6.5±0.3) or N (7.0±2.7) groups. In the M group, the levels of PRA and PAC were significantly lower than those in NL or N groups. Log UAE was positively correlated with ARR (r=0.34, p Conclusion: These results suggest that a high ARR level, which did not fulfill confirmatory criteria for PA, was associated with diabetic nephropathy. The relative increase in PAC to PRA might contribute to the development of diabetic nephropathy, even if PAC remains normal level. Disclosure M. Higa: None. T. Suzuki: None. T. Kido: None. M. Zenri: None. K. Nao: None. M. Hijikata: None. K. Yamashita: None. K. Ikehara: None. T. Ichijo: None.

Pulse-induced vibration modes and their natural frequencies were analytically investigated on buckled diaphragm structures that enhance the sensitivity of piezoelectric ultrasonic microsensors. The diaphragm was modeled as a simplified one-dimensional beam and the natural frequency was analytically calculated using low of the conservation of energy. The strain by lateral stretching in vibration on the buckled structure was taken into account in the potential energy as well as the strain by bending deformation, and the natal frequency was expressed as a function of the buckling deflection. The analytical results were compared with those of the experimental measurement and they were in good agreement with each other from the viewpoint of the frequency change of each vibration mode and mode degeneration by approaching frequencies.

Buckling of multilayered diaphragm structures was analytically investigated and its results were utilized for new designs of the structure. Sensitivity of ultrasonic microsensors on piezoelectric diaphragm structure is enhanced by an adequate buckling of the diaphragm caused by the stress combination of the multilayered structure. One dimensional multilayered beam was modeled for the analysis, and three kinds of strains caused by residual stress, bending deformation and lateral stretching by buckling were taken into account in the analysis. The analytical buckling behavior was in good agreement with experimental results from the viewpoints of buckling limit stress and buckling deflections. As new designs of the structure, thickness of a compressive stress layer or of a tensile stress layer was varied. Thicker compressive layer acted as an enhancer for the buckling owing to larger in-plain expanding force rather than a reducer for the buckling due to larger rigidity against bending.

This study assessed the relationship between changes in autonomic nervous system activity during impacted mandibular third molar extraction and a patient's postoperative psychological status, with the overarching aim of informing the development of interventions to reduce dental phobia and anxiety. We hypothesized that changes in autonomic nervous system activity during tooth extraction are related to postoperative psychology.In our prospective cohort study, heart rate variability, heart rate (HR), and systolic blood pressure (SBP) were recorded during impacted mandibular third molar extraction. Heart rate variability values were dichotomized as either low frequency (LF 0.04-0.15 Hz) or high frequency (HF0.15 Hz). The relative ratios (intraoperative vs baseline) of LF/HF, HF, HR, and SBP were divided into high and low groups based on their median values; the State Anxiety Inventory (STAI-S) results were compared between the groups with high and low relative ratios.Data of 34 female patients (age, 28.23 ± 1.05 years) were analyzed. Postoperative STAI-S values were significantly lower than preoperative values. Patients in the high LF/HF group had a significantly lower change in STAI-S values than those in the low LF/HF group (P.05). There were no significant differences in the change in STAI-S values between the groups with high and low HF, HR, or SBP.Patients with low sympathetic nervous system activity had lower anxiety; the LF/HF index was the most sensitive indicator for changes in stress. Additional studies are required to develop optimal interventions for reducing sympathetic nerve activity in patients with dental phobia.

Context Radioactive 131I (RAI) for the treatment of differentiated thyroid cancer is known to induce bone marrow suppression, which occurs approximately 1 month after treatment. However, it is unknown whether RAI therapy for Graves’ disease causes bone marrow suppression. Objective This study aimed to evaluate the short- and long-term effects of RAI therapy on bone marrow function in patients with Graves’ disease. Methods In this retrospective cohort study, we included patients with Graves’ disease who received RAI therapy only once between 2003 and 2019 at Tokyo Women’s Medical University. Blood cell counts at baseline were compared with counts at 1, 2, 4, 12, 24, 48, 144, and 240 weeks after RAI therapy. Moreover, changes in white blood cell (WBC) count and leukopenia at 1 week after RAI treatment were compared by baseline patient characteristics. Results We enrolled 48 patients. Leukopenia was observed in 6 patients at 1 week after RAI treatment, and the overall WBC count significantly decreased (P Conclusion These data showed that RAI treatment induced transient reduction in the WBC count 1 week after treatment, although WBC levels were subsequently restored.

Polyunsaturated fatty acid (PUFA) is an essential class of dietary fatty acids, because of the lack of endogenous enzymes for desaturation in humans. Previous research on n-3 PUFA has demonstrated several health benefits and antiatherogenic actions, but n-6 PUFA have not received much research attention. We investigated whether serum fatty acid composition, especially n-6 PUFAs and desaturase activity, is associated with obesity in type 2 diabetic patients. Subjects were 80 type 2 diabetic patients (age: 60.3±13.9 years) who had no EPA agent intake. They were divided into two groups: obese group (n=52) with a BMI more than 25 kg/m2 and non-obese group (n=28) with a BMI less than 25 kg/m2. Fatty acid levels in serum were measured using gas chromatography. The desaturase activity for n-6 PUFAs was calculated as the arachidonic acid/dihomo-gamma-linolenic acid (DGLA) ratio for Δ5 desaturase (D5D). The obese group revealed a higher saturated fatty acid (SFA) and DGLA levels than those in the non-obese group. No significant difference was observed in the serum n-3 PUFA levels between the two groups. The D5D index of the obese group was significantly lower than that of the non-obese group. Serum DGLA levels showed significant positive correlations with waist circumference, BMI, triglyceride, and hepatic AST and ALT levels. Moreover, SFA showed a significant positive correlation with BMI. The levels of D5D index showed a significant negative correlation with BMI. Increase in serum DGLA levels was related to the number of metabolic factors. These results suggest that type 2 diabetic patients with obesity had changes in their blood fatty acid profile, especially increased DGLA levels. The high levels of blood DGLA indicate downregulation of n-6 metabolism, probably caused by the decreased activity of D5D. The fat quality in the diet and changes in desaturase activity might contribute to the development of obesity. Disclosure M. Saito: None. M. Higa: None. T. Suzuki: None. M. Michishita: None. M. Hijikata: None. K. Yamashita: None. K. Ikehara: None. T. Ichijo: None.

Nonalcoholic fatty liver disease (NAFLD), which is currently the most prevalent liver disorder, not only leads to chronic liver disease but is also associated with cardiovascular mortality. Several studies have conclusively established that increased arterial stiffness is an independent risk factor for cardiovascular events and that the brachial-ankle pulse velocity (baPWV) is a useful clinical indicator of arterial stiffness for early evaluation of functional and structural changes in vessel walls. The aim of this study was to assess whether ultrasonographically diagnosed fatty liver disease is associated with arterial stiffness and carotid intima-media thickness (CIMT) in type 2 diabetic patients. The subjects were 294 type 2 diabetic patients (age: 66.4±10.3 years). Patients with and without fatty liver (FL) were categorized into the FL group (n=155), and non-FL group (n=139), respectively. The baPWV was measured as an index of arterial stiffness, and structural changes in vessel walls were assessed using the CIMT obtained with B-mode ultrasonography. BMI, waist circumference, blood pressure, serum LDL-C, triglyceride (TG), and HbA1c levels, as well as the baPWV and CIMT levels were significantly higher in the FL than in the non-FL group. Serum levels of TG, hepatic AST, age, waist circumference and systolic blood pressure showed significant positive correlations with baPWV, respectively. However, no significant association was observed between the CIMT and serum hepatic AST levels. Multiple regression analysis showed that serum hepatic AST and ALT were independently associated with increased baPWV. Our findings suggest that NAFLD is associated with increased arterial stiffness. This is a clinically significant observation because it implicates arterial stiffness in the pathogenesis of NAFLD, suggesting that abdominal obesity and low-grade inflammation might be key etiopathogenetic contributors to both hepatic steatosis and macrovascular disease in type 2 diabetic patients. Disclosure M. Higa: None. M. Hijikata: None. K. Yamashita: None. T. Suzuki: None. M. Saito: None. M. Michishita: None. K. Ikehara: None. T. Ichijo: None.

From 29 November 2016 to 24 January 2017, sixty-three cases of H5N6 highly pathogenic avian influenza virus (HPAIV) infections were detected in wild birds in Ibaraki Prefecture, Japan. Here, we analyzed the genetic, temporal, and geographic correlations of these 63 HPAIVs to elucidate their dissemination throughout the prefecture. Full-genome sequence analysis of the Ibaraki isolates showed that 7 segments (PB2, PB1, PA, HA, NP, NA, NS) were derived from G1.1.9 strains while the M segment was from G1.1 strains; both groups of strains circulated in south China. Pathological studies revealed severe systemic infection in dead swans (the majority of dead birds and the only species necropsied), thus indicating high susceptibility to H5N6 HPAIVs. Coalescent phylogenetic analysis using the 7 G1.1.9-derived segments enabled detailed analysis of the short-term evolution of these highly homologous HPAIVs. This analysis revealed that the H5N6 HPAIVs isolated from wild birds in Ibaraki Prefecture were divided into 7 groups. Spatial analysis demonstrated that most of the cases concentrated around Senba Lake originated from a single source, and progeny viruses were transmitted to other locations after the infection expanded in mute swans. In contrast, within just a 5-km radius of the area in which cases were concentrated, three different intrusions of H5N6 HPAIVs were evident. Multi-segment analysis of short-term evolution showed that not only was the invading virus spread throughout Ibaraki Prefecture but also that, despite the small size of this region, multiple invasions had occurred during winter 2016-2017.

Background Secretion of hormones, which antagonize the action of insulin, is facilitated in response to surgery, and acute resistance to the action of insulin develops. Our aim is to elucidate the effects of intraoperative glycemic control by glucose-insulin (GI) infusion on postoperative complications and outcomes in major oral and maxillofacial surgery. Findings Thirty patients aged ≥ 60 years undergoing a radical operation of oral malignant tumors with tissue reconstruction (≥ 8 h) were analyzed. In the GI group, regular insulin was continuously applied with glucose-added acetate Ringer’s solution (5–10 g glucose per 500 mL). Blood glucose was adjusted within the target concentration of 80–120 mg/dL. In the control group, combination of acetate Ringer’s solution containing 1% (W/V) glucose and lactate Ringer’s solution, which contains no glucose, was employed. Perioperative clinical parameters, incidence of hypoalbuminemia, and postoperative complications, i.e., surgical site infection, necrosis of a reconstructed flap, bacteremia, hypotension, or pneumonia, were compared. Both serum total protein and albumin concentrations (postoperative day 1 [Day1]) were higher in the GI group. The mean infusion rate of glucose during surgery (mg/kg/h) was independently associated with the decrease in both serum total protein and albumin concentrations from the control to Day1. No difference was found between the groups in the incidence of postoperative complications and the days required until discharge, except less incidence of hypoalbuminemia in the GI group. Conclusions Application of additional glucose during major oral and maxillofacial surgery preserved serum albumin concentration. However, it did not lead to less postoperative complications and less days until discharge.

Metal Organic Decomposition (MOD)-made BaTiO3 (BT) thin films were prepared for Resistive Random Access Memory (ReRAM) under various annealing conditions and investigated for improving the properties of bipolar-type resistive switching, focusing on the relation between oxygen vacancies and the behavior of resistive hysteresis. BT thin films with both pre- and final- annealing in nitrogen showed the resistive hysteresis of bipolar-type switching with current ON/OFF ratios of 2 orders of magnitude for both bias polarities. Finally they showed the endurance property with the 106 switching cycles. It was suggested that oxygen vacancies near the oxide surface (both interfaces at metal electrode/oxide and between layer-by-layered oxide layers) are increased by N2 annealing and enhanced the interface-type resistive switching. Pre-annealing in N2 was also found to be very effective to improve endurance properties, implying that not only the electrode/oxide interface but also the middle part of the film would contribute the interface-type mechanism.

The importance of cosyntropin stimulation during adrenal vein sampling (AVS) is not fully established, partly due to insufficient AVS data relating the presence and absence of cosyntropin stimulation with postoperative outcome. Therefore, we investigated differences in AVS indices before and after cosyntropin stimulation, and determined whether unstimulated or stimulated AVS indices better correlated with treatment outcome. A retrospective study was conducted in two parts: one with 185 patients who underwent AVS and the other with 81 patients who underwent unilateral adrenalectomy for unilateral aldosterone oversecretion. The selectivity index (SI), lateralized ratio (LR), and contralateral ratio (CR) before and after cosyntropin stimulations were determined, along with blood pressure outcome 1 year after surgery. Primary aldosteronism was diagnosed according to the Japanese Endocrine Society 2009 guidelines. The percentage of AVS patients with successful catheterization, defined as unstimulated SI > 2 before and stimulated SI > 5, increased after cosyntropin stimulation from 52% to 93% and from 74% to 98% for the right and left adrenal veins, respectively. LR decreased after cosyntropin stimulation (P

Vibration mode and resonance frequency of piezoelectric MEMS ultrasonic sensors was investigated on buckled diaphragm structures. The buckling of the diaphragms was introduced intrinsically through residual stress control of the piezoelectric film, and extrinsically through converse piezoelectric stress. Several vibration modes were generated on the diaphragms as the response to an ultrasound pulse, and their natural frequencies changed with the buckling deflection. The intrinsic buckling increased the natural frequency and some vibration modes were superposed and degraded. The extrinsic buckling once decreased the natural frequency in a small buckling range, and increased it in a large one, which made the vibration mode simplified and thus improved piezoelectric output waveforms would be expected.

The aim of our study was to investigate whether high β-glucan-containing barley (7.2 g per 100 g) improves postprandial plasma glucose levels and suppresses postprandial insulin levels during a meal tolerance test in type 2 diabetic patients. A meal tolerance test (500 kcal) was conducted using two types of test meals: a test meal with white rice (WR) alone (WR diet) and a test meal with WR mixed with 50% barley (BR diet) as staple food. The side dish was the same in the both meals. The changes in plasma glucose and serum C-peptide immunoreactivity (CPR) levels for 180 minutes after ingestion of the test meals were compared. Ten patients with type 2 diabetes (age 52.5 ± 15.1 years, and 7 males and 3 females) were included in this study. The mean HbA1c level and body mass index were 8.8 ± 1.4%, and 29.7 ± 4.5 kg/m2, respectively. Plasma glucose levels after ingestion of the WR diet or BR diet peaked at 60 minutes, which showed no significant differences between the two types of test meals. However, the incremental area under the curve (IAUC) of plasma glucose levels after ingestion of BR diet was significantly lower than that of WR diet. The serum CPR levels at 180 min and their IAUC over 180 minutes after ingestion of BR diet were significantly lower than those of WR diet. Conclusion: Increase in postprandial plasma glucose and insulin levels was suppressed by mixing high-β-glucan barley with WR in type 2 diabetic patients.

Vibrating energy conversion efficiency was investigated on piezoelectric transducers fabricated on MEMS buckled diaphragm structures from the viewpoint of crystal orientation of sol-gel derived lead-zirconate-titanate (PZT) films. The crystal orientation dominates in-plane stress and spontaneous polarization direction of the PZT films. The in-plane stress affects the static buckling of the diaphragm where a large convex buckling results in a high mechanical conversion efficiency from the flexural vibration to the in-plain vibration. The polarization direction affects the intrinsic piezoelectric conversion efficiency. The crystal orientation of the sol-gel PZT was controlled through pyrolysis temperature between 250°C and 350°C, resulting in a texture variation from (100)-oriented films to (111)-oriented ones. Highly (111)-oriented films showed large polarizations but small buckling deflections, while highly (100)-oriented films showed vice versa. Intermediately textured films with 40-45% (111)-orientation index showed the highest conversion efficiency.

Aim: Polyunsaturated fatty acids (PUFAs) are essential fatty acids, because they cannot be synthesized in the body and must be taken from food, but excessive intake may cause obesity. Therefore, the measurement of serum fatty acid composition is useful for monitoring the fat composition of the diet. In recent years, accumulating evidence has indicated the importance of gut microbiota in maintaining human health. The aim of our study was to evaluate the relationship between fatty acid composition and gut microbiota in obese patients with type 2 diabetes. Research Design and Method: The subjects included 100 patients (age: 60.3±13.9 years, BMI 27.5±5.8 kg/m2) who were not taking EPA agents. They were divided into two groups, i.e., obese group (n=64) with a BMI of greater than 25 kg/m2 and non-obese group (n=36) with a BMI less than 25 kg/m2. Serum levels of fatty acids were measured using gas chromatography. In 45 of 100 patients, gut microbiota profiles were measured using T-RFLP methods. Results: The serum levels of dihomo-gamma-linolenic acid (DGLA), which is an n-6 PUFA, and palmitic acid, a saturated fatty acid (SFA), were significantly higher in the obese group than in the non-obese group. No significant differences were observed in the serum levels of n-3 PUFA. The ratio of Firmicutes/Bacteroidetes in the fecal microbiota was significantly lower in the patients with high serum levels of DGLA. The rate of Bacteroidetes showed a significant positive correlation with serum DGLA and palmitic acid. Conclusion: These results suggest that high levels of serum DGLA may play an important role in the development of not only obesity but also gut microbiota in type 2 diabetes patients. The fat quality in the diet might contribute to the development of obesity. Disclosure M. Higa: None. M. Kawai: None. R. Eto: None. F. Ayako: None. G. Sato: None. M. Hijikata: None. K. Yamashita: None. T. Ichijo: None.

Aim: Elevated saturated fatty acid (SFA) and decreased polyunsaturated fatty acid (PUFA) levels, especially n-3 PUFAs levels are important in the development of obesity and metabolic syndrome, but there are few accounts of the relationship between fatty acid composition and diabetic kidney disease. We investigated whether serum fatty acid composition, especially SFA and PUFA, are associated with urine albumin excretion (UAE) and estimated glomerular filtration rate (eGFR) in obese type 2 diabetic patients. Research Design and Method: The subjects were 85 patients (age: 60.3±13.9 years old, 47 male and 38 female) who were not taking EPA agents. They were divided into two groups, i.e., Obese group (n=54) with a BMI of more than 25 kg/m2 and non-Obese group (n=31) with a BMI below 25 kg/m2. Serum levels of fatty acids were measured by gas chromatography. Results: In the Obese group, the serum levels of palmitic acids and stearic acids, which belong to SFA, and dihomo-gamma-linolenic acid (DGLA), which is an n-6 PUFA, were significantly higher than those in the non-Obese group. No significant differences were seen in the serum levels of n-3 PUFA. UAE in the Obese group was 218.8±88.9 mg/gCr, which tended to be higher than that in the non-Obese group (135.9±49.0 mg/gCr), but there were no significant differences in eGFR between the two groups. The serum levels of palmitic acids, stearic acids, and DGLA showed significant positive correlations with UAE and eGFR in the Obese group, while no significant correlation was seen in the non-Obese group. Palmitic acids and DGLA were correlated with serum adiponectin and leptin levels. Conclusion: These results suggest that an excessive lipid intake may play an important role in the development of not only obesity but also diabetic kidney disease. The high levels of blood SFA and n-6 PUFA might contribute to the diabetic kidney disease progression via hyperfiltration and inflammatory effects in type 2 diabetes patients with obesity. Disclosure M. Kawai: None. R. Eto: None. F. Ayako: None. G. Sato: None. M. Hijikata: None. K. Yamashita: None. T. Ichijo: None. M. Higa: None.

It is well known the primary aldosteronism (PA) is most common endocrinological hypertension and accounted for 10% among all hypertension population, and it develops cardiovascular disease more frequently than blood pressure matched essential hypertension. Many literatures have been reported patients with obesity often shows hyperaldosteronism by hyperactivation of sympathetic nerves, over secretion from adipocytes themselves, or aldosterone-secreting factors from adipocytes. Thus, we investigated the impact of BMI on diagnosis of PA in this study. We investigated 328 cases of adrenal venous sampling performed patients with PA in our hospital since 2007, including 125 males and 203 females, and their mean age was 56.1 ± 11.8 years old. We evaluated the relationship of those patients’ body mass index (BMI) with gender, systolic and diastolic blood pressure (SBP and DBP, respectively), serum sodium, serum potassium, plasma renin activity (PRA), plasma aldosterone concentration (PAC), aldosterone-renin ratio (ARR), ACTH, cortisol, and the ratio of patients who showed 1 mg dexamethasone suppression test positive, and none of each showed statistical relationship with BMI. In confirmatory tests, we evaluated those values of PRA at 120 min. in upright furosemide test, either higher values of ARR at 60min. or 90 min. in captopril challenge test, and PAC at 4 hours in saline infusion test (SIT), also positive ratio of those test considered by PRA 20, and PAC>6.0 in those tests, respectively. In adrenal venous sampling (AVS), we evaluated lateralized ratio (LR) and contralateral ratio (CR) and those positive ratios considered by LR >4 or CR4 and CR

We have investigated time course of interaction between phospholipid membrane of liposome and amyloid-beta (Aβ) protein, which is a causative agent of Alzheimer’s Disease (AD), by Dielectric Dispersion Analysis (DDA), especially for frequency range of 1–6 GHz. Two dielectric relaxations derived from bound water on liposome are observed and one of their relaxation width (Δe) suggested chronological change dependent on Aβ aggregation and fibrillization. We have newly used normal human serum as a solvent to investigate the interaction between the liposome and Aβ in the serum. Time course of interaction between the liposome and Aβ(1–40) in the human serum, thereafter the change of relaxation width (Δ(Δe)) as a parameter of Aβ concentration showed dynamic behavior of Δe, related to the aggregation and fibrillization of Aβ(1–40). In particular, a low concentration of Aβ (1 μM) has been successfully discriminated this time. Compared to the Aβ concentration in the blood (e.g. 50–200 nM) or cerebrospinal fluid (e.g. 700–4000 nM) of an AD patient, we consider that this DDA technique enables to evaluate Aβ and diagnose AD from the cerebrospinal fluid and would also be available from the blood by improving the sensitivity several times.

The dynamic behavior of amyloid-beta protein (Aβ) fibrillization on cell membrane is closely related to the progression of Alzheimer’s disease (AD). In this paper, we reports a new approach for real-time monitoring of the fibrillization process of Aβ on lipid membrane using a miniaturized cantilever-based liposome biosensor, which contributes to the technology development of Aβ label-free detection and the mechanism elucidation of Aβ fibrillization on cell membrane. 1,2-Dipalmitoyl-sn- glycero -3-phosphocholine (DPPC) liposome as model cell membrane was immobilized on the cantilever surface and Aβ(1–40) was selected as a target protein in this work. Liposome-Aβ interaction is evaluated by detecting the resistance change rate of the strain gauge embedded in the cantilever, which is directly proportional to the deflection of cantilever. 24-h real-time monitoring result clearly shows chronological change in the resistance with the progress of Aβ fibrillization on liposomes. Moreover, it is found that the extent of liposome-Aβ interaction is closely dependent on the aggregate state and concentration of Aβ but is less dependent on the type of used solvent (water or serum). It is indicated that DPPC liposome shows sufficient affinity and selectivity to Aβ even in serum. In particular, a concentration of Aβ as low as 1 μM can be detected using the cantilever-based liposome biosensor. Furthermore, it is confirmed that this biosensor has a potential of recognizing different states of Aβ. We expect that the cantilever-based liposome biosensor becomes an effective tool for accelerating amyloid related research and developing the early diagnosis approach of AD.

Accumulating evidence suggests that interaction between amyloid-β (Aβ) and cell membrane is crucial to the pathogenesis of Alzheimer's disease (AD), and thus an increasing understanding of the impact of membrane composition on Aβ-membrane interaction becomes essential for the mechanism elucidation of Aβ-membrane interaction and the early diagnosis of AD. In this work, electrically neutral phosphatidylcholine (PC) as the most major class of membrane phospholipids, including 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), and Aβ(1–40) as the most common amyloid protein were selected as the research subjects, and a developed cantilever-based biosensor, on which liposomes comprised of PC lipids were immobilized, was applied to characterize in real time the interactions between Aβ(1–40) and membranes comprised of PC lipids with different hydrophobic acyl chains, and to evaluate the effect of cholesterol incorporated in membrane on Aβ-membrane interaction during the whole process of Aβ(1–40) fibrillization. The results illustrate that the interaction between Aβ(1–40) and PC membrane can be divided into three stages, which are related to the change in molecular states of Aβ. More importantly, it is found that membranes comprised of PC lipids with shorter saturated acyl chains show higher interaction ability with Aβ(1–40), and the incorporation of cholesterol into PC bilayer can remarkably accelerate and strengthen Aβ(1–40)-membrane interaction. These results confirm that hydrophobicity is the main driving force for the interactions between Aβ(1–40) and PC membranes. In return, the above results enlightened us to apply the current micro-cantilever immobilized with cholesterol-containing DPPC liposomes to challenge the detection of low-concentration Aβ(1–40). This time 50-nM Aβ(1–40) in aqueous solution has been effectively detected, suggesting that this proposed detection technique would contribute to Aβ detection and early diagnosis of AD in the future.

We have previously developed a NiCr strain-gauge cantilever-based biosensor with liposomes as sensing biomolecules immobilized on the cantilever surface to investigate time course of dynamic behaviour of amyloid-beta (1-40) protein on lipid membrane [1] . In this work, we attempt to improve effectively the sensitivity of the cantilever sensor by incorporating liposome with cholesterol to enhance Aβ-membrane interaction. Consequently, the sensitivity of the biosensor is significantly improved as 50-nM Aβ(1-40) has been detected. This result shows the possibility of detecting Aβ(1-40) in plasma of Alzheimer's disease (AD) patients because Aβ concentration in the plasma of AD patients is reported to be in the range from 75 to 100 nM [2] .

We have successfully detected fibrillization process of amyloid-beta(1-40) protein (Aβ(1-40)) as causative compounds of Alzheimer's disease by our developed bio array sensing system utilizing different phospholipid liposomes encapsulating fluorescent molecules. The fluorescent intensity is dependent on the leakage of fluorescent molecules through perturbed lipid membrane of liposome. Therefore, the intensity considerably depends on the liposome-Aβ interaction strength on fibrillization process of Aβ(1-40). It is noted that the behavior of the fluorescent intensity corresponded to that of our cantilever sensor when measuring the interaction. Moreover, difference in Aβ(1-40) concentration or liposome-Aβ(1-40) interaction strength was successfully discriminated by principal component analysis. Consequently, we believe that the fluorescent liposome sensor is very effective for discriminating aggregation and fibrillization processes and concentrations of Aβ(1-40).

Vibration modes of MEMS piezoelectric diaphragms responding to an ultrasound pulse were investigated and influence of top electrodes to the vibration modes was discussed. The top electrode has a centrosymmetric shape divided into inner part for ultrasonic sensing and outer part for resonant frequency tuning. Piezoelectric output signal is generated in the inner electrode by centrosymmetric vibrations. The piezoelectric diaphragms were fabricated in flat or buckled shape and the top electrodes of various thickness were formed on them. Pulse-induced vibration modes were evaluated by using scanning laser Doppler vibrometry. The buckled diaphragms showed resonant peaks in a narrower frequency range compared to the flat diaphragm. The top electrode showed an influence on the vibration modes so that vibrations with a large amplitude spontaneously concentrated in the sensing electrode area, even in the case of a thin electrode film around 10nm.

Complications during local anesthesia include increased blood pressure and vasovagal reflex, which are caused by changes in the autonomic nervous system. The commonly used local anesthetic preparations are lidocaine to which the vasoconstrictor epinephrine is added (lidocaine-epinephrine) and prilocaine to which the vasoconstrictor felypressin is added (prilocaine-felypressin); however, their effects during dental treatment are unclear. We examined the effects of these 2 different local anesthetic preparations on the autonomic nervous system and circulation during extraction of the impacted mandibular third molar.In this randomized controlled trial, 40 female patients scheduled for extraction of an impacted mandibular third molar were randomized to the lidocaine-epinephrine group or prilocaine-felypressin group. Heart rate variability, heart rate, and systolic blood pressure were recorded during the experiment. Descriptive and bivariate statistics were computed, and the P value was set at .05.The low frequency-high frequency ratio was significantly increased in the prilocaine-felypressin group during extraction compared with that in the lidocaine-epinephrine group (P .05). In the lidocaine-epinephrine group, a significant decrease in the high-frequency component was observed during bone removal and extraction compared with that at rest (P .05). In both groups, a significant increase in systolic blood pressure was observed during local anesthesia, incision and reflection of the flap, bone removal, separation of the tooth crown, extraction, and suturing compared with that at rest (P .01).This study is the first to investigate the differences in the influence of 2 different local anesthetic preparations on the autonomic nervous system during extraction of the mandibular third molar. Changes in circulatory dynamics during tooth extraction with the 2 different local anesthetic preparations were the result of a decrease in parasympathetic nervous activity with lidocaine-epinephrine and an increase in sympathetic nervous activity with prilocaine-felypressin.