Assessment of exercise-induced stress via automated measurement of salivary cortisol concentrations and the testosterone-to-cortisol ratio: a preliminary study.

In this study, our aim was to validate whether the automated measurement of salivary testosterone and cortisol concentrations and the testosterone-to-cortisol (T/C) ratio, considering their individual circadian rhythms can be used to assess the stress response of male athletes to different exercise intensities accurately and effectively. We measured the salivary testosterone and cortisol concentrations and their respective serum concentrations that were collected from 20 male long-distance runners via passive drooling in the morning and evening for two consecutive days involving different exercise intensities. An electrochemiluminescence immunoassay was performed to evaluate the salivary testosterone and cortisol concentrations. The results showed a positive correlation between the salivary testosterone and cortisol concentrations and their respective serum concentrations. The participants were divided into two groups: with and without interval training. The interval training group showed a significantly higher rate of change in the salivary cortisol concentration and a significantly lower rate of change in the T/C ratio in the evening interval training on day 1 than lower-intensity running on day 2. Our results indicated that the salivary cortisol concentrations and the T/C ratio could distinguish between exercises at different intensities, which may be beneficial for detecting differences in stress responses among athletes.

Age-Related Sex Differences in Glucose Tolerance by 75 g Oral Glucose Tolerance Test in Japanese.

To elucidate the age-related sex difference in glucose tolerance, we conducted 75 g oral glucose tolerance tests in 1156 participants. Participants were divided into four groups, namely, young (22−29) males, young females, middle-aged (>50) males, and middle-aged females. According to the Japanese Clinical Practice Guideline for Diabetes 2019, the prevalence of normal glucose tolerance (NGT) was significantly lower in middle-aged than in young participants. The prevalence of high-normal fasting plasma glucose (FPG) was higher, and NGT was lower in young males (high-normal FPG 15.2%, NGT 82.0%) than young females (high-FPG 3.9%, NGT 94.3%). Combined glucose intolerance (CGI) was higher and NGT was lower in middle-aged males (CGI 10.2%, NGT 25.2%) than in middle-aged females (CGI 3.3%, NGT 39.8%). FPG and body mass index (BMI) were the lowest and Homeostatic model assessment beta cell function (HOMA-ß) was the highest in young females, followed by young males, middle-aged females, and middle-aged males. Multiple linear regression analysis revealed that BMI weakly correlated with HOMA-ß and Matsuda index in all subjects except young females. The superior glucose tolerance in females was apparent in young, but attenuated in middle-aged females. The differences are due to the higher insulin secretion potential and lower BMI in young females.

Serological Screening of Immunoglobulin G against SARS-CoV-2 Nucleocapsid and Spike Protein before and after Two Vaccine Doses among Healthcare Workers in Japan.

This study sought to evaluate the effects of two vaccine doses and the extent of SARS-CoV-2 infection among healthcare workers. We measured immunoglobulin G antibody titers against SARS-CoV-2 nucleocapsid and spike protein among healthcare workers at Gunma University Hospital. In March 2021, prior to BNT-162b2 vaccination, two of 771 participants were seropositive for nucleocapsid and spike protein, whereas 768 were seronegative. The remaining one participant was seropositive for nucleocapsid protein but seronegative for spike protein. A total of 769 participants were seropositive for spike protein after two vaccination doses. The two seropositive participants prior to vaccination showed the highest antibody titers after the second vaccination. They were probably infected with SARS-CoV-2 without clinical symptoms before March 2021. Four weeks after the second vaccination, a younger age was associated with higher antibody titers against SARS-CoV-2 spike protein. Thirty-two weeks after the second vaccination, blood samples were collected from 342 of 769 participants. Antibody titers at 32 weeks after the second vaccination significantly decreased compared with those at 4 weeks after the second vaccination among all age groups. The rate of decrease in antibody titers between 4 and 32 weeks after the second vaccination was greater in the female participants. No sex differences were observed in the antibody titers within each age group. BNT-162b2 vaccination thus induced seroconversion in an age-dependent manner. Serological screening could further establish the likelihood of subclinical SARS-CoV-2 infection.

Association Between Insulin Resistance and Cardinal Rheological Parameters in Young Healthy Japanese Individuals During 75g Oral Glucose Tolerance Test.

BACKGROUND: Insulin resistance is a well-known predictor and risk factor for type 2 diabetes mellitus (T2DM). Higher hematocrit induced by higher insulin resistance affects blood rheology. OBJECTIVE: This study intended to reveal the association between indices of insulin resistance and hemorheological parameters during a 75 g oral glucose tolerance test (75-g OGTT). METHODS: A total of 575 healthy young Japanese participants took 75-g OGTT. We then analyzed the association between insulin resistance indices and hematological parameters. RESULTS: The Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was significantly correlated with hematocrit (Ht), hemoglobin (Hb), red blood cell (RBC), white blood cell (WBC), platelet count, lipid parameters and body mass index (BMI). The Matsuda index was negatively correlated with RBC count, WBC count, platelet count, total cholesterol (TC), low-density lipoprotein- cholesterol (LDL-C), triglyceride (TG), and positively correlated with high-density lipoprotein- cholesterol (HDL-C). The disposition index was negatively correlated with Hb, RBC count, LDL-C and BMI, and positively correlated with HDL-C. The Homeostasis Model Assessment of beta cell (HOMA-ß) was positively correlated with WBC count, platelet count, TC, LDL-C and TG. The insulinogenic index was positively correlated with WBC count, platelet count and TC. Multiple regression analysis revealed that HOMA-IR was independently associated with TG, and the Matsuda index was independently associated with TG, WBC count, and platelet count. The insulinogenic index was independently associated with WBC count. CONCLUSION: Cardinal rheological parameters reflected insulin resistance and release even in young healthy Japanese individuals within the physiological range of glycemic control.

Single-photon emission from isolated monolayer islands of InGaN.

We identify and characterize a novel type of quantum emitter formed from InGaN monolayer islands grown using molecular beam epitaxy and further isolated via the fabrication of an array of nanopillar structures. Detailed optical analysis of the characteristic emission spectrum from the monolayer islands is performed, and the main transmission is shown to act as a bright, stable, and fast single-photon emitter with a wavelength of ~400 nm.

Preemptive angioplasty for contralateral leg stenosis following EXCLUDER Iliac Branch Endoprosthesis implantation.

The GORE EXCLUDER Iliac Branch Endoprosthesis (IBE) device is designed to seal off a common iliac artery (CIA) aneurysm, preserving the internal iliac artery during endovascular aortic repair. We report the case of an 84-year-old man with isolated saccular right CIA aneurysm (35 mm) and a relatively small terminal aorta (24 mm). The IBE device was successfully placed, and intraoperative angiography revealed no leakage or delay. However, postoperative computed tomography revealed marked compression of the contralateral leg by a bridging component. Although his ankle-brachial index was preserved, its acute occlusion was judged highly possible; we decided to perform preemptive angioplasty. The angiography revealed the stenosis only in the left anterior oblique view, and angioplasty was uneventfully performed. The leg was successfully patent at 1-year follow-up. When compression by IBE and bridging component in the terminal aorta is expected, caution should be preserved at intraoperative angiography following the device deployment.

Prolonged plasma glucose elevation on oral glucose tolerance test in young healthy Japanese individuals.

AIMS: This study aims to assess insulin secretion and resistance through oral glucose tolerance test (OGTT) among young Japanese individuals. SUBJECTS AND METHODS: We enrolled 595 young healthy Japanese individuals aged 22-29 years. They underwent an OGTT, and their results were divided into 4 groups (I-IV), according to the time at which their plasma glucose concentration declined below the fasting glucose concentration (30, 60 or 120 minutes or never as groups I, II, III and IV, respectively). RESULTS: We classified 575 normal glucose-tolerant subjects into 4 groups (I-IV) with I: 28 (4.9%), II: 120 (20.9%), III: 143 (24.9%) and IV: 284 (49.4%) individuals. The Matsuda, insulinogenic and disposition indices were decreased from groups I to IV. ROC curves of disposition index reflecting the composition of insulin secretion and sensitivity classified the prolonged glucose elevation group (group III + IV) from the rapid glucose lowering group (group II; AUC = 0.847). CONCLUSIONS: Even in a young and healthy Japanese individual within the physiological range of glycaemic control, there is a sequential decrease in insulin sensitivity and secretion.

Rapidly Progressed Distal Arch Aneurysm with Distal Open Stent Graft-Induced New Entry Caused by "Spring-Back" Force.

The J Graft Open Stent Graft (JOSG) is used for the frozen elephant trunk procedure in Japan. We report a 70-year-old male who developed a rapidly progressing distal arch aneurysm caused by a distal stent graft-induced new entry (DSINE) 7 months after the procedure. The JOSG was originally implanted at the curved part of the distal arch. It created its initial DSINE on the greater curve and rapidly "sprang" back in 2 months. Urgent thoracic endovascular aortic repair fixed this serious complication. We should remember such rapid progression of DSINE by JOSG and treat its initial sign earlier.

Risk Factors for Atrial Fibrillation Recurrence After Cox Maze IV Performed Without Pre-exclusion.

BACKGROUND: New guidelines from The Society of Thoracic Surgeons recommend adding surgical ablation as a concomitant procedure for class I indications. We performed the maze procedure for all patients who experienced atrial fibrillation (AF) before cardiac surgery, without surgeon pre-exclusion. METHODS: We retrospectively analyzed 83 patients, aged 71 ± 11 years (22% >80 years), who underwent Cox maze IV for persistent AF between 2014 and 2017. The mean AF duration (AFD) was 6.9 ± 8.6 years and European System for Cardiac Operative Risk Evaluation II was 7.2 ± 6.8. RESULTS: The 30-day mortality was 2.4%. During follow-up (mean, 675 days), the 1-, 2-, and 3-year survival rates were 92%, 86%, and 82%, respectively. No strokes were observed despite a mean CHA2DS2-VASC (Congestive heart failure, Hypertension, Age [≥65 = 1 point, ≥75 = 2 points], Diabetes, and Stroke/transient ischemic attack [2 points], vascular disease, Sex [female = 1 point]) score of 4.1 (expected stroke rate, 4%/y). Twelve patients required a new pacemaker; 56 of 73 survivors (77%) remained AF free. Multivariate logistic regression identified preoperative AFD, f wave size, and mean heart rate per Holter as important risk factors for AF recurrence, with AFD as the most important: 98% of patients with AFD less than 5 years remained AF free. Although the AF-free rate with the AFD of 5 or more years was only 55%, their symptoms improved without heart failure readmission. Concomitant atrial plication was performed more frequently in the group with AFD for 5 or more years, with greater atrial volume reduction and appreciable increases in stroke volume. CONCLUSIONS: The Cox maze IV procedure performed without pre-exclusion showed reasonable survival rates. Although AF recurred in patients with longer AFD, they fared well with substantial increases in stroke volume. Concomitant atrial volume reduction may have contributed to these additional benefits.

[Surgical Treatment of Aortic Stenosis Combined with Bilateral Pheochromocytomas in a Dialysis Patient].

We report a case of a dialysis patient with severe aortic stenosis(AS) along with bilateral pheochromocytomas. A 52-year-old man presented with syncope and was diagnosed with severe AS. Although aortic valve replacement(AVR) was scheduled, bilateral pheochromocytomas were found during preoperative examination. There was a high possibility of developing hemodynamical crisis during AVR, and we planned to perform adrenalectomy prior to AVR. To avoid circulatory collapse just after adrenalectomy, balloon aortic valvuloplasty (BAV) was performed beforehand. Two weeks after the adrenalectomy, AVR was performed in a stable condition.

[Euglycemic Diabetic Ketoacidosis Caused by a Sodium-glucose Co-transporter (SGLT) 2 Inhibitor after Coronary Artery Bypass Grafting].

A 65-year-old woman with type Ⅱ diabetes and unstable angina presented with chest pain due to in-stent restenosis. Her regular medication comprised an sodium-glucose co-transporter( SGLT) 2 inhibitor. Because of unstable hemodynamic status, semi-emergency coronary artery bypass grafting (CABG) was performed. Postoperatively, the cardiac and hemodynamic status stabilized, but there was progression of metabolic acidosis. Based on the presence of massive urinary ketone bodies without hyper glycosuria, the patient was diagnosed with euglycemic diabetic ketoacidosis( DKA) caused by an SGLT2 inhibitor. Ketoacidosis without elevated blood glucose( i.e., euglycemic DKA) has been reported to be associated with intake of an SGLT2 inhibitor, which promoted glucose excretion in the urine. Our patient developed euglycemic DKA due to the progression of myocardial ischemia and surgical stress. Guidelines in other countries have stipulated that SGLT2 inhibitor should be stopped 24 hours preoperatively. In our case, euglycemic DKA occurred even when the SGLT2 inhibitor was stopped for more than 24 hours preoperatively. Further studies on the withdrawal of an SGLT2 inhibitor in the appropriate perioperative period are required.

Extended Posterior Leaflet Augmentation for Ischemic Mitral Regurgitation　- Augmented Posterior Leaflet Snuggling up to Anterior Leaflet.

BACKGROUND: The ideal surgical technique for ischemic mitral regurgitation (MR) is controversial. We introduced an extended posterior mitral leaflet (PML) augmentation technique for functional MR with severe tethering, which detached the PML from the annulus almost completely and augmented it with a large 3×6-cm oval pericardial patch. Methods and Results: A total of 17 mitral repairs using the new technique were performed for ischemic MR with no 30-day mortality and 2 hospital deaths. The NYHA class was III in 47% and IV in 13%. The EuroSCORE II was 9.7±4.9. The ring size was 32±1.4 mm. Concomitant coronary bypass was performed in 67% and left ventricular repair in 28%. The mechanism of leaflet closure was evaluated using transthoracic echocardiography in 15 survivors. MR decreased to none or trivial with a significant increase in coaptation length (Pre: 4.6±0.8 mm vs. Post: 9.8±2.5 mm; P<0.001). The PML flexibly moved forward and tightly contacted as if "snuggling up" to the anterior leaflet. There were no late deaths, heart failure readmissions or MR recurrences during follow-up (850±181 days). All patients remained in NYHA I or II. CONCLUSIONS: Extended PML augmentation for ischemic MR showed excellent early results with deep leaflet coaptation through a "snuggling up" phenomenon, which would help prevent late MR recurrence.

Biological Antioxidant Potential Negatively Correlates With Carotid Artery Intima-Media Thickness.

Oxidative stress is a crucial factor in the pathogenesis and development of cardiovascular disease. Recently, simplified methods for the detection of reactive oxygen species (ROS) using the derivatives of reactive oxygen metabolites (d-ROMs) test as an index of ROS products and the biological antioxidant potential (BAP) test as an index of antioxidant potential have been utilized. These methods are easy to perform, quick, inexpensive since they use small equipment, and provide reliable results compared with established oxidative stress and antioxidant markers. Because oxidative stress has been shown to represent the balance of production of ROS and antioxidant capacity, it is more appropriate to evaluate ROS and antioxidant capacity simultaneously. However, no study has examined the associations among d-ROMs, BAP values, and carotid artery intima-media thickness (IMT) concurrently. Therefore, we studied the associations among d-ROMs, BAP values, and the carotid artery IMT. Carotid artery IMT, blood pressure (BP), fasting circulating d-ROMs, BAP, glucose metabolism, lipid, and C-reactive protein levels were measured in 95 subjects (age: 49.5 ± 13.8 years; men: 41; women: 54), including 42 healthy subjects and 53 patients with hypertension, dyslipidemia, and diabetes mellitus who were not on medication. The results of multiple regression analysis revealed that dependent carotid artery IMT determinants remained significantly associated with age, systolic BP, total cholesterol, and BAP, whereas dependent BAP determinants remained significantly associated with body mass index and carotid artery IMT. BAP was strongly correlated with carotid artery IMT in our cohort. Our results suggest that BAP may be a useful risk marker for carotid atherosclerosis.

Fasting serum insulin levels and insulin resistance are associated with blood rheology in Japanese young adults without diabetes.

OBJECTIVES: To evaluate fasting serum insulin levels and insulin resistance, and their association with blood rheology, in Japanese young adults without diabetes. METHODS: Blood samples were analysed and blood rheology was estimated using haematological parameters. Whole blood passage time was measured using a Hitachi MC-FAN(©) microchannel array flow analyser. RESULTS: Out of 151 subjects (mean age, 24.1 ± 1.5 years), fasting serum insulin levels and insulin resistance (using homeostasis model assessment-estimated insulin resistance [HOMA-IR]), were positively correlated with longer whole blood passage times and higher values for haematocrit (Hct), haemoglobin (Hb), fibrinogen, body weight, body mass index (BMI), triglycerides, and low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio, and were negatively correlated with HDL-C. Whole blood passage time correlated with body weight, BMI, LDL-C/HDL-C ratio, Hct, Hb, white blood cell (WBC) count, platelet count, fibrinogen, fasting serum insulin levels, and HOMA-IR. Multiple regression analysis revealed that whole blood passage time was independently associated with Hct, fibrinogen levels, and WBC count. CONCLUSIONS: Fasting serum insulin levels and insulin resistance were associated with blood rheology, and may influence blood rheology by modulating haematological parameters and lipid parameters in young adults without diabetes.

Impaired blood rheology is associated with endothelial dysfunction in patients with coronary risk factors.

To investigate the relationship between blood rheology and endothelial function in patients with coronary risk factors, brachial arterial flow-mediated vasodilatation (FMD), an index of endothelial function and blood passage time (BPT), an index of blood rheology, and fasting blood cell count, glucose metabolism, and plasma fibrinogen, lipid, C-reactive protein, and whole blood viscosity levels were measured in 95 patients with coronary risk factors and 37 healthy controls. Brachial arterial FMD after reactive hyperemia was assessed by ultrasonography. BPT was assessed using the microchannel method. In healthy controls, BPT significantly correlated with FMD (r = - 0.325, p <  0.05), HDL cholesterol (r = - 0.393, p <  0.05), body mass index (BMI; r = 0.530, p <  0.01), and plasma fibrinogen concentration (r = 0.335, p <  0.05). In a multivariate regression analysis adjusted for all clinical variables, BPT remained significantly associated with BMI and fibrinogen, but not with FMD, in healthy controls. In patients with coronary risk factors, BPT significantly correlated with FMD (r = - 0.331, p <  0.01), HDL cholesterol (r = - 0.241, p <  0.05), BMI (r = 0.290, p <  0.01), hematocrit (r = 0.422, p <  0.001), white blood cell count (r = 0.295, p <  0.01), platelet count (r = 0.204, p <  0.05), and insulin (r = 0.210, p <  0.05). In a multivariate regression analysis adjusted for all clinical variables, BPT remained strongly associated with FMD and hematocrit in patients with coronary risk factors. These data indicate that BPT is closely associated with FMD in patients with coronary risk factors and suggest that the measurement of blood rheology using the microchannel method may be useful in evaluating brachial arterial endothelial function as a marker of atherosclerosis in these patients.

Type 2 Iodothyronine Deiodinase Activity Is Required for Rapid Stimulation of PI3K by Thyroxine in Human Umbilical Vein Endothelial Cells.

Thyroid hormones (THs) exert a number of physiological effects on the cardiovascular system. Some of the nongenomic actions of T3 are achieved by cross coupling the TH receptor (TR) with the phosphatidylinositol 3-kinase (PI3K)/protein kinase Akt (Akt) pathway. We observed that both T3 and T4 rapidly stimulated Akt phosphorylation and Ras-related C3 botulinum toxin substrate 1 (Rac1) activation, which resulted in cell migration, in a PI3K-dependent manner in human umbilical vein endothelial cells (HUVECs). We identified the expression of type 2 iodothyronine deiodinase (D2), which converts T4 to T3, and TRα1 in HUVECs. D2 activity was significantly stimulated by (Bu)2cAMP in HUVECs. The blockade of D2 activity through transfection of small interfering RNA (siRNA) specific to D2 as well as by addition of iopanoic acid, a potent D2 inhibitor, abolished Akt phosphorylation, Rac activation, and cell migration induced by T4 but not by T3. The inhibition of TRα1 expression by the transfection of siRNA for TRα1 canceled Akt phosphorylation, Rac activation, and cell migration induced by T3 and T4. These findings suggest that conversion of T4 to T3 by D2 is required for TRα1/PI3K-mediated nongenomic actions of T4 in HUVECs, including stimulation of Akt phosphorylation and Rac activation, which result in cell migration.

Relationship between carotid artery intima-media thickness and small dense low-density lipoprotein cholesterol concentrations measured by homogenous assay in Japanese subjects.

BACKGROUND: Small dense low-density lipoprotein cholesterol (sdLDL-C) concentrations correlate more strongly with coronary heart disease than other LDL-C and large LDL particle concentrations. We investigated the association between carotid artery intima-media thickness (IMT) and sdLDL-C concentrations in Japanese subjects. METHODS: Carotid artery IMT, blood pressure (BP), fasting plasma sdLDL-C, glucose metabolism, lipid, and C-reactive protein concentrations were measured in 97 native Japanese subjects. Carotid artery IMT was assessed by ultrasonography, and sdLDL-C concentrations were measured by a homogenous assay. Pearson's correlation coefficient analyses and multiple regression analyses were used to examine the relationships between carotid artery IMT values, sdLDL-C values, and other clinical variables. RESULTS: After multiple regression analysis, including age, sex, body mass index, systolic BP, diastolic BP, fasting plasma glucose, HbA1c, estimated glomerular filtration rate (eGFR), total-C, high-density lipoprotein (HDL)-C, triglyceride, LDL-C, non-HDL-C, large buoyant LDL-C, and sdLDL-C, carotid artery IMT remained significantly associated with age, systolic BP, diastolic BP, and sdLDL-C, whereas sdLDL-C remained significantly associated with age, total-C, HDL-C, triglycerides, and carotid artery IMT. CONCLUSIONS: When measured by a homogenous assay, carotid artery IMT may have a closer relationship with sdLDL-C concentrations than other lipid parameters in Japanese subjects. sdLDL-C may be a potentially useful risk marker when assessing carotid artery IMT in Japanese subjects.

Glucagon-like peptide-1 stimulates type 3 iodothyronine deiodinase expression in a mouse insulinoma cell line.

AIMS: The pathophysiological roles of thyroid hormones in glucose metabolism remain uncertain. Type 3 iodothyronine deiodinase (D3) converts thyroxine (T4) and 3,5,3'-triiodothyronine (T3) to 3,3',5'-triiodothyronine (rT3) and 3,3'-diiodothyronine (T2), respectively, inactivating thyroid hormones in a cell-specific fashion. In the present study, we identified D3 expression in MIN6 cells derived from a mouse insulinoma cell line and examined the mechanisms regulating D3 expression in these cells. MAIN METHODS: We characterized D3 activity using HPLC analysis, and examined the effect of GLP-1 or exendin-4 on D3 expression and cAMP accumulation in MIN6 cells. We also measured insulin secretion from MIN6 cells exposed to GLP-1 and T3. KEY FINDINGS: We identified enzyme activity that catalyzes the conversion of T3 to T2 in MIN6 cells, which showed characteristics compatible with those for D3. D3 mRNA was identified in these cells using RT-PCR analysis. Forskolin rapidly stimulated D3 mRNA and D3 activity. Glucagon-like peptide-1 (GLP-1) increased D3 expression in a dose-dependent manner, and this effect was inhibited by the protein kinase A (PKA) inhibitor H-89. Exendin-4, a GLP-1 receptor agonist, also stimulated D3 expression in MIN6 cells. These results suggest that a cAMP-PKA-mediated pathway participates in GLP-1-stimulated D3 expression in MIN6 cells. Furthermore, GLP-1 stimulated insulin secretion was suppressed by the addition of T3 in MIN6 cells. SIGNIFICANCE: Our findings indicate that GLP-1 regulates intracellular T3 concentration in pancreatic ß cells via a cAMP-PKA-D3-mediated pathway that may also regulate ß-cell function.