Gender Differences in Patients with Gastric Adenocarcinoma.

Background: Gastric cancer (GC) epidemiology and outcomes vary by gender. Methods: We reviewed 18,436 GC patients from 2008 to 2018 and looked for gender differences in clinical characteristics and survival. Results: The gender proportion was 71% male and 29% female. Males had a significantly (p < 0.001) higher proportion of differentiated GC (66.3%) and a lower proportion of undifferentiated GC (26.3%). Diagnosis through medical check-ups was more common in males (30.0% vs. 26.4%, p < 0.001). Clinical staging revealed 54.6% of males and 52.9% of females had localized disease without lymph node metastasis (LNM), while distant metastasis occurred in 17.4% of males and 16.9% of females (p < 0.001). Kaplan-Meier survival curves indicated females had a significantly higher overall survival (p = 0.0018). The survival advantage for females was evident in the early stages, with a significant difference in localized disease without LNM (p < 0.001) and localized disease with LNM (p = 0.0026, log-rank test) but not in the advanced stages. Multivariate Cox regression analysis showed a significantly reduced mortality risk in females (p < 0.001). Conclusions: Significant gender differences exist with regard to pathological type, presentation, clinical stage, and overall survival. These findings suggest gender-specific strategies for screening, diagnosis, and treatment.

C16, a PKR inhibitor, suppresses cell proliferation by regulating the cell cycle via p21 in colorectal cancer.

Double-stranded RNA-activated protein kinase R (PKR) is highly expressed in colorectal cancer (CRC). However, the role of PKR in CRC remains unclear. The aim of this study was to clarify whether C16 (a PKR inhibitor) exhibits antitumor effects and to identify its target pathway in CRC. We evaluated the effects of C16 on CRC cell lines using the MTS assay. Enrichment analysis was performed to identify the target pathway of C16. The cell cycle was analyzed using flow cytometry. Finally, we used immunohistochemistry to examine human CRC specimens. C16 suppressed the proliferation of CRC cells. Gene Ontology (GO) analysis revealed that the cell cycle-related GO category was substantially enriched in CRC cells treated with C16. C16 treatment resulted in G1 arrest and increased p21 protein and mRNA expression. Moreover, p21 expression was associated with CRC development as observed using immunohistochemical analysis of human CRC tissues. C16 upregulates p21 expression in CRC cells to regulate cell cycle and suppress tumor growth. Thus, PKR inhibitors may serve as a new treatment option for patients with CRC.

Association between bowel movement frequency and erectile dysfunction in patients with ulcerative colitis: a cross-sectional study.

The association between ulcerative colitis (UC) and erectile dysfunction (ED) has been previously reported. Numerous previous studies have also reported an association between gastrointestinal symptoms and ED. Constipation and diarrhea are common in patients with UC. However, the specific association between bowel movement frequency and ED remains unclear. The aim of this study is to investigate the association between bowel movement frequency and ED in 164 patients with UC. The definition of ED, moderate to severe ED, and severe ED was the Sexual Health Inventory for Men score <22, <12, and <8, respectively. Bowel movement frequency was divided into three categories: (1) high (More than once a day), (2) normal (once a day, reference), and low (less than one time/day). The definition of constipation was based on the Rome I criteria and/or medication for constipation. The prevalence of constipation and ED was 10.4% and 86.0%, respectively. The rate of high, normal, and low bowel movement frequency was 56.1%, 25.0%, and 18.9%, respectively. High bowel movement frequency was independently and positively associated with ED and moderate to severe ED (ED: adjusted odds ratio [OR] 4.42, 95% confidence interval [CI] 1.35-15.98; moderate to severe: adjusted OR 2.98, 95% CI 1.22-7.61). Low bowel movement frequency was independently and positively associated with moderate to severe ED and severe ED (moderate to severe: adjusted OR 3.96, 95% CI 1.27-13.08; severe: adjusted OR 3.20, 95% CI 1.08-9.86). No association between constipation and ED was found. In conclusion, in Japanese patients with UC, both high and low bowel movement frequency were independently and positively associated with ED.

Real-world NUDT15 genotyping and thiopurine treatment optimization in inflammatory bowel disease: a multicenter study.

BACKGROUND: This study evaluated the effectiveness of NUDT15 codon 139 genotyping in optimizing thiopurine treatment for inflammatory bowel disease (IBD) in Japan, using real-world data, and aimed to establish genotype-based treatment strategies. METHODS: A retrospective analysis of 4628 IBD patients who underwent NUDT15 codon 139 genotyping was conducted. This study assessed the purpose of the genotyping test and subsequent prescriptions following the obtained results. Outcomes were compared between the Genotyping group (thiopurine with genotyping test) and Non-genotyping group (thiopurine without genotyping test). Risk factors for adverse events (AEs) were analyzed by genotype and prior genotyping status. RESULTS: Genotyping test for medical purposes showed no significant difference in thiopurine induction rates between Arg/Arg and Arg/Cys genotypes, but nine Arg/Cys patients opted out of thiopurine treatment. In the Genotyping group, Arg/Arg patients received higher initial doses than the Non-genotyping group, while Arg/Cys patients received lower ones (median 25 mg/day). Fewer AEs occurred in the Genotyping group because of their lower incidence in Arg/Cys cases. Starting with < 25 mg/day of AZA reduced AEs in Arg/Cys patients, while Arg/Arg patients had better retention rates when maintaining ≥ 75 mg AZA. Nausea and liver injury correlated with thiopurine formulation but not dosage. pH-dependent mesalamine reduced leukopenia risk in mesalamine users. CONCLUSIONS: NUDT15 codon 139 genotyping effectively reduces thiopurine-induced AEs and improves treatment retention rates in IBD patients after genotype-based dose adjustments. This study provides data-driven treatment strategies based on genotype and identifies risk factors for specific AEs, contributing to a refined thiopurine treatment approach.

Effects of BNT162b2 mRNA Covid-19 vaccine on vascular function.

The effects of Covid-19 vaccines on vascular function are still controversial. We evaluated the effects of BNT162b2 vaccine (BioNTech and Pfizer) on endothelial function assessed by flow-mediated vasodilation (FMD) and vascular smooth muscle function assessed by nitroglycerine-induced vasodilation (NID). This study was a prospective observational study. A total of 23 medical staff at Hiroshima University Hospital were enrolled in this study. FMD and NID were measured before vaccination and two weeks and six months after the 2nd dose of vaccination. FMD was significantly smaller two weeks after the 2nd dose of vaccination than before vaccination (6.5±2.4% and 8.2±2.6%, p = 0.03). FMD was significantly larger at six months than at two weeks after the 2nd dose of vaccination (8.2±3.0% and 6.5±2.4%, p = 0.03). There was no significant difference between FMD before vaccination and that at six months after the 2nd dose of vaccination (8.2±2.6% to 8.2±3.0%, p = 0.96). NID values were similar before vaccination and at two weeks, and six months after vaccination (p = 0.89). The BNT162b2 Covid-19 vaccine temporally impaired endothelial function but not vascular smooth muscle function, and the impaired endothelial function returned to the baseline level within six months after vaccination.

A nationwide survey of facial onset sensory and motor neuronopathy in Japan.

The epidemiology and etiology of facial onset sensory and motor neuronopathy (FOSMN), a rare syndrome that initiates with facial sensory disturbances followed by bulbar symptoms, remain unknown. To estimate the prevalence of FOSMN in Japan and establish the characteristics of this disease, we conducted a nationwide epidemiological survey. In the primary survey, we received answers from 604 facilities (49.8%), leading to an estimated number of 35.8 (95% confidential interval: 21.5-50.2) FOSMN cases in Japan. The secondary survey collected detailed clinical and laboratory data from 21 cases. Decreased or absent corneal and pharyngeal reflexes were present in over 85% of the cases. Electrophysiological analyses detected blink reflex test abnormalities in 94.1% of the examined cases. Immunotherapy was administered in 81% of cases and all patients received intravenous immunoglobulin. Among them, 35.3% were judged to have temporary beneficial effects evaluated by the physicians in charge. Immunotherapy tended to be effective in the early stage of disease. The spreading pattern of motor and sensory symptoms differed between cases and the characteristics of the motor-dominant and sensory-dominant cases were distinct. Cases with motor-dominant progression appeared to mimic amyotrophic lateral sclerosis. This is the first nationwide epidemiological survey of FOSMN in Japan. The clinical course of FOSMN is highly variable and motor-dominant cases developed a more severe condition than other types of cases. Because clinical interventions tend to be effective in the early phase of the disease, an early diagnosis is desirable.

Non-invasive blood glucose estimation method based on the phase delay between oxy- and deoxyhemoglobin using visible and near-infrared spectroscopy.

Significance: Many researchers have attempted to estimate blood glucose levels (BGLs) noninvasively using near-infrared (NIR) spectroscopy. However, the optical absorption change induced by blood glucose is weak in the NIR region and often masked by interference from other components such as water and hemoglobin. Aim: Instead of using direct optical absorption by glucose, this study proposes an index calculated from oxy- and deoxyhemoglobin signals that shows a good correlation with BGLs while using conventional visible and NIR spectroscopy. Approach: The metabolic index, which is based on tissue oxygen consumption, was derived through analytical methods and further verified and reproduced in a series of glucose challenge experiments. Blood glucose estimation units were prototyped by utilizing commercially available smart devices. Results: Our experimental results showed that the phase delay between the oxy- and deoxyhemoglobin signals in near-infrared spectroscopy correlates with BGL measured by a conventional continuous glucose monitor. The proposed method was also confirmed to work well with visible spectroscopy systems based on smartphone cameras. The proposed method also demonstrated excellent repeatability in results from a total of 19 oral challenge tests. Conclusions: This study demonstrated the feasibility of non-invasive glucose monitoring using existing photoplethysmography sensors for pulse oximeters and smartwatches. Evaluating the proposed method in diabetic or unhealthy individuals may serve to further increase its practicality.

A new grading assessment of eosinophilic esophagitis using red dichromatic imaging: A pilot study.

BACKGROUND AND AIMS: The endoscopic reference score (EREFS) using white light imaging (WLI) is used for evaluating the severity of findings objectively in patients with eosinophilic esophagitis (EoE). A novel image-enhanced endoscopy, red dichromatic imaging (RDI) can visualize deeper vessels in the gastrointestinal tract, which could assess edema more precise than WLI. METHODS: A total of 21 consecutive patients with EoE were prospectively evaluated. Patients were categorized by three grades based on the visibility of vessels with RDI. Clinical features, such as peak eosinophil counts (PEC) and presence of symptoms, were reviewed. RESULTS: There were 10 patients with RDI Grade 0/1, and 11 patients with RDI Grade 2. PEC and the prevalence of heartburn were significantly higher in patients with RDI Grade 2 than in patients with RDI Grade 0/1. CONCLUSIONS: The severity of eosinophilic infiltration could be predicted more precisely using RDI than by evaluating with WLI.

Seasonal variations in endothelium-dependent flow-mediated vasodilation and endothelium-independent nitroglycerine-induced vasodilation.

Cardiovascular mortality has been shown to vary seasonally. However, it has not been determined whether vascular function is affected by the season. The purpose of this study was to investigate the associations of vascular function with season and outdoor temperature. Between April 2007 and March 2022, measurements of flow-mediated vasodilation (FMD) of the brachial artery as an index of endothelial function and nitroglycerine-induced vasodilation (NID) as an index of endothelium-independent vasodilation were performed in 2190 subjects. There was no significant seasonal difference in FMD (spring, 3.9 ± 3.1%; summer, 3.5 ± 3.0%; fall, 3.7 ± 3.0%; winter, 3.6 ± 3.2%; P = 0.14). There was no significant correlation between FMD and daily mean outdoor temperature (r = -0.02, P = 0.25). Multivariate analyses revealed that neither season (ß = -0.020, P = 0.31) nor outdoor temperature (ß = 0.005, P = 0.81) was significantly associated with FMD after adjustment for other confounding factors. There were significant seasonal differences in NID (spring, 12.8 ± 6.3%; summer, 12.0 ± 6.1%; fall, 11.7 ± 6.1%; winter, 12.3 ± 5.9%; P = 0.02). However, multivariate analysis revealed that there was no significant association between season and NID after adjustment for other confounding factors (ß = -0.012, P = 0.56). There was no significant correlation between NID and daily outdoor mean temperature (r = -0.03, P = 0.17). Multivariate analysis revealed that outdoor temperature was not significantly associated with NID (ß = -0.006, P = 0.78). There was no significant association of FMD or NID with season or outdoor temperature, suggesting that it is not necessary to take into account the effects of season and outdoor temperature on vascular function when interpreting the results of FMD and NID measurements. Public trials registry number: UMIN000039512.

Serum albumin levels as a useful complementary marker for erectile dysfunction in ulcerative colitis: A cross-sectional study.

OBJECTIVE: Recently, a close association between ulcerative colitis (UC) and erectile dysfunction (ED) was reported. An inverse relationship between serum albumin and ED is found in patients with chronic disease. However, the association between serum albumin levels and ED in patients with UC is unclear. This study aims to investigate this issue in Japanese patients with UC. METHODS: One hundred and thirty-six Japanese male UC patients were enrolled in this study. Information on serum albumin levels and medications for UC from medical records, Sexual Health Inventory for Men (SHIM) score information from self-administered questionnaires and information on the severity of UC from physician reports were obtained from medical records, self-administered questionnaires, and reports from physicians. The participants were divided into tertiles based on the total protein, serum globulin, serum albumin, aspartate aminotransferase, and C-reactive protein levels. The definition of ED and severe ED was SHIM score < 22 and SHIM score < 8, respectively. The association between these serum markers and ED was assessed by multivariate logistic regression. RESULTS: The prevalence of severe ED in the low, moderate, and high albumin groups was 66.0%, 51.0%, and 28.3%, respectively. After adjusting for confounding factors, the low albumin group was independently and positively associated with severe ED (adjusted odds ratio: 2.74, 95% confidence interval: 1.03-7.48, p for trend =0.044). No association between other marker and ED was found. CONCLUSION: Serum albumin was independently inversely associated with severe ED in Japanese patients with UC. Hypoalbuminemia might be a useful complementary marker for assessing the prevalence and severity of ED in UC patients.

Percentage of mean arterial pressure as a marker of atherosclerosis for detecting patients with coronary artery disease.

The percentage of mean arterial pressure (%MAP) is the height of the mean arterial waveform divided by the peak amplitude of the waveform of pulse volume recording. The purpose of this study was to determine whether the cutoff value of 45% for %MAP at the ankle, which is recommended for the diagnosis of lower extremity artery disease, in combination with ankle-brachial index (ABI) is useful for detecting patients with clinical coronary artery disease (CAD) and investigate the optimal cutoff value of %MAP to diagnose patients with CAD.　We measured ABI and %MAP in 2213 subjects　(mean age: 61.2 ± 15.5 years). Multivariate analysis revealed that %MAP ≥ 45% was significantly associated with a higher risk of CAD after adjusting for traditional cardiovascular risk factors (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.43-3.21; p < 0.001). However, the association was no longer significant after adjusting for ABI (OR, 1.39; 95% CI, 0.83-2.33; p = 0.21), whereas ABI was significantly associated with CAD (OR, 0.98; 95% CI, 0.97-0.99; p = 0.005). The optimal cutoff value of %MAP derived from a receiver operating characteristic curve to diagnose CAD was 40.3%. Multivariate analysis revealed that %MAP ≥ 40.3% was significantly associated with a higher risk of CAD (OR, 1.63; 95% CI, 1.19-2.24; p = 0.002) independent of ABI (OR, 0.98; 95% CI, 0.97-0.99; p = 0.002). The cutoff value of 40.3%, but not 45%, for %MAP may be useful for detecting patients with advanced atherosclerosis and for cardiovascular risk assessment independent of ABI. REGISTRATION INFORMATION: http://www.umin.ac.jp (University Hospital Medical Information Network Clinical Trials Registry) (UMIN000039512).

Noonan Syndrome-related Myeloproliferative Disorder Occurring in the Neonatal Period: Case Report and Literature Review.

Noonan syndrome-related myeloproliferative disorder (NS/MPD) and juvenile myelomonocytic leukemia (JMML) are rare MPDs that occur in young children. We herein report a case of NS/MPD with neonatal onset. The patient had a characteristic appearance and high monocyte count in the peripheral blood and bone marrow. Genetic testing showed the E139D mutation in PTPN11 ; however, the patient did not meet all the diagnostic criteria for JMML, and we thus diagnosed him with NS/MPD. Eight other cases of NS/MPD with neonatal onset are also summarized. The initial presentation varied, and the prognosis was considered poor compared with previous reports of NS/MPD.

Aging is Associated With Constipation in Japanese Patients With Ulcerative Colitis: A Post Hoc Analysis.

Aim: Age is a risk factor for constipation. Constipation is common in patients with ulcerative colitis (UC) and has been positively associated with disease activity, but evidence is limited. This study aimed to assess the association between disease activity and constipation in patients with UC. Methods: The study subjects consisted of 290 Japanese UC patients. The definition of constipation was based on Rome I criteria and/or medication for constipation. Information on and lifestyle habits was obtained from a self-administered questionnaire. Mucosal healing (MH) was defined as Mayo endoscopic subscore 0. Clinical remission (CR) was defined as both the absence of rectal bleeding and no abnormally high stool frequency (<3 times per day). Results: The prevalence of constipation is not associated with MH, CR, duration of UC and disease extent of UC. The prevalence of constipation among age groups, <40, 40-49 years, 50-59 years, 60-69 years, and >70 years was 10.0%, 5.8%, 15.7%, 11.8%, and 25.6%, respectively. >70 years was independently and positively associated with the prevalence of constipation (adjusted odds ratio 3.64 [95% confidence interval 1.26, 10.95], p for trend: .001). Conclusions: Aging was independently and positively associated with the prevalence of constipation in UC.

Urethral hemangioma: How to investigate as a cause of hematuria after male sexual activities.

Introduction: Urethral hemangioma is an extremely rare occurrence and is not typically considered a common cause of hematuria. Since 2000, only 22 male cases have been reported. Case presentation: A 45-year-old man presented with recurrent painless gross hematuria and the passage of blood clots after ejaculation. The patient underwent a transurethral resection of a 6-mm hemangioma. This isolated sessile lesion was situated between the distal end of the verumontanum and the external sphincter, following an induced erection. The patient remained asymptomatic during the 1-month follow-up visit. Conclusion: This study included the assessment of patient symptoms, diagnoses, and treatments and the literature review of 22 patients. We propose that relaxation of the external urethral sphincter muscle under general anesthesia and artificially inducing an erection can aid in the identification of urethral hemangiomas near the verumontanum during cystourethroscopy.

Which Coronary Artery Should Be Preferred for Starting the Coronary Spasm Provocation Test?

BACKGROUND: The spasm provocation test (SPT) is a critical test for diagnosing vasospastic angina (VSA). However, the choice of vessel to be preferred for initiating the SPT-the right coronary artery (RCA) or the left coronary artery (LCA)-is unclear. This study aimed to assess SPT results including SPT-related complications while initiating the SPT in the RCA and LCA. METHODS: We enrolled 225 patients who underwent coronary angiography and SPTs. The SPT was first performed in the RCA in 133 patients (RCA group) and the LCA in 92 patients (LCA group). We defined VSA as >90% narrowing of the coronary artery during the SPT, accompanied by chest pain and/or ST-T changes on the electrocardiogram. When coronary spasm occurs in two or more major coronary arteries, it is referred to as a multivessel spasm (MVS). SPT-related complications comprised atrial fibrillation, ventricular fibrillation, and unstable hemodynamics following catecholamine use. Analyses using propensity score matching (PSM) were performed in 120 patients. RESULTS: No significant differences in the frequencies of VSA and complications were observed between the two groups (RCA: 79% and 19%, respectively; LCA: 85% and 22%, respectively). In both groups, spasms were most frequently provoked in the left anterior descending coronary artery (both p < 0.001) whereas spasms in the left circumflex coronary artery (LCX) were higher in the LCA group than in the RCA group (p = 0.015). Furthermore, no significant difference in the frequency of MVS was observed between both groups (RCA: 50%, LCA: 62%; p = 0.122). After PSM, no significant difference in the frequencies of VSA and complications were observed between the two groups (RCA: 82% and 15%, respectively; LCA: 88% and 18%, respectively). The frequencies of LCX spasms (RCA: 8%, LCA: 23%; p = 0.022) and MVS (RCA: 40%, LCA: 62%; p = 0.020) were higher in the LCA group than in the RCA group. CONCLUSIONS: Although the diagnostic rate of VSA and frequency of SPT-related complications were similar in the two groups, the frequency of MVS was higher in the LCA group than in the RCA group because of the increase in the number of LCX spasms. A routine SPT may be started from the LCA.

Severity of Nocturia and Constipation in Patients With Ulcerative Colitis.

OBJECTIVE: To investigate the association between nocturia and constipation in patients with ulcerative colitis (UC). Constipation has recently been recognized as an important symptom in patients with UC. Although nocturia has been associated with constipation in the general population, the association between nocturia and constipation in UC patients is uncertain. METHODS: Consecutive series of 290 Japanese patients with UC, Information on constipation, nocturia, and lifestyle habits was obtained using self-administered questionnaires. The definition of constipation was based on Rome I criteria and/or current medication for constipation. Patients were divided into three groups based on nighttime urination: (1) no nocturia, (2) mild nocturia (nocturnal urination - one), and (3) serious nocturia (nocturnal urination - two or more). Multivariate logistic regression was used to evaluate the association between nocturia and constipation. RESULTS: Among all of the UC patients, the prevalence of mild nocturia, serious nocturia, and constipation was 35.2%, 26.9%, and 12.4%, respectively. The prevalence of constipation in the none, mild, and serious nocturia groups was 8.2%, 10.8%, and 20.5%, respectively. After adjustment for confounders such as age, sex, current drinking, current smoking, body mass index, and steroid use, nocturia severity was independently and positively associated with constipation (adjusted odds ratio for mild nocturia: 1.55 [95% confidence interval: 0.57-4.28], serious nocturia: 3.19 [95% confidence interval: 1.09-9.81], P for trend=.035). CONCLUSION: The severity of nocturia is positively associated with constipation, and physicians should consider the interrelationships between nocturia and constipation in managing UC patients.

KCNJ5 mutation is a predictor for recovery of endothelial function after adrenalectomy in patients with aldosterone-producing adenoma.

The relationship of KCNJ5 mutation with vascular function and vascular structure in aldosterone-producing adenoma (APA) patients before and after adrenalectomy remains unclear. The purpose of this study was to evaluate the influence of KCNJ5 mutation on vascular function and vascular structure in APA and the effects of adrenalectomy on vascular function and vascular structure in APA patients with and those without KCNJ5 mutation. Flow-mediated vasodilation (FMD), nitroglycerine-induced vasodilation (NID), brachial artery intima-media thickness (IMT), and brachial-ankle pulse wave velocity (baPWV) were measured to assess vascular function and vascular structure in 46 APA patients with KCNJ5 mutation and 23 APA patients without KCNJ5 mutation and in 69 matched pairs of patients with essential hypertension (EHT). FMD, NID, brachial IMT and baPVW were evacuated before adrenalectomy and at 12 weeks after adrenalectomy in APA patients with KCNJ5 mutation and APA patients without KCNJ5 mutation. FMD and NID were significantly lower in APA patients than in patients with EHT. There was no significant difference in FMD or NID between patients with and those without KCNJ5 mutation. In APA patients with KCNJ5 mutation, FMD and NID after adrenalectomy were significantly higher than those before adrenalectomy. In APA patients without KCNJ5 mutation, only NID after adrenalectomy was significantly higher than that before adrenalectomy. Endothelial function in APA patients with KCNJ5 mutation was improved by adrenalectomy in the early postoperative period. KCNJ5 mutation is a predictor for early resolution of endothelial function by adrenalectomy. This study was approved by principal authorities and ethical issues in Japan (URL for Clinical Trial: http://www.umin.ac.jp/ctr/index.htm Registration Number for Clinical Trial: UMIN000003409).

Frequency and Clinical Impact of Family History of Coronary Artery Disease in Patients with Vasospastic Angina.

BACKGROUND: Family history (FH) of coronary artery disease (CAD) [FH-CAD] is a well-known risk factor for atherosclerotic CAD. However, FH-CAD frequency in patients with vasospastic angina (VSA) remains unknown, and the clinical characteristics and prognosis of VSA patients with FH-CAD are unclear. Therefore, this study compared FH-CAD frequency between patients with atherosclerotic CAD and those with VSA and examined the clinical characteristics and prognosis of VSA patients with FH-CAD. METHODS: Coronary angiography and spasm provocation tests (SPT) were used to investigate chest pain of coronary artery origin in patients classified into atherosclerotic CAD (362 cases), VSA (221 cases; positive for SPT) and non-VSA (73 cases; negative for SPT) groups, with FH-CAD being defined. In the VSA group, flow-mediated vasodilation (FMD) and nitroglycerin-independent vasodilation (NID) via brachial artery echocardiography and clinical symptoms in the groups with and without FH-CAD were checked, with Kaplan-Meier curves revealing major adverse cardiovascular events (cardiac death and rehospitalisation for cardiovascular disease) between the two groups. RESULTS: The atherosclerotic CAD group had a significantly lower FH-CAD frequency (12%, p = 0.029) than the VSA (19%) and non-VSA groups (19%). FH-CAD was more common in females in the VSA and non-VSA groups than in the atherosclerotic CAD group (p < 0.001). Nonpharmacological treatment for CAD in FH-CAD was more common in the atherosclerotic CAD group (p = 0.017). In the VSA group, FH-CAD tended to be more common in females (p = 0.052). Although no differences in FMD of the brachial artery were observed between the groups, the FH-CAD (+) group had significantly higher NID than the FH-CAD (-) group (p = 0.023). Kaplan-Meier's analysis revealed a similar prognosis between the two groups, and other clinical characteristics did not differ. CONCLUSION: Patients with VSA have a higher FH-CAD frequency than those with atherosclerotic CAD, especially in females. Although FH-CAD may affect vascular function in patients with VSA, its effect on the severity and prognosis of VSA appears to be minimal. FH-CAD and its confirmation may assist in CAD diagnosis, especially in female patients.

Dynamics study of the post-transition-state-bifurcation process of the (HCOOH)H+ → CO + H3O+/HCO+ + H2O dissociation: application of machine-learning techniques.

The process of protonated formic acid dissociating from the transition state was studied using ring-polymer molecular dynamics (RPMD), classical MD, and quasi-classical trajectory (QCT) simulations. Temperature had a strong influence on the branching fractions for the HCO+ + H2O and CO + H3O+ dissociation channels. The RPMD and classical MD simulations showed similar behavior, but the QCT dynamics were significantly different owing to the excess energies in the quasi-classical trajectories. Machine-learning analysis identified several key features in the phase information of the vibrational motions at the transition state. We found that the initial configuration and momentum of a hydrogen atom connected to a carbon atom and the shrinking coordinate of the CO bond at the transition state play a role in the dynamics of HCO+ + H2O production.

Endothelial Function Is Preserved in Patients with Wild-Type Transthyretin Amyloid Cardiomyopathy.

Heart failure (HF) is associated with endothelial dysfunction. Vascular function per se plays an important role in cardiac function, whether it is a cause or consequence. However, there is no information on vascular function in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM). The purpose of this study was to evaluate vascular function in patients with ATTRwt-CM. We measured flow-mediated vasodilation (FMD) as an index of endothelial function and nitroglycerine-induced vasodilation (NID) as an index of vascular smooth muscle function and brachial artery intima-media thickness (bIMT) and brachial-ankle pulse wave velocity (baPWV) as indices of arterial stiffness in 22 patients with ATTRwt-CM and in 22 one-by-one matched control patients using vascular function confounding factors. FMD was significantly greater in patients with ATTRwt-CM than in the controls (5.4 ± 3.4% versus 3.5 ± 2.4%, p = 0.038) and the N-terminal pro-brain natriuretic peptide (NT-proBNP) level was significantly greater in patients with ATTRwt-CM than in the controls (2202 ± 1478 versus 470 ± 677 pg/mL, p < 0.001). There were no significant differences in NID, bIMT or baPWV between the two groups. There was a significant relationship between NT-proBNP and FMD in patients with ATTRwt-CM (r = 0.485, p = 0.022). NT-proBNP showed no significant relationships with NID, bIMT or baPWV. Conclusions: Endothelial function was preserved in patients with ATTRwt-CM. Patients with ATTRwt-CM may have compensatory effects with respect to endothelial function through elevation of BNP.