Pulse Wave Research Articles

#1186 Novel T-cell subsets as early non-invasive biomarkers of vascular damage in chronic kidney disease progression

Abstract Background and Aims The exploration of early biomarkers for diagnosing vascular alterations in CKD-MBD holds significant clinical potential. Previous evidence has demonstrated profound alterations in immune cell populations linked to vascular homeostasis in CKD dialysis patients. This study aimed to evaluate the utility of immune cell populations as early and progressive biomarkers for non-dialysis CKD patients, examining their correlation with vascular damage. Method A total of 43 non-dialysis CKD patients and 38 sex- and age-matched controls were included in the study. Patients were categorized into four groups based on their estimated glomerular filtration rate (eGFR): CKD-2/3a, CKD-3b, CKD-4, and CKD-5. The assessment of left carotid adventitial neovascularization and intima-media thickness (cIMT) was conducted using ultrasensitive ultrasonography without contrast, specifically employing Superb Microvascular Image (SMI) technology. Pulse wave velocity (PWV) was measured to determine aortic stiffness, utilizing the Complior Analyzer. Immunosescencent T-cells (CD4+CD28null), angiogenic T-cells (Tang) (CD3+CD31+CD184+) and their subsets (CD4+Tang, CD8+Tang and CD28nullTang) were quantified by flow cytometry in Peripheral Blood Mononuclear Cells. Results No significant differences in age and body mass index were observed between the control group and the four CKD stages. Notably, the values of estimated glomerular filtration rate (eGFR) exhibited a significant and progressive decrease, as indicated in the Table 1. Biochemical parameters related to CKD-MBD are also detailed in the same table. The carotid intima-media thickness (cIMT) was found to be significantly higher in CKD-5 compared to CKD 2-3a (CKD 2-3a = 0.66 ± 0.14 mm, CKD-5 = 0.80 ± 0.12 mm, p = 0.03). In patients at stage 4 of CKD, there was an increased number of adventitial vasa vasorum (control = 0.53 ± 1.33, CKD-4 = 1.67 ± 2.04, p = 0.0009) and a greater area of adventitial neovascularization in the carotid artery compared to the control group (control = 0.51 ± 1.31%, CKD-4 = 2.67 ± 2.27%, p = 0.0003). PWV was significantly higher in CKD-5 (control = 10.81 ± 2.01 m/s, CKD-5 = 12.91 ± 3.70 m/s, p = 0.045). Additionally, a significant correlation was observed between PWV and both the number of adventitial vasa vasorum at the carotid artery (r = 0.24, p = 0.028) and the area of adventitial neovascularization (r = 0.34, p = 0.002). CD4+CD28null T-cells were increased in CKD patients compared to control group (control = 24.99[5.52], CKD = 27.35[8.58], p = 0.004). Although no differences were found in total levels of Tang in CKD patients (control = 1.64 ± 0.89, CKD= 1.5 ± 1.02, p = 0.757), a strong negative correlation was observed across CKD stages (trend analysis for stages: r = −0.361, p = 0.017). Moreover, CKD patients had altered CD8+ and CD4+ Tang frequencies (CD4+Tang: control = 39.52[18.46], CKD = 33.60[12.84], p = 0.054; CD8+Tang: control = 40.03[14.38], CKD = 48.25[13.16], p = 0.012) and Tang CD28null were increased in CKD patients (control = 44.14[11.99], CKD = 48.62[12.08], p = 0.004). Finally, Tang frequency was significantly correlated with the number of adventitial vasa vasorum (r = 0.368, p = 0.032), area of adventitial neovascularization (r = −0.401, p = 0.019), PWV (r = −0.341, p = 0.048) and cIMT (r = −0.364, p = 0.034). Conclusion Carotid adventitial neovascularization, cIMT and PWV demonstrated an increase in advanced CKD stages, implying that they may possess limited clinical utility as early markers of vascular damage in the initial stages of CKD. Immunosenescence and vascular damage traits were found across the CKD spectrum. Altered Tang frequency may be considered a progressive biomarker of impaired vascular homeostasis in CKD.

#2404 Predictors of mortality in patients with chronic kidney disease stages 3-4 without heart disease

Abstract Background and Aims Cardiovascular disease is common in patients with chronic kidney disease (CKD). This may, at least in part, explain the high risk of mortality in this patient group. The aim of the present study was to identify factors associated with mortality in patients with CKD stages 3 and 4 without a diagnosis of heart disease. Method Study subjects were derived from a cohort of patients with CKD stages 3 and 4 who were recruited from our Nephrology Outpatient Clinic between February 2009 and December 2011. Ninety-one patients without a diagnosis of heart disease were included in this cross-sectional study. Mortality data were collected in April 2023. Results All-cause mortality was 28.6% (26 patients) during a mean follow-up of 11.2 ± 2.7 years. Comparison of baseline data between non-survivors and survivors showed that non-survivors were significantly older, had lower glomerular filtration rate (GFR), higher ambulatory systolic blood pressure (ASBP), less nocturnal dipping of ASBP, higher carotid–femoral pulse wave velocity (cfPWV) and higher serum levels of troponin T (TnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) [Tables 1 and 2]. In addition, the proportion of patients with diabetes and on treatment with beta-blockers was elevated in non-survivors [Tables 1 and 2]. There were no statistically significant differences between groups in smoking history, treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, diuretics, calcium channel blockers, alpha-blockers, statins, active vitamin D analogs, calcium-based or non-calcium-based phosphate binders. In a binary logistic regression analysis, to identify independent predictors of mortality, we included age, gender, baseline GFR, serum NT-proBNP, TnT, cfPWV, percent of nocturnal dipping of ASBP, diagnosis of diabetes, and treatment with beta-blockers. Only less nocturnal dipping of ASBP (Exp [β] value of 0.86, 95% CI 0.77–0.97, p = 0.016) and advancing age (Exp [β] value of 0.91, 95% CI 0.84–0.99, p = 0.024) significantly predicted all-cause mortality. Conclusion In patients with CKD stage 3 and 4 without a diagnosis of heart disease only older age and less nocturnal dipping of ASBP were independently associated with mortality. Although baseline levels of serum NT-proBNP and TnT were elevated in non-survivors, neither serum NT-proBNP nor TnT showed independent associations with mortality in this cohort.

The beneficial effects of monoglucosyl hesperidin and monoglucosyl rutin on vascular flexibility: a randomized, placebo-controlled, double-blind, parallel-group study

Background: There is mounting evidence that the intake of polyphenols can help prevent cardiovascular complications. Furthermore, multiple intakes of different polyphenol compounds are expected to have a synergistic effect. However, few studies have examined the preventive effect of simultaneous polyphenol intake on cardiovascular complications in healthy adults. Objective: The present study aimed to evaluate the efficacy of daily intake of 70 mg of monoglucosyl hesperidin (MH) alone, or in combination with 140 mg of monoglucosyl rutin (MR), in improving vascular flexibility. Methods: This 8-week study was conducted on 66 healthy male and female participants with a relatively high body mass index (BMI) and low vascular flexibility. The participants were randomly assigned to an MH group (MH alone), MHMR group (combination of MH and MR), or placebo group by a computer-generated list (each n = 22). Participants took two tablets per day of either MH, MHMR or placebo during the intervention. Outcomes included vascular function indices, capillary flow, and inflammatory markers. Assessment points were at 4 weeks (4w) and 8 weeks (8w) of the intervention. Results: The primary outcome was flow-mediated dilation. In an analysis including participants whose left brachial-ankle pulse wave velocity (baPWV) was ≥1232.5 cm/s at baseline in the per-protocol set, the MHMR group showed significant improvement compared with the placebo group in flow-mediated dilation, maximum post-avascularization artery diameter, baPWV (each and average of both legs), and E-selectin at 8w. Conclusion: These results indicated that MH, in combination with MR, may act on vascular endothelial cells to improve vascular flexibility in healthy adults with a relatively lowvascular flexibility. (UMIN000046054). Keywords: Monoglucosyl hesperidin; Monoglucosyl rutin; flow-mediated dilation; E-selectin; pulse wave velocity, body mass index, vascular flexibility

#2032 Heart rate-adjusted augmentation index reduces after switching low-flux dialyzers to medium cut-off dialyzers in maintenance hemodialysis patients

Abstract Background and Aims Arterial stiffness affects almost all maintenance hemodialysis (MHD) patients and is one of the most important predictors of cardiovascular morbidity and mortality. Medium cut-off (MCO) membrane technology provides higher clearance of large-middle uraemic toxin and cytokines compared to conventional dialyzers. In this case-control study, we investigated the change in the arterial stiffness parameters after the transition to MCO dialyzers in MHD patients receiving treatment with low-flux dialyzers. Method We conducted a prospective, single-center cross-over study including 19 MHD patients receiving treatment with low-flux dialyzers. Baseline and repeated parameters were measured from the brachial artery on a mid-week HD session at 0th, 120th, and 240th minutes, and the average of the three measurements were analyzed. The repeated parameters were measured two weeks after the switching to MCO dialyzers which were decided by the clinician according to clinical indication. Results The median age was 71 (51, 79) years, and 57.9% of the patients were female. The frequency of diabetes was 36.8%, and hypertension was 73.7%. 21.1% patients were smokers. 31.6% of the patients had a history of cardiovascular disease. Two weeks after switching to MCO dialyzers, the Kt/Vs, urea reduction ratios, laboratory parameters, systolic, diastolic, and mean arterial pressures remained similar to baseline. The mean pulse wave velocity was 10.3 m/s (8.4, 11.0) with low-flux dialyzers and 10.2 m/s (7.0, 11.5) with MCO dialyzers (p = 0.38). The mean heart rate adjusted augmentation index [AIx(75)] was 20.0% (15.0, 30.3) with low-flux dialyzers and 13.0% (11.0, 22.0) with MCO dialyzers (p = 0.04). Conclusion Our study showed that the rapid effect of MCO membranes is the reduction in peripheral wave reflections defined by AIx(75). Additional long-term diseases are required to determine whether MCO dialyzers might improve the cardiovascular prognosis of MHD patients.

#1943 The association of uncarboxylated, non-phosphorylated Matrix Gla protein with arterial stiffness in hemodialysis and peritoneal dialysis patients

Abstract Background and Aims Vitamin K deficiency has been identified as a marker of vascular calcification AND STIFNESS and an independent cardiovascular risk factor in hemodialysis (HD) and peritoneal dialysis (PD) patients, as the most powerful inhibitor of vascular calcification, Matrix Gla Protein requires vitamin K to become activated. However, until to date, it has not yet been clarified whether hepatic or extrahepatic markers of vitamin K status reflect the arterial status of dialysis patients. In this study we aimed to investigate the association of vitamin K deficiency with arterial stiffness in End-Stage Kidney Disease (ESKD) patients. Method In 42 ESKD patients undergoing either HD or PD, we measured plasma levels of the inactive vitamin-K dependent Matrix Gla Protein (dp-ucMGP) and serum levels of prothrombin (PIVKA-II) as markers of extrahepatic and hepatic insufficiency of vitamin K (CARIM Institute, Maastricht, Netherlands). In these patients we determined arterial stiffness parameters (pulse wave velocity-PWV) by the Mobil-O-Graph device (IEM, Stolberg, Germany). Results Serum PIVKA-II was associated with T2D duration (r = −0.38, p = 0.013), phosphorus levels (r = −0.41, p = 0.009) serum albumin (r = −0.33, p = 0.036) Spearman's rho test, and the type of transporter in PD patients (p = 0.039), Kruskal-Wallis test. Plasma dp-ucMGP was associated with PWV (r = 0.51, p = 0.001), peripheral (r = −0.37, p = 0.016) and central diastolic blood pressure (BP) (r = −0.34, p = 0.026) and age (r = 0.41, p = 0.007), Spearman's rho. Patients with T2DM, history of acute myocardial infarction and those receiving warfarin had significantly increased levels of circulating dp-ucMGP (p = 0.036, p = 0.039 and p < 0.0001, respectively, Kruskal-Wallis). Warfarin was associated with a 2.5-fold and a 23-fold increase in dp-ucMGP and PIVKA-II levels, respectively. Stepwise multiple regression analysis showed that PWV (p = 0.001, B = 494, 95% CI: 242-746) was an independent predictor of dp-ucMGP, independent of age, T2T2, history of myocardial infraction and diastolic BP. Conclusion Elevated plasma dp-ucMGP levels (suggesting extrahepatic vitamin K deficiency) were associated with increased arterial stiffness in dialysis patients.

#723 The impact of kidney function on arterial stiffness in COVID-19 survivors: an analysis from CARTESIAN Study

Abstract Background and Aims SARS-CoV-2 pandemic has been linked to an increased incidence of cardiovascular events, potentially due to accelerated vascular aging [1]. Conversely, impaired kidney function is known to contribute to the pathogenesis of heightened arterial stiffness, independent of traditional cardiovascular risk factors [2]. This study aimed to assess the impact of COVID-19 on arterial stiffness among a cohort of survivors of the first pandemic wave, with varying degrees of infection severity. The assessment was conducted at 6 ± 3 (T1) and 12 ± 3 months (T2) post-infection, with the population stratified based on kidney function. Method the CARTESIAN study, a large international multicenter cohort study, was designed to assess the long-term effects of COVID-19 on vascular aging. A total of 938 subjects were stratified into three groups based on their estimated glomerular filtration rate (eGFR) percentiles using the CKD-EPI_2021 equation: 1) >75th percentile, 2) 75th-25th percentile, and 3) <25th percentile, respectively. The same population was further categorized based on the severity of COVID-19 into three groups: 1) patients who were not hospitalized (No-Hosp), 2) subjects requiring hospitalization in a medical unit (Hosp), or 3) those in an intensive care unit (ICU). Arterial stiffness was evaluated using carotid-femoral pulse wave velocity (cf-PWV). A hierarchical repeated measures mixed model analysis was conducted to compare cf-PWV across these groups (>75th, 75th-25th, and <25th groups, respectively). Results in the cross-section analysis (T1) <25th group exhibited higher age, increased cardiovascular risk factors, and higher prevalence of severe COVID-19 compared to the >75th group. Using hierarchical linear modeling, the <25th exhibited higher cf-PWV than the >75th group, even after adjusting for both all the random and fixed variables, included the three COVID-19 group (+0.51 m/s, p = 0.013). In longitudinal analysis, globally, no substantial changes were found in the cf-PWV between T1 and T2, remained significantly higher in the <25th group compared to the >75th group (p = 0.003), in a linear mixed model adjusted for all the random and fixed variables. Interestingly, a significant interaction between eGFR groups* COVID-19 groups was found in repeated measures analysis (p = 0.039). In particular, within ICU group, we found a significant increase of cf-PWV between 6- and 12-months in <25th group, from 8.64 [7.59-9.31] to 9.41 [8.89-10.41] m/s, p = 0.021) (Fig. 1). Conclusion the findings suggest that individuals with both lower eGFR and a history of severe COVID-19 may be at a heightened risk of accelerated arterial aging. Understanding these dynamics is crucial for targeted interventions to mitigate long-term cardiovascular consequences in COVID-19 survivors with kidney disease.

#220 Acute vascular response to hemodialysis as measured by serum syndecan-1 and endothelin-1 levels, as well as vascular stiffness

Abstract Background and Aims End-stage kidney disease (ESKD) patients on chronic hemodialysis (HD) have very high cardiovascular risk. Acute vascular changes during dialysis mediated partially by factors of the endothelium may have a crucial role in the cardiovascular (CV) disease of HD patients. Aim To study acute vascular changes during HD measured by applanation tonometry and to assess the role of syndecan-1 (SDC-1), endothelin-1 (ET-1), and traditional and non-traditional CV risk factors in these changes. Method 29 consecutive chronic HD patients (median age: 65.6 ± 10.4 years; 52% men) were included in the study. Pre-, mid-, and post-HD plasma SDC-1 and ET-1 levels and routine biochemical parameters were measured. Applanation tonometry (SphygmoCor, AtCor Medical) was performed before HD. Results As assessed by trend analysis, SDC-1 levels increased significantly during HD (p = 0.004). ET-1 levels were decreasing during HD. Male patients had significantly higher ET-1 levels than women. Patients were divided into 2 groups based on their pulse wave velocity (PWV): PWV ≥12 m/s and PWV <12 m/s. Pre-HD and mid-HD SDC-1 levels were significantly higher in the group with PWV ≥12 m/s (10.174 ± 2.568 vs. 7.928 ± 1.794 ng/ml, p = 0.013, and 10.319 ± 3.482 vs. 8.248 ± 1.793 ng/ml, p = 0.044, respectively). Post-HD ET-1 levels were significantly higher in the patient group having PWV ≥12 m/s (10.88 ± 3.00 vs. 8.05 ± 3.48 pg/l, p = 0.027). Patients having PWV ≥12 m/s had significantly higher pre-HD peripheral and aortic systolic blood pressure than the patients having lower PWV (147.4 ± 73.3 vs. 134.1 ± 72.2 mmHg, p = 0.038, and 130.7 ± 16.6 vs. 122.5 ± 14.9 mmHg, p = 0.016, respectively). Mid-HD and post-HD blood pressures were not different. We found a positive correlation between total cholesterol and the decrease in SDC-1 levels during HD (r = 0.539; p = 0.008). Pre-, mid-, and post-HD SDC-1 correlated significantly with the ultrafiltration volume during HD (r = 0.432, p = 0.019; r = 0.377, p = 0.044; and r = 0.401, p = 0.012, respectively). Conclusion SDC-1 and ET-1 may contribute to the vascular changes observed during HD, and they have correlations with some traditional and non-traditional CV risk factors.

GHz-rate 57-fs acousto-optic mode-locking fiber laser based on cascaded all-fiber pulse compression.

We demonstrate a compact ultrafast fiber laser system that can deliver 1.87 GHz pulse train at 1550 nm with a pulse energy of 52 pJ and an ultrashort pulse duration of 57 fs. While an acousto-optic mode-locking fiber laser was used as the seed light source at GHz rate, a stage of Er-doped fiber amplifier boosted the laser power to ∼320 mW, giving a pulse energy of ∼170 pJ. Then, a pulse compression setup was constructed, providing a high compression ratio of ∼10 with a total efficiency of ∼32%. In the cascaded compression configuration, multiple fiber samples with alternately normal and anomalous dispersion were fused together, providing efficient nonlinear spectral broadening while suppressing excessive pulse broadening over propagation. This GHz-rate ultrafast fiber laser, with compact configuration, broad optical spectrum, and high time-resolving ability could be used as the seed light source for constructing high-rate, high-power ultrafast laser systems and may find a few applications in optical measurements and microwave photonics.

Role of endogenous GLP-1 on arterial stiffness and renal haemodynamics following bariatric surgery.

Cardiovascular trials have revealed the positive impact of GLP-1 receptor agonists (GLP-1 RAs) on cardiovascular outcomes in type 2 diabetes (T2D). However, the specific effects of endogenous GLP-1 on arterial stiffness and renal function remain understudied. This study aimed to explore the influence of endogenous GLP-1 response post-bariatric surgery on arterial stiffness and renal haemodynamic. Thirty individuals with morbid obesity and without T2D, scheduled for Roux-en-Y Gastric Bypass (RYGB), were included. Clinical parameters, 3-hour oral glucose tolerance test (OGTT) with serial sampling for glycaemia, GLP-1 and insulin, carotid-femoral pulse wave velocity (cf-PWV), carotid distensibility coefficient (carotid-DC) and renal resistive index (RRI) measurements were conducted pre-surgery and 1-year post-surgery. Participants were categorized into high-response and low-response groups based on their post-surgery increase in GLP-1 (median increase of 104% and 1%, respectively, pre- vs. post-surgery). Post-surgery, high-response group demonstrated a greater reduction in cf-PWV (p = .033) and a greater increase (p = .043) in carotid DC compared to low-response group. These enhancements were observed independently of weight loss or blood pressure changes. High-response group exhibited a reduction in RRI (p = .034), although this association was influenced by improvement in pulse pressure. Finally, a multivariate stepwise regression analysis indicated that the percentage increase of GLP1, Δ-GLP1(AUC)%, was the best predictor of percentage decrease in cf-PWV (p = .014). Elevated endogenous GLP-1 response following RYGB was associated with improved arterial stiffness and renal resistances, suggesting potential cardio-renal benefits. The findings underscore the potential role of endogenous GLP-1 in influencing vascular and renal haemodynamics independent of traditional weight loss.

Carotid-femoral pulse wave velocity score, an estimator of cognitive performance in the elderly: results from the Toledo Study for Healthy Aging.

Ageing-related changes in the vascular wall influence the function of different organs; for this reason, we assessed how arterial stiffness measured by carotid-femoral pulse wave velocity (cf-PWV) modulates: the basal cognitive performance and the change in cognitive performance over the follow-up time. We developed a prospective, population-based cohort study with 1581 participants aged > 65years were obtained from the Toledo Study for Healthy Aging. Participants from the second wave (2011-2013) were selected for the cross-sectional analysis. Those who also performed the cognitive assessment in the third wave (2015-2017) were selected for the prospective analysis. Arterial stiffness was evaluated by cf-PWV. Multivariate segmented regression models were used to evaluate the association between cf-PWV scores and basal neuropsychological evaluation scores and change of neuropsychological evaluation scores along follow-up. Cross-sectional analysis showed that as cf-PWV grew within the cf-PWV (5- < 10) category an improvement was observed in 7-min test, free short-term memory, and hole peg test. Furthermore, in the cf-PWV (> 13-18) category a decrease was observed in total short-term memory, free long-term memory, and total long-term memory. Prospective analysis showed a progressive worsening of cognitive function as cf-PWV increases within the cf-PWV (> 13-18) category in 7-min test, object denomination, immediate and short-term memory, and hole peg test, while in the cf-PWV (5- < 10) category, there was observed a decrease in Cumulative Executive Dysfunction Index score and short-term memory. In conclusion, a higher cf-PWV score is associated with worse cognitive performance, and with a worse evolution, reinforcing the need to plan interventions to delay arterial stiffness and its consequences.

Association between A/G ratio and arterial stiffness among Chinese type 2 diabetics: A cross-sectional study

BackgroundThe android-to-gynoid fat ratio (A/G ratio), an emerging indicator of obesity independent of body mass index (BMI), has yet to be conclusively associated with arterial stiffness in type 2 diabetes mellitus (T2DM). This study aimed to construct a nomogram to estimate arterial stiffness risk in diabetics and explore the interaction effect between A/G ratio and traditional obesity indicators on arterial stiffness. Methods1313 diabetics were divided into 2 groups based on arterial stiffness identified by brachial ankle pulse wave velocity (baPWV), and demographic and clinical features were measured. The LASSO and multivariate logistics regression were used to develop the nomogram. Calibration curve, decision curve analysis (DCA) and receiver operating characteristic (ROC) were applied to assess calibration and clinical usefulness. Interaction effect analysis was performed to quantify the interactive relationship of A/G ratio and obesity indicators on arterial stiffness. Results6 independent predictors (age, gender, A/G ratio, SBP, LDL-C and HbA1C) were screened to construct a nomogram prediction model. The calibration curve demonstrated satisfactory agreement between predicted and actual probability, and the nomogram exhibited clinical beneficial at the threshold between 8 % and 95 % indicated by DCA. The area under curve (AUC) was 0.918 and 0.833 for training and external set, respectively. Further investigation revealed A/G ratio and BMI acted positively synergistically towards arterial stiffness, and in BMI-based subgroup analysis, elevated A/G ratio was a significant risk factor for arterial stiffness, especially in normal BMI. ConclusionsA/G ratio showed a substantial association with arterial stiffness, and the nomogram, incorporating age, gender, A/G ratio, SBP, LDL-C, and HbA1c, exhibited high predictive value. A/G ratio measurement in BMI-normal individuals assisted in identifying cardiovascular diseases early.

Intracranial pressure following surgery of an unruptured intracranial aneurysm—a model for normal intracranial pressure in humans

ObjectiveOptimizing the treatment of several neurosurgical and neurological disorders relies on knowledge of the intracranial pressure (ICP). However, exploration of normal ICP and intracranial pressure pulse wave amplitude (PWA) values in healthy individuals poses ethical challenges, and thus the current documentation remains scarce. This study explores ICP and PWA values for healthy adults without intracranial pathology expected to influence ICP.MethodsAdult patients (age > 18 years) undergoing surgery for an unruptured intracranial aneurysm without any other neurological co-morbidities were included. Patients had a telemetric ICP sensor inserted, and ICP was measured in four different positions: supine, lateral recumbent, standing upright, and 45-degree sitting, at day 1, 14, 30, and 90 following the surgery.ResultsICP in each position did not change with time after surgery. Median ICP was 6.7 mmHg and median PWA 2.1 mmHg in the supine position, while in the upright standing position median ICP was − 3.4 mmHg and median PWA was 1.9 mmHg. After standardization of the measurements from the transducer site to the external acoustic meatus, the median ICPmidbrain was 8.3 mmHg in the supine position and 1.2 mmHg in the upright standing position.ConclusionOur study provides insights into normal ICP dynamics in healthy adults following a uncomplicated surgery for an unruptured aneurysm. These results suggest a slightly wider normal reference range for invasive intracranial pressure than previously suggested, and present the first normal values for PWA in different positions. Further studies are, however, essential to enhance our understanding of normal ICP.Trial registration The study was preregistered at www.clinicaltrials.gov (NCT03594136) (11 July 2018)

Osteocalcin: A Potential Marker of Peripheral Arterial Stiffness in Hypertensive Patients.

Background and Objectives: Brachial-ankle pulse wave velocity (baPWV) is an established independent risk factor for cardiovascular events, cardiovascular mortality, and all-cause mortality. Osteocalcin (OC) is recognized to be associated with vascular function. The present study assessed the correlation between serum OC levels and peripheral arterial stiffness (PAS) measured through baPWV in hypertensive patients. Materials and Methods: Fasting blood samples were collected from 120 hypertensive participants. The serum total OC levels were measured using a commercial enzyme-linked immunosorbent assay kit, whereas the baPWV device was used to detect PAS. The PAS group had left or right baPWV > 18.0 m/s. Results: Among the hypertensive patients, 24 (20.0%) were classified into the PAS group. The PAS group exhibited a significantly older age (p = 0.011), higher prevalence of diabetes (p = 0.010), systolic blood pressure (p = 0.019), levels of serum fasting glucose (p = 0.003), blood urea nitrogen (p = 0.024), creatinine (p = 0.004), C-reactive protein (p = 0.007), OC (p = 0.002), and lower estimated glomerular filtration rate (p = 0.004) than the non-PAS group. Age (odds ratio [OR]: 1.076, 95% CI: 1.004-1.153, p = 0.037) and serum OC level (OR: 1.797, 95% confidence interval (CI): 1.077-3.000, p = 0.025) were independent factors linked to PAS in hypertensive patients in the multivariate logistic regression analysis. Conclusions: Serum OC levels and older age are positively associated with PAS in hypertensive patients.

Lipoprotein glomerulopathy with markedly increased arterial stiffness successfully treated with a combination of fenofibrate and losartan: a case report

BackgroundLipoprotein glomerulopathy (LPG) is a apolipoprotein E (ApoE)-related glomerular disease and has been associated with type III hyperlipidemia. Without appropriate treatment, chronic kidney disease (CKD) caused by LPG progresses, and approximately half of the patients develop end-stage kidney disease within 1–27 years of disease onset. However, few studies have highlighted the clinical course of cardiovascular diseases (CVDs) in patients with LPG. Herein, we report the first case of LPG in which the CVD risk was assessed using arterial stiffness.Case presentationA 32-year-old Japanese man was referred to our hospital due to persistent proteinuria. Kidney biopsy showed markedly dilated capillary lumens containing pale-stained thrombi, which stained positively with Oil Red O. Electron microscopy revealed the presence of thrombi in the capillary lumen with low electron density and vacuoles of various sizes in part of the thrombi. Toluidine blue and Sudan IV stains were used to stain the thin sections of Epon-embedded tissue samples for electron microscopy. Sudan IV-positive droplets were observed in the capillary lumens, vascular walls, and cytoplasm of tubular cells. Increased serum ApoE concentration was observed. Liquid chromatography-tandem mass spectrometry of laser-microdissected glomeruli from paraffin sections revealed an increase in ApoE. Direct deoxyribonucleic acid sequencing of ApoE revealed a heterozygous ApoE Sendai mutation (Arg145Pro). The patient was finally diagnosed with LPG with heterozygosity for ApoE-Sendai mutation (Arg145Pro). Notably, at the time of diagnosis, he had markedly increased arterial stiffness for his age. Arterial stiffness was measured using brachial-ankle pulse wave velocity (baPWV), which was equivalent to that of a 56-year-old man. After three months of treatment with fenofibrate and losartan, a significant reduction in proteinuria was achieved along with an improvement in baPWV. Furthermore, these effects were maintained despite the lack of decrease in serum ApoE levels.ConclusionHerein, we report the case of a patient with LPG with markedly increased arterial stiffness at the time of diagnosis, in whom combination therapy with fenofibrate and losartan successfully improved proteinuria and arterial stiffness. To the best of our knowledge, this is the first case report of LPG in which CVD risk was assessed using arterial stiffness.

Sgr A*, M87* and OJ287 as Extreme Central Binaries of Supermassive Black Holes- -Confirmation and extension of decameter radio wave observation results through VLBI data comparison

Based on a deduced 2153±5 s orbiting period of the extreme central binary of the supermassive black hole (ECB-SMBH), at Sgr A*,that is confirmed being based on the decameter radio wave pulse observations compared with 1.3 mm wavelength very long baseline interferometry (VLBI) data from the event horizon telescope (EHT-Data), we depict moving images of Sgr A* from EHT-Data, confirming further the existence of ECB-SMBH. The results show that radio wave images of the two members of ECB-SMBH are radio-bright objects due to emissions caused by source agents accreting from a thick disk toward ECB-SMBH. We extend the confirmed concept of ECB-SMBH to the interpretation of M87*, based on two images released by Miyoshi et al. in 2022 using EHT-Data and by Lu et al. in 2023 using the 3.5 mm wavelength data from the Global Millimeter VLBI Arrays as core telescopes. For the double brilliant spots displayed in two different images of M87*, we consider them the same two objects that shift locations during the 369-day interval of the observation periods of the two images. It is concluded that M87* A and M87* B (temporarily named) are orbiting with a period of 168.8 d at velocities of (6.28±0.54)% and (16.7±1.5)% of the speed of light, respectively. For the existence of ECB-SMBH, the condition of “no gravitational wave radiation” from the SMBH is essential. Regarding the secondary BH of blazar OJ 287, we find around 58~60-year period oscillation of the orbiting period, which is recently in a shortening phase. By applying the concept of ECB-SMBH to the OJ287 primary BH, whose orbiting period is approximately 1.6 yr, we interpret that the orbital period variation of the secondary BH is not due to the radiation of gravitational waves but is caused by the orbital motions of ECB-SMBH

Femtosecond pulse train-facilitated periodic nanostructuring on TiN films via laser-oxidation

Laser-induced periodic surface structure is a universal phenomenon observed when solid materials are irradiated with pulsed lasers. Typically, these structures are generated using Gaussian pulses. Here, we investigate the formation of periodic nanostructures on titanium nitride thin films using two different laser sources: Gaussian pulses and femtosecond pulse trains generated through a Fabry-Perot cavity. Our findings indicate that the formation of self-organized nanostructures on the thin films can occur through either laser-induced oxidation or laser ablation processes, depending on laser fluence, scanning speed, and pulse duration. Interestingly, when utilizing femtosecond pulse trains, we observe that the range of laser fluence thresholds for oxidative nanostructure formation is significantly wider compared to Gaussian pulses. To comprehend the underlying mechanisms driving these observations, we employ a two-temperature model to calculate the ultrafast dynamics of hot electrons when exposed to laser irradiation. Our results reveal that the initial sub-pulse generates a substantial population of hot electrons, exciting surface plasmons and resulting in the creation of a periodic energy distribution. Before these hot electrons can dissipate, subsequent sub-pulses reach the thin film, re-exciting a large number of hot electrons. Consequently, the periodic energy distribution persists for an extended duration, creating more favorable conditions for the formation of periodic oxidative nanostructures when using pulse trains. These findings contribute to a comprehensive understanding of the mechanisms involved in the formation of periodic nanostructures under femtosecond laser irradiation.

THz-TDS with gigahertz Yb-based dual-comb lasers: noise analysis and mitigation strategies

We investigate terahertz time-domain spectroscopy using a low-noise dual-frequency-comb laser based on a single spatially multiplexed laser cavity. The laser cavity includes a reflective biprism, which enables generation of a pair of modelocked output pulse trains with slightly different repetition rates and highly correlated noise characteristics. These two pulse trains are used to generate the THz waves and detect them by equivalent time sampling. The laser is based on Yb:CALGO, operates at a nominal repetition rate of 1.18 GHz, and produces 110 mW per comb with 77 fs pulses around 1057 nm. We perform THz measurements with Fe-doped photoconductive antennas, operating these devices with gigahertz 1 µm lasers for the first time, to our knowledge, and obtain THz signal currents approximately as strong as those from reference measurements at 1.55 µm and 80 MHz. We investigate the influence of the laser’s timing noise properties on THz measurements, showing that the laser’s timing jitter is quantitatively explained by power-dependent shifts in center wavelength. We demonstrate reduction in noise by simple stabilization of the pump power and show up to 20 dB suppression in noise by the combination of shared pumping and shared cavity architecture. The laser’s ultra-low-noise properties enable averaging of the THz waveform for repetition rate differences from 1 kHz to 22 kHz, resulting in a dynamic range of 55 dB when operating at 1 kHz and averaging for 2 s. We show that the obtained dynamic range is competitive and can be well explained by accounting for the measured optical delay range, integration time, as well as the measurement bandwidth dependence of the noise from transimpedance amplification. These results will help enable a new approach to high-resolution THz-TDS enabled by low-noise gigahertz dual-comb lasers.

Relative strengths of sum and difference frequency generation in perturbative high harmonic wave mixing

High harmonic generation (HHG) modulated by a weak laser field allows the perturbative wave mixing process which involves sum and difference frequency generations (SFG and DFG). The relative strengths of SFG and DFG have been extensively discussed in the literature but are still ambiguous. Here we experimentally study the relative strengths between SFG and DFG channels by applying a frequency-offset second-harmonic perturbing laser field collinearly in a thin gaseous nonlinear medium. It shows that SFG is favored for low harmonic orders, but DFG dominates for high-energy photons, when only short trajectories of high harmonics are considered. A semi-classical model incorporating both modulations to the tunneling ionization and the electron propagation steps by the perturbing laser field for a train of attosecond pulses explains the experimental results.

Arterial Stiffness Is an Important Predictor of Heart Failure with Preserved Ejection Fraction (HFpEF)—The Effects of Phosphate Retention

Heart failure with preserved ejection fraction (HFpEF) is a major health concern. There is a growing recognition of the causal interplay between arterial stiffness and HFpEF. We recently reported that phosphate retention is a trigger for arterial stiffness. This study focuses on whether arterial stiffness due to phosphate retention could be a predictor for HFpEF. Methods: The subjects of this study were 158 patients (68 males and 90 females, mean age 74.8 ± 11.2). HFpEF was defined according to the guidelines of the ESC 2019. Pulse wave velocity (PWV) and central systolic blood pressure (CSBP) were used as markers for arterial stiffness and afterload, respectively. We measured serum levels of fibroblast growth factor 23 (FGF23) as a marker of phosphate retention. Results: The serum levels of FGF23 had a significant relationship with PWV. PWV had significant relationships with LV mass index, plasma BNP levels, and relative wall thickness, e′, and E/e′ (p &lt; 0.001, respectively). Multivariate logistic regression analysis revealed that higher PWV values and hypertension were significant predictors for the dependent factor (HFpEF). Arterial stiffness amplified afterload, leading to LV concentric hypertrophy and diastolic dysfunction. This study presents that arterial stiffness is a key predictor of HFpEF, and that phosphate retention is involved in the pathology of HFpEF.

Artificial Neuron Based on the Bloch-Point Domain Wall in Ferromagnetic Nanowires.

Nanomagnetism and spintronics are currently active areas of research, with one of the main goals being the creation of low-energy-consuming magnetic memories based on nanomagnet switching. These types of devices could also be implemented in neuromorphic computing by crafting artificial neurons (ANs) that emulate the characteristics of biological neurons through the implementation of neuron models such as the widely used leaky integrate-and-fire (LIF) with a refractory period. In this study, we have carried out numerical simulations of a 120 nm diameter, 250 nm length ferromagnetic nanowire (NW) with the aim of exploring the design of an artificial neuron based on the creation and destruction of a Bloch-point domain wall. To replicate signal integration, we applied pulsed trains of spin currents to the opposite faces of the ferromagnetic NW. These pulsed currents (previously studied only in the continuous form) are responsible for inducing transitions between the stable single vortex (SV) state and the metastable Bloch point domain wall (BP-DW) state. To ensure the system exhibits leak and refractory properties, the NW was placed in a homogeneous magnetic field of the order of mT in the axial direction. The suggested configuration fulfills the requirements and characteristics of a biological neuron, potentially leading to the future creation of artificial neural networks (ANNs) based on reversible changes in the topology of magnetic NWs.