Zero-spindle spectral drill: real-time spectral measurement in a fixed Fabry-Pérot cavity.

An optical configuration for Fabry-Pérot cavity scanning using a geometric phase shifter, known as the "spectral drill," is improved to acquire a spectrum in real-time. Previously, the resonance condition of the spectral drill is swept by the mechanical rotation of a phase plate comprising a geometric phase shifter, and the acquisition time is limited. In this work, using a q-plate and a camera instead of phase plate rotation and a photo detector, we remove all the spinning mechanics and increase the acquisition rate by a factor 720. This technique will be applied to locking laser frequency.

Related factors for worsening renal function following percutaneous transluminal renal angioplasty (PTRA) in patients with atherosclerotic renal artery stenosis.

PURPOSE: To identify candidates for PTRA in terms of the preservation of renal function, we herein evaluated factors that caused worsening renal function (WRF) after PTRA. METHODS: We evaluated 92 patients with atherosclerotic renal artery stenosis (mean age 70.7 ± 8.4 years). WRF was defined as a ≥0.3 mg/dL increase in creatinine levels after PTRA compared to before PTRA. RESULTS: A total of 92 patients exhibited non-WRF 83 (90.2%), WRF 9 (9.8%). Significant differences were observed in serum creatinine levels between two groups both before (non-WRF 1.34 ± 0.49 versus WRF 1.70 ± 0.68 mg/dL, p = 0.0462) and after PTRA (non-WRF 1.31 ± 0.43 versus WRF 2.42 ± 1.12 mg/dL, p < 0.0001). Patients with WRF had higher comorbidity rate of diabetes mellitus (DM) (non-WRF 31.3% versus WRF 66.7%, p = 0.0345) and proteinuria (non-WRF 27.7% versus WRF 66.7%, p = 0.0169), and had higher systolic blood pressure (non-WRF 143.6 ± 18.7 versus WRF 157.1 ± 19.9 mmHg, p = 0.0436), higher plasma B-type natriuretic peptide (BNP) levels, and larger left atrial and left ventricular end-diastolic dimensions before PTRA. Patients with WRF had a higher rate of taking diuretics (non-WRF 27.7% versus WRF 66.7%, p = 0.0169) after PTRA. Multiple logistic regression analysis revealed that comorbidity of DM was an independent related factor for WRF (comorbidity of DM, yes: OR 31.0, 95% CI 2.44-1024.62, p = 0.0055). CONCLUSIONS: Comorbidity of DM, coexisting of proteinuria, high creatinine level, high blood pressure, high BNP levels, and large left atrial and ventricular dimensions were related to WRF after PTRA in patients with atherosclerotic renal artery stenosis.

Terahertz wave parametric amplifier.

The importance of terahertz (THz) wave techniques has been demonstrated in various fields, and the range of applications is now expanding rapidly. However, the practical implementation of THz science to solve the real-world problems is restricted due to the lack not only of convenient high power THz wave emitters and sensitive detectors but also of efficient quasi-optical active devices such as amplifiers. In this work, we demonstrate the direct amplification of THz waves in room temperature using magnesium oxide-doped lithium niobate (MgO:LiNbO3) crystals as the nonlinear gain medium. The input THz wave is injected as a seed beam along with the pump beam into the nonlinear crystal and it is amplified by the optical parametric process. We report gain in excess of 30 dB with an input THz pulse energy of less than 1 pJ. We believe that this demonstration will contribute to the convenience and further applicability of THz frequency techniques.

High-power, single-longitudinal-mode terahertz-wave generation pumped by a microchip Nd:YAG laser [Invited].

We report on the development of a high-peak-power, single-longitudinal-mode and tunable injection-seeded terahertz-wave parametric generator using MgO:LiNbO3, which operates at room temperature. The high peak power (> 120 W) is enough to allow easy detection by commercial and calibrated pyroelectric detectors, and the spectral resolution (< 10 GHz) is the Fourier transform limit of the sub-nanosecond terahertz-wave pulse. The tunability (1.2-2.8 THz) and the small footprint size (A3 paper, 29.7 × 42 cm) are suitable for a variety of applications.

Impact of Percutaneous Transluminal Renal Angioplasty on Autonomic Nervous System and Natriuresis in Hypertensive Patients With Renal Artery Stenosis.

Background We investigated the early postoperative effect of percutaneous transluminal renal angioplasty on ambulatory blood pressure (BP) and the circadian characteristics of natriuresis and autonomic nerve activity. Methods and Results A total of 64 patients with hypertension with hemodynamically significant renal artery stenosis (mean age, 60.0±21.0 years; 31.3% fibromuscular dysplasia) who underwent angioplasty were included, and circadian characteristics of natriuresis as well as heart rate variability indices, including 24-hour BP, low-frequency and high-frequency (HF) components, and the percentage of differences between adjacent normal R-R intervals >50 ms were evaluated using an oscillometric device, TM-2425, both at baseline and 3 days after angioplasty. In both the fibromuscular dysplasia and atherosclerotic stenosis groups, 24-hour systolic BP (fibromuscular dysplasia, -19±14; atherosclerotic renal artery stenosis, -11±9 mm Hg), percentage of differences between adjacent normal R-R intervals >50 ms, HF, brain natriuretic peptide, and nighttime urinary sodium excretion decreased (all P<0.01), and heart rate increased (both P<0.05) after angioplasty. In both groups, revascularization increased the night/day ratios of percentage of differences between adjacent normal R-R intervals >50 ms (both P<0.01) and HF, and decreased those of low frequency/HF (all P<0.05) and nighttime urinary sodium excretion (fibromuscular dysplasia, 1.17±0.15 to 0.78±0.09; atherosclerotic renal artery stenosis, 1.37±0.10 to 0.99±0.06, both P<0.01). Multiple logistic regression analysis indicated that a 1-SD increase in baseline low frequency/HF was associated with at least a 15% decrease in 24-hour systolic BP after angioplasty (odds ratio, 2.30 [95% CI, 1.03-5.67]; P<0.05). Conclusions Successful revascularization results in a significant BP decrease in the early postoperative period. Intrarenal perfusion might be a key modulator of the circadian patterns of autonomic nerve activity and natriuresis, and pretreatment heart rate variability evaluation seems to be important for treatment success.

Verification of dose distribution in high dose-rate brachytherapy for cervical cancer using a normoxic N-vinylpyrrolidone polymer gel dosimeter.

The polymer gel dosimeter has been proposed for use as a 3D dosimeter for complex dose distribution measurement of high dose-rate (HDR) brachytherapy. However, various shapes of catheter/applicator for sealed radioactive source transport used in clinical cases must be placed in the gel sample. The absorbed dose readout for the magnetic resonance (MR)-based polymer gel dosimeters requires calibration data for the dose-transverse relaxation rate (R2) response. In this study, we evaluated in detail the dose uncertainty and dose resolution of three calibration methods, the multi-sample and distance methods using the Ir-192 source and the linear accelerator (linac) method using 6MV X-rays. The use of Ir-192 sources increases dose uncertainty with steep dose gradients. We clarified that the uniformly irradiated gel sample improved the signal-to-noise ratio (SNR) due to the large slice thickness of MR images and could acquire an accurate calibration curve using the linac method. The curved tandem and ovoid applicator used for intracavitary irradiation of HDR brachytherapy for cervical cancer were reproduced with a glass tube to verify the dose distribution. The results of comparison with the treatment planning system (TPS) calculation by gamma analysis on the 3%/2 mm criterion were in good agreement with a gamma pass rate of 90%. In addition, the prescription dose could be evaluated accurately. We conclude that it is easy to place catheter/applicator in the polymer gel dosimeters, making them a useful tool for verifying the 3D dose distribution of HDR brachytherapy with accurate calibration methods.

Comparison of mesenchymal stem cells from adipose tissue and bone marrow for ischemic stroke therapy.

BACKGROUND AIMS: Transplantation of mesenchymal stromal cells (MSC) derived from bone marrow (BM) or adipose tissue is expected to become a cell therapy for stroke. The present study compared the therapeutic potential of adipose-derived stem cells (ASC) with that of BM-derived stem cells (BMSC) in a murine stroke model. METHODS: ASC and BMSC were isolated from age-matched C57BL/6J mice. These MSC were analyzed for growth kinetics and their capacity to secrete trophic factors and differentiate toward neural and vascular cell lineages in vitro. For in vivo study, ASC or BMSC were administrated intravenously into recipient mice (1 × 10(5) cells/mouse) soon after reperfusion following a 90-min middle cerebral artery occlusion. Neurologic deficits, the degree of infarction, expression of factors in the brain, and the fate of the injected cells were observed. RESULTS: ASC showed higher proliferative activity with greater production of vascular endothelial cell growth factor (VEGF) and hepatocyte growth factor (HGF) than BMSC. Furthermore, in vitro conditions allowed ASC to differentiate into neural, glial and vascular endothelial cells. ASC administration showed remarkable attenuation of ischemic damage, although the ASC were not yet fully incorporated into the infarct area. Nonetheless, the expression of HGF and angiopoietin-1 in ischemic brain tissue was significantly increased in ASC-treated mice compared with the BMSC group. CONCLUSIONS: Compared with BMSC, ASC have great advantages for cell preparation because of easier and safer access to adipose tissue. Taken together, our findings suggest that ASC would be a more preferable source for cell therapy for brain ischemia than BMSC.

Three-dimensional Winston-Lutz test using reusable polyvinyl alcohol-iodide (PVA-I) radiochromic gel dosimeter.

Medical linear-accelerator-based stereotactic radiosurgery (SRS) using a stereotactic apparatus or image-guided radiotherapy system for intracranial lesions is performed widely in clinical practice. In general, Winston-Lutz (WL) tests using films or electric portal imaging devices (EPIDs) have been performed as pre-treatment and routine quality assurance (QA) for the abovementioned treatment. Two-dimensional displacements between the radiation isocentre and mechanical isocentre are analysed from the test; therefore, it is difficult to identify the three-dimensional (3D) isocentre position intuitively. In this study, we developed an innovative 3D WL test for SRS-QA using a novel radiochromic gel dosimeter based on a polyvinyl alcohol-iodide (PVA-I) complex that can be reused after annealing. A WL gel phantom that was consisted of the PVA-I gel dosimeter poured into a tall acrylic container and an embedded small tungsten sphere was used as a position detector. A flatbed scanner was used to analyse the isocentre position. The measured 3D isocentre accuracy from the gel-based WL test was within 0.1 mm compared with that obtained from the EPID-based WL test. Furthermore, excellent reusability of the WL gel phantom was observed in long-term SRS isocentre verification, in which clinical SRS cases involving repeated irradiation and annealing were analysed. These results demonstrate the high accuracy and reliable evaluation of the isocentre position using an innovative test. In addition, the clinical-based routine SRS-QA using the PVA-I gel dosimeter demonstrates a highly convenience while affording an easy and fast analysis process.

Associations Between Arterial Stiffness Indices and Chronic Kidney Disease Categories in Essential Hypertensive Patients.

BACKGROUND: This study investigated the association between arterial stiffness indices and asymptomatic chronic kidney disease (CKD) risk categories in hypertensive patients. METHODS: Arterial stiffness indices, including 24-hour brachial and aortic systolic blood pressure (SBP) and pulse wave velocity (PWV), were measured by an oscillometric Mobil-O-Graph device, brachial-ankle PWV (baPWV) by a volume-plethysmographic method, and renal resistive index (RI) by ultrasonography, in 184 essential hypertensive patients (66.0 ± 17.1 years, 47.3% male). CKD was categorized into 3 stages based on the Kidney Disease Improving Global Outcomes (KDIGO) criteria, using a combination of estimated glomerular filtration and albuminuria. RESULTS: The 24-hour aortic PWV (aPWV), baPWV, and RI increased with worsening severity of CKD risk category (all P < 0.01 for trend). Multivariate logistic regression analysis found that a 1 SD increase of nighttime aortic SBP (odds ratio [OR] 1.52), PWV (OR 4.80), or RI (OR 1.75) was an independent predictor of high or very-high CKD stage (all P < 0.05). After adjustment for potential confounders, day-to-night change in brachial SBP as well as in aPWV differed among groups (P < 0.05, respectively). In a multivariate regression model, day-to-night changes in aortic SBP and PWV, and RI were independently associated with day-to-night brachial SBP change. CONCLUSIONS: In hypertension, circadian hemodynamics in high CKD stage are characterized by higher nighttime values of aortic SBP and PWV and disturbed intrarenal hemodynamics. Further, the blunted nocturnal BP reduction in these patients might be mediated via disturbed intrarenal hemodynamics and circadian hemodynamic variation in aortic SBP and arterial stiffness.

The stent-eluting drugs sirolimus and paclitaxel suppress healing of the endothelium by induction of autophagy.

Clinical studies have indicated that the stent-eluting drugs sirolimus and paclitaxel impact restenosis; however, it is still elusive how these drugs affect the vascular endothelium at the molecular and cellular levels. The purpose of this study was to determine whether sirolimus and paclitaxel induce molecular and cellular alterations in the vascular endothelium. Endothelial regrowth was assessed in human aortic endothelial cells and rat aortic endothelium. Molecular and cellular alterations were analyzed in human aortic endothelial cells by Western blot analysis, transmission electron microscopy, and immunofluorescence staining. Green fluorescent protein-LC3 mice were used to analyze autophagic endothelium. Here, we show that sirolimus and paclitaxel differentially induce self-digesting autophagy in vascular endothelial cells with changes in expression of LC3B, p53, and Bcl-2, considerably suppressing re-endothelialization and revascularization. These results suggest that phenotypic alteration in the endothelium by sirolimus or paclitaxel might affect the rates of late stent thrombosis, myocardial infarction, and mortality.

Alzheimer disease-associated peptide, amyloid beta40, inhibits vascular regeneration with induction of endothelial autophagy.

OBJECTIVE: Although the majority of cases of Alzheimer disease (AD) are known to be attributable to the sporadic (nongenetic) form of the disease, the mechanism underlying its cause and progression still remains unclear. METHODS AND RESULTS: We found that vascular beta-amyloid (Abeta), Abeta40, inhibited the proliferative activity of human brain vascular endothelial cells (HBECs) without toxic effects on them. This peptide also inhibited tube formation and migration of HBECs. Moreover, Abeta40 inhibited ex vivo hippocampal revascularization, reendothelialization, and the differentiation of adult endothelial progenitor cells. Importantly, Abeta40 suppressed the proliferative activity of HBECs through the induction of "self-digesting" autophagy. This induction involved the intracellular regulation of class 3 phosphatidylinositol 3-kinase (PI3K) as well as Akt signaling in HBECs. Furthermore, tissue culture of murine brain sections from GFP-LC3 transgenic mice revealed that Abeta40 not only reduced the vessel density in hippocampal lesions, but also induced autophagy in neurovascular ECs. CONCLUSIONS: Our present findings indicate that the initial progression of AD might be in part driven by Abeta40-induced endothelial autophagy and impairment of neurovascular regeneration, suggesting important implications for therapeutic approaches to AD.

Insight into the Role of Angiopoietins in Ageing-Associated Diseases.

Angiopoietin (Ang) and its receptor, TIE signaling, contribute to the development and maturation of embryonic vasculature as well as vascular remodeling and permeability in adult tissues. Targeting both this signaling pathway and the major pathway with vascular endothelial growth factor (VEGF) is expected to permit clinical applications, especially in antiangiogenic therapies against tumors. Several drugs targeting the Ang-TIE signaling pathway in cancer patients are under clinical development. Similar to how cancer increases with age, unsuitable angiogenesis or endothelial dysfunction is often seen in other ageing-associated diseases (AADs) such as atherosclerosis, Alzheimer's disease, type 2 diabetes, chronic kidney disease and cardiovascular diseases. Thus, the Ang-TIE pathway is a possible molecular target for AAD therapy. In this review, we focus on the potential role of the Ang-TIE signaling pathway in AADs, especially non-cancer-related AADs. We also suggest translational insights and future clinical applications of this pathway in those AADs.

Impact of Percutaneous Revascularization on Left Ventricular Mass and Its Relationship to Outcome in Hypertensive Patients With Renal Artery Stenosis.

BACKGROUND: We investigated the effects of percutaneous transluminal renal angioplasty on left ventricular (LV) mass, and the impact of LV mass reduction on outcomes. METHODS: A total of 144 hypertensive patients with renal artery stenosis (RAS) (mean age 69 years; 22.2% fibromuscular dysplasia (FMD)) who underwent angioplasty were included. Echocardiography was performed at baseline and after 1 year, and patients were thereafter followed up for a median of 5.6 years for primary composite outcomes. RESULTS: In both the FMD and atherosclerotic stenosis (ARAS) groups, LV mass decreased after angioplasty, but the decrease in LV mass index (-15.4 ± 18.3% vs. -0.8 ± 27.8%, P < 0.01) as well as the regression rate of LV hypertrophy was greater in FMD. Multiple logistic regression analysis indicated that FMD (odds ratio (OR) 2.94, P < 0.01), severe RAS (≥90%) (OR 2.94, P < 0.05), and higher LV mass index at baseline (OR 2.94 for 1 SD increase, P < 0.001) were independent predictors of LV mass index decrease of at least 20%. The primary composite outcomes occurred in 45 patients (31.3%). In FMD, lower LV mass index after 1 year (hazard ratio 2.81 for 1 SD increase, P < 0.05) or regression of LV mass (hazard ratio 0.75 for 5% decrease, P = 0.054) showed a tendency to be associated with better outcomes; however, these associations were not found in ARAS. CONCLUSIONS: Hypertensive patients with ARAS have less regression of LV mass in response to angioplasty than those with FMD, and LV mass regression is less useful as a surrogate marker of outcomes especially in ARAS.

Verification of dose distribution in high-dose-rate brachytherapy using a nanoclay-based radio-fluorogenic gel dosimeter.

Dose distributions have become more complex with the introduction of image-guided brachytherapy in high-dose-rate (HDR) brachytherapy treatments. Therefore, to correctly execute HDR, conducting a quality assurance programme for the remote after-loading system and verifying the dose distribution in the patient treatment plan are necessary. The characteristics of the dose distribution of HDR brachytherapy are that the dose is high near the source and rapidly drops when the distance from the source increases. Therefore, a measurement tool corresponding to the characteristic is required. In this study, using an Iridium-192 (Ir-192) source, we evaluated the basic characteristics of a nanoclay-based radio-fluorogenic gel (NC-RFG) dosimeter that is a fluorescent gel dosimeter using dihydrorhodamine 123 hydrochloride as a fluorescent probe. The two-dimensional dose distribution measurements were performed at multiple source positions to simulate a clinical plan. Fluorescence images of the irradiated NC-RFG were obtained at a high resolution (0.04 mm pixel-1) using a gel scanner with excitation at 465 nm. Good linearity was confirmed up to a dose range of 100 Gy without dose rate dependence. The dose distribution measurement at the five-point source position showed good agreement with the treatment planning system calculation. The pass ratio by gamma analysis was 92.1% with a 2%/1 mm criterion. The NC-RFG dosimeter demonstrates to have the potential of being a useful tool for quality assurance of the dose distribution delivered by HDR brachytherapy. Moreover, compared with conventional gel dosimeters such as polymer gel and Fricke gel dosimeters it solves the problems of diffusion, dose rate dependence and inhibition of oxygen-induced reactions. Furthermore, it facilitates dose data to be read in a short time after irradiation, which is useful for clinical use.

Tunability enhancement of a terahertz-wave parametric generator pumped by a microchip Nd:YAG laser.

We have enhanced the tunability of a terahertz-wave parametric generator using MgO:LiNbO3 pumped by a subnanosecond, passively Q-switched, microchip Nd:YAG laser. This pump source allows high-intensity pumping without damage to the nonlinear crystal and generates a narrow linewidth and tunable terahertz wave with injection seeding by an external cavity diode laser for the idler wave. The high-intensity pumping causes a gain curve broadening of the terahertz-wave parametric generation, especially in the high-frequency region. We obtained an output terahertz wave with a tuning range of 0.9-3 THz (100-330 microm), a peak power of 100 mW, and a linewidth of less than 10 GHz. This room temperature operated, palm-sized source promises to be a widely tunable terahertz-wave source that is suited to a variety of applications.

Overexpression of immediate early gene X-1 (IEX-1) enhances gamma-radiation-induced apoptosis of human glioma cell line, U87-MG.

Malignant gliomas are usually incurable even if adjuvant therapy is delivered after neurosurgical treatment. Therefore, to enhance their radiation-induced apoptosis, it is important to detect the mechanism(s) leading to the death of malignant glioma cells. We report that apoptosis was induced in a time-dependent manner after gamma-radiation and that irradiated U87-MG cells (human glioblastoma cell line) expressed immediate early gene X-1 (IEX-1) with p53. We also document that their apoptotic sensitivity to gamma-radiation was enhanced by the overexpression of IEX-1. Our findings suggest that IEX-1 may represent a new factor for the enhancement of radiation-induced apoptosis of human glioma cells.

Association Between Circadian Hemodynamic Characteristics and Target Organ Damage in Patients With Essential Hypertension.

BACKGROUND: This study investigated the association between circadian hemodynamic characteristics and asymptomatic hypertensive organ damage. METHODS: Circadian hemodynamics, including 24-hour brachial and aortic systolic blood pressure (SBP), pulse wave velocity (PWV), augmentation index (AIx@75), cardiac index, and total vascular resistance (TVR), were evaluated using an oscillometric device, Mobil-O-Graph, in 284 essential hypertensive patients (67.8 ± 16.0 years, 54% female). Hypertensive target organ damage (TOD), namely carotid wall thickening, left ventricular hypertrophy, and albuminuria, was assessed in all patients. RESULTS: Office SBP and 24-hour brachial and aortic SBP all increased with increasing number of organs involved (all P < 0.01 for trend). After multivariate logistic regression analysis, 24-hour brachial SBP (odds ratio [OR] = 1.04 for 1 mm Hg increase, P < 0.001) as well as aortic SBP (OR = 1.03 for 1 mm Hg increase, P < 0.05) maintained significance. Percent decrease during nighttime in brachial SBP, PWV, and TVR, but not cardiac index, showed a significant graded relationship with the number of organs involved. In a multivariate stepwise regression model, the nighttime values of brachial SBP, PWV, and TVR emerged as independent predictors of the presence of TOD. CONCLUSION: In essential hypertension, 24-hour aortic SBP could be a marker of subclinical TOD, and further, the blunted nocturnal BP reduction in TOD patients might be mediated by disturbed circadian hemodynamic variations in aortic SBP, vascular resistance, and arterial stiffness.

Dose distribution verification in high-dose-rate brachytherapy using a highly sensitive normoxic N-vinylpyrrolidone polymer gel dosimeter.

Rapid technological advances in high-dose-rate brachytherapy have led to a requirement for greater accuracy in treatment planning system calculations and in the verification of dose distributions. In high-dose-rate brachytherapy, it is important to measure the dose distribution in the low-dose region at a position away from the source in addition to the high-dose range in the proximity of the source. The aim of this study was to investigate the accuracy of a treatment plan designed for prostate cancer in the low-dose range using a normoxic N-vinylpyrrolidone-based polymer gel (VIPET gel) dosimeter containing inorganic salt as a sensitizer (iVIPET). The dose response was evaluated on the basis of the transverse relaxation rate (R2) measured by magnetic resonance scanning. In the verification of the treatment plan, gamma analysis showed that the dose distributions obtained from the polymer gel dosimeter were in good agreement with those calculated by the treatment planning system. The gamma passing rate according to the 2%/2 mm criterion was 97.9%. The iVIPET gel dosimeter provided better accuracy for low doses than the normal VIPET gel dosimeter, demonstrating the potential to be a useful tool for quality assurance of the dose distribution delivered by high-dose-rate brachytherapy.

Interference terahertz label-free imaging for protein detection on a membrane.

We demonstrate a highly sensitive imaging method combined a terahertz time-domain spectroscopy and an interference effect for label-free protein detection on a polyvinylidene difluoride membrane. The method is based on terahertz time-domain spectroscopy and uses an interference effect. Biotin is linked to the membrane using poly ethylene glycol or poly ethylene glycol methyl ether to prevent it from being washed off. Binding of the biotin with streptavidin is then observed by measuring the terahertz signal change due to the variation of the membrane refractive index. We demonstrate the detection of the binding streptavidin protein in gradually decreasing concentrations, down to 27 ng mm-2, using the image recorded at 1.5 THz.