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The human MAS-related G protein-coupled receptor X1 (MRGPRX1) is a member of the GPCR family. The receptor is primate specific and expressed in the sensory neurons of dorsal root ganglion and trigeminal ganglion, where it is considered to be involved in the pain perception. The MRGPRX1 has unusual binding mechanism, as it is activated by several different ligands as well as several different fragments of precursor proteins. Thus, we hypothesize that it is activated by several unknown compounds as well since the receptor is still classified as orphan. Here, we describe the isolation of two novel endogenous ligands for the MRGPRX1 from human platelet preparation. The isolated ligands are hemoglobin β-chain fragments, known members of the hemorphin family. [ABSTRACT FROM AUTHOR]

Summary: Objective: To unveil the three-dimensional (3D) distribution of talocrural and posterior subtalar articular cartilage thickness in the elderly cadavers using 3D computed tomography (CT) and a 3D-digitizer and to evaluate the relationship between subchondral bone plate density and the overlying cartilage thickness. Design: Sixteen tali and 16 calcanei from eight cadavers were scanned with 3D-CT to create bone surface models, and with a 3D-digitizer to make cartilage surface models. These two surface models were merged using surface registration method. Articular cartilage thickness was evaluated as the distance between the two models, and the distribution was mapped. The anatomic cartilage thickness of five tali and five calcanei was compared with the distance between the cartilage and bone surface models to calculate optimum threshold for extracting the subchondral bone plate. Generalized estimating equations were used for comparison and measurement errors. Canonical correlation analysis was performed to determine the strength of association between subchondral bone plate threshold and cartilage thickness. Results: The talar-subtalar articular cartilage tended to be the thickest of the three joints. In the talocrural joint, the anterior region was the thinnest, and increasing cartilage thickness was seen toward the posterior. In the talar-subtalar joint, the central region was the thickest. Mean measurement errors were 0.059±0.066mm, 0.038±0.040mm, and 0.018±0.065mm in the talocrural, talar-subtalar, and calcaneal-subtalar joints, respectively. The canonical correlation coefficient was 0.995 (P <0.001). Conclusions: The articular cartilage thickness was distributed in the elderly hindfoot. The subchondral bone plate density was significantly correlated with the anatomic cartilage thickness. [ABSTRACT FROM AUTHOR]

Abstract: Basal cell adenocarcinoma (BCAC) is a rare malignant neoplasm in the salivary glands and BCAC of the minor salivary glands is exceedingly rare. Only nine cases of palatal BCACs of the minor salivary gland have been reported. BCAC is a low-grade malignant tumour which shares many histologic characteristics with basal cell adenoma. Histological differentiation between the two is difficult and they are often discriminated only by invasion of local structures or by perineural or vascular invasive figures. The authors describe the case of a 69-year-old man with a massive BCAC of a palatal minor salivary gland that progressed into the nasal cavity and pterygopalatine fossa and was treated by a subtotal maxillectomy. This is a highly locally advanced case which required a wider surgical excision range than other previously reported BCAC cases of the palatal minor salivary glands. In this case, the proper diagnosis could not be made by local biopsy alone. It should be kept in mind that it may be difficult to distinguish BCAC from basal cell adenoma by microscopic examination of biopsy specimens alone. [Copyright &y& Elsevier]

Abstract: Our previous study suggests that “the neuropeptidergic system” might promote a diversity of the mechanisms that regulate signal transmission in the hippocampus. Cholecystokinin (CCK) is the mostly expressed neuropeptide gene in the hippocampus. Here, we investigated whether CCK regulates immediate-early genes (Egr1/zif268 and Fos), critical indicators of cortical neuronal activity. We showed that CCK increased Egr1/zif268 promoter activity in a neuronal cell line, which is transfected with CCK B receptor. Unexpectedly, in living hippocampal slices, CCK significantly suppressed cAMP-induced expression of Egr1/zif268 and Fos through CCK B receptor activation. This suppression was involved in activating GABA B and cannabinoid 1 receptors. In addition to transient CCK modulation of action potentials on hippocampal principal neurons, we suggest that release of endogenous CCK might indirectly produce the suppression of cAMP-dependent gene expression in the hippocampus. [Copyright &y& Elsevier]

Summary: Objective: To elucidate in vivo hip instability by comparing normal hips to hips with acetabular dysplasia by evaluating three-dimensional (3D) translations of the femoral head center (FHC) at different hip positions using magnetic resonance imaging (MRI). Design: Forty normal hips and 22 dysplastic female hips were examined. MRI was performed at four different positions bilaterally: neutral, 45° of flexion, 15° of extension, and the Patrick position. Femoral and pelvic bones were separately extracted at the neutral position and superimposed over the images of each different position using voxel-based registration. The distance between the acetabular center and FHC at neutral position was defined as 3D-migration. The distance between FHC at neutral position and that at each different position was defined as 3D-translation. Two-way repeated measures analysis of variance was performed to consider the dependency between right and left-side data, and multiple linear regression analyses were performed to assess independent relationships. Results: The center-edge (CE) angle was the determinant for 3D-migration (β =−0.415, P =0.001), and there was a statistical significant difference in 3D-migration between normal female hips and dysplastic hips (P =0.047). From neutral to the Patrick position, the FHC of normal and dysplastic hips translated postero-infero-medially by 1.12±0.39mm (0.45–1.85mm) and 1.97±0.84mm (0.95–4.34mm), respectively, and the difference between the groups was statistically significant (P =0.005). CE angle was the determinant for 3D-translation from neutral to the Patrick position (β =−0.730, P <0.001). The average root mean square error in 3D-translation was 0.172mm and 0.193mm for intra- and interobserver reproducibility, respectively. Conclusions: Hip instability was increased in proportion to the severity of acetabular dysplasia. A 3D MRI voxel-based registration technique can show in vivo morphology and kinematics of the native hip without exposure to radioactivity. [Copyright &y& Elsevier]

Abstract: We have developed efficient spectrally selective infrared (IR) emitters that can be utilized for thermophotovoltaic (TPV) power generation by using stainless steel (SUS304) substrates coated with - FeSi2 thin films. To develop spectrally selective emitters, we theoretically propose antireflection (AR) coatings consisting of a single layer of a dielectric material having a high refractive index (∼5) and are appropriate for use with metals such as stainless steels in the IR region. This type of AR coating is fabricated by sputtering a - FeSi2 thin film on a polished SUS304 substrate. The reflectance in the IR region is successfully reduced to less than 10%. In addition, the AR properties are stable even at 700 K in air. Therefore, metals with AR coatings of - FeSi2 can be applied to IR emitters in TPV systems. [Copyright &y& Elsevier]

Summary: Objective: The aim of this study was to evaluate the three-dimensional (3D) distribution of the acetabular articular cartilage thickness in cadaveric elderly individuals, measured using a new method with a 3D-digitizer and computed tomography (CT) and to validate this method using a thresholding technique. Design: Twenty cadaveric hemipelves without fracture, previous hip surgery, or macroscopic degenerative changes were digitized by a 3D-digitizer to make 3D cartilage surface models, and scanned by 3D-CT to create 3D bone surface models. These two surface models were then merged using a surface registration method. Acetabular articular cartilage thickness was evaluated as the distance between the two surface models, and the distribution was mapped. Tests for accuracy and reproducibility were performed by comparing the cartilage thickness of five human femoral heads measured by stereomicroscopy with the distance between the cartilage and bone surface models. Results: The superolateral cartilage tended to be the thickest in all acetabula. The smallest category (0–0.5mm) of articular cartilage thickness existed at the posteroinferior lunate surface. In this new method, the mean measurement error was 0.018±0.044mm for the average optimum threshold and the intraclass correlation coefficients were 0.99 in surface registration and 0.94 in data acquisition for reproducibility, indicating high accuracy and reproducibility. Conclusions: The proposed method for measuring articular cartilage using a 3D-digitizer and 3D-CT was accurate and reproducible. In the elderly individuals, acetabular articular cartilage tended to be thicker in the superolateral area and there was the thinnest category (0–0.5mm) on the posteroinferior lunate surface of the acetabulum. The contour generated along 480 Hounsfield units (HU) was closest to the subchondral bone contour in the elderly hip. [Copyright &y& Elsevier]

Abstract: Yttria-stabilized zirconia (YSZ) was epitaxially grown on both Si(001) and Si(111) substrates using a RF magnetron sputtering method. While YSZ(001) was grown on Si(001) with a cubic on cubic relation, YSZ(111) film on Si(111) with six-fold symmetry on surface showed two variants; cubic on cubic (type A) and 180° rotation about surface normal along [111] (type B). X-ray diffraction method confirmed single domain YSZ with type B structure when samples were prepared with the relatively slow deposition rate and low substrate temperature. Interestingly, in a reverse pairing of substrate and film, Si deposited on YSZ(111) substrates showed single domain with type A structure. [Copyright &y& Elsevier]

Purpose Blood flow through the left ventricular assist device (LVAD) is dependent on the rotation speed of the impeller, and inversely dependent on the differential pressure across the LVAD (HQ relationship). We developed a novel approach to estimate intraventricular pressure difference (IVPD) in patients with LVAD and assess the change of IVPD according to pump speed during ramp study. Methods We developed in-house code of 1-dimensional incompressible Euler equation written in MATLAB (MathWorks, Natick, MA, USA) which allows us to measure IVPD by analyzing transesophageal echocardiographic images. Color M-mode images in mid-esophageal long axis view were obtained at 3 different pump speeds (low, optimized, high) in 10 patients who had LVAD implant (Figure). The optimal rotation speed was defined by stable hemodynamic conditions and the septal shape on transesophageal imaging. Pairwise comparison between each group was performed using Steel-Dwass analysis. Results Images were successfully obtained in all patients. Median IVPD values were 0.88 mmHg [IQR 0.73 - 1.02] at pre-LVAD implant, 1.86 mmHg [IQR 1.50 - 2.15] at low speed, 2.12 mmHg [IQR 1.72 - 2.71] at optimal speed, 2.09 mmHg [IQR1.72 - 2.31] at high speed, respectively (figure). There was significant difference between pre-implantation and the remaining 3 groups (p <0.005). IVPD was highest at optimal speed in 7 cases, at high speed in 2 cases, and at low speed in 1 case. Conclusion These data illustrate a novel approach to estimate IVPD during early diastole in patients with LVAD. Importantly, data suggests that setting of pump speed can be informed by analyzing IVPD during early diastole. [ABSTRACT FROM AUTHOR]

Purpose Right ventricular (RV) failure remains a major concern in heart failure (HF) patients undergoing LVAD surgery. We aimed to measure flow kinetic energy (KE) of the RV outflow tract (OT) - a new marker of RV global systolic function - and assess its relationship to well-established echocardiographic and hemodynamic parameters of RV performance in heart failure (HF) and LVAD pts. Methods Twenty-one subjects were prospectively enrolled: 12 HF pts (2 NYHA Class II and 10 Class IV), 3 HeartMate II (HMII) and 6 healthy controls (C). Echocardiographic parameters of RV function (TAPSE, St', Et', IVA, MPI) and RV inflow-outflow color Doppler images were recorded on all pts. Invasive hemodynamic parameters of RV function and RV failure risk score (RVFRS) were collected in all Class IV pts. KE-RVOT was derived from color Doppler images using a vector flow mapping proprietary software, Echo VFM® (Cardio Flow Design, Tokyo, Japan) (Figure). Kruskal-Wallis test was performed for comparison of each group. Correlation between KE-RVOT and echocardiographic/hemodynamic parameters as well as RVFRS was assessed by linear regression analysis. Results KERVOT (Median ± IQR) was higher in C (56.98 [37.63 to 97.21] mW/m) than in Class II HF (26.60 [26.14 to 27.05] mW/m, p <0.05) and further declined in Class IV HF (7.45 [4.87 to 10.46] mW/m, p <0.05)). LVAD therapy partially restored KE-RVOT (23.17 [9.77 to 25.03] mW/m, p <0.05)) to levels similar to Class II HF (Figure). KE-RVOT was significantly related to TAPSE, St', CVP/PCWP, and PAPi (r = 0.5887, 0.6671, -0.6942, and 0.7899, respectively, all p <0.05) but not to RVFRS. Conclusion KE-RVOT, a novel noninvasive measure of RV function, strongly correlates with well-established markers of RV performance. The utility of KE-RVOT in prediction of RV failure post LVAD requires further study. [ABSTRACT FROM AUTHOR]

Purpose In advanced heart failure (HF) patients, a normal cardiac output is restored after continuous-flow left ventricular assist device (CF-LVAD) implantation. Previous studies have suggested that cerebral autoregulation is preserved. However, it is not known whether CF-LVAD therapy affects the cerebrovascular reactivity to a metabolic challenge. Hypothesis CF-LVAD patients will have a similar cerebrovascular response to a CO 2 -retention challenge compared with HF patients and healthy controls. Methods Angle-corrected Doppler ultrasound images of the middle cerebral artery (MCA) were recorded immediately before and at the end of a 30s breathhold in 10 healthy controls, 4 HF and 7 CF-LVAD (HM II) patients. Time-averaged maximum blood velocity (TAMAX), peak flow velocity (Vmax), Pulsatility Index (PI) and Resistance Index (RI) were determined by tracing of the blood velocity envelope. Statistical differences were determined with 2-way ANOVA (% change is illustrated graphically). Results In the MCA, significant baseline differences in TAMAX, Vmax, PI and RI existed between groups (all P < 0.05). Breathhold increased TAMAX and Vmax, although the difference was significantly greater in healthy controls (P = 0.04). Conversely, the CO 2 -retention challenge did not affect PI or RI in any group (Fig. 1 & 2). Conclusion A metabolic challenge has a differential impact on cerebrovascular hemodynamics of HF and CF-LVAD patients compared with healthy controls. The pilot data suggest that cerebrovascular reserve may be altered already in HF and not further modulated after CF-LVAD implantation. [ABSTRACT FROM AUTHOR]

Purpose De novo aortic insufficiency is one of unresolved complications after left ventricular assist device (LVAD) implant. It has been hypothesized that decreased and oscillatory wall shear stress (WSS) on the aortic valve following LVAD implantation cause leaflet degeneration resulting in AI. We developed novel approach to measure WSS on the aortic valve using vector flow mapping (VFM) images. Methods Aortic root color Doppler image was obtained using intraoperative epiaortic echocardiogram in 6 patients who received LVAD implant and 8 patients undergoing LVAD explant and heart transplant. As a control group, we enrolled 5 patients undergoing CABG surgery. Using obtained images, WSS and oscillatory shear index (OSI) on the right coronary cusp (RCC) was calculated with off-line software, Echo VFM® (Cardio Flow Design, Tokyo, Japan) (Figure). Results Image analysis was successful in all patients. The WSS on the ventricularis of the RCC was significantly lower in the LVAD group compared to control (0.09±0.06 vs. 0.35±0.27 Pa, p <0.01). In LVAD patients, ventricularis WSS was constantly low during whole cardiac cycle (Figure). The WSS on the fibrosa was similar between groups (LVAD 0.12±0.09 vs. control 0.17±0.15 Pa, p =0.405). The OSI was not significantly different between groups both on the ventricularis (LVAD 0.149±0.139 vs, control 0.081±0.067 Pa, p =0.458) and on the fibrosa (LVAD 0.144±0.130 vs. control 0.161±0.167 Pa, p =0.779). Conclusion Significantly lower WSS on the ventricularis may be accountable for AV degeneration and subsequent De Novo AI in patients with LVAD. [ABSTRACT FROM AUTHOR]

Purpose It has been proposed that the high prevalence of bleeding events in continuous-flow left ventricular assist device (CF-LVAD) patients may be lowered by increasing von Willebrand factor-release via augmented peripheral pulsatility (PI). However, the hemostatic effects of increased PI may be offset by concomitant increases in local wall shear stress (WSS) - which is known to stimulate the endothelial release of anti-thrombotic factors (NO, prostacyclin, thrombomodulin). Hypothesis Higher pulsatility in the middle cerebral artery of CF-LVAD patients will be significantly associated with increased local WSS. Methods Video loops of color Doppler recordings from the middle cerebral artery were obtained in 8 HeartMate II (HM II) patients and 8 healthy controls. Data were analyzed offline with validated vector flow mapping software. WSS was calculated as: viscosity*(du/dy), according to Newton's law. Viscosity was corrected by using individuals' hematocrit. Importantly, we determined not only peak WSS but also WSS per beat (area under the curve) and WSS/min (WSS/beat * heart rate). PI was measured from angle-corrected pulsed-wave Doppler velocities. Results Peak WSS and WSS/beat were lower in HM II (P = 0.05) but WSS/min was not different (P > 0.05). Supporting our hypothesis, WSS and pulsatility index (PI) were strongly correlated non-linearly in HM II patients (r2 = 0.94) and shared a common linear slope with healthy controls between a PI of ∼0.45 and ∼0.90 (Fig. 1). Conclusion In CF-LVAD patients, a strong curvilinear relationship was noted between cerebral PI and WSS, with linear increases in WSS shown above a PI of ∼0.45. These data suggest a threshold for PI and its interaction with endothelium-dependent hemostatic and anti-thrombotic activity. Future work is warranted to investigate whether alteration of the PI-WSS relationship will influence the release of hemostatic or anti-thrombotic factors and reduce cerebral bleeding in CF-LVAD patients. [ABSTRACT FROM AUTHOR]