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Neuroinflammation and cholinergic dysfunction, leading to cognitive impairment, are hallmarks of aging and neurodegenerative disorders, including Alzheimer's disease (AD). Acetylcholinesterase inhibitors (AChEI), the symptomatic therapy in AD, attenuate and delay the cognitive deficit by enhancing cholinergic synapses. The α7 nicotinic acetylcholine (ACh) receptor has shown a double-edged sword feature, as it binds with high affinity Aβ1–42, promoting intracellular accumulation and Aβ-induced tau phosphorylation, but also exerts neuroprotection by stimulating anti-apoptotic pathways. Moreover, it mediates peripheral and central anti-inflammatory response, being the effector player of the activation of the cholinergic anti-inflammatory pathway (CAIP), that, by decreasing the release of TNF-α, IL-1β, and IL-6, it may have a role in improving cognition. The finding in preclinical models that, in addition to their major function (choline esterase inhibition) AChEIs have neuroprotective properties mediated via α7nAChR and modulate innate immunity, possibly as a result of the increased availability of acetylcholine activating the CAIP, pave the way for new pharmacological intervention in AD and other neurological disorders that are characterized by neuroinflammation. CHRFAM7A is a human-specific gene acting as a dominant negative inhibitor of α7nAChR function, also suggesting a role in affecting human cognition and memory by altering α7nAChR activities in the central nervous system (CNS). This review will summarize the current knowledge on the cholinergic anti-inflammatory pathway in aging-related disorders, and will argue that the presence of the human-restricted CHRFAM7A gene might play a fundamental role in the regulation of CAIP and in the response to AChEI. [ABSTRACT FROM AUTHOR]

Introduction: This study aims to investigate how image settings affect carotid Intima-Media-Thickness (IMT) and diameter estimation performed with Carotid Studio (Quipu-Srl). Methods: Fourteen healthy volunteers (24.4 ± 4.4 years; eight men) were recruited. Longitudinal scans 3-cm-deep of common-carotid-arteries with the same region-of-interest were obtained by expert operator, starting from a "default-setup" (central Time Gain Compensation-TGC; gain: 50 dB; no persistence filter) and adjusting one parameter at a time (oblique TGC; gain: 10 dB increments from 30 to 70 dB; persistence filter). The acquisition was performed twice, and repeatability was expressed for each setup as Coefficient of Variation (CV). Significant changes (p ≤ 0.05) compared with the "default-setup" were analysed by Wilcoxon signed-rank-test. Results: Sixty and 70 dB gain resulted in overestimating IMT (from 0.460 ± 0.001 to 0.506 ± 0.030 mm and 0.538 ± 0.011 mm, p = 0.002 and 0.023 respectively vs. default-50 dB), underestimating the mean diameter (from 6.044 ± 0.040 mm to 5.763 ± 0.004 mm, p = 0.008 and to 5.698 ± 0.225 mm, p = 0.002), and for 70 dB, increasing IMT CV from 2.14 ± 1.92% to 6.85 ± 5.23% (p = 0.01) and diameter CV from 1.79 ± 1.22% to 4.77 ± 4.71% (p = 0.05). Distension CV increased from 5.71 ± 4.31% to 10.84 ± 5.91% (p = 0.041) and to 12.59 ± 7.97% (p = 0.021) for 60 and 70 dB respectively. Persistence and TGC did not affect repeatability, whereas diameter (5.955 ± 0.033 mm, p = 0.005) and distension (from 0.816 ± 0.019 mm to 0.655 ± 0.018 mm, p = 0.002) values were underestimated when persistence filter was active. Discussion: Precision and reproducibility of carotid parameters, automatically assessed by Carotid Studio, are affected by high gain levels, due to image grey-level saturation. Persistence filter activation leads to underestimate diameter and distension, possibly due to mathematical operator behaviour and image temporal filtering. Since ultrasound setup significantly affects carotid parameter assessment, it should be reported and replicated in follow-up scans. Highlights: We investigated how ultrasound imaging setup may affect carotid parameters. Carotid parameters' reproducibility was lower with high-gain values. Persistence filter leads to underestimation of diameter and distension. The scan projection seems to influence carotid parameter estimation. Image depth should be kept at the lowest attainable value for best repeatability. [ABSTRACT FROM AUTHOR]

Background: The intense exercise effect evaluation on the cardiovascular system can help to profile and reduce the risks (1-3). This work aims at assessing cardiovascular adaptation in runners by a multi-site non-invasive approach. Methods: 49 runners (A) trained for 8.5 ± 8.9 years, 3.9 ± 1.4 days/week and 15 sedentary (S) subjects matched by sex, age, BMI, baseline brachial pressures and heart rate underwent ultrasound semi-automatic assessment of the vascular system (arterial mean diameters, MD, and distensibility, DC, of abdominal aorta, common carotid, common femoral, brachial artery) and of cardiac parameters. Central pressurebased (applanation tonometry) hemodynamic properties according to the reservoir theory were derived. Results: Cardiac parameters related to dimensions, mass and volumes showed significantly higher values in A compared to S (A/S: Left Ventricular Internal diameter, 29 ± 3 mm/27 ± 3 mm; Left Ventricular Mass, 161 ± 31 g/141 ± 25 g; Aortic root size 30 ± 3 mm/27 ± 2 mm; Stroke Volume, 76 ± 13 mL/69 ± 16 mL; Arterial Elastance, 7 ± 1 mm HgmL-1/6 ± 1 mm HgmL-1). MD was greater in each large arterial site in A than in S reporting a trend in the carotid and significant differences in aorta and femoral artery (aorta: 16 ± 2 mm/13 ± 1 mm; femoral: 10 ± 1 mm/9 ± 1 mm). DC evidenced a lowering trend in A for each arterial site except for the brachial artery. Hemodynamic parameters showed higher reservoir pressure in A compared to S (Pressure reservoir integral, 14 ± 4/11 ± 3). Conclusions: Strenuous exercise induced a well-known cardiac remodeling which can be hypothesized to be slower in the arterial tree because of highly differentiated and complex mechanism aiming to heart protection. Accordingly, the increased reservoir pressure in runners could be interpreted as sentinel parameter of vascular "fatigue". [ABSTRACT FROM AUTHOR]

Rationale and Aim: Essential hypertension is characterized by extensive alterations of arterial geometry and mechanical properties: increased stiffness, dilation and wall of large arteries, increased thickness in muscular arteries, small artery remodeling. This study is aimed at exploring function and structure of the digital arteries of the hand, muscular arteries with an internal diameter of 500–1000 mm, easily accessible by ultrahigh frequency ultrasound. Methods: 24 hypertensive women (HT) and 37 healthy controls (C) were recruited. 5’-videoclips of left palmar digital arteries were obtained by VevoMD (FUJIFILM, VisualSonics, Toronto, Canada), by means of a 70 MHz probe (axial-lateral resolution 30–65 mm). An automatic system (Cvsuite, Quipu srl; Pisa, Italy) was used to measure intima-media thickness (IMT) and diameter. Distensibility and stiffness were then calculated using left brachial pulse pressure (PP - oscillometric) Results: HT and C had similar age (57 ± 11 vs 53 ± 11 years, p = 0.22), BMI (24.9 ± 4.6 vs 24.5 ± 4.2 vs kg/m2, p = 0.80) and mean blood pressure (BP, 95 ± 12 vs 91 ± 12 mmHg, p = 0.24); HT showed slighlty higher PP (54 ± 14 vs 47 ± 10, p = 0.07). Palmar digital lumen tended to be higher in HT (804 ± 201 vs 696 ± 191 mm, p = 0.10), while IMT was similar (120 ± 23 vs 125 ± 36 mm, p = 0.81). Distensibility was reduced (21.4 ± 18.2 vs 29.0 ± 18.8 kPa 1, p < 0.05), while stiffness was increased (7.95 ± 2.22 vs 6.72 ± 2.11 m/s, p < 0.005). Conclusions: This is the first report of the presence of altered mechanical properties (i.e. increased stiffness) in muscular arteries with lumen <1000 mm of essential hypertensive women. These findings suggest that increased hemodynamic load characterizing hypertension lead to a different vascular phenotype in each arterial segment. [ABSTRACT FROM AUTHOR]

Purpose/Background/Objectives: Recently great attention has been placed on innovative cardiovascular biomarkers obtained from wave separation (WS), wave intensity analysis (WIA) and the reservoir-wave (RW) concept. Pressure waveforms needed to implement these techniques can be obtained in different ways. Aim of this study was to evaluate differences in WS, WIA and RW parameters obtained deriving pressure curves in different ways. Methods: Twenty-two individuals (49 ± 17 years, 59% males) were examined. Common carotid blood flow waveforms were obtained from Pulsed-Wave Doppler images. Carotid pressure waveforms were obtained in four different ways: 1) standard method, i.e., with applanation tonometry; 2) linear scaling from ultrasound (US)-derived diameter curve; 3) exponential scaling from US-derived diameter curve; 4) linear scaling from an accelero-metric-derived diameter signal. In each case, reflection magnitude (RM) and reflection index (RI) were obtained from WS. The amplitude of the first positive peak (W1), of the second positive peak (W2) and of the negative one (Wb) were calculated from WIA; the maximum of the reservoir (maxPr) and the excess (maxPex) pressure were achieved from RW. Results: According to the intra-class coefficient values, the agreement between the standard method and all the others was excellent in case of RM, RI, maxPrand maxPex(0.82–0.97), while reached only a fair/good level in case of W1, W2and Wb(0.44–0.82). Conclusions: The use of alternative carotid pressure waveforms does not influence the cardiovascular parameters obtained by WS and RW, while those derived by WIA are affected by the carotid pressure curve employed. [ABSTRACT FROM AUTHOR]

Purpose/Background/Objectives: Carotid plaque vulnerability assessment is essential for the identification of high-risk patients. A specific mouse model for the study of carotid atherosclerosis has been recently developed. Aim of this study was to develop a predictive mathematical model for carotid plaque vulnerability assessment based on the post processing of micro-Ultrasound (mUS) images only. Methods: 17 ApoE-/- male mice (16 weeks) were employed. After three weeks of high-fat diet, a tapered cast, designed to induce the formation of an unstable plaque upstream from the cast and a stable one downstream from it, was surgically placed around the right common carotid. mUS examination was repeated before the surgical procedure and after three months from it. Color-Doppler, B-mode and Pulsed-wave Doppler images were acquired to assess morphological, functional and hemodynamic parameters. In particular, texture analysis was applied on both the atherosclerotic lesions post-processing B-mode images. Peak velocity (Vp), Relative Turbolence Intensity (rTI) and velocity range (rangevel) were assessed from PW-Doppler images. Relative Distension (relD) and Pulse Wave Velocity (PWV) were evaluated for both the regions. All the mUS indexes underwent a feature reduction process and were used to train different machine learning approaches. Results: The downstream region presented higher PWV values than the upstream one; furthermore, it was characterized by higher values of rTI and rangevel. The weighted kNN classifier supplied the best providing 92.6% accuracy, 91% sensitivity and 94% specificity. Conclusions: The mathematical predictive model could represent a valid approach to be translated in the clinical field and easily employed in clinical practice. [ABSTRACT FROM AUTHOR]