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Flexible Endoscopic Robots In article number 2200403, Shuxin Wang, Chaoyang Shi, and colleagues propose a novel distal continuum joint based on the hybrid pneumatic and cable‐driven approach, which achieves excellent bending characteristics in both flexible and rigid states, variable stiffness, and high loading capacity for flexible gastrointestinal endoscopy. The presented method demonstrates an effective and practical approach for flexible endoscopic robots to achieve flexibility for access and rigidity for operation.

Nicotinamide adenine dinucleotide (NAD + ) has emerged as a critical co-substrate for enzymes involved in the beneficial effects of regular calorie restriction on healthspan. As such, the use of NAD + precursors to augment NAD + bioavailability has been proposed as a strategy for improving cardiovascular and other physiological functions with aging in humans. Here we provide the evidence in a 2 × 6-week randomized, double-blind, placebo-controlled, crossover clinical trial that chronic supplementation with the NAD + precursor vitamin, nicotinamide riboside (NR), is well tolerated and effectively stimulates NAD + metabolism in healthy middle-aged and older adults. Our results also provide initial insight into the effects of chronic NR supplementation on physiological function in humans, and suggest that, in particular, future clinical trials should further assess the potential benefits of NR for reducing blood pressure and arterial stiffness in this group. Declining NAD + levels have been linked to aging-associated pathologies. Here the authors present results of a double-blind, randomized crossover trial on 30 healthy middle-aged individuals to show that nicotinamide riboside effectively elevates NAD + levels in humans, appears to be well tolerated, and may have potential to improve cardiovascular parameters.

Increased risk of premature cardiovascular disease (CVD) is well recognized in systemic lupus erythematosus (SLE). Aberrant type I-Interferon (IFN)-neutrophil interactions contribute to this enhanced CVD risk. In lupus animal models, the Janus kinase (JAK) inhibitor tofacitinib improves clinical features, immune dysregulation and vascular dysfunction. We conducted a randomized, double-blind, placebo-controlled clinical trial of tofacitinib in SLE subjects (ClinicalTrials.gov NCT02535689). In this study, 30 subjects are randomized to tofacitinib (5 mg twice daily) or placebo in 2:1 block. The primary outcome of this study is safety and tolerability of tofacitinib. The secondary outcomes include clinical response and mechanistic studies. The tofacitinib is found to be safe in SLE meeting study’s primary endpoint. We also show that tofacitinib improves cardiometabolic and immunologic parameters associated with the premature atherosclerosis in SLE. Tofacitinib improves high-density lipoprotein cholesterol levels ( p  = 0.0006, CI 95%: 4.12, 13.32) and particle number ( p  = 0.0008, CI 95%: 1.58, 5.33); lecithin: cholesterol acyltransferase concentration ( p  = 0.024, CI 95%: 1.1, −26.5), cholesterol efflux capacity ( p  = 0.08, CI 95%: −0.01, 0.24), improvements in arterial stiffness and endothelium-dependent vasorelaxation and decrease in type I IFN gene signature, low-density granulocytes and circulating NETs. Some of these improvements are more robust in subjects with STAT4 risk allele. Increased risk of premature cardiovascular disease in systemic lupus erythematosus (SLE) is not well understood, but in animal models, the Janus kinase inhibitor tofacitinib improves related phenotypes. Here the authors report a Phase 1 double-blind randomized trial that shows tofacitinib is safe and well tolerated in in patients with SLE.

Purpose The dietary egg-protein hydrolysate Newtricious (NWT)-03 has previously demonstrated improvements in blood pressure and metabolic profiles. However, the long-term effects on vascular function and cardiometabolic risk markers are unknown. Methods Forty-four older (aged 60–75) adults with overweight/obesity experiencing elevated Subjective Cognitive Failures (SCF) were randomized into a 36-week, double-blind, placebo-controlled trial. Participants either consumed 5.7 g of an egg-protein hydrolysate (NWT-03) or maltodextrin placebo. Endothelial function (brachial artery flow-mediated vasodilation [FMD] and carotid artery reactivity [CAR] responses after a cold pressor test), arterial stiffness (carotid-to-femoral pulse wave velocity [PWV c-f ]), retinal microvascular calibers, and cardiometabolic risk markers (insulin sensitivity using a 7-point oral glucose tolerance test, serum lipid profiles, and blood pressure) were evaluated. Results FMD observed a non-significant trend towards a 0.3 percentage point (pp) increase in the intervention compared to the placebo group (95% CI: [0.0, 0.7]; p = 0.08), and a significant intervention effect was observed on CAR responses based on a 0.7 pp improvement after a cold pressor test (95% CI: [0.1, 1.3]; p = 0.03). No significant overall changes were observed for arterial stiffness as measured by PWV c-f . Retinal microvascular calibers and cardiometabolic parameters also did not change. Conclusion Long-term supplementation with 5.7 g of the egg-protein hydrolysate NWT-03 for 36 weeks improved vascular endothelial function in older adults with overweight/obesity experiencing elevated SCF, which may benefit cardiovascular disease risk. No overall changes in other vascular function markers, retinal microvascular calibers or cardiometabolic risk markers were observed. Clinical Trial Registration The study was registered at ClinicalTrials.gov in January 2021 as NCT04831203: https://clinicaltrials.gov/study/NCT04831203

Quasi-zero stiffness (QZS) vibration isolators show great advantages in low frequency vibration isolation and often developed by compensating the negative stiffness of the bistable structure by linear spring. To overcome the limitation of the bistable property, this paper utilizes linear stiffness (linear spring) and nonlinear stiffness (repulsive magnets) respectively to compensate the general negative stiffness (rhombus structure), and realizes two types of vibration isolators, the QZS-L and QZS-N isolator. Static models are established to characterize the stiffness property and reveal two basic principles for realizing QZS. The realization of QZS in the QZS-L isolator requires large deformation, but it can be achieved under small deformation in the QZS-N system. Both the QZS-L isolator and QZS-N isolator have weak asymmetry in stiffness, which leads to bias in steady-state response. And the former has stronger asymmetry and greater bias. The adjustment method of the QZS-L and QZS-N isolators for different loads is also elaborated separately. A unified dynamic model is established and the displacement transmissibility is derived to evaluate the vibration isolation performance of the two system. The QZS-L isolator is a softening system with a left-shifted resonance peak, while the QZS-N behave as a hardening system with a right-shifted resonance peak. Both isolators have a low resonant frequency and a wide isolation frequency band. Moreover, the initial isolation frequency can become lower when adjusted for larger loads. Comprehensive comparisons and discussions of static characteristics, isolation band, and zero offset are instructive in designing low frequency vibration isolators.

Abstract Background: Arterial stiffening increases with age and blood pressure and is associated with cardiovascular disease (CVD), but the relationship between blood pressure lowering and arterial stiffening is still uncertain, especially in older people. This study aimed to evaluate the effect of intensive blood pressure treatment on the progression of arterial stiffness and risk of CVD in older patients with hypertension. Methods: The Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial was a multicenter, randomized, controlled trial performed at 42 clinical centers throughout China, and 8511 patients aged 60–80 years with essential hypertension were enrolled and randomly assigned to systolic blood pressure (SBP) target of 110 mmHg to <130 mmHg (intensive treatment) or 130 mmHg to <150 mmHg (standard treatment). Patients underwent repeated examinations of the brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) at baseline, and the arterial stiffness was evaluated at the 3-year follow-up. A total of 5339 patients who had twice repeated measurements were included in this study. Changes in arterial stiffness between the intensive and standard treatment groups were analyzed using a multivariate linear regression model. The Cox proportional hazard regression model was used to evaluate the effect of intensive treatment on primary CVD outcomes. Results: The changes in baPWV were 61.5 cm/s (95% confidence interval [CI]: 49.8–73.2 cm/s) in the intensive treatment group and 98.4 cm/s (95% CI: 86.7–110.1 cm/s) in the standard treatment group (P <0.001). Intensive treatment significantly delayed the progression of arterial stiffness, with an annual change of 23.1 cm·s–1·year–1 vs. 36.7 cm·s–1·year–1 of baPWV in the intensive and standard treatment groups, respectively. During a median follow-up period of 3.36 years, primary CVD outcomes occurred in 77 (2.9%) patients in the intensive treatment group compared with 93 (3.5%) in the standard treatment group. Intensive treatment resulted in a significantly lower CVD risk in patients aged 70–80 years or with SBP <140 mmHg. Conclusion: Intensive blood pressure control with an SBP target of 110 mmHg to <130 mmHg could delay the progression of arterial stiffness and reduce the risk of CVD in older patients with hypertension. Clinical trial registration: http://www.clinicaltrials.gov; No. NCT03015311.

Background Premature arterial stiffening and atherosclerosis are increased in patients with inflammatory arthropathies such as rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). The proinflammatory protein calprotectin is associated with inflammatory arthropathies, vascular pathology, and acute coronary events. We examined the long-term effects of treatment with tumor necrosis factor (TNF)-α antagonists on aortic stiffness and carotid intima media thickness (CIMT) in patients with inflammatory arthropathies, and the relationships to the levels of calprotectin. Methods Fifty-five patients with RA, AS, or PsA and a clinical indication for anti-TNF-α therapy were included and followed with regular examinations for 1 year. Thirty-six patients starting with anti-TNF-α therapy were compared with a nontreatment group of 19 patients. Examinations included assessments of aortic stiffness (aortic pulse wave velocity, aPWV), CIMT, and plasma calprotectin. Results After 1 year, aPWV (mean (s.d.)) was improved in the treatment group, but not in the control group (−0.54 [0.79] m/s vs. 0.06 [0.61] m/s, respectively; P = 0.004), and CIMT progression (median (quartile cut-points, 25th and 75th percentiles)) was reduced in the treatment group compared to the control group (−0.002 [-0.038, 0.030] mm vs. 0.030 [0.011, 0.043] mm, respectively; P = 0.01). In multivariable analyses, anti-TNF-α therapy over time was associated with improved aPWV (P = 0.02) and reduced CIMT progression (P = 0.04), and calprotectin was longitudinally associated with aPWV (P = 0.02). Conclusions Long-term anti-TNF-α therapy improved aortic stiffness and CIMT progression in patients with inflammatory arthropathies. Calprotectin may be a soluble biomarker reflecting aortic stiffening in these patients.

The close relationship between hypertension and dietary sodium intake is widely recognized and supported by several studies. A reduction in dietary sodium not only decreases the blood pressure and the incidence of hypertension, but is also associated with a reduction in morbidity and mortality from cardiovascular diseases. Prolonged modest reduction in salt intake induces a relevant fall in blood pressure in both hypertensive and normotensive individuals, irrespective of sex and ethnic group, with larger falls in systolic blood pressure for larger reductions in dietary salt. The high sodium intake and the increase in blood pressure levels are related to water retention, increase in systemic peripheral resistance, alterations in the endothelial function, changes in the structure and function of large elastic arteries, modification in sympathetic activity, and in the autonomic neuronal modulation of the cardiovascular system. In this review, we have focused on the effects of sodium intake on vascular hemodynamics and their implication in the pathogenesis of hypertension.

The negative stiffness exhibited by bi-stable mechanisms together with the tunable superelasticity offered by shape memory alloy (SMA) wires can enhance the dynamic resilience of a structure in the context of vibration isolation. The effects of negative stiffness and superelastic damping in base-isolated structures are here explored by carrying out an extensive study of the nonlinear dynamic response via pathfollowing, bifurcation analysis, and time integration. The frequency-response curves of the isolated structure, with and without the negative stiffness contribution, are numerically obtained for different excitation amplitudes to construct the acceleration and displacement transmissibility curves. The advantages of negative stiffness, such as damping augmentation and reduced acceleration/displacement transmissibility, as well as the existence of rich bifurcation scenarios toward quasi-periodicity and chaos, are discussed.

A quasi-zero-stiffness (QZS) vibration isolator is an ideal device for low-frequency vibration isolation. However, its stiffness increases steeply against the displacement, which renders a QZS isolator to be less effective in an ultra-low-frequency range. Aiming at solving this issue, a new nonlinear ultra-low-frequency vibration isolator with a dual quasi-zero-stiffness (DQZS) mechanism is put forward by combining two subordinate QZS mechanisms with a vertical linear spring in parallel. The subordinate mechanism itself has a QZS feature, which provides negative stiffness along the vertical direction through an oblique link rod. The parameter design of the isolator is carried out to fulfil quasi-zero stiffness, which shows that the stiffness–displacement curve is much lower and more flat than the traditional QZS (TQZS) isolator in a wide displacement range. The dynamic behaviours of the DQZS vibration isolation system (VIS) are determined by employing the harmonic balance method, and the vibration isolation performance is evaluated by using theoretical, numerical and experimental transmissibility. It shows that both the beginning frequency of the vibration isolation and the peak transmissibility of the DQZS VIS are lower than the TQZS isolator, which indicates better vibration isolation performance of this ultra-low-stiffness DQZS VIS.