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We report that increasing nitric oxide bioavailability via 8 wk of inorganic nitrate/nitrite supplementation improves maximal aerobic exercise capacity in patients with type 2 diabetes mellitus. Similarly, we observed a rightward shift in the gas exchange threshold. Taken together, these data indicate inorganic nitrate/nitrite may serve as a means to improve fitness in patients with type 2 diabetes mellitus.

BACKGROUND & AIMS: Peripheral artery disease (PAD) is characterized by elevated blood pressure (BP), low nitric oxide availability (NO), and exaggerated pressor responses to sympatho-excitatory stressors. Inorganic nitrate reduces peripheral BP in healthy and chronically diseased populations. The objective of this study was to investigate the effects of eight-weeks of sodium nitrate (NaNO(3)) supplementation on indices of BP in PAD patients. METHODS & RESULTS: 21 patients with PAD were recruited to participate in this study, undergoing 8-weeks of NaNO(3) (n=13; 73±9 years) or placebo (n=8; 69±10 years) supplementation. BP responsiveness to a cold pressor test (CPT) were examined prior to and following the supplementation period. The systolic BP response (change from rest) during the first (26±10 vs. 19±11mmHg) and second minutes (32±10 vs. 26±12mmHg) of CPT were reduced following NaNO(3) (P

AIMS Patients with type 2 diabetes mellitus (T2DM) have reduced vasodilatory responses during exercise partially attributable to low nitric oxide (NO) levels. Low NO contributes to greater α-adrenergic mediated vasoconstriction in contracting skeletal muscle. We hypothesized boosting NO bioavailability via 8wks of active beetroot juice (BRA, 4.03 mmol nitrate, 0.29 mmol nitrite, n = 19) improves hyperemia, via reduced α-mediated vasoconstriction, during handgrip exercise relative to nitrate/nitrite-depleted beetroot juice (BRP, n = 18) in patients with T2DM. METHODS Forearm blood flow (FBF) and vascular conductance (FVC) were calculated at rest and during handgrip exercise (20%max, 20contractions·min-1). Phenylephrine (α1-agonist) and dexmedetomidine (α2-agonist) were infused intra-arterially during independent trials to determine the influence of α-mediated vasoconstriction on exercise hyperemia. Vasoconstriction was quantified as the percent-reduction in FVC during α-agonist infusion, relative to pre-infusion, as well as the absolute change in %FVC during exercise relative to the respective rest trial (magnitude of sympatholysis). RESULTS ΔFBF (156 ± 69 to 175 ± 73 ml min-1) and ΔFVC (130 ± 54 to 156 ± 63 ml min-1·100 mmHg-1, both P

The balance of angiogenic factors, including vascular endothelial growth factor (VEGF), and angiostatic factors, like thrombospondin-1 (TSP-1) and endostatin, controls striated muscle angiogenic responses to exercise training. The effect of age on circulating levels of these factors following a bout of exercise is unclear. The authors hypothesized that older adults would have lower circulating VEGF but higher TSP-1 and endostatin after exercise compared with young adults. Ten young and nine older participants cycled for 45 min at 60% estimated HRmax. Serum [VEGF], [TSP-1], and [endostatin] obtained before (PREX), immediately after (POSTX0), and 3 hr after (POSTX3) exercise were analyzed. [VEGF] increased in older adults only from PREX to POSTX0 (p p

Objectives Patients chronically treated with angiotensin-converting enzyme inhibitors (ACEIs) may develop hypotension after induction of general anesthesia. A fraction of these patients are resistant to therapeutic doses of vasopressors, which poses serious concerns for hemodynamic management. The authors hypothesized that the patients who develop refractory hypotension, compared with those who do not, show lower central arterial stiffness due to the profound effect of ACEIs. Design Prospective observational study. Setting Single tertiary center. Interventions Fifty surgical patients chronically treated with ACEIs were enrolled. Prior to surgery, all the patients had central arterial stiffness assessment measured by carotid-femoral pulse-wave velocity. Patients were categorized into 2 groups according to the systolic blood pressure response during the first 10 minutes after induction of general anesthesia: a vasopressor-resistant hypotension group requiring more than 200 µg phenylephrine, or a control group requiring no more than 200 µg of phenylephrine to maintain systolic blood pressure above 90 mmHg during the study period. Measurements and Main Results Carotid-femoral pulse-wave velocity was significantly lower in the vasopressor-resistant hypotension group compared to the control group (7.6 [7.2-8.3] m/s v 9.9 [8.7-12.0] m/s, p = 0.001 [Hodges-Lehman median difference 2.2, 95% confidence interval = 1.1-4.4]). Conclusion These findings suggested that preoperative measurement of carotid-femoral pulse-wave velocity in patients chronically treated with ACEIs could help identify patients at increased risk of developing hypotension refractory to vasopressors after induction of general anesthesia.

BACKGROUND: Prolonged times to tracheal extubation are those from end of surgery (dressing on the patient) to extubation 15 minutes or longer. They are so long that others in the operating room (OR) generally have exhausted whatever activities can be done. They cause delays in the starts of surgeons' to-follow cases and are associated with longer duration workdays. Anesthesiologists rate them as being inferior quality. We compare prolonged times to extubation between a teaching hospital in the United States with a phase I postanesthesia care unit (PACU) and a teaching hospital in Japan without a PACU. Our report is especially important during the coronavirus disease 2019 (COVID-19) pandemic. Anesthesiologists with some patients undergoing general anesthetics and having initial PACU recovery in the ORs where they had surgery can learn from the Japanese anesthesiologists with all patients recovering in ORs. METHODS: The historical cohort study included all patients undergoing gynecological surgery at a US hospital (N = 785) or Japanese hospital (N = 699), with the time from OR entrance to end of surgery of at least 4 hours. RESULTS: The mean times from end of surgery to OR exit were slightly longer at the US hospital than at the Japanese hospital (mean difference 1.9 minutes, P < .0001). The mean from end of surgery to discharge to surgical ward at the US hospital also was longer (P < .0001), mean difference 2.2 hours. The sample standard deviations of times from end of surgery until tracheal extubation was 40 minutes for the US hospital versus 4 minutes at the Japanese hospital (P < .0001). Prolonged times to tracheal extubation were 39% of cases at the US hospital versus 6% at the Japanese hospital; relative risk 6.40, 99% confidence interval (CI), 4.28-9.56. Neither patient demographics, case characteristics, surgeon, anesthesiologist, nor anesthesia provider significantly revised the risk ratio. There were 39% of times to extubation that were prolonged among the patients receiving neither remifentanil nor desflurane (all such patients at the US hospital) versus 6% among the patients receiving both remifentanil and desflurane (all at the Japanese hospital). The relative risk 7.12 (99% CI, 4.59-11.05) was similar to that for the hospital groups. CONCLUSIONS: Differences in anesthetic practice can facilitate major differences in patient recovery soon after anesthesia, useful when the patient will recover initially in the OR or if the phase I PACU is expected to be unable to admit the patient.

Findings presented in this article are the first to show patients with type 2 diabetes mellitus have blunted hyperemic and vasodilatory responses to dynamic handgrip exercise. Moreover, we illustrate greater α1-adrenergic-mediated vasoconstriction may contribute to our initial observations. Collectively, these data suggest patients with type 2 diabetes may have impaired functional sympatholysis, which can contribute to their reduced exercise capacity.

Blood flow (BF) and vasodilator responses to knee-extension exercise are attenuated in older adults across an exercise transient (onset, kinetics, and steady-state), and reduced nitric oxide bioavailability (NO) has been hypothesized to be a primary mechanism contributing to this attenuation. We tested the hypothesis acute dietary nitrate (NO3−) supplementation (~ 4.03 mmol NO3− and 0.29 mmol NO2−) would improve leg vasodilator responses across an exercise transient during lower limb exercise in older adults. Older (n = 10) untrained adults performed single and rhythmic knee-extension contractions at 20% and 40% work-rate maximum (WRmax) prior to and 2-h after consuming a NO3− or placebo beverage in a double-blind, randomized fashion. Femoral artery BF was measured by Doppler ultrasound. Vascular conductance was calculated using BF and mean arterial pressure. Acute ingestion of dietary NO3− enhanced plasma [NO3−] and [NO2−] (P 0.05). Leg vasodilator kinetics during rhythmic exercise remained unchanged following NO3− and placebo ingestion (P > 0.05). The key findings of this study are that despite increasing plasma [NO3−] and [NO2−], acute dietary NO3− intake had no effect on (1) rapid hyperaemic or vasodilator responses at the onset of exercise; (2) hyperaemic and vasodilator responses during steady-state submaximal exercise; or (3) kinetics of vasodilation preceding steady-state responses. Collectively, these findings suggest that low dose dietary NO3− supplementation does not improve hyperaemic and vasodilator responses across an exercise transient in older adults.

We propose a simple theory suggesting that basic employment protection can improve economy-wide welfare as it mitigates a time inconsistency problem that makes a firm’s promise to workers less credible. By tilting the bargaining power in renegotiations on contract terms toward workers, basic employment protection can incentivize workers to invest in firm-specific human capital and allow firms to keep operating. This contrasts to the case of rigid labor protection, which forces firms to go bankrupt too often with economic costs. We test for the effects using a quasi-natural experiment: US workers gained basic protections between the early-1970s and the mid-1990s, but in years varying by state. We find employment protection to benefit the growth of knowledge-intensive industries. We corroborate another prediction that stronger bargaining powers of workers vis-A -vis other stakeholders since contemporaneous bank branch deregulations (i.e., reduction in banks’ monopoly powers) also benefit knowledge-intensive industries. Although labor and financial reforms are rarely jointly investigated, we confirm that the direct positive effect of basic employment protection prevails when correcting for (changes in) creditors’ powers and vice versa. Since the findings do not maintain for R&D-intensive industries, we interpret the firm-specific human capital in our theory broadly, as for white-collar jobs.

BACKGROUND Patients with type 2 diabetes mellitus (T2DM) have increased cardiovascular risk due to elevated blood pressure (BP). As low levels of nitric oxide (NO) may contribute to increased BP, we determined if increasing NO bioavailability via eight weeks of supplementation with beetroot juice containing inorganic nitrate/nitrite (4.03 mmol nitrate, 0.29 mmol nitrite) improves peripheral and central BP relative to nitrate/nitrite-depleted beetroot juice. METHODS Peripheral and central BP were assessed at heart-level in supine subjects using a brachial artery catheter and applanation tonometry, respectively. RESULTS Nitrate/nitrite supplementation reduced peripheral systolic BP (148 ± 16 to 142 ± 18 mm Hg, P < 0.05) but not placebo (150 ± 19 to 149 ± 17 mm Hg, P = 0.93); however, diastolic BP was unaffected (supplement-by-time P = 0.08). Central systolic BP (131 ± 16 to 127 ± 17 mm Hg) and augmented pressure (13.3 ± 6.6 to 11.6 ± 6.9 mm Hg, both P < 0.05) were reduced after nitrate/nitrite, but not placebo (134 ± 17 to 135 ± 16 mm Hg, P = 0.62; 14.1 ± 6.6 to 15.2 ± 7.4 mm Hg, P = 0.20); central diastolic BP was unchanged by the interventions (supplement-by-time P = 0.16). Inorganic nitrate/nitrite also reduced AIx (24.3 ± 9.9% to 21.0 ± 9.6%) whereas no changes were observed following placebo (24.6 ± 9.3% to 25.6 ± 9.9%, P = 0.46). CONCLUSIONS Inorganic nitrate/nitrite supplementation improves peripheral and central BP as well as AIx in T2DM. CLINICAL TRIALS REGISTRATION Trial Number NCT02804932.

We present positive evidence of price stability of cryptocurrencies as a medium of exchange. For the sample years from 2016 to 2020, the prices of major cryptocurrencies are found to be stable, relative to major financial assets. Specifically, after filtering out the less-than-one-month cycles, we investigate the daily returns in US dollars of the major cryptocurrencies (i.e., Bitcoin, Ethereum, and Ripple) as well as their comparators (i.e., major legal tenders, the Euro and Japanese yen, and the major stock indexes, S&P 500 and MSCI World Index). We examine the stability of the filtered daily returns using three different measures. First, the Pearson correlations increased in later years in our sample. Second, based on the dynamic time-warping method that allows lags and leads in relations, the similarities in the daily returns of cryptocurrencies with their comparators have been present even since 2016. Third, we check whether the cumulative sum of errors to predict cryptocurrency prices, assuming stable relations with comparators' daily returns, does not exceeds the bounds implied by the Black-Scholes model. This test, in other words, does not reject the efficient market hypothesis., 127 pages

We design and conduct a firm-level survey on the use of COVID-19-related government programs, in collaboration with Tokyo Shoko Research, LTD (TSR). Combining the survey results with the financial statements of the respondent firms, we investigate the factors behind the allocation of various government programs. We find that firms that had low credit scores in 2019, before the COVID-19 pandemic, were more likely to apply for and receive the subsidies and concessional loans offered by the Japanese government in 2020, controlling for the sales growth after the onset of the pandemic. Firms with low credit scores are not necessarily zombies, which are defined to be the firms that are non-viable but kept alive by assistance from creditors and/or the government. Our result suggests that the government assistance may have subsidized some poorly performing firms that were not yet zombies before the pandemic.

This article uses the Longitudinal Employer‐Household Dynamics to evaluate how local industry concentration affects earnings losses for displaced workers. “Concentrated industries” are those industries with a high employment share within a labor market. This article compares earnings changes between displaced workers and job stayers within concentrated industries to the same within less concentrated industries. A separate comparison is made based on the expected level of job availability within the labor market. The findings show that earnings changes for displaced workers relative to job stayers are 7–13% higher within concentrated industries when job loss occurs during periods of high job availability. Earnings changes are 4.5–6% lower, however, when the same comparison is made during periods of low job availability. When firms are hiring workers, they are more likely to hire those previously employed within the same industry, since these workers have accumulated more relevant human capital.

We confirm, with a twist, that listing to a stock exchange can mitigate financial constraints of firms, using Japanese firm-level data of 20 years, 1995–2014, controlling for the main-bank relationship and majority owner influence. Compared to a similar unlisted firm, a listed firm has a lower marginal product of capital on average and more new borrowings during recessions. Theoretically, we argue that these are the key pieces of evidence that indicate less tight financial constraints for the listed firms than the unlisted firms. However, the listed firms do not borrow more on average over time. They rather maintain a lower leverage so that they can mitigate the borrowing constraints. We also find that the listed firms do not face lower interest rates.

Objectives Lung isolation techniques are designed to facilitate surgical exposure in thoracic surgical patients and provide one-lung ventilation (OLV). Some patients have a tracheostomy in situ, which makes the management of the airway and OLV difficult. The objective of this retrospective study was to review cases that had a tracheostomy prior to thoracic surgery and evaluate the clinical use and efficiency with the airway management and lung isolation devices. Design This was a retrospective data analysis. Setting Tertiary care university hospital. Interventions After institutional review board approval, the authors reviewed 3,225 charts of patients who had thoracic surgery involving OLV. Seventy patients were identified who had tracheostomy in situ. Each case was reviewed regarding airway management and lung isolation technique. Measurements and Main Results The authors identified 70 patients who had a tracheostomy in situ. The cases were divided into 2 groups: a fresh tracheostomy stoma 7 days (n = 64). The authors collected information regarding the devices used to manage the airway and lung isolation techniques. The devices used to manage the airway include the Shiley cuffed low pressure tracheostomy tube, single-lumen endotracheal tube (SLT), or double-lumen endotracheal tube (DLT). Devices used to manage OLV included SLTs, with or without bronchial blockers, or DLTs. Flexible fiberoptic bronchoscopy was used to assess the airway and confirm the position of the lung isolation device. Six cases had an early-stage fresh tracheostomy stoma where the Shiley tracheostomy tube was used for ventilation followed by the use of a bronchial blocker. In contrast, for the patients who had a long-term stoma, the following devices were used: (1) a SLT plus a bronchial blocker in 38 cases, a Shiley tracheostomy tube plus bronchial blocker in 15 cases, use of a SLT guided into a selective bronchus in 7 cases, and use of a DLT in 4 cases. In all cases, flexible fiberoptic bronchoscopy was used and no complications occurred secondary to airway management or OLV. Conclusion In patients undergoing thoracic surgery and OLV, and with a fresh tracheostomy stoma in situ, the authors recommend the use of the Shiley tracheostomy tube plus a bronchial blocker. In patients with a long-term tracheostomy stoma, a SLT can be used selectively to intubate 1 bronchus. In addition, an SLT or a Shiley tube can be used in conjunction with an independent bronchial blocker, such as the Arndt wire-guided bronchial blocker, Cohen tip-deflecting blocker, Fuji Uniblocker, or EZ-Blocker. DLTs are the least frequently used device for OLV in tracheostomized patients.

Patients with type 2 diabetes mellitus (T2DM) exhibit diminished exercise capacity likely attributable to reduced skeletal muscle blood flow (i.e., exercise hyperemia). A potential underlying mechanism of the impaired hyperemic response to exercise could be inadequate blunting of sympathetic-mediated vasoconstriction (i.e., poor functional sympatholysis). Therefore, we studied the hyperemic and vasodilatory responses to handgrip exercise in patients with T2DM as well as vasoconstriction to selective α-agonist infusion. Forearm blood flow (FBF) and vascular conductance (FVC) were examined in patients with T2DM (

To estimate strength of a scopolamine transdermal delivery system (TDS) in vivo, using residual drug vs. pharmacokinetic analyses with the goal of scientifically supporting a single and robust method for use across the dosage form and ultimately facilitate the development of more consistent and clinically meaningful labeling. A two-arm, open-label, crossover pharmacokinetic study was completed in 26 volunteers. Serum samples were collected and residual scopolamine was extracted from worn TDS. Delivery extent and rate were estimated by (1) numeric deconvolution and (2) steady-state serum concentration determined from graphical and non-compartmental analyses. In residual drug analyses, mean ± SD scopolamine release rate was 0.015 ± 0.002 mg/h (11% RSD), vs. 0.016 ± 0.006 mg/h (35% RSD) from numeric deconvolution, 0.015 ± 0.005 mg/h (34% RSD) from graphical analysis, and 0.015 ± 0.007 mg/h (44% RSD) from non-compartmental analysis. In residual drug analyses, total drug released was 1.09 ± 0.11 mg (10% RSD), vs. 1.12 ± 0.40 mg (35% RSD) from numeric deconvolution, 1.07 ± 0.35 mg (33% RSD) from graphical analysis, and 1.07 ± 0.45 (42% RSD) from non-compartmental analysis. Extent and rate of scopolamine release were comparable by both approaches, but pharmacokinetic analysis demonstrated greater inter-subject variability.

Blood flow (BF) and vasodilator responses to knee-extension exercise are attenuated in older adults across an exercise transient (onset, kinetics, and steady-state), and reduced nitric oxide bioavailability (NO) has been hypothesized to be a primary mechanism contributing to this attenuation. We tested the hypothesis acute dietary nitrate (NOOlder (n = 10) untrained adults performed single and rhythmic knee-extension contractions at 20% and 40% work-rate maximum (WRAcute ingestion of dietary NOThe key findings of this study are that despite increasing plasma [NO

Objective Selective breeding for desirable traits is becoming popular in aquaculture. In Miyagi prefecture, Japan, a selectively bred population of Coho salmon (Oncorhynchus kisutch) has been established with the original, randomly breeding population maintained separately. Since they have been bred without family records, the genetic diversity within these populations remains unknown. In this study, we estimated the genetic diversity and key quantitative genetic parameters such as heritability and genomic breeding value for body size traits by means of genomic best linear unbiased prediction to assess the genetic health of these populations. Results Ninety-nine and 83 females from the selective and random groups, respectively, were genotyped at 2350 putative SNPs by means of double digest restriction associated DNA sequencing. The genetic diversity in the selectively bred group was low, as were the estimated heritability and prediction accuracy for length and weight (h2 = 0.26–0.28; accuracy = 0.34), compared to the randomly bred group (h2 = 0.50–0.60; accuracy = 0.51–0.54). Although the tested sample size was small, these results suggest that further selection is difficult for the selectively bred population, while there is some potential for the randomly bred group, especially with the aid of genomic information. Electronic supplementary material The online version of this article (10.1186/s13104-018-3663-4) contains supplementary material, which is available to authorized users.

Peripheral artery disease (PAD) is characterized by a reduced blood flow (BF) and an elevated blood pressure (pressor) response during lower extremity exercise. Although PAD is evident in the upper extremities, no studies have determined BF and pressor responses during upper extremity exercise in PAD. Emerging evidence suggests that inorganic nitrate supplementation may serve as an alternative dietary strategy to boost nitric oxide bioavailability, improving exercising BF and pressor responses during exercise. The present study investigated 1) BF and pressor responses to forearm exercise in patients with PAD ( n = 21) relative to healthy age-matched control subjects ( n = 16) and 2) whether 8 wk of NaNO3supplementation influenced BF and pressor responses to forearm exercise in patients with PAD. Patients with moderate to severe PAD were randomly assigned to a NaNO3(1 g/day, n = 13)-treated group or a placebo (microcrystalline cellulose, n = 8)-treated group. Brachial artery forearm BF (FBF; via Doppler) and blood pressure (via finger plethysmography) were measured during mild-intensity (~3.5-kg) and moderate-intensity (~7-kg) handgrip exercise. The absolute change (from baseline) in FBF was reduced (except in the 3.5-kg condition) and BP responses were increased in patients with PAD compared with healthy control subjects in 3.5- and 7-kg conditions (all P < 0.05). Plasma nitrate and nitrite were elevated, exercising (7-kg) ΔFBF was improved (from 141 ± 17 to 172 ± 20 ml/min), and mean arterial pressure response was reduced (from 13 ± 1 to 9 ± 1 mmHg, P < 0.05) in patients with PAD that received NaNO3supplementation for 8 wk relative to those that received placebo. These results suggest that the BF limitation and exaggerated pressor response to moderate-intensity forearm exercise in patients with PAD are improved with 8 wk of NaNO3supplementation.NEW & NOTEWORTHY Peripheral artery disease (PAD) results in an exaggerated pressor response and reduced blood flow during lower limb exercise; however, the effect of PAD in the upper limbs has remained unknown. These results suggest that 8 wk of inorganic nitrate supplementation improves the blood flow limitation and exaggerated pressor response to moderate-intensity forearm exercise in PAD.

Key points Contraction-mediated blunting of postjunctional α-adrenergic vasoconstriction (functional sympatholysis) is attenuated in skeletal muscle of ageing males, brought on by altered postjunctional α1 - and α2 -adrenergic receptor sensitivity. The extent to which postjunctional α-adrenergic vasoconstriction occurs in the forearms at rest and during exercise in postmenopausal women remains unknown. The novel findings indicate that contraction-mediated blunting of α1 - (via intra-arterial infusion of phenylephrine) but not α2 -adrenergic (via intra-arterial infusion of dexmedetomidine) vasoconstriction was attenuated in postmenopausal women compared to young women. Additional important findings revealed that postjunctional α-adrenergic vasoconstrictor responsiveness at rest does not appear to be affected by age in women. Collectively, these results contribute to our understanding of local neurovascular control at rest and during exercise with age in women. Abstract Contraction-mediated blunting of postjunctional α-adrenergic vasoconstriction (functional sympatholysis) is attenuated in older males; however, direct confirmation of this effect remains unknown in postmenopausal women (PMW). The present study examined whether PMW exhibit augmented postjunctional α-adrenergic receptor vasoconstriction at rest and during forearm exercise compared to young women (YW). Eight YW (24 ± 1 years) and eight PMW (65 ± 1 years) completed a series of randomized experimental trials: (1) at rest, (2) under high flow (adenosine infusion) conditions and (3) during 6 min of forearm exercise at relative (20% of maximum) and absolute (7 kg) intensities. Phenylephrine (α1 -agonist) or dexmedetomidine (α2 -agonist) was administered during the last 3 min of each trial to elicit α-adrenergic vasoconstriction. Forearm vascular conductance (FVC) was calculated from blood flow and blood pressure. Vasoconstrictor responsiveness was identified as the change in FVC (%) during α-adrenergic agonist infusions from baseline (resting trial) or from steady-state conditions (high flow and exercise trials). During resting and high flow trials, the %FVC during α1 - and α2 -agonist stimulation was similar between YW and PMW. During exercise, α1 -mediated vasoconstriction was blunted in YW vs. PMW at relative (-6 ± 2% vs. -15 ± 3%) and absolute (-4 ± 2% vs. -14 ± 5%) workloads, such that blood flow and FVC were lower in PMW (P 0.05) and absolute (-19 ± 3% vs. -18 ± 4%; P > 0.05) workloads. Collectively, these findings demonstrate that despite similar α-adrenergic vasoconstrictor responsiveness at rest, PMW have a decreased ability to attenuate α1 -adrenergic vasoconstriction in contracting skeletal muscle.

Aging is associated with increased peripheral chemoreceptor activity, reduced nitric oxide (NO) bioavailability, and attenuation of cardiovagal baroreflex sensitivity (BRS), collectively increasing the risk of cardiovascular disease. Evidence suggests that NO may attenuate peripheral chemoreflex sensitivity and increase BRS. Exogenous inorganic nitrate ([Formula: see text]) increases NO bioavailability via the [Formula: see text]-[Formula: see text]-NO pathway. Our hypothesis was that inorganic [Formula: see text] supplementation would attenuate peripheral chemoreflex sensitivity and enhance spontaneous cardiovagal BRS in older adults. We used a randomized, placebo-controlled crossover design in which 13 older (67 ± 3 yr old) adults ingested beetroot powder containing (BRA) or devoid of (BRP) [Formula: see text] and [Formula: see text] daily over 4 wk. Spontaneous cardiovagal BRS was assessed over 15 min of rest and was quantified using the sequence method. Chemoreflex sensitivity was assessed via ~5 min of hypoxia (10% fraction of inspired O2) and reported as the slope of the relationship between O2 saturation (%[Formula: see text]) and minute ventilation (in l/min) or heart rate (in beats/min). Ventilatory responsiveness to hypoxia was reduced after BRA (from −0.14 ± 0.04 to −0.05 ± 0.02 l·min−1·%[Formula: see text]−1, P = 0.01) versus BRP (from −0.10 ± 0.05 to −0.11 ± 0.05 l·min−1·%[Formula: see text]−1, P = 0.80), with no differences in heart rate responsiveness (BRA: from −0.47 ± 0.06 to −0.33 ± 0.04 beats·min−1·%[Formula: see text]−1, BRP: from −0.48 ± 0.07 to −0.42 ± 0.06 beats·min−1·%[Formula: see text]−1) between conditions (interaction effect, P = 0.41). Spontaneous cardiovagal BRS was unchanged after BRA and BRP (interaction effects, P = 0.69, 0.94, and 0.39 for all, up, and down sequences, respectively), despite a reduction in resting systolic and mean arterial blood pressure in the experimental (BRA) group ( P < 0.01 for both). These findings illustrate that inorganic [Formula: see text] supplementation attenuates peripheral chemoreflex sensitivity without concomitant change in spontaneous cardiovagal BRS in older adults. NEW & NOTEWORTHY Exogenous inorganic nitrate supplementation attenuates ventilatory, but not heart rate, responsiveness to abbreviated hypoxic exposure in older adults. Additionally, inorganic nitrate reduces systolic and mean arterial blood pressure without affecting spontaneous cardiovagal baroreflex sensitivity. These findings suggest that inorganic nitrate may attenuate sympathetically oriented pathologies associated with aging.

Mechanical circulatory support in failing Fontan patients with Fontan circuit failure remains challenging. Herein, we describe a failing fenestrated Fontan patient who underwent systemic ventricular assist device support leaving the fenestration open. Perioperative course and hemodynamics during mechanical support are described in detail.

Summary Dynamic ultrasound-guided short-axis needle tip navigation is a novel technique for vascular access. After venipuncture, the needle and catheter are further advanced within the vessel lumen under real-time ultrasound guidance with constant visualisation of the needle tip in the short-axis view. This can minimise the risk of transfixing the cannulated vessel. We compared two techniques for non-visible saphenous vein cannulation under general anaesthesia in children weighing ≥ 3 kg and less than four years of age: dynamic ultrasound-guided short-axis needle tip navigation technique (ultrasound group) vs. landmark technique. Venous cannulation was performed by three experienced anaesthetists. The primary outcome measure was first-attempt success rate. Success rate within 10 min was a secondary outcome. A total of 102 patients were randomly allocated to either the ultrasound group or the landmark group. First-attempt success rate was 90% in the ultrasound group compared with 51% in the landmark group, p

We determined if local increases in brachial artery shear during repetitive muscle contractions induce changes in protein expression of endothelial nitric oxide synthase (eNOS) and/or phosphorylated (p-)eNOS at Ser1177, the primary activation site on eNOS, in endothelial cells (ECs) of humans. Seven young male subjects (25 ± 1 yr) performed 20 separate bouts (3 min each) of rhythmic forearm exercise at 20% of maximum over a 2-h period. Each bout of exercise was separated by 3 min of rest. An additional six male subjects (24 ± 1 yr) served as time controls (no exercise). ECs were freshly isolated from the brachial artery using sterile J-wires through an arterial catheter at baseline and again after the 2-h exercise or time control period. Expression of eNOS or p-eNOS Ser1177 in ECs was determined via immunofluorescence. Brachial artery mean shear rate was elevated compared with baseline and the time control group throughout the 2-h exercise protocol ( P < 0.001). p-eNOS Ser1177 expression was increased 57% in ECs in the exercise group [0.06 ± 0.01 vs. 0.10 ± 0.02 arbitrary units (au), P = 0.02] but not in the time control group (0.08 ± 0.01 vs. 0.07 ± 0.01 au, P = 0.72). In contrast, total eNOS expression did not change in either the exercise (0.13 ± 0.04 vs. 0.12 ± 0.03 au) or time control (0.12 ± 0.03 vs. 0.11 ± 0.03 au) group ( P > 0.05 for both). Our novel results suggest that elevations in brachial artery shear increase eNOS Ser1177 phosphorylation in the absence of changes in total eNOS in ECs of young healthy male subjects, suggesting that this model is sufficient to alter posttranslational modification of eNOS activity in vivo in humans. NEW & NOTEWORTHY Elevations in brachial artery shear in response to forearm exercise increased endothelial nitric oxide synthase Ser1177 phosphorylation in brachial artery endothelial cells of healthy humans. Our present study provides the first evidence in humans that muscle contraction-induced increases in conduit arterial shear lead to in vivo posttranslational modification of endothelial nitric oxide synthase activity in endothelial cells.

Extreme ultraviolet lithography (EUVL) technology is one of the leading candidates under consideration for enabling the next generation of devices, for 7nm node and beyond. As the focus shifts to driving down the 'effective' k1 factor and enabling the second generation of EUV patterning, new techniques and methods must be developed to reduce the overall defectivity, mitigate pattern collapse, and eliminate film-related defects. A typical defect Pareto for EUV line-space patterning is dominated by bridging defects and pattern collapse. Regarding pattern collapse, careful attention needs to be paid to optimizing the rinse process to avoid the large forces that cause collapse during drying. In this paper, we present an optimized rinse technology that works to prevent that pattern collapse, especially on EUV line/space patterns below 40nm pitch. Additionally, this paper reviews the ongoing progress in track-based processes (coating, developer) that are required to enable EUV patterning. This work is especially focused on defect mitigation during film coating and resist developing processes, which have a direct effect on the occurrence of bridging defects during pattern transfer.

Using the firm-level data of 33 countries over 10 years (2008–2017), we find that the listed firms have lower returns on assets than the similar unlisted firms, in most countries. The result is associated with a higher capital-labor ratio of listed firms, implying that the listed firms face less financial constraints. Moreover, we investigate the institutional factors that exacerbate or mitigate the listing advantages (i.e., ROA difference) across the countries. Compared to English origin law, countries with German and Scandinavian legal origins strongly narrow the listing advantages but the French legal origin shows mixed results. Overall, the listing advantages seem narrowed with stronger creditor’s rights but show unclear associations with the strength of corporate governance.

Aging is associated with elevated blood pressure (peripheral and aortic; BP) and aortic augmentation index (AIx) which may contribute to aortic BP. Although inorganic nitrate consumption reduces peripheral BP in both young and older adults, the effects of nitrate consumption on aortic BP and wave reflection in young and older adults is unknown. Therefore, we sought to characterize the effects of nitrate consumption on aortic BP and AIx in young and older adults.Noninvasive aortic pressure waveforms were synthesized from high-fidelity radial pressure waveforms via applanation tonometry before and following (60, 90, 120, 150, and 180 min) consumption of a nitrate-rich beetroot juice in 26 healthy adults (young: 25 ± 4 years, n = 14; older: 64 ± 5 years, n = 12). Aortic BP and indices of aortic wave reflection (AIx and AIx normalized for heart rate; AIx@75bpm) were calculated from the generated aortic pressure waveform.Nitrate consumption increased plasma nitrite in both groups 60-180 min following beetroot consumption (P 0.001). Nitrate consumption reduced peripheral and aortic BP in both young and older adults (P 0.05), with the change being similar between age groups. Conversely, indices of aortic wave reflection were reduced only in young adults following nitrate consumption (range of change from baseline over time: AIx@75bpm, -4.3 to -8.8%, P 0.05), whereas aortic AIx remained unchanged in the older adults.Taken together, our results suggest that acute dietary nitrate supplementation reduces peripheral and aortic BP similarly in young and older adults despite differential effects on aortic AIx between age groups.

With aging, there tends to be an increase in retrograde and oscillatory shear in peripheral conduit arteries of humans. Whether the increase in shear rate is due to the aging process or an effect of a less active lifestyle that often accompanies aging is unknown. Therefore, we examined whether chronic endurance exercise training attenuates conduit artery retrograde and oscillatory shear in older adults.Brachial and common femoral artery mean blood velocities and diameter were determined via Doppler ultrasound under resting conditions, and shear rate was calculated in 13 young (24 ± 2 years), 17 older untrained (66 ± 3 years), and 16 older endurance exercise-trained adults (66 ± 7 years).Brachial artery retrograde (-9.1 ± 6.4 vs. -12.6 ± 9.4 s(-1); P = 0.35) and oscillatory (0.14 ± 0.08 vs. 0.14 ± 0.08 arbitrary units; P = 0.99) shear were similar between the older trained and untrained groups, whereas brachial artery retrograde and oscillatory shear were greater in older untrained compared to young adults (-5.0 ± 3.4, 0.08 ± 0.05 s(-1) arbitrary units, P = 0.017 and 0.048, respectively). There was no difference between the young and older trained brachial retrograde (P = 0.29) and oscillatory (P = 0.07) shear. Common femoral artery retrograde (-6.3 ± 2.9 s(-1)) and oscillatory (0.21 ± 0.08 arbitrary units) shear were reduced in older trained compared to the older untrained group (-10.4 ± 4.1 and 0.30 ± 0.09 s(-1) arbitrary units, both P = 0.005 and 0.006, respectively), yet similar to young adults (-7.1 ± 3.5 and 0.19 ± 0.06 s(-1) arbitrary units, P = 0.81 and 0.87, respectively).Our results suggest that chronic endurance exercise training in older adults ameliorates retrograde and oscillatory shear rate patterns, particularly in the common femoral artery.

This preliminary observational study evaluated a specific ultrasound technique for venous access. Ultrasound was utilized for navigating a needle and catheter within the vessel lumen after venopuncture. One hundred adult obese surgical patients without visible vessels on their upper extremities were enrolled. Forty-five different operators ranging from medical students to attending anesthesia faculty performed venous cannulation with the specific ultrasound technique. Veins in 95 patients were cannulated successfully on the first attempt. This ultrasound-guided protocol facilitates navigation of both the catheter and needle within a vessel, increasing the first-attempt success rate of peripheral venous cannulation in adult obese patients.