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Background: Supine hypertension affects most patients with orthostatic hypotension (OH) due to autonomic failure, but it is often untreated for fear of worsening OH. We hypothesized that increasing intrathoracic pressure with continuous positive airway pressure (CPAP) had a Valsalva-like blood-pressure-lowering effect that could be used to treat nocturnal supine hypertension in these patients, while reducing nocturnal pressure diuresis and improving daytime OH. Methods: In Protocol 1, we determined the acute hemodynamic effects of increasing levels of CPAP (0, 4, 8, 12, and 16 cm H 2 O, 3 minutes each) in 26 patients with autonomic failure and supine hypertension studied while awake and supine. In Protocol 2 (n=11), we compared the effects of overnight therapy with CPAP (8–12 cm H 2 O for 8 hours) versus placebo on nocturnal supine hypertension, nocturnal diuresis and daytime OH in a 2-night crossover study. Results: In Protocol 1, acute CPAP (4–16 cm H 2 O) decreased systolic blood pressure in a dose-dependent manner (maximal drop 22±4 mmHg with CPAP 16) due to reductions in stroke volume (−16+3%) and cardiac output (−14±3%). Systemic vascular resistance and heart rate remained unchanged. In Protocol 2, overnight CPAP lowered nighttime systolic blood pressure (maximal change −23±5 versus placebo −1±7 mmHg; P =0.023) and was associated with lower nighttime diuresis (609±84 versus placebo 1004±160 mL; P =0.004) and improved morning orthostatic tolerance (AUC upright SBP 642±121 versus placebo 410±109 mmHg*min; P =0.014). Conclusions: CPAP is a novel nonpharmacologic approach to treat the supine hypertension of autonomic failure while improving nocturia and daytime OH. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03312556.

Supine hypertension affects most patients with autonomic failure (AF), complicates the treatment of orthostatic hypotension (OH) and induces nocturnal pressure diuresis, resulting in nocturnal volume depletion and worsening of daytime OH. However, it is often untreated for fear of worsening OH. We previously showed that continuous positive airway pressure (CPAP 4, 8, 12 and 16 cm H 2 O, each for 3 min) had an acute, dose-dependent, blood-pressure (BP)-lowering effect in these patients (maximal systolic BP [SBP] drop 22±4 mmHg with CPAP 16) driven by reductions in stroke volume (-16+3%) and cardiac output (-14±3%), suggesting a Valsalva-like effect. In this study, we hypothesized that overnight CPAP therapy can improve nocturnal supine hypertension, nocturia and daytime OH. Eleven AF patients with supine hypertension (age 74±2 years, 8 men, supine SBP 179±7 mmHg) had placebo or CPAP (8-12 cm H 2 O) applied for 8 hours (10pm-6am) in 2 separate nights. Supine BP was measured every 2 hr from 8pm-8am. Morning orthostatic tolerance was assessed at 8am. SBP significantly decreased during overnight CPAP therapy compared to placebo (Figure; P=0.044 by mixed-effects model) with a maximal reduction of 25±5 mmHg at 4 hours of CPAP. This BP effect was associated with lower nighttime diuresis (609±84 versus placebo 1004±160 mL; P=0.004) and improved morning orthostatic tolerance (AUC upright SBP 642±121 versus placebo 410±109 mmHg*min; P=0.014). In conclusion, CPAP is potentially a novel non-pharmacologic approach to treat the supine hypertension of AF that can improve nocturia and daytime OH.

Slow breathing exercises are a key component to many mind-body practices used for stress reduction and modulation of autonomic tone, and it has been shown to reduce blood pressure acutely. Long-term effects on blood pressure and autonomic tone are not well documented. We studied 95 healthy participants (41±4 years, 76% female) who performed slow breathing exercises for 12 weeks and examined the effect of slow breathing on systolic blood pressure, diastolic blood pressure, and autonomic tone.At baseline average BP was 105±11/67±8 mmHg. Among the 11 participants with elevated blood pressure, BP was 126±11.0/ 80±5 mmHg. Our comparison group, that received no intervention, consisted of 30 participants with baseline mean BP 125±19/ 71±10 mmHg.SBP and DBP decreased significantly (−2.4±7.3 and -1.6±5.5 mmHg, respectively) at 12 weeks for all participants who practiced slow breathing. The comparison group showed no significant changes in blood pressure. Blood pressure reduced further among slow breathing participants with baseline SBP over 120mmHg and/or DBP over 90mmHg (−10.3±7.9 and -3.8±5.5 mmHg, respectively). In our regression model, baseline SBP was associated with further decreases in SBP from baseline to 12 weeks. No significant changes were observed in spectral analyses from baseline to 12 weeks or correlations between spectral analyses in blood pressure.In conclusion, 12-weeks of slow breathing exercises resulted in a significant reduction of blood pressure in the absence of significant changes in autonomic tone as measured by spectral analyses. Further research into the mechanisms and effectiveness of slow breathing on cardiovascular health is needed.

This study assessed cardio-respiratory fitness (CRF), and 24-hour sleep, sedentary behaviour (SB) and physical activity (PA) in Australian truck drivers. Participants (n=37 men) attended clinic sessions for an exercise test to exhaustion to establish CRF, and wore an accelerometer (ActigraphGT3X+) to estimate sleep, SB, and PA. Relative to normative values, CRF was 'below percentile 25' in 51% of drivers (mean [SD] VO = 30.1 [7.6] mL.kg .min ). Accelerometer data indicated that total vigorous (3.5-4.5 minutes/day), and sustained moderate-to-vigorous intensity PA (>5 minutes; 0.5-1.6 bouts/day) were limited. The findings show there is a need to design and test PA interventions that can improve poor levels of CRF in truck drivers.

Hybrid organic-inorganic perovskites have shown incredible promise as active materials for photovoltaic devices, but their instability to light remains a significant roadblock in realizing these applications. Changing the organic cation has been shown to affect light-induced degradation. As a strategy for increasing the stability of these materials, we replaced varying percentages of methylammonium ion in the archetypical methylammonium lead iodide (MAPbI

IntroductionEpidemiological evidence suggests that both poor cardiovascular fitness and low muscle mass or strength markedly increase the rate of cognitive decline and incident dementia in older adults. Results from exercise trials for the improvement of cognition in older adults with mild cognitive impairment (MCI) have reported mixed results. This is possibly due to insufficient exercise intensities. The aim of the Balance, Resistance, And INterval (BRAIN) Training Trial is to determine the effects of two forms of exercise, high-intensity aerobic interval training (HIIT) and high-intensity power training (POWER) each compared with a sham exercise control group on cognition in older adults with MCI.Methods and analysisOne hundred and sixty community-dwelling older (≥ 60 years) people with MCI have been randomised into the trial. Interventions are delivered supervised 2–3 days per week for 12 months. The primary outcome measured at baseline, 6 and 12 months is performance on a cognitive composite score measuring the executive domain calculated from a combination of computerised (NeuroTrax) and paper-and-pencil tests. Analyses will be performed via repeated measures linear mixed models and generalised linear mixed models of baseline, 6-month and 12-month time points, adjusted for baseline values and covariates selected a priori. Mixed models will be constructed to determine the interaction of GROUP × TIME.Ethics and disseminationEthical approval was obtained from the University of Sydney (HREC Ref.2017/368), University of Queensland (HREC Ref. 2017/HE000853), University of British Columbia (H16-03309), and Vancouver Coastal Health Research Institute (V16-03309) Human Research Ethics. Dissemination will be via publications, conference presentations, newsletter articles, social media, talks to clinicians and consumers and meetings with health departments/managers.It is expected that communication of results will allow for the development of more effective evidence-based exercise prescription guidelines in this population while investigating the benefits of HIIT and POWER on subclinical markers of disease.Trial registration numberACTRN12617001440314 Australian New Zealand Clinical Trials Registry.

The coupled electronic-ionic response in various MAPb(I1-xBrx)3-based inverted perovskite solar cells (PSCs) is studied in-operando by impedance spectroscopy (IS) under varied AM1.5G light intensities and electrical biases. We show that the concentration of Br- in the composition significantly alters the capacitance and resistive response of the PSC under external stimuli. For example, we observed that the low frequency capacitance does not increase proportionally with light intensity, instead it is highly dependent on the amount of Br- in the composition. We found that the recombination resistance (Rrec) has a linear inverse relationship with light intensity in MAPbI3 and MAPbBr3 whereas, the mixed compositions show deviation. Interestingly, the deviation of Rrec from linearity also scales with the increase in Br- concentration. Upon applying an electrical bias, a large deviation of Rrec from linearity was observed all mixed halide compositions exhibited a non-linear inverse trend. We further report the diffusion coefficient (D) for each MAPb(I1-xBrx)3 composition under different light intensity. Notably, the D values decreased on changing the composition from MAPbI3 (10-7 cm2 s-1) to MAPb(I0.8Br0.2)3 and MAPbBr3 (10-8 cm2 s-1). On the other hand, mixed compositions containing more than 20% Br- concentration show faster diffusion kinetics. Overall, our results emphasize on the complex and intertwined nature of electronic and ionic response in PSC that is tunable by changing the halide composition.

Postural Tachycardia Syndrome (POTS) is characterized by frequent orthostatic symptoms and excessive heart rate increase (>= 30 bpm) on standing in the absence of orthostatic hypotension for more than 6 months. We and others have described a vestibulo-sympathetic reflex that can be engaged by galvanic vestibular stimulation to modulate sympathetic activity (Biaggioni et al., 2000; Kaufmann et al., 2002; Monahan & Ray, 2002; Ray & Carter, 2003, Bent, Macefield et al. 2006). We hypothesize that habituation to sinusoidal galvanic vestibular stimulation will improve orthostatic tolerance. We studied 6 patients with POTS (30.5+/6.0 years, BMI 22.8+/-2.9 kg/m 2 ) in two sessions using sinusoidal galvanic vestibular stimulation (sGVS 0.025 Hz, 2mA) or sham (0.01 mA). Stimulation was applied near mastoid process for 30 min in semi-recumbent position before orthostatic challenge. Patient were upright for a maximum of 15 minutes after each stimulation. Orthostatic change in Vanderbilt Orthostatic Symptom Score (dVOSS), orthostatic heart rate increase (dHR) and blood pressure response were recorded. Non-parametric Wilcoxon test for paired measures with significance level p

The splanchnic vasculature is the largest blood volume reservoir in the human body. Reduced capacitance of this vascular bed, in part due to sympathetic venoconstriction, is proposed to play a role in hypertension and heart failure. Thus, interventions that increase splanchnic capacitance or decrease sympathetic activity may be beneficial in these conditions. In a proof-of-concept study in healthy and hypertensive subjects, we evaluated whether venodilation with nitroglycerin (NTG; Study 1) or sympathetic withdrawal with trimethaphan (Study 2) increase splanchnic capacitance and reduce cardiac and stroke volumes. In Study 1 (n=10, 36±4 yrs, BMI 26.1±1.7, 4 men), abdominal and chest scintigrams, to measure regional blood volumes, were obtained before and after 0.6 mg sublingual NTG. Splanchnic capacitance (volume-pressure relationships, VPR) and compliance (VPR slope) were estimated by recording abdominal scintigrams during progressive escalation of intrathoracic pressure using continuous positive airway pressure (CPAP) at 0, 4, 8, 12, and 16 cm H 2 O, each for ≤2 min. We found that NTG increased splanchnic blood volume at rest (4%, IQR 1.81-9.95; Pslope =0.46 and P intercept =0.01), indicating an increase in splanchnic capacitance. This was associated with a decrease in cardiac blood volume (-9%, IQR 2.2-10.3; Pslope =0.12 and P intercept

OBJECTIVES/HYPOTHESIS Mandibular distraction osteogenesis (MDO) is a safe and effective surgery to address respiratory and feeding issues due to micrognathia in patients with Robin Sequence (RS). Previous studies examining postoperative complications in neonates receiving MDO have considered 4 kg as the cut-off for low weight; however, an increasing number of MDO interventions are performed in infants

We address two aims: Aim 1 (Fitness Review) compares the effect of higher cardiorespiratory fitness (CRF) (e.g., endurance athletes) with lower CRF (e.g., sedentary adults) on cerebrovascular outcomes, including middle cerebral artery velocity (MCAv), cerebrovascular reactivity and resistance, and global cerebral blood flow, as assessed by transcranial Doppler (TCD) or magnetic resonance imaging (MRI). Aim 2 (Exercise Training Review) determines the effect of exercise training on cerebrovascular outcomes. Systematic review of studies with meta-analyses where appropriate. Certainty of evidence was assessed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Twenty studies (18 using TCD) met the eligibility criteria for Aim 1, and 14 studies (8 by TCD) were included for Aim 2. There was a significant effect of higher CRF compared with lower CRF on cerebrovascular resistance (effect size = -0.54, 95% confidence interval = -0.91 to -0.16) and cerebrovascular reactivity (0.98, 0.41-1.55). Studies including males only demonstrated a greater effect of higher CRF on cerebrovascular resistance than mixed or female studies (male only: -0.69, -1.06 to -0.32; mixed and female studies: 0.10, -0.28 to 0.49). Exercise training did not increase MCAv (0.05, -0.21 to 0.31) but showed a small nonsignificant improvement in cerebrovascular reactivity (0.60, -0.08 to 1.28; P = 0.09). Exercise training showed heterogeneous effects on regional but little effect on global cerebral blood flow as measured by MRI. High CRF positively effects cerebrovascular function, including decreased cerebrovascular resistance and increased cerebrovascular reactivity; however, global cerebral blood flow and MCAv are primarily unchanged following an exercise intervention in healthy and clinical populations.NEW & NOTEWORTHY Higher cardiorespiratory fitness is associated with lower cerebrovascular resistance and elevated cerebrovascular reactivity at rest. Only adults with a true-high fitness based on normative data exhibited elevated middle cerebral artery velocity. The positive effect of higher compared with lower cardiorespiratory fitness on resting cerebrovascular resistance was more evident in male-only studies when compared with mixed or female-only studies. A period of exercise training resulted in negligible changes in middle cerebral artery velocity and global cerebral blood flow, with potential for improvements in cerebrovascular reactivity.

Davids, CJ, Raastad, T, James, L, Gajanand, T, Smith, E, Connick, M, McGorm, H, Keating, S, Coombes, JS, Peake, JM, and Roberts, LA. Similar morphological and functional training adaptations occur between continuous and intermittent blood flow restriction. J Strength Cond Res 35(7): 1784-1793, 2021-The aim of the study was to compare skeletal muscle morphological and functional outcomes after low-load resistance training using 2 differing blood flow restriction (BFR) protocols. Recreationally active men and women (n = 42 [f = 21], 24.4 ± 4.4 years) completed 21 sessions over 7 weeks of load-matched and volume-matched low-load resistance training (30% 1 repetition maximum [1RM]) with either (a) no BFR (CON), (b) continuous BFR (BFR-C, 60% arterial occlusion pressure [AOP]), or (c) intermittent BFR (BFR-I, 60% AOP). Muscle mass was assessed using peripheral quantitative computed tomography before and after training. Muscular strength, endurance, and power were determined before and after training by assessing isokinetic dynamometry, 1RM, and jump performance. Ratings of pain and effort were taken in the first and final training session. An alpha level of p < 0.05 was used to determine significance. There were no between-group differences for any of the morphological or functional variables. The muscle cross sectional area (CSA) increased pre-post training (p = 0.009; CON: 1.6%, BFR-C: 1.1%, BFR-I: 2.2%). Maximal isometric strength increased pre-post training (p < 0.001; CON: 9.6%, BFR-C: 14.3%, BFR-I: 19.3%). Total work performed during an isokinetic endurance task increased pre-post training (p < 0.001, CON: 3.6%, BFR-C: 9.6%, BFR-I: 11.3%). Perceptions of pain (p = 0.026) and effort (p = 0.033) during exercise were higher with BFR-C; however, these reduced with training (p = 0.005-0.034). Overall, these data suggest that when 30% 1RM loads are used with a frequency of 3 times per week, the addition of BFR does not confer superior morphological or functional adaptations in recreationally active individuals. Furthermore, the additional metabolic stress that is proposed to occur with a continuous BFR protocol does not seem to translate into proportionally greater training adaptations. The current findings promote the use of both intermittent BFR and low-load resistance training without BFR as suitable alternative training methods to continuous BFR. These approaches may be practically applicable for those less tolerable to pain and discomfort associated with ischemia during exercise.

A new 11 amino acid linear peptide named roseabol A (1) and the known compound 13-oxo-trans-9,10-epoxy-11(E)-octadecenoic acid (2) were isolated from the fungus Clonostachys rosea. Combined NMR and MS analysis revealed that roseabol A (1) contained amino acid residues characteristic of the peptaibol family of peptides such as isovaline, α-aminoisobutyric acid, hydroxyproline, leucinol, and an N-terminal isovaleric acid moiety. The amino acid sequence was established by a combination of NMR studies and tandem MS fragmentation analyses, and the absolute configurations of the constituent amino acids of 1 were determined by the advanced Marfey’s method. Compound 2 showed inhibitory activity against Merkel cell carcinoma, a rare and difficult-to-treat type of skin cancer, with an IC50 value of 16.5 μM.

NEW FINDINGS What is the topic of this review? We have conducted a systematic review and meta-analysis on the current evidence for the effect of heat therapy on blood pressure and vascular function. What advances does it highlight? We found that heat therapy reduced mean arterial, systolic and diastolic blood pressure. We also observed that heat therapy improved vascular function, as assessed via brachial artery flow-mediated dilatation. Our results suggest that heat therapy is a promising therapeutic tool that should be optimized further, via mode and dose, for the prevention and treatment of cardiovascular disease risk factors. ABSTRACT Lifelong sauna exposure is associated with reduced cardiovascular disease risk. Recent studies have investigated the effect of heat therapy on markers of cardiovascular health. We aimed to conduct a systematic review with meta-analysis to determine the effects of heat therapy on blood pressure and indices of vascular function in healthy and clinical populations. Four databases were searched up to September 2020 for studies investigating heat therapy on outcomes including blood pressure and vascular function. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to assess the certainty of evidence. A total of 4522 titles were screened, and 15 studies were included. Healthy and clinical populations were included. Heat exposure was for 30-90 min, over 10-36 sessions. Compared with control conditions, heat therapy reduced mean arterial pressure [n = 4 studies; mean difference (MD): -5.86 mmHg, 95% confidence interval (CI): -8.63, -3.10; P

Postural tachycardia syndrome (POTS), a syndrome characterized by orthostatic symptoms and a heart rate increase of at least 30 beats per minute in the absence of hypotension upon standing, is often accompanied by increased sympathetic activity and low blood volume. A common non-pharmacologic recommendation for patients with POTS is a high-sodium (HS) diet with the goal of bolstering circulating blood volume. The objective of this study is to assess the effects of 6 days of a HS diet on endothelial function in POTS. A total of 14 patients with POTS and 13 age-matched healthy controls, all females, were studied following 6 days on a low-sodium (LS) diet (10 mEq/day) and 6 days on a HS diet (300 mEq/day) in a crossover design. We measured endothelial function following reactive hyperemia in the brachial artery using flow-mediated dilation (FMD), leg blood flow (LBF) using strain gauge plethysmography in the calf, and reactive hyperemic index (RHI) in the microcirculation of the hand using pulsatile arterial tonometry. On the LS diet, FMD% did not differ between patients with POTS and the healthy controls although peak brachial artery diameter was lower for the patient group. RHI was higher for the patient group than for the controls, but there were no differences in post-ischemic LBF increase. On the HS diet, there were no between-group differences in FMD%, LBF increase, or RHI. In summary, a HS diet for 6 days did not induce endothelial dysfunction. This non-pharmacologic treatment used for patients with POTS does not negatively affect endothelial function when used for a sub-acute duration. ClinicalTrials.gov NCT01550315; March 9, 2012.

We aimed to examine the agreement between submaximal cardiopulmonary exercise testing (CPET) measures and peak oxygen consumption (VO) in adults with epilepsy. Data from a randomized controlled trial with adults with epilepsy (N = 21) were analyzed. VO was assessed using indirect calorimetry during a treadmill graded maximal CPET. Oxygen uptake efficiency slope (OUES) was calculated from the relationship between oxygen uptake and minute ventilation during the entire test (OUES) and the first 2 (OUES), 3 (OUES), and 4 (OUES) minutes of the CPET. The strength of the association between measures was tested by Pearson correlation. Linear regression models were used to predict VO based on OUES from the different testing durations. Agreement between measured and predicted maximal values was tested using intraclass correlation coefficient (ICC) and Bland-Altman plots. OUES, OUES, and OUES were highly associated with absolute (r = 0.84, r = 0.76, r = 0.75, respectively) and relative (r = 0.84, r = 0.78, r = 0.78, respectively) VO. Agreement (ICC = 0.83) between CPET-measured and OUES-predicted VO values was stronger with OUES than the other time-based OUES markers. Bland-Altman plot showed satisfactory agreement between predicted and measured CPET measures with the narrowest limits of agreement observed with the OUES. No potential bias was identified between these two measurements (p = 0.33). Changes in absolute (r = 0.77) and relative (r = 0.88) VOpeak were highly associated with the change in OUES. OUES can be used as a surrogate for maximal cardiorespiratory fitness in adults with epilepsy. Studies with larger samples size are encouraged to confirm our findings in a more heterogeneous population.

From 2016 to 2040 the number of people with dementia in the United Kingdom is expected to increase by 57%, while 70% percent of it is due to a higher life expectancy. Thus, we analyzed the overall and age-stratified effect of physical activity on risk of dementia in participants with mild cognitive impairment (MCI) of the English Longitudinal Study of Ageing (ELSA). Participants of the ELSA, aged over 50 with MCI, were followed-up nine times between 2002 and 2019. Physical activity was assessed using a self-reported, validated questionnaire and participants were classified as inactive, low, or moderate-to-high active. Medical diagnosis of dementia was self-reported or determined using the Informant Questionnaire on Cognitive Decline in the Elderly. Data from 521 participants with MCI were analyzed (56% women; mean [SD] age, 68.7 [10.6]). Over 17-year follow-up, 20.5 (95%CI: 17.3 to 24.2)% were diagnosed with dementia. The risk of incident dementia was reduced in participants engaging in low (HR: 0.34; 95%CI: 0.22 to 0.54) or moderate-to-high (HR: 0.16; 95%CI: 0.08 to 0.33) levels of physical activity. Risk of dementia in adults aged 80 or more engaging in low or moderate-to-high levels of physical activity was not different from inactive adults aged between 50 and 69 years. Results were sustained after competing risk regression model and sensitivity analyses to reduce the impact of reverse causality. Physical activity appears to minimize the risk associated with aging in older adults with MCI.

The purpose of this study is to evaluate endothelial function in postural tachycardia syndrome (PoTS), a poorly understood chronic condition characterized by a state of consistent orthostatic tachycardia (delta heart rate ≥30 beats per minute) upon standing without orthostatic hypotension. Nineteen patients with PoTS and 9 healthy controls were studied after 3 days of a fixed, caffeine-free, normal sodium (150 milliequivalents/day) diet. All participants underwent autonomic function testing, including sinus arrhythmia, valsalva maneuver, hyperventilation, cold pressor, handgrip, and a standing test with catecholamine measurements, followed by endothelial function testing. We analyzed 3 measures of endothelial function: percent brachial flow-mediated dilation, digital pulsatile arterial tonometry, and postischemic percent leg blood flow. Flow-mediated dilation was significantly lower in patients with PoTS (6.23±3.54% for PoTS) than in healthy controls (10.6±4.37% for controls versus, P =0.014). PoTS and controls had similar digital pulsatile arterial tonometry (1.93±0.40 arbitrary units for controls versus 2.13±0.63 arbitrary units for PoTS). PoTS had similar but suggestive percent leg blood flow to controls (313±158% for PoTS versus 468±236% for controls, P =0.098). Patients with PoTS have significantly reduced flow-mediated dilation compared with healthy controls, suggesting that PoTS is characterized by endothelial dysfunction in conduit arteries. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01308099.

Background Splanchnic venous pooling induced by upright posture triggers a compensatory increase in heart rate ( HR ), a response that is exaggerated in patients with postural tachycardia syndrome. To assess whether abdominal compression attenuates orthostatic tachycardia and improves symptoms, 18 postural tachycardia syndrome patients (32±2 years) were randomized to receive either abdominal compression (40 mm Hg applied with an inflatable binder ≈2 minutes before standing) or propranolol (20 mg) in a placebo‐controlled, crossover study. Methods and Results Systolic blood pressure, HR , and symptoms were assessed while seated and standing, before and 2 hours postdrug. As expected, propranolol decreased standing HR compared with placebo (81±2 versus 98±4 beats per minute; P P =0.002). Compression had no effect on standing HR (96±4 beats per minute) but increased standing systolic blood pressure compared with placebo and propranolol (106±2 mm Hg; P HR (81±2 beats per minute for both interventions) but prevented the decrease in standing systolic blood pressure produced by propranolol (98±2 versus 93±2 mm Hg for propranolol; P =0.029), and significantly improved total symptom burden (−6±2 versus −1±2 for propranolol; P =0.041). Conclusions Splanchnic venous compression alone did not improve HR or symptoms but prevented the blood pressure decrease produced by propranolol. The combination was more effective in improving symptoms than either alone. Splanchnic venous compression can be a useful adjuvant therapy to propranolol in postural tachycardia syndrome. Registration URL : https://www.clini​caltr​ials.gov ; Unique identifier: NCT 00262470.

Only a small fraction of the antigens expressed by malaria parasites have been evaluated as vaccine candidates. A successful malaria subunit vaccine will likely require multiple antigenic targets to achieve broad protection with high protective efficacy. Here we describe protective efficacy of a novel antigen, Plasmodium yoelii (Py) E140 (PyE140), evaluated against P. yoelii challenge of mice. Vaccines targeting PyE140 reproducibly induced up to 100% sterile protection in both inbred and outbred murine challenge models. Although PyE140 immunization induced high frequency and multifunctional CD8+ T cell responses, as well as CD4+ T cell responses, protection was mediated by PyE140 antibodies acting against blood stage parasites. Protection in mice was long-lasting with up to 100% sterile protection at twelve weeks post-immunization and durable high titer anti-PyE140 antibodies. The E140 antigen is expressed in all Plasmodium species, is highly conserved in both P. falciparum lab-adapted strains and endemic circulating parasites, and is thus a promising lead vaccine candidate for future evaluation against human malaria parasite species.

We studied ion transport in hybrid organic–inorganic perovskite p-i-n devices as a function of applied bias under device operating conditions. Using electrochemical impedance spectroscopy (EIS) and equivalent circuit modeling, we elucidated various resistive and capacitive elements in the device. We show that ion migration is predictably influenced by a low applied forward bias, characterized by an increased capacitance at the hole-transporting (HTM) and electron-transporting material (ETM) interfaces, as well as in bulk. However, unlike observations in n-i-p devices, we found that there is a capacitive discharge leading to ion redistribution in the bulk at high forward biases. Furthermore, we show that a chemical double-layer capacitance buildup as a result of ion accumulation impacts the electronic properties of the device, likely by inducing either charge pinning or charge screening, depending on the direction of the ion-induced field. Lastly, we extrapolate ion diffusion coefficients (∼10–7 cm2 s–1) a...

Postural Tachycardia Syndrome (POTS) is a chronic disorder characterized by symptoms of orthostatic intolerance such as fatigue, lightheadedness, dizziness, palpitations, dyspnea, chest discomfort and remarkable tachycardia upon standing. Non-invasive transdermal vagal stimulators have been applied for the treatment of epilepsy, anxiety, depression, headache, and chronic pain syndromes. Anti-inflammatory and immunomodulating effects after transdermal vagal stimulation raised interest for applications in other diseases. Patients with sympathetic overactivity, reduced cardiac vagal drive and presence of systemic inflammation like POTS may benefit from tVNS. This article will address crucial methodological aspects of tVNS and provide preliminary results of its acute and chronic use in POTS, with regards to its potential effectiveness on autonomic symptoms reduction and heart rate modulation.

T cells are critical effectors of host immunity that target intracellular pathogens, such as the causative agents of HIV, tuberculosis, and malaria. The development of vaccines that induce effective cell-mediated immunity against such pathogens has proved challenging; for tuberculosis and malaria, many of the antigens targeted by protective T cells are not known. Here, we report a novel approach for screening large numbers of antigens as potential targets of T cells. Malaria provides an excellent model to test this antigen discovery platform because T cells are critical mediators of protection following immunization with live sporozoite vaccines and the specific antigen targets are unknown. We generated an adenovirus array by cloning 312 highly expressed pre-erythrocytic Plasmodium yoelii antigens into adenovirus vectors using high-throughput methodologies. The array was screened to identify antigen-specific CD8+ T cells induced by a live sporozoite vaccine regimen known to provide high levels of sterile protection mediated by CD8+ T cells. We identified 69 antigens that were targeted by CD8+ T cells induced by this vaccine regimen. The antigen that recalled the highest frequency of CD8+ T cells, PY02605, induced protective responses in mice, demonstrating proof of principle for this approach in identifying antigens for vaccine development.

Using a methylammonium selective membrane in conjunction with electrochemical impedance spectroscopy, we measured ion migration in methylammonium lead triiodide (MAPbI3) with a millisecond (ms) time constant under illumination. These values were consistent with the reported values of ionic conduction in thin-film perovskite solar cells. We monitored an electrochemical impedance response arising from ionic conductivity through MAPbI3 and a methylammonium selective layer. We could fit this complex impedance response to an intuitive circuit model, which revealed an ionic species moving on a ms time scale. Electrospray ionization mass spectrometry (ESI-MS) revealed direct chemical evidence of methylammonium diffusion into the ion-selective layer. We found no experimental evidence indicating the mobility of lead ions or protons, suggesting that the mobile species observed under illumination is likely methylammonium.

Background: Obesity is associated with sympathetic activation which results in insulin resistance and a blunted insulin-mediated microvascular recruitment. We propose that removal of sympathetic vasoconstriction can result in improvement of insulin-mediated vasodilation and subsequently in sensitivity to insulin-mediated glucose uptake. Methods: We blocked sympathetic vasoconstriction in an isolated forearm model during a hyperinsulinemic euglycemic clamp to determine the effect of insulin recruitment on microvascular circulation using contrast-enhanced ultrasonography (CEU). We studied 9 obese human subjects (age 41±6 years, BMI 37±3 kg*m -2 , SBP 125±6 mm Hg). We assessed the effects of insulin on microvascular recruitment and glucose uptake on two separate occasions, randomly assigned and at least one month apart, during an intrabrachial infusion of the alpha-adrenergic blocker phentolamine (PHE, 25 micrograms/min, blocked day) or saline (SAL, Control day). Subjects were studied at baseline (BSL) and at the end of the clamp (CLAMP). Results: As expected forearm blood flow increased after insulin alone (67±27%, p=0.016) and with alpha blockade and insulin (140± 22%, p=0.0011). Microvascular blood volume (MBV, index of microvascular recruitment), showed a significant increased during PHE compared to SAL (figure). Muscle glucose uptake trended towards increase with PHE but did not reach statistical significance (p=0.0558). There were no systemic effects due to sympathetic blockade. Conclusions: This data shows that sympathetic vasoconstriction contributes to the blunted insulin-mediated microvascular recruitment seen in obesity.

Supine hypertension affects about half of patients with primary autonomic failure (AF), complicates the treatment of orthostatic hypotension (OH) and induces nocturnal polyuria, resulting in worsening of morning OH. We previously showed that short exposure to local passive heat (40-42°C applied for ≤2 hours over abdomen and pelvis with a heating pad) acutely decreased systolic blood pressure (BP) by -25±5 mmHg in AF patients with supine hypertension due to decreases in stroke volume (-29±5%) and cardiac output (-30±5%). In this study, we hypothesized that local passive heat therapy applied overnight would lower nocturnal BP and polyuria, and improve early morning OH in these patients. Ten AF patients with supine hypertension (age 76±2 years, 6 men, supine systolic BP 168±3 mmHg) received passive heat (38°C with a water-perfused heating pad placed under the torso) or placebo, in a 2-night crossover study. Supine BP was monitored every 2 hr from 8pm-8am. Heat therapy was applied from 10pm-6am. Morning orthostatic tolerance was assessed at 8 am. Systolic BP significantly decreased during overnight heat therapy compared to placebo (Figure; P

Slow breathing, an integral part of different body mind relaxation practices, might modulate autonomic tone and lower bp. It is unknown if extended exhalation technique (E>I) will have different effects than common slow breathing (E=I). We hypothesized that E>I will have a greater impact on blood pressure. We studied 86 healthy participants (41±4 years, 76% female) randomly assigned to E=I (n=41) or E>I (n=45) daily exercise guided by Yoga teachers over 12 weeks. We measured blood pressure, autonomic tone by spectral analysis of heart rate and blood pressure variability and cardio-vagal baroreflex sensitivity by spontaneous sequence technique (BRS) at baseline and at 12 weeks. For comparison, we included two groups without breathing interventions: normotensives (NTN), n=14 SBP 114± 5 mm Hg and hypertensives (HTN), n=15 SBP 141± 3 mm Hg, that were studied on two separate visits at least one month apart. SBP significantly decreased at 12 weeks for both intervention groups, 3.5 ± 6.6 mm Hg for E>I (pI (E>I: 3.07±1.2 ms/mmHg, E=I:-0.24±0.8 ms/mmHg, p(time)=0.013, p(timeXgroup)=0.019.In conclusion, 12 weeks of slow breathing exercises resulted in a significant reduction of blood pressure and changes in baroreflex sensitivity independently of the type of breathing.

Implementation of social distancing reduced the incidence of coronavirus disease (COVID-19) cases. Nevertheless, this strategy has other undesirable effects such as physical inactivity and psychological distress, which are associated with cognitive impairment. We aimed to examine whether physical activity during social distancing restrictions could reduce the risk of subjective memory decline in adults. Participants (n=2321) completed the baseline assessment of PAMPA cohort (Prospective Study About Mental and Physical Health), a ambispective cohort study conducted in southern Brazil. An online-based, self-administered questionnaire assessed physical activity and self-rated memory in two different periods: before and during social distancing. Data collection was executed from June 22nd to July 23rd 2020. Adjusted Poisson regression models were performed and values reported in prevalence ratio (PR) with 95% confidence interval (CI). Participants presented with a mean age of 38.2 (95%CI: 37.5, 38.9) years. Most were women (76.6%), had at least a university degree (66.7%), and were overweight or obese (53.3%). Subjective memory decline was reported by 30.0% (95%CI: 27.7%, 32.4%) of respondents. Most individuals with subjective memory decline reported being physically inactive during the pandemic of COVID-19. Participants were less likely to experience subjective memory decline if they either became (PR: 0.56; 95%CI: 0.36, 0.89) or remained (PR: 0.68; 95%CI: 0.49, 0.93) physically active compared to inactive respondents. Physical activity participation during social distancing reduced the likelihood of subjective memory decline in adults. Physical activity should be highlighted as a potential alternative to reduce the burden of the COVID-19 pandemic on cognitive function and mental health., Highlights • 1 in 3 participants had subjective memory decline during social distancing. • Physical activity during social distancing reduced risk of subjective memory decline. • Young adults and women reported a higher prevalence of subjective memory decline.

The synthesis and characterization of regioregular aliphatic polyketones is reported. Poly(1-oxoheptamethylene), a semicrystalline polyketone, was prepared via ruthenium-catalyzed ring-opening metathesis polymerization (ROMP) of a ketal-protected 7-membered cyclic ketone followed by subsequent hydrogenation and deprotection. Temperature and catalyst studies of the ROMP reaction guided the preparation of polyketones with high monomer conversions, molecular weights as high as 30 kDa, and dispersities as low as 1.4. Because of the symmetric nature of the monomer, the polymer has ketones spaced every six methylene units apart. The thermal properties of this polyketone were investigated by differential scanning calorimetry, revealing a peak melting range of 160–165 °C. A related polymer, poly(1-oxooctamethylene), was also prepared in a similar fashion, and a peak melting range of only 130–133 °C was observed. This difference in melting range is attributed to the lack of the regioregularity in poly(1-oxooctamet...

Hybrid organic–inorganic perovskites (HOIPs) have emerged as an important class of materials because they exhibit many properties suitable for efficient energy conversion and storage. Although HOIPs have been the subject of many studies, the underlying origins of many of their properties remain a matter of debate. Ion transport is a case in point. Even though many in the HOIP research community accept ion transport as the cause of many of HOIPs observed properties, salient details such as the chemical identity of the migrating ion or ions and the mechanism of transport remain unclear. Complicating factors such as the possibility of multiple mobile ions, coupled electronic–ionic transport, instability, and unique organic–inorganic character have led to a range of conclusions and opinions about ion transport in HOIPs. An exponential increase in the number of publications and data in a very short time span have not led to convergence of opinions. In this chapter, we integrate key experimental and computational findings to highlight the fundamental results in the area of ion migration in HOIPs and our current understanding on the nature of ion migration in these materials.

Correction for ‘The use of ion-selective membranes to study cation transport in hybrid organic–inorganic perovskites’ by Emily C. Smith et al., Phys. Chem. Chem. Phys., 2019, 21, 20720–20726.

Background. The licensing of herpes zoster vaccine has demonstrated that therapeutic vaccination can help control chronic viral infection. Unfortunately, human trials of immunodeficiency virus (HIV) vaccine have shown only marginal efficacy.Methods. In this double-blind study, 17 HIV-infected individuals with viral loads of 350 cells/μL were randomly assigned to the vaccine or placebo arm. Vaccine recipients received 3 intramuscular injections of HIV DNA (4 mg) coding for clade B Gag, Pol, and Nef and clade A, B, and C Env, followed by a replication-deficient adenovirus type 5 boost (1010 particle units) encoding all DNA vaccine antigens except Nef. Humoral, total T-cell, and CD8+ cytotoxic T-lymphocyte (CTL) responses were studied before and after vaccination. Single-copy viral loads and frequencies of latently infected CD4+ T cells were determined.Results. Vaccination was safe and well tolerated. Significantly stronger HIV-specific T-cell responses against Gag, Pol, and Env, with increased polyfunctionality and a broadened epitope-specific CTL repertoire, were observed after vaccination. No changes in single-copy viral load or the frequency of latent infection were observed.Conclusions. Vaccination of individuals with existing HIV-specific immunity improved the magnitude, breadth, and polyfunctionality of HIV-specific memory T-cell responses but did not impact markers of viral control.Clinical Trials Registration.

CD4 T follicular helper (TFH) cells interact with and stimulate the generation of antigen-specific B cells. TFH cell interaction with B cells correlates with production of SIV-specific immunoglobulins. However, the fate of TFH cells and their participation in SIV-induced antibody production is not well understood. We investigated the phenotype, function, location, and molecular signature of TFH cells in rhesus macaques. Similar to their human counterparts, TFH cells in rhesus macaques represented a heterogeneous population with respect to cytokine function. In a highly differentiated subpopulation of TFH cells, characterized by CD150lo expression, production of Th1 cytokines was compromised while IL-4 production was augmented, and cells exhibited decreased survival, cycling, and trafficking capacity. TFH cells exhibited a distinct gene profile that was markedly altered by SIV infection. TFH cells were infected by SIV; yet, in some animals, these cells actually accumulated during chronic SIV infection. Generalized immune activation and increased IL-6 production helped drive TFH differentiation during SIV infection. Accumulation of TFH cells was associated with increased frequency of activated germinal center B cells and SIV-specific antibodies. Therefore, chronic SIV does not disturb the ability of TFH cells to help B cell maturation and production of SIV-specific immunoglobulins.

To examine the effect of level of moral responsibility on response to being harmed, 80 undergraduates each were initially given 10 raffle tickets. Half of the participants subsequently had 9 of their 10 tickets taken away and given to a fellow participant, whereas half did not. In each of these harm-done conditions, half of the participants were led to believe that the fellow participant intentionally took 9 of their tickets (either successfully or not), whereas half believed that the fellow participant did not intend them harm. Participants were then given a chance to take tickets from the fellow. Responses revealed two independent processes, one to reestablish distributive justice after tickets had been taken and the other to retaliate for harm intended. Level of moral responsibility had no effect on pursuit of distributive justice, but high moral responsibility restrained pursuit of retributive (retaliatory) justice. Possible reasons are proposed.

Kesterson Reservoir in Merced County, California was formerly used as a storage and evaporation facility for Se-contaminated agricultural drain water. Very little Se entered the shallow aquifer below the ponds with percolating pond water. With few localized exceptions, most of the Se was removed from the water and retained in the first decimeter of soil, which was rich in decaying organic matter. Where it was present in groundwater, Se was nearly always associated with nitrate. Nitrate induces mildly oxidizing conditions (Eh ≈ 350 mV) and inhibits microbial fixation of Se. In the absence of nitrate, relatively reducing conditions prevail in the groundwater (Eh ≈ -50 mV), and Se is quickly removed. Selenate follows oxygen and nitrate in the order that soil microbes utilize electron acceptors. The process of Se removal from water by soil was reproduced in the laboratory, and the effect of nitrate was confirmed. This natural process might be applied to water treatment for Se removal. The deep water ecosystem at Kesterson Reservoir was highly productive. Vegetation growing in water treatment ponds should supply enough organic matter to maintain anaerobic conditions in the sediment. This process, including algae culture, was operated in an outdoor 79 cm column for 100 days. At percolation rates of 15 and 30 m yr−1 Se removal averaged 94%, with an additional 2% converted to volatile compounds.

The development and heterogeneity of proanthocyanidins in bark tissue of Pseudotsuga menziesii Franco (Douglas-fir) were analyzed chemically in extracts by means of the butanol–HCl reagent and histochemically with freehand sections by the nitroso reagent. About twice as much proanthocyanidin on a dry weight basis was found in the bark of mature hypocotyls as in the bark from 1- to 4-year-old stems and increment cores from 80-year-old trees. The proanthocyanidins were widely distributed in the vacuoles of epidermal cells, phellem, and the vascular cambial zone, but were randomly distributed in parenchyma cells within the phloem and the cortex. Only procyanidins were found in young, growing tissues, in parenchyma cells in the secondary phloem, in the vascular cambial zone, and in the bark of 80-year-old trees. Prodelphinidins were found in addition to procyanidins in the bark of 6-month-old hypocotyls and 1.5- to 4-year-old plants, possibly only in the cortical and phellem (cork) cells. Comparisons were made with nitroso reagent positive products in needles.