Randomized Crossover Study Research Articles

#1478 Effect of low vs standard dialysate sodium on 48-h ambulatory blood pressure in patients with intradialytic hypertension: a randomized crossover study

Abstract Background and Aims Intradialytic hypertension (IDH) is associated with increased risk for cardiovascular events and mortality. Patients with IDH exhibit higher 48-h blood pressure (BP) levels than patients without this condition. Volume and sodium excess are considered a major factor contributing in the development of this phenomenon. This study evaluated the effect of low (137 mEq/L) compared to standard (140 mEq/L) dialysate sodium concentration on 48-h BP in patients with IDH. Method In this randomized, single-blind, crossover study, 29 patients with IDH underwent 4 hemodialysis sessions with low (137 mEq/L) followed by 4 sessions with standard (140 mEq/L) dialysate sodium or vice-versa. Mean 48-h BP, pre-/post-dialysis and intradialytic BP, pre-dialysis weight, interdialytic weight gain (IDWG) and lung ultrasound B-lines were assessed. Results Mean 48-h SBP/DBP were significantly lower with low compared to standard dialysate sodium concentration (137.6 ± 17.0/81.4 ± 13.7 mmHg with low vs 142.9 ± 14.5/84.0 ± 13.9 mmHg with standard dialysate sodium, p = 0.005/p = 0.007 respectively); SBP/DBP levels were also significantly lower during the 44-h and different 24-h periods. Low dialysate sodium significantly reduced post-dialysis (SBP/DBP: 150.3 ± 22.3/91.2 ± 15.1 mmHg with low vs 166.6 ± 17.3/94.5 ± 14.9 mmHg with standard dialysate sodium, p < 0.001/p = 0.134 respectively) and intradialytic (141.4 ± 18.0/85.0 ± 13.4 mmHg with low vs 147.5 ± 13.6/88.1 ± 12.5 mmHg with standard dialysate sodium, p = 0.034/p = 0.013, respectively) BP compared with standard dialysate sodium. Pre-dialysis weight, IDWG and pre-dialysis B-lines were also significantly decreased with low dialysate sodium. Conclusion Low dialysate sodium concentration significantly reduced 48-h ambulatory BP compared with standard dialysate sodium in patients with IDH. These findings support low dialysate sodium as a major non-pharmacologic approach for BP management in patients with IDH. Registered at ClinicalTrials.gov with study number NCT05430438.

#1488 Dialysate sodium and short-term blood pressure variability in patients with intradialytic hypertension: a randomized crossover study

Abstract Background and Aims Increased blood pressure (BP) variability (BPV) is associated with high cardiovascular risk in hemodialysis. Patients with intradialytic hypertension (IDH) also exhibited an increased cardiovascular risk than hemodialysis patients without this condition. The impact of non-pharmacological BP-lowering interventions on BPV in this population remains unknown. This analysis evaluated the effect of low (137 mEq/L) compared to standard (140 mEq/L) dialysate sodium concentration on short-term BPV in patients with IDH. Method In a randomized cross-over manner, 29 patients with IDH underwent 4 hemodialysis sessions with low (137 mEq/L) followed by 4 sessions with standard (140 mEq/L) dialysate sodium or vice versa according to randomization arm. 48-h ABPM was performed from the start of the 4th session on each dialysate sodium. BPV indices during the 48-h, 24-h, day-time and night-time periods were calculated with validated formulas. Results Mean 48-h BP was lower by 5.3/2.6 mmHg with low compared to standard dialysate sodium concentration, (p = 0.005/p = 0.007) respectively). All 48-h systolic BPV indices examined showed non-significant differences between low and standard dialysate sodium (SBP-SD: 16.99 ± 5.39 vs. 16.98 ± 4.33 mmHg; p = 0.982; SBP-wSD: 15.93 ± 5.02 vs. 16.12 ± 4.16 mmHg, p = 0.769; SBP-ARV: 11.99 ± 3.67 vs. 11.45 ± 3.35 mmHg, p = 0.392 and SBP-CV: 12.36 ± 3.65 vs. 11.92 ± 3.18%, p = 0.302, with low vs. standard dialysate sodium, respectively). Diastolic BPV indices were numerically, but not statistically, lower with low dialysate sodium. Overall, significant differences were observed in some further comparisons relevant to a trend for lower BPV during daytime 2 and higher BVP during nighttime 2 during treatment with low dialysate sodium. Conclusion Low dialysate sodium concentration does not affect BPV levels in patients with IDH. Future research should further explore alternative interventions to reduce BP and BPV in this high-risk population.

#2703 Venous chambers vary in the reduction capacity of air microbubbles: a randomized study of chronic haemodialysis patients

Abstract Background and Aims The extracorporeal circuit (ECC) enables haemodialysis (HD) of patients. When the blood passes the ECC air contamination occurs, and consequently microbubbles (MBs) enter into the patient. MBs are verified at autopsy of HD patients and are covered by clots manifested as microemboli that are deposited within the lung, heart and brain tissue. A venous chamber is inserted in the ECC to reduce air contamination. However, venous chambers in clinical use have limited capacity in eliminating MBs from entering the return bloodline. In an in vitro study, the Emboless® chamber showed better results in comparison to models commonly used clinically (the best of the clinical models was the Fresenius 5008). Our aim was to determine if the Emboless® venous chamber differed in its capacity to limit MB exposure compared to the Fresenius 5008 (F5008) during HD and hemodiafiltration (HDF). Method Twenty chronic HD patients were included in a cross-over randomized study to compare the Emboless® to the F5008 venous chamber during HD. Each patient underwent a total of four dialyses divided into two paired series. This resulted in 80 studied dialyses, of which 32 included HDF. Dialyzers, blood-pump speed, HD or HDF, and ultrafiltration was the same between the pairs. MBs (20-500 µm, merged in intervals of 5 µm) were measured with an ultrasound device adjusted for HD (BCC200, GAMPT) at the ‘inlet’ and ‘outlet’ of the venous chamber. Measurements of MBs were done in the HD mode during the first 30 minutes, and if HDF was prescribed the measurement proceeded for another 30 minutes after the switch to the HDF mode (time was extended if fewer than 1000 MBs were detected at the inlet). The percentage of change in the ‘outlet’ versus ‘inlet’ counts was compared (paired Wilcoxon test). A total reduction was equal to −100%, while an increase (+) of MBs (worsening) was expressed as an unlimited percentage. If a diameter of an MB was without counts, it was not included in the analysis. Results For patients during HD, the median change of MBs in the outlet versus the inlet bloodline was −39% with the F5008 (n = 3807) and −76% with the Emboless® (n = 3805) venous chambers (p < 0.001, Fig. 1). For patients during HDF, the median change of MBs in the outlet versus the inlet bloodline was −28% with the F5008 (n = 1549) and −70% with the Emboless® (n = 1517) venous chambers (p < 0.001, Fig. 2). Conclusion Fewer MBs and subsequently fewer microemboli entered the patient using the Emboless® compared to the Fresenius 5008 venous chamber during HD, as well as during HDF. In considering previous autopsy studies, our results support less patient tissue damage when using the Emboless® venous chamber.

A Randomized Crossover Study in Single-Sided Deafness Comparing a Cartilage Conduction CROS System and an Air-Conduction CROS System.

To investigate if cartilage conduction (CC) rerouting devices are noninferior to air-conduction (AC) rerouting devices for single-sided deafness (SSD) patients by measuring objective and subjective performance using speech-in-noise tests that resemble a realistic hearing environment, sound localization tests, and standardized questionnaires. Prospective, single-subject randomized, crossover study. Anechoic room inside a university. Nine adults between 21 and 58 years of age with severe or profound unilateral sensorineural hearing loss. Patients' baseline hearing was assessed; they then used both the cartilage conduction contralateral routing of signals device (CC-CROS) and an air-conduction CROS hearing aid (AC-CROS). Patients wore each device for 2 weeks in a randomly assigned order. Three main outcome measures were 1) speech-in-noise tests, measuring speech reception thresholds; 2) proportion of correct sound localization responses; and 3) scores on the questionnaires, "Abbreviated Profile of Hearing Aid Benefit" (APHAB) and "Speech, Spatial, and Qualities of Hearing Scale" with 12 questions (SSQ-12). Speech reception threshold improved significantly when noise was ambient, and speech was presented from the front or the poor-ear side with both CC-CROS and AC-CROS. When speech was delivered from the better-ear side, AC-CROS significantly improved performance, whereas CC-CROS had no significant effect. Both devices mainly worsened sound localization, whereas the APHAB and SSQ-12 scores showed benefits. CC-CROS has noninferior hearing-in-noise performance except when the speech was presented to the better ear under ambient noise. Subjective measures showed that the patients realized the effectiveness of both devices.

Effects of Breaking Up Sitting on Gut Hormone Responses and Subsequent Compensatory Behaviors in Physically Inactive Adults.

The effects of breaking up sitting on gut hormone responses and free-living energy compensatory behaviors are still unclear in people of Asian ethnicity. Twenty-six Asians including 13 lean individuals (Lean) and 13 individuals with centrally overweight/obesity (OW), aged between 20 and 45 yr, completed a randomized crossover study with either 5.5-h uninterrupted sitting (SIT) or 5.5-h sitting with 2-min walking at 6.4 km·h -1 every 20 min (ACTIVE) in the laboratory. Blood samples were collected at regular time points to examine postprandial glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and glucose-dependent insulinotropic polypeptide (GIP) concentrations. Free-living physical activity and energy intake were recorded using wearable devices and weighed food diaries outside the laboratory until midnight. Paired t -tests were conducted to compare responses between trials. Postprandial GLP-1 and PYY incremental area under the curve values were higher in the ACTIVE trial versus SIT in both Lean and OW groups (all, P < 0.05), but there was no difference in GIP in either group (both, P > 0.05). There were no differences in free-living physical activity (volume and intensity) or energy intake (total and macronutrients) between trials in either group (all, P > 0.05), resulting in greater total physical activity over the 24-h monitoring period in ACTIVE trial versus SIT trial (both, P < 0.05). Breaking up sitting increases postprandial GLP-1 and PYY concentrations in Asians, but does not induce subsequent behavioral compensation, resulting in greater 24-h physical activity levels and lower relative energy intake, in inactive individuals irrespective of bodyweight status.

Effect of olfactory stimulation from aromatherapy on the autonomic nervous activity during aerobic exercises

Variations in the autonomic nervous system activity during exercise therapy in patients with cardiovascular diseases may lead to adverse events. Aromatherapy may reduce these adverse events by enhancing parasympathetic nervous activity (PNA). However, the effects of aromatherapy during exercise remain relatively unknown. This study aimed to evaluate the effect of aromatherapy on autonomic nervous activity during exercise and recovery. This randomized crossover study included 20 healthy men subjected to both aroma and placebo conditions which involved rest and moderate-intensity aerobic exercise on a cycle ergometer, followed by recovery. Blood pressure, heart rate variability indices, and SpO2 were measured during the rest, exercise, and recovery phases. Moreover, aroma preferences and emotional changes in response to the aroma were assessed. Under the placebo condition, high frequency (HF), root mean square of successive differences indices, and heart rate showed delayed recovery (P < 0.05). Furthermore, a moderate positive correlation was identified between aroma preference, pleasant emotions induced by aromatherapy, and the HF index (P < 0.05). These results indicate that aromatherapy facilitates the recovery of PNA after exercise. Furthermore, these effects were more pronounced among individuals who exhibited a stronger preference for and more positive emotions toward aromas.

The Production, Assessment, and Utility of 3D-Printed Video Laryngoscopes in Eastern India: A Low-Cost Alternative to Conventional Video Laryngoscopes.

Introduction Recognizing the limitations of traditional direct laryngoscopes, particularly in difficult airway situations, video laryngoscopy has emerged as a potentially safer and more effective alternative. This study evaluated the utility of two 3D-printed video laryngoscopes: a standard geometry video laryngoscope (SGVL), resembling the traditional Macintosh blade, and a hyper-angulated video laryngoscope (HAVL) with a more curved design. Their performance was compared to a standard Macintosh direct laryngoscope across various intubation parameters. By leveraging the cost-effectiveness of 3D printing with polylactic acid, the study aimed to assess the potential of this technology to improve airway management across diverse clinical settings and varying levels of physician expertise. Methods This prospective randomized crossover study compared the effectiveness of 3D-printed video laryngoscopes (VL) and a standard direct laryngoscope in intubation. After obtaining IRB approval, physicians from various specialties across multiple centers participated. Participants received training on SGVL, HAVL, and DL intubation using an instructional video and hands-on practice. The training was standardized for all participants. The primary outcome measures were time to successful intubation, number of attempts, and time to visualize vocal cords. Participants were randomized to use all three laryngoscopes on a manikin, with a maximum of two attempts per scope. A 30-minute break separated each laryngoscope evaluation. Successful intubation was defined as the single insertion of each laryngoscope and bougie, followed by endotracheal tube placement and confirmation of lung inflation. Results Ninety-eight doctors, mostly from the EM team (73.5%) and ICU team (23.4%). Teams consist of consultants, residents, and medical officers of the concerned departments. Forty-eight of the participants (49%) were novice operators (<25 intubations). Successful first-attempt intubation in those with <1 year of experience with intubation (n=33) was highest for SGVL (97%) compared to DL (82%) and HAVL (67%). Participants who learned intubation through self-directed learning exhibited a higher acceptance of VL and achieved 100% success on their first attempt. Among those who followed modules or workshops, 97% had successful first-attempt intubation with VL. The average time taken to visualize the vocal cords was lower in SGVL compared to DL (5.6 vs. 7.5 seconds) (p<0.001). The HAVL also had a lower average time compared to the DL (7.1 vs. 7.5 secs) (p<0.001). However, the time taken to intubate using DL (24.2 ±8.7 sec) was similar to SGVL (28.1 ±13 sec). Lastly, the intubation time using HAVL was the longest (49.6 ±35.5 sec). The time to intubate with DL and SGVL had Spearman's rho of 0.64 (p<0.001), and DL and HAVL had 0.59 (p<0.001). Conclusions The ease of use and its cost-effective nature make 3D-printed VLs beneficial in situations where traditional VLs may not be available, especially in simulation and training.

Validation of a bupropion, dextromethorphan, and omeprazole cocktail for simultaneous phenotyping of cytochrome P450 2B11, 2D15, and 3A12 activities in dogs.

Develop a cytochrome P450 (CYP) phenotyping cocktail for dogs using specific substrates for hepatic P450 enzymes CYP2B11, CYP2D15, and CYP3A12 and determine whether alternative sampling methods (saliva and urine) or single time point samples could be used instead of multiple blood sampling. 12 healthy client-owned dogs (8 females and 4 males) from February 2019 to May 2019. In a randomized crossover study, dogs received oral administration of the probe drug bupropion (75 mg), dextromethorphan (30 mg), or omeprazole (40 mg) alone or as a 3-drug combination (Program in Individualized Medicine [PrIMe] cocktail) to evaluate simultaneous phenotyping of CYP2B11, CYP2D15, and CYP3A12. Pharmacokinetic profiles for the probe drugs and metabolites were determined using plasma, saliva, and urine. Dogs received probe drugs alone or combined. Pharmacokinetic profiles up to 6 hours postdose for the probe drugs and metabolites were determined using plasma, saliva, and urine. The PrIMe cocktail was well tolerated. There was no statistically significant interaction between the probe drugs when administered together. Single time point plasma metabolic ratios at 4 hours postdose for all probe drugs strongly correlated with the corresponding area under the plasma concentration-versus-time curve (AUC) ratios. Saliva AUC metabolic ratios for CYP3A12 and CYP2D15 and 6-hour urine for CYP2B11 and CYP2D15 were correlated with plasma AUC ratios. The PrIMe cocktail can be used for simultaneous CYP phenotyping using plasma 4-hour single time point sample metabolic ratios. Saliva and urine sampling are suitable for specific CYPs. The PrIMe cocktail has potential as a useful tool in dogs to detect clinically important CYP-mediated drug-drug interactions, identify novel pharmacogenes, determine the drug-metabolizing phenotype of individual dogs, aid in individualized dose selection, and evaluate the effects of various physiological states on drug metabolism.

Multiomic Signatures of Traffic-Related Air Pollution in London Reveal Potential Short-Term Perturbations in Gut Microbiome-Related Pathways.

This randomized crossover study investigated the metabolic and mRNA alterations associated with exposure to high and low traffic-related air pollution (TRAP) in 50 participants who were either healthy or were diagnosed with chronic pulmonary obstructive disease (COPD) or ischemic heart disease (IHD). For the first time, this study combined transcriptomics and serum metabolomics measured in the same participants over multiple time points (2 h before, and 2 and 24 h after exposure) and over two contrasted exposure regimes to identify potential multiomic modifications linked to TRAP exposure. With a multivariate normal model, we identified 78 metabolic features and 53 mRNA features associated with at least one TRAP exposure. Nitrogen dioxide (NO2) emerged as the dominant pollutant, with 67 unique associated metabolomic features. Pathway analysis and annotation of metabolic features consistently indicated perturbations in the tryptophan metabolism associated with NO2 exposure, particularly in the gut-microbiome-associated indole pathway. Conditional multiomics networks revealed complex and intricate mechanisms associated with TRAP exposure, with some effects persisting 24 h after exposure. Our findings indicate that exposure to TRAP can alter important physiological mechanisms even after a short-term exposure of a 2 h walk. We describe for the first time a potential link between NO2 exposure and perturbation of the microbiome-related pathways.

Effect of 60-Min Single Bout of Resistance Exercise, Reformer Pilates, on Vascular Function Parameters in Older Adults: A Randomized Crossover Study

Introduction: Aging leads to vascular endothelial dysfunction and muscle impairment. While resistance exercise improves muscular function, its acute effects on vascular function vary in the literature, with some studies reporting detrimental effects. These findings indicate the need for exercises that optimize muscle function without compromising vascular function. Reformer Pilates (RP) is a low-impact exercise involving an adjustable sliding platform. However, the acute effects of RP on vascular function among older adults remain unknown. Therefore, this study aimed to investigate the acute effects of RP on vascular function in older adults. Methods: Overall, 17 participants (age: 65 ± 2.76 years, body mass index: 23.42 ± 3.68 kg/m2) were examined and assigned to control and RP conditions under a randomized crossover design. The RP condition involved a 3.5–5 omnibus perceived exertion scale with 19 exercise postures for 60 min. Brachial artery flow-mediated dilation (FMD), brachial-ankle pulse wave velocity (baPWV), and blood pressure were measured at baseline and 0, 10, 30, and 60 min after exercise. Results: RP significantly improved FMD at all time points compared with that at baseline (p < 0.05). baPWV increased at 0 min post-RP but returned to baseline levels at other time points. Additionally, RP showed improved FMD at 0, 10, and 30 min compared with that in the control condition (p < 0.05). However, no significant differences were observed in blood pressure or mean arterial pressure in either condition. Conclusion: RP enhanced FMD and regulated blood pressure for approximately 60 min post-exercise, suggesting its suitability for older adults to enhance vascular function and control blood pressure during exercise. Nonetheless, longitudinal resistance training intervention studies are needed to validate these findings.

Low dialysate sodium and 48-h ambulatory blood pressure in patients with intradialytic hypertension: a randomized crossover study.

Intradialytic-hypertension (IDH) is associated with increased risk for cardiovascular events and mortality. Patients with IDH exhibit higher 48-h blood pressure (BP) levels than patients without this condition. Volume and sodium excess are considered a major factor contributing in the development of this phenomenon. This study evaluated the effect of low (137mEq/L) compared to standard (140mEq/L) dialysate sodium concentration on 48-h BP in patients with IDH. In this randomized, single-blind, crossover study, 29 patients with IDH underwent 4 hemodialysis sessions with low (137mEq/L) followed by 4 sessions with standard (140mEq/L) dialysate sodium or vice-versa. Mean 48-h BP, pre-/post-dialysis and intradialytic BP, pre-dialysis weight, interdialytic weight gain (IDWG) and lung ultrasound B-lines were assessed. Mean 48-h SBP/DBP were significantly lower with low compared to standard dialysate sodium concentration (137.6±17.0/81.4±13.7mmHg with low vs 142.9±14.5/84.0±13.9mmHg with standard dialysate sodium, p=0.005/p=0.007 respectively); SBP/DBP levels were also significantly lower during the 44-h and different 24-h periods. Low dialysate sodium significantly reduced post-dialysis (SBP/DBP: 150.3±22.3/91.2±15.1mmHg with low vs 166.6±17.3/94.5±14.9mmHg with standard dialysate sodium, p<0.001/p=0.134 respectively) and intradialytic (141.4±18.0/85.0±13.4mmHg with low vs 147.5±13.6/88.1±12.5mmHg with standard dialysate sodium, p=0.034/p=0.013, respectively) BP compared with standard dialysate sodium. Pre-dialysis weight, IDWG and pre-dialysis B-lines were also significantly decreased with low dialysate sodium. Low dialysate sodium concentration significantly reduced 48-h ambulatory BP compared with standard dialysate sodium in patients with IDH. These findings support low dialysate sodium as a major non-pharmacologic approach for BP management in patients with IDH.Registered at ClinicalTrials.gov with study number NCT05430438.

Toe Box Shape of Running Shoes Affects In-Shoe Foot Displacement and Deformation: A Randomized Crossover Study.

Long-distance running is popular but associated with a high risk of injuries, particularly toe-related injuries. Limited research has focused on preventive measures, prompting exploration into the efficacy of raised toe box running shoes. This study aimed to investigate the effect of running shoes with raised toe boxes on preventing toe injuries caused by distance running. A randomized crossover design involved 25 male marathon runners (height: 1.70 ± 0.02 m, weight: 62.6 + 4.5 kg) wearing both raised toe box (extended by 8 mm along the vertical axis and 3 mm along the sagittal axis) and regular toe box running shoes. Ground reaction force (GRF), in-shoe displacement, and degree of toe deformation (based on the distance change between the toe and the metatarsal head) were collected. Wearing raised toe box shoes resulted in a significant reduction in vertical (p = 0.001) and antero-posterior (p = 0.015) ground reaction forces during the loading phase, with a notable increase in vertical ground reaction force during the toe-off phase (p < 0.001). In-shoe displacement showed significant decreased movement in the forefoot medial (p < 0.001) and rearfoot (medial: p < 0.001, lateral: p < 0.001) and significant increased displacement in the midfoot (medial: p = 0.002, lateral: p < 0.001). Impact severity on the hallux significantly decreased (p < 0.001), while impact on the small toes showed no significant reduction (p = 0.067). Raised toe box running shoes offer an effective means of reducing toe injuries caused by long-distance running.

Brown Fat: A Beta Way to Burn Calories, but Which Beta?

Brown fat is a thermogenic tissue that may have therapeutic value for the treatment of obesity and diabetes. That brown fat is under sympathetic control is indisputable, but considerable controversy exists as to which of the beta-adrenergic receptor subtypes, b1AR, b2AR or b3AR, is the primary regulator. The purpose of the current study was to determine if co-administration of the b3AR agonist, mirabegron, would increase energy expenditure and brown fat activation more than non-selective bAR stimulation (isoproterenol) alone. 14 healthy, active young adults (8 males, 6 females) participated in a randomized crossover study. Energy expenditure in a temperature-controlled room (22.1 deg C, 48.5% relative humidity) was determined at rest and after ingestion of placebo or mirabegron (100mg), prior to intravenous administration of isoproterenol (30 minutes at 6, 12, and 24 ng/kg fat free mass/min). Brown fat activity was estimated using supraclavicular skin temperature assessed via infrared thermography. Baseline energy expenditure was not different ( P=0.42) prior to placebo (1487±106 kcal/day; (mean±SE)) and mirabegron (1424±104 kcal/day). Non-selective bAR stimulation increased energy expenditure above baseline (11.6±5.5, 15.2±6.3 and 20.1±6.0%; P&lt;0.05); additional b3AR stimulation did not augment this response (18.0±3.8, 23.2±4.2 and 27.8±4.5%; P&gt;0.05). Baseline supraclavicular skin temperature was not different ( P=0.95) prior to placebo (35.004±0.967◦C) and mirabegron (34.992±0.967◦C). Only the greatest dose of non-selective bAR stimulation increased supraclavicular skin temperature above baseline (0.236±0.082◦C); additional b3AR stimulation did not augment this response (0.100±0.082◦C; P=0.09). Co-administration of a b3AR agonist did not increase energy expenditure and brown fat activation more than non-selective bAR stimulation alone. These preliminary data imply that the b3AR might not be the primary regulator of brown fat activation in humans. Offce of Naval Research N00014-21-1-2276. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Central and peripheral cardiovascular responses after acute dietary nitrate supplementation in post-menopausal women

The transition to menopause is accompanied by augmented cardiovascular disease risk, partially attributed to reduced nitric oxide (NO) bioavailability. Despite a lower arterial stiffness than men, postmenopausal women are susceptible to increased aortic pulsatile hemodynamic load because of greater pressure wave reflection and vascular dysfunction. Increasing bioavailable NO with dietary nitrate has shown promise to reduce aortic (aSBP) and brachial (bSBP) systolic pressure healthy postmenopausal women. However, there are limited reports comparing hypertensive (HTN) and normotensive (NTN) postmenopausal women regarding wave separation analysis and vascular function following dietary nitrate supplementation. This study investigated if acute dietary nitrate supplementation would improve aortic hemodynamics, wave reflection characteristics, vascular stiffness, and vasodilatory function. We hypothesized that dietary nitrate would lower pulse wave velocity in hypertensives, lower aortic and brachial blood pressures and forward and backward wave magnitude and increase microvascular, but not macrovascular function in both groups. Fourteen postmenopausal women (n=7 HTN; n=7 NTN) participated in a two-day randomized crossover study design with dietary nitrate (nitrate rich, NR) or a placebo control (NP). Central and peripheral hemodynamics and carotid-femoral pulse wave velocity (cfPWV) were performed with a SphygmoCOR Excel, simultaneous resting macro- and- microvascular function was assessed using flow-mediated vasodilation (FMD) and post occlusive reactive hyperemia (PORH) using near-infrared spectroscopy. aSBP was reduced significantly following NR supplement within groups (HTN: NP 126±2 NR 120±1mmHg) and NTN group (NP 110± 1 NR 104±3mmHg p&lt;0.05). Forward pulse height HTN (NP 29±1.4 NR 26.3±1.4mmHg) NTN (NP 25.6±0.9 NR 24±2.7mmHg) and reflected pulse height HTN (NP 18.2±0.08 NR 17.2±0.4mmHg) NTN (NP 17.7±0.2 NR 15.7±1.07mmHg) were not different. cfPWV was faster in the HTN group and slowed with a NR supplement (HTN: NP 8.2±0.29 NR 7.4±0.31m/s; NTN NP 7.1±0.23 NR 6.6±0.62m/s p&lt;0.05). A significant interaction for %FMD was found (HTN: NP 7.3±0.8 NR 6.2±0.8%; NTN NP 6.6±0.7 NR 9.4±0.7%). Further, we found no difference in the NIRS derived microvascular function measurements (HTN: NP 1.9±0.2 NR 1.7±0.3%/s; NTN NP 1.6±0.1 NR 1.4±0.2%/s p&gt;0.05). These data indicate that dietary nitrate consumption led to a substantial reduction in aortic hemodynamics and reduced pulse wave velocity regardless of hypertension status. Interestingly, macrovascular, but not microvascular vasodilatory function was improved in the NTN women only. Dietary nitrate supplementation appears to have differential effects when considering HTN and NTN postmenopausal women. Supported with funds from The University of Wisconsin-La Crosse RSEL graduate grant. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effect of Volitional Modification of Breath Frequency on Attention and Mood States: An Exploratory Randomized Crossover Study.

Previously, yoga breathing improved mood states and attention but the effect of varying breath frequency on mood and attention was not clear. The objective of this study was to determine the effects of changes in breath frequency on attention, mood, vigor, and affect states. Thirty participants (mean age ± standard deviation, 27.3 ± 4.2 years) were assessed on 2 separate days practicing either high-frequency yoga breathing (HFYB, breath frequency 54.23/min) or bumblebee yoga breathing (BBYB, breath frequency 3.97/min) in random order. Assessments included blood pressure (BP), cancellation test scores, Nijmegen (to check for hyperventilation), respiration (rate, height of the breath wave [depth], and duration of inhalation relative to exhalation), mood states, vigor, and affect states. Diastolic BP increased after HFYB, whereas systolic BP decreased after BBYB, after both sessions scores in a cancellation test increased (changes in cancellation test performance suggest alertness and test-directed attention), also global vigor (signifying mental energy) and global affect (related to being "happy" and "calm") scores increased, whereas negative mood decreased after HFYB session (P < 0.05, Wilcoxon signed-rank test). Both HFYB and BBYB increased attention test scores, possibly due to cortical activation (HFYB) or relaxation (BBYB). In HFYB, breath frequency and inspiration duration increased suggestive of increased sympathetic activity, accounting for increased vigor, positive affect, and diastolic BP. In contrast in BBYB, low breath frequency, higher breath amplitude, and prolonged expiration suggestive of parasympathetic activity may account for the decreased systolic BP after BBYB.

Randomized trial of pharmacokinetic and pharmacodynamic effects of 13.2 mg intranasal epinephrine treatment in congestion

BackgroundNasal congestion could affect the absorption of an epinephrine nasal spray (ENS). ObjectiveTo compare the pharmacokinetics of 13.2 mg ENS with nasal congestion vs without congestion and vs intramuscular (IM) treatments. MethodsThis phase I, open-label, 4-period randomized crossover study enrolled 51 healthy adults with seasonal allergies into cohorts that received a single dose of 13.2 mg ENS (NDS1C; Bryn Pharma, Lebanon, New Jersey) administered as 2 consecutive sprays in either opposite nostrils (cohort 1) or the same nostril (cohort 2). Both cohorts received 13.2 mg ENS with and without nasal allergen challenge (NAC), 0.3 mg IM epinephrine by autoinjector, and 0.5 mg IM epinephrine by manual syringe (MS). ResultsThe ENS after NAC resulted in higher extent and peak exposures and more rapid time to maximum plasma concentration vs ENS without NAC and IM treatments. In cohort 1, the maximum observed baseline-adjusted epinephrine plasma concentration (pg/mL) of ENS with NAC, IM autoinjector, IM MS, or ENS without NAC was 458.0, 279.0, 364.2, and 270.1, respectively, and in cohort 2 was 436.3, 228.2, 322.3, and 250.8, respectively. The maximum observed baseline-adjusted epinephrine plasma concentration geometric mean ratio (90% CI) for ENS with NAC vs without NAC in cohort 1 was 170% (123%-234%), and in cohort 2 was 174% (115%-263%). In cohort 1, the time to maximum plasma concentration was 15, 21, 45, and 25 minutes, respectively, and in cohort 2 was 18, 20, 45, and 20 minutes, respectively (P < .01 for ENS with NAC vs IM MS). The postdose mean heart rate and blood pressure remained stable and relatively similar to predose values regardless of plasma epinephrine concentration. Mild nausea and headache were the most common adverse events with ENS. ConclusionThe 13.2 mg ENS with congestion exhibited enhanced absorption vs IM treatments and ENS without congestion and seemed to be well tolerated. There was no clinically impactful relationship between pharmacodynamic effects and plasma epinephrine concentration.

Acute effects of prismatic adaptation on penalty kick accuracy and postural control in young soccer players: A pilot study

BackgroundPrismatic adaptation (PA) is a visuomotor technique using prismatic glasses that are capable of moving the visual field and to affect the excitability of certain brain areas. The aim of this pilot study was to explore potential acute effects of PA on penalty kick accuracy and postural control in youth soccer players. MethodsIn this randomized crossover study, seven young male soccer players performed three PA sessions (rightward PA, r-PA; leftward PA, l-PA; sham PA, s-PA) with a washout period of 1-week between them. Immediately before and after each PA session, penalty kick accuracy and postural control were assessed. ResultsWe detected an increase in penalty kick accuracy following PA, regardless of the deviation side of the prismatic glasses (F1,5 = 52.15; p = 0.08; ηp2 = 0.981). In detail, our results showed an increase in the penalty kick accuracy toward the right target of the football goal following r-PA and toward the left target of the football goal following l-PA. We detected a significant effect on the sway path length (F2,12 = 10.42; p = 0.002; ηp2 = 0.635) and the sway average speed (F2,12 = 9.17; p = 0.004; ηp2 = 0.605) parameters in the stabilometric test with open eyes following PA, regardless of the deviation side of the prismatic glasses. In detail, our results showed a significant difference in both the stabilometric parameters (p = 0.016 and p = 0.009, respectively) only following l-PA. ConclusionThe findings of this pilot study indicate that PA could positively affect penalty kick accuracy and postural control suggesting that PA could be used as a visual training technique in athletes.

The metabolic effects of habitual leg shaking: A randomized crossover trial.

The adverse effects of sedentary behavior on obesity and chronic diseases are well established. However, the prevalence of sedentary behavior has increased, with only a minority of individuals meeting the recommended physical activity guidelines. This study aimed to investigate whether habitual leg shaking, a behavior traditionally considered unfavorable, could serve as an effective strategy to improve energy metabolism. A randomized crossover study was conducted, involving 15 participants (mean [SD] age, 25.4 [3.6]; mean [SD] body mass index, 22 [3]; 7 women [46.7%]). The study design involved a randomized sequence of sitting and leg shaking conditions, with each condition lasting for 20 min. Energy expenditure, respiratory rate, oxygen saturation, and other relevant variables were measured during each condition. Compared to sitting, leg shaking significantly increased total energy expenditure [1.088 kj/min, 95% confidence interval, 0.69-1.487 kj/min], primarily through elevated carbohydrate oxidation. The average metabolic equivalent during leg shaking exhibited a significant increase from 1.5 to 1.8. Leg shaking also raised respiratory rate, minute ventilation, and blood oxygen saturation levels, while having no obvious impact on heart rate or blood pressure. Electromyography data confirmed predominant activation of lower leg muscles and without increased muscle fatigue. Intriguingly, a significant correlation was observed between the increased energy expenditure and both the frequency of leg shaking and the muscle mass of the legs. Our study provides evidence that habitual leg shaking can boost overall energy expenditure by approximately 16.3%. This simple and feasible approach offers a convenient way to enhance physical activity levels.

Comparative Pharmacokinetics and Safety Assessment of 1st- and 2nd-Generation Zinpentraxin Alfa Drug Products in Healthy Volunteers: A Randomized Crossover Study.

Zinpentraxin alfa is a recombinant form of the human pentraxin-2 that was studied in idiopathic pulmonary fibrosis (IPF). To improve the purity and yield of the drug material, a 2nd-generation drug product was developed. To characterizeand compare the pharmacokinetic (PK) properties of the 1st- and 2nd-generation zinpentraxin alfa, PK studies were conducted in healthy volunteers (HVs). In a phase 1 randomized, double-blind, 2-sequence crossover, sequential 2-stage study (ISRCTN59409907), single intravenous (IV) doses of 1st- and 2nd-generation zinpentraxin alfa at 10mg/kg were studied with a blinded interim analysis (IA) at the end of stage 1. Bioequivalence (BE) was achieved for the maximum observed plasma concentration (Cmax), but the overall exposure was higher for the 2nd- compared to the 1st-generation zinpentraxin alfa. The study was stopped after stage 1 as the gating criteria were met based on the result of the blinded IA. Safety profiles were similar for the 1st- and 2nd-generation drug products, and antidrug antibody (ADA) was not observed in this study.

Positive Effect of a Cooling Cap on Functional Performance in Thermosensitive People with Multiple Sclerosis: A Randomized Controlled Trial

Background. Up to 80% of people with MS experience worsening of their condition upon an increase in body temperature. Therefore, various options of cooling are being evaluated to help improve physical performance in people with MS. Most previous studies used active cooling methods. Our aim was to study the effect of simple device providing passive cooling. Methods. A randomized crossover study was conducted in 21 thermosensitive people with mild to moderate disability. Subjects were tested immediately before and after intervention (experimental or sham cooling). The assessment included timed 25-foot walk test, the 2- and 6-minute walk test, nine-hole peg test, and symbol digit modalities test. Results. A significant improvement was found in the experimental group in timed 25-foot walk test (p=0.011) and in nine-hole peg test for dominant hand (p=0.033). No significant improvement was found in the control group (sham cooling). Conclusions. Wearing cooling cap can improve short-term functional performance (walking and fine motor skills) in thermosensitive people with MS. This passive cooling method can be considered as a symptomatic treatment for some people with MS. This trial is registered with ISRCTN56350227.