Sex differences in forearm vasoconstrictor response to voluntary apnea.

Clinical evidence indicates that obstructive sleep apnea is more common and more severe in men compared with women. Sex differences in the vasoconstrictor response to hypoxemia-induced sympathetic activation might contribute to this clinical observation. In the current laboratory study, we determined sex differences in the acute physiological responses to maximal voluntary end-expiratory apnea (MVEEA) during wakefulness in healthy young men and women (26 ± 1 yr) as well as healthy older men and women (64 ± 2 yr). Mean arterial pressure (MAP), heart rate (HR), brachial artery blood flow velocity (BBFV, Doppler ultrasound), and cutaneous vascular conductance (CVC, laser Doppler flowmetry) were measured, and changes in physiological parameters from baseline were compared between groups. The breath-hold duration and oxygen-saturation nadir were similar between groups. In response to MVEEA, young women had significantly less forearm vasoconstriction compared with young men (ΔBBFV: 2 ± 7 vs. -25 ± 6% and ΔCVC: -5 ± 4 vs. -31 ± 4%), whereas ΔMAP (12 ± 2 vs. 16 ± 3 mmHg) and ΔHR (4 ± 2 vs. 6 ± 3 bpm) were comparable between groups. The attenuated forearm vasoconstriction in young women was not observed in postmenopausal women (ΔBBFV -21 ± 5%). We concluded that young women have blunted forearm vasoconstriction in response to MVEEA compared with young men, and this effect is not evident in older postmenopausal women. These data suggest that female sex hormones dampen neurogenic vasoconstriction in response to apnea-induced hypoxemia.

ß-Adrenergic blockade enhances coronary vasoconstrictor response to forehead cooling.

Forehead cooling activates the sympathetic nervous system and can trigger angina pectoris in susceptible individuals. However, the effect of forehead cooling on coronary blood flow velocity (CBV) is not well understood. In this human experiment, we tested the hypotheses that forehead cooling reduces CBV (i.e., coronary vasoconstriction) and that this vasoconstrictor effect would be enhanced under systemic ß-adrenergic blockade. A total of 30 healthy subjects (age range, 23-79 years) underwent Doppler echocardiography evaluation of CBV in response to 60 s of forehead cooling (1°C ice bag on forehead). A subset of subjects (n = 10) also underwent the procedures after an intravenous infusion of propranolol. Rate pressure product (RPP) was used as an index of myocardial oxygen demand. Consistent with our first hypothesis, forehead cooling reduced CBV from 19.5 ± 0.7 to 17.5 ± 0.8 cm/s (P < 0.001), whereas mean arterial pressure increased by 11 ± 2 mmHg (P < 0.001). Consistent with our second hypothesis, forehead cooling reduced CBV under propranolol despite a significant rise in RPP. The current studies indicate that forehead cooling elicits a sympathetically mediated pressor response and a reduction in CBV, and this effect is augmented under ß-blockade. The results are consistent with sympathetic activation of ß-receptor coronary vasodilation in humans, as has been demonstrated in animals.

Exploring sport participation in individuals with spinal cord injury: A qualitative thematic synthesis.

CONTEXT: Individuals with spinal cord injury (SCI) are susceptible to various physical, psychological, and social challenges. Sport is an activity that may holistically address these concerns. No existing research provides an overview of the current landscape of SCI-specific sport participation. OBJECTIVE: To synthesize the findings of qualitative studies exploring the perceptions of people with SCI participating in sport, in relation to physical, psychological, and social health. METHODS: This thematic synthesis included studies published in APA PsycInfo, CINAHL, Embase, Emcare, Medline, and PubMed. Eligible articles studied adults who had a SCI for ≥12 months and explored experiences following ≥3 months of sport participation using qualitative or mixed-methods. Articles were excluded if participants with SCI composed less than one-third of the study sample. From 8473 unique titles and abstracts screened, 47 articles underwent full-text review and 14 articles were included. The Mixed Methods Appraisal Tool was used to critically appraise the 13 qualitative studies and one mixed-methods study. RESULTS: The overarching theme was that sport facilitates the progression to living an enriching life with SCI. Four sub-themes were identified within this theme: adjusting to SCI, factors influencing sport initiation, outcomes resulting from sport participation, and reshaping views of SCI. Participants detailed many benefits of sport, including improved fitness, independence, confidence, and sense of community. Beyond the participants themselves, sport helped reshape views of SCI by breaking stereotypes and inspiring others. CONCLUSION: Sport can play a crucial role in facilitating the progression to living an enriching life following SCI.

Spatial characteristics of reactive stepping among people living with chronic incomplete spinal cord injury.

Objective: Compare the spatial characteristics of reactive stepping between individuals with chronic motor incomplete spinal cord injuries (iSCI) and able-bodied (AB) individuals.Design: Cross sectional.Setting: Lyndhurst Centre.Participants: Twelve individuals with iSCI (3 males, 53.6 ± 15.2 years old) and 11 age- and sex-matched AB individuals (3 males, 54.8 ± 14.0 years old).Interventions: The Lean-and-Release test was used to elicit reactive stepping. A horizontal cable, attached at waist height, was released when 8-12% body weight was supported in a forward lean position. Participants underwent up to 10 Lean-and-Release trials in a session. Kinematic and kinetic data were recorded.Outcome measures: The length, width and height of the first reactive step of each trial were calculated. Standard deviation between trials was calculated to represent the variability in step length, width and height within a participant. Among participants with iSCI, correlation coefficients were used to explore the relationship between step length and width variability and (1) Lean-and-Release test behavioral responses, (2) 3-month fall history, and (3) lower extremity strength.Results: Step length (P = 0.94), width (P = 0.52) and height (P = 0.97), normalized for participant height, did not differ between groups. Participants with iSCI showed greater variability in step length (P = 0.02) and width (P = 0.01), but not height (P = 0.32). No correlation was found between step length or width variability and behavioral responses, 3-month fall history, or lower extremity strength.Conclusions: Individuals with iSCI showed increased variability in length and width of reactive stepping compared to AB individuals, which may contribute to their impaired ability to execute single-step reactive responses.Trial registration: ClinicalTrials.gov identifier: NCT02960178.

The impact of sport participation for individuals with spinal cord injury: A scoping review.

BACKGROUND: Spinal cord injury (SCI) leads to various physical, psychological, and social challenges. Sport is a holistic physical activity that may target these challenges. No literature systematically summarizes the overall impact of sport participation for those with SCI. OBJECTIVE: To comprehensively report the findings of quantitative studies investigating the impact of sport on the physical, psychological, and social health of individuals with SCI. METHODS: Six databases were searched: APA PsycInfo, CINAHL, Embase, Emcare, Ovid Medline, and PubMed (non-Medline). Studies were included if (a) participants were adults with SCI for ≥12 months, (b) outcomes resulting from ≥3 months of sport participation were investigated, (c) sport occurred in the community setting, and (d) comparisons of sport and non-sport conditions were analyzed. Details regarding study characteristics, participants, sport(s), and outcomes were extracted. Methodological quality was assessed using the Modified Downs and Black checklist. RESULTS: Forty-nine studies were included. Study quality ranged from poor to moderate. Sport participation showed favourable results for outcomes including function, quality of life, and community integration. Mixed results were found for outcomes including cardiac function, depressive symptoms, and employment. No significant associations were found for postural control, resilience, and education. CONCLUSIONS: The review findings suggest sport may be a promising intervention for addressing some challenges associated with SCI.

Recommendations for the Design and Delivery of Transitions-Focused Digital Health Interventions: Rapid Review.

BACKGROUND: Older adults experience a high risk of adverse events during hospital-to-home transitions. Implementation barriers have prevented widespread clinical uptake of the various digital health technologies that aim to support hospital-to-home transitions. OBJECTIVE: To guide the development of a digital health intervention to support transitions from hospital to home (the Digital Bridge intervention), the specific objectives of this review were to describe the various roles and functions of health care providers supporting hospital-to-home transitions for older adults, allowing future technologies to be more targeted to support their work; describe the types of digital health interventions used to facilitate the transition from hospital to home for older adults and elucidate how these interventions support the roles and functions of providers; describe the lessons learned from the design and implementation of these interventions; and identify opportunities to improve the fit between technology and provider functions within the Digital Bridge intervention and other transition-focused digital health interventions. METHODS: This 2-phase rapid review involved a selective review of providers' roles and their functions during hospital-to-home transitions (phase 1) and a structured literature review on digital health interventions used to support older adults' hospital-to-home transitions (phase 2). During the analysis, the technology functions identified in phase 2 were linked to the provider roles and functions identified in phase 1. RESULTS: In phase 1, various provider roles were identified that facilitated hospital-to-home transitions, including navigation-specific roles and the roles of nurses and physicians. The key transition functions performed by providers were related to the 3 categories of continuity of care (ie, informational, management, and relational continuity). Phase 2, included articles (n=142) that reported digital health interventions targeting various medical conditions or groups. Most digital health interventions supported management continuity (eg, follow-up, assessment, and monitoring of patients' status after hospital discharge), whereas informational and relational continuity were the least supported. The lessons learned from the interventions were categorized into technology- and research-related challenges and opportunities and informed several recommendations to guide the design of transition-focused digital health interventions. CONCLUSIONS: This review highlights the need for Digital Bridge and other digital health interventions to align the design and delivery of digital health interventions with provider functions, design and test interventions with older adults, and examine multilevel outcomes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2020-045596.

Fatigue and Discomfort During Spatially Distributed Sequential Stimulation of Tibialis Anterior.

Neuromuscular electrical stimulation is conventionally applied through a single pair of electrodes over the muscle belly, denominated single electrode stimulation (SES). SES is limited by discomfort and incomplete motor-unit recruitment, restricting electrically-evoked torque and promoting premature fatigue-induced torque-decline. Sequential stimulation involving rotation of pulses between multiple pairs of electrodes has been proposed as an alternative, denominated spatially distributed sequential stimulation (SDSS). The present aim was to compare discomfort, maximal-tolerated torque, and fatigue-related outcomes between SES and SDSS of tibialis anterior. Ten healthy participants completed two experimental sessions. The self-reported discomfort at sub-maximal torque, the maximal-tolerated torque, fatigue-induced torque-decline during, and doublet-twitch torque at 10- and 100-Hz before and after, 300 intermittent (0.6-s-ON-0.6-s-OFF) isokinetic contractions were compared between SES and SDSS. SDSS stimulation improved fatigue-related outcomes, whereas increased discomfort and reduced maximal-tolerated torque. SDSS holds promise for reducing fatigue. However, limited torque production and associated discomfort may limit its utility for rehabilitation/training.

The mesophilic archaeon Methanosarcina acetivorans counteracts uracil in DNA with multiple enzymes: EndoQ, ExoIII, and UDG.

Cytosine deamination into uracil is one of the most prevalent and pro-mutagenic forms of damage to DNA. Base excision repair is a well-known process of uracil removal in DNA, which is achieved by uracil DNA glycosylase (UDG) that is found in all three domains of life. However, other strategies for uracil removal seem to have been evolved in Archaea. Exonuclease III (ExoIII) from the euryarchaeon Methanothermobacter thermautotrophicus has been described to exhibit endonuclease activity toward uracil-containing DNA. Another uracil-acting protein, endonuclease Q (EndoQ), was recently identified from the euryarchaeon Pyrococcus furiosus. Here, we describe the uracil-counteracting system in the mesophilic euryarchaeon Methanosarcina acetivorans through genomic sequence analyses and biochemical characterizations. Three enzymes, UDG, ExoIII, and EndoQ, from M. acetivorans exhibited uracil cleavage activities in DNA with a distinct range of substrate specificities in vitro, and the transcripts for these three enzymes were detected in the M. acetivorans cells. Thus, this organism appears to conduct uracil repair using at least three distinct pathways. Distribution of the homologs of these uracil-targeting proteins in Archaea showed that this tendency is not restricted to M. acetivorans, but is prevalent and diverse in most Archaea. This work further underscores the importance of uracil-removal systems to maintain genome integrity in Archaea, including 'UDG lacking' organisms.

Do peripheral and/or central chemoreflexes influence skin blood flow in humans?

Voluntary apnea activates the central and peripheral chemoreceptors, leading to a rise in sympathetic nerve activity and limb vasoconstriction (i.e., brachial blood flow velocity and forearm cutaneous vascular conductance decrease to a similar extent). Whether peripheral and/or central chemoreceptors contribute to the cutaneous vasoconstrictor response remains unknown. We performed three separate experiments in healthy young men to test the following three hypotheses. First, inhibition of peripheral chemoreceptors with brief hyperoxia inhalation (100% O2) would attenuate the cutaneous vasoconstrictor response to voluntary apnea. Second, activation of the peripheral chemoreceptors with 5 min of hypoxia (10% O2, 90% N2) would augment the cutaneous vasoconstrictor response to voluntary apnea. Third, activation of the central chemoreceptors with 5 min of hypercapnia (7% CO2, 30% O2, 63% N2) would have no influence on cutaneous responses to voluntary apnea. Studies were performed in the supine posture with skin temperature maintained at thermoneutral levels. Beat-by-beat blood pressure, heart rate, brachial blood flow velocity, and cutaneous vascular conductance were measured and changes from baseline were compared between treatments. Relative to room air, hyperoxia attenuated the vasoconstrictor response to voluntary apnea in both muscle (-16 ± 10 vs. -40 ± 12%, P = 0.023) and skin (-14 ± 6 vs. -24 ± 5%, P = 0.033). Neither hypoxia nor hypercapnia had significant effects on cutaneous responses to apnea. These data indicate that skin blood flow is controlled by the peripheral chemoreceptors but not the central chemoreceptors.

Ascorbic acid does not enhance hypoxia-induced vasodilation in healthy older men.

In response to hypoxia, a net vasodilation occurs in the limb vasculature in young healthy humans and this is referred to as "hypoxia-induced vasodilation". We performed two separate experiments to determine (1) if hypoxia-induced forearm vasodilation is impaired in older men (n = 8) compared to young men (n = 7) and (2) if acute systemic infusion of ascorbic acid would enhance hypoxia-induced vasodilation in older men (n = 8). Heart rate, mean arterial pressure, oxygen saturation, minute ventilation, forearm vascular conductance (FVC, Doppler ultrasound), and cutaneous vascular conductance (CVC, laser Doppler flowmetry) were recorded continuously while subjects breathed 10% oxygen for 5 min. Changes from baseline were compared between groups and between treatments. The older adults had a significantly attenuated increase in FBF (13 ± 4 vs. 30 ± 7%) and FVC (16 ± 4 vs. 30 ± 7%) in response to 5 min of hypoxia. However, skin blood flow responses were comparable between groups (young: 35 ± 9, older: 30 ± 6%). In Experiment 2, FVC responses to 5 min of breathing 10% oxygen were not significantly different following saline (3 ± 10%) and ascorbic acid (8 ± 10%) in the older men. Ascorbic acid also had no physiological effects in the young men. These findings advance our basic understanding of how aging influences vascular responses to hypoxia and suggest that, in healthy humans, hypoxia-induced vasodilation is not restrained by reactive oxygen species.

Forearm vascular responses to mental stress in healthy older adults.

Forearm vascular conductance (FVC) increases in response to mental stress (verbal mental arithmetic) in young people. However, the effect of healthy aging and mental stress on FVC is unknown. In this study, we tested the hypothesis that FVC and cutaneous vascular conductance (CVC) would be attenuated in older adults compared to young adults. In 13 young (27 ± 1 year) and 11 older (62 ± 1 year) subjects, we quantified heart rate (HR), mean arterial pressure (MAP), FVC (Doppler ultrasound), and CVC (laser Doppler flowmetry) in response to a 3-min bout of mental stress in the supine posture. Changes from baseline were compared between groups and physiological variables were also correlated. Older adults had a blunted HR response to mental stress (Δ = 7 ± 2 vs. 14 ± 2 beats/min) but ΔMAP was comparable between groups (Δ = 11 ± 2 mmHg vs. 9 ± 1). During the third minute of mental stress, the %ΔFVC (-2 ± 5 vs. 31 ± 12%) and %ΔCVC (2 ± 6 vs. 31 ± 15%) were both impaired in older adults compared to young subjects. There was no relationship between ΔHR and %ΔCVC in either group, but there was a positive relationship between ΔHR and %ΔFVC in both young subjects (R = 0.610, P < 0.027) and older subjects (R = 0.615, P < 0.044), such that larger tachycardia was associated with higher forearm vasodilation. These data indicate that older adults have impaired forearm vasodilation in response to mental stress.

Tactile stimulation of the oropharynx elicits sympathoexcitation in conscious humans.

Tactile stimulation of the oropharynx (TSO) elicits the gag reflex and increases heart rate (HR) and mean arterial pressure (MAP) in anesthetized patients. However, the interaction between upper-airway defense reflexes and the sympathetic nervous system has not been investigated in conscious humans. In Experiment 1, beat-by-beat measurements of HR, MAP, muscle sympathetic nerve activity (MSNA), and renal vascular resistance (RVR) were measured during TSO and tactile stimulation of the hard palate (Sham) in the supine posture. In Experiment 2, TSO was performed before (pre) and after (post) inhalation of 4% lidocaine via nebulizer. Rate pressure product (RPP) was determined. Compared with Sham, TSO elicited the gag reflex and increased RPP [absolute change (Δ)36 ± 6 vs. 17 ± 5%], MSNA (Δ122 ± 39 vs. 19 ± 19%), and RVR (Δ55 ± 11 vs. 4 ± 4%). This effect occurred within one to two cardiac cycles of TSO. The ΔMAP (12 ± 3 vs. 6 ± 1 mmHg) and the ΔHR (10 ± 3 vs. 3 ± 3 beats/min) were also greater following TSO compared with Sham. Lidocaine inhalation blocked the gag reflex and attenuated increases in MAP (Δpre: 16 ± 2; Δpost: 5 ± 2 mmHg) and HR (Δpre: 12 ± 3; Δpost: 2 ± 2 beats/min) in response to TSO. When mechanically stimulated, afferents in the oropharynx not only serve to protect the airway but also cause reflex increases in MSNA, RVR, MAP, and HR. An augmented sympathoexcitatory response during intubation and laryngoscopy may contribute to perioperative cardiovascular morbidity and mortality.

Renal vasoconstriction is augmented during exercise in patients with peripheral arterial disease.

Peripheral arterial disease (PAD) patients have augmented blood pressure increases during exercise, heightening their cardiovascular risk. However, it is unknown whether patients have exaggerated renal vasoconstriction during exercise and if oxidative stress contributes to this response. Eleven PAD patients and 10 controls (CON) performed 4-min mild, rhythmic, plantar flexion exercise of increasing intensity (0.5-2 kg) with each leg (most and least affected in PAD). Eight patients also exercised with their most affected leg during ascorbic acid (AA) infusion. Renal blood flow velocity (RBFV; Doppler ultrasound), mean arterial blood pressure (MAP; Finometer), and heart rate (HR; electrocardiogram [ECG]) were measured. Renal vascular resistance (RVR), an index of renal vasoconstriction, was calculated as MAP/RBFV. Baseline RVR and MAP were similar while HR was higher in PAD than CON (2.08 ± 0.23 vs. 1.87 ± 0.20 au, 94 ± 3 vs. 93 ± 3 mmHg, and 72 ± 3 vs. 59 ± 3 bpm [P < 0.05] for PAD and CON, respectively). PAD had greater RVR increases during exercise than CON, specifically during the first minute (PAD most: 26 ± 5% and PAD least: 17 ± 5% vs. CON: 3 ± 3%; P < 0.05). AA did not alter baseline RVR, MAP, or HR. AA attenuated the augmented RVR increase in PAD during the first minute of exercise (PAD most: 33 ± 4% vs. PAD most with AA: 21 ± 4%; P < 0.05). In conclusion, these findings suggest that PAD patients have augmented renal vasoconstriction during exercise, with oxidative stress contributing to this response.