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It is unclear whether impaired cardiac and/or vascular function contribute to exercise intolerance in patients with type 2 diabetes. PURPOSE: Magnetic resonance imaging (MRI) was used to determine whether reductions in cardiac output and/or femoral arterial blood flow contribute to reduced aerobic capacity in patients with type 2 diabetes. METHODS: Cardiac and femoral arterial blood flow MRI scans were performed at rest and during low-intensity leg exercise in eight patients with type 2 diabetes and 11 healthy individuals. Maximal aerobic capacity (V O2max) and maximal oxygen pulse were also determined in all participants. RESULTS: V O2max was 20% lower and maximal oxygen pulse was 16% lower in patients with type 2 diabetes (P < 0.05), whereas maximal heart rate was the same between groups. Low-intensity exercise induced a 20% increase in heart rate and cardiac output as well as a 60-70% increase in femoral blood flow in both groups (P < 0.05). Femoral arterial blood flow indexed to thigh lean mass was reduced during exercise in patients with type 2 diabetes compared with healthy individuals. Stroke volume indexed to fat-free mass was lower in patients with type 2 diabetes, but greater heart rate allowed cardiac output to be maintained during submaximal exercise. CONCLUSIONS: These findings suggest that impaired femoral arterial blood flow, an indirect marker of muscle perfusion, affects low-intensity exercise performance in patients with type 2 diabetes. However, because of lower exercising stroke volume, we propose that femoral arterial blood flow and, possibly, cardiac output, limit V O2max in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

The article presents a comment on Shelhamer's proposal of using a network theory to assess and promote resilience in astronauts traveling to the planet Mars, in which reasons human spaceflights is not the best setting to apply network theory are discussed.

Intermittent hypoxia (IH) is commonly associated with pathological conditions, particularly obstructive sleep apnoea. However, IH is also increasingly used to enhance health and performance and is emerging as a potent non-pharmacological intervention against numerous diseases. Whether IH is detrimental or beneficial for health is largely determined by the intensity, duration, number and frequency of the hypoxic exposures and by the specific responses they engender. Adaptive responses to hypoxia protect from future hypoxic or ischaemic insults, improve cellular resilience and functions, and boost mental and physical performance. The cellular and systemic mechanisms producing these benefits are highly complex, and the failure of different components can shift long-term adaptation to maladaptation and the development of pathologies. Rather than discussing in detail the well-characterized individual responses and adaptations to IH, we here aim to summarize and integrate hypoxia-activated mechanisms into a holistic picture of the body's adaptive responses to hypoxia and specifically IH, and demonstrate how these mechanisms might be mobilized for their health benefits while minimizing the risks of hypoxia exposure., (© 2023 The Authors. The Journal of Physiology © 2023 The Physiological Society.)

Calisthenics is a form of bodyweight exercise that involves dynamic and rhythmic exercises. The physiological responses during and after calisthenics remain unclear. This study examined whether a bout of full-body calisthenics, a form of circuit resistance exercise that involves bodyweight movements, yields greater excess post-exercise oxygen consumption (EPOC) than steady-state exercise (SSE) at matched oxygen consumption. Twenty-two young adults (age = 22.1 ± 2.4 years; four females) participated in two separate, oxygen consumption ( V ˙ O 2 ) matched exercise sessions: full-body calisthenics (nine body weight exercises, 15 reps × 4 sets) and SSE (running on a treadmill at 60-90% of V ˙ O 2 max). Energy expenditure, substrate utilization, and EPOC were measured during exercise and 60 min of recovery. SSE showed higher peak V ˙ O 2 and heart rate during exercise than those during calisthenics. However, the post-exercise V ˙ O 2 and energy expenditure above baseline level during the first 10 min of recovery were significantly higher with calisthenics than with SSE (0-5 min: 1.7 ± 0.5 vs. 1.0 ± 0.6; 6-10 min: 0.5 ± 0.4 vs. 0.1 ± 0.2 kcal/min; 31-60 min recovery: -0.1 ± 0.3 vs. -0.2 ± 0.2; all p  < .05). During calisthenics, participants utilized a significantly higher proportion of energy from carbohydrates (85 vs. 73%; p  < .01) but after exercise, they used a greater proportion of fat as the energy source (71 vs. 50%; p  < .01) compared to SSE. Full-body calisthenics, a circuit-style bodyweight exercise, may be more effective than V ˙ O 2 matched SSE in triggering greater EPOC and fat metabolism. Further efforts are warranted to demonstrate whether different amounts of skeletal muscle mass groups indeed lead to varying EPOC responses and energy use.

Background: Shoulder osteoarthritis can cause significant pain and disability. It is thought that the wider principles of osteoarthritis management can be applied in the management of people with shoulder osteoarthritis, but most prior research has been conducted with people experiencing osteoarthritis of the hip and knee. There is a paucity of evidence to guide the non-surgical management of shoulder osteoarthritis and limited understanding of current physiotherapy practice., Objective: We aimed to investigate the current treatment recommendations by physiotherapists in the UK for people with shoulder OA., Methods: An online survey using a clinical vignette was designed and distributed to UK registered physiotherapists with experience of managing people with shoulder osteoarthritis, via social media and professional networks. Descriptive statistics were used to analyse demographic and multiple-choice questions, and free text responses were summarised narratively., Results: 114 respondents accessed the survey with 110 valid responses; 105 (95%) respondents would offer face-to-face consultations, with 89 (81%) respondents expecting to offer 2-4 appointments. 108 (98%) respondents would offer advice/education; 79 (72%) would offer weight management; 82 (75%) prescribed exercises to improve movement; and 101 (92%) offered exercises to increase strength. If a person lived with obesity or had a treatment preference, the majority of respondents would change their recommendations., Conclusion: This is the first survey of NHS physiotherapy practice for people with shoulder osteoarthritis. The responses largely align with NICE guidelines; despite this alignment, it is not known whether such guideline-based care is acceptable to people with shoulder osteoarthritis or clinically effective., (© 2024 The Author(s). Musculoskeletal Care published by John Wiley & Sons Ltd.)

Squatting, a traditional resistance exercise classified as strength training, relies on anaerobic pathways, but its aerobic aspects remain unclear. We examined heart rate and oxygen demand during squats, exploring variations across different strength statuses. It fills gaps in understanding the cardiorespiratory effects of squatting, especially during multiple sets. Twenty-two young healthy resistance trained men (age: 28 ± 4 years) participated. Maximal oxygen consumption (V̇O 2 max) and 1 repetition maximum (RM) of squat were measured. Participants performed 5 sets of squat exercises at 65% of 1RM for 10 repetitions with 3-min rest intervals. Heart rate and pulmonary gas exchange were measured during the squat exercise. Participants were divided into high strength (HS; upper 50%) and low strength (LS; lower 50%) groups based on a median split of their 1 RM squat values (normalized to their body weight). During 5 sets of squat exercise, oxygen consumption (V̇O 2 ) increased up to 47.8 ± 8.9 ml/kg/min, corresponding to 100.6% of predetermined V̇O 2 max. The HS group achieved a greater highest point of V̇O 2 in relation to V̇O 2 max than the LS group (108.0 vs. 93.7%). During the exercise intervals, V̇O 2 exceeded V̇CO 2 , while during the rest intervals, V̇CO 2 surpassed V̇O 2 . Our findings suggest that the oxygen demand during squatting is notably substantial, which may vary according to the training status., (© 2024. The Author(s).)

Aging is associated with vascular endothelial dysfunction observed through a progressive loss of flow-mediated dilation caused partly by a decreased nitric oxide bioavailability. Intermittent hypoxia, consisting of alternating short bouts of breathing hypoxic and normoxic air, was reported to either maintain or improve vascular function in young adults. The aim of this study was to determine the impact of age on the vascular response to intermittent hypoxia. Twelve young adults and 11 older adults visited the laboratory on two occasions. Plasma nitrate concentrations and brachial artery flow-mediated dilation were assessed before and after exposure to either intermittent hypoxia or a sham protocol. Intermittent hypoxia consisted of eight 4-min hypoxic cycles at a targeted oxygen saturation of 80% interspersed with breathing room air to resaturation, and the sham protocol consisted of eight 4-min normoxic cycles interspersed with breathing room air. Vascular responses were assessed during intermittent hypoxia and the sham protocol. Intermittent hypoxia elicited a brachial artery vasodilation but did not change brachial artery shear rate in both young and older adults. Plasma nitrate concentrations were not significantly affected by intermittent hypoxia compared with the sham protocol in both groups. Brachial artery flow-mediated dilation was not acutely affected by intermittent hypoxia or the sham protocol in either young or older adults. In conclusion, the brachial artery vasodilatory response to intermittent hypoxia was not influenced by age. Intermittent hypoxia increased brachial artery diameter but did not acutely affect endothelium-dependent vasodilation in young or older adults. NEW & NOTEWORTHY The objective of this study was to determine the impact of age on the vascular response to intermittent hypoxia. Eight 4-min bouts of hypoxia at a targeted oxygen saturation of 80% induced a brachial artery vasodilation in both young and older adults, indicating that age does not influence the vasodilatory response to intermittent hypoxia. Intermittent hypoxia did not acutely affect brachial artery flow-mediated dilation in young or older adults.

Aims: Patients with type 2 diabetes have a 20% lower total blood volume than age- and weight-matched healthy adults, suggesting a reduced capacity to transport oxygen in this population. Intermittent hypoxia, consisting of alternating short bouts of breathing hypoxic and normoxic air, increases erythropoietin levels, the hormone regulating red blood cell production, in young and older adults. The objective of this study was to determine the effect of a single session of intermittent hypoxia on erythropoietin levels and hemoglobin mass, the absolute mass of hemoglobin contained in red blood cells, in patients with type 2 diabetes., Methods: Ten patients with type 2 diabetes were exposed to an intermittent hypoxia protocol consisting of eight 4-min cycles at a targeted oxygen saturation of 80% interspersed with normoxic cycles to resaturation. Erythropoietin and hemoglobin mass responses to intermittent hypoxia in patients with type 2 diabetes were compared to previously published data from an identical intermittent hypoxia protocol performed in age-matched older adults., Results: Intermittent hypoxia increased erythropoietin levels in older adults but did not induce any change in erythropoietin levels in patients with type 2 diabetes (3.2 ± 2.2 vs. 0.2 ± 2.7 mU/ml, p = 0.01). Hemoglobin mass indexed to body weight was 21% lower in patients with type 2 diabetes than in older adults (8.1 ± 1.7 vs. 10.2 ± 2.1 g/kg, p < 0.01)., Conclusions: These findings suggest an impaired erythropoietin response to decreased oxygen levels in patients with type 2 diabetes, which may contribute to the reduced oxygen transport capacity observed in this population., (© 2024. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Background: Clinical guidelines recommend treatment by a physiotherapist for people with shoulder pain due to rotator cuff disorder. Despite this recommendation, research evidence supporting the effectiveness of treatment by a physiotherapist is uncertain. While developing a randomised controlled trial to test the effectiveness of treatment by a physiotherapist for people with shoulder pain due to rotator cuff disorders, we first aimed to understand current practice as a basis for defining usual care., Methods: An online survey was developed based on a clinical vignette used in a previous survey exploring physiotherapy practice for people with shoulder pain due to rotator cuff disorder. UK-based physiotherapists were invited to complete the survey via X and email across professional networks., Results: One Hundred Seventy complete responses were received. 167 (98%) respondents would offer advice/education to patients with shoulder rotator cuff disorders; 146 (86%) would use isotonic exercise (including concentric/eccentric strengthening); 20 (12%) would offer a corticosteroid injection; 7 (4%) would use joint mobilisation. 168/169 (99%) would offer in-person assessment; 115 (68%) expect to deliver treatment over three to four sessions. Fifty percent agreed there is uncertainty about the effectiveness of physiotherapy treatment for patients with shoulder rotator cuff disorders. Seventy six percent agreed that patients with this condition can recover without physiotherapy intervention., Conclusions: Exercise and advice remain the most common treatments offered by physiotherapists for people with shoulder pain due to rotator cuff disorder. Corticosteroid injections are infrequently considered. Uncertainty about the effectiveness of treatment by a physiotherapist for shoulder pain due to rotator cuff disorder is evident., (© 2024 The Authors. Musculoskeletal Care published by John Wiley & Sons Ltd.)

Background: Once a decision to undergo rotator cuff repair surgery is made, patients are placed on the waiting list. It can take weeks or months to receive surgery. There has been a call to move from waiting lists to 'preparation' lists to better prepare patients for surgery and to ensure it remains an appropriate treatment option for them., Objective: To evaluate the feasibility, as measured by recruitment rates, treatment fidelity and follow-up rates, of a future multi-centre randomised controlled trial to compare the clinical and cost-effectiveness of undertaking a physiotherapist-led exercise programme while waiting for surgery versus usual care (waiting-list control)., Design: Two-arm, multi-centre pilot randomised controlled trial with feasibility objectives in six NHS hospitals in England., Method: Adults (n = 76) awaiting rotator cuff repair surgery were recruited and randomly allocated to a programme of physiotherapist-led exercise (n = 38) or usual care control (n = 38)., Results: Of 302 eligible patients, 76 (25%) were randomised. Of 38 participants randomised to physiotherapist-led exercise, 28 (74%) received the exercise programme as intended. 51/76 (67%) Shoulder Pain and Disability Index questionnaires were returned at 6-months. Of 76 participants, 32 had not received surgery after 6-months (42%). Of those 32, 20 were allocated to physiotherapist-led exercise; 12 to usual care control., Conclusions: A future multi-centre randomised controlled trial is feasible but would require planning for variable recruitment rates between sites, measures to improve treatment fidelity and opportunity for surgical exit, and optimisation of follow-up. A fully powered, randomised controlled trial is now needed to robustly inform clinical decision-making., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Eight 4-min cycles of intermittent hypoxia represent the shortest hypoxic exposure to increase erythropoietin (EPO) levels in young adults. The impact of aging on the EPO response to a hypoxic stimulus remains equivocal. Thus, the objective of this study was to determine the effect of the same intermittent hypoxia protocol on EPO levels in older adults. Twenty-two participants (12 women, age: 53 ± 7 yr) were randomly assigned to an intermittent hypoxia group (IH, n = 11) or an intermittent normoxia group (IN, n = 11). Intermittent hypoxia consisted of eight 4-min cycles at a targeted oxygen saturation of 80% interspersed with normoxic cycles to resaturation. Air was made hypoxic by titrating nitrogen into a breathing circuit. Intermittent normoxia consisted of the same protocol, but nitrogen was not added to the breathing circuit. EPO levels were measured before and 4.5 h after the beginning of each protocol. Intermittent hypoxia lowered oxygen saturation to 82 ± 3%, which corresponded to a fraction of inspired oxygen of 10.9 ± 1.0%. There was a greater increase in EPO levels following intermittent hypoxia than intermittent normoxia (IH: 3.2 ± 2.2 vs. IN: 0.7 ± 0.8 mU/mL, P < 0.01). A single session of eight 4-min cycles of hypoxia increased EPO levels, the glycoprotein stimulating red blood cell production, in older adults. Exposure to intermittent hypoxia has therefore the potential to increase oxygen-carrying capacity in a population with reduced red blood cell volume. NEW & NOTEWORTHY We previously identified the shortest intermittent hypoxia protocol necessary to increase erythropoietin levels in young adults. The objective of this study was to determine whether the same intermittent hypoxia protocol increases erythropoietin levels in older adults. Eight 4-min bouts of hypoxia, representing a hypoxic duration of 32 min at a targeted oxygen saturation of 80%, increased erythropoietin levels in older adults, suggesting that exposure to intermittent hypoxia has the potential to increase oxygen-carrying capacity in an aging population.

Sudden blood flow restoration to an ischemic vessel paradoxically damages endothelial cells. Ischemic preconditioning, caused by repeated bouts of brief ischemia using local or remote cuff inflation before reperfusion, attenuates endothelial dysfunction following an ischemia-reperfusion injury in young adults but does not consistently protect endothelial function in older adults prone to ischemic events. Intermittent exposure to systemic hypoxemia, induced via brief bouts of breathing low levels of oxygen, attenuates endothelial dysfunction following an ischemia-reperfusion injury in young adults. The aim of this study was to determine whether systemic hypoxic preconditioning protects against ischemia-reperfusion injury in older adults. Twelve adults (five women, 57 ± 9 yr) participated in this randomized crossover trial. Endothelium-dependent vasodilation was assessed by brachial artery flow-mediated dilation using a semiautomated diagnostic ultrasound system before and after a 20-min blood flow occlusion that was preceded by either intermittent hypoxia, consisting of three 4-min hypoxic cycles at an oxygen saturation of 80% interspersed with 4-min room air cycles, or intermittent normoxia, consisting of three 4-min normoxic cycles separated by 4-min room air cycles. When preceded by intermittent normoxia, ischemia-reperfusion injury reduced flow-mediated dilation by 4.1 ± 2.6% (6.5 ± 1.7 to 2.4 ± 1.7%). In contrast, flow-mediated dilation was reduced by 2.0 ± 1.5% when ischemia-reperfusion injury was preceded by intermittent hypoxia (5.6 ± 1.7 to 3.6 ± 2.3%). In conclusion, hypoxic preconditioning significantly attenuated the reduction in brachial artery flow-mediated dilation induced by an ischemia-reperfusion injury in older adults at greater risk for ischemic events.

We tested the hypotheses that spontaneous baroreflex control of integrated muscle sympathetic nerve activity (MSNA) burst occurrence and action potential (AP) subpopulations would be blunted in older compared with young adults and that sympathetic transduction will be blunted in older adults relative to young adults. Integrated muscle sympathetic nerve activity (MSNA) and the underlying sympathetic APs were obtained using microneurography and a continuous wavelet analysis approach, respectively, during 5 min of supine rest in 13 older (45-75 yr, 6 females) and 14 young (21-30 yr, 7 females) adults. Baroreflex threshold relationships were quantified as the slope of the linear regression between MSNA burst occurrence (%) and diastolic blood pressure (mmHg), or AP cluster firing probability (%) and diastolic blood pressure (mmHg). Integrated MSNA baroreflex threshold gain was greater in older compared with young adults (older: -5.7 ± 2.6%/mmHg vs. young: -2.7 ± 1.4%/mmHg, P < 0.001). Similarly, the baroreflex threshold gain of AP clusters was modified by aging (group-by-cluster effect: P < 0.001) such that older adults demonstrated greater baroreflex threshold gains of medium-sized AP clusters (e.g., Cluster 4 , older: -8.2 ± 3.2%/mmHg vs. young: -3.6 ± 1.9%/mmHg, P = 0.003) but not for the smallest-sized ( Cluster 1 , older: -1.6 ± 1.9%/mmHg vs. young: -1.0 ± 1.7%/mmHg, P > 0.999) and largest-sized ( Cluster 10 , older: -0.5 ± 0.5%/mmHg vs. young: -0.2 ± 0.1%/mmHg, P = 0.819) AP clusters compared with young adults. In contrast, the peak change in mean arterial pressure (MAP) following a spontaneous MSNA burst (i.e., sympathetic transduction) was impaired with aging (older: -0.7 ± 0.3 mmHg vs. young: 1.8 ± 1.2 mmHg, P < 0.001). We conclude that aging is associated with elevated baroreflex control over high-probability AP content of sympathetic bursts that may compensate for impaired sympathetic neurovascular transduction. NEW & NOTEWORTHY The present study demonstrates for the first time that the spontaneous baroreflex threshold gains of integrated muscle sympathetic nerve activity burst occurrence and medium-sized action potential clusters are greater in older compared with young adults. Since sympathetic transduction was blunted in older compared with young adults, we interpret the data to indicate that the central arc of the baroreflex is enhanced in older adults to compensate for impairments in the peripheral arc.

Introduction: High-intensity interval training is an effective tool to improve cardiovascular fitness and maximal anaerobic power. Different methods of high-intensity interval training have been studied but the effects of repeated maximal effort cycling with very short exercise time (i.e., 4 s) and short recovery time (15-30 s) might suit individuals with limited time to exercise., Purpose: We examined the effects of training at near maximal anaerobic power during cycling (PC) on maximal anaerobic power, peak oxygen consumption (V˙O2peak), and total blood volume in 11 young healthy individuals (age: 21.3 ± 0.5 yr) (six men, five women)., Methods: Participants trained three times a week for 8 wk performing a PC program consisting of 30 bouts of 4 s at an all-out intensity (i.e., 2 min of exercise per session). The cardiovascular stress progressively increased over the weeks by decreasing the recovery time between sprints (30-24 s to 15 s), and thus, total session time decreased from 17 to <10 min., Results: Power cycling elicited a 13.2% increase in V˙O2peak (Pre: 2.86 ± 0.18 L·min-1, Post: 3.24 ± 0.21 L·min-1; P = 0.003) and a 7.6% increase in total blood volume (Pre: 5139 ± 199 mL, Post: 5529 ± 342 mL; P < 0.05). Concurrently, maximal anaerobic power increased by 17.2% (Pre: 860 ± 53 W, Post: 1,009 ± 71 W; P < 0.001)., Conclusions: A PC training program employing 30 bouts of 4 s duration for a total of 2 min of exercise, resulting in a total session time of less than 10 min in the last weeks, is effective for improving total blood volume, V˙O2peak and maximal anaerobic power in young healthy individuals over 8 wk. These observations require reconsideration of the minimal amount of exercise needed to significantly increase both maximal aerobic and anaerobic power., (Copyright © 2021 by the American College of Sports Medicine.)

Prior data suggest that, relative to the early follicular phase, women in the late follicular phase are protected against endothelial ischemia-reperfusion (I/R) injury when estradiol concentrations are highest. In addition, endothelial I/R injury is consistently observed in men with naturally low endogenous estradiol concentrations that are similar to those of women in the early follicular phase. Therefore, the purpose of this study was to determine whether the vasodeleterious effect of I/R injury differs between women in the early follicular phase of the menstrual cycle and age-matched men. We tested the hypothesis that I/R injury would attenuate endothelium-dependent vasodilation to the same extent in women and age-matched men with similar circulating estradiol concentrations. Endothelium-dependent vasodilation was assessed via brachial artery flow-mediated dilation (duplex ultrasound) in young healthy men ( n = 22) and women ( n = 12) before (pre-I/R) and immediately after (post-I/R) I/R injury, which was induced via 20 min of arm circulatory arrest followed by 20-min reperfusion. Serum estradiol concentrations did not differ between sexes (men 115.0 ± 33.9 pg·mL -1 vs. women 90.5 ± 40.8 pg·mL -1 ; P = 0.2). The magnitude by which I/R injury attenuated endothelium-dependent vasodilation did not differ between men (pre-I/R 5.4 ± 2.4% vs. post-I/R 3.0 ± 2.7%) and women (pre-I/R 6.1 ± 2.8% vs. post-I/R 3.7 ± 2.7%; P = 0.9). Our data demonstrate that I/R injury similarly reduces endothelial function in women in the early follicular phase of the menstrual cycle and age-matched men with similar estradiol concentrations.

The current study evaluated the hypothesis that 6 mo of exercise-based cardiac rehabilitation (CR) would improve sympathetic neural recruitment in patients with ischemic heart disease (IHD). Microneurography was used to evaluate action potential (AP) discharge patterns within bursts of muscle sympathetic nerve activity (MSNA), in 11 patients with IHD (1 female; 61 ± 9 yr) pre (pre-CR) and post (post-CR) 6 mo of aerobic and resistance training-based CR. Measures were made at baseline and during maximal voluntary end-inspiratory (EI-APN) and end-expiratory apneas (EE-APN). Data were analyzed during 1 min of baseline and the second half of apneas. At baseline, overall sympathetic activity was less post-CR (all P < 0.01). During EI-APN, AP recruitment was not observed pre-CR (all P > 0.05), but increases in both within-burst AP firing frequency (Δpre-CR: 2 ± 3 AP spikes/burst vs. Δpost-CR: 4 ± 3 AP spikes/burst; P = 0.02) and AP cluster recruitment (Δpre-CR: -1 ± 2 vs. Δpost-CR: 2 ± 2; P < 0.01) were observed in post-CR tests. In contrast, during EE-APN, AP firing frequency was not different post-CR compared with pre-CR tests (Δpre-CR: 269 ± 202 spikes/min vs. Δpost-CR: 232 ± 225 spikes/min; P = 0.54), and CR did not modify the recruitment of new AP clusters (Δpre-CR: -1 ± 3 vs. Δpost-CR: 0 ± 1; P = 0.39), or within-burst firing frequency (Δpre-CR: 3 ± 3 AP spikes/burst vs. Δpost-CR: 2 ± 2 AP spikes/burst; P = 0.21). These data indicate that CR improves some of the sympathetic nervous system dysregulation associated with cardiovascular disease, primarily via a reduction in resting sympathetic activation. However, the benefits of CR on sympathetic neural recruitment may depend upon the magnitude of initial impairment.

Objectives: The SPeEDy study (Surgery vs. physiotherapist-led exercise for traumatic tears of the rotator cuff) is a two-arm, parallel group, pilot and feasibility randomised controlled trial aiming to evaluate the feasibility of a future main trial. In this paper, the development process and the resultant physiotherapist-led exercise programme used in the SPeEDy study is described., Methods: Thirteen physiotherapists and three patients met to discuss and develop the key principles that should underpin the exercise programme., Results: Taking in to account the current research evidence and incorporating expert clinical and patient opinion, the group developed an individualised, structured and progressive physiotherapist-led exercise programme based on the principle of self dosing. Exercise prescription within the programme is based on establishing the current functional capacity of the patient in relation to the most challenging shoulder movements and is supported over approximately six contact sessions across a 12-week period., Conclusion: The SPeEDy study aims to recruit 76 participants across eight hospitals and will provide high quality evidence about the feasibility of a future main randomised controlled trial in a clinical area where there is a lack of evidence from randomised controlled trials to support clinical decision-making. ClinicalTrials.gov (NCT04027205) - Registered on 19 July 2019. Available via https://clinicaltrials.gov/ct2/show/NCT04027205., (Copyright © 2020 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.)

Few minutes of hypoxic exposure stabilizes hypoxia-inducible factor-1α, resulting in erythropoietin (EPO) gene transcription and production. The objective of this study was to identify the shortest intermittent hypoxia protocol necessary to increase serum EPO levels in healthy individuals. In a first experiment, spontaneous EPO changes under normoxia (NORM) and the EPO response to five 4-min cycles of intermittent hypoxia (IH5) were determined in six individuals. In a second experiment, the EPO response to eight 4-min cycles of intermittent hypoxia (IH8) and 120 min of continuous hypoxia (CONT) was determined in six individuals. All hypoxic protocols were performed at a targeted arterial oxygen saturation of 80%. There was no significant change in EPO levels in response to normoxia or in response to five cycles of intermittent hypoxia (NORM: 9.5 ± 1.8 to 10.5 ± 1.8, IH5: 11.4 ± 2.3 to 13.4 ± 2.1 mU/mL, main effect for time P = 0.35). There was an increase in EPO levels in response to eight cycles of intermittent hypoxia and 120 min of continuous hypoxia, with peak levels observed 4.5 h after the onset of hypoxia (IH8: 11.2 ± 2.0 to 16.7 ± 2.2, CONT: 11.1 ± 3.8 to 19.4 ± 3.8 mU/mL, main effect for time P < 0.01). Eight cycles of intermittent hypoxia increased EPO levels to a similar extent as 120 min of continuous hypoxia (main effect for condition P = 0.36). Eight 4-min cycles of intermittent hypoxia represent the shortest protocol to increase serum EPO levels in healthy individuals. NEW & NOTEWORTHY The objective of this study was to identify the shortest intermittent hypoxia protocol necessary to increase serum erythropoietin levels in healthy individuals. Eight 4-min bouts of intermittent hypoxia, representing a hypoxic duration of 32 min at an arterial oxygen saturation of 80%, significantly increased erythropoietin levels in healthy individuals. These findings suggest that a short session of intermittent hypoxia has the potential to increase oxygen-carrying capacity.

Ischemic preconditioning attenuates the reduction in brachial artery endothelial function following an ischemia-reperfusion injury. Brief bouts of systemic hypoxemia could similarly mitigate the blunted vasodilatory response induced by an ischemia-reperfusion injury. The aim of the present study was to determine whether an acute bout of intermittent hypoxia protects against an ischemia-reperfusion injury in young healthy individuals. Brachial artery endothelial function was assessed by flow-mediated dilation in 16 young healthy individuals before and after a 20-min upper arm blood flow occlusion to induce ischemia-reperfusion injury. Blood flow occlusion was preceded by either intermittent hypoxia or intermittent normoxia. Intermittent hypoxia consisted of three 4-min hypoxic cycles at an arterial oxygen saturation of 87 ± 3% separated by 4-min normoxic cycles. Intermittent hypoxia resulted in a lower arterial oxygen saturation than intermittent normoxia (hypoxia: 87 ± 3% vs. normoxia: 99 ± 1%, P < 0.01), which was equivalent to a lower fraction of inspired oxygen (hypoxia: 0.123 ± 0.013 and normoxia: 0.210 ± 0.003, P < 0.01). When preceded by intermittent normoxia, blood flow occlusion resulted in a blunted flow-mediated dilation. In contrast, the reduction in flow-mediated dilation following blood flow occlusion was attenuated by prior exposure to intermittent hypoxia (hypoxia: 6.4 ± 1.9 to 4.4 ± 2.3% and normoxia: 7.1 ± 2.5 to 4.0 ± 2.4%, time × condition interaction P = 0.048). Exposure to intermittent hypoxia did not affect mean arterial pressure (hypoxia: 92 ± 9 mmHg and normoxia: 89 ± 8 mmHg, P = 0.19) or cardiac output (hypoxia: 5.8 ± 1.1 L·min -1 and normoxia: 5.3 ± 1.1 L·min -1 , P = 0.29). In conclusion, hypoxic preconditioning attenuates the reduction in flow-mediated dilation induced by blood flow occlusion in young healthy individuals. Intermittent hypoxia represents a potential strategy to mitigate the effect of ischemia-reperfusion injury associated with ischemic events. NEW & NOTEWORTHY Ischemia-reperfusion injury induced by restoration of blood flow following occlusion impairs flow-mediated dilation, a marker of endothelium-dependent vasodilation. In young healthy adults, exposure to intermittent hypoxia, consisting of alternating short bouts of breathing hypoxic and normoxic air, before an ischemia-reperfusion injury significantly attenuated the reduction in flow-mediated dilation. Thus, hypoxic preconditioning represents a potential strategy to mitigate the effect of ischemia-reperfusion injury associated with ischemic events.

Intermittent hypoxia, defined as alternating bouts of breathing hypoxic and normoxic air, has the potential to improve oxygen-carrying capacity through an erythropoietin-mediated increase in hemoglobin mass. The purpose of this study was to determine the effect of a single session of intermittent hypoxia on erythropoietin levels and hemoglobin mass in young healthy individuals. Nineteen participants were randomly assigned to an intermittent hypoxia group (Hyp, n = 10) or an intermittent normoxia group (Norm, n = 9). Intermittent hypoxia consisted of five 4-min hypoxic cycles at a targeted arterial oxygen saturation of 90% interspersed with 4-min normoxic cycles. Erythropoietin levels were measured before and two hours following completion of the protocol. Hemoglobin mass was assessed the day before and seven days after exposure to intermittent hypoxia or normoxia. As expected, the intermittent hypoxia group had a lower arterial oxygen saturation than the intermittent normoxia group during the intervention (Hyp: 89 ± 1 vs. Norm: 99 ± 1%, p < 0.01). Erythropoietin levels did not significantly increase following exposure to intermittent hypoxia (Hyp: 8.2 ± 4.5 to 9.0 ± 4.8, Norm: 8.9 ± 1.7 to 11.1 ± 2.1 mU·mL -1 , p = 0.15). Hemoglobin mass did not change following exposure to intermittent hypoxia. This single session of intermittent hypoxia was not sufficient to elicit a significant rise in erythropoietin levels or hemoglobin mass in young healthy individuals.

Transfer RNA-derived fragments (tRFs) exist in all branches of life. They are involved in RNA degradation, regulation of gene expression, ribosome biogenesis. In archaebacteria, kinetoplastid, yeast, and human cells, they were also shown to regulate translation. In Arabidopsis, the tRFs population fluctuates under developmental or environmental conditions but their functions are yet poorly understood. Here, we show that populations of long (30-35 nt) or short (19-25 nt) tRFs produced from Arabidopsis tRNAs can inhibit in vitro translation of a reporter gene. Analysing a series of oligoribonucleotides mimicking natural tRFs, we demonstrate that only a limited set of tRFs possess the ability to affect protein synthesis. Out of a dozen of tRFs, only two deriving from tRNA Ala (AGC) and tRNA Asn (GUU) strongly attenuate translation in vitro . Contrary to human tRF(Ala), the 4 Gs present at the 5' extremity of Arabidopsis tRF(Ala) are not implicated in this inhibition while the G 18 and G 19 residues are essential. Protein synthesis inhibition by tRFs does not require complementarity with the translated mRNA but, having the capability to be associated with polyribosomes, tRFs likely act as general modulation factors of the translation process in plants.

Discovery of therapeutic avenues to provide the benefits of exercise to patients with enforced sedentary behavior patterns would be of transformative importance to health care. Work in model organisms has demonstrated that benefits of exercise can be provided to stationary animals by daily intermittent stimulation of adrenergic signaling. Here, we examine as a proof of principle whether exposure of human participants to virtual reality (VR) simulation of exercise can alter sympathovagal balance in stationary humans. In this study, 24 participants performed 15 minutes of cycling exercise at standardized resistance, then repeated the exercise with a virtual reality helmet that provided an immersive environment. On a separate day, they each controlled a virtual environment for 15 minutes to simulate exercise without actual cycling exercise. Response to each treatment was assessed by measuring heart rate (HR), norepinephrine, and heart rate variability, and each participant's response to virtual exercise was compared internally to his/her response to the actual cycling. We found that neither post-exercise norepinephrine nor post-exercise HR was significantly increased by VR simulation. However, heart rate variability measured during virtual exercise was comparable to actual cycling in participants that engaged in moderate exercise, but not in those that engaged in high-intensity exercise. These findings suggest that virtual exercise has the potential to mimic some effects of moderate exercise. Further work will be needed to examine the longitudinal effects of chronic exposure to VR-simulated exercise., Competing Interests: The authors have declared that no competing interests exist.

Purpose: The effect of menstrual blood loss on oxygen-carrying capacity remains equivocal. The purpose of this study was to determine the effect of menstrual blood loss on hemoglobin mass in young, healthy women., Methods: Twenty-one women (age, 23 ± 6 yr; height, 168 ± 7 cm; weight, 66.1 ± 12.6 kg) with regular menstrual cycles, either using (n = 10) or not using oral contraceptives, participated in the study. Hemoglobin mass was assessed using carbon monoxide rebreathing on three separate occasions over the course of one menstrual cycle., Results: Visits for women not using oral contraceptives were performed in the early follicular phase (3 ± 1 d after the onset of menses), late follicular phase (1 ± 1 d after the surge of luteinizing hormone in urine), and luteal phase (9 ± 1 d after the late follicular visit). Visits for women using oral contraceptives were performed in the early follicular phase (3 ± 1 d after the onset of menses), late follicular phase (15 ± 3 d after the onset of menses), and luteal phase (9 ± 2 d after the late follicular visit). Hemoglobin mass was not affected by menstrual cycle phase (early follicular, 618 ± 61; late follicular, 610 ± 65; luteal, 607 ± 68 g; P = 0.52). Interestingly, when normalized to weight, hemoglobin mass was 12% higher in women using oral contraceptives in comparison to nonusers (10.0 ± 1.2 vs 8.9 ± 1.2 g·kg, P < 0.05)., Conclusion: Menstrual blood loss had no measurable effect on hemoglobin mass in eumenorrheic women. However, oral contraceptive use resulted in a greater oxygen-carrying capacity, potentially leading to a greater maximal oxygen uptake.

Polyethylene glycol transfection of plant protoplasts represents an efficient method to incorporate foreign DNA and study transient gene expression. Here, we describe an optimized protocol to deliver small noncoding RNAs into Arabidopsis thaliana protoplasts. An example of application is provided by demonstrating the incorporation of a 20 nt long small noncoding RNA deriving from the 5' extremity of an A. thaliana cytosolic alanine tRNA into freshly isolated protoplasts.

Heart failure (HF) is a complex and multifaceted disease. The disease affects multiple organ systems, including the respiratory system. This review provides three unique examples illustrating how the cardiovascular and respiratory systems interrelate because of the pathology of HF. Specifically, these examples outline the impact of HF pathophysiology on 1 ) respiratory mechanics and the mechanical "cost" of breathing; 2 ) mechanical interactions of the heart and lungs; and on 3 ) abnormalities of pulmonary gas exchange during exercise, and how this may be applied to treatment. The goal of this review is to, therefore, raise the awareness that HF, though primarily a disease of the heart, is accompanied by marked pathology of the respiratory system.

We propose that abnormalities of the pulmonary system contribute significantly to the exertional dyspnea and exercise intolerance observed in patients with chronic heart failure. Interventions designed to address the deleterious pulmonary manifestations of heart failure may, therefore, yield promising improvements in exercise tolerance in this population.

Background Autonomic dysregulation represents a hallmark of coronary artery disease (CAD). Therefore, we investigated the effects of exercise-based cardiac rehabilitation (CR) on autonomic function and neuro-cardiovascular stress reactivity in CAD patients. Methods and Results Twenty-two CAD patients (4 women; 62±8 years) were studied before and following 6 months of aerobic- and resistance-training-based CR. Twenty-two similarly aged, healthy individuals (CTRL; 7 women; 62±11 years) served as controls. We measured blood pressure, muscle sympathetic nerve activity, heart rate, heart rate variability (linear and nonlinear), and cardiovagal (sequence method) and sympathetic (linear relationship between burst incidence and diastolic blood pressure) baroreflex sensitivity during supine rest. Furthermore, neuro-cardiovascular reactivity during short-duration static handgrip (20s) at 40% maximal effort was evaluated. Six months of CR lowered resting blood pressure (P<0.05), as well as muscle sympathetic nerve activity burst frequency (48±8 to 39±11 bursts/min; P<0.001) and burst incidence (81±7 to 66±17 bursts/100 heartbeats; P<0.001), to levels that matched CTRL and improved sympathetic baroreflex sensitivity in CAD patients (P<0.01). Heart rate variability (all P>0.05) and cardiovagal baroreflex sensitivity (P=0.11) were unchanged following CR, yet values were not different pre-CR from CTRL (all P>0.05). Furthermore, before CR, CAD patients displayed greater blood pressure and muscle sympathetic nerve activity reactivity to static handgrip versus CTRL (all P<0.05); yet, responses were reduced following CR (all P<0.05) to levels observed in CTRL. Conclusions Six months of exercise-based CR was associated with marked improvement in baseline autonomic function and neuro-cardiovascular stress reactivity in CAD patients, which may play a role in the reduced cardiac risk and improved survival observed in patients following exercise training.