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Aims:\ud \ud Heart failure with reduced ejection fraction (HFrEF) induces skeletal muscle mitochondrial abnormalities that contribute to exercise limitation; however, specific mitochondrial therapeutic targets remain poorly established. This study quantified the relationship and contribution of distinct mitochondrial respiratory states to prognostic whole‐body measures of exercise limitation in HFrEF.\ud \ud \ud \ud Methods and results:\ud \ud Male patients with HFrEF (n = 22) were prospectively enrolled and underwent ramp‐incremental cycle ergometry cardiopulmonary exercise testing to determine exercise variables including peak pulmonary oxygen uptake (V̇O2peak), lactate threshold (V̇O2LT), the ventilatory equivalent for carbon dioxide (V̇E/V̇CO2LT), peak circulatory power (CircPpeak), and peak oxygen pulse. Pectoralis major was biopsied for assessment of in situ mitochondrial respiration. All mitochondrial states including complexes I, II, and IV and electron transport system (ETS) capacity correlated with V̇O2peak (r = 0.40–0.64; P < 0.05), V̇O2LT (r = 0.52–0.72; P < 0.05), and CircPpeak (r = 0.42–0.60; P < 0.05). Multiple regression analysis revealed that combining age, haemoglobin, and left ventricular ejection fraction with ETS capacity could explain 52% of the variability in V̇O2peak and 80% of the variability in V̇O2LT, respectively, with ETS capacity (P = 0.04) and complex I (P = 0.01) the only significant contributors in the model.\ud \ud \ud \ud Conclusions:\ud \ud Mitochondrial respiratory states from skeletal muscle biopsies of patients with HFrEF were independently correlated to established non‐invasive prognostic cycle ergometry cardiopulmonary exercise testing indices including V̇O2peak, V̇O2LT, and CircPpeak. When combined with baseline patient characteristics, over 50% of the variability in V̇O2peak could be explained by the mitochondrial ETS capacity. These data provide optimized mitochondrial targets that may attenuate exercise limitations in HFrEF.

Fatiguing expiratory muscle work in otherwise resting humans elicits an increase in sympathetic motor outflow; whether limb blood flow ([Formula: see text]) and leg vascular resistance (LVR) are affected remains unknown. We found that fatiguing expiratory resistive loaded breathing (ERL) did not affect group mean [Formula: see text] or LVR. However, within-breath oscillations in [Formula: see text] may reflect a sympathetically mediated vasoconstriction that was counteracted by transient increases in [Formula: see text] due to the mechanical effects of high intra-abdominal pressure during ERL.

The mechanism(s) of exercise intolerance at V˙O2max remain poorly understood. In health, standard ramp-incremental (RI) exercise is limited by fatigue-induced reductions in maximum voluntary cycling power. Whether neuromuscular fatigue also limits exercise when the RI rate is slow and RI peak power at intolerance is lower than standard RI exercise, is unknown.In twelve healthy participants, maximal voluntary cycling power was measured during a short (~6 s) isokinetic effort at 80 rpm (Piso) at baseline and, using an instantaneous switch from cadence-independent to isokinetic cycling, immediately at the limit of RI exercise with RI rates of 50, 25, and 10 W·min-1 (RI-50, RI-25, and RI-10). Breath-by-breath pulmonary gas exchange was measured throughout.Baseline Piso was not different among RI rates (analysis of variance; P0.05). Tolerable duration increased with decreasing RI rate (RI-50, 411 ± 58 s vs RI-25, 732 ± 93 s vs RI-10, 1531 ± 288 s; P0.05). At intolerance, V˙O2peak was not different among RI rates (analysis of variance; P0.05), but RI peak power decreased with RI rate (RI-50, 361 ± 48 W vs RI-25, 323 ± 39 W vs RI-10, 275 ± 38 W; P0.05). Piso at intolerance was 346 ± 43 W, 353 ± 45 W, and 392 ± 69 W for RI-50, RI-25, and RI-10, respectively (P0.05 for RI-10 vs RI-50 and RI-25). At intolerance, in RI-50 and RI-25, Piso was not different from RI peak power (P0.05), thus there was no "power reserve." In RI-10, Piso was greater than RI peak power at intolerance (P0.001), that is, there was a "power reserve."In RI-50 and RI-25, the absence of a power reserve suggests the neuromuscular fatigue-induced reduction in Piso coincided with V˙O2max and limited the exercise. In RI-10, the power reserve suggests neuromuscular fatigue was insufficient to limit the exercise, and additional mechanisms contributed to intolerance at V˙O2max.

BACKGROUND: Cardiovascular magnetic resonance (CMR) image acquisition techniques during exercise typically requires either transient cessation of exercise or complex post-processing, potentially compromising clinical utility. We evaluated the feasibility and reproducibility of a navigated image acquisition method for ventricular volumes assessment during continuous physical exercise. METHODS: Ten healthy volunteers underwent supine cycle ergometer (Lode) exercise CMR on two separate occasions using a free-breathing, multi-shot, navigated, balanced steady-state free precession cine pulse sequence. Images were acquired at 3-stages, baseline and during steady-state exercise at 55% and 75% maximal heart rate (HR(max)), based on a prior supine cardiopulmonary exercise test. Intra-and inter-observer variability and inter-scan reproducibility were derived. Clinical feasibility was tested in a separate cohort of patients with severe mitral regurgitation (n=6). RESULTS: End-diastolic volume (EDV) of both LV and RV decreased during exercise at 55% and 75% HR(max), although a reduction in RVEDV index was only observed at 75% HR(max). Ejection fractions (EF) for both ventricles were significantly higher at 75% HR(max) compared to their respective baselines (LVEF 68%±3% vs. 58%±5%, P=0.001; RVEF 66%±4% vs. 58%±7%, P=0.02). Intra-observer and inter-observer reproducibility of LV parameters was excellent at all 3-stages. Although measurements of RVESV were more variable during exercise, the reproducibility of both RVEF and RV cardiac index was excellent (CV

Endothelial cell phenotype and endothelial function are regulated by hemodynamic forces, particularly wall shear stress (WSS). During a single bout of exercise, the specific exercise protocol can affect in-exercise WSS patterns and, consequently, endothelial function. MicroRNAs might provide a biomarker of in-exercise WSS pattern to indicate whether a specific exercise bout will have a positive effect on endothelial function. We evaluated the effect of acute interval (IT) and continuous (CON) in-exercise WSS patterns upon postexercise endothelial function and circulating microRNA (miR)-21 expression. Methods and results: 13 participants performed CON and 3 different IT exercise protocols matched for duration and intensity on separate days. Oxygen uptake, heart rate, and brachial artery blood flow were recorded throughout the exercise. Brachial artery flow-mediated dilation (FMD) was performed pre-exercise and 15 min postexercise. Plasma samples were acquired pre-exercise and 6 h postexercise to determine miR-21 expression. In-exercise shear rate (SR) patterns (a surrogate of WSS) differed according to the CON or IT work-rate profile. In-exercise anterograde SR was greater in CON than IT exercise ( P < 0.05), but retrograde SR was equivalent between exercise protocols ( P > 0.05). Oscillatory shear index was higher during IT versus CON exercise ( P < 0.05). Postexercise FMD increased (pre: 7.08% ± 2.95%, post: 10.54% ± 4.24%, P < 0.05), whereas miR-21 expression was unchanged (pre: 12.0% ± 20.7% cel-miR-39, post: 11.1 ± 19.3% cel-miR-39, P > 0.05) with no effect of exercise protocol ( P > 0.05). Conclusions: CON and IT exercise induced different SR patterns but equivalent improvements in acute endothelial function. The absence of change in miR-21 expression suggests that miR-21 is not a suitable biomarker of exercise-induced SR. NEW & NOTEWORTHY Interval exercise has the potential to negatively impact vascular adaptations because of repeated oscillations in vascular shear. To our knowledge, we are the first to continuously assess exercise-induced shear throughout different acute exercise protocols and examine its relationship with acute endothelial function and a circulating biomarker of shear (miR-21). These experiments provide clear data indicating enhancement of the acute vascular response from differing interval exercise protocols, with the study also providing detailed vascular and shear responses for future reference.

The asymptote of the hyperbolic power-duration relationship, critical power (CP), demarcates sustainable from non-sustainable exercise. CP is a salient parameter within the theoretical framework determining exercise tolerance. However, measuring CP is time consuming – typically 4 constant-power exercise tests to intolerance, or a 3-min all-out sprint is required.To determine whether 30 s of maximal isokinetic cycling, immediately following the limit of tolerance, approximates CP.Fifteen participants (7 women, 8 men, 23±5 yr, 71±12 kg, V̇O2peak 4.39±1.04 L·min−1; 61±9 mL·kg·min−1) completed 4 constant supra-CP exercise tests to intolerance. Each test was followed immediately by a 30 s maximal isokinetic effort at 80 rpm. Mean isokinetic power was compared to the known CP.Mean±SD CP was 159±47 W (CI95 133, 185 W). Maximal isokinetic power immediately following intolerance was greater (p0.07). However, this closest estimation, following the longest duration constant-power test, resulted in 21 W of mean bias and wide limits of agreement (±84 W).Isokinetic power measured immediately following intolerance consistently overestimated critical power. Thus, an adjunct of 30 s maximal isokinetic cycling immediately following the limit of tolerance does not approximate critical power.

Purpose; We aimed to measure 1) the dynamics of locomotor fatigue during constant supra-critical power cycling, and 2) the magnitude of any reserve in locomotor power at intolerance to constant and ramp-incremental cycling in recreationally-active volunteers.\ud \ud \ud \ud Methods; Fifteen participants (7 women and 8 men, 22±3 yr, 3.34±0.67 L.min-1 V[Combining Dot Above]O2peak) completed ramp-incremental and very-heavy constant power (205±46 W) exercise to the limit of tolerance. Immediately following intolerance, the ergometer was switched into the isokinetic mode and participants completed a short (~5 s) maximal isokinetic effort at 70 rpm. The time course of locomotor fatigue during constant supra-critical power exercise was characterized with these short maximal isokinetic sprints at 30, 60, 120, 180 s and at the limit of tolerance. Each bout was terminated following the isokinetic sprint.\ud \ud \ud \ud Results; Constant power exercise duration was 312±37 s. Isokinetic power production at 30, 60, 120, 180 s and the limit of tolerance (at 312±37 s) was 609±165, 503±195, 443±157, 449±133, and 337±94 W, respectively. Of the total decline in isokinetic power, ~36% occurred within the first minute of exercise and significant (p

Venous thromboembolism (VTE) is a known risk with some forms of hormonal contraception, and should be considered by health care providers when counselling patients about their contraceptive options. Various other risk factors exist for VTE, including family history of VTE and a personal history of VTE or thrombophilia. This article will summarize various known risk factors for VTE, as well as what is known about the VTE risk imparted by the use of different contraceptives.

Background CMR image acquisition techniques during exercise typically require transient cessation of exercise or complex post-processing analysis, potentially compromising its clinical utility. We evaluated the feasibility and reproducibility of a novel image acquisition Method for the assessment of biventricular physiological response during continuous physical exercise. Methods 10 healthy volunteers (80% men, age 25±2 years) underwent supine cycle ergometer (Lode) induced exercise CMR (Philips 1.5T Ingenia) on two separate occasions using a free-breathing, multi-shot, navigated, balanced steady-state free precession cine pulse sequence. Individual target heart rates (HR) for both moderate and high-intensity exercise were prescribed based on a prior supine cardiopulmonary exercise test (CPET). The scan protocol included a short axis ventricular volume stack and a 40 phase 4-chamber cine. Images were acquired at baseline, and during steady-state moderate and high-intensity exercise (55% and 75% maximal heart rate, respectively). Data were analysed by two independent observers and left and right ventricular (LV, RV) indices calculated. Results End-diastolic volume (EDV) of both LV and RV decreased during moderate and high-intensity exercise, although the reduction in indexed RVEDV (RVEDVi) was only observed during maximal exercise (table 1). Similarly, a significant reduction in end-systolic volumes (ESV) was seen in both ventricles, whilst the reduction in indexed LVESV (LVESVi) was only evident during high-intensity exercise. Ejection fraction (EF) increased from rest to moderate and high intensity exercise in the LV (LVEF 58±5% vs 61±8% vs 68±3%, respectively; p Intra-observer reproducibility of LV parameters was excellent at all three stages (Table 2), although measurements of RVESV were more variable. The reproducibility of both RVEF and RV cardiac indexes was however excellent. Similarly, inter-observer reproducibility of LV volumes, EF and cardiac indexes was excellent. Inter-scan LV and RV ejection fraction were highly reproducible at all 3 stages; RVESVi reproducibility was suboptimal. Conclusion This exercise CMR protocol using a novel free-breathing, multi-shot, navigated imaging Method allows simultaneous assessment of the left and right ventricular response to continuous exercise. Intra and inter-observer reproducibility were excellent. Clinical feasibility and utility now needs to be established.

Resume Objectif Fournir des lignes directrices aux fournisseurs de soins quant a l'utilisation de modes de contraception pour la prevention de la grossesse et quant a la promotion d'une sexualite saine. Issues Orientation des praticiens canadiens en ce qui concerne l'efficacite globale, le mecanisme d'action, les indications, les contre-indications, les avantages n'etant pas lies a la contraception, les effets indesirables, les risques et le protocole de mise en œuvre des modes de contraception abordes; planification familiale dans le contexte de la sante sexuelle et du bien-etre general; methodes de counseling en matiere de contraception; et accessibilite et disponibilite des modes de contraception abordes au Canada. Resultats La litterature publiee a ete recuperee par l'intermediaire de recherches menees dans MEDLINE et The Cochrane Library entre janvier 1994 et janvier 2015 au moyen d'un vocabulaire controle (p. ex. contraception , sexuality , sexual health ) et de mots cles (p. ex. contraception , family planning , hormonal contraception , emergency contraception ) appropries. Les resultats ont ete restreints aux analyses systematiques, aux etudes observationnelles et aux essais comparatifs randomises / essais cliniques comparatifs publies en anglais entre janvier 1994 et janvier 2015. Les recherches ont ete mises a jour de facon reguliere et integrees a la directive clinique jusqu'en juin 2015. La litterature grise (non publiee) a ete identifiee par l'intermediaire de recherches menees dans les sites Web d'organismes s'interessant a l'evaluation des technologies dans le domaine de la sante et d'organismes connexes, dans des collections de directives cliniques, dans des registres d'essais cliniques et aupres de societes de specialite medicale nationales et internationales. Valeurs La qualite des resultats a ete evaluee au moyen des criteres decrits dans le rapport du Groupe d'etude canadien sur les soins de sante preventifs (Tableau).

Objective To provide guidelines for health care providers on the use of contraceptive methods to prevent pregnancy and on the promotion of healthy sexuality. Outcomes Guidance for Canadian practitioners on overall effectiveness, mechanism of action, indications, contraindications, non-contraceptive benefits, side effects and risks, and initiation of cited contraceptive methods; family planning in the context of sexual health and general well-being; contraceptive counselling methods; and access to, and availability of, cited contraceptive methods in Canada. Evidence Published literature was retrieved through searches of Medline and The Cochrane Database from January 1994 to January 2015 using appropriate controlled vocabulary (e.g., contraception, sexuality, sexual health) and key words (e.g., contraception, family planning, hormonal contraception, emergency contraception). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies published in English from January 1994 to January 2015. Searches were updated on a regular basis and incorporated in the guideline to June 2015. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. Values The quality of the evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1).

Objective To provide guidelines for health care providers on the use of contraceptive methods to prevent pregnancy and on the promotion of healthy sexuality. Outcomes Guidance for Canadian practitioners on overall effectiveness, mechanism of action, indications, contraindications, non-contraceptive benefits, side effects and risks, and initiation of cited contraceptive methods; family planning in the context of sexual health and general wellbeing; contraceptive counselling methods; and access to and availability of cited contraceptive methods in Canada. Evidence Published literature was retrieved through searches of Medline and The Cochrane Database from January 1994 to January 2015 using appropriate controlled vocabulary (e.g., contraception, sexuality, sexual health) and key words (e.g., contraception, family planning, hormonal contraception, emergency contraception). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies published in English from January 1994 to January 2015. Searches were updated on a regular basis and incorporated in the guideline to June 2015. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. Values The quality of the evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1).

This study aimed to investigate the effects of a single session of sprint interval training (SIT) and a single extended sprint (ES), matched for total work, on metabolic health biomarkers.Ten overweight/obese men aged 26.9±6.2years participated. Following a pre-trial incremental exercise test and SIT familiarization, each participant undertook three 2-day trials in randomized order. On Day 1 participants either undertook no exercise (CON), four maximal 30-s sprints, with 4.5min recovery between each (SIT), or a single maximal extended sprint (ES) matched with SIT for work done. On Day 2, participants had a fasting blood sample taken, undertook an oral glucose tolerance test to determine insulin sensitivity index (ISI), and had blood pressure measured.Total work done during exercise did not differ between SIT and ES (61.7±2.9 vs. 61.3±2.8kJ; p=0.741). Mean power was higher in SIT than ES (518±21 vs. 306±16W, p0.0005), resulting in a shorter high-intensity exercise duration in SIT (120±0 vs. 198±10s, p0.0005). ISI was 44.6% higher following ES than CON (9.4±2.1 vs. 6.5±1.3; p=0.022), but did not differ significantly between SIT and CON (6.6±0.9 vs. 6.5±1.3; p=0.208). However, on the day following exercise fat oxidation in the fasted state was increased by 63% and 38%, compared to CON, in SIT and ES, respectively (p0.05 for both), with a concomitant reduction in carbohydrate oxidation (p0.05).A single ES, which may represent a more time-efficient alternative to SIT, can increase insulin sensitivity and increase fat oxidation in overweight overweight/obese sedentary men.

Athletes who train regularly can develop left ventricular (LV) hypertrophy, which can be difficult to differentiate from hypertrophic cardiomyopathy (HCM), the leading cause of sudden cardiac death in young athletes. Current guidelines advise that patients with HCM should avoid competitive sport

Background Athletic training leads to remodelling of both left and right ventricles with increased myocardial mass and cavity dilatation. Whether changes in cardiac strain parameters occur in response to training is less well established. In this study we investigated the relationship in trained athletes between cardiovascular magnetic resonance (CMR) derived strain parameters of cardiac function and fitness. Methods: Thirty five endurance athletes and 35 age and sex matched controls underwent CMR at 3.0 T including cine imaging in multiple planes and tissue tagging by spatial modulation of magnetization (SPAMM). CMR data were analysed quantitatively reporting circumferential strain and torsion from tagged images and left and right ventricular longitudinal strain from feature tracking of cine images. Athletes performed a maximal ramp-incremental exercise test to determine the lactate threshold (LT) and maximal oxygen uptake (V̇O2max). Results: LV circumferential strain at all levels, LV twist and torsion, LV late diastolic longitudinal strain rate, RV peak longitudinal strain and RV early and late diastolic longitudinal strain rate were all lower in athletes than controls. On multivariable linear regression only LV torsion (beta = −0.37, P = 0.03) had a significant association with LT. Only RV longitudinal late diastolic strain rate (beta = −0.35, P = 0.03) had a significant association with V̇O2max. Conclusions: This cohort of endurance athletes had lower LV circumferential strain, LV torsion and biventricular diastolic strain rates than controls. Increased LT, which is a major determinant of performance in endurance athletes, was associated with decreased LV torsion. Further work is needed to understand the mechanisms by which this occurs.

Objective— Circulating progenitor cells (CPC) have emerged as potential mediators of vascular repair. In experimental models, CPC mobilization is critically dependent on nitric oxide (NO). South Asian ethnicity is associated with reduced CPC. We assessed CPC mobilization in response to exercise in Asian men and examined the role of NO in CPC mobilization per se. Methods and Results— In 15 healthy, white European men and 15 matched South Asian men, CPC mobilization was assessed during moderate-intensity exercise. Brachial artery flow-mediated vasodilatation was used to assess NO bioavailability. To determine the role of NO in CPC mobilization, identical exercise studies were performed during intravenous separate infusions of saline, the NO synthase inhibitor l -NMMA, and norepinephrine. Flow-mediated vasodilatation (5.8%±0.4% vs 7.9%±0.5%; P =0.002) and CPC mobilization (CD34 + /KDR + 53.2% vs 85.4%; P =0.001; CD133 + /CD34 + /KDR + 48.4% vs 73.9%; P =0.05; and CD34 + /CD45 − 49.3% vs 78.4; P =0.006) was blunted in the South Asian group. CPC mobilization correlated with flow-mediated vasodilatation and l -NMMA significantly reduced exercise-induced CPC mobilization (CD34 + /KDR + −3.3% vs 68.4%; CD133 + /CD34 + /KDR + 0.7% vs 71.4%; and CD34 + /CD45 − −30.5% vs 77.8%; all P Conclusion— In humans, NO is critical for CPC mobilization in response to exercise. Reduced NO bioavailability may contribute to imbalance between vascular damage and repair mechanisms in South Asian men.

Augmented breaths promote respiratory instability and have been implicated in triggering periods of sleep-disordered breathing. Since respiratory instability is well known to be exacerbated by hypocapnia, we asked whether one of the destabilizing effects of hypocapnia might be related to an increased prevalence of augmented breaths. With this question in mind, we first sought to determine whether hypoxia-induced augmented breaths are more prevalent when hypocapnia is also present. To do this, we studied the breath-by-breath ventilatory responses of a group of freely behaving adult rats in a variety of different respiratory background conditions. We found that the prevalence of augmented breaths was dramatically increased during hypocapnic-hypoxia compared with room air conditions. When hypocapnia was prevented during exposure to hypoxia by adding 5% CO2 to the inspired air, the rate of occurrence of augmented breaths was no greater than that observed in room air. The addition of CO2 alone to room air had no effect on the prevalence of augmented breaths. We conclude that in spontaneously breathing rats, hypoxia promotes the generation of augmented breaths, but only in poikilocapnic conditions, where hypocapnia develops. Our results, therefore, reveal a means by which CO2 exerts a stabilizing influence on breathing, which may be of particular relevance during sleep in conditions commonly associated with respiratory instability.

The World Health Organization and a number of national bodies recommend adults undertake at least 150 min/week of moderate intensity physical activity, or 75 min/week of vigorous intensity physical activity. However, a large proportion of the population do not achieve these targets. Lack of time is often cited as a primary barrier,1 and many researchers have suggested that high-intensity interval training (HIIT), with interval durations from 10 s to 4 min and intensities ranging from 85% maximal heart rate (HRmax) to ‘all out’ efforts, may provide a time-efficient solution to improve public health.2 A wealth of evidence has demonstrated that HIIT can elicit a range of health benefits such as improved cardiorespiratory fitness, insulin sensitivity and vascular function, with these benefits being of at least a similar magnitude to those seen with standard moderate intensity physical activity interventions.3 ,4 These data are clear and convincing. However, they largely emanate from …

A recent bout of high-intensity exercise can alter the balance of aerobic and anaerobic energy provision during subsequent exercise above the lactate threshold (θL). However, it remains uncertain whether such “priming” influences the tolerable duration of subsequent exercise through changes in the parameters of aerobic function [e.g., θL, maximum oxygen uptake (V̇o2max)] and/or the hyperbolic power-duration (P-t) relationship [critical power (CP) and the curvature constant (W′)]. We therefore studied six men performing cycle ergometry to the limit of tolerance; gas exchange was measured breath-by-breath and arterialized capillary blood [lactate] was measured at designated intervals. On different days, each subject completed 1) an incremental test (15 W/min) for estimation of θL and measurement of the functional gain (ΔV̇o2/ΔWR) and V̇o2peak and 2) four constant-load tests at different work rates (WR) for estimation of CP, W′, and V̇o2max. All tests were subsequently repeated with a preceding 6-min supra-CP priming bout and an intervening 2-min 20-W recovery. The hyperbolicity of the P-t relationship was retained postpriming, with no significant difference in CP (241 ± 39 vs. 242 ± 36 W, post- vs. prepriming), V̇o2max (3.97 ± 0.34 vs. 3.93 ± 0.38 l/min), ΔV̇o2/ΔWR (10.7 ± 0.3 vs. 11.1 ± 0.4 ml·min−1·W−1), or the fundamental V̇o2 time constant (25.6 ± 3.5 vs. 28.3 ± 5.4 s). W′ (10.61 ± 2.07 vs. 16.13 ± 2.33 kJ) and the tolerable duration of supra-CP exercise (−33 ± 11%) were each significantly reduced, despite a less-prominent V̇o2 slow component. These results suggest that, following supra-CP priming, there is either a reduced depletable energy resource or a residual fatigue-metabolite level that leads to the tolerable limit before this resource is fully depleted.

To provide guidelines for health care providers on the use of contraceptive methods to prevent pregnancy and on the promotion of healthy sexuality.Guidance for Canadian practitioners on overall effectiveness, mechanism of action, indications, contraindications, non-contraceptive benefits, side effects and risks, and initiation of cited contraceptive methods; family planning in the context of sexual health and general well-being; contraceptive counselling methods; and access to, and availability of, cited contraceptive methods in Canada.Published literature was retrieved through searches of Medline and The Cochrane Database from January 1994 to January 2015 using appropriate controlled vocabulary (e.g., contraception, sexuality, sexual health) and key words (e.g., contraception, family planning, hormonal contraception, emergency contraception). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies published in English from January 1994 to January 2015. Searches were updated on a regular basis and incorporated in the guideline to June 2015. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies.The quality of the evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table). Chapter 1: Contraception in Canada Summary Statements 1. Canadian women spend a significant portion of their lives at risk of an unintended pregnancy. (II-2) 2. Effective contraceptive methods are underutilized in Canada, particularly among vulnerable populations. (II-2) 3. Long-acting reversible contraceptive methods, including contraceptive implants and intrauterine contraception (copper-releasing and levonorgestrel-releasing devices/systems), are the most effective reversible contraceptive methods and have the highest continuation rates. (II-1) 4. Canada currently does not collect reliable data to determine the use of contraceptive methods, abortion rates, and the prevalence of unintended pregnancy among reproductive-age women. (II-2) 5. A universal subsidy for contraceptive methods as provided by many of Canada's peer nations and a few Canadian provinces may produce health system cost-savings. (II-2) 6. Health Canada approval processes for contraceptives have been less efficient than those of other drug approval agencies and Health Canada processes for other classes of pharmaceuticals. (II-2) 7. It is feasible and safe for contraceptives and family planning services to be provided by appropriately trained allied health professionals such as midwives, registered nurses, nurse practitioners, and pharmacists. (II-2) Recommendations 1. Contraceptive counselling should include a discussion of typical use failure rates and the importance of using the contraceptive method consistently and correctly in order to avoid pregnancy. (II-2A) 2. Women seeking contraception should be counselled on the wide range of effective methods of contraception available, including long-acting reversible contraceptive methods (LARCs). LARCs are the most effective methods of reversible contraception, have high continuation rates, and should be considered when presenting contraceptive options to any woman of reproductive age. (II-2A) 3. Family planning counselling should include counselling on the decline of fertility associated with increasing female age. (III-A) 4. Health policy supporting a universal contraception subsidy and strategies to promote the uptake of highly effective methods as cost-saving measures that improve health and health equity should be considered by Canadian health decision makers. (III-B) 5. Canadian health jurisdictions should consider expanding the scope of practice of other trained professionals such as nurses, nurse practitioners, midwives, and pharmacists and promoting task-sharing in family planning. (II-2B) 6. The Canadian Community Health Survey should include adequate reproductive health indicators in order for health care providers and policy makers to make appropriate decisions regarding reproductive health policies and services in Canada. (III-B) 7. Health Canada processes and policies should be reviewed to ensure a wide range of modern contraceptive methods are available to Canadian women. (III-B) Chapter 2: Contraceptive Care and Access Summary Statements 8. Although there are many contraceptive options in Canada, only a narrow range of contraceptive methods are commonly used by those of reproductive age. (II-3) 9. Condom use decreases with longer relationship tenure and when the sexual partner is considered to be the main partner, likely due to a lower perceived risk of sexually transmitted infection in that relationship. Condom use may also decrease markedly as an unintended consequence when an effective non-barrier method, such as hormonal contraception or intrauterine contraception, is initiated. (II-3) 10. Family planning counselling provides a natural segue into screening for concerns about sexual function or intimate partner violence. (III) 11. Well-informed and well-motivated individuals who have developed skills to practise safer sex behaviours are more likely to use contraceptive and safer sex methods effectively and consistently. (II-2) Recommendations 8. Comprehensive family planning services, including abortion services, should be accessible to all Canadians regardless of geographic location. These services should be confidential, non-judgemental, and respectful of individuals' privacy and cultural contexts. (III-A) 9. A contraceptive visit should include history taking, screening for contraindications, dispensing or prescribing a method of contraception, and exploring contraceptive choice and adherence in the broader context of the individual's sexual behaviour, reproductive health risk, social circumstances, and relevant belief systems. (III-B) 10. Health care providers should provide practical information on the wide range of contraceptive options and their potential non-contraceptive benefits and assist women and their partners in determining the best user-method fit. (III-B) 11. Health care providers should assist women and men in developing the skills necessary to negotiate the use of contraception and the correct and consistent use of a chosen method. (III-B) 12. Contraceptive care should include discussion and management of the risk of sexually transmitted infection, including appropriate recommendations for condom use and dual protection, STI screening, post-exposure prophylaxis, and Hepatitis B and human papillomavirus vaccination. (III-B) 13. Health care providers should emphasize the use of condoms not only for protection against sexually transmitted infection, but also as a back-up method when adherence to a hormonal contraceptive may be suboptimal. (I-A) 14. Health care providers should be aware of current media controversies in reproductive health and acquire relevant evidence-based information that can be briefly and directly communicated to their patients. (III-B) 15. Referral resources for intimate partner violence, sexually transmitted infections, sexual dysfunction, induced abortion services, and child protection services should be available to help clinicians provide contraceptive care in the broader context of women's health. (III-B) Chapter 3: Emergency Contraception Summary Statements 12. The copper intrauterine device is the most effective method of emergency contraception. (II-2) 13. A copper intrauterine device can be used for emergency contraception up to 7 days after unprotected intercourse provided that pregnancy has been ruled out and there are no other contraindications to its insertion. (II-2) 14. Levonorgestrel emergency contraception is effective up to 5 days (120 hours) after intercourse; its effectiveness decreases as the time between unprotected intercourse and ingestion increases. (II-2) 15. Ulipristal acetate for emergency contraception is more effective than levonorgestrel emergency contraception up to 5 days after unprotected intercourse. This difference in effectiveness is more pronounced as the time from unprotected intercourse increases, especially after 72 hours. (I) 16. Hormonal emergency contraception (levonorgestrel emergency contraception and ulipristal acetate for emergency contraception) is not effective if taken on the day of ovulation or after ovulation. (II-2) 17. Levonorgestrel emergency contraception may be less effective in women with a body mass index25 kg/m2 and ulipristal acetate for emergency contraception may be less effective in women with a body mass index35 kg/m2. However, hormonal emergency contraception may still retain some effectiveness regardless of a woman's body weight or body mass index. (II-2) 18. Hormonal emergency contraception is associated with higher failure rates when women continue to have subsequent unprotected intercourse. (II-2) 19. Hormonal contraception can be initiated the day of or the day following the use of levonorgestrel emergency contraception, with back-up contraception used for the first 7 days. (III) 20. Hormonal contraception can be initiated 5 days following the use of ulipristal acetate for emergency contraception, with back-up contraception used for the first 14 days. (III) Recommendations 16. All emergency contraception should be initiated as soon as possible after unprotected intercourse. (II-2A) 17. Women should be informed that the copper intrauterine device (IUD) is the most effective method of emergency contraception and can be used by any woman with no contraindications to IUD use. (II-3A) 18.

To provide guidelines for health care providers on the use of contraceptive methods to prevent pregnancy and on the promotion of healthy sexuality.Guidance for Canadian practitioners on overall effectiveness, mechanism of action, indications, contraindications, non-contraceptive benefits, side effects and risks, and initiation of cited contraceptive methods; family planning in the context of sexual health and general well-being; contraceptive counselling methods; and access to, and availability of, cited contraceptive methods in Canada.Published literature was retrieved through searches of Medline and The Cochrane Database from January 1994 to January 2015 using appropriate controlled vocabulary (e.g., contraception, sexuality, sexual health) and key words (e.g., contraception, family planning, hormonal contraception, emergency contraception). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies published in English from January 1994 to January 2015. Searches were updated on a regular basis and incorporated in the guideline to June 2015. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies.The quality of the evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table). Chapter 1: Contraception in Canada Summary Statements 1. Canadian women spend a significant portion of their lives at risk of an unintended pregnancy. (II-2) 2. Effective contraceptive methods are underutilized in Canada, particularly among vulnerable populations. (II-2) 3. Long-acting reversible contraceptive methods, including contraceptive implants and intrauterine contraception (copper-releasing and levonorgestrel-releasing devices/systems), are the most effective reversible contraceptive methods and have the highest continuation rates. (II-1) 4. Canada currently does not collect reliable data to determine the use of contraceptive methods, abortion rates, and the prevalence of unintended pregnancy among reproductive-age women. (II-2) 5. A universal subsidy for contraceptive methods as provided by many of Canada's peer nations and a few Canadian provinces may produce health system cost-savings. (II-2) 6. Health Canada approval processes for contraceptives have been less efficient than those of other drug approval agencies and Health Canada processes for other classes of pharmaceuticals. (II-2) 7. It is feasible and safe for contraceptives and family planning services to be provided by appropriately trained allied health professionals such as midwives, registered nurses, nurse practitioners, and pharmacists. (II-2) Recommendations 1. Contraceptive counselling should include a discussion of typical use failure rates and the importance of using the contraceptive method consistently and correctly in order to avoid pregnancy. (II-2A) 2. Women seeking contraception should be counselled on the wide range of effective methods of contraception available, including long-acting reversible contraceptive methods (LARCs). LARCs are the most effective methods of reversible contraception, have high continuation rates, and should be considered when presenting contraceptive options to any woman of reproductive age. (II-2A) 3. Family planning counselling should include counselling on the decline of fertility associated with increasing female age. (III-A) 4. Health policy supporting a universal contraception subsidy and strategies to promote the uptake of highly effective methods as cost-saving measures that improve health and health equity should be considered by Canadian health decision makers. (III-B) 5. Canadian health jurisdictions should consider expanding the scope of practice of other trained professionals such as nurses, nurse practitioners, midwives, and pharmacists and promoting task-sharing in family planning. (II-2B) 6. The Canadian Community Health Survey should include adequate reproductive health indicators in order for health care providers and policy makers to make appropriate decisions regarding reproductive health policies and services in Canada. (III-B) 7. Health Canada processes and policies should be reviewed to ensure a wide range of modern contraceptive methods are available to Canadian women. (III-B) Chapter 2: Contraceptive Care and Access Summary Statements 8. Although there are many contraceptive options in Canada, only a narrow range of contraceptive methods are commonly used by those of reproductive age. (II-3) 9. Condom use decreases with longer relationship tenure and when the sexual partner is considered to be the main partner, likely due to a lower perceived risk of sexually transmitted infection in that relationship. Condom use may also decrease markedly as an unintended consequence when an effective non-barrier method, such as hormonal contraception or intrauterine contraception, is initiated. (II-3) 10. Family planning counselling provides a natural segue into screening for concerns about sexual function or intimate partner violence. (III) 11. Well-informed and well-motivated individuals who have developed skills to practise safer sex behaviours are more likely to use contraceptive and safer sex methods effectively and consistently. (II-2) Recommendations 8. Comprehensive family planning services, including abortion services, should be accessible to all Canadians regardless of geographic location. These services should be confidential, non-judgemental, and respectful of individuals' privacy and cultural contexts. (III-A) 9. A contraceptive visit should include history taking, screening for contraindications, dispensing or prescribing a method of contraception, and exploring contraceptive choice and adherence in the broader context of the individual's sexual behaviour, reproductive health risk, social circumstances, and relevant belief systems. (III-B) 10. Health care providers should provide practical information on the wide range of contraceptive options and their potential non-contraceptive benefits and assist women and their partners in determining the best user-method fit. (III-B) 11. Health care providers should assist women and men in developing the skills necessary to negotiate the use of contraception and the correct and consistent use of a chosen method. (III-B) 12. Contraceptive care should include discussion and management of the risk of sexually transmitted infection, including appropriate recommendations for condom use and dual protection, STI screening, post-exposure prophylaxis, and Hepatitis B and human papillomavirus vaccination. (III-B) 13. Health care providers should emphasize the use of condoms not only for protection against sexually transmitted infection, but also as a back-up method when adherence to a hormonal contraceptive may be suboptimal. (I-A) 14. Health care providers should be aware of current media controversies in reproductive health and acquire relevant evidence-based information that can be briefly and directly communicated to their patients. (III-B) 15. Referral resources for intimate partner violence, sexually transmitted infections, sexual dysfunction, induced abortion services, and child protection services should be available to help clinicians provide contraceptive care in the broader context of women's health. (III-B) Chapter 3: Emergency Contraception Summary Statements 12. The copper intrauterine device is the most effective method of emergency contraception. (II-2) 13. A copper intrauterine device can be used for emergency contraception up to 7 days after unprotected intercourse provided that pregnancy has been ruled out and there are no other contraindications to its insertion. (II-2) 14. Levonorgestrel emergency contraception is effective up to 5 days (120 hours) after intercourse; its effectiveness decreases as the time between unprotected intercourse and ingestion increases. (II-2) 15. Ulipristal acetate for emergency contraception is more effective than levonorgestrel emergency contraception up to 5 days after unprotected intercourse. This difference in effectiveness is more pronounced as the time from unprotected intercourse increases, especially after 72 hours. (I) 16. Hormonal emergency contraception (levonorgestrel emergency contraception and ulipristal acetate for emergency contraception) is not effective if taken on the day of ovulation or after ovulation. (II-2) 17. Levonorgestrel emergency contraception may be less effective in women with a body mass index25 kg/m2 and ulipristal acetate for emergency contraception may be less effective in women with a body mass index35 kg/m2. However, hormonal emergency contraception may still retain some effectiveness regardless of a woman's body weight or body mass index. (II-2) 18. Hormonal emergency contraception is associated with higher failure rates when women continue to have subsequent unprotected intercourse. (II-2) 19. Hormonal contraception can be initiated the day of or the day following the use of levonorgestrel emergency contraception, with back-up contraception used for the first 7 days. (III) 20. Hormonal contraception can be initiated 5 days following the use of ulipristal acetate for emergency contraception, with back-up contraception used for the first 14 days. (III) Recommendations 16. All emergency contraception should be initiated as soon as possible after unprotected intercourse. (II-2A) 17. Women should be informed that the copper intrauterine device (IUD) is the most effective method of emergency contraception and can be used by any woman with no contraindications to IUD use. (II-3A) 18.

Introduction Uterine perforation is an uncommon yet well-known complication of copper intrauterine devices and the levonorgestrel intrauterine system (IUS). While initial extrauterine placement at the time of insertion is felt to be the cause of perforation in most cases, some hypothesize that delayed transmural migration and subsequent perforation can occur with slightly malpositioned or even properly placed devices. Case A 46-year-old female had a 52-mg levonorgestrel IUS inserted for menstrual management and contraception. We arranged a follow-up ultrasound as the uterus was enlarged on bimanual examination and the cavity sounded to 11 cm. This ultrasound was completed 6 days after insertion and reported the IUS to be in the “upper uterine cavity”. Over time, transmural displacement and perforation of the horizontal arms of the device occurred. Computed tomography scans performed over 2 years for nongynecologic indications document this gradual migration. A retrospective review of initial ultrasound images showed no evidence of uterine defect, embedment or perforation but the cavity length did appear to be less than 11 cm. Conclusions While initial extrauterine placement at the time of insertion is the most common mechanism of perforation, delayed transmural migration is another mechanism that can occur.

The tolerable duration of continuous high-intensity exercise is determined by the hyperbolic Speed-tolerable duration (S-tLIM) relationship. However, application of the S-tLIM relationship to normalize the intensity of High-Intensity Interval Training (HIIT) has yet to be considered, with this the aim of present study. Subjects completed a ramp-incremental test, and series of 4 constant-speed tests to determine the S-tLIM relationship. A sub-group of subjects (n = 8) then repeated 4 min bouts of exercise at the speeds predicted to induce intolerance at 4 min (WR4), 6 min (WR6) and 8 min (WR8), interspersed with bouts of 4 min recovery, to the point of exercise intolerance (fixed WR HIIT) on different days, with the aim of establishing the work rate that could be sustained for 960 s (i.e. 4×4 min). A sub-group of subjects (n = 6) also completed 4 bouts of exercise interspersed with 4 min recovery, with each bout continued to the point of exercise intolerance (maximal HIIT) to determine the appropriate protocol for maximizing the amount of high-intensity work that can be completed during 4×4 min HIIT. For fixed WR HIIT tLIM of HIIT sessions was 399±81 s for WR4, 892±181 s for WR6 and 1517±346 s for WR8, with total exercise durations all significantly different from each other (P0.050). However, there was significantly less high-intensity work completed during bouts 2 (153.5±40. 9 m), 3 (136.9±38.9 m), and 4 (136.7±39.3 m), compared with bout 1 (264.9±58.7 m; P>0.050). These data establish that WR6 provides the appropriate work rate to normalize the intensity of HIIT between subjects. Maximal HIIT provides a protocol which allows the relative contribution of the work rate profile to physiological adaptations to be considered during alternative intensity-matched HIIT protocols.

Background Circulating progenitor cells (CPCs) have emerged as potential mediators of vascular repair. In experimental models CPC mobilisation is critically dependent on nitric oxide (NO). South Asian ethnicity is associated with reduced CPCs; we assessed CPC mobilisation in response to exercise in Asian men and examined the role of NO in CPC mobilisation per se. Methods In 15 healthy white European men and 15 matched South Asian men, CPC mobilisation (relative % increase from pre- to post-exercise) was assessed during moderate intensity exercise using flow cytometry. Three subsets of CPCs were studied (CD34+/KDR+, CD133+/CD34+/KDR+ or CD34+/CD45−) and were expressed as a % of circulating lymphocytes). Brachial artery flow mediated vasodilatation (FMD) was used to assess NO bioavailability. To determine the role of NO in CPC mobilisation, identical exercise studies were performed during intravenous separate infusions of saline, the NO synthase inhibitor L-NMMA, and norepinephrine. Results Groups were well matched for age, blood pressure, indices of obesity and circulating lipids; however the South Asian group exhibited insulin resistance as measured by the HOMA-IR score (1.3±0.2 vs 0.8±0.1; p=0.047). FMD (5.8±0.4% vs 7.9±0.5%; p=0.002) and basal CPC numbers (CD34+/KDR+: 0.030% vs 0.046%, p=0.05; CD133+/CD34+/KDR+: 0.008% vs 0.014%, p=0.026; CD34+/CD45−: 0.011% vs 0.018%, p=0.044) were lower in the South Asian group. CPC mobilisation (CD34+/KDR+ 53.2% vs 85.4%, p=0.001; CD133+/CD34+/KDR+ 48.4% vs 73.9%, p=0.05; CD34+/CD45− 49.3% vs 78.4, p=0.006) was blunted in the South Asian group. CPC mobilisation correlated with FMD and L-NMMA significantly reduced exercise induced CPC mobilisation (CD34+/KDR+ −3.3% vs 68.4%; CD133+/CD34+/KDR+ 0.7% vs 71.4%; CD34+/CD45− −30.5% vs 77.8%; all p Conclusions In humans NO is critical for CPC mobilisation in response to exercise. Reduced NO bioavailability may contribute to imbalance between vascular damage and repair mechanisms in South Asian men. This project was supported by the British Heart Foundation.