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Blood volume (BV) is an important clinical parameter and is usually reported per kg of body mass (BM). When fat mass is elevated, this underestimates BV/BM. One aim was to study if differences in BV/BM related to sex, age, and fitness would decrease if normalized to lean body mass (LBM). The analysis included 263 women and 319 men (age: 10-93 years, body mass index: 14-41 kg/m 2 ) and 107 athletes who underwent assessment of BV and hemoglobin mass (Hb mass ), body composition, and cardiorespiratory fitness. BV/BM was 25% lower (70.3 ± 11.3 and 80.3 ± 10.8 mL/kg BM ) in women than men, respectively, whereas BV/LBM was 6% higher in women (110.9 ± 12.5 and 105.3 ± 11.2 mL/kg LBM ). Hb mass /BM was 34% lower (8.9 ± 1.4 and 11.5 ± 11.2 g/kg BM ) in women than in men, respectively, but only 6% lower (14.0 ± 1.5 and 14.9 ± 1.5 g/kg LBM )/LBM. Age did not affect BV. Athlete's BV/BM was 17.2% higher than non-athletes, but decreased to only 2.5% when normalized to LBM. Of the variables analyzed, LBM was the strongest predictor for BV (R 2  = .72, p < .001) and Hb mass (R 2  = .81, p < .001). These data may only be valid for BV/Hb mass when assessed by CO re-breathing. Hb mass /LBM could be considered a valuable clinical matrix in medical care aiming to normalize blood homeostasis., (© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Aims: To objectively study cardiorespiratory fitness (CRF) and physical activity (PA) and to evaluate limiting factors of exercise intolerance associated with poor CRF after severe pre-eclampsia., Methods: In this single-centre, cross-sectional study, CRF was measured as peak oxygen uptake (VO 2peak ) during a cardiopulmonary exercise test (CPET) on a treadmill in women 7 years after severe pre-eclampsia. Ninety-six patients and 65 controls were eligible to participate. Cardiac output (CO) was measured by impedance cardiography. PA was measured using accelerometers., Results: In 62 patients and 35 controls (mean age 40 ± 3 years), the VO 2peak (in mL·kg-1·min-1) values were 31.4 ± 7.2 and 39.1 ± 5.4, respectively (p<0.01). In the patients, the COpeak was (9.6 L·min-1), 16% lower compared to controls (p<0.01). Twelve patients (19%) had a cardiac limitation to CPET. Twenty-three (37%) patients and one (3%) control were classed as unfit, with no cardiopulmonary limitations. The patients demonstrated 25% lower PA level (in counts per minute; p<0.01) and 14% more time being sedentary (p<0.01), compared with the controls. Twenty-one patients (34%) compared with four (17%) controls did not meet the World Health Organization's recommendations for PA (p=0.02). Body mass index and PA level accounted for 65% of the variability in VO 2peak ., Conclusion: Significantly lower CRF and PA levels were found in patients on long-term follow-up after severe pre-eclampsia. CPET identified cardiovascular limitations in one third of patients. One third appeared unfit, with adiposity and lower PA levels. These findings highlight the need for clinical follow-up and exercise interventions after severe pre-eclampsia.

Background: Cancer therapy-related cardiotoxicity is a major cause of cardiovascular morbidity in childhood cancer survivors. The aims of this study were to investigate systolic myocardial function and its association to cardiorespiratory fitness in pediatric childhood cancer survivors., Methods: In this sub-study of the international study "Physical Activity and fitness in Childhood Cancer Survivors" (PACCS), echocardiographic measures of left ventricular global longitudinal strain (LV-GLS) and right ventricular longitudinal strain (RV-LS) were measured in 128 childhood cancer survivors aged 9-18 years and in 23 age- and sex-matched controls. Cardiorespiratory fitness was measured as peak oxygen consumption achieved on treadmill and correlated to myocardial function., Results: Mean LV-GLS was reduced in the childhood cancer survivors compared to the controls, -19.7% [95% confidence interval (CI) -20.1% to -19.3%] vs. -21.3% (95% CI: -22.2% to -20.3%) ( p  = 0.004), however, mainly within normal range. Only 13% of the childhood cancer survivors had reduced LV longitudinal strain z -score. Mean RV-LS was similar in the childhood cancer survivors and the controls, -23.2% (95% CI: -23.7% to -22.6%) vs. -23.3% (95% CI: -24.6% to -22.0%) ( p  = 0.8). In the childhood cancer survivors, lower myocardial function was associated with lower peak oxygen consumption [correlation coefficient ( r ) = -0.3 for LV-GLS]. Higher doses of anthracyclines ( r  = 0.5 for LV-GLS and 0.2 for RV-LS) and increasing time after treatment ( r  = 0.3 for LV-GLS and 0.2 for RV-LS) were associated with lower myocardial function., Conclusions: Left ventricular function, but not right ventricular function, was reduced in pediatric childhood cancer survivors compared to controls, and a lower left ventricular myocardial function was associated with lower peak oxygen consumption. Furthermore, higher anthracycline doses and increasing time after treatment were associated with lower myocardial function, implying that long-term follow-up is important in this population at risk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Engan, Diab, Brun, Raastad, Torsvik, Omdal, Ghavidel, Greve, Ruud, Edvardsen and Leirgul.)

Background: Anthracycline-based chemotherapy has been mainstay of adjuvant breast cancer therapy for decades. Although effective, anthracyclines place long-term breast cancer survivors at risk of late effects, such as reduced cardiorespiratory fitness and increased risk of cardiovascular disease. Previous research has shown beneficial effects of exercise training on cardiorespiratory fitness, but the effects of exercise on limiting factors for cardiorespiratory fitness, cardiovascular risk factors, and patient-reported outcomes in long-term survivors are less clear. Whether previous exposure to breast cancer therapy modulates the effects of exercise is also unknown., Objective: The primary aim of the CAUSE (Cardiovascular Survivors Exercise) trial is to examine the effect of aerobic exercise on cardiorespiratory fitness in anthracycline-treated long-term breast cancer survivors. Secondary aims are to examine effects of exercise training on limiting factors for cardiorespiratory fitness, cardiovascular risk factors, and patient-reported outcomes, and to compare baseline values and effects of exercise training between similar-aged women with and those without prior breast cancer. A third aim is to examine the 24-month postintervention effects of aerobic exercise on primary and secondary outcomes., Methods: The CAUSE trial is a 2-armed randomized controlled trial, where 140 long-term breast cancer survivors, 8-12 years post diagnosis, are assigned to a 5-month nonlinear aerobic exercise program with 3 weekly sessions or to standard care. Seventy similar-aged women with no history of cancer will undergo the same exercise program. Cardiorespiratory fitness measured as peak oxygen consumption (VO 2peak ), limiting factors for VO 2peak (eg, cardiac function, pulmonary function, hemoglobin mass, blood volume, and skeletal muscle characteristics), cardiovascular risk factors (eg, hypertension, diabetes, dyslipidemia, obesity, physical activity level, and smoking status), and patient-reported outcomes (eg, body image, fatigue, mental health, and health-related quality of life) will be assessed at baseline, post intervention, and 24 months post intervention., Results: A total of 209 patients were included from October 2020 to August 2022, and postintervention assessments were completed in January 2023. The 24-month follow-up will be completed in February 2025., Conclusions: The findings from the CAUSE trial will provide novel scientific understanding of the potential benefits of exercise training in long-term breast cancer survivors., Trial Registration: ClinicalTrials.gov NCT04307407; https://clinicaltrials.gov/ct2/show/NCT04307407., International Registered Report Identifier (irrid): DERR1-10.2196/45244., (©Tormod Skogstad Nilsen, Mali Sæter, Sebastian Imre Sarvari, Kristin Valborg Reinertsen, Sara Hassing Johansen, Elisabeth Rustad Edvardsen, Jostein Hallén, Elisabeth Edvardsen, May Grydeland, Cecilie Essholt Kiserud, Hanne Cathrine Lie, Paul André Solberg, Torbjørn Wisløff, Adam Philip Sharples, Truls Raastad, Kristina Hermann Haugaa, Lene Thorsen. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 15.03.2023.)

Genetic introgression of farmed salmon into wild populations can damage the genetic integrity of wild stocks and is therefore considered as an environmental threat. One possible solution is to induce sterility in farmed salmon. We have searched for proteins potentially essential for germline survival in Atlantic salmon. One of these is the argonaute protein Piwil1, known to be required for germ cell survival. To examine Piwil1 function in salmon, we induced indels in the N domain by CRISPR-Cas9. The encoded domain is present in all vertebrate Piwi proteins and has been linked to Tdrd1 protein interaction and PAZ lobe structure. The F0 founder generation of piwil1 crispant males and females displayed a mosaic pattern of piwil1 mutations, exhibiting highly mutated alleles (53%-97%) in their fin gDNA samples. In general, piwil1 crispants carried germ cells, went through puberty and became fertile, although a transient and partial germ cell loss and delays during the spermatogenic process were observed in many male crispants, suggesting that Piwil1 functions during salmon spermatogenesis. By crossing highly mutated F0 founders, we produced F1 fish with a mixture of: loss-of-function alleles ( - ); functional in frame mutated alleles ( + ) and wt alleles ( + ). In F1, all piwil1 -/- fish lacked germ cells, while piwil1 +/+ siblings showed normal ovaries and testes. Yet, most juvenile F1 piwil1 +/ - males and females displayed an intermediate phenotype with a higher somatic/germ cell ratio without an increase in germ cell apoptosis, suggestive of a gene dose effect on the number of germ cells and/or insufficient replacement of lost germ cells in heterozygous fish. Interestingly, the two longest in-frame indels in the N domain also ensured germ cell loss. Hence, the loss of 4-6 aa in this region Phe130 - Ser136 may result in crucial changes of the protein structure, potentially affecting piRNA binding of the PAZ lobe, and/or affecting the binding of Piwil1 interacting proteins such as Tdrd protein, with critical consequences for the survival of primordial germ cells. In conclusion, we show that loss of piwil1 leads to loss of germ cells in salmon and that part of the N domain of Piwil1 is crucial for its function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 F. L, K. O, E, L, R. B, B, P. G, T. J, R. W and A.)

Background: Estimated peak oxygen consumption (Vo 2 peak) is widely used in oncology; however, estimated Vo 2 peak equations were developed in noncancer settings., Objectives: The aim of this study was to evaluate the validity of estimated Vo 2 peak in women with primary breast cancer and to develop oncology-specific estimated Vo 2 peak equations., Methods: Vo 2 peak was directly measured (TrueOne 2400, Parvo Medics) during 380 cardiopulmonary exercise tests in women previously treated for breast cancer (mean age: 59 ± 10 years; 3.1 ± 1.2 years post-therapy). The American College of Sports Medicine (ACSM), the Fitness Registry and the Importance of Exercise National Database (FRIEND), and heart failure (HF)-FRIEND equations were used to estimate Vo 2 peak. New equations were developed using patient and peak (Onc peak ) or submaximal (Onc sub ) exercise test characteristics., Results: The median differences between measured and estimated Vo 2 peak were 7.0 mL O 2 ·kg -1 ·min -1 , 3.9 mL O 2 ·kg -1 ·min -1 , and -0.2 mL O 2 ·kg -1 ·min -1 for ACSM, FRIEND, and HF-FRIEND, respectively. The number of estimated Vo 2 peak values within ±3.5 mL O 2 ·kg -1 ·min -1 of the measured values was 70 (18%), 164 (43%), and 306 (81%) for ACSM, FRIEND, and HF-FRIEND, respectively. The Onc peak and Onc Sub models included body mass index, age, a history of chemotherapy or radiation, the peak measured heart rate, and the treadmill grade and/or speed. The median differences between measured and estimated Vo 2 peak were 0.02 mL O 2 ·kg -1 ·min -1 (Onc peak ) and -0.2 mL O 2 ·kg -1 ·min -1 (Onc sub ). Eighty-six percent (n = 325) and 76% (n = 283) estimated Vo 2 peak values were within ±3.5 mL O 2 ·kg -1 ·min -1 of the measured Vo 2 peak values for Onc peak and Onc sub , respectively., Conclusions: HF-FRIEND or oncology-specific equations could be applied to estimate Vo 2 peak in patients previously treated for breast cancer in settings where cardiopulmonary exercise tests are not available. (Trial Comparing the Effects of Linear Versus Nonlinear Aerobic Training in Women With Operable Breast Cancer [EXCITE]; NCT01186367., Competing Interests: This study was supported by a research grant from the National Cancer Institute (R01-CA142566) awarded to Dr Jones and grants from AKTIV Against Cancer and the Memorial Sloan Kettering Cancer Center Support Grant/Core Grant (P30 CA008748). Dr Jones has stock ownership in Pacylex, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)

Background: Survivors of childhood cancer represent a growing population with a long life expectancy but high risks of treatment-induced morbidity and premature mortality. Regular physical activity (PA) may improve their long-term health; however, high-quality empirical knowledge is sparse., Objective: The Physical Activity and Fitness in Childhood Cancer Survivors (PACCS) study comprises 4 work packages (WPs) aiming for the objective determination of PA and self-reported health behavior, fatigue, and quality of life (WP 1); physical fitness determination (WP 2); the evaluation of barriers to and facilitators of PA (WP 1 and 3); and the feasibility testing of an intervention to increase PA and physical fitness (WP 4)., Methods: The PACCS study will use a mixed methods design, combining patient-reported outcome measures and objective clinical and physiological assessments with qualitative data gathering methods. A total of 500 survivors of childhood cancer aged 9 to 18 years with ≥1 year after treatment completion will be recruited in follow-up care clinics in Norway, Denmark, Finland, Germany, and Switzerland. All participants will participate in WP 1, of which approximately 150, 40, and 30 will be recruited to WP 2, WP3, and WP 4, respectively. The reference material for WP 1 is available from existing studies, whereas WP 2 will recruit healthy controls. PA levels will be measured using ActiGraph accelerometers and self-reports. Validated questionnaires will be used to assess health behaviors, fatigue, and quality of life. Physical fitness will be measured by a cardiopulmonary exercise test, isometric muscle strength tests, and muscle power and endurance tests. Limiting factors will be identified via neurological, pulmonary, and cardiac evaluations and the assessment of body composition and muscle size. Semistructured, qualitative interviews, analyzed using systematic text condensation, will identify the perceived barriers to and facilitators of PA for survivors of childhood cancer. In WP 4, we will evaluate the feasibility of a 6-month personalized PA intervention with the involvement of local structures., Results: Ethical approvals have been secured at all participating sites (Norwegian Regional Committee for Medical Research Ethics [2016/953 and 2018/739]; the Oslo University Hospital Data Protection Officer; equivalent institutions in Finland, Denmark [file H-19032270], Germany, and Switzerland [Ethics Committee of Northwestern and Central Switzerland, project ID: 2019-00410]). Data collection for WP 1 to 3 is complete. This will be completed by July 2022 for WP 4. Several publications are already in preparation, and 2 have been published., Conclusions: The PACCS study will generate high-quality knowledge that will contribute to the development of an evidence-based PA intervention for young survivors of childhood cancer to improve their long-term care and health. We will identify physiological, psychological, and social barriers to PA that can be targeted in interventions with immediate benefits for young survivors of childhood cancer in need of rehabilitation., International Registered Report Identifier (irrid): DERR1-10.2196/35838., (©Hanne C Lie, Sigmund Anderssen, Corina Silvia Rueegg, Truls Raastad, May Grydeland, Lene Thorsen, Trine Stensrud, Elisabeth Edvardsen, Marie Hamilton Larsen, Ingrid Kristin Torsvik, Lars Peder Bovim, Miriam Götte, Päivi Maria Lähteenmäki, Susi Kriemler, Hanne Bækgaard Larsen, Martin Kaj Fridh, Kristin Ørstavik, Henrik Brun, Iren Matthews, Else Hornset, Ellen Ruud. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 08.03.2022.)

Background: Poor cardiorespiratory fitness (CRF) is a cardinal feature of post-treatment primary lung cancer. The most effective exercise therapy regimen to improve CRF has not been determined., Methods: In this parallel-group factorial randomized controlled trial, lung cancer survivors with poor CRF (below age-sex sedentary values) were randomly allocated to receive 48 consecutive supervised sessions thrice weekly of (i) aerobic training (AT)-cycle ergometry at 55% to >95% of peak oxygen consumption (VO 2 peak); (ii) resistance training (RT)-lower and upper extremity exercises at 50-85% of maximal strength; (iii) combination training (CT)-AT plus RT; or (iv) stretching attention control (AC) for 16 weeks. The primary endpoint was change in CRF (VO 2 peak, mL O 2 ·kg -1 ·min -1 ). Secondary endpoints were body composition, muscle strength, patient-reported outcomes, tolerability (relative dose intensity of exercise), and safety. Analysis of covariance determined change in primary and secondary endpoints from baseline to post-intervention (Week 17) with adjustment for baseline values of the endpoint and other relevant clinical covariates., Results: Ninety patients (65 ± 9 years; 66% female) were randomized (AT, n = 24; RT, n = 23; CT, n = 20; and AC, n = 23) of the planned n = 160. No serious adverse events were observed. For the overall cohort, the lost-to-follow-up rate was 10%. Mean attendance was ≥75% in all groups. In intention-to-treat analysis, VO 2 peak increased 1.1 mL O 2 ·kg -1 ·min -1 [95% confidence interval (CI): 0.0, 2.2, P = 0.04] and 1.4 mL O 2 ·kg -1 ·min -1 (95% CI: 0.2, 2.5, P = 0.02) in AT and CT, respectively, compared with AC. There was no difference in VO 2 peak change between RT and AC (-0.1 mL O 2 ·kg -1 ·min -1 , 95% CI: -1.2, 1.0, P = 0.88). Favourable improvements in maximal strength and body composition were observed in RT and CT groups compared with AT and AC groups (Ps < 0.05). No between-group changes were observed for any patient-reported outcomes. Relative dose intensity of exercise was lower in RT and CT compared with AT (Ps < 0.05)., Conclusions: In the context of a smaller than planned sample size, AT and CT significantly improved VO 2 peak in lung cancer survivors; however, the tolerability-to-benefit ratio was superior for AT and hence may be the preferred modality to target impaired CRF in post-treatment lung cancer survivors., (© 2021 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Objective: To evaluate changes in pulmonary function and feasibility of portable continuous laryngoscopy during maximal uphill running., Methods: Healthy volunteers participated in an uphill race. Forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC) were obtained before and 5 and 10 min after finishing the race. Capillary blood lactate concentration ([BLa - ]) and Borg score for perceived exertion were registered immediately after the race. One participant wore a portable video-laryngoscope during the race, and the video was assessed for technical performance., Results: Twenty adult subjects participated with a mean (SD) age of 40.2 (9.7) years. Mean (SD) race duration and post-exercise [BLa - ] was 13.9 (2.3) min and 10.7 (2.1) mmol/L, respectively, and the median (range) Borg score for perceived exertion was 9 (5-10). Mean percentage change (95% CI) 5 and 10 min post-exercise in FEV 1 were 6.9 (3.7 to 10.2) % and 5.9 (2.7 to 9.0) %, respectively, and in FVC 5.2 (2.3 to 8.1) % and 4.7 (1.6 to 7.9) %, respectively. The recorded video of the larynx was of good quality., Conclusions: Maximal aerobic field exercise induced bronchodilatation in the majority of the healthy non-asthmatic participants. It is feasible to perform continuous video-laryngoscopy during heavy uphill exercise., Competing Interests: Competing interests: EE received salary from GlaxoSmithKline with no potential conflicts of interest with respect to the research, authorship and/or publication of this article. The other authors have no conflicts of interest relevant to this article to disclose., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Objectives: (1) To describe the cardiorespiratory fitness (CRF) in an adult cystic fibrosis population related to sex and age, (2) to evaluate the cause of low CRF and (3) to study the association between peak oxygen uptake (VO 2 peak) and forced expiratory volume in 1 s (FEV 1 )., Methods: A total of 204 cardiopulmonary treadmill exercise tests (CPETs) performed by 116 patients were included. VO 2 peak, gas exchange, heart rate, oxygen saturation and ventilatory variables were measured.A low CRF was defined as a VO 2 peak <80% of predicted, ventilatory limitation was defined as a breathing reserve <15%, exercise hypoxaemia was defined as an oxygen saturation <88% and ventilation-perfusion mismatch was defined as a minute ventilation/ventilatory equivalent for carbon dioxide slope ≥34. In patients who had performed three or more CPETs, the annual change in FEV 1 and VO 2 peak were calculated using linear regression., Results: The VO 2 peak was 40.6±11.5 and 35.2±8.9 mL kg -1 min -1 , which was 87±23 and 93±20 in percentage of predicted for men and women, respectively. VO 2 peak was moderately affected by age, for men (r=-0.36, p<0.001) and women (r=-0.53, p<0.001), respectively. In 45 of 101 tests where CRF was low, no cardiorespiratory limiting factors were identified. The correlation coefficient between VO 2 peak and FEV 1 was r=0.64 (p<0.001). In participants with a low CRF, FEV 1 ranged from 20% to 112% of predicted., Conclusions: The correlation between VO 2 peak and FEV 1 was moderate. The majority of the tests resulted in a VO 2 peak within normal limits. Interestingly, 44% of the tests with a low VO 2 peak could be explained by deconditioning. Thus, exercise therapy may be beneficial for these patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The original article [1] contains errors in Tables 1 and 3: Table 1 erroneously mentions use of a treadmill which should instead state 'bicycle', and Table 3 has a minor typesetting mistake.

Objective: To perform a comprehensive evaluation of and identify correlates for physical fitness in consecutive patients with juvenile idiopathic arthritis (JIA) who have been diagnosed in the era of biologics and to compare the results with those obtained in healthy controls., Methods: The study cohort included 60 patients with JIA (50 girls) ages 10-16 years and 60 age- and sex-matched controls. The JIA group included 30 patients with persistent oligoarticular JIA and 30 patients with extended oligoarticular or polyarticular disease. Measures of physical fitness included cardiorespiratory fitness (CRF) by peak oxygen uptake (Vo 2peak ) during a continuous graded treadmill exercise test, muscle strength by isokinetic and isometric knee and hand grip evaluations, and bone mineral density (BMD) and body composition by dual-energy x-ray absorptiometry. Physical activity was assessed by accelerometry., Results: Forty-two percent of the patients were being treated with biologic drugs. Patients with JIA demonstrated lower muscle strength and total body BMD compared to controls, but there were no differences in CRF and body composition. Physical fitness was comparable between the persistent oligoarticular and extended oligoarticular/polyarticular-JIA groups. In patients with JIA, we identified associations between higher vigorous physical activity and higher CRF and muscle strength, but did not find any association between physical fitness and disease variables., Conclusion: In this cohort of patients with JIA, we found suboptimal muscle strength and BMD compared to controls, but no differences in CRF and body composition. Vigorous physical activities appeared important for optimizing muscle strength and CRF in patients with JIA; the importance of such activities should be highlighted in patient education., (© 2018, American College of Rheumatology.)

Objectives: Patients with end-stage renal disease (ESRD) undergoing haemodialysis (HD) have significantly reduced cardiorespiratory fitness and health-related quality of life (HRQoL). Our hypothesis was that high-intensity interval training (HIIT) is a feasible and safe form of exercise during HD and that HIIT would elicit greater change in cardiorespiratory fitness and HRQoL compared with moderate-intensity continuous training (MICT)., Methods: Twenty patients were randomised to either HIIT (n=6), MICT (n=8) (two times a week within 22 weeks) or usual care (n=6). Feasibility was assessed by session attendance and adherence to exercise intensity. Safety was assessed by adverse event reporting. Efficacy was determined from change in peak oxygen uptake (VO 2peak ), 6 min walk distance and a HRQoL questionnaire (the COOP-WONCA chart)., Results: Eleven patients (55%) completed premeasurements and postmeasurements. The main reason for drop-out was due to kidney transplant during follow-up. The patients completed the same number of sessions in each group and adhered to the target heart rates after habituation. There were no adverse events. In the HIIT group, two of the three patients increased VO 2peak by 46% and 53%, respectively. Three of the five patients in the MICT group increased their VO 2peak by 6%, 18% and 36%, respectively., Conclusions: This pilot study demonstrated that HIIT is a feasible and safe exercise model for intradialytic exercise in patients undergoing HD. There might be a considerable potential of intradialytic HIIT in patients undergoing HD. Further studies with larger sample sizes are needed to determine if HIIT is an optimal approach in patients with ESRD undergoing HD., Trial Registration Number: NCT01728415., Competing Interests: Competing interests: EE received salary from GlaxoSmithKline with no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Knowledge of the effect of marine protein hydrolysate (MPH) supplementation to promote recovery after high intensity performance training is scarce. The aim of this study was to examine the effect of MPH supplementation to whey protein (WP) and carbohydrate (CHO): (CHO-WP-MPH), on short-term recovery following high intensity performance, compared to an isoenergetic and isonitrogenous supplement of WP and CHO: (CHO-WP), in male cyclists., Methods: This was a double-blinded crossover study divided into three phases. Fourteen healthy men participated. In phase I, an incremental bicycle exercise test was performed for establishment of intensities used in phase II and III. In phase II (9-16 days after phase 1), the participants performed first one high intensity performance cycling session, followed by nutrition supplementation (CHO-WP-MPH or CHO-WP) and 4 hours of recovery, before a subsequent high intensity performance cycling session. Phase III (1 week after phase II), was similar to phase II except for the nutrition supplementation, where the participants received the opposite supplementation compared to phase II. Primary outcome was difference in time to exhaustion between the cycling sessions, after nutrition supplementations containing MPH or without MPH. Secondary outcomes were differences in heart rate (HR), respiratory exchange ratio (RER), blood lactate concentration and glucose., Results: The mean age of the participants was 45.6 years (range 40-58). The maximal oxygen uptake (mean ± SD) measured at baseline was 54.7 ± 4.1 ml∙min - 1 ∙kg - 1 . There were no significant differences between the two nutrition supplementations measured by time to exhaustion at the cycling sessions (mean diff  = 0.85 min, p = 0.156, 95% confidence interval (CI), - 0.37, 2.06), HR (mean diff  = 0.8 beats pr.min, p = 0.331, 95% CI, - 0.9, 2.5), RER (mean diff  = - 0.05, p = 0.361, 95% CI -0.07 - 0.17), blood lactate concentration (mean diff  = - 0.24, p = 0.511, 95% CI, - 1.00, 0.53) and glucose (mean diff  = 0.23, p = 0.094, 95% CI, - 0.05, 0.51)., Conclusions: A protein supplement with MPH showed no effects on short-term recovery in middle-aged healthy male cyclists compared to a protein supplement without MPH., Trial Registration: The study was registered 02.05.2017 at ClinicalTrials.gov (Protein Supplements to Cyclists, NCT03136133 , https://clinicaltrials.gov/ct2/show/NCT03136133?cond=marine+peptides&rank=1 .

Background: Poor cardiorespiratory fitness is previously reported in patients with juvenile idiopathic arthritis (JIA) measured both by maximal and submaximal exercise tests, but a submaximal exercise test with acceptable measurement properties is currently lacking for both clinical and research purposes in this patient population. The objectives of this study were to evaluate the measurement properties and performance of a submaximal treadmill test in patients with JIA, and to compare the results with those obtained in controls., Methods: Fifty-nine patients (50 girls), aged 10-16 years, with oligo- (n = 30) and polyarticular (n = 29) JIA, and 59 age- and sex-matched controls performed an eight-minute submaximal treadmill test for estimating peak oxygen uptake (VO 2peak ) followed by a maximal treadmill test measuring VO 2peak directly. During the submaximal treadmill test, the study participants walked with no inclination at a speed between 3.2-7.2 km/h for four minutes, and then continued to walk at the same speed for four minutes with five % inclination. VO 2peak was directly measured during a continuous graded exercise test on treadmill until exhaustion. Thirty-seven patients participated in the evaluation of the reliability. Criterion validity and reliability were evaluated with interclass correlation coefficient (ICC); measurement errors by Bland-Altman plot, standard error of measurement and smallest detectable change., Results: In patients with JIA, the ICC (95% CI) for criterion validity was acceptable at group level 0.71 (0.51, 0.82), but not at individual level. The test-retest reliability and inter-rater reliability were acceptable at individual (0.84 (0.71, 0.91) and 0.92 (0.83, 0.96), respectively) and group levels (0.91 (0.83, 0.96) and 0.96 (0.91, 0.98), respectively). The measurement errors (for test-retest reliability/inter-rater reliability) were large. Bland-Altman plots showed no systematic differences, but a large variability for both the validity and reliability. The performance of and estimated VO 2peak from the submaximal test were not associated with disease variables and were comparable between patients and controls., Conclusion: The submaximal treadmill test is valid for use in patients with JIA on group level, but not on individual level. The reliability is acceptable. Due to large measurement errors, the submaximal treadmill test is not optimal for use in daily clinical practice to estimate VO 2peak in individual patients.

Objectives: To compare cardiorespiratory fitness (CRF) expressed as maximal oxygen uptake (VO2max) between patients with long-term JDM and controls and between patients with active and inactive disease, as well as to explore exercise limiting factors and associations between CRF and disease variables., Methods: JDM patients (n = 45) and age- and gender-matched controls (n = 45) performed a cardiopulmonary exercise test (CPET) on a treadmill until exhaustion. Physical activity was measured by accelerometers. Disease activity, damage and muscle strength/function were assessed by validated tools. Clinically inactive disease was defined according to PRINTO criteria., Results: The mean disease duration was 20.8 (s.d. 11.9) years and 29/45 (64%) patients had inactive disease. A low VO2max was found in 27% of patients vs 4% of controls (P = 0.006). The mean VO2max and maximal ventilation (VEmax) were lower in patients with active and inactive disease compared with controls. Patients with active disease also had lower maximal voluntary ventilation (MVV) compared with controls and lower VEmax and MVV compared with those with inactive disease. Patients with inactive disease had lower physical activity levels compared with controls. VO2max correlated negatively with disease damage in patients with inactive disease and positively with muscle strength/function in patients with active disease., Conclusion: CRF was lower in JDM patients, both with active and inactive disease, compared with controls after a mean 20 years disease duration. Cardiopulmonary exercise test results suggested different limiting factors contributing to the reduced CRF according to disease activity, including deconditioning in inactive disease and reduced ventilatory capacity in active disease. Further research is needed to verify this., (© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Maximal heart rate (HR) is commonly defined as the highest HR obtained during a progressive exercise test to exhaustion. Maximal HR is considered one of the criteria to assess maximum exertion in exercise tests, and is broadly used when prescribing exercise intensity. The aim of the present study was to compare peak HR measurements during maximal treadmill running and active play in obese children and adolescents., Design: Comparison of peak heart rate during active play vs. maximal treadmill running in 39 (7⁻17 years old, 18 males) obese children and adolescents., Methods: Heart rate was recorded during intensive active play sessions, as well as during a progressive running test on a treadmill until exhaustion. HR, respiratory exchange ratio (RER), and oxygen uptake were continuously measured during the test. The criteria for having reached maximal effort was a subjective assessment by the technician that the participants had reached his or her maximal effort, and a RER above 1.00 or reporting perceived exertion (RPE) above 17 using the Borg-RPE 6⁻20 -Scale., Results: Thirty-four children had a RER ≥1.00, and 37 reported a RPE ≥ 17. Thirty-two children fulfilled both criteria. During active play, peak HR was significantly ( p < 0.0001) increased (4%) (mean and 95% confidence intervals; 204 (201, 207) beats/min), compared to during maximal treadmill running (196 (194, 199) beats/min), respectively., Conclusion: The results of the present study indicate that peak heart rate measurements during progressive running to exhaustion in obese children and adolescents cannot necessarily be determined as maximal heart rate.

Purpose: This study's purpose was to examine whether established risk categories of waist circumference (WC)-normal, high risk, and very high health risk-reflected significant differences in cardiorespiratory fitness (CRF) and physical activity (PA) level., Methods: CRF was directly measured as maximal oxygen uptake during a progressive graded treadmill test to exhaustion in 722 individuals (349 women) aged 20-85 years. WC was measured between the lower rib and the iliac crest. Objectively measured PA was assessed using an accelerometer., Results: Men in the normal risk group (WC < 94 cm) had a 31% higher CRF and 43% higher level of moderate-to-vigorous PA than men in the very high risk group (with a WC > 102 cm). Corresponding numbers for women within normal (WC < 80 cm) and very high risk group (WC > 88 cm) were 25% and 18% ( p  < 0.05). There was a high negative correlation between CRF and WC in men ( r  = -0.68), and a moderate correlation for women ( r  = -0.49; p  < 0.001). For each cm increase in WC, CRF was reduced by 0.48 and 0.27 mL/kg/min in men and women, respectively ( p  < 0.001)., Conclusion: The recommended WC thresholds for abdominal obesity reflected significant differences in CRF for both men and women, and could serve as a useful instrument for estimating health-related differences in CRF.

Background: Given the risk of developing acute and long-term adverse effects in patients receiving cisplatin-based chemotherapy for testicular cancer (TC), risk-reducing interventions, such as physical activity (PA), may be relevant. Limited knowledge is available on the challenges met when conducting PA intervention trials in patients with TC during and shortly after chemotherapy. The aims of the present feasibility study are therefore to determine patient recruitment, compliance and adherence to a PA intervention., Results: Patients with metastatic TC referred to cisplatin-based chemotherapy were eligible. They followed an individual low-threshold PA intervention, including counseling from a personal coach during and 3 months after chemotherapy. Outcomes were recruitment rate, compliance rate and adherence to the intervention including preferences for type of PA and barriers for PA. During 8 months 12 of 18 eligible patients were invited, all consented, but three dropped out. Walking and low intensity activities were preferred and nausea and feeling unwell were the most often reported barriers towards PA., Discussion: In order to achieve adequate recruitment, compliance and complete data in future PA intervention trials, close cooperation with treating physicians, individual PA plans and availability of personalized coaching are required. Trial registration NCT01749774, November 2012, ClinicalTrials.gov.

Background: Air travel may imply a health hazard for patients with cystic fibrosis (CF) due to hypobaric environment in the aircraft cabin. The objective was to identify pre-flight variables, which might predict severe hypoxaemia in adult CF patients during air travel., Methods: Thirty adult CF-patients underwent pre-flight evaluation with spirometry, arterial oxygen tension (PaO 2 ), pulse oximetry (SpO 2 ) and cardiopulmonary exercise testing (CPET) at sea level (SL). The results were related to the PaO 2 obtained during a hypoxia-altitude simulation test (HAST) in which a cabin altitude of 2438 m (8000 ft) was simulated by breathing 15.1% oxygen., Results: Four patients fulfilled the criteria for supplemental oxygen during air travel (PaO 2 HAST  < 6.6 kPa). While walking slowly during HAST, another eleven patients dropped below PaO 2 HAST 6.6 kPa. Variables obtained during CPET (PaO 2 CPET , SpO 2 CPET , minute ventilation/carbon dioxide output, maximal oxygen uptake) showed the strongest correlation to PaO 2 HAST ., Conclusions: Exercise testing might be of value for predicting in-flight hypoxaemia and thus the need for supplemental oxygen during air travel in CF patients. Trial registration The study is retrospectively listed in the ClinicalTrials.gov Protocol Registration System: NCT01569880 (date; 30/3/2012).

Aim: To evaluate the effect of lung cancer surgery on cardiorespiratory fitness (CRF), and to assess the agreement between the predicted postoperative (ppo) V̇O 2peak and actually measured postoperative peak oxygen uptake (V̇O 2peak )., Methods: Before and 4-6 weeks after lung cancer surgery, 70 patients (35 women) underwent measurements of pulmonary function and CRF via a cardiopulmonary exercise test. In addition, the 23 non-exercising patients underwent measurements after 6 months. The ppo V̇O 2peak calculated from the number of functional segments removed was compared with the actually measured postoperative values of V̇O 2peak for accuracy and precision., Results: After surgery, the V̇O 2peak decreased from 23.9±5.8 to 19.2±5.5 mL/kg/min (-19.6±15.7%) (p<0.001). The breathing reserve increased by 5% (p=0.001); the oxygen saturation remained unchanged (p=0.30); the oxygen pulse decreased by -1.9 mL/beat (p<0.001); the haemoglobin concentration decreased by 0.7 g/dL (p=0.001). The oxygen pulse was the strongest predictor for change in V̇O 2peak ; adjusted linear squared: r 2 =0.77. Six months after surgery, the V̇O 2peak remained unchanged (-3±15%, p=0.27). The ppo V̇O 2peak (mL/kg/min) was 18.6±5.4, and the actually measured V̇O 2peak was 19.2±5.5 (p=0.24). However, the limits of agreement were large (CI -7.4 to 8.2). The segment method miscalculated the ppo V̇O 2peak by more than ±10 and ±20% in 54% and 25% of the patients, respectively., Conclusions: The reduction in V̇O 2peak and lack of improvement 6 months after lung cancer surgery cannot be explained by the loss of functional lung tissue. Predicting postoperative V̇O 2peak based on the amount of lung tissue removed is not recommendable due to poor precision., Trial Registration Number: NCT01748981.

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world's oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits.

Background: Previous studies on type 2 diabetes have shown an association between exercise capacity and insulin resistance. In patients with coronary artery disease (CAD) exercise capacity is often reduced due to exercise-induced ischemia. We have investigated the association between glucometabolic control, including the homeostatic model assessment (HOMA) of insulin resistance, and exercise capacity in patients with type 2 diabetes and CAD with and without exercise-induced ischemia., Methods: In 137 patients (age 63.1 ± 7.9) cardiopulmonary exercise testing on treadmill was performed using a modified Balke protocol. The highest oxygen uptake (VO2peak) was reported as 30-s average. Fasting blood samples were drawn for determination of glucose, insulin and HbA1c. Insulin resistance (IR) was assessed by the HOMA2-IR computer model. Exercise-induced ischemia was defined as angina and/ or ST-depression in ECG ≥ 0.1 mV during the exercise test., Results: HOMA2-IR was inversely correlated to VO2peak (r = -0.328, p < 0.001), still significant after adjusting for age, gender, smoking and BMI. Patients with HOMA2-IR above the median value (1.3) had an adjusted odds ratio of 3.26 (95 % CI 1.35 to 7.83, p = 0.008) for having VO2peak below median (23.8 mL/kg/min). Insulin levels were inversely correlated to VO2peak (r = -0.245, p = 0.010), also after adjusting for age and gender, but not after additional adjustment for BMI. The correlation between HOMA2-IR and VO2peak was also significant in the subgroups with (n = 51) and without exercise-induced ischemia (n = 86), being numerically stronger in the group with ischemia (r = -0.430, p = 0.003 and r = -0.276, p = 0.014, respectively). Fasting glucose and HbA1c were not correlated with VO2peak or AT., Conclusions: Insulin resistance, as estimated by fasting insulin and the HOMA index, was inversely associated with exercise capacity in patients with type 2 diabetes and CAD, the association being more pronounced in the subgroup with exercise-induced ischemia. These results indicate that insulin resistance is related to exercise capacity in type 2 diabetic patients with CAD, possibly even more so in patients with exercise-induced ischemia compared to those without.

Objective: To describe different end criteria for reaching maximal oxygen uptake (VO2max) during a continuous graded exercise test on the treadmill, and to explore the manner by which different end criteria have an impact on the magnitude of the VO2max result., Methods: A sample of 861 individuals (390 women) aged 20-85 years performed an exercise test on a treadmill until exhaustion. Gas exchange, heart rate, blood lactate concentration and Borg Scale6-20 rating were measured, and the impact of different end criteria on VO2max was studied;VO2 leveling off, maximal heart rate (HRmax), different levels of respiratory exchange ratio (RER), and postexercise blood lactate concentration., Results: Eight hundred and four healthy participants (93%) fulfilled the exercise test until voluntary exhaustion. There were no sex-related differences in HRmax, RER, or Borg Scale rating, whereas blood lactate concentration was 18% lower in women (P<0.001). Forty-two percent of the participants achieved a plateau in VO2; these individuals had 5% higher ventilation (P = 0.033), 4% higher RER (P<0.001), and 5% higher blood lactate concentration (P = 0.047) compared with participants who did not reach a VO2 plateau. When using RER ≥1.15 or blood lactate concentration ≥8.0 mmol•L(-1), VO2max was 4% (P = 0.012) and 10% greater (P<0.001), respectively. A blood lactate concentration ≥8.0 mmol•L(-1) excluded 63% of the participants in the 50-85-year-old cohort., Conclusions: A range of typical end criteria are presented in a random sample of subjects aged 20-85 years. The choice of end criteria will have an impact on the number of the participants as well as the VO2max outcome. Suggestions for new recommendations are given.

Background: Bovine tuberculosis (TB) caused by Mycobacterium bovis is primarily a disease of ruminants, particularly cattle (Bos primigenius) and buffalo (Syncerus caffer), and is endemic in most developing countries. To date, studies done in Uganda have documented the prevalence of M. bovis in cattle, humans and wild life, in addition to non-tuberculous mycobacteria in pigs. Pigs are increasingly becoming an important component of the livestock sector and share the human ecosystem in rural Uganda. It is therefore of public health interest that they are not a source of human infections. As a follow up to previously published findings on mycobacteria in pigs, this study was aimed at investigating the occurrence and molecular characteristics of M. bovis detected in slaughter pigs in Mubende district, Uganda. One hundred fifty mesenteric lymph nodes with lesions suggestive of mycobacterial infections were collected from approximately one thousand slaughtered pigs in Mubende district over a period of five months. The isolation and identification of M. bovis was done using conventional mycobacteriological methods. Mycobacteria belonging to the Mycobacterium tuberculosis complex (MTC) were identified to species level using deletion analysis. Molecular typing was done using Spoligotyping and MIRU-VNTR analysis. Molecular data were analysed and interpreted using MIRU-VNTR plus, SpolDB4.0 and the Mycobacterium bovis spoligo database., Results: Of the examined animals, one boar and two sows from Madudu Sub County were infected with M. bovis which presented as lesions of a deep yellow colour and a grit-like texture in the mesenteric lymph nodes. This represents 2% (3/150) of the lymph nodes where lesions suggestive of mycobacterial infections were detected. Molecular analysis revealed that the isolates from the infected pigs showed identical MIRU-VNTR profile and spoligotype (SB1469)., Conclusions: This is the first study documenting the occurrence of M. bovis in slaughter pigs in Uganda, revealing that one in fifty slaughter pigs with suspected lesions in mesenteric lymph nodes were infected. Molecular analysis revealed that the isolates were identical, showing a spoligotype previously reported from humans and cattle in the north eastern part of the Uganda cattle corridor. This finding is of public health importance, therefore there is a need for close cooperation between medical and veterinary professionals in designing and implementing control and prevention measures that safeguard the public from this potential source of zoonotic TB in Uganda.

Ticks can be transported over large distances and across geographical barriers by avian hosts. During the spring migrations of 2003 to 2005, 9,768 passerine birds from 4 bird observatories along the southern coastline of Norway were examined for ticks. Altogether, 713 birds carried a total of 517 larvae and 1,440 nymphs. The highest prevalence of tick infestation was observed in thrushes and dunnock (Prunella modularis). The degree of tick infestation varied during each season, between localities, and from year to year. Blackbirds (Turdus merula) caught in localities with many ticks had greater infestation than those from localities with few or no ticks, suggesting local tick recruitment. A similar study performed during 1965–1970 involving 2 of the bird observatories in the present study found ticks on 4.2% of birds, while we found infestation of 6.9% at the same localities (P < 0.001). With the exception of 10 nymphs and 1 larva, the predominant tick was Ixodes ricinus. Seven nymphs of Hyalomma rufipes and 1 larva of Dermacentor sp. were also found. No species of Dermacentor had previously been found in Norway.

Several bird species have advanced the timing of their spring migration in response to recent climate change. European short-distance migrants, wintering in temperate areas, have been assumed to be more affected by change in the European climate than long-distance migrants wintering in the tropics. However, we show that long-distance migrants have advanced their spring arrival in Scandinavia more than short-distance migrants. By analyzing a long-term data set from southern Italy, we show that long-distance migrants also pass through the Mediterranean region earlier. We argue that this may reflect a climate-driven evolutionary change in the timing of spring migration.

Background: Atrioventricular septal defect (AVSD) is a complex congenital heart disease with an incidence of 0.1-0.2 per cent. We wanted to produce an overview of all children in our catchment area born with AVSD in a defined period of time and to evaluate our follow up routines in respect of AVSD., Material and Methods: The medical case-notes of 53 children born with AVSD between 1983 and 1995 were examined., Results: Eleven children had died. 42 were offered an extended examination. 36 of the 53 children (68%) had Down's syndrome; 77% (28/36) of these had complete AVSD versus 52% (9/17) of the children without Down's syndrome. The difference was not statistically significant. Children with Down's syndrome had lower maximal oxygen uptake (p = 0.01) and lower maximal pulse rate (p = 0.02). We did not find any significant association with degree of atrioventricular insufficiency, size of left atrium or pro-atrial natriuretic peptide (pro-ANP). Moreover, no association existed between the degree of atrioventricular incompetence and exercise tolerance tested on the treadmill. ECG, 24-hour ambulatory taped ECG, blood tests and chest X-ray gave no additional information., Interpretation: Children with AVSD who have been operated on, should be examined ambulatory every year or every second year. Clinical examination and echocardiography seem to be the most important aspect of the evaluation.