Search

The objective of this work was to investigate myonuclear permanence and transcriptional regulation as mechanisms for cellular muscle memory after strength training in humans. Twelve untrained men and women performed 10 weeks of unilateral elbow-flexor strength training followed by 16 weeks of de-training. Thereafter, 10 weeks' re-training was conducted with both arms: the previously trained arm and the contralateral untrained control arm. Muscle biopsies were taken from the trained arm before and after both training periods and from the control arm before and after re-training. Muscle biopsies were analysed for fibre cross-sectional area (fCSA), myonuclei and global transcriptomics (RNA sequencing). During the first training period, myonuclei increased in type 1 (13 ± 17%) and type 2 (33 ± 23%) fibres together with a 30 ± 43% non-significant increase in mixed fibre fCSA (P = 0.069). Following de-training, fCSA decreased in both fibre types, whereas myonuclei were maintained, resulting in 33% higher myonuclear number in previously trained vs. control muscle in type 2 fibres. Furthermore, in the previously trained muscle, three differentially expressed genes (DEGs; EGR1, MYL5 and COL1A1) were observed. Following re-training, the previously trained muscle showed larger type 2 fCSA compared to the control (P = 0.035). However, delta change in type 2 fCSA was not different between muscles. Gene expression was more dramatically changed in the control arm (1338 DEGs) than in the previously trained arm (822 DEGs). The sustained higher number of myonuclei in the previously trained muscle confirms myonuclear accretion and permanence in humans. Nevertheless, because of the unclear effect on the subsequent hypertrophy with re-training, the physiological benefit remains to be determined. KEY POINTS: Muscle memory is a cellular mechanism that describes the capacity of skeletal muscle fibres to respond differently to training stimuli if the stimuli have been previously encountered. This study overcomes past methodological limitations related to the choice of muscles and analytical procedures. We show that myonuclear number is increased after strength training and maintained during de-training. Increased myonuclear number and differentially expressed genes related to muscle performance and development in the previously trained muscle did not translate into a clearly superior responses during re-training. Because of the unclear effect on the subsequent hypertrophy and muscle strength gain with re-training, the physiological benefit remains to be determined., (© 2024 The Author(s). The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Background: Physical activity is well known for its multiple health benefits and although the knowledge of the underlying molecular mechanisms is increasing, our understanding of the role of epigenetics in long-term training adaptation remains incomplete. In this intervention study, we included individuals with a history of > 15 years of regular endurance or resistance training compared to age-matched untrained controls performing endurance or resistance exercise. We examined skeletal muscle DNA methylation of genes involved in key adaptation processes, including myogenesis, gene regulation, angiogenesis and metabolism., Results: A greater number of differentially methylated regions and differentially expressed genes were identified when comparing the endurance group with the control group than in the comparison between the strength group and the control group at baseline. Although the cellular composition of skeletal muscle samples was generally consistent across groups, variations were observed in the distribution of muscle fiber types. Slow-twitch fiber type genes MYH7 and MYL3 exhibited lower promoter methylation and elevated expression in endurance-trained athletes, while the same group showed higher methylation in transcription factors such as FOXO3, CREB5, and PGC-1α. The baseline DNA methylation state of those genes was associated with the transcriptional response to an acute bout of exercise. Acute exercise altered very few of the investigated CpG sites., Conclusions: Endurance- compared to resistance-trained athletes and untrained individuals demonstrated a different DNA methylation signature of selected skeletal muscle genes, which may influence transcriptional dynamics following a bout of acute exercise. Skeletal muscle fiber type distribution is associated with methylation of fiber type specific genes. Our results suggest that the baseline DNA methylation landscape in skeletal muscle influences the transcription of regulatory genes in response to an acute exercise bout., (© 2024. The Author(s).)

While under physiological conditions angiotensin-converting enzyme 2 (ACE2) is an antagonist of vasoconstrictive agents in the renin-angiotensin-aldosterone system (RAAS), in the context of SARS coronavirus 2 (SARS-CoV-2) ACE2 serves as the gateway into cells. Furthermore, RAAS has previously been shown to be influenced by exercise training and is suggested to be involved in skeletal muscle mass maintenance. Given this connection, the investigation of circulating ACE2 plasma protein concentration before and following acute and chronic endurance and resistance exercise could increase the understanding of the implications of the exposure of athletes to SARS-CoV-2. Therefore, this study investigated levels of circulating ACE2 in lifelong high-level trained endurance and resistance athletes and control subjects in response to either acute endurance or resistance exercise. Results show no baseline differences in absolute ACE2 concentration between groups, but a strong negative correlation with levels of fitness and positive correlation with BMI in control subjects. Furthermore, acute endurance exercise significantly increased ACE2 levels across all groups, but only in the strength group in response to resistance exercise. This indicates that circulating ACE2 plasma levels are influenced by levels of fitness and health, and that acute endurance exercise has a stronger effect on plasma ACE2 levels than resistance exercise., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background: Mobilization of certain immune cells may improve the ability of the immune system to combat tumor cells, but the effect of acute exercise on mobilizing immune cells has been sparsely investigated in cancer patients. Therefore, we examined how acute exercise influences circulating immune cells in breast cancer patients., Methods: Nineteen newly diagnosed breast cancer patients aged 36-68 performed 30 minutes of moderate-intensity exercise with a cycle ergometer. Blood samples were collected at various time points: at rest, at 15 (E15) and 30 minutes (E30) after onset of the exercise, and at 30 and 60 minutes post-exercise. We analyzed several immune cell subsets using flow cytometry., Results: Acute exercise increased the number of total leukocytes, neutrophils, lymphocytes, monocytes, basophils, total T-cells, CD4 + T-cells, T helper (Th) 2-cells, Th 17-cells, CD8 + T-cells, CD4 - CD8 - T-cells, CD56 + natural killer (NK) cells, and CD14 - CD16 + monocytes. Many of the changes were transient. Proportions of NK-cells and CD8 + T-cells increased, while the proportion of myeloid derived suppressor cells (MDSCs) reduced, and proportion of regulatory T-cells remained unchanged by exercise. Several associations were detected between cell mobilizations and disease state. For instance, tumor size correlated negatively with NK cell mobilization at E15, and progesterone receptor positivity correlated negatively with CD8 + T-cell mobilization., Conclusion: The findings show that the proportions of CD8 + T-cells and NK cells increased and the proportion of MDSCs proportion decreased in breast cancer patients after 30-minute exercise, suggesting a change in the profile of circulating immune cells towards more cytotoxic/anti-tumorigenic. The mobilization of some immune cells also appears to be related to the disease state., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Koivula, Lempiäinen, Neuvonen, Norha, Hollmén, Sundberg, Rundqvist, Minn, Rinne and Heinonen.)

Objective: In acute chest pain management, risk stratification tools, including medical history, are recommended. We compared the fraction of patients with sufficient clinical data obtained using computerized history taking software (CHT) versus physician-acquired medical history to calculate established risk scores and assessed the patient-by-patient agreement between these 2 ways of obtaining medical history information., Materials and Methods: This was a prospective cohort study of clinically stable patients aged ≥ 18 years presenting to the emergency department (ED) at Danderyd University Hospital (Stockholm, Sweden) in 2017-2019 with acute chest pain and non-diagnostic ECG and serum markers. Medical histories were self-reported using CHT on a tablet. Observations on discrete variables in the risk scores were extracted from electronic health records (EHR) and the CHT database. The patient-by-patient agreement was described by Cohen's kappa statistics., Results: Of the total 1000 patients included (mean age 55.3 ± 17.4 years; 54% women), HEART score, EDACS, and T-MACS could be calculated in 75%, 74%, and 83% by CHT and in 31%, 7%, and 25% by EHR, respectively. The agreement between CHT and EHR was slight to moderate (kappa 0.19-0.70) for chest pain characteristics and moderate to almost perfect (kappa 0.55-0.91) for risk factors., Conclusions: CHT can acquire and document data for chest pain risk stratification in most ED patients using established risk scores, achieving this goal for a substantially larger number of patients, as compared to EHR data. The agreement between CHT and physician-acquired history taking is high for traditional risk factors and lower for chest pain characteristics., Clinical Trial Registration: ClinicalTrials.gov NCT03439449., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Aim: The influence on acute skeletal muscle transcriptomics of neuromuscular electrical stimulation (NMES), as compared to established exercises, is poorly understood. We aimed to investigate the effects on global mRNA-expression in the quadriceps muscle early after a single NMES-session, compared to the effects of voluntary knee extension exercise (EX), and to explore the discomfort level., Methods: Global vastus lateralis muscle gene expression was assessed (RNA-sequencing) in 30 healthy participants, before and 3 h after a 30-min session of NMES and/or EX. The NMES-treatment was applied using textile electrodes integrated in pants and set to 20% of each participant's pre-tested MVC mean (±SD) 200 (±80) Nm. Discomfort was assessed using Visual Analogue Scale (VAS, 0-10). The EX-protocol was performed at 80% of 1-repetition-maximum., Results: NMES at 20% of MVC resulted in VAS below 4 and induced 4448 differentially expressed genes (DEGs) with 80%-overlap of the 2571 DEGs of EX. Genes well-known to be up-regulated following exercise, for example, PPARGC1A, ABRA, VEGFA, and GDNF, were also up-regulated by NMES. Gene set enrichment analysis demonstrated many common pathways after EX and NMES. Also, some pathways were exclusive to either EX, for example, muscle tissue proliferation, or to NMES, for example, neurite outgrowth and connective tissue proliferation., Conclusion: A 30-min NMES-session at 20% of MVC with NMES-pants, which can be applied with an acceptable level of discomfort, induces over 4000 DEGs, of which 80%-overlap with DEGs of EX. NMES can induce exercise-like molecular effects, that potentially can lead to health and performance benefits in individuals who are unable to perform resistance exercise., (© 2024 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)

Background: The Covid-19 pandemic has tested health care organizations worldwide. Responses have demonstrated great variation and Sweden has been an outlier in terms of both strategy and how it was enacted, making it an interesting case for further study. The aim of this study was to explore how health care leaders experienced the challenges and responses that emerged during the initial wave of the Covid-19 pandemic, and to analyze these experiences through an organizational resilience lens., Methods: A qualitative interview study with 12 senior staff members who worked directly with or supervised pandemic efforts. Transcripts were analyzed using traditional content analysis and the codes directed to the Integrated Resilience Attributes Framework to understand what contributed to or hindered organizational resilience, i.e. how organizations achieve their goals by utilizing existing resources during crises., Results/findings: Organizational resilience was found at the micro (situated) and meso (structural) system levels as individuals and organizations dealt with acute shortages and were forced to rapidly adapt through individual sacrifices, resource management, process management, and communications and relational capacity. Poor systemic resilience related to misaligned responses and a lack of learning from previous experiences, negatively impacted the anticipatory phase and placed greater pressure on individuals and organizations to respond. Conventional crisis leadership could hamper innovation, further cement chronic challenges, and generate a moral tension between centralized directives and clinical microsystem experiences., Conclusions: The pandemic tested the resilience of the health care system, placing undue pressure on micro and meso systems responses. With improved learning capabilities, some of this pressure may be mitigated as it could raise the anticipatory resilience potential, i.e. with better health systems learning, we may need fewer heroes. How crisis leadership could better align decision-making with frontline needs and temper short-term acute needs with a longer-term infinite mindset is worth further study., (© 2024. The Author(s).)

Background: The menstrual cycle and its impact on training and performance are of growing interest. However, evidence is lacking whether periodized exercise based on the menstrual cycle is beneficial. The primary purpose of this proposed randomized, controlled trial, the IMPACT study, is to evaluate the effect of exercise periodization during different phases of the menstrual cycle, i.e., comparing follicular phase-based and luteal phase-based training with regular training during the menstrual cycle on physical performance in well-trained women., Methods: Healthy, well-trained, eumenorrheic women between 18 and 35 years (n = 120) will be recruited and first assessed for physical performance during a run-in menstrual cycle at different cycle phases and then randomized to three different interventions: follicular phase-based training, luteal phase-based training, or regular training during three menstrual cycles. The training intervention will consist of high-intensity spinning classes followed by strength training. The menstrual cycle phases will be determined by serum hormone analysis throughout the intervention period. Assessment of aerobic performance (primary outcome) and muscle strength, body composition, and blood markers will be performed at baseline and at the end of the intervention., Discussion: With a robust methodology, this study has the potential to provide evidence of the differential effects of exercise periodization during different phases of the menstrual cycle in female athletes., Trial Registration: ClinicalTrials.gov NCT05697263 . Registered on 25 January 2023., (© 2024. The Author(s).)

Objective: Long-term high-level exercise training leads to improvements in physical performance and multi-tissue adaptation following changes in molecular pathways. While skeletal muscle baseline differences between exercise-trained and untrained individuals have been previously investigated, it remains unclear how training history influences human multi-omics responses to acute exercise., Methods: We recruited and extensively characterized 24 individuals categorized as endurance athletes with >15 years of training history, strength athletes or control subjects. Timeseries skeletal muscle biopsies were taken from M. vastus lateralis at three time-points after endurance or resistance exercise was performed and multi-omics molecular analysis performed., Results: Our analyses revealed distinct activation differences of molecular processes such as fatty- and amino acid metabolism and transcription factors such as HIF1A and the MYF-family. We show that endurance athletes have an increased abundance of carnitine-derivates while strength athletes increase specific phospholipid metabolites compared to control subjects. Additionally, for the first time, we show the metabolite sorbitol to be substantially increased with acute exercise. On transcriptional level, we show that acute resistance exercise stimulates more gene expression than acute endurance exercise. This follows a specific pattern, with endurance athletes uniquely down-regulating pathways related to mitochondria, translation and ribosomes. Finally, both forms of exercise training specialize in diverging transcriptional directions, differentiating themselves from the transcriptome of the untrained control group., Conclusions: We identify a "transcriptional specialization effect" by transcriptional narrowing and intensification, and molecular specialization effects on metabolomic level Additionally, we performed multi-omics network and cluster analysis, providing a novel resource of skeletal muscle transcriptomic and metabolomic profiling in highly trained and untrained individuals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Exercise training has tremendous systemic tissue-specific health benefits, but the molecular adaptations to long-term exercise training are not completely understood. We investigated the skeletal muscle proteome of highly endurance-trained, strength-trained, and untrained individuals and performed exercise- and sex-specific analyses. Of the 6,000+ proteins identified, >650 were differentially expressed in endurance-trained individuals compared with controls. Strikingly, 92% of the shared proteins with higher expression in both the male and female endurance groups were known mitochondrial. In contrast to the findings in endurance-trained individuals, minimal differences were found in strength-trained individuals and between females and males. Lastly, a co-expression network and comparative literature analysis revealed key proteins and pathways related to the health benefits of exercise, which were primarily related to differences in mitochondrial proteins. This network is available as an interactive database resource where investigators can correlate clinical data with global gene and protein expression data for hypothesis generation., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

The aim was to investigate the effects of physical activity on prescription (PAP) compared with standard care (SC) in adult drug-naïve T2D patients. A randomized control trial was conducted with drug-naïve T2D patients attending an out-patient clinic Vietnam. Participants were randomly assigned to the PAP group (n+=+44) or the SC group (n+=+43). The PAP group received individualized recommendations for PA, intensive face-to-face training every two weeks. The SC group received the standard recommendations according to WHO guidelines. The mean HbA1c level change was larger (-10.6±6.4 mmol/mol) in the PAP group than in the SC group (-2.4±5.8 mmol/mol) (p<0.001). A one thousand step counts per day increase was significantly associated with a decrease of -2.43 mmol/mol in HbA1c [β=-2.43, 95%CI: (-2.94, -1.92]) in the PAP group. The fasting plasma glucose levels of the PAP group decreased significantly compared with the SC group. The VO2-max increased significantly more in the PAP group than in the SC group. PAP had clear positive effects on health-related Quality of Life [mean between group difference: 9.54 (95%CI 5.84,13.23)]. Insulin resistance, BMI, waist circumference, total cholesterol, LDL cholesterol and triglycerides were significantly more decreased in the PAP group than in the control group. In conclusion, the fact that even a small change in mean step counts over three months had a beneficial effect on health-related outcomes in drug-naïve T2D patients can have large implications for treatment and management practices, not least in a middle-income country like Vietnam., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Aim: While manual quantification is still considered the gold standard for skeletal muscle histological analysis, it is time-consuming and prone to investigator bias. To address this challenge, we assembled an automated image analysis pipeline, FiNuTyper (Fiber and Nucleus Typer)., Methods: We integrated recently developed deep learning-based image segmentation methods, optimized for unbiased evaluation of fresh and postmortem human skeletal muscle, and utilized SERCA1 and SERCA2 as type-specific myonucleus and myofiber markers after validating them against the traditional use of MyHC isoforms., Results: Parameters including cross-sectional area, myonuclei per fiber, myonuclear domain, central myonuclei per fiber, and grouped myofiber ratio were determined in a fiber-type-specific manner, revealing that a large degree of sex- and muscle-related heterogeneity could be detected using the pipeline. Our platform was also tested on pathological muscle tissue (ALS and IBM) and adapted for the detection of other resident cell types (leucocytes, satellite cells, capillary endothelium)., Conclusion: In summary, we present an automated image analysis tool for the simultaneous quantification of myofiber and myonuclear types, to characterize the composition and structure of healthy and diseased human skeletal muscle., (© 2023 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)

Background: Patients with severe mental disorders suffer from higher rates of poor somatic health and have shorter life expectancy than the average population. Physical activity can treat and prevent several diseases, e.g. cardiovascular and metabolic disorders as well as psychiatric symptoms. It is therefore of utmost importance to develop effective methods to integrate physical activity into psychiatric care. To meet this need, the physical activity intervention Braining was developed. This study aims to describe Braining, to assess the number of patients reached during the first years of pilot testing, to analyze clinical data in the group of patients participating in Braining 2017-2020 and to assess the intervention., Methods: In this descriptive retrospective study we analyzed data from all patients participating in Braining training sessions ≥ 3 times (n = 239), the Braining Participants. Regular patients at the clinic served as a comparison. Furthermore, medical records were studied for a smaller cohort (n = 51), the Braining Pilot Cohort. Data was analyzed using Chi-square and Fisher's tests., Results: During the introduction period of Braining, 580 patients attended an information meeting about Braining, or at least one training session. 239 patients participated in ≥ 3 training sessions, considered to be participants of Braining. These Braining Participants (n = 239), ages 19 to 82, males 23.4%, attended between 3 and 308 training sessions (median 9). The main diagnoses were affective and anxiety disorders. Number of diagnoses ranged from 0 to 10 (median = 2). For the subsample, the Braining Pilot Cohort (n = 51), participants attended between 3 and 208 training sessions (median = 20). Twelve percent were working full-time, and symptom severity of depression and general anxiety was moderate. Two thirds had ≥ 3 different classes of medication. Regarding metabolic morbidity, 28 had been diagnosed with hypertension, though blood lipids, blood glucose as well as blood pressure were within the normal range. Thirty-seven percent were prescribed Physical Activity on Prescription during 2017-2020. One severe adverse event was reported., Conclusions: The Braining intervention reached all age-groups and patients with a wide and representative diagnostic panorama, suggesting that Braining could be a promising and safe method for implementing physical activity in a psychiatric patient population., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The skeletal muscle and the immune system are heavily affected by the space environment. The crosstalk between these organs, although established, is not fully understood. This study determined the nature of immune cell changes in the murine skeletal muscle following (hindlimb) unloading combined with an acute session of irradiation (HLUR). Our findings show that 14 days of HLUR induces a significant increase of myeloid immune cell infiltration in skeletal muscle., (© 2023. The Author(s).)

The role of exercise in cancer prevention and control is increasingly recognized, and based on preclinical studies, it is hypothesized that mobilization of leukocytes plays an important role in the anti-tumor effect. Thus, we examined how 10-min acute exercise modulates immune cells in newly diagnosed breast cancer patients. Blood samples were taken at rest, immediately after exercise and 30 min after exercise and phenotypic characterization of major leukocyte subsets was done using 9-color flow cytometry. Total leukocyte count increased by 29%, CD8 + T cell count by 34%, CD19 + B cell count by 18%, CD56 + CD16 + NK cell count by 130%, and CD14 + CD16 + monocyte count by 51% immediately after acute exercise. Mobilization of CD45 + , CD8 + , CD19 + , and CD56 + CD16 + cells correlated positively with exercising systolic blood pressure, heart rate percentage of age predicted maximal heart rate, rate pressure product, and mean arterial pressure. Our findings indicate that a single bout of acute exercise of only 10 min can cause leukocytosis in breast cancer patients. Mobilization of leukocytes appear to be directly related to the intensity of exercise. It is possible that the positive effect of exercise on oncologic outcome might be partly due to immune cell mobilization as documented in the present study., (© 2023. The Author(s).)

Background: Physical activity is essential to improve health and reduce the risk of recurrence of stroke or transient ischemic attack (TIA). Still, people post stroke or TIA are often physically inactive and the availability of physical activity promotion services are often limited. This study builds on an existing Australian telehealth-delivered programme (i-REBOUND- Let's get moving) which provides support for home-based physical activity for people post stroke or TIA. The aim of this study is to test the feasibility, acceptability, and preliminary effects of a mobile Health (mHealth) version of the i-REBOUND programme for the promotion of physical activity in people post stroke or TIA living in Sweden., Methods: One hundred and twenty participants with stroke or TIA will be recruited via advertisement. A parallel-group feasibility randomised controlled trial design with a 1:1 allocation ratio to 1) i-REBOUND programme receiving physical exercise and support for sustained engagement in physical activity through behavioural change techniques, or 2) behavioural change techniques for physical activity. Both interventions will proceed for six months and be delivered digitally through a mobile app. The feasibility outcomes (i.e., reach, adherence, safety and fidelity) will be monitored throughout the study. Acceptability will be assessed using the Telehealth Usability Questionnaire and further explored through qualitative interviews with a subset of both study participants and the physiotherapists delivering the intervention. Clinical outcomes on preliminary effects of the intervention will include blood pressure, engagement in physical activity, self-perceived exercise self-efficacy, fatigue, depression, anxiety, stress and health-related quality of life and will be measured at baseline and at 3, 6 and 12 months after the baseline assessments., Discussion: We hypothesise that the mHealth delivery of the i-REBOUND programme will be feasible and acceptable in people post stroke/TIA living in rural and urban regions of Sweden. The results of this feasibility trial will inform the development of full-scale and appropriately powered trial to test the effects and costs of mHealth delivered physical activity for people after stroke or TIA., Trial Registration: ClinicalTrials.gov Identifier: NCT05111951. Registered November 8, 2021., (© 2023. The Author(s).)

Background: Studies have shown that acute exercise can mobilize several leukocyte subpopulations in healthy individuals. Our aim was to investigate whether a 10-min acute exercise has an effect on immune cell proportions in lymphoma patients. Methods: This study included seven lymphoma patients referred to curative oncologic therapy. Three had Hodgkin and four non-Hodgkin lymphoma, one was female, and their mean age was 51. Patients underwent a 10-min acute exercise on a bicycle ergometer at moderate exercise intensity. Whole blood samples were taken at rest, immediately after exercise, and 30 min after exercise. Leukocyte subpopulation levels were determined using flow cytometry. Results: Proportions of total NK cells and CD56 + CD16 + NK cells of total leukocytes increased immediately after exercise and decreased back to baseline at 30 min post-exercise. Proportion of CD8 + T cells of total T cells increased and proportion of CD4 + T cells of total T cells decreased immediately after exercise, and both returned to baseline at 30 min post-exercise. There was no change in the proportions of B cells, granulocytes, or monocytes. Exercising diastolic blood pressure correlated positively with changes in total NK cell and CD56 + CD16 + NK cell proportions, and exercising mean arterial pressure correlated positively with change in CD56 + CD16 + NK cell proportion. Conclusion: Our findings indicate that a single acute exercise bout of only 10 min can cause leukocytosis in lymphoma patients, particularly on cytotoxic T cells and NK cells, which are the most important immune cells fighting against cancer., 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 © 2023 Koivula, Lempiäinen, Rinne, Hollmén, Sundberg, Rundqvist, Minn and Heinonen.)

Objective: To evaluate the effectiveness of Tobacco Cessation on Prescription (TCP) compared to standard treatment in socioeconomically disadvantaged areas in Swedish primary healthcare (PHC)., Study Design: A pragmatic cluster randomized controlled trial, where randomization was conducted at the PHC center level using a computer-generated random allocation sequence., Setting: 18 PHC centers in socioeconomically disadvantaged areas in Stockholm., Participants: 250 adult daily tobacco users (56% female, 41% foreign born) with Swedish social security numbers and permanent resident permits, fluent in Swedish or Arabic, of which 140 responded to the follow-up at 6 months and 139 to the follow-up at 12 months. No blinding was applied., Interventions: TCP (tobacco cessation counseling for ≥10 minutes, an individualized prescription for tobacco cessation treatment and follow-up on ≥1 occasion) compared to standard treatment., Primary and Secondary Outcome Measures: The primary outcome was self-reported 7-day abstinence at 6 months and the secondary outcomes included self-reported 7-day abstinence at 12 months and 3-month continued abstinence at 6 and 12 months follow-up., Results: PHC centers were randomized to the intervention group (n = 8) and control group (n = 10). At the PHC centers, 250 patients (TCP n = 188, standard treatment n = 62) were recruited. There was a statistically significant effect of TCP compared to standard treatment for the outcomes 7-day abstinence at 6 months (OR adjusted 5.4, 95% CI 1.57 to 18.93) and 3-month continued abstinence at 6 (OR adjusted 6.4, 95% CI 1.30 to 31.27) and 12 months follow-up (OR adjusted 7.8, 95% CI 1.25 to 48.82)., Conclusions: TCP may be effective in achieving abstinence from tobacco use compared to standard treatment in the given setting but due to several limitations, resulting in high attrition rates and a low statistical power in the study, more research is needed to evaluate this., Trial Registration: ISRCTN 11498135., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Leppänen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Objective: Chest pain is one of the most common complaints in emergency departments (EDs). Self-reported computerized history taking (CHT) programmes can be used for interpretation of the clinical significance of medical information coming directly from patients. The adoption of CHT in clinical practice depends on reactions and attitudes to the technology from patients and their belief that the technology will have benefits for their medical care. The study objective was to explore the user experience of the self-reported CHT programme Clinical Expert Operating System (CLEOS) in the setting of patients visiting an ED for acute chest pain., Methods: This qualitative interview study is part of the ongoing CLEOS-Chest Pain Danderyd Study. A subset (n = 84) of the larger sample who had taken part in self-reported history taking during waiting times at the ED were contacted by telephone and n = 54 (64%) accepted participation. An interview guide with open-ended questions was used and the text was analysed using directed content analysis., Results: The patients' experiences of the CLEOS programme were overall positive although some perceived it as extensive. The programme was well accepted and despite the busy environment, patients were highly motivated and deemed it helpful to make a diagnosis. Six categories of user experience emerged: The clinical context, The individual context, Time aspect, Acceptability of the programme, Usability of the programme and Perceptions of usefulness in a clinical setting., Conclusions: The programme was well accepted by most patients in the stressful environment at ED although some found it difficult to answer all the questions. Adjustments to the extent of an interview to better suit the context of the clinical use should be a future development of the programme. The findings suggest that CHT programmes can be integrated as a standard process for collecting self-reported medical history data in the ED setting., (© 2022 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Introduction: Long COVID-19, where symptoms persist 12 weeks after the initial SARS-CoV-2-infection, is a substantial problem for individuals and society in the surge of the pandemic. Common symptoms are fatigue, postexertional malaise and cognitive dysfunction. There is currently no effective treatment and the underlying mechanisms are unknown, although several hypotheses exist, with chronic inflammation as a common denominator. In prospective studies, hyperbaric oxygen therapy (HBOT) has been suggested to be effective for the treatment of similar syndromes such as chronic fatigue syndrome and fibromyalgia. A case series has suggested positive effects of HBOT in long COVID-19. This randomised, placebo-controlled clinical trial will explore HBOT as a potential treatment for long COVID-19. The primary objective is to evaluate if HBOT improves health-related quality of life (HRQoL) for patients with long COVID-19 compared with placebo/sham. The main secondary objective is to evaluate whether HBOT improves endothelial function, objective physical performance and short-term HRQoL., Methods and Analysis: A randomised, placebo-controlled, double-blind, phase II clinical trial in 80 previously healthy subjects debilitated due to long COVID-19, with low HRQoL. Clinical data, HRQoL questionnaires, blood samples, objective tests and activity metre data will be collected at baseline. Subjects will be randomised to a maximum of 10 treatments with hyperbaric oxygen or sham treatment over 6 weeks. Assessments for safety and efficacy will be performed at 6, 13, 26 and 52 weeks, with the primary endpoint (physical domains in RAND 36-Item Health Survey) and main secondary endpoints defined at 13 weeks after baseline. Data will be reviewed by an independent data safety monitoring board., Ethics and Dissemination: The trial is approved by the Swedish National Institutional Review Board (2021-02634) and the Swedish Medical Products Agency (5.1-2020-36673). Positive, negative and inconclusive results will be published in peer-reviewed scientific journals with open access., Trial Registration Number: NCT04842448., Competing Interests: Competing interests: AK and PL disclose funding from Swedish Heart-Lung Foundation (HLF) and Stockholm Health Council for the present trial. AK disclose funding from Oura Health Oy with complimentary hardware and software for the Oura rings. MS discloses funding from Swedish Research Council and Dysautonomia International during the trial and previously from HLF. MS also disclose consulting fees from the Swedish Agency for Health Technology Assessment of Social Services, speaker honoraria from Orion Pharma, Werfen, and has filed a patent for pharmacological treatment in post-COVID postural orthostatic tachycardia syndrome. JK declares consulting fee for statistical work in this trial. LA-H, AH, SEG, SA-E, EB, CJS, JP, KM, KRW, XZ, SBC, MR, JB and MN-B declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Depression is common, increasing among adolescents and carries risk of disability, lower educational achievements, cardiovascular disease, substance abuse, self-harm and suicide. The effects of evidence-based treatments with medication or psychotherapy are modest. Aerobic exercise is a promising intervention for adolescents with depression, but available studies are hampered by methodological shortcomings. This study aims to evaluate aerobic group exercise versus an active comparator of leisure group activities in adolescents from clinical services with mild-to-moderate depression., Methods and Analysis: This study is a multicentre randomised controlled trial at four psychiatric clinics in Sweden. Participants (n=122) will be randomised 1:1 to group exercise delivered by exercise professionals and supported by mental health (MH) workers or leisure activities lead by the same MH workers for 1 hour three times a week for 12 weeks. Participants will be assessed at baseline, single blind after 13 weeks and 26 weeks and openly after 1 year. Participants randomised to the leisure group will be offered exercise in the open phase. The primary outcome is clinician-rated Children's Depression Rating Scale-Revised. Secondary outcomes are self-rated Quick Inventory of Depressive Symptomatology, self-rated functioning; clinician-rated improvement and functioning; objectively measured aerobic capacity, muscular strength, muscular endurance, body composition and presence or activity of selected biological markers of neuroprotection and neuroinflammation in blood samples. Further outcomes are cost-effectiveness and adolescents', parents' and coaches' experiences of the interventions and an exploration of how the adolescents' health and lifestyle are influenced by the interventions through qualitative interviews., Ethics and Dissemination: The study is approved by the Swedish Ethical Review Authority (Ref. 2021-05307-01). Informed consent in writing will be provided from patients and parents of participants below 15 years of age. The results of this study will be communicated to the included participants and healthcare providers and also submitted for publication in peer-reviewed journals., Trial Registration Number: NCT05076214., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This study investigated body composition measures in highly trained and untrained individuals using whole-body magnetic resonance imaging (MRI). Additionally, correlations between these measures and skeletal muscle gene expression were performed. Thirty-six individuals were included: endurance-trained males (ME, n = 8) and females (FE, n = 7), strength-trained males (MS, n = 7), and untrained control males (MC, n = 8) and females (FC, n = 6). MRI scans were performed, and resting M. vastus lateralis (VL) biopsies were subjected to RNA sequencing. Liver fat fraction, visceral adipose tissue volume (VAT), total body fat, and total lean tissue were measured from MRI data. Additionally, cross-sectional area (CSA) and fat signal fraction (FSF) were calculated from Mm. pectoralis, M. erector spinae and M. multifidus combined, Mm. quadriceps, and Mm. triceps surae (TS). Liver fat fraction, VAT, and total body fat relative to body weight were lower in ME and FE compared with corresponding controls. MS had a larger CSA across all four muscle groups and lower FSF in all muscles apart from TS compared with MC. ME had a lower FSF across all muscle groups and a larger CSA in all muscles except TS than MC. FE athletes showed a higher CSA in Mm. pectoralis and Mm. quadriceps and a lower CSA in TS than FC with no CSA differences found in the back muscles investigated. Surprisingly, the only difference in FSF between FE and FC was found in Mm. pectoralis. Lastly, correlations between VL gene expression and VL CSA as well as FSF showed that genes positively correlated with CSA revealed an enrichment of the oxidative phosphorylation and thermogenesis pathways, while the genes positively correlated with FSF showed significant enrichment of the spliceosome pathway. Although limited differences were found with training in females, our study suggests that both regular endurance and resistance training are useful in maintaining muscle mass, reducing adipose tissue deposits, and reducing muscle fat content in males., (© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Introduction: Infectious disease misinformation is widespread and poses challenges to disease control. There is limited evidence on how to effectively counter health misinformation in a community setting, particularly in low-income regions, and unsettled scientific debate about whether misinformation should be directly discussed and debunked, or implicitly countered by providing scientifically correct information., Methods: The Contagious Misinformation Trial developed and tested interventions designed to counter highly prevalent infectious disease misinformation in Sierra Leone, namely the beliefs that (1) mosquitoes cause typhoid and (2) typhoid co-occurs with malaria. The information intervention for group A (n=246) explicitly discussed misinformation and explained why it was incorrect and then provided the scientifically correct information. The intervention for group B (n=245) only focused on providing correct information, without directly discussing related misinformation. Both interventions were delivered via audio dramas on WhatsApp that incorporated local cultural understandings of typhoid. Participants were randomised 1:1:1 to the intervention groups or the control group (n=245), who received two episodes about breast feeding., Results: At baseline 51% believed that typhoid is caused by mosquitoes and 59% believed that typhoid and malaria always co-occur. The endline survey was completed by 91% of participants. Results from the intention-to-treat, per-protocol and as-treated analyses show that both interventions substantially reduced belief in misinformation compared with the control group. Estimates from these analyses, as well as an exploratory dose-response analysis, suggest that direct debunking may be more effective at countering misinformation. Both interventions improved people's knowledge and self-reported behaviour around typhoid risk reduction, and yielded self-reported increases in an important preventive method, drinking treated water., Conclusion: These results from a field experiment in a community setting show that highly prevalent health misinformation can be countered, and that direct, detailed debunking may be most effective., Trial Registration Number: NCT04112680., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: Chest pain is one of the most common chief complaints in emergency departments (EDs). Collecting an adequate medical history is challenging but essential in order to use recommended risk scores such as the HEART score (based on history, electrocardiogram, age, risk factors, and troponin). Self-reported computerized history taking (CHT) is a novel method to collect structured medical history data directly from the patient through a digital device. CHT is rarely used in clinical practice, and there is a lack of evidence for utility in an acute setting., Objective: This substudy of the Clinical Expert Operating System Chest Pain Danderyd Study (CLEOS-CPDS) aimed to evaluate whether patients with acute chest pain can interact effectively with CHT in the ED., Methods: Prospective cohort study on self-reported medical histories collected from acute chest pain patients using a CHT program on a tablet. Clinically stable patients aged 18 years and older with a chief complaint of chest pain, fluency in Swedish, and a nondiagnostic electrocardiogram or serum markers for acute coronary syndrome were eligible for inclusion. Patients unable to carry out an interview with CHT (eg, inadequate eyesight, confusion or agitation) were excluded. Effectiveness was assessed as the proportion of patients completing the interview and the time required in order to collect a medical history sufficient for cardiovascular risk stratification according to HEART score., Results: During 2017-2018, 500 participants were consecutively enrolled. The age and sex distribution (mean 54.3, SD 17.0 years; 213/500, 42.6% women) was similar to that of the general chest pain population (mean 57.5, SD 19.2 years; 49.6% women). Common reasons for noninclusion were language issues (182/1000, 18.2%), fatigue (158/1000, 15.8%), and inability to use a tablet (152/1000, 15.2%). Sufficient data to calculate HEART score were collected in 70.4% (352/500) of the patients. Key modules for chief complaint, cardiovascular history, and respiratory history were completed by 408 (81.6%), 339 (67.8%), and 291 (58.2%) of the 500 participants, respectively, while 148 (29.6%) completed the entire interview (in all 14 modules). Factors associated with completeness were age 18-69 years (all key modules: Ps<.001), male sex (cardiovascular: P=.04), active workers (all key modules: Ps<.005), not arriving by ambulance (chief complaint: P=.03; cardiovascular: P=.045), and ongoing chest pain (complete interview: P=.002). The median time to collect HEART score data was 23 (IQR 18-31) minutes and to complete an interview was 64 (IQR 53-77) minutes. The main reasons for discontinuing the interview prior to completion (n=352) were discharge from the ED (101, 28.7%) and tiredness (95, 27.0%)., Conclusions: A majority of patients with acute chest pain can interact effectively with CHT on a tablet in the ED to provide sufficient data for risk stratification with a well-established risk score. The utility was somewhat lower in patients 70 years and older, in patients arriving by ambulance, and in patients without ongoing chest pain. Further studies are warranted to assess whether CHT can contribute to improved management and prognosis in this large patient group., Trial Registration: ClinicalTrials.gov NCT03439449; https://clinicaltrials.gov/ct2/show/NCT03439449., International Registered Report Identifier (irrid): RR2-10.1136/bmjopen-2019-031871., (©Helge Brandberg, Carl Johan Sundberg, Jonas Spaak, Sabine Koch, David Zakim, Thomas Kahan. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 27.04.2021.)

Purpose: Healing outcome after Achilles Tendon Rupture (ATR) is variable and unsatisfactory. Many ATR patients still exhibit pain, functional deficits and limitations in walking one-year post-surgery. The present study was designed to investigate the association between the expression of healing biomarkers and patient outcome after ATR., Methods: Tendon biopsies were collected from 25 ATR patients during surgery. At 1-year post surgery, all patients completed questionnaires; Achilles tendon Total Rupture Score (ATRS) and Foot and Ankle Outcome Score (FAOS), and were tested for functional outcomes by heel-rise test. In biopsies, FGF, COL III, FN, COL I and MMP-9 mRNA levels were assessed by quantitative RT-PCR while protein expression was studied by immunohistochemistry (IHC)., Results: Our analysis confirmed the presence of FGF, COL III, FN, COL I and MMP-9 at mRNA and protein levels in tendon biopsies. FGF gene expression associated positively with improved total ATRS and better functional outcomes. Additionally, FGF mRNA levels were associated with less pain, less running limitations and less loss in physical activity. In addition, higher COL III mRNA expression was associated with more tendon strength., Conclusion: Our findings indicate that FGF gene expression is associated with improved patient-reported outcome. FGF expression in surgical biopsies could potentially be used to assist the prognostic evaluation of patient outcome and may be used as a predictor for healing. However, further studies are needed to evaluate the role of FGF in Achilles tendon healing., Level of Evidence: II.

Reaching the recommendation on physical activity (PA) for health is highly important to effectively manage blood glucose in patients with type 2 diabetes (T2D). The aims of this study were to assess the level and pattern of PA among T2D outpatients and to relate PA levels to glucose control. A cross-sectional study was conducted in outpatient clinics in Hanoi, Vietnam. PA levels were reported using the Global Physical Activity Questionnaire (GPAQ) version 2.0. Participants meeting the WHO recommendations on PA for health or not were respectively categorized as "sufficiently active" and "insufficiently active". FPG < 7.2 mmol/L was defined as controlled plasma glucose. In total, 407 participants with T2D (55% women, mean (SD) age 61.6 (9.7) years) were included. The fraction of T2D outpatients reporting as insufficiently active was 21%. The lowest amount of energy expenditure was from transport activities (travel from and to places). On multivariate logistic regression, being sufficiently active was associated with a two-fold increased likelihood of having better glycemic control. The findings warrant action plans to increase physical activity in general and in specific active transport for T2D patients in Vietnam.

Introduction: Human skeletal muscle is thought to have heightened sensitivity to exercise stimulus when it has been previously trained (i.e., it possesses "muscle memory"). We investigated whether basal and acute resistance exercise-induced gene expression and cell signaling events are influenced by previous strength training history., Methods: Accordingly, 19 training naïve women and men completed 10 wk of unilateral leg strength training, followed by 20 wk of detraining. Subsequently, an acute resistance exercise session was performed for both legs, with vastus lateralis biopsies taken at rest and 1 h after exercise in both legs (memory and control)., Results: The phosphorylation of AMPK and eEF2 was higher in the memory leg than that in the control leg at both time points. The postexercise phosphorylation of 4E-BP1 was higher in the memory leg than that in the control leg. The memory leg had lower basal mRNA levels of total PGC1α and, unlike the control leg, exhibited increases in PGC1α-ex1a transcripts after exercise. In the genes related to myogenesis (SETD3, MYOD1, and MYOG), mRNA levels differed between the memory and the untrained leg; these effects were evident primarily in the male subjects. Expression of the novel gene SPRYD7 was lower in the memory leg at rest and decreased after exercise only in the control leg, but SPRYD7 protein levels were higher in the memory leg., Conclusion: In conclusion, several key regulatory genes and proteins involved in muscular adaptations to resistance exercise are influenced by previous training history. Although the relevance and mechanistic explanation for these findings need further investigation, they support the view of a molecular muscle memory in response to training.

To better understand the health benefits of lifelong exercise in humans, we conduct global skeletal muscle transcriptomic analyses of long-term endurance- (9 men, 9 women) and strength-trained (7 men) humans compared with age-matched untrained controls (7 men, 8 women). Transcriptomic analysis, Gene Ontology, and genome-scale metabolic modeling demonstrate changes in pathways related to the prevention of metabolic diseases, particularly with endurance training. Our data also show prominent sex differences between controls and that these differences are reduced with endurance training. Additionally, we compare our data with studies examining muscle gene expression before and after a months-long training period in individuals with metabolic diseases. This analysis reveals that training shifts gene expression in individuals with impaired metabolism to become more similar to our endurance-trained group. Overall, our data provide an extensive examination of the accumulated transcriptional changes that occur with decades-long training and identify important "exercise-responsive" genes that could attenuate metabolic disease., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate why boards of directors engage in occupational health and safety (OHS) and what influences their level of engagement., Methods: Thirty-four board members and chief executive officers at large companies from the manufacturing, construction, trade, and health/social care sectors were interviewed. An inductive thematic analysis was conducted., Results: Five drivers organized along a continuum explain why boards engage: legal compliance, untoward events, external expectations/regulations, business drivers, and moral values. Certain factors influence the level of engagement: board's OHS competence, owner's agenda, and competing needs., Conclusions: Boards continuously prioritize among multiple foci. If a board's total engagement is likened to a pie, the size of the OHS slice will depend on the drivers, as well as on the influencing factors. We suggest that even boards with many drivers can down-prioritize OHS under certain conditions.

Background: Low physical performance is a predictor of morbidity and mortality. This study looks at long-term effects of an exercise intervention on maximal step-up height (MSH) in individuals with low physical function. Factors associated with changes in MSH was studied., Methods: Female patients ( n  = 101), mean (SD) age of 52 (11) years, were recruited for a 3-month group exercise intervention including 2-3 sessions/week of mixed aerobic fitness and strength training. MSH, weight, body mass index (BMI), waist circumference, maximal oxygen consumption (VO 2 -max), self-reported health (SF-36) and physical activity (PA) were measured at baseline (T0), after 3 months (T1) and after 14-30 (mean 22) months (T2). Relationships between changes in MSH (cm) and age, baseline MSH, time to follow-up, changes in anthropometric measurements, VO 2 -max, SF-36 and PA were studied with regression analyses., Results: MSH, significantly, increased from T0 to T1, 27.2 (5.7) to 29.0 (5.5) cm and decreased to 25.2 (5.5) cm at T2. Time to follow-up (B = - 0.42, p  < 0.001) and change in BMI (B = - 0.29, p  = 0.012) correlated significantly to changes in MSH. Waist circumference, VO 2 -max, PF and exercise/physical activity levels were significantly improved at T2, while BMI did not change. In a univariate logistic regression model, maintenance of MSH correlated to the extent of mixed training (OR 3.33, 95% CI 1.25-8.89). In a multivariate logistic regression model adjusted for important factors the correlation was not significant. However, MSH was significantly higher in individuals participating in 2-3 session per week compared to one session., Conclusions: A 3-month group exercise intervention increased MSH, improved fitness, decreased risk in female patients with elevated cardio-metabolic risk. After an average of 22 months MSH was reduced while positive effects remained for waist circumference, VO 2 -max, physical function and physical activity. However, regular group exercise 2-3 times per week with mixed aerobic fitness and strength training was associated with maintenance of MSH in a subgroup of patients. We suggest that such an intervention including regular support from healthcare professionals is a successful approach for maintaining improved leg-muscle strength among primary care patients., Trial Registration: ISRCTN21220201 September 18, 2019, retrospectively registered., Competing Interests: Competing interestsLAN has a patent relating to the device used for the step-up height assessments described in the manuscript, but has no financial relationship with any company or organisation. JK works as an independent consultant in biostatistics. He declares no conflicts of interest. The other authors declare that they have no competing interests., (© The Author(s) 2020.)

Objective: To investigate the potential of an acute bout of transcranial electrical stimulation to induce anabolic signalling., Design: Experimental intervention on healthy subjects., Subjects: Ten healthy subjects, 5 women and 5 men (mean age (standard deviation (SD) 32 years (SD 4))., Methods: The quadriceps muscle was stimulated at a frequency of 10 Hz for 10 s, followed by 20 s of rest, repeated 40 times over 20 min. Electromyography and force data were collected for all transcranial electrical stimulation sequences. Muscle biopsies were obtained from the vastus lateralis muscle before and 1 and 3 h after stimulation., Results: One bout of transcranial electrical stimulation decreased phosphorylation of AKT at Thr308 (1 h: -29%, 3 h: -38%; p < 0.05) and mTOR phosphorylation at Ser2448 (1 h: -10%; ns, 3 h: -21%; p < 0.05), both in the anabolic pathway. Phosphorylation of AMPK, ACC and ULK1 were not affected. c-MYC gene expression was unchanged following transcranial electrical stimulation, but rDNA transcription decreased (1 h: -28%, 3 h: -19%; p < 0.05). PGC1α-ex1b mRNA increased (1 h: 2.3-fold, 3 h: 2.6-fold; p < 0.05), which also correlated with vastus lateralis electromyography activity, while other PGC-1α variants were unchanged., Conclusion: Acute transcranial electrical stimulation of skeletal muscle in weight-bearing healthy individuals did not induce anabolic signalling, and some signs of impaired muscle anabolism were detected, suggesting limited potential in preventing muscle wasting.

Introduction: Management of acute chest pain focuses on diagnosis or safe rule-out of an acute coronary syndrome (ACS). We aim to determine the additional value of self-reported computerised history taking (CHT)., Methods and Analysis: Prospective cohort study design with self-reported, medical histories collected by a CHT programme (Clinical Expert Operating System, CLEOS) using a tablet. Women and men presenting with acute chest pain to the emergency department at Danderyd University Hospital (Stockholm, Sweden) are eligible. CHT will be compared with standard history taking for completeness of data required to calculate ACS risk scores such as History, ECG, Age, Risk factors and Troponin (HEART), Global Registry of Acute Coronary Events (GRACE), and Thrombolysis in Myocardial Infarction (TIMI). Clinical outcomes will be extracted from hospital electronic health records and national registries. The CLEOS-Chest Pain Danderyd Study project includes (1) a feasibility study of CHT, (2) a validation study of CHT as compared with standard history taking, (3) a paired diagnostic accuracy study using data from CHT and established risk scores, (4) a clinical utility study to evaluate the impact of CHT on the management of chest pain and the use of resources, and (5) data mining, aiming to generate an improved risk score for ACS. Primary outcomes will be analysed after 1000 patients, but to allow for subgroup analysis, the study intends to recruit 2000 or more patients. This ongoing project may lead to new and more effective ways for collecting thorough, accurate medical histories with important implications for clinical practice., Ethics and Dissemination: This study has been reviewed and approved by the Stockholm Regional Ethical Committee (now Swedish Ethical Review Authority). Results will be published, regardless of the outcome, in peer-reviewed international scientific journals., Trial Registration Number: This study is registered at https://www.clinicaltrials.gov (unique identifier: NCT03439449)., Competing Interests: Competing interests: DZ is the inventor on US patents for technology related to the CLEOS program. All patent rights and copyrights to technology, language, images and knowledge content are assigned without royalty rights by DZ to Karolinska Institutet, Stockholm, Sweden, which is a public university. Apart from Karolinska Institutet and its subsidiaries, no individuals or companies may be owners or receive royalties or other revenue from use of CLEOS technology, language, images, knowledge content or from clinical insights and/or computer algorithms generated from analysis of data acquired by the program. All CLEOS-CPDS steering group members (see above) will have full access to the final trial data set., (© 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.)

Medical experts are one of the main sources used by journalists in reporting on medical science. This study aims to 1) identify problems that medical experts encounter in contacts with the media representatives, 2) elucidate their attitudes about interactions with journalists and 3) reflect on solutions that could improve the quality of medical journalism. By using in-depth interviews, focus groups and a survey directed to 600 medical experts in 21 countries, this cohort study elucidates medical experts' experiences and views on participating in popular media. A strong interest in interacting with the media was identified among the experts, where nearly one fifth of the respondents in the survey claimed that they contacted the media more than 10 times per year. Six obstacles for improving the quality of medical reporting in the media were found: deadlines, headlines, choice of topic or angle, journalist's level of medical knowledge, differences in professional culture and colleagues' opinions. The main concern among experts was that short deadlines and exaggerated headlines could harm journalistic quality. It is possible that this is partly due to ongoing changes in the media landscape with many new platforms and less control functions. Nevertheless, for several reasons many experts have great interest in interacting with the media, something that could contribute to better communication and fewer misunderstandings. Our results highlight factors like expert networks, media training for scientists and regular meetings that may facilitate communication between medical experts and medical reporters., Competing Interests: The authors have declared that no competing interests exist.

Background: The news media is a key source for health and medical information, and relies to a large degree on material from press releases (PR). Medical universities are key players in the dissemination of PRs. This study aims to 1) explore the relation between the quality of press releases (PRs) from medical universities and their corresponding news stories (NSs) and 2) to identify the likelihood that specific scientific and interest-raising measures appear or are omitted in PRs and NSs., Methods and Findings: In this retrospective study using quantitative content analysis, PRs (n = 507) from 21 medical universities in Germany, the Netherlands, Sweden, the USA and the UK were retrieved. Of all PRs, 33% had media coverage, resulting in 496 NSs. With two codebooks, 18 scientific (e.g. reporting the study design of the study correctly) and 7 interest-raising measures (e.g. words like 'ground-breaking') were evaluated in the PRs and NSs. For all measures the percentage of presence in NSs and PRs was calculated, together with a Mean PR Influence Factor. Quality of PRs and NSs was defined as a score, based on 12 of the 18 scientific measures. Mean (SD) NS quality score was 6.5 (1.7) which was significantly lower than the PR score of 8.0 (1.5). The two quality scores were significantly correlated. Quality measures that were frequently omitted included reporting important study limitations (present in 21% of PRs, 21% of NSs), funding (59% of PRs, 7% of NSs) and conflicts of interest (16% of PRs, 3% of NSs). We did not evaluate the quality of the scientific papers (SPs), and can therefore not determine if the quality of PRs and NSs is associated with the quality of SPs., Conclusions: This large study of medical university press releases and corresponding news stories showed that important measures of a scientific study such as funding and study limitations were omitted to a very large extent. The lay public and health personnel as well as policy makers, politicians and other decision makers may be misled by incomplete and partly inaccurate representations of scientific studies which could negatively affect important health-related behaviours and decisions., Competing Interests: JK is a paid employee of Biostatistics AB and AL is a paid employee of the National Swedish Broadcasting Corporations. JK also received fees for statistical consultancy, unrelated to this manuscript. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The burden of type 2 diabetes is increasing rapidly, not least in Sub-Saharan Africa, and disadvantaged populations are disproportionally affected. Self-management is a key strategy for people at risk of or with type 2 diabetes, but implementation is a challenge. The objective of this study is to assess the determinants of self-management from an implementation perspective in three settings: two rural districts in Uganda, an urban township in South Africa, and socio-economically disadvantaged suburbs in Sweden. Data collection followed an exploratory multiple-case study design, integrating data from interviews, focus group discussions, and observations. Data collection and analysis were guided by a contextualized version of a transdisciplinary framework for self-management. Findings indicate that people at risk of or with type 2 diabetes are aware of major self-management strategies, but fail to integrate these into their daily lives. Depending on the setting, opportunities to facilitate implementation of self-management include: improving patient-provider interaction, improving health service delivery, and encouraging community initiatives supporting self-management. Modification of the physical environment (e.g. accessibility to healthy food) and the socio-cultural environment (i.e. norms, values, attitudes, and social support) may have an important influence on people's lifestyle. Regarding the study methodology, we learned that this innovative approach can lead to a comprehensive analysis of self-management determinants across different settings. An important barrier was the difficult contextualization of concepts like perceived autonomy and self-efficacy. Intervention studies are needed to confirm whether the pathways suggested by this study are valid and to test the proposed opportunities for change., Competing Interests: The authors have declared that no competing interests exist.

This paper reports on the use of reciprocal learning for identifying, adopting and adapting a type 2 diabetes self-management support intervention in a multisite implementation trial conducted in a rural setting in a low-income country (Uganda), a periurban township in a middle-income country (South Africa) and socioeconomically disadvantaged suburbs in a high-income country (Sweden). The learning process was guided by a framework for knowledge translation and structured into three learning cycles, allowing for a balance between evidence, stakeholder interaction and contextual adaptation. Key factors included commitment, common goals, leadership and partnerships. Synergistic outcomes were the cocreation of knowledge, interventions and implementation methods, including reverse innovations such as adaption of community-linked models of care. Contextualisation was achieved by cross-site exchanges and local stakeholder interaction to balance intervention fidelity with local adaptation. Interdisciplinary and cross-site collaboration resulted in the establishment of learning networks. Limitations of reciprocal learning relate to the complexity of the process with unpredictable outcomes and the limited generalisability of results., Competing Interests: Competing interests: None declared.

Exercise has been suggested to ameliorate the detrimental effects of chemotherapy on skeletal muscle. The aim of this study was to compare the effects of different exercise regimens with usual care on skeletal muscle morphology and mitochondrial markers in patients being treated with chemotherapy for breast cancer. Specifically, we compared moderate-intensity aerobic training combined with high-intensity interval training (AT-HIIT) and resistance training combined with high-intensity interval training (RT-HIIT) with usual care (UC). Resting skeletal muscle biopsies were obtained pre- and postintervention from 23 randomly selected women from the OptiTrain breast cancer trial who underwent RT-HIIT, AT-HIIT, or UC for 16 wk. Over the intervention, citrate synthase activity, muscle fiber cross-sectional area, capillaries per fiber, and myosin heavy chain isoform type I were reduced in UC, whereas RT-HIIT and AT-HIIT were able to counteract these declines. AT-HIIT promoted up-regulation of the electron transport chain protein levels vs. UC. RT-HIIT favored satellite cell count vs. UC and AT-HIIT. There was a significant association between change in citrate synthase activity and self-reported fatigue. AT-HIIT and RT-HIIT maintained or improved markers of skeletal muscle function compared with the declines found in the UC group, indicating a sustained trainability in addition to the preservation of skeletal muscle structural and metabolic characteristics during chemotherapy. These findings highlight the importance of supervised exercise programs for patients with breast cancer during chemotherapy.-Mijwel, S., Cardinale, D. A., Norrbom, J., Chapman, M., Ivarsson, N., Wengström, Y., Sundberg, C. J., Rundqvist, H. Exercise training during chemotherapy preserves skeletal muscle fiber area, capillarization, and mitochondrial content in patients with breast cancer.

Background: Advanced therapeutic strategies are often accompanied by significant adverse effects, which warrant equally progressive countermeasures. Physical exercise has proven an effective intervention to improve physical function and reduce fatigue in patients undergoing chemotherapy. Effects of high-intensity interval training (HIIT) in this population are not well established although HIIT has proven effective in other clinical populations. The aim of the OptiTrain trial was to examine the effects of concurrent resistance and high-intensity interval training (RT-HIIT) or concurrent moderate-intensity aerobic and high-intensity interval training (AT-HIIT), to usual care (UC) on pain sensitivity and physiological outcomes in patients with breast cancer during chemotherapy., Methods: Two hundred and forty women were randomized to 16 weeks of RT-HIIT, AT-HIIT, or UC., Outcomes: cardiorespiratory fitness, muscle strength, body mass, hemoglobin levels, and pressure-pain threshold., Results: Pre- to post-intervention, RT-HIIT (ES = 0.41) and AT-HIIT (ES = 0.42) prevented the reduced cardiorespiratory fitness found with UC. Handgrip strength (surgery side: RT-HIIT vs. UC: ES = 0.41, RT-HIIT vs. AT-HIIT: ES = 0.28; non-surgery side: RT-HIIT vs. UC: ES = 0.35, RT-HIIT vs. AT-HIIT: ES = 0.22) and lower-limb muscle strength (RT-HIIT vs. UC: ES = 0.66, RT-HIIT vs. AT-HIIT: ES = 0.23) were significantly improved in the RT-HIIT. Increases in body mass were smaller in RT-HIIT (ES = - 0.16) and AT-HIIT (ES = - 0.16) versus UC. RT-HIIT reported higher pressure-pain thresholds than UC (trapezius: ES = 0.46, gluteus: ES = 0.53) and AT-HIIT (trapezius: ES = 0.30)., Conclusion: Sixteen weeks of RT-HIIT significantly improved muscle strength and reduced pain sensitivity. Both exercise programs were well tolerated and were equally efficient in preventing increases in body mass and in preventing declines in cardiorespiratory fitness. These results highlight the importance of implementing a combination of resistance and high-intensity interval training during chemotherapy for women with breast cancer.

Introduction: Type 2 diabetes (T2D) is increasingly contributing to the global burden of disease. Health systems in most parts of the world are struggling to diagnose and manage T2D, especially in low-income and middle-income countries, and among disadvantaged populations in high-income countries. The aim of this study is to determine the added benefit of community interventions onto health facility interventions, towards glycaemic control among persons with diabetes, and towards reduction in plasma glucose among persons with prediabetes., Methods and Analysis: An adaptive implementation cluster randomised trial is being implemented in two rural districts in Uganda with three clusters per study arm, in an urban township in South Africa with one cluster per study arm, and in socially disadvantaged suburbs in Stockholm, Sweden with one cluster per study arm. Clusters are communities within the catchment areas of participating primary healthcare facilities. There are two study arms comprising a facility plus community interventions arm and a facility-only interventions arm. Uganda has a third arm comprising usual care. Intervention strategies focus on organisation of care, linkage between health facility and the community, and strengthening patient role in self-management, community mobilisation and a supportive environment. Among T2D participants, the primary outcome is controlled plasma glucose; whereas among prediabetes participants the primary outcome is reduction in plasma glucose., Ethics and Dissemination: The study has received approval in Uganda from the Higher Degrees, Research and Ethics Committee of Makerere University School of Public Health and from the Uganda National Council for Science and Technology; in South Africa from the Biomedical Science Research Ethics Committee of the University of the Western Cape; and in Sweden from the Regional Ethical Board in Stockholm. Findings will be disseminated through peer-reviewed publications and scientific meetings., Trial Registration Number: ISRCTN11913581; Pre-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The striated activator of rho-signaling (STARS) protein acts as a link between external stimuli and exercise adaptation such as muscle hypertrophy. However, the acute and long-term adaptational response of STARS is still unclear. This study aimed at investigating the acute and long-term endurance training response on the mRNA and protein expression of STARS and its related upstream and downstream factors in human skeletal muscle. mRNA and protein levels of STARS and related factors were assessed in skeletal muscle of healthy young men and women following an acute bout of endurance exercise (n = 15) or 12 weeks of one-legged training (n = 23). Muscle biopsies were obtained before (acute and long-term), at 30 min, 2, and 6 h following acute exercise, and at 24 h following both acute exercise and long-term training. Following acute exercise, STARS mRNA was significantly elevated 3.9-fold at 30 min returning back to baseline 24 h after exercise. STARS protein levels were numerically but nonsignificantly increased 7.2-fold at 24 h. No changes in STARS or ERRα mRNA or STARS protein expression were seen following long-term training. PGC-1α mRNA increased 1.7-fold following long-term training. MRTF-A mRNA was increased both following acute exercise and long-term training, in contrast to SRF mRNA and protein which did not change. STARS mRNA is acutely upregulated with exercise, but there is no cumulative effect to long-term training as seen in PGC-1α mRNA expression. Exercise intensity might play a role in manifestation of protein expression, suggesting a more complex regulation of STARS., (© 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Purpose: Exercise training is an effective and safe way to counteract cancer-related fatigue (CRF) and to improve health-related quality of life (HRQoL). High-intensity interval training has proven beneficial for the health of clinical populations. The aim of this randomized controlled trial was to compare the effects of resistance and high-intensity interval training (RT-HIIT), and moderate-intensity aerobic and high-intensity interval training (AT-HIIT) to usual care (UC) in women with breast cancer undergoing chemotherapy. The primary endpoint was CRF and the secondary endpoints were HRQoL and cancer treatment-related symptoms., Methods: Two hundred and forty women planned to undergo chemotherapy were randomized to supervised RT-HIIT, AT-HIIT, or UC. Measurements were performed at baseline and at 16 weeks. Questionnaires included Piper Fatigue Scale, EORTC-QLQ-C30, and Memorial Symptom Assessment Scale., Results: The RT-HIIT group was superior to UC for CRF: total CRF (p = 0.02), behavior/daily life (p = 0.01), and sensory/physical (p = 0.03) CRF. Role functioning significantly improved while cognitive functioning was unchanged for RT-HIIT compared to declines shown in the UC group (p = 0.04). AT-HIIT significantly improved emotional functioning versus UC (p = 0.01) and was superior to UC for pain symptoms (p = 0.03). RT-HIIT reported a reduced symptom burden, while AT-HIIT remained stable compared to deteriorations shown by UC (p < 0.01). Only RT-HIIT was superior to UC for total symptoms (p < 0.01)., Conclusions: 16 weeks of resistance and HIIT was effective in preventing increases in CRF and in reducing symptom burden for patients during chemotherapy for breast cancer. These findings add to a growing body of evidence supporting the inclusion of structured exercise prescriptions, including HIIT, as a vital component of cancer rehabilitation., Trial Registration: Clinicaltrials.gov Registration Number: NCT02522260.

Chromatin immunoprecipitation (ChIP) is an invaluable method for studying interactions between histone proteins and genomic DNA regions and transcriptional regulation using antibodies to enrich genomic regions associated with these epitopes. Either to monitor the presence of histones with post-translational modifications at specific genomic locations or to measure transcription factor interactions with a candidate target gene, protein-DNA complexes are most commonly crosslinked using formaldehyde, which stabilizes these transient interactions. Chromatin is then fragmented to allow separation of genomic fragments bound by the histone or transcription factor of interest away from those that are unbound. Following immunoprecipitation, formaldehyde crosslinks are reversed and enriched DNA fragments are purified. While some investigators have successfully performed ChIP experiments from crosslinked skeletal muscle in cell culture, the process is relatively inefficient compared to whole tissue. This chapter provides protocols specifically designed for the crosslinking and immunoprecipitation of human skeletal muscle biopsy samples in preparation for chromatin immunoprecipitation-sequencing (ChIP-seq).