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Epicardium-derived cells (EPDC) and atrial stromal cells (ASC) display cardio-regenerative potential, but the molecular details are still unexplored. Signals which induce activation, migration and differentiation of these cells are largely unknown. Here we have isolated rat ventricular EPDC and rat/human ASC and performed genetic and proteomic profiling. EPDC and ASC expressed epicardial/mesenchymal markers (WT-1, Tbx18, CD73,CD90, CD44, CD105), cardiac markers (Gata4, Tbx5, troponin T) and also contained phosphocreatine. We used cell surface biotinylation to isolate plasma membrane proteins of rEPDC and hASC, Nano-liquid chromatography with subsequent mass spectrometry and bioinformatics analysis identified 396 rat and 239 human plasma membrane proteins with 149 overlapping proteins. Functional GO-term analysis revealed several significantly enriched categories related to extracellular matrix (ECM), cell migration/differentiation, immunology or angiogenesis. We identified receptors for ephrin and growth factors (IGF, PDGF, EGF, anthrax toxin) known to be involved in cardiac repair and regeneration. Functional category enrichment identified clusters around integrins, PI3K/Akt-signaling and various cardiomyopathies. Our study indicates that EPDC and ASC have a similar molecular phenotype related to cardiac healing/regeneration. The cell surface proteome repository will help to further unravel the molecular details of their cardio-regenerative potential and their role in cardiac diseases.
Population genomics of prokaryotes has been studied in depth in only a small number of primarily pathogenic bacteria, as genome sequences of isolates of diverse origin are lacking for most species. Here, we conducted a large‐scale survey of population structure in prevalent human gut microbial species, sampled from their natural environment, with a culture‐independent metagenomic approach. We examined the variation landscape of 71 species in 2,144 human fecal metagenomes and found that in 44 of these, accounting for 72% of the total assigned microbial abundance, single‐nucleotide variation clearly indicates the existence of sub‐populations (here termed subspecies). A single subspecies (per species) usually dominates within each host, as expected from ecological theory. At the global scale, geographic distributions of subspecies differ between phyla, with Firmicutes subspecies being significantly more geographically restricted. To investigate the functional significance of the delineated subspecies, we identified genes that consistently distinguish them in a manner that is independent of reference genomes. We further associated these subspecies‐specific genes with properties of the microbial community and the host. For example, two of the three Eubacterium rectale subspecies consistently harbor an accessory pro‐inflammatory flagellum operon that is associated with lower gut community diversity, higher host BMI, and higher blood fasting insulin levels. Using an additional 676 human oral samples, we further demonstrate the existence of niche specialized subspecies in the different parts of the oral cavity. Taken together, we provide evidence for subspecies in the majority of abundant gut prokaryotes, leading to a better functional and ecological understanding of the human gut microbiome in conjunction with its host.
Voltage-gated calcium channels (VGCCs) are widely distributed within the central nervous system (CNS) and presumed to play an important role in the pathophysiology of a broad spectrum of CNS disorders including Alzheimer’s and Parkinson’s disease as well as multiple sclerosis. Several calcium channel blockers have been in clinical practice for many years so that their toxicity and side effects are well studied. However, these drugs are primarily used for the treatment of cardiovascular diseases and most if not all effects on brain functions are secondary to peripheral effects on blood pressure and circulation. While the use of calcium channel antagonists for the treatment of CNS diseases therefore still heavily depends on the development of novel strategies to specifically target different channels and channel subunits, this review is meant to provide an impulse to further emphasize the importance of future research towards this goal.
This article presents a search for flavour-changing neutral currents in the decay of a top quark into an up-type (\({q = c, u}\)) quark and a Higgs boson, where the Higgs boson decays into two photons. The proton-proton collision data set analysed amounts to 36.1 fb\(^{−1}\) at \(\sqrt{s} = 13\) TeV collected by the ATLAS experiment at the LHC. Top quark pair events are searched for, where one top quark decays into \(qH\) and the other decays into \(bW\). Both the hadronic and leptonic decay modes of the \(W\) boson are used. No significant excess is observed and an upper limit is set on the \({t → cH}\) branching ratio of 2.2 × 10\(^{−3}\) at the 95% confidence level, while the expected limit in the absence of signal is 1.6 × 10\(^{−3}\). The corresponding limit on the \(tcH\) coupling is 0.090 at the 95% confidence level. The observed upper limit on the \({t → uH}\) branching ratio is 2.4 × 10\(^{−3}\).
A measurement of \(b\)-hadron pair production is presented, based on a data set corresponding to an integrated luminosity of 11.4 fb\(^{−1}\) of proton-proton collisions recorded at \(\sqrt{s}=8\) TeV with the ATLAS detector at the LHC. Events are selected in which a \(b\)-hadron is reconstructed in a decay channel containing \(J/ψ → μμ\), and a second \(b\)-hadron is reconstructed in a decay channel containing a muon. Results are presented in a fiducial volume defined by kinematic requirements on three muons based on those used in the analysis. The fiducial cross section is measured to be 17.7 ± 0.1(stat.) ± 2.0(syst.) nb. A number of normalised differential cross sections are also measured, and compared to predictions from the PHYTHIA8, HERWIG++, MADGRAPH5_AMC@NLO+PYTHIA8 and SHERPA event generators, providing new constraints on heavy flavour production.
A search for high-energy neutrino emission correlated with gamma-ray bursts outside the electromagnetic prompt-emission time window is presented. Using a stacking approach of the time delays between reported gamma-ray burst alerts and spatially coincident muon-neutrino signatures, data from the Antares neutrino telescope recorded between 2007 and 2012 are analysed. One year of public data from the IceCube detector between 2008 and 2009 have been also investigated. The respective timing profiles are scanned for statistically significant accumulations within 40 days of the Gamma Ray Burst, as expected from Lorentz Invariance Violation effects and some astrophysical models. No significant excess over the expected accidental coincidence rate could be found in either of the two data sets. The average strength of the neutrino signal is found to be fainter than one detectable neutrino signal per hundred gamma-ray bursts in the Antares data at 90% confidence level.
Sleep is a highly conserved and essential behaviour in many species, including the fruit fly Drosophila melanogaster. In the wild, sensory signalling encoding environmental information must be integrated with sleep drive to ensure that sleep is not initiated during detrimental conditions. However, the molecular and circuit mechanisms by which sleep timing is modulated by the environment are unclear. Here we introduce a novel behavioural paradigm to study this issue. We show that in male fruit flies, onset of the daytime siesta is delayed by ambient temperatures above 29°C. We term this effect Prolonged Morning Wakefulness (PMW). We show that signalling through the TrpA1 thermo-sensor is required for PMW, and that TrpA1 specifically impacts siesta onset, but not night sleep onset, in response to elevated temperatures. We identify two critical TrpA1-expressing circuits and show that both contact DN1p clock neurons, the output of which is also required for PMW. Finally, we identify the circadian blue-light photoreceptor CRYPTOCHROME as a molecular regulator of PMW, and propose a model in which the Drosophila nervous system integrates information encoding temperature, light, and time to dynamically control when sleep is initiated. Our results provide a platform to investigate how environmental inputs co-ordinately regulate sleep plasticity.
Background: Although there is solid evidence for the efficacy of in vivo and virtual reality (VR) exposure therapy for a specific phobia, there is a significant debate over whether techniques promoting distraction or relaxation have impairing or enhancing effects on treatment outcome. In the present pilot study, we investigated the effect of diaphragmatic breathing (DB) as a relaxation technique during VR exposure treatment.
Method: Twenty-nine patients with aviophobia were randomly assigned to VR exposure treatment either with or without diaphragmatic breathing (six cycles per minute). Subjective fear ratings, heart rate and skin conductance were assessed as indicators of fear during both the exposure and the test session one week later.
Results: The group that experienced VR exposure combined with diaphragmatic breathing showed a higher tendency to effectively overcome the fear of flying. Psychophysiological measures of fear decreased and self-efficacy increased in both groups with no significant difference between the groups.
Conclusions: Our findings indicate that diaphragmatic breathing during VR exposure does not interfere with the treatment outcome and may even enhance treatment effects of VR exposure therapy for aviophobic patients.
Natural Killer cells (NK) are lymphocytes with the potential to recognize and lyse cells which escaped T-cell mediated lysis due to their aberrant HLA expression profiles. Killer cell immunoglobulin-like receptors (KIR) influence NK-cell activity by mediation of activating or inhibitory signals upon interaction with HLA-C (C1, C2) ligands. Therefore, absence of ligands for donor inhibitory KIRs following hematopoietic stem cell transplantation (HSCT) may have an influence on its outcome. Previous studies showed that C1 negative patients have a decreased HSCT outcome. Our study, based on a cohort of 200 C1-negative patients, confirmed these findings for the endpoints: overall survival (OS: HR = 1.41, CI = 1.14–1.74, p = 0.0012), disease free survival (DFS: HR = 1.27, CI = 1.05–1.53, p = 0.015), treatment related mortality (TRM: HR = 1.41, CI = 1.01–1.96, p = 0.04), and relapse incidence (RI: HR = 1.33, CI = 1.01–1.75, p = 0.04) all being inferior when compared to C1-positive patients (n = 1246). Subsequent analysis showed that these findings applied for patients with myeloid malignancies but not for patients with lymphoproliferative diseases (OS: myeloid: HR = 1.51, CI = 1.15–1.99, p = 0.003; lymphoblastic: HR = 1.26, CI = 0.91–1.75, p = 0.16; DFS: myeloid: HR = 1.31, CI = 1.01–1.70, p = 0.04; lymphoblastic: HR = 1.21, CI = 0.90–1.61, p = 0.21; RI: myeloid: HR = 1.31, CI = 1.01–1.70, p = 0.04; lymphoblastic: HR = 1.21, CI = 0.90–1.61, p = 0.21). Interestingly, within the C1-negative patient group, transplantation with KIR2DS2 resulted in better OS (9/10 matched: HR = 0.24, CI = 0.08–0.67, p = 0.007) as well as DFS (9/10 matched: HR = 0,26, CI = 0.11–0.60, p = 0.002), and transplantation with KIR2DS1 positive donors was associated with a decreased RI (HR = 0.30, CI = 0.13–0.69, p = 0.005). TRM was increased when the donor was positive for KIR2DS1 (HR = 2.61, CI = 1.26–5.41, p = 0.001). Our findings suggest that inclusion of KIR2DS1/2/5 and KIR3DS1-genotyping in the unrelated donor search algorithm of C1-ligand negative patients with myeloid malignancies may prove to be of clinical relevance.
Background: Consensus guidelines are useful to improve clinical decision making. Therefore, the methodological evaluation of these guidelines is of paramount importance. Low quality information may guide to inadequate or harmful clinical decisions.
Objective: To evaluate the methodological quality of consensus guidelines published in implant dentistry using a validated methodological instrument.
Methods: The six implant dentistry journals with impact factors were scrutinised for consensus guidelines related to implant dentistry. Two assessors independently selected consensus guidelines, and four assessors independently evaluated their methodological quality using the Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument. Disagreements in the selection and evaluation of guidelines were resolved by consensus. First, the consensus guidelines were analysed alone. Then, systematic reviews conducted to support the guidelines were included in the analysis. Non-parametric statistics for dependent variables (Wilcoxon signed rank test) was used to compare both groups.
Results: Of 258 initially retrieved articles, 27 consensus guidelines were selected. Median scores in four domains (applicability, rigour of development, stakeholder involvement, and editorial independence), expressed as percentages of maximum possible domain scores, were below 50% (median, 26%, 30.70%, 41.70%, and 41.70%, respectively). The consensus guidelines and consensus guidelines + systematic reviews data sets could be compared for 19 guidelines, and the results showed significant improvements in all domain scores (p < 0.05).
Conclusions: Methodological improvement of consensus guidelines published in major implant dentistry journals is needed. The findings of the present study may help researchers to better develop consensus guidelines in implant dentistry, which will improve the quality and trust of information needed to make proper clinical decisions.
Accurate and detailed spatial soil information is essential for environmental modelling, risk assessment and decision making. The use of Remote Sensing data as secondary sources of information in digital soil mapping has been found to be cost effective and less time consuming compared to traditional soil mapping approaches. But the potentials of Remote Sensing data in improving knowledge of local scale soil information in West Africa have not been fully explored. This study investigated the use of high spatial resolution satellite data (RapidEye and Landsat), terrain/climatic data and laboratory analysed soil samples to map the spatial distribution of six soil properties–sand, silt, clay, cation exchange capacity (CEC), soil organic carbon (SOC) and nitrogen–in a 580 km2 agricultural watershed in south-western Burkina Faso. Four statistical prediction models–multiple linear regression (MLR), random forest regression (RFR), support vector machine (SVM), stochastic gradient boosting (SGB)–were tested and compared. Internal validation was conducted by cross validation while the predictions were validated against an independent set of soil samples considering the modelling area and an extrapolation area. Model performance statistics revealed that the machine learning techniques performed marginally better than the MLR, with the RFR providing in most cases the highest accuracy. The inability of MLR to handle non-linear relationships between dependent and independent variables was found to be a limitation in accurately predicting soil properties at unsampled locations. Satellite data acquired during ploughing or early crop development stages (e.g. May, June) were found to be the most important spectral predictors while elevation, temperature and precipitation came up as prominent terrain/climatic variables in predicting soil properties. The results further showed that shortwave infrared and near infrared channels of Landsat8 as well as soil specific indices of redness, coloration and saturation were prominent predictors in digital soil mapping. Considering the increased availability of freely available Remote Sensing data (e.g. Landsat, SRTM, Sentinels), soil information at local and regional scales in data poor regions such as West Africa can be improved with relatively little financial and human resources.
Hyperglycemia (HG) stimulates the production of reactive oxygen species in the heart through activation of NADPH oxidase 2 (NOX2). This production is independent of glucose metabolism but requires sodium/glucose cotransporters (SGLT). Seven SGLT isoforms (SGLT1 to 6 and sodium-myoinositol cotransporter-1, SMIT1) are known, although their expression and function in the heart remain elusive. We investigated these 7 isoforms and found that only SGLT1 and SMIT1 were expressed in mouse, rat and human hearts. In cardiomyocytes, galactose (transported through SGLT1) did not activate NOX2. Accordingly, SGLT1 deficiency did not prevent HG-induced NOX2 activation, ruling it out in the cellular response to HG. In contrast, myo-inositol (transported through SMIT1) reproduced the toxic effects of HG. SMIT1 overexpression exacerbated glucotoxicity and sensitized cardiomyocytes to HG, whereas its deletion prevented HG-induced NOX2 activation. In conclusion, our results show that heart SMIT1 senses HG and triggers NOX2 activation. This could participate in the redox signaling in hyperglycemic heart and contribute to the pathophysiology of diabetic cardiomyopathy.
Background: Fruits and vegetables are rich in compounds with proposed antioxidant, anti-allergic and anti-inflammatory properties, which could contribute to reduce the prevalence of asthma and allergic diseases.
Objective: We investigated the association between asthma, and chronic rhino-sinusitis (CRS) with intake of fruits and vegetables in European adults.
Methods: A stratified random sample was drawn from the Global Allergy and Asthma Network of Excellence (GA\(^2\)LEN) screening survey, in which 55,000 adults aged 15–75 answered a questionnaire on respiratory symptoms. Asthma score (derived from self-reported asthma symptoms) and CRS were the outcomes of interest. Dietary intake of 22 subgroups of fruits and vegetables was ascertained using the internationally validated GA\(^2\)LEN Food Frequency Questionnaire. Adjusted associations were examined with negative binomial and multiple regressions. Simes procedure was used to control for multiple testing.
Results: A total of 3206 individuals had valid data on asthma and dietary exposures of interest. 22.8% reported having at least 1 asthma symptom (asthma score ≥1), whilst 19.5% had CRS. After adjustment for potential confounders, asthma score was negatively associated with intake of dried fruits (β-coefficient −2.34; 95% confidence interval [CI] −4.09, −0.59), whilst CRS was statistically negatively associated with total intake of fruits (OR 0.73; 95% CI 0.55, 0.97). Conversely, a positive association was observed between asthma score and alliums vegetables (adjusted β-coefficient 0.23; 95% CI 0.06, 0.40). None of these associations remained statistically significant after controlling for multiple testing.
Conclusion and clinical relevance: There was no consistent evidence for an association of asthma or CRS with fruit and vegetable intake in this representative sample of European adults.
A precise and rapid adjustment of fluxes through metabolic pathways is crucial for organisms to prevail in changing environmental conditions. Based on this reasoning, many guiding principles that govern the evolution of metabolic networks and their regulation have been uncovered. To this end, methods from dynamic optimization are ideally suited since they allow to uncover optimality principles behind the regulation of metabolic networks. We used dynamic optimization to investigate the influence of toxic intermediates in connection with the efficiency of enzymes on the regulation of a linear metabolic pathway. Our results predict that transcriptional regulation favors the control of highly efficient enzymes with less toxic upstream intermediates to reduce accumulation of toxic downstream intermediates. We show that the derived optimality principles hold by the analysis of the interplay between intermediate toxicity and pathway regulation in the metabolic pathways of over 5000 sequenced prokaryotes. Moreover, using the lipopolysaccharide biosynthesis in Escherichia coli as an example, we show how knowledge about the relation of regulation, kinetic efficiency and intermediate toxicity can be used to identify drug targets, which control endogenous toxic metabolites and prevent microbial growth. Beyond prokaryotes, we discuss the potential of our findings for the development of antifungal drugs.
A new cyclic dipeptide, petrocidin A (\(\textbf{1}\)), along with three known compounds—2,3-dihydroxybenzoic acid (\(\textbf{2}\)), 2,3-dihydroxybenzamide (\(\textbf{3}\)), and maltol (\(\textbf{4}\))—were isolated from the solid culture of \(Streptomyces\) sp. SBT348. The strain \(Streptomyces\) sp. SBT348 had been prioritized in a strain collection of 64 sponge-associated actinomycetes based on its distinct metabolomic profile using liquid chromatography/high-resolution mass spectrometry (LC-HRMS) and nuclear magnetic resonance (NMR). The absolute configuration of all α-amino acids was determined by HPLC analysis after derivatization with Marfey’s reagent and comparison with commercially available reference amino acids. Structure elucidation was pursued in the presented study by mass spectrometry and NMR spectral data. Petrocidin A (\(\textbf{1}\)) and 2,3-dihydroxybenzamide (\(\textbf{3}\)) exhibited significant cytotoxicity towards the human promyelocytic HL-60 and the human colon adenocarcinoma HT-29 cell lines. These results demonstrated the potential of sponge-associated actinomycetes for the discovery of novel and pharmacologically active natural products.
Detailed information on the land cover types present and the horizontal position of the land–water interface is needed for sensitive coastal ecosystems throughout the Arctic, both to establish baselines against which the impacts of climate change can be assessed and to inform response operations in the event of environmental emergencies such as oil spills. Previous work has demonstrated potential for accurate classification via fusion of optical and SAR data, though what contribution either makes to model accuracy is not well established, nor is it clear what shorelines can be classified using optical or SAR data alone. In this research, we evaluate the relative value of quad pol RADARSAT-2 and Landsat 5 data for shoreline mapping by individually excluding both datasets from Random Forest models used to classify images acquired over Nunavut, Canada. In anticipation of the RADARSAT Constellation Mission (RCM), we also simulate and evaluate dual and compact polarimetric imagery for shoreline mapping. Results show that SAR data is needed for accurate discrimination of substrates as user’s and producer’s accuracies were 5–24% higher for models constructed with quad pol RADARSAT-2 and DEM data than models constructed with Landsat 5 and DEM data. Models based on simulated RCM and DEM data achieved significantly lower overall accuracies (71–77%) than models based on quad pol RADARSAT-2 and DEM data (80%), with Wetland and Tundra being most adversely affected. When classified together with Landsat 5 and DEM data, however, model accuracy was less affected by the SAR data type, with multiple polarizations and modes achieving independent overall accuracies within a range acceptable for operational mapping, at 89–91%. RCM is expected to contribute positively to ongoing efforts to monitor change and improve emergency preparedness throughout the Arctic.
\(Enterococcus\) species cause increasing numbers of infections in hospitals. They contribute to the increasing mortality rates, mostly in patients with comorbidities, who suffer from severe diseases. \(Enterococcus\) resistances against most antibiotics have been described, including novel antibiotics. Therefore, there is an ongoing demand for novel types of antibiotics that may overcome bacterial resistances. We discovered a novel class of antibiotics resulting from a simple one-pot reaction of indole and \(o\)-phthaldialdehyde. Differently substituted indolyl benzocarbazoles were yielded. Both the indole substitution and the positioning at the molecular scaffold influence the antibacterial activity towards the various strains of \(Enterococcus\) species with the highest relevance to nosocomial infections. Structure-activity relationships are discussed, and the first lead compounds were identified as also being effective in the case of a vancomycin resistance.
High-energy jets recoiling against missing transverse energy (MET) are powerful probes of dark matter at the LHC. Searches based on large MET signatures require a precise control of the \({Z(ν\overline{ν})}+\) jet background in the signal region. This can be achieved by taking accurate data in control regions dominated by \(Z(ℓ^+ℓ^−)+\) jet, \(W(ℓν)+\) jet and \(γ+\) jet production, and extrapolating to the \({Z(ν\overline{ν})}+\) jet background by means of precise theoretical predictions. In this context, recent advances in perturbative calculations open the door to significant sensitivity improvements in dark matter searches. In this spirit, we present a combination of state-of-the-art calculations for all relevant \(V+\) jets processes, including throughout NNLO QCD corrections and NLO electroweak corrections supplemented by Sudakov logarithms at two loops. Predictions at parton level are provided together with detailed recommendations for their usage in experimental analyses based on the reweighting of Monte Carlo samples. Particular attention is devoted to the estimate of theoretical uncertainties in the framework of dark matter searches, where subtle aspects such as correlations across different \(V+\) jet processes play a key role. The anticipated theoretical uncertainty in the \({Z(ν\overline{ν})}+\) jet background is at the few percent level up to the TeV range.
Background: Allergic rhinitis and asthma as single entities affect more boys than girls in childhood but more females in adulthood. However, it is unclear if this prevalence sex-shift also occurs in allergic rhinitis and concurrent asthma. Thus, our aim was to compare sex-specifc differences in the prevalence of coexisting allergic rhinitis and asthma in childhood, adolescence and adulthood.
Methods: Post-hoc analysis of systematic review with meta-analysis concerning sex-specific prevalence of allergic rhinitis. Using random-effects meta-analysis, we assessed male–female ratios for coexisting allergic rhinitis and asthma in children (0–10 years), adolescents (11–17) and adults (> 17). Electronic searches were performed using MEDLINE and EMBASE for the time period 2000–2014. We included population-based observational studies, reporting coexisting allergic rhinitis and asthma as outcome stratifed by sex. We excluded non-original or non-population-based studies, studies with only male or female participants or selective patient collectives.
Results: From a total of 6539 citations, 10 studies with a total of 93,483 participants met the inclusion criteria. The male–female ratios (95% CI) for coexisting allergic rhinitis and asthma were 1.65 (1.52; 1.78) in children (N = 6 studies), 0.61 (0.51; 0.72) in adolescents (N = 2) and 1.03 (0.79; 1.35) in adults (N = 2). Male–female ratios for allergic rhinitis only were 1.25 (1.19; 1.32, N = 5) in children, 0.80 (0.71; 0.89, N = 2) in adolescents and 0.98 (0.74; 1.30, N = 2) in adults, respectively.
Conclusions: The prevalence of coexisting allergic rhinitis and asthma shows a clear male predominance in childhood and seems to switch to a female predominance in adolescents. This switch was less pronounced for allergic rhinitis only.
Background: Beyond survival of nowadays >80%, modern childhood cancer treatment strives to preserve long-term health and quality of life. However, the majority of today’s survivors suffer from short- and long-term adverse effects such as cardiovascular and pulmonary diseases, obesity, osteoporosis, fatigue, depression, and reduced physical fitness and quality of life. Regular exercise can play a major role to mitigate or prevent such late-effects. Despite this, there are no data on the effects of regular exercise in childhood cancer survivors from randomized controlled trials (RCTs). \(Primary\) \(outcome\) of the current RCT is therefore the effect of a 12-months exercise program on a composite cardiovascular disease risk score in childhood cancer survivors. \(Secondary\) \(outcomes\) are single cardiovascular disease risk factors, glycaemic control, bone health, body composition, physical fitness, physical activity, quality of life, mental health, fatigue and adverse events (safety).
Methods: A total of 150 childhood cancer survivors aged ≥16 years and diagnosed ≥5 years prior to the study are recruited from Swiss paediatric oncology clinics. Following the baseline assessments patients are randomized 1:1 into an intervention and control group. Thereafter, they are seen at month 3, 6 and 12 for follow-up assessments. The intervention group is asked to add ≥2.5 h of intense physical activity/week, including 30 min of strength building and 2 h of aerobic exercises. In addition, they are told to reduce screen time by 25%. Regular consulting by physiotherapists, individual web-based activity diaries, and pedometer devices are used as motivational tools for the intervention group. The control group is asked to keep their physical activity levels constant.
Discussion: The results of this study will show whether a partially supervised exercise intervention can improve cardiovascular disease risk factors, bone health, body composition, physical activity and fitness, fatigue, mental health and quality of life in childhood cancer survivors. If the program will be effective, all relevant information of the SURfit physical activity intervention will be made available to interested clinics that treat and follow-up childhood cancer patients to promote exercise in their patients.