Older adults with reduced cerebrovascular reactivity exhibit high white matter hyperintensity burden.

Cerebrovascular reactivity (CVR) deficits may contribute to small vessel disease, such as white matter hyperintensities (WMH). Moreover, apolipoprotein-e4 (APOE4) carriers at genetic risk for Alzheimer's disease exhibit cerebrovascular dysfunction relative to non-carriers. We examined whether older adults, and APOE4 carriers specifically, with diminished CVR would exhibit higher WMH burden. Independently living older adults (N = 125, mean age = 69.2 years; SD = 7.6; 31.2% male) free of dementia or clinical stroke underwent brain MRI to quantify cerebral perfusion during CVR to hypercapnia and hypocapnia and determine WMH volume. Adjusting for age, sex and intracranial volume, hierarchical regression analysis revealed a significant association between whole brain CVR to hypercapnia and WMH overall [B = -.02, 95% CI (-.04, -.008), p =.003] and in APOE4 carriers [B = -.03, 95% CI (-.06, -.009), p =.009]. Findings suggest deficits in cerebral vasodilatory capacity are associated with WMH burden in older adults and future studies are warranted to further delineate the effect of APOE4 on precipitating WMH.

A Systematic Review of the Association between Psychological Resilience and Improved Psychosocial Outcomes in Prostate Cancer Patients. Could Resilience Training Have a Potential Role?

PURPOSE: A high incidence of psychosocial problems in prostate cancer patients has been reported including anxiety, depression and distress. These can add to the patients' disease burden and have been associated with unfavorable cancer treatment outcomes. Interventions designed to address them have found limited success, but psychological resilience (PR) training has never been formally tested. The measurement of PR in prostate cancer patients has been described and has been associated with more favorable psychosocial outcomes in these patients but it has never been systematically reviewed. The aim of this study was to conduct the first systematic review of those studies that have measured it using standardized scales and to determine the potential for resilience training to help overcome the significant psychosocial problems faced by prostate cancer patients. MATERIALS AND METHODS: We searched the literature to identify articles that measured PR among prostate cancer patients. RESULTS: Of 384 articles identified by the search criteria, there were 19 studies suitable for inclusion regarding 5,417 patients. The most commonly-used scale was the original Connor-Davidson Resilience Scale, or an abbreviated version of it. Possible scores range from 0 to 100, mean scores from these studies ranged from 72.9 to 87.1 (standard deviations varied between 13.2 and 16.3). PR was consistently associated with improved psychological outcomes including depression, anxiety and distress, although these were measured with a wide variety of methods making it difficult to quantify the effects. There was also evidence of PR mediating the physical effects of prostate cancer and treatment including urinary symptoms, fatigue and insomnia. CONCLUSIONS: As resilience training has been successful in other cancer settings, it seems likely that it could improve the significant adverse psychosocial outcomes that have been reported in prostate cancer patients and trials designed to objectively test it should be encouraged.

Heart rhythm in vitro: measuring stem cell-derived pacemaker cells on microelectrode arrays.

Background: Cardiac arrhythmias have markedly increased in recent decades, highlighting the urgent need for appropriate test systems to evaluate the efficacy and safety of new pharmaceuticals and the potential side effects of established drugs. Methods: The Microelectrode Array (MEA) system may be a suitable option, as it provides both real-time and non-invasive monitoring of cellular networks of spontaneously active cells. However, there is currently no commercially available cell source to apply this technology in the context of the cardiac conduction system (CCS). In response to this problem, our group has previously developed a protocol for the generation of pure functional cardiac pacemaker cells from mouse embryonic stem cells (ESCs). In addition, we compared the hanging drop method, which was previously utilized, with spherical plate-derived embryoid bodies (EBs) and the pacemaker cells that are differentiated from these. Results: We described the application of these pacemaker cells on the MEA platform, which required a number of crucial optimization steps in terms of coating, dissociation, and cell density. As a result, we were able to generate a monolayer of pure pacemaker cells on an MEA surface that is viable and electromechanically active for weeks. Furthermore, we introduced spherical plates as a convenient and scalable method to be applied for the production of induced sinoatrial bodies. Conclusion: We provide a tool to transfer modeling and analysis of cardiac rhythm diseases to the cell culture dish. Our system allows answering CCS-related queries within a cellular network, both under baseline conditions and post-drug exposure in a reliable and affordable manner. Ultimately, our approach may provide valuable guidance not only for cardiac pacemaker cells but also for the generation of an MEA test platform using other sensitive non-proliferating cell types.

In silico analysis of overall survival with YBX1 in male and female solid tumours.

The Y-box binding protein-1 (YBX1) gene codes for a multifunctional oncoprotein that is increasingly being linked to the regulations of many aspects of cancer cell biology. Disparities in treatment outcomes between male and female cancer patients are increasingly reported. This study aimed to examine the relationship between YBX1 expression and overall survival in male and female patients with solid tumours. Overall survival and YBX1 expression data for cohorts of male and female cancer patients obtained from freely available databases were analysed with a cox proportional hazard model with covariates of biological sex and YBX1 expression. Kaplan-Meier curves and Violin plots were constructed for segregated male and female cohorts. High YBX1 expression was significantly associated with poor survival in 2 female-only and 4 mixed-sex cancer sites. In female lung cancer patients, better survival and lower YBX1 expression were identified. The clinical importance of YBX1 expression in cancer ought to be evaluated in a sex-specific manner, especially in lung cancer.

Is biomedical research self-correcting? Modelling insights on the persistence of spurious science.

The reality that volumes of published biomedical research are not reproducible is an increasingly recognized problem. Spurious results reduce trustworthiness of reported science, increasing research waste. While science should be self-correcting from a philosophical perspective, that in insolation yields no information on efforts required to nullify suspect findings or factors shaping how quickly science may be corrected. There is also a paucity of information on how perverse incentives in the publishing ecosystem favouring novel positive findings over null results shape the ability of published science to self-correct. Knowledge of factors shaping self-correction of science remain obscure, limiting our ability to mitigate harms. This modelling study introduces a simple model to capture dynamics of the publication ecosystem, exploring factors influencing research waste, trustworthiness, corrective effort and time to correction. Results from this work indicate that research waste and corrective effort are highly dependent on field-specific false positive rates and time delays to corrective results to spurious findings are propagated. The model also suggests conditions under which biomedical science is self-correcting and those under which publication of correctives alone cannot stem propagation of untrustworthy results. Finally, this work models a variety of potential mitigation strategies, including researcher- and publisher-driven interventions.

Impact of human papillomavirus age-related prevalence and vaccination levels on interpretation of cervical screening modalities: a modelling study.

OBJECTIVE: Cervical screening is a life-saving intervention, which reduces the incidence of and mortality from cervical cancer in the population. Human papillomavirus (HPV) based screening modalities hold unique promise in improving screening accuracy. HPV prevalence varies markedly by age, as does resultant cervical intraepithelial neoplasia (CIN), with higher rates recorded in younger women. With the advent of effective vaccination for HPV drastically reducing prevalence of both HPV and CIN, it is critical to model how the accuracy of different screening approaches varies with age cohort and vaccination status. This work establishes a model for the age-specific prevalence of HPV factoring in vaccine coverage and predicts how the accuracy of common screening modalities is affected by age profile and vaccine uptake. DESIGN: Modelling study of HPV infection rates by age, ascertained from European cohorts prior to the introduction of vaccination. Reductions in HPV due to vaccination were estimated from the bounds predicted from multiple modelling studies, yielding a model for age-varying HPV and CIN grades 2 and above (CIN2+) prevalence. SETTING: Performance of both conventional liquid-based cytology (LBC) screening and HPV screening with LBC reflex (HPV reflex) was estimated under different simulated age cohorts and vaccination levels. PARTICIPANTS: Simulated populations of varying age and vaccination status. RESULTS: HPV-reflex modalities consistently result in much lower incidence of false positives than LBC testing, with an accuracy that improves even as HPV and CIN2+ rates decline. CONCLUSIONS: HPV-reflex tests outperform LBC tests across all age profiles, resulting in greater test accuracy. This improvement is especially pronounced as HPV infection rates fall and suggests HPV-reflex modalities are robust to future changes in the epidemiology of HPV.

BET-inhibitor DYB-41 reduces pulmonary inflammation and local and systemic cytokine levels in LPS-induced acute respiratory distress syndrome: an experimental rodent study.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a form of respiratory failure stemming from various underlying conditions that ultimately lead to inflammation and lung fibrosis. Bromodomain and Extra-Terminal motif (BET) inhibitors are a class of medications that selectively bind to the bromodomains of BET motif proteins, effectively reducing inflammation. However, the use of BET inhibitors in ARDS treatment has not been previously investigated. In our study, we induced ARDS in rats using endotoxin and administered a BET inhibitor. We evaluated the outcomes by examining inflammation markers and lung histopathology. RESULTS: Nine animals received treatment, while 12 served as controls. In the lung tissue of treated animals, we observed a significant reduction in TNFα levels (549 [149-977] pg/mg vs. 3010 [396-5529] pg/mg; p = 0.009) and IL-1ß levels (447 [369-580] pg/mg vs. 662 [523-924] pg/mg; p = 0.012), although IL-6 and IL-10 levels showed no significant differences. In the blood, treated animals exhibited a reduced TNFα level (25 [25-424] pg/ml vs. 900 [285-1744] pg/ml, p = 0.016), but IL-1ß levels were significantly higher (1254 [435-2474] pg/ml vs. 384 [213-907] pg/ml, p = 0.049). No differences were observed in IL-6 and IL-10 levels. There were no significant variations in lung tissue levels of TGF-ß, SP-D, or RAGE. Histopathological analysis revealed substantial damage, with notably less perivascular edema (3 vs 2; p = 0.0046) and visually more inflammatory cells. However, two semi-quantitative histopathologic scoring systems did not indicate significant differences. CONCLUSIONS: These preliminary findings suggest a potential beneficial effect of BET inhibitors in the treatment of acute lung injury and ARDS. Further validation and replication of these results with a larger cohort of animals, in diverse models, and using different BET inhibitors are needed to explore their clinical implications.

Multi-modal assessment of a cardiac stem cell therapy reveals distinct modulation of regional scar properties.

BACKGROUND: The initial idea of functional tissue replacement has shifted to the concept that injected cells positively modulate myocardial healing by a non-specific immune response of the transplanted cells within the target tissue. This alleged local modification of the scar requires assessment of regional properties of the left ventricular wall in addition to commonly applied measures of global morphological and functional parameters. Hence, we aimed at investigating the effect of cardiac cell therapy with cardiovascular progenitor cells, so-called cardiac induced cells, on both global and regional properties of the left ventricle by a multimodal imaging approach in a mouse model. METHODS: Myocardial infarction was induced in mice by ligation of the left anterior descending artery, the therapy group received an intramyocardial injection of 1 × 106 cardiac induced cells suspended in matrigel, the control group received matrigel only. [18F]FDG positron emission tomography imaging was performed after 17 days, to assess regional glucose metabolism. Three weeks after myocardial infarction, cardiac magnetic resonance imaging was performed for morphological and functional assessment of the left ventricle. Following these measurements, hearts were excised for histological examinations. RESULTS: Cell therapy had no significant effect on global morphological parameters. Similarly, there was no difference in scar size and capillary density between therapy and control group. However, there was a significant improvement in contractile function of the left ventricle - left ventricular ejection fraction, stroke volume and cardiac output. Regional analysis of the left ventricle identified changes of wall properties in the scar area as the putative mechanism. Cell therapy reduced the thinning of the scar and significantly improved its radial contractility. Furthermore, the metabolic defect, assessed by [18F]FDG, was significantly reduced by the cell therapy. CONCLUSION: Our data support the relevance of extending the assessment of global left ventricular parameters by a structured regional wall analysis for the evaluation of therapies targeting at modulation of healing myocardium. This approach will enable a deeper understanding of mechanisms underlying the effect of experimental regenerative therapies, thus paving the way for a successful translation into clinical application.

Effects of oxygen-prebreathing on tissue nitrogenation in normobaric and hyperbaric conditions.

BACKGROUND: Breathing pure oxygen causes nitrogen washout from tissues, a method commonly deployed to prevent decompression sickness from hypobaric exposure. Theoretically prebreathing oxygen increases the capacity for nitrogen uptake and potentially limits supersaturation during dives of short duration. We aimed to use 13N2, a radioactive nitrogen isotope, to quantify tissue nitrogen following normobaric and hyperbaric exposures. METHODS: Twenty Sprague Dawley rats were divided in 4 conditions; normobaric prebreathe, normobaric control, hyperbaric prebreathe, hyperbaric control. Prebreathed rats breathed oxygen for 1 h prior to the experiment whilst controls breathed air. Normobaric rats breathed air containing 13N2 at 100 kPa for 30 min, whereas hyperbaric rats breathed 13N2 at 700 kPa before being decompressed and sedated using air-isoflurane (without 13N2 for a few minutes). After euthanization, blood, brain, liver, femur and thigh muscle were analyzed by gamma counting. RESULTS: At normobaria prebreathing oxygen resulted in higher absolute nitrogen counts in blood (p = .034), as well as higher normalized counts in both the liver and muscle (p = .034). However, following hyperbaric exposure no differences were observed between conditions for any organ (p>.344). Both bone and muscle showed higher normalized counts after hyperbaria compared to normobaria. CONCLUSIONS: Oxygen prebreathing caused nitrogen elimination in normobaria that led to a larger "sink" and uptake of 13N2. The lack of difference between conditions in hyperbaria could be due to the duration and depth of the dive mitigating the effect of prebreathing. In the hyperbaric conditions the lower counts were likely due to off-gassing of nitrogen during the sedation procedure, suggest a few minutes was enough to off-gas in rodents. The higher normalized counts under hyperbaria in bone and muscle likely relate to these tissues being slower to on and off-gas nitrogen. Future experiments could include shorter dives and euthanization while breathing 13N2 to prevent off-gassing.

Region of Attainable Redaction, an extension of Ellipse of Insignificance analysis for gauging impacts of data redaction in dichotomous outcome trials.

In biomedical science, it is a reality that many published results do not withstand deeper investigation, and there is growing concern over a replicability crisis in science. Recently, Ellipse of Insignificance (EOI) analysis was introduced as a tool to allow researchers to gauge the robustness of reported results in dichotomous outcome design trials, giving precise deterministic values for the degree of miscoding between events and non-events tolerable simultaneously in both control and experimental arms (Grimes, 2022). While this is useful for situations where potential miscoding might transpire, it does not account for situations where apparently significant findings might result from accidental or deliberate data redaction in either the control or experimental arms of an experiment, or from missing data or systematic redaction. To address these scenarios, we introduce Region of Attainable Redaction (ROAR), a tool that extends EOI analysis to account for situations of potential data redaction. This produces a bounded cubic curve rather than an ellipse, and we outline how this can be used to identify potential redaction through an approach analogous to EOI. Applications are illustrated, and source code, including a web-based implementation that performs EOI and ROAR analysis in tandem for dichotomous outcome trials is provided.

Effects of physical activity and exercise on Nucleobindin-2 gene expression and Nesfatin-1 concentration: A rapid review.

The aim of this rapid review is to examine the research evidence that presents the effects of physical activity and exercise on Nucleobindin-2 (NUCB2) gene expression and Nesfatin-1 concentration. Five databases (PubMed, Science Direct, Springer, Wiley, and Google Scholar) were searched for eligible studies from the earliest available date to August 2023. In human studies, Nesfatin-1 concentration either remains unchanged or increases after exercise training. It appears that higher exercise intensity and longer duration of training accentuate the increase of blood Nesfatin-1 concentration. The few human studies that have examined the acute response of exercise on Nesfatin-1 concentration from blood draws show conflicting results. There is a severe lack of biopsy studies in humans which warrants attention. All published animal studies have used the mouse model. The majority show that regular exercise training increases tissue NUCB2/Nesfatin-1. In some animal studies, where the effects of exercise on tissue Nesfatin-1 concentration has been seen as significant, there has been no significant effect of exercise on plasma Nesfatin-1 concentration. All animal studies evaluated the effect of endurance training except one which used resistance training. No animal studies have investigated the effects of acute exercise, which warrants investigation. In conclusion, human and animal studies have shown that physical training can increase NUCB2/Nesfatin-1, but research evidence examining the effect of acute exercise is in its infancy. In addition, future comparative studies are needed to compare the effects of different training protocols on NUCB2/Nesfatin-1 in humans and animals.

Retinal Microvascular Density and Perfusion during an Insulin-Induced Hypoglycemia Episode: A Warning Call.

Aim: To evaluate retinal vascular perfusion and density by optical coherence tomography angiography (OCTA) before, during, and after hypoglycemia in individuals with diabetes mellitus with or without diabetic retinopathy (DR). Methods: A focused clinical history was performed, followed by an ophthalmological examination to document retinopathy status. OCTA was performed at baseline, at hypoglycemia, and at glucose normalization. Eye tracking and eye alignment devices on the platform were used to obtain a macular thickness cube (512 × 128) and vascular perfusion and density protocols of 3 × 3 mm. Retinal vascular reactivity was analyzed with superficial plexus vascular perfusion and density protocols on OCTA. Results: Fifty-two participants encompassing 97 eyes fulfilled the eligibility criteria. Their mean age was 42.9 ± 15.1 years (range, 22 to 65), and 20 (38.2%) were men. We found a statistically significant difference in vascular perfusion and density when comparing all groups at baseline. The controls had higher vascular perfusion and density values than the cases. Vascular perfusion and density were significantly reduced in all groups during the hypoglycemia episode, except for vascular density in DR cases. Conclusion: Acute hypoglycemia significantly alters the retinal vascularity in DM patients with and without DR, suggesting that repeated episodes of acute hypoglycemia could exacerbate retinopathy in the long term.

BPIFB4 and its longevity-associated haplotype protect from cardiac ischemia in humans and mice.

Long-living individuals (LLIs) escape age-related cardiovascular complications until the very last stage of life. Previous studies have shown that a Longevity-Associated Variant (LAV) of the BPI Fold Containing Family B Member 4 (BPIFB4) gene correlates with an extraordinarily prolonged life span. Moreover, delivery of the LAV-BPIFB4 gene exerted therapeutic action in murine models of atherosclerosis, limb ischemia, diabetic cardiomyopathy, and aging. We hypothesize that downregulation of BPIFB4 expression marks the severity of coronary artery disease (CAD) in human subjects, and supplementation of the LAV-BPIFB4 protects the heart from ischemia. In an elderly cohort with acute myocardial infarction (MI), patients with three-vessel CAD were characterized by lower levels of the natural logarithm (Ln) of peripheral blood BPIFB4 (p = 0.0077). The inverse association between Ln BPIFB4 and three-vessel CAD was confirmed by logistic regression adjusting for confounders (Odds Ratio = 0.81, p = 0.0054). Moreover, in infarcted mice, a single administration of LAV-BPIFB4 rescued cardiac function and vascularization. In vitro studies showed that LAV-BPIFB4 protein supplementation exerted chronotropic and inotropic actions on induced pluripotent stem cell (iPSC)-derived cardiomyocytes. In addition, LAV-BPIFB4 inhibited the pro-fibrotic phenotype in human cardiac fibroblasts. These findings provide a strong rationale and proof of concept evidence for treating CAD with the longevity BPIFB4 gene/protein.

Sarcomeric network analysis of ex vivo cultivated human atrial appendage tissue using super-resolution microscopy.

Investigating native human cardiac tissue with preserved 3D macro- and microarchitecture is fundamental for clinical and basic research. Unfortunately, the low accessibility of the human myocardium continues to limit scientific progress. To overcome this issue, utilizing atrial appendages of the human heart may become highly beneficial. Atrial appendages are often removed during open-heart surgery and can be preserved ex vivo as living tissue with varying durability depending on the culture method. In this study, we prepared living thin myocardial slices from left atrial appendages that were cultured using an air-liquid interface system for overall 10 days. Metabolic activity of the cultured slices was assessed using a conventional methyl thiazolyl tetrazolium (MTT) assay. To monitor the structural integrity of cardiomyocytes within the tissue, we implemented our recently described super-resolution microscopy approach that allows both qualitative and quantitative in-depth evaluation of sarcomere network based on parameters such as overall sarcomere content, filament size and orientation. Additionally, expression of mRNAs coding for key structural and functional proteins was analyzed by real-time reverse transcription polymerase chain reaction (qRT-PCR). Our findings demonstrate highly significant disassembly of contractile apparatus represented by degradation of [Formula: see text]-actinin filaments detected after three days in culture, while metabolic activity was constantly rising and remained high for up to seven days. However, gene expression of crucial cardiac markers strongly decreased after the first day in culture indicating an early destructive response to ex vivo conditions. Therefore, we suggest static cultivation of living myocardial slices derived from left atrial appendage and prepared according to our protocol only for short-termed experiments (e.g. medicinal drug testing), while introduction of electro-mechanical stimulation protocols may offer the possibility for long-term integrity of such constructs.

CCR2 macrophage response determines the functional outcome following cardiomyocyte transplantation.

BACKGROUND: The immune response is a crucial factor for mediating the benefit of cardiac cell therapies. Our previous research showed that cardiomyocyte transplantation alters the cardiac immune response and, when combined with short-term pharmacological CCR2 inhibition, resulted in diminished functional benefit. However, the specific role of innate immune cells, especially CCR2 macrophages on the outcome of cardiomyocyte transplantation, is unclear. METHODS: We compared the cellular, molecular, and functional outcome following cardiomyocyte transplantation in wildtype and T cell- and B cell-deficient Rag2del mice. The cardiac inflammatory response was assessed using flow cytometry. Gene expression profile was assessed using single-cell and bulk RNA sequencing. Cardiac function and morphology were determined using magnetic resonance tomography and immunohistochemistry respectively. RESULTS: Compared to wildtype mice, Rag2del mice show an increased innate immune response at steady state and disparate macrophage response after MI. Subsequent single-cell analyses after MI showed differences in macrophage development and a lower prevalence of CCR2 expressing macrophages. Cardiomyocyte transplantation increased NK cells and monocytes, while reducing CCR2-MHC-IIlo macrophages. Consequently, it led to increased mRNA levels of genes involved in extracellular remodelling, poor graft survival, and no functional improvement. Using machine learning-based feature selection, Mfge8 and Ccl7 were identified as the primary targets underlying these effects in the heart. CONCLUSIONS: Our results demonstrate that the improved functional outcome following cardiomyocyte transplantation is dependent on a specific CCR2 macrophage response. This work highlights the need to study the role of the immune response for cardiomyocyte cell therapy for successful clinical translation.

Cell Programming for Cardiovascular Disease Modeling and Therapy.

Cardiovascular diseases have a high mortality due to a very limited regenerative potential of lost cardiomyocytes and therefore are one of the leading causes of death in developed countries [...].

Youth Sport Participation Experiences From the Perspective of Hispanic/Latinx Parents and Their Children.

Hispanic/Latinx communities remain an underserved population in terms of health and physical activity opportunities. The rise of sport specialization can jeopardize these opportunities. Understanding the appeal and welcomeness that minoritized populations feel toward sport and sport specialization culture can play an important role in health promotion and breaking down barriers that widen the gap on physical activity levels in Hispanic/Latinx communities. To date, these studies have not qualitatively investigated Hispanic/Latinx youth sport dyads (parent and child) and how sport specialization perceptions have affected their sport participation experiences. We used a qualitative interpretative phenomenological analysis to explore experiences of Hispanic/Latinx high school athletes. We engaged in semistructured interviews with 12 parent-child dyads. The following 3 interrelated themes emerged: (a) expectations of youth sport participation, (b) meeting expectations of youth sport participation, (c) and (mis)alignment of cultures. Dyads describe a negative youth sport experience when both cultures do not align because of the rise in sport specialization and pay-to-play culture. Findings indicate that dyads understand what is necessary to participate in organized sport and do this by methods that are rooted in their Hispanic/Latinx culture.

New Approaches in Heart Research: Prevention Instead of Cardiomyoplasty?

Cardiovascular diseases are the leading cause of death in industrialized nations. Due to the high number of patients and expensive treatments, according to the Federal Statistical Office (2017) in Germany, cardiovascular diseases account for around 15% of total health costs. Advanced coronary artery disease is mainly the result of chronic disorders such as high blood pressure, diabetes, and dyslipidemia. In the modern obesogenic environment, many people are at greater risk of being overweight or obese. The hemodynamic load on the heart is influenced by extreme obesity, which often leads to myocardial infarction (MI), cardiac arrhythmias, and heart failure. In addition, obesity leads to a chronic inflammatory state and negatively affects the wound-healing process. It has been known for many years that lifestyle interventions such as exercise, healthy nutrition, and smoking cessation drastically reduce cardiovascular risk and have a preventive effect against disorders in the healing process. However, little is known about the underlying mechanisms, and there is significantly less high-quality evidence compared to pharmacological intervention studies. Due to the immense potential of prevention in heart research, the cardiologic societies are calling for research work to be intensified, from basic understanding to clinical application. The topicality and high relevance of this research area are also evident from the fact that in March 2018, a one-week conference on this topic with contributions from top international scientists took place as part of the renowned "Keystone Symposia" ("New Insights into the Biology of Exercise"). Consistent with the link between obesity, exercise, and cardiovascular disease, this review attempts to draw lessons from stem-cell transplantation and preventive exercise. The application of state-of-the-art techniques for transcriptome analysis has opened new avenues for tailoring targeted interventions to very individual risk factors.