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› Physical activity and exercise are low-cost interventions in primary and secondary prevention of several noncommunicable disease (e.g. cardiovascular diseases, chronic kidney disease, neurodegenerative and neurovascular disease). › In the context of demographic change, the relative and absolute numbers of patients with neurological, especially neurodegenerative disease, will increase. Based on missing causal therapies and high costs, non-pharmacological (e.g. physical activity) approaches for healthy aging are gaining attention. › Epidemiological, observational, and randomized controlled studies have shown that physical activity can enhance brain plasticity and improve cognitive vitality over lifespan. However, the underlying neurobiological mechanisms are still largely unknown. Physical activity can influence different risk factors for neurovascular and neurodegenerative diseases (e.g. arterial hypertension, obesity). Moreover, physical activity can induce cellular and molecular changes (level 1) followed by structural and functionals brain changes (level 2) and/or behavioural adaptations (level 3). › In this clinical review we summarize the role of physical activity in the prevention and therapy of neurological disease. [ABSTRACT FROM AUTHOR]

Purpose: Computer-based medical training scenarios, derived from patient's records, often lack variability, modifiability, and availability. Furthermore, generating image datasets and creating scenarios is resource-intensive. Therefore, patient authoring tools for rapid dataset-independent creation of virtual patients (VPs) is a pressing need., Methods: An authoring tool and a virtual catheterization laboratory environment were developed. The tool allows customised VP generation through a real-time morphable heart model and Euroscore parameters. The generated VP can be examined inside the vCathLab using a fluoroscopy and monitoring device, both on desktop and immersive virtual reality. Seven board-certified experts evaluated the proposed method from three aspects, i.e. System Usability Scale, qualitative feedback, and its performance in VR., Results: All participants agreed that this method could provide the necessary information and is anatomically correct within an educational context. Its modifiability, variability, and simplicity were well recognised. The prototype achieved excellent usability score and considerable performance results., Conclusion: We present a highly variable VP authoring tool that enhances variability in medical training scenarios. Although this work does not aim to explore didactic aspects, the potential of using this approach in an educational context has been confirmed in our study. Accordingly, these aspects can benefit from a thorough investigation in the future. In addition, our tool can be improved to provide more realistic parameter ranges for procedure-specific cases., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interest. Ethics approval: For this type of study, formal consent is not required. Consent to participate and publication: Informed consent was obtained from all individual participants., (© 2024. The Author(s).)

Cardiovascular risk factors (high blood pressure, smoking, overweight, type 2 diabetes, dyslipidemia, physical inactivity) substantially rise with increasing age, particularly after middle age, whereby women are affected to a much greater extent. In the population of Saxony-Anhalt the prevalence of cardiovascular risk factors is clearly increased and the population structure in Saxony-Anhalt is particularly characterized by a high average age as well as high morbidity and mortality rates due to cardiovascular diseases. Saxony-Anhalt therefore provides a model character for the demographic development in Europe. This review article discusses strategies for the implementation of target group-specific cardiovascular preventive strategies in the Federal State of Saxony-Anhalt with special consideration of age and sex. When preventive medicine facilities are established and innovative treatment possibilities for patients with cardiovascular risks are created, prevention should also become available in rural areas., (© 2024. The Author(s).)

The neurotrophic growth factor brain-derived neurotrophic factor (BDNF) plays a crucial role in various neurodegenerative and psychiatric diseases, such as Alzheimer's disease, schizophrenia and depression. BDNF has been proposed as a potential biomarker for diagnosis, prognosis and monitoring therapy. Understanding the factors influencing BDNF levels and whether they follow a circadian rhythm is essential for interpreting fluctuations in BDNF measurements. We aimed to investigate the circadian rhythm of BDNF by collecting multiple peripheral venous blood samples from young, healthy male participants at 12 different time points over 24 h. In addition, vital parameters, cortisol and insulin like growth factor 1 (IGF1) were measured to explore potential regulatory mechanisms, interfering variables and their correlations with BDNF concentration. The findings revealed that plasma BDNF did not exhibit any significant fluctuations over 24 h, suggesting the absence of a circadian rhythm. However, serum BDNF levels decreased during sleep. Furthermore, serum BDNF showed a positive correlation with heart rate but a negative correlation with IGF1. No significant correlation was observed between cortisol and BDNF or IGF1. Although plasma BDNF suggests steady-state conditions, the decline of serum BDNF during the nocturnal period could be attributed to physical inactivity and associated with reduced haemodynamic blood flow (heart rate reduction during sleep). The type of sample collection (peripheral venous cannula vs. blood sampling using a butterfly system) does not significantly affect the measured BDNF levels. The sample collection during the day did not significantly affect BDNF analysis, emphasizing the importance of considering activity levels rather than timing when designing standardized protocols for BDNF assessments., (© 2024 The Author(s). Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Background : Preserving health and physical fitness is critical to ensure independent living across the lifespan. Lower levels of physical fitness are associated with age-related cognitive decline and a higher prevalence of mild cognitive impairment (MCI). Thus, this study investigates the influence of a six-month dance intervention on selected measures of physical fitness in older adults with MCI. Methods : In this randomized controlled trial, 55 patients with MCI were randomized into a sportive dance training (IG; n = 26; age: 70.7 ± 5.6 years; 62% female) or an inactive control group (CG; n = 24; age: 69.1 ± 6.8 years; 46% female). The dance group received two 90 min dance training sessions per week over a duration of six-months, which focused on learning dance movement patterns. During the training sessions, heart rate was measured to control exercise intensity. Physical fitness was assessed using cardiopulmonary exercise testing (CPET), lower limb functional fitness via sit-to-stand test, handgrip strength, and heart rate variability (HRV). Results : We observed that the dance intervention preserved the cardiorespiratory fitness as measured by maximal oxygen uptake (VO 2max ) during CPET, which decreased in the CG. Furthermore, participants in the IG demonstrated increases in leg and handgrip strength, although these were not statistically significant. HRV displayed a non-significant decrease following the intervention. Conclusion s : The results of this randomized controlled trial suggest that sportive dance training can preserve elements of physical fitness (i.e., cardiorespiratory fitness) in older adults with MCI. Although improvements in the other parameters (i.e., leg and handgrip strength) were statistically non-significant, likely due to the small sample size, stabilizing muscular fitness and preventing age-related decline in older adults with MCI is important for maintaining functional independence. For future studies, we recommend a longer training duration paired with precise control of regular physical activity levels, an important confounding factor.

The aim of the presented review is to summarize the literature data on the accuracy and clinical applicability of artificial intelligence (AI) models as a valuable alternative to the current guidelines in predicting cardiac resynchronization therapy (CRT) response and phenotyping of patients eligible for CRT implantation. This systematic review was performed according to the PRISMA guidelines. After a search of Scopus, PubMed, Cochrane Library, and Embase databases, 675 records were identified. Twenty supervised (prediction of CRT response) and 9 unsupervised (clustering and phenotyping) AI models were analyzed qualitatively (22 studies, 14,258 patients). Fifty-five percent of AI models were based on retrospective studies. Unsupervised AI models were able to identify clusters of patients with significantly different rates of primary outcome events (death, heart failure event). In comparison to the guideline-based CRT response prediction accuracy of 70%, supervised AI models trained on cohorts with > 100 patients achieved up to 85% accuracy and an AUC of 0.86 in their prediction of response to CRT for echocardiographic and clinical outcomes, respectively. AI models seem to be an accurate and clinically applicable tool in phenotyping of patients eligible for CRT implantation and predicting potential responders. In the future, AI may help to increase CRT response rates to over 80% and improve clinical decision-making and prognosis of the patients, including reduction of mortality rates. However, these findings must be validated in randomized controlled trials., (© 2023. The Author(s).)

In the embryonic human heart, complex dynamic shape changes take place in a short period of time on a microscopic scale, making this development difficult to visualize. However, spatial understanding of these processes is essential for students and future cardiologists to properly diagnose and treat congenital heart defects. Following a user centered approach, the most crucial embryological stages were identified and translated into a virtual reality learning environment (VRLE) to enable the understanding of the morphological transitions of these stages through advanced interactions. To address individual learning types, we implemented different features and evaluated the application regarding usability, perceived task load, and sense of presence in a user study. We also assessed spatial awareness and knowledge gain, and finally obtained feedback from domain experts. Overall, students and professionals rated the application positively. To minimize distraction from interactive learning content, such VRLEs should consider features for different learning types, allow for gradual habituation, and at the same time provide enough playful stimuli. Our work previews how VR can be integrated into a cardiac embryology education curriculum.

A persisting problem in the clinical operative routine is surgery-associated venous thromboembolisms with the possible complications. The competent and reliably realized prophylaxis of thromboembolism is part of the original and elementary tasks of the surgeon, both the operator as well as the clinically active physician. Many preventive approaches were developed and established in the daily management but a residual risk for development of thrombosis still remains. Under this aspect a search was carried out particularly with respect to scientific literature with review and guideline character on the topic of risk stratification, prophylactic procedures in general and for specific indications., (© 2022. The Author(s).)

Mitochondrial functionality is crucial for the execution of physiologic functions of metabolically active cells in the respiratory tract including airway epithelial cells (AECs). Cigarette smoke is known to impair mitochondrial function in AECs. However, the potential contribution of mitochondrial dysfunction in AECs to airway infection and airway epithelial barrier dysfunction is unknown. In this study, we used an in vitro model based on AECs exposed to cigarette smoke extract (CSE) followed by an infection with Streptococcus pneumoniae ( Sp ). The levels of oxidative stress as an indicator of mitochondrial stress were quantified upon CSE and Sp treatment. In addition, expression of proteins associated with mitophagy, mitochondrial content, and biogenesis as well as mitochondrial fission and fusion was quantified. Transcriptional AEC profiling was performed to identify the potential changes in innate immune pathways and correlate them with indices of mitochondrial function. We observed that CSE exposure substantially altered mitochondrial function in AECs by suppressing mitochondrial complex protein levels, reducing mitochondrial membrane potential and increasing mitochondrial stress and mitophagy. Moreover, CSE-induced mitochondrial dysfunction correlated with reduced enrichment of genes involved in apical junctions and innate immune responses to Sp , particularly type I interferon responses. Together, our results demonstrated that CSE-induced mitochondrial dysfunction may contribute to impaired innate immune responses to Sp .

Background : Pseudoaneurysms (PSAs) are concerning complications after arterial invasive interventions. Therapeutic options include manual ultrasound-assisted compression, pressure dressings, surgical intervention and thrombin injection. Compression of neighboring veins is obvious. However, the incidence of deep vein thrombosis (DVT) in patients with PSA has not previously been investigated. Patients and methods : In this retrospective, nonrandomized study 238 patients with PSA were analyzed from 2013 to 2018. In 149 patients, all of the parameters were complete for participating. PSAs were treated according to the local standard therapy with either ultrasound-guided compression followed by compression bandage or thrombin injection. Treatment success was evaluated 24 hours later, and the venous system was examined for the presence of DVT. Results : Peripheral DVT was found in 25.4% patients after ultrasound-assisted compression and subsequent pressure bandages, but only 6.4% of patients had DVT after thrombin injection (p = 0.013). Lower leg veins, particularly veins of the crural muscles, were primarily affected. Significantly more PSAs were successfully treated without the occurrence of DVT in the thrombin injection group compared to the compression group (93.6 vs. 69.0%; p = 0.001). Conclusions : Our study revealed that the use of thrombin injections resulted in a significantly lower rate of postinterventional DVT and a higher total number of successfully treated PSAs compared to compression therapy.

Rationale: While thrombin is the key protease in thrombus formation, other coagulation proteases, such as fXa (factor Xa) or aPC (activated protein C), independently modulate intracellular signaling via partially distinct receptors., Objectives: To study the differential effects of fXa or fIIa (factor IIa) inhibition on gene expression and inflammation in myocardial ischemia-reperfusion injury., Methods and Results: Mice were treated with a direct fIIa inhibitor (fIIai) or direct fXa inhibitor (fXai) at doses that induced comparable anticoagulant effects ex vivo and in vivo (tail-bleeding assay and FeCl 3 -induced thrombosis). Myocardial ischemia-reperfusion injury was induced via left anterior descending ligation. We determined infarct size and in vivo aPC generation, analyzed gene expression by RNA sequencing, and performed immunoblotting and ELISA. The signaling-only 3K3A-aPC variant and inhibitory antibodies that blocked all or only the anticoagulant function of aPC were used to determine the role of aPC. Doses of fIIai and fXai that induced comparable anticoagulant effects resulted in a comparable reduction in infarct size. However, unbiased gene expression analyses revealed marked differences, including pathways related to sterile inflammation and inflammasome regulation. fXai but not fIIai inhibited sterile inflammation by reducing the expression of proinflammatory cytokines (IL [interleukin]-1β, IL-6, and TNFα [tumor necrosis factor alpha]), as well as NF-κB (nuclear factor kappa B) and inflammasome activation. This anti-inflammatory effect was associated with reduced myocardial fibrosis 28 days post-myocardial ischemia-reperfusion injury. Mechanistically, in vivo aPC generation was higher with fXai than with fIIai. Inhibition of the anticoagulant and signaling properties of aPC abolished the anti-inflammatory effect associated with fXai, while inhibiting only the anticoagulant function of aPC had no effect. Combining 3K3A-aPC with fIIai reduced the inflammatory response, mimicking the fXai-associated effect., Conclusions: We showed that specific inhibition of coagulation via direct oral anticoagulants had differential effects on gene expression and inflammation, despite comparable anticoagulant effects and infarct sizes. Targeting individual coagulation proteases induces specific cellular responses unrelated to their anticoagulant effect.

Vascular smooth muscle cells (VSMCs) loaded with lipid droplets (LDs) are markers of atherosclerosis. In this disease, inflammatory Group IIA-secreted phospholipase A 2 s (GIIA sPLA 2 s) are highly expressed in VSMCs, but their actions in these cells are unknown. Here, we investigated the ability of myotoxin III (MT-III), an ophidian GIIA sPLA 2 sharing structural and functional features with mammalian GIIA sPLA 2 s, to induce LD formation and lipid metabolism factors involved in this effect. Modulation of VSMC phenotypes by this sPLA 2 was also evaluated. Incubation of VSMCs with MT-III significantly increased the number of LDs. MT-III upregulated scavenger receptor type 1 (SR-A1) and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) protein expression and enhanced acetylated-low density lipoprotein (acLDL) uptake by VSMCs, revealing the ability of a GIIA PLA 2 to modulate scavenger receptor activities. MT-III induced translocation and protein expression of PPAR-γ and -β/δ. Inhibition of peroxisome proliferator-activated receptors (PPARs) and diacylglycerol O-acyltransferase (DGAT) and acyl-CoA:cholesterolacyltransferase (ACAT) enzymes abrogated MT-III-induced LD formation. Moreover, in response to MT-III, VSMCs acquired phagocytic activity and expressed macrophage markers CD68 and MAC-2. In conclusion, MT-III is able to stimulate VSMCs and recruit factors involved in lipid uptake and metabolism, leading to the formation of VSMC-derived foam cells with acquisition of macrophage-like markers and functions.

Introduction: Economic topics appear in the medical studies curriculum at different times. Despite socio-political relevance, there is hardly any information about the degree of understanding that medical students have of "economics in medicine". The present study addresses the questions: What understanding of "economics in medicine" do medical students have before the start of the Practical Year? To what extent is economic teaching content understood as "economization" from outside the profession? Method: Magdeburg medical students in the 5 th year of study, who participated in preparatory seminars for the Practical Year (PY) in 2014 and 2015 (60 participants each), assessed the relevance of various seminar topics four months prior to the start of the semester. On the basis of a three-stage qualitative-reconstructive partial evaluation, students' economic understanding is explored through secondary analysis: deductive derivation of the analysis units; integrative basic method ("segmentation", "micro-linguistic detailed analysis", "central theme"); development of a theoretical model by placing the central themes in context following Grounded Theory. Results: Based on the theory, 19 free-text answers with economic reference were identified from the total of all free-text answers. Each answer was assigned to at least one of a total of six themes of the students' understanding of economics: de-professionalizing economization, deciding and working economically, ambivalent requirements for efficiency and equity, the doctor as an entrepreneur, economics as relevant learning content, PY as a conflict-laden setting for economized working and learning. The theoretical model contains social, praxeological and professional references, which can themselves be ambivalent and conflicting. Conclusion: Despite their critical attitude, the surveyed medical students are neither hostile to economics nor do they regard economics in medicine as a taboo subject. Economic learning content is recognized as relevant. Educational formats that tackle the tension between patient and system orientation in a problem-oriented manner can be a productive setting for economic reflection., Competing Interests: The authors declare that they have no competing interests.

JAK2-V617F-positive chronic myeloproliferative neoplasia (CMN) commonly displays dysfunction of integrins and adhesion molecules expressed on platelets, erythrocytes, and leukocytes. However, the mechanism by which the 2 major leukocyte integrin chains, β1 and β2, may contribute to CMN pathophysiology remained unclear. β1 (α4β1; VLA-4) and β2 (αLβ2; LFA-1) integrins are essential regulators for attachment of leukocytes to endothelial cells. We here showed enhanced adhesion of granulocytes from mice with JAK2-V617F knockin (JAK2+/VF mice) to vascular cell adhesion molecule 1- (VCAM1-) and intercellular adhesion molecule 1-coated (ICAM1-coated) surfaces. Soluble VCAM1 and ICAM1 ligand binding assays revealed increased affinity of β1 and β2 integrins for their respective ligands. For β1 integrins, this correlated with a structural change from the low- to the high-affinity conformation induced by JAK2-V617F. JAK2-V617F triggered constitutive activation of the integrin inside-out signaling molecule Rap1, resulting in translocation toward the cell membrane. Employing a venous thrombosis model, we demonstrated that neutralizing anti-VLA-4 and anti-β2 integrin antibodies suppress pathologic thrombosis as observed in JAK2+/VF mice. In addition, aberrant homing of JAK2+/VF leukocytes to the spleen was inhibited by neutralizing anti-β2 antibodies and by pharmacologic inhibition of Rap1. Thus, our findings identified cross-talk between JAK2-V617F and integrin activation promoting pathologic thrombosis and abnormal trafficking of leukocytes to the spleen.

Purpose: Cell fate determinants Scrib and Llgl1 influence self-renewal capacity of hematopoietic stem cells (HSCs). Scrib-deficient HSCs are functionally impaired and lack sufficient repopulation capacity during serial transplantation and stress. In contrast, loss of Llgl1 leads to increased HSC fitness, gain of self-renewal capacity and expansion of the stem cell pool. Here, we sought to assess for shared and unique molecular functions of Llgl1 and Scrib by analyzing their interactome in hematopoietic cells., Methods: Interactome analysis was performed by affinity purification followed by mass spectrometry. Motility, migration and adhesion were assessed on primary murine HSCs, which were isolated by FACS sorting following conditional deletion of Scrib or Llgl1, respectively. Imaging of Scrib-deficient HSCs was performed by intravital 2-photon microscopy., Results: Comparison of Scrib and Llgl1 interactome analyses revealed involvement in common and unique cellular functions. Migration and adhesion were among the cellular functions connected to Scrib but not to Llgl1. Functional validation of these findings confirmed alterations in cell adhesion and migration of Scrib-deficient HSCs in vitro and in vivo. In contrast, genetic inactivation of Llgl1 did not affect adhesion or migratory capacity of hematopoietic stem cells., Conclusion: Our data provide first evidence for an evolutionarily conserved role of the cell fate determinant Scrib in HSC adhesion and migration in vitro and in vivo, a unique function that is not shared with its putative complex partner Llgl1.

Background: Hyperthermia often ends fatally and must therefore be promptly recognized and adequately treated., Case: A 28-year-old man participated in a long-distance race (3 km) on a hot summer day (28 °C). The runner collapsed, had to vomit but continued the run and reached the finish. Neurologically, the patient presented with intermittent cerebral seizures. External cooling batteries were immediately applied and cold infusions were started. The patient was admitted to the intensive care unit of the university hospital (body temperature 40.2 °C). After a few hours, a manifest disseminated intravascular coagulopathy developed with multiple organ failure. It took 12 l of volume replacement, 8 units of fresh frozen plasma and 2 units of erythrocyte concentrates in the first 12 h to stabilize the patient. Although with the help of forced external cooling and application of cold infusions, the body temperature could be lowered to 38 °C by the next morning, the overall situation of the patient continued to deteriorate. Despite dialysis and massive substitution of coagulation factors, the patient could not be sufficiently stabilized and died of brain edema., Conclusion: Not only the old or young children are subject to the potential danger of a fatal heat stroke but also young athletic persons after normal sports activities (3 km run). Cooling must be started immediately and the patient must be hospitalized as a vital emergency. If hemostasis fails due to the heat-related loss of hepatogenic protein synthesis, a viscious circle begins, which, as in the reported case, is irreversible despite maximum therapy and substitution.

Pseudoaneurysms (PSAs) are commonly known as complications associated with invasive interventions. Because of the pulsatile in- and outflow of blood through the neck of PSAs, they tend to grow and, in the worse cases, can rupture. Therapeutic options are compression therapy, using a compression bandage and ultrasound-guided compression, and thrombin injection. Manual ultrasound-guided compression is widely performed and is successful in most cases. In general, it is combined with a subsequently applied compression bandage. Thrombin injection is a more difficult technique, but it has a higher success rate. This article gives an overview of the characteristics of PSAs, their diagnostic characteristics and the therapeutic methods used to treat them. Complications associated with compression or thrombin injection are also explained in detail., Competing Interests: The authors declare that they have no conflict of interest., (Georg Thieme Verlag KG Stuttgart · New York.)

A 49-year-old male patient presented due to recurrent pain and swelling in the left leg. The patient had had deep venous thrombosis with pulmonary embolism 5 years previously. Since then, he had been treated with Vit-k-antagonists. Pronounced paraumbilical collateral circulation of unknown origin was striking. Doppler sonographic evaluation pointed to May-Thurner syndrome. This was confirmed by phlebography. Venous stenting of the stenosis in the left iliac vein achieved long-term symptom improvement. This case report is intended to draw attention to the rare May-Thurner syndrome as an important differential diagnosis of deep vein thrombosis and, at the same time, identify diagnostic and therapeutic treatment strategies.

In addition to haematoma and arteriovenous fistula, the iatrogenic pseudoaneurysm is a common complication of vascular access that is caused by a perforation in the arterial wall. Iatrogenic pseudoaneurysms can progress in size and lead to rupture and active bleeding. Over the previous few decades, therapeutic methods have evolved from surgical repair to less invasive options, such as ultrasound-guided compression therapy (UGCT) and ultrasound-guided thrombin injection (UGTI). This paper presents an overview of the diagnostic and treatment modalities used in femoral pseudoaneurysms as well as a comprehensive summary of previous studies that analysed the success and complication rates of UGCT and UGTI.

Background: Transcatheter aortic valve replacement (TAVR) has been demonstrated to be an established therapy for high-risk, inoperable patients with severe symptomatic aortic valve stenosis. For patients with moderate surgical risk, TAVR is equivalent to conventional aortic valve surgery. However, atrial fibrillation (AF) is also present in many of these patients, thus requiring post-implantation oral anticoagulation therapy in addition to the inhibition of thrombocyte aggregation, which poses the risk of bleeding complications. The aim of our work was to investigate the influence of AF on mortality and the occurrence of bleeding, vascular and cerebrovascular complications related to TAVR according to the VARC-2 criteria., Methods: Two hundred eighty-three patients who underwent TAVR between March 2010 and April 2016 were retrospectively examined. In total, 257 patients who underwent transfemoral access were included in this study. The mean patient age was 81 ± 6 years, 54.1% of the patients were women, and 42.4% had pre-interventional AF., Results: Compared to patients with sinus rhythm (SR, n = 148), patients with AF (n = 109) had an almost three-fold higher incidence of major vascular complications (AF 14.7% vs. SR 5.4%, p = 0.016) and life-threatening bleeding (AF 11.9% vs. SR 4.1%, p = 0.028) during the first 30 post-procedural days. However, the rate of cerebrovascular complications (AF 3.7% vs. SR 2.7%, p = 0.726) did not significantly differ between the two groups. Overall mortality was significantly higher in patients with AF during the first month (AF 8.3% vs. SR 2.0%, p = 0.032) and the first year (AF 28.4% vs. SR 15.3%; p = 0.020) following TAVR., Conclusion: Patients with AF had significantly more severe bleeding complications after TAVR, which were significantly related to mortality. Future prospective randomized studies must clarify the optimal anticoagulation therapy for patients with AF after TAVR., Trial Registration: DRKS00011798 on DRKS (Date 17.03.2017).

Background/Aim Surgical and other disciplines have been noticing difficulties in recruiting junior staff for several years. In response to a decrease in interest within study courses, surgical associations recommend better supervision during undergraduate practical education as "clerkships" in order to increase the attractiveness of surgery. This clerkship has an initiation function, as students for the first time - albeit marginally - can act as physicians. The aim of this study was to investigate the impact of clerkships on the disciplinary orientations and preferences of undergraduates' perceptions of specialist training. Methods Medical students of the Otto-von-Guericke University Medical School at Magdeburg were interviewed at 4 different time points in their clinical training (n = 373). The questionnaire included different dimensions on i) their choice of the subjects of clerkships and ii) on their clerkship experiences. Questions were subdivided into 5 basic topics, including 5 options to answer according to "Likert's scale" ranging from 1 to 5 ("completely true" to "does not apply at all"). Data were statistically analysed. Results Clerkships are an important component of medical studies. Undergraduate medical students deliberately use clerkships to get to know and to discriminate between medical disciplines they consider as possible choices for later specialisation. Their own assessment as well as reported experiences of specific clinics, departments or supervisors influence decision-making with regard to medical disciplines and locations/institutions for clerkships. The contents of the clerkships is expected to be closely related to the medical curricula. Students expect a detailed insight and practical, cross-departmental, interdisciplinary integration and collaboration in the medical discipline selected for clerkship. Clerkship experience in surgery affects the students' preference for surgical disciplines. They are a relevant predictor. Conclusion High-quality teaching - an important part of practical undergraduate training (clerkship) is effective in fostering a subsequent surgical orientation. Preference for surgical specialisation can be strengthened during medical studies by preparing seminars and extended practical experiences during clerkship., Competing Interests: Interessenkonflikt: Die Autoren geben an, dass kein Interessenkonfliktbesteht., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Systemic treatment with sirolimus, as used for immunosuppression in transplant patients, results in markedly low rates of in-stent restenosis. Since the underlying mechanisms remain obscure, we aimed to determine the molecular and cellular effects of systemic sirolimus treatment on vascular remodeling processes., Methods and Results: Systemic sirolimus treatment significantly reduced smooth muscle cell (SMC) proliferation 14days after wire-induced injury and neointima formation 28days after injury in C57BL/6 mice, while simultaneously impairing re-endothelialization. Interestingly, in vitro, sirolimus had no direct effect on the proliferation of SMC or endothelial cells (EC) at serum concentrations observed after systemic application. In contrast, sirolimus reduced the adhesion of leukocytes (CD45 + ) and bone marrow-derived progenitor cells (CD34 + ) to activated EC by down-regulating the adhesion molecules ICAM-1 and VCAM-1. In addition, sirolimus treatment also significantly reduced the upregulation of ICAM-1 and VCAM-1 and the recruitment of monocytic cells (MOMA-2 + ) in neointimal lesions in vivo., Conclusion: Our findings show that systemic sirolimus treatment effectively prevents SMC and EC proliferation in vivo without directly affecting these cells. Instead, sirolimus prevents neointima formation and re-endothelialization by attenuating the inflammatory response after injury with secondary effects on SMC and EC proliferation. Thus, despite a similar net effect, the mechanisms of systemic sirolimus treatment are largely different from the local effects achieved after application of sirolimus-eluting stents., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Following myocardial infarction (MI), peri-infarct myocardial edema formation further impairs cardiac function. Extracellular RNA (eRNA) released from injured cells strongly increases vascular permeability. This study aimed to assess the role of eRNA in MI-induced cardiac edema formation, infarct size, cardiac function, and survival after acute MI and to evaluate the therapeutic potential of ribonuclease 1 (RNase-1) treatment as an eRNA-degrading intervention., Methods and Results: C57BL/6J mice were subjected to MI by permanent ligation of the left anterior descending coronary artery. Plasma eRNA levels were significantly increased compared with those in controls starting from 30 minutes after ligation. Systemic application of RNase-1, but not DNase, significantly reduced myocardial edema formation 24 hours after ligation compared with controls. Consequently, eRNA degradation by RNase-1 significantly improved the perfusion of collateral arteries in the border zone of the infarcted myocardium 24 hours after ligation of the left anterior descending coronary artery, as detected by micro-computed tomography imaging. Although there was no significant difference in the area at risk, the area of vital myocardium was markedly larger in mice treated with RNase-1 compared with controls, as detected by Evans blue and 2,3,5-triphenyltetrazolium chloride staining. The increase in viable myocardium was associated with significantly preserved left ventricular function, as assessed by echocardiography. Moreover, RNase-1 significantly improved 8-week survival following MI., Conclusions: eRNA is an unrecognized permeability factor in vivo, associated with myocardial edema formation after acute MI. RNase-1 counteracts eRNA-induced edema formation and preserves perfusion of the infarction border zone, reducing infarct size and protecting cardiac function after MI., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

A 72-year-old female patient presented with increasing dyspnea of unclear origin classified as New York Heart Association stage III (NYHA III). Using transesophageal echocardiography a patent foramen ovale (PFO) and right heart failure could be diagnosed. Right heart catheterization revealed a large left to right shunt due to an arteriovenous malformation in the liver. Because of additional telangiectasia of the lips the presumptive diagnosis was Rendu-Osler-Weber disease. Typical nosebleeds and other symptoms of the disease were lacking and only two out of four Curaçao criteria were positive; therefore, genetic testing was performed, which verified the clinical diagnosis. Off-label use of the angiogenesis inhibitor bevacizumab was initiated as the therapeutic strategy and led to an improvement in the symptomatic dyspnea.

Animal models point towards a key role of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) in mediating exercise-induced structural and functional changes in the hippocampus. Recently, also platelet derived growth factor-C (PDGF-C) has been shown to promote blood vessel growth and neuronal survival. Moreover, reductions of these neurotrophic and angiogenic factors in old age have been related to hippocampal atrophy, decreased vascularization and cognitive decline. In a 3-month aerobic exercise study, forty healthy older humans (60 to 77years) were pseudo-randomly assigned to either an aerobic exercise group (indoor treadmill, n=21) or to a control group (indoor progressive-muscle relaxation/stretching, n=19). As reported recently, we found evidence for fitness-related perfusion changes of the aged human hippocampus that were closely linked to changes in episodic memory function. Here, we test whether peripheral levels of BDNF, IGF-I, VEGF or PDGF-C are related to changes in hippocampal blood flow, volume and memory performance. Growth factor levels were not significantly affected by exercise, and their changes were not related to changes in fitness or perfusion. However, changes in IGF-I levels were positively correlated with hippocampal volume changes (derived by manual volumetry and voxel-based morphometry) and late verbal recall performance, a relationship that seemed to be independent of fitness, perfusion or their changes over time. These preliminary findings link IGF-I levels to hippocampal volume changes and putatively hippocampus-dependent memory changes that seem to occur over time independently of exercise. We discuss methodological shortcomings of our study and potential differences in the temporal dynamics of how IGF-1, VEGF and BDNF may be affected by exercise and to what extent these differences may have led to the negative findings reported here., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Aerobic exercise in young adults can induce vascular plasticity in the hippocampus, a critical region for recall and recognition memory. In a mechanistic proof-of-concept intervention over 3 months, we investigated whether healthy older adults (60-77 years) also show such plasticity. Regional cerebral blood flow (rCBF) and volume (rCBV) were measured with gadolinium-based perfusion imaging (3 Tesla magnetic resonance image (MRI)). Hippocampal volumes were assessed by high-resolution 7 Tesla MRI. Fitness improvement correlated with changes in hippocampal perfusion and hippocampal head volume. Perfusion tended to increase in younger, but to decrease in older individuals. The changes in fitness, hippocampal perfusion and volume were positively related to changes in recognition memory and early recall for complex spatial objects. Path analyses indicated that fitness-related changes in complex object recognition were modulated by hippocampal perfusion. These findings indicate a preserved capacity of the aging human hippocampus for functionally relevant vascular plasticity, which decreases with progressing age.

Background: The myocardial infarct size can be reduced by pharmacological postconditioning using cardioprotective agents. Neuregulin-1β is a potential candidate, but previous studies in an isolated heart model of ischemia and reperfusion displayed controversial results. An in situ model of ischemia/reperfusion was used to clarify whether the remote application of neuregulin-1β can reduce the reperfusion injury. A second aim was to evaluate, if the effects are specific for reperfused tissue or if this is a general antiapoptotic effect. In addition, the contributing molecular mechanisms were investigated., Methods: In an open chest model, mouse hearts were subjected to a regional ischemia (45-minute) using ligature of the left anterior descending artery. Neuregulin-1β (80 ng/kg) was given using an intraperitoneal bolus injection 5 minutes before reopening of the ligature followed by a 30-minute reperfusion., Results: Remote application of recombinant neuregulin-1β protected the heart from reperfusion injury without influencing hemodynamics. This beneficial effect specifically targets reperfusion injury. In contrast, nonreperfused needle trauma was not reduced by neuregulin-1β when applied remotely. Pharmacological blocking experiments and enzyme activation analysis using Western blot analysis revealed a crucial involvement of the antiapoptotic reperfusion injury salvage kinase cascade. In contrast, contribution of the survivor activating factor enhancement pathways to this early cardioprotection was not observed., Conclusions: Remote application of neuregulin-1β protects hearts from early reperfusion injury by activation of the reperfusion injury salvage kinase pathway without relevant effects on intracardiac pressures in myocardial infarction. Besides its potential pharmacological application, neuregulin-1β might act as an endogenously produced mediator in remote postconditioning., (Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Collateral vessel growth is a physiological process that is not equally pronounced in all people. After the development of a haemodynamically relevant stenosis in vascular systems, blood flow is directed through a collateral circulation to supply ischaemic tissue. This collateral circulation exists on the capillary level and by definition, is not composed of real new vessels. Postnatal vasculogenesis (true neovascularisation) occurs in the adult organism in tumour vascularisation, wound healing, in the endometrium, and in the context of chronic diseases such as rheumatoid arthritis and psoriasis. Reopening of the occluded vessel or use of artificial bypass grafts are the most attractive therapeutic approaches for treating peripheral arterial and coronary artery disease. These strategies have been exhausted in many patients; therefore augmentation of arteriogenesis can be more useful. Arteriogenesis, the promotion of natural collateral growth, is a hot topic in vascular research. Monocytes play a key role in arteriogenesis by "homing" to areas of collateral vessel growth and locally secrete multiple essential growth factors. Furthermore, stem cells of different origins, endothelial progenitor cells or mononuclear cells are currently being used to promote vessel growth. Also, the application of growth factors such as VEGF, MCP-1, GM-CSF have been already used in clinical trials. This review article describes the physiology and pathophysiology of vascular stenoses and their compensation mechanisms. The review also gives an overview of current treatment approaches and new strategies for non-operable PAD patients. The article presents the current cell and growth factor-related studies, as well as results of balloon dilatation and stent implantation or bypass surgery studies for improvement of revascularisation., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: We investigated the relationship of impaired autonomic function and severity of illness in chronic heart failure (CHF) and multiple-organ dysfunction syndrome (MODS) as an end stage of CHF. Furthermore, we assessed the link of parasympathetic modulation of the heart rate and inflammatory activation in CHF and MODS., Methods: Sixty-five patients admitted for worsening of CHF were retrospectively enrolled in this study. In addition, 65 age- and sex-matched patients with pronounced MODS were assigned for comparison of autonomic function and C-reactive protein in patients with CHF or MODS, respectively. Heart rate variability (HRV) parameters of the time and frequency domain as markers of autonomic function were analyzed from 24-hour Holter electrocardiograms., Results: The more pronounced the severity of illness as expressed by the Acute Physiology and Chronic Health Evaluation score, the more the HRV was impaired. This effect was particularly seen for overall variability (SD of RR intervals) and HRV parameters characterizing the parasympathetic modulations of the heart rate (high, very low frequency power). C-reactive protein levels as markers of inflammation were inversely related to high and very low frequencies., Conclusion: Our results allow for speculation that autonomic dysfunction in CHF indicates a beginning of uncoupled interorgan communication potentially leading to MODS as characterized by disruption of communication between the organs., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: The phosphatase PTEN represents an important physiological inhibitor of phosphatidylinositol-3 kinase (PI3-K)/protein kinase B (Akt) signalling, however, the functional role of PTEN in the initial phase of angioplasty-induced vascular injury remains elusive. In the present study we sought to determine PTEN's effect on vascular smooth muscle cell (VSMC) apoptosis following acute injury in vivo and in vitro., Methods and Results: Immunohistochemistry indicated a faint basal expression and equal distribution of PTEN in uninjured rat carotid arteries. 12 h following balloon-injury, PTEN expression was strongly increased in apoptotic (TUNEL+) VSMC. In vitro, stimulation with serum or different growth factors or subjecting VSMC to cyclic stretch had no effect on PTEN expression, whereas stimulation with H2O2 robustly increased PTEN expression in a time- and dose-dependent manner. To evaluate the functional role of PTEN expression, human VSMC were transduced with WT-PTEN. Overexpression of PTEN increased the number of apoptotic VSMC (19.8%±4.4 vs. 5.6%±2.3; P<0.001) as determined by TUNEL assay. In contrast, siRNA-mediated knock-down of PTEN attenuated the basal as well as H2O2-induced apoptosis of VSMC. Mechanistically, overexpression of PTEN prevented serum-induced Akt-phosphorylation, whereas siRNA-mediated knock down of PTEN augmented Akt-activation. Moreover, co-transfection of PTEN and a constitutive active Akt mutant prevented PTEN-dependent augmentation of VSMC apoptosis, indicating, that PTEN regulates VSMC apoptosis by inhibition of Akt phosphorylation/activation., Conclusion: By interfering with the PI3-K/Akt-dependent survival signalling, the oxidative stress-induced up regulation of PTEN in VSMC of injured arteries augments the sensitivity of VSMC to apoptotic stimuli in the early phase following vascular injury, augmenting the initial injury and cell loss of the injured vessel wall. Thus, these data add to our understanding of PTEN's role during vascular remodelling.

Diagnosis of Churg-Strauss syndrome should be considered in young asthmatics with fatigue and eosinophilia. On the base of the etiopathology of a 19-year old man, who was initially admitted because of dyspnoea, fever and acute chest pain, we show that eosinophilia gives an important hint for further diagnostic and is the key trend parameter. Histologically an eosinophilic myocarditis could be shown in the myocardial biopsy. High dose prednisolone induced a clear improvement in symptoms, with decrease of the inflammatory signs and the eosinophilia and a clear improvement of the left ventricular function.

Cardiovascular magnetic resonance (CMR) is an accurate, reproducible and well-validated imaging technique for the measurement of left ventricular and right ventricular volumes, function, and mass. In patients who have heart failure, CMR is ideally suited both for the initial assessment of fundamental parameters of cardiac function and longitudinal follow-up. Because of its accuracy, the decision to implement therapeutic measures based on cutoff values for ventricular ejection fraction can be made with confidence. Because the above-mentioned parameters correlate with morbidity and mortality, CMR can be used to estimate the prognosis of an individual patient and to obtain surrogate parameters in clinical trials. The process of ventricular remodeling after cardiac injury and reverse remodeling using medical and interventional therapy can be assessed using relatively small sample sizes, which puts CMR in the forefront of imaging techniques in remodeling research.

Physiologically, platelets perform important tasks to maintain the homeostasis of the vascular wall and the surrounding environment. In pathologic conditions, however, platelets contribute to the formation of atherosclerotic plaques as well as to atherothrombotic events (i.e., acute myocardial infarction). This review aims to elucidate the role of platelets in atherogenesis and atherothrombosis and to provide an insight into current and future strategies for platelet inhibition.