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Enhanced sympathetic activity at the ventricular myocardium can destabilize repolarization, increasing the risk of death. Sympathetic activity is known to cluster in low-frequency bursts; therefore, we hypothesized that sympathetic activity induces periodic low-frequency changes of repolarization. We developed a technique to assess the sympathetic effect on repolarization and identified periodic components in the low-frequency spectral range (≤0.1 Hz), which we termed periodic repolarization dynamics (PRD). We investigated the physiological properties of PRD in multiple experimental studies, including a swine model of steady-state ventilation (n=7) and human studies involving fixed atrial pacing (n=10), passive head-up tilt testing (n=11), low-intensity exercise testing (n=11), and beta blockade (n=10). We tested the prognostic power of PRD in 908 survivors of acute myocardial infarction (MI). Finally, we tested the predictive values of PRD and T-wave alternans (TWA) in 2,965 patients undergoing clinically indicated exercise testing. PRD was not related to underlying respiratory activity (P<0.001) or heart-rate variability (P=0.002). Furthermore, PRD was enhanced by activation of the sympathetic nervous system, and pharmacological blockade of sympathetic nervous system activity suppressed PRD (P≤0.005 for both). Increased PRD was the strongest single risk predictor of 5-year total mortality (hazard ratio 4.75, 95% CI 2.94-7.66; P<0.001) after acute MI. In patients undergoing exercise testing, the predictive value of PRD was strong and complementary to that of TWA. We have described and identified low-frequency rhythmic modulations of repolarization that are associated with sympathetic activity. Increased PRD can be used as a predictor of mortality in survivors of acute MI and patients undergoing exercise testing. ClinicalTrials.gov NCT00196274. This study was funded by Angewandte Klinische Forschung, University of Tübingen (252-1-0).

Isolation of huge quantities of primary cells from whole organs like the heart becomes increasingly important, especially for the emerging research field of tissue engineering and regenerative medicine. This study deals with the isolation of pig cardiomyocytes, in contrast to the standard mouse or rat models, because we aimed to draw attention to the species, which are genetically more closely related to the human organism. The bigger operative and veterinary expenditure of the pig-heart model can only be justified by a technique that supplies a big amount of qualitative high-grade cardiomyocytes. In our model, the quality is guaranteed by protection of the heart, already in situ, by a cardioplegia and a careful application of collagenase to soften the tissue. The construction of a new apparatus which includes enormous costs was not necessary, since the perfusion equipment was realized from two commercially available HLMsets, which were modified and connected to each other. Our model makes it possible to rinse the whole myocardium, which leads to a better output than models that only prepare a part of the myocardium around a coronary artery. The careful harvesting of high-grade cardiomyocytes is an important source of successful cell cultures to be used for numerous experimental applications, may reduce animal experiments and, additionally, represents a chance for perfusionists to become an important partner in interdisciplinary research projects. Perfusion (2007) 22, 137—142.

Entanglement lies at the heart of quantum mechanics, and in recent years has been identified as an essential resource for quantum information processing and computation 1 , 2 , 3 , 4 . The experimentally challenging production of highly entangled multi-particle states is therefore important for investigating both fundamental physics and practical applications. Here we report the creation of highly entangled states of neutral atoms trapped in the periodic potential of an optical lattice. Controlled collisions between individual neighbouring atoms are used to realize an array of quantum gates, with massively parallel operation. We observe a coherent entangling–disentangling evolution in the many-body system, depending on the phase shift acquired during the collision between neighbouring atoms. Such dynamics are indicative of highly entangled many-body states; moreover, these are formed in a single operational step, independent of the size of the system 5 , 6 .

Children with rare tumours and malformations may benefit from innovative imaging, including patient-specific 3D models that can enhance communication and surgical planning. The primary aim was to evaluate the impact of patient-specific 3D models on communication with families. The secondary aims were to assess their influence on medical management and to establish an efficient post-processing workflow. From 2021 to 2024, we prospectively included patients aged 3 months to 18 years with rare tumours or malformations. Families completed questionnaires before and after the presentation of a 3D model generated from MRI sequences, including peripheral nerve tractography. Treating physicians completed a separate questionnaire before surgical planning. Analyses were performed in R. Among 21 patients, diagnoses included 11 tumours, 8 malformations, 1 trauma, and 1 pancreatic pseudo-cyst. Likert scale responses showed improved family understanding after viewing the 3D model (mean score 3.94 to 4.67) and a high overall evaluation (mean 4.61). Physicians also rated the models positively. An efficient image post-processing workflow was defined. Although manual 3D reconstruction remains time-consuming, these preliminary results show that colourful, patient-specific 3D models substantially improve family communication and support clinical decision-making. They also highlight the need for supporting the development of MRI-based automated segmentation softwares using deep neural networks, which are clinically approved and usable in routine practice.

Subretinal implants aim to replace photoreceptor function in patients suffering from degenerative retinal disease like retinitis pigmentosa by topically applying electrical stimuli in the subretinal space. This study-as a last step before upcoming human trials-explored a newly developed surgical technique for permanent implantation of complex subretinal implants with extra-ocular parts. The implant consisted of a microphoto-diode array (MPDA) with 1550 electrodes and a 4x4 array of gold electrodes for direct electrical stimulation; both were mounted onto a polyimide foil for transscleral placement into the subretinal space. The foil carried connection lanes to a silicone cable that was implanted under the skin and led to a stimulator box in the animal's neck. Surgery was performed in 11 domestic pigs. Improved vitreo-retinal surgical technique consisted of a 180 degrees peripheral retinotomy and use of diathermy to penetrate the choroid in order to avoid choroidal haemorrhage. Subretinal forceps were used to place the implant safely onto the retinal pigment epithelium before the retina was flattened, peripheral laser photocoagulation was applied and the eye was filled with silicon oil. The implant was stabilized by a scleral fixation patch, use of a metal clamp with bone screws on the animal's skull and a tissue ring under the animal's skin in the neck. Behaviour was observed in the freely moving animals after direct subretinal electrical stimulation and funduscopy, optical coherence tomography, fluorescein angiography and histology were performed. All implants were successfully placed subretinally. In three animals a proliferative vitreo-retinopathy was observed after approximately 2 weeks. Otherwise, funduscopy and OCT demonstrated complete retinal attachment and FA showed no retinal vascular abnormalities over and around the implant. The animals showed clear behavioural reactions to electrical stimulation over the whole examination period. Histological examination failed to show any voltage-induced alteration in the cellular architecture of the retina overlying the stimulation electrodes. This study demonstrates the feasibility of a new surgical procedure for highly safe and controlled implantation of complex subretinal devices with extra-ocular parts. The new implant design proved to be safely implantable in free-moving pigs for an observation period of 4 weeks.

IntroductionWomen with gestational diabetes mellitus (GDM) have a higher risk of developing type 2 diabetes mellitus compared with women who never had GDM. Consequently, the question of structured aftercare for GDM has emerged. In all probability, many women do not receive care according to the guidelines. In particular, the process and interaction between obstetrical, diabetic, gynaecological, paediatric and general practitioner care lacks clear definitions. Thus, our first goal is to analyse the current aftercare situation for women with GDM in Germany, for example, the participation rate in aftercare diabetes screening, as well as reasons and attitudes stated by healthcare providers to offer these services and by patients to participate (or not). Second, we want to develop an appropriate, effective and patient-centred care model.Methods and analysisThis is a population-based mixed methods study using both quantitative and qualitative research approaches. In various working packages, we evaluate data of the GestDiab register, of the Association of Statutory Health Insurance Physicians of North Rhine and the participating insurance companies (AOK Rheinland/Hamburg, BARMER, DAK Gesundheit, IKK classic, pronova BKK). In addition, quantitative (postal surveys) and qualitative (interviews) surveys will be conducted with randomly selected healthcare providers (diabetologists, gynaecologists, paediatricians and midwives) and affected women, to be subsequently analysed. All results will then be jointly examined and evaluated.Ethics and disseminationThe study was approved by the ethics committee of the Faculty of Medicine, Heinrich-Heine-University Düsseldorf (Ethics Committee No.: 2019-738). Participants of the postal surveys and interviews will be informed in detail about the study and the use of data as well as the underlying data protection regulations before voluntarily participating. The study results will be disseminated through peer-reviewed journals, conferences and public information.Trial registration numberDRKS00020283.

Purpose The efficacy of drug-eluting balloons has been demonstrated in clinical trials. The drug predominantly used is paclitaxel because of its lipophilic properties and the rapid onset of action. The aim of the investigation was to evaluate the feasibility and efficacy of an alternative balloon coating with rapamycin that can be applied on site. Methods The balloon coating (3.0/18 and 3.0/12 mm, Cathy No. 4, Translumina GmbH) with rapamycin was conducted with a coating machine (Translumina GmbH). Concentrations were 2, 2 × 2, 3, and 4 %. Measurements regarding the amount of substance released to the vessel wall were carried out on explanted porcine coronaries by means of ultraviolet and visible-light spectroscopy. Inflation time varied between 30 and 120 s. The biological effect of the coating was evaluated in a porcine peripheral overstretch and stent implantation model. Results The amount of rapamycin on the balloon surface ranged from 558 ± 108 μg for the 2 % solution to 1,441 ± 228 μg in the 4 % solution. An amount of 95 ± 63–193 ± 113 μg was released into the vessel wall. The quantitative measurements of the angiographic examinations 4 weeks after treatment revealed a reduction of diameter stenosis from 20.6 ± 17.4 % in the control group to 11.6 ± 5.5 % in the drug-eluting balloon group. Conclusion A balloon coating with rapamycin omitting an excipient is possible with a dose-adjustable coating machine. However, the biological effects are moderate, which make further optimization of the coating process and evaluation of appropriate excipients necessary.