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When intense lightwaves accelerate electrons through a solid, the emerging high-order harmonic (HH) radiation offers key insights into the material1-11. Sub-optical-cycle dynamics-such as dynamical Bloch oscillations2-5, quasiparticle collisions6,12, valley pseudospin switching13 and heating of Dirac gases10-leave fingerprints in the HH spectra of conventional solids. Topologically non-trivial matter14,15 with invariants that are robust against imperfections has been predicted to support unconventional HH generation16-20. Here we experimentally demonstrate HH generation in a three-dimensional topological insulator-bismuth telluride. The frequency of the terahertz driving field sharply discriminates between HH generation from the bulk and from the topological surface, where the unique combination of long scattering times owing to spin-momentum locking17 and the quasi-relativistic dispersion enables unusually efficient HH generation. Intriguingly, all observed orders can be continuously shifted to arbitrary non-integer multiples of the driving frequency by varying the carrier-envelope phase of the driving field-in line with quantum theory. The anomalous Berry curvature warranted by the non-trivial topology enforces meandering ballistic trajectories of the Dirac fermions, causing a hallmark polarization pattern of the HH emission. Our study provides a platform to explore topology and relativistic quantum physics in strong-field control, and could lead to non-dissipative topological electronics at infrared frequencies.

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Searching for quantum functionalities requires access to the electronic structure, constituting the foundation of exquisite spin-valley-electronic, topological, and many-body effects. All-optical band-structure reconstruction could directly connect electronic structure with the coveted quantum phenomena if strong lightwaves transported localized electrons within preselected bands. Here, we demonstrate that harmonic sideband (HSB) generation in monolayer tungsten diselenide creates distinct electronic interference combs in momentum space. Locating these momentum combs in spectroscopy enables super-resolution tomography of key band-structure details in situ. We experimentally tuned the optical-driver frequency by a full octave and show that the predicted super-resolution manifests in a critical intensity and frequency dependence of HSBs. Our concept offers a practical, all-optical, fully three-dimensional tomography of electronic structure even in microscopically small quantum materials, band by band.

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Burns and thermal injuries from other causes often affect exposed body regions such as the hands. Besides aesthetic aspects, deep dermal burns of the skin are often critical from a functional point of view, especially for important subcutaneous structures. This article reports the course of two patients who received enzymatic debridement with bromelain-based salve as a treatment for deep grade burns of the hands.

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OBJECTIVES: To determine the shaping ability of reciprocating files without/with post-manufacturing heat treatment (Reciproc®/Reciproc blue®, VDW) when used by six operators of similar level of experience. MATERIALS AND METHODS: Plastic training blocs with curved root canals (5 mm radius, 55° angle) were mounted in a dental manikin. Each operator prepared six specimens with each instrument system using the file sizes R25, R40 and R50 consecutively. Specimens were photographed, and deviations from the centre of the canal were measured at intervals of 0.5 mm and averaged for the apical, middle and coronal part of the canal. Data were tested for significance using the Mann-Whitney U test and two-way ANOVA with instrument systems and operators serving as factors. RESULTS: Deviations were observed towards the outer curvature in the apical and coronal and to the inner curvature in the middle segment of the canal. They were larger after using larger size instruments and were smaller when using Reciproc blue® compared to Reciproc®. Significant differences among operators were observed in the middle (all sizes) and coronal part of the canals (only sizes R25 und R40). Coronally, interaction between the main factors was significant as well. CONCLUSIONS: Post-manufacturing heat treatment significantly improved shaping ability of the reciprocating file system Reciproc®. The observed differences among operators suggest the possibility of further improvement by providing specific training for prospective users. CLINICAL RELEVANCE: Maintenance of root canal curvature may be improved by using post-manufacturing heat-treated instruments, but specific training should be recommended as well.

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BACKGROUND: The biggest obstacle to overcome for routine treatment of various pathologies with fresh osteochondral allograft is the availability of tissue for transplantation. Large fresh osteochondral allografts are usually harvested from organ donors, but in contrast to organs, tissues can be procured after cardiac arrest. OBJECTIVE: Medical staff as well the general public are much less aware of the possibilities and requirements of tissue donation compared to organ donation. This review aims to highlight the current situation of organ and tissue donation in Europe and to raise this much needed awareness. MATERIAL AND METHODS: For this research, PubMed database was scanned using the terms "tissue/organ donation", "bone donation/transplantation", "cartilage transplantation/allografts" and "osteochrondral allografts". RESULTS: Relatives of potential donors are often not approached because physicians and nurses do not feel sufficiently prepared for this task and, thus, are reluctant to address this topic. Different options could alleviate the pressure medical staff is feeling. Furthermore, there are different factors influencing consent that can be addressed to increase donation rates. CONCLUSION: Currently, a lot of potential concerning musculoskeletal tissue grafts remains unused. Most importantly, families should be encouraged to speak about their potenzial will to donate and educational programs should be established to increase trust in organ and tissue donation and the allocation system and to increase knowledge about the importance of transplantation medicine. But joined efforts of different parts of the medical systems and different organizations involved in tissue transplantation should improve the situation for patients waiting for much needed transplants.

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Fresh osteochondral allografts are a well-established treatment for large, full-thickness cartilage defects. The clinical outcome for carefully selected patients is very favorable, especially for the young and active and graft survival up to 25 years has been described in the literature. Furthermore, a high patient satisfaction rate has been reported, but the biggest obstacle to overcome is the availability of tissue for transplantation. Large fresh bone allografts for cartilage damage repair only can be harvested from organ donors following organ removal or cadaveric donors, preferably in the setting of an operation room to minimize possible contamination of the tissue. Apart from the logistic challenges this entails, an experienced recovery team is needed. Furthermore, the public as well as medical staff is much less aware of the possibility and requirements of tissue donation than organ donation and families of deceased are rarely approached for bone and cartilage donation. This review aims to highlight the current situation of organ and tissue donation in Europe with special focus on the processing of bones and possible safety and quality concerns. We analyze what may prevent consent and what might be done to improve the situation of tissue donation.

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The success of corneal transplantation highly depends on the quality of the used graft. Various factors play a crucial role such as a perfect stroma without optically relevant, centrally located cloudiness or changes (e. g. scars) or an adherent Descemet membrane. One of the most important parameters is the quality of the endothelial cell layer with a sufficiently large endothelial cell count. An open question is so far whether the donor age affects corneal quality and therefore has an impact on the success of transplantation. A comprehensive review of the available literature revealed that a large amount of scientific data on the influence of donor age exist to answer this question. In a variety of studies, no significant dependence of graft quality of donor age could be detected. Rather the studies prove that graft survival depends primarily on the state of the endothelial cell layer, and postoperative endothelial cell loss must be considered as a major cause of graft failure. Extensive quality assurance procedures in tissue preparation and cornea processing in the eye banks in Germany (Europe) ensures that only corneas with tested high quality are allocated for transplantation regardless of the donor age. Against the background of an aging population, the use of grafts from older donors should not be waived.

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Effective cryopreservation protocols are essential for long-term storage of cells and their subsequent clinical application. Freezing protocols are generally considered as safe; however, putative effects on epigenetic marks have not yet been studied in detail. While post-thaw cell survival rates have been used to evaluate the success of cryopreservation protocols, increasing evidence suggests that freezing may be associated with deviations from the physiological epigenetic marks with putative long-term effects on the cells and/or their derivatives. A better understanding of the underlying mechanisms would be beneficial for improving safety and effectiveness of freezing protocols. The purpose of this review is to provide current information regarding epigenetic alterations (DNA methylation and histone modification patterns) associated with cryopreservation.

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Cryopreservation is a technique that has been extensively used for storage of multipotent mesenchymal stromal cells (MSCs) in regenerative medicine. Therefore, improving current cryopreservation procedures in terms of increasing cell viability and functionality is important. In this study, we optimized the cryopreservation protocol of MSCs derived from the common marmoset Callithrix jacchus (cj), which can be used as a non-human primate model in various pathological and transplantation studies and have a great potential for regenerative medicine. We have investigated the effect of the active control of the nucleation temperature using induced nucleation at a broad range of temperatures and two different dimethylsulfoxide concentrations (Me2SO, 5% (v/v) and 10%, (v/v)) to evaluate the overall effect on the viability, metabolic activity and recovery of cells after thawing. Survival rate and metabolic activity displayed an optimum when ice formation was induced at -10 °C. Cryomicroscopy studies indicated differences in ice crystal morphologies as well as differences in intracellular ice formation with different nucleation temperatures. High subzero nucleation temperatures resulted in larger extracellular ice crystals and cellular dehydration, whereas low subzero nucleation temperatures resulted in smaller ice crystals and intracellular ice formation.

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We sought to determine the ability of quantitative myocardial perfusion reserve index (MPRI) by cardiac magnetic resonance (CMR) and high-sensitive troponin T (hsTnT) for the prediction of cardiac allograft vasculopathy (CAV) and cardiac outcomes in heart transplant (HT) recipients. In 108 consecutive HT recipients (organ age 4.1±4.7 years, 25 [23%] with diabetes mellitus) who underwent cardiac catheterization, CAV grade by International Society for Heart & Lung Transplantation (ISHLT) criteria, MPRI, late gadolinium enhancement (LGE) and hsTnT values were obtained. Outcome data including cardiac death and urgent revascularization ("hard cardiac events") and revascularization procedures were prospectively collected. During a follow-up duration of 4.2±1.4 years, seven patients experienced hard cardiac events and 11 patients underwent elective revascularization procedures. By multivariable analysis, hsTnT and MPRI both independently predicted cardiac events, surpassing the value of LGE and CAV by ISHLT criteria. Furthermore, hsTnT and MPRI provided complementary value. Thus, patients with high hsTnT and low MPRI showed the highest rates of cardiac events (annual event rate=14.5%), while those with low hsTnT and high MPRI exhibited excellent outcomes (annual event rate=0%). In conclusion, comprehensive "bio-imaging" using hsTnT, as a marker of myocardial microinjury, and CMR, as a marker of microvascular integrity and myocardial damage by LGE, may aid personalized risk-stratification in HT recipients.

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The purpose of our study was to investigate whether the quantification of myocardial blush grade (MBG) during surveillance coronary angiography can predict long-term outcome after heart transplantation (HT). In 105 HT recipients who underwent cardiac catheterization, cardiac allograft vasculopathy (CAV) was assessed visually using the ISHLT grading scale (prospective cohort study). MBG was quantified by dividing the plateau of contrast agent gray-level intensity (G(max)) by the time-to-peak intensity (T(max)). In a subgroup (n = 72), myocardial perfusion index by cardiac magnetic resonance imaging (CMR) was assessed. During a mean follow-up duration of 2.7 (standard deviation [SD] 1.0) years, 26 patients experienced cardiac events, including 7 with cardiac death and 19 who underwent coronary revascularization. G(max)/T(max) was related to CAV by ISHLT criteria and to subsequent cardiac events. By univariate analysis, patient age, organ age, CAV, MBG and myocardial perfusion index by CMR were all predictive for cardiac events. Multivariable analysis demonstrated that G(max)/T(max) provided the most robust prediction of cardiac death (hazard ratio [HR] = 0.2, 95% confidence interval [CI] = 0.06-0.64, p < 0.01) and cardiac events (HR = 0.52, 95% CI = 0.32-0.84, p < 0.01), beyond clinical parameters and the presence of CAV. G(max)/T(max) is a valuable surrogate parameter of microvascular integrity, which is associated with cardiac death and revascularization procedures after HT.

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BACKGROUND: About 2-7% of familial cardiomyopathy cases are caused by a mutation in the gene encoding cardiac troponin I (TNNI3). The related clinical phenotype is usually severe with early onset. Here we report on all currently known mutations in the Dutch population and compared these with those described in literature. METHODS: TheTNNI3 gene was screened for mutations in all coding exons and flanking intronic sequences in a large cohort of cardiomyopathy patients. All Dutch index cases carrying a TNNI3 mutation that are described in this study underwent extensive cardiological evaluation and were listed by their postal codes. RESULTS: In 30 families, 14 different mutations were identified. Three TNNI3 mutations were found relatively frequently in both familial and non-familial cases of hypertrophic cardiomyopathy (HCM) or restrictive cardiomyopathy (RCM). Haplotype analysis showed that p.Arg145Trp and p.Ser166Phe are founder mutations in the Netherlands, while p.Glu209Ala is not. The majority of Dutch TNNI3 mutations were associated with a HCM phenotype. Mean age at diagnosis was 36.5 years. Mutations causing RCM occurred less frequently, but were identified in very young children with a poor prognosis. CONCLUSION: In line with previously published data, we found TNNI3 mutations to be rare and associated with early onset and severe clinical presentation.

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An increasing number of patients suffering from cardiovascular disease, especially coronary artery disease (CAD), are treated with aspirin and/or clopidogrel for the prevention of major adverse events. Unfortunately, there are no specific, widely accepted recommendations for the perioperative management of patients receiving antiplatelet therapy. Therefore, members of the Perioperative Haemostasis Group of the Society on Thrombosis and Haemostasis Research (GTH), the Perioperative Coagulation Group of the Austrian Society for Anesthesiology, Reanimation and Intensive Care (ÖGARI) and the Working Group Thrombosis of the European Society of Cardiology (ESC) have created this consensus position paper to provide clear recommendations on the perioperative use of anti-platelet agents (specifically with semi-urgent and urgent surgery), strongly supporting a multidisciplinary approach to optimize the treatment of individual patients with coronary artery disease who need major cardiac and non-cardiac surgery. With planned surgery, drug eluting stents (DES) should not be used unless surgery can be delayed for ≥12 months after DES implantation. If surgery cannot be delayed, surgical revascularisation, bare-metal stents or pure balloon angioplasty should be considered. During ongoing antiplatelet therapy, elective surgery should be delayed for the recommended duration of treatment. In patients with semi-urgent surgery, the decision to prematurely stop one or both antiplatelet agents (at least 5 days pre-operatively) has to be taken after multidisciplinary consultation, evaluating the individual thrombotic and bleeding risk. Urgently needed surgery has to take place under full antiplatelet therapy despite the increased bleeding risk. A multidisciplinary approach for optimal antithrombotic and haemostatic patient management is thus mandatory.

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BACKGROUND: Guidelines and practice standards for sedation in endoscopy have been developed by various national professional societies. No attempt has been made to assess consensus among internationally recognized experts in this field. AIM: To identify areas of consensus and dissent among international experts on a broad range of issues pertaining to the practice of sedation in digestive endoscopy. METHODS: Thirty-two position statements were reviewed during a 1 (1/2)-day meeting. Thirty-two individuals from 12 countries and four continents, representing the fields of gastroenterology, anaesthesiology and medical jurisprudence heard evidence-based presentations on each statement. Level of agreement among the experts for each statement was determined by an open poll. RESULTS: The principle recommendations included the following: (i) sedation improves patient tolerance and compliance for endoscopy, (ii) whenever possible, patients undergoing endoscopy should be offered the option of having the procedure either with or without sedation, (iii) monitoring of vital signs as well as the levels of consciousness and pain/discomfort should be performed routinely during endoscopy, and (iv) endoscopists and nurses with appropriate training can safely and effectively administer propofol to low-risk patients undergoing endoscopic procedures. CONCLUSIONS: While the standards of practice vary from country to country, there was broad agreement among participants regarding most issues pertaining to sedation during endoscopy.

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High-fidelity simulation uses simulators that combine all of the physiological and pharmacological responses of a human in a manikin. These simulators change and respond to the users and trainees. Using simulators for teaching sedation in the field of gastroenterology unifies all the advantages of manikins. To understand the pharmacological and pharmacodynamical principles of drugs used for sedation in different clinical scenarios, such as cardiopulmonary diseases, a high-fidelity simulator is extremely useful. Respiratory complications and airway problems are the main side effects when using sedatives. To overcome these problems, exercise of precautionary measures are highly demanded to avoid hazards. High-fidelity simulation is increasingly being used for the development of crisis resource management. There are still limitations in using simulators for education and training. At present, applying simulation for teaching is expensive. The start-up costs and the expenses for instructors and technicians are high. Moreover, no direct evidence has demonstrated that simulation training improves actual patient safety outcome and, therefore, a lot of research in this field remains to be done. Even so, confidence is growing in the validity of medical simulation as the training tool of the future.

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Unexpected bleeding in the perioperative period is largely caused by impaired inherited or drug-induced primary haemostasis. Standard tests for plasma coagulation are predominantly employed to gauge the risk of bleeding. In accordance with several reports the subcommittee for perioperative coagulation (AGPG) of the Austrian Society of Anaesthesia, Resuscitation and Intensive Care (OGARI) recommends the use of a standardised questionnaire to detect an increased risk of bleeding. Accordingly, healthy patients of the American Society of Anesthesiologists (ASA) grades I and II without any suspicion of impaired haemostasis who are scheduled for procedures without expected transfusion requirements, need no standard tests for coagulation. In all other patients (including patients taking medication affecting coagulation, or patients who are unable to provide adequate information) platelet count, platelet function, aPTT, PT, and fibrinogen levels should be assessed.

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A resistance index (RI) of 0.8 or higher was shown to be a strong predictor of kidney allograft and patient survival. Uncertainties persist since the intrarenal RI is closely associated with the vascular stiffness of the allograft recipient. To clarify the diagnostic value of RI further, we analyzed parameters of vascular stiffness of the recipient and intrarenal RI of the renal allograft. In a prospective study laboratory and clinical parameters, pulse wave velocity (PWV), intima media thickness (IMT) and RI were obtained in 76 kidney allograft patients. We found that the RI values significantly correlated with the PWV (p < 0.05) and the recipients age (p < 0.01) but not with the donor age and renal function. Using multiple regression analysis recipient age, PWV, pulse pressure (PP) and IMT were identified as independent factors influencing RI values. For a more correct interpretation of the RI values in renal allografts parameters of vascular stiffness such as IMT, PP or PWV should be included.

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