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Abstract Background Telemedicine provides specialized medical expertise in underserved areas where neurological expertise is frequently not available on a daily basis for hospitalized stroke patients. While tele-consultations are well established in acute stroke assessment, the value of telemedicine-based ward-rounds in the subsequent in-patient stroke management is unknown. Methods Four telemedicine stroke networks in Germany, implemented in eight out of 16 federal states, participate in this prospective observational multi-center study. We plan to enroll 523 patients hospitalized due to acute (suspected or confirmed) stroke or transient ischemic attack. Each recruited patient will receive both a tele-consultation and an on-site consultation at the same day within the first three days after hospital admission. We will test non-inferiority of telemedicine-based assessments in ward-rounds in terms of quality of medical assessment and recommendations for hospitalized stroke patients. The correctness of the medical assessment and recommendation is defined as positive evaluation (binary, correct vs. in-correct) of six out of six predefined quality indicators by at least two out of three blinded independent raters. The non-inferiority margin for the difference in proportions of correct assessments is set to 5%-points. Discussion If non-inferiority of telemedicine-based ward-rounds compared to on-site ward-rounds by a neurologist were demonstrated, telemedicine-based neurological consultation for post-acute stroke patients may contribute to deliver evidence-based high-quality stroke care more easily in underserved regions. Trial registration DRKS - DRKS00028671 ( https://drks.de/search/de/trial/DRKS00028671 ; registration date 09-27-2022).

Introduction and purposeBasilar artery occlusion (BAO) is still one of the most devastating neurological conditions associated with high morbidity and mortality. In the present study, we aimed to assess the role of posterior circulation collaterals as predictors of outcome in the BASICS trial and to compare two grading systems (BATMAN score and PC-CS) in terms of prognostic value.MethodsWe performed a sub-analysis of the BASICS trial. Baseline clinical and imaging variables were analyzed. For the imaging analysis, baseline CT and CTA were analyzed by a central core lab. Only those patients with good or moderate quality of baseline CTA and with confirmed BAO were included. Multivariable binary logistic regression analysis was used to test the independent association of clinical and imaging characteristics with a favorable outcome at 3 months (defined as a modified Rankin Score of ≤3). ROC curve analysis was used to assess and compare accuracy between the two collateral grading systems.ResultsThe mean age was 67.0 (±12.5) years, 196 (65.3%) patients were males and the median NIHSS was 21.5 (IQR 11–35). Median NCCT pc-ASPECTS was 10 (IQR10-10) and median collateral scores for BATMAN and PC-CS were 8 (IQR 7–9) and 7 (IQR 6–8) respectively. Collateral scores were associated with favorable outcome at 3 months for both BATMAN and PC-CS but only with a modest accuracy on ROC curve analysis (AUC 0.62, 95% CI [0.55–0.69] and 0.67, 95% CI [0.60–0.74] respectively). Age (OR 0.97, 95% CI [0.95–1.00]), NIHSS (OR 0.91, 95% CI [0.89–0.94]) and collateral score (PC-CS – OR 1.2495% CI [1.02–1.51]) were independently associated with clinical outcome.ConclusionThe two collateral grading systems presented modest prognostic accuracy. Only the PC-CS was independently associated with a favorable outcome at 3 months.

The addition of boron to the advanced high-strength steels (AHSS) enhances grain boundary cohesion and can play a significant role in intergranular degradation phenomena such as Zn-assisted liquid metal embrittlement (LME). The objective of this study is to reveal a thorough understanding of the effect of B on LME behaviour, where the welding test results indicated substantial improvement even at relatively low B concentration. Here, we adopted the strategy of identifying LME-sensitive grain boundaries, followed by characterizing grain boundary chemistry. EBSD measurements and prior austenite grain (PAG) reconstruction provided strong evidence of intergranular LME crack propagation via PAGBs. Further transmission electron microscopy and energy dispersive X-ray spectroscopy investigations demonstrated an asymmetric Mn profile along the PAGB in B-free steel. Therefore, we propose that B addition and consequently, lower grain boundary energy appears to prevent Mn segregation. Based on our observation, we conclude that B seems to have the similar desired effect on Zn diffusion along the PAGBs and eventually mitigates Zn-assisted LME.

Optimization of the galvannealing for cutting-edge 3rd generation AHSS requires detailed structural and chemical characterization. Alloying elements such as Si dramatically modify the steel surface, forming an oxide layer during pre-annealing, which suppresses the desired interfacial interaction. Progress is impossible without understanding the phases' interplay at the steel-coating interface. We investigated this area in high-Si (1.49 wt%) galvanized AHSS at different annealing times via TEM and revealed that while hot-dip galvanizing at 460 °C the surface oxide prevents the desired Fe-Al reaction and liquid Zn penetrating gaps in the oxide membrane forms a δ phase layer underneath. Located between the steel substrate and the oxide layer, the δ phase can grow during subsequent annealing due to incoming liquid Zn, while Fe diffusion into the coating is suppressed. The oxide film remains stable even after long-term annealing (120 s at 480 °C) separating the coating from the reaction zone. The growing δ layer interacting with the steel substrate consumes dissolved Si. Reaching a certain threshold concentration, supersaturated δ decomposes forming a δ matrix with Fe-Si-Al-based nanoprecipitates. Using EDX data, phase configuration was refined via Thermo-Calc by the Fe–Zn–Si–Al system simulation suggesting that nanoprecipitates are based on Al- and Si-rich type of α-Fe.

Designing Advanced High-Strength Steels assumes fine-tuning of alloying elements to enhance performance properties. This affects the kinetics of Fe-Zn interaction during further galvannealing. A key role here belongs to the inhibition layer at the steel/coating interface. Applying mutually-reinforcing TEM techniques, we traced the evolution of Zn-Fe phases in low- and high-Si steels during galvannealing. It has been shown that conventional room temperature Ga FIB for TEM sample preparation is applicable only to annealed low-Si steel, a coating of which comprises equilibrium Zn-Fe compounds. The phases were validated via electron microscopy and diffraction methods. In contrast, even relatively long annealing of the high-Si steel was not sufficient to form stable Zn-Fe phases pointing to a hampering of the interphase reactions. As-galvanized and annealed high-Si specimens contain almost pure Zn and are affected by Ga via a eutectic reaction during FIB preparation. Thus, low-temperature FIB has been applied for reliable Zn-coated steel preparation. We refined with HRTEM the inhibition layer structures specific for low- and high-Si steel grades. While the typical Fe2Al5-xZnx interface layer has been found in the low-Si samples, for high-Si ones the formation of a quite stable Si-Mn mixed oxide membrane, which drastically hinders Fe-Al reaction, has been disclosed.

Grain boundary wetting as a preliminary stage for zinc-induced grain boundary weakening and embrittlement in a Zn-coated press-hardened 20MnB8 steel was analyzed using electron backscatter diffraction, Auger electron spectroscopy, energy dispersive X-ray analysis, atom probe tomography and transmission electron microscopy. Microcracks at prior austenite grain boundaries were observed. Structures that developed after microcrack formation were identified: for example, Zn/Fe intermetallic phases with grain sizes smaller than 100 nm were present at the crack surfaces and the wedge-shaped crack tips. An electrolytically coated reference sample that underwent the same heat treatment as the press-hardened material but without the application of tensile stress was investigated in order to find the initial cause of the microcracks. On this sample, Zn, in the order of one atomic layer, was found along prior austenite grain boundaries several micrometers away from the actual Zn/Fe phases in the coating. The resulting grain boundary weakening with the Zn wetting of prior austenitic grain boundaries during austenitization and/or hot forming is a necessary precondition for microcrack formation.

Background: Neurocardiac dysfunction worsens clinical outcome and increases mortality in stroke survivors. We hypothesized that heart rate variability (HRV) biofeedback improves neurocardiac function by modulating autonomic nervous system activity after acute ischaemic stroke (AIS).Methods: We randomly allocated (1:1) 48 acute ischaemic stroke patients to receive nine sessions of HRV- or sham biofeedback over 3 days in addition to comprehensive stroke unit care. Before and after the intervention patients were evaluated for HRV via standard deviation of normal-to-normal intervals (SDNN, primary outcome), root mean square of successive differences between normal heartbeats (RMSSD), a predominantly parasympathetic measure, and for sympathetic vasomotor and sudomotor function. Severity of autonomic symptoms was assessed via survey of autonomic symptom scale total impact score (TIS) at baseline and after 3 months.Results: We included 48 patients with acute ischaemic stroke [19 females, ages 65 (4.4), median (interquartile range)]. Treatment with HRV biofeedback increased HRV post intervention [SDNN: 43.5 (79.0) ms vs. 34.1 (45.0) ms baseline, p = 0.015; RMSSD: 46.0 (140.6) ms vs. 29.1 (52.2) ms baseline, p = 0.015] and alleviated autonomic symptoms after 3 months [TIS 3.5 (8.0) vs. 7.5 (7.0) baseline, p = 0.029], which was not seen after sham biofeedback (SDNN: p = 0.63, RMSSD: p = 0.65, TIS: 0.06). There were no changes in sympathetic vasomotor and sudomotor function (p = ns).Conclusions: Adding HRV biofeedback to standard stroke unit care led to improved neurocardiac function and sustained alleviation of autonomic symptoms after acute ischaemic stroke, which was likely mediated by a predominantly parasympathetic mechanism.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03865225.

BackgroundIn Parkinson’s disease (PD), alpha-synuclein accumulation in cutaneous autonomic pilomotor and sudomotor nerve fibers has been linked to autonomic nervous system disturbances even in the early stages of the disease. This study aims to assess the association between alpha-synuclein-mediated structural autonomic nerve fiber damage and function in PD, elucidate the role of neuropathy progression during the early disease stages, and test reproducibility and external validity of pilomotor function assessment using quantitative pilomotor axon-reflex test and sudomotor function via quantitative direct and indirect test of sudomotor function.Methods/designA prospective controlled study will be conducted at four study sites in Europe and the USA. Fifty-two male and female patients with idiopathic PD (Hoehn and Yahr 1–2) and 52 age- and sex-matched healthy controls will be recruited. Axon-reflex-mediated pilomotor erection will be induced by iontophoresis of phenylephrine on the dorsal forearm. Silicone impressions of the response will be obtained, scanned, and quantified for pilomotor muscle impressions by number, impression size, and area of axon-reflex spread. Axon-reflex-mediated sweating following acetylcholine iontophoresis will be quantified for number and size of droplets and axon-reflex spread. Sympathetic skin responses, autonomic and motor symptoms will be evaluated. Tests will be performed at baseline, after 2 weeks, 1, 2, and 3 years. Skin biopsies will be obtained at baseline and after 3 years and will be analyzed for nerve fiber density and alpha-synuclein accumulation.DiscussionWe anticipate that progression of autonomic nerve dysfunction assessed via pilomotor and sudomotor axon-reflex tests is related to progression of autonomic symptom severity and alpha-synuclein deposition. Potential applications of the techniques include interventional studies evaluating disease-modifying approaches and clinical assessment of autonomic dysfunction in patients with PD.Clinical trail registrationTRN NCT03043768.