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Background: Symptoms in acute cerebral sinus venous thrombosis (CSVT) are highly variable, ranging from headaches to fatal stroke, and the basis for this high inter-individual variability is poorly understood. The present study aimed to assess whether acute CSVT significantly alters regional cerebral blood flow (CBF), if findings differ from CBF patterns know from large-artery occlusion in stroke, and whether the pattern of CBF alterations depends on clot location. Therefore, we retrospectively analyzed 12 patients with acute CSVT 10.6 ± 4.6 days after symptom onset and ten healthy volunteers who underwent [ 15 O]water PET (two scans each, 300 ± 14 MBq [ 15 O]water). Static image datasets (15-75 s after injection; normalized to cerebellum) reflecting relative CBF (rCBF) were analyzed using voxel- and region-of-interest-based analysis (AAL3-atlas). We mirrored datasets of patients with left-sided CSVT to harmonize the affected hemisphere., Results: Seven and five patients showed right- and left-sided CSVT, respectively. The superior sagittal sinus (SSS) was involved in 8/12 patients. CSVT patients had extensive rCBF deficits in the voxel-based analysis with accentuation in the right (ipsilateral) frontal cortex and caudate nucleus compared to controls, which were most pronounced in cortical areas in those with involvement of the SSS (8/12), and in subcortical areas in those without involvement of the SSS (4/12; p < 0.05, false discovery rate corrected). ROI-analysis demonstrated significant frontal (p = 0.01) and caudate nucleus (p = 0.008) rCBF deficits driven by patients with and without SSS occlusion, respectively., Conclusions: [ 15 O]water PET was able to visualize characteristic patterns of impaired rCBF, which were different from intracranial large-artery occlusion in acute ischemic stroke, and exhibited substantial rCBF alterations depending on the involvement of the SSS. Our findings provide novel insights into the effects of disturbed venous drainage on CBF in acute CSVT, which may aid in understanding the pathophysiology, and guide future therapy of acute CSVT., Competing Interests: Declarations. Ethics approval and consent to participate: This study was performed in line with the principles of the Declaration of Helsinki. Ethics approval was granted by the Ethics Committee of Albert-Ludwigs University of Freiburg, Germany. The need for written informed consent was waived by the local ethics committee (19 December 2023/No 23-1549-S1-retro). Consent for publication: The need for written informed consent for publication by the included participants was waived by the local ethics committee (19 December 2023/No 23-1549-S1-retro). Competing interests: The authors have no relevant financial or non-financial interests to disclose., (© 2024. The Author(s).)

Background and Purpose: Complicated American Heart Association (AHA) lesion type VI plaques (cCAPs), characterized by the presence of intraplaque hemorrhage, surface defect or thrombus, are strongly associated with ischemic stroke and stroke recurrence. Hemodynamics seem to play a relevant role for their development. Thus, we investigated the association of 4D flow-MRI derived local wall shear stress (WSS) and oscillatory shear stress (OSI) with the presence of cCAPs in patients with mild to moderate internal carotid artery (ICA) stenosis., Materials and Methods: From a prospective and consecutive cross-sectional study with 121 patients with high cardiovascular risk, 39 patients (49 carotid arteries) demonstrated a 10-50% ICA-stenosis and were included in this analysis. Plaque composition was determined according to the modified AHA classification of lesions by high-resolution multi-contrast 3T-MRI. We determined WSS (minimum, mean and maximum) and OSI in vivo by 4D flow-MRI at different locations within the stenosis (upstream, stenosis center and downstream). We studied the association of each hemodynamic parameter with the presence cCAPs by logistic regression analysis adjusted for age, sex and plaque thickness., Results: 11 (22.4%) of the 49 ICA-stenosis in our cohort showed cCAP. WSS and OSI at the beginning of the stenosis did not differ between complicated and stable plaques. By contrast, WSS was significantly higher in the stenosis center and poststenotic region in cCAPs. OSI was significantly higher in the stenosis center of stable plaques. Logistic regression analysis revealed a significant association for WSS mean (OR per SD increase 1.97, 95%-CI 1.14-3.39, p=0.015) and for WSS max (OR per SD increase 1.84; 95%-CI 1.10-3.08; p=0.020), but not for WSS min and OSI with the presence of cCAPs., Conclusions: Higher wall shear stress in ICA stenosis was significantly associated with the presence of cCAPs underlining the potential role of hemodynamics in their development., Abbreviations: cCAP, complicated carotid artery plaque; WSS, wall shear stress; OSI, oscillatory shear index., (© 2024 by American Journal of Neuroradiology.)

Purpose: Atherosclerosis of the carotid artery is a major risk factor for stroke. Quantitative assessment of the carotid vessel wall can be based on cross-sections of three-dimensional (3D) black-blood magnetic resonance imaging (MRI). To increase reproducibility, a reliable automatic segmentation in these cross-sections is essential., Approach: We propose an automatic segmentation of the carotid artery in cross-sections perpendicular to the centerline to make the segmentation invariant to the image plane orientation and allow a correct assessment of the vessel wall thickness (VWT). We trained a residual U-Net on eight sparsely sampled cross-sections per carotid artery and evaluated if the model can segment areas that are not represented in the training data. We used 218 MRI datasets of 121 subjects that show hypertension and plaque in the ICA or CCA measuring ≥ 1.5    mm in ultrasound., Results: The model achieves a high mean Dice coefficient of 0.948/0.859 for the vessel's lumen/wall, a low mean Hausdorff distance of 0.417 / 0.660    mm , and a low mean average contour distance of 0.094 / 0.119    mm on the test set. The model reaches similar results for regions of the carotid artery that are not incorporated in the training set and on MRI of young, healthy subjects. The model also achieves a low median Hausdorff distance of 0.437 / 0.552    mm on the 2021 Carotid Artery Vessel Wall Segmentation Challenge test set., Conclusions: The proposed method can reduce the effort for carotid artery vessel wall assessment. Together with human supervision, it can be used for clinical applications, as it allows a reliable measurement of the VWT for different patient demographics and MRI acquisition settings., (© 2024 The Authors.)

Background: The apnea test (AT) is an important component in the determination of brain death/death by neurologic criteria (BD/DNC) and often entails disconnecting the patient from the ventilator followed by tracheal oxygen insufflation to ensure adequate oxygenation. To rate the test as positive, most international guidelines state that a lack of spontaneous breathing must be demonstrated when the arterial partial pressure of carbon dioxide (PaCO 2 ) ≥ 60 mm Hg. However, the loss of positive end-expiratory pressure that is associated with disconnection from the ventilator may cause rapid desaturation. This, in turn, can lead to cardiopulmonary instability (especially in patients with pulmonary impairment and diseases such as acute respiratory distress syndrome), putting patients at increased risk. Therefore, this prospective study aimed to investigate whether a modified version of the AT (mAT), in which the patient remains connected to the ventilator, is a safer yet still valid alternative., Methods: The mAT was performed in all 140 BD/DNC candidates registered between January 2019 and December 2022: after 10 min of preoxygenation, (1) positive end-expiratory pressure was increased by 2 mbar (1.5 mm Hg), (2) ventilation mode was switched to continuous positive airway pressure, and (3) apnea back-up mode was turned off (flow trigger 10 L/min). The mAT was considered positive when spontaneous breathing did not occur upon PaCO 2 increase to ≥ 60 mm Hg (baseline 35-45 mm Hg). Clinical complications during/after mAT were documented., Results: The mAT was possible in 139/140 patients and had a median duration of 15 min (interquartile range 13-19 min). Severe complications were not evident. In 51 patients, the post-mAT arterial partial pressure of oxygen (PaO 2 ) was lower than the pre-mAT PaO 2 , whereas it was the same or higher in 88 cases. In patients with pulmonary impairment, apneic oxygenation during the mAT improved PaO 2 . In 123 cases, there was a transient drop in blood pressure at the end of or after the mAT, whereas in 12 cases, the mean arterial pressure dropped below 60 mm Hg., Conclusions: The mAT is a safe and protective means of identifying patients who no longer have an intact central respiratory drive, which is a critical factor in the diagnosis of BD/DNC. Clinical trial registration DRKS, DRKS00017803, retrospectively registered 23.11.2020, https://drks.de/search/de/trial/DRKS00017803., (© 2024. The Author(s).)

TFF3 is a typical secretory poplypeptide of mucous epithelia belonging to the trefoil factor family (TFF) of lectins. In the intestine, respiratory tract, and saliva, TFF3 mainly exists as a high-molecular-mass complex with IgG Fc binding protein (FCGBP), which is indicative of a role in mucosal innate immunity. For the first time, we identified different forms of TFF3 in the endocervix, i.e., monomeric and homodimeric TFF3, as well as a high-molecular-mass TFF3-FCGBP complex; the latter also exists in a hardly soluble form. Immunohistochemistry co-localized TFF3 and FCGBP. Expression analyses of endocervical and post-menopausal vaginal specimens revealed a lack of mucin and TFF3 transcripts in the vaginal specimens. In contrast, genes encoding other typical components of the innate immune defense were expressed in both the endocervix and vagina. Of note, FCGBP is possibly fucosylated. Endocervical specimens from transgender individuals after hormonal therapy showed diminished expression, particularly of FCGBP. Furthermore, mucus swabs from the endocervix and vagina were analyzed concerning TFF3, FCGBP, and lysozyme. It was the aim of this study to illuminate several aspects of the cervico-vaginal innate immune barrier, which is clinically relevant as bacterial and viral infections are also linked to infertility, pre-term birth and cervical cancer.

Background: A broader distribution of bedside color-coded duplex sonography (CCD) for detection of cerebral circulatory arrest (CCA) would be important to improve its use in the diagnosis of irreversible loss of brain function (ILBF-Dx)., Question: Is extracranial compared to the commonly applied transcranial CCD of the brain-supplying vessels (ECCD vs. TCCD) equivalent for the detection of CCA in ILBF-Dx regarding specificity and sensitivity?, Material and Methods: Study period January 2019-June 2022, screening of 136 and inclusion of 114 patients with severe brain lesions > 24 h after onset of fixed and dilated pupils, apnea and completed ILBF-Dx. Exclusion of patients without brainstem areflexia and guideline-conform applicability of CCD. Complementary ECCD (and TCCD, if other method used for irreversibility detection)., Results: Detection of ILBF (ILBF+) in 86.8% (99/114), no ILBF (ILBF-) in 13.2% (15/114). ECCD was fully feasible in all patients; findings matching CCA were found in 94/99 ILBF+ cases (ECCD+) and not in 5 patients (ECCD-). All 15 patients with ILBF- showed ECCD- findings. Thus, the specificity of ECCD was 1.0, and the sensitivity was 0.949. TCCD showed CCA in 56 patients (TCCD+), and ECCD+ was also found in all of them. An inconclusive result of TCCD in ILBF+ was found in 38 cases, with parallel ECCD+ in all of these patients. In 20 cases, TCCD did not show CCA (TCCD-), these also showed ECCD-. Of these patients 15 were ILBF- and 5 were ILBF+., Discussion: TCCD was not completely feasible or inconclusive in one third of the cases, whereas ECCD was always feasible. ECCD showed high validity with respect to the detection of CCA. Therefore, the possibility of using ECCD alone to detect CCA in ILBF-Dx should be discussed., (© 2023. The Author(s).)

Introduction: Complicated carotid artery plaques (cCAPs) are associated with an increased risk of rupture and subsequent stroke. The geometry of the carotid bifurcation determines the distribution of local hemodynamics and could thus contribute to the development and composition of these plaques. Therefore, we studied the role of carotid bifurcation geometry in the presence of cCAPs., Methods: We investigated the association of individual vessel geometry with carotid artery plaque types in the Carotid Plaque Imaging in Acute Stroke (CAPIAS) study. After excluding arteries without plaque or with insufficient MRI quality, 354 carotid arteries from 182 patients were analyzed. Individual parameters of carotid geometry [i.e., internal carotid artery (ICA)/common carotid artery (CCA) ratio, bifurcation angle, and tortuosity) were derived from time-of-flight MR images. The lesion types of carotid artery plaques were determined according to the American Heart Association classification of lesions by multi-contrast 3T-MRI. The association between carotid geometry and a cCAP was studied using logistic regression after adjusting for age, sex, wall area, and cardiovascular risk factors., Results: Low ICA/CCA ratios (OR per SD increase 0.60 [95%CI: 0.42-0.85]; p  = 0.004) and low bifurcation angles (OR 0.61 [95%CI: 0.42-0.90]; p  = 0.012) were significantly associated with the presence of cCAPs after adjusting for age, sex, cardiovascular risk factors, and wall area. Tortuosity had no significant association with cCAPs. Only ICA/CCA ratio remained significant in a model containing all three geometric parameters (OR per SD increase 0.65 [95%CI: 0.45-0.94]; p  = 0.023)., Conclusions: A steep tapering of the ICA relative to the CCA and, to a lesser extent, a low angle of the carotid bifurcation were associated with the presence of cCAPs. Our findings highlight the contribution of bifurcation geometry to plaque vulnerability. Thus, assessment of carotid geometry could be helpful in identifying patients at risk of cCAPs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Strecker, Kopczak, Saam, Sepp, Hennemuth, Mayerhofer, Poli, Ziemann, Poppert, Schindler and Harloff.)

We comprehensively studied morphological and functional aortic aging in a population study using modern three-dimensional MR imaging to allow future comparison in patients with diseases of the aortic valve or aorta. We followed 80 of 126 subjects of a population study (20 to 80 years of age at baseline) using the identical methodology 6.0 ± 0.5 years later. All underwent 3 T MRI of the thoracic aorta including 3D T1 weighted MRI (spatial resolution 1 mm 3 ) for measuring aortic diameter and plaque thickness and 4D flow MRI (spatial/temporal resolution = 2 mm 3 /20 ms) for calculating global and regional aortic pulse wave velocity (PWV) and helicity of aortic blood flow. Mean diameter of the ascending aorta (AAo) decreased and plaque thickness increased significantly in the aortic arch (AA) and descending aorta (DAo) in females. PWV of the thoracic aorta increased (6.4 ± 1.5 to 7.0 ± 1.7 m/s and 6.8 ± 1.5 to 7.3 ± 1.8 m/s in females and males, respectively) over time. Local normalized helicity volumes (LNHV) decreased significantly in the AAo and AA (0.33 to 0.31 and 0.34 to 0.32 in females and 0.34 to 0.32 and 0.32 to 0.28 in males). By contrast, helicity increased significantly in the DAo in both genders (0.28 to 0.29 and 0.29 to 0.30, respectively). 3D MRI was able to characterize changes in aortic diameter, plaque thickness, PWV and helicity during six years in our population. Aortic aging determined by 3D multi-parametric MRI is now available for future comparisons in patients with diseases of the aortic valve or aorta., (© 2023. The Author(s).)

Background: Undetermined stroke etiology hampers optimal secondary prevention in a large proportion of young patients. We explored whether genetic screening for clonal hematopoiesis of indetermined potential (CHIP), a novel risk factor for stroke, could identify patients with myeloid precursor lesions or covert myeloid neoplasm requiring specific treatment., Methods: We performed targeted sequencing on 56 genes recurrently mutated in hematologic neoplasms in a prospective cohort of patients with acute brain ischemia between 18 and 60 years. CHIP prevalence was compared with age-matched healthy controls from the Nijmegen Biomedical Study (n=1604) and the UK Biobank (n=101 678). Patients with suspicion of high-risk CHIP or myeloid neoplasm were invited for further hematologic evaluation., Results: We included 248 consecutive patients (39% women) of whom 176 (71%) had cryptogenic stroke etiology. Fifty-one (21%) patients had CHIP, 3-fold more than in the general population (7.7% versus 2.6% for the Nijmegen Biomedical Study and 11.9% versus 4.1% for UK Biobank; P <0.001 for both). Patients with CHIP were older (median [interquartile range], 53 [50-59] versus 51 [41-56] years; P <0.001), had higher carotid intima-media thickness (0.68 [0.58-0.80] versus 0.59 [0.51-0.73] mm; P =0.009), and had higher burden of atherosclerosis (29.4% versus 16.7%; P =0.04). We invited 11 patients (4.4%) for further hematologic assessment, which in 7 led to the diagnosis of high-risk CHIP and in 2 to the new diagnosis of a myeloproliferative neoplasm with indication for cytoreductive therapy., Conclusions: Using genetic screening for myeloid disorders in patients with stroke of predominantly undetermined etiology, we found a 3-fold higher CHIP prevalence than in the general population. We identified high-risk CHIP and previously covert myeloproliferative neoplasms as potential stroke etiologies in 4.4% and 1% of patients, respectively. Our findings demonstrate the diagnostic and therapeutic yield of genetic screening in young patients with stroke. Future studies should investigate the role of CHIP for stroke recurrence and optimal secondary prevention.

Background: Transcranial color-coded duplex sonography (TCCD) can be used as an ancillary test for determining irreversible loss of brain function (ILBF) when demonstration of cerebral circulatory arrest (CCA) is required. However, visualization of the intracranial vessels by TCCD is often difficult, or even impossible, in this patient cohort due to elevated intracranial pressure, an insufficient transtemporal bone window, or warped anatomical conditions. Since extracranial color-coded duplex sonography (ECCD) can be performed without restriction in the aforementioned situations, we investigated the feasibility of omitting TCCD altogether, such that the ILBF examination would be simplified, without compromising on its reliability., Methods: A total of 122 patients were prospectively examined by two experienced neurointensivists for the presence of ILBF from 01/2019-12/2021. Inclusion criteria were (i) the presence of a severe cerebral lesion on cranial CT or MRI, and (ii) brainstem areflexia. Upon standardized clinical examination, 9 patients were excluded due to incomplete brainstem areflexia, and a further 22 due to the presence of factors with a potentially confounding influence on apnea testing, EEG or sonography. A total of 91 patients were enrolled and underwent needle-EEG recording for >30 min (= gold standard), as well as ECCD and TCCD. The sonographer was blinded to the EEG result., Results: All patients whose ECCD result was consistent with ILBF had this diagnosis confirmed by EEG ( n = 77; specificity: 1). Both ECCD and EEG were not consistent with ILBF in a further 12 patients. In the remaining two patients, ECCD detected reperfusion due to long-lasting cerebral hypoxia; however, ILBF was ultimately confirmed by EEG (sensitivity: 0.975). This yielded a positive predictive value (PPV) of one and a negative predictive value of 0.857 for the validity of ECCD in ILBF confirmation. TCCD was not possible/inconclusive in 31 patients (34%)., Conclusions: The use of ECCD for the confirmation of ILBF is associated with high levels of specificity and a high positive predictive value when compared to needle-electrode EEG. This makes ECCD a potential alternative to the ancillary tests currently used in this setting, but confirmation in a multi-center trial is warranted., Trial Registration: https://www.drks.de, DRKS00017803., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lambeck, Strecker, Niesen and Bardutzky.)

Background: Complicated nonstenosing carotid artery plaques (CAPs) are an under-recognized cause of stroke., Objectives: The purpose of this study was to determine whether complicated CAP ipsilateral to acute ischemic anterior circulation stroke (icCAP) are associated with recurrent ischemic stroke or transient ischemic attack (TIA)., Methods: The CAPIAS (Carotid Plaque Imaging in Acute Stroke) multicenter study prospectively recruited patients with ischemic stroke restricted to the territory of a single carotid artery. Complicated (AHA-lesion type VI) CAP were defined by multisequence, contrast-enhanced carotid magnetic resonance imaging obtained within 10 days from stroke onset. Recurrent events were assessed after 3, 12, 24, and 36 months. The primary outcome was recurrent ischemic stroke or TIA., Results: Among 196 patients enrolled, 104 patients had cryptogenic stroke and nonstenosing CAP. During a mean follow-up of 30 months, recurrent ischemic stroke or TIA occurred in 21 patients. Recurrent events were significantly more frequent in patients with icCAP than in patients without icCAP, both in the overall cohort (incidence rate [3-year interval]: 9.50 vs 3.61 per 100 patient-years; P = 0.025, log-rank test) and in patients with cryptogenic stroke (10.92 vs 1.82 per 100 patient-years; P = 0.003). The results were driven by ipsilateral events. A ruptured fibrous cap (HR: 4.91; 95% CI: 1.31-18.45; P = 0.018) and intraplaque hemorrhage (HR: 4.37; 95% CI: 1.20-15.97; P = 0.026) were associated with a significantly increased risk of recurrent events in patients with cryptogenic stroke., Conclusions: Complicated CAP ipsilateral to acute ischemic anterior circulation stroke are associated with an increased risk of recurrent ischemic stroke or TIA. Carotid plaque imaging identifies high-risk patients who might be suited for inclusion into future secondary prevention trials. (Carotid Plaque Imaging in Acute Stroke [CAPIAS]; NCT01284933)., Competing Interests: Funding Support and Author Disclosures This work was supported by the Vascular Dementia Research Foundation and the German Research Foundation (DFG) as part of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy, ID 390857198) and CRC 1123 (B3). Dr Schindler was supported by a grant from the German Research Foundation (DFG) (SCHI 1394/1-1). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Indication of transesophageal echocardiography (TEE) in patients ≤60 years with brain ischemia is uncertain., Methods: This prospective double-blinded study included patients with cryptogenic acute ischemic stroke or transient ischemic attack (TIA) ≥18 and ≤60 years. After routine diagnostics, all patients underwent patent foramen ovale (PFO) screening by transcranial Doppler (TCD) bubble test, carotid ultrasound for atherosclerosis screening (intima-media-thickness >0.90 mm or plaques), and TEE. We calculated sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) of the combined non-invasive ultrasound to predict therapy-relevant TEE findings., Results: We included 240 consecutive patients (median 51 years, 39% women) of which 68 (28.3%) had both a negative bubble test and no carotid atherosclerosis. Of these, 66 (97.1%) had unremarkable TEE findings; in one patient a small PFO was found and closed subsequently, in another patient a 4.9 mm thick aortic atheroma was found, and double platelet inhibition initiated. Of the other 172 (71.7%) patients, 93 (54%) had PFO and 9 (5.2%) complex aortic plaques. No other therapy-relevant findings were present in both groups. Non-invasive ultrasound had a sensitivity of 98.0%, specificity of 47.8%, NPV of 97.1%, and PPV of 58.1% for therapy-relevant TEE findings., Conclusions: Bubble test and carotid ultrasound could be used for the individual decision for/against TEE in patients with cryptogenic stroke ≤60 years. If they are unremarkable, TEE can be omitted with high safety regarding secondary prevention. If bubble test is positive and/or carotid ultrasound shows atherosclerosis, TEE should be carried out if PFO or aortic atheroma are potentially relevant for further patient management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mayerhofer, Kanz, Guschlbauer, Anderson, Asmussen, Grundmann, Strecker and Harloff.)

Background: Aortic stiffness is associated with a higher incidence of cardiovascular events including stroke. The primary aim of this study was to evaluate whether increased pulse wave velocity (PWV), a marker of stiffness, is an independent predictor of aortic atheroma. The secondary aim was to test whether increased PWV reinforces retrograde blood flow from the descending aorta (DAo), a mechanism of stroke., Methods: We performed a cross-sectional case-control study with prospective data acquisition. In all, 40 stroke and 60 ophthalmic patients matched for age and cardiovascular risk factors were included. Multicontrast magnetic resonance imaging (MRI) protocol of the aorta tailored to allow a detailed plaque analysis using 3-dimensional (D) T1-weighted bright blood, T2-weighted and proton density-weighted black blood, and hemodynamic assessment using 4D flow MRI was applied. Individual PWV was calculated based on 4D flow MRI data using the time-to-foot of the blood flow waveform. The extent of maximum retrograde blood flow from the proximal DAo into the arch was quantified., Results: PWV was higher in stroke patients compared with controls (7.62±2.59 vs. 5.96±2.49 m/s; P=0.005) and in patients with plaques (irrespective of thickness) compared with patients without plaques (7.47±2.89 vs. 5.62±1.89 m/s; P=0.002). Increased PWV was an independent predictor of plaque prevalence and contributed significantly to a predictor model explaining 36.5% (Nagelkerke R2) of the variance in plaque presence. Maximum retrograde flow extent from the proximal DAo was not correlated with PWV., Conclusions: Aortic stiffness was higher in stroke patients and associated with a higher prevalence of plaques. Increased PWV was an independent predictor of plaque presence. Accordingly, regional PWV seems to be a valuable biomarker for the assessment and management of aortic atherosclerosis. However, no association was found for increased retrograde flow extent from the DAo., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Selective therapeutic hypothermia (TH) showed promising preclinical results as a neuroprotective strategy in acute ischemic stroke. We aimed to assess safety and feasibility of an intracarotid cooling catheter conceived for fast and selective brain cooling during endovascular thrombectomy in an ovine stroke model.Transient middle cerebral artery occlusion (MCAO, 3 h) was performed in 20 sheep. In the hypothermia group (n = 10), selective TH was initiated 20 minutes before recanalization, and was maintained for another 3 h. In the normothermia control group (n = 10), a standard 8 French catheter was used instead. Primary endpoints were intranasal cooling performance (feasibility) plus vessel patency assessed by digital subtraction angiography and carotid artery wall integrity (histopathology, both safety). Secondary endpoints were neurological outcome and infarct volumes.Computed tomography perfusion demonstrated MCA territory hypoperfusion during MCAO in both groups. Intranasal temperature decreased by 1.1 °C/3.1 °C after 10/60 minutes in the TH group and 0.3 °C/0.4 °C in the normothermia group (p < 0.001). Carotid artery and branching vessel patency as well as carotid wall integrity was indifferent between groups. Infarct volumes (p = 0.74) and neurological outcome (p = 0.82) were similar in both groups.Selective TH was feasible and safe. However, a larger number of subjects might be required to demonstrate efficacy.

Introduction: Carotid geometry and wall shear stress (WSS) have been proposed as independent risk factors for the progression of carotid atherosclerosis, but this has not yet been demonstrated in larger longitudinal studies. Therefore, we investigated the impact of these biomarkers on carotid wall thickness in patients with high cardiovascular risk. Methods: Ninety-seven consecutive patients with hypertension, at least one additional cardiovascular risk factor and internal carotid artery (ICA) plaques (wall thickness ≥ 1.5 mm and degree of stenosis ≤ 50%) were prospectively included. They underwent high-resolution 3D multi-contrast and 4D flow MRI at 3 Tesla both at baseline and follow-up. Geometry (ICA/common carotid artery (CCA)-diameter ratio, bifurcation angle, tortuosity and wall thickness) and hemodynamics [WSS, oscillatory shear index (OSI)] of both carotid bifurcations were measured at baseline. Their predictive value for changes of wall thickness 12 months later was calculated using linear regression analysis for the entire study cohort (group 1, 97 patients) and after excluding patients with ICA stenosis ≥10% to rule out relevant inward remodeling (group 2, 61 patients). Results: In group 1, only tortuosity at baseline was independently associated with carotid wall thickness at follow-up (regression coefficient = -0.52, p < 0.001). However, after excluding patients with ICA stenosis ≥10% in group 2, both ICA/CCA-ratio (0.49, p < 0.001), bifurcation angle (0.04, p = 0.001), tortuosity (-0.30, p = 0.040), and WSS (-0.03, p = 0.010) at baseline were independently associated with changes of carotid wall thickness at follow-up. Conclusions: A large ICA bulb and bifurcation angle and low WSS seem to be independent risk factors for the progression of carotid atherosclerosis in the absence of ICA stenosis. By contrast, a high carotid tortuosity seems to be protective both in patients without and with ICA stenosis. These biomarkers may be helpful for the identification of patients who are at particular risk of wall thickness progression and who may benefit from intensified monitoring and treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Strecker, Krafft, Kaufhold, Hüllebrandt, Treppner, Ludwig, Köber, Hennemuth, Hennig and Harloff.)

Objectives: To describe the perceptions of Australian occupational therapists of their role, knowledge and skills in enabling older adults with delirium to participate in meaningful occupations., Methods: This is a mixed-methods cross-sectional study. Participants (n = 91) completed an online survey, with quantitative data analysed descriptively and qualitative data subjected to content analysis., Results: Occupational therapists had good general delirium knowledge, but less understanding of specific risk factors. Participants asserted the importance of occupational therapy assessment and treatment for older people experiencing delirium and generally felt confident or somewhat confident in their skills. While all participants provided collaborative care with multidisciplinary team members, only a minority thought colleagues had a satisfactory knowledge of the occupational therapy role with delirium., Conclusion: Currently, the role of occupational therapy with older people experiencing delirium remains emerging rather than established, and there are many opportunities for further research and development in this practice area., (© 2020 AJA Inc.)

Positive psychology deals with factors that make life most worth living and focuses on enhancing individual potentials. Particularly, character strengths can positively contribute to well-being and work-related health, bearing a promising potential for professions, such as physicians, who are at risk for burnout or mental illnesses. This study aims to identify beneficial character strengths by examining the quantitative and qualitative data. In a cross-sectional multi-method study, 218 hospital physicians completed an online survey assessing their character strengths and their general and work-related well-being, comprising thriving, work engagement, and burnout dimensions (outcome variables). Quantitative data were analyzed for the total sample and by tertiary split. Additionally, interview-gathered opinions of four resident physicians and four medical specialist educators were collected to expand the perspective on which character strengths might be beneficial for the well-being of the resident physicians. The highest significant correlations between character strengths and outcome variables were found for hope and thriving ( r = 0.67), zest , and work engagement ( r = 0.67) as well as emotional exhaustion ( r = -0.47), perseverance/leadership and depersonalization ( r = -0.27), bravery , and reduced personal accomplishment ( r = -0.39). Tertiary splits revealed that some correlations were not consistent across the entire scale continuum, for example, creativity was only significantly correlated with comparatively high levels of thriving ( r = 0.28) or forgiveness with comparatively high levels of depersonalization ( r = -0.34). Humility , s ocial intelligence , and teamwork showed predominantly low correlations with all outcome variables ( r = -0.17 - 0.34), although humility was stated by all interviewed medical specialist educators to be the most relevant for the well-being at work, and the latter two by three resident physicians, respectively. Different perspectives resulting from quantitative and qualitative data in terms of beneficial character strengths for work-related well-being may be driven by different work experiences, professional understandings, generational beliefs, or social expectations. Some significant correlations between character strengths and well-being outcomes varied depending on low, medium, or high outcomes. This raises questions about suitable work-related well-being interventions, as simple single intervention approaches (one intervention fits all) may not work for the respective outcome levels. These new findings warrant further research on how to foster the well-being of resident physicians at work., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kachel, Huber, Strecker, Höge and Höfer.)

Research on applying signature character strengths demonstrated positive effects on well-being, health and work behavior. Future health care professionals represent a group at risk for impaired well-being due to high study demands. This study investigates potential long-term protective effects on well-being. In total, 504 medical students participated in a longitudinal online study, with at least 96 providing complete data at all three time points (time lag: 1 year). Data on individual signature character strengths and their applicability, thriving (subjective and psychological well-being), work engagement, burnout, mental and physical health were collected. Longitudinal relations of signature character strengths' applicability and well-being, mental and physical health were tested with cross-lagged panel analyses. Moreover, indirect longitudinal mediation effects via work engagement and emotional exhaustion were considered. Cross-lagged panel analyses demonstrated significant positive effects of thriving on signature character strengths' applicability at later time points ( β = 0.20 to 0.27) indicating that higher levels of well-being might be mandatory first to have access to one's own signature character strengths in a naturalistic setting. Disentangling thriving, the effect was only significant for psychological well-being (t1-t2: β = 0.23; t2-t3: β = 0.27). Across all three time points, significant indirect effects via work engagement on the relation of the applicability of signature character strengths and well-being were identified ( r = 0.15), whereas significant indirect effects on mental and physical health were only evident at t2 (both: r = 0.06) and t3 (mental health: r = 0.11). A longitudinal mediation analysis via work engagement revealed a significant indirect effect ( a ∗ b = 0.13). These results call for further research as previous studies showed that the applicability of signature character strengths affected well-being, not vice versa. The 'broaden-and-build' theory (positive emotions broaden one's consciousness and hereupon individuals build new enduring resources and skills) and the assumption of well-being in a "top-down" model (trait-like predisposition to interpret life experiences in positive ways coloring one's evaluation of satisfaction in various domains accordingly) could possibly explain these novel results., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Huber, Bair, Strecker, Höge and Höfer.)

Character strengths profiles in the specific setting of medical professionals are widely unchartered territory. This paper focused on an overview of character strengths profiles of medical professionals (medical students and physicians) based on literature research and available empirical data illustrating their impact on well-being and work engagement. A literature research was conducted and the majority of peer-reviewed considered articles dealt with theoretical or conceptually driven 'virtues' associated with medical specialties or questions of ethics in patient care (e.g., professionalism, or what makes a good physician). The virtues of compassion, courage, altruism, and benevolence were described most often. Only a limited number of papers addressed character strengths of medical students or physicians according to the VIA-classification. Those articles showed that the VIA-character strengths fairness, honesty , kindness , and teamwork were considered most often by respondents to be particularly important for the medical profession. Available cross-sectional (time span: six years) and longitudinal (time span: three years) data regarding VIA-character strengths profiles of medical professionals were analyzed ( N = 584 medical students, 274 physicians). These profiles were quite homogenous among both groups. The character strengths fairness , honesty , judgment , kindness , and love had the highest means in both samples. Noteworthy differences appeared when comparing medical specialties, in particular concerning general surgeons and psychiatrists, with the former reporting clearly higher levels of e.g., honesty ( d = 1.02) or prudence ( d = 1.19). Long-term results revealed significant positive effects of character strengths on well-being and work engagement (e.g., perseverance on physicians' work engagement) but also significant negative effects (e.g., appreciation of beauty and excellence on students' well-being). Further, hope was significantly associated both positively with physicians' well-being and negatively with students' work engagement, possibly indicating specific issues concerning medical education or hospital working conditions. According to the modern-day physician's pledge, medical professionals should pay attention to their own well-being and health. Therefore, promoting self-awareness and character building among medical professionals could be a beneficial strategy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Huber, Strecker, Kachel, Höge and Höfer.)

Introduction: The indication of transesophageal echocardiography (TEE) in acute stroke is unclear. Thus, we systematically studied the impact of TEE on determining stroke etiology and secondary prevention in patients of different age-groups with cryptogenic stroke. Methods: Four hundred and eighty five consecutive patients with acute retinal or cerebral ischemia were prospectively included and underwent routine stroke workup including TEE. Stroke etiology was identified according to the TOAST classification and patients were divided in those with determined and cryptogenic stroke etiology without TEE results. Then, the frequency of high- and potential-risk sources in TEE was evaluated in <55, 55-74, and ≥75 year-old patients with cryptogenic stroke etiology. Results: Without TEE, stroke etiology was cryptogenic in 329(67.8%) patients and TEE determined possible etiology in 158(48.4%) of them. In patients aged <55, 55-74, ≥75, TEE detected aortic arch plaques ≥4 mm thickness in 2(1.2%), 37(23.0%), and 33(40.2%) and plaques with superimposed thrombi in 0(0.0%), 5(3.1%), and 7(8.5%); left atrial appendage peak emptying flow velocity ≤30cm/s in 0(0.0%), 1(0.6%), and 2(2.4%), spontaneous echo contrast in 0(0.0%), 1(0.6%), and 6(7.3%), endocarditis in 0(0.0%), 0(0.0%), and 1(1.2%) and patent foramen ovale (PFO) plus atrial septum aneurysm (ASA) in 18(20.9%), 32(19.9%), and 14(17.1%), respectively. TEE changed secondary prevention in 16.4% of these patients following guidelines of 2010/11 and still 9.4% when applying the guidelines of 2020. Conclusions: TEE was highly valuable for determining stroke etiology and influenced individual secondary prevention based on available treatment guidelines and expert opinion in most cases. In young patients the impact of TEE was limited to the detection of septal anomalies. By contrast, in older patients TEE detected high numbers of complex aortic atheroma and potential indicators of paroxysmal atrial fibrillation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Strecker, Günther and Harloff.)

Background: The underlying etiology of ischemic stroke remains unknown in up to 30% of patients., Objectives: This study explored the causal role of complicated (American Heart Association-lesion type VI) nonstenosing carotid artery plaques (CAPs) in cryptogenic stroke (CS)., Methods: CAPIAS (Carotid Plaque Imaging in Acute Stroke) is an observational multicenter study that prospectively recruited patients aged older than 49 years with acute ischemic stroke that was restricted to the territory of a single carotid artery on brain magnetic resonance imaging (MRI) and unilateral or bilateral CAP (≥2 mm, NASCET [North American Symptomatic Carotid Endarterectomy Trial] <70%). CAP characteristics were determined qualitatively and quantitatively by high-resolution, contrast-enhanced carotid MRI at 3T using dedicated surface coils. The pre-specified study hypotheses were that that the prevalence of complicated CAP would be higher ipsilateral to the infarct than contralateral to the infarct in CS and higher in CS compared with patients with cardioembolic or small vessel stroke (CES/SVS) as a combined reference group. Patients with large artery stroke (LAS) and NASCET 50% to 69% stenosis served as an additional comparison group., Results: Among 234 recruited patients, 196 had either CS (n = 104), CES/SVS (n = 79), or LAS (n = 19) and complete carotid MRI data. The prevalence of complicated CAP in patients with CS was significantly higher ipsilateral (31%) to the infarct compared with contralateral to the infarct (12%; p = 0.0005). Moreover, the prevalence of ipsilateral complicated CAP was significantly higher in CS (31%) compared with CES/SVS (15%; p = 0.02) and lower in CS compared with LAS (68%; p = 0.003). Lipid-rich and/or necrotic cores in ipsilateral CAP were significantly larger in CS compared with CES/SVS (p < 0.05)., Conclusions: These findings substantiate the role of complicated nonstenosing CAP as an under-recognized cause of stroke. (Carotid Plaque Imaging in Acute Stroke [CAPIAS]; NCT01284933)., Competing Interests: Author Relationship With Industry This work was supported by the Vascular Dementia Research Foundation and the German Research Foundation (DFG) as part of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy). Dr. Schindler was supported by a grant from the German Research Foundation (DFG) (SCHI 1394/1-1). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The posterior wall of the proximal internal carotid artery (ICA) is the predilection site for the development of stenosis. To optimally prevent stroke, identification of new risk factors for plaque progression is of high interest. Therefore, we studied the impact of carotid geometry and wall shear stress on cardiovascular magnetic resonance (CMR)-depicted wall thickness in the ICA of patients with high cardiovascular disease risk., Methods: One hundred twenty-one consecutive patients ≥50 years with hypertension, ≥1 additional cardiovascular risk factor and ICA plaque ≥1.5 mm thickness and < 50% stenosis were prospectively included. High-resolution 3D-multi-contrast (time of flight, T1, T2, proton density) and 4D flow CMR were performed for the assessment of morphological (bifurcation angle, ICA/common carotid artery (CCA) diameter ratio, tortuosity, and wall thickness) and hemodynamic parameters (absolute/systolic wall shear stress (WSS), oscillatory shear index (OSI)) in 242 carotid bifurcations., Results: We found lower absolute/systolic WSS, higher OSI and increased wall thickness in the posterior compared to the anterior wall of the ICA bulb (p < 0.001), whereas this correlation disappeared in ≥10% stenosis. Higher carotid tortuosity (regression coefficient = 0.764; p < 0.001) and lower ICA/CCA diameter ratio (regression coefficient = - 0.302; p < 0.001) were independent predictors of increased wall thickness even after adjustment for cardiovascular risk factors. This association was not found for bifurcation angle, WSS or OSI in multivariate regression analysis., Conclusions: High carotid tortuosity and low ICA diameter were independent predictors for wall thickness of the ICA bulb in this cross-sectional study, whereas this association was not present for WSS or OSI. Thus, consideration of geometric parameters of the carotid bifurcation could be helpful to identify patients at increased risk of carotid plaque generation. However, this association and the potential benefit of WSS measurement need to be further explored in a longitudinal study.

Core fucosylation of N-glycans is catalyzed by fucosyltransferase 8 and is associated with various types of cancer. Most reported fucosyltransferase inhibitors contain non-drug-like features, such as charged groups. New starting points for the development of inhibitors of fucosyltransferase 8 using a fragment-based strategy are presented. Firstly, we discuss the potential of a new putative binding site of fucosyltransferase 8 that, according to a molecular dynamics (MD) simulation, is made accessible by a significant motion of the SH3 domain. This might enable the design of completely new inhibitor types for fucosyltransferase 8. Secondly, we have performed a docking study targeting the donor binding site of fucosyltransferase 8, and this yielded two fragments that were linked and trimmed in silico. The resulting ligand was synthesized. Saturation transfer difference (STD) NMR confirmed binding of the ligand featuring a pyrazole core that mimics the guanine moiety. This ligand represents the first low-molecular-weight compound for the development of inhibitors of fucosyltransferase 8 with drug-like properties., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The original Values in Action Inventory of Strengths (VIA-IS) is an international 240 item validated self-report questionnaire measuring character strengths. A validated and reliable English 120-item short form (VIA-120) is available. However, there is limited information about the psychometric properties of the German VIA-120. This article addresses this gap and reports the reliability, validity and comparability of the German VIA-120 with the German VIA-240 version. Two independent samples were recruited: a general population sample ( N = 1073, Sample 1) and a sample consisting of medical students and physicians ( N = 685, Sample 2). Internal consistency of the VIA-120-scales ranged from α = .58 (modesty) to α = .87 (spirituality) in Sample 1 and α = .63 (honesty) to α = .90 (spirituality) in Sample 2. Intercorrelations between the scales of the 120-item version and the original 240-Items version (Sample 1) ranged from r = .52 (hope) to r = .89 (prudence). Criterion validity with the Satisfaction with Life Scale (SWLS) and the Brief Inventory of Thriving (BIT) was demonstrated. The comparison of the factor structure between the original and the short form showed a good convergence (Tucker's Phi .93-.99 Sample 1, .95-.98 Sample 2). Overall, the German VIA-120 was reliable, showed good convergence with the German VIA-240 and thus presents a similar level of validity for the assessment of character strengths. This study provides the first indication that the VIA 120 short form is comparable regarding the validity and reliability of the original VIA 240-item version indicating its potential to be used in large scale research studies., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest. Research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Signature character strengths can foster health-related outcomes in work and private life, thus being particularly important for endangered occupational groups like physicians. However, situational circumstances need to allow character strengths demonstration (applicability) first to enable their application. Therefore, this study addresses the role of (1) applicability of signature character strengths in work and private life beyond their possession and (2) relationships with well-being, work engagement, and burnout dimensions (emotional exhaustion, depersonalization, and reduced personal accomplishment). Hospital physicians ( N = 274) completed an online survey examining their signature character strengths and applicability, well-being, work engagement, and burnout dimensions. The top-five individual signature character strengths were fairness, honesty, judgment, kindness, and love. Hierarchical multiple linear regressions revealed that the possession as well as the applicability of signature character strengths was important in work and private life, but to different degrees. Possessing fairness, honesty, or kindness indicated significant positive relations with subjective well-being, whereas judgment and kindness seemed to negatively interact with reduced personal accomplishment. Hospital physicians' applicability of fairness, honesty, judgment, and love was particularly essential for their psychological well-being and work engagement, whereas the applicability of fairness (reduced personal accomplishment) and judgment (emotional exhaustion, depersonalization) at work interacted negatively with the respective outcomes. Therefore, creating awareness for individual signature character strengths as well as providing applicability in hospitals and private life could be a promising approach to improve physicians' well-being and consequently patient care as well as the performance of the health-care system in general.

Previous research demonstrated that the applicability of signature character strengths at work is associated with employee well-being. However, there is a lack of research on possible antecedents of the applicability of signature character strengths in the occupational domain. In this study we examined whether the perceived socio-moral climate of medical departments has a positive impact on the applicability of hospital physicians' signature character strengths and whether it relates to work engagement, hedonic subjective well-being (SWB) and eudaimonic psychological well-being (PWB). Based on cross-sectional data of N = 165 hospital physicians in Austria, we tested mediation models with perceived socio-moral climate as predictor, applicability of signature character strengths as mediator, and work engagement, SWB and PWB as outcomes. Additionally, we collected longitudinal data (time-lag T1-T2: 6 months) from a sub-sample ( n = 69) for testing the relationship between the perceived socio-moral climate and the applicability of signature character strengths over time. The cross-sectional results showed indirect effects of the perceived socio-moral climate on work engagement and eudaimonic well-being via the applicability of signature character strengths at work. Results from a cross-lagged panel analysis suggested an impact of socio-moral climate at T1 on the applicability of signature character strengths 6 months later (T2), but also an even stronger reversed effect of the applicability of signature character strengths at T1 on perceived socio-moral climate at T2.

In most of their work settings, the health and well-being of hospital physicians are at risk. Trends of work intensification and changing laws in the European Union and beyond have heightened the call for taking a closer look at the workplace and training conditions of hospital physicians. This study aims to identify specific work characteristics (such as autonomy, social support, cognitive demands, and skill adequacy), in order to determine conditions for the applicability of individual character strengths at work and in turn for increased work engagement and well-being. We examined our hypotheses based on cross-sectional ( N = 173) and longitudinal self-report data ( N = 72) of hospital physicians in Austria. The results identified significant indirect effects of skill adequacy, cognitive demands, autonomy, and social support at work - via the applicability of individual character strengths at work - on work engagement and general well-being. Longitudinal analyses additionally confirmed autonomy as a thriving work characteristic for promoting the applicability of individual character strengths over time (time lag: 6 months). This study revealed the value of enabling and preserving the applicability of character strengths in a hospital work setting and focused - for the first time - on its predicting work characteristics. Furthermore, it emphasizes the importance of securing skill adequacy early in the training of young physicians and encouraging, as well as, sustaining autonomy in their daily work life.

Reports of medical students experiencing burnout-related symptoms (e.g., cynicism) have increased in recent years. Little is known about the developmental process of this phenomenon and its relations with signature character strengths and well-being. The aim of this longitudinal analysis was to explore changes in the level of cynicism of medical students while in preclinical education. We further examined how the applicability of signature character strengths and well-being are related to this developmental process. Medical students ( N = 99) participated in three online surveys over 3 years during medical school. Latent growth modeling, latent class growth modeling, general mixed modeling was conducted, and post hoc mixed ANOVA, Friedman test and Welch test analyses were examined. The results showed an increase in cynicism among medical students from first to last measurement. Two groups with distinct developmental trajectory patterns of cynicism were identified. Students with high levels of cynicism ( high-level group) and students with changing levels of cynicism ( increasing group) perceived higher applicability of signature character strengths in private life compared to the study context. Moreover, the high-level group experienced significantly lower psychological well-being (in particular mastery, optimism, and relationship) in their first year of medical education. This explorative study offers a comprehensive understanding of cynicism development in medical students during medical school and its relations to the applicability of signature character strengths and well-being. Prospective replication studies are needed to replicate the results obtained in this study., (Copyright © 2020 Kachel, Huber, Strecker, Höge and Höfer.)

Background: Work demands, resources and stressors affecting health, well-being and motivation also exist in the work of university students. There is a shortage of measures for analyzing work characteristics in this setting., Objective: This article addresses that shortage of measures and describes the development and the validation of the short Work Analysis Measure for Students (WA-S Screening)., Methods: In study 1 (N = 422 students in Austria) the final version of the measure was developed based on analyzing the factor structure and psychometric properties of items and scales. Study 2 (N = 333 German-speaking students in Germany, Austria and Switzerland) was conducted for a cross validation and analyzing the criterion validity., Results: An eight-scale structure of the WA-S Screening was supported in study 1 and 2. The scales have shown to be significantly associated with burnout and work engagement in study 2., Conclusions: The examinations indicate that the WA-S Screening is a short, reliable and valid instrument to identify critical, health-promoting work characteristics in the context of studying at university.

Background: Hemodynamic alterations of extracranial veins are considered an etiologic factor in multiple sclerosis (MS). However, ultrasound and MRI studies could not confirm a pathophysiological link. Because of technical challenges using standard diagnostics, information about the involvement of superficial intracranial veins in proximity to the affected brain in MS is scarce., Purpose: To comprehensively investigate the hemodynamics of intracranial veins and of the venous outflow tract in MS patients and controls., Study Type: Prospective., Population: Twenty-eight patients with relapsing-remitting MS (EDSS1.9 ± 1.1; range 0-3) and 41 healthy controls., Field Strength/sequence: 3T/2D phase-contrast and time-resolved 4D flow MRI, extra- and transcranial sonography., Assessment: Hemodynamics within the superficial and deep intracranial venous system and outflow tract including the internal, basal, and great cerebral vein, straight, superior sagittal, and transverse sinuses, internal jugular and vertebral veins. Sonography adhered to the chronic cerebrospinal venous insufficiency (CCSVI) criteria., Statistical Tests: Multivariate repeated measure analysis of variance, Student's two-sample t-test, chi-square, Fisher's exact test; separate analysis of the entire cohort and 32 age- and sex-matched participants., Results: Multi- and univariate main effects of the factor group (MS patient vs. control) and its interactions with the factor vessel position (lower flow within dorsal superior sagittal sinus in MS, 3 ± 1 ml/s vs. 3.8 ± 1 ml/s; P < 0.05) in the uncontrolled cohort were attributable to age-related differences. Age- and sex-matched pairs showed a different velocity gradient in a single segment within the deep cerebral veins (great cerebral vein, vena cerebri magna [VCM] 7.6 ± 1.7 cm/s; straight sinus [StS] 10.5 ± 2.2 cm/s vs. volunteers: VCM 9.2 ± 2.3 cm/s; StS 10.2 ± 2.3 cm/s; P = 0.01), reaching comparable velocities instantaneously downstream. Sonography was not statistically different between groups., Data Conclusion: Consistent with previous studies focusing on extracranial hemodynamics, our comprehensive analysis of intracerebral venous blood flow did not reveal relevant differences between MS patients and controls. Level of Evidence 1. Technical Efficacy Stage 3. J. Magn. Reson. Imaging 2020;51:205-217., (© 2019 International Society for Magnetic Resonance in Medicine.)

Human blood group B galactosyltransferase (GTB) catalyzes the galactosylation of the H antigen and is responsible for the formation of the blood group antigen of phenotype B. The ABO blood group system is well studied and routinely serotyped before transfusion and transplantation. Blood type subgroups have been repeatedly linked to an increased occurrence of diseases (e.g., a highly increased incidence rate for pancreatic cancer for individuals with blood group phenotype B). 3-Phenyl-5-(piperazin-1-yl)-1,2,4-thiadiazole 1 has previously been described to inhibit GTB with a K i value of 800 μm. In this work, we describe a computer-guided fragment-growing approach for the optimization of this fragment that was subsequently realized by synthesizing the most promising ligands. Enlarging the phenyl moiety of fragment 1 to a naphthyl moiety resulted in ligand 3-(naphthalene-1-yl)-5-(piperazin-1-yl)-1,2,4-thiadiazole 2 a, which shows a threefold improvement in binding affinity (K i =271 μm)., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

To quantify stiffness of the descending aorta (DAo) in stroke patients using 4D flow MRI and compare results with transesophageal echocardiography (TEE). 48 acute stroke patients undergoing 4D flow MRI and TEE were included. Intima-media-thickness (IMT) was measured in the DAo and the aorta was scrutinized for atherosclerotic plaques using TEE. Stiffness of the DAo was determined by (a) 4D flow MRI at 3 T by calculating pulse wave velocity (PWV) and by (b) TEE calculating arterial strain, stiffness index, and distensibility coefficient. Mean IMT was 1.43 ± 1.75. 7 (14.6%) subjects had no sign of atherosclerosis, 10 (20.8%) had IMT-thickening or plaques < 4 mm, and 31 (66.7%) had at least one large and/or complex plaque in the aorta. Increased IMT significantly correlated (p < 0.001) with increased DAo stiffness in MRI (PWV r = 0.66) and in TEE (strain r = 0.57, stiffness index r = 0.64, distensibility coefficient r = 0.57). Patients with at least IMT-thickening had significantly higher stiffness values compared to patients without atherosclerosis. However, no difference was observed between patients with plaques < 4 mm and patients with plaques ≥ 4 mm. PWV and TEE parameters of stiffness correlated significantly [strain (r = - 0.36; p = 0.011), stiffness index (r = 0.51; p = 0.002), and distensibility coefficient (r = - 0.59; p < 0.001)]. 4D flow MRI and TEE-based parameters of aortic stiffness were associated with markers of atherosclerosis such as IMT-thickness and presence of plaques. We believe that 4D flow MRI is a promising tool for future studies of aortic atherosclerosis, due to its longer coverage of the aorta and non-invasiveness.