Cooling dynamics of droplets exposed to solid surface freezing and vitrification.

Solid surface freezing or vitrification (SSF/SSV) can be done by depositing droplets of a sample, e.g., cells in a preservation solution, onto a pre-cooled metal surface. It is used to achieve higher cooling rates and concomitant higher cryosurvival rates compared to immersion of samples into liquid nitrogen. In this study, numerical simulations of SSF/SSV were conducted by modeling the cooling dynamics of droplets of cryoprotective agent (CPA) solutions. It was assumed that deposited droplets attain a cylindrical bottom part and half-ellipsoidal shaped upper part. Material properties for heat transfer simulations including density, heat capacity and thermal conductivity were obtained from the literature and extrapolated using polynomial fitting. The impact of CPA type, i.e., glycerol (GLY) and dimethyl sulfoxide (DMSO), CPA concentration, and droplet size on the cooling dynamics was simulated at different CPA mass fractions at temperatures ranging from -196 to 25 °C. Simulations show that glycerol solutions cool faster compared to DMSO solutions, and cooling rates increase with decreasing CPA concentration. However, we note that material property data for GLY and DMSO solutions were obtained in different temperature and concentration ranges under different conditions, which complicated making an accurate comparison. Experimental studies show that samples that freeze have a delayed cooling response early on, whereas equilibration times are similar compared to samples that vitrify. Finally, as proof of concept, droplets of human red blood cells (RBCs) were cryopreserved using SSV/SSF comparing the effect of GLY and DMSO on cryopreservation outcome. At 20% (w/w), similar hemolysis rates were found for GLY and DMSO, whereas at 40%, GLY outperformed DMSO.

Power spectral estimate for discrete data.

The identification of cycles in periodic signals is a ubiquitous problem in time series analysis. Many real-world datasets only record a signal as a series of discrete events or symbols. In some cases, only a sequence of (non-equidistant) times can be assessed. Many of these signals are furthermore corrupted by noise and offer a limited number of samples, e.g., cardiac signals, astronomical light curves, stock market data, or extreme weather events. We propose a novel method that provides a power spectral estimate for discrete data. The edit distance is a distance measure that allows us to quantify similarities between non-equidistant event sequences of unequal lengths. However, its potential to quantify the frequency content of discrete signals has so far remained unexplored. We define a measure of serial dependence based on the edit distance, which can be transformed into a power spectral estimate (EDSPEC), analogous to the Wiener-Khinchin theorem for continuous signals. The proposed method is applied to a variety of discrete paradigmatic signals representing random, correlated, chaotic, and periodic occurrences of events. It is effective at detecting periodic cycles even in the presence of noise and for short event series. Finally, we apply the EDSPEC method to a novel catalog of European atmospheric rivers (ARs). ARs are narrow filaments of extensive water vapor transport in the lower troposphere and can cause hazardous extreme precipitation events. Using the EDSPEC method, we conduct the first spectral analysis of European ARs, uncovering seasonal and multi-annual cycles along different spatial domains. The proposed method opens new research avenues in studying of periodic discrete signals in complex real-world systems.

Identification of tools used to assess the external validity of randomized controlled trials in reviews: a systematic review of measurement properties.

BACKGROUND: Internal and external validity are the most relevant components when critically appraising randomized controlled trials (RCTs) for systematic reviews. However, there is no gold standard to assess external validity. This might be related to the heterogeneity of the terminology as well as to unclear evidence of the measurement properties of available tools. The aim of this review was to identify tools to assess the external validity of RCTs. It was further, to evaluate the quality of identified tools and to recommend the use of individual tools to assess the external validity of RCTs in future systematic reviews. METHODS: A two-phase systematic literature search was performed in four databases: PubMed, Scopus, PsycINFO via OVID, and CINAHL via EBSCO. First, tools to assess the external validity of RCTs were identified. Second, studies investigating the measurement properties of these tools were selected. The measurement properties of each included tool were appraised using an adapted version of the COnsensus based Standards for the selection of health Measurement INstruments (COSMIN) guidelines. RESULTS: 38 publications reporting on the development or validation of 28 included tools were included. For 61% (17/28) of the included tools, there was no evidence for measurement properties. For the remaining tools, reliability was the most frequently assessed property. Reliability was judged as "sufficient" for three tools (very low certainty of evidence). Content validity was rated as "sufficient" for one tool (moderate certainty of evidence). CONCLUSIONS: Based on these results, no available tool can be fully recommended to assess the external validity of RCTs in systematic reviews. Several steps are required to overcome the identified difficulties to either adapt and validate available tools or to develop a better suitable tool. TRIAL REGISTRATION: Prospective registration at Open Science Framework (OSF): https://doi.org/10.17605/OSF.IO/PTG4D .

A multifactorial interdisciplinary intervention to prevent functional and mobility decline for more participation in (pre-)frail community-dwelling older adults (PromeTheus): study protocol for a multicenter randomized controlled trial.

BACKGROUND: Age-related decline in physical capacity can lead to frailty, associated with an increased vulnerability to adverse health outcomes and greater healthcare utilization. In an aging population, effective strategies to prevent physical decline and frailty, and preserve independence are needed. Prevention programs for vulnerable community-dwelling older adults are, however, often not yet established and implemented in routine practice. Research on the feasibility, implementation, and (cost-)effectiveness of multifactorial, interdisciplinary intervention programs that take advantage of available services of healthcare providers is also limited. The main aim of this study is to evaluate the effectiveness of such an intervention program (PromeTheus) to prevent functional and mobility decline for more participation in community-dwelling (pre-)frail older adults. METHODS: The study is designed as a three-center, randomized controlled trial with a 12-month intervention period. Four hundred community-dwelling (pre-)frail (Clinical Frailty Scale score 4-6) older adults (≥70 years) will be randomized in a 1:1 ratio to the intervention group (IG) or the control group (CG). The IG will receive the PromeTheus program consisting of obligatory home-based physical exercises (Weight-bearing Exercise for Better Balance) accompanied by physiotherapists and facultative counseling services (person-environment-fit, coping with everyday life, nutrition, group-based activities) delivered via existing healthcare structures (e.g., social workers, nutritionists). The CG will receive usual care and a one-time counseling session on recommendations for physical activity and nutrition. Primary outcomes assessed at months 6 and 12 are the function component of the Late-Life Function and Disability Instrument and the University of Alabama at Birmingham Life-Space Assessment. Secondary outcomes are disability, physical capacity and activity, frailty, nutritional status, falls, fear of falling, health status, and psychosocial components. Process and economic evaluations are also conducted. Primary statistical analyses will be based on the intention-to-treat principle. DISCUSSION: Compared to usual care, the PromeTheus program is expected to result in higher function and mobility, greater independence and lower need for care, and more participation. As the PromeTheus program draws on existing German healthcare structures, its large-scale translation and delivery will be feasible, if evidence of (cost-)effectiveness and successful implementation can be demonstrated. TRIAL REGISTRATION: German Clinical Trials Register, . Registered on March 11, 2021.

Adherence to evidence-based practice across healthcare professionals in Germany: results from a cross-sectional, nationwide survey.

BACKGROUND: Adherence to evidence-based practice (EBP) is considered a key competence to improve healthcare quality. In this study, we aimed to describe the EBP adherence of healthcare professionals working in Germany and to explore barriers and facilitators regarding the implementation of EBP in clinical practice. METHODS: A nationwide online survey was performed among healthcare professionals in Germany from January to April 2018 using the German version of the Evidence-based Practice Inventory (EBPI) questionnaire for a comprehensive assessment of adherence to EBP. Univariate logistic regression analyses were performed to explore the association between demographic and professional determinants and each EBPI dimension. RESULTS: We analysed data of 889 participants, including 318 physical therapists, 154 occupational therapists, 137 midwifes and 280 participants of six other healthcare professions. Approximately 70% of the participants generally demonstrated a positive attitude towards EBP and believed that EBP was useful in clinical practice. Broadly, 80% of the respondents evaluated themselves as being able to enact EBP behaviour in clinical practice. In contrast, less than 70% preferred to use quantitative information instead of their intuition to inform their habitual clinical behaviour. Still, 20 to 30% reported that EBP did not sufficiently account for their clinical experience and differences between patients. The strongest facilitators to EBP adherence across at least three dimensions of the EBPI were the availability of ≥ 60 min for scientific literature at work (OR: 9.67; 95% CI: 5.86; 16.30), followed by a master or higher academic degree (OR: 9.09, 95% CI: 5.86; 14.28) and the involvement in ≥ 1 scientific publication (OR: 7.06, 95% CI: 5.10; 9.85). CONCLUSIONS: This study showed that healthcare professionals in Germany in general had a positive attitude towards EBP although they currently do not consider EBP principles in its entirety. The most important determinant positively influencing a healthcare professional's decision to perform EBP was the time available for scientific literature at work. German healthcare professionals experience similar barriers towards the implementation of EBP in clinical practice compared to other international healthcare settings. These barriers should be targeted by future research. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00013792). Registered 19 January 2018.

Primary surgery versus primary rehabilitation for treating anterior cruciate ligament injuries: a living systematic review and meta-analysis.

OBJECTIVE: Compare the effectiveness of primarily surgical versus primarily rehabilitative management for anterior cruciate ligament (ACL) rupture. DESIGN: Living systematic review and meta-analysis. DATA SOURCES: Six databases, six trial registries and prior systematic reviews. Forward and backward citation tracking was employed. ELIGIBILITY CRITERIA: Randomised controlled trials that compared primary reconstructive surgery and primary rehabilitative treatment with or without optional reconstructive surgery. DATA SYNTHESIS: Bayesian random effects meta-analysis with empirical priors for the OR and standardised mean difference and 95% credible intervals (CrI), Cochrane RoB2, and the Grading of Recommendations Assessment, Development and Evaluation approach to judge the certainty of evidence. RESULTS: Of 9514 records, 9 reports of three studies (320 participants in total) were included. No clinically important differences were observed at any follow-up for self-reported knee function (low to very low certainty of evidence). For radiological knee osteoarthritis, we found no effect at very low certainty of evidence in the long term (OR (95% CrI): 1.45 (0.30 to 5.17), two studies). Meniscal damage showed no effect at low certainty of evidence (OR: 0.85 (95% CI 0.45 to 1.62); one study) in the long term. No differences were observed between treatments for any other secondary outcome. Three ongoing randomised controlled trials were identified. CONCLUSIONS: There is low to very low certainty of evidence that primary rehabilitation with optional surgical reconstruction results in similar outcome measures as early surgical reconstruction for ACL rupture. The findings challenge a historical paradigm that anatomic instability should be addressed with primary surgical stabilisation to provide optimal outcomes. PROSPERO REGISTRATION NUMBER: CRD42021256537.

Revealing recurrent regimes of mid-latitude atmospheric variability using novel machine learning method.

The low-frequency variability of the extratropical atmosphere involves hemispheric-scale recurring, often persistent, states known as teleconnection patterns or regimes, which can have a profound impact on predictability on intra-seasonal and longer timescales. However, reliable data-driven identification and dynamical representation of such states are still challenging problems in modeling the dynamics of the atmosphere. We present a new method, which allows us both to detect recurring regimes of atmospheric variability and to obtain dynamical variables serving as an embedding for these regimes. The method combines two approaches from nonlinear data analysis: partitioning a network of recurrent states with studying its properties by the recurrence quantification analysis and the kernel principal component analysis. We apply the method to study teleconnection patterns in a quasi-geostrophical model of atmospheric circulation over the extratropical hemisphere as well as to reanalysis data of geopotential height anomalies in the mid-latitudes of the Northern Hemisphere atmosphere in the winter seasons from 1981 to the present. It is shown that the detected regimes as well as the obtained set of dynamical variables explain large-scale weather patterns, which are associated, in particular, with severe winters over Eurasia and North America. The method presented opens prospects for improving empirical modeling and long-term forecasting of large-scale atmospheric circulation regimes.

Visual Hallucinations following Coronary Artery Bypass Grafting: A Prospective Study.

Background and Objectives: After major heart surgery, some patients report visual hallucinations that cannot be attributed to psychosis or delirium. This study aimed to investigate the hallucination incidence in patients after coronary artery bypass grafting with (on-pump) and without (off-pump) extracorporeal circulation. Materials and Methods: A total of 184 consecutive patients listed for elective on- or off-pump coronary artery bypass grafting were prospectively enrolled into the study. Preoperative baseline investigations 24-48 h before surgery (t0) and postoperative follow-up 24-48 h (t1) and 5-6 days (t2) after surgery included cognitive testing and a clinical visual acuity test (Landolt rings). Patients reporting visual hallucinations were interviewed using a structured survey to record the type, timing, duration, and frequency of their hallucinations. All the patients received a neurological examination and cranial magnetic resonance imaging if indicated. Results: Of the patients in the sample, 155 patients underwent on-pump bypass surgery, and 29 patients received off-pump surgery. Of these, 25 patients in the on-pump group, but none in the off-pump group, reported transient visual hallucinations (p = 0.020), which could not be attributed to stroke, delirium, psychosis, migraine, or severely impaired vision. Significant correlations were observed for the occurrence of visual hallucinations and the amount of nicotine consumption and aortic clamp/extracorporeal circulation time. Conclusions: Transient visual hallucinations occur in a noticeable proportion of patients after on-pump heart surgery. Knowledge of the phenomenon's benignity is important for patients to prevent anxiety and uncertainty and for treating physicians to avoid unnecessary medication and drug-induced delirium.

Pharmacological Comparison of Mitragynine and 7-Hydroxymitragynine: In Vitro Affinity and Efficacy for µ-Opioid Receptor and Opioid-Like Behavioral Effects in Rats.

Relationships between µ-opioid receptor (MOR) efficacy and effects of mitragynine and 7-hydroxymitragynine are not fully established. We assessed in vitro binding affinity and efficacy and discriminative stimulus effects together with antinociception in rats. The binding affinities of mitragynine and 7-hydroxymitragynine at MOR (Ki values 77.9 and 709 nM, respectively) were higher than their binding affinities at κ-opioid receptor (KOR) or δ-opioid receptor (DOR). [35S]guanosine 5'-O-[γ-thio]triphosphate stimulation at MOR demonstrated that mitragynine was an antagonist, whereas 7-hydroxymitragynine was a partial agonist (Emax = 41.3%). In separate groups of rats discriminating either morphine (3.2 mg/kg) or mitragynine (32 mg/kg), mitragynine produced a maximum of 72.3% morphine-lever responding, and morphine produced a maximum of 65.4% mitragynine-lever responding. Other MOR agonists produced high percentages of drug-lever responding in the morphine and mitragynine discrimination assays: 7-hydroxymitragynine (99.7% and 98.1%, respectively), fentanyl (99.7% and 80.1%, respectively), buprenorphine (99.8% and 79.4%, respectively), and nalbuphine (99.4% and 98.3%, respectively). In the morphine and mitragynine discrimination assays, the KOR agonist U69,593 produced maximums of 72.3% and 22.3%, respectively, and the DOR agonist SNC 80 produced maximums of 34.3% and 23.0%, respectively. 7-Hydroxymitragynine produced antinociception; mitragynine did not. Naltrexone antagonized all of the effects of morphine and 7-hydroxymitragynine; naltrexone antagonized the discriminative stimulus effects of mitragynine but not its rate-decreasing effects. Mitragynine increased the potency of the morphine discrimination yet decreased morphine antinociception. Here we illustrate striking differences in MOR efficacy, with mitragynine having less than 7-hydroxymitragynine. SIGNIFICANCE STATEMENT: At human µ-opioid receptor (MOR) in vitro, mitragynine has low affinity and is an antagonist, whereas 7-hydroxymitragynine has 9-fold higher affinity than mitragynine and is an MOR partial agonist. In rats, intraperitoneal mitragynine exhibits a complex pharmacology including MOR agonism; 7-hydroxymitragynine has higher MOR potency and efficacy than mitragynine. These results are consistent with 7-hydroxymitragynine being a highly selective MOR agonist and with mitragynine having a complex pharmacology that combines low efficacy MOR agonism with activity at nonopioid receptors.

A generic outcome assessment of mobility capacity in neurorehabilitation: measurement properties of the de Morton Mobility Index.

BACKGROUND: Mobility capacity is a key outcome domain in neurorehabilitation. The de Morton Mobility Index (DEMMI), an established and generic outcome assessment of mobility capacity in older patients, is promising for use in neurorehabilitation. The aim of this study was to examine the measurement properties of the DEMMI in rehabilitation inpatients with neurological conditions. METHODS: Cross-sectional study including a mixed sample of adult inpatients in a neurorehabilitation hospital. Structural validity, unidimensionality and measurement invariance (Rasch analysis), construct validity, internal consistency reliability, and inter-rater reliability of the DEMMI (scale range: 0-100 points) were established. The minimal detectable change, the 95% limits of agreement, and possible floor and ceiling effects were calculated to indicate interpretability. RESULTS: We analyzed validity (n = 348) and reliability (n = 133) in two samples. In both samples, the majority of participants had a sub-acute stroke or Parkinson's disease. Rasch analysis indicated unidimensionality with an overall fit to the model (chi-square = 59.4, P = 0.074). There was no relevant measurement invariance by disease group. Hypotheses-based correlation analyses (DEMMI and other functional outcome assessments) showed sufficient construct validity. Internal consistency reliability (Cronbach's alpha = 0.94) and inter-rater reliability (intraclass correlation coefficient = 0.94; 95% confidence interval: 0.91-0.95) were sufficient. The minimal detectable change with 90% confidence was 15.0 points and the limits of agreement were 39%. No floor or ceiling effects were observed. CONCLUSIONS: Results indicate sufficient measurement properties of the DEMMI in rehabilitation inpatients with neurological conditions. The DEMMI can be used as a generic outcome assessment of mobility capacity in neurorehabilitation. TRIAL REGISTRATION: German Clinical Trials Register ( DRKS00004681 ). Registered May 6, 2013.

A rare cause of stroke: fail-implanted venous port catheter system - a case report.

BACKGROUND: We present the case of a 75-year-old female with acute embolic cerebral infarction caused by a fail-implanted venous port catheter system in the left subclavian artery. CASE PRESENTATION: A 75-year-old woman presented to our emergency room after acute onset of a right-sided hemiparesis and dysarthria. Within 2 days after admission, she developed a left-sided hemiparesis, ataxia with concordant gait disturbance and incoordination of the left upper limb. DWI-MRI showed acute multiple infarcts in both cerebral and cerebellar hemispheres. Laboratory examination, 24-h Holter electrocardiography and transthoracic echocardiography provided no pathological findings. Further examination revealed an arterially fail-implanted port catheter, placed in the left subclavian artery with its tip overlying the ascending aorta, as the source of cerebral embolism. CONCLUSION: This is the first case report of thromboembolic, cerebral infarction due to a misplaced venous port catheter in the subclavian artery, emphasizing the imperative need for a thorough diagnostic workup, when embolism is suspected but cannot be proven at first glance.

Responsiveness and interpretability of commonly used outcome assessments of mobility capacity in older hospital patients with cognitive spectrum disorders.

BACKGROUND: In older hospital patients with cognitive spectrum disorders (CSD), mobility should be monitored frequently with standardised and psychometrically sound measurement instruments. This study aimed to examine the responsiveness, minimal important change (MIC), floor effects and ceiling effects of commonly used outcome assessments of mobility capacity in older patients with dementia, delirium or other cognitive impairment. METHODS: In a cross-sectional study that included acute older hospital patients with CSD (study period: 02/2015-12/2015), the following mobility assessments were applied: de Morton Mobility Index (DEMMI), Hierarchical Assessment of Balance and Mobility (HABAM), Performance Oriented Mobility Assessment, Short Physical Performance Battery, 4-m gait speed test, 5-times chair rise test, 2-min walk test, Timed Up and Go test, Barthel Index mobility subscale, and Functional Ambulation Categories. These assessments were administered shorty after hospital admission (baseline) and repeated prior to discharge (follow-up). Global rating of mobility change scales and a clinical anchor of functional ambulation were used as external criteria to determine the area under the curve (AUC). Construct- and anchor-based approaches determined responsiveness. MIC values for each instrument were established from different anchor- and distribution-based approaches. RESULTS: Of the 63 participants (age range: 69-94 years) completing follow-up assessments with mild (Mini Mental State Examination: 19-24 points; 67%) and moderate (10-18 points; 33%) cognitive impairment, 25% were diagnosed with dementia alone, 13% with delirium alone, 11% with delirium superimposed on dementia and 51% with another cognitive impairment. The follow-up assessment was performed 10.8 ± 2.5 (range: 7-17) days on average after the baseline assessment. The DEMMI was the most responsive mobility assessment (all AUC > 0.7). For the other instruments, the data provided conflicting evidence of responsiveness, or evidence of no responsiveness. MIC values for each instrument varied depending on the method used for calculation. The DEMMI and HABAM were the only instruments without floor or ceiling effects. CONCLUSIONS: Most outcome assessments of mobility capacity seem insufficiently responsive to change in older hospital patients with CSD. The significant floor effects of most instruments further limit the monitoring of mobility alterations over time in this population. The DEMMI was the only instrument that was able to distinguish clinically important changes from measurement error. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00005591). Registered February 2, 2015.

An investigation of the measurement properties of the de Morton Mobility Index for measuring mobility capacity in hospital patients with Parkinson's disease.

OBJECTIVE: To examine the measurement properties of the de Morton Mobility Index (DEMMI), a performance-based clinical outcome assessment of mobility capacity, in hospital patients with Parkinson's disease. DESIGN: Cross-sectional study. PARTICIPANTS: Hospital patients with Parkinson's disease. MAIN OUTCOME MEASURE(S): Structural validity and unidimensionality (Rasch analysis), construct validity, internal consistency reliability, and inter-rater reliability of the de Morton Mobility Index (scale range: 0-100 points) were established. The minimal detectable change, the 95% limits of agreement and possible floor and ceiling effects were calculated to indicate interpretability. RESULTS: We analysed validity (n = 100; mean age: 70 years; 71% male) and reliability (n = 47; mean age: 71 years; 68% male) in two samples. The mean Hoehn and Yahr stage was 3.2 and the mean disease duration was 12 years in both samples. Rasch analysis indicated unidimensionality with an overall fit to the model (chi-square = 21.49, P = 0.122). Seventy-three percent of hypotheses on construct validity were confirmed. Internal consistency reliability (Cronbach's alpha = 0.91) and inter-rater reliability (intraclass correlation coefficient = 0.88; 95% confidence interval: 0.80 to 0.93) were sufficient. The minimal detectable change with 90% confidence was 17.5 points and the limits of agreement were 31%. No floor or ceiling effects were observed. The mean administration time was 6.6 minutes. CONCLUSION: This study provides evidence of unidimensionality, sufficient internal consistency reliability, inter-rater reliability, construct validity, and feasibility of the de Morton Mobility Index in hospital patients with Parkinson's disease. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00004681). Registered May 6, 2013.

Validation of the German Version of Functional Oral Intake Scale (FOIS-G) for Flexible Endoscopic Evaluation of Swallowing (FEES).

The Functional Oral Intake Scale (FOIS) is the most frequently used scale for the evaluation of functional oral intake by dysphagia patients. FOIS was validated using data from Videofluoroscopic Swallowing Study (VFSS). Until now, a validated German version of FOIS for Flexible Endoscopic Evaluation of Swallowing (FEES) is lacking. The aim of this study was a cross-cultural validation of the German version of FOIS (FOIS-G) for FEES. The translation of the original FOIS was carried out according to the Translation, Review, Adjudication, Pretesting, Documentation (TRAPD) translation methodology. For the validation process, six experienced language therapists (SLT) retrospectively analyzed charts of 93 stroke patients. Inclusion criteria were comprised of stroke, clinical examination by an SLT within 24 h of admission, and FEES within 72 h of admission. The validity was calculated by comparison with Modified Rankin Scale (MRS), Barthel Index (BI), the Penetration-Aspiration-Scale (PAS), and a water swallow test. Spearman rank correlation of all paired raters ranged from rs = 0.96 to rs = 0.99, and percentage agreement ranged from 81 to 94%. The overall agreement between all raters was calculated by Fleiss kappa (0.83) (s.e. 0.02). There is a significant correlation between the BI and the MRS with the FOIS-G (rs = 0.301, p = 0.003 for BI; rs = - 0.366, p < 0.001 for MRS), between the PAS and the FOIS-G (rs = - 0.758, p < 0.001), as well as between the 70 ml-water-test and the FOIS-G (rs = 0.470, p < 0.001). FOIS-G is a valid instrument for the evaluation of the functional oral intake of food and liquids in dysphagia patients.

BAFF serum and CSF levels in patients with multiple sclerosis and infectious nervous system diseases.

PURPOSE: Multiple sclerosis (MS) is the most common immune-mediated CNS disease, characterised by demyelination and progressive neurological disability. The B-cell activating factor BAFF has been described as one important factor in the pathophysiology of different autoimmune diseases. METHODS: We measured BAFF levels in the serum and cerebrospinal fluid (CSF) in 50 consecutive patients with MS and 35 patients with infectious CNS disease (ID). 52 patients with other, non-inflammatory disorders (OND), served as controls. RESULTS: BAFF-serum levels in ID patients were higher than in patients diagnosed with MS (ID 0.55 ± 0.24 ng/ml, MS 0.43 ± 0.14 ng/ml, OND 0.45 ± 0.24 ng/ml; p = 0.09). Interestingly, MS patients had lower BAFF CSF levels compared to the controls and ID patients, and the CSF levels in the latter were elevated compared to those of the controls (MS 0.17 ± 0.11 ng/ml, OND 0.25 ± 0.14 ng/ml, ID 0.97 ± 0.78 ng/ml; p < 0.001). CONCLUSIONS: The ID patients' having higher absolute BAFF levels in the CSF than in the serum indicates that the increased BAFF CSF levels were caused by intrathecal synthesis rather than passive transfer via a disturbed blood-brain-barrier. The significantly decreased BAFF CSF levels in MS patients were a surprising result of our study. Although it has been reported that astrocytes in active MS lesions can express BAFF, the soluble form was not increased in the CSF of MS patients. It remains unclear whether the inflammatory features of active MS plaques are truly represented by the CSF compartment.

Evaluation of a new wireless technique for continuous electroencephalography monitoring in neurological intensive care patients.

A novel wireless eight-channel electroencephalography (EEG) headset specially developed for ICUs was tested in regard of comparability with standard 10/20 EEG systems. The continuous EEG (cEEG) derivations via CerebAir EEG headset (Nihon Kohden Europe, Rosbach, Germany) and internationally standardized 10/20 reference EEGs as the diagnostic standard were performed in a mixed collective on a neurointensive care unit (neuro-ICU). The derivations were verified for comparability in detection of EEG background activity, epileptiform discharges, and seizure patterns. Fifty-two patients with vigilance reduction following serious neurological or metabolic diseases were included, and both methods were applied and further analyzed in 47. EEG background activity matched in 24 of 45 patients (53%; p = 0.126), epileptiform discharges matched in 32 (68%) patients (p = 0.162), and seizure activity matched in 98%. Overall, in 89% of the patients, cEEG detected the same or additional ICU-relevant EEG patterns. The tested wireless cEEG headset is a useful monitoring tool in patients with consciousness disorders. The present study indicates that long-term measurements with the wireless eight-channel cEEG lead to a higher seizure and epileptiform discharge detection compared to intermittent 10/20 EEG derivations in the ICU setting.

Minispheroids as a Tool for Ligament Tissue Engineering: Do the Self-Assembly Techniques and Spheroid Dimensions Influence the Cruciate Ligamentocyte Phenotype?

Spheroid culture might stabilize the ligamentocyte phenotype. Therefore, the phenotype of lapine cruciate ligamentocyte (L-CLs) minispheroids prepared either by hanging drop (HD) method or by using a novel spheroid plate (SP) and the option of methyl cellulose (MC) for tuning spheroid formation was tested. A total of 250 and 1000 L-CLs per spheroid were seeded as HDs or on an SP before performing cell viability assay, morphometry, gene expression (qRT-PCR) and protein immunolocalization after 7 (HD/SP) and 14 (SP) days. Stable and viable spheroids of both sizes could be produced with both methods, but more rapidly with SP. MC accelerated the formation of round spheroids (HD). Their circular areas decreased significantly during culturing. After 7 days, the diameters of HD-derived spheroids were significantly larger compared to those harvested from the SP, with a tendency of lower circularity suggesting an ellipsoid shape. Gene expression of decorin increased significantly after 7 days (HD, similar trend in SP), tenascin C tended to increase after 7 (HD/SP) and 14 days (SP), whereas collagen type 1 decreased (HD/SP) compared to the monolayer control. The cruciate ligament extracellular matrix components could be localized in all mini-spheroids, confirming their conserved expression profile and their suitability for ligament tissue engineering.

Minimal important change and responsiveness of the Migraine Disability Assessment Score (MIDAS) questionnaire.

BACKGROUND: The MIDAS is the most used questionnaire to evaluate migraine-related disability, but its utility to assess treatment response remains unclear. Our aim was to estimate the MIDAS' minimal important change (MIC) value and its responsiveness. METHODS: A total of 103 patients were enrolled in a non-pharmacological, preference-based clinical trial. MIDAS and global rating of self-perceived change (GRoC) scores were collected at baseline, after 5 weeks of treatment, 4-weeks and 3-months follow-up after treatment. Anchor-based approaches were used to establish MIC values and responsiveness. FINDINGS: In all 3 timepoint comparisons, MIDAS presented a MIC of 4.5 points. A moderate positive correlation was identified between the MIDAS change and GRoC scores. The area under the curve ranged from 0.63 to 0.68. CONCLUSIONS: This study showed that MIDAS has a limited responsiveness to change. A change of 4.5 points or more represents a clinically important change for patients with high frequent migraine and chronic migraine receiving non-pharmacological treatment.

Impaired Cerebrovascular Autoregulation in Large Vessel Occlusive Stroke after Successful Mechanical Thrombectomy: A Prospective Cohort Study.

INTRODUCTION: Successful thrombectomy improves morbidity and mortality after stroke. The present prospective, observational cohort study investigated a potential correlation between the successful restoration of tissue perfusion by mechanical thrombectomy and intact cerebrovascular autoregulation (CA). OBJECTIVE: Status of CA in patients with large vessel occlusive stroke after thrombectomy. METHODS: After thrombectomy CA was measured using transcranial Doppler ultrasound. For this purpose a moving correlation index (Mxa) based on spontaneous arterial blood pressure fluctuations and corresponding cerebral blood flow velocity changes was calculated. CA impairment was defined by Mxa values more than .3. RESULTS: Twenty patients with an acute occlusion of the middle cerebral artery or distal internal carotid artery were included. A successful recanalization of the occluded vessel via interventional thrombectomy was achieved in 10 of these patients (successful recanalization group), while in 10 patients mechanical recanalization failed or could not be applied (no recanalization group). Mean Mxa at stroke side was .58 ± .21 Table 2a in patients with successful intervention. At the unaffected hemisphere Mxa was .50 ± .20 Table 2a in successful recanalization group and .45 ± .24 Table 2b in no recanalization group without statistically significant differences. Based on the previously defined Mxa cut off more than .3, CA impairment was observable in all successful recanalized patients and in 8 of 10 patients with unsuccessful interventional treatment. CONCLUSIONS: These results suggest that brain perfusion may be affected due to impaired CA even after successful mechanical thrombectomy. Therefore, a tight blood pressure management is of great importance in post-thrombectomy stroke treatment to avoid cerebral hypo- and hyperperfusion.

Adjustment of oral diet based on flexible endoscopic evaluation of swallowing (FEES) in acute stroke patients: a cross-sectional hospital-based registry study.

BACKGROUND: Diagnosing dysphagia in acute stroke patients is crucial, as this comorbidity determines morbidity and mortality; we therefore investigated the impact of flexible nasolaryngeal endoscopy (FEES) in acute stroke patients. METHODS: The FEES investigation as performed in acute stroke patients treated at a large university hospital, allocated as a standard procedure for all patients suspected of dysphagia. We correlated our findings with baseline data, disability status, pneumonia, duration of hospitalisation, necessity for mechanical ventilation and treatment on the intensive care unit. The study was designed as a cross-sectional hospital-based registry. RESULTS: We investigated 152 patients. The median age was 73; 94 were male. Ischemic stroke was diagnosed in 125 patients (82.2%); 27 (17.8%) suffered intracerebral haemorrhage. Oropharyngeal dysphagia was diagnosed in 72.4% of the patients, and was associated with higher stroke severity on admission (median NIHSS 11 [IQR 6-17] vs. 7 [4-12], p = .013; median mRS 5 [IQR 4-5] vs. 4 [IQR 3-5], p = .012). Short-term mortality was higher among patients diagnosed with dysphagia (7.2% vs. 0%, p = .107). FEES examinations revealed that only 30.9% of the patients had an oral diet appropriate for their swallowing abilities. A change of oral diet was associated with a better outcome at discharge (mRS; p = .006), less need of mechanical ventilation (p = .028), shorter period of hospitalisation (p = .044), and lower rates of pneumonia (p = .007) and mortality (p = .011). CONCLUSION: Due to the inability of clinical assessments to detect silent aspiration, FEES might be better suited to identify stroke patients at risk and may contribute to a better functional outcome and lower rates of pneumonia and mortality. Our findings also point to a low awareness of dysphagia, even in a specialised stroke centre. FEES in acute stroke patients helps to adjust the oral diet for the vast majority of stroke patients (69.1%) based on their swallowing abilities, potentially avoiding severe complications.