Background and Purpose: This study aims to assess the number of patients with acute ischemic cerebrovascular events seeking in-patient medical emergency care since the implementation of social distancing measures in the coronavirus disease 2019 (COVID-19) pandemic. Methods: In this retrospective multicenter study, data on the number of hospital admissions due to acute ischemic stroke or transient ischemic attack and numbers of reperfusion therapies performed in weeks 1 to 15 of 2020 and 2019 were collected in 4 German academic stroke centers. Poisson regression was used to test for a change in admission rates before and after the implementation of extensive social distancing measures in week 12 of 2020. The analysis of anonymized regional mobility data allowed for correlations between changes in public mobility as measured by the number and length of trips taken and hospital admission for stroke/transient ischemic attack. Results: Only little variation of admission rates was observed before and after week 11 in 2019 and between the weeks 1 and 11 of 2019 and 2020. However, reflecting the impact of the COVID-19 pandemic, a significant decrease in the number of admissions for transient ischemic attack was observed (−85%, −46%, −42%) in 3 of 4 centers, while in 2 of 4 centers, stroke admission rates decreased significantly by 40% and 46% after week 12 in 2020. A relevant effect on reperfusion therapies was found for 1 center only (thrombolysis, −60%; thrombectomy, −61%). Positive correlations between number of ischemic events and mobility measures in the corresponding cities were identified for 3 of 4 centers. Conclusions: These data demonstrate and quantify decreasing hospital admissions due to ischemic cerebrovascular events and suggest that this may be a consequence of social distancing measures, in particular because hospital resources for acute stroke care were not limited during this period. Hence, raising public awareness is necessary to avoid serious healthcare and economic consequences of undiagnosed and untreated strokes and transient ischemic attacks.
The axonal microtubule stabilizing protein tau is hyperphosphorylated in several neurodegenerative conditions, including Alzheimer's disease, yet the genes that regulate tau phosphorylation are largely unknown. Disabled-1 (Dab1) is a cytoplasmic adapter protein that interacts with apolipoprotein E (ApoE) receptors and controls neuronal positioning during embryonic brain development. We have investigated the role of Dab1 in tau phosphorylation. We found that wild-type Dab1, but not a mutant lacking tyrosine phosphorylation sites, protects mice from the hyperphosphorylation of tau. However, the absence of Dab1 is not sufficient to cause tau hyperphosphorylation, because hyperphosphorylation is manifested only when Dab1 is mutated in specific mouse strain backgrounds. Tau hyperphosphorylation correlates with early death in susceptible mouse strains, and it occurs in the neurons of the hippocampus and dentate gyrus. By quantitative trait locus (QTL) analysis of Dab1-deficient mice on a hybrid strain background, we uncovered one significant and three suggestive chromosomal loci that modulate tau phosphorylation. Two of these QTL regions contain genes that are defective in early onset Alzheimer's disease. Our findings suggest that Dab1 gene disruption sensitizes mice to tau hyperphosphorylation contingent on specific haplotypes that are linked to Alzheimer's disease loci. Dab1 mutant mice provide an animal model for studying the relationships between ApoE receptors, tau hyperphosphorylation, and Alzheimer's disease.
LRP1b and the closely related LRP1 are large members of the low-density lipoprotein receptor family. At the protein level LRP1b is 55% identical to LRP1, a multifunctional and developmentally essential receptor with roles in cargo transport and cellular signaling. Somatic LRP1b mutations frequently occur in non-small cell lung cancer and urothelial cancers, suggesting a role in the modulation of cellular growth. In contrast to LRP1, LRP1b-deficient mice develop normally, most likely due to its restricted expression pattern and functional compensation by LRP1 or other receptors. LRP1b is expressed predominantly in the brain, and a differentially spliced form is present in the adrenal gland and in the testis. Despite the presence of a potential furin cleavage site and in contrast to LRP1, immunoblotting for LRP1b reveals the presence of a single 600-kDa polypeptide species. Using a yeast two-hybrid approach, we have identified two intracellular proteins, the postsynaptic density protein 95 and the aryl hydrocarbon receptor-interacting protein, that bind to the intracellular domain of LRP1b. In addition, we have found several potential ligands that bind to the extracellular domain. Analysis of LRP1b knockout mice may provide further insights into the role of LRP1b as a tumor suppressor and into the mechanisms of cancer development.The low-density lipoprotein (LDL) receptor family comprises seven closely related receptors in mammals. These receptors share a typical arrangement of ligand-binding domains, epidermal growth factor homology domains, and YWTD propeller domains in their extracellular part and contain a cytoplasmic tail with at least one NPXY motif. Two LDL receptor family members, i.e., the LDL receptor and the LDL receptorrelated protein 1 (LRP1) are widely expressed in nearly all cells, while the pattern of the other members (very low density lipoprotein [VLDL] receptor, apoER2, and megalin) is more restricted. The biological functions of the receptors are highly diverse and include the uptake of lipoproteins and other ligands, the regulation of cell surface proteinase activity, the regulation of Ca 2ϩ homeostasis, and important functions in brain development and neurotransmission. Besides their classical role in receptor-mediated endocytosis, evidence is now accumulating that many of the family members play important roles in signal transduction through adaptor molecules that bind to their cytoplasmic tails (8).Two very large receptors of the LDL receptor family have been well characterized. LRP1 contains 31 ligand-binding repeats and binds a variety of ligands, including apoE-carrying lipoproteins, ␣2-macroglobulin, and proteinases and their inhibitors. A unique feature of LRP1 is the fact that this receptor is cleaved by furin in a late secretory compartment, which results in a carboxyl-terminal 85-kDa fragment and a noncovalently linked 515-kDa subunit. LRP1 can bind numerous ligands and has been implicated in a variety of biological functions, including lipoprotein metabolism, the regulation of the ...
This was the first study evaluating the bCAM for a German ED and when performed by EPs during routine work. The bCAM showed good specificity, but only moderate sensitivity. Nevertheless, application of the bCAM most likely improves the delirium detection rate in German EDs. However, it should only be applied by trained physicians to maximize diagnostic accuracy and hence improve the bCAM's sensitivity. Future studies should refine the bCAM.
sTBL served as an equivalent alternative to small group interactive seminars for imparting knowledge and teaching CR skills, and was particularly advantageous for teaching CR in the setting of a complex neurologic topic. Furthermore, students reported a strong preference for the sTBL approach, making it a promising tool for effectively teaching neurology.
ObjectiveTo evaluate the learnability and feasibility of a new technique comprising a needle-guidance-system (NGS) for ultrasound-assisted lumbar puncture.MethodUsing a randomized crossover study design, 24 medical students were asked to perform an ultrasound-assisted lumbar puncture on a gel phantom using two different techniques that each included a paramedian insertion site. Procedure 1 (P1) used a pre-procedural ultrasound scan to predetermine the ideal insertion point. Procedure 2 (P2) applied a new technique comprising an NGS for performing real-time ultrasound-guided lumbar puncture. Success rates and performance times for both procedures were compared. Participants were also asked to complete a post-study questionnaire, both to quantitatively assess the workload involved and state their personal preferences.ResultsIn comparison to the pre-procedural scan (P1), the NGS (P2) was associated with a significant increase in the number of successful punctures per participant (5 (P2) [interquartile range: 3.3–5.0] vs. 3 (P1) [interquartile range: 1.3–4.0], p = 0.005), and led to a significant reduction in performance time (118 seconds vs. 80.6 seconds, p < 0.001). In terms of workload perception, NGS use was associated with significantly better performances and lower frustration levels, as rated by students in the post-study questionnaire. Finally, 23/24 participants stated their preference for P2.ConclusionOur newly-developed technique for real-time ultrasound-guided lumbar puncture proved to be learnable and feasible for novices, and only required a small amount of training. The use of an NGS therefore has the potential to serve as a key feature of the ultrasound-assisted lumbar puncture.
BackgroundIn the field of Neurology good clinical reasoning skills are essential for successful diagnosing and treatment. Team-based learning (TBL), an active learning and small group instructional strategy, is a promising method for fostering these skills. The aim of this pilot study was to examine the effects of a supplementary TBL-class on students’ clinical decision-making skills.MethodsFourth- and fifth-year medical students participated in this pilot study (static-group comparison design). The non-treatment group (n = 15) did not receive any additional training beyond regular teaching in the neurology course. The treatment group (n = 11) took part in a supplementary TBL-class optimized for teaching clinical reasoning in addition to the regular teaching in the neurology course. Clinical decision making skills were assessed using a key-feature problem examination. Factual and conceptual knowledge was assessed by a multiple-choice question examination.ResultsThe TBL-group performed significantly better than the non-TBL-group (p = 0.026) in the key-feature problem examination. No significant differences between the results of the multiple-choice question examination of both groups were found.ConclusionsIn this pilot study participants of a supplementary TBL-class significantly improved clinical decision-making skills, indicating that TBL may be an appropriate method for teaching clinical decision making in neurology. Further research is needed for replication in larger groups and other clinical fields.
Objective To survey medical students on the lumbar puncture (LP) procedure in terms of their existing knowledge, practical experience and attitudes, and to determine whether the completion of a single standardized seminar that includes practical training on phantoms can alter these parameters. Methods The survey was completed by medical students undertaking the curricular neurology course. Students were asked to describe their practical experience in different bedside procedures, and document how they perceive LP in terms of their own knowledge, confidence and attitude. Students then participated in a newly designed 90‐min seminar that included practical training on phantoms and placed special emphasis both on the patients' point of view during the procedure and the benefits of an atraumatic approach. All students who completed the seminar were required to complete the survey for a second time. Results Among the 153 participants, LP was associated with the lowest baseline levels of experience and confidence compared to other bedside procedures. Attitudes, knowledge, and confidence related to the various aspects of LP all showed significant improvement after the seminar. Conclusion A single standardized LP seminar with simulation training alters medical students' attitudes toward LP through improving their level of knowledge and confidence. This may have important implications in doctors‐to‐be on their stance toward LP and resultant advice to future patients regarding this important procedure.
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