Reducing Readmission Rates By Improving Transitions Of Care For Stroke Patients In The Pre-Covid And Covid Eras

Introduction: Acute cerebrovascular disease ranks among the top causes of 30-day readmissions. Studies have shown that enhancing and streamlining transitions of care (TOC) for patients can improve readmission rates for many conditions. Our research explores the impact of in-person and telemedicine TOC stroke clinic on readmission rates at an urban comprehensive stroke center. Methods: Participants were identified by ICD-10 diagnoses corresponding with stroke or transient ischemic attack at Thomas Jefferson University Hospital (TJUH). Starting in January of 2019, an in-person TOC clinic visit with a vascular neurologist or nurse practitioner was automatically scheduled within 1-3 weeks for patients discharged to home. When coronavirus precautions began, these visits transitioned to telemedicine. Follow-up telephone surveys assessing self-efficacy, confidence and perceived value of TOC clinic were administered. Readmission statistics were collected from the TJUH electronic health record. Preliminary data analysis was performed in SPSS. Results: 208 individuals (113 in-person, 95 telemedicine) seen in TOC clinic were included in preliminary analysis. The 30-day all-cause readmission rate was 5.8% (12 patients). Of these readmissions, 2 were seen in the clinic (2.1%), and 10 were evaluated via telemedicine (8.8%). Chi Square revealed a between group difference (X2 = 4.318, p = 0.038). Participants in both the in-person group (u = 8.421, SD = 1.835) and telemedicine group (u = 8.100, SD = 1.875) considered TOC a valuable experience. Analysis of perceived TOC value did not differ between groups (t = 0.654, p = 0.515). Discussion: Stroke readmissions represent a significant source of morbidity, mortality and healthcare spending in the United States. Overall, there were fewer readmissions among TJUH TOC clinic patients compared to institutional and national 30-day stroke readmission rates. Understanding the relative impact of an in-person and telemedicine TOC stroke clinic will provide valuable information as healthcare systems navigate the post-COVID era

A CERTain Role for Ceramide in Taxane-Induced Cell Death

An unexpected benefit of functional genomic screens is that at times they answer questions that they were not designed to ask. A siRNA screen reported by Swanton et al. in this issue of Cancer Cell reveals that silencing of spindle assembly checkpoint genes facilitates mitotic slippage, resulting in escape from taxane-induced cell death, aneuploidy, and chromosomal instability, hallmarks of taxane resistance. Unexpectedly, the screen disclosed that the sphingolipid ceramide is a key regulator of the taxane-mediated spindle assembly checkpoint and taxane-induced cell death. Ceramide metabolism thus serves as a legitimate target for modulation of taxane effect on tumors

Integration of economic shifts in the european development in the second half of the XXth century

Purpose: The article analyzes those processes having initiated the development of the European and political integration. The article is focused on the genesis and the development of the Council for Mutual Economic Assistance, the European Union, NATO and the Warsaw Pact. Design/Methodology/Approach: By applying the system analysis method as well as dialectical and historical methods, the authors have attempted to reveal the significance of those events resulted in modern international organizations establishment. Findings: Authors have analyzed the XX century trends in integration and highlighted Western Europe as the most productive in the process. Authors have provided the USSR and post-USSR integration overview to reveal the European development patterns. Practical Implications: The research results may be implemented into political and educational courses as well as to be used by official authorities. Originality/Value: The main contribution of this study is the deep integration trends'analysis and the emphasis on the unipolar-bipolar-multipolar world's concept.peer-reviewe

Acid-Sphingomyelinase Triggered Fluorescently Labeled Sphingomyelin Containing Liposomes in Tumor Diagnosis after Radiation-Induced Stress

In liposomal delivery, a big question is how to release the loaded material into the correct place. Here, we will test the targeting and release abilities of our sphingomyelin-consisting liposome. A change in release parameters can be observed when sphingomyelin-containing liposome is treated with sphingomyelinase enzyme. Sphingomyelinase is known to be endogenously released from the different cells in stress situations. We assume the effective enzyme treatment will weaken the liposome making it also leakier. To test the release abilities of the SM-liposome, we developed several fluorescence-based experiments. In in vitro studies, we used molecular quenching to study the sphingomyelinase enzyme-based release from the liposomes. We could show that the enzyme treatment releases loaded fluorescent markers from sphingomyelin-containing liposomes. Moreover, the release correlated with used enzymatic activities. We studied whether the stress-related enzyme expression is increased if the cells are treated with radiation as a stress inducer. It appeared that the radiation caused increased enzymatic activity. We studied our liposomes' biodistribution in the animal tumor model when the tumor was under radiation stress. Increased targeting of the fluorescent marker loaded to our liposomes could be found on the site of cancer. The liposomal targeting in vivo could be improved by radiation. Based on our studies, we propose sphingomyelin-containing liposomes can be used as a controlled release system sensitive to cell stress

Alterations to Sphingomyelin Metabolism Affect Hemostasis and Thrombosis

BACKGROUND: Our recent studies suggest that sphingomyelin levels in the plasma membrane influence TF (tissue factor) procoagulant activity. The current study was performed to investigate how alterations to sphingomyelin metabolic pathway would affect TF procoagulant activity and thereby affect hemostatic and thrombotic processes. METHODS: Macrophages and endothelial cells were transfected with specific siRNAs or infected with adenoviral vectors to alter sphingomyelin levels in the membrane. TF activity was measured in factor X activation assay. Saphenous vein incision-induced bleeding and the inferior vena cava ligation-induced flow restriction mouse models were used to evaluate hemostasis and thrombosis, respectively. RESULTS: Overexpression of SMS (sphingomyelin synthase) 1 or SMS2 in human monocyte-derived macrophages suppresses ATP-stimulated TF procoagulant activity, whereas silencing SMS1 or SMS2 increases the basal cell surface TF activity to the same level as of ATP-decrypted TF activity. Consistent with the concept that sphingomyelin metabolism influences TF procoagulant activity, silencing of acid sphingomyelinase or neutral sphingomyelinase 2 or 3 attenuates ATP-induced enhanced TF procoagulant activity in macrophages and endothelial cells. Niemann-Pick disease fibroblasts with a higher concentration of sphingomyelin exhibited lower TF activity compared with wild-type fibroblasts. In vivo studies revealed that LPS+ATP-induced TF activity and thrombin generation were attenuated in ASMase--/-- mice, while their levels were increased in SMS--/--mice. Further studies revealed that acid sphingomyelinase deficiency leads to impaired hemostasis, whereas SMS2 deficiency increases thrombotic risk. CONCLUSIONS: Overall, our data indicate that alterations in sphingomyelin metabolism would influence TF procoagulant activity and affect hemostatic and thrombotic processes

Stroke Centers of Excellence in the United States: Certification, Access and Outcomes

Introduction: Stroke is a leading cause of morbidity, mortality and healthcare costs in the United States. Evidence suggests that certified stroke centers have improved patient outcomes relative to non-certified hospitals. Our study explains the process, associated cost, quality and geographic proclivities of different certifying organizations. Methods: Data was collected from published literature, information on certifying organizations’ websites and through direct communication with representatives of The Joint Commission (TJC), Det Norske Veritas and Germanischer Lloyd (DNV-GL), and Healthcare Facilities Accreditation Program (HFAP). Geographic mapping of thrombectomy capable centers and comprehensive stroke centers was performed with the ArcGIS online tool. Results: Among the three certifying organizations, standards for recognition as acute, primary, thrombectomy capable and comprehensive stroke centers are not standardized. At the time of this review, there were 1406 TJC-certified stroke centers, 241 DNV-GL certified stroke centers and 66 HFAP-certified stroke centers in the United States. Cost for certification was similar with price scaled by complexity of capabilities. Quality metrics revealed a significantly higher rate of tPA administration and shorter door-to-needle time for TJC and DNV-GL centers than HFAP. All primary stroke centers exhibited improved in-hospital, 30-day and 1-year mortality when compared to non-stroke centers. Discussion: Despite lack of standardization of criteria between organizations, certification provides a mechanism for ensuring hospitals deliver higher standards of stroke care. Understanding variations in quality and scope of different organizations enables targeting of at-risk regions to maximize access and availability of care

SILAC-based phosphoproteomics reveals an inhibitory role of KSR1 in p53 transcriptional activity via modulation of DBC1

BACKGROUND We have previously identified kinase suppressor of ras-1 (KSR1) as a potential regulatory gene in breast cancer. KSR1, originally described as a novel protein kinase, has a role in activation of mitogen-activated protein kinases. Emerging evidence has shown that KSR1 may have dual functions as an active kinase as well as a scaffold facilitating multiprotein complex assembly. Although efforts have been made to study the role of KSR1 in certain tumour types, its involvement in breast cancer remains unknown. METHODS A quantitative mass spectrometry analysis using stable isotope labelling of amino acids in cell culture (SILAC) was implemented to identify KSR1-regulated phosphoproteins in breast cancer. In vitro luciferase assays, co-immunoprecipitation as well as western blotting experiments were performed to further study the function of KSR1 in breast cancer. RESULTS Of significance, proteomic analysis reveals that KSR1 overexpression decreases deleted in breast cancer-1 (DBC1) phosphorylation. Furthermore, we show that KSR1 decreases the transcriptional activity of p53 by reducing the phosphorylation of DBC1, which leads to a reduced interaction of DBC1 with sirtuin-1 (SIRT1); this in turn enables SIRT1 to deacetylate p53. CONCLUSION Our findings integrate KSR1 into a network involving DBC1 and SIRT1, which results in the regulation of p53 acetylation and its transcriptional activity

Decreased formation of inositol trisphosphate in Madin-Darby canine kidney cells under conditions of [beta]-glucosidase inhibition

Recent work has demonstrated the enhancement of hormone-stimulated inositol trisphosphate formation in renal epithelial cells under conditions of glucosylceramide depletion. The role of glucosylceramide metabolism was explored further by exposing Madin-Darby canine kidney (MDCK) cells to the [beta]-glucosidase inhibitor conduritol B epoxide, which produced time-dependent and concentration-dependent increases in glucosylceramide levels and decreased bradykinin-stimulated inositol trisphosphate formation from isolated MDCK cell membranes. These data provide further support for an association between glucosylceramide levels and hormone-stimulated inositol trisphosphate formation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30238/1/0000632.pd

Methyl 4,6-bis­(4-fluoro­phen­yl)-2-oxo­cyclo­hex-3-ene-1-carboxyl­ate

The 3-cyclo­hexene units adopt envelope conformations in each of the two independent mol­ecules that comprise the asymmetric unit of the title compound, C20H16F2O3. The dihedral angles between the two fluoro­phenyl rings are 79.7 (2) and 73.7 (2)° in the two mol­ecules. In one of the mol­ecules, two C—H groups of the cyclo­hexene ring are disordered over two sets of sites in a 0.818 (13):0.182 (13) ratio, the major and minor components corresponding to the two enanti­omeric forms of the mol­ecule. Weak inter­molecular C—H⋯O inter­actions help to stabilize the crystal structure