Introduction Coronavirus disease 2019 (COVID-19) has substantially impacted the healthcare delivery system in Tehran, Iran. The country’s first confirmed positive test for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was on February 18, 2020. Since then, the number of cases has steadily increased in Iran and worldwide. Emergency medical services (EMS) quickly adapted its operations to accommodate a greater number of patients, and it worked to decrease the risk of COVID-19 spread among EMS personnel, given the disease’s high transmissibility. Methods We evaluated the chief complaint as well as the pattern and number of EMS calls and dispatches during the 28-day intervals before and after the February 18, 2020, COVID-19 outbreak in Iran. Results EMS calls increased from 355,241 in the pre-outbreak period to 1,589,346 in the post-outbreak period, a 347% increase (p<0.001). EMS dispatches rose more modestly from 82,282 to 99,926, a 21% increase (p<0.001). The average time on telephone hold decreased from 10.6 ± 12.7 seconds pre-outbreak to 9.8 ± 11.8 seconds post-outbreak, a 7% decrease (p<0.001). The average length of call also decreased from 1.32 ± 1.42 minutes pre-outbreak to 1.06 ± 1.28 minutes post-outbreak, a 20% decrease (p<0.001). The highest number of daily dispatches occurred during the second and third weeks of the four-week post-outbreak period, peaking at 4557 dispatches/day. After the first reported case of SARS-CoV-2, there were significant increases in chief complaints of fever (211% increase, p<0.001) and respiratory symptoms (245% increase, p<0.001). Conclusion The number of EMS calls and dispatches in Tehran increased 347% and 20%, respectively, after the outbreak of COVID-19. Despite this, the time on hold for EMS response decreased. The Tehran EMS system accomplished this by increasing personnel hours, expanding call-center resources, and implementing COVID-19-specific training.
Evidence suggests that amyloid β-protein (Aβ) oligomers may be seminal pathogenic agents in Alzheimer's disease (AD). If so, developing oligomer-targeted therapeutics requires an understanding of oligomer structure. This has been difficult due to the instability of these non-covalently associated Aβ assemblies. We previously used rapid, zero-length, in situ chemical cross-linking to stabilize oligomers of Aβ40. These enabled us to isolate pure, stable populations of dimers, trimers, and tetramers and to determine their structure-activity relationships. However, equivalent methods applied to Aβ42 did not produce stable oligomers. We report here that the use of an Aβ42 homologue, [F10, Y42]Aβ42, coupled with sequential denaturation/dissociation and gel electrophoresis procedures, provides the means to produce highly pure, stable populations of oligomers of sizes ranging from dimer through dodecamer that are suitable for structure-activity relationship determination.
As intracerebral hemorrahge becomes more frequent as a result of an aging population with greater comorbidities, rapid identification and reversal of precipitators becomes increasingly paramount. The aformentioned population will ever more likely be on some form of anticoagulant therapy. Understanding the mechanisms of these agents and means by which to reverse them early on is critical in managing the acute intracerebral hemorrhage.
Protein and peptide oligomers are thought to play important roles in the pathogenesis of a number of neurodegenerative diseases. For this reason, considerable effort has been devoted to understanding the oligomerization process and to determining structure-activity relationships among the many types of oligomers that have been described. We discuss here a method for producing pure populations of amyloid β-protein (Aβ) of specific sizes using the most pathologic form of the peptide, Aβ42. This work was necessitated because Aβ oligomerization produces oligomers of many different sizes that are non-covalently associated, which means that dissociation or further assembly may occur. These characteristics preclude rigorous structure-activity determinations. In studies of Aβ40, we have used the method of photo-induced cross-linking of unmodified proteins (PICUP) to produce zero-length carbon-carbon bonds among the monomers comprising each oligomer, thus stabilizing the oligomers. We then isolated pure populations of oligomers by fractionating the oligomers by size using SDS-PAGE and then extracting each population from the stained gel bands. Although this procedure worked well with the shorter Aβ40 peptide, we found that a significant percentage of Aβ42 oligomers had not been stabilized. Here, we discuss a new method capable of yielding stable Aβ42 oligomers of sizes from dimer through dodecamer.
Early administration of tissue plasminogen activator (tPA) improves morbidity and mortality in acute ischemic stroke (AIS). However, the strict NINDS exclusion criteria, especially the emphasis on last known well times (LKWT) which are often unreliable in the acute setting, restrits tPA use to only 2-5% of all AIS patients. The MR-Witness and WAKE-UP trials propose using MRI diffusion-to-flair mismatch in these cases to better judge the age of an infarct, but the impact of this on post-discharge outcomes has not yet been reported. We conducted a retrospective analysis of all AIS patients in one comprehensive stroke center to further investigate this question. Of our total 1016 patients, 165 (16.2%) received tPA and 58 (5.7%) underwent mechanical thrombectomy. 380 patients (37.4%) were refused tPA due to an NINDS exclusion other than LKWT, 246 (24.2%) due to minimal or resolving neurological deficits, and 6 (0.6%) due to family preference. The remaining 161 patients (15.8%) were refused tPA only because of an unreliable LKWT. Statistical analyses comparing these 161 patients to the 165 who received tPA revealed no differences in age (p=0.306), gender (p=0.214), race, or even NIHSS score on presentation (p=0.306). However, while the total hospital stay was similar in both groups (p=0.954), patients who received tPA had significantly better post-discharge outcomes, with more patients going to acute rehab or home (p=0.033). In summary, comprehensive stroke centers generally out-perform national tPA administration averages (16.2% in our stroke center compared to 2-5% nationally). However, our study showed that a large percentage of AIS patients are still refused tPA only because of an unreliable LKWT. Obtaining emergent MRIs to assess diffusion-to-flair mismatch in these cases may increase the number of people with AIS eligible for tPA and substantially improve their post-discharge outcomes.
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