181 research outputs found
A concise synthesis of carbasugars isolated from Streptomyces lincolnensis
(–)-Quinic acid was used as a starting material in the hemisynthesis of two epimeric carbasugars
isolated from Streptomyces lincolnensis. Previous 10–12 steps syntheses for the carbasugars
have been herein shortened to 4–6 steps by using quinic acid as a chiron, based on a
regioselective reduction step, with stereoinversion of a tertiary center. Both C-5 epimers of (1R,
2R, 3R)-5-(hydroxymethyl)cyclohexane-1,2,3-triol were obtained in up to 76% overall yield.publishe
A COMPARISON OF CHOLINESTERASE DISTRIBUTION IN THE CEREBELLUM OF SEVERAL SPECIES *
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65142/1/j.1471-4159.1964.tb06717.x.pd
International Experience of Mechanical Thrombectomy During the COVID-19 Pandemic: Insights from STAR and ENRG
Background: In response to the COVID-19 pandemic, many centers altered stroke triage protocols for the protection of their providers. However, the effect of workflow changes on stroke patients receiving mechanical thrombectomy (MT) has not been systematically studied.
Methods: A prospective international study was launched at the initiation of the COVID-19 pandemic. All included centers participated in the Stroke Thrombectomy and Aneurysm Registry (STAR) and Endovascular Neurosurgery Research Group (ENRG). Data was collected during the peak months of the COVID-19 surge at each site. Collected data included patient and disease characteristics. A generalized linear model with logit link function was used to estimate the effect of general anesthesia (GA) on in-hospital mortality and discharge outcome controlling for confounders.
Results: 458 patients and 28 centers were included from North America, South America, and Europe. Five centers were in high-COVID burden counties (HCC) in which 9/104 (8.7%) of patients were positive for COVID-19 compared with 4/354 (1.1%) in low-COVID burden counties (LCC) (P<0.001). 241 patients underwent pre-procedure GA. Compared with patients treated awake, GA patients had longer door to reperfusion time (138 vs 100 min, P=<0.001). On multivariate analysis, GA was associated with higher probability of in-hospital mortality (RR 1.871, P=0.029) and lower probability of functional independence at discharge (RR 0.53, P=0.015).
Conclusion: We observed a low rate of COVID-19 infection among stroke patients undergoing MT in LCC. Overall, more than half of the patients underwent intubation prior to MT, leading to prolonged door to reperfusion time, higher in-hospital mortality, and lower likelihood of functional independence at discharge.info:eu-repo/semantics/publishedVersio
Mechanisms and treatment of ischaemic stroke: insights from genetic associations
The precise pathophysiology of ischaemic stroke is unclear, and a greater understanding of the different mechanisms that underlie large-artery, cardioembolic and lacunar ischaemic stroke subtypes would enable the development of more-effective, subtype-specific therapies. Genome-wide association studies (GWASs) are identifying novel genetic variants that associate with the risk of stroke. These associations provide insight into the pathophysiological mechanisms, and present opportunities for novel therapeutic approaches. In this Review, we summarize the genetic variants that have been linked to ischaemic stroke in GWASs to date and discuss the implications of these associations for both our understanding and treatment of ischaemic stroke. The majority of genetic variants identified are associated with specific subtypes of ischaemic stroke, implying that these subtypes have distinct genetic architectures and pathophysiological mechanisms. The findings from the GWASs highlight the need to consider whether therapies should be subtype-specific. Further GWASs that include large cohorts are likely to provide further insights, and emerging technologies will complement and build on the GWAS findings
Global impact of COVID-19 on stroke care and IV thrombolysis
Objective To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods. Methods We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. Results There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] -11.7 to -11.3, p < 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI -13.8 to -12.7, p < 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI -13.7 to -10.3, p = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2-9.8, p < 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions. Conclusions The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.Paroxysmal Cerebral Disorder
Cholinesterases: Structure, Role, and Inhibition
Acetilkolinesteraza (AChE; E.C. 3.1.1.7) i butirilkolinesteraza (BChE; E.C. 3.1.1.8) enzimi su koji se zbog svoje uloge u organizmu intenzivno istražuju unutar područja biomedicine i toksikologije. Iako strukturno homologni, ovi enzimi razlikuju se prema katalitičkoj aktivnosti, odnosno specifi čnosti prema supstratima koje mogu hidrolizirati te selektivnosti za vezanje mnogih liganada. U ovom radu dan je pregled dosadašnjih istraživanja kolinesteraza i njihovih interakcija s ligandima i inhibitorima te su izdvojene aminokiseline
aktivnog mjesta koje sudjeluju u tim interakcijama.Enzymes acetylcholinesterase (AChE; E.C. 3.1.1.7) and butyrylcholinesterase (BChE; E.C. 3.1.1.8) have intensively been investigated in biomedicine and toxicology due to important role in organisms. Even if structurally homologous, they differ in catalytic activity, specificity, for substrates, and selectivity in binding to many ligands. This paper compiles the results of research on cholinesterases and their interactions with ligands and inhibitors, and identifies amino acids of active sites involved in these interactions
O,O-Silyl Group Migrations in Quinic Acid Derivatives : An Opportunity for Divergent Synthesis
The O,O-silyl group migrations on a quinic acid-derived cyclitol have been studied, and the ease of migration was observed to be dependent on the silicon substituents and reaction conditions. Conditions were found to improve the formation of a main isomer during the O,O-silyl group migrations that could be integrated into the formal synthesis of vitamin D receptor modulator VS-105 and in the first total synthesis of a metabolite from the African ant Crematogaster nigriceps.acceptedVersionPeer reviewe
Deoxygenative Divergent Synthesis : En Route to Quinic Acid Chirons
The installation of vicinal mesylate and silyl ether groups in a quinic acid derivative generates a system prone for stereoselective borane-catalyzed hydrosilylation through a siloxonium intermediate. The diversification of the reaction conditions allowed the construction of different defunctionalized fragments foreseen as useful synthetic fragments. The selectivity of the hydrosilylation was rationalized on the basis of deuteration experiments and computational studies.peerReviewe
Deoxygenative Divergent Synthesis : En Route to Quinic Acid Chirons
The installation of vicinal mesylate and silyl ether groups in a quinic acid derivative generates a system prone for stereoselective borane-catalyzed hydrosilylation through a siloxonium intermediate. The diversification of the reaction conditions allowed the construction of different defunctionalized fragments foreseen as useful synthetic fragments. The selectivity of the hydrosilylation was rationalized on the basis of deuteration experiments and computational studies.peerReviewe
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