Synthesis of enantiomerically enriched benzimidazole-triazoles: Application as organocatalyst for asymmertric Diels-Alder reaction

93-1014-(Benzimidazolylmethyl)-1,2,3-triazole derivatives 8a-g and 9a-g have been developed using click chemistry protocol in regioselective manner and in high yields. These compounds have geometry to behave as chiral tweezers due to the presence of flexibly bound pi-rich hetero-aryl rings in addition to a chiral center. The synthesized chiral benzimidazole-triazoles have been found to be useful as organocatalysts for the enantioselective Diels-Alder (DA) reaction between anthrone 10 and maleimide detivatives 11a-g. Enantioselectivity levels have been found to be dependent on several factors including nature of substituents in benzimidazole-triazoles 8a-g and 9a-g

Underutilization of Endovascular Therapy in Black Patients With Ischemic Stroke: An Analysis of State and Nationwide Cohorts

BACKGROUND AND PURPOSE: Endovascular therapy (EVT) is a very effective treatment but relies on specialized capabilities that are not available in every hospital where acute ischemic stroke is treated. Here, we assess whether access to and utilization of this therapy has extended uniformly across racial and ethnic groups. METHODS: We conducted a retrospective, population-based study using the 2019 Texas Inpatient Public Use Data File. Acute ischemic stroke cases and EVT use were identified using the RESULTS: Among 40 814 acute ischemic stroke cases in Texas in 2019, 54% were White, 17% Black, and 21% Hispanic. Black patients had similar admissions to EVT-performing hospitals and greater admissions to comprehensive stroke centers (CSCs) compared with White patients (EVT 62% versus 62%, CONCLUSIONS: We found no evidence of disparity in presentation to EVT-performing hospitals or CSCs; however, lower rates of EVT were observed in Black patients

A convenient route to benzimidazole fused chiral heterocyclic bases

707-712<span style="font-size:11.0pt;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-bidi-font-family:="" mangal;mso-ansi-language:en-gb;mso-fareast-language:en-us;mso-bidi-language:="" hi"="" lang="EN-GB">An efficient synthetic protocol has been developed to obtain new chiral heterocyclic bases pyrrolo-benzimidazoles (DHP-Bz) and thiazolo-benzimidazoles (DHT-Bz). Notable characteristic of both series of the fused heterocycles is the presence of a chiral center. Chiral HPLC separations of the fused heterocycles have been achieved. These molecules possess structural features well-suited to function as chiral organocatalysts after resolution, apart from potential biological activities.</span

Effect of concomitant administration of L-glutamine and cycloart-23-ene-3β, 25-diol (B2) with sitagliptin in GLP-1 (7-36) amide secretion, biochemical and oxidative stress in streptozotocin - nicotinamide induced diabetic Sprague Dawley rats.

Previously we have reported that, cycloart-23-ene-3β, 25-diol (called as B2) and L-glutamine stimulated glucagon like peptide-1 (GLP-1) (7-36) amide secretion diabetic rats. The objective of present investigation was to investigate the concomitant administration of cycloart-23-ene-3β, 25-diol+sitagliptin and L-glutamine+sitagliptin in streptozotocin - nicotinamide induced diabetic Sprague Dawley. Type 2 diabetes was induced in overnight fasted male Sprague Dawley rats pre-treated with nicotinamide (100 mg/kg, i.p.) followed by administration of streptozotocin (55 mg/kg, i.p.) 20 min after. The rats were divided into; I- non-diabetic, II- diabetic control, III- Sitagliptin (5 mg/kg, p.o.)+cycloart-23-ene-3β, 25-diol (1 mg/kg, p.o.), IV- Sitagliptin (5 mg/kg, p.o.)+L-glutamine (1000 mg/kg, p.o.). The concomitant treatment of cycloart-23-ene-3β, 25-diol and L-glutamine with sitagliptin was 8 weeks. Plasma glucose, body weight, food and water intake were determined every week. Glycosylated haemoglobin, lipid profile, plasma and colonic active (GLP-1) (7-36) amide, plasma and pancreatic insulin, histology of pancreata and biomarkers of oxidative stress were measured after 8(th) week treatment. Concomitant administration of cycloart-23-ene-3β, 25-diol and L-glutamine with sitagliptin significantly (p<0.001) reduced plasma glucose, glyoxylated haemoglobin, lipid profile and oxidative stress parameters compared to diabetic control groups. Both concomitant treatment increased plasma and pancreatic insulin as well as plasma and colonic active (GLP-1) (7-36) amide secretion. Histological analysis by Gomori staining observed less destruction of pancreatic β cells. The result obtained from this study; it is concluded that concomitant administration of cycloart-23-ene-3β, 25-diol+sitagliptin and L-glutamine+sitagliptin showed additive antihyperglycaemic effect in diabetic rats

Effect of COVID‐19 on Acute Ischemic Stroke Hospitalizations and Treatments: Population‐Level Experience

Background Several studies have reported changes in the volume and type of acute ischemic stroke (AIS) hospitalizations during the early stage of the COVID‐19 pandemic. However, population‐based assessments, which include lower volume centers and more comprehensive geographic areas, are limited. Here, we evaluate an entire state‐level experience during the first peak COVID pandemic and compare against a 1‐year prior historical period. Methods We conducted a retrospective population‐based study using the Texas Inpatient Public Use Data File, capturing all discharges from hospitals in the State of Texas, except federal hospitals. AIS admission volumes, patient characteristics, proportions of large vessel occlusion (LVO), admission rates to comprehensive stroke centers, use of intravenous tissue plasminogen activator and endovascular treatment, and patient outcomes were compared between April 1, 2019 and June 30, 2019 (historical control period) and April 1, 2020 and June 30, 2020 (pandemic period). Results A total of 9277 hospitalized AIS cases were identified during the pandemic period, a decrease of 12% (10 524) compared with the control period. Cases without LVO dropped by 15%, whereas LVO cases dropped by only 5%. There were no significant differences in age or race and ethnicity of patients. While admission rates to comprehensive stroke centers (39.6% versus 39.4%, P=0.81) and endovascular treatment use in LVO (17.0% versus 16.3%, P=0.45) were not different between the 2 periods, the use of intravenous tissue plasminogen activator (15.0% versus 13.6%, relative risk [RR], 0.90; 95% CI, 0.84–0.97; P=0.004) decreased. The percentage of patients who died or were discharged to hospice increased from 7.2% to 8.25% (RR, 1.17; 95% CI. 1.06–1.29; P=0.001). Conclusions This study from a statewide population‐level analysis confirms smaller hospital‐based cohorts observing decreasing numbers of milder AIS admissions, and lower use of thrombolysis. Although LVO admissions and endovascular treatment use were largely unchanged, these findings suggest missed treatment opportunities for patients with AIS in the pandemic

Duration of Ischemia Affects Outcomes Independent of Infarct Size in Stroke

Background Delays in endovascular reperfusion for patients with large vessel occlusion stroke are known to worsen outcomes, and the mechanism is believed to be time‐dependent expansion of the ischemic infarction. In this study, we hypothesize that delays in onset to reperfusion (OTR) assert an effect on outcomes independent of effects of final infarct (FI). Methods We performed a subgroup analysis from the prospective multicenter COMPLETE (International Acute Ischemic Stroke Registry With the Penumbra System Aspiration Including the 3D Revascularization Device; Penumbra, Inc) registry for 257 patients with anterior circulation large vessel occlusion who underwent endovascular therapy with successful reperfusion (modified treatment in cerebral infarction score 2b/3). FI was measured by Alberta Stroke Program Early CT score and volume on 24‐ to 48‐hour computed tomography or magnetic resonance imaging. The likelihood of 90‐day good functional outcome (modified Rankin scale 0–2) was assessed by OTR and absolute risk difference (ARD) was estimated using multivariable logistic regressions adjusting for patient characteristics including FI. Results In univariable analysis, longer OTR was associated with a decreased likelihood of good functional outcome (ARD –3% [95% CI –4.5 to –1.0]/h delay). In multivariable analysis accounting for FI, the association between OTR and functional outcome remained significant (ARD –2% [95% CI –3.5 to –0.4]/h delay) with similar ARD. This finding was maintained in the subset of patients with FI imaging using CT only, using Alberta Stroke Program Early CT Score or volumetric FI measurements, and also in patients with larger versus smaller FIs. Conclusions The impact of OTR on outcomes appears to be mostly through a mechanism that is independent of FI. Our findings suggest that although the field has moved toward imaging infarct core definitions of eligibility for endovascular treatment, time remains an important predictor of outcome, independent of infarct core

Women With Large Vessel Occlusion Acute Ischemic Stroke Are Less Likely to Be Routed to Comprehensive Stroke Centers

Background Prehospital routing of patients with large vessel occlusion (LVO) acute ischemic stroke (AIS) to centers capable of performing endovascular therapy may improve clinical outcomes. Here, we explore whether distance to comprehensive stroke centers (CSCs), stroke severity, and sex are associated with direct‐to‐CSC prehospital routing in patients with LVO AIS. Methods and Results In this cross‐sectional study, we identified consecutive patients with LVO AIS from a prospectively collected multihospital registry throughout the greater Houston area from January 2019 to June 2020. Primary outcome was prehospital routing to CSC and was compared between men and women using modified Poisson regression including age, sex, race or ethnicity, first in‐hospital National Institutes of Health Stroke Scale score, travel time, and distances to the closest primary stroke center and CSC. Among 503 patients with LVO AIS, 413 (82%) were routed to CSCs, and women comprised 46% of the study participants. Women with LVO AIS compared with men were older (73 versus 65, P<0.01) and presented with greater National Institutes of Health Stroke Scale score (14 versus 12, P=0.01). In modified Poisson regression, women were 9% less likely to be routed to CSCs compared with men (adjusted relative risk [aRR], 0.91 [0.84–0.99], P=0.024) and distance to nearest CSC ≤10 miles was associated with 38% increased chance of routing to CSC (aRR, 1.38 [1.26–1.52], P<0.001). Conclusions Despite presenting with more significant stroke syndromes and living within comparable distance to CSCs, women with LVO AIS were less likely to be routed to CSCs compared with men. Further study of the mechanisms behind this disparity is needed

Photomicrographs of histological changes of rat pancreata (Gomori stain).

<p>A) Non-diabetic: Normal histological structure of rat pancreata showing average sized islets (red arrow) and normal sized β cells. B) Diabetic control rat pancreata showing β cells slightly elongated with more destruction (++++). C) Concomitant administration of sitagliptin (5 mg/kg, p.o.) with cycloart-23-ene-3β, 25-diol (1 mg/kg, p.o.) treated rat pancreata showing slightly elongated of the β cells with less destruction (+). D) Concomitant administration of sitagliptin (5 mg/kg, p.o.) with L-glutamine (1000 mg/kg, p.o.) treated rat pancreata showing slightly elongated of the β cells with less destruction (+). <b><i>Grade:</i></b> – No injury; Grade: ++++ severe injury; Grade: ++ mild injury; Grade: + Very mild injury.</p

Effect of concomitant administration of cycloart-23-ene-3β, 25-diol and L-glutamine with sitagliptin on plasma insulin.

<p>Values are mean ± S.E.M., n = 6 in each group; statistical analysis by one way- ANOVA followed by Post hoc Tukey’s test using Graphpad Instat software; <i>p</i> value^#<0.001 compared to non-diabetic groups; *<0.05; **<0.01; ***<0.001 compared to diabetic control group.</p