Time Kills: Impact of Socioeconomic Deprivation on Timely Access to Guideline-Concordant Treatment in Foregut Cancer.

BACKGROUND: Receipt of guideline-concordant treatment (GCT) is associated with improved prognosis in foregut cancers. Studies show that patients living in areas of high neighborhood deprivation have worse healthcare outcomes; however, its effect on GCT in foregut cancers has not been evaluated. We studied the impact of the area deprivation index (ADI) as a barrier to GCT. STUDY DESIGN: A single-institution retrospective review of 498 foregut cancer patients (gastric, pancreatic, and hepatobiliary adenocarcinoma) from 2018 to 2022 was performed. GCT was defined based on National Comprehensive Cancer Network guidelines. ADI, a validated measure of neighborhood disadvantage was divided into terciles (low, medium, and high) with high ADI indicating the most disadvantage. RESULTS: Of 498 patients, 328 (66%) received GCT: 66%, 72%, and 59% in pancreatic, gastric, and hepatobiliary cancers, respectively. Median (interquartile range) time from symptoms to workup was 6 (3 to 13) weeks, from diagnosis to oncology appointment was 4 (1 to 10) weeks, and from oncology appointment to treatment was 4 (2 to 10) weeks. Forty-six percent were diagnosed in the emergency department. On multivariable analyses, age 75 years or older (odds ratio [OR] 0.39 [95% CI 0.18 to 0.87]), Black race (OR 0.52 [95% CI 0.31 to 0.86]), high ADI (OR 0.25 (95% CI 0.14 to 0.48]), 6 weeks or more from symptoms to workup (OR 0.44 [95% CI 0.27 to 0.73]), 4 weeks or more from diagnosis to oncology appointment (OR 0.76 [95% CI 0.46 to 0.93]), and 4 weeks or more from oncology appointment to treatment (OR 0.63 [95% CI 0.36 to 0.98]) were independently associated with nonreceipt of GCT. CONCLUSIONS: Residence in an area of high deprivation predicts nonreceipt of GCT. This is due to multiple individual- and system-level barriers. Identifying these barriers and developing effective interventions, including community outreach and collaboration, leveraging telehealth, and increasing oncologic expertise in underserved areas, may improve access to GCT.

Antimicrobial activity of methanolic extracts of Vernonia cinerea against Xanthomonas oryzae and identification of their compounds using in silico techniques.

Bacterial Leaf Blight (BLB) disease is an extremely ruinous disease in rice, caused by Xanthomonas oryzae pv. oryzae (Xoo). Although various chemicals are available to manage BLB, they are toxic to the environment as well as humans. Hence there is a need to develop new pesticides as alternatives to hazardous chemicals. Therefore, a study was carried out to discover new potent natural pesticides against Xoo from different solvent extracts of Vernonia cinerea. Among all the fractions, the methanolic extract showed the highest inhibition zone. Further, to gain mechanistic insight of inhibitory action, 40 molecules of methanolic extracts were subjected for in silico study against two enzymes D-alanine-D-alanine ligase (Ddl) and Peptide deformylase (PDF). In silico study showed Rutin and Methanone, [1,4-dimethyl-7-(1- methylethyl)-2- azulenyl]phenyl have a good binding affinity with Ddl while Phenol, 2,4-bis(1-phenylethyl)- and 1,2-Benzenedicarboxylic acid, diisooctyl ester showed an excellent binding affinity to PDF. Finally, the system biology approach was applied to understand the agrochemical's effect in the cell system of bacteria against both the enzymes. Conclusively, these four-hit compounds may have strong potential against Xoo and can be used as biopesticides in the future.

Identification of bioactive molecule from Withania somnifera (Ashwagandha) as SARS-CoV-2 main protease inhibitor.

SARS-CoV-2 is the causative agent of COVID-19 and has been declared as pandemic disease by World Health Organization. Lack of targeted therapeutics and vaccines for COVID-2019 have triggered the scientific community to develop new vaccines or drugs against this novel virus. Many synthetic compounds and antimalarial drugs are undergoing clinical trials. The traditional medical practitioners widely use Indian medicinal plant Withania somnifera (Ashwagandha) natural constituents, called withanolides for curing various diseases. The main protease (Mpro) of SARS-CoV-2 plays a vital role in disease propagation by processing the polyproteins which are required for its replication. Hence, it denotes a significant target for drug discovery. In the present study, we evaluate the potential of 40 natural chemical constituents of Ashwagandha to explore a possible inhibitor against main protease of SARS-CoV-2 by adopting the computational approach. The docking study revealed that four constituents of Ashwagandha; Withanoside II (-11.30 Kcal/mol), Withanoside IV (-11.02 Kcal/mol), Withanoside V (-8.96 Kcal/mol) and Sitoindoside IX (-8.37 Kcal/mol) exhibited the highest docking energy among the selected natural constituents. Further, MD simulation study of 100 ns predicts Withanoside V possess strong binding affinity and hydrogen-bonding interactions with the protein active site and indicates its stability in the active site. The binding free energy score also correlates with the highest score of -87.01 ± 5.01 Kcal/mol as compared to other selected compounds. In conclusion, our study suggests that Withanoside V in Ashwagandha may be serve as a potential inhibitor against Mpro of SARS-CoV-2 to combat COVID-19 and may have an antiviral effect on nCoV.Communicated by Ramaswamy H. Sarma.