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Introduction: This work utilizes predictive modeling in drug discovery to unravel potential candidate genes from Escherichia coli that are implicated in antimicrobial resistance; we subsequently target the gidB, MacB, and KatG genes with some compounds from plants with reported antibacterial potentials. Method: The resistance genes and plasmids were identified from 10 whole-genome sequence datasets of E. coli; forty two plant compounds were selected, and their 3D structures were retrieved and optimized for docking. The 3D crystal structures of KatG, MacB, and gidB were retrieved and prepared for molecular docking, molecular dynamics simulations, and ADMET profiling. Result: Hesperidin showed the least binding energy (kcal/mol) against KatG (-9.3), MacB (-10.7), and gidB (-6.7); additionally, good pharmacokinetic profiles and structure-dynamics integrity with their respective protein complexes were observed. Conclusion: Although these findings suggest hesperidin as a potential inhibitor against MacB, gidB, and KatG in E. coli, further validations through in vitro and in vivo experiments are needed. This research is expected to provide an alternative avenue for addressing existing antimicrobial resistances associated with E. coli's MacB, gidB, and KatG.
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INTRODUCTION: Despite considerable research on the comparison of enteral and parenteral nutrition in patients with acute pancreatitis, there is an ongoing debate about the optimal timing of nutrition initiation, invasiveness of interventions, impact on outcomes, and patient tolerance. Given the gap that still exists in the literature, we investigated the relationship between the mode of nutrition and critical outcomes such as mortality rates, inpatient complications, length of hospitalization, and discharge disposition, using comprehensive national-level data. In addition, we investigated the impact of early enteral nutrition on outcomes in acute pancreatitis. METHODS: All adult discharges for acute pancreatitis between 2016 and 2018 were analyzed from the National (Nationwide) Inpatient Sample (NIS). Discharges of minors and those involving mixed nutrition were excluded from the analysis. Enteral nutrition and parenteral nutrition subgroups were identified using the International Classification of Diseases, 10th revision (ICD-10) codes. Disease severity was defined using the 2013 revised Atlanta Classification of Acute Pancreatitis, along with the All Patient Refined Diagnosis Related Group (APR-DRG)'s severity of illness and likelihood of mortality variables. Complications were identified using ICD-10 codes from the secondary diagnoses variables within the NIS dataset. Multivariable logistic regression analyses were employed to assess associations between the mode of nutrition and the outcomes of interest. RESULTS: A total of 379,410 hospitalizations were studied. About 2,011 (0.53%) received enteral nutrition, while 4,174 (1.1%) received parenteral nutrition. The mean age of the study was 51.7 years (SD 0.1). About 2,280 mortalities were recorded in the study. After adjustments, enteral nutrition was associated with significantly lower odds of mortality (adjusted OR (aOR): 0.833; 95%CI: 0.497-0.933; P<0.001). Parenteral nutrition was linked with significantly greater odds of mortality (aOR: 6.957; 95%CI: 4.730-10.233; P<0.001). Both enteral nutrition and parenteral nutrition were associated with augmented odds of complications and prolonged hospitalization (P<0.001) compared to normal oral feeding. Initiation of enteral nutrition within 24 hours of admission did not improve the odds of mortality in this study (aOR: 5.619; 95%CI: 1.900-16.615; P=0.002). CONCLUSION: Enteral nutrition demonstrates better outcomes in mortality rates and systemic complications compared to parenteral nutrition in patients unable to maintain normal oral feeding.