Molecular dynamics simulations in pre-polymerization mixtures for peptide recognition.

CONTEXT: Molecularly imprinted polymers (MIPs) have promising applications as synthetic antibodies for protein and peptide recognition. A critical aspect of MIP design is the selection of functional monomers and their adequate proportions to achieve materials with high recognition capacity toward their targets. To contribute to this goal, we calibrated a molecular dynamics protocol to reproduce the experimental trends in peptide recognition of 13 pre-polymerization mixtures reported in the literature for the peptide toxin melittin. METHODS: Three simulation conditions were tested for each mixture by changing the box size and the number of monomers and cross-linkers surrounding the template in a solvent-explicit environment. Fully atomistic MD simulations of 350 ns were conducted with the AMBER20 software, with ff19SB parameters for the peptide, gaff2 parameters for the monomers and cross-linkers, and the OPC water model. Template-monomer interaction energies under the LIE approach showed significant differences between high-affinity and low-affinity mixtures. Simulation systems containing 100 monomers plus cross-linkers in a cubic box of 90 Å3 successfully ranked the mixtures according to their experimental performance. Systems with higher monomer densities resulted in non-specific intermolecular contacts that could not account for the experimental trends in melittin recognition. The mixture with the best recognition capacity showed preferential binding to the 13-26-α-helix, suggesting a relevant role for this segment in melittin imprinting and recognition. Our findings provide insightful information to assist the computational design of molecularly imprinted materials with a validated protocol that can be easily extended to other templates.

Intravenous antibiotic therapy after laparoscopic appendectomy in acute complicated appendicitis: the patient clinical response is the key.

INTRODUCTION: The guidelines about acute complicated appendicitis (ACA) recommend 3-5 days of postoperative intravenous antibiotics (IVA). Nevertheless, the time selected by the surgeon can vary according to patient clinical response, ACA type, and professional experience. Once an adequate clinical response is obtained, the change from IVA to oral antibiotic (OA) could be realized without the waiting time established with satisfactory results. OBJECTIVE: Determine if a short course of IVA and/or switch to oral route is safe based on the patient clinical response. MATERIALS AND METHODS: Observational prospective cohort study from a general surgery reference center database since July 2019. RESULTS AND CONCLUSION: 48 patients with ACA intraoperative findings were included. Regarding postoperative antibiotic management, only preoperative IVA: 7 (14.58%), IVA 1-3 days: 1 (20.83%), IVA 1-3 days and change to OA: 21 (43.75%), IVA > 3 days: 6 (12.5%), and only OA: 3 (27.08%). The bivariate analysis did not show statistically significant differences in reconsultation (p = 0.81), rehospitalization (p = 0.44), and surgical site infection (p = 0.56) between the antibiotic scheme based on the postoperative clinical response and the traditional one regarding intra-abdominal collection rate, the hospital stays, and hospitalization costs.

INTRODUCTION: Las guías sobre apendicitis aguda complicada (ACA) recomiendan 3-5 días de antibióticos intravenosos (IVA) postoperatorios. No obstante, el tiempo seleccionado por el cirujano puede variar según la respuesta clínica del paciente, tipo de ACA y experiencia profesional. Una vez obtenida una adecuada respuesta clínica, el cambio de IVA a antibiótico oral (OA) podría realizarse sin esperar el tiempo establecido con resultados satisfactorios. OBJETIVO: Determinar si un ciclo corto de IVA y/o el cambio a OA según la respuesta clínica del paciente es seguro. MATERIALES Y MÉTODOS: Estudio observacional de cohorte prospectivo a partir de la base de datos de un centro de referencia en cirugía general desde julio del 2019. RESULTADOS Y CONCLUSIÓN: Se incluyeron 48 pacientes con hallazgos intraoperatorios de ACA. En cuanto al manejo antibiótico postoperatorio, solo IVA preoperatorio: 7 (14.58%), IVA 1-3 días: 1 (20.83%), IVA 1-3 días y cambio OA: 21 (43.75%), IVA > 3 días: 6 (12.5%) y solo OA: 3 (27.08%). El análisis bivariado no mostró diferencias estadísticamente significativas en la reconsulta (p = 0.81), la rehospitalización (p = 0.44) y la infección del sitio operatorio (p = 0.56) entre el esquema de antibióticos basado en la respuesta clínica postoperatoria y el tradicional con respecto a tasa de colección intrabdominal, estancia hospitalaria y costos de hospitalización.