RESUMEN
The highly conserved 5' untranslated region (5'UTR) of the HIV-1 RNA genome is central to the regulation of virus replication. NMR and biochemical experiments support a model in which the 5'UTR can transition between at least two conformational states. In one state the genome remains a monomer, as the palindromic dimerization initiation site (DIS) is sequestered via base pairing to upstream sequences. In the second state, the DIS is exposed, and the genome is competent for kissing loop dimerization and packaging into assembling virions where an extended dimer is formed. According to this model the conformation of the 5'UTR determines the fate of the genome. In this work, the dynamics of this proposed conformational switch and the factors that regulate it were probed using multiple single-molecule and in-gel ensemble FRET assays. Our results show that the HIV-1 5'UTR intrinsically samples conformations that are stabilized by both viral and host factor binding. Annealing of tRNALys3, the primer for initiation of reverse transcription, can promote the kissing dimer but not the extended dimer. In contrast, HIV-1 nucleocapsid (NC) promotes formation of the extended dimer in both the absence and presence of tRNALys3 Our data are consistent with an ordered series of events that involves primer annealing, genome dimerization, and virion assembly.
Asunto(s)
Regiones no Traducidas 5'/genética , Genoma Viral/genética , VIH-1/genética , ARN Viral/genética , Emparejamiento Base/genética , Dimerización , Genómica/métodos , Conformación de Ácido Nucleico , Nucleocápside/genética , ARN de Transferencia/genética , Virión/genética , Ensamble de Virus/genética , Replicación Viral/genéticaRESUMEN
At our institution, multimodal opiate-sparing pain management is the cornerstone of our enhanced recovery program for autologous breast reconstruction. The purpose of this study was to compare postoperative outcomes and pain control metrics following implementation of an enhanced recovery program with two different regional analgesia approaches. METHODS: This retrospective cohort study identified 145 women who underwent autologous breast reconstruction from 2015 to 2017. Three groups were included: historical control patients (n = 46) and enhanced recovery patients that received multimodal pain management including a postoperative transversalis abdominis plane block with either a continuous local anesthetic catheter (n = 60) or a single-shot of liposomal bupivacaine (n = 39). The primary outcome was pain scores in the first three postoperative days. Secondary outcomes were opioid consumption in oral morphine equivalents and length of stay. RESULTS: Postoperative pain scores were similar across all three groups until postoperative day 3. Length of stay was significantly shorter in both of the enhanced recovery cohorts (3.0 [3.0, 4.0]) compared with control patients (4.0 [4.0, 5.0], P < 0.001). Likewise, average total oral morphine equivalents consumption was significantly reduced in enhanced recovery patients (continuous catheter 215.9 (95% CI, 165.4-266.3); liposomal bupivacaine 211.0 (95% CI, 154.8-267.2); control 518.4 (95% CI 454.2-582.7), P < 0.001). Neither length of stay (P = 0.953), nor oral morphine equivalents consumption (P = 0.883) differed by type of regional analgesia. CONCLUSION: Compared with control patients, both approaches to regional transversalis abdominis plane block analgesia as part of an opiate-sparing enhanced recovery pain management strategy were successful, but neither superior to the other.
RESUMEN
ABSTRACT: Enhanced recovery after surgery (ERAS) and perioperative surgical home (PSH) initiatives are widely utilized to improve quality of patient care. Despite their established benefits, implementation still has significant barriers. We developed a survey for perioperative clinicians to gather information on perception and knowledge of ERAS/PSH programs to guide future expansion of these programs at our institution. The survey included questions about familiarity with ERAS/PSH and perceived value, perceived barriers to protocol implementation, preferred learning methods and prioritization of various ERAS/PSH protocol elements into care delivery and provider education. Faculty surgeons and anesthesiologists, in addition to advanced practice nurses and postgraduate physician trainees in the Departments of Surgery and Anesthesiology were asked to complete the survey. Overall survey participation was 25% (223/888). About half of survey respondents had provided care to a patient on an ERAS/PSH protocol, and a majority felt at least somewhat knowledgeable about ERAS/PSH protocols. Perception of the value of ERAS/PSH was positive. Participants were enthusiastic about on-going learning, with multimodal pain management being the topic of most interest and learning by direct participation in care of protocol patients being the favored educational approach. A significant majority of participants felt that upcoming health providers should receive formal ERAS/PSH education as part of their training. Based on our survey results, we plan to explore teaching methods that successfully engage learners of all levels of clinical expertise and also overcome the major barriers to gaining knowledge about ERAS/PSH identified by study participants, most notably lack of time for busy clinicians.
Asunto(s)
Anestesiólogos/psicología , Actitud del Personal de Salud , Recuperación Mejorada Después de la Cirugía , Atención Perioperativa/psicología , Cirujanos/psicología , Adulto , Anestesiólogos/educación , Protocolos Clínicos , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Persona de Mediana Edad , Cirujanos/educación , Encuestas y Cuestionarios , Centros de Atención TerciariaRESUMEN
Importance: Postoperative delirium in older adults is a common and costly complication after surgery. Cognitive reserve affects the risk of postoperative delirium, and thus preoperative augmentation of reserve as a preventive technique is of vital interest. Objective: To determine whether cognitive prehabilitation reduces the incidence of postoperative delirium among older adults. Design, Setting, and Participants: This was a prospective, single-blinded randomized clinical trial conducted from March 2015 to August 2019 at the Ohio State University Wexner Medical Center in Columbus. Patients 60 years and older undergoing major, noncardiac, nonneurological surgery under general anesthesia, with an expected hospital stay of at least 72 hours, were eligible for trial inclusion. Patients were excluded for preoperative cognitive dysfunction and active depression. Interventions: Participation in electronic, tablet-based preoperative cognitive exercise targeting memory, speed, attention, flexibility, and problem-solving functions. Main Outcomes and Measures: The primary outcome was incidence of delirium between postoperative day 0 to day 7 or discharge, as measured by a brief Confusion Assessment Method, Memorial Delirium Assessment Scale, or a structured medical record review. Secondary outcomes compared delirium characteristics between patients in the intervention and control groups. Results: Of the 699 patients approached for trial participation, 322 completed consent and 268 were randomized. Subsequently, 17 patients were excluded, leaving 251 patients in the primary outcome analysis. A total of 125 patients in the intervention group and 126 control patients were included in the final analysis (median [interquartile range] age, 67 [63-71] years; 163 women [64.9%]). Ninety-seven percent of the patients in the intervention group completed some brain exercise (median, 4.6 [interquartile range, 1.31-7.4] hours). The delirium rate among control participants was 23.0% (29 of 126). With intention-to-treat analysis, the delirium rate in the intervention group was 14.4% (18 of 125; P = .08). Post hoc analysis removed 4 patients who did not attempt any cognitive exercise from the intervention group, yielding a delirium rate of 13.2% (16 of 121; P = .04). Secondary analyses among patients with delirium showed no differences in postoperative delirium onset day or duration or total delirium-positive days across study groups. Conclusions and Relevance: The intervention lowered delirium risk in patients who were at least minimally compliant. The ideal activities, timing, and effective dosage for cognitive exercise-based interventions to decrease postoperative delirium risk and burden need further study. Trial Registration: ClinicalTrials.gov Identifier: NCT02230605.