APOBEC3 proteins constitute a family of cytidine deaminases that provide intracellular resistance to retrovirus replication and transposition of endogenous retroelements. One family member, APOBEC3A (hA3A), is an orphan, without any known antiviral activity. We show that hA3A is catalytically active and that it, but none of the other family members, potently inhibits replication of the parvovirus adeno-associated virus (AAV). hA3A was also a potent inhibitor of the endogenous LTR retroelements, MusD, IAP, and the non-LTR retroelement, LINE-1. Its function was dependent on the conserved amino acids of the hA3A active site, consistent with a role for cytidine deamination, although mutations in retroelement sequences were not found. These findings demonstrate the potent activity of hA3A, an APOBEC3 family member with no previously identified function. They also highlight the functional differences between APOBEC3 proteins. The APOBEC3 family members have distinct functions and may have evolved to resist various classes of genetic elements.

No abstract

Objectives: To evaluate whether the presence of preexisting right ventricular (RV) dysfunction in high-risk patients undergoing non-emergent major vascular surgery is associated independently with higher incidents of postoperative cardiac complications and a longer length of hospital stay. Design: Retrospective chart review. Setting: Singlecenter university hospital setting. Participants: The patient population consisted of those identified as American Society of Anesthesiologists classification III and above who had a preoperative echocardiogram within 1 year of undergoing nonemergent major vascular surgery between January 2010 and May 2017. Measurements and Main Results: After multivariate analyses, RV dysfunction (RVD) is associated independently with a higher incidence of postoperative major cardiac complications with an odds ratio = 6.3 (95% confidence interval [CI], 1.038.5; p = 0.046). In addition, patients with RVD had a 50% longer length of stay than those without RVD (incident rate ratio [95% CI], 1.5 [1.21.8]; p < 0.001). Conclusion: In this retrospective study of high-risk patients undergoing major vascular surgery, RV dysfunction was associated independently with a higher incidence of postoperative major cardiovascular events and longer length of hospital stays. Based on current findings, the prognostic value of RVD extends beyond the cardiac surgical cohort. Knowledge in management of patients with RVD in the perioperative setting should be understood by all anesthesiologists. Of note, a future study with a larger sample size is needed to validate the current findings given the small sample size of this study.

We have previously developed a simulated cardiovascular physiology model for in-silico testing and validation of novel closed-loop controllers. To date, a detailed model of the right heart and pulmonary circulation was not needed, as previous controllers were not intended for use in patients with cardiac or pulmonary pathology. With new development of controllers for vasopressors, and looking forward, for combined vasopressor-fluid controllers, modeling of right-sided and pulmonary pathology is now relevant to further in-silico validation, so we aimed to expand our existing simulation platform to include these elements. Our hypothesis was that the completed platform could be tuned and stabilized such that the distributions of a randomized sample of simulated patients' baseline characteristics would be similar to reported population values. Our secondary outcomes were to further test the system in representing acute right heart failure and pulmonary artery hypertension. After development and tuning of the right-sided circulation, the model was validated against clinical data from multiple previously published articles. The model was considered 'tuned' when 100% of generated randomized patients converged to stability (steady, physiologically-plausible compartmental volumes, flows, and pressures) and 'valid' when the means for the model data in each health condition were contained within the standard deviations for the published data for the condition. A fully described right heart and pulmonary circulation model including non-linear pressure/volume relationships and pressure dependent flows was created over a 6-month span. The model was successfully tuned such that 100% of simulated patients converged into a steady state within 30 s. Simulation results in the healthy state for central venous volume (3350 ± 132 ml) pulmonary blood volume (405 ± 39 ml), pulmonary artery pressures (systolic 20.8 ± 4.1 mmHg and diastolic 9.4 ± 1.8 mmHg), left atrial pressure (4.6 ± 0.8 mmHg), PVR (1.0 ± 0.2 wood units), and CI (3.8 ± 0.5 l/min/m) all met criteria for acceptance of the model, though the standard deviations of LAP and CI were somewhat narrower than published comparators. The simulation results for right ventricular infarction also fell within the published ranges: pulmonary blood volume (727 ± 102 ml), pulmonary arterial pressures (30 ± 4 mmHg systolic, 12 ± 2 mmHg diastolic), left atrial pressure (13 ± 2 mmHg), PVR (1.6 ± 0.3 wood units), and CI (2.0 ± 0.4 l/min/m) all fell within one standard deviation of the reported population values and vice-versa. In the pulmonary hypertension model, pulmonary blood volume of 615 ± 90 ml, pulmonary arterial pressures of 80 ± 14 mmHg systolic, 36 ± 7 mmHg diastolic, and the left atrial pressure of 11 ± 2 mmHg all met criteria for acceptance. For CI, the simulated value of 2.8 ± 0.4 l/min/m once again had a narrower spread than most of the published data, but fell inside of the SD of all published data, and the PVR value of 7.5 ± 1.6 wood units fell in the middle of the four publishe...

Background: The prognostic value of right ventricular systolic dysfunction in high-risk patients undergoing non-emergent open abdominal surgery is unknown. Here, we aim to evaluate whether presence of preexisting right ventricular systolic dysfunction in this surgical cohort is independently associated with higher incidence of postoperative major adverse cardiac events and all-cause in-hospital mortality. Methods: This is a single-centered retrospective study. Patients identified as American Society Anesthesiology Classification III and IV who had a preoperative echocardiogram within 1 year of undergoing non-emergent open abdominal surgery between January 2010 and May 2017 were included in the study. Incidence of postoperative major cardiac adverse events and all-cause in-hospital mortality were collected. Multivariable logistic regression was performed in a step-wise manner to identify independent association between preexisting right ventricular systolic dysfunction with outcomes of interest. Results: Preexisting right ventricular systolic dysfunction was not associated with postoperative major adverse cardiac events ( P = 0.26). However, there was a strong association between preexisting right ventricular systolic dysfunction and all-cause in-hospital mortality ( P = 0.00094). After multivariate analysis, preexisting right ventricular systolic dysfunction continued to be an independent risk factor for all-cause in-hospital mortality with an odds ratio of 18.9 (95% CI: 1.8-201.7; P = 0.015). Conclusion: In this retrospective study of high-risk patients undergoing non-emergent open abdominal surgery, preexisting right ventricular systolic dysfunction was found to have a strong association with all-cause in-hospital mortality.