Nicole M. Zimmerman

BACKGROUND: The relative contributions of intraoperative and postoperative hypotension to perioperative morbidity remain unclear. We determined the association between hypotension and a composite of 30-day myocardial infarction and death over three periods: (1) intraoperative, (2) remaining day of surgery, and (3) during the initial four postoperative days. METHODS: This was a substudy of POISE-2, a 10,010-patient factorial-randomized trial of aspirin and clonidine for prevention of myocardial infarction. Clinically important hypotension was defined as systolic blood pressure less than 90 mmHg requiring treatment. Minutes of hypotension was the exposure variable intraoperatively and for the remaining day of surgery, whereas hypotension status was treated as binary variable for postoperative days 1 to 4. We estimated the average relative effect of hypotension across components of the composite using a distinct effect generalized estimating model, adjusting for hypotension during earlier periods. RESULTS: Among 9,765 patients, 42% experienced hypotension, 590 (6.0%) had an infarction, and 116 (1.2%) died within 30 days of surgery. Intraoperatively, the estimated average relative effect across myocardial infarction and mortality was 1.08 (98.3% CI, 1.03, 1.12; P < 0.001) per 10-min increase in hypotension duration. For the remaining day of surgery, the odds ratio was 1.03 (98.3% CI, 1.01, 1.05; P < 0.001) per 10-min increase in hypotension duration. The average relative effect odds ratio was 2.83 (98.3% CI, 1.26, 6.35; P = 0.002) in patients with hypotension during the subsequent four days of hospitalization. CONCLUSIONS: Clinically important hypotension-a potentially modifiable exposure-was significantly associated with a composite of myocardial infarction and death during each of three perioperative periods, even after adjustment for previous hypotension.

Herpesviruses are large, ubiquitous DNA viruses with complex host interactions, yet many of the proteins encoded by these viruses have not been functionally characterized. As a first step in functional characterization, we determined the subcellular localization of 234 epitope-tagged proteins from herpes simplex virus, cytomegalovirus, and Epstein-Barr virus. Twenty-four of the 93 proteins with nuclear localization formed subnuclear structures. Twelve of these localized to the nucleolus, and five at least partially localized with promyelocytic leukemia (PML) bodies, which are known to suppress viral lytic infection. In addition, two proteins disrupted Cajal bodies, and 19 of the nuclear proteins significantly decreased the number of PML bodies per cell, including six that were shown to be SUMO-modified. These results have provided the first functional insights into over 120 previously unstudied proteins and suggest that herpesviruses employ multiple strategies for manipulating nuclear bodies that control key cellular processes.

Background. The recovery of motor function following stroke is largely dependent on motor learning–related neuroplasticity. It has been hypothesized that intensive aerobic exercise (AE) training as an antecedent to motor task practice may prime the central nervous system to optimize motor recovery poststroke. Objective. The objective of this study was to determine the differential effects of forced or voluntary AE combined with upper-extremity repetitive task practice (RTP) on the recovery of motor function in adults with stroke. Methods. A combined analysis of 2 preliminary randomized clinical trials was conducted in which participants (n = 40) were randomized into 1 of 3 groups: (1) forced exercise and RTP (FE+RTP), (2) voluntary exercise and RTP (VE+RTP), or (3) time-matched stroke-related education and RTP (Edu+RTP). Participants completed 24 training sessions over 8 weeks. Results. A significant interaction effect was found indicating that improvements in the Fugl-Meyer Assessment (FMA) were greatest for the FE+RTP group ( P = .001). All 3 groups improved significantly on the FMA by a mean of 11, 6, and 9 points for the FE+RTP, VE+RTP, and Edu+RTP groups, respectively. No evidence of a treatment-by-time interaction was observed for Wolf Motor Function Test outcomes; however, those in the FE+RTP group did exhibit significant improvement on the total, gross motor, and fine-motor performance times ( P ≤ .01 for all observations). Conclusions. Results indicate that FE administered prior to RTP enhanced motor skill acquisition greater than VE or stroke-related education. AE, FE in particular, should be considered as an effective antecedent to enhance motor recovery poststroke.