Compensatory Muscle Activation During Unstable Overhead Squat Using a Water-filled Training Tube.

Glass, SC, and Albert, RW. Compensatory muscle activation during unstable overhead squat using a water-filled training tube. J Strength Cond Res 32(5): 1230-1237, 2018-The purpose of this study was to assess compensatory muscle activation of core and support muscle during an overhead squat using a water-filled training tube. Eleven experienced weightlifting (age = 20.10 ± 0.99, mass 89.17 ± 6.88 kg) men completed 3, 30-second trials of an overhead squat using an 11.4 kg tube that was partially filled with water. A central valve allowed 3 conditions of water movement: 50% open, 100% open, and a stable(S), closed valve condition. Subjects completed 8-10 repetitions within each condition. Electromyographic (EMG) electrodes were placed over the belly of the vastus lateralis, deltoid, rectus abdominus, and paraspinal muscles and recorded during concentric and eccentric (ECC) phases. Integrated EMG were computed and converted to percent maximal voluntary contraction (%MVC). Compensatory activation was assessed using the natural log of the coefficient of variation of %MVC across repetitions. A 1-way repeated-measures analysis of variance across (phase, condition) was used. Significant compensatory muscle activation was seen in the deltoid muscle during ECC (100% open = 3.60 ± 0.50 > stable LogCV = 3.06 ± 0.45). In addition, paraspinal muscle activity was also more variable during the ECC phase (50% open LogCv = 3.28 ± 0.26 > stable = 2.77 ± 0.67). We conclude that the water-filled training tube induces compensatory muscle activation in the deltoid and paraspinal muscles during the ECC phase of the overhead squat.

A novel high-throughput cell-based assay aimed at identifying inhibitors of DNA metabolism in bacteria.

Bacterial biosensor strains can be useful tools for the discovery and characterization of antibacterial compounds. A plasmid-based reporter vector containing a transcriptional fusion between the recA promoter and green fluorescence protein gene was introduced into an Escherichia coli ΔtolC strain to create a biosensor strain that selectively senses inhibitors of DNA metabolism via the SOS response. The strain was used to develop a high-throughput assay to identify new inhibitors of DNA metabolism. Screening of the AstraZeneca compound library with this strain identified known inhibitors of DNA metabolism, as well as novel chemotypes. The cellular target of one novel series was elucidated as DNA gyrase through genetic characterization of laboratory-generated resistant mutants followed by 50% inhibitory concentration measurements in a DNA gyrase activity assay. These studies validated the use of this antibiotic biosensor strain to identify novel selective inhibitors of DNA metabolism by high-throughput screening.

Selective inhibitors of bacterial t-RNA-(N(1)G37) methyltransferase (TrmD) that demonstrate novel ordering of the lid domain.

The tRNA-(N(1)G37) methyltransferase (TrmD) is essential for growth and highly conserved in both Gram-positive and Gram-negative bacterial pathogens. Additionally, TrmD is very distinct from its human orthologue TRM5 and thus is a suitable target for the design of novel antibacterials. Screening of a collection of compound fragments using Haemophilus influenzae TrmD identified inhibitory, fused thieno-pyrimidones that were competitive with S-adenosylmethionine (SAM), the physiological methyl donor substrate. Guided by X-ray cocrystal structures, fragment 1 was elaborated into a nanomolar inhibitor of a broad range of Gram-negative TrmD isozymes. These compounds demonstrated no activity against representative human SAM utilizing enzymes, PRMT1 and SET7/9. This is the first report of selective, nanomolar inhibitors of TrmD with demonstrated ability to order the TrmD lid in the absence of tRNA.

Inhibitors of the acetyltransferase domain of N-acetylglucosamine-1-phosphate-uridylyltransferase/glucosamine-1-phosphate-acetyltransferase (GlmU). Part 2: Optimization of physical properties leading to antibacterial aryl sulfonamides.

A previously described aryl sulfonamide series, originally found through HTS, targets GlmU, a bifunctional essential enzyme involved in bacterial cell wall synthesis. Using structure-guided design, the potency of enzyme inhibition was increased in multiple isozymes from different bacterial species. Unsuitable physical properties (low LogD and high molecular weight) of those compounds prevented them from entering the cytoplasm of bacteria and inhibiting cell growth. Further modifications described herein led to compounds that possessed antibacterial activity, which was shown to occur through inhibition of GlmU. The left-hand side amide and the right-hand side sulfonamides were modified such that enzyme inhibitory activity was maintained (IC(50) <0.1 µM against GlmU isozymes from Gram-negative organisms), and the lipophilicity was increased giving compounds with LogD -1 to 3. Antibacterial activity in an efflux-pump deficient mutant of Haemophilus influenzae resulted for compounds such as 13.

Graphical user interface simplifies infusion pump programming and enhances the ability to detect pump-related faults.

BACKGROUND: Drug administration errors are frequent and are often associated with the misuse of IV infusion pumps. One source of these errors may be the infusion pump's user interface. METHODS: We used failure modes-and-effects analyses to identify programming errors and to guide the design of a new syringe pump user interface. We designed the new user interface to clearly show the pump's operating state simultaneously in more than 1 monitoring location. We evaluated anesthesia residents in laboratory and simulated environments on programming accuracy and error detection between the new user interface and the user interface of a commercially available infusion pump. RESULTS: With the new user interface, we observed the number of programming errors reduced by 81%, the number of keystrokes per task reduced from 9.2 ± 5.0 to 7.5 ± 5.5 (mean ± SD), the time required per task reduced from 18.1 ± 14.1 seconds to 10.9 ± 9.5 seconds and significantly less perceived workload. Residents detected 38 of 70 (54%) of the events with the new user interface and 37 of 70 (53%) with the existing user interface, despite no experience with the new user interface and extensive experience with the existing interface. CONCLUSIONS: The number of programming errors and workload were reduced partly because it took less time and fewer keystrokes to program the pump when using the new user interface. Despite minimal training, residents quickly identified preexisting infusion pump problems with the new user interface. Intuitive and easy-to-program infusion pump interfaces may reduce drug administration errors and infusion pump-related adverse events.

Evaluation of an integrated graphical display to promote acute change detection in ICU patients.

OBJECTIVE: The purpose of this study was to evaluate ICU nurses' ability to detect patient change using an integrated graphical information display (IGID) versus a conventional tabular ICU patient information display (i.e. electronic chart). DESIGN: Using participants from two different sites, we conducted a repeated measures simulator-based experiment to assess ICU nurses' ability to detect abnormal patient variables using a novel IGID versus a conventional tabular information display. Patient scenarios and display presentations were fully counterbalanced. MEASUREMENTS: We measured percent correct detection of abnormal patient variables, nurses' perceived workload (NASA-TLX), and display usability ratings. RESULTS: 32 ICU nurses (87% female, median age of 29 years, and median ICU experience of 2.5 years) using the IGID detected more abnormal variables compared to the tabular display [F(1, 119)=13.0, p<0.05]. There was a significant main effect of site [F(1, 119)=14.2], with development site participants doing better. There were no significant differences in nurses' perceived workload. The IGID display was rated as more usable than the conventional display [F(1, 60)=31.7]. CONCLUSION: Overall, nurses reported more important physiological information with the novel IGID than tabular display. Moreover, the finding of site differences may reflect local influences in work practice and involvement in iterative display design methodology. Information displays developed using user-centered design should accommodate the full diversity of the intended user population across use sites.

Inhibitors of acetyltransferase domain of N-acetylglucosamine-1-phosphate-uridyltransferase/glucosamine-1-phosphate-acetyltransferase (GlmU). Part 1: Hit to lead evaluation of a novel arylsulfonamide series.

A novel arylsulfonamide-containing series of compounds represented by 1, discovered by highthroughput screening, inhibit the acetyltransferase domain of N-acetylglucosamine-1-phosphate-uridyltransferase/glucosamine-1-phosphate-acetyltransferase (GlmU). X-ray structure determination confirmed that inhibitor binds at the site occupied by acetyl-CoA, indicating that series is competitive with this substrate. This letter documents our early hit-to-lead evaluation of the chemical series and some of the findings that led to improvement in in-vitro potency against Gram-negative and Gram-positive bacterial isozymes, exemplified by compound 40.

Discovery of bacterial NAD⁺-dependent DNA ligase inhibitors: improvements in clearance of adenosine series.

Optimization of clearance of adenosine inhibitors of bacterial NAD(+)-dependent DNA ligase is discussed. To reduce Cytochrome P-450-mediated metabolic clearance, many strategies were explored; however, most modifications resulted in compounds with reduced antibacterial activity and/or unchanged total clearance. The alkyl side chains of the 2-cycloalkoxyadenosines were fluorinated, and compounds with moderate antibacterial activity and favorable pharmacokinetic properties in rat and dog were identified.

Discovery of bacterial NAD+-dependent DNA ligase inhibitors: optimization of antibacterial activity.

Optimization of adenosine analog inhibitors of bacterial NAD(+)-dependent DNA ligase is discussed. Antibacterial activity against Streptococcus pneumoniae and Staphylococcus aureus was improved by modification of the 2-position substituent on the adenine ring and 3'- and 5'-substituents on the ribose. Compounds with logD values 1.5-2.5 maximized potency and maintained drug-like physical properties.

Graphical arterial blood gas visualization tool supports rapid and accurate data interpretation.

A visualization tool that integrates numeric information from an arterial blood gas report with novel graphics was designed for the purpose of promoting rapid and accurate interpretation of acid-base data. A study compared data interpretation performance when arterial blood gas results were presented in a traditional numerical list versus the graphical visualization tool. Critical-care nurses (n = 15) and nursing students (n = 15) were significantly more accurate identifying acid-base states and assessing trends in acid-base data when using the graphical visualization tool. Critical-care nurses and nursing students using traditional numerical data had an average accuracy of 69% and 74%, respectively. Using the visualization tool, average accuracy improved to 83% for critical-care nurses and 93% for nursing students. Analysis of response times demonstrated that the visualization tool might help nurses overcome the "speed/accuracy trade-off" during high-stress situations when rapid decisions must be rendered. Perceived mental workload was significantly reduced for nursing students when they used the graphical visualization tool. In this study, the effects of implementing the graphical visualization were greater for nursing students than for critical-care nurses, which may indicate that the experienced nurses needed more training and use of the new technology prior to testing to show similar gains. Results of the objective and subjective evaluations support the integration of this graphical visualization tool into clinical environments that require accurate and timely interpretation of arterial blood gas data.

Graphical arterial blood gas visualization tool supports rapid and accurate data interpretation.

A visualization tool that integrates numeric information from an arterial blood gas report with novel graphics was designed for the purpose of promoting rapid and accurate interpretation of acid-base data. A study compared data interpretation performance when arterial blood gas results were presented in a traditional numerical list versus the graphical visualization tool. Critical-care nurses (n = 15) and nursing students (n = 15) were significantly more accurate identifying acid-base states and assessing trends in acid-base data when using the graphical visualization tool. Critical-care nurses and nursing students using traditional numerical data had an average accuracy of 69% and 74%, respectively. Using the visualization tool, average accuracy improved to 83% for critical-care nurses and 93% for nursing students. Analysis of response times demonstrated that the visualization tool might help nurses overcome the "speed/accuracy trade-off" during high-stress situations when rapid decisions must be rendered. Perceived mental workload was significantly reduced for nursing students when they used the graphical visualization tool. In this study, the effects of implementing the graphical visualization were greater for nursing students than for critical-care nurses, which may indicate that the experienced nurses needed more training and use of the new technology prior to testing to show similar gains. Results of the objective and subjective evaluations support the integration of this graphical visualization tool into clinical environments that require accurate and timely interpretation of arterial blood gas data.

Response surface model predictions of emergence and response to pain in the recovery room: An evaluation of patients emerging from an isoflurane and fentanyl anesthetic.

INTRODUCTION: Sevoflurane-remifentanil interaction models that predict responsiveness and response to painful stimuli have been evaluated in patients undergoing elective surgery. Preliminary evaluations of model predictions were found to be consistent with observations in patients anesthetized with sevoflurane, remifentanil, and fentanyl. This study explored the feasibility of adapting the predictions of sevoflurane-remifentanil interaction models to an isoflurane-fentanyl anesthetic. We hypothesized that model predictions adapted for isoflurane and fentanyl are consistent with observed patient responses and are similar to the predictions observed in our previous work with sevoflurane-remifentanil/fentanyl anesthetics. METHODS: Twenty-five patients scheduled for elective surgery received a fentanyl-isoflurane anesthetic. Model predictions of unresponsiveness were recorded at emergence, and predictions of a response to noxious stimulus were recorded when patients first required analgesics in the recovery room. Model predictions were compared with observations with graphical and temporal analyses. Results were also compared with our previous predictions after the administration of a sevoflurane-remifentanil/fentanyl anesthetic. RESULTS: Although patients were anesthetized, model predictions indicated a high likelihood that patients would be unresponsive (> or = 99%). After the termination of the anesthetic, model predictions of responsiveness well described the actual fraction of patients observed to be responsive during emergence. Half of the patients woke within 2 min of the 50% model-predicted probability of unresponsiveness; 70% woke within 4 min. Similarly, predictions of a response to a noxious stimulus were consistent with the number of patients who required fentanyl in the recovery room. Model predictions after the administration of an isoflurane-fentanyl anesthetic were similar to model predictions after a sevoflurane-remifentanil/fentanyl anesthetic. DISCUSSION: The results confirmed our study hypothesis; model predictions for unresponsiveness and no response to painful stimuli, adapted to isoflurane-fentanyl were consistent with observations. These results were similar to our previous study comparing model predictions and patient observations after a sevoflurane-remifentanil/fentanyl anesthetic.

A simulation-based evaluation of a graphic cardiovascular display.

INTRODUCTION: A graphic presentation of complex information can facilitate early detection and management of adverse events. Prior work found that graphical presentation of selected cardiovascular variables led to earlier detection of a simulated ischemic event. Based on these findings, a second evaluation explored the utility of a graphical cardiovascular display (GCD) in a variety of simulated adverse cardiopulmonary events for two different display configurations. In this evaluation, we revised the GCD to present hemodynamic variables with or without a pulmonary artery catheter. Our hypotheses were that the revised GCD would improve detection of adverse cardiopulmonary events and add no additional perceived workload. METHODS: Sixteen anesthesiologists and anesthesia residents were enrolled in a simulation-based evaluation of the GCD. Participants were randomly split into two groups balanced for expertise and asked to manage six simulated adverse cardiopulmonary events. The GCD was present in half of the simulations, balanced across scenarios and groups. Participants' verbalizations and actions during each scenario were recorded and transcribed. Transcripts of treatment interventions were subsequently rated by two blinded expert anesthesiologists. Perceived workload, time to detection, and proper treatment of the adverse event were compared between groups. RESULTS: Experts ranked anesthesiologists using the GCD as being more effective overall and individually in three of six scenarios. Use of the GCD was demonstrated to influence the time to detection and the time to treatment of some critical events. There were no workload differences between display groups. DISCUSSION: Treatment intervention by participants using the GCD was rated superior by two blinded experts. The presence of the GCD resulted in a modest improvement in the time to detect myocardial ischemia and increased pulmonary capillary wedge pressure. The GCD may be a useful adjunct to monitor patients during adverse cardiopulmonary events.

The evaluation of a pulmonary display to detect adverse respiratory events using high resolution human simulator.

OBJECTIVE: Authors developed a picture-graphics display for pulmonary function to present typical respiratory data used in perioperative and intensive care environments. The display utilizes color, shape and emergent alerting to highlight abnormal pulmonary physiology. The display serves as an adjunct to traditional operating room displays and monitors. DESIGN: To evaluate the prototype, nineteen clinician volunteers each managed four adverse respiratory events and one normal event using a high-resolution patient simulator which included the new displays (intervention subjects) and traditional displays (control subjects). Between-group comparisons included (i) time to diagnosis and treatment for each adverse respiratory event; (ii) the number of unnecessary treatments during the normal scenario; and (iii) self-reported workload estimates while managing study events. MEASUREMENTS: Two expert anesthesiologists reviewed video-taped transcriptions of the volunteers to determine time to treat and time to diagnosis. Time values were then compared between groups using a Mann-Whitney-U Test. Estimated workload for both groups was assessed using the NASA-TLX and compared between groups using an ANOVA. P-values < 0.05 were considered significant. RESULTS: Clinician volunteers detected and treated obstructed endotracheal tubes and intrinsic PEEP problems faster with graphical rather than conventional displays (p < 0.05). During the normal scenario simulation, 3 clinicians using the graphical display, and 5 clinicians using the conventional display gave unnecessary treatments. Clinician-volunteers reported significantly lower subjective workloads using the graphical display for the obstructed endotracheal tube scenario (p < 0.001) and the intrinsic PEEP scenario (p < 0.03). CONCLUSION: Authors conclude that the graphical pulmonary display may serve as a useful adjunct to traditional displays in identifying adverse respiratory events.

The beat goes on: rhythmic modulation of cortical potentials by imagined tapping.

A frequency analysis was used to tag cortical activity from imagined rhythmic movements. Participants synchronized overt and imagined taps with brief visual stimuli presented at a constant rate, alternating between left and right index fingers. Brain potentials were recorded from across the scalp and topographic maps made of their power at the alternation frequency between left and right taps. Two prominent power foci occurred in each hemisphere for both overt and imagined taps, one over sensorimotor cortex and the other over posterior parietal cortex, with homologous foci in opposite hemispheres arising from oscillations 180 degrees out of phase. These findings demonstrate temporal isomorphism at a neural level between overt and imagined movements and illustrate a new approach to studying covert actions.

Development and evaluation of a graphical anesthesia drug display.

BACKGROUND: Usable real-time displays of intravenous anesthetic concentrations and effects could significantly enhance intraoperative clinical decision-making. Pharmacokinetic models are available to estimate past, present, and future drug effect-site concentrations, and pharmacodynamic models are available to predict the drug's associated physiologic effects. METHODS: An interdisciplinary research team (bioengineering, architecture, anesthesiology, computer engineering, and cognitive psychology) developed a graphic display that presents the real-time effect-site concentrations, normalized to the drugs' EC(95), of intravenous drugs. Graphical metaphors were created to show the drugs' pharmacodynamics. To evaluate the effect of the display on the management of total intravenous anesthesia, 15 anesthesiologists participated in a computer-based simulation study. The participants cared for patients during two experimental conditions: with and without the drug display. RESULTS: With the drug display, clinicians administered more bolus doses of remifentanil during anesthesia maintenance. There was a significantly lower variation in the predicted effect-site concentrations for remifentanil and propofol, and effect-site concentrations were maintained closer to the drugs' EC(95). There was no significant difference in the simulated patient heart rate and blood pressure with respect to experimental condition. The perceived performance for the participants was increased with the drug display, whereas mental demand, effort, and frustration level were reduced. In a post-simulation questionnaire, participants rated the display to be a useful addition to anesthesia monitoring. CONCLUSIONS: The drug display altered simulated clinical practice. These results, which will inform the next iteration of designs and evaluations, suggest promise for this approach to drug data visualization.