Publications by authors named "Tyler Harris"

32 Publications

Determining the spectral transmittance of photochromic contact lenses.

Cont Lens Anterior Eye 2021 Jan 15:101406. Epub 2021 Jan 15.

ICS Laboratories, 1072 Industrial Pkwy North, Brunswick, OH, 44212, USA. Electronic address:

Purpose: This study evaluates the spectral transmission of photochromic contact lenses.

Method: A custom built photochromic filter transmission testing device (ICS photochromic bench) was developed to measure the spectral transmission of light adaptive filters. The spectral properties of seven contact lenses were measured using the ICS photochromic bench at 23⁰C and 35⁰C in their exposed (darkening) state at time points 0 s, 45 s, 90 s, and 15 min. and their unexposed (fading) state at 45 s, 15 min. and 20 min.. Mixed between and within repeated measures ANOVA (MRM-ANOVAs) and generalized additive modeling (GAMs) were used to compare the effects of temperature and solar exposure time on spectral transmittance of photochromic contact lenses.

Results: The mean (±SD) transmission of photochromic contact lenses in the exposed state were 94.7 ± 0.2, 39.1 ± 1.4, 27.0 ± 0.7 and 14.7 ± 1.0, and 93.7 ± 0.9, 38.8 ± 2.4, 30.2 ± 1.8, and 26.1 ± 1.0 at times 0 s, 45 s, 90 s, and 15 min. at 23⁰C and 35⁰C respectively. The mean (±SD) transmission of photochromic contact lenses in the unexposed state were 18.3 ± 1.5, 71.3 ± 2.4, and 80.2 ± 2.4, and 39.1 ± 1.0, 90.6 ± 1.0 and 91.1 ± 0.9 at times 45 s, 15 min. and 20 min. at 23⁰C and 35⁰C respectively. There was a significant decrease in light transmission as solar exposure time increased (GAM, MRM-ANOVA, p < 0.05). There was a significant effect of temperature and solar exposure time on the photochromic contact lenses (GAM, MRM-ANOVA, p < 0.05). The differences in the light transmitted by the photochromic contact lenses occurred at time 90 s and 15 min (Tukey HSD, at 90 s and 15 min, p < 0.05), where contact lenses at a temperature of 35⁰C showed greater light transmission than that at 23⁰C. There were differences in spectral transmittance based on the temperature of the contact lens. Contact lenses at 35⁰C transmitted more light than at 23⁰C at all unexposed times (MRM-ANOVA, p < 0.05).

Conclusion: Spectral transmission of photochromic contact lenses were successfully measured with the ICS photochromic bench. Temperature appears to influence both the activation and deactivation of photochromic contact lenses such that the higher the temperature, the greater the light transmission.
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http://dx.doi.org/10.1016/j.clae.2021.01.001DOI Listing
January 2021

Augmented Reality Forward Damage Control Procedures for Nonsurgeons: A Feasibility Demonstration.

Mil Med 2020 01;185(Suppl 1):521-525

Womack Army Medical Center, 2817 Reilly Road, Fort Bragg, NC 28310.

Introduction: This article presents an emerging capability to project damage control procedures far forward for situations where evacuation to a formal surgical team is delayed. Specifically, we demonstrate the plausibility of using a wearable augmented reality (AR) telestration device to guide a nonsurgeon through a damage control procedure.

Methods: A stand-alone, low-profile, commercial-off-the-shelf wearable AR display was utilized by a remotely located surgeon to synchronously guide a nonsurgeon through proximal control of the distal external iliac artery on a surgical manikin. The manikin wound pattern was selected to simulate a rapidly exsanguinating junctional hemorrhage not controllable by nonsurgical means.

Results: This capability demonstration displayed successful use of AR technology, telecommunication, and procedural training and guidance in a single test pilot. The assisted physician assistant was able to rapidly control the simulated external iliac artery injury on this model. The telestration system used was commercially available for use with available civilian cell phone, wireless and satellite networks, without the need for dedicated high-speed networks.

Conclusions: A nonsurgeon, using a wearable commercial on-visual-axis telestration system, successfully performed a damage control procedure, demonstrating the plausibility of this approach.
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http://dx.doi.org/10.1093/milmed/usz298DOI Listing
January 2020

Lipoic Acid Decorated Gold Nanoparticles and Their Application in the Detection of Lead Ions.

J Nanomed Nanotechnol 2019 12;10(6). Epub 2019 Dec 12.

Center for Nanotechnology, Department of Natural Sciences, Coppin State University, 2500 W. North Ave, Baltimore, MD, USA.

A simple colorimetric method has been developed for the detection of lead (Pb) in water samples using lipoic acid-functionalized gold nanoparticles. The lipoic acid-functionalized gold nanoparticles are induced to aggregate in the presence of the Pb which results in a change in the color of the functionalized gold nanoparticles. The change in color and the amount of Pb producing the change could be monitored via UV-visible spectrophotometry. A good correlation coefficient of 0.9927 was obtained for the calibration curve of the colorimetric method. The method was applied in the determination of Pb in water samples and the results compared to that of measurement carried out with Atomic Absorption Spectroscopy.
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http://dx.doi.org/10.35248/2157-7439.19.10.539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986728PMC
December 2019

Perceptions of coach doping confrontation efficacy and athlete susceptibility to intentional and inadvertent doping.

Scand J Med Sci Sports 2019 Oct 22;29(10):1647-1654. Epub 2019 Jun 22.

Department of Kinesiology, Michigan State University, East Lansing, Michigan, USA.

Objectives: We tested a conceptually grounded model linking athlete perceptions of strength and conditioning and technical coach doping confrontation efficacy (DCE) with athletes' doping self-regulatory efficacy (SRE), doping moral disengagement (MD), and susceptibility to intentional and inadvertent doping.

Design: Cross-sectional, correlational.

Methods: Participants were high-level athletes (n  = 532; n  = 290) recruited in Australia (n = 261), the UK (n = 300), and the USA (n = 261). All participants completed questionnaires assessing the variables alongside a variant of the randomized response technique to estimate the prevalence of doping.

Results: The estimated prevalence of intentional doping in the sample was 13.9%. Structural equation modeling established: (a) perceptions of technical and strength and conditioning coaches' DCE positively predicted doping SRE; (b) doping SRE negatively predicted doping MD; (c) doping MD positively predicted susceptibility to intentional and inadvertent doping; and (d) the predictive effects of coach perceptions on susceptibility to doping were mediated by doping SRE and doping MD. Multisample analyses demonstrated these predictive effects were invariant between males and females and across the three countries represented.

Conclusions: The findings show the conceptually grounded model to offer extended understanding of how multiple individuals within the athlete support personnel network may influence athlete doping.
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http://dx.doi.org/10.1111/sms.13489DOI Listing
October 2019

Strength in numbers: Crowdsourcing the most relevant literature in pediatric cardiology.

Congenit Heart Dis 2018 Sep 3;13(5):794-798. Epub 2018 Sep 3.

Lillie Frank Abercrombie Section of Cardiology, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas.

Objective: The growing body of medical literature in pediatric cardiology has made it increasingly difficult for individual providers to stay abreast of the most current, meaningful articles to help guide practice. Crowdsourcing represents a collaborative process of obtaining information from a large group of individuals, typically from an online or web-based community, and could serve a potential mechanism to pool individual efforts to combat this issue. This study aimed to utilize crowdsourcing as a novel way to generate a list of the most relevant, current publications in congenital heart disease, utilizing input from an international group of professionals in the field of pediatric cardiology.

Design And Setting: All members of the PediHeartNet Google group, an international email distribution list of medical professionals with an interest in pediatric cardiology, were queried in 2017 to submit literature that they considered to be most relevant to their current practice. A Google Form submission platform was used. The articles were evaluated by a multi-institutional panel of four experts in pediatric cardiology using the Delphi method via an electronic evaluation form until a consensus was reached regarding whether the article merited inclusion in the final list.

Results: In total, 260 articles were submitted by members of the PediHeartNet Google group. Expert review using the Delphi method resulted in a list of 108 articles. The final collection of articles was published on a publicly available educational website.

Conclusions: Crowdsourcing represents a novel approach for generating a high-yield, comprehensive, yet practical list of the most relevant recent publications in pediatric cardiology. The same techniques could be easily applied to any medical subspecialty. By enlisting the input of frontline providers, the value and relevance of such a list will be significant. A web-based platform for publication of the list allows for real-time updates to ensure continued relevance.
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http://dx.doi.org/10.1111/chd.12669DOI Listing
September 2018

Biliary Stenosis and Gastric Outlet Obstruction: Late Complications After Acute Pancreatitis With Pancreatic Duct Disruption.

Pancreas 2018 07;47(6):772-777

Department of Interventional Radiology.

Objectives: Pancreatic duct disruption (PDD) after acute pancreatitis can cause pancreatic collections in the early phase and biliary stenosis (BS) or gastric outlet obstruction (GOO) in the late phase. We aimed to document those late complications after moderate or severe acute pancreatitis.

Methods: Between September 2010 and August 2014, 141 patients showed pancreatic collections on computed tomography. Percutaneous drainage was primarily performed for patients with signs or symptoms of uncontrolled pancreatic juice leakage. Pancreatic duct disruption was defined as persistent amylase-rich drain fluid or a pancreatic duct cut-off on imaging. Clinical course of the patients who developed BS or GOO was investigated.

Results: Among the 141 patients with collections, 33 patients showed PDD in the pancreatic head/neck area. Among them, 9 patients (27%) developed BS 65 days after onset and required stenting for 150 days, and 5 patients (15%) developed GOO 92 days after onset and required gastric decompression and jejunal tube feeding for 147 days (days shown in median). All 33 patients recovered successfully without requiring surgical intervention.

Conclusions: Anatomic proximity of the bile duct or duodenum to the site of PDD and severe inflammation seemed to contribute to the late onset of BS or GOO. Conservative management successfully reversed these complications.
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http://dx.doi.org/10.1097/MPA.0000000000001064DOI Listing
July 2018

Rational Modification of a Metallic Substrate for CVD Growth of Carbon Nanotubes.

Sci Rep 2018 Mar 12;8(1):4349. Epub 2018 Mar 12.

Department of Chemical Engineering, Kansas State University, Manhattan, KS, 66506, USA.

Growth of high quality, dense carbon nanotube (CNT) arrays via catalytic chemical vapor deposition (CCVD) has been largely limited to catalysts supported on amorphous alumina or silica. To overcome the challenge of conducting CNT growth from catalysts supported on conductive substrates, we explored a two-step surface modification that involves ion beam bombardment to create surface porosity and deposition of a thin AlO barrier layer to make the surface basic. To test the efficacy of our approach on a non-oxide support, we focus on modification of 316 stainless steel (SS), a well-known inactive substrate for CNT growth. Our study reveals that ion beam bombardment of SS has the ability to reduce film thickness of the AlO barrier layer required to grow CNTs from Fe catalysts to [Formula: see text] 5 nm, which is within the threshold for the substrate to remain conductive. Additionally, catalysts supported on ion beam-damaged SS with the same AlO thickness show improved particle formation, catalyst stability, and CNT growth efficiency, as well as producing CNTs with higher quality and density. Under optimal reaction conditions, this modification approach can lead to CNT growth on other nontraditional substrates and potentially benefit applications that require CNTs be grown on a conductive substrate.
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http://dx.doi.org/10.1038/s41598-018-22467-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5847581PMC
March 2018

Small molecule adjuvants that suppress both chromosomal and mcr-1 encoded colistin-resistance and amplify colistin efficacy in polymyxin-susceptible bacteria.

Bioorg Med Chem 2017 10 9;25(20):5749-5753. Epub 2017 Sep 9.

Department of Chemistry, North Carolina State University, Raleigh, NC, 27695-8024, USA. Electronic address:

Bacterial resistance to polymyxin antibiotics has taken on a new and more menacing form. Common are genomically-encoded resistance mechanisms to polymyxins, specifically colistin (polymyxin E), however, the plasmid-borne mobile colistin resistance-1 (mcr-1) gene has recently been identified and poses a new threat to global public health. Within six months of initial identification in Chinese swine in November 2015, the first human clinical isolation in the US was reported (Apr. 2016). Herein we report successful reversion of mcr-1-driven colistin resistance in Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia coli with adjuvants we previously reported as modulators of chromosomally-encoded colistin resistance. Further screening of our in-house library of nitrogen-dense heterocycles has identified additional chemical scaffolds that actively attenuate colistin resistance. Ultimately, we present a diverse cohort of adjuvants that both sensitize colistin-resistant and colistin-susceptible bacteria to this antibiotic, thus providing a potential avenue to both reduce colistin dosage and toxicity, and overcome colistin resistance.
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http://dx.doi.org/10.1016/j.bmc.2017.08.055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632226PMC
October 2017

Pediatric heart disease simulation curriculum: Educating the pediatrician.

Congenit Heart Dis 2017 Jul 26;12(4):546-553. Epub 2017 May 26.

Divisions of Cardiology and Critical Care Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Background: Training guidelines state that pediatricians should be able to diagnose, manage, and triage patients with heart disease. Acutely ill cardiac patients present infrequently and with high acuity, yet residents receive less exposure to acute cardiac conditions than previous generations. Trainees must learn to manage these situations despite this gap. Simulation has been used successfully to train learners to provide acute care. We hypothesized that a simulation-based cardiac curriculum would improve residents' ability to manage cardiac patients.

Methods: Pediatric residents completed 4 simulation cases followed by debriefing and a computer presentation reviewing the learning objectives. Subjects returned at 1 month for postintervention cases and again at 4-6 months to measure knowledge retention. Cases were scored by 2 raters using a dichotomous checklist. We used repeated measure ANOVA and effect size to compare groups and intra-class correlation (ICC) to assess inter-rater reliability.

Results: Twenty-five participants were enrolled. Scores were low on pretesting but showed significant improvement (P < .05) in all 4 cases. No decay was noted on late testing. Pre-post effect sizes ranged from 1.1 to 2.1, demonstrating meaningful improvement. Inter-rater reliability (ICC) ranged from 0.61 to 0.93 across cases.

Conclusions: This novel simulation-based curriculum targets a gap in pediatric training and offers an effective way to train pediatricians. We plan to expand this curriculum to new populations of participants and have integrated it into our resident cardiology rotation.
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http://dx.doi.org/10.1111/chd.12483DOI Listing
July 2017

Diagnosis and Diagnostic Modalities in Pediatric Patients with Elevated Troponin.

Pediatr Cardiol 2016 Dec 29;37(8):1469-1474. Epub 2016 Aug 29.

Division of Cardiology, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University School of Medicine, 225 East Chicago Avenue, Chicago, IL, 60611, USA.

Care of adults with coronary artery disease focuses on troponins to rapidly move patients to catheterization. Troponins are increasingly drawn in children, but emergent catheterization may not be indicted. We sought to establish etiologies of troponin elevation and ascertain the yield of diagnostic tests, in this population. Retrospective review of patients from January 1, 2002, to December 31, 2011, who had any elevated troponin during the study period. Patients were excluded for recent cardiac surgery, "significant" congenital heart disease, if they were neonates in the NICU or were on ECMO. Twenty-four patients made up our study group: 17/24 (71 %) had myocarditis or cardiomyopathy. Three had coronary-related diagnoses: 1 ALCAPA and 2 Kawasaki syndrome. The most useful testing for making or confirming the diagnoses included ECG, CXR and ECHO. Fourteen had right heart catheterization which was useful in 10/14. Nine had MRI which was useful in 7/9 (all five cases of suspected myocarditis). Left heart catheterization was completed in 10/24 cases, but in no case made or changed the diagnosis. This study confirms that children with elevated troponins differ from adults. The most common cause is myocarditis or cardiomyopathy, whereas coronary-related ischemia is rare. Diagnosis with ECG, CXR and ECHO is typically adequate. Focused use of right heart catheterization and MRI may be useful. In pediatric patients with elevated troponins, left heart catheterization and coronary angiography should be reserved for a highly selective group, and adult "door-to-balloon time" protocols should not be applied routinely.
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http://dx.doi.org/10.1007/s00246-016-1459-7DOI Listing
December 2016

Discontinuous Pulmonary Artery.

World J Pediatr Congenit Heart Surg 2017 01 22;8(1):106-110. Epub 2016 Jun 22.

1 Divisions of Cardiovascular-Thoracic Surgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.

We describe the diagnosis and surgical repair of a five-month-old infant with a congenital discontinuous right pulmonary artery. Initial echocardiogram failed to show the right pulmonary artery and revealed systemic left pulmonary artery pressure based on the tricuspid regurgitation jet. Computed tomographic angiography confirmed the diagnosis of discontinuous right pulmonary artery. The right pulmonary artery appeared essentially normal in size, and there were no significant aortopulmonary collateral arteries. Using cardiopulmonary bypass and aortic transection, we created an anastomosis between the right and the main pulmonary arteries augmented anteriorly by a pericardial patch. Postoperative lung perfusion scan demonstrated balanced pulmonary blood flow to the lungs. Pulmonary hypertension resolved over three weeks in the postoperative period, an expected outcome in this age-group.
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http://dx.doi.org/10.1177/2150135115618871DOI Listing
January 2017

Glycation Reactivity of a Quorum-Sensing Signaling Molecule.

Angew Chem Int Ed Engl 2016 Mar 17;55(12):4002-6. Epub 2016 Feb 17.

The Skaggs Institute for Chemical Biology and Departments of Chemistry, Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.

Reported herein is that (4S)-4,5-dihydroxy-2,3-pentanedione (DPD) can undergo a previously undocumented non-enzymatic glycation reaction. Incubation of DPD with viral DNA or the antibiotic gramicidin S resulted in significant biochemical alterations. A protein-labeling method was consequently developed that facilitated the identification of unrecognized glycation targets of DPD in a prokaryotic system. These results open new avenues toward tracking and understanding the fate and function of the elusive quorum-sensing signaling molecule.
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http://dx.doi.org/10.1002/anie.201511911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4965832PMC
March 2016

Better Outcomes if Percutaneous Drainage Is Used Early and Proactively in the Course of Necrotizing Pancreatitis.

J Vasc Interv Radiol 2016 Mar 21;27(3):418-25. Epub 2016 Jan 21.

Center for Pancreatic and Liver Disease, St. Luke's Health System, 100 E. Idaho St., Suite 301, Boise, ID 83712.

Purpose: To compare outcomes after percutaneous catheter drainage (PCD) for acute necrotizing pancreatitis versus those in a randomized controlled trial as a reference standard.

Materials And Methods: Between September 2010 and August 2014, CT-guided PCD was the primary treatment for 39 consecutive patients with pancreatic necrosis. The indication for PCD was the clinical finding of uncontrolled pancreatic juice leakage rather than infected necrosis. Subsequent to PCD, the drains were proactively studied with fluoroscopic contrast medium every 3 days to ensure patency and position. Drains were ultimately maneuvered to the site of leakage. These 39 patients were compared with 43 patients from the Pancreatitis, Necrosectomy versus Step-up Approach (PANTER) trial.

Results: The CT severity index was similar between studies (median of 8 in each). Time from onset of acute pancreatitis to PCD was shorter in the present series (median, 23 d vs 30 d). The total number of procedures (PCD and subsequent fluoroscopic drain studies) per patient was greater in the present series (mean, 14 vs 2). More patients in the PANTER trial had organ failure (62% vs 84%), required open or endoscopic necrosectomy (0% vs 60%), and experienced in-hospital mortality (0% vs 19%; P < .05 for all).

Conclusions: Even though patients in the present series had a similar CT severity index as those in the PANTER trial, the former group showed lower incidences of organ failure, need for necrosectomy, and in-hospital mortality. The use of a proactive PCD protocol early, before the development of severe sepsis, appeared to be effective.
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http://dx.doi.org/10.1016/j.jvir.2015.11.054DOI Listing
March 2016

Direct Percutaneous Repair of Left Ventricular Pseudoaneurysm via Transthoracic Deployment of a Ventricular Septal Defect Closure Device.

Tex Heart Inst J 2015 Aug 1;42(4):362-6. Epub 2015 Aug 1.

In this case report, we describe direct percutaneous delivery of a muscular-ventricular-septal-defect occluder device to close a left ventricular pseudoaneurysm. The occluder was positioned and deployed with the aid of concurrent transthoracic ultrasonography, transesophageal echocardiography, and fluoroscopy. In contrast with previously published reports, we describe and illustrate a direct transthoracic route across the pseudoaneurysmal sac, which obviated the need for indirect transfemoral or transapical approaches.
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http://dx.doi.org/10.14503/THIJ-14-4243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4567105PMC
August 2015

Gold nanoparticles to improve HIV drug delivery.

Future Med Chem 2015 ;7(9):1097-107

Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7005, USA.

Background: Antiretroviral therapy (ART) has improved lifespan and quality of life of patients infected with the HIV-1. However, ART has several potential limitations, including the development of drug resistance and suboptimal penetration to selected anatomic compartments. Improving the delivery of antiretroviral molecules could overcome several of the limitations of current ART.

Results & Conclusion: Two to ten nanometer diameter inorganic gold crystals serve as a base scaffold to combine molecules with an array of properties in its surface. We show entry into different cell types, antiviral activity of an HIV integrase inhibitor conjugated in a gold nanoparticle and penetration into the brain in vivo without toxicity. Herein, gold nanoparticles prove to be a promising tool to use in HIV therapy.
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http://dx.doi.org/10.4155/fmc.15.57DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4501014PMC
April 2016

Onchocerca volvulus Molting Inhibitors Identified through Scaffold Hopping.

ACS Infect Dis 2015 May 18;1(5):198-202. Epub 2015 Mar 18.

Departments of Chemistry and Immunology and Microbial Science, The Skaggs Institute for Chemical Biology, and The Worm Institute of Research and Medicine, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.

The anthelmintic closantel has shown promise in abrogating the L3 molting of Onchocerca volvulus, the causative agent of the infectious disease onchocerciasis. In our search for alternative scaffolds, we utilized a fragment replacement/modification approach to generate novel chemotypes with improved chitinase inhibitory properties. Further evaluation of the compounds unveiled the potential of urea-tropolones as potent inhibitors of O. volvulus L3 molting.
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http://dx.doi.org/10.1021/acsinfecdis.5b00017DOI Listing
May 2015

Loneliness and social isolation as risk factors for mortality: a meta-analytic review.

Perspect Psychol Sci 2015 Mar;10(2):227-37

Department of Psychology.

Actual and perceived social isolation are both associated with increased risk for early mortality. In this meta-analytic review, our objective is to establish the overall and relative magnitude of social isolation and loneliness and to examine possible moderators. We conducted a literature search of studies (January 1980 to February 2014) using MEDLINE, CINAHL, PsycINFO, Social Work Abstracts, and Google Scholar. The included studies provided quantitative data on mortality as affected by loneliness, social isolation, or living alone. Across studies in which several possible confounds were statistically controlled for, the weighted average effect sizes were as follows: social isolation odds ratio (OR) = 1.29, loneliness OR = 1.26, and living alone OR = 1.32, corresponding to an average of 29%, 26%, and 32% increased likelihood of mortality, respectively. We found no differences between measures of objective and subjective social isolation. Results remain consistent across gender, length of follow-up, and world region, but initial health status has an influence on the findings. Results also differ across participant age, with social deficits being more predictive of death in samples with an average age younger than 65 years. Overall, the influence of both objective and subjective social isolation on risk for mortality is comparable with well-established risk factors for mortality.
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http://dx.doi.org/10.1177/1745691614568352DOI Listing
March 2015

Disarming Pseudomonas aeruginosa virulence factor LasB by leveraging a Caenorhabditis elegans infection model.

Chem Biol 2015 Apr 16;22(4):483-491. Epub 2015 Apr 16.

The Skaggs Institute for Chemical Biology and Departments of Chemistry and Immunology and the Worm Institute for Research and Medicine (WIRM), La Jolla, CA 92037, USA. Electronic address:

The emergence of antibiotic resistance places a sense of urgency on the development of alternative antibacterial strategies, of which targeting virulence factors has been regarded as a "second generation" antibiotic approach. In the case of Pseudomonas aeruginosa infections, a proteolytic virulence factor, LasB, is one such target. Unfortunately, we and others have not been successful in translating in vitro potency of LasB inhibitors to in vivo efficacy in an animal model. To overcome this obstacle, we now integrate in silico and in vitro identification of the mercaptoacetamide motif as an effective class of LasB inhibitors with full in vivo characterization of mercaptoacetamide prodrugs using Caenorhabditis elegans. We show that one of our mercaptoacetamide prodrugs has a good selectivity profile and high in vivo efficacy, and confirm that LasB is a promising target for the treatment of bacterial infections. In addition, our work highlights that the C. elegans infection model is a user-friendly and cost-effective translational tool for the development of anti-virulence compounds.
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http://dx.doi.org/10.1016/j.chembiol.2015.03.012DOI Listing
April 2015

A percutaneous drainage protocol for severe and moderately severe acute pancreatitis.

Surg Endosc 2015 Nov 29;29(11):3282-91. Epub 2015 Jan 29.

Center for Pancreatic and Liver Disease, St. Luke's Health System, 100 East Idaho Street, Suite 301, Boise, ID, 83712, USA.

Background: According to the revised Atlanta classification, severe and moderately severe acute pancreatitis (AP) includes patients with pancreatic and peripancreatic collections with or without organ failure. These collections suggest the presence of pancreatic juice leakage. The aim of this study was to evaluate the efficacy of a percutaneous catheter drainage (PCD) protocol designed to control leakage and decrease disease severity.

Methods: Among 663 patients with clinical AP, 122 were classified as moderately severe or severe AP (all had collections). The computed tomography severity index (CTSI) score was calculated. The indication for PCD was based on progressive clinical signs and symptoms. Drain patency, position, and need for additional drainage sites were assessed using CT scans and drain studies initially every 3 days using a proactive protocol. Drain fluid was examined for amylase concentration and microbiological culture. Clinicopathological variables for patients with and without PCD were compared. Since there was no mortality, we used prolonged drainage time to measure the success of PCD. Within the group treated with PCD, variables that resulted in prolonged drainage time were analyzed.

Results: PCD was used in 47/122 (39 %) patients of which 33/47 (70 %) had necrosis. PCD cases had a median CTSI of 8 and were classified as moderately severe AP (57 %) and severe AP (43 %). Inhospital mortality was zero. Surgical necrosectomy was not required for patients with necrosis. Independent risk factors for prolonged drainage time were persistent organ failure >48 h (P = 0.001), CTSI 8-10 (P = 0.038), prolonged duration of amylase-rich fluid in drains (P < 0.001), and polymicrobial culture fluid in drains (P = 0.015).

Conclusions: A proactive PCD protocol persistently maintaining drain patency advanced to the site of leak controlled the prolonged amylase in drainage fluid resulting in a mortality rate of zero.
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http://dx.doi.org/10.1007/s00464-015-4077-1DOI Listing
November 2015

Spontaneous spinal epidural abscess in a 21-month-old child.

Am J Emerg Med 2014 Dec 24;32(12):1558.e1-2. Epub 2014 May 24.

1000 Monroe NW, Dept of Emergency Medicine, Grand Rapids, MI 49503, USA. Electronic address:

Spontaneous epidural abscess formation is a rare finding in all populations and even more so in the pediatric population. Its rarity and varied presentations often lead to misdiagnosis. We present a pediatric case in which the diagnosis of spontaneous spinal epidural abscess was missed upon initial presentation and subsequently identified at a later visit to the emergency department. Literature suggests utilizing three simple physical exam findings that may improve the first visit diagnosis of spontaneous epidural abscesses in children. Findings of any two of the following signs should guide the clinician to consider SEA as a possibility prior to discharge: fever, back or neck pain, extremity weakness or inability to walk.
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http://dx.doi.org/10.1016/j.ajem.2014.05.029DOI Listing
December 2014

A platform stratifying a sequestering agent and a pharmacological antagonist as a means to negate botulinum neurotoxicity.

ACS Chem Neurosci 2014 Aug 11;5(8):632-6. Epub 2014 Jul 11.

Departments of Chemistry, Immunology and Microbial Sciences, and The Skaggs Institute for Chemical Biology, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.

Botulinum neurotoxicity is characterized by peripheral neuromuscular blockade/flaccid paralysis that can lead to respiratory failure and ultimately death. Current therapeutic options provide relief in a pre-exposure scenario, but there are no clinically approved postexposure medical countermeasures. Here, we introduce a platform that utilizes a combination of a toxin sequestering agent and a pharmacological antagonist to ablate botulinum neurotoxicity in a well-defined mouse lethality assay. The platform was constructed to allow for ready exchange of sequestering agent and/or pharmacological antagonist for therapeutic optimization. As such, we attempted to improve upon the pharmacological antagonist, a potassium channel blocker, 3,4-diaminopyridine, through a prodrug approach; thus, a complete kinetic decomposition pathway is described. These experiments provide the first proof-of-principle that a synergistic combination strategy can be used to reduce toxin burden in the peripheral using a sequestering antibody, while restoring muscle action via a pharmacological small molecule antagonist.
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http://dx.doi.org/10.1021/cn500135hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4140587PMC
August 2014

Small molecule downregulation of PmrAB reverses lipid A modification and breaks colistin resistance.

ACS Chem Biol 2014 Jan 28;9(1):122-7. Epub 2013 Oct 28.

Department of Chemistry, North Carolina State University , Raleigh, North Carolina 27695, United States.

Infections caused by multi-drug resistant bacteria, particularly Gram-negative bacteria, are an ever-increasing problem. While the development of new antibiotics remains one option in the fight against bacteria that have become resistant to currently available antibiotics, an attractive alternative is the development of adjuvant therapeutics that restore the efficacy of existing antibiotics. We report a small molecule adjuvant that suppresses colistin resistance in multidrug resistant Acinetobacter baumannii and Klebsiella pneumoniae by interfering with the expression of a two-component system. The compound downregulates the pmrCAB operon and reverses phosphoethanolamine modification of lipid A responsible for colistin resistance. Furthermore, colistin-susceptible and colistin-resistant bacteria do not evolve resistance to combination treatment. This represents the first definitive example of a compound that breaks antibiotic resistance by directly modulating two-component system activity.
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http://dx.doi.org/10.1021/cb400490kDOI Listing
January 2014

Visceral blood flow modulation: potential therapy for morbid obesity.

Cardiovasc Intervent Radiol 2013 Jun 5;36(3):803-8. Epub 2013 Feb 5.

Department of Vascular and Interventional Radiology, University of California, Los Angeles, 757 Westwood Blvd., Suite 1638, Los Angeles, CA 90095-7437, USA.

We present this preliminary investigation into the safety and feasibility of endovascular therapy for morbid obesity in a swine model. A flow-limiting, balloon-expandable covered stent was placed in the superior mesenteric artery of three Yorkshire swine after femoral arterial cutdown. The pigs were monitored for between 15 and 51 days after the procedure and then killed, with weights obtained at 2-week increments. In the two pigs in which the stent was flow limiting, a reduced rate of weight gain (0.42 and 0.53 kg/day) was observed relative to the third pig (0.69 kg/day), associated with temporary food aversion and signs of mesenteric ischemia in one pig.
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http://dx.doi.org/10.1007/s00270-013-0560-zDOI Listing
June 2013

Potent small-molecule suppression of oxacillin resistance in methicillin-resistant Staphylococcus aureus.

Angew Chem Int Ed Engl 2012 Nov 9;51(45):11254-7. Epub 2012 Oct 9.

Department of Chemistry, North Carolina State University, Raleigh, 27695, USA.

Shields down! Adjuvant molecules that have the ability to restore the susceptibility of multi-drug-resistant bacteria, such as MRSA, to clinically available antibiotics are a promising alternative to the development of novel antimicrobials. Pictured is a potent small molecule (1) that, at sub-minimum inhibitory concentration (sub-MIC) levels, lowers the MIC of oxacillin (2) against a number of MRSA strains by up to 512-fold.
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http://dx.doi.org/10.1002/anie.201206911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829614PMC
November 2012

Overcoming today's PACS/RIS challenges.

Health Manag Technol 2012 May;33(5):16-7

Merge Healthcare.

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May 2012

Patients' perspective about risks and benefits of treatment for peripheral arterial disease.

J Vasc Interv Radiol 2011 Dec;22(12):1657-61

Rhode Island Hospital, Brown University, Providence, RI, USA.

Purpose: To report the results of a standard gamble-type survey conducted to explore patients' heuristics in regard to therapy for peripheral arterial disease (PAD).

Materials And Methods: Patients presenting to a vascular and interventional radiology practice because of suspected PAD were asked to indicate their threshold for risk of amputation during a curative procedure for intermittent claudication (IC) and for risk of death from a curative medication for critical limb ischemia (CLI). Possible relationships of risk threshold with age, gender, ankle-brachial index (ABI), and functional claudication distance were assessed with univariate statistics followed by multivariable generalized linear mixed models of risk acceptance at various risk levels.

Results: Study participants were 20 patients (40% women), with median age of 64 years, functional claudication distance of 1 block, and ABI of 0.72. In the IC scenario, up to 1% risk of above-knee amputation was found to be the median risk acceptable to patients for undergoing a curative procedure. In the CLI scenario, the median risk acceptance for mortality from a curative medication was up to 1%. The multivariable model for the IC scenario revealed significantly greater acceptance of risk at a given level among older patients and women. No significant predictor was delineated by the multivariable model for the CLI scenario.

Conclusions: Overall, patients have a low threshold for complications of PAD therapy, consistent with endovascular but not with open surgical strategies. However, considerable variation in preferences underlines the value of individualized treatment strategies.
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http://dx.doi.org/10.1016/j.jvir.2011.08.027DOI Listing
December 2011

Utilization of lower extremity arterial disease diagnostic and revascularization procedures in Medicare beneficiaries 2000-2007.

AJR Am J Roentgenol 2011 Aug;197(2):W314-7

Department of Diagnostic Imaging, Rhode Island Hospital/Brown University, Providence, RI, USA.

Objective: The recent escalation in lower extremity revascularization procedures suggests a concomitant increase in peripheral arterial disease (PAD) screening. We hypothesized that self-referring physicians would show the greatest growth in noninvasive physiologic testing for PAD and similar trends for revascularization procedures. We compared utilization rates for self-referring specialties (vascular surgery, interventional radiology, and cardiology) with the utilization rate for a referral-based specialty (diagnostic radiology), assuming the latter to be "basal"--that is, responsive only to changes in demographics and medical knowledge.

Materials And Methods: We analyzed 100% procedure-specific claims for services provided to Medicare Part B beneficiaries during 6 years over an 8-year span (2000-2007). We extracted all Current Procedural Terminology codes for lower extremity vascular noninvasive physiologic studies, peripheral arterial stent placement, and transluminal angioplasty. Utilization volumes were adjusted per 100,000 beneficiaries. Compound annual growth rates were calculated.

Results: Utilization of both noninvasive physiologic and revascularization services increased steadily over the study period. Growth rates of diagnostic services provided by interventional radiologists (7%) and vascular surgeons (8%) were slightly higher than the basal rate (7%), with cardiologists (14%) at the top of the list. For revascularization procedures, vascular surgery showed the greatest growth (28%), a rate more than twice that of cardiology (13%); radiology experienced a decrease in volumes (-2%).

Conclusion: Self-referring specialists are screening large volumes of Medicare beneficiaries for lower extremity PAD at an accelerated rate compared with testing done by those who do not self-refer. Similar trends exist for endovascular interventions.
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http://dx.doi.org/10.2214/AJR.10.6132DOI Listing
August 2011

A facile synthesis of 1,5-disubstituted-2-aminoimidazoles: antibiotic activity of a first generation library.

Bioorg Med Chem Lett 2011 Aug 15;21(15):4516-9. Epub 2011 Jun 15.

Department of Chemistry, North Carolina State University, Raleigh, NC 27695, USA.

An efficient synthetic route to 1,5-disubstituted 2-aminoimidazoles from readily available amino acids and aldehydes has been developed. A library of simple analogues was synthesized and several compounds were shown to exhibit notable antibiotic activity against a variety of bacterial strains including multi-drug resistant isolates.
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http://dx.doi.org/10.1016/j.bmcl.2011.05.123DOI Listing
August 2011

Case 168: rhabdoid predisposition syndrome--familial cancer syndromes in children.

Radiology 2011 Apr;259(1):298-302

Department of Diagnostic Imaging, Brown University School of Medicine, Rhode Island Hospital, 593 Eddy St, Providence, RI 02903, USA.

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http://dx.doi.org/10.1148/radiol.10092219DOI Listing
April 2011

Spontaneous pneumomediastinum: an uncommon cause of chest pain.

Med Health R I 2010 Sep;93(9):287-8

The Warren Alpert Medical School of Brown University, Rhode Island, USA.

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September 2010