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1.
Faraday Discuss ; 2024 May 20.
Article in English | MEDLINE | ID: mdl-38766898

ABSTRACT

In bimolecular collisions between open-shell radicals and increasingly-larger alkanes, the relative impact configurations open the possibility of reactive and nonreactive outcomes that are isomer specific. To model the interaction potential between molecular scattering partners, observables are needed from experiments that can quantify both the initial molecular orientations and internal energies on multidimensional potential energy surfaces. Recent work by our group demonstrated that upon infrared (IR) excitation, the dynamics of the nitric oxide-methane collision complex (NO-CH4) are dependent on the initial monomer geometries, as small changes in configuration substantially affect the energies, electronic couplings, and predissociation pathways due to the Jahn-Teller effect. This study focuses on the isomer-specific scattering mechanisms between NO and ethane (C2H6), encoded in the spectroscopic and dynamical signatures of the NO-C2H6 collision complex. IR action spectroscopy with 1 + 1 resonance-enhanced multiphoton ionization of NO products was employed to characterize the fundamental CH stretch transitions of NO-C2H6, as well as to initiate the nonreactive decay mechanisms of the complex. Furthermore, velocity map imaging (VMI) was utilized to explore the dynamics prior to and following IR excitation of NO-C2H6, imprinted on the NO photoproducts. This work compares the dynamics from NO-C2H6 and NO-CH4 vibrational predissociation, in which substantial differences are observed in the energy exchange mechanisms during the evolution of the collision complexes to products.

2.
Phys Rev Lett ; 132(15): 156001, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38682961

ABSTRACT

We have studied the power dependence of superfluid Helmholtz resonators in flat (750 and 1800 nm) rectangular channels. In the A phase of superfluid ^{3}He, we observe a nonlinear response for velocities larger than a critical value. The small size of the channels stabilizes a static uniform texture that eliminates dissipative processes produced by changes in the texture. For such a static texture, the lowest velocity dissipative process is due to the pumping of surface bound states into the bulk liquid. We show that the temperature dependence of the critical velocity observed in our devices is consistent with this surface-state dissipation. Characterization of the force-velocity curves of our devices may provide a platform for studying the physics of exotic surface bound states in superfluid ^{3}He.

3.
J Am Coll Surg ; 238(5): 874-879, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38258825

ABSTRACT

BACKGROUND: Human error is impossible to eliminate, particularly in systems as complex as healthcare. The extent to which judgment errors in particular impact surgical patient care or lead to harm is unclear. STUDY DESIGN: The American College of Surgeons NSQIP (2018) procedures from a single institution with 30-day morbidity or mortality were examined. Medical records were reviewed and evaluated for judgment errors. Preoperative variables associated with judgment errors were examined using logistic regression. RESULTS: Of the surgical patients who experienced a morbidity or mortality, 18% (31 of 170) experienced an error in judgment during their hospitalization. Patients with hepatobiliary procedure (odds ratio [OR] 5.4 [95% CI 1.23 to 32.75], p = 0.002), insulin-dependent diabetes (OR 4.8 [95% CI 1.2 to 18.8], p = 0.025), severe COPD (OR 6.0 [95% CI 1.6 to 22.1], p = 0.007), or with infected wounds (OR 8.2 [95% CI 2.6 to 25.8], p < 0.001) were at increased risk for judgment errors. CONCLUSIONS: Specific procedure types and patients with certain preoperative variables had higher risk for judgment errors during their hospitalization. Errors in judgment adversely impacted the outcomes of surgical patients who experienced morbidity or mortality in this cohort. Preventing or mitigating errors and closely monitoring patients after an error in judgment is prudent and may improve surgical safety.


Subject(s)
Hospitalization , Judgment , Humans , Risk Factors , Morbidity , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control
4.
J Phys Chem A ; 127(50): 10540-10554, 2023 Dec 21.
Article in English | MEDLINE | ID: mdl-38085923

ABSTRACT

The molecular chromophores within brown carbon (BrC) aerosols absorb solar radiation at visible and near-ultraviolet wavelengths. This contributes to the overall warming of the troposphere and the photochemical aging of aerosols. In this investigation, we combine a suite of experimental and theoretical methods to reveal the conformation-specific ultraviolet and infrared spectroscopy of 2-phenylpyrrole (2PhPy)─an extended π-conjugated pyrrole derivative and a model BrC chromophore─along with its water microsolvated molecular complexes (2PhPy:nH2O, n = 1-3). Using resonant two-photon ionization and double-resonance holeburning techniques alongside MP3 (ground state) and ADC(3) (excited state) torsional potential energy surfaces and discrete variable representation simulations, we characterized the ultraviolet spectra of 2PhPy and 2PhPy:1H2O. This analysis revealed evidence for Herzberg-Teller vibronic coupling along the CH wagging and NH stretching coordinates of the aromatic rings. Conformation-specific infrared spectroscopy revealed extended hydrogen-bonding networks of the 2PhPy:nH2O complexes. Upon stepwise addition of H2O solvation, the nearest H2O acceptor forms a strong, noncovalent interaction with the pyrrole NH donor, while the second and third H2O partners interface with the phenyl and pyrrole aromatic rings through growing van der Waals π/H atom stabilization. A local-mode Hamiltonian approach was employed for comparison with the experimental spectra, thus identifying the vibrational spectral signatures to specific 2PhPy:nH2O oscillators.

5.
J Phys Chem A ; 127(24): 5171-5182, 2023 Jun 22.
Article in English | MEDLINE | ID: mdl-37285367

ABSTRACT

Bimolecular collision outcomes sensitively depend on the chemical functionality and relative orientations of the colliding partners that define the accessible reactive and nonreactive pathways. Accurate predictions from multidimensional potential energy surfaces demand a full characterization of the available mechanisms. Therefore, there is a need for experimental benchmarks to control and characterize the collision conditions with spectroscopic accuracy to accelerate the predictive modeling of chemical reactivity. To this end, the bimolecular collision outcomes can be investigated systematically by preparing reactants in the entrance channel prior to reaction. Herein, we investigate the vibrational spectroscopy and infrared-driven dynamics of the bimolecular collision complex between nitric oxide and methane (NO-CH4). We recorded the vibrational spectroscopy of NO-CH4 in the CH4 asymmetric stretching region using resonant ion-depletion infrared spectroscopy and infrared action spectroscopy, thus revealing a significantly broad spectrum centered at 3030 cm-1 that extends over 50 cm-1. The asymmetric CH stretch feature of NO-CH4 is explained by CH4 internal rotation and attributed to transitions involving three different nuclear spin isomers of CH4. The vibrational spectra also show extensive homogeneous broadening due to the ultrafast vibrational predissociation of NO-CH4. Additionally, we combine infrared activation of NO-CH4 with velocity map imaging of NO (X2Π, ν″ = 0, J″, Fn, Λ) products to develop a molecular-level understanding of the nonreactive collisions of NO with CH4. The anisotropy of the ion image features is largely determined by the probed rotational quantum number of NO (J″) products. For a subset of NO fragments, the ion images and total kinetic energy release (TKER) distributions show an anisotropic component at low relative translation (∼225 cm-1) indicating a prompt dissociation mechanism. However, for other detected NO products, the ion images and TKER distributions are bimodal, in which the anisotropic component is accompanied by an isotropic feature at high relative translation (∼1400 cm-1) signifying a slow dissociation pathway. In addition to the predissociation dynamics following vibrational excitation, the Jahn-Teller dynamics prior to infrared activation need to be considered to fully describe the product spin-orbit distributions. Therefore, we correlate the Jahn-Teller mechanisms of NO-CH4 to the symmetry-restricted NO (X2Π, ν″ = 0, J″, Fn, Λ) + CH4 (ν″) product outcomes.

6.
Article in English | MEDLINE | ID: mdl-36532301

ABSTRACT

Established guidelines describe minimum requirements for reporting algorithms in healthcare; it is equally important to objectify the characteristics of ideal algorithms that confer maximum potential benefits to patients, clinicians, and investigators. We propose a framework for ideal algorithms, including 6 desiderata: explainable (convey the relative importance of features in determining outputs), dynamic (capture temporal changes in physiologic signals and clinical events), precise (use high-resolution, multimodal data and aptly complex architecture), autonomous (learn with minimal supervision and execute without human input), fair (evaluate and mitigate implicit bias and social inequity), and reproducible (validated externally and prospectively and shared with academic communities). We present an ideal algorithms checklist and apply it to highly cited algorithms. Strategies and tools such as the predictive, descriptive, relevant (PDR) framework, the Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence (SPIRIT-AI) extension, sparse regression methods, and minimizing concept drift can help healthcare algorithms achieve these objectives, toward ideal algorithms in healthcare.

7.
Ann Surg ; 276(5): e347-e352, 2022 11 01.
Article in English | MEDLINE | ID: mdl-35946794

ABSTRACT

OBJECTIVE: While errors can harm patients they remain poorly studied. This study characterized errors in the care of surgical patients and examined the association of errors with morbidity and mortality. BACKGROUND: Errors have been reported to cause <10% or >60% of adverse events. Such discordant results underscore the need for further exploration of the relationship between error and adverse events. METHODS: Patients with operations performed at a single institution and abstracted into the American College of Surgeons National Surgical Quality Improvement Program from January 1, 2018, to December 31, 2018 were examined. This matched case control study comprised cases who experienced a postoperative morbidity or mortality. Controls included patients without morbidity or mortality, matched 2:1 using age (±10 years), sex, and Current Procedural Terminology (CPT) group. Two faculty surgeons independently reviewed records for each case and control patient to identify diagnostic, technical, judgment, medication, system, or omission errors. A conditional multivariable logistic regression model examined the association between error and morbidity. RESULTS: Of 1899 patients, 170 were defined as cases who experienced a morbidity or mortality. The majority of cases (n=93; 55%) had at least 1 error; of the 329 matched control patients, 112 had at least 1 error (34%). Technical errors occurred most often among both cases (40%) and controls (23%). Logistic regression demonstrated a strong independent relationship between error and morbidity (odds ratio=2.67, 95% confidence interval: 1.64-4.35, P <0.001). CONCLUSION: Errors in surgical care were associated with postoperative morbidity. Reducing errors requires measurement of errors.


Subject(s)
Postoperative Complications , Quality Improvement , Case-Control Studies , Humans , Morbidity , Odds Ratio , Postoperative Complications/etiology , Risk Factors
8.
J Surg Res ; 267: 309-319, 2021 11.
Article in English | MEDLINE | ID: mdl-34175585

ABSTRACT

BACKGROUND: Unplanned reoperations and unplanned readmissions can increase morbidity and mortality. Few studies however, have explored the association of reoperation and readmission among general surgery patients. Our aim was to examine this relationship in selected abdominal operations. METHODS: Data from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Participant Use Data Files from 2014 to 2018 were utilized. Six groups of operations, defined by ACS NSQIP procedure codes for ventral hernia repair, colectomy, appendectomy, proctectomy, small bowel resection, and gastrectomy, were assessed. Patients discharged ≤ 14 days after operation were included in the study. This time period was selected to reduce ACS NSQIP 30 day post-surgery follow-up bias. Unplanned reoperations were defined as those occurring during the index hospitalization. The primary outcome was unplanned readmission that occurred ≤ 14 days from the date of discharge. Logistic regression models were used to examine variables associated with unplanned readmission for each procedure group. RESULTS: A total of 787,118 patients were included: ventral hernia repair 35.2%, colectomy 30.6%, appendectomy 26.5%, proctectomy 3.7%, small bowel resection 3.2%, and gastrectomy 0.8%. Unplanned reoperation was independently associated with unplanned readmission for ventral hernia repair (OR 2.84, 95% CI 2.28-3.54, P < 0.001), colectomy (OR 1.58, CI 1.42- 1.76, P < 0.001), appendectomy (OR 2.91, CI 2.21-3.84, P < 0.001), and proctectomy (OR 1.41, CI 1.10-1.81, P = 0.006). Other clinically relevant covariates associated with readmission were partially dependent functional status before colectomy (OR 1.34, CI 1.23-1.46, P < 0.001), ventral hernia repair (OR 1.79, CI 1.54-2.09, P < 0.001), and small bowel resection (OR 1.44, CI 1.18-1.77, P < 0.001; and ASA 4/5 classification for colectomy (OR 2.71, CI 2.36-3.11, P < 0.001), proctectomy (OR 2.10, CI 1.48-2.97, P < 0.001), ventral hernia repair (OR 8.19, CI 6.78-9.88, P < 0.001), appendectomy (OR 2.80, CI 2.35-3.34, P < 0.001), and small bowel resection (OR 3.42, CI 2.20-5.32, P < 0.001). ASA 2, ASA 3 classification, age, and sex were also associated with unplanned readmission for most procedures. CONCLUSIONS: Unplanned reoperations are associated with an increase in unplanned readmission after selected abdominal operations included in this study. This factor should be considered in discharge and follow-up planning to help reduce unplanned readmissions.


Subject(s)
Hernia, Ventral , Patient Readmission , Hernia, Ventral/surgery , Humans , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Reoperation , Retrospective Studies , Risk Factors
9.
Respir Care ; 66(7): 1049-1058, 2021 07.
Article in English | MEDLINE | ID: mdl-33879565

ABSTRACT

BACKGROUND: Transpulmonary pressure (PL) is used to assess pulmonary mechanics and guide lung-protective mechanical ventilation (LPV). PL is recommended to individualize LPV settings for patients with high pleural pressures and hypoxemia. We aimed to determine whether PL-guided LPV settings, pulmonary mechanics, and oxygenation improve and differ from non-PL-guided LPV among obese patients after 24 h on mechanical ventilation. Secondary outcomes included classification of hypoxemia severity, count of ventilator-free days, ICU length of stay, and overall ICU mortality. METHODS: This is a retrospective analysis of data. Ventilator settings, pulmonary mechanics, and oxygenation were recorded on the initial day of PL measurement and 24 h later. PL-guided LPV targeted inspiratory PL < 20 cm H2O and expiratory PL of 0-6 cm H2O. Comparisons were made to repeat measurements. RESULTS: Twenty subjects (13 male) with median age of 49 y, body mass index 47.5 kg/m2, and SOFA score of 8 were included in our analysis. Fourteen subjects received care in a medical ICU. PL measurement occurred 16 h after initiating non-PL-guided LPV. PL-guided LPV resulted in higher median PEEP (14 vs 18 cm H2O, P = .009), expiratory PL (-3 vs 1 cm H2O, P = .02), respiratory system compliance (30.7 vs 44.6 mL/cm H2O, P = .001), and [Formula: see text] (156 vs 240 mm Hg, P = .002) at 24 h. PL-guided LPV resulted in lower [Formula: see text] (0.53 vs 0.33, P < .001) and lower PL driving pressure (10 vs 6 cm H2O, P = .001). Tidal volume (420 vs 435 mL, P = .64) and inspiratory PL (7 vs 7 cm H2O, P = .90) were similar. Subjects had a median of 7 ventilator-free days, and median ICU length of stay was 14 d. Three of 20 subjects died within 28 d after ICU admission. CONCLUSIONS: PL-guided LPV resulted in higher PEEP, lower [Formula: see text], improved pulmonary mechanics, and greater oxygenation when compared to non-PL-guided LPV settings in adult obese subjects.


Subject(s)
Positive-Pressure Respiration , Respiration, Artificial , Adult , Humans , Lung , Male , Obesity , Respiratory Mechanics , Retrospective Studies , Tidal Volume
10.
Crit Care Explor ; 2(12): e0294, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33364604

ABSTRACT

Coronavirus disease 2019 can lead to sudden and severe respiratory failure that mandates endotracheal intubation, a procedure much more safely performed under elective rather than emergency conditions. Early warning of rising risk of this event could benefit both patients and healthcare providers by reducing the high risk of emergency intubation. Current illness severity scoring systems, which usually update only when clinicians measure vital signs or laboratory values, are poorly suited for early detection of this kind of rapid clinical deterioration. We propose that continuous predictive analytics monitoring, a new approach to bedside management, is more useful. The principles of this new practice anchor in analysis of continuous bedside monitoring data, training models on diagnosis-specific paths of deterioration using clinician-identified events, and continuous display of trends in risks rather than alerts when arbitrary thresholds are exceeded.

11.
Crit Care Explor ; 2(12): e0278, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33251517

ABSTRACT

Obtaining informed consent for commonly performed ICU procedures is often compromised by variability in communication styles and inadequate verbal descriptions of anatomic concepts. The objective of this study was to evaluate the efficacy of an audiovisual module in improving the baseline knowledge of ICU procedures among patients and their caregivers. DESIGN: Prospective, observational study. SETTING: Forty-eight-bed adult surgical ICU at a tertiary care center. SUBJECTS: Critically ill surgical patients and their legally authorized representatives. INTERVENTIONS: An audiovisual module describing eight commonly performed ICU procedures. MEASUREMENTS AND MAIN RESULTS: Fifty-nine subjects were enrolled and completed an 11-question pre- and postvideo test of knowledge regarding commonly performed ICU procedures and a brief satisfaction survey. Twenty-nine percent had a healthcare background. High school was the highest level of education for 37% percent of all subjects. Out of 11 questions on the ICU procedure knowledge test, subjects scored an average 8.0 ± 1.9 correct on the pretest and 8.4 ± 2.0 correct on the posttest (p = 0.055). On univariate logistic regression, having a healthcare background was a negative predictor of improved knowledge (odds ratio, 0.185; 95% CI, 0.045-0.765), indicating that those with a health background had a lower probability of improving their score on the posttest. Among subjects who did not have a healthcare background, scores increased from 7.7 ± 1.9 to 8.3 ± 2.1 (p = 0.019). Seventy-five percent of all subjects indicated that the video was easy to understand, and 70% believed that the video improved their understanding of ICU procedures. CONCLUSIONS: Audiovisual modules may improve knowledge and comprehension of commonly performed ICU procedures among critically ill patients and caregivers who have no healthcare background.

12.
J Phys Chem A ; 123(44): 9587-9593, 2019 Nov 07.
Article in English | MEDLINE | ID: mdl-31600079

ABSTRACT

Pasteur was the first to realize Earth's homochirality. Consequently, he attempted to design experiments revealing a mechanism that would expose life's chiral preference. Some of these experiments involved the application of magnetic fields to chemical reactions. His experiments failed, in part, because B-fields are pseudo-vectors and cannot couple preferentially to one handedness. However, extremely large magnetic fields cause the Maxwell equations to break down. This allows the motions of spin and charge densities in paramagnetic anion radicals to produce polarized axial B-fields that can undergo preferential coupling to one handedness. Hence, when a racemic mixture of paramagnetic organic molecules passes by an extremely large external gradated magnetic field, the enantiomers experience different torque forces and acquire different translational directions. B-fields of the required magnitude are unknown on this planet. In fact, they would be lethal, thereby eliminating any chance of Pasteur's success. On the other hand, Duncan and co-workers have recently discovered and garnered physical understanding of magnetars in interstellar space. Some of these neutron star systems produce B-fields greater than the quantum electrodynamic field strength, which is more than enough to generate the required torque for the interstellar enantiomeric separation. In space, chiralitically enriched materials can be deposited on planetesimals and result in homochiral "islands" on the planets. The formation of magnetars is a consequence of weak force events. We assert that, in interstellar space, a plethora of enantiomerically enriched dust clouds resulted from inter-magnetar-paramagnetic molecule force fields.

13.
Arterioscler Thromb Vasc Biol ; 39(1): 73-88, 2019 01.
Article in English | MEDLINE | ID: mdl-30580567

ABSTRACT

Objective- The goal of this study was to determine the role of ZFP148 (zinc-finger protein 148) in aneurysm formation. Approach and Results- ZFP148 mRNA expression increased at day 3, 7, 14, 21, and 28 after during abdominal aortic aneurysm formation in C57BL/6 mice. Loss of ZFP148 conferred abdominal aortic aneurysm protection using ERTCre+ ZFP148 flx/flx mice. In a third set of experiments, smooth muscle-specific loss of ZFP148 alleles resulted in progressively greater protection using novel transgenic mice (MYH [myosin heavy chain 11] Cre+ flx/flx, flx/wt, and wt/wt). Elastin degradation, LGAL3, and neutrophil staining were significantly attenuated, while α-actin staining was increased in ZFP148 knockout mice. Results were verified in total cell ZFP148 and smooth muscle-specific knockout mice using an angiotensin II model. ZFP148 smooth muscle-specific conditional mice demonstrated increased proliferation and ZFP148 was shown to bind to the p21 promoter during abdominal aortic aneurysm formation. ZFP148 smooth muscle-specific conditional knockout mice also demonstrated decreased apoptosis as measured by decreased cleaved caspase-3 staining. ZFP148 bound smooth muscle marker genes via chromatin immunoprecipitation analysis mediated by NF-1 (neurofibromin 1) promote histone H3K4 deacetylation via histone deacetylase 5. Transient transfections and chromatin immunoprecipitation analyses demonstrated that NF-1 was required for ZFP148 protein binding to smooth muscle marker genes promoters during aneurysm formation. Elimination of NF-1 using shRNA approaches demonstrated that NF-1 is required for binding and elimination of NF-1 increased BRG1 recruitment, the ATPase subunit of the SWI/SWF complex, and increased histone acetylation. Conclusions- ZFP148 plays a critical role in multiple murine models of aneurysm formation. These results suggest that ZFP148 is important in the regulation of proliferation, smooth muscle gene downregulation, and apoptosis in aneurysm development.


Subject(s)
Aortic Aneurysm, Abdominal/etiology , DNA-Binding Proteins/metabolism , Myocytes, Smooth Muscle/metabolism , Neurofibromin 1/metabolism , Transcription Factors/metabolism , Acetylation , Angiotensin II/pharmacology , Animals , Aortic Aneurysm, Abdominal/metabolism , Apoptosis , Cell Proliferation , Cyclin-Dependent Kinase Inhibitor p21/genetics , Female , Histones/metabolism , Humans , Male , Mice , Mice, Inbred C57BL , bcl-2 Homologous Antagonist-Killer Protein/genetics
14.
Arterioscler Thromb Vasc Biol ; 38(4): 843-853, 2018 04.
Article in English | MEDLINE | ID: mdl-29472233

ABSTRACT

OBJECTIVE: Neutrophils promote experimental abdominal aortic aneurysm (AAA) formation via a mechanism that is independent from MMPs (matrix metalloproteinases). Recently, we reported a dominant role of IL (interleukin)-1ß in the formation of murine experimental AAAs. Here, the hypothesis that IL-1ß-induced neutrophil extracellular trap formation (NETosis) promotes AAA was tested. APPROACH AND RESULTS: NETs were identified through colocalized staining of neutrophil, Cit-H3 (citrullinated histone H3), and DNA, using immunohistochemistry. NETs were detected in human AAAs and were colocalized with IL-1ß. In vitro, IL-1RA attenuated IL-1ß-induced NETosis in human neutrophils. Mechanistically, IL-1ß treatment of isolated neutrophils induced nuclear localization of ceramide synthase 6 and synthesis of C16-ceramide, which was inhibited by IL-1RA or fumonisin B1, an inhibitor of ceramide synthesis. Furthermore, IL-1RA or fumonisin B1 attenuated IL1-ß-induced NETosis. In an experimental model of murine AAA, NETs were detected at a very early stage-day 3 of aneurysm induction. IL-1ß-knockout mice demonstrated significantly lower infiltration of neutrophils to aorta and were protected from AAA. Adoptive transfer of wild-type neutrophils promoted AAA formation in IL-1ß-knockout mice. Moreover, treatment of wild-type mice with Cl-amidine, an inhibitor NETosis, significantly attenuated AAA formation, whereas, treatment with deoxyribonuclease, a DNA digesting enzyme, had no effect on AAA formation. CONCLUSIONS: Altogether, the results suggest a dominant role of IL-1ß-induced NETosis in AAA formation.


Subject(s)
Aorta, Abdominal/metabolism , Aortic Aneurysm, Abdominal/metabolism , Extracellular Traps/metabolism , Interleukin-1beta/metabolism , Neutrophils/metabolism , Animals , Aorta, Abdominal/drug effects , Aorta, Abdominal/pathology , Aortic Aneurysm, Abdominal/genetics , Aortic Aneurysm, Abdominal/pathology , Aortic Aneurysm, Abdominal/prevention & control , Ceramides/metabolism , Disease Models, Animal , Extracellular Traps/drug effects , Humans , Image Processing, Computer-Assisted/methods , Interleukin-1beta/deficiency , Interleukin-1beta/genetics , Membrane Proteins/metabolism , Mice , Mice, Knockout , Microscopy, Fluorescence/methods , Neutrophils/drug effects , Neutrophils/pathology , Neutrophils/transplantation , Ornithine/analogs & derivatives , Ornithine/pharmacology , Receptors, Interleukin-1/metabolism , Signal Transduction , Sphingosine N-Acyltransferase/metabolism
15.
J Vasc Surg ; 66(1): 232-242.e4, 2017 07.
Article in English | MEDLINE | ID: mdl-28274752

ABSTRACT

OBJECTIVE: The purpose of this study was to establish a reliable, chronic model of abdominal aortic aneurysm (AAA). METHODS: Wild-type 8-week-old C56BL/6 male mice (n = 120) were equally divided into three groups: (1) BAPN group: 0.2% 3-aminopropionitrile fumarate salt (BAPN) drinking water was provided to mice 2 days before surgery until the end of study. Sham aneurysm induction surgery was performed using 5 µL of heat deactivated elastase. (2) Elastase group: mice were given regular drinking water without BAPN. During aneurysm induction surgery, 5 µL of the active form of elastase (10.3 mg protein/mL, 5.9 U/mg protein) was applied on top of the infrarenal abdominal aorta adventitia for 5 minutes. (3) BAPN+elastase group: mice were given BAPN drinking water and the active form of elastase application, as above. On postoperative days 7, 14, 21, 28, and 100, aortic samples were collected for histology, cytokine array, and gelatin zymography after aortic diameter measurement. RESULTS: Compared with the elastase group, the BAPN+elastase group had a higher AAA formation rate (93% vs 65%; P < .01) with more advanced AAAs (25 of 42 vs 1 of 40 for stage II and III; P < .001). Aneurysms from the BAPN+elastase group demonstrated persistent long-term growth (221.5% ± 36.6%, 285.8% ± 78.6%, and 801% ± 160% on days 21, 28, and 100, respectively; P < .001), with considerable thrombus formation (54%) and rupture (31%) at the advanced stages of AAA development. Cytokine levels (pro-matrix metalloproteinase 9, interleukin-1ß, interleukin-6, chemokine [C-C motif] ligand 5, triggering receptor expressed on myeloid cells 1, monocyte chemotactic protein 1, and tissue inhibitor of metalloproteinase 1) in the BAPN+elastase group were higher than in the elastase group on day 7. After day 7, cytokine levels returned to baseline, with the exception of elevated matrix metalloproteinase 2 activity. By histology, CD3-positive T cells in the BAPN+elastase group were elevated on days 28 and 100. CONCLUSIONS: A combination of oral BAPN administration and periaortic elastase application induced a chronic, advanced-stage AAA with characteristics of persistent aneurysm growth, thrombus formation, and spontaneous rupture. Future studies should use this model, especially for examining tissue remodeling during the late stages of aneurysm development.


Subject(s)
Aminopropionitrile/analogs & derivatives , Aorta, Abdominal/pathology , Aortic Aneurysm, Abdominal/chemically induced , Pancreatic Elastase , Animals , Aorta, Abdominal/metabolism , Aortic Aneurysm, Abdominal/blood , Aortic Aneurysm, Abdominal/pathology , Aortic Rupture/chemically induced , Chronic Disease , Cytokines/blood , Dilatation, Pathologic , Disease Models, Animal , Disease Progression , Inflammation Mediators/blood , Male , Mice, Inbred C57BL , Thrombosis/chemically induced , Time Factors
16.
FASEB J ; 30(12): 4192-4201, 2016 12.
Article in English | MEDLINE | ID: mdl-27619672

ABSTRACT

The role of resolvins in abdominal aortic aneurysm (AAA) has not been established. We hypothesized that treatment with D-series resolvins (RvD2 or RvD1) would attenuate murine AAA formation through alterations in macrophage polarization and cytokine expression. Male C57/B6 mice (n = 9 per group) 8 to 12 wk old received RvD2 (100 ng/kg/treatment), RvD1 (100 ng/kg/treatment), or vehicle only every third day beginning 3 d before abdominal aortic perfusion with elastase as prevention. Aortas were collected 14 d after elastase perfusion. Cytokine analysis (n = 5 per group) or confocal microscopy (n = 4 per group) was performed. In a separate experiment, RvD2 was provided to mice with small AAAs 3 d after elastase treatment (n = 8 per group). Additionally, apolipoprotein E knockout mice treated with angiotensin II (1000 ng/kg) were treated with RvD2 or vehicle alone (n = 10 per group) in a nonsurgical model of AAA. To determine the effect of RvD2 on macrophage polarization, confocal staining for macrophages, M1 and M2 macrophage subtypes, α-actin, and DAPI was performed. Mean aortic dilation was 96 ± 13% for vehicle-treated mice, 57 ± 9.7% for RvD2-treated mice, and 61 ± 11% for RvD1-treated mice (P < 0.0001). Proinflammatory cytokines macrophage chemotactic protein 1, C-X-C motif ligand 1, and IL-1ß were significantly elevated in control animals compared to RvD2- and RvD1-treated animals (P < 0.05), resulting in a reduction of matrix metalloproteinase 2 and 9 activity in resolvin-treated mice in both elastase and angiotensin II models. Treatment of existing small AAAs with RvD2 demonstrated a 25% reduction in aneurysm size at d 14 compared to vehicle alone (P = 0.018). Confocal histology demonstrated a prevalence of M2 macrophages within the aortic medium in mice treated with RvD2. Resolvin D2 exhibits a potent protective effect against experimental AAA formation. Treatment with RvD2 significantly influences macrophage polarization and decreases several important proinflammatory cytokines. Resolvins and the alteration of macrophage polarization represent potential future targets for prevention of AAA.-Pope, N. H., Salmon, M., Davis, J. P., Chatterjee, A., Su, G., Conte, M. S., Ailawadi, G., Upchurch, G. R., Jr. D-series resolvins inhibit murine abdominal aortic aneurysm formation and increase M2 macrophage polarization.


Subject(s)
Aortic Aneurysm, Abdominal/metabolism , Docosahexaenoic Acids/pharmacology , Macrophages/drug effects , Matrix Metalloproteinase 2/metabolism , Actins/metabolism , Animals , Aortic Aneurysm, Abdominal/prevention & control , Cytokines/metabolism , Disease Models, Animal , Interleukin-1beta/metabolism , Macrophages/cytology , Macrophages/metabolism , Mice, Inbred C57BL , Mice, Knockout
17.
J Vasc Surg ; 63(6): 1602-1612.e2, 2016 06.
Article in English | MEDLINE | ID: mdl-26817611

ABSTRACT

BACKGROUND: Testosterone is theorized to play a major role in the pathophysiology of abdominal aortic aneurysms (AAAs) because this disease occurs primarily in men. The role of the androgen receptor (AR) in the formation of AAAs has not been well elucidated, and therefore, it is hypothesized that androgen blockade will attenuate experimental aortic aneurysm formation. METHODS: Aortas of 8- to 12-week-old male C57Bl/6 wild-type (WT) mice or male AR knockout (AR(-/-)) mice were perfused with purified porcine pancreatic elastase (0.35 U/mL) to induce AAA formation. Two groups of WT male mice were treated with the AR blockers flutamide (50 mg/kg) or ketoconazole (150 mg/kg) twice daily by intraperitoneal injection. Aortas were harvested on day 14 after video micrometry was used to measure AAA diameter. Cytokine arrays and histologic analysis were performed on aortic tissue. Groups were compared using an analysis of variance and a Tukey post hoc test. RESULTS: Flutamide and ketoconazole treatment (mean ± standard error of the mean) attenuated AAA formation in WT mice (84.2% ± 22.8% [P = .009] and 91.5% ± 18.2% [P = .037]) compared with WT elastase (121% ± 5.23%). In addition, AR(-/-) mice showed attenuation of AAA growth (64.4% ± 22.7%; P < .0001) compared with WT elastase. Cytokine arrays of aortic tissue revealed decreased levels of proinflammatory cytokines interleukin (IL)-α, IL-6, and IL-17 in flutamide-treated and AR(-/-) groups compared with controls. CONCLUSIONS: Pharmacologic and genetic AR blockade cause attenuation of AAA formation. Therapies for AR blockade used in prostate cancer may provide medical treatment to halt progression of AAAs in humans.


Subject(s)
Androgen Antagonists/pharmacology , Aorta, Abdominal/drug effects , Aortic Aneurysm, Abdominal/prevention & control , Flutamide/pharmacology , Gene Deletion , Ketoconazole/pharmacology , Receptors, Androgen/drug effects , Receptors, Androgen/deficiency , Animals , Aorta, Abdominal/metabolism , Aorta, Abdominal/pathology , Aortic Aneurysm, Abdominal/chemically induced , Aortic Aneurysm, Abdominal/genetics , Aortic Aneurysm, Abdominal/metabolism , Cytokines/metabolism , Disease Models, Animal , Disease Progression , Gene Expression Regulation , Genotype , Humans , Inflammation Mediators/metabolism , Male , Mice, Inbred C57BL , Mice, Knockout , Pancreatic Elastase , Phenotype , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, Androgen/genetics , Receptors, Androgen/metabolism , Time Factors
18.
Surg Innov ; 23(1): 62-9, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26002112

ABSTRACT

BACKGROUND: The percutaneous endoscopic gastrostomy (PEG) is a ubiquitous feeding tube with high rates of accidental dislodgement, with significant morbidity and health care costs. We hypothesized use of a decoupling device is a safe and effective mechanism to reduce dislodgements. STUDY DESIGN: We studied a prospective cohort of 100 patients from an academic center. Enrollment included patients requiring PEG tube placement with follow up extending through an individual's lifetime use of their PEG tube. The primary endpoint was accidental dislodgement of the principally placed PEG tube. The secondary endpoint was time to accidental dislodgement of the PEG tube. RESULTS: All 100 patients received the SafetyBreak device and had complete follow-up. Half of the patients had at least a single episode of device decoupling, indicating prevention of dislodgement of the PEG. Eight patients ultimately had dislodgement, resulting in a significantly lower dislodgement rate when compared with a historical cohort (P = .036) and significantly longer survival of the PEG (log rank = 0.005). When compared with a concurrent cohort (without the device) there was also significantly lower dislodgement rate (P = .03) and a trend toward longer survival of the PEG (log rank = 0.08). CONCLUSIONS: When compared with both a historical and concurrent cohort of patients, the SafetyBreak device reduces accidental dislodgement of PEG tubes. As an increasing number of PEGs are being placed, an increasing number of patients are at risk for dislodgement. The SafetyBreak device is an innovative, economical solution to the problem of accidental dislodgement of the PEG tube.


Subject(s)
Biomedical Engineering/instrumentation , Biomedical Engineering/statistics & numerical data , Endoscopy/instrumentation , Gastrostomy/instrumentation , Gastrostomy/statistics & numerical data , Aged , Biomedical Engineering/standards , Cohort Studies , Equipment Design , Equipment Failure , Female , Gastrostomy/adverse effects , Gastrostomy/standards , Humans , Male , Middle Aged , Patient Safety , Prospective Studies
19.
J Surg Res ; 199(1): 249-58, 2015 Nov.
Article in English | MEDLINE | ID: mdl-25958166

ABSTRACT

BACKGROUND: No medical therapies are yet available to slow abdominal aortic aneurysm (AAA) growth. This study sought to investigate the effect of different genders of bone marrow-derived mesenchymal stem cells (MSC) on AAA growth in a murine AAA model. Given the decreased rate of AAA in women, it is hypothesized that female MSC would attenuate AAA growth more so than male MSC. MATERIALS AND METHODS: Aortas of 8-10-wk-old male C57Bl/6 mice were perfused with purified porcine pancreatic elastase to induce AAA formation. Bone marrow-derived MSC from male and female mice were dosed via tail vein injection (3 million cells per dose, 500 µL of volume per injection) on postaortic perfusion days 1, 3, and 5. Aortas were harvested after 14 d. RESULTS: Mean aortic dilation in the elastase group was 121 ± 5.2% (mean ± standard error of the mean), while male MSC inhibited AAA growth (87.8 ± 6.9%, P = 0.008) compared with that of elastase. Female MSC showed the most marked attenuation of AAA growth (75.2 ± 8.3% P = 0.0004). Proinflammatory cytokines tumor necrosis factor α, interleukin 1ß, and monocyte chemotactic protein-1 (MCP-1) were only decreased in tissues treated with female MSC (P = 0.017, P = 0.001, and P < 0.0001, respectively, when compared with elastase). CONCLUSIONS: These data exhibit that female MSC more strongly attenuate AAA growth in the murine model. Furthermore, female MSC and male MSC inhibit proinflammatory cytokines at varying levels. The effects of MSC on aortic tissue offer a promising insight into biologic therapies for future medical treatment of AAAs in humans.


Subject(s)
Aortic Aneurysm, Abdominal/therapy , Bone Marrow Transplantation/methods , Mesenchymal Stem Cell Transplantation/methods , Animals , Aortic Aneurysm, Abdominal/metabolism , Aortic Aneurysm, Abdominal/pathology , Biomarkers/metabolism , Cytokines/metabolism , Female , Male , Mice , Mice, Inbred C57BL , Sex Factors
20.
Am Surg ; 80(11): 1164-8, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25347510

ABSTRACT

Gastric prolapse (GP) after laparoscopic adjustable gastric banding (LAGB) remains a complication that has the potential to result in significant morbidities. The purpose of this study was to evaluate the incidence of GP after LAGB and to determine its impact on patient outcomes among the morbidly obese. From 2005 to 2012, 379 consecutive morbidly obese patients underwent LAGB procedures at a single institution. Patients were placed into two groups based on the occurrence of gastric prolapse (GP vs no GP). Patient demographics and risk factors, operative features, and postoperative outcomes were analyzed by univariate analyses to assess the impact of GP. Average patient age was 47 ± 29 years and patients were commonly female (80%) with a median body mass index (BMI) of 44 kg/m(2). Incidence of GP was 4.2 per cent (n = 16). LAGB median BMIs at 1 month and 1 year were 41 and 36 kg/m2. There was no difference in 1-year weight loss (BMI GP: 36 kg/m(2) vs no GP: 36 kg/m(2), P = 0.617). Laparoscopic gastric banding results in significant weight reduction and a low incidence of gastric prolapse. Gastric prolapse has no difference in 1-year postoperative median BMI when compared with patients who did not prolapse.


Subject(s)
Gastroplasty/methods , Obesity, Morbid/surgery , Postoperative Complications/epidemiology , Stomach Diseases/epidemiology , Adult , Comorbidity , Female , Humans , Incidence , Male , Middle Aged , Prolapse , Retrospective Studies , Risk Factors , Treatment Outcome , Virginia/epidemiology
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