Distinct Origins and Transmission Pathways of blaKPC Enterobacterales across Three U.S. States.

Carbapenem-resistant Enterobacterales (CRE) are among the most concerning antibiotic resistance threats due to high rates of multidrug resistance, transmissibility in health care settings, and high mortality rates. We evaluated the potential for regional genomic surveillance to track the spread of blaKPC-carrying CRE (KPC-CRE) by using isolate collections from health care facilities in three U.S. states. Clinical isolates were collected from Connecticut (2017 to 2018), Minnesota (2012 to 2018), and Tennessee (2016 to 2017) through the U.S. Centers for Disease Control and Prevention's Multi-site Gram-negative Surveillance Initiative (MuGSI) and additional surveillance. KPC-CRE isolates were whole-genome sequenced, yielding 255 isolates from 214 patients across 96 facilities. Case report data on patient comorbidities, facility exposures, and interfacility patient transfer were extracted. We observed that in Connecticut, most KPC-CRE isolates showed evidence of importation from outside the state, with limited local transmission. In Minnesota, cases were mainly from sporadic importation and transmission of blaKPC-carrying Klebsiella pneumoniae ST258, and clonal expansion of blaKPC-carrying Enterobacter hormaechei ST171, primarily at a single focal facility and its satellite facilities. In Tennessee, we observed transmission of diverse strains of blaKPC-carrying Enterobacter and Klesbiella, with evidence that most derived from the local acquisition of blaKPC plasmids circulating in an interconnected regional health care network. Thus, the underlying processes driving KPC-CRE burden can differ substantially across regions and can be discerned through regional genomic surveillance. This study provides proof of concept that integrating genomic data with information on interfacility patient transfers can provide insights into locations and drivers of regional KPC-CRE burden that can enable targeted interventions.

Reduced graphene oxide influences morphology and thermal properties of silk/cellulose biocomposites.

In recent decades, research into biomaterials such as silk or cellulose has rapidly expanded due to their abundance, low cost, and tunable morphological as well as physicochemical properties. Cellulose is appealing due to its crystalline and amorphous polymorphs while silk is attractive due to its tunable secondary structure formations which is made up of flexible protein fibers. When these two biomacromolecules are mixed, their properties can be modified by changing their material composition and fabrication methodology, e.g., solvent type, coagulation agent, and temperature. Reduced graphene oxide (rGO) can be used to increase molecular interactions and stabilization of natural polymers. In this study, we sought to determine how small amounts of rGO affect the carbohydrate crystallinity and protein secondary structure formation as well as physicochemical properties and how they affect overall ionic conductivity of cellulose-silk composites. Properties of fabricated silk and cellulose composites with and without rGO were investigated using Fourier Transform Infrared Spectroscopy, Scanning Electron Microscopy, X-Ray Scattering, Differential Scanning Calorimetry, Dielectric Relaxation Spectroscopy, and Thermogravimetric Analysis. Our results show that addition of rGO influenced morphological and thermal properties of cellulose-silk biocomposites, specifically through cellulose crystallinity and silk ß-sheet content which further impacted ionic conductivity.

Polymersome Poration and Rupture Mediated by Plasmonic Nanoparticles in Response to Single-Pulse Irradiation.

The self-assembly of amphiphilic diblock copolymers into polymeric vesicles, commonly known as polymersomes, results in a versatile system for a variety of applications including drug delivery and microreactors. In this study, we show that the incorporation of hydrophobic plasmonic nanoparticles within the polymersome membrane facilitates light-stimulated release of vesicle encapsulants. This work seeks to achieve tunable, triggered release with non-invasive, spatiotemporal control using single-pulse irradiation. Gold nanoparticles (AuNPs) are incorporated as photosensitizers into the hydrophobic membrane of micron-scale polymersomes and the cargo release profile is controlled by varying the pulse energy and nanoparticle concentration. We have demonstrated the ability to achieve immediate vesicle rupture as well as vesicle poration resulting in temporal cargo diffusion. Additionally, changing the pulse duration, from femtosecond to nanosecond, provides mechanistic insight into the photothermal and photomechanical contributors that govern membrane disruption in this polymer-nanoparticle hybrid system.

The Impact of Composition and Morphology on Ionic Conductivity of Silk/Cellulose Bio-Composites Fabricated from Ionic Liquid and Varying Percentages of Coagulation Agents.

Blended biocomposites created from the electrostatic and hydrophobic interactions between polysaccharides and structural proteins exhibit useful and unique properties. However, engineering these biopolymers into applicable forms is challenging due to the coupling of the material's physicochemical properties to its morphology, and the undertaking that comes with controlling this. In this particular study, numerous properties of the Bombyx mori silk and microcrystalline cellulose biocomposites blended using ionic liquid and regenerated with various coagulation agents were investigated. Specifically, the relationship between the composition of polysaccharide-protein bio-electrolyte membranes and the resulting morphology and ionic conductivity is explored using numerous characterization techniques, including scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray scattering, atomic force microscopy (AFM) based nanoindentation, and dielectric relaxation spectroscopy (DRS). The results revealed that when silk is the dominating component in the biocomposite, the ionic conductivity is higher, which also correlates with higher ß-sheet content. However, when cellulose becomes the dominating component in the biocomposite, this relationship is not observed; instead, cellulose semicrystallinity and mechanical properties dominate the ionic conduction.

Nanoscale Wetting and Energy Transmission at Solid/Liquid Interfaces.

Understanding the effects and limitations of solid/liquid interfaces on energy transport is crucial to applications ranging from nanoscale thermal engineering to chemical synthesis. Until now, the majority of experimental evidence regarding solid/liquid interactions has been limited to macroscale observations and experiments. The lack of experimental works exploring nanoscale solid/liquid interactions has been accentuated as the body of knowledge from theory and simulations at these scales has exploded in recent years. In this study, we expand on current nanoscale thermal measurement techniques in order to more fully understand solid/liquid interfacial energy transport. We use thermal ablation threshold measurements on thick Au films in various liquids as a metric to describe thermal transport at the Au/liquid interface. Furthermore, using ultrafast pump-probe experiments, we gain insight into this transport through picosecond ultrasonic coupling at solid/liquid interfaces with known macroscopic observations. We find significant variations in both the ablation threshold and the damping of the acoustic modes within the Au films depending on nanoscopic interactions at the solid/liquid interface rather than typical macroscale metrics such as acoustic mismatch, measured contact angle, and work of adhesion.

Dynamics of high frequency brain activity.

Evidence suggests that electroencephalographic (EEG) activity extends far beyond the traditional frequency range. Much of the prior study of >120 Hz EEG is in epileptic brains. In the current work, we measured EEG activity in the range of 200 to 2000 Hz, in the brains of healthy, spontaneously behaving rats. Both arrhythmic (1/f-type) and rhythmic (band) activities were identified and their properties shown to depend on EEG-defined stage of sleep/wakefulness. The inverse power law exponent of 1/f-type noise is shown to decrease from 3.08 in REM and 2.58 in NonREM to a value of 1.99 in the Waking state. Such a trend represents a transition from long- to short-term memory processes when examined in terms of the corresponding Hurst index. In addition, treating the 1/f-type activity as baseline noise reveals the presence of two, newly identified, high frequency EEG bands. The first band (ψ) is centered between 260-280 Hz; the second, and stronger, band is a broad peak in the 400-500 Hz range (termed ω). Both of these peaks display lognormal distributions. The functional significance of these frequency bands is supported by the variation in the strength of the peaks with EEG-defined sleep/wakefulness.

Production of Metal Nanoparticles by Pulsed Laser-ablation in Liquids: A Tool for Studying the Antibacterial Properties of Nanoparticles.

The emergence of multidrug-resistant bacteria is a global clinical concern leading some to speculate about our return to a "pre-antibiotics" era of medicine. In addition to efforts to identify novel small-molecule antimicrobial drugs, there has been great interest in the use of metal nanoparticles as coatings for medical devices, wound dressings, and consumer packaging, due to their antimicrobial properties. The wide variety of methods available for nanoparticle synthesis results in a broad spectrum of chemical and physical properties which can affect antibacterial efficacy. This manuscript describes the pulsed laser-ablation in liquids (PLAL) method to create nanoparticles. This approach allows for the fine tuning of nanoparticle size, composition, and stability using post-irradiation methods as well as the addition of surfactants or volume excluders. By controlling particle size and composition, a large range of physical and chemical properties of metal nanoparticles can be explored which may contribute to their antimicrobial efficacy thereby opening new avenues for antibacterial development.

Swine Farming Is a Risk Factor for Infection With and High Prevalence of Carriage of Multidrug-Resistant Staphylococcus aureus.

BACKGROUND: Livestock-associated Staphylococcus aureus (LA-SA) has been documented worldwide. However, much remains unknown about LA-SA colonization and infection, especially in rural environments. METHODS: We conducted a large-scale prospective study of 1342 Iowans, including individuals with livestock contact and a community-based comparison group. Nasal and throat swabs were collected to determine colonization at enrollment, and skin infection swabs over 17 months were assessed for S. aureus. Outcomes included carriage of S. aureus, methicillin-resistant S. aureus (MRSA), tetracycline-resistant S. aureus (TRSA), multidrug-resistant S. aureus (MDRSA), and LA-SA. RESULTS: Of 1342 participants, 351 (26.2%; 95% confidence interval [CI], 23.8%-28.6%) carried S. aureus. MRSA was isolated from 34 (2.5%; 95% CI, 1.8%-3.5%) and LA-SA from 131 (9.8%; 95% CI, 8.3%-11.5%) of the 1342 participants. Individuals with current swine exposure were significantly more likely to carry S. aureus (prevalence ratio [PR], 1.8; 95% CI, 1.4-2.2), TRSA (PR, 8.4; 95% CI, 5.6-12.6), MDRSA (PR, 6.1; 95% CI, 3.8-10.0), and LA-SA (PR, 5.8; 95% CI, 3.9-8.4) than those lacking exposure. Skin infections (n = 103) were reported from 67 individuals, yielding an incidence rate of 6.6 (95% CI, 4.9-8.9) per 1000 person-months. CONCLUSIONS: Current swine workers are 6 times more likely to carry MDRSA than those without current swine exposure. We observed active infections caused by LA-SA. This finding suggests that individuals with livestock contact may have a high prevalence of exposure to, and potentially infection with, antibiotic-resistant S. aureus strains, including LA-SA strains.

Image-based gating of intravascular ultrasound pullback sequences.

Intravascularultrasound (IVUS) sequences recorded in vivo are subject to a wide array of motion artifacts as the majority of these studies are performed within the coronary arteries of a beating heart. To eliminate these artifacts, an electrocardiogram (ECG) signal is typically used to gate (collect) those frames recorded at the points in time associated with a particular fraction of the cardiac cycle. However, this technique may be suboptimal for a number of reasons, among which is the difficulty of determining the optimal fraction at which to gate. This value is generally nonobvious. To circumvent this problem, we introduce a frame-gating method for IVUS pullbacks that mimics ECG (i.e., in the sense that it selects only one frame per cardiac cycle), but will automatically choose the fraction of the cycle that renders the most stable gated frame set. Stability here is gauged by measuring interframe similarity. Our method operates exclusively on the imagery data and does not require ECG or any form of image segmentation or other high-level image analysis. To validate our algorithm, we compare its behavior versus true ECG gating.

A new method for assessment of plaque vulnerability based on vasa vasorum imaging, by using contrast-enhanced intravascular ultrasound and differential image analysis.

BACKGROUND: Increased neovascularization in vasa vasorum and atherosclerotic plaques has recently been identified as a common feature of inflammation and plaque vulnerability. Microbubble contrast agents, which have been used for intravascular imaging, can be used to trace neovascularization. The aim of the study was to detect and evaluate the density of vasa vasorum in non-culprit coronary atherosclerotic plaques of patients with acute coronary syndrome. METHODS: We have studied intravascular ultrasound (IVUS) signals before, during, and after intracoronary injection of microbubbles, proximal to non-culprit atherosclerotic plaques in 16 patients with acute coronary syndrome. Analyses were accomplished using a computational algorithm for the detection of contrast perfusion in such contrast-enhanced sequences. Perfusion density was evaluated by the mean enhancement in the region of interest provided by this difference-imaging technique. RESULTS: Qualitative and quantitative analysis of the pre- and post-injection images showed a significant enhancement in the grey-scale intensity of intima-media and adventitia after injection (intima-media: from 6.0+/-2.5 to 7.9+/-3.3%, p=0.006 and adventitia: from 7.1+/-2.2 to 7.6+/-2.5%, p=0.035). CONCLUSIONS: Contrast-enhanced intravascular imaging is a novel, yet clinically available, technique that has the potential to enhance IVUS-based characterization of atherosclerotic plaques. The technique introduces a new perspective to the detection of vulnerable plaques and warrants further investigations.

One-class acoustic characterization applied to blood detection in IVUS.

Intravascular ultrasound (IVUS) is an invasive imaging modality capable of providing cross-sectional images of the interior of a blood vessel in real time and at normal video framerates (10-30 frames/s). Low contrast between the features of interest in the IVUS imagery remains a confounding factor in IVUS analysis; it would be beneficial therefore to have a method capable of detecting certain physical features imaged under IVUS in an automated manner. We present such a method and apply it to the detection of blood. While blood detection algorithms are not new in this field, we deviate from traditional approaches to IVUS signal characterization in our use of 1-class learning. This eliminates certain problems surrounding the need to provide "foreground" and "background" (or, more generally, n-class) samples to a learner. Applied to the blood-detection problem on 40 MHz recordings made in vivo in swine, we are able to achieve approximately 95% sensitivity with approximately 90% specificity at a radial resolution of approximately 600 microm.

Detection of perivascular blood flow in vivo by contrast-enhanced intracoronary ultrasonography and image analysis: an animal study.

1. Acute coronary syndromes are mostly the result of coronary plaque rupture. Diagnostic techniques focusing on the early detection of those plaques that are prone to rupture are still limited. Increased neovascularization in the adventitia and within the atherosclerotic plaque have recently been identified as common features of inflammation and plaque vulnerability. Contrast-enhanced intravascular imaging with microbubbles can be used to trace perfusion. 2. In the present study, we examined the perivascular network of the left anterior descending coronary arteries and left circumflex arteries of four domestic, clinically healthy pigs using intracoronary ultrasound after injection of microbubbles with a differential imaging technique (ACES; Computational Biomedicine Laboratory, University of Houston, Houston, TX, USA). Our aim was to detect blood flow into the coronary lumen and perivascular flow in contrast-enhanced images. Eleven regions of interest (ROI), including perivascular structures, were compared with regard to their grey scale level before and after the injection of SonoVue (0.06 mL/kg; Bracco Diagnostics, Princeton, NJ, USA). 3. A statistically significant (P = 0.018) enhancement was found in the echogenicity of the total perivascular space (adventitial region and perivascular vessels), as indicated by an increase in grey level intensity from 8.33 +/- 0.80 (before) to 10.11 +/- 0.88 (after microbubble injection). A significant enhancement of the 11 selected ROI (perivascular structures) was also recorded after the injection of microbubbles (from 7.92 +/- 2.14 to 14.03 +/- 2.44; P = 0.008). 4. We believe that the detection of perivascular structures with contrast-enhanced intracoronary ultrasonography combined with proper image processing may reinforce our future efforts in the detection of vasa vasorum, an active participant in the creation of acute coronary events.

Contrast-enhanced intravascular ultrasound: combining morphology with activity-based assessment of plaque vulnerability.

Acute coronary syndromes are the result of coronary plaque rupture in the majority of cases. Available diagnostic techniques that focus on the early detection of plaques that are prone to rupture are still limited. Increased neovascularization in the vasa vasorum of the atherosclerotic plaque has been identified recently as a common feature of inflammation and plaque vulnerability. Microbubbles, which have been used for ultrasound imaging, can be used to trace neovascularization. We present recent advances in contrast agents and contrast-enhanced intravascular ultrasound that may be used for the detection of vasa vasorum, including fundamental and harmonic contrast imaging. Identification of vasa vasorum proliferation in atherosclerotic plaques presents important clinical implications; in particular it could provide a means to detect vulnerability in vivo, thereby guiding targeted treatments.

Vasa vasorum imaging: a new window to the clinical detection of vulnerable atherosclerotic plaques.

Complications of vulnerable atherosclerotic plaques (rupture, luminal and mural thrombosis, intraplaque hemorrhage, rapid progression to stenosis, spasm, and so forth) lead to heart attacks and strokes. It remains difficult to identify what plaques are vulnerable to these complications. Despite recent developments such as thermography, spectroscopy, and magnetic resonance imaging, none of them is approved for clinical use. Intravascular ultrasound (IVUS), a relatively old yet widely available clinical tool for guiding intracoronary procedures, is increasingly used for characterization of atherosclerotic plaques. However, inability of IVUS in measuring plaque activity limits its value in detection of vulnerable plaques. In this review, we present new information suggesting that microbubble contrast-enhanced IVUS can measure activity and inflammation within atherosclerotic plaques by imaging vasa vasorum density. An increasing body of evidence indicates that vasa vasorum density may be a strong marker for plaque vulnerability. We suggest that a combination of structural assessment (cap thickness, lipid core, calcification, etc) and vasa vasorum density imaging by IVUS can serve as the most powerful clinically available tool for characterization of vulnerable plaques. Due to space limitations, all IVUS images and movies are posted on the website of the Ultimate IVUS Collaborative Project: http://www.ultimateivus.com.

Intravascular ultrasound-based imaging of vasa vasorum for the detection of vulnerable atherosclerotic plaque.

Vulnerable plaques are dangerous atherosclerotic lesions that bear a high risk of complications that can lead to heart attacks and strokes. These plaques are known to be chronically inflamed. The vasa vasorum (VV) are microvessels that nourish vessel walls. Proliferation of VV is part of the "response to injury" phenomenon in the process of plaque formation. Recent evidence has shown strong correlations between neovessel formation and macrophage infiltration in atherosclerotic plaque, suggesting VV density as a surrogate marker of plaque inflammation and vulnerability. We have developed a novel method for imaging and analyzing the density and perfusion of VV in human coronary atherosclerotic plaques using intravascular ultrasound (IVUS). Images are taken during the injection of a microbubble contrast agent and the spatiotemporal changes of the IVUS signal are monitored using enhancement-detection techniques. We present analyses of in vivo human coronary cases that, for the first time, demonstrate the feasibility of IVUS imaging of VV.