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Chronic wound infections are a silent pandemic in danger of becoming a global healthcare crisis. Innovations to control infections and improve healing are required. In the context of this challenge, researchers are exploiting plasma-activated hydrogel therapy (PAHT) for use either alone or in combination with other antimicrobial strategies. PAHT involves the cold atmospheric pressure plasma activation of hydrogels with reactive oxygen and nitrogen species to decontaminate infections and promote healing. This opinion article describes PAHT for wound treatment and provides an overview of current research and outstanding challenges in translating the technology for medical use. A 'blueprint' of an autonomous PAHT is presented in the final section that can move the management and treatment of wounds from the clinical setting to the community.

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While blood-contacting materials are widely deployed in medicine in vascular stents, catheters, and cannulas, devices fail in situ because of thrombosis and restenosis. Furthermore, microbial attachment and biofilm formation is not an uncommon problem for medical devices. Even incremental improvements in hemocompatible materials can provide significant benefits for patients in terms of safety and patency as well as substantial cost savings. Herein, a novel but simple strategy is described for coating a range of medical materials, that can be applied to objects of complex geometry, involving plasma-grafting of an ultrathin hyperbranched polyglycerol coating (HPG). Plasma activation creates highly reactive surface oxygen moieties that readily react with glycidol. Irrespective of the substrate, coatings are uniform and pinhole free, comprising O─C─O repeats, with HPG chains packing in a fashion that holds reversibly binding proteins at the coating surface. In vitro assays with planar test samples show that HPG prevents platelet adhesion and activation, as well as reducing (>3 log) bacterial attachment and preventing biofilm formation. Ex vivo and preclinical studies show that HPG-coated nitinol stents do not elicit thrombosis or restenosis, nor complement or neutrophil activation. Subcutaneous implantation of HPG coated disks under the skin of mice shows no evidence of toxicity nor inflammation.

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Background: Human immunodeficiency virus (HIV) is associated with increased risk of heart failure (HF) but data regarding phenotypes of heart failure and outcomes after HF diagnosis, especially within the safety-net which is where half of people with HIV in the United States receive care, are less clear. Methods: Using an electronic health record cohort of all individuals with HF within a municipal safety-net system from 2001-2019 linked to the National Death Index Plus, we compared HF phenotypes, all-cause mortality, HF hospitalization, and cause of death for individuals with and without HIV. Results: Among people with HF (n=14,829), 697 individuals had HIV (4.7%). Persons with HIV (PWH) were diagnosed with HF ten years younger on average. A higher proportion of PWH had a reduced ejection fraction at diagnosis (37.9% vs 32.7%). Adjusted for age, sex, and risk factors, coronary artery disease on angiography was similar by HIV status. HIV was associated with 55% higher risk of all-cause mortality (HR 1.55; 95% CI 1.37-1.76; P<0.001) and lower odds of HF hospitalization (OR 0.51; 95% CI 0.39-0.66; P<0.001). Among PWH with HF, cause of death was less often attributed to cardiovascular disease (22.5% vs 54.6% uninfected; P<0.001) and more to substance use (17.9% vs 9.3%; P<0.001), consistent with autopsy findings in a subset (n=81). Conclusions: Among people with HF who receive care within a municipal safety-net system, HIV infection is associated with higher mortality, despite lower odds of HF hospitalization, attributable to non-cardiovascular causes including substance-related and HIV-related mortality.

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This case report describes a patient in their 60s with gastroesophageal reflex disease who presented to the emergency department after loss of consciousness during dinner and daily intermittent chest discomfort.

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Diagnosing biofilm infections has remained a constant challenge for the last 50 years. Existing diagnostic methods struggle to identify the biofilm phenotype. Moreover, most methods of biofilm analysis destroy the biofilm making the resultant data interpretation difficult. In this study we introduce Fourier Transform Infra-Red (FTIR) spectroscopy as a label-free, non-destructive approach to monitoring biofilm progression. We have utilised FTIR in a novel application to evaluate the chemical composition of bacterial biofilms without disrupting the biofilm architecture. S. epidermidis (RP62A) was grown onto calcium fluoride slides for periods of 30 min-96 h, before semi-drying samples for analysis. We report the discovery of a chemical marker to distinguish between planktonic and biofilm samples. The appearance of new proteins in biofilm samples of varying maturity is exemplified in the spectroscopic data, highlighting the potential of FTIR for identifying the presence and developmental stage of a single biofilm.

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The global clinical and socioeconomic impact of chronic wounds is substantial. The main difficulty that clinicians face during the treatment of chronic wounds is the risk of infection at the wound site. Infected wounds arise from an accumulation of microbial aggregates in the wound bed, leading to the formation of polymicrobial biofilms that can be largely resistant to antibiotic therapy. Therefore, it is essential for studies to identify novel therapeutics to alleviate biofilm infections. One innovative technique is the use of cold atmospheric plasma (CAP) which has been shown to possess promising antimicrobial and immunomodulatory properties. Here, different clinically relevant biofilm models will be treated with cold atmospheric plasma to assess its efficacy and killing effects. Biofilm viability was assessed using live dead qPCR, and morphological changes associated with CAP evaluated using scanning electron microscopy (SEM). Results indicated that CAP was effective against Candida albicans and Pseudomonas aeruginosa, both as mono-species biofilms and when grown in a triadic model system. CAP also significantly reduced viability in the nosocomial pathogen, Candida auris. Staphylococcus aureus Newman exhibited a level of tolerance to CAP therapy, both when grown alone or in the triadic model when grown alongside C. albicans and P. aeruginosa. However, this degree of tolerance exhibited by S. aureus was strain dependent. At a microscopic level, biofilm treatment led to subtle changes in morphology in the susceptible biofilms, with evidence of cellular deflation and shrinkage. Taken together, these results indicate a promising application of direct CAP therapy in combatting wound and skin-related biofilm infections, although biofilm composition may affect the treatment efficacy.

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We present the concept of a versatile drug-loaded composite hydrogel that can be activated using an argon-based cold atmospheric plasma (CAP) jet to deliver both a drug and CAP-generated molecules, concomitantly, in a tissue target. To demonstrate this concept, we utilized the antibiotic gentamicin that is encapsulated in sodium polyacrylate (PAA) particles, which are dispersed within a poly(vinyl alcohol) (PVA) hydrogel matrix. The final product is a gentamicin-PAA-PVA composite hydrogel suitable for an on-demand triggered release using CAP. We show that by activating using CAP, we can effectively release gentamicin from the hydrogel and also eradicate the bacteria effectively, both in the planktonic state and within a biofilm. Besides gentamicin, we also successfully demonstrate the applicability of the CAP-activated composite hydrogel loaded with other antimicrobial agents such as cetrimide and silver. This concept of a composite hydrogel is potentially adaptable to a range of therapeutics (such as antimicrobials, anticancer agents, and nanoparticles) and activatable using any dielectric barrier discharge CAP device.

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Wounds can commonly become infected with polymicrobial biofilms containing bacterial and fungal microorganisms. Microbial colonization of the wound can interfere with sufficient healing and repair, leading to high rates of chronicity in certain individuals, which can have a huge socioeconomic burden worldwide. One route for alleviating biofilm formation in chronic wounds is sufficient treatment of the infected area with topical wound washes and ointments. Thus, the primary aim here was to create a complex in vitro biofilm model containing a range of microorganisms commonly isolated from the infected wound milieu. These polymicrobial biofilms were treated with three conventional anti-biofilm wound washes, chlorhexidine (CHX), povidone-iodine (PVP-I), and hydrogen peroxide (H2O2), and efficacy against the microorganisms assessed using live/dead qPCR. All treatments reduced the viability of the biofilms, although H2O2 was found to be the most effective treatment modality. These biofilms were then co-cultured with 3D skin epidermis to assess the inflammatory profile within the tissue. A detailed transcriptional and proteomic profile of the epidermis was gathered following biofilm stimulation. At the transcriptional level, all treatments reduced the expression of inflammatory markers back to baseline (untreated tissue controls). Olink technology revealed a unique proteomic response in the tissue following stimulation with untreated and CHX-treated biofilms. This highlights treatment choice for clinicians could be dictated by how the tissue responds to such biofilm treatment, and not merely how effective the treatment is in killing the biofilm.

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Background: Transbronchial microwave ablation (MWA) is a promising novel therapy. Despite advances in bronchoscopy and virtual navigation, real time image guidance of probe delivery is lacking, and distal maneuverability is limited. Cone-beam computed tomography (CBCT) based augmented fluoroscopy guidance using steerable sheaths may help overcome these shortcomings. The aim of this study was to evaluate feasibility and accuracy of augmented fluoroscopy guided transbronchial MWA with a steerable sheath and without a bronchoscope. Methods: In this prospective study, procedures were performed under general anesthesia. Extra-bronchial lung synthetic targets were placed percutaneously. Target and airways extracted from CBCT, with planned bronchial parking point close to the target were overlaid on live fluoroscopy. Endobronchial navigation was solely performed under augmented fluoroscopy guidance. A 6.5 Fr steerable sheath was parked in the bronchus per plan, and a flexible MWA probe was inserted coaxially then advanced through the bronchus wall towards the target. Final in-target position was confirmed by CBCT. Only one ablation of 100 W-5 min was performed per target. Animals were euthanized and pathology analysis of the lungs was performed. Results: Eighteen targets with a median largest diameter of 9 mm (interquartile range, 7-11 mm) were ablated in 9 pigs. Median needle-target center distance was 2 mm (interquartile range, 0-4 mm), and was higher for lower/middle than for upper lobes [0 mm (interquartile range, 0-4 mm) vs. 4 mm (interquartile range, 3-8 mm), P=0.04]. No severe complications or pneumothorax occurred. Two cases of rib fractures in the ablation zone resolved after medical treatment. Median longest axis of the ablation zone on post-ablation computed tomography was 38 mm (interquartile range, 30-40 mm). Histology showed coagulation necrosis of ablated tissue. Conclusions: Transbronchial MWA under augmented fluoroscopy guidance using a steerable sheath is feasible and accurate.

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The signal to noise ratio and corresponding visibility of power cables as seen by military aircrafts is critical for crew safety. During low altitude operations, rotorcraft systems must be able to navigate these power lines during flight. Many of these military missions are flown at night which means the reflective bands including the visible, near infrared and short-wave infrared do not provide sufficient light. However, the emissive bands of the mid-wave infrared (MWIR) and long-wave infrared (LWIR) can be used to distinguish the location of these wires. LWIR sensors are typically used for pilotage applications. In both the LWIR and MWIR, the signal to noise depends on the wire emissivity and reflectivity as well as the ground and sky background path radiance. The signal to noise ratio is strongly dependent on the elevation of the viewing angle. In this paper, we model the signal to noise ratio as a function of elevation viewing angle using wire reflectivity and emissivity as well as MODTRAN calculations for path radiance. We also take MWIR and LWIR measurements to compare these two bands to the modelling results. We provide a summary of both model and measurements and make conclusions.

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The main bactericidal components of cold atmospheric plasma (CAP) are thought to be reactive oxygen and nitrogen species (RONS) and UV-radiation, both of which have the capacity to cause DNA damage and mutations. Here, the mutagenic effects of CAP on Escherichia coli were assessed in comparison to X- and UV-irradiation. DNA damage and mutagenesis were screened for using a diffusion-based DNA fragmentation assay and modified Ames test, respectively. Mutant colonies obtained from the latter were quantitated and sequenced. CAP was found to elicit a similar mutation spectrum to X-irradiation, which did not resemble that for UV implying that CAP-produced RONS are more likely the mutagenic component of CAP. CAP treatment was also shown to promote resistance to the antibiotic ciprofloxacin. Our data suggest that CAP treatment has mutagenic effects that may have important phenotypic consequences.

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Airborne target detection in the infrared has been classically known as infrared search and track or IRST. From a military point of view, it can be described as target detection at long ranges where the target image is subpixel in size. Here, the target is "unresolved." It can also describe the detection of aircraft near the observer using distributed apertures in a spherical detection field. From a commercial point of view, an important application is drone detection near live airport operations. As drones become more common, the dual-use functionality of IRST systems is expanding. Technology improvements for IRST systems include the wide proliferation of infrared staring focal planes. New readout integrated circuits allow for time-delay-integration of large format detectors. Stare-step sensors in the future appear to be as common as gimbal-scanned thermal imagers. Detection probability analysis and IRST sensor design is different than targeting system design. We provide a tutorial here on IRST system calculations as well as discussions on broadband versus spectral calculations and new technology considerations.

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The targeting task performance (TTP) model for prediction of target identification range suggests that boost filtering with a well-sampled, low-noise long-wave infrared (LWIR) sensor can substantially increase target ID range (by enhancing contrast at high spatial frequencies). We model a notional high-performance LWIR imaging system with a high F-number, deep electron wells, and a small-pitch focal plane array. System analysis performed with the Night Vision Integrated Performance Model (NVIPM) predicts that a range enhancement upwards of 50% is achievable with Wiener restoration applied to imagery from the modeled sensor. Human perception experiments were performed on simulated target imagery, with range through different boost filters (including a Wiener restoration filter) compared to the no-post-filter case. The TTP model was found to significantly overestimate the performance improvement due to boost and restoration filtering. Alternate predictions based on the Johnson criteria were also performed, and these underestimated the impact of boost. We speculate on reasons for the discrepancy and on promising avenues for future research. Sensor parameters, NVIPM predictions, filter parameters, and experimental data are provided.

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BACKGROUND: Innovative models of family engagement and support are needed in the intensive care unit (ICU) during times of restricted visitation such as the COVID-19 pandemic. Limited understanding of the factors affecting the uptake and outcomes of different family support models hinders the implementation of best practices. We aimed to conduct a rapid pre-implementation evaluation of stakeholder-perceived facilitators and barriers to design implementation strategies to support a novel program using medical students to facilitate family-centered care in the ICU. METHODS: We conducted a 2-step process. In step 1, we gathered contextual data via interview-style open-ended questions sent to clinicians and navigator stakeholders via email. We used electronic data collection due to the physical distancing requirements, the need to prioritize brief data collection for respondent burden, and the need for rapid knowledge gain. A codebook based on the Consolidated Framework for Implementation Research (CFIR), an integrated framework from the field of implementation science, was used to analyze the findings. In step 2, a pilot of the intervention was implemented with 3 navigators over 2 weeks. Implementation strategies were developed to target barriers identified by the pre-implementation evaluation. RESULTS: Fourteen (70%) of the identified stakeholders responded to the survey. Ten constructs encompassing all five CFIR domains were present in responses as implementation influencers, with the Intervention domain most frequently represented. Through these results and operational feedback from navigators during the pilot period, stakeholders selected multiple implementation strategies: audit and provide feedback, develop educational materials, conduct ongoing training, promote adaptability, assess and redesign workflow, identify and prepare champions, and engage community resources. CONCLUSIONS: We demonstrated how a conceptually based pre-implementation program evaluation can be used to rapidly inform optimal implementation strategies. We report key factors to inform design and implementation strategies for a novel ICU family engagement navigator program that may be useful to others wishing to adopt similar programs.

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Plasma polymerization of (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) yields thin films containing stable nitroxide radicals that have properties analogous to that of nitric oxide (NO) without short lifetimes. This property gives TEMPO films a wide variety of potential applications. Typically, control of the final film chemistry is difficult and the plasma discharge conditions must be tailored to in order to maximize the retention of these nitroxide groups during the polymerization and deposition process. In this study, plasma diagnostics and surface analysis of the deposited films were carried out to determine the optimal plasma conditions for the retention of nitroxide groups. These techniques included energy-resolved mass spectrometry, heated planar probe ion current measurements, deposition rate measurements, and x-ray photoelectron spectroscopy (XPS). Results show that operating the plasma with a combination of low input powers and high pressures produces a collisional discharge in which fragmentation of the TEMPO molecule is suppressed, leading to good retention of nitroxide groups. Ion energy distribution functions and quartz crystal microbalance measurements support the soft landing theory of ion deposition on the substrate within this γ-mode, in which the flux of low energy, soft landed ions form the primary contribution to film growth. XPS analysis of deposited polymers shows 75.7% retention of N-O groups in the polymer films deposited in a 25 Pa 5 W discharge.

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OBJECTIVES: The aims of this secondary analysis were to: (a) characterize medication use following hospital discharge for patients with chronic kidney disease (CKD), and (b) investigate relationships of medication use with the primary composite outcome of acute care utilization 90 days after hospitalization. METHODS: The CKD-Medication Intervention Trial (CKD-MIT) enrolled acutely ill hospitalized patients with CKD stages 3-5 not dialyzed (CKD 3-5 ND). In this post hoc analysis, data for medication use were characterized, and the relationship of medication use with the primary outcome was evaluated using Cox proportional hazards models. RESULTS: Participants were taking a mean of 12.6 (standard deviation=5.1) medications, including medications from a wide variety of medication classes. Nearly half of study participants were taking angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARB). ACE inhibitor/ARB use was associated with decreased risk of the primary outcome (hazard ratio=0.51; 95% confidence interval 0.28-0.95; p=0.03) after adjustment for baseline estimated glomerular filtration rate, age, sex, race, blood pressure, albuminuria, and potential nephrotoxin use. CONCLUSIONS: A large number, variety, and complexity of medications were used by hospitalized patients with CKD 3-5 ND. ACE inhibitor or ARB use at hospital discharge was associated with a decreased risk of 90-day acute care utilization.

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Here, a reaction-based indicator displacement hydrogel assay (RIA) was developed for the detection of hydrogen peroxide (H2O2) via the oxidative release of the optical reporter Alizarin Red S (ARS). In the presence of H2O2, the RIA system displayed potent biofilm inhibition for Methicillin-resistant Staphylococcus aureus (MRSA), as shown through an in vitro assay quantifying antimicrobial efficacy. This work demonstrated the potential of H2O2-responsive hydrogels containing a covalently bound diol-based drug for controlled drug release.

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Deposition chemistry from plasma is highly dependent on both the chemistry of the ions arriving at surfaces and the ion energy. Typically, when measuring the energy distribution of ions arriving at surfaces from plasma, it is assumed that the distributions are the same for all ionic species. Using ethyl acetate as a representative organic precursor molecule, we have measured the ion chemistry and ion energy as a function of pressure and power. We show that at low pressure (<2 Pa) this assumption is valid; however, at elevated pressures ion-molecule collisions close to the deposition surface affect both the energy and chemistry of these ions. Smaller ions are formed close to the surface and have lower energy than larger ionic species which are formed in the bulk of the plasma. The changes in plasma chemistry therefore are closely linked to the physics of the plasma-surface interface.