Search

Pamela J McCabe,1 Lynette G Stuart-Mullen,1 Christopher J McLeod,2 Thomas O Byrne,3 Monika M Schmidt,2 Megan E Branda,3 Joan M Griffin3,4 1Mayo Clinic Department of Nursing, Mayo Clinic College of Medicine and Science, Mayo Clinic, Rochester, MN, USA; 2Department of Cardiovascular Diseases, Mayo Clinic College of Medicine and Science, Mayo Clinic, Rochester, MN, USA; 3Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA; 4Division of Healthcare Policy and Research, Mayo Clinic, Rochester, MN, USA Background: Higher levels of patient activation for self-managing health are associated with positive clinical and health care utilization outcomes. Identifying a patient’s activation level can guide clinicians to tailor interventions to improve their health. Effective self-management of atrial fibrillation (AF) requires patient activation to participate in treatment decisions, prevent complications, and manage risk factors. Yet, little is known about activation in patients with AF. The purpose of this descriptive study was to identify patient activation levels and factors associated with activation in patients with AF. Methods: Patients (N=123), 66% male, with a mean (SD) age of 59.9 (11.3) years seeking treatment for AF at an arrhythmia clinic completed the Patient Activation Measure (PAM), Atrial Fibrillation Severity Scale, Knowledge about Atrial Fibrillation test, Hospital Anxiety Depression Scale, Godin Leisure-Time Exercise Questionnaire, and Patient Assessment of Chronic Illness Care. Sociodemographic and clinical data were obtained from medical records. PAM scores were categorized into Levels 1–4. Associations among patient-reported outcomes, sociodemographic, and clinical variables were analyzed using Fisher’s exact tests and Kruskal–Wallis procedures. Results: The PAM scores of nearly half (45.5%) of the patients were at Level 3, while the scores of 38% were at Level 4. Male sex (P=0.02), higher education (P=0.004), being employed (P=0.005), lower body mass index (P=0.03), tobacco abstinence (P=0.02), less AF symptom burden (P=0.006), less depression (P≤0.0001) and anxiety (P=0.006), greater knowledge of AF (P=0.01), and higher levels of physical activity (P=0.02) were associated with higher activation levels. Conclusion: Higher levels of patient activation in those with AF were associated with a more positive health status and educational attainment. Additional research to describe activation in patients with AF is warranted to identify patients at risk for low activation and to tailor interventions to activation level. Keywords: atrial fibrillation, self-management, patient activation, patient engagement, chronic illness care

OBJECTIVE: The purpose of this study was to determine how the range of measured maternal glycemia in pregnancy relates to risk of obesity in childhood. RESEARCH DESIGN AND METHODS: Universal gestational diabetes mellitus (GDM) screening (a 50-g glucose challenge test [GCT]) was performed in two regions (Northwest and Hawaii) of a large diverse HMO during 1995-2000, and GDM was diagnosed/treated using a 3-h 100-g oral glucose tolerance test (OGTT) and National Diabetes Data Group (NDDG) criteria. Measured weight in offspring (n = 9,439) was ascertained 5-7 years later to calculate sex-specific weight-for-age percentiles using U.S. norms (1963-1994 standard) and then classified by maternal positive GCT (1 h >or= 7.8 mmol/l) and OGTT results (1 or >or=2 of the 4 time points abnormal: fasting, 1 h, 2 h, or 3 h by Carpenter and Coustan and NDDG criteria). RESULTS: There was a positive trend for increasing childhood obesity at age 5-7 years (P < 0.0001; 85th and 95th percentiles) across the range of increasing maternal glucose screen values, which remained after adjustment for potential confounders including maternal weight gain, maternal age, parity, ethnicity, and birth weight. The risk of childhood obesity in offspring of mothers with GDM by NDDG criteria (treated) was attenuated compared with the risks for the groups with lesser degrees of hyperglycemia (untreated). The relationships were similar among Caucasians and non-Caucasians. Stratification by birth weight also revealed these effects in children of normal birth weight (

Single-molecule surface-enhanced Raman spectroscopy (SM-SERS) is a powerful experimental technique for label-free sensing, imaging, and chemical analysis. Although Raman spectroscopy itself is an extremely "feeble" phenomenon, the intense interaction of optical fields with metallic nanostructures in the form of plasmonic hotspots can generate Raman signals from single molecules. While what constitutes a true single-molecule signal has taken some years for the scientific community to establish, many SERS experiments, even those not specifically attempting single-molecule sensitivity, have observed fluctuation in both the SERS intensity and spectral features. In this Perspective, we discuss the impact that fluctuating SERS signals have had on the continuing advancement of SM-SERS, along with challenges and current and potential future applications.

Objective: When the expectant mother is faced with an unforeseen event during pregnancy, she may experience emotional fragility and depression. This study was carried out to test the association between the time of diagnosis of critical congenital heart disease (CCHD) and depressive symptoms in puerperal women., Method: A case-control study. All mothers answered a semi-structured questionnaire and the Edinburgh Postnatal Depression Scale (EPDS). Pearson's correlation and multiple linear regression analysis were used to determine factors associated with depression., Results: 50 puerperal women, 23 cases and 27 controls. The proportion of puerperal depressive symptoms was 26.1 % among mothers of infants prenatally diagnosed with CCHD and 77.8 % among mothers of infants postnatally diagnosed (p = 0.001 [OR] 9.917; 95 % CI 2.703-36.379). Multiple linear regression analysis showed that the use of psychotropic drugs and time of diagnosis were significantly associated with puerperal depressive symptoms., Conclusion: Prenatal diagnosis of CCHD was associated with significantly lower levels of depressive symptoms., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Editora Ltda.)

Deformable colloids and macromolecules adsorb at interfaces as they decrease the interfacial energy between the two media. The deformability, or softness, of these particles plays a pivotal role in the properties of the interface. In this study, we employ a comprehensive in situ approach, combining neutron reflectometry with molecular dynamics simulations, to thoroughly examine the profound influence of softness on the structure of microgel Langmuir monolayers under compression. Lateral compression of both hard and soft microgel particle monolayers induces substantial structural alterations, leading to an amplified protrusion of the microgels into the aqueous phase. However, a critical distinction emerges: hard microgels are pushed away from the interface, in stark contrast to the soft ones, which remain firmly anchored to it. Concurrently, on the air-exposed side of the monolayer, lateral compression induces a flattening of the surface of the hard monolayer. This phenomenon is not observed for the soft particles as the monolayer is already extremely flat even in the absence of compression. These findings significantly advance our understanding of the key role of softness on both the equilibrium phase behavior of the monolayer and its effect when soft colloids are used as stabilizers of responsive interfaces and emulsions.

Background: The DiamondTemp ablation (DTA) system is a novel temperature-controlled irrigated radiofrequency (RF) ablation system that accurately measures tip-tissue temperatures for real-time power modulation. Lesion morphologies from longer RF durations with the DTA system have not been previously described. We sought to evaluate lesion characteristics of the DTA system when varying the application durations., Methods: A bench model using porcine myocardium was used to deliver discrete lesions in a simulated clinical environment. The DTA system was power-limited at 50 W with temperature set-points of 50 °C and 60 °C (denoted Group&#95;50 and Group&#95;60). Application durations were randomized with a range of 5-120 s., Results: In total, 280 applications were performed. Steam pops were observed in five applications: two applications at 90 s and three applications at 120 s. Lesion size (depth and maximum width) increased significantly with longer applications, until 60 s for both Group&#95;50 and Group&#95;60 (depth: 4.5 ± 1.2 mm and 5.6 ± 1.3 mm; maximum width: 9.3 ± 2.7mm and 11.2 ± 1.7mm, respectively). As lesions transition from resistive to conductive heating (longer than 10 s), the maximum width progressed in a sub-surface propagation. Using a "Time after Temperature 60 °C" (TaT 60 ) analysis, depths of 2-3 mm occur in 0-5 s and depths plateau at 4.6 ± 0.8 mm between 20 and 30 s., Conclusions: The DTA system rapidly creates wide lesions with lesion depth increasing over time with application durations up to 60 s. Using a TaT 60 approach is a promising ablation guidance that would benefit from further investigation., (© 2023. The Author(s).)

In situ interfacial rheology and numerical simulations are used to investigate microgel monolayers in a wide range of packing fractions, ζ&#95;{2D}. The heterogeneous particle compressibility determines two flow regimes characterized by distinct master curves. To mimic the microgel architecture and reproduce experiments, an interaction potential combining a soft shoulder with the Hertzian model is introduced. In contrast to bulk conditions, the elastic moduli vary nonmonotonically with ζ&#95;{2D} at the interface, confirming long-sought predictions of reentrant behavior for Hertzian-like systems.

IL-12 is a potent cytokine that can promote innate and adaptive anticancer immunity, but its clinical development has been limited by toxicity when delivered systemically. Intratumoral (i.t.) administration can expand the therapeutic window of IL-12 and other cytokines but is in turn limited by rapid drug clearance from the tumor, which reduces efficacy, necessitates frequent administration, and increases systemic accumulation. To address these limitations, we developed an anchored IL-12 designated ANK-101, composed of an engineered IL-12 variant that forms a stable complex with the FDA-approved vaccine adjuvant aluminum hydroxide (Alhydrogel). Following i.t. administration of murine ANK-101 (mANK-101) in early intervention syngeneic mouse tumors, the complex formed a depot that was locally retained for weeks as measured by IVIS or SPECT/CT imaging, while unanchored protein injected i.t. was cleared within hours. One or 2 i.t. injections of mANK-101 induced single-agent antitumor activity across a diverse range of syngeneic tumors, including models resistant to checkpoint blockade at doses where unanchored IL-12 had no efficacy. Local treatment with mANK-101 further induced regressions of noninjected lesions, especially when combined with systemic checkpoint blockade. Antitumor activity was associated with remodeling of the tumor microenvironment, including prolonged IFN-γ and chemokine expression, recruitment and activation of T and NK cells, M1 myeloid cell skewing, and increased antigen processing and presentation. Subcutaneous administration of ANK-101 in cynomolgus macaques was well tolerated. Together, these data demonstrate that ANK-101 has an enhanced efficacy and safety profile and warrants future clinical development.

Background: As the COVID-19 pandemic continues, efforts to better understand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral shedding and transmission in both unvaccinated and vaccinated populations remain critical to informing public health policies and vaccine development. The utility of using real time RT-PCR cycle threshold values (C T values) as a proxy for infectious viral litres from individuals infected with SARS-CoV-2 is yet to be fully understood. This retrospective observational cohort study compares quantitative infectious viral litres derived from a focus-forming viral titre assay with SARS-CoV-2 RT-PCR C T values in both unvaccinated and vaccinated individuals infected with the Delta strain., Methods: Nasopharyngeal swabs positive for SARS-CoV-2 by RT-PCR with a C T value <27 collected from 26 June to 17 October 2021 at the University of Vermont Medical Center Clinical Laboratory for which vaccination records were available were included. Partially vaccinated and individuals <18 years of age were excluded. Infectious viral litres were determined using a micro-focus forming assay under BSL-3 containment., Results: In total, 119 specimens from 22 unvaccinated and 97 vaccinated individuals met all inclusion criteria and had sufficient residual volume to undergo viral titring. A negative correlation between RT-PCR C T values and viral litres was observed in both unvaccinated and vaccinated groups. No difference in mean C T value or viral titre was detected between vaccinated and unvaccinated groups. Viral litres did not change as a function of time since vaccination., Conclusions: Our results add to the growing body of knowledge regarding the correlation of SARS-CoV-2 RNA levels and levels of infectious virus. At similar C T values, vaccination does not appear to impact an individual's potential infectivity when infected with the Delta variant., Competing Interests: All authors report no conflicts of interest relevant to this article., (© 2023 The Authors.)

Previous studies have documented natural infections of SARS-CoV-2 in various domestic and wild animals. More recently, studies have been published noting the susceptibility of members of the Cervidae family, and infections in both wild and captive cervid populations. In this study, we investigated the presence of SARS-CoV-2 in mammalian wildlife within the state of Vermont. 739 nasal or throat samples were collected from wildlife throughout the state during the 2021 and 2022 harvest season. Data was collected from red and gray foxes (Vulpes vulples and Urocyon cineroargentus, respectively), fishers (Martes pennati), river otters (Lutra canadensis), coyotes (Canis lantrans), bobcats (Lynx rufus rufus), black bears (Ursus americanus), and white-tailed deer (Odocoileus virginianus). Samples were tested for the presence of SARS-CoV-2 via quantitative RT-qPCR using the CDC N1/N2 primer set and/or the WHO-E gene primer set. Surprisingly, we initially detected a number of N1 and/or N2 positive samples with high cycle threshold values, though after conducting environmental swabbing of the laboratory and verifying with a second independent primer set (WHO-E) and PCR without reverse transcriptase, we showed that these were false positives due to plasmid contamination from a construct expressing the N gene in the general laboratory environment. Our final results indicate that no sampled wildlife were positive for SARS-CoV-2 RNA, and highlight the importance of physically separate locations for the processing of samples for surveillance and experiments that require the use of plasmid DNA containing the target RNA sequence. These negative findings are surprising, given that most published North America studies have found SARS-CoV-2 within their deer populations. The absence of SARS-CoV-2 RNA in populations sampled here may provide insights in to the various environmental and anthropogenic factors that reduce spillover and spread in North American's wildlife populations., (© 2023. Springer Nature Limited.)

The softness of microgels depends on many aspects, such as particle characteristic lengths, sample concentration, chemical composition of the sample, and elastic moduli of the particle. Here, the response to crowding of ionic microgels is studied. Charged and uncharged ionic microgels are studied in concentrated suspensions of both neutral and ionic microgels with the same swollen size. The combination of small-angle X-ray and neutron scattering with contrast variation allows us to probe both the particle-to-particle arrangement and the response of individual ionic microgels to crowding. When the ionic microgels are uncharged, initial isotropic deswelling followed by faceting is observed. Therefore, the ionizable groups in the polymeric network do not affect the response of the ionic microgel to crowding, which is similar to what has been reported for neutral microgels. In contrast, the kind of microgels composing the matrix plays a key role once the ionic microgels are charged. If the matrix is composed of neutral microgels, a pronounced faceting and negligible deswelling is observed. When only charged ionic microgels are present in the suspension, isotropic deswelling without faceting is dominant.

At the start of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, there was much uncertainty about the role of children in infection and transmission dynamics. Through the course of the pandemic, it became clear that children were susceptible to SARS-CoV-2 infection, although they were experiencing a notable lack of severe disease outcomes as compared to the adult population. This trend held true with the emergence of new SARS-CoV-2 variants, even in paediatric populations that were ineligible to be vaccinated. The difference in disease outcomes has prompted questions about the virological features of SARS-CoV-2 infection in this population. In order to determine if there was any difference in the infectivity of the virus produced by children with coronavirus disease 2019 (COVID-19), we compared viral RNA levels (clinical RT-qPCR C T ) and infectious virus titres from 144 SARS-CoV-2-positive clinical samples collected from children aged 0 to 18 years old. We found that age had no impact on the infectiousness of SARS-CoV-2 within our cohort, with children of all ages able to produce high levels of infectious virus., Competing Interests: The authors declare that there are no conflicts of interest., (© 2023 The Authors.)

This paper presents Project PHoENIX, which stands for Participatory, Human-centered, Equitable, Neurodiverse, Inclusive, eXtended reality. The project aims to co-produce research with autistic users to create a virtual reality (VR) environment that is highly usable, accessible, and sensitive to the needs and preferences of these individuals. Project PHoENIX utilizes participatory design within a learning experience design (LXD) frame to locate autistic people, their caregivers, and providers centrally in the processes of immersive technology design and development, as well as research design and execution. An overarching literature review on VR and autism and issues of limited design precedent of VR environments with autistic participants is provided, as well as details on the Project PHoENIX design framework, project description, and project design outcomes. Details are provided on how the online VR environment was co-designed and co-developed through collaborative research with autistic stakeholders while being sensitive to their needs and preferences. Research findings and implications are discussed regarding the design process, constraints, principles, and insights. The paper concludes by discussing lessons learned and how this project can provide much-needed design precedent for advancing the field towards a more inclusive, human-centered, and neurodiverse VR research and development paradigms., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© Association for Educational Communications & Technology 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Major advances have been seen in techniques and devices for performing percutaneous coronary interventions (PCIs) for chronic total occlusions (CTOs), but there are limited real-world practice data from developing countries., Objectives: To report clinical and angiographic characteristics, procedural aspects, and clinical outcomes of CTO PCI performed at dedicated centers in Brazil., Methods: Included patients underwent CTO PCI at centers participating in the LATAM CTO Registry, a Latin American multicenter registry dedicated to prospective collection of these data. Inclusion criteria were procedures performed in Brazil, age 18 years or over, and presence of CTO with PCI attempt. CTO was defined as a 100% lesion in an epicardial coronary artery, known or estimated to have lasted at least 3 months., Results: Data on 1196 CTO PCIs were included. Procedures were performed primarily for angina control (85%) and/or treatment of moderate/severe ischemia (24%). Technical success rate was 84%, being achieved with antegrade wire approaches in 81% of procedures, antegrade dissection and re-entry in 9%, and retrograde approaches in 10%. In-hospital adverse cardiovascular events occurred in 2.3% of cases, with a mortality rate of 0.75%., Conclusions: CTOs can be treated effectively in Brazil by using PCI, with low complication rates. The scientific and technological development observed in this area in the past decade is reflected in the clinical practice of dedicated Brazilian centers.

The concept of plasmonic "hotspots" is central to the broad field of nanophotonics. In surface-enhanced Raman scattering (SERS), hotspots can increase Raman scattering efficiency by orders of magnitude. Hotspot dimensions may range from a few nanometers down to the atomic scale and are able to generate SERS signals from single molecules. However, these single-molecule SERS signals often show significant fluctuations, and the concept of intense, localized, yet static hotspots has come into question. Recent experiments have shown these SERS intensity fluctuations (SIFs) to occur over an extremely wide range of timescales, from seconds to microseconds, due to the various physical mechanisms causing SERS and the dynamic nature of light-matter interaction at the nanoscale. The underlying source of single-molecule SERS fluctuations is therefore likely to be a complex interplay of several different effects at different timescales. A high-speed acquisition system that captures a full SERS spectrum with microsecond time resolution can therefore provide information about these dynamic processes. Here, we show an acquisition system that collects at a rate of 100,000 SERS spectra per second, allowing high-speed characterization. We find that while each individual SIF event will enhance a different portion of the SERS spectrum, including a single peak, over 10s to 100s of microseconds, the SIF events overall do not favor one region of the spectrum over another. These high-speed SIF events can therefore occur with relatively equal probability over a broad spectral range, covering both the anti-Stokes and the Stokes sides of the spectrum, sometimes leading to anomalously large anti-Stokes peaks. This indicates that both temporally and spectrally transient hotspots drive the SERS fluctuations at high speeds.

Objective: This study's aim was to verify whether a psychoeducational intervention, with a brief expressive posttraumatic growth (PTG) component, could reduce heart failure (HF) patients' hospital readmissions and promote their quality of life (QoL) and PTG., Methods: It adopted a parallel randomized clinical trial design, and its participants comprised HF patients from a hospital in Southern Brazil. All the participants completed the World Health Organization Quality of Life Assessment and Posttraumatic Growth Inventory questionnaires at the pre (T1: baseline) and post (T2) assessments of the intervention. Although patients in the control group (CG) underwent only regular outpatient consultations, those in the intervention group (IG) supplemented their regular consultations, with two additional individual visits to promote health and psychological education. At the 1-year follow-up, hospital readmissions were assessed., Results: Of the 142 patients recruited at baseline (72 and 70 in the CG and IG, respectively), as 19 dropped out at follow-up, only 123 (63 and 60 in the CG and IG, respectively) were reassessed after approximately 378 days. They included 65% men aged 64 (11) years, 58% had low incomes, and 67% had less than high school education. The IG participants' risk of readmission got reduced by 52% ( p = .023), and they also showed significant improvements in their total QoL and positive psychological growth at the 6-month follow-up assessment., Conclusions: The two-session psychoeducational intervention proved to be protective for Southern Brazilian HF patients in the IG, as it effectively reduced their hospital readmission rates by half compared with the CG, as well as improved their QoL and promoted their positive psychological growth., Trial Registration: ClinicalTrials.gov identifier: NCT04870918 ., (Copyright © 2023 by the American Psychosomatic Society.)

Introduction: Contact force has been used to titrate lesion formation for radiofrequency ablation. Pulsed field ablation (PFA) is a field-based ablation technology for which limited evidence on the impact of contact force on lesion size is available., Methods: Porcine hearts (n = 6) were perfused using a modified Langendorff set-up. A prototype focal PFA catheter attached to a force gauge was held perpendicular to the epicardium and lowered until contact was made. Contact force was recorded during each PFA delivery. Matured lesions were cross-sectioned, stained, and the lesion dimensions measured., Results: A total of 82 lesions were evaluated with contact forces between 1.3 and 48.6 g. Mean lesion depth was 4.8 ± 0.9 mm (standard deviation), mean lesion width was 9.1 ± 1.3 mm, and mean lesion volume was 217.0 ± 96.6 mm 3 . Linear regression curves showed an increase of only 0.01 mm in depth (depth = 0.01 × contact force + 4.41, R 2  = 0.05), 0.03 mm in width (width = 0.03 × contact force + 8.26, R 2  = 0.13) for each additional gram of contact force, and 2.20 mm 3 in volume (volume = 2.20 × contact force + 162, R 2  = 0.10)., Conclusion: Increasing contact force using a bipolar, biphasic focal PFA system has minimal effects on acute lesion dimensions in an isolated porcine heart model and achieving tissue contact is more important than the force with which that contact is made., (© 2023 Medtronic Inc and The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Background and Aims: The dynamics and implications of intracoronary thrombus constituency in patients with ST-segment elevation myocardial infarction (STEMI) are not fully understood. We evaluated the expression of CD34, CD61and factor VIII surface markers in thrombi of patients with STEMI and its association with clinical and angiographic characteristics and major adverse cardiovascular events (MACE)., Methods: Patients presenting with STEMI undergoing aspiration thrombectomy during primary percutaneous coronary intervention (pPCI) were included. Morphological, histopathological and immunohistochemical aspects of thrombi were assessed by two pathologists blinded to clinical variables and outcomes., Results: The mean age of the 245 patients included was 58 ± 12 years old, and 70 % were men. Regarding the thrombi microscopic patterns, 61 % were classified as recent, 20 % as lytic and 19 % as organized. There were higher levels of the CD61 index in patients with a history of heart failure. Smokers presented lower CD61 positive cells and CD61 index, but this association did not remain significant after multivariable analysis. There was an inverse correlation between CD61 positive cells and CD61 index with the time from onset of pain to the first medical contact, but no other significant association amongst clinical characteristics and antigenic expression. There was higher expression of the CD61 antigen in patients with in-hospital MACE, but statistical significance was borderline (p = 0.06)., Conclusions: In this cohort of patients with STEMI, immunohistochemistry of coronary thrombus showed a significantly higher platelet content in patients with previous heart failure and a trend in those with in-hospital MACE. Thrombus' platelet content was inversely related to ischemic time., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

The structural characterization of microgels at interfaces is fundamental to understand both their 2D phase behavior and their role as stabilizers that enable emulsions to be broken on demand. However, this characterization is usually limited by available experimental techniques, which do not allow a direct investigation at interfaces. To overcome this difficulty, here we employ neutron reflectometry, which allows us to probe the structure and responsiveness of the microgels in-situ at the air-water interface. We investigate two types of microgels with different cross-link density, thus having different softness and deformability, both below and above their volume phase transition temperature, by combining experiments with computer simulations of in silico synthesized microgels. We find that temperature only affects the portion of microgels in water, while the strongest effect of the microgels softness is observed in their ability to protrude into the air. In particular, standard microgels have an apparent contact angle of few degrees, while ultra-low cross-linked microgels form a flat polymeric layer with zero contact angle. Altogether, this study provides an in-depth microscopic description of how different microgel architectures affect their arrangements at interfaces, and will be the foundation for a better understanding of their phase behavior and assembly., (© 2022. The Author(s).)

Introduction: On-target, off-tumor toxicity severely limits systemic dosing of cytokines and agonist antibodies for cancer. Intratumoral administration is increasingly being explored to mitigate this problem. Full exploitation of this mode of administration must include a mechanism for sustained retention of the drug; otherwise, rapid diffusion out of the tumor eliminates any advantage., Areas Covered: We focus here on strategies for anchoring immune agonists in accessible formats. Such anchoring may utilize extracellular matrix components, cell surface receptor targets, or exogenously administered particulate materials. Promising alternative strategies not reviewed here include slow release from the interior of a material depot, expression following local transfection, and conditional proteolytic activation of masked molecules., Expert Opinion: An effective mechanism for tissue retention is a critical component of intratumorally anchored cytokine therapy, as leakage leads to decreased tumor drug exposure and increased systemic toxicity. Matching variable drug release kinetics with receptor-mediated cellular uptake is an intrinsic requirement for the alternative strategies mentioned above. Bioavailability of an anchored form of the administered drug is key to obviating this balancing act.

Anisotropic, submicrometer-sized particles are versatile systems providing interesting features in creating ordering in two-dimensional systems. Combining hard ellipsoids with a soft shell further enhances the opportunities to trigger and control order and alignment. In this work, we report rich 2D phase behavior and show how softness affects the ordering of anisotropic particles at fluid oil-water interfaces. Three different core-shell systems were synthesized such that they have the same elliptical hematite-silica core but differ with respect to thickness and stiffness of the soft microgel shell. Compression isotherms, the shape of individual core-shell microgels, and their 2D order at a decane-water interface are investigated by means of the Langmuir-Blodgett technique combined with ex-situ atomic force microscopy (AFM) imaging as well as dissipative particle dynamics (DPD) simulations. We show how the softness, size, and anisotropy of the microgel shell affect the side-to-side vs tip-to-tip ordering of anisotropic hybrid microgels as well as the alignment with respect to the direction of compression in the Langmuir trough. A large, soft microgel shell leads to an ordered structure with tip-to-tip alignment directed perpendicular to the direction of compression. In contrast, a thin and harder microgel shell leads to side-to-side ordering orientated parallel to the compression direction. In addition, the thin and harder microgel shell induces clustering of the microgels in the dilute state, indicating the presence of strong capillary interactions. Our findings highlight the relevance of softness for the complex ordering of anisotropic hybrid microgels at interfaces.

With the COVID-19 pandemic caused by SARS-CoV-2 now in its second year, there remains an urgent need for diagnostic testing that can identify infected individuals, particularly those who harbor infectious virus. Various RT-PCR strategies have been proposed to identify specific viral RNA species that may predict the presence of infectious virus, including detection of transcriptional intermediates (e.g., subgenomic RNA [sgRNA]) and replicative intermediates (e.g., negative-strand RNA species). Using a novel primer/probe set for detection of subgenomic (sg)E transcripts, we successfully identified 100% of specimens containing culturable SARS-CoV-2 from a set of 126 clinical samples (total sgE C T values ranging from 12.3 to 37.5). This assay showed superior performance compared to a previously published sgRNA assay and to a negative-strand RNA assay, both of which failed to detect target RNA in a subset of samples from which we isolated live virus. In addition, total levels of viral RNA (genome, negative-strand, and sgE) detected with the WHO/Charité primer-probe set correlated closely with levels of infectious virus. Specifically, infectious virus was not detected in samples with a C T above 31.0. Clinical samples with higher levels of viral RNA also displayed cytopathic effect (CPE) more quickly than those with lower levels of viral RNA. Finally, we found that the infectivity of SARS-CoV-2 samples is significantly dependent on the cell type used for viral isolation, as Vero E6 cells expressing TMRPSS2 extended the analytical sensitivity of isolation by more than 3 C T compared to parental Vero E6 cells and resulted in faster isolation. Our work shows that using a total viral RNA Ct cutoff of > 31 or specifically testing for sgRNA can serve as an effective rule-out test for the presence of culturable virus., (© 2021 The Authors. Published under the terms of the CC BY 4.0 license.)

Objective: Anger may cause adverse cardiovascular responses, but the effects of anger management on clinical cardiovascular outcomes are insufficiently understood. We sought to assess the influence of anger management through a cognitive behavioral intervention on endothelial function in patients with a recent myocardial infarction (MI)., Methods: Patients with ST-elevation MI and a low anger control score were enrolled during hospitalization in a randomized, parallel, controlled clinical trial. Intervention was anger management with cognitive behavioral techniques implemented by a psychologist in two individual monthly sessions. The primary end point was the between-group difference in the variation of flow-mediated dilation (FMD) in the brachial artery from baseline to the 3-month follow-up. The second end point comprised major cardiovascular events at 24-month follow-up., Results: A total of 43 patients (age = 56 [9] years; 23.3% women) were randomized to the intervention group and 47 patients (age = 58 [10] years; 19.1% women) to the control group. Baseline clinical characteristics were not statistically different between groups. Both groups showed a significant improvement in anger control from baseline to end point; however, the difference in intergroup variation was not statistically significant. The difference in FMD variation from baseline to the 3-month follow-up was significantly higher in the intervention group. The partial η2 was 0.057 (p = .024), indicating a medium effect size. There was no difference between groups regarding major cardiovascular events., Conclusions: Anger management by cognitive behavioral techniques may improve endothelial function in post-MI patients with low anger control, but it remains unclear via which mechanism these effects occurred. Further studies with larger numbers of patients, assessments of changes in anger, improved comparability of preintervention FMD, and longer follow-up are warranted.Trial Registration:ClinicalTrials.gov identifier: NCT02868216., (Copyright © 2021 by the American Psychosomatic Society.)

Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants pose a challenge to controlling the COVID-19 pandemic. Previous studies indicate that clinical samples collected from individuals infected with the Delta variant may contain higher levels of RNA than previous variants, but the relationship between levels of viral RNA and infectious virus for individual variants is unknown. We measured infectious viral titer (using a microfocus-forming assay) and total and subgenomic viral RNA levels (using RT-PCR) in a set of 162 clinical samples containing SARS-CoV-2 Alpha, Delta, and Epsilon variants that were collected in identical swab kits from outpatient test sites and processed soon after collection. We observed a high degree of variation in the relationship between viral titers and RNA levels. Despite this, the overall infectivity differed among the three variants. Both Delta and Epsilon had significantly higher infectivity than Alpha, as measured by the number of infectious units per quantity of viral E gene RNA (5.9- and 3.0-fold increase; P < 0.0001, P = 0.014, respectively) or subgenomic E RNA (14.3- and 6.9-fold increase; P < 0.0001, P = 0.004, respectively). In addition to higher viral RNA levels reported for the Delta variant, the infectivity (amount of replication competent virus per viral genome copy) may be increased compared to Alpha. Measuring the relationship between live virus and viral RNA is an important step in assessing the infectivity of novel SARS-CoV-2 variants. An increase in the infectivity for Delta may further explain increased spread, suggesting a need for increased measures to prevent viral transmission., Competing Interests: Competing interest statement: K.R.J. and A.L.G. report contract testing from Abbot, and A.L.G. reports research support from Merck and Gilead., (Copyright © 2022 the Author(s). Published by PNAS.)

Shared decision making (SDM) has been advocated to improve patient care, patient decision acceptance, patient-provider communication, patient motivation, adherence, and patient reported outcomes. Documentation of SDM is endorsed in several society guidelines and is a condition of reimbursement for selected cardiovascular and cardiac arrhythmia procedures. However, many clinicians argue that SDM already occurs with clinical encounter discussions or the process of obtaining informed consent and note the additional imposed workload of using and documenting decision aids without validated tools or evidence that they improve clinical outcomes. In reality, SDM is a process and can be done without decision tools, although the process may be variable. Also, SDM advocates counter that the low-risk process of SDM need not be held to the high bar of demonstrating clinical benefit and that increasing the quality of decision making should be sufficient. Our review leverages a multidisciplinary group of experts in cardiology, cardiac electrophysiology, epidemiology, and SDM, as well as a patient advocate. Our goal is to examine and assess SDM methodology, tools, and available evidence on outcomes in patients with heart rhythm disorders to help determine the value of SDM, assess its possible impact on electrophysiological procedures and cardiac arrhythmia management, better inform regulatory requirements, and identify gaps in knowledge and future needs.

The uterine myometrium is the rarest location for an ectopic pregnancy resulting in the so-called ' intramural or intramyometrial ectopic pregnancy '. It presents a particular diagnostic and therapeutic challenge for the treating physician. If passed undiagnosed can lead to life-threatening uterine rupture, which may warrant hysterectomy, leaving the woman with irreversible infertility. Different treatment modalities have been proposed for the management of this condition. In this case report, we are describing a rare case of intramural ectopic pregnancy and reporting the use of hysteroscopy for the surgical management of this case for the first time in the literature., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

There is an urgent need for antiviral agents that treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We screened a library of 1900 clinically safe drugs against OC43, a human beta coronavirus that causes the common cold, and evaluated the top hits against SARS-CoV-2. Twenty drugs significantly inhibited replication of both viruses in cultured human cells. Eight of these drugs inhibited the activity of the SARS-CoV-2 main protease, 3CLpro, with the most potent being masitinib, an orally bioavailable tyrosine kinase inhibitor. X-ray crystallography and biochemistry show that masitinib acts as a competitive inhibitor of 3CLpro. Mice infected with SARS-CoV-2 and then treated with masitinib showed >200-fold reduction in viral titers in the lungs and nose, as well as reduced lung inflammation. Masitinib was also effective in vitro against all tested variants of concern (B.1.1.7, B.1.351, and P.1)., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

The residue from chicken mechanically separated meat (MSM) is a potential source for the extraction of collagen. However, this process requires the removal of many covalent crosslinks, which makes it quite complex. Ultrasound has been successfully used to extract collagen; it reduces the process time and increases the yield. However, information regarding the effects of this treatment on the structural and functional properties of proteins is still very limited. Therefore, the aims of the present study were to obtain collagen from chicken MSM residue and to test the effects of pre-treatment with ultrasonic probe and enzymatic extraction with pepsin in its yield, as well as to evaluate the properties of extracted collagen using gel electrophoresis, Fourier-transform infrared spectroscopy, solubility, and differential scanning calorimetry. Both the ultrasound and the enzymatic extraction had a positive effect on the extraction yield of collagen from chicken MSM residue without affecting its integrity. Using ultrasound led to an increase of up to 40% in yield when compared to treatments without ultrasound application. Five extraction treatments were considered. The extracted collagen exhibited high thermal stability (43.9-47.0 °C) and mainly type I structure. The use of ultrasound as pre-treatment, together with enzymatic extraction with pepsin, were effective in increasing the extraction yield of collagen from chicken MSM residue, as well as preserving the triple helical structure of the native collagen., (© Association of Food Scientists & Technologists (India) 2020.)

[Figure: see text].

ATP-Citrate-Lyase is a key enzyme of cholesterol biosynthesis. Its liver-specific inhibition by the bempedoic acid opens new possibilities to effectively escalate a cholesterol-lowering therapy while avoiding muscle-related side effects. Herein, we present the properties of this new first-in-class pharmaceutical agent and discuss potential consequences for pharmacotherapy., Competing Interests: A. El-Armouche weist auf Forschungs- und/oder Vortragstätigkeiten hin für Boehringer Ingelheim, Novartis, Bayer, Novo Nordisk, Sanofi Aventis, Daiichi Sankyo und Berlin Chemie. Die anderen Autorinnen/Autoren geben keinen Interessenkonflikt an., (Thieme. All rights reserved.)

Background: People with atrial fibrillation (AF) have lower reported quality of life and increased risk of heart attack, death, and stroke. Lifestyle modifications can improve arrhythmia-free survival/symptom severity. Shared medical appointments (SMAs) have been effective at targeting lifestyle change in other chronic diseases and may be beneficial for patients with AF., Objective: To determine if perceived self-management and satisfaction with provider communication differed between patients who participated in SMAs compared to patients in standard care. Secondary objectives were to examine differences between groups for knowledge about AF, symptom severity, and healthcare utilization., Methods: We conducted a retrospective analysis of data collected where patients were assigned to either standard care (n = 62) or a SMA (n = 59). Surveys were administered at pre-procedure, 3, and 6 months., Results: Perceived self-management was not significantly different at baseline (p = 0.95) or 6 months (p = 0.21). Patients in SMAs reported more knowledge gain at baseline (p = 0.01), and higher goal setting at 6 months (p = 0.0045). Symptom severity for both groups followed similar trends., Conclusion: Patients with AF who participated in SMAs had similar perceived self-management, patient satisfaction with provider communication, symptom severity, and healthcare utilization with their counterparts, but had a statistically significant improvement in knowledge about their disease., Competing Interests: The authors have declared that no competing interests exist.

Background/aim: Postoperative infection in implant-based reconstructive breast surgery is a common problem. The preoperative application of a disinfecting washing agent may reduce postoperative infection rates. This retrospective analysis aimed to evaluate whether preoperative Octenisan ® application yields a reduction in postoperative complications or infection rates in breast reconstructive surgery., Patients and Methods: Between 2016 and 2019, 127 women received implant-based breast reconstruction at the municipal hospital of Cologne, Holweide, Germany. A total of 197 treatments were performed. After giving consent, patients were asked to use Octenisan ® wash lotion for five days before breast reconstructive surgery. All patients were asked by a simple questionnaire whether they performed showering and washing according to the proposed protocol. In 96 cases patients did adhere to the protocol. In 101 cases they did not. Patient cohorts were then divided into patients who had applied Octenisan ® wash lotion and patients who had not. Endpoints were defined as minor complications with no implant loss and major complications with consecutive implant loss., Results: Patient adherence to the application regimen was 48.7%. Overall minor complications occurred in 34.4% with preoperative Octenidine usage and 36.6% without preoperative Octenidine usage. Major complications happened in 7% with preoperative Octenidine and 5% without Octenidine. Overall, there was no significant difference concerning minor or major complication rates., Conclusion: Preoperative washing protocols involving the Octenisan ® wash lotion is relatively cheap and easy to follow. There is evidence that washing protocols result in a reduction of S. aureus infections leading to a better perioperative outcome. Octenisan ® is safe to use in implant-based breast reconstructive surgery and is not associated with higher risks for patients. Our study did not yield any significant reduction in perioperative and postoperative complication and infection rates. This is attributed to a relatively low study population. Wash lotion compliance was only 48.7%. Proper patient education is crucial. With those preliminary data, it is now possible to design a larger analysis since patient adherence to washing protocol with Octenisan ® wash lotion has been established., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: The purpose of this study was to compare the incidence of, and adjusted hazards for, cardiometabolic morbidities among adults with and without cerebral palsy or spina bifida., Methods: Privately insured beneficiaries were included if they had an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic code for cerebral palsy or spina bifida (n = 15,302). Adults without cerebral palsy or spina bifida were also included (n = 1,935,480). Incidence estimates of common cardiometabolic morbidities were compared at 4 years of enrollment. Survival models were used to quantify unadjusted and adjusted hazard ratios (HRs) for incident cardiometabolic morbidities., Results: Adults living with cerebral palsy or spina bifida had a higher 4-year incidence of any cardiometabolic morbidity (41.5% vs 30.6%) as compared to adults without cerebral palsy or spina bifida, and differences were to a clinically meaningful extent. Fully adjusted survival models demonstrated that adults with cerebral palsy or spina bifida had a greater hazard for any cardiometabolic morbidity (HR: 1.52; 95% confidence interval [CI]: 1.47, 1.57), and all but 1 cardiometabolic disorder (nonalcoholic fatty liver disease) and ranged from HR: 1.20 (1.15, 1.25) for hypercholesterolemia to HR: 1.86 (1.74, 1.98) for heart failure., Conclusions: Adults with cerebral palsy or spina bifida have a significantly higher incidence of, and risk for, common cardiometabolic morbidities, as compared to adults without cerebral palsy or spina bifida. Efforts are needed to facilitate the development of improved clinical screening algorithms and early interventions to reduce risk of cardiometabolic disease onset and progression in these higher-risk populations., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently identified coronavirus that causes the respiratory disease known as coronavirus disease 2019 (COVID-19). Despite the urgent need, we still do not fully understand the molecular basis of SARS-CoV-2 pathogenesis. Here, we comprehensively define the interactions between SARS-CoV-2 proteins and human RNAs. NSP16 binds to the mRNA recognition domains of the U1 and U2 splicing RNAs and acts to suppress global mRNA splicing upon SARS-CoV-2 infection. NSP1 binds to 18S ribosomal RNA in the mRNA entry channel of the ribosome and leads to global inhibition of mRNA translation upon infection. Finally, NSP8 and NSP9 bind to the 7SL RNA in the signal recognition particle and interfere with protein trafficking to the cell membrane upon infection. Disruption of each of these essential cellular functions acts to suppress the interferon response to viral infection. Our results uncover a multipronged strategy utilized by SARS-CoV-2 to antagonize essential cellular processes to suppress host defenses., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

The phase behavior of supersoft spheres is explored using solutions of ultralow cross-linked poly(N-isopropylacrylamide)-based microgels as a model system. For these microgels, the effects of the electric charges on their surfaces can be neglected and therefore only the role of softness on the phase behavior is investigated. The samples show a liquid-to-crystal transition at higher volume fraction with respect to both hard spheres and stiffer microgels. Furthermore, stable body centered cubic (bcc) crystals are observed in addition to the expected face centered cubic (fcc) crystals. Small-angle x-ray and neutron scattering with contrast variation allow the characterization of both the microgel-to-microgel distance and the architecture of single microgels in crowded solutions. The measurements reveal that the stable bcc crystals depend on the interplay between the collapse and the interpenetration of the external shell of the ultralow cross-linked microgels.

Background: Women seem to be more susceptible to psychosocial stress than men, and stress is associated with worse outcomes after acute myocardial infarction (AMI)., Objectives: To investigate whether the female gender is an independent predictor of risk for stress and to compare stress levels between women and men after AMI., Methods: Cross-sectional study of a case series. Patients aged 18 to 65 years who were treated for AMI at the study facility between January 2017 and June 2018 were eligible. The presence of stress was assessed using Lipp's Stress Symptoms Inventory for Adults (ISSL), which categorizes stress into four phases (alertness, resistance, near-exhaustion, and exhaustion), through a list of physical and psychological symptoms. Data were analyzed using SPSS Version 24.0. The significance level was set at p<0.05., Results: Of the 330 respondents, 89% of women and 70% of men experienced stress. The female gender was associated with nearly threefold higher odds of experiencing stress (EXP (B)2.79, p = 0.02). Regarding the phases of stress, women were more often in the near-exhaustion and exhaustion phases, while men were more often in the resistance phase., Conclusions: This study showed that women are most often in the third and fourth phases of stress, i.e., in situations of long-standing psychosocial stress. These findings can assist in the development of gender-specific strategies for health promotion and disease prevention, aiming to minimize the effects of stress in this population.

The role of electrostatics on the interfacial properties of polyelectrolyte microgels has been discussed controversially in the literature. It is not yet clear if, or how, Coulomb interactions affect their behavior under interfacial confinement. In this work, we combine compression isotherms, atomic force microscopy imaging, and computer simulations to further investigate the behavior of pH-responsive microgels at oil-water interfaces. At low compression, charged microgels can be compressed more than uncharged microgels. The in-plane effective area of charged microgels is found to be smaller in comparison to uncharged ones. Thus, the compressibility is governed by in-plane interactions of the microgels with the interface. At high compression, however, charged microgels are less compressible than uncharged microgels. Microgel fractions located in the aqueous phase interact earlier for charged than for uncharged microgels because of their different swelling perpendicular to the interface. Therefore, the compressibility at high compression is controlled by out-of-plane interactions. In addition, the size of the investigated microgels plays a pivotal role. The charge-dependent difference in compressibility at low compression is only observed for small but not for large microgels, while the behavior at high compression does not depend on the size. Our results highlight the complex nature of soft polymer microgels as compared to rigid colloidal particles. We clearly demonstrate that electrostatic interactions affect the interfacial properties of polyelectrolyte microgels.

Infections often impact care of hospice patients; however, limited guidance exists for end-of-life infection management. Regardless of patient prognosis, appropriate antibiotic use is necessary for maintaining quality of life. Antibiotics may be associated with serious adverse events, posing safety risks to patients that should be factored into the appropriateness determination. Fluoroquinolone antibiotics are prescribed frequently in hospice. There are 8 fluoroquinolone drug safety warnings regarding risk for serious adverse events communicated by the US Food and Drug Administration. A retrospective chart review at a hospice pharmacy services provider identified decedents who used a fluoroquinolone during a 1-month period. Charts were evaluated for the presence of risk factors for serious adverse events, including advanced age (86.0%), orders for multiple QTc prolongation risk medications (51.5%), hypertension (64.1%), and concomitant corticosteroids (22.9%). Findings demonstrate notable risk with the use of at least 1 class of antibiotics in a hospice population. STAMPS is a hospice decision support tool, developed to guide symptom-driven antibiotic use that incorporates safety assessment and individual goals of care into infection management planning. The tool can also serve as a framework for patient-centered communications about appropriate antibiotic use in hospice between providers, patients, and families.