Diabetic Cardiomyopathy and Cell Death: Focus on Metal-Mediated Cell Death.

Cardiac myocyte death is an essential initiator of the pathogenesis and progression of various etiological cardiomyopathies, including diabetic cardiomyopathy (DCM), a disease that has been reported since 1972. Cardiac cell death has been detected in the hearts of patients with diabetes and in animal models, and the role of cell death in the pathogenesis of DCM has been extensively investigated. The first review by the authors, specifically focusing on "Cell death and diabetic cardiomyopathy," was published in the journal, Cardiovascular Toxicology in 2003. Over the past two decades, studies investigating the role of cardiac cell death in the pathogenesis of DCM have gained significant attention, resulting in the discovery of several new kinds of cell death involving different mechanisms, including apoptosis, necroptosis, pyroptosis, autophagy, ferroptosis, and cuproptosis. After the 20th anniversary of the review published in 2003, we now provide an update with a focus on the potential role of metal-mediated cell death, ferroptosis, and cuproptosis in the development of DCM in compliance with this special issue. The intent of our review is to further stimulate work in the field to advance the body of knowledge and continue to drive efforts to develop more advanced therapeutic approaches to prevent cell death, particularly metal-dependent cell death, and, ultimately, to reduce or prevent the development of DCM.

Comparison of Dose-Response Relationships for Two Isolates of SARS-CoV-2 in a Nonhuman Primate Model of Inhalational COVID-19.

Background: As the COVID-19 pandemic has progressed, numerous variants of SARS-CoV-2 have arisen, with several displaying increased transmissibility. Methods: The present study compared dose-response relationships and disease presentation in nonhuman primates infected with aerosols containing an isolate of the Gamma variant of SARS-CoV-2 to the results of our previous study with the earlier WA-1 isolate of SARS-CoV-2. Results: Disease in Gamma-infected animals was mild, characterized by dose-dependent fever and oronasal shedding of virus. Differences were observed in shedding in the upper respiratory tract between Gamma- and WA-1-infected animals that have the potential to influence disease transmission. Specifically, the estimated median doses for shedding of viral RNA or infectious virus in nasal swabs were approximately 10-fold lower for the Gamma variant than the WA-1 isolate. Given that the median doses for fever were similar, this suggests that there is a greater difference between the median doses for viral shedding and fever for Gamma than for WA-1 and potentially an increased range of doses for Gamma over which asymptomatic shedding and disease transmission are possible. Conclusions: These results complement those of previous studies, which suggested that differences in exposure dose may help to explain the range of clinical disease presentations observed in individuals with COVID-19, highlighting the importance of public health measures designed to limit exposure dose, such as masking and social distancing. The dose-response data provided by this study are important to inform disease transmission and hazard modeling, as well as to inform dose selection in future studies examining the efficacy of therapeutics and vaccines in animal models of inhalational COVID-19.

Traveling tunable laser projector for UV-blue disinfection dose determinations.

As the COVID-19 pandemic was overtaking the world in the spring of 2020, the National Institute of Standards and Technology (NIST) began collaborating with the National Biodefense Analysis and Countermeasures Center to study the inactivation of SARS-CoV-2 after exposure to different ultraviolet (UV) and blue light wavelengths. This paper describes a 1 kHz pulsed laser and projection system used to study the doses required to inactive SARS-CoV-2 over the wavelength range of 222 to 488 nm. This paper builds on NIST's previous work for water pathogen inactivation using UV laser irradiation. The design of the laser and projection system and its performance in a Biosafety Level 3 (BSL-3) laboratory are given. The SARS-CoV-2 inactivation results (published elsewhere by Schuit, M.A., et al., expected 2022) demonstrate that a tunable laser projection system is an invaluable tool for this research.

SARS-CoV-2 inactivation by ultraviolet radiation and visible light is dependent on wavelength and sample matrix.

Numerous studies have demonstrated that SARS-CoV-2 can be inactivated by ultraviolet (UV) radiation. However, there are few data available on the relative efficacy of different wavelengths of UV radiation and visible light, which complicates assessments of UV decontamination interventions. The present study evaluated the effects of monochromatic radiation at 16 wavelengths from 222 nm through 488 nm on SARS-CoV-2 in liquid aliquots and dried droplets of water and simulated saliva. The data were used to generate a set of action spectra which quantify the susceptibility of SARS-CoV-2 to genome damage and inactivation across the tested wavelengths. UVC wavelengths (≤280 nm) were most effective for inactivating SARS-CoV-2, although inactivation rates were dependent on sample type. Results from this study suggest that UV radiation can effectively inactivate SARS-CoV-2 in liquids and dried droplets, and provide a foundation for understanding the factors which affect the efficacy of different wavelengths in real-world settings.

Use of fetal tele-echo at small regional hospitals increases the rate of prenatal diagnosis of congenital heart disease.

BACKGROUND: To improve the rate of prenatal diagnosis of Congenital heart disease (CHD) in Kentucky, four fetal tele-echocardiography sites were established at regional hospitals in Kentucky: Ashland in 2011, Paducah in 2014, Lexington in 2014, and Owensboro in 2016. METHODS: A 13-year retrospective review of medical records at Norton Children's Hospital was performed to identify patients with CHD who had cardiac surgery or intervention prior to one year of age. The rate of prenatal diagnosis prior to establishing any fetal tele-echocardiography sites was compared to the rate of prenatal diagnosis after the sites were established. Independent t-tests were used to determine if there was a statistically significant increase in the rate of prenatal diagnosis. RESULTS: 1287 patients had cardiac surgery or cath lab intervention prior to one year of age at our institution from June 2005 to December 2018 and were included in the analysis. Seventeen patients were excluded due to incomplete medical records. The rate of prenatal diagnosis prior to the implementation of the first fetal tele-echocardiography site was 13.8% and after the sites were established, the prenatal diagnosis rate was 39.7% (p < 0.01). CONCLUSION: Increasing the number of fetal tele-echocardiography sites at small regional hospitals in Kentucky was associated with a statistically significant increase in the rate of prenatal diagnosis for patients less than 1 year of age who had cardiac surgery or cath lab intervention at Norton Children's Hospital in Louisville. Fetal tele-echocardiography is an effective method to improve the rate of prenatal diagnosis in regions served by small regional hospitals with limited access to fetal echocardiography.

Norwood Operation With Partial Left Ventriculectomy for Neonatal Dilated Cardiomyopathy.

The combination of severe fetal mitral regurgitation diagnosed in utero, aortic stenosis, left ventricular dilatation, and dysfunction is associated with extremely poor prognosis. We report a neonate who underwent Norwood operation and left ventricular exclusion using partial left ventriculotomy and Alfieri mitral valve stitch. Left ventricular exclusion eliminated right ventricular compression and allowed survival and progression to subsequent second-stage palliation.

Seroconversion and fever are dose-dependent in a nonhuman primate model of inhalational COVID-19.

While evidence exists supporting the potential for aerosol transmission of SARS-CoV-2, the infectious dose by inhalation remains unknown. In the present study, the probability of infection following inhalation of SARS-CoV-2 was dose-dependent in a nonhuman primate model of inhalational COVID-19. The median infectious dose, assessed by seroconversion, was 52 TCID50 (95% CI: 23-363 TCID50), and was significantly lower than the median dose for fever (256 TCID50, 95% CI: 102-603 TCID50), resulting in a group of animals that developed an immune response post-exposure but did not develop fever or other clinical signs of infection. In a subset of these animals, virus was detected in nasopharyngeal and/or oropharyngeal swabs, suggesting that infected animals without signs of disease are able to shed virus and may be infectious, which is consistent with reports of asymptomatic spread in human cases of COVID-19. These results suggest that differences in exposure dose may be a factor influencing disease presentation in humans, and reinforce the importance of public health measures that limit exposure dose, such as social distancing, masking, and increased ventilation. The dose-response data provided by this study are important to inform disease transmission and hazard modeling, and, ultimately, mitigation strategies. Additionally, these data will be useful to inform dose selection in future studies examining the efficacy of therapeutics and vaccines against inhalational COVID-19, and as a baseline in healthy, young adult animals for assessment of the importance of other factors, such as age, comorbidities, and viral variant, on the infectious dose and disease presentation.

The Stability of an Isolate of the SARS-CoV-2 B.1.1.7 Lineage in Aerosols Is Similar to 3 Earlier Isolates.

BACKGROUND: Our laboratory previously examined the influence of environmental conditions on the stability of an early isolate of SARS-CoV-2 (hCoV-19/USA/WA-1/2020) in aerosols generated from culture medium or simulated saliva. However, genetic differences have emerged among SARS-CoV-2 lineages, and it is possible that these differences may affect environmental stability and the potential for aerosol transmission. METHODS: The influence of temperature, relative humidity, and simulated sunlight on the decay of 4 SARS-CoV-2 isolates in aerosols, including 1 belonging to the recently emerged B.1.1.7 lineage, were compared in a rotating drum chamber. Aerosols were generated from simulated respiratory tract lining fluid to represent aerosols originating from the deep lung. RESULTS: No differences in the stability of the isolates were observed in the absence of simulated sunlight at either 20°C or 40°C. However, a small but statistically significant difference in the stability was observed between some isolates in simulated sunlight at 20°C and 20% relative humidity. CONCLUSIONS: The stability of SARS-CoV-2 in aerosols does not vary greatly among currently circulating lineages, including B.1.1.7, suggesting that the increased transmissibility associated with recent SARS-CoV-2 lineages is not due to enhanced survival in the environment.

Intravascular Targeted Temperature Management: One Hospital's Experience.

Sudden cardiac arrest (SCA) is one of the leading causes of death in adults around the world. And in some patients, SCA is followed by a return of spontaneous circulation (ROSC) and remain unresponsive. International guidelines recommend therapeutic hypothermia within 4 hours of ROSC for patients' survival. A medium-sized tertiary teaching hospital in the Midwestern United States was not achieving the recommendations of therapeutic hypothermia therapy. A root cause analysis identified multiple factors contributed to therapy delay. In March 2019, this hospital embarked on a 6-month trial of an intravascular targeted temperature management (ITTM) system to meet the recommendations. Donabedian's model guided the trial and included patients who suffered an SCA, with ROSC and remained unresponsive. Descriptive analysis was completed to compare the patients before and after the trial. The trial included interprofessional education of the ITTM system, policies, orders, and new process for initiating the therapy. A total of nine patients were included in the trial and with an average time to target temperature was 3.28 hours compared with 8.81 hours before the trial. The trial demonstrated ITTM was successful in meeting the recommendations. Paired with the promising research on the system's effectiveness, we have demonstrated that intravascular cooling can be implemented to reach the international recommendations. These reductions in treatment delays may prompt improved outcomes for individuals in the post-SCA population.

Comparison of the performance of aerosol sampling devices for measuring infectious SARS-CoV-2 aerosols.

To assess the risk of aerosol transmission of SARS-CoV-2, measurements of the airborne viral concentrations in proximity to infected individuals, the persistence of the virus in aerosols, and the dose of the virus needed to cause infection following inhalation are required. For studies aimed at quantifying these parameters, an aerosol sampling device needs to be employed. A number of recent studies have reported the detection of both genetic material and infectious SARS-CoV-2 virus in air samples collected in clinical settings. Previous studies have demonstrated that the efficiency of different samplers for collection and preservation of the infectivity of microorganisms can vary as a function of the specific microorganism. In the present study, the performance of eight common low-flow aerosol sampling devices were compared for their ability to collect and preserve the infectivity of airborne SARS-CoV-2 contained in small particle aerosols. The influence of sampling duration on recovery of infectious virus was also evaluated. Similar concentrations of infectious SARS-CoV-2 were measured in aerosols for the majority of the samplers tested, with the exception of the midget impingers, which measured significantly lower concentrations of SARS-CoV-2. Additionally, in three of the four impingers tested, additional clean airflow through the device following collection of infectious virus resulted in a decrease of the infectious concentration of virus over time, suggesting that virus was being inactivated and these devices may not be suitable for sampling for long durations. Further, RNA copies in the samples over time did not correspond with the losses of infectious SARS-CoV-2 observed in the impingers samples. These data can be utilized to inform interpretation of current studies on the SARS-CoV-2 viral loads in air samples, as well as inform sampling device selection in future studies.

The influence of temperature, humidity, and simulated sunlight on the infectivity of SARS-CoV-2 in aerosols.

Recent evidence suggests that respiratory aerosols may play a role in the spread of SARS-CoV-2 during the ongoing COVID-19 pandemic. Our laboratory has previously demonstrated that simulated sunlight inactivated SARS-CoV-2 in aerosols and on surfaces. In the present study, we extend these findings to include the persistence of SARS-CoV-2 in aerosols across a range of temperature, humidity, and simulated sunlight levels using an environmentally controlled rotating drum aerosol chamber. The results demonstrate that temperature, simulated sunlight, and humidity are all significant factors influencing the persistence of infectious SARS-CoV-2 in aerosols, but that simulated sunlight and temperature have a greater influence on decay than humidity across the range of conditions tested. The time needed for a 90% decrease in infectious virus ranged from 4.8 min at 40 °C, 20% relative humidity, and high intensity simulated sunlight representative of noon on a clear day on the summer solstice at 4°N latitude, to greater than two hours under conditions representative of those expected indoors or at night. These results suggest that the persistence of infectious SARS-CoV-2 in naturally occurring aerosols may be affected by environmental conditions, and that aerosolized virus could remain infectious for extended periods of time under some environmental conditions. The present study provides a comprehensive dataset on the influence of environmental parameters on the survival of SARS-CoV-2 in aerosols that can be utilized, along with data on viral shedding from infected individuals and the inhalational infectious dose, to inform future modeling and risk assessment efforts.

Airborne SARS-CoV-2 Is Rapidly Inactivated by Simulated Sunlight.

Aerosols represent a potential transmission route of COVID-19. This study examined effect of simulated sunlight, relative humidity, and suspension matrix on stability of SARS-CoV-2 in aerosols. Simulated sunlight and matrix significantly affected decay rate of the virus. Relative humidity alone did not affect the decay rate; however, minor interactions between relative humidity and other factors were observed. Mean decay rates (± SD) in simulated saliva, under simulated sunlight levels representative of late winter/early fall and summer were 0.121 ±â€…0.017 min-1 (90% loss, 19 minutes) and 0.306 ±â€…0.097 min-1 (90% loss, 8 minutes), respectively. Mean decay rate without simulated sunlight across all relative humidity levels was 0.008 ±â€…0.011 min-1 (90% loss, 286 minutes). These results suggest that the potential for aerosol transmission of SARS-CoV-2 may be dependent on environmental conditions, particularly sunlight. These data may be useful to inform mitigation strategies to minimize the potential for aerosol transmission.

Simulated Sunlight Rapidly Inactivates SARS-CoV-2 on Surfaces.

Previous studies have demonstrated that SARS-CoV-2 is stable on surfaces for extended periods under indoor conditions. In the present study, simulated sunlight rapidly inactivated SARS-CoV-2 suspended in either simulated saliva or culture media and dried on stainless steel coupons. Ninety percent of infectious virus was inactivated every 6.8 minutes in simulated saliva and every 14.3 minutes in culture media when exposed to simulated sunlight representative of the summer solstice at 40°N latitude at sea level on a clear day. Significant inactivation also occurred, albeit at a slower rate, under lower simulated sunlight levels. The present study provides the first evidence that sunlight may rapidly inactivate SARS-CoV-2 on surfaces, suggesting that persistence, and subsequently exposure risk, may vary significantly between indoor and outdoor environments. Additionally, these data indicate that natural sunlight may be effective as a disinfectant for contaminated nonporous materials.

The Use of Tai-Chi to Reduce Anxiety Among Nursing Students Undergoing Simulation.

This study sought to examine tai-chi as an anxiety-reducing method to increase self-efficacy and improve performance among baccalaureate nursing students experiencing a patient care simulation. The sample included 63 nursing students enrolled in a traditional or second-degree nursing program. The study used a randomized control group pretest-posttest design. Students in the experimental group experienced significant reductions in cognitive and somatic anxiety, along with an increase in self-efficacy and improved performance. Tai-chi can be an effective technique to reduce anxiety and improve self-efficacy and performance among nursing students in simulations.

Message Heard: Insights for Doctoral Program Design From Community Partners.

Developing a nursing doctoral program requires, among other considerations, thoughtful reflection on opportunities for graduates, and needs of the health-care community. To educate nurse clinicians, scientists, and leaders prepared to address complex health-care issues, colleges of nursing must engage with community stakeholders during program development. One college embraced this opportunity to dialogue through a series of semistructured focus groups and surveys to inform community partners of the developing doctoral program plan and to hear their related ideas and opinions. Themes arising from qualitative data analysis included driving forces, the value of education, and differing doctoral roles. The findings were far more enlightening than anticipated and ultimately guided the direction of program development. This study affirmed the power of meaningful dialogue with community partners to ensure a well-educated nursing workforce with the skills needed to advance nursing practice in the changing health-care environment.

The Effect of Autogenic Training on Self-Efficacy, Anxiety, and Performance on Nursing Student Simulation.

The increased anxiety experienced by nursing students during simulations can serve as a significant barrier to learning. The use of anxiety-reducing techniques such as autogenic training (AT) can mitigate the negative effects of anxiety and improve the overall learning experience. The investigators in this study sought to understand the effect of AT on student performance and self-efficacy during simulation experiences. The use of AT was an effective technique to decrease anxiety and increase performance among nursing students during nursing simulations. Reducing anxiety during simulations can improve the student learning experience.

Successful Fetal Tele-Echo at a Small Regional Hospital.

BACKGROUND: Prenatal diagnosis of complex congenital heart disease (CHD) has been shown to improve newborn outcomes. The rate of prenatal diagnosis and access to fetal echocardiography vary widely across the United States. INTRODUCTION: A clinical fetal tele-echo service was established at King's Daughters Medical Center (KDMC) in Ashland, KY, a region in eastern Kentucky that is 3 h from the nearest congenital heart surgeon. The aim of this study was to determine if fetal tele-echo utilizing local sonographers at a small regional hospital can accurately and efficiently identify fetuses with complex CHD. METHODS: Medical records were reviewed for all mother-infant pairs who had fetal tele-echoes performed at KDMC and interpreted by University of Louisville pediatric cardiology between March 2011 and December 2013. Findings on fetal tele-echo were compared to newborn echo and clinical course, and divided into four groups: (1) Correct-no difference between fetal tele-echo and newborn echo, (2) Likely Correct-normal fetal tele-echo and benign newborn course, (3) Major Difference-one that affected newborn clinical course, and (4) Minor Difference-did not affect clinical course. RESULTS: Seventy-five mother-infant pairs were analyzed. Fetal tele-echoes were Correct in 21%, Likely Correct in 56%, showed Major Differences in 0%, and showed Minor Differences in 23%. For identifying complex CHD, fetal tele-echo had a sensitivity and specificity of 100%. The average number of fetal echocardiograms per mother-infant pair was 1.1. DISCUSSION: Fetal tele-echocardiography performed by local sonographers at a small regional hospital can accurately and efficiently identify fetuses with complex CHD.

Three-Dimensional Reconstruction of Intracardiac Anatomy Using CTA and Surgical Planning for Double Outlet Right Ventricle: Early Experience at a Tertiary Care Congenital Heart Center.

BACKGROUND: Although transthoracic echocardiography (TTE) routinely establishes the diagnosis of double outlet right ventricle (DORV), it can be suboptimal for depicting exact ventricular septal defect (VSD) position, especially with respect to the outflow tracts. Advanced imaging with computed tomography angiography (CTA) can help visualize structures and relationships not easily seen by echo. Using computer-aided design, we have the ability to create three-dimensional (3D) models of the intracardiac anatomy, which can be helpful for better depicting the overall anatomy to assist surgical planning. METHODS: Patients with a diagnosis of DORV were retrospectively reviewed at our institution from October 2013 to April 2015. Patients who preoperatively underwent both TTE and CTA with 3D reconstruction of the intracardiac anatomy were included. Computed tomography angiography findings with 3D intracardiac model creation were compared to the surgical findings. RESULTS: Twenty-five patients underwent surgical repair of DORV during the study period. Five patients had CTA with 3D reconstruction, in addition to the standard TTE images, and were included in the study. In all five cases, CTA with 3D reconstruction of the intracardiac anatomy accurately depicted the VSD position relative to important adjacent structures, including the outflow tracts. CONCLUSION: Three-dimensional reconstruction of the intracardiac anatomy using CTA data can provide accurate data for presurgical planning of DORV repair and has the potential for being especially useful in patients for whom intracardiac anatomy and VSD position cannot be well seen by TTE. A larger prospective analysis is warranted to help validate this approach.

Large bilateral adrenal haemorrhages in a newborn with unrepaired cyanotic CHD.

Management of newborns with cyanotic CHD and bilateral adrenal haemorrhages has not previously been described in the literature. These abnormalities present unique challenges due to the potential for haemodynamic instability, need for open heart surgery and associated systemic anticoagulation in the newborn period, and the risk of catastrophic bleeding.

Weaving the tapestry of learning: simulation, standardized patients, and virtual communities.

Using situated cognition learning theory, nursing faculty developed simulated clinical learning experiences integrating virtual communities and standardized patients. These learning experiences provide authenticity and realism not easily achieved using the individual techniques in isolation. The authors describe the process of weaving these strategies into a rich learning experience for students.