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Introduction: Lactate is a common biomarker used in multiple surgical subspecialties. No one has previously measured coronary sinus lactate reduction as a result of drug administration. We therefore tested the hypothesis that IV geranylgeranylacetone (GGA), a novel agent used to treat human peptic ulcer disease, would result in reduced coronary sinus lactate production. Method(s): New Zealand adult rabbits (N=5 each) received IV 50 mg/kg GGA 24 hours before intervention, which consisted of Langendorff perfusion, 30 min of global normothermic cardioplegic arrest, followed by reperfusion. Myocardial release of lactate was measured. HSP70 was quantified by western blot. Differences between GGA+ and GGA- groups pre- and post-ischemia were analyzed by unpaired t-tests. Result(s): In the GGA- group, lactate increased immediately at one minute and throughout the duration of reperfusion. However, in GGA+ hearts, lactate also increased at one min of reperfusion but then continued to decrease throughout the remainder of reperfusion. Lactate was significantly less at every time point of reperfusion in GGA+. Integrated lactate area was significantly less throughout reperfusion in GGA+. Conclusion(s): GGA induced caused a marked decrease in coronary sinus lactate release during reperfusion. Simultaneously intravenously GGA induced myocardial HSP70i and reduced myocardial damage. Further study of the effects and mechanisms involved is indicated. Application to other organs is useful as well. Heat shock proteins (HSPS) are also antithrombotic. Given the thrombotic nature of Covid, induction of HSPS may be beneficial in decreasing the cardiac thoracic and vascular complications of Covid and allowing faster resolution of this disease during to vascular complications.
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PurposeThe purpose of this study is to demonstrate the power of affective pedagogies and playful literacies to resist neoliberal framings of video game play and design in educational contexts. Design/methodology/approachFocusing on the Giga-Games Camp, a video game design camp for adolescents, the authors mobilize different methodological impulses across a number of different registers, using interview data to trace institutional arcs, focal frames from a GoPro camera to see vitality in action and descriptions of platform events to follow these lines through the shift to online instruction brought on by the COVID-19 pandemic. FindingsThe authors narrate three transversal movements of the Giga-Games Camp to reveal how play-centered pedagogies can challenge the neoliberal tendency to assimilate young people's video gaming practices as a vehicle for future-proof science, technology, engineering and mathematics learning. Originality/valueThe authors offer the concept of actually existing vitality rights to describe how attending seriously to vitality in learning spaces will often manifest organically in very real strategies to reimagine and restructure preexisting, neoliberally sedimented uses of space, institutional configurations and constellations of sociopolitical power.
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The spread of SARS-CoV-2 and its variants, leads to global pandemic endangering human life and health. The primary challenge for the scientific community is to find a potential cure for the disease which can act on the emerging variants of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). Due to the absence of effective medical treatment for the diseases, the healthcare system around the world was at a standstill. The nsp12 and nsp14 are one of the important proteins which are involved in the replication and proofreading of SARS-CoV-2 respectively. Both the non-structural proteins have highly conserved regions and served as a popular target for corona virus inhibitors for drug screening. In this study, the primary aim is to find the potential inhibitors, both phytochemical and nonphytochemical, which could act on variants to inhibit the activity of nsp12 and nsp14. Also to compare the binding affinity of nsp12 and nsp14 with phytochemicals and nonphytochemicals. A combination of mutational landscape, structure-based virtual screening and molecular dynamics (MD) simulation approaches were utilized in this work. From the mutational landscape, two functionally active mutations were observed in nsp12 and single mutation was observed in nsp14 of SARS CoV-2 Variants. The molecular simulation is performed for drugs Cepharanthine (phytochemical) and Hypericin (phytochemical) with top binding affinity for nsp12 variants and for molecules Hypericin (phytochemical) and conivaptan (non-Phytochemical) having top binding affinity with nsp14 wildtype and variants.
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Background:: Most research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy has been on acute infections with limited data on the effect of distant infection. Aim:: We examined placental pathology and neonatal outcomes in distant SARS-CoV-2 infection earlier in pregnancy compared to acute infections late in pregnancy/at birth and to non-SARS-CoV-2 infected patients with other placental pathologies/clinical presentations. Methods:: Placentas birthed to unvaccinated patients with SARS-CoV-2 reverse transcription–polymerase chain reaction (RT-PCR) testing and serology testing results from time of delivery were included in this study. A total of 514 singleton placentas between April 18, 2020, and July 26, 2021, were included: 77 acute SARS-CoV-2 infection (RT-PCR positive and serology negative);222 distant SARS-CoV-2 infection (RT-PCR negative but serology IgG-positive);and 215 non-SARS-Cov-2 infected (RT-PCR negative, serology negative, and history negative) with other placental pathologies: preeclampsia/hypertension, intrauterine growth restriction (IUGR), diabetes, chorioamnionitis, and meconium. Placental pathology findings, Apgar scores, and neonatal birth weights were compared. Results:: Placentas from the acute group had significantly more villous agglutination (10.4%, P = 0.015) and eosinophilic T-cell vasculitis (5.2%, P = 0.004) compared to placentas from the distant group (2.7% and 0%) and non-SARS-CoV-2 placentas (1.9% and 0.9%). One acute case showed SARS-CoV-2 placentitis and resulted in preterm delivery at 25 weeks. Both the preeclampsia/hypertension and the IUGR groups showed significantly more maternal vascular malperfusion findings compared to the acute (6.5%, 6.5% and 1.3%) and distant (7.7%, 7.7%, and 3.2%) groups. Fetal vascular malperfusion findings such as thrombosis of fetal vessels (17.4% P = 0.042) and intramural fibrin deposition (21.7% P = 0.026) were significantly higher in the IUGR group compared to acute (7.8%;2.6%) and distant (3.6%;8.1%) infection. Many neonates born to patients infected with SARS-CoV-2 had birth weights outside of 95% confidence range of observed birth weights. There was no association of Apgar scores with infection status or placental pathology. Conclusion:: Acute and distant SARS-CoV-2 infections present differing placental pathology. Relevance for Patients:: SARS-CoV-2 infection during pregnancy has demonstrable effects on the placenta with potential significant impacts for maternal and fetal health. Prevention of maternal SARS-CoV-2 infection, primarily through vaccination, remains the best mitigation strategy to prevent sequelae of maternal SARS-CoV-2 infection.
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Purpose: Background: Ischemia reperfusion(IR) increases lactate. No one has examined if cardiac-specific coronary sinus lactate(CSL) can be reduced with prior cytoprotective heat shock protein 70(hsp70i) induction. We previous demonstrated improved IR in vivo with inducted hsp70i. Geranylgeranylacetone(GGA), an hsp70i inducer, has never been administered IV preischemically. Interventions to decrease CSL may improve clinical parameters. Methods: Rabbit hearts underwent 30 cold cardioplegic ischemia then 60 min reperfusion. One group received IVGGA 24 hours prior(GGA+) and the other vehicle(GGA-). CSlactate was collected prior to ischemia and throughout reperfusion. We aimed to determine IVGGA effects on myocardial hsp70i and lactate. Hsp70 western blot was performed. Results: Baseline CSlactate was similar between GGA+ and GGA-(Figure 1). Both peaked CSlactate at 1 minute reperfusion. However GGA+ peak was less. At every time point GGA+ was less. GGA+ CSlactate continued to decrease throughout reperfusion however in GGA- CSlactate increased later. Integrated CS lactate area was less for GGA+(Figure 1). Conclusion: In summary, protective IVGGA resulted in five lactate benefits: lactate was less at 1 minute reperfusion peak,decreased faster in early reperfusion, was reduced at all time points, does not have a second rise and lastly results in overall less integrated lactate production in GGA+. GGA induced hsp70. IVGGA may have clinical applications in endothelial protection in IR and COVID.
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This work-in-progress paper studied the impact of COVID-19 ramifications on first-year engineering student sense of belonging at one research intensive institution in the southeast that hosts a strong engineering program. In response to COVID-19, the vast majority of collegiate institutions have shifted courses to remote, hybrid, or hyflex formats, which may result in diverse engineering students facing a “triple threat” to their sense of belonging in engineering courses since (a) STEM disciplines, (b) minoritized student identity, and (c) remote course formatting can all impede belonging. Diminished sense of belonging can, in turn, impact student retention and persistence, potentially intensifying imbalances that already exist in STEM fields. Therefore, this study sought to examine students' sense of belonging and factors that could contribute to increased belonging for diverse engineering students, especially in remote courses. Using a concurrent, mixed methods design in the Fall of 2020, the preliminary data in this manuscript highlight survey responses from 282 students (54% response rate), 7 focus groups with a total of 28 students, course observations, and student demographic data. Key variables and concepts for the study include sense of belonging (measured with an existing 4-item scale for which the institution has historical engineering student responses as well as with qualitative interview questions), which is an empirically documented forecaster of student success, and the Community of Inquiry framework, broken into three constructs of teaching, social and cognitive presence designed to examine key elements of an online course (measured with an existing 34-item survey and qualitative interview questions). Preliminary findings suggest no statistically significant differences in sense of belonging, teaching presence, social presence or cognitive presence between students in marginalized and dominant identity groups (continued analysis of qualitative data will reveal nuances between groups not apparent in survey data);however, belonging was higher for students who attended class physically versus virtually most of the time. In addition, compared to a past (pre-pandemic) comparison, social presence was lower for all fall 2020 students. This project is supported via an NSF RAPID award created by the IUSE program in the Division of Undergraduate Education (Education and Human Resources Directorate), using funds from the Coronavirus Aid, Relief, and Economic Security (CARES) Act. © American Society for Engineering Education, 2021
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This paper is focused on a course redesign transitioning from a hardware-based course into a course taught remotely. The J. B. Speed School of Engineering (SSoE) at the University of Louisville (UofL) has a two-course sequence that all first-year SSoE students are required to complete. This two-course sequence is designed to introduce incoming students to the profession and fundamentals of engineering. The first course is titled Engineering Methods, Tools, & Practice I (ENGR 110), and primarily focuses on introduction to and practice with fundamental engineering skills. The second course, Engineering Methods, Tools, & Practice II (ENGR 111) is typically a makerspace-based course primarily focused on application and integration of the fundamentals learned in ENGR 110. Included amongst numerous skills institutionally identified as “fundamental” were programming and basic circuitry. Therefore, all disciplines of SSoE engineering students are exposed to the basics of circuitry and programming through ENGR 111 pedagogy. Due to the COVID-19 pandemic, this makerspace course is to be taught remotely in the spring semester of 2021. The instructional team felt that there were too many shared tools and teams were too close together to safely continue the course in a makerspace environment. This remote teaching has posed the instructional team some unique challenges due to the hands-on nature of the ENGR 111 course. Students are typically in face-to-face teams of 3 or 4 students and each group is given an Arduino, breadboard, and circuit components. The given assignments start out with basic circuity and Arduino programming, followed by utilizing an Arduino to communicate with created circuits. The assignments are designed to help the first-year students gain comfort in circuitry and programming. The instructional team has decided to use Tinkercad, which is a free online collection of software tools provided by Autodesk. Many people are only aware of Tinkercad as a 3D modeling programming, however in 2017 Autodesk merged its “123D Circuits” into Tinkercad [1] [2]. This makes Tinkercad an ideal platform to use for circuitry and Arduino programming. The paper will further describe the design of the assignments, instructional team expectations from the students, the environment in which the students are using Tinkercad, as well as looking at expected course outcomes using the platform. This topic is a work in progress as data for evidence-based analyses will not be fully procured until after publication. © American Society for Engineering Education, 2021
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Background: Patients receiving chronic hemodialysis (HD) are highly vulnerable in all settings. It is unknown whether the COVID-19 pandemic has disproportionately affected the care of chronic HD patients in low (LIC) and low-middle income (LMIC) settings. This survey aimed to identify global challenges and inequities in HD care delivery during the COVID-19 pandemic. Methods: The Dialysis Outcomes and Practice Patterns Study (DOPPS) and the International Society of Nephrology (ISN) conducted a global online survey of HD units (HDU). Sample HDUs included DOPPS sites in China, a random sample stratified by region and HDU population, and an open invitation via ISN's membership list. The survey assessed availability of COVID-19 diagnostics and personal protective equipment, the impact of COVID-19 on HD delivery and patient outcomes from COVID-19. Responses were stratified by country income according to World Bank classification. Results: Responses were received from 412 HDUs across 78 countries (Table 1). Conclusions: Striking global inequities were identified in access to COVID-19 diagnostics, infection prevention, and access to routine HD care during the pandemic. Higher apparent mortality in patients on chronic HD in LICs and LMICs is likely multifactorial, reflecting poorer access to the diagnosis and care of COVID-19, as well as greater disruptions to HD delivery. Urgent action is required to address these inequities, which disproportionately affect low-income settings, exacerbate pre-existing vulnerabilities and lead to worse outcomes.
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Background: Haemodialysis units (HDUs) have had to rapidly adapt practices and policies to safely continue life-sustaining HD services during the COVID-19 pandemic. We aimed to describe the impact of COVID-19 in different parts of the world. Methods: The Dialysis Outcomes and Practice Patterns Study (DOPPS) and International Society of Nephrology (ISN) collaborated to web-survey individual HDUs. Responses were obtained in three ways: (1) a survey of DOPPS sites in China (May/ June 2020), (2) a random sample (20 units if > 40 units/ country;all units if < 40) stratified by region and HDU census (November 2020 -March 2021), and (3) an open invitation via ISN's membership list and social media (March 2021). Responses were compared between the ten ISN regions. Results: There were returns from 412 HDUs (46% public sector, 79% urban;70% adult, 2% paediatric, 28% adult & paediatric) from 78 countries (9% low-, 24% lowermiddle-, 28% upper-middle-, 39% high-income). Conclusions: The COVID-19 pandemic has had a significant impact on dialysis services and staffing worldwide. Differences in uptake of policies and practices across regions have likely been because of variable access to resources to enable implementation of diagnostic testing algorithms and adequate supply of PPE to implement infection prevention and control recommendations. Guidance should be consistent, adaptable to (nearly) all situations and locations, and evidence based. Going forward, the operationalisation of vaccine programs should be incorporated into guidelines. Disruptions to dialysis services should be minimised, and resource provision (including vaccines) prioritised by policymakers and governments in future waves of COVID-19 and pandemics if we are to protect HD patients, staff, and services.
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Background: Home dialysis may be able to minimize SARS-CoV2 exposure risks. The pandemic may have introduced unique challenges related to supply disruption and care delivery changes. We sought to assess the global burden of COVID-19 on peritoneal dialysis units (PD) and understand PD unit practice changes during this time. Methods: The Peritoneal Dialysis/Dialysis Outcomes and Practice Patterns Study (PDOPPS/DOPPS) and International Society of Nephrology (ISN) administered a webbased survey (1) to dialysis units selected based on a random sample stratified by region (November 2020 -March 2021), and (2) to an open invitation via ISN's membership list and social media (March 2021). Responses were compared across 10 ISN regions. Results: Returned surveys included 167 PD facilities across 52 countries. Changes in several care domains including clinic communication and frequency, labwork frequency, method of communication, masking policies, changes in handling of PD effluent among infected individuals, PD supply disruption, access to methods of PD catheter insertion and frequency of new patient training are highlighted (table). Conclusions: Variability exists in routine PD care, and the availability and use of PPE, disruption in PD supplies among the different regions reflecting the availability of the resources and infrastructure differences. LMIC tended to be more severely impacted-this gap needs to be addressed in anticipation of future pandemics for treatment continuity. Although remote technology use among PD patients to communicate with their physicians has increased during the pandemic, optimal communication frequency, methods and schedule of routine bloodwork needs to be better elucidated.
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Introduction: The re-deployment of anaesthetic trainees to support COVID-19 patients in intensive care, reduced elective surgery and pauses to trainee rotations1 have affected access to training. The 2020 PATRN swift survey examined the impact on UK paediatric anaesthetic training following the first wave of the pandemic. Method: Sixteen questions, designed by the PATRN committee, focussed on trainee experience of paediatric anaesthesia from March-August 2020. Paediatric anaesthesia experience in the UK occurs at all stages with the option for an 'advanced' module. The survey was reviewed by members of the Association of Paediatric Anaesthetists of Great Britain and Ireland (APAGBI) Scientific Committee before distribution. Distribution was via email to UK traineesy College Tutors through The Royal College of Anaesthetists (RCOA) and APAGBI trainee members from December 2020March 2021. Results: 90/170 (53%) of respondents were due to complete a paediatric training module, representing all stages of training. Only 23% (n=21) remained working in paediatric anaesthesia, mainly trainees completing higher or advanced modules (n=19). The majority of trainees who experienced disruption with re-deployment was to support adult intensive care (33/69;48%). Most trainees felt they had insufficient paediatric experience for progression of training (37/69;54%) and did not have enough cases to achieve module completion (32/66;48%). This was due to re-deployment or a lack of elective training lists. Conclusion: Paediatric anaesthesia is a 'hands-on' specialty and requires experience for confidence. New annual competency progression outcomes2 have been created to identify missed training due to COVID-19. There will be an impact in the short-term for covering on-call cases and longer term on workforce if training extensions result in delays to completion. Access to training needs to be prioritised, especially for junior trainees most affected by re-deployment. There should be ongoing discussions nationally on how to address these issues.
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Introduction: Many variations of the Kermack-McKendrick SIR model were proposed in the early stages of the SARS-CoV-2 pandemic to study the transmission of COVID-19. The current state-of-the-art 16 compartment model developed by Tuite et. al (2020) is used to simulate the influence of government policies and leverage early available clinical information to predict the dynamics of the disease. As much of the world is now experiencing a second wave and vaccines have been approved and are being deployed;it is critical to be able to accurately predict the trajectory of cases while integrating information about these new model states and parameters. Challenges for accurate predictions are two-fold: firstly, the mechanistic model must capture the essential dynamics of the pandemic as well provide meaningful information on quantities of interest (e.g. demand for hospital resources), and secondly, the model parameters need to be calibrated using epidemiological and clinical data. Methods: To address the first challenge, we propose a compartmental model that expands upon model developed by Tuite et al. (2020) to capture the effects of vaccination, reinfection, asymptomatic carriers, inadequate access to hospital resources, and long-term health complications. As the complexity of the model increases, the inference task becomes more difficult and prone to over-fitting. As such, the nonlinear sparse Bayesian learning (NSBL) algorithm is proposed for parameter estimation. Results: The algorithm is demonstrated for noisy and incomplete synthetic data generated from an SIRS model with three uncertain parameters (infection rate, recovery rate and the rate temporary immunity is lost). As an example, Figure 1 shows the calibration of the three uncertain model parameters within a Bayesian framework while avoiding over-fitting by inducing sparsity in the parameters. Assuming there is little prior information available for the parameters, they are first assigned non-informative priors. Before NSBL, the model (red curve) is over-parameterized, and fails to predict the decline of the (blue) infection curve. The NSBL algorithm makes use of automatic relevance determination (ARD) priors, and finds one of the model parameters to be irrelevant to the dynamics. Removing the irrelevant parameter and re-calibrating enables the model (green curve) to capture the peak of the infection curve. Conclusion: An optimally calibrated model will allow for the concurrent forecasting of many hypothetical scenarios and provide clinically relevant predictions.
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Background: The COVID-19 pandemic caused unprecedented disruption to dialysis patients care globally. Facility surveys were distributed to assess the impact of COVID-19 pandemic on hemodialysis (HD) and peritoneal dialysis (PD) practices. Methods: Medical Director (MD) and Nurse Manager (NM) Surveys (MDS, NMS) are being distributed in May/June 2020 to 723 clinics enrolled in the Dialysis (in-center HD, DOPPS) or Peritoneal (PDOPPS) Dialysis Outcomes and Practice Patterns Study in Canada, China, Japan, the United States, 7 European countries, 5 Gulf Cooperative Council countries, and China metropolitan areas (Beijing, Guangzhou, Shanghai). Surveys content includes the number of COVID-19 cases, testing, and clinical management, screening, infection control, staffing, patient transportation, and psychological support. Results: As of 27 May 2020, we have 80 MDS (China, Europe, US = 33, 38, 5) and 101 NMS (45, 46, 9) responses from DOPPS sites. The following percentages are presented sequentially for China, Europe, and US. Among MDs, 0%, 67%, 67% reported at least one confirmed COVID-19 case among dialysis patients, and 85%, 70%, 66% reported being on the late phase of the COVID-19 curve. 40%, 23%, 100% of MDs were more likely to recommend home dialysis;19%, 5%, 29% reported an increase in missed dialysis treatments;30%, 24%, 50% were more likely to prescribe potassium binders;and 75%, 68%, 43% had greater challenges obtaining vascular access interventions. Among NMs, 30%, 9%, 40% reported current limitations in access to COVID-19 testing;and 61%, 51%, 29% reported having, or risk of, shortage in staffing. Conclusions: Early results indicate many clinics in Europe and US have had COVID-19 cases, but sites in the three DOPPS-China cities have avoided COVID-19 to date. In all regions, shortages of human and medical resources were common, as were changes to dialysis delivery/practice including more skipped sessions, greater use of potassium binders, and preferentially recommending home dialysis. Over the next month, we expect hundreds more responses, and will compare approaches in PD and HD clinics. These data will inform guidance for dialysis care as the COVID-19 pandemic ensues.