Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 25
Filter
1.
Circulation ; Cardiovascular Quality & Outcomes.:e009032, 2023.
Article in English | MEDLINE | ID: covidwho-2194407

ABSTRACT

The COVID-19 pandemic exposed the consequences of systemic racism in the United States with Black, Hispanic, and other racial and ethnic diverse populations dying at disproportionately higher rates than White Americans. Addressing the social and health disparities amplified by COVID-19 requires in part restructuring of the healthcare system, particularly the diversity of the healthcare workforce to better reflect that of the US population. In January 2021, the Association of Black Cardiologists hosted a virtual roundtable designed to discuss key issues pertaining to medical workforce diversity and to identify strategies aimed at improving racial and ethnic diversity in medical school, graduate medical education, faculty, and leadership positions. The Nurturing Diverse Generations of the Medical Workforce for Success with Authenticity roundtable brought together diverse stakeholders and champions of diversity and inclusion to discuss innovative ideas, solutions, and opportunities to address workforce diversification.

2.
14th International Conference on Computer Supported Education, CSEDU 2022 ; 1:297-303, 2022.
Article in English | Scopus | ID: covidwho-2110614

ABSTRACT

In the aftermath of COVID-19, remote working has become the norm, and graduates now need an even wider range of skills, which traditional classrooms and internships do not always provide. Working in multiple time zones, within global multi-cultural teams, and only ever meeting colleagues through online technology are just some of the challenges, which require a new type of global graduate. Transversal skills including leadership, collaboration, innovation, digital, green, organization and communication skills are critical. The disruption from COVID-19 also presents unprecedented opportunities to develop more inclusive approaches to internships and international experiences, to level the playing field for students with special needs, from underrepresented groups or with caring commitments. In this position paper, we present a new Global Innovation internship model that has the aim of allowing students to complete technology internships and projects by working together virtually on real world challenges, guided by experienced industry and academic mentors. The model is being developed as part of an Erasmus+ funded project, and the partnership includes seven Higher Education Institutions from six different countries around the world. This position paper describes the design and development of a pilot programme of the Global Innovations internship model. Copyright © 2022 by SCITEPRESS – Science and Technology Publications, Lda. All rights reserved.

3.
Life Sci Alliance ; 6(1), 2023.
Article in English | PubMed | ID: covidwho-2081438

ABSTRACT

New therapeutic targets are a valuable resource for treatment of SARS-CoV-2 viral infection. Genome-wide association studies have identified risk loci associated with COVID-19, but many loci are associated with comorbidities and are not specific to host-virus interactions. Here, we identify and experimentally validate a link between reduced expression of EXOSC2 and reduced SARS-CoV-2 replication. EXOSC2 was one of the 332 host proteins examined, all of which interact directly with SARS-CoV-2 proteins. Aggregating COVID-19 genome-wide association studies statistics for gene-specific eQTLs revealed an association between increased expression of EXOSC2 and higher risk of clinical COVID-19. EXOSC2 interacts with Nsp8 which forms part of the viral RNA polymerase. EXOSC2 is a component of the RNA exosome, and here, LC-MS/MS analysis of protein pulldowns demonstrated interaction between the SARS-CoV-2 RNA polymerase and most of the human RNA exosome components. CRISPR/Cas9 introduction of nonsense mutations within EXOSC2 in Calu-3 cells reduced EXOSC2 protein expression and impeded SARS-CoV-2 replication without impacting cellular viability. Targeted depletion of EXOSC2 may be a safe and effective strategy to protect against clinical COVID-19.

4.
American Journal of Respiratory and Critical Care Medicine ; 205:2, 2022.
Article in English | English Web of Science | ID: covidwho-1880909
5.
Topics in Antiviral Medicine ; 30(1 SUPPL):182, 2022.
Article in English | EMBASE | ID: covidwho-1880287

ABSTRACT

Background: The SARS-CoV-2 pandemic has sickened over 245 million people, and has killed more than 5 million worldwide. Recent data proves that vaccinations are highly effective in preventing Covid-19 disease, however antigenic drift and other functional mutations in the virus genome reduce the efficacy of vaccines, indicating that the development of antiviral treatments remain a crucial priority. We report potent antiviral activity against SARS-CoV-2 for a promising, novel class of nitrogen-based heterocyclic compounds. Methods: 232 compounds based on the same class of nitrogen-based hetereocyclic molecules were synthesized to final purity of greater than 99%. This library was screened for antiviral phenotypes in a cytopathic effect (CPE) assay using VeroE6 cells and the SARS-CoV-2 WA1 isolate. Based on the results of the WA1 CPE screen, 47 lead candidates were structurally analyzed, and this information was utilized to design 56 additional compounds. A second antiviral CPE-based screen was performed using these 103 candidates in VeroE6 cells with the SARS-CoV-2 delta variant. Antiviral assays studying SARS-CoV-1 (Urbani) and MERS-CoV were performed in Vero 76 cells utilizing a Neutral Red cytopathic effect assay. Results: Within the same class of structurally related small molecules, we tested an initial set of 232 compounds using a CPE-based assay with VeroE6 cells and the USA/WA1 SARS-CoV-2 isolate. Of the compounds tested, 124 demonstrated potency 10 to 540-times higher than a Remdesivir control tested in parallel. Importantly, we observed no detectable toxicity for the vast majority of these compounds when tested up to a concentration of 30 μ M. The lead candidate in this screen displayed an IC50 of 0.02 μ M and a selectivity index of >1,500. Based on structural analysis of an initial 47 lead candidates, we synthesized 56 new molecules, and tested all 103 in a CPE-based assay using the delta variant, also observing efficacy against this variant of concern. Examples of this same class of compounds also display antiviral activity against SARS-CoV-1 (Urbani) and MERS-CoV in cell-based assays. Conclusion: We have identified a novel class of antiviral compounds with potent activity against SARS-CoV-2. High potency against both the early WA1 isolate and the more recent delta variant, as well as efficacy against SARS-CoV-1 and MERS-CoV, suggest that this class of antiviral compounds has pan-Coronavirus antiviral activity.

6.
J Patient Saf ; 2022 May 25.
Article in English | MEDLINE | ID: covidwho-1865023

ABSTRACT

OBJECTIVES: Opioid misuse has resulted in significant morbidity and mortality in the United States, and safer opioid use represents an important challenge in the primary care setting. This article describes a research collaborative of health service researchers, systems engineers, and clinicians seeking to improve processes for safer chronic opioid therapy management in an academic primary care center. We present implementation results and lessons learned along with an intervention toolkit that others may consider using within their organization. METHODS: Using iterative improvement lifecycles and systems engineering principles, we developed a risk-based workflow model for patients on chronic opioids. Two key safe opioid use process metrics-percent of patients with recent opioid treatment agreements and urine drug tests-were identified, and processes to improve these measures were designed, tested, and implemented. Focus groups were conducted after the conclusion of implementation, with barriers and lessons learned identified via thematic analysis. RESULTS: Initial surveys revealed a lack of knowledge regarding resources available to patients and prescribers in the primary care clinic. In addition, 18 clinicians (69%) reported largely "inheriting" (rather than initiating) their chronic opioid therapy patients. We tracked 68 patients over a 4-year period. Although process measures improved, full adherence was not achieved for the entire population. Barriers included team structure, the evolving opioid environment, and surveillance challenges, along with disruptions resulting from the 2019 novel coronavirus. CONCLUSIONS: Safe primary care opioid prescribing requires ongoing monitoring and management in a complex environment. The application of a risk-based approach is possible but requires adaptability and redundancies to be reliable.

7.
Sustainability ; 14(6):3499, 2022.
Article in English | ProQuest Central | ID: covidwho-1765890

ABSTRACT

In the spring of 2021, the University of San Diego’s Department of Integrated Engineering taught the course, “Integrated Approach to Energy”, the second offering of a new required course, to nine second-year engineering students. The sociotechnical course covered modern energy concepts, with an emphasis on renewable energies and sustainability, and it exposed the students to other ways of being, knowing, and doing that deviated from the dominant masculine Western White colonial discourse. Following the course completion, we interviewed five students by using a semistructured protocol to explore how they perceived of and communicated about engineers and engineering. We sought to identify the takeaways from their course exposure to sustainability and the sociotechnical paradigm, which were central to the course. The findings suggest that the students were beginning to form sociotechnical descriptions, and that they were still developing their understanding and perceptions of engineers and engineering. Moreover, we observed that they were still wrestling with how best to integrate sustainability into those perceptions. There was an a-la-carte feel to the students’ conceptualizations of sustainability as it related to engineering, as in, “you can ‘do’ sustainability with engineering, but do not have to”. We argue that engineering students likely need these pedagogical paradigms (sociotechnical engineering and sustainability) woven through the entirety of their engineering courses if they are to fully accept and integrate them into their own constructs about engineers and engineering.

8.
Molecular Genetics and Metabolism ; 132:S354-S356, 2021.
Article in English | EMBASE | ID: covidwho-1735110

ABSTRACT

Previous studies of genome sequencing (GS) in critically ill childrenhave made use of either modified hardware or working procedureswhich would be difficult, if not impossible, to integrate into existingclinical workflows1. Our lab’s transition from exome sequencing (ES) to GS offered an opportunity to implement in-house rapid genomesequencing (rGS) in critically ill children in a manner which couldintegrate with existing clinical workflows. We conducted a feasibilityand implementation pilot by offering rGS to child-parent triosconcurrently undergoing clinical rapid ES (rES) via a reference lab.The purpose of this study was to identify and address operationalbarriers to implementation of a rGS program capable of communicatinga preliminary result within 7 days of consent. We consideredthis time span to be more reflective of clinical realities than lab-quotedturnaround times (TAT) which typically start at sample receipt andthus do not account for challenges in sample acquisition and pre-testcounseling in a critical care setting, nor the impact of shipping times.Here we present data on TAT and lessons learned from the first 27subjects enrolled.Using rapid cycle improvement methodologies, we identified fourdistinct but inter-related workflows requiring optimization:1. Pre-analytic: patient identification through acquisition ofsamples2. Wet-lab: extraction through sequencing3. Bioinformatics: secondary and tertiary analysis as well as rapididentification of causal variants4. Return of resultsFigure 1 summarizes TAT across cases, demonstrating the markedimprovements in TAT with our programmatic approach to improvement.We used our first 9 cases to determine a baseline TAT for theentire process and to delineate the 4 main workflows (above). Atbaseline, excluding cases delayed by COVID-19 restrictions, mean TATwas 17.12 days (3 sequential deviant range: 7.05–27.19 days).Following deployment of our programmatic approach to rGS, meanTAT fell to 6.19 days (3 sequential deviant range: 0.51–11.87 days).Table 1 summarizes the observations and insights, by workflow, whichimpacted upon TAT and/or implementation. The single biggest impacton TAT was optimization of bioinformatics by removing all manualsteps between starting sequencing and producing human interpretable,filtered, annotated output of high-priority variants for interpretation.The second biggest source of improvement was optimization ofthe sequencing itself as well as prioritizing sample processing for andaccess to sequencing runs. While variant ranking is helpful in identifying causal variants, in 9/10 cases with a diagnostic findingthe causal variant(s)were obvious to the study teamwithin minutes ofviewing the annotated variant list, regardless of variant rank. (Figure Presented) As time required for sequencing and analytic workflows fell, therelative contribution of other workflows to overall TAT shifted and itbecame more obvious that early identification and utilization of thisapproach is very important in lowering overall time to diagnosis(Figure 2). In 6/10 cases with a diagnostic finding, the initial approachof the clinical team was NOT rES (and thus patients were not eligiblefor rGS on a research basis). Had rGS been the initial diagnosticmodality chosen, a diagnosis could have been reached in a median 12days sooner (range 2–28 days). There were also several cases wheresequencing was delayed when one or both parents did not present tothe lab to provide a blood sample in a timely manner. Optimization ofsequencing or analytic workflows cannot meaningfully improveoutcomes either of these situations.Our findings suggest some important considerations for institutionsdeveloping or seeking to improve rapid sequencing programs for acuteand critically ill children: (Table Presented) • Optimization of computational resource utilization and phenotypecuration saves more time than improved variant filtering orprioritization.• Obtaining samples from parents is non-trivial.• Even trained geneticists may fail to recognize appropriatecandidates for rGS.

9.
Clin Microbiol Rev ; 35(1): e0009421, 2022 01 19.
Article in English | MEDLINE | ID: covidwho-1522897

ABSTRACT

Individuals suffering from severe viral respiratory tract infections have recently emerged as "at risk" groups for developing invasive fungal infections. Influenza virus is one of the most common causes of acute lower respiratory tract infections worldwide. Fungal infections complicating influenza pneumonia are associated with increased disease severity and mortality, with invasive pulmonary aspergillosis being the most common manifestation. Strikingly, similar observations have been made during the current coronavirus disease 2019 (COVID-19) pandemic. The copathogenesis of respiratory viral and fungal coinfections is complex and involves a dynamic interplay between the host immune defenses and the virulence of the microbes involved that often results in failure to return to homeostasis. In this review, we discuss the main mechanisms underlying susceptibility to invasive fungal disease following respiratory viral infections. A comprehensive understanding of these interactions will aid the development of therapeutic modalities against newly identified targets to prevent and treat these emerging coinfections.


Subject(s)
COVID-19 , Coinfection , Respiratory Tract Infections , Viruses , Humans , SARS-CoV-2
10.
Nat Commun ; 12(1): 6343, 2021 11 03.
Article in English | MEDLINE | ID: covidwho-1500461

ABSTRACT

Peptide secondary metabolites are common in nature and have diverse pharmacologically-relevant functions, from antibiotics to cross-kingdom signaling. Here, we present a method to design large libraries of modified peptides in Escherichia coli and screen them in vivo to identify those that bind to a single target-of-interest. Constrained peptide scaffolds were produced using modified enzymes gleaned from microbial RiPP (ribosomally synthesized and post-translationally modified peptide) pathways and diversified to build large libraries. The binding of a RiPP to a protein target leads to the intein-catalyzed release of an RNA polymerase σ factor, which drives the expression of selectable markers. As a proof-of-concept, a selection was performed for binding to the SARS-CoV-2 Spike receptor binding domain. A 1625 Da constrained peptide (AMK-1057) was found that binds with similar affinity (990 ± 5 nM) as an ACE2-derived peptide. This demonstrates a generalizable method to identify constrained peptides that adhere to a single protein target, as a step towards "molecular glues" for therapeutics and diagnostics.


Subject(s)
Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Peptides/chemistry , Peptides/pharmacology , SARS-CoV-2/drug effects , COVID-19/drug therapy , COVID-19/virology , Drug Design , Drug Evaluation, Preclinical , Humans , Kinetics , Models, Molecular , Peptides/genetics , Protein Binding , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism
11.
J Ambul Care Manage ; 44(4): 293-303, 2021.
Article in English | MEDLINE | ID: covidwho-1447660

ABSTRACT

COVID-19 necessitated significant care redesign, including new ambulatory workflows to handle surge volumes, protect patients and staff, and ensure timely reliable care. Opportunities also exist to harvest lessons from workflow innovations to benefit routine care. We describe a dedicated COVID-19 ambulatory unit for closing testing and follow-up loops characterized by standardized workflows and electronic communication, documentation, and order placement. More than 85% of follow-ups were completed within 24 hours, with no observed staff, nor patient infections associated with unit operations. Identified issues include role confusion, staffing and gatekeeping bottlenecks, and patient reluctance to visit in person or discuss concerns with phone screeners.


Subject(s)
Ambulatory Care Facilities/organization & administration , COVID-19/therapy , Continuity of Patient Care/organization & administration , Pneumonia, Viral/therapy , Respiratory Care Units/organization & administration , Adult , Aged , Boston/epidemiology , COVID-19/epidemiology , Female , Humans , Male , Middle Aged , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Referral and Consultation/statistics & numerical data , SARS-CoV-2 , Systems Analysis , Workflow
13.
Pathology ; 53:S50-S51, 2021.
Article in English | PMC | ID: covidwho-1386423

ABSTRACT

Introduction: The gold standard for diagnosing SARS-CoV-2 infection remains RT-PCR;however serological testing has an important role in epidemiology and assessment of vaccine responses. We expressed the receptor binding domain (RBD) of the spike (S) protein as a glycosylphosphatidylinositol (GPI)-anchored protein on CHO cells transfected with a generated construct and determined binding of RBD specific antibodies by immunofluorescence (IF) and flow cytometry (FACS) assays. Methods and results: IF and FACS demonstrated cell surface RBD expression using anti-S RBD mAb and macaque immune sera. GPI anchored expression was confirmed through loss of positive cells on FACS post GPI anchor cleavage with phosphoinositide phospholipase C (PI-PLC). Binding of antibodies from COVID-19 convalescent sera to RBD- and mock-transfectants was performed by FACS. Positive results on serial dilutions of patient sera down to 1:3200 were observed and compared to in-house RBD ELISA which lost positivity at a 1:800 dilution. Soluble recombinant ACE2 bound to RBD-CHOs and binding was inhibited by COVID-19 convalescent sera indicating the RBD was expressed in a functional conformation and that neutralising antibodies were detected. Conclusion: Mammalian cells expressing GPI-anchored RBD can successfully be used to detect previous SARS-CoV-2 infection and likely indicate the presence of neutralising antibodies in COVID-19 survivors.

17.
Sustainability ; 13(13):7188, 2021.
Article in English | ProQuest Central | ID: covidwho-1304723

ABSTRACT

Engineers are increasingly called on to develop sustainable solutions to complex problems. Within engineering, however, economic and environmental aspects of sustainability are often prioritized over social ones. This paper describes how efficiency and sustainability were conceptualized and interrelated by students in a newly developed second-year undergraduate engineering course, An Integrated Approach to Energy. This course took a sociotechnical approach and emphasized modern energy concepts (e.g., renewable energy), current issues (e.g., climate change), and local and personal contexts (e.g., connecting to students’ lived experiences). Analyses of student work and semi-structured interview data were used to explore how students conceptualized sustainability and efficiency. We found that in this cohort (n = 17) students often approached sustainability through a lens of efficiency, believing that if economic and environmental resources were prioritized and optimized, sustainability would be achieved. By exploring sustainability and efficiency together, we examined how dominant discourses that privilege technical over social aspects in engineering can be replicated within an energy context.

18.
Sustainability ; 12(21):9145, 2020.
Article in English | ProQuest Central | ID: covidwho-1299579

ABSTRACT

What do engineering students in 2020 need to know about energy to be successful in the workplace and contribute to addressing society’s issues related to energy? Beginning with this question, we have designed a new course for second-year engineering students. Drawing on the interdisciplinary backgrounds of our diverse team of engineering instructors, we aimed to provide an introduction to energy for all engineering students that challenged the dominant discourse in engineering by valuing students’ lived experiences and bringing in examples situated in different cultural contexts. An Integrated Approach to Energy was offered for the first time in Spring 2020 for 18 students. In this paper, we describe the design of the course including learning objectives, content, and pedagogical approach. We assessed students’ learning using exams and the impact of the overall course using interviews. Students demonstrated achievement of the learning objectives in technical areas. In addition, interviews revealed that they learned about environmental, economic, and social aspects of engineering practice. We intend for this course to serve as a model of engineering as a sociotechnical endeavor by challenging students with scenarios that are technically demanding and require critical thinking about contextual implications.

20.
American Journal of Respiratory and Critical Care Medicine ; 203(9), 2021.
Article in English | EMBASE | ID: covidwho-1277069

ABSTRACT

RATIONALE: The novel coronavirus disease 2019 (COVID-19) is a rapidly spreading global viral pandemic with a high-risk of mortality in selected populations (i.e. elderly, immunocompromised, cardiopulmonary diseases). A hyperinflammatory state caused by excessive inflammatory cytokine production (i.e. TNFα, IL-1β, IL6, IL-8) has been attributed to the pathobiology of COVID-19-mediated acute respiratory distress syndrome, worsened lung fibrosis and increased mortality. Inflammation and inflammatory disorders signal primarily through the MAPK pathway. Activation of p38α is important for regulating inflammation, and aberrant p38α activation is associated in the pathobiology of diseases such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease and tissue fibrosis. The downstream target of p38α is the protein MAPKAPK2 (MK2) and is responsible for transcriptional production of pro-inflammatory cytokines also elevated in COVID-19 inflammation. Further evidence in other severe viral illnesses (i.e. Dengue, Influenza, CMV) show activation of p38-MK2 signaling axis for mediating inflammation. Potentially, COVID-19 mediated inflammatory cytokine production may signal through p38α-MK2 axis and MK2 pathway blockade may suppress unwanted inflammation. However, it remains unknown whether reducing the inflammatory state can improve COVID-19 outcomes particularly in those with pre-existing conditions. We hypothesized that blockading this pathway would reduce inflammatory cytokine burden and improve respiratory failure-free survival in moderate-severe COVID-19 infected patients. Methods: We designed an investigator-initiated trial (IND#:149790;ClinicalTrials.gov Identifier: NCT04481685) using an oral MK2 inhibitor (ATI-450, Aclaris Pharmaceuticals) in COVID-19. This single-center trial is a Phase IIa, doubleblinded, randomized placebo-controlled proof-of-concept study. COVID-19 positive hospitalized patients with pulmonary signs and symptoms of moderate-severe hypoxic respiratory distress were randomized to ATI-450 or placebo twice-daily for up to 14 days. Results: Study enrollment is completed (n=20 subjects;n=11 male;median age 63 years old). The primary endpoint of this trial is respiratory failure-free survival at 14 days. Secondary endpoints include: changes in WHO-Ordinal scale, additional respiratory and survival outcomes, biochemical assays of circulating cytokines, and safety endpoints. Given the incomplete knowledge of MK2 pathway blockade effects on immune cell function, this study will further explore immune cell characterization in COVID-19 patients treated with ATI-450 via immunophenotyping and 10X Genomics single-cell gene expression analysis. We surmise that myeloid cell activation following COVID-19 infection contributes to localized and systemic tissue injury and will examine the effect of MK2 pathway blockade on eliciting myeloid cell inflammatory activation-suppression. Conclusion: Analyses of the safety, efficacy, and biology of MK2 inhibition, via ATI-450, in treating moderate-severe COVID-19 will be presented.

SELECTION OF CITATIONS
SEARCH DETAIL