The SARS-CoV-2 SSHHPS Recognized by the Papain-like Protease

Viral proteases are highly specific and recognize conserved cleavage site sequences of ∼6–8 amino acids. Short stretches of homologous host–pathogen sequences (SSHHPS) can be found spanning the viral protease cleavage sites. We hypothesized that these sequences corresponded to specific host protein targets since >40 host proteins have been shown to be cleaved by Group IV viral proteases and one Group VI viral protease. Using PHI-BLAST and the viral protease cleavage site sequences, we searched the human proteome for host targets and analyzed the hit results. Although the polyprotein and host proteins related to the suppression of the innate immune responses may be the primary targets of these viral proteases, we identified other cleavable host proteins. These proteins appear to be related to the virus-induced phenotype associated with Group IV viruses, suggesting that information about viral pathogenesis may be extractable directly from the viral genome sequence. Here we identify sequences cleaved by the SARS-CoV-2 papain-like protease (PLpro) in vitro within human MYH7 and MYH6 (two cardiac myosins linked to several cardiomyopathies), FOXP3 (an X-linked Treg cell transcription factor), ErbB4 (HER4), and vitamin-K-dependent plasma protein S (PROS1), an anticoagulation protein that prevents blood clots. Zinc inhibited the cleavage of these host sequences in vitro. Other patterns emerged from multispecies sequence alignments of the cleavage sites, which may have implications for the selection of animal models and zoonosis. SSHHPS/nsP is an example of a sequence-specific post-translational silencing mechanism

Does dual operator CPR help minimize interruptions in chest compressions?

Aims: Basic Life Support Guidelines 2005 emphasise the importance of reducing interruptions in chest compressions (no-flow duration) yet at the same time stopped recommending Dual Operator CPR. Dual Operator CPR (where one rescuer does ventilations and one chest compressions) could potentially minimize no-flow duration compared to Single Operator CPR. This study aims to determine if Dual Operator CPR reduces no-flow duration compared to Single Operator CPR. Methodology: This was a prospective randomised controlled crossover trial. Medical students were randomised into 'Dual Operator' or 'Single Operator' CPR groups. Both groups performed 4 min of CPR according to their group allocation on a resuscitation manikin before crossing over to perform the other technique one week later. Results: Fifty participants were recruited. Dual Operator CPR achieved slightly lower no-flow durations than the Single Operator CPR (28.5% (S.D. = 3.7) versus 31.6% (S.D. = 3.6), P <= 0.001). Dual Operator CPR was associated with slightly more rescue breaths per minute (4.9 (S.D. = 0.5) versus 4.5 (S.D. = 0.5), P = 0.009. There was no difference in compression depth, compression rate, duty cycle, rescue breath flow rate or rescue breath volume. Conclusions: Dual Operator CPR with a compression to ventilation rate of 30: 2 provides marginal improvement in no-flow duration but CPR quality is otherwise equivalent to Single Operator CPR. There seems little advantage to adding teaching on Dual Operator CPR to lay/trained first responder CPR programs

Telemedicine REsuscitation and Arrest Trial (TREAT): A feasibility study of real-time provider-to-provider telemedicine for the care of critically ill patients

Background: Protocol-based resuscitation strategies in the Emergency Department (ED) improve survival for out-of-hospital cardiac arrest (OHCA) and severe sepsis but implementation has been inconsistent. Objective: To determine the feasibility of a real-time provider-to-provider telemedical intervention for the treatment of OHCA and severe sepsis. Materials and methods: A three-center pilot study utilizing a “hub-spoke model” with an academic medical center acting both as the hub for teleconsultation as well as a spoke hospital enrolling patients. Eligible patients were adults presenting with either return of spontaneous circulation (ROSC) following OHCA or with severe sepsis. Telemedical encounters were monitored for quality of interface and patient level data (demographics, physiologic, laboratory, treatment) were abstracted. Results: Over a 12-week period, there were 80 text alerts. Of 38 OHCA alerts, 13 achieved ROSC (34.2%), 85% underwent teleconsultation (11/13). Of 42 “lactate ≥4 mmol/L” alerts, 33.3% (14/42) were determined to have severe sepsis and underwent teleconsultation. Mean time from OHCA teleconsultation request to live connection: 3.7 min (95% CI 1.6–5.8); mean call duration: 71.7 min (95% CI 34.6–108.8). Mean time from sepsis teleconsultation request to connection: 8.4 min (95% CI 4.5–12.3); mean call duration: 61.5 min (95% CI 37.2–85.8). Discussion: Telemedicine provides a robust and reliable means of quickly bringing expertise virtually to the bedside at the most proximal point in a patient’s hospital care. Conclusions: Real time ED-based telemedical consultation for patients with ROSC after OHCA or severe sepsis has the potential to improve the dissemination and implementation of evidence-based care

Documenting Social Media Engagement as Scholarship: A New Model for Assessing Academic Accomplishment for the Health Professions.

BACKGROUND The traditional model of promotion and tenure in the health professions relies heavily on formal scholarship through teaching, research, and service. Institutions consider how much weight to give activities in each of these areas and determine a threshold for advancement. With the emergence of social media, scholars can engage wider audiences in creative ways and have a broader impact. Conventional metrics like the h-index do not account for social media impact. Social media engagement is poorly represented in most curricula vitae (CV) and therefore is undervalued in promotion and tenure reviews. OBJECTIVE The objective was to develop crowdsourced guidelines for documenting social media scholarship. These guidelines aimed to provide a structure for documenting a scholar's general impact on social media, as well as methods of documenting individual social media contributions exemplifying innovation, education, mentorship, advocacy, and dissemination. METHODS To create unifying guidelines, we created a crowdsourced process that capitalized on the strengths of social media and generated a case example of successful use of the medium for academic collaboration. The primary author created a draft of the guidelines and then sought input from users on Twitter via a publicly accessible Google Document. There was no limitation on who could provide input and the work was done in a democratic, collaborative fashion. Contributors edited the draft over a period of 1 week (September 12-18, 2020). The primary and secondary authors then revised the draft to make it more concise. The guidelines and manuscript were then distributed to the contributors for edits and adopted by the group. All contributors were given the opportunity to serve as coauthors on the publication and were told upfront that authorship would depend on whether they were able to document the ways in which they met the 4 International Committee of Medical Journal Editors authorship criteria. RESULTS We developed 2 sets of guidelines: Guidelines for Listing All Social Media Scholarship Under Public Scholarship (in Research/Scholarship Section of CV) and Guidelines for Listing Social Media Scholarship Under Research, Teaching, and Service Sections of CV. Institutions can choose which set fits their existing CV format. CONCLUSIONS With more uniformity, scholars can better represent the full scope and impact of their work. These guidelines are not intended to dictate how individual institutions should weigh social media contributions within promotion and tenure cases. Instead, by providing an initial set of guidelines, we hope to provide scholars and their institutions with a common format and language to document social media scholarship

Mitochondrial dysfunction reactivates α-fetoprotein expression that drives copper-dependent immunosuppression in mitochondrial disease models

Signaling circuits crucial to systemic physiology are widespread, yet uncovering their molecular underpinnings remains a barrier to understanding the etiology of many metabolic disorders. Here, we identified a copper-linked signaling circuit activated by disruption of mitochondrial function in the murine liver or heart that resulted in atrophy of the spleen and thymus and caused a peripheral white blood cell deficiency. We demonstrated that the leukopenia was caused by alpha-fetoprotein, which required copper and the cell surface receptor CCR5 to promote white blood cell death. We further showed that alpha-fetoprotein expression was upregulated in several cell types upon inhibition of oxidative phosphorylation. Collectively, our data argue that alpha-fetoprotein may be secreted by bioenergetically stressed tissue to suppress the immune system, an effect that may explain the recurrent or chronic infections that are observed in a subset of mitochondrial diseases or in other disorders with secondary mitochondrial dysfunction.Peer reviewe