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The Streptococcal C5a peptidase (ScpA) specifically inactivates the human complement factor hC5a, a potent anaphylatoxin recently identified as a therapeutic target for treatment of COVID-19 infections. Biologics used to modulate hC5a are predominantly monoclonal antibodies. Here we present data to support an alternative therapeutic approach based on the specific inactivation of hC5a by ScpA in studies using recombinant hC5a (rhC5a). Initial characterization of ScpA confirmed activity in human serum and against rhC5a desArg (rhC5adR), the predominant hC5a form in blood. A new FRET based enzyme assay showed that ScpA cleaved rhC5a at near physiological concentrations (K m 185 nM). Surface Plasmon Resonance (SPR) and Isothermal Titration Calorimetry (ITC) studies established a high affinity ScpA-rhC5a interaction (K D 34 nM, K D ITC 30.8 nM). SPR analyses also showed that substrate binding is dominated (88% of ΔG°bind) by interactions with the bulky N-ter cleavage product (PN, 'core' residues 1-67) with interactions involving the C-ter R74 contributing most of the remaining ΔG°bind. Furthermore, reduced binding affinity following mutation of a subset of positively charged Arginine residues of PN and in the presence of higher salt concentrations, highlighted the importance of electrostatic interactions. These data provide the first in-depth study of the ScpA-C5a interaction and indicate that ScpA's ability to efficiently cleave physiological concentrations of C5a is driven by electrostatic interactions between an exosite on the enzyme and the 'core' of C5a. The results and methods described herein will facilitate engineering of ScpA to enhance its potential as a therapeutic for excessive immune response to infectious disease.Remote delivery of language and cognitive training is becoming increasingly prevalent within special education settings, and the recent COVID-19 pandemic has challenged many providers to pivot to telehealth models. This technical article outlines a procedure for developing computerized discrete-trial training programs using commonly available software, as well as a description of how to adapt this strategy to teach chained tasks remotely. Within this article, we describe how to establish unidirectional and bidirectional remote interfaces to work directly with learners. Finally, we conducted a field test of these approaches with programs adapted from two standardized curricula PEAK and PRISM. We conclude the article by discussing barriers and potential solutions that we observed while field-testing these procedures within special education settings in response to the wide-scale emigration to remote teaching due to the COVID-19 pandemic.
The online version contains supplementary material available at 10.1007/s40617-020-00544-6.
The online version contains supplementary material available at 10.1007/s40617-020-00544-6.
With the recent announcement that Step 1 score reporting will soon change to pass/fail, residency programs will need to reconsider their recruitment processes.
We (1) evaluated the feasibility of blinding residency programs to applicants' Step 1 scores and their number of attempts throughout the recruitment process; (2) described the selection process that resulted from the blinding; and (3) reviewed if a program's initial rank list, created before scores were known, would be changed before submission for the Match.
During the 2018-2019 and 2019-2020 recruitment seasons, all programs at a single sponsoring institution were invited to develop selection criteria in the absence of Step 1 data, and to remain blinded to this data throughout recruitment. Participating programs were surveyed to determine factors affecting feasibility and metrics used for residency selection. Once unblinded to Step 1 scores, programs had the option to change their initial rank lists.
Of 24 residency programs, 4 participated (17%) in the first year emergency medicine, neurology, pediatrics, and psychiatry. The second year had the same participants, with the addition of family and community medicine and radiation oncology (n = 6, 25%). Each program was able to determine mission-specific qualities in the absence of Step 1 data. In both years, one program made changes to the final rank list.
It was feasible for programs to establish metrics for residency recruitment in the absence of Step 1 data, and most programs made no changes to final rank lists after Step 1 scores were known.
It was feasible for programs to establish metrics for residency recruitment in the absence of Step 1 data, and most programs made no changes to final rank lists after Step 1 scores were known.
Daily attending rounds (AR) are a cornerstone of teaching and patient care in academic health centers. Interruptions in health care are common and can cause increased risk of errors, incomplete work, and decreased decision-making accuracy. Interruptions to AR may diminish a trainee's capacity to learn and retain information.
We characterized and quantified interruptions that occur during AR.
We used a mixed
methods design combining a prospective observational study with a qualitative study. AR were observed January to March 2020 to characterize interruptions, followed by semi-structured interviews with the observed physicians to elucidate the effect of interruptions on workflow and the educational value of rounds.
There were 378 observed interruptions over the course of 30 AR sessions, averaging 12.6 (range 1-22, median 13) interruptions per rounding session. Bedside nursing staff was the most common source of interruptions (25%) and consultant recommendations was the most common topic of interruption (21%). Most interruptions occurred during patient presentations (76%), and the most common method of interaction was text message (24%). Most team members described negative effects of interruptions, including loss of focus and missing critical clinical information; some also reported that certain interruptions had positive effects on education and clinical care. Interns were more likely to report negative emotional reactions to interruptions.
AR are frequently interrupted for non-urgent topics by a variety of methods and sources. Negative effects included loss of focus, missed information, and increased stress. Proactive communication, particularly between physicians and nurses, was suggested to reduce interruptions.
AR are frequently interrupted for non-urgent topics by a variety of methods and sources. Negative effects included loss of focus, missed information, and increased stress. Proactive communication, particularly between physicians and nurses, was suggested to reduce interruptions.
Residency applications have increased in the last decade, creating growing challenges for applicants and programs.
We evaluated factors associated with application and match into obstetrics and gynecology residency.
During the annual in-training examination administered to all obstetrics and gynecology residents in the United States, residents were surveyed on the residency application process.
Ninety-five percent (5094 of 5347) residents responded to the survey. Thirty-six percent reported applying to 30 or fewer programs, 26.7% applied to more than 31 programs, and 37.1% opted not to answer this question. Forty-nine percent of residents received honors in their obstetrics and gynecology clerkship and 37.1% did not. The majority of residents (88.6%) reported scoring between 200 and 250 on USMLE Step 1. Eighty-six percent matched into one of their top 5 programs. The only factor associated with matching in residents' top 5 programs was receiving honors in their clerkship (OR 1.29; 95% CI 1.08-1.54;
< .005). The only factor associated with matching below the top 5 programs was a couples match (OR 0.56; 95% CI 0.43-0.72;
< .001). In choosing where to apply, residents identified program location and reputation as the most important factors, while for ranking, location and residency culture were the most important.
Most obstetrics and gynecology residents reported matching into their top 5 choices. Receiving an honors grade in the clerkship was the only factor associated with matching in applicants' top 5 programs. Location was the most important factor for applying to and ranking of programs.
Most obstetrics and gynecology residents reported matching into their top 5 choices. Receiving an honors grade in the clerkship was the only factor associated with matching in applicants' top 5 programs. Location was the most important factor for applying to and ranking of programs.
Literature examining the feedback supervisors give to residents during case discussions in the realms of communication, collaboration, and professional roles (intrinsic roles) focuses on analyses of written feedback and self-reporting.
We quantified how much of the supervisors' verbal feedback time targeted residents' intrinsic roles and how well feedback time was aligned with the role targeted by each case. We analyzed the educational goals of this feedback. We assessed whether feedback content differed depending on whether the residents implied or explicitly expressed a need for particular feedback.
This was a mixed-methods study conducted from 2017 to 2019. We created scripted cases for radiology and internal medicine residents to present to supervisors, then analyzed the feedback given both qualitatively and quantitatively. https://www.selleckchem.com/products/hth-01-015.html The cases were designed to highlight the CanMEDS intrinsic roles of communicator, collaborator, and professional.
Radiologists (n = 15) spent 22% of case discussions providing feedback on intrinsic roles (48% aligned) 28% when the case targeted the communicator role, 14% for collaborator, and 27% for professional. Internists (n = 15) spent 70% of discussions on intrinsic roles (56% aligned) 66% for communicator, 73% for collaborator, and 72% for professional. Radiologists' goals were to offer advice (66%), reflections (21%), and agreements (7%). Internists offered advice (41%), reflections (40%), and clarifying questions (10%). We saw no consistent effects when residents explicitly requested feedback on an intrinsic role.
Case discussions represent frequent opportunities for substantial feedback on intrinsic roles, largely aligned with the clinical case. Supervisors predominantly offered monologues of advice and agreements.
Case discussions represent frequent opportunities for substantial feedback on intrinsic roles, largely aligned with the clinical case. Supervisors predominantly offered monologues of advice and agreements.
The residency selection process relies on subjective information in applications, as well as subjective assessment of applications by reviewers. This inherent subjectivity makes residency selection prone to poor reliability between those reviewing files.
We compared the interrater reliability of 2 assessment tools during file review one rating applicant traits (ie, leadership, communication) and the other using a global rating of application elements (ie, curriculum vitae, reference letters).
Ten file reviewers were randomized into 2 groups, and each scored 7 general surgery applications from the 2019-2020 cycle. The first group used an element-based (EB) scoring tool, while the second group used a trait-based (TB) scoring tool. Feedback was collected, discrimination capacities were measured using variation in scores, and interrater reliability (IRR) was calculated using intraclass correlation (ICC) in a 2-way random effects model.
Both tools identified the same top-ranked and bottom-ranked applicants; however, discrepancies were noted for middle-ranked applicants.
Website: https://www.selleckchem.com/products/hth-01-015.html
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