Framework for an interprofessional experience addressing health and disability for health professional students.

BACKGROUND AND PURPOSE: A Health and Disabilities Interprofessional Education (IPE) course was implemented to join three healthcare disciplines together to collaboratively plan, implement, and reflect on professional roles and responsibilities. The goal and purpose of this course was to create an advancement of interprofessional education and practice within health science professions early in their students' programs utilizing innovative teaching methods working directly with individuals with disabilities. EDUCATIONAL ACTIVITY AND SETTING: 72 students were assigned to interprofessional teams of 10-11 people. Through asynchronous and synchronous learning activities, student teams worked together to plan and conduct community-based client interviews. FINDINGS: Quantitative and qualitative evaluation methods were used to explore the impact of interprofessional experiential learning experiences. Qualitative data showed a greater awareness and understanding of the different roles and responsibilities in interprofessional teams as well as a greater appreciation for the value of interacting with persons with disabilities (PWD) during their training. Quantitative data showed a significant change in students' understanding of their roles and responsibilities as a member of an interprofessional team, their confidence with working with PWD in a future healthcare capacity, as well as their understanding of how the social determinants of health may influence the healthcare experience of a PWD. SUMMARY: Interprofessional education and experiential learning opportunities are good ways to facilitate "real" patient care experiences and team roles and responsibilities. This enables healthcare students to practice communication, build relationships, and understand the lived experience of their patients.

Opioid prescription patterns among commercially insured children with and without cerebral palsy.

PURPOSE: This study aimed to describe opioid prescription patterns for children with vs. without cerebral palsy (CP). METHODS: This cohort study used commercial claims from 01/01/2015-12/31/2016 and included children aged 2-18 years old with and without CP. Opioid prescription patterns (proportion exposed, number of days supplied) were described. A zero-inflated generalized linear model compared the proportion exposed to opioids in the follow-up year (2016) and, among those exposed, the number of days supplied opioids between cohorts before and after adjusting for age, gender, race, U.S. region of residence, and the number of co-occurring neurological/neurodevelopmental disabilities (NDDs). RESULTS: A higher proportion of children with (n = 1,966) vs. without (n = 1,219,399) CP were exposed to opioids (12.1% vs. 5.3%), even among the youngest age group (2-4 years: 9.6% vs. 1.8%), and had a greater number of days supplied (median [interquartile range], 8 [5-13] vs. 6 [4-9] days; P < 0.05). Comparing children with opioid exposure with vs. without CP, a greater number of days supplied was identified for older age, Asian race/ethnicity, and without co-occurring NDDs, and a lower number of days supplied was observed for Black race/ethnicity and with ≥1 co-occurring NDDs. CONCLUSION: Children with CP are more likely to be exposed to opioids and have a higher number of days supplied.

The endogenous Mtv8 locus and the immunoglobulin repertoire.

The vast diversity of mammalian adaptive antigen receptors allows for robust and efficient immune responses against a wide number of pathogens. The antigen receptor repertoire is built during the recombination of B and T cell receptor (BCR, TCR) loci and hypermutation of BCR loci. V(D)J recombination rearranges these antigen receptor loci, which are organized as an array of separate V, (D), and J gene segments. Transcription activation at the recombining locus leads to changes in the local three-dimensional architecture, which subsequently contributes to which gene segments are utilized for recombination. The endogenous retrovirus (ERV) mouse mammary tumor provirus 8 (Mtv8) resides on mouse chromosome 6 interposed within the large array of light chain kappa V gene segments. As ERVs contribute to changes in genomic architecture by driving high levels of transcription of neighboring genes, it was suggested that Mtv8 could influence the BCR repertoire. We generated Mtv8-deficient mice to determine if the ERV influences V(D)J recombination to test this possibility. We find that Mtv8 does not influence the BCR repertoire.

Risk of post-fracture pneumonia and its association with cardiovascular events and mortality in adults with intellectual disabilities.

Objective: Fragility fractures are associated with an increased risk of pneumonia, which is a leading cause of death in adults with intellectual disabilities; however, the timing and complications of post-fracture pneumonia are underinvestigated. The objectives of this study were to determine the 30-day pneumonia rate post-fracture and the association of post-fracture pneumonia with mortality and cardiovascular events among adults with intellectual disabilities. Methods: This retrospective cohort study was conducted using Medicare and commercial claims from 01 January 2011 to 31 December 2016. Incidence of pneumonia 30 days after a fragility fracture among adults ≥18 years old with intellectual disabilities (Fx cohort) was compared to the incidence among matched adults with intellectual disabilities without fractures (w/oFx cohort) and the general population of patients with an incident fragility fracture (GP+Fx). For the Fx cohort, Cox regression was used to examine the adjusted association of time-varying pneumonia (within 30 days post-fracture) with mortality and incidence of cardiovascular events 0-30, 31-365, and 366-730 days post-fracture. Results: There was a high-early rate of pneumonia within 30 days post-fracture for young, middle-aged, and elderly adults with intellectual disabilities (n = 6,183); this rate was 2.2- to 6.1-fold higher than the rate among the w/oFx (n = 12,366) and GP+Fx (n = 363,995) cohorts (all P < 0.05). For the Fx cohort, post-fracture 30-day incidence of pneumonia was associated with an increased 30-day rate of mortality (adjusted HR [aHR] = 5.19; 95% confidence interval [CI] = 3.68-7.32), heart failure (aHR = 2.96; 95% CI = 1.92-4.56), and cerebrovascular disease (aHF = 1.48; 95% CI = 0.93-2.35; P = 0.098), with sustained effects to 1 year for heart failure (aHR = 1.61; 95% CI = 1.19-2.17) and 2 years for mortality (aHR = 1.39; 95% CI = 1.06-1.83), and without evidence of effect modification by age. Discussion: Adults with intellectual disabilities are vulnerable to post-fracture pneumonia within 30 days, and complications arising from this, across the adult lifespan, and not only during the elderly years.

Heart rate and autonomic biomarkers distinguish convulsive epileptic vs. functional or dissociative seizures.

OBJECTIVE: 20-40% of individuals whose seizures are not controlled by anti-seizure medications exhibit manifestations comparable to epileptic seizures (ES), but there are no EEG correlates. These events are called functional or dissociative seizures (FDS). Due to limited access to EEG-monitoring and inconclusive results, we aimed to develop an alternative diagnostic tool that distinguishes ES vs. FDS. We evaluated the temporal evolution of ECG-based measures of autonomic function (heart rate variability, HRV) to determine whether they distinguish ES vs. FDS. METHODS: The prospective study includes patients admitted to the University of Rochester Epilepsy Monitoring Unit. Participants are 18-65 years old, without therapies or co-morbidities associated with altered autonomics. A habitual ES or FDS is recorded during admission. HRV analysis is performed to evaluate the temporal changes in autonomic function during the peri­ictal period (150-minutes each pre-/post-ictal). We determined if autonomic measures distinguish ES vs. FDS. RESULTS: The study includes 53 ES and 46 FDS. Temporal evolution of HR and autonomics significantly differ surrounding ES vs. FDS. The pre-to-post-ictal change (delta) in HR differs surrounding ES vs. FDS, stratified for convulsive and non-convulsive events. Post-ictal HR, total autonomic (SDNN & Total Power), vagal (RMSSD & HF), and baroreflex (LF) function differ for convulsive ES vs. convulsive FDS. HR distinguishes non-convulsive ES vs. non-convulsive FDS with ROC>0.7, sensitivity>70%, but specificity<50%. HR-delta and post-ictal HR, SDNN, RMSSD, LF, HF, and Total Power each distinguish convulsive ES vs. convulsive FDS (ROC, 0.83-0.98). Models with HR-delta and post-ictal HR provide the highest diagnostic accuracy for convulsive ES vs. convulsive FDS: 92% sensitivity, 94% specificity, ROC 0.99). SIGNIFICANCE: HR and HRV measures accurately distinguish convulsive, but not non-convulsive, events (ES vs. FDS). Results establish the framework for future studies to apply this diagnostic tool to more heterogeneous populations, and on out-of-hospital recordings, particularly for populations without access to epilepsy monitoring units.

Short Report: Where do caregivers of persons with intellectual or developmental disabilities obtain information about medication?

BACKGROUND/AIMS/METHODS: Medication information is available from many sources. This short report provides a simple description of where caregivers of people with intellectual/developmental disability (IDD) obtain medication information, and compares these sources between family caregivers and direct support professionals (DSP). PROCEDURES/OUTCOMES: Cross-sectional study design using an internet-based survey of caregivers, aged 18 years or older, who provided support to adults with IDD. The primary outcome is the source of medication information reported by caregivers. RESULTS/CONCLUSIONS: Eighty-nine caregivers responded. Health care professionals were the primary source (87.6 %) of medication information, followed by the internet (77.5 %). There was no difference between caregiver groups for these two sources. The prescription label/information sheet was the next most common source (56.2 %), with significantly more family (76.2 %) versus DSP (38.3 %), p < 0.001. A medication reference was also common (43.8 %), with 28.6 % of family and 57.4 % of DSP, p = 0.006. House manager/nurse was next, with 16.9 %, and television/radio as a source (10.1 %), no difference between groups. Lastly, friends or coworkers were 7.9 %, with no DSP endorsing this option, p = 0.006. IMPLICATIONS: Caregivers obtain medication information from a variety of sources, with health care professionals being the primary source. The internet was also very common, which may be worrisome, due to the wide range of level of quality of information available. Educational interventions should be developed to provide caregivers with tools to be able identify and use legitimate medication information.

High cardiorespiratory disease burden following a fracture among adults with intellectual disabilities.

BACKGROUND: Adults with intellectual disabilities have a greater risk for fragility fractures that begin to accumulate early in the adult lifespan, which may contribute to accelerated health declines. The objective was to determine if fragility fractures were associated with an increased 2-year rate of cardiorespiratory diseases among adults with intellectual disabilities. METHOD: This retrospective cohort study used nationwide administrative claims data from 01/01/2011-12/31/2016 from the Medicare fee-for-service database. 2-year incidence of cardiorespiratory diseases were compared between adults ≥18 years old with intellectual disabilities with (n = 6183) vs. without (n = 67,842) an incident fragility fracture after confounder adjustment using Cox regression. RESULTS: Fracture at the vertebral column, hip, non-proximal femur, tibia/fibula, and multiple sites had an elevated hazard ratio (HR) compared to those with no fracture for pneumonia, respiratory failure, heart failure, and cerebrovascular disease (HR range, 1.15-2.09, all P < 0.05), while humerus and radius/ulna fracture were associated with an elevated HR for congestive heart failure and cerebrovascular disease (HR range, 1.38-1.72, all P < 0.05). CONCLUSIONS: Fragility fractures were associated with an increased incidence of cardiorespiratory diseases among adults with intellectual disabilities.

Site of vulnerability on SARS-CoV-2 spike induces broadly protective antibody against antigenically distinct Omicron subvariants.

The rapid evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants has emphasized the need to identify antibodies with broad neutralizing capabilities to inform future monoclonal therapies and vaccination strategies. Herein, we identified S728-1157, a broadly neutralizing antibody (bnAb) targeting the receptor-binding site (RBS) that was derived from an individual previously infected with WT SARS-CoV-2 prior to the spread of variants of concern (VOCs). S728-1157 demonstrated broad cross-neutralization of all dominant variants, including D614G, Beta, Delta, Kappa, Mu, and Omicron (BA.1/BA.2/BA.2.75/BA.4/BA.5/BL.1/XBB). Furthermore, S728-1157 protected hamsters against in vivo challenges with WT, Delta, and BA.1 viruses. Structural analysis showed that this antibody targets a class 1/RBS-A epitope in the receptor binding domain via multiple hydrophobic and polar interactions with its heavy chain complementarity determining region 3 (CDR-H3), in addition to common motifs in CDR-H1/CDR-H2 of class 1/RBS-A antibodies. Importantly, this epitope was more readily accessible in the open and prefusion state, or in the hexaproline (6P)-stabilized spike constructs, as compared with diproline (2P) constructs. Overall, S728-1157 demonstrates broad therapeutic potential and may inform target-driven vaccine designs against future SARS-CoV-2 variants.

Trajectories of medication use and polypharmacy among children with cerebral palsy.

BACKGROUND: Children with cerebral palsy (CP) may have chronic exposure to polypharmacy to address several medical needs, but there is little research on the topic to inform surveillance methods and clinical practice. OBJECTIVE: To identify the trajectories of medication number and pediatric polypharmacy (≥2 concurrent medications) exposure over 3.5 years among children with CP. METHODS: This cohort study used commercial claims from January 1, 2015, to December 31, 2018 (4-year period). Children with CP, aged 5-18 years by January 1, 2016, and with continuous health plan enrollment for all 4 years, were included and categorized as with or without co-occurring neurological/ RESULTS: Of the 1,252 children with CP, 600 were in the CP only cohort (mean [SD]; age, 11.4 [4.1] years; 46.0% female) and 652 were in the CP + NDDs cohort (age, 11.9 [4.1] years; 41.3% female; 32.7% had ≥2 of the NDDs). For the primary GBTM, 3 trajectory groups were identified for CP only: on average, no prescribed medications (69.7% of the cohort), 1 medication/month (24.8%), and 4 medications/month (5.5%). Five trajectory groups were identified for CP + NDDs: 0 (22.4%), 1 (25.6%), 2 (25.2%), 4 (18.4%), and 6 (8.4%) prescribed medications/month. For the secondary GBTM, 3 trajectory groups were identified for CP only: 80.5% were characterized as negligible probability of polypharmacy exposure, 10.8% as low probability, and 8.7% as high probability. Five trajectory groups were identified for CP + NDDs: 37.9% as negligible probability of polypharmacy exposure, 32.8% as constantly high probability, and 29.2% as changing probability (eg, increasing/decreasing). CONCLUSIONS: Children with CP are chronically exposed to differing levels of polypharmacy. Findings can help establish polypharmacy surveillance practices. Studies need to determine if polypharmaceutical strategies are balanced to optimize health and development for children with CP. DISCLOSURES: Dr Whitney is supported by the University of Michigan Office of Health Equity and Inclusion Diversity Fund. The funding source had no role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.

Seeking health information online among U.S. pregnant women: findings from the 2009-2018 National Health Interview Surveys.

Seeking health information online has gained in popularity. However, few studies have investigated seeking health information online among U.S. pregnant women. The aim of this study was to investigate the patterns, trends, and characteristics of pregnant women in the U.S. who seek health information online. We obtained data from the National Health Interview Survey from 2009 to 2018. The study population consisted of women aged 18 to 49 years who self-reported being pregnant. Complex survey weighting and Chi-squared tests were used to evaluate trends and compare characteristics of online users and nonusers. Multivariable logistic regression analyses were used to evaluate characteristics associated with seeking health information online. Significantly more pregnant women sought health information online in 2018 compared to 2009 (72.9 percent, standard error [SE]: 3.3, 95 percent confidence interval [CI]: 66.3 percent-79.5 percent, vs. 60.7 percent, SE: 3.3, 95 percent CI: 54.0 percent-67.4 percent, p < .01). Pregnant women who were identified as white or Black, who had more education, and who had higher incomes were significantly more likely to report seeking health information online. Healthcare providers should actively initiate conversations to address the safety, accuracy, and reliability of online health information for their pregnant patients.

Induction of natural IgE by glucocorticoids.

IgE mediates allergic responses by coating mast cell or basophil surfaces and inducing degranulation upon binding a specific allergen. IgE can also be spontaneously produced in the absence of foreign allergens; yet the origin, regulation, and functions of such "natural" IgE still remain largely unknown. Here, we find that glucocorticoids enhance the production of IgE in B cells both in vivo and ex vivo without antigenic challenge. Such IgE production is promoted by B cell-intrinsic glucocorticoid receptor signaling that reinforces CD40 signaling and synergizes with the IL-4/STAT6 pathway. In addition, we found that rare B cells in the mesenteric lymph nodes are responsible for the production of glucocorticoid-inducible IgE. Furthermore, locally produced glucocorticoids in the gut may induce natural IgE during perturbations of gut homeostasis, such as dysbiosis. Notably, mice preemptively treated with glucocorticoids were protected from subsequent pathogenic anaphylaxis. Together, our results suggest that glucocorticoids, classically considered to be broadly immunosuppressive, have a selective immunostimulatory role in B cells.

Gut commensal bacteria enhance pathogenesis of a tumorigenic murine retrovirus.

The influence of the microbiota on viral transmission and replication is well appreciated. However, its impact on retroviral pathogenesis outside of transmission/replication control remains unknown. Using murine leukemia virus (MuLV), we found that some commensal bacteria promoted the development of leukemia induced by this retrovirus. The promotion of leukemia development by commensals is due to suppression of the adaptive immune response through upregulation of several negative regulators of immunity. These negative regulators include Serpinb9b and Rnf128, which are associated with a poor prognosis of some spontaneous human cancers. Upregulation of Serpinb9b is mediated by sensing of bacteria by the NOD1/NOD2/RIPK2 pathway. This work describes a mechanism by which the microbiota enhances tumorigenesis within gut-distant organs and points at potential targets for cancer therapy.

Asymmetrical forward and reverse developmental trajectories determine molecular programs of B cell antigen receptor editing.

During B lymphopoiesis, B cell progenitors progress through alternating and mutually exclusive stages of clonal expansion and immunoglobulin (Ig) gene rearrangements. Great diversity is generated through the stochastic recombination of Ig gene segments encoding heavy and light chain variable domains. However, this commonly generates autoreactivity. Receptor editing is the predominant tolerance mechanism for self-reactive B cells in the bone marrow (BM). B cell receptor editing rescues autoreactive B cells from negative selection through renewed light chain recombination first at Igκ then Igλ loci. Receptor editing depends on BM microenvironment cues and key transcription factors such as NF-κB, FOXO, and E2A. The specific BM factor required for receptor editing is unknown. Furthermore, how transcription factors coordinate these developmental programs to promote usage of the λ chain remains poorly defined. Therefore, we used two mouse models that recapitulate pathways by which Igλ light chain-positive B cells develop. The first has deleted J kappa (Jκ) genes and hence models Igλ expression resulting from failed Igκ recombination (Igκdel). The second models autoreactivity by ubiquitous expression of a single-chain chimeric anti-Igκ antibody (κ-mac). Here, we demonstrated that autoreactive B cells transit asymmetric forward and reverse developmental trajectories. This imparted a unique epigenetic landscape on small pre-B cells, which opened chromatin to transcription factors essential for Igλ recombination. The consequences of this asymmetric developmental path were both amplified and complemented by CXCR4 signaling. These findings reveal how intrinsic molecular programs integrate with extrinsic signals to drive receptor editing.

Unreasonable minds and imperfect self-defense.

Western legal systems recognize the right to self-defense as a right of individuals, under certain circumstances, to use physical force to defend themselves from an aggressor. This right requires an honest and reasonable belief of the person asserting it regarding the circumstances in which force is used. Some jurisdictions also permit a defense of imperfect self-defense, allowing for reduced culpability for the crime of homicide if a person's beliefs are honest but unreasonable. If the unreasonable belief is based on a mental illness, however, the defense is disallowed in every jurisdiction in the United States. This development relies upon an untenable position that false beliefs produced by mental disorders should be excluded based on erroneous assumptions about psychotic illness. This article argues that the current precedent is incoherent with the core structure of criminal responsibility and in tension with current scientific understandings and should change to do justice.

A perspective review of cannabis use and sexual offenses.

Substance abuse is an established risk factor for crime and violence, including sexual violence. Nevertheless, the link between cannabis use and sexual offenses remains poorly understood. Cannabis use has a broad effect on sexual functioning and can have both acute and lasting adverse effects on psychological functioning, which in turn can elevate the risk of sexual offending behavior. Yet there is a scarcity of studies that have examined the link between cannabis use and sexual offending. To help fill the gap, this perspective review investigates the link between substance use and crime with a particular emphasis on cannabis use and its effects on sexual and psychological functioning. It then explores how these mechanisms may contribute to sexual offenses and recidivism, with a final discussion on how cannabis use should be conceptualized as a risk factor for sexual violence.

Factors associated with use of medication for behavioral challenges in adults with intellectual and developmental disability.

BACKGROUND/AIMS: Persons with intellectual or developmental disabilities and who exhibit challenging behaviors are often prescribed medication to control behavior. Little is known about the environmental factors that may be associated with taking these medications. METHODS AND OUTCOMES: This study examined the association between individual and intermediate or environmental factors and the documented use of medication for clients with intellectual or developmental disabilities (IDD) who exhibit challenging behavior, using the 2014-15 National Core Indicators Adult Consumer Survey dataset. RESULTS AND CONCLUSIONS: Individual-level variables associated with a higher likelihood of taking medication for persons with IDD exhibiting challenging behaviors included being of younger age, male gender, having moderate or severe intellectual disability, being ambulatory, communicating verbally, having a behavioral plan, requiring support for behavioral challenges, and having a history of mental illness. Environment-level variables included infrequently eating out and having less everyday choice. This study found that restrictions in opportunities to make choices in their life was associated with a greater likelihood of being on a medication for persons with IDD who exhibit challenging behavior. Living in group home settings also increased the likelihood of medication use. A limitation of the study is a lack of information on why medications were prescribed and whether they were intended to treat the challenging behavior. IMPLICATIONS: This work has important implications for health providers, as addressing malleable social factors may provide an avenue for reducing challenging behaviors without the need for medication.

Cross-Neutralization of Emerging SARS-CoV-2 Variants of Concern by Antibodies Targeting Distinct Epitopes on Spike.

Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have arisen that exhibit increased viral transmissibility and partial evasion of immunity induced by natural infection and vaccination. To address the specific antibody targets that were affected by recent viral variants, we generated 43 monoclonal antibodies (mAbs) from 10 convalescent donors that bound three distinct domains of the SARS-CoV-2 spike. Viral variants harboring mutations at K417, E484, and N501 could escape most of the highly potent antibodies against the receptor binding domain (RBD). Despite this, we identified 12 neutralizing mAbs against three distinct regions of the spike protein that neutralize SARS-CoV-2 and variants of concern (VOCs), including B.1.1.7 (alpha), P.1 (gamma), and B.1.617.2 (delta). Notably, antibodies targeting distinct epitopes could neutralize discrete variants, suggesting that different variants may have evolved to disrupt the binding of particular neutralizing antibody classes. These results underscore that humans exposed to the first pandemic wave of prototype SARS-CoV-2 possess neutralizing antibodies against current variants and that it is critical to induce antibodies targeting multiple distinct epitopes of the spike that can neutralize emerging variants of concern. IMPORTANCE We describe the binding and neutralization properties of a new set of human monoclonal antibodies derived from memory B cells of 10 coronavirus disease 2019 (COVID-19) convalescent donors in the first pandemic wave of prototype SARS-CoV-2. There were 12 antibodies targeting distinct epitopes on spike, including two sites on the RBD and one on the N-terminal domain (NTD), that displayed cross-neutralization of VOCs, for which distinct antibody targets could neutralize discrete variants. This work underlines that natural infection by SARS-CoV-2 induces effective cross-neutralization against only some VOCs and supports the need for COVID-19 vaccination for robust induction of neutralizing antibodies targeting multiple epitopes of the spike protein to combat the current SARS-CoV-2 VOCs and any others that might emerge in the future.

Cross neutralization of emerging SARS-CoV-2 variants of concern by antibodies targeting distinct epitopes on spike.

Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have arisen that exhibit increased viral transmissibility and partial evasion of immunity induced by natural infection and vaccination. To address the specific antibody targets that were affected by recent viral variants, we generated 43 monoclonal antibodies (mAbs) from 10 convalescent donors that bound three distinct domains of the SARS-CoV-2 spike. Viral variants harboring mutations at K417, E484 and N501 could escape most of the highly potent antibodies against the receptor binding domain (RBD). Despite this, we identified 12 neutralizing mAbs against three distinct regions of the spike protein that neutralize SARS-CoV-2 and the variants of concern, including B.1.1.7 (alpha), P.1 (gamma) and B.1.617.2 (delta). Notably, antibodies targeting distinct epitopes could neutralize discrete variants, suggesting different variants may have evolved to disrupt the binding of particular neutralizing antibody classes. These results underscore that humans exposed to wildtype (WT) SARS-CoV-2 do possess neutralizing antibodies against current variants and that it is critical to induce antibodies targeting multiple distinct epitopes of the spike that can neutralize emerging variants of concern.

The Impact of an Early Clinical Experience on Pharmacy Student Learning About Ambulatory Care Practice.

Objective. To determine whether student confidence in their knowledge of ambulatory care pharmacy and ability to contribute to patient care in this setting increased after participating in an ambulatory care introductory pharmacy practice experience (IPPE), and whether it changed student interest in pursuing a career in ambulatory care pharmacy.Methods. Second-year pharmacy students (n=86) completed a required ambulatory care experience which included four hours of didactic work and 13.5 hours of clinic experience with an ambulatory care pharmacist. Before and after the experience, students completed an eight-question survey in which they rated their confidence in their knowledge of ambulatory care practice and in providing patient care in this setting, as well as their interest in a career in ambulatory care. A five-point Likert scale was used to assess student confidence (1=not at all confident, 5=very confident) and interest in ambulatory care (1=not at all interested, 5=extremely interested). The Wilcoxon signed rank test was used to compare pre-post survey responses.Results. Eighty-five pharmacy students completed both the pre- and post-survey. Median scores on the post-intervention test increased from 3 to 4 in seven of the domains assessed. Student interest in a career in ambulatory care remained unchanged.Conclusion. An ambulatory care IPPE increased student confidence in their understanding of ambulatory care pharmacy practice and caring for patients in this setting.

Profiling B cell immunodominance after SARS-CoV-2 infection reveals antibody evolution to non-neutralizing viral targets.

Dissecting the evolution of memory B cells (MBCs) against SARS-CoV-2 is critical for understanding antibody recall upon secondary exposure. Here, we used single-cell sequencing to profile SARS-CoV-2-reactive B cells in 38 COVID-19 patients. Using oligo-tagged antigen baits, we isolated B cells specific to the SARS-CoV-2 spike, nucleoprotein (NP), open reading frame 8 (ORF8), and endemic human coronavirus (HCoV) spike proteins. SARS-CoV-2 spike-specific cells were enriched in the memory compartment of acutely infected and convalescent patients several months post symptom onset. With severe acute infection, substantial populations of endemic HCoV-reactive antibody-secreting cells were identified and possessed highly mutated variable genes, signifying preexisting immunity. Finally, MBCs exhibited pronounced maturation to NP and ORF8 over time, especially in older patients. Monoclonal antibodies against these targets were non-neutralizing and non-protective in vivo. These findings reveal antibody adaptation to non-neutralizing intracellular antigens during infection, emphasizing the importance of vaccination for inducing neutralizing spike-specific MBCs.