Comedy, consensus, and conflict framework: Comedy as a norm violation can build consensus or escalate conflict in negotiations.

In this work, we propose that humor violates norms that can build consensus or escalate conflict in negotiations. Drawing on social identity theory, we propose that humor commits norm violations that are more likely to be perceived as benign among ingroup observers in negotiations, but perceived as offensive to outgroup observers in negotiations. We introduce the Comedy, Consensus, and Conflict Framework to shed light on the interpersonal effect of humor on negotiations. When humor is expressed to an ingroup observer, relative to neutral communication, humor is more likely to violate weak norms that govern social group membership resulting in the violation as being perceived as benign, which promotes cooperative behaviors in negotiations such as concessions and collaborative problem-solving. By contrast, when humor is expressed to an outgroup observer, relative to neutral communication, humor is more likely to violate strong norms that define social group membership resulting in the violation as being interpreted as offensive, which triggers competitive behaviors in negotiations such as aggressive offers and hardened positions. Furthermore, we suggest that humor not only generates appraisals of social identity threats, but also affective responses that influence negotiation behavior. Finally, we expand our theoretical model about humor to consider key relational factors that influence norm strength, which motivates whether negotiators appraise norm violations as offensive or benign.

Association of Depression and Antidepressant Use With Driving Behaviors in Older Adults: A LongROAD Study.

Older adults aged 70 and older who drive have higher crash death rates per mile driven compared to middle aged (35-54 years) adults who drive in the US. Prior studies have found that depression and or antidepressant medication use in older adults are associated with an increase in the vehicular crash rate. Using data from the prospective multi-site AAA Longitudinal Research on Aging Drivers Study, this analysis examined the independent and interdependent associations of self-reported depression and antidepressant use with driving behaviors that can increase motor vehicle crash risk such as hard braking, speeding, and night-time driving in adults over age 65. Of the 2951 participants, 6.4% reported having depression and 21.9% were on an antidepressant medication. Correcting for age, race, gender, and education level, participants on an antidepressant had increased hard braking events (1.22 [1.10-1.34]) but self-reported depression alone was not associated with changes in driving behaviors.

Making Recommendations for an Evaluation and Treatment Algorithm for Patients with Ear Fullness and No Objective Abnormalities.

OBJECTIVE: To make recommendations for evaluation, approach to counseling and treatment for patients who present with ear fullness without abnormalities on otomicroscopic examination, standard audiometric studies, or imaging results. METHODS: Retrospective chart review of adult patients in a tertiary referral center presenting with ear fullness and/or otalgia without external, middle, and/or inner ear pathologies. Data collected include demographics (age and gender), laterality and duration of symptoms, co-morbid conditions and final diagnoses of temporomandibular joint (TMJ) dysfunction, intermittent Eustachian tube dysfunction (iETD), migraine disorder, and anxiety. RESULTS: In the span of 8 years of a single neurotologist's practice, 964 patients presented with ear fullness. After excluding all instances where external, middle, and inner ear disorders were identified and where audiometric and radiologic findings were abnormal, 263 patients had ear fullness and no objective causes. Women were more likely than men to complain of ear fullness and/or otalgia and were also more likely to present with no objective abnormalities ( p < 0.05). Patients who reported isolated ear fullness were more likely to be diagnosed with iETD, whereas patients who reported pain were more likely to be diagnosed with TMJ dysfunction (TMJD). Fourteen patients (5.3%) had completely unexplained sensation of ear fullness. CONCLUSIONS: There were 94.7% of the patients presenting with unexplained ear fullness were diagnosed as having a possible contribution of TMJ dysfunction, IETD, migraine disorder, anxiety, or a combination of these conditions to their symptomatology. Directing treatments toward these diagnoses may alleviate symptoms of ear fullness or, if unsuccessful, provide an avenue for counseling in the framework of functional neurologic disorders.

Human iN neuronal model of schizophrenia displays dysregulation of chromogranin B and related neuropeptide transmitter signatures.

Schizophrenia (SZ) is a serious mental illness and neuropsychiatric brain disorder with behavioral symptoms that include hallucinations, delusions, disorganized behavior, and cognitive impairment. Regulation of such behaviors requires utilization of neurotransmitters released to mediate cell-cell communication which are essential to brain functions in health and disease. We hypothesized that SZ may involve dysregulation of neurotransmitters secreted from neurons. To gain an understanding of human SZ, induced neurons (iNs) were derived from SZ patients and healthy control subjects to investigate peptide neurotransmitters, known as neuropeptides, which represent the major class of transmitters. The iNs were subjected to depolarization by high KCl in the culture medium and the secreted neuropeptides were identified and quantitated by nano-LC-MS/MS tandem mass spectrometry. Several neuropeptides were identified from schizophrenia patient-derived neurons, including chromogranin B (CHGB), neurotensin, and natriuretic peptide. Focusing on the main secreted CHGB neuropeptides, results revealed differences in SZ iNs compared to control iN neurons. Lower numbers of distinct CHGB peptides were found in the SZ secretion media compared to controls. Mapping of the peptides to the CHGB precursor revealed peptides unique to either SZ or control, and peptides common to both conditions. Also, the iNs secreted neuropeptides under both KCl and basal (no KCl) conditions. These findings are consistent with reports that chromogranin B levels are reduced in the cerebrospinal fluid and specific brain regions of SZ patients. These findings suggest that iNs derived from SZ patients can model the decreased CHGB neuropeptides observed in human SZ.

Systematic literature review of the impact of psychiatric pharmacists.

Introduction: Pharmacists focusing on psychotropic medication management and practicing across a wide variety of healthcare settings have significantly improved patient-level outcomes. The Systematic Literature Review Committee of the American Association of Psychiatric Pharmacists was tasked with compiling a comprehensive database of primary literature highlighting the impact of psychiatric pharmacists on patient-level outcomes. Methods: A systematic search of literature published from January 1, 1961, to December 31, 2022, was conducted using PubMed and search terms based on a prior American Association of Psychiatric Pharmacists literature review. Publications describing patient-level outcome results associated with pharmacist provision of care in psychiatric/neurologic settings and/or in relation to psychotropic medications were included. The search excluded articles for which there was no pharmacist intervention, no psychiatric disorder treatment, no clinical outcomes, no original research, no access to full text, and/or no English-language version. Results: A total of 4270 articles were reviewed via PubMed, with 4072 articles excluded based on title, abstract, and/or full text in the initial pass and 208 articles selected for inclusion. A secondary full-text review excluded 11 additional articles, and 5 excluded articles were ultimately included based on a secondary review, for a final total of 202 articles meeting the inclusion criteria. A comprehensive database of these articles was compiled, including details on their study designs and outcomes. Discussion: The articles included in the final database had a wide range of heterogeneity. While the overall impact of psychiatric pharmacists was positive, the study variability highlights the need for future publications to have more consistent, standardized outcomes with stronger study designs.

A National Survey of Perceptions Around Conditions Associated With Pharmacy Faculty Workload Equity.

OBJECTIVE: To assess pharmacy faculty members' perceptions of conditions associated with workload equity and factors that can improve workload equity. METHODS: A 26-item survey instrument was developed and distributed via email to members of the American Association of Colleges of Pharmacy Council of Faculties. Questions pertained to the workload distribution, fairness in assignment, and perception of the conditions associated with workload equity (transparency, context, credit, clarity, norms, and accountability) as well as institutional and individual demographics. RESULTS: A total of 662 responses were obtained (response rate 15.9%). Respondents' demographics were comparable to available national data. Approximately 41% of respondents reported their institutions did not have a written faculty workload policy. Most respondents reported their workload assignment was fair (highest with research/scholarship) but reported only moderate alignment between assigned and actual workloads. The rating level for what domains the primary decision maker uses to assign workload was highest for context, followed by credit, clarity, and transparency. Transparency was reported as the most needed condition to improve faculty perception of workload equity. Respondents also rated increasing trust between leadership and faculty and increasing productivity and accountability as the most important reasons to minimize workload inequities. CONCLUSION: This was the first national survey of pharmacy faculty perceptions around the conditions associated with workload equity. Though additional research is needed in this area, programs can work to implement strategies associated with all of the conditions, particularly transparency, to improve faculty perceptions of equity.

Pretreatment characteristics associated with symptom reduction during group cognitive processing therapy versus exposure therapy for PTSD: an exploratory study of Veterans.

Exposure and cognitive-based therapies are both effective for PTSD, but knowledge of which intervention is best for which patient is lacking. This lack of knowledge is particularly noticeable for group treatments, as no study has examined whether responses to different group therapies are associated with different pretreatment characteristics. Here, we explored whether pretreatment levels of three types of psychological characteristics-PTSD symptom clusters, posttraumatic cognitions, and emotion regulation difficulties-were associated with symptom reduction during group-delivered cognitive versus exposure-based PTSD treatment. Participants were Veterans with PTSD drawn from two previous clinical trials: one of group CPT (GCPT; n = 32) and the other of group-based exposure therapy (GBET; n = 21). Growth curve modeling was used to identify pretreatment variables that predicted weekly PTSD symptom changes during each therapy. Higher posttraumatic cognitions at pretreatment predicted steeper PTSD symptom reduction during GCPT but not GBET. Additionally, symptom reduction during each therapy was associated with different pretreatment emotion regulation difficulties: difficulties with goal-directed behavior for GBET and lack of emotional clarity and limited access to emotion regulation strategies for GCPT. These findings suggest that assigning Veterans to a group PTSD therapy that better matches their pretreatment psychological profile might facilitate a better therapeutic response.

Antidepressant prescribing in transgender and nonbinary individuals diagnosed with gender dysphoria and mood or anxiety disorders.

Introduction: Transgender and nonbinary (TGNB) individuals are highly stigmatized members of society and are significantly at higher risk of having mood or anxiety-related disorders compared to non-TGNB individuals. Methods: In this retrospective cohort study, antidepressant prescribing data were collected from TGNB adults diagnosed with gender dysphoria (GD) and mood or anxiety-related disorder between January 2005 and October 2021. The primary outcome was to compare the number of active outpatient antidepressant prescriptions at the time of GD diagnosis between gender identities. The secondary outcomes were to compare antidepressant class utilization between gender identities as well as the prevalence of concurrent mood or anxiety-related disorder diagnoses between gender identities. Results: Of 131 patients who met inclusion criteria, there was no significant difference in number of active antidepressant prescriptions between gender identities at the time of the GD diagnosis (p = .357). However, transgender females were prescribed bupropion at significantly higher rates than other gender identities (p = .046). Approximately 38% of patients did not have an active antidepressant prescription at the time of GD diagnosis despite concurrent mood or anxiety-related diagnoses. The prevalence of generalized anxiety disorder was significantly greater among transgender males (p = .044). Discussion: Although the number of active antidepressant prescriptions between gender identities were similar in this study, we found 38% of patients were not prescribed any antidepressants at time of GD and mood or anxiety-related disorders. This serendipitous finding elucidates a potential gap in mental health care among transgender adults.

Combinatorial immune refocusing within the influenza hemagglutinin RBD improves cross-neutralizing antibody responses.

The receptor-binding domain (RBD) of influenza virus hemagglutinin (HA) elicits potently neutralizing yet mostly strain-specific antibodies. Here, we evaluate the ability of several immunofocusing techniques to enhance the functional breadth of vaccine-elicited immune responses against the HA RBD. We present a series of "trihead" nanoparticle immunogens that display native-like closed trimeric RBDs from the HAs of several H1N1 influenza viruses. The series includes hyperglycosylated and hypervariable variants that incorporate natural and designed sequence diversity at key positions in the receptor-binding site periphery. Nanoparticle immunogens displaying triheads or hyperglycosylated triheads elicit higher hemagglutination inhibition (HAI) and neutralizing activity than the corresponding immunogens lacking either trimer-stabilizing mutations or hyperglycosylation. By contrast, mosaic nanoparticle display and antigen hypervariation do not significantly alter the magnitude or breadth of vaccine-elicited antibodies. Our results yield important insights into antibody responses against the RBD and the ability of several structure-based immunofocusing techniques to influence vaccine-elicited antibody responses.

mRNA-based VP8* nanoparticle vaccines against rotavirus are highly immunogenic in rodents.

Despite the availability of live-attenuated oral vaccines, rotavirus remains a major cause of severe childhood diarrhea worldwide. Due to the growing demand for parenteral rotavirus vaccines, we developed mRNA-based vaccine candidates targeting the viral spike protein VP8*. Our monomeric P2 (universal T cell epitope)-VP8* mRNA design is equivalent to a protein vaccine currently in clinical development, while LS (lumazine synthase)-P2-VP8* was designed to form nanoparticles. Cyro-electron microscopy and western blotting-based data presented here suggest that proteins derived from LS-P2-VP8* mRNA are secreted in vitro and self-assemble into 60-mer nanoparticles displaying VP8*. mRNA encoded VP8* was immunogenic in rodents and introduced both humoral and cellular responses. LS-P2-VP8* induced superior humoral responses to P2-VP8* in guinea pigs, both as monovalent and trivalent vaccines, with encouraging responses detected against the most prevalent P genotypes. Overall, our data provide evidence that trivalent LS-P2-VP8* represents a promising mRNA-based next-generation rotavirus vaccine candidate.

Microglia promote remyelination independent of their role in clearing myelin debris.

Multiple sclerosis (MS) is an inflammatory disease characterized by myelin loss. While therapies exist to slow MS progression, no treatment currently exists for remyelination. Remyelination, linked to reduced disability in MS, relies on microglia and monocyte-derived macrophages (MDMs). This study aims to understand the role of microglia during remyelination by lineage tracing and depleting them. Microglial lineage tracing reveals that both microglia and MDMs initially accumulate, but microglia later dominate the lesion. Microglia and MDMs engulf equal amounts of inhibitory myelin debris, but after microglial depletion, MDMs compensate by engulfing more myelin debris. Microglial depletion does, however, reduce the recruitment and proliferation of oligodendrocyte progenitor cells (OPCs) and impairs their subsequent differentiation and remyelination. These findings underscore the essential role of microglia during remyelination and offer insights for enhancing this process by understanding microglial regulation of remyelination.

Grit, Subjective Happiness, Satisfaction With Life, and Academic Resilience Among Pharmacy and Physical Therapy Students at Two Universities.

OBJECTIVE: The primary objective of this study was to compare grit, subjective happiness, satisfaction with life, and academic resilience among pharmacy and occupational therapy/physical therapy (OT/PT) students at 2 distinct universities using the short grit scale, subjective happiness scale (SHS), satisfaction with life scale (SWLS), and the academic resilience scale (ARS-30). METHODS: In January 2019, investigators administered an online survey to students at 2 universities using a cross-sectional, voluntary, anonymous survey design using grit scale, SHS, SWLS, and ARS-30. Descriptive statistics, t tests, a 2-way analysis of variance, Pearson correlation, and regression analyses were used to examine the relationship between these scores. RESULTS: There were 227 respondents who consented to participate in the study and completed all 4 surveys. The overall response rate for pharmacy students was 44% and 43% for OT/PT students, with most pharmacy and OT/PT students in the 19-25-year range. Grit scores did not differ between pharmacy students and OT/PT students, while SHS scores were significantly higher in OT/PT students. Subjective happiness was higher in the private university, with young, female students at the private university reporting higher SHS scores. Although the grit score was not correlated with SWLS, SHS, or ARS-30 scores, the SWLS was correlated with SHS. The SHS was a strong predictor of academic resilience in both OT/PT and pharmacy students. CONCLUSION: Subjective happiness and satisfaction with life were found to be strong predictors of academic resilience among pharmacy students. Colleges of pharmacy may consider administering the SHS and/or SWLS at baseline and annually to measure well-being.

De novo design of monomeric helical bundles for pH-controlled membrane lysis.

Targeted intracellular delivery via receptor-mediated endocytosis requires the delivered cargo to escape the endosome to prevent lysosomal degradation. This can in principle be achieved by membrane lysis tightly restricted to endosomal membranes upon internalization to avoid general membrane insertion and lysis. Here, we describe the design of small monomeric proteins with buried histidine containing pH-responsive hydrogen bond networks and membrane permeating amphipathic helices. Of the 30 designs that were experimentally tested, all expressed in Escherichia coli, 13 were monomeric with the expected secondary structure, and 4 designs disrupted artificial liposomes in a pH-dependent manner. Mutational analysis showed that the buried histidine hydrogen bond networks mediate pH-responsiveness and control lysis of model membranes within a very narrow range of pH (6.0-5.5) with almost no lysis occurring at neutral pH. These tightly controlled lytic monomers could help mediate endosomal escape in designed targeted delivery platforms.

Sex differences in peripheral immune cell activation: Implications for pain and pain resolution.

Decades of research into chronic pain has deepened our understanding of the cellular mechanisms behind this process. However, a failure to consider the biological variable of sex has limited the application of these breakthroughs into clinical application. In the present study, we investigate fundamental differences in chronic pain between male and female mice resulting from inflammatory activation of the innate immune system. We provide evidence that female mice are more sensitive to the effects of macrophages. Injecting small volumes of media conditioned by either unstimulated macrophages or macrophages stimulated by the inflammatory molecule TNFα lead to increased pain sensitivity only in females. Interestingly, we find that TNFα conditioned media leads to a more rapid resolution of mechanical hypersensitivity and altered immune cell recruitment to sites of injury. Furthermore, male and female macrophages exhibit differential polarization characteristics and motility after TNFα stimulation, as well as a different profile of cytokine secretions. Finally, we find that the X-linked gene Tlr7 is critical in the facilitating the adaptive resolution of pain in models of acute and chronic inflammation in both sexes. Altogether, these findings suggest that although the cellular mechanisms of pain resolution may differ between the sexes, the study of these differences may yield more targeted approaches with clinical applications.

Combinatorial immune refocusing within the influenza hemagglutinin head elicits cross-neutralizing antibody responses.

The head domain of influenza hemagglutinin (HA) elicits potently neutralizing yet mostly strain-specific antibodies during infection and vaccination. Here we evaluated a series of immunogens that combined several immunofocusing techniques for their ability to enhance the functional breadth of vaccine-elicited immune responses. We designed a series of "trihead" nanoparticle immunogens that display native-like closed trimeric heads from the HAs of several H1N1 influenza viruses, including hyperglycosylated variants and hypervariable variants that incorporate natural and designed sequence diversity at key positions in the periphery of the receptor binding site (RBS). Nanoparticle immunogens displaying triheads or hyperglycosylated triheads elicited higher HAI and neutralizing activity against vaccine-matched and -mismatched H1 viruses than corresponding immunogens lacking either trimer-stabilizing mutations or hyperglycosylation, indicating that both of these engineering strategies contributed to improved immunogenicity. By contrast, mosaic nanoparticle display and antigen hypervariation did not significantly alter the magnitude or breadth of vaccine-elicited antibodies. Serum competition assays and electron microscopy polyclonal epitope mapping revealed that the trihead immunogens, especially when hyperglycosylated, elicited a high proportion of antibodies targeting the RBS, as well as cross-reactive antibodies targeting a conserved epitope on the side of the head. Our results yield important insights into antibody responses against the HA head and the ability of several structure-based immunofocusing techniques to influence vaccine-elicited antibody responses.

"Put me in Coach!" Engaging Faculty to Form a Winning Assessment Team.

This commentary uses the metaphor of an athletic team model to provide guidance when managing a successful assessment committee and assessment processes. To become a winning team, a joint effort must be exerted by players, coaches, and the athletic director. The topics of developing a team of productive members, creating, and implementing an assessment plan, forming a positive culture, and establishing leadership are discussed. Examples and advice are provided to assist with promoting an engaged faculty to form a well-rounded and productive assessment committee with clearly defined roles and responsibilities.

We Must Do Better to Ensure Equity, Transparency, and Clarity in Service Workload.

Assessment of faculty workload is challenging due to the diverse set of definitions and expectations at individual schools/colleges of pharmacy. The service component of faculty workload is complicated to assess and evaluate due to institutional variances in policies and procedures for assigning service commitments and lack of clarity in how service is regarded toward promotion and tenure decisions. This commentary discusses the challenges of service as a component of faculty workload including lack of clear definitions and time dedicated to service. The commentary also presents potential solutions that schools/colleges should consider in defining service expectations. These solutions include strategies on how administrators should: set expectations, engage faculty at all ranks and series, and measure outcomes to ensure equity of service workload to build a culture of collective citizenship.

Evaluation of a Well-being Promotion (WelPro) Program on Advanced Pharmacy Practice Experience (APPE) Student Burnout.

OBJECTIVE: The objective of this study is to evaluate the Well-being Promotion (WelPro) program and its effect on burnout in Advanced Pharmacy Practice Experience (APPE) students at the University of California, San Francisco. METHODS: A longitudinal cohort study evaluating the WelPro program was conducted in the class of 2021 (Transformation, a 3-year all-year-round curriculum, and Pathway (P), a 4-year traditional curriculum) APPE students. The primary and secondary aims were to evaluate changes in emotional exhaustion (EE) scores from the beginning of year (BOY) to end of year (EOY) for the class of 2021 students and compare EOY EE scores between the classes of 2021 (P) and 2020 (P) students using the Maslach Burnout Inventory-Human Services Survey for Medical Personnel (MBI-HSS [MP]) survey. Independent and paired t tests were used to evaluate EE scores; Wilcoxon signed-rank test and Wilcoxon Mann-Whitney rank sum test were used to evaluate ordinal data. RESULTS: Evaluable survey response rates were 69.6% BOY and 57.7% EOY for the class of 2021 students and 78.7% EOY for the class of 2020 (P) students. No differences in EE scores were observed for the matched class of 2021 from BOY to EOY and between classes of 2021 (P) and 2020 (P) students. CONCLUSION: WelPro did not change EE scores for class of 2021 APPE students. Given multiple confounding factors in the study, additional studies are warranted to determine the effectiveness of such a program on APPE student burnout.

Perceptions and Practices for Evaluating Faculty Workload by Pharmacy Education Administration/Leadership.

OBJECTIVE: To assess how department chairs/administrators define, measure, and evaluate faculty workload to better understand practices within the Academy. METHODS: An 18-item survey was distributed to department chairs/administrators via American Association of Colleges of Pharmacy Connect. Participants identified if they are a primary decision maker for faculty workload, whether their program has a workload policy, how workload is calculated, and how faculty satisfaction with workload equity is measured. RESULTS: Of 71 participants initiating the survey, data from 64 participants from 52 colleges/schools were eligible for analysis. Leaders of practice departments reported that their faculty spend an average of 38% of their time on teaching (compared to 46% for non-practice departments), 13% on research (vs 37%), 12% on service (vs 16%), and 36% on clinical practice (vs 0%). Most survey participants (n = 57, 89%) are at schools/colleges with a tenure system, and about 24 participants reported that faculty workload metrics differ across departments/divisions. Teaching assignments and service are reportedly negotiable between faculty and supervisors, and workload expectations are widely variable. The majority indicated they do not analyze faculty satisfaction with workload fairness (n = 35) and faculty do not provide evaluative feedback on how supervisors assign faculty workload (n = 34). Of 6 priorities considered when determining workload, 'support college/school strategies and priorities' ranked highest (1.92) and 'trust between the chair and faculty' ranked lowest (4.87). CONCLUSION: Overall, only half of the participants reported having a clear, written process of quantifying faculty workload. The use of workload metrics may be needed for evidence-based decision-making for personnel management and resource allocation.

hACE2-Induced Allosteric Activation in SARS-CoV versus SARS-CoV-2 Spike Assemblies Revealed by Structural Dynamics.

SARS-CoV and SARS-CoV-2 cell entry begins when spike glycoprotein (S) docks with the human ACE2 (hACE2) receptor. While the two coronaviruses share a common receptor and architecture of S, they exhibit differences in interactions with hACE2 as well as differences in proteolytic processing of S that trigger the fusion machine. Understanding how those differences impact S activation is key to understand its function and viral pathogenesis. Here, we investigate hACE2-induced activation in SARS-CoV and SARS-CoV-2 S using hydrogen/deuterium-exchange mass spectrometry (HDX-MS). HDX-MS revealed differences in dynamics in unbound S, including open/closed conformational switching and D614G-induced S stability. Upon hACE2 binding, notable differences in transduction of allosteric changes were observed extending from the receptor binding domain to regions proximal to proteolytic cleavage sites and the fusion peptide. Furthermore, we report that dimeric hACE2, the native oligomeric form of the receptor, does not lead to any more pronounced structural effect in S compared to saturated monomeric hACE2 binding. These experiments provide mechanistic insights into receptor-induced activation of Sarbecovirus spike proteins.