Structural basis for potent neutralization of human respirovirus type 3 by protective single-domain camelid antibodies.

Respirovirus 3 is a leading cause of severe acute respiratory infections in vulnerable human populations. Entry into host cells is facilitated by the attachment glycoprotein and the fusion glycoprotein (F). Because of its crucial role, F represents an attractive therapeutic target. Here, we identify 13 F-directed heavy-chain-only antibody fragments that neutralize recombinant respirovirus 3. High-resolution cryo-EM structures of antibody fragments bound to the prefusion conformation of F reveal three distinct, previously uncharacterized epitopes. All three antibody fragments bind quaternary epitopes on F, suggesting mechanisms for neutralization that may include stabilization of the prefusion conformation. Studies in cotton rats demonstrate the prophylactic efficacy of these antibody fragments in reducing viral load in the lungs and nasal passages. These data highlight the potential of heavy-chain-only antibody fragments as effective interventions against respirovirus 3 infection and identify neutralizing epitopes that can be targeted for therapeutic development.

What's Gender Got to Do With It: Accounting for Differences in Incident Guideline Discordant Prescribing for PTSD Among Women and Men Veterans.

Objectives: Women veterans are more likely than men veterans to receive medications that Department of Veterans Affairs clinical practice guidelines recommend against to treat posttraumatic stress disorder (PTSD). To understand this difference, we examined potential confounders in incident prescribing of guideline discordant medications (GDMs) in veterans with PTSD.Methods: Veterans receiving care for PTSD during 2020 were identified using Veterans Health Administration administrative data. PTSD diagnosis was established by the presence of at least 1 ICD-10 coded outpatient encounter or inpatient hospitalization during the calendar year 2020. Incident GDM prescribing was assessed during 2021, including benzodiazepines, antipsychotics, select anticonvulsants, and select antidepressants. Log-binomial regression was used to estimate the difference in risk for GDM initiation between men and women, adjusted for patient, prescriber, and facility-level covariates, and to identify key confounding variables.Results: Of 704,699 veterans with PTSD, 16.9% of women and 10.1% of men initiated a GDM, an increased risk of 67% for women [relative risk (RR) = 1.67; 95% CI, 1.65-1.70]. After adjustment, the gender difference decreased to 1.22 (95% CI, 1.20-1.24) in a fully specified model. Three key confounding variables were identified: bipolar disorder (RR = 1.60; 95% CI, 1.57-1.63), age (<40 years: RR = 1.20 [1.18-1.22]; 40-54 years: RR = 1.13 [1.11-1.16]; ≥65 years: RR = 0.64 [0.62-0.65]), and count of distinct psychiatric medications prescribed in the prior year (RR = 1.14; 1.13-1.14).Conclusions: Women veterans with PTSD were 67% more likely to initiate a GDM, where more than half of this effect was explained by bipolar disorder, age, and prior psychiatric medication. After adjustment, women veterans remained at 22% greater risk for an incident GDM, suggesting that other factors remain unidentified and warrant further investigation.

Universal paramyxovirus vaccine design by stabilizing regions involved in structural transformation of the fusion protein.

The Paramyxoviridae family encompasses medically significant RNA viruses, including human respiroviruses 1 and 3 (RV1, RV3), and zoonotic pathogens like Nipah virus (NiV). RV3, previously known as parainfluenza type 3, for which no vaccines or antivirals have been approved, causes respiratory tract infections in vulnerable populations. The RV3 fusion (F) protein is inherently metastable and will likely require prefusion (preF) stabilization for vaccine effectiveness. Here we used structure-based design to stabilize regions involved in structural transformation to generate a preF protein vaccine antigen with high expression and stability, and which, by stabilizing the coiled-coil stem region, does not require a heterologous trimerization domain. The preF candidate induces strong neutralizing antibody responses in both female naïve and pre-exposed mice and provides protection in a cotton rat challenge model (female). Despite the evolutionary distance of paramyxovirus F proteins, their structural transformation and local regions of instability are conserved, which allows successful transfer of stabilizing substitutions to the distant preF proteins of RV1 and NiV. This work presents a successful vaccine antigen design for RV3 and provides a toolbox for future paramyxovirus vaccine design and pandemic preparedness.

Disentangling the coping process in White rural men who carry guns.

Affluent White rural men have the highest rates of gun ownership in the United States. However, few studies have specifically examined reasons and motivations for gun ownership and gun behaviors in this population. Therefore, this study sought to examine the relationship between stress variables, namely masculine gender role stress, adverse childhood experiences (ACEs), and income level, and subsequent pro-gun beliefs and amount of time an individual carried a gun within this population. Results indicated that only two measures of pro-gun beliefs (i.e., believing guns keep one safe, believing guns are present in one's social sphere) were correlated with percentage of time an individual carried. Additionally, ACEs were positively correlated with believing guns influence how others perceive oneself, levels of masculine gender role stress, and income. These results suggest that White rural gun owners who have increased ACEs have decreased income and tend to believe that owning guns impacts their social status with peers. However, increased ACEs do not influence belief about guns keeping one safe, believing guns are present in one's social sphere, or gun carriage. Instead, White rural gun owners without childhood adversity may be more susceptible to believing their safety depends on guns and belongingness within their social sphere. Future research should assess reasons why affluent White rural men find it important to maintain their safety in the context of gun ownership.

College students' perceptions of positive and negative drinking-related sexual experiences.

Objective: During young adulthood, drinking and sexual behaviors are both normative and inextricably linked. While this association is well documented, little is known about how students define positive and negative drinking-related sexual experiences. Methods: Thirty-five undergraduates participated in a focus group about sexual experiences in the context of drinking. Thematic analysis was utilized to identify themes in the data. Results: Students' descriptions of positive drinking-related sexual encounters included having a good time, feeling safe, maintaining control over alcohol, as well as feeling safe in drinking contexts where sexual partners are located. Students' perceptions of negative experiences included specific consequences such as a damaged reputation, loss of control due to alcohol, and concern of engagement in sex when they or a partner was too intoxicated to consent. Conclusion: Gaining a better understanding of how college students view positive and negative drinking-related sexual experiences could inform interventions aimed at promoting student well-being.

RE-AIM for rural health innovations: perceptions of (mis) alignment between the RE-AIM framework and evaluation reporting in the Department of Veterans Affairs Enterprise-Wide Initiatives program.

Background: The Department of Veterans Affairs (VA) Office of Rural Health (ORH) supports national VA program offices' efforts to expand health care to rural Veterans through its Enterprise-Wide Initiatives (EWIs) program. In 2017, ORH selected Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM), an implementation science framework, to structure the EWI evaluation and reporting process. As part of its mandate to improve EWI program evaluation, the Center for the Evaluation of Enterprise-Wide Initiatives conducted a qualitative evaluation to better understand EWI team' perceptions of, and barriers and facilitators to, the EWI evaluation process. Methods: We conducted 43 semi-structured interviews with 48 team members (e.g., evaluators, program office leads, and field-based leads) representing 21 EWIs from April-December 2020. Questions focused on participants' experiences using strategies targeting each RE-AIM dimension. Interviews were inductively analyzed in MAXQDA. We also systematically reviewed 51 FY19-FY20 EWI annual reports to identify trends in misapplications of RE-AIM. Results: Participants had differing levels of experience with RE-AIM. While participants understood ORH's rationale for selecting a common framework to structure evaluations, the perceived misalignment between RE-AIM and EWIs' work emerged as an important theme. Concerns centered around 3 sub-themes: (1) (Mis)Alignment with RE-AIM Dimensions, (2) (Mis)Alignment between RE-AIM and the EWI, and (3) (Mis)Alignment with RE-AIM vs. other Theories, Models, or Frameworks. Participants described challenges differentiating between and operationalizing dimensions in unique contexts. Participants also had misconceptions about RE-AIM and its relevance to their work, e.g., that it was meant for established programs and did not capture aspects of initiative planning, adaptations, or sustainability. Less commonly, participants shared alternative models or frameworks to RE-AIM. Despite criticisms, many participants found RE-AIM useful, cited training as important to understanding its application, and identified additional training as a future need. Discussion: The selection of a shared implementation science framework can be beneficial, but also challenging when applied to diverse initiatives or contexts. Our findings suggest that establishing a common understanding, operationalizing framework dimensions for specific programs, and assessing training needs may better equip partners to integrate a shared framework into their evaluations.

Veterans with chronic pain: Examining gender differences in pain type, overlap, and the impact of post-traumatic stress disorder.

BACKGROUND: Women are more likely to experience multiple overlapping pain conditions (MOPCs) relative to men. Post-traumatic stress disorder can negatively impact the severity and trajectory of chronic pain and its treatment. Specific associations between gender, post-traumatic stress disorder (PTSD), and MOPCs require further examination. METHODS: A cohort of all Veterans in 2021 who met criteria for one or more of 12 chronic pain types was created using national Veterans Health Administration administrative data. MOPCs were defined as the number of pain types for which each patient met criteria. Multivariable logistic regression models estimated gender differences in frequency for each of the 12 pain subtypes, after controlling for demographics and comorbidities. Negative binomial regression was used to estimate gender differences in the count of MOPCs and to explore moderation effects between gender and PTSD. RESULTS: The cohort included 1,936,859 Veterans with chronic pain in 2021, which included 12.5% women. Among those with chronic pain, women Veterans had higher rates of MOPCs (mean = 2.3) relative to men (mean = 1.9): aIRR = 1.31, 95% CI: 1.30-1.32. PTSD also served as an independent risk factor for MOPCs in adjusted analysis (aIRR = 1.23, 95% CI: 1.23-1.24). The interaction term between gender and PTSD was not significant (p = 0.87). Independent of PTSD, depressive disorders also served as a strong risk factor for MOPCs (aIRR = 1.37, 95% CI: 1.36-1.37). CONCLUSIONS: Individuals with MOPCs and PTSD may have complex treatment needs. They may benefit from highly coordinated trauma-sensitive care and integrated interventions that simultaneously address pain and PTSD. SIGNIFICANCE: Women were significantly more likely than men to experience MOPCs. PTSD was also significantly, independently, associated with MOPCs. Patients, particularly women, may benefit from tailored interventions that address both trauma and MOPCs.

Looking out for You and Me: College students' Strategies for Preventing Sexual Assault in Drinking Contexts.

Background: Sexual assault and heavy alcohol use are prevalent and interrelated public health concerns on university campuses. Surprisingly, however, few alcohol harm reduction interventions address this intersection to help students reduce both personal and community risks for sexual assault in college drinking contexts. Objectives: In the current study, students (ages 18-24) shared strategies they use to protect themselves and others from sexual assault in college drinking contexts, as well as challenges to implementing these strategies. A series of six focus groups were conducted across two universities in the U.S. (N = 35). Participants responded to open-ended questions focused on drinking and sexual assault (e.g., What are some of the things students might do to avoid or address situations where they feel pressured of coerced to hook up or have sex when they do not want to?). Results: Thematic analyses demonstrated students' awareness of protective behavioral and bystander intervention strategies that could help reduce vulnerability to experience sexual assault for themselves or others in drinking contexts. Perceived barriers to using bystander intervention strategies included student's own and friends' heavy drinking (decreased inhibitions, loss of autonomy), ambiguity in deciphering risk (lack of familiarity, minimization, diffusion of responsibility), and gender (gender norms, power imbalances). Conclusions: This study informs the development of interventions that help students identify strategies and overcome barriers to reduce risks for sexual assault in college drinking contexts.

Clinical Characteristics of Adolescents With Juvenile Idiopathic Arthritis Transitioning to Adult Rheumatology Care in Canada: Results From the CAPRI Registry.

OBJECTIVE: Using Canadian Alliance of Pediatric Rheumatology Investigators (CAPRI) juvenile idiopathic arthritis (JIA) registry data, we describe (1) clinical characteristics of patients with JIA transitioning to adult care, (2) prevalence of disease-related damage and complications, and (3) changes in disease activity during the final year prior to transfer. METHODS: Registry participants who turned 17 years between February 2017 and November 2021 were included. Clinical characteristics and patient-reported outcomes (PROs) at the last recorded pediatric rheumatology visit, and changes observed in the year prior to that visit were analyzed. Physicians completed an additional questionnaire characterizing cumulative disease-related damage and adverse events by age 17 years. RESULTS: At their last visit, 88 of 131 participants (67%) had inactive and 42 (32%) had active disease. Overall, 96 (73%) were on medications and 41 (31%) were on biologic disease-modifying antirheumatic drugs. Among 80 participants for whom the additional questionnaire was completed, 26% had clinically detected joint damage, 31% had joint damage on imaging, 14% had uveitis, and 7.5% had experienced at least 1 serious adverse event. During the final year, 44.2% of patients were in remission, 28.4% attained inactive disease, and 27.4% became or remained active. Mean scores of PROs were stable overall during that last year, but a minority reported marked worsening. CONCLUSION: A substantial proportion of youth with JIA transitioning to adult care in Canada had a high disease burden, which was reflected by their degree of disease activity, joint damage, or ongoing medication use. These results will inform pediatric and adult providers of anticipated needs during transition of care.

Conceptualizations of interprofessional communication in intensive care units: findings from a scoping review.

BACKGROUND: Clinical errors in intensive care units (ICUs) are consistently attributed to communication errors. Despite its importance for patient safety and quality in critical care settings, few studies consider interprofessional communication as more than the basic exchange of information. METHODS: We conducted a scoping review of interprofessional communication in ICUs to (1) characterize how communication is defined and measured and (2) identify contributions the field of health communication can make to team communication in ICUs. Through a series of queries in PubMed and Communication and Mass Media Complete databases, we identified and compared persistent gaps in how communication is framed and theorized in 28 publications from health services and 6 from social science outlets. We identified research priorities and suggested strategies for discussing communication more holistically in future health services research. RESULTS: 34 articles published from 1999 to 2021 were included. Six explicitly defined communication. Six were published in social science journals, but none were authored by a communication studies scholar. Half of the articles addressed communication as a transaction focused on information transfer, and the other half addressed communication as a process. CONCLUSIONS: Methodological implications are identified with the intent to encourage future interdisciplinary collaboration for studying communication in ICUs. We discuss the importance of (1) using language to describe communication that facilitates interdisciplinary engagement, (2) prioritizing communication as a process and using qualitative methods to provide insight, and (3) engaging health communication theories and experts to assist in developing more fruitful research questions and designs.

Discovery and Characterization of a Pan-betacoronavirus S2-binding antibody.

Three coronaviruses have spilled over from animal reservoirs into the human population and caused deadly epidemics or pandemics. The continued emergence of coronaviruses highlights the need for pan-coronavirus interventions for effective pandemic preparedness. Here, using LIBRA-seq, we report a panel of 50 coronavirus antibodies isolated from human B cells. Of these antibodies, 54043-5 was shown to bind the S2 subunit of spike proteins from alpha-, beta-, and deltacoronaviruses. A cryo-EM structure of 54043-5 bound to the pre-fusion S2 subunit of the SARS-CoV-2 spike defined an epitope at the apex of S2 that is highly conserved among betacoronaviruses. Although non-neutralizing, 54043-5 induced Fc-dependent antiviral responses, including ADCC and ADCP. In murine SARS-CoV-2 challenge studies, protection against disease was observed after introduction of Leu234Ala, Leu235Ala, and Pro329Gly (LALA-PG) substitutions in the Fc region of 54043-5. Together, these data provide new insights into the protective mechanisms of non-neutralizing antibodies and define a broadly conserved epitope within the S2 subunit.

Narrative Sense-Making During COVID-19: Using Stories to Understand Birth in a Global Pandemic.

Women who gave birth in the spring and summer of 2020 contended with a host of challenging factors. In addition to facing pregnancy, labor, and delivery during an emerging global pandemic, women grappled with health care restrictions that altered their birth experience. To explore how women made sense of their birth during COVID-19, we analyzed written narratives from 71 women who gave birth in the United States from March to July 2020. Based on tenets of communicated narrative sense-making, the themes that emerged from our data suggest that women framed the role of the pandemic as either completely overshadowing their birth experience or as an inconvenience. Women also wrote about threats to their agency as patients, mothers, and caregivers, as well as the evolving emotional toll of the pandemic that often prompted feelings of fear and sadness, along with self-identified anxiety and depression. We discuss these findings in light of the literature on birth stories as essential sites of narrative sense-making for women and their families.

'We need a culture change': military sexual trauma through the lens of rape culture.

Military sexual trauma remains a critical concern within the US military. One possible explanation for the persistence of this trauma is the presence of rape culture. This study examined perceptions of military sexual trauma within the framework of rape culture (i.e. traditional gender roles, sexism, adversarial sexual beliefs, hostility toward women, and acceptance of violence), in addition to associated factors, to address the US Department of Defense's call to focus on the role of culture on military sexual trauma. Focusing on culture is important as subtle norms in culture shape our behaviour and impact the excusal/perpetration of military sexual trauma. Identifying these norms may provide insight into factors to target in prevention efforts to reduce/eliminate military sexual trauma. Forty-two US service members responded to a series of open-ended questions. Standard content analysis procedures were utilised to determine themes. Results paint a complex picture of military sexual trauma, with participants demonstrating concern regarding military sexual trauma, but minimal acknowledgement of behaviour change to reduce military sexual trauma. These results are consistent with the observed increase in prevalence of military sexual trauma and decrease in reporting of it since 2018. Adding to the existing literature, participants noted the continued existence of rape culture within the military and the need for cultural change to address military sexual trauma.

Rheumatoid Arthritis Care Experiences of Black People Living in Canada: A Qualitative Study to Inform Health Service Improvements.

OBJECTIVE: To understand experiences related to rheumatoid arthritis (RA) care and propose service-level strategies to reduce and mitigate inequities for Black people living in Canada. METHODS: Purposive and respondent driven sampling was used to recruit participants for qualitative interviews to explore population factors relevant to RA care and challenges and facilitators for access to health care services, medications, and enacting preferred treatment plans. Thematic analysis was conducted using the Braun and Clarke method with inductive and deductive coding and critical race theory guiding analysis. RESULTS: Six women and two men with RA, and two women health care professionals, expressed how their racial identity contributed to their understanding of RA, preferences for treatment, and outcome goals. Health care access was influenced by financial limitations and racism, by exclusion, and discrimination, and also by cultural norms in seeking health care and awareness about RA within the Black community. Participants experienced health system fragmentation and were not connected to ancillary supports. Treatment decision-making was influenced by the legacy of oppression and medical experimentation on Black people and the predominance of biomedical approaches emphasized by health care providers. Holistic and cultural approaches, provided in safe, trauma-informed care environments, with flexibility in service models, are desired. Partnerships between arthritis care services and Black community organizations are proposed to promote community awareness and knowledge about arthritis and provide support mechanisms for patients within their community. CONCLUSION: Our study highlights unique considerations based on race and ethnicity and provides suggestions for arthritis care to mitigate inequities for Black people living with arthritis.

Expectancy violations and boundary management when giving birth during a pandemic: implications for supporting women.

BACKGROUND: Few life events are as profound as the birth of a child. Yet for those who gave birth during the COVID-19 pandemic, the birth experience and the care of their newborn child were altered in significant ways. METHOD: In this study, we examined the stories of women who gave birth during the COVID-19 pandemic using expectations violations theory and communication privacy management theory. RESULTS: Based on focus group interviews with 65 women from 19 states across the U.S., we found that policies imposed by institutions and visitation rules negotiated by women were prominent in women's birth stories. Policies that affect territorial access to mothers and babies shaped communication to manage health and safety, resulted in intense emotional responses, and affected relationships with women's partners and families. CONCLUSIONS: Our findings offer practical implications for both health care systems and health care providers. Systems must communicate proactively to offer compassionate patient care, and physicians should offer guidance to help new parents manage visitors.

"I'm Not Comfortable With COVID, But ": Dilemmas and Decision-Making to Mitigate Risks Among Mothers Who Gave Birth During the COVID-19 Pandemic.

Individuals have faced unprecedented uncertainty and risk surrounding the COVID-19 pandemic, and decision-making dilemmas have been complicated by quickly evolving and often contradictory recommendations for staying healthy. Using tenets of problematic integration theory and risk orders theory, we analyzed interview data from 50 mothers who gave birth during the pandemic to understand how uncertainty and risk perceptions shaped their decision-making about keeping themselves and their infants healthy in the first year after birth. Results describe how some mothers in our sample made sense of their decision-making to prioritize first-order risks to their own and their family's physical health, and other mothers prioritized second-order risks to their relationships and identities. We also discuss the social nature of mitigating risk during the COVID-19 pandemic and the catalysts for shifting risk perceptions. Theoretical and practical implications include improving public health messaging and clinical conversations to enable individuals to effectively manage social and identity needs alongside serious threats to physical health.

A decade of progress in juvenile idiopathic athritis treatments and outcomes in Canada: results from ReACCh-Out and the CAPRI registry.

OBJECTIVE: To assess changes in juvenile idiopathic arthritis (JIA) treatments and outcomes in Canada, comparing a 2005-2010 and a 2017-2021 inception cohorts. METHODS: Patients enrolled within three months of diagnosis in the Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh-Out) and the Canadian Alliance of Pediatric Rheumatology Investigators Registry (CAPRI) cohorts were included. Cumulative incidences of drug starts and outcome attainment within 70 weeks of diagnosis were compared with Kaplan Meier survival analysis and multivariable Cox regression. RESULTS: The 2005-2010 and 2017-2021 cohorts included 1128 and 721 patients, respectively. JIA category distribution and baseline clinical juvenile idiopathic arthritis disease activity (cJADAS10) scores at enrolment were comparable. By 70 weeks, 6% of patients (95% CI 5, 7) in the 2005-2010 and 26% (23, 30) in the 2017-2021 cohort had started a biologic DMARD (bDMARD), and 43% (40, 47) and 60% (56, 64) had started a conventional DMARD (cDMARD), respectively. Outcome attainment was 64% (61, 67) and 83% (80, 86) for Inactive disease (Wallace criteria), 69% (66, 72) and 84% (81, 87) for minimally active disease (cJADAS10 criteria), 57% (54, 61) and 63% (59, 68) for pain control (<1/10), and 52% (47, 56) and 54% (48, 60) for a good health-related quality of life. CONCLUSION: Although baseline disease characteristics were comparable in the 2005-2010 and 2017-2021 cohorts, cDMARD and bDMARD use increased with a concurrent increase in minimally active and inactive disease. Improvements in parent and patient reported outcomes were smaller than improvements in disease activity.

Mitigating diagnostic performance bias in a skin-tone balanced dermatology curriculum.

INTRODUCTION: Individuals with skin of colour (SoC) have delayed diagnosis and poorer outcomes when presenting with some dermatologic conditions when compared to individuals with light skin (LS). The objective of this study was to determine if diagnostic performance bias can be mitigated by a skin-tone balanced dermatology curriculum. METHODOLOGY: A prospective randomised intervention study occurred over 2 weeks in 2020 at a Canadian medical school. A convenience sample of all first-year medical students (n = 167) was chosen. In week 1, all participants had access to dermatology podcasts and were randomly allocated to receive non-analytic training (NAT; online patient 'cards') on either SoC cases or LS cases. In week 2, all participants received combined training (CT; NAT and analytic training through workshops on how to apply dermatology diagnostic rules for all skin tones). Participating students completed two formative assessments after weeks 1 and 2. RESULTS: Ninety-two students participated in the study. After week 1, both groups had a lower diagnostic performance on SoC (p = 0.0002 and p = 0.002 for students who trained on LS 'cards' and SoC 'cards', respectively). There was a significant decrease in mean skin tone difference in both groups after week 2 (initial training on SoC: 5.8% (SD 12.2) pre, -1.4% (14.7) post, p = 0.007; initial training on LS: 7.8% (15.4) pre, -4.0% (11.8%) post, p = 0.0001). Five students participated in a post-study survey in 2023, and all found the curriculum enhanced their diagnostic skills in SoC. CONCLUSIONS: SoC performance biases of medical students disappeared after CT in a skin tone-balanced dermatology curriculum.