Adjuvant Delivery Method and Nanoparticle Charge Influence Peptide Amphiphile Micelle Vaccine Bioactivity.

Vaccines are an indispensable public health measure that have enabled the eradication, near elimination, and prevention of a variety of pathogens. As research continues and our understanding of immunization strategies develops, subunit vaccines have emerged as exciting alternatives to existing whole vaccine approaches. Unfortunately, subunit vaccines often possess weak antigenicity, requiring delivery devices and adjuvant supplementation to improve their utility. Peptide amphiphile micelles have recently been shown to function as both delivery devices and self-adjuvanting systems that can be readily associated with molecular adjuvants to further improve vaccine-mediated host immunity. While promising, many "design rules" associated with the plethora of underlying adjustable parameters in the generation of a peptide amphiphile micelle vaccine have yet to be uncovered. This work explores the impact micellar adjuvant complexation method and incorporated antigen type have on their ability to activate dendritic cells and induce antigen specific responses. Interestingly, electrostatic complexation of CpG to micelles resulted in improved in vitro dendritic cell activation over hydrophobic association and antigen|adjuvant co-localization influenced cell-mediated, but not antibody-mediated immune responses. These exciting results complement those previously published to build the framework of a micelle vaccine toolbox that can be leveraged for future disease-specific formulations.

The power of written word: Reflection reduces errors of omission.

BACKGROUND: Medical trainees are expected to perform complex tasks while experiencing interruptions, which increases susceptibility to errors of omission. In our study, we examine whether documentation of clinical encounters increases reflective thinking and reduces errors of omission among novice learners in a simulated setting. METHODS: In 2021, 56 senior medical students participated in a simulated paging curriculum involving urgent inpatient cross-cover scenarios (sepsis and atrial fibrillation). Students responded to pages from standardized registered nurses (SRNs) via telephone, gathered history, and discussed clinical decision-making. Following the phone encounter, students documented a brief note (documentation encounter). A 'phone' score (number of checklist items completed in the phone encounter) and a 'combined' score (number of checklist items completed in the phone and documentation encounters) were calculated. Data were analyzed for differences between the phone scores (control) and combined scores using T-tests and McNemar test of symmetry. FINDINGS: Fifty-four students (96%) participated. Combined scores were higher than phone scores for sepsis (72.8 ± 11.3% vs. 67.9 ± 11.9%, p < 0.001) and atrial fibrillation (74.0 ± 10.1% vs. 67.6 ± 10.0%, p < 0.001) cases. Important items, such as ordering blood cultures for sepsis (p = 0.023) and placing the patient on telemetry for atrial fibrillation (p = 0.013), were more likely to be present when a note was documented. DISCUSSION: This study suggests that documentation provides a mechanism for learners to reflect, which could increase important diagnostic and therapeutic interventions. CONCLUSION: Documentation by novice medical learners may improve patient care by allowing for reflection and reducing errors of omission.

Photopolymerization Parameters Influence Mechanical, Microstructural, and Cell Loading Properties of Rapidly Fabricated Cell Scaffolds.

Engineered scaffolds are commonly used to assist in cellular transplantations, providing crucial support and specific architecture for a variety of tissue engineering applications. Photopolymerization as a fabrication technique for cell scaffolds enables precise spatial and temporal control of properties and structure. One simple technique to achieve a two-dimensional structure is the use of a patterned photomask, which results in regionally selective photo-cross-linking. However, the relationships between photopolymerization parameters like light intensity and exposure time and outcomes like structural fidelity and mechanical properties are not well-established. In this work, we used photopolymerization to generate degradable polycaprolactone triacrylate (PCLTA) scaffolds with a defined microstructure. We examined the impact of light intensity and exposure time on scaffold properties such as shear modulus and micropore structure. To assess feasibility in a specific application and determine the relationship between parameter-driven properties and cell loading, we cultured retinal progenitor cells on the PCLTA scaffolds. We found that light intensity and polymerization time directly impact the scaffold stiffness and micropore structure, which in turn influenced the cell loading capacity of the scaffold. Because material stiffness and topography are known to impact cell viability and fate, understanding the effect of scaffold fabrication parameters on mechanical and structural properties is critical to optimizing cell scaffolds for specific applications.

Collaboration in interprofessional teams: A needs assessment of factors that impact new resident physicians.

Many resident physicians struggle with effective interprofessional collaboration (IPC), but characterization of their challenges is not well known. This study examines gaps in IPC skills for graduating medical students entering residency. A needs assessment was completed to evaluate factors that impact resident physicians' ability to effectively collaborate with other healthcare professionals. This study included online surveys of 123 recent medical school graduates, 21 semi-structured interviews of residency program directors, and 3 focus groups of healthcare professionals who interacted with residents. Survey results were analyzed for means and narratives from surveys, interviews, and focus groups were analyzed for themes. We found that graduates felt they did not have a strong understanding of other providers' roles and did not feel well prepared to handle conflict with other providers or navigate interprofessional team dynamics. Themes emerging from narrative data generally aligned with the Interprofessional Education Collaborative core competencies including understanding team roles, communicating effectively, and working effectively in a team, but these interviews also elucidated an additional theme, overcoming system barriers. Data from this work can inform curricula in preparation for the transition to residency. The authors also offer an educational framework for learning effective IPC as a new team member.

Biocompatibility of Human Induced Pluripotent Stem Cell-Derived Retinal Progenitor Cell Grafts in Immunocompromised Rats.

Loss of photoreceptor cells is a primary feature of inherited retinal degenerative disorders including age-related macular degeneration and retinitis pigmentosa. To restore vision in affected patients, photoreceptor cell replacement will be required. The ideal donor cells for this application are induced pluripotent stem cells (iPSCs) because they can be derived from and transplanted into the same patient obviating the need for long-term immunosuppression. A major limitation for retinal cell replacement therapy is donor cell loss associated with simple methods of cell delivery such as subretinal injections of bolus cell suspensions. Transplantation with supportive biomaterials can help maintain cellular integrity, increase cell survival, and encourage proper cellular alignment and improve integration with the host retina. Using a pig model of retinal degeneration, we recently demonstrated that polycaprolactone (PCL) scaffolds fabricated with two photon lithography have excellent local and systemic tolerability. In this study, we describe rapid photopolymerization-mediated production of PCL-based bioabsorbable scaffolds, a technique for loading iPSC-derived retinal progenitor cells onto the scaffold, methods of surgical transplantation in an immunocompromised rat model and tolerability of the subretinal grafts at 1, 3, and 6 months of follow-up (n = 150). We observed no local or systemic toxicity, nor did we observe any tumor formation despite extensive clinical evaluation, clinical chemistry, hematology, gross tissue examination and detailed histopathology. Demonstrating the local and systemic compatibility of biodegradable scaffolds carrying human iPSC-derived retinal progenitor cells is an important step toward clinical safety trials of this approach in humans.

Re-defining gender diversity through an equitable and inclusive lens.

Gender diversity in radiology has centered on the societal construct of the gender binary, with significant work focused on increasing the number of women in radiology. Along with this critically important goal, it is imperative that we acknowledge gender is more expansive than a binary category because it represents a spectrum of gender identities. The discussion of this spectrum is lacking in our conversations around gender diversity and equity in radiology. Addressing equity for people of all gender identities is beneficial for us all. We define three key areas of focus: (1) improving fundamental knowledge about gender diversity and application of this knowledge in education, (2) recruiting and retaining gender-diverse physicians and (3) specific diversity, equity and inclusion (DEI) policy to support gender-affirming environments. Improved understanding and inclusion of the full spectrum of gender in these areas will improve diversity and equity, and, in turn, enhance creativity and innovation in radiology.

Diagnostic accuracy of cytology for the detection of bacterial infection in fluid samples from veterinary patients.

BACKGROUND: Bacterial sepsis is a relatively common, life-threatening condition with a high case fatality rate. The current primary diagnostic tools for detecting bacterial infection in fluids are bacterial culture and fluid cytology. While culture is the gold standard, it can take up to several days for results to be made available to clinicians, which can delay recognition of bacterial sepsis and negatively impact patient outcomes. OBJECTIVES: The aim of this study was to evaluate the diagnostic accuracy of cytology for detecting bacterial infection in body fluids. METHODS: We retrospectively reviewed 10 years of medical records at the Ohio State University's Veterinary Medical Center for mammalian patients with both cytology and bacterial culture of fluid samples, including body cavity fluids (abdominal and thoracic effusion), blood, joint fluid, and CSF. The overall sensitivity and specificity of cytology relative to the reference method of bacterial culture was recorded, as well as among the subcategories of fluid type. RESULTS: The overall sensitivity and specificity of cytology for the diagnosis of sepsis were 42.6% and 93.0%, respectively. Individual sensitivities and specificities were also calculated for each fluid type. Thoracic fluid cytology had relatively high sensitivity and low specificity, in contrast to the other fluid types analyzed. CONCLUSIONS: Overall, cytology is poorly sensitive but highly specific for the detection of bacterial infection in fluid samples. The results from this study will allow a better comparison between the diagnostic accuracy of cytology and emerging diagnostic tests for the detection of bacterial sepsis in mammalian patients.

Full-Thickness Oral Mucoperiosteal Defects: Challenges and Opportunities.

Regenerative engineering strategies for the oral mucoperiosteum, as may be needed following surgeries, such as cleft palate repair and tumor resection, are underdeveloped compared with those for maxillofacial bone. However, critical-size tissue defects left to heal by secondary intention can lead to complications, such as infection, fistula formation, scarring, and midface hypoplasia. This review describes current clinical practice for replacing mucoperiosteal tissue, including autografts and allografts. Potentially paradigm-shifting experimental regenerative engineering strategies for mucoperiosteal wound healing, such as hybrid grafts and engineered matrices, are also discussed. Throughout the review, the advantages and disadvantages of each replacement or regeneration strategy are outlined in the context of clinical outcomes, quality of life for the patient, availability of materials, and cost of care. Finally, future directions for research and development in the area of mucoperiosteum repair are proposed, with an emphasis on identifying globally available and affordable solutions for promoting mucoperiosteal regeneration. Impact statement Unassisted oral mucoperiosteal wound healing can lead to severe complications such as infection, fistulae, scarring, and developmental abnormalities. Thus, strategies for promoting wound healing must be considered when mucoperiosteal defects are incident to oral surgery, as in palatoplasty or tumor resection. Emerging mucoperiosteal tissue engineering strategies, described in this study, have the potential to overcome the limitations of current standard-of-care donor tissue grafts. For example, the use of engineered mucoperiosteal biomaterials could circumvent concerns about tissue availability and immunogenicity. Moreover, employment of tissue engineering strategies may improve the equity of oral wound care by increasing global affordability and accessibility of materials.

Interprofessional experiences to bridge the medical school to residency transition: a pilot program.

Interprofessional experiences during medical school are often delivered during pre-clinical years, but less is known about the value of clinical students. Our institution implemented a specialty-specific interprofessiona curriculum during Residency Preparation Courses (RPCs) for senior students including didactics, clinical experiences, and a simulated paging curriculum. Our aim was to determine whether this intervention improved perceptions of interprofesiona roles. We distributed anonymous surveys before (pre-survey) and after (post-survey, collected within 2 weeks of course completion) the RPC to 90 students with questions related to interprofessional roles using a 5-point scale (1 = strongly disagree, 5 = strongly agree). Three months after the start of residency, we sent follow-up surveys inquiring about the usefulness of RPC components (1 = not at all useful, 5 = extremely useful). Response rates were 84.4% pre-survey, 63.3% post-survey, and 41.1% follow-up survey. Post-surveys indicated improvement in self-reported ability in all domains: understanding one's contributions to interprofessional teams (3.9 to 4.4, p < .0001), understanding other team members' contributions (3.9 to 4.4, p < .0001), learning from interprofessional team members (4.2 to 4.6, p = .0002), accounting for interprofessional perspectives (4.2 to 4.6, p < .0001), and co-developing effective care plans (3.9 to 4.4, p < .0001). Follow-up surveys rated clinical experiences as slightly-to-moderately useful (2.3 ± 1.0) and paging curriculum very-to-extremely useful (4.3 ± 1.0). This study demonstrates the value of interprofessional education for advanced students.

Associations Between Psychosocial Measures and Digital Media Use Among Transgender Youth: Cross-sectional Study.

BACKGROUND: Transgender, nonbinary, and gender-diverse (TNG) youth encounter barriers to psychosocial wellness and also describe exploring identities and communities on the web. Studies of cisgender youth connect increased digital technology use with lower well-being, parent relationships, and body image scores as well as increased loneliness and fear of missing out (FOMO). However, little is known about the psychosocial factors associated with digital technology use among TNG compared with cisgender youth. OBJECTIVE: This study aims to examine the associations between psychosocial measures and digital technology use and its importance for cisgender and TNG youth. METHODS: We surveyed a nationally representative sample of adolescents (aged 13-18 years) about psychosocial wellness and digital technology use. Psychosocial measures included assessment of well-being, parental relationships, body image, loneliness, and FOMO. Digital media use assessments included the short Problematic and Risky Internet Use Screening Scale-3 and the Adolescent Digital Technology Interactions and Importance (ADTI) scale and subscales. We compared psychosocial measures between gender identity groups. We also compared stratified correlations for psychosocial measures (well-being, parent relationships, body image, loneliness, and FOMO) with ADTI and Problematic and Risky Internet Use Screening Scale-3 scores between gender identity groups. All comparisons were adjusted for age, race, and ethnicity. RESULTS: Among 4575 adolescents, 53 (1.16%) self-identified as TNG youth. TNG youth had lower scores for well-being (23.76 vs 26.47; P<.001), parent relationships (19.29 vs 23.32; P<.001), and body image (13.50 vs 17.12; P<.001), and higher scores for loneliness (9.28 vs 6.55; P<.001) and FOMO (27.93 vs 23.89; P=.004), compared with cisgender peers. In a pattern different from that of their cisgender peers, better well-being scores and body image for TNG youth predicted higher problematic internet use (PIU) scores (correlation coefficients of 0.32 vs -0.07; P=.004 and 0.26 vs -0.21; P=.002, respectively). FOMO was a stronger positive predictor of higher ADTI total and subscale scores for cisgender youth compared with TNG youth. CONCLUSIONS: Overall, this study supports previously demonstrated disparities in the psychosocial wellness of TNG youth and adds that these disparities include loneliness and FOMO. This study shows prediction of PIU by both higher well-being and better body image, indicating that PIU may not be unilaterally driven by problematic factors among TNG youth. We suggest that this may be because of the specific digital media functions that TNG youth engage with as a disenfranchised population.

Student Perceptions of educational handovers.

BACKGROUND: Educational handovers can provide competency information about graduating medical students to residency program directors post-residency placement. Little is known about students' comfort with this novel communication. OBJECTIVE: To examine graduated medical students' perceptions of educational handovers. METHODS: The authors created and distributed an anonymous survey to 166 medical students at a single institution following graduation in the spring of 2018. Within this cohort, 40 students had an educational handover sent to their future program director. The survey explored comfort level with handovers (1=very uncomfortable; 5=very comfortable) and ideal content (e.g., student strengths, areas for improvement, goals, grades received after residency application). Respondents self-reported their performance in medical school and whether a handover was sent. Correlation analyses examined relationships between performance and other variables. T-tests examined differences between students who did and did not have a handover letter sent. RESULTS: The survey response rate was 40.4% (67/166) - 47.8% of students felt comfortable with handovers, 19.4% were neutral, and 32.8% were uncomfortable. There was no correlation between self-reported medical school performance and comfort level. Respondents felt most strongly that strengths should be included, followed by goals. Those who had a handover letter sent expressed significantly higher comfort level (3.8 ± 1.0 vs. 2.6 ±1.3, p=0.003) with this communication. CONCLUSION: Medical students reported varying levels of comfort with educational handovers; however, those who had handovers sent had more positive perceptions. In order to improve the education continuum, it is essential to engage students in the development of this handover communication.

At the Margins: Comparing School Experiences of Nonbinary and Binary-Identified Transgender Youth.

BACKGROUND: Transgender, nonbinary, and gender nonconforming (TNG) young people are a diverse group, including young people with gender identities beyond the gender binary. Whereas nonbinary youth experience disparities in victimization and mental health, school belonging, support, and resources have not been well described. METHODS: We conducted an online survey of TNG young people (ages 12-22) in Wisconsin to assess school belonging, safety, support, and resources. We compared responses among participants with nonbinary versus binary identities using mulvariate analysis of variance, multivariate analysis of covariance, chi-square and logistic regression analysis. RESULTS: A total of 287 TNG young people met inclusion criteria (average age 18.2 ± 2.5 years). More than 40% of participants identified as nonbinary. Nonbinary participants were less likely to be out to teachers, but more likely to utilize supportive staff as a resource compared to binary-identified TNG peers. There were no significant differences in school safety and belonging. CONCLUSIONS: Most school experiences do not vary significantly between TNG young people with binary versus nonbinary gender identities, though nonbinary young people are less likely to be out at school. Future research should examine factors that impact whether nonbinary young people share their gender identity and access school support services.

Development of High-Resolution Three-Dimensional-Printed Extracellular Matrix Scaffolds and Their Compatibility with Pluripotent Stem Cells and Early Retinal Cells.

Purpose: Widely used approaches for retinal disease modeling and in vitro therapeutic testing can be augmented by using tissue-engineered scaffolds with a precise 3-dimensional structure. However, the materials currently used for these scaffolds are poorly matched to the biochemical and mechanical properties of the in vivo retina. Here, we create biopolymer-based scaffolds with a structure that is amenable to retinal tissue engineering and modeling. Methods: Optimal two-photon polymerization (TPP) settings, including laser power and scanning speed, are identified for 4 methacrylated biopolymer formulations: collagen, gelatin, hyaluronic acid (HA), and a 50/50 mixture of gelatin/HA, each with methylene blue as a photoinitiator. For select formulations, fabrication accuracy and swelling are determined and biocompatibility is evaluated by using human induced pluripotent stem cells and rat postnatal retinal cells. Results: TPP is feasible for each biopolymer formulation, but it is the most reliable for mixtures containing gelatin and the least reliable for HA alone. The mean size of microscaffold pores is within several microns of the intended value but the overall structure size is several times greater than the modeled volume. The addition of HA to gelatin scaffolds increases cell viability and promotes neuronal phenotype, including Tuj-1 expression and characteristic morphology. Conclusion: We successfully determined a useful range of TPP settings for 4 methacrylated biopolymer formulations. When crosslinked, these extracellular matrix-derived molecules support the growth and attachment of retinal cells. We anticipate that when combined with existing patient-specific approaches, this technique will enable more efficient and accurate retinal disease modeling and therapeutic testing in vitro than current techniques allow.

The Role of Ames Dwarfism and Calorie Restriction on Gut Microbiota.

The gut microbiome (GM) represents a large and very complex ecosystem of different microorganisms. There is an extensive interest in the potential role of the GM in different diseases including cancer, diabetes, cardiovascular diseases, and aging. The GM changes over the lifespan and is strongly associated with various age-related diseases. Ames dwarf (df/df) mice are characterized by an extended life- and healthspan, and although these mice are protected from many age-related diseases, their microbiome has not been studied. To determine the role of microbiota on longevity animal models, we investigated the changes in the GM of df/df and normal control (N) mice, by comparing parents before mating and littermate mice at three distinct time points during early life. Furthermore, we studied the effects of a 6-month calorie restriction (CR), the most powerful intervention extending the lifespan. Our data revealed significant changes of the GM composition during early life development, and we detected differences in the abundance of some bacteria between df/df and N mice, already in early life. Overall, the variability of the microbiota by genotype, time-point, and breeding pair showed significant differences. In addition, CR caused significant changes in microbiome according to gastrointestinal (GI) location (distal colon, ileum, and cecum), genotype, and diet. However, the overall impact of the genotype was more prominent than that of the CR. In conclusion, our findings suggest that the gut microbiota plays an important role during postnatal development in long-living df/df mice and CR dietary regimen can significantly modulate the GM.