A single institution, cross-sectional study on medical student preferences for collaborators in interprofessional education.

BACKGROUND: While the importance of interprofessional education in medical training has been well-established, no specific framework has been used uniformly or shown to be most effective in the creation of interprofessional education (IPE) sessions. Further, prior studies have demonstrated that students have preferences for the design of these experiences. In this study, we sought to understand medical student preference for interprofessional teammates and motivations for this choice. METHODS: In this single-institution, cross-sectional analysis of the Duke IPE Clinic, participating students from September 2019-March 2020 completed a voluntary electronic survey that queried preferences for which health professions students (Doctor of Physical Therapy (DPT), Accelerated Bachelor of Science in Nursing (ABSN), Nurse Practitioner (NP), Pharmacy, and Physician's Associate (PA)) they would want to work with, and the motivating reason. Preferences and reasons were compared between first-year medical students (MS1s) and third- and fourth-year medical students (MS3s/MS4s). RESULTS: In total, 132 students participated. We found that MS1s most preferred interprofessional teammates with a more similar area of study (PA, NP), whereas MS3s/MS4s most preferred classmates with a less similar area of study (pharmacy, DPT, ABSN). MS1 students frequently selected their first-choice preference because the profession seemed most similar, while MS3/MS4 students often selected their first-choice preference because the profession seemed most different. CONCLUSIONS: Medical students earlier in training have more interest in working with professions they view as similar whereas senior students prefer to work with professions they view as more different. This information is important for designing educational IPE opportunities.

Photodistributed Toxic Epidermal Necrolysis: Case Report and Review of Current Literature.

Importance: Cases of photodistributed Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been infrequently reported since the first documented case in 1989. This emerging clinical entity and its underlying mechanism have yet to be fully characterized. Objective: To report a case of photodistributed SJS/TEN and highlight similarities to other cases reported in the literature. Design, Setting, and Participants: Case report and literature review of published cases of photodistributed SJS/TEN. The case report describes a 29-year-old woman with recent lamotrigine and trimethoprim-sulfamethoxazole exposure who developed TEN in a photodistributed pattern 1 day after prolonged sun exposure. A search of PubMed using the keywords toxic epidermal necrolysis, Stevens-Johnson syndrome, photo-distributed, photo-induced, and sun-exposed was performed to identify other cases reported in the literature. Results: Literature review revealed 8 previously reported cases of healthy individuals with known drug and UV radiation (UVR) exposures who subsequently developed SJS or TEN with photodistribution. Cases reviewed were skewed demographically to young women aged 19 to 48 years (8 of 9 patients) with all cases reporting UVR exposure 24 to 72 hours prior to the onset of symptoms. Conclusions and Relevance: Photodistributed TEN has been increasingly described in the literature and may represent a distinct variant of SJS/TEN. While the pathogenesis remains unclear, the role of UVR as a "second hit" is suggested by the data presented in the cases documented thus far.

Skin Injury Activates a Rapid TRPV1-Dependent Antiviral Protein Response.

The skin serves as the interface between the body and the environment and plays a fundamental role in innate antimicrobial host immunity. Antiviral proteins (AVPs) are part of the innate host defense system and provide protection against viral pathogens. How breach of the skin barrier influences innate AVP production remains largely unknown. In this study, we characterized the induction and regulation of AVPs after skin injury and identified a key role of TRPV1 in this process. Transcriptional and phenotypic profiling of cutaneous wounds revealed that skin injury induces high levels of AVPs in both mice and humans. Remarkably, pharmacologic and genetic ablation of TRPV1-mediated nociception abrogated the induction of AVPs, including Oas2, Oasl2, and Isg15 after skin injury in mice. Conversely, stimulation of TRPV1 nociceptors was sufficient to induce AVP production involving the CD301b+ cells‒IL-27‒mediated signaling pathway. Using IL-27 receptor‒knockout mice, we show that IL-27 signaling is required in the induction of AVPs after skin injury. Finally, loss of TRPV1 signaling leads to increased viral infectivity of herpes simplex virus. Together, our data indicate that TRPV1 signaling ensures skin antiviral competence on wounding.

Single-Cell RNA Sequencing Reveals Cellular and Transcriptional Changes Associated With M1 Macrophage Polarization in Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent abscesses, nodules, and sinus tracts in areas of high hair follicle and sweat gland density. These sinus tracts can present with purulent drainage and scar formation. Dysregulation of multiple immune pathways drives the complexity of HS pathogenesis and may account for the heterogeneity of treatment response in HS patients. Using transcriptomic approaches, including single-cell sequencing and protein analysis, we here characterize the innate inflammatory landscape of HS lesions. We identified a shared upregulation of genes involved in interferon (IFN) and antimicrobial defense signaling through transcriptomic overlap analysis of differentially expressed genes (DEGs) in datasets from HS skin, diabetic foot ulcers (DFUs), and the inflammatory stage of normal healing wounds. Overlap analysis between HS- and DFU-specific DEGs revealed an enrichment of gene signatures associated with monocyte/macrophage functions. Single-cell RNA sequencing further revealed monocytes/macrophages with polarization toward a pro-inflammatory M1-like phenotype and increased effector function, including antiviral immunity, phagocytosis, respiratory burst, and antibody-dependent cellular cytotoxicity. Specifically, we identified the STAT1/IFN-signaling axis and the associated IFN-stimulated genes as central players in monocyte/macrophage dysregulation. Our data indicate that monocytes/macrophages are a potential pivotal player in HS pathogenesis and their pathways may serve as therapeutic targets and biomarkers in HS treatment.

Laser-Assisted Delivery of Topical Cidofovir in the Treatment of Plantar Warts

Recalcitrant plantar warts pose a therapeutic challenge. Cidofovir is a viral DNA polymerase inhibitor that has been used in treatment of verrucae with greater success than traditional treatments in some cases. Laser-assisted drug delivery enhances drug penetration beyond the epidermis and is particularly well-suited, though under-utilized, to target palmoplantar verrucae. We report the use of an erbium:yttrium-aluminum-garnet (Er:YAG) ablative fractional laser (AFL) followed by topical cidofovir in treating recalcitrant plantar warts. Two patients were treated with a 2940-nm Er:YAG laser at depths of 1.2-1.5 mm followed by topical application of cidofovir 75 mg/mL. Both patients exhibited a significant reduction in lesion size and improvement in symptoms. AFL-assisted delivery of topical cidofovir represents a promising therapeutic option for recalcitrant plantar warts. J Drugs Dermatol. 2019;18(7):663-665.

The skin transcriptome in hidradenitis suppurativa uncovers an antimicrobial and sweat gland gene signature which has distinct overlap with wounded skin.

Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory skin disease resulting in non-healing wounds affecting body areas of high hair follicle and sweat gland density. The pathogenesis of HS is not well understood but appears to involve dysbiosis-driven aberrant activation of the innate immune system leading to excessive inflammation. Marked dysregulation of antimicrobial peptides and proteins (AMPs) in HS is observed, which may contribute to this sustained inflammation. Here, we analyzed HS skin transcriptomes from previously published studies and integrated these findings through a comparative analysis with a published wound healing data set and with immunofluorescence and qPCR analysis from new HS patient samples. Among the top differently expressed genes between lesional and non-lesional HS skin were members of the S100 family as well as dermcidin, the latter known as a sweat gland-associated AMP and one of the most downregulated genes in HS lesions. Interestingly, many genes associated with sweat gland function, such as secretoglobins and aquaporin 5, were decreased in HS lesional skin and we discovered that these genes demonstrated opposite expression profiles in healing skin. Conversely, HS lesional and wounded skin shared a common gene signature including genes encoding for S100 proteins, defensins, and genes encoding antiviral proteins. Overall, our results suggest that the pathogenesis of HS may be driven by changes in AMP expression and altered sweat gland function, and may share a similar pathology with chronic wounds.

The Skin and Intestinal Microbiota and Their Specific Innate Immune Systems.

The skin and intestine are active organs of the immune system that are constantly exposed to the outside environment. They support diverse microbiota, both commensal and pathogenic, which encompass bacteria, viruses, fungi, and parasites. The skin and intestine must maintain homeostasis with the diversity of commensal organisms present on epithelial surfaces. Here we review the current literature pertaining to epithelial barrier formation, microbial composition, and the complex regulatory mechanisms governing the interaction between the innate immune system and microbiota in the skin and intestine. We also compare and contrast the skin and intestine-two different organ systems responsible creating a protective barrier against the external environment, each of which has unique mechanisms for interaction with commensal populations and host repair.

A Review of Methods for Monitoring Adverse Events in Pediatric Psychopharmacology Clinical Trials.

Pediatric psychotropic prescription rates are rising, emphasizing the need for careful monitoring of drug safety in this population. Currently, no standardized assessments are used in clinical trials for adverse event (AE) elicitation focused on long-term drug treatment in pediatric patients. Despite a lack of standardized AE elicitation methods in psychiatric clinical trials, it is clear that psychiatric medications have developmentally dependent AEs that differ from those observed in adults. In this review, we discuss the use of general inquiry elicitation, drug-specific checklists, and systematic elicitation scales for AE reporting in pediatric psychopharmacology trials. The checklists evaluated include the Barkley Side Effect Rating Scales (SERS), the Pittsburg side effect rating scale, and the Systematic Monitoring of Adverse events Related to TreatmentS (SMARTS) checklist. The systematic assessment scales discussed include the Systematic Assessment for Treatment of Emergent Events (SAFTEE) and the Safety Monitoring Uniform Report Form (SMURF). We review the advantages and disadvantages of each method and discuss the need for optimal assessment of AEs. AE instruments that are created and utilized for pediatric psychiatric trials must begin to incorporate symptoms that are relevant to this population and account for the nature of the disorders to better characterize treatment-emergent AEs and monitor long-term safety.