Interleukin 9 Alters Epithelial Barrier and E-cadherin in Eosinophilic Esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic TH2-assocated inflammatory condition accompanied by substantial impairments in epithelial barrier function and increased numbers of interleukin 9 (IL-9) expressing inflammatory cells. While IL-9 is known to affect barrier function in the intestine, the functional effects of IL-9 on the esophagus are unclear. Herein we aimed to understand the expression of the IL-9 receptor and effects of IL-9 on the epithelium in EoE. METHODS: We used esophageal biopsies from pediatric EoE patients with active and inactive disease to analyze the expression of the IL-9 receptor, the adherens junction protein E-cadherin and the tight junction protein claudin-1. We treated primary human esophageal epithelial cells with IL-9 to understand its effects on E-cadherin expression and function. RESULTS: Active EoE subjects had increased epithelial expression of IL-9 receptor mRNA and protein (P < 0.05) and decreased membrane bound E-cadherin (P < 0.01) and claudin-1 (P < 0.05) expression. IL-9 receptor expression and mislocalized claudin-1 positively correlated and while membrane bound E-cadherin expression negatively correlated with the degree of histologic epithelial remodeling (P < 0.05). IL-9 decreased epithelial resistance in stratified primary human esophageal epithelial cells (P < 0.01) and membrane bound E-cadherin in epithelial cell monolayers (P < 0.01). CONCLUSIONS: These data suggest that IL-9, its receptor, and its effects on E-cadherin may be important mechanisms for epithelial barrier disruption in EoE.

Probiotics normalize the gut-brain-microbiota axis in immunodeficient mice.

The gut-brain-microbiota axis is increasingly recognized as an important regulator of intestinal physiology. Exposure to psychological stress causes activation of the hypothalamic-pituitary-adrenal (HPA) axis and causes altered intestinal barrier function, intestinal dysbiosis, and behavioral changes. The primary aim of this study was to determine whether the effects of psychological stress on intestinal physiology and behavior, including anxiety and memory, are mediated by the adaptive immune system. Furthermore, we wanted to determine whether treatment with probiotics would normalize these effects. Here we demonstrate that B and T cell-deficient Rag1(-/-) mice displayed altered baseline behaviors, including memory and anxiety, accompanied by an overactive HPA axis, increased intestinal secretory state, dysbiosis, and decreased hippocampal c-Fos expression. Both local (intestinal physiology and microbiota) and central (behavioral and hippocampal c-Fos) changes were normalized by pretreatment with probiotics, indicating an overall benefit on health conferred by changes in the microbiota, independent of lymphocytes. Taken together, these findings indicate a role for adaptive immune cells in maintaining normal intestinal and brain health in mice and show that probiotics can overcome this immune-mediated deficit in the gut-brain-microbiota axis.

A Question of Scale? Generalizability of the Ottawa and Chen Scales to Render Entrustment Decisions for the Core EPAs in the Workplace.

PURPOSE: Assessments of the Core Entrustable Professional Activities (Core EPAs) are based on observations of supervisors throughout a medical student's progression toward entrustment. The purpose of this study was to compare generalizability of scores from 2 entrustment scales: the Ottawa Surgical Competency Operating Room Evaluation (Ottawa) scale and an undergraduate medical education supervisory scale proposed by Chen and colleagues (Chen). A secondary aim was to determine the impact of frequent assessors on generalizability of the data. METHOD: For academic year 2019-2020, the Virginia Commonwealth University School of Medicine modified a previously described workplace-based assessment (WBA) system developed to provide feedback for the Core EPAs across clerkships. The WBA scored students' performance using both Ottawa and Chen scales. Generalizability (G) and decision (D) studies were performed using an unbalanced random-effects model to determine the reliability of each scale. Secondary G- and D-studies explored whether faculty who rated more than 5 students demonstrated better reliability. The Phi-coefficient was used to estimate reliability; a cutoff of at least 0.70 was used to conduct D-studies. RESULTS: Using the Ottawa scale, variability attributable to the student ranged from 0.8% to 6.5%. For the Chen scale, student variability ranged from 1.8% to 7.1%. This indicates the majority of variation was due to the rater (42.8%-61.3%) and other unexplained factors. Between 28 and 127 assessments were required to obtain a Phi-coefficient of 0.70. For 2 EPAs, using faculty who frequently assessed the EPA improved generalizability, requiring only 5 and 13 assessments for the Chen scale. CONCLUSIONS: Both scales performed poorly in terms of learner-attributed variance, with some improvement in 2 EPAs when considering only frequent assessors using the Chen scale. Based on these findings in conjunction with prior evidence, the authors provide a root cause analysis highlighting challenges with WBAs for Core EPAs.

Generalizability of the Ottawa Surgical Competency Operating Room Evaluation (O-SCORE) Scale to Assess Medical Student Performance on Core EPAs in the Workplace: Findings From One Institution.

PURPOSE: Assessment of the Core Entrustable Professional Activities for Entering Residency (Core EPAs) requires direct observation of learners in the workplace to support entrustment decisions. The purpose of this study was to examine the internal structure validity evidence of the Ottawa Surgical Competency Operating Room Evaluation (O-SCORE) scale when used to assess medical student performance in the Core EPAs across clinical clerkships. METHOD: During the 2018-2019 academic year, the Virginia Commonwealth University School of Medicine implemented a mobile-friendly, student-initiated workplace-based assessment (WBA) system to provide formative feedback for the Core EPAs across all clinical clerkships. Students were required to request a specified number of Core EPA assessments in each clerkship. A modified O-SCORE scale (1 = "I had to do" to 4 = "I needed to be in room just in case") was used to rate learner performance. Generalizability theory was applied to assess the generalizability (or reliability) of the assessments. Decision studies were then conducted to determine the number of assessments needed to achieve a reasonable reliability. RESULTS: A total of 10,680 WBAs were completed on 220 medical students. The majority of ratings were completed on EPA 1 (history and physical) (n = 3,129; 29%) and EPA 6 (oral presentation) (n = 2,830; 26%). Mean scores were similar (3.5-3.6 out of 4) across EPAs. Variance due to the student ranged from 3.5% to 8%, with the majority of the variation due to the rater (29.6%-50.3%) and other unexplained factors. A range of 25 to 63 assessments were required to achieve reasonable reliability (Phi > 0.70). CONCLUSIONS: The O-SCORE demonstrated modest reliability when used across clerkships. These findings highlight specific challenges for implementing WBAs for the Core EPAs including the process for requesting WBAs, rater training, and application of the O-SCORE scale in medical student assessment.

Use and Perception of Contraception among Genders in Santo Domingo, Dominican Republic.

BACKGROUND: The prevalence of contraception in the Dominican Republic is among the highest of Latin American countries. Prior research has assessed the general perception of contraception in Latin America, examined determinants of contraceptive use among Dominican women, and explored their perceived reproductive control. Little research has explored the specific role each sexual partner, male and female, has in determining the use of contraception in Latin American countries. OBJECTIVE: This study aims to address the gap in research regarding the specific role each sexual partner has in determining the contraception use in Latin American countries by evaluating male and female perception and use of contraception, and their perceived reproductive control. METHODS: A one-time survey was administered to adult patients of two short-term medical missions located in Santo Domingo, Dominican Republic. The difference in overall responses to dichotomous questions and ordinal questions were tested using binomial Z-test and nonparametric Chi-Square Goodness-of-Fit test. Bivariate analyses were conducted using cross tabulation with Chi-Square test. FINDINGS: The majority of participants of both genders are in favor of contraception use, believe they have the power to avoid an unplanned pregnancy, and view their partners' wishes regarding the use of contraception as important. However, significantly more females than males are in favor of contraception use (p-value = 0.01). Specific subgroups of men and women answered the survey in ways that suggest traditional values may be at odds with individuals' willingness to use contraception. CONCLUSIONS: There is an overall acceptance of contraception use and perception of reproductive control among both genders in our population, with a greater proportion of females in favor of contraception use than males (p-value = 0.01). Changing cultural norms may be coming into conflict with established beliefs and practices in the Dominican Republic, such as its machismo culture.

Bridging the Gap: Including Patient Voices in Short-Term Medical Mission Evaluations.

BACKGROUND: Several studies have evaluated short term medical missions (STMM), but most have been from the perspective of the STMM teams providing their own suggestions [1]; few surveys have assessed the perceptions of patients who seek medical care at these STMM clinics [2]. OBJECTIVES: This project evaluates the efficiency, quality, and value of the services provided by a STMM clinic established in the community of Paraíso in Santo Domingo Norte, Dominican Republic, as perceived by the patients. Study results will allow organizers to make improvements to these clinics and will contribute to a broader understanding of the benefit and value of medical services provided by STMMs. METHODS: A mixed method, cross-sectional survey was created which consisted of 11 questions and a medication quiz. The survey questions were based on items used in prior surveys, as well as the participant responses to those surveys, and attempted to address perceived efficiency, quality, value, and effectiveness of services provided, as well as the impact on the community. FINDINGS: Two-hundred sixty-six patients were invited to complete the survey, and 117 (44%) were enrolled in the study. The majority of survey responses were positive and highlighted patients' satisfaction with provider skills and communication. Of note, many responses identified longer than anticipated wait times during two portions of the patient encounter and self-reported deferral of local care to receive care with the STMM. Additionally, although average medication quiz scores were high, average scores decreased with age. CONCLUSIONS: This study brings to light patient perceptions of services at a STMM in the community of Paraíso in Santo Domingo Norte, Dominican Republic. Survey responses highlight the importance of efforts to: minimize clinic wait time; enhance collaboration between local providers and STMMs to reduce deferral of care; and improve medication knowledge among the geriatric population.