Correction: Linking bacterial enterotoxins and alpha defensin 5 expansion in the Crohn's colitis: A new insight into the etiopathogenetic and differentiation triggers driving colonic inflammatory bowel disease.

[This corrects the article DOI: 10.1371/journal.pone.0246393.].

Linking bacterial enterotoxins and alpha defensin 5 expansion in the Crohn's colitis: A new insight into the etiopathogenetic and differentiation triggers driving colonic inflammatory bowel disease.

Evidence link bacterial enterotoxins to apparent crypt-cell like cells (CCLCs), and Alpha Defensin 5 (DEFA5) expansion in the colonic mucosa of Crohn's colitis disease (CC) patients. These areas of ectopic ileal metaplasia, positive for Paneth cell (PC) markers are consistent with diagnosis of CC. Retrospectively, we: 1. Identified 21 patients with indeterminate colitis (IC) between 2000-2007 and were reevaluation their final clinical diagnosis in 2014 after a followed-up for mean 8.7±3.7 (range, 4-14) years. Their initial biopsies were analyzed by DEFA5 bioassay. 2. Differentiated ulcer-associated cell lineage (UACL) analysis by immunohistochemistry (IHC) of the CC patients, stained for Mucin 6 (MUC6) and DEFA5. 3. Treated human immortalized colonic epithelial cells (NCM460) and colonoids with pure DEFA5 on the secretion of signatures after 24hr. The control colonoids were not treated. 4. Treated colonoids with/without enterotoxins for 14 days and the spent medium were collected and determined by quantitative expression of DEFA5, CCLCs and other biologic signatures. The experiments were repeated twice. Three statistical methods were used: (i) Univariate analysis; (ii) LASSO; and (iii) Elastic net. DEFA5 bioassay discriminated CC and ulcerative colitis (UC) in a cohort of IC patients with accuracy. A fit logistic model with group CC and UC as the outcome and the DEFA5 as independent variable differentiator with a positive predictive value of 96 percent. IHC staining of CC for MUC6 and DEFA5 stained in different locations indicating that DEFA5 is not co-expressed in UACL and is therefore NOT the genesis of CC, rather a secretagogue for specific signature(s) that underlie the distinct crypt pathobiology of CC. Notably, we observed expansion of signatures after DEFA5 treatment on NCM460 and colonoids cells expressed at different times, intervals, and intensity. These factors are key stem cell niche regulators leading to DEFA5 secreting CCLCs differentiation 'the colonic ectopy ileal metaplasia formation' conspicuously of pathogenic importance in CC.

Engaging the community through a longitudinal, interprofessional, interinstitutional experiential learning collaboration.

Background Interprofessional education (IPE) and training in community settings is not commonly described in the literature. Studies primarily focus on clinical education of interprofessional teams in clinical practice and primary care. This is a description of a longitudinal, collaborative interinstitutional IPE project that engages community partners (CP) while delivering core IPE competencies. Interprofessional Education Activity: Twenty-seven students from five universities representing ten healthcare academic programs participated in the project. Participating CP were non-profit agencies developed to meet the needs of specific vulnerable, underserved populations. Students were divided into teams and then paired with CP. This was a six-month project, with students committing to 30 hours over two semesters. At the end of the project, students presented project deliverables to CP, faculty collaborative and other students. Interprofessional education collaborative (IPEC) domains were qualitatively assessed and students completed the Interprofessional Socialization and Valuing Scale (ISVS) at the beginning and conclusion of the project. Students provided written reflections at the conclusion of the project. Faculty completed the Team Observed Structured Clinical Encounter (TOSCE). Discussion" Twenty-seven students (100%) students completed the project and twenty-one students (77.8%) completed the evaluation tools. Students demonstrated a statistically significant difference between pre- and post-project ISVS total scores (5.81 +/- 0.64 vs. 6.51 +/- 0.37). Teamwork, communication skills, and increased comfort with those from other professions were common themes in the student reflections. Implications: Community-based IPE provides a venue for healthcare professionals to engage and partner with community organizations. This project demonstrates an effective inter-institutional, interprofessional method of delivering IPE.

Neurosurgery Elective for Preclinical Medical Students with and without a Home Neurosurgery Program.

BACKGROUND: Preclinical neurosurgery electives have been shown to increase student familiarity with neurosurgery, yet the impact on students without a home neurosurgery program is unknown. We conducted a preclinical neurosurgery elective in a mixed cohort of students with and without home neurosurgery programs to 1) evaluate changes in neurosurgery perceptions, 2) discern differences between cohorts, and 3) identify important factors in those considering neurosurgery. METHODS: A yearly elective was offered to students at Vanderbilt University School of Medicine (VUSM; home program) or Meharry Medical College (MMC; no home program) from 2017 to 2018. Each class included a student-led presentation, faculty academic lecture, and faculty round-table discussion. Precourse and postcourse surveys were completed. RESULTS: Thirty-two students completed the course. VUSM students (n = 15) showed no changes in initial perceptions, whereas MMC students (n = 17) had multiple improved perceptions, including collegiality (P = 0.001) and family achievability (P = 0.010), and believed residency to be less rigorous than their initial perceptions (P = 0.046). Fourteen students (44%) showed an increase in the likelihood of considering a neurosurgical career; eight (57%) were MMC students. These 14 students had improved perceptions of neurosurgery as less emotionally draining (P = 0.042), with favorable collegiality (P = 0.003) and work/life balance (P = 0.001) but did not believe residency to be less difficult (P = 0.102) or have added financial security (P = 0.380). CONCLUSIONS: Early exposure to neurosurgery at medical schools without home programs through preclinical electives may improve students' perceptions of neurosurgery, provide valuable information about the benefits and rigors of neurosurgery, and allow students to make informed decisions about further pursuit of neurosurgery.

Time from Screening Mammography to Biopsy and from Biopsy to Breast Cancer Treatment among Black and White, Women Medicare Beneficiaries Not Participating in a Health Maintenance Organization.

PURPOSE: There is a breast cancer mortality gap adversely affecting Black women in the United States. This study assessed the relationship between number of days between abnormal mammogram, biopsy, and treatment among Medicare (Part B) beneficiaries ages 65 to 74 and 75 to 84 years, accounting for race and comorbidity. METHODS: A cohort of non-Hispanic Black and non-Hispanic White women residing in the continental United States and receiving no services from a health maintenance organization was randomly selected from the Center for Medicare and Medicaid Services denominator file. The cohort was followed from 2005 to 2008 using Center for Medicare and Medicaid Services claims data. The sample included 4,476 women (weighted n = 70,731) with a diagnosis of breast cancer. Cox proportional hazard modeling was used to identify predictors of waiting times. FINDINGS: Black women had a mean of 16.7 more days between biopsy and treatment (p < .001) and 15.7 more days from mammogram to treatment (p = .003) than White women. Median duration from abnormal mammogram to treatment exceeded National Quality Measures for Breast Centers medians regardless of race, age, or number of comorbidities (overall 43 days vs. the National Quality Measures for Breast Centers value of 28 days). CONCLUSIONS: Medical care delays may contribute, in part, to the widening breast cancer mortality gap between Black women and White women. Further study, with additional clinical and social information, is needed to broaden scientific understanding of racial determinants and assess the clinical significance of mammogram to treatment times among Medicare beneficiaries.

What are the implications of implementation science for medical education?

BACKGROUND: Derived from multiple disciplines and established in industries outside of medicine, Implementation Science (IS) seeks to move evidence-based approaches into widespread use to enable improved outcomes to be realized as quickly as possible by as many as possible. METHODS: This review highlights selected IS theories and models, chosen based on the experience of the authors, that could be used to plan and deliver medical education activities to help learners better implement and sustain new knowledge and skills in their work settings. RESULTS: IS models, theories and approaches can help medical educators promote and determine their success in achieving desired learner outcomes. We discuss the importance of incorporating IS into the training of individuals, teams, and organizations, and employing IS across the medical education continuum. Challenges and specific strategies for the application of IS in educational settings are also discussed. CONCLUSIONS: Utilizing IS in medical education can help us better achieve changes in competence, performance, and patient outcomes. IS should be incorporated into curricula across disciplines and across the continuum of medical education to facilitate implementation of learning. Educators should start by selecting, applying, and evaluating the teaching and patient care impact one or two IS strategies in their work.

Primary Breast Lymphoma: A Rare Clinical Entity.

Localized primary breast lymphoma is very rare. The typical clinical and radiographic presentation of isolated primary breast lymphoma mimics that of breast adenocarcinoma. Histologic diagnosis of primary breast lymphoma relies heavily on Hematoxylin and Eosin pathologic evaluation and immunohistochemical staining. Cytotoxic systemic chemotherapy is the primary treatment for this disease with the occasional need for adjuvant radiation therapy or surgical resection. This case report outlines the diagnosis and management of a patient with primary breast lymphoma.

Foreign body ingestion and management: "I swallowed a crack pipe".

There is a wide variety of objects that find their way into the human gastrointestinal tract, either accidentally or deliberately. In this case a crack pipe was ingested in its entirety. Despite the seemingly rare and random nature that this scenario presents, this patient's care serves to reinforce what should be done to successfully manage a patient with an ingested foreign body, as well as the important issues related to crack cocaine abuse.

Magnetic resonance imaging of suspicious breast masses seen on one mammographic view.

The purpose of this study was to assess the utility of contrast-enhanced breast magnetic resonance imaging (MRI) in identifying lesions unidentified on the craniocaudal projection. The authors reviewed five patients with suspicious mammographic lesions not imaged on the craniocaudal mammogram who were referred for contrast-enhanced MRI and underwent subsequent preoperative needle localization in four of the five cases. Five patients, ages 56 to 69 years, had suspicious lesions identified on mediolateral oblique (MLO) or mediolateral (ML) projections only. Ultrasound did not identify the lesion in any of these cases. MRI identified suspicious breast lesions measuring 5 to 12 mm in size. These were located high on the chest wall or in the upper inner quadrant. Suspicious lesions seen only on the MLO or ML projections may reside high on the chest wall or in the upper inner quadrant. Lesions in these locations may be typically excluded on the craniocaudal projection during mammography. Breast MRI has the advantage of imaging the entire breast and is particularly useful for these lesions. In this series, MRI prevented delay in breast cancer diagnosis.

Selective Modulation of Paracortical Dendritic Cells and T-Lymphocytes in Breast Cancer Sentinel Lymph Nodes.

Sentinel nodes (SNs), the nodes nearest a primary tumor on the direct lymphatic drainage path, are the site of earliest metastases, and in melanoma show striking immune modulation. We evaluated SNs from breast cancer patients for evidence of similar immune perturbation. The purpose of this study was to evaluate whether SNs from patients with breast cancer show the alterations in the histology and cytology of the paracortical areas seen in SNs from patients with melanoma. Formalin-fixed and paraffin-embedded sections from 32 SNs and 32 nonsentinel nodes (NSNs) from patients with breast cancer were evaluated. Sections were stained with hematoxylin and eosin and with antibodies to S-100 protein and HLA-DR, DQ, and DP to identify interdigitating dendritic cells (IDCs), and by an antibody to CD43RA to delineate T lymphocytes. By computerized image analysis we evaluated the distribution, frequency, immunophenotype, and activation status of IDCs and associated T lymphocytes in SNs and NSNs. Average areas occupied by S-100-positive dendritic cells (DCs) in SNs and NSNs were 0.13% and 19.98%, respectively, of total nodal area (p < 0.0001). The average density of S-100-positive IDCs in SNs was 11.00/mm2 and in NSNs was 257.88/mm2 (p < 0.0001). In SNs 43.55% of DCs (4.93/mm2) were nondendritic, 51.92% (5.69/mm2) had short dendrites, and 5.2% were mature with long dendrites (0.62/mm2). In SNs the ratio of immature to mature IDCs was 7.95:1. In NSNs, 8.09% of DCs (8.5/mm2) were nondendritic, 28.22% (67.46/mm2) had short dendrites, and 63.07% (145.96/mm2) were mature DCs with long dendrites. The ratio of immature to mature DCs in NSNs was 1:6.66. The average areas occupied by HLA class II-positive DCs in SNs and NSNs were 4.21% and 31.82%, respectively, of total nodal area. The frequency of coexpression of S-100 and HLA class II by immature IDCs without dendrites was 11.27% in SNs and 15.00% in NSNs. In both SNs and NSNs (p < 0.001) all mature S-100-positive IDCs with long dendrites expressed HLA class II. CD43RA-positive T lymphocytes occupied 20.06% of total nodal area in SNs and 63.57% in NSNs (p < 0.0001). The SNs from breast cancer patients are profoundly immune modulated with, by comparison to NSNs, markedly reduced paracortical areas, densities of paracortical DCs, frequency of S-100-positive IDCs coexpressing HLA class II, and a predominance of immature nondendritic and poorly dendritic DCs.