DNA methylation defines regional identity of human intestinal epithelial organoids and undergoes dynamic changes during development.

OBJECTIVE: Human intestinal epithelial organoids (IEOs) are increasingly being recognised as a highly promising translational research tool. However, our understanding of their epigenetic molecular characteristics and behaviour in culture remains limited. DESIGN: We performed genome-wide DNA methylation and transcriptomic profiling of human IEOs derived from paediatric/adult and fetal small and large bowel as well as matching purified human gut epithelium. Furthermore, organoids were subjected to in vitro differentiation and genome editing using CRISPR/Cas9 technology. RESULTS: We discovered stable epigenetic signatures which define regional differences in gut epithelial function, including induction of segment-specific genes during cellular differentiation. Established DNA methylation profiles were independent of cellular environment since organoids retained their regional DNA methylation over prolonged culture periods. In contrast to paediatric and adult organoids, fetal gut-derived organoids showed distinct dynamic changes of DNA methylation and gene expression in culture, indicative of an in vitro maturation. By applying CRISPR/Cas9 genome editing to fetal organoids, we demonstrate that this process is partly regulated by TET1, an enzyme involved in the DNA demethylation process. Lastly, generating IEOs from a child diagnosed with gastric heterotopia revealed persistent and distinct disease-associated DNA methylation differences, highlighting the use of organoids as disease-specific research models. CONCLUSIONS: Our study demonstrates striking similarities of epigenetic signatures in mucosa-derived IEOs with matching primary epithelium. Moreover, these results suggest that intestinal stem cell-intrinsic DNA methylation patterns establish and maintain regional gut specification and are involved in early epithelial development and disease.

The Department of Veterans Affairs Biorepository Brain Bank: a national resource for amyotrophic lateral sclerosis research.

Our objective was to describe a unique national resource to facilitate amyotrophic lateral sclerosis (ALS) research, the Department of Veterans Affairs Biorepository Brain Bank. Enrolled veterans receive biannual telephone follow-up to collect clinical data until death including the ALS Functional Rating Scale-Revised (ALSFRS-R). A comprehensive post mortem examination is performed and a wide range of fixed and frozen brain and spinal cord samples are banked. As of December 2012, 240 veterans were enrolled from 47 states and post mortem tissue recoveries were performed on 100 veterans from 37 states. Average disease duration was 13.5 (range 3-45) years. Average follow-up for living subjects was 3.1 years and average ALSFRS-R score was 23.5 compared to 25.9 (12-24 months earlier), indicating slow disease progression. ALS was confirmed by post mortem examination in 97% of cases. Eighty-six percent of cases were TDP-43-positive. Additional neuropathological diagnoses include Lewy body disease (13%), frontotemporal lobar degeneration (6.3%), chronic traumatic encephalopathy with motor neuron disease (3.2%), and Alzheimer's disease (2.1%). Tissue RIN values were ≥ 4.0 in 88% of cases. In conclusion, the availability of high quality fixed and frozen CNS tissue from this well characterized cohort is an important resource to facilitate research into genetic and environmental risk factors and clinical pathological relationships in ALS.

Athletic Training Education Program Directors' Perceptions on Job Selection, Satisfaction, and Attrition.

OBJECTIVE: To determine the potential reasons for becoming a program director and reasons for leaving the program director position within athletic training education programs accredited by the Commission on Accreditation of Allied Health Education Programs (CAAHEP); in addition, to describe the most and least beneficial and satisfying aspects of the program director position. DESIGN AND SETTING: In 1999, we sent a validated survey to athletic training education program directors of CAAHEP-accredited athletic training education programs. SUBJECTS: Of 113 athletic training education program directors of accredited undergraduate programs, 83 participated, for a response rate of 73.4%. MEASUREMENTS: The survey consisted of open-ended questions regarding potential reasons for becoming a program director and possibly leaving the program direction position and most and least beneficial and satisfying aspects of the position. We used inductive content analysis to determine themes for the responses to the open-ended questions. Descriptive statistics, including percentages, were calculated to report the data. RESULTS: Academic environment was the primary theme for becoming an athletic training education program director and professional appointment was the primary theme for possibly leaving the position. Professional advancement and student growth and success were the primary themes for the most beneficial and satisfying aspects. Workload and student issues and discipline were the primary themes for the least beneficial and satisfying aspects. CONCLUSIONS: Factors that affect job selection, satisfaction, and attrition are related to academic environment, teaching, students, professional advancement, program development/advancement, workload, personal issues, and athletics.

Dilemmas of Program Directors: Then and Now.

OBJECTIVE: To describe the current roles and responsibilities of program directors of athletic training education programs accredited by the Commission on Accreditation of Allied Health Education Programs (CAAHEP) and to address the dilemmas of program directors' credibility with student athletic trainers, tenure and promotion, and clinical involvement in athletics. DESIGN AND SETTING: We sent a survey to all program directors who direct CAAHEP athletic training education programs. SUBJECTS: Eighty-three of 113 program directors of undergraduate programs participated in the study-a response rate of 73.4%. MEASUREMENTS: The survey consisted of demographic data: degree, age, major, years of experience as program director, and route to certification and questions concerning title, job responsibilities, expectations, and academic appointment. RESULTS: Most respondents (72%) indicated that their title was program director, and they had a median of 9 years of experience. Sixty-two percent had been certified as an athletic trainer for a median of 18.5 years. Forty-three percent had doctoral degrees and held the rank of assistant professor. Ninety-six percent indicated teaching was the primary duty and expectation of their program director's position. CONCLUSIONS: The dilemmas of tenure and promotion, decreased clinical involvement, and student athletic trainers' perceptions of program directors remain problematic. The dilemmas still exist as they did 12 years ago and are becoming more involved due to educational reform. Program directors must be able to communicate their roles and responsibilities to their administrators.