Somatic and intergenerational G4C2 hexanucleotide repeat instability in a human C9orf72 knock-in mouse model.

Expansion of a G4C2 repeat in the C9orf72 gene is associated with familial Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). To investigate the underlying mechanisms of repeat instability, which occurs both somatically and intergenerationally, we created a novel mouse model of familial ALS/FTD that harbors 96 copies of G4C2 repeats at a humanized C9orf72 locus. In mouse embryonic stem cells, we observed two modes of repeat expansion. First, we noted minor increases in repeat length per expansion event, which was dependent on a mismatch repair pathway protein Msh2. Second, we found major increases in repeat length per event when a DNA double- or single-strand break (DSB/SSB) was artificially introduced proximal to the repeats, and which was dependent on the homology-directed repair (HDR) pathway. In mice, the first mode primarily drove somatic repeat expansion. Major changes in repeat length, including expansion, were observed when SSB was introduced in one-cell embryos, or intergenerationally without DSB/SSB introduction if G4C2 repeats exceeded 400 copies, although spontaneous HDR-mediated expansion has yet to be identified. These findings provide a novel strategy to model repeat expansion in a non-human genome and offer insights into the mechanism behind C9orf72 G4C2 repeat instability.

Perceptions and Attitudes toward Community Health and Interprofessional Education in Students with and without an Additional Community Medicine-Focused Program.

The Rural Medical Education (RMED) Program at the University of Illinois College of Medicine Rockford campus, and part of the National Center for Rural Health Professions, strives to recruit students from rural areas, who, after completing residency, return to rural Illinois as primary care physicians. RMED students meet monthly to learn about the community and public health in rural communities. Furthermore, they complete a 16-week rural preceptorship during their fourth year. During the fourth year of medical school, all RMED students, as well as the students following the regular curriculum, are asked to complete a survey, related to the understanding of medical students' views of community and interprofessional education. We aimed to identify how the community-based curriculum affects the students' understanding and appreciation of community as they go into rural health practice. The results showed that students in the RMED Program are more aware of the community they are part of, as well as being more interested in becoming part of their community. RMED students reported a statistically significantly higher rating of feeling appreciated and accepted by their community and rated their confidence in their abilities in the community statistically significantly higher. Interestingly, RMED students were not more likely to be more familiar with several health professions and programs within their community, compared to non-RMED students. Results comparing self-rated capabilities for RMED students within the community both before and after adding components of an interprofessional education curriculum showed no statistically significant changes. These results support previous research, while also providing more support for the development of successful interprofessional education courses.

Giving Back to Get Back: Assessment of Native and Non-Native American Perceptions of Generativity.

Previous research has shown the negative effects of loneliness on quality of life, all-cause mortality, and morbidity. Generativity is the concept of giving something back to younger generations and is theorized to improve a sense of meaning and fulfillment in elders' lives. This survey study examined the relationships between three constructs: generativity, loneliness, and quality of life in elders living in rural Northern California in a largely Native American community (N=98). While causation cannot be determined in this cross-sectional study, the findings suggest that improving the level of generativity in rural elders may enhance their quality of life. Creating venues in which elders can interact with younger generations may be beneficial in the future.

Impact of a rural interprofessional health professions summer preceptorship educational experience on participants' attitudes and knowledge.

BACKGROUND: A six-week rural interprofessional health professions summer preceptorship provided an interprofessional training experience (IPE) for upper level baccalaureate and post-baccalaureate/graduate level health professions students in Dixon, Illinois, USA. There are three distinct yet complementary components of this forty hours per week summer preceptorship: Numerous interprofessional clinical shadowing experiences, a community service-learning project carried out as a team and weekly classroom sessions. This study assesses knowledge and attitude changes about IPE among students who participated in this Rural Interprofessional Health Professions Summer Preceptorship between 2006 and 2011. METHODS: Fifty-two students over the six program years were asked to complete an identical pre-/post-questionnaire. The questionnaire included scales on seven topics, two of which addressed knowledge and attitudes about IPE: (i) Understanding of their own and other professions' work roles and (ii) Perceived ability to work effectively in interprofessional teams and make use of skills of other professions. Fifty of the fifty two (96.1%) students completed both the pre- and post-tests. RESULTS: Positive changes from the pre- to the post-tests were observed for the scales that related to interaction with other professions and assessment of their professional skills and students' understanding of the roles of other professions. Pre- versus post-preceptorship students also reported greater experience working as a member of an interprofessional team and an increase in their support for interprofessional education within a rural setting being required for all health professions students. CONCLUSION: A rural interprofessional health professions summer preceptorship that includes preceptor shadowing, a community service-learning project and classroom work proved to be an effective approach to developing interprofessional health care teams, increasing the knowledge and skills of participating students and creating positive attitudes toward interactions with other professions.

A decade of rural physician workforce outcomes for the Rockford Rural Medical Education (RMED) Program, University of Illinois.

PURPOSE: To report on the retention and practice outcomes of the University of Illinois College of Medicine at Rockford Rural Medical Education (RMED) Program and to examine distance from influential locations in relation to graduates' current practice location. METHOD: The RMED Program recruits candidates from rural backgrounds, provides a supplemental curriculum addressing rural topics and experiences, and tracks graduates' practice location and specialty choice outcomes. Practice location and specialty were compared for 160 RMED graduates and 2,663 non-RMED graduates, from 1997 to 2007. Rural status was based on rural-urban commuting codes. Comparisons were made using cross-tabulation with calculation of chi-square or odds ratios to assess differences. RESULTS: RMED graduates were 14.4 times more likely than non-RMED graduates to choose family medicine; 6.7 times more likely to choose a primary care practice specialty; 17.2 times more likely to be currently practicing in a rural location; and 12.8 times more likely to be currently practicing in a primary care shortage zip code. Analysis of current RMED graduates' practice locations indicates that 41.9% were within 90 miles of their fourth-year preceptorship community. Among RMED graduates practicing in Illinois, 62.1% and 73.3% were located within 60 and 90 miles, respectively, of their hometown. CONCLUSIONS: Recruitment of students combined with a rural-focused curriculum yielded positive outcomes related to primary care practice and decisions regarding practice location. RMED graduates were considerably more likely than non-RMED graduates to choose family medicine, choose a primary care specialty, and be currently practicing in a rural location.