Search

LRRK2 polymorphisms (G2019S/N2081D) that increase susceptibility to Parkinsons disease and Crohns disease (CD) lead to LRRK2 kinase hyperactivity and suppress autophagy. This connection suggests that LRRK2 kinase inhibition, a therapeutic strategy being explored for Parkinsons disease, may also benefit patients with CD. Paneth cell homeostasis is tightly regulated by autophagy, and their dysfunction is a precursor to gut inflammation in CD. Here, we found that patients with CD and mice carrying hyperactive LRRK2 polymorphisms developed Paneth cell dysfunction. We also found that LRRK2 kinase can be activated in the context of interactions between genes (genetic autophagy deficiency) and the environment (cigarette smoking). Unexpectedly, lamina propria immune cells were the main intestinal cell types that express LRRK2, instead of Paneth cells as previously suggested. We showed that LRRK2-mediated pro-inflammatory cytokine release from phagocytes impaired Paneth cell function, which was rescued by LRRK2 kinase inhibition through activation of autophagy. Together, these data suggest that LRRK2 kinase inhibitors maintain Paneth cell homeostasis by restoring autophagy and may represent a therapeutic strategy for CD.

Data generated through the U.S. Department of Labor (2018) showed employment rates among persons with disabilities (PEOPLE WITH DISABILITIES) is 20.7% compared to 68.4% of nondisabled workers. In 2012, half [...], Objective: This study examined a work-related intervention designed to assist people with serious mental illness (SMI) in overcoming employment barriers. Methods: A pre-post-test experimental design was used to investigate the effects of a 10-session, prevocational seminaron self-efficacy and work motivation among adults with SMI residing in an inpatient psychiatric facility. Three one-way ANCOVAs were applied to analyze post-test results for the dependent measures. Findings: Although significant findings were not found regarding the effectiveness of the prevocational seminar on self-efficacy, other interesting discoveries were made. One noteworthy outcome was persons with SMI wanted to work but experienced barriers, including discrimination, decreased motivation, and work disincentives that impeded their return to employment. Conclusions and Implications for Practice: Vocational rehabilitation (VR) counselors continue to face challenges in their efforts to increase employment among persons with SMI. The results from the present study underscore the need for skills training and innovative VR strategies to mitigate barriers to employment among persons with SMI. Key Words: serious mental illness, employment, prevocational training, self-efficacy, work motivation

Background: The omental patch repair is the gold standard for the repair of perforated peptic ulcers. This can be performed open or laparoscopically. However, in the event of non‐viable or inadequate omentum available at the time of surgery the falciform ligament has been reportedly used to as an alternative. Nonetheless, evidence for its safety is scant. This study aims to determine differences in patient outcomes when comparing the two repair techniques. Methods: Following ethics approval, patients who underwent surgical repair of perforated peptic ulcers using omental or falciform patch repair, between 1 January 2010 and 31 December 2017, across all three Western Australian tertiary hospital services and at least 18 years of age were included. Data were collected by reviewing medical records of included patients. Results: Three hundred twenty‐nine patients who underwent either open or laparoscopic repairs were included. Thirty‐seven patients had falciform repairs and were mostly ASA of 2 compared to 292 patients receiving omental patch repair who were mostly ASA 3. Falciform patch repairs were more commonly used in duodenal ulcer perforations. There were no statistically significant differences in patient outcomes between the omental patch and falciform ligament groups. This included post‐operative intra‐abdominal sepsis, return to theatre, post‐operative ICU admission, inpatient mortality, 30‐day readmission and ulcer healing on follow‐up gastroscopy. Conclusions: This study demonstrates safety, efficacy and similar outcomes for patients receiving the falciform ligament patch repair compared with omental patch repair. [ABSTRACT FROM AUTHOR]

Being a part of an ethnic minority group and a student with a disability (SWD) often presents as a barrier to college retention and graduation rates among members of this marginalized group. Purpose: To examine educators' awareness of racial and institutional influences that impact African American SWD. Method: Data for this study were gathered using a snowball sampling technique that surveyed 145 educators at colleges and universities in 16 U.S. states. An exploratory factor analysis with a varimax rotation procedure was used to group items of the Culture and Disability Awareness Scale for Postsecondary Educators into more specific categories. Results: A 3-factor solution explaining 58% of the variance was considered to be most interpretable. The extracted factors were entitled as follows: (a) disability-related issues, (b) personal wellness, and (c) faculty involvement. Conclusion: The results suggest the survey respondents' level of awareness and knowledge was poorer regarding racial and cultural statements in comparison to institutional influences. Implications for practice, education, and future research are discussed.

Environmental enteric dysfunction (EED) is a diffuse small bowel disorder associated with poor growth, inadequate responses to oral vaccines, and nutrient malabsorption in millions of children worldwide. We identify loss of the small intestinal Paneth and goblet cells that are critical for innate immunity, reduced villous height, increased bile acids, and dysregulated nicotinamide adenine dinucleotide (NAD+) synthesis signaling as potential mechanisms underlying EED and which also correlated with diminished length-for-age z score. Isocaloric low-protein diet (LPD) consumption in mice recapitulated EED histopathology and transcriptomic changes in a microbiota-independent manner, as well as increases in serum and fecal bile acids. Children with refractory EED harbor single-nucleotide polymorphisms in key enzymes involved in NAD+ synthesis. In mice, deletion of Nampt, the gene encoding the rate-limiting enzyme in the NAD+ salvage pathway, from intestinal epithelium also reduced Paneth cell function, a deficiency that was further aggravated by LPD. Separate supplementation with NAD+ precursors or bile acid sequestrant partially restored LPD-associated Paneth cell defects and, when combined, fully restored all histopathology defects in LPD-fed mice. Therapeutic regimens that increase protein and NAD+ contents while reducing excessive bile acids may benefit children with refractory EED. Editor's summary: Environmental enteric dysfunction (EED) is an acquired condition of the small intestine that is associated with inflammation, poor nutrient absorption, and stunted growth in children. Malique et al. examined a cohort of children with EED and found pathophysiological changes in the cellular composition of the small bowel as well as increased serum bile acids and decreased nicotinamide adenine dinucleotide (NAD+). Work in a mouse model of EED suggested that increased dietary protein and NAD+ as well as reduction of bile acids should be further investigated as potential therapeutic avenues for this disorder. —Catherine Charneski [ABSTRACT FROM AUTHOR]