Efron, Philip A.

Abstract Parkinson’s disease (PD) is the fastest growing neurodegenerative disease in the world1. Gastrointestinal (GI) dysfunction can occur decades before motor impairments and in up to 80% of individuals living with PD2,3,4. We investigated peripheral relationships that may underlie environmental contributions to mechanisms along the gut-blood axis that contribute to PD pathogenesis. Single-cell multiomic spatial molecular imaging (SMI) of colonic tissue localized inflammatory injury within epithelial cells that appear to be associated with iron mishandling in both inflammatory bowel disease (IBD) and PD biosamples. We found that both the single-cell SMI of RNA and protein revealed parallel cross-modal dysregulation in the gut epithelium, in both IBD and PD biosamples. These data are accompanied by plasma (PD) and stool (IBD) protein depletion of CCL22. Our findings suggest iron mishandling along the gut barrier likely contributes to systemic inflammation, which may be the catalyst that primes circulating immune cells to body-first PD pathogenesis.

Abstract Parkinson’s disease (PD) is the fastest growing neurodegenerative disease in the world 1 . Gastrointestinal (GI) dysfunction can occur decades before motor impairments and in up to 80% of individuals living with PD 2,3,4 . We investigated peripheral relationships that may underlie mechanisms along the gut-blood axis that contribute to PD pathogenesis. Single-cell multiomic spatial molecular imaging (SMI) of colonic tissue localized inflammatory injury within epithelial cells that appear to be associated with iron mishandling in both inflammatory bowel disease (IBD) and PD biosamples. We found that both the single-cell SMI of RNA and protein revealed parallel cross-modal dysregulation in the gut epithelium, in both IBD and PD biosamples. These data are accompanied by plasma (PD) and stool (IBD) protein depletion of CCL22. Our findings suggest iron mishandling along the gut barrier likely contributes to systemic inflammation, which may be the catalyst that primes circulating immune cells to body-first PD pathogenesis.

Objectives: In the United States, physician training in Critical Care Medicine has developed as a subspecialty of different primary boards, despite significant commonality in knowledge and skills. The Society of Critical Care Medicine appointed a multidisciplinary Task Force to examine alternative approaches for future training. Design: The Task Force reviewed the literature and conducted informal discussions with key stakeholders. Specific topics reviewed included the history of critical care training, commonalities among subspecialties, developments since a similar review in 2004, international experience, quality patient care, and financial and workforce issues. Main Results: The Task Force believes that options for future training include establishment of a 1) primary specialty of critical care; 2) unified fellowship and certification process; or 3) unified certification process with separate fellowship programs within the current specialties versus 4) maintaining multiple specialty-based fellowship programs and certification processes. Conclusions: 1) Changing the current Critical Care Medicine training paradigms may benefit trainees and patient care. 2) Multiple pathways into critical care training for all interested trainees are desirable for meeting future intensivist workforce demands. 3) The current subspecialties within separate boards are not “distinct and well-defined field[s] of medical practice” per the American Board of Medical Specialties. Recommendations for first steps are as follows: 1) as the society representing multidisciplinary critical care, the Society of Critical Care Medicine has an opportunity to organize a meeting of all stakeholders to discuss the issues regarding Critical Care Medicine training and consider cooperative approaches for the future. 2) A common Critical Care Medicine examination, possibly with a small percentage of base-specialty–specific questions, should be considered. 3) Institutions with multiple Critical Care Medicine fellowship programs should consider developing joint, multidisciplinary training curricula. 4) The boards that offer Critical Care Medicine examinations, along with national critical care societies, should consider ways to shorten training time.