Neuropathogenic Forms of Huntingtin and Androgen Receptor Inhibit Fast Axonal Transport

AbstractHuntington's and Kennedy's disease are autosomal dominant neurodegenerative diseases caused by pathogenic expansion of polyglutamine tracts. Expansion of glutamine repeats must in some way confer a gain of pathological function that disrupts an essential cellular process and leads to loss of affected neurons. Association of huntingtin with vesicular structures raised the possibility that axonal transport might be altered. Here we show that polypeptides containing expanded polyglutamine tracts, but not normal N-terminal huntingtin or androgen receptor, directly inhibit both fast axonal transport in isolated axoplasm and elongation of neuritic processes in intact cells. Effects were greater with truncated polypeptides and occurred without detectable morphological aggregates

Impact of a Dedicated Emergency Medicine Teaching Resident Rotation at a Large Urban Academic Center

Introduction: In the face of declining bedside teaching and increasing emergency department (ED) crowding, balancing education and patient care is a challenge. Dedicated shifts by teaching residents (TRs) in the ED represent an educational intervention to mitigate these difficulties. We aimed to measure the perceived learning and departmental impact created by having TR.Methods: TRs were present in the ED from 12pm-10pm daily, and their primary roles were to provide the following: assist in teaching procedures, give brief “chalk talks,” instruct junior trainees on interesting cases, and answer clinical questions in an evidence-based manner. This observational study included a survey of fourth-year medical students (MSs), residents and faculty at an academic ED. Surveys measured the perceived effect of the TR on teaching, patient flow, ease of procedures, and clinical care.Results: Survey response rates for medical students, residents, and faculty are 56%, 77%, and 75%, respectively. MSs perceived improved procedure performance with TR presence and the majority agreed that the TR was a valuable educational experience. Residents perceived increased patient flow, procedure performance, and MS learning with TR presence. The majority agreed that the TR improved patient care. Faculty agreed that the TR increased resident and MS learning, as well as improved patient care and procedure performance.Conclusion: The presence of a TR increased MS and resident learning, improved patient care and procedure performance as perceived by MSs, residents and faculty. A dedicated TR program can provide a valuable resource in achieving a balance of clinical education and high quality healthcare

Impact of a Dedicated Emergency Medicine Teaching Resident Rotation at a Large Urban Academic Center

Introduction: In the face of declining bedside teaching and increasing emergency department (ED) crowding, balancing education and patient care is a challenge. Dedicated shifts by teaching residents (TRs) in the ED represent an educational intervention to mitigate these difficulties. We aimed to measure the perceived learning and departmental impact created by having TR.Methods: TRs were present in the ED from 12pm-10pm daily, and their primary roles were to provide the following: assist in teaching procedures, give brief “chalk talks,” instruct junior trainees on interesting cases, and answer clinical questions in an evidence-based manner. This observational study included a survey of fourth-year medical students (MSs), residents and faculty at an academic ED. Surveys measured the perceived effect of the TR on teaching, patient flow, ease of procedures, and clinical care.Results: Survey response rates for medical students, residents, and faculty are 56%, 77%, and 75%, respectively. MSs perceived improved procedure performance with TR presence and the majority agreed that the TR was a valuable educational experience. Residents perceived increased patient flow, procedure performance, and MS learning with TR presence. The majority agreed that the TR improved patient care. Faculty agreed that the TR increased resident and MS learning, as well as improved patient care and procedure performance.Conclusion: The presence of a TR increased MS and resident learning, improved patient care and procedure performance as perceived by MSs, residents and faculty. A dedicated TR program can provide a valuable resource in achieving a balance of clinical education and high quality healthcare

Impact of a Dedicated Emergency Medicine Teaching Resident Rotation at a Large Urban Academic Center

INTRODUCTION: In the face of declining bedside teaching and increasing emergency department (ED) crowding, balancing education and patient care is a challenge. Dedicated shifts by teaching residents (TRs) in the ED represent an educational intervention to mitigate these difficulties. We aimed to measure the perceived learning and departmental impact created by having TR. METHODS: TRs were present in the ED from 12pm–10pm daily, and their primary roles were to provide the following: assist in teaching procedures, give brief “chalk talks,” instruct junior trainees on interesting cases, and answer clinical questions in an evidence-based manner. This observational study included a survey of fourth-year medical students (MSs), residents and faculty at an academic ED. Surveys measured the perceived effect of the TR on teaching, patient flow, ease of procedures, and clinical care. RESULTS: Survey response rates for medical students, residents, and faculty are 56%, 77%, and 75%, respectively. MSs perceived improved procedure performance with TR presence and the majority agreed that the TR was a valuable educational experience. Residents perceived increased patient flow, procedure performance, and MS learning with TR presence. The majority agreed that the TR improved patient care. Faculty agreed that the TR increased resident and MS learning, as well as improved patient care and procedure performance. CONCLUSION: The presence of a TR increased MS and resident learning, improved patient care and procedure performance as perceived by MSs, residents and faculty. A dedicated TR program can provide a valuable resource in achieving a balance of clinical education and high quality healthcare

Impact of a Dedicated Emergency Medicine Teaching Resident Rotation at a Large Urban Academic Center

Introduction: In the face of declining bedside teaching and increasing emergency department (ED) crowding, balancing education and patient care is a challenge. Dedicated shifts by teaching residents (TRs) in the ED represent an educational intervention to mitigate these difficulties. We aimed to measure the perceived learning and departmental impact created by having TR. Methods: TRs were present in the ED from 12pm-10pm daily, and their primary roles were to provide the following: assist in teaching procedures, give brief “chalk talks,” instruct junior trainees on interesting cases, and answer clinical questions in an evidence-based manner. This observational study included a survey of fourth-year medical students (MSs), residents and faculty at an academic ED. Surveys measured the perceived effect of the TR on teaching, patient flow, ease of procedures, and clinical care. Results: Survey response rates for medical students, residents, and faculty are 56%, 77%, and 75%, respectively. MSs perceived improved procedure performance with TR presence and the majority agreed that the TR was a valuable educational experience. Residents perceived increased patient flow, procedure performance, and MS learning with TR presence. The majority agreed that the TR improved patient care. Faculty agreed that the TR increased resident and MS learning, as well as improved patient care and procedure performance. Conclusion: The presence of a TR increased MS and resident learning, improved patient care and procedure performance as perceived by MSs, residents and faculty. A dedicated TR program can provide a valuable resource in achieving a balance of clinical education and high quality healthcare

Finding useful biomarkers for Parkinson's disease

Parkinson’s Disease affects more than 4 million people worldwide, and biomarkers to bolster the therapeutic development pipeline are urgently needed. The recent advent of an “ecosystem” of shared biosample biorepositories and data enables us to consider how to focus PD biomarker activity to best translate efforts into real-world impact

De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy

Purpose This study aims to provide a comprehensive description of the phenotypic and genotypic spectrum of SNAP25 developmental and epileptic encephalopathy (SNAP25-DEE) by reviewing newly identified and previously reported individuals. Methods Individuals harboring heterozygous missense or loss-of-function variants in SNAP25 were assembled through collaboration with international colleagues, matchmaking platforms, and literature review. For each individual, detailed phenotyping, classification, and structural modeling of the identified variant were performed. Results The cohort comprises 23 individuals with pathogenic or likely pathogenic de novo variants in SNAP25. Intellectual disability and early-onset epilepsy were identified as the core symptoms of SNAP25-DEE, with recurrent findings of movement disorders, cerebral visual impairment, and brain atrophy. Structural modeling for all variants predicted possible functional defects concerning SNAP25 or impaired interaction with other components of the SNARE complex. Conclusion We provide a comprehensive description of SNAP25-DEE with intellectual disability and early-onset epilepsy mostly occurring before the age of two years. These core symptoms and additional recurrent phenotypes show an overlap to genes encoding other components or associated proteins of the SNARE complex such as STX1B, STXBP1, or VAMP2. Thus, these findings advance the concept of a group of neurodevelopmental disorders that may be termed “SNAREopathies.