Stougaardrobb0736

OBJECTIVE To investigate the genotype-phenotype correlation between neurofibromatosis 1 (NF1) germline mutations and imaging features of neurofibromas on whole-body MRI (WBMRI) by using radiomics image analysis techniques. MATERIALS AND METHODS Twenty-nine patients with NF1 who had known germline mutations determined by targeted next-generation sequencing were selected from a previous WBMRI study using coronal short tau inversion recovery sequence. Each tumor was segmented in WBMRI and a set of 59 imaging features was calculated using our in-house volumetric image analysis platform, 3DQI. A radiomics heatmap of 59 imaging features was analyzed to investigate the per-tumor and per-patient associations between the imaging features and mutation domains and mutation types. Linear mixed-effect models and one-way analysis of variance tests were performed to assess the similarity of tumor imaging features within mutation groups, between mutation groups, and between randomly selected groups. RESULTS A total of 218 ne 5.2%). CONCLUSION This preliminary study identified the NF1 radiogenomics linkage between NF1 causative mutations and MRI radiomic features, i.e., the correlation between NF1 genotype and imaging phenotype on WBMRI. © 2020 American Academy of Neurology.OBJECTIVE To examine the association between fractures and Parkinson disease (PD) during the 5-year prodromal phase as compared to controls. METHODS We performed a population-based case-control study of Medicare beneficiaries in the United States from 2004 to 2009. We identified 89,632 incident PD cases and 117,760 comparable controls 66-90 years of age in 2009. PD case status was the outcome, and noncranial fracture the independent variable. We used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for association between fracture and PD in yearly time intervals prior to PD diagnosis/control reference date, after adjusting for covariates. RESULTS There were 39,606 total fractures (25.4% cases, 14.3% controls) over the 5 years prior to the PD diagnosis/control reference date. PD was positively associated with fractures even after adjusting for age, sex, race/ethnicity, Charlson comorbidity index, alcohol use, tobacco use, and osteoporosis. The association between PD and fracture was evident at yearly time windows prior to PD diagnosis/control reference date. The association between PD and each type of fracture strengthened as the PD diagnosis/control reference date approached (all time interaction p values ≤0.02). Among beneficiaries with a mechanism of injury, the majority were attributed to falls (74.6% cases, 72.8% controls). CONCLUSION Fractures occur more commonly during the prodromal period of PD compared to controls, especially as diagnosis date approached, suggesting that patients with PD may experience unrecognized motor and nonmotor symptoms. © 2020 American Academy of Neurology.OBJECTIVE The emergence of coronavirus disease 2019 (COVID-19) presents a challenge for neurologists caring for patients with preexisting neurologic conditions hospitalized for COVID-19 or for evaluation of patients who suffer neurologic complications during COVID-19 infection. We conducted a scoping review of available literature on COVID-19 to assess the potential impact on neurologists in terms of prevalent comorbidities and incidence of new neurologic events in patients hospitalized with COVID-19. METHODS We searched Medline/PubMed, CINAHL (EBSCO), and SCOPUS databases for adult patients with preexisting neurologic disease that were diagnosed and hospitalized for COVID-19, or reported incidence of secondary neurologic events following diagnosis of COVID-19. Pooled descriptive statistics of clinical data and comorbidities were examined. RESULTS Among screened articles, 322 of 4,014 (8.0%) of hospitalized patients diagnosed and treated for COVID-19 had a preexisting neurologic illness. Four retrospective studies demonstrated an increased risk of secondary neurologic complications in hospitalized patients with COVID-19 (incidence of 6%, 20% and 36.4%, respectively). Inconsistent reporting and limited statistical analysis among these studies did not allow for assessment of comparative outcomes. CONCLUSION Emerging literature suggests a daunting clinical relationship between COVID-19 and neurologic illness. Neurologists need to be prepared to reorganize their consultative practices to serve the neurologic needs of patients during this pandemic. © 2020 American Academy of Neurology.ANO1 (TMEM16A) is a Ca2+-activated Cl- channel (CaCC) expressed in peripheral somatosensory neurons that are activated by painful (noxious) stimuli. These neurons also express the Ca2+-permeable channel and noxious heat sensor TRPV1, which can activate ANO1. Here, we revealed an intricate mechanism of TRPV1-ANO1 channel coupling in rat dorsal root ganglion (DRG) neurons. Simultaneous optical monitoring of CaCC activity and Ca2+ dynamics revealed that the TRPV1 ligand capsaicin activated CaCCs. However, depletion of endoplasmic reticulum (ER) Ca2+ stores reduced capsaicin-induced Ca2+ increases and CaCC activation, suggesting that ER Ca2+ release contributed to TRPV1-induced CaCC activation. ER store depletion by plasma membrane-localized TRPV1 channels was demonstrated with an ER-localized Ca2+ sensor in neurons exposed to a cell-impermeable TRPV1 ligand. Proximity ligation assays established that ANO1, TRPV1, and the IP3 receptor IP3R1 were often found in close proximity to each other. Stochastic optical reconstruction microscopy (STORM) confirmed the close association between all three channels in DRG neurons. Together, our data reveal the existence of ANO1-containing multichannel nanodomains in DRG neurons and suggest that coupling between TRPV1 and ANO1 requires ER Ca2+ release, which may be necessary to enhance ANO1 activation. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.In this issue of Science Signaling, Temprine et al report that up-regulation of the translesion DNA polymerase Polκ mediates resistance to BRAF pathway-targeted inhibitors and starvation in melanoma cells. These results exemplify the role that Polκ plays in cellular adaptation to stress. Akt Inhibitor VIII Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.