Evaluating the Safety of Simultaneous Intracranial Electroencephalography and Functional Magnetic Resonance Imaging Acquisition Using a 3 Tesla Magnetic Resonance Imaging Scanner

Background: The unsurpassed sensitivity of intracranial electroencephalography (icEEG) and the growing interest in understanding human brain networks and ongoing activities in health and disease have make the simultaneous icEEG and functional magnetic resonance imaging acquisition (icEEG-fMRI) an attractive investigation tool. However, safety remains a crucial consideration, particularly due to the impact of the specific characteristics of icEEG and MRI technologies that were safe when used separately but may risk health when combined. Using a clinical 3-T scanner with body transmit and head-receive coils, we assessed the safety and feasibility of our icEEG-fMRI protocol. Methods: Using platinum and platinum-iridium grid and depth electrodes implanted in a custom-made acrylic-gel phantom, we assessed safety by focusing on three factors. First, we measured radio frequency (RF)-induced heating of the electrodes during fast spin echo (FSE, as a control) and the three sequences in our icEEG-fMRI protocol. Heating was evaluated with electrodes placed orthogonal or parallel to the static magnetic field. Using the configuration with the greatest heating observed, we then measured the total heating induced in our protocol, which is a continuous 70-min icEEG-fMRI session comprising localizer, echo-planar imaging (EPI), and magnetization-prepared rapid gradient-echo sequences. Second, we measured the gradient switching-induced voltage using configurations mimicking electrode implantation in the frontal and temporal lobes. Third, we assessed the gradient switching-induced electrode movement by direct visual detection and image analyses. Results: On average, RF-induced local heating on the icEEG electrode contacts tested were greater in the orthogonal than parallel configuration, with a maximum increase of 0.2°C during EPI and 1.9°C during FSE. The total local heating was below the 1°C safety limit across all contacts tested during the 70-min icEEG-fMRI session. The induced voltage was within the 100-mV safety limit regardless of the configuration. No gradient switching-induced electrode displacement was observed. Conclusion: We provide evidence that the additional health risks associated with heating, neuronal stimulation, or device movement are low when acquiring fMRI at 3 T in the presence of clinical icEEG electrodes under the conditions reported in this study. High specific absorption ratio sequences such as FSE should be avoided to prevent potential inadvertent tissue heating

Awareness and preparedness of healthcare workers against the first wave of the COVID-19 pandemic: A cross-sectional survey across 57 countries.

BACKGROUND: Since the COVID-19 pandemic began, there have been concerns related to the preparedness of healthcare workers (HCWs). This study aimed to describe the level of awareness and preparedness of hospital HCWs at the time of the first wave. METHODS: This multinational, multicenter, cross-sectional survey was conducted among hospital HCWs from February to May 2020. We used a hierarchical logistic regression multivariate analysis to adjust the influence of variables based on awareness and preparedness. We then used association rule mining to identify relationships between HCW confidence in handling suspected COVID-19 patients and prior COVID-19 case-management training. RESULTS: We surveyed 24,653 HCWs from 371 hospitals across 57 countries and received 17,302 responses from 70.2% HCWs overall. The median COVID-19 preparedness score was 11.0 (interquartile range [IQR] = 6.0-14.0) and the median awareness score was 29.6 (IQR = 26.6-32.6). HCWs at COVID-19 designated facilities with previous outbreak experience, or HCWs who were trained for dealing with the SARS-CoV-2 outbreak, had significantly higher levels of preparedness and awareness (p<0.001). Association rule mining suggests that nurses and doctors who had a 'great-extent-of-confidence' in handling suspected COVID-19 patients had participated in COVID-19 training courses. Male participants (mean difference = 0.34; 95% CI = 0.22, 0.46; p<0.001) and nurses (mean difference = 0.67; 95% CI = 0.53, 0.81; p<0.001) had higher preparedness scores compared to women participants and doctors. INTERPRETATION: There was an unsurprising high level of awareness and preparedness among HCWs who participated in COVID-19 training courses. However, disparity existed along the lines of gender and type of HCW. It is unknown whether the difference in COVID-19 preparedness that we detected early in the pandemic may have translated into disproportionate SARS-CoV-2 burden of disease by gender or HCW type

BUTYRATE REDUCES FREE CHOLESTEROL ACCUMULATION IN NIEMANN-PICK DISEASE TYPE C1 CELLS (NOVA SCOTIA FORM) THROUGH THE INDUCTION OF ACID SPHINGOMYELINASE

Niemann-Pick disease type C (NPC) is an inherited disorder caused by mutations in either the NPC1 or the NPC2 gene that affect intracellular free cholesterol trafficking. Most cases of NPC have mutations in the NPC1 gene. Acid sphingomyelinase (ASM) is a lysosomal enzyme in which an inherited deficiency leads to Niemann-Pick disease types A and B (NPDA/NPDB). Despite having a normal ASM gene, NPC cells have a secondary defect in ASM activity ; the mechanism remains to be fully elucidated. Butyrate, one of the short chain fatty acids, is known as an inducer of ASM. We investigated the effects of butyrate on ASM activity and mRNA expression in normal and NPC1 mutant (Nova Scotia form ; NPC1^) lymphoblasts. After incubation with 10 mM butyric acid for 24 h, ASM activity was significantly increased by 3.3- and 4.6-fold in normal and NPC1^ cells, respectively (p cells was restored to normal levels by treatment of 10 mM butyric acid. In quantitative RT-PCR analysis, butyric acid significantly increased ASM mRNA levels in both types of cells (p lymphoblasts. Free cholesterol levels in cells treated with or without 10 mM butyric acid were 0.019±0.002 and 0.026±0.006 μg/μg protein, respectively, demonstrating that butyric acid significantly decreased free cholesterol levels in NPC1^ cells (p cells, NPDB and NPC1^ fibroblasts were treated with 10 mM butyric acid and stained with filipin. We found that butyric acid dramatically reduced the accumulation of intracellular free cholesterol in NPC1^ cells, but it did not affect NPDB cells. These data suggest that ASM induced by butyrate is related to intracellular cholesterol trafficking and metabolism in NPC1^ cells. ASM inducers, such as butyrate, may reduce the accumulation of intracellular free cholesterol in NPC1^ cells