Faculty Bibliography
Searched for:
Department/Unit:Neurology
Total Results:
24282
Mechanical circulatory support in the intensive care unit
PMID: 35993668
ISSN: 1537-1913
CID: 5331492
Toward Precision Phenotyping of Multiple Sclerosis
The classification of multiple sclerosis (MS) has been established by Lublin in 1996 and revised in 2013. The revision includes clinically isolated syndrome, relapsing-remitting, primary progressive and secondary progressive MS, and has added activity (i.e., formation of white matter lesions or clinical relapses) as a qualifier. This allows for the distinction between active and nonactive progression, which has been shown to be of clinical importance. We propose that a logical extension of this classification is the incorporation of additional key pathological processes, such as chronic perilesional inflammation, neuroaxonal degeneration, and remyelination. This will distinguish MS phenotypes that may present as clinically identical but are driven by different combinations of pathological processes. A more precise description of MS phenotypes will improve prognostication and personalized care as well as clinical trial design. Thus, our proposal provides an expanded framework for conceptualizing MS and for guiding development of biomarkers for monitoring activity along the main pathological axes in MS.
PMCID:9427000
PMID: 36041861
ISSN: 2332-7812
CID: 5332122
Interpretability, Then What? Editing Machine Learning Models to Reflect Human Knowledge and Values
[S.l.] : Association for Computing Machinery, 2022
pp. 4132-4142
ISBN: 9781450393850
CID: 5329952
The Unified Multiple System Atrophy Rating Scale: Status, Critique, and Recommendations
PMID: 36074648
ISSN: 1531-8257
CID: 5332552
Tackling the Unmet Therapeutic Needs in Nonsurgical Treatments for Epilepsy
PMID: 36066899
ISSN: 2168-6157
CID: 5332412
Transcriptional regulation of Acsl1 by CHREBP and NF-kappa B in macrophages during hyperglycemia and inflammation
Acyl-CoA synthetase 1 (ACSL1) is an enzyme that converts fatty acids to acyl-CoA-derivatives for lipid catabolism and lipid synthesis in general and can provide substrates for the production of mediators of inflammation in monocytes and macrophages. Acsl1 expression is increased by hyperglycemia and inflammatory stimuli in monocytes and macrophages, and promotes the pro-atherosclerotic effects of diabetes in mice. Yet, surprisingly little is known about the mechanisms underlying Acsl1 transcriptional regulation. Here we demonstrate that the glucose-sensing transcription factor, Carbohydrate Response Element Binding Protein (CHREBP), is a regulator of the expression of Acsl1 mRNA by high glucose in mouse bone marrow-derived macrophages (BMDMs). In addition, we show that inflammatory stimulation of BMDMs with lipopolysaccharide (LPS) increases Acsl1 mRNA via the transcription factor, NF-kappa B. LPS treatment also increases ACSL1 protein abundance and localization to membranes where it can exert its activity. Using an Acsl1 reporter gene containing the promoter and an upstream regulatory region, which has multiple conserved CHREBP and NF-kappa B (p65/RELA) binding sites, we found increased Acsl1 promoter activity upon CHREBP and p65/RELA expression. We also show that CHREBP and p65/RELA occupy the Acsl1 promoter in BMDMs. In primary human monocytes cultured in high glucose versus normal glucose, ACSL1 mRNA expression was elevated by high glucose and further enhanced by LPS treatment. Our findings demonstrate that CHREBP and NF-kappa B control Acsl1 expression under hyperglycemic and inflammatory conditions.
PMCID:9439225
PMID: 36054206
ISSN: 1932-6203
CID: 5332252
Perceptions Regarding the SARS-CoV-2 Pandemic's Impact on Neurocritical Care Delivery: Results From a Global Survey
BACKGROUND:The SARS-CoV-2 (COVID-19) pandemic has impacted many facets of critical care delivery. METHODS:An electronic survey was distributed to explore the pandemic's perceived impact on neurocritical care delivery between June 2020 and March 2021. Variables were stratified by World Bank country income level, presence of a dedicated neurocritical care unit (NCCU) and experiencing a COVID-19 patient surge. RESULTS:Respondents from 253 hospitals (78.3% response rate) from 47 countries (45.5% low/middle income countries; 54.5% with a dedicated NCCU; 78.6% experienced a first surge) participated in the study. Independent of country income level, NCCU and surge status, participants reported reductions in NCCU admissions (67%), critical care drug shortages (69%), reduction in ancillary services (43%) and routine diagnostic testing (61%), and temporary cancellation of didactic teaching (44%) and clinical/basic science research (70%). Respondents from low/middle income countries were more likely to report lack of surge preparedness (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.8-5.8) and struggling to return to prepandemic standards of care (OR, 12.2; 95% CI, 4.4-34) compared with respondents from high-income countries. Respondents experiencing a surge were more likely to report conversion of NCCUs and general-mixed intensive care units (ICUs) to a COVID-ICU (OR 3.7; 95% CI, 1.9-7.3), conversion of non-ICU beds to ICU\ beds (OR, 3.4; 95% CI, 1.8-6.5), and deviations in critical care and pharmaceutical practices (OR, 4.2; 95% CI 2.1-8.2). Respondents from hospitals with a dedicated NCCU were less likely to report conversion to a COVID-ICU (OR, 0.5; 95% CI, 0.3-0.9) or conversion of non-ICU to ICU beds (OR, 0.5; 95% CI, 0.3-0.9). CONCLUSION/CONCLUSIONS:This study reports the perceived impact of the COVID-19 pandemic on global neurocritical care delivery, and highlights shortcomings of health care infrastructures and the importance of pandemic preparedness.
PMID: 34882104
ISSN: 1537-1921
CID: 5326642
Tracking Multisite Seizure Propagation Using Ictal High-Gamma Activity
INTRODUCTION/BACKGROUND:Spatial patterns of long-range seizure propagation in epileptic networks have not been well characterized. Here, we use ictal high-gamma activity (HGA) as a proxy of intense neuronal population firing to map the spatial evolution of seizure recruitment. METHODS:Ictal HGA (80-150 Hz) was analyzed in 13 patients with 72 seizures recorded by stereotactic depth electrodes, using previously validated methods. Distinct spatial clusters of channels with the ictal high-gamma signature were identified, and seizure hubs were defined as stereotypically recruited nonoverlapping clusters. Clusters correlated with asynchronous seizure terminations to provide supportive evidence for independent seizure activity at these sites. The spatial overlap between seizure hubs and interictal ripples was compared. RESULTS:Ictal HGA was detected in 71% of seizures and 10% of implanted contacts, enabling tracking of contiguous and noncontiguous seizure recruitment. Multiple seizure hubs were identified in 54% of cases, including 43% of patients thought preoperatively to have unifocal epilepsy. Noncontiguous recruitment was associated with asynchronous seizure termination (odds ratio = 19.7; p = 0.029). Interictal ripples demonstrated greater spatial overlap with ictal HGA in cases with single seizure hubs compared with those with multiple hubs (100% vs. 66% per patient; p = 0.03). CONCLUSIONS:Ictal HGA may serve as a useful adjunctive biomarker to distinguish contiguous seizure spread from propagation to remote seizure sites. High-gamma sites were found to cluster in stereotyped seizure hubs rather than being broadly distributed. Multiple hubs were common even in cases that were considered unifocal.
PMCID:8611231
PMID: 34812578
ISSN: 1537-1603
CID: 5325822
Epigenetic priming enhances antitumor immunity in platinum-resistant ovarian cancer
BackgroundImmune checkpoint inhibitors (ICIs) have modest activity in ovarian cancer (OC). To augment their activity, we used priming with the hypomethylating agent guadecitabine in a phase II study.MethodsEligible patients had platinum-resistant OC, normal organ function, measurable disease, and received up to 5 prior regimens. The treatment included guadecitabine (30 mg/m2) on days 1-4, and pembrolizumab (200 mg i.v.) on day 5, every 21 days. The primary endpoint was the response rate. Tumor biopsies, plasma, and PBMCs were obtained at baseline and after treatment.ResultsAmong 35 evaluable patients, 3 patients had partial responses (8.6%), and 8 (22.9%) patients had stable disease, resulting in a clinical benefit rate of 31.4% (95% CI: 16.9%-49.3%). The median duration of clinical benefit was 6.8 months. Long-interspersed element 1 (LINE1) was hypomethylated in post-treatment PBMCs, and methylomic and transcriptomic analyses showed activation of antitumor immunity in post-treatment biopsies. High-dimensional immune profiling of PBMCs showed a higher frequency of naive and/or central memory CD4+ T cells and of classical monocytes in patients with a durable clinical benefit or response (CBR). A higher baseline density of CD8+ T cells and CD20+ B cells and the presence of tertiary lymphoid structures in tumors were associated with a durable CBR.ConclusionEpigenetic priming using a hypomethylating agent with an ICI was feasible and resulted in a durable clinical benefit associated with immune responses in selected patients with recurrent OC.Trial registrationClinicalTrials.gov NCT02901899.FundingUS Army Medical Research and Material Command/Congressionally Directed Medical Research Programs (USAMRMC/CDMRP) grant W81XWH-17-0141; the Diana Princess of Wales Endowed Professorship and LCCTRAC funds from the Robert H. Lurie Comprehensive Cancer Center; Walter S. and Lucienne Driskill Immunotherapy Research funds; Astex Pharmaceuticals; Merck & Co.; National Cancer Institute (NCI), NIH grants CCSG P30 CA060553, CCSG P30 CA060553, and CA060553.
PMCID:9282926
PMID: 35671108
ISSN: 1558-8238
CID: 5321562
Learning to use electronic travel AIDS for visually impaired in virtual reality
[S.l.] : SPIE, 2022
pp. ?-?
ISBN: 9781510649651
CID: 5315132
