Faculty Bibliography

The positive solvatochromism of three dyes, with a spectral behavior strongly dependents on the medium dipolarity/polarizability, was studied theoretically. Both a polarizable continuum-solvent model (CSM) and explicit solvent molecules were employed to model solvent effects. The CSM approach, coupled with ten different TDDFT methods, yielded unsatisfactory results in eleven solvents. The explicit-solvation calculations, thought of much higher computational cost, yielded excellent results. As CSM schemes are known correctly model non-specific electrostatic effects, our results indicate that the traditionally considered non-specific nature of solvent dipolarity needs to be reconsidered, requiring the explicit consideration of the solute-solvent interactions for their accurate theoretical description.

OBJECTIVE:Alzheimer disease (AD) risk factors are present throughout the lifespan. This randomized controlled trial evaluated the effectiveness of various online education strategies concerning AD risk reduction and brain health in younger populations. METHOD:High school and college students were recruited via social media (Facebook and Instagram) to join AlzU.org, an evidence-based education portal, and were randomized to 1 of 4 courses: highly interactive webinar lessons narrated by actor Seth Rogen (celebrity webinar) or a physician (doctor webinar), minimally interactive video lessons with Seth Rogen (celebrity video), or minimally interactive video lessons (control). Surveys were administered at baseline and postcourse. The primary outcome was change in knowledge of AD risk reduction assessed by pre vs post lesson quiz scores. Secondary outcomes included change in awareness of AD research, hopefulness about AD, interest in pursuing health care, willingness to volunteer, and likelihood of recommending AlzU.org. RESULT:A total of 721 participants joined. A total of 281 (38.9%) completed the course. Among college students, quiz score improvements were greater in celebrity webinar and celebrity video vs doctor webinar and control. Among high school students, no differences were found in quiz scores. In both groups, celebrity webinar, celebrity video, and doctor webinar resulted in greater improvements in awareness that nutrition and exercise may reduce AD risk vs controls. Among college students, celebrity webinar and celebrity video group participants felt more hopeful about the future of AD and more likely to recommend AlzU.org vs doctor webinar and control participants. Among college students, celebrity webinar, celebrity video, and doctor webinar participants were more willing to volunteer for AD causes and pursue health care careers vs controls. CONCLUSION:Online education involving a celebrity may be an effective strategy for educating college students about AD risk reduction strategies. Further studies are warranted in high school students.

Neurologic infections during pregnancy represent a significant cause of maternal and fetal morbidity and mortality. Immunologic alterations during pregnancy increase the susceptibility of the premature brain to damage. This chapter summarizes the epidemiology, pathophysiology, and clinical manifestations in the pregnant woman and the infant, and the diagnosis, treatment, and prevention of the major viral, parasitic, and bacterial infections known to affect pregnancy. These organisms include herpes virus, parvovirus, cytomegalovirus, varicella, rubella, Zika virus, toxoplasmosis, malaria, group B streptococcus, listeriosis, syphilis, and tuberculosis. There is an emphasis on the important differences in diagnosis, treatment, and fetal outcome between trimesters. An additional overview is provided on the spectrum of neurologic sequelae of an affected infant, which ranges from developmental delay to hydrocephalus and seizures.

OBJECTIVES:To describe the spectrum of pediatric inflammatory neurologic diseases and compare the sensitivity of ancillary testing for these diagnoses. METHODS:We analyzed clinical features and outcomes of 98 children with an immune-mediated central nervous system disorder. We compared sensitivities of each diagnostic modality. RESULTS:-methyl-d-aspartate receptor encephalitis (anti-NMDAR encephalitis) (n = 15; 15.3%), encephalitis not otherwise specified (n = 12; 12.2%), and "Other" (n = 26; 26.5%). "Other" included acute transverse myelitis, neuromyelitis optica, central nervous system lupus, primary central nervous system vasculitis, Rasmussen encephalitis, opsoclonus myoclonus ataxia syndrome, and clinically isolated syndrome. The mean age of onset of all diagnoses was 7.9 ± 5.5 years. The diagnostic sensitivity of magnetic resonance imaging (MRI) for acute demyelinating encephalomyelitis and multiple sclerosis was 92.3% and 94.4%, respectively. Cerebrospinal fluid was sensitive for multiple sclerosis in 92.3%, where 75% of patients had cerebrospinal fluid oligoclonal bands. Electroencephalogram (EEG) coupled with cerebrospinal fluid studies was highly sensitive for anti-NMDAR encephalitis (100%). EEG was sensitive for acute demyelinating encephalomyelitis and encephalitis not otherwise specified (77.8% and 80%). No diagnostic studies were sensitive for acute cerebellar ataxia. Seventy-three percent of patients with multiple sclerosis had residual deficits. Thirty-six percent of anti-NMDAR encephalitis patients were nonverbal and wheel-chair bound. CONCLUSIONS:We found that MRI is useful for detecting multiple sclerosis and acute demyelinating encephalomyelitis, cerebrospinal fluid is helpful in diagnosing multiple sclerosis and anti-NMDAR encephalitis, and EEG is often abnormal in suspected anti-NMDAR encephalitis, acute demyelinating encephalomyelitis, and encephalitis not otherwise specified. Neurologic outcome at follow-up was unfavorable in patients with multiple sclerosis and anti-NMDAR encephalitis.

In the present study, we combine linguistic annotation of oral texts in Russian with the registration of BOLD signal in functional MRI experiments to determine how and where semantic categories are represented in the human brain. Using the same stimuli material, we also analyze the differences in cortical activation in three thematic domains: description of nature, description of working principles of technical devices and more self-referential texts, addressing the question of human identity in conflict situations. We discuss methodological problems within the two approaches (microanalysis and macroanalysis) to study brain activation in natural conditions, i.e. under a continuous speech flow. Within the thematic domain studies, only minimally significant differences in brain activation were registered during the listening to texts from the three thematic groups. This outcome leads to the conclusion that the approach of thematic group contrasts (cognitive subtraction methodology) is not sufficient to study the mechanisms of text comprehension, and should be replaced by the modeling of multidimensional representations of semantic categories in time. Within the semantic category approach, we describe the neurolinguistic process of text understanding as the activation of 15 clusters responsible for semantic categories (e.g. "Conflict", "Mental", "Social"). Our data demonstrate that the clusters are widely distributed across the human brain. In contrast to the previous studies, we suggest that deep subcortical structures are involved in the processing of certain categories as well. The observed lateralization of category processing underlines the involvement of the right hemisphere in the processing of meaning.

Background: Inadequate norepinephrine (NE) release in neurogenic orthostatic hypotension (nOH) causes blood pressure to fall on standing and debilitating symptoms of cerebral hypoperfusion. Ampreloxetine, a novel, long-acting NE reuptake inhibitor, potentiates the effects of endogenous NE, and may improve symptoms of nOH. The objective of the study was to explore the durability of effect and safety of once-daily oral ampreloxetine for the symptomatic treatment of nOH in subjects with synucleinopathies.
Method(s): In an open-label, phase 2, exploratory, multicenter study, subjects received open-label ampreloxetine (3-20 mg) once-daily for up to 20 weeks, with 4-week follow-up after ampreloxetine withdrawal and restarting alternative pressor agents. Assessments included Orthostatic Hypotension Symptom Assessment Item 1 (OHSA#1; dizziness, lightheadedness, feeling faint), OHSA and Orthostatic Hypotension Daily Activities Scale (OHDAS) composite scores, and Patient Global Impression of Severity (PGI-S).
Result(s): Seventeen symptomatic subjects (baseline OHSA#1 score >4) were enrolled (mean age, 65 years). At Week 4, mean (SD) improvement on OHSA#1 was -3.8 (3.1) points; approximately 77% of subjects reported >=1-point improvement (minimal clinically important difference). At Week 20, mean improvement was -3.1 (3.0) points; approximately 86% reported >=1-point improvement. Symptom improvement was observed as early as Week 1 and was sustained throughout the study. Deterioration to baseline symptom severity was after ampreloxetine withdrawal. Similar trends were seen in OHSA and OHDAS composite scores, and PGI-S. Most common adverse events were urinary tract infection (24%), hypertension (19%), and headache (14%), with no study-drug related serious adverse events.
Conclusion(s): Ampreloxetine showed durable symptom improvement in symptomatic subjects with nOH over 20 weeks, with return to baseline symptom severity after ampreloxetine withdrawal. Ampreloxetine was well tolerated with a favorable safety profile. These encouraging open-label findings are being evaluated further in ongoing Phase 3, double-blind, confirmatory studies in subjects with nOH and synucleinopathies.
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Background: In neurogenic orthostatic hypotension (nOH), blood pressure (BP) falls due to inadequate norepinephrine (NE) release when upright. Ampreloxetine, a novel, long-acting NE reuptake inhibitor, potentiates effects of endogenous NE and has shown durable symptom improvement in subjects with nOH associated with synucleinopathies. The objective of this study was to evaluate measures of BP regulation in subjects with symptomatic nOH treated with open-label ampreloxetine.
Method(s): In a phase 2, multicenter, exploratory study, subjects received ampreloxetine once-daily (3-20 mg) for up to 20 weeks, with 4-week follow-up after ampreloxetine withdrawal and restarting other pressor agents. Assessments included Orthostatic Hypotension Symptom Assessment Item 1 score (OHSA#1; dizziness, lightheadedness, feeling faint); standing, sitting, and supine systolic BP (SBP); standing duration; and plasma NE.
Result(s): Seventeen symptomatic subjects (baseline OHSA#1 score >4) were enrolled (mean age, 65 years). Standing and sitting SBP, standing duration, plasma NE, and symptoms improved from Weeks 1 to 20. Mean increase in 3-minute standing SBP from baseline was 9.0 mmHg at Week 4 and 10.8 mmHg at Week 20; >50% of subjects maintained SBP >80 mmHg. Sitting SBP changes were less, with little change in supine SBP. At Week 4, 67% of subjects could stand for >5 mins, 31% improvement from baseline. NE plasma levels rose from pre-dose to Week 4 (1664.93-2231.67 pmol/l). After ampreloxetine withdrawal and restarting other pressor agents, standing SBP remained increased; however, nOH symptoms deteriorated to baseline. Ampreloxetine was well tolerated.
Conclusion(s): Ampreloxetine has previously demonstrated durable symptom improvement in nOH. Symptom improvement was accompanied by increase in standing and sitting SBP, standing duration, and NE plasma levels, with little effect on supine SBP. These encouraging findings are being evaluated further in ongoing Phase 3, double-blind, confirmatory studies in subjects with nOH and synucleinopathies.
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