Faculty Bibliography

We reviewed data on the American diet from 1800 to 2019. Methods: We examined food availability and estimated consumption data from 1800 to 2019 using historical sources from the federal government and additional public data sources. Results: Processed and ultra-processed foods increased from <5 to >60% of foods. Large increases occurred for sugar, white and whole wheat flour, rice, poultry, eggs, vegetable oils, dairy products, and fresh vegetables. Saturated fats from animal sources declined while polyunsaturated fats from vegetable oils rose. Non-communicable diseases (NCDs) rose over the twentieth century in parallel with increased consumption of processed foods, including sugar, refined flour and rice, and vegetable oils. Saturated fats from animal sources were inversely correlated with the prevalence of NCDs. Conclusions: As observed from the food availability data, processed and ultra-processed foods dramatically increased over the past two centuries, especially sugar, white flour, white rice, vegetable oils, and ready-to-eat meals. These changes paralleled the rising incidence of NCDs, while animal fat consumption was inversely correlated.

Epilepsy is a common neurological disorder affecting over 70 million people worldwide, with a high rate of pharmaco-resistance, diverse comorbidities including progressive cognitive and behavioural disorders, and increased mortality from direct (e.g. sudden unexpected death in epilepsy, accidents, drowning) or indirect effects of seizures and therapies. Extensive research with animal models and human studies provides limited insights into the mechanisms underlying seizures and epileptogenesis, and these have not translated into significant reductions in pharmaco-resistance, morbidities or mortality. To help define changes in molecular signalling networks associated with seizures in epilepsy with a broad range of aetiologies, we examined the proteome of brain samples from epilepsy and control cases. Label-free quantitative mass spectrometry was performed on the hippocampal cornu ammonis 1-3 region (CA1-3), frontal cortex and dentate gyrus microdissected from epilepsy and control cases (n = 14/group). Epilepsy cases had significant differences in the expression of 777 proteins in the hippocampal CA1 - 3 region, 296 proteins in the frontal cortex and 49 proteins in the dentate gyrus in comparison to control cases. Network analysis showed that proteins involved in protein synthesis, mitochondrial function, G-protein signalling and synaptic plasticity were particularly altered in epilepsy. While protein differences were most pronounced in the hippocampus, similar changes were observed in other brain regions indicating broad proteomic abnormalities in epilepsy. Among the most significantly altered proteins, G-protein subunit beta 1 (GNB1) was one of the most significantly decreased proteins in epilepsy in all regions studied, highlighting the importance of G-protein subunit signalling and G-protein-coupled receptors in epilepsy. Our results provide insights into common molecular mechanisms underlying epilepsy across various aetiologies, which may allow for novel targeted therapeutic strategies.

Background and Aims: Prolonged post-stroke cardiac rhythm monitoring (PCM) reveals a substantial proportion of ischemic stroke (IS) patients with atrial fibrillation (AF) not detected by conventional rhythm monitoring strategies. However, there is uncertainty regarding the potential benefit of PCM with respect to secondary stroke prevention.
Method(s): We performed a comprehensive literature search in MEDLINE, SCOPUS and conference proceedings to identify studies reporting stroke recurrence rates in patients with history of recent IS or transient ischemic attack (TIA) receiving PCM compared with patients receiving short-term cardiac rhythm monitoring. The meta-analysis was conducted according to PRISMA methodology.
Result(s): We included 8 studies (5 RCTs, 3 observational) that evaluated 2994 patients with a recent IS/TIA; 60% of the index events classified as cryptogenic stroke (CS) or embolic stroke of undetermined source (ESUS). Patients receiving PCM after their index event had a higher rate of AF detection [Risk Ratio (RR)=4.03, 95%CI:2.66-6.11)] and anticoagulant initiation (RR=2.01, 95%CI: 1.43-2.83), and a lower risk of subsequent IS (RR=0.57, 95%CI: 0.41-0.81) during the follow-up period of each study (range: 3-36 months) compared with those receiving conventional cardiac monitoring. Subgroup analyses by study type, PCM method (implantable vs. non-implantable devices) and index stroke event (CS/ESUS vs. other categories) uncovered no significant differences in the effect estimates of AF detection, anticoagulant utilization or subsequent IS recurrence.
Conclusion(s): PCM is associated with increased detection of paroxysmal AF, increased anticoagulant utilization and a low rate of subsequent ischemic stroke. The clinical impact of PCM deserves to be further investigated within the setting of large RCTs with adequate follow-up periods

Critical illness and sepsis are commonly associated with subclinical seizures. COVID-19 frequently causes severe critical illness, but the incidence of electrographic seizures in patients with COVID-19 has been reported to be low. This retrospective case series assessed the incidence of and risks for electrographic seizures in patients hospitalized with COVID-19 who underwent continuous video electroencephalography monitoring (cvEEG) between March 1st, 2020 and June 30th, 2020. One hundred and twenty-two patients were initially identified who resulted SARS-CoV-2 nasopharyngeal RT-PCR swab positivity with any electroencephalography order placed in the EMR. Seventy-nine patients met study inclusion criteria: age ≥18 years, >1 h of cvEEG monitoring, and positive SARS-CoV-2 nasopharyngeal swab PCR. Six (8%) of the 79 patients suffered electrographic seizures (ES), three of whom suffered non-convulsive status epilepticus. Acute hyperkinetic movements were the most common reason for cvEEG in patients with ES (84%). None of the patients undergoing cvEEG for persistent coma (29% of all patients) had ES. Focal slowing (67 vs. 10%), sporadic interictal epileptiform discharges (EDs; 33 vs. 6%), and periodic/rhythmic EDs (67 vs. 1%) were proportionally more frequent among patients with electrographic seizures than those without these seizures. While 15% of patients without ES had generalized periodic discharges (GPDs) with triphasic morphology on EEG, none of the patients with ES had this pattern. Further study is required to assess the predictive values of these risk factors on electrographic seizure incidence and subsequent outcomes.

Background: Modern, highly efficient hemodialysis (HD) results in rapid decline of blood urea. Urea gradients across the blood-brain barrier (BBB) can drive water movements. A positive urea gradient, i.e. brain urea to plasma urea, can result in brain swelling and impair brain function. We explored the dialytic changes of urea in blood and cerebrospinal fluid (CSF) to better understand intradialytic osmotic gradients across the BBB and provide insights that support the development of brain-protective HD.
Method(s): Two HD patients (39 and 26 years old) with ventriculo-peritoneal (VP) shunts were enrolled into this one-week IRB-approved study with a Monday/Wednesday/ Friday dialysis schedule. CSF was collected via VP shunt tap 2 hrs before and 2 hrs after HD (Wednesday and Friday), and Tuesday and Thursday. Plasma samples were collected concurrently with CSF and during HD. In addition, the patients underwent test of executive function (Trail Making Test Part B; TMT B) and global cognitive function (Montreal Cognitive Assessment; MoCA) on Monday.
Result(s): Urea was removed efficiently from patients' blood by HD. While patient A showed a small post-HD plasma-to-CSF urea gradient, it was highly positive (~ 60 mg/dL) in patient B (Fig. 1). TMT B and MoCA score were normal for patient A but not patient B (TMT B 415 sec; TMT B error count: 2; MoCA score: 11).
Conclusion(s): Our patients showed very different post-HD plasma-to-CSF gradients. Theoretically, the positive gradient in patient B would favor intradialytic brain swelling. Patient B showed impaired neurological testing results which are not related to patient's pre-existing neurological conditions. We can only speculate if and to what extent trans-BBB water movements driven by dialytic urea dynamics may have impacted the patient's cognitive functions?. We believe that patient-specific levels of osmotic stress need to be considered when developing neuro-protective HD technologies

Significant immunological, physical and neurological benefits of breastfeeding in infancy are well-established, but to what extent these gains persist into later childhood remain uncertain. This study examines the association between breastfeeding duration and subsequent domain-specific cognitive performance in a diverse sample of 9-10-year-olds enrolled in the Adolescent Brain Cognitive Development (ABCD) Study®. The analyses included 9,116 children that attended baseline with their biological mother and had complete neurocognitive and breastfeeding data. Principal component analysis was conducted on data from an extensive battery of neurocognitive tests using varimax-rotation to extract a three-component model encompassing General Ability, Executive Functioning, and Memory. Propensity score weighting using generalized boosted modeling was applied to balance the distribution of observed covariates for children breastfed for 0, 1-6, 7-12, and more than 12 months. Propensity score-adjusted linear regression models revealed significant association between breastfeeding duration and performance on neurocognitive tests representing General Ability, but no evidence of a strong association with Executive Function or Memory. Benefits on General Ability ranged from a 0.109 (1-6 months) to 0.301 (>12 months) standardized beta coefficient difference compared to those not breastfed. Results indicate clear cognitive benefits of breastfeeding but that these do not generalize to all measured domains, with implications for public health policy as it pertains to nutrition during infancy.