Faculty Bibliography

BACKGROUND:Economic and social marginalization among American Indians and Alaska Natives (AI/ANs) results in higher chronic disease prevalence. Potential causal associations between toxic environmental exposures and adverse health outcomes within AI/AN communities are not well understood. OBJECTIVES/OBJECTIVE:This review examines epidemiological literature on exposure to toxicants and associated adverse health outcomes among AI/AN populations. METHODS:PubMed, Embase, Cochrane, Environment Complete, Web of Science Plus, DART, and ToxLine were searched for English-language articles. The following data were extracted: lead author's last name, publication year, cohort name, study location, AI/AN tribe, study initiation and conclusion, sample size, primary characteristic, environmental exposure, health outcomes, risk estimates, and covariates. RESULTS:About 31 articles on three types of environmental exposures met inclusion criteria: persistent organic pollutants (POPs), heavy metals, and open dumpsites. Of these, 17 addressed exposure to POPs, 10 heavy metal exposure, 2 exposure to both POPs and heavy metals, and 2 exposure to open dumpsites. Studies on the Mohawk Nation at Akwesasne; Yupik on St. Lawrence Island, Alaska; Navajo Nation; Gila River Indian Community; Cheyenne River Sioux; 197 Alaska Native villages; and 13 tribes in Arizona, Oklahoma, North Dakota, and South Dakota that participated in the Strong Heart Study support associations between toxicant exposure and various chronic conditions including cardiovascular conditions, reproductive abnormalities, cancer, autoimmune disorders, neurological deficits, and diabetes. DISCUSSION/CONCLUSIONS:The complex interplay of environmental and social factors in disease etiology among AI/ANs is a product of externally imposed environmental exposures, systemic discrimination, and modifiable risk behaviors. The connection between environmental health disparities and adverse health outcomes indicates a need for further study.

During the coronavirus disease 2019 (COVID-19) pandemic, the World Health Organization recommended measures to mitigate the outbreak such as social distancing and confinement. Since these measures have been put in place, anecdotal reports describe a decrease in the number of endovascular therapy (EVT) treatments for acute ischemic stroke due to large vessel occlusion. The purpose of our study was to determine the effect on EVT for patients with acute ischemic stroke during the COVID-19 confinement. In this retrospective, observational study, data were collected from November 1, 2019, to April 15, 2020, at 17 stroke centers in countries where confinement measures have been in place since March 2020 for the COVID-19 pandemic (Switzerland, Italy, France, Spain, Portugal, Germany, Canada, and United States). This study included 1600 patients treated by EVT for acute ischemic stroke. Date of EVT and symptom onset-to-groin puncture time were collected. Mean number of EVTs performed per hospital per 2-week interval and mean stroke onset-to-groin puncture time were calculated before confinement measures and after confinement measures. Distributions (non-normal) between the 2 groups (before COVID-19 confinement versus after COVID-19 confinement) were compared using 2-sample Wilcoxon rank-sum test. The results show a significant decrease in mean number of EVTs performed per hospital per 2-week interval between before COVID-19 confinement (9.0 [95% CI, 7.8-10.1]) and after COVID-19 confinement (6.1 [95% CI, 4.5-7.7]), (P<0.001). In addition, there is a significant increase in mean stroke onset-to-groin puncture time (P<0.001), between before COVID-19 confinement (300.3 minutes [95% CI, 285.3-315.4]) and after COVID-19 confinement (354.5 minutes [95% CI, 316.2-392.7]). Our preliminary analysis indicates a 32% reduction in EVT procedures and an estimated 54-minute increase in symptom onset-to-groin puncture time after confinement measures for COVID-19 pandemic were put into place.

BACKGROUND:As the COVID-19 pandemic developed, reports of neurological dysfunctions spanning the central and peripheral nervous systems have emerged. The spectrum of acute neurological dysfunctions may implicate direct viral invasion, para-infectious complications, neurological manifestations of systemic diseases, or co-incident neurological dysfunction in the context of high SARS-CoV-2 prevalence. A rapid and pragmatic approach to understanding the prevalence, phenotypes, pathophysiology and prognostic implications of COVID-19 neurological syndromes is urgently needed. METHODS:The Global Consortium to Study Neurological dysfunction in COVID-19 (GCS-NeuroCOVID), endorsed by the Neurocritical Care Society (NCS), was rapidly established to address this need in a tiered approach. Tier-1 consists of focused, pragmatic, low-cost, observational common data element (CDE) collection, which can be launched immediately at many sites in the first phase of this pandemic and is designed for expedited ethical board review with waiver-of-consent. Tier 2 consists of prospective functional and cognitive outcomes assessments with more detailed clinical, laboratory and radiographic data collection that would require informed consent. Tier 3 overlays Tiers 1 and 2 with experimental molecular, electrophysiology, pathology and imaging studies with longitudinal outcomes assessment and would require centers with specific resources. A multicenter pediatrics core has developed and launched a parallel study focusing on patients ages <18 years. Study sites are eligible for participation if they provide clinical care to COVID-19 patients and are able to conduct patient-oriented research under approval of an internal or global ethics committee. Hospitalized pediatric and adult patients with SARS-CoV-2 and with acute neurological signs or symptoms are eligible to participate. The primary study outcome is the overall prevalence of neurological complications among hospitalized COVID-19 patients, which will be calculated by pooled estimates of each neurological finding divided by the average census of COVID-19 positive patients over the study period. Secondary outcomes include: in-hospital, 30 and 90-day morality, discharge modified Rankin score, ventilator-free survival, ventilator days, discharge disposition, and hospital length of stay. RESULTS:In a one-month period (3/27/20-4/27/20) the GCS-NeuroCOVID consortium was able to recruit 71 adult study sites, representing 17 countries and 5 continents and 34 pediatrics study sites. CONCLUSIONS:This is one of the first large-scale global research collaboratives urgently assembled to evaluate acute neurological events in the context of a pandemic. The innovative and pragmatic tiered study approach has allowed for rapid recruitment and activation of numerous sites across the world-an approach essential to capture real-time critical neurological data to inform treatment strategies in this pandemic crisis.

INTRODUCTION/BACKGROUND:The prognostic role of racial and socioeconomic factors in patients with glioblastoma is controversially debated. We aimed to evaluate how these factors may affect survival outcomes in an overall and cause-specific manner using large, national cancer registry cohort data in the temozolomide chemoradiation era. METHODS:The National Cancer Institute's Surveillance, Epidemiology, and End Results database was queried for patients diagnosed with glioblastoma between 2005 and 2016. Overall survival was assessed using Cox proportional hazard models using disease intrinsic and extrinsic factors. Cause-specific mortality was assessed using cumulative incidence curves and modeled using multivariate cumulative risk regression. RESULTS:A total of 28,952 patients met the prespecified inclusion criteria and were included in this analysis. The following factors were associated with all-cause mortality: age, calendar year of diagnosis, sex, treatment receipt, tumor size, tumor location, extent of resection, median household income, and race. Asian/Pacific Islanders and Hispanic Whites had lower mortality compared to Non-Hispanic Whites. Cause-specific mortality was associated with both racial and socioeconomic groups. After adjusting for treatment and tumor-related factors, Asian/Pacific and black patients had lower glioblastoma-specific mortality. However, lower median household income and black race were associated with significantly higher non-glioblastoma mortality. CONCLUSIONS:Despite the aggressive nature of glioblastoma, racial and socioeconomic factors influence glioblastoma-specific and non-glioblastoma associated mortality. Our study shows that patient race has an impact on glioblastoma-associated mortality independently of tumor and treatment related factors. Importantly, socioeconomic and racial differences largely contribute to non-glioblastoma mortality, including death from other cancers, cardio- and cerebrovascular events.

Migraine and sleep disorders in children exhibit a bidirectional relationship. This relationship is based on shared pathophysiology. Migraine involves activation of the trigeminal vascular system. Nociceptive neurons that innervate the dura release various vasoactive peptides. Calcitonin gene-related peptide is the most active of these peptides. Neural pathways that are involved in sleep generation are divided into those responsible for circadian rhythm, wake promotion, non-rapid eye movement, and rapid eye movement sleep activation. Sleep state switches are a critical component of these systems. The cerebral structures, networks, and neurochemical systems that are involved in migraine align closely with those responsible for the regulation of sleep. Neurochemical systems that are involved with both the pathogenesis of migraine and regulation of sleep include adenosine, melatonin, orexin, and calcitonin gene-related peptide. Sleep disorders represent the most common comorbidity with migraine in childhood. The prevalence of parasomnias, obstructive sleep apnea, and sleep-related movement disorders is significantly greater in children migraineurs. Infantile colic is a precursor of childhood migraine. Treatment of comorbid sleep disorders is important for the appropriate management of children with migraine. Sleep-based behavioral interventions can be of substantial benefit. These interventions are particularly important in children due to limited evidence for effective migraine pharmacotherapy.

KEY POINTS/CONCLUSIONS:Individuals with Hereditary Sensory & Autonomic Neuropathy type III (HSAN III), also known as Riley-Day syndrome or Familial Dysautonomia, do not have functional muscle spindle afferents but do have essentially normal cutaneous mechanoreceptors Lack of muscle spindle feedback from the legs may account for the poor proprioception at the knee and the ataxic gait typical of HSAN III Given that functional muscle spindle afferents are also absent in the upper limb, we assessed whether proprioception at the elbow was likewise compromised Passive joint angle matching showed that proprioception was normal at the elbow, suggesting that individuals with HSAN III rely more on cutaneous afferents around the elbow ABSTRACT: Hereditary Sensory & Autonomic Neuropathy type III (HSAN III) is a rare neurological condition that features a marked ataxic gait that progressively worsens over time. We have shown that functional muscle spindle afferents are absent in the upper and lower limbs in HSAN III, and we have argued that this may account for the ataxia. We recently used passive joint angle matching to demonstrate that proprioception of the knee joint is very poor in HSAN III but can be improved towards normal by application of elastic kinesiology tape across the knee joints, which we attribute to the presence of intact cutaneous mechanoreceptors. Here we assessed whether proprioception was equally compromised at the elbow joint, and whether it could be improved through taping. Proprioception at the elbow joint was assessed using passive joint angle matching in 12 HSAN III patients and 12 age-matched controls. There was no difference in absolute error, gradient or correlation coefficient of the relationship between joint angles of the reference and indicator arms. Unlike at the knee, taping did not improve elbow proprioception in either group. Clearly, the lack of muscle spindles compromised proprioception at the knee but not at the elbow, and we suggest that the HSAN III patients rely more on proprioceptive signals from the skin around the elbow. This article is protected by copyright. All rights reserved.

The method for assessing the level of nitric oxide (II) (NO) by voltammetric monitoring of nitrite ions was carried out on models M1 and M2 of polarized macrophages induced from monocytes of human peripheral blood with the addition of lipopolysaccharide (LPS) and interleukin-4 (IL-4), respectively. The model of induction of M1 and M2 macrophages was used in the work to achieve the corresponding shifts in the functional status of studied cells. Ethyl nitrite (EtONO) was used as a standard compound of nitrite ions for electrochemical measurements. Electrochemical determination of nitrite ions was performed by anodic linear sweep voltammetry in the first-order derivative mode (ALSV FOD) in Britton-Robinson (BR) buffer with pH 4.02 on carbon ink modified graphite electrode. EtONO calibrations were linear over a concentration range from 2 to 9 μmol L^-1 with corresponding regression equation y = 0.768c - 0.048. Limit of detection (LOD) (S/N = 3) was 0.38 μmol L^-1. The results of the study showed the fundamental possibility of using voltammetry to assess indirectly the production of nitric oxide by cells in supernatants of the monocytic macrophage lineage. The level of nitric oxide metabolites (nitrite ions) in supernatants was associated with the functional state of macrophages.

Our perspective on anatomy frequently depends on how this anatomy is utilized in clinical practice, and by which methods knowledge is acquired. The thrombectomy revolution, of which the middle cerebral artery (MCA) is the most common target, is an example of a clinical paradigm shift with a unique perspective on cerebrovascular anatomy. This article reviews important features of MCA anatomy in the context of thrombectomy. Recognizing that variation, frequently explained by evolutionary concepts, is the rule when it comes to branching pattern, vessel morphology, territory, or collateral potential is key to successful thrombectomy strategy.