Publications by authors named "Steven Levine"

289 Publications

oCriteria to evaluate the reliability of interaction studies with insecticidal proteins.

Authors:
Steven L Levine

J Invertebr Pathol 2021 Mar 17:107577. Epub 2021 Mar 17.

Global Regulatory Sciences, Bayer CropScience, Chesterfield, MO USA 63017. Electronic address:

This paper recommends five criteria to evaluate the reliability of interaction studies with insecticidal proteins. However, these criteria are broadly applicable to an interaction analysis with any type of substance. The recommended criteria reflect the consensus of the literature on interaction analysis from decades of research in fields such as pharmacology and toxicology. The criteria can be used to interrogate the experimental design, assay methodology, data analysis, and interpretation of the results. These criteria will be useful to researchers to help identify the strengths and potential weaknesses of interaction studies and to help define the limits of interpretation of the data. The criteria will also be useful to risk assessors evaluating the reliability of interaction data as part of an environmental risk assessment, and to inform a weight of evidence analysis when there are contradictory results. In addition, these criteria can be used prospectively by researchers to help avoid common pitfalls that are apparent in some interaction studies. Five examples have been provided, with studies from the literature, that demonstrate how these criteria can be objectively and consistently applied to score the reliability of interaction studies with insecticidal proteins that differ in design and methodology.
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http://dx.doi.org/10.1016/j.jip.2021.107577DOI Listing
March 2021

Body Lateropulsion in Stroke: Case Report and Systematic Review of Stroke Topography and Outcome.

J Stroke Cerebrovasc Dis 2021 May 27;30(5):105680. Epub 2021 Feb 27.

Departments of Neurology and Emergency Medicine, SUNY Downstate Health Sciences University, Brooklyn, NY 11203, USA; Jaffe Stroke Center, Maimonides Medical Center, Brooklyn, NY 11219, USA; Department of Neurology, King's County Hospital Center, Brooklyn, NY 11203, USA. Electronic address:

Introduction: Body lateropulsion (BLP) is seen in neurological lesions involving the pathways responsible for body position and verticality. We report a case of isolated body lateropulsion (iBLP) as the presentation of lateral medullary infarction and conducted a systematic literature review.

Methods: MEDLINE and EMBASE databases were searched up to December 3, 2020.

Inclusion Criteria: age ≥ 18, presence of BLP, confirmed stroke on imaging.

Exclusion Criteria: age < 18, qualitative reviews, studies with inadequate patient data. Statistical analysis was performed using IBM® SPSS® Statistics 20.

Results: A 64-year-old man presented with acute-onset iBLP. Brain MRI demonstrated acute infarction in the right caudolateral medulla. His symptoms progressed with ipsilateral Horner syndrome over the next 24 hours and contralateral hemisensory loss 10 days later. Repeat MRI showed an increase in infarct size. BLP resolved partially at discharge. Systematic review: 418 abstracts were screened; 59 studies were selected reporting 103 patients. Thirty-three patients had iBLP (32%). BLP was ipsilateral to stroke in 70 (68%) and contralateral in 32 (32%). The most common stroke locations were medulla (n = 63, 59%), pons (n = 16, 15%), and cerebellum (n = 16, 15%). Four strokes were cortical, 3 frontal and 1 temporoparietal (3%). The most common etiology was large-artery atherosclerosis (LAA) in 20 patients (32%), followed by small-vessel occlusion in 12 (19%). Seventeen (27%) had large-vessel occlusion (LVO), 12 involving the vertebral artery. Sixty (98%) had some degree of resolution of BLP; complete in 41 (70%). Median time-to-resolution was 14 days (IQR 10-21). There was no relationship between time-to-resolution and age, sex, side of BLP or side of stroke.

Conclusion: BLP was commonly seen with medullary infarction and was the isolated finding in one-third. LAA and LVO were the most common etiologies. Recovery of BLP was early and complete in most cases.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105680DOI Listing
May 2021

Intracranial Hemorrhage in COVID-19 Patients.

J Stroke Cerebrovasc Dis 2021 Apr 8;30(4):105603. Epub 2021 Jan 8.

Department of Neurology, Comprehensive Stroke Center, Maimonides Medical Center, 948 48th St, 2nd Fl, Brooklyn, NY 11219, United States; Department of Surgery/Division of Neurosurgery, Maimonides Medical Center, Brooklyn, NY, United States; Department of Neurology & Stroke Center, SUNY Downstate Health Sciences University, Brooklyn, NY, United States. Electronic address:

Objective: To describe the clinical, laboratory, temporal, radiographic, and outcome features of acute Intracranial Hemorrhage (ICH) in COVID-19 patients.

Methods: Retrospective, observational, consecutive case series of patients admitted with ICH to Maimonides Medical Center from March 1 through July 31, 2020, who had confirmed or highly suspected COVID-19. Demographic, clinical, laboratory, imaging, and outcome data were analyzed. ICH rates among all strokes were compared to the same time period in 2019 in two-week time intervals. Correlation of systolic blood pressure variability (SBPV) and neutrophil-to-lymphocyte ratio (NLR) to clinical outcomes were performed.

Results: Of 324 patients who presented with stroke, 65 (20%) were diagnosed with non-traumatic ICH: 8 had confirmed and 3 had highly suspected COVID-19. Nine (82%) had at least one associated risk factor for ICH. Three ICHs occurred during inpatient anticoagulation. More than half (6) suffered either deep or cerebellar hemorrhages; only 2 were lobar hemorrhages. Two of 8 patients with severe pneumonia survived. During the NYC COVID-19 peak period in April, ICH comprised the highest percentage of all strokes (40%), and then steadily decreased week-after-week (p = 0.02). SBPV and NLR were moderately and weakly positively correlated to discharge modified Rankin Scale, respectively.

Conclusions: COVID-19 associated ICH is often associated with at least one known ICH risk factor and severe pneumonia. There was a suggestive relative surge in ICH among all stroke types during the first peak of the NYC pandemic. It is important to be vigilant of ICH as a possible and important manifestation of COVID-19.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831866PMC
April 2021

A Simplified Method for the Histochemical Detection of Iron in Paraffin Sections: Intracellular Iron Deposits in Central Nervous System Tissue.

ASN Neuro 2021 Jan-Dec;13:1759091420982169

Kansas Intellectual and Developmental Disabilities Research Center, University of Kansas Medical Center, Kansas City, Kansas, United States.

Although all cells contain iron, most histochemical methods fail to reveal the presence of iron within many cells of the central nervous system (CNS), particularly neurons. Previously, a sensitive method was developed that limited the extraction of iron in paraffin sections, and this method revealed staining within neurons. However, the staining was often too robust making it difficult to discern discrete intracellular structures. In 1970, a study incorporated acetone in an iron histochemical procedure to facilitate the demarcation of staining features. In the present study, both acetone and limits to iron extraction were included in a simplified staining procedure. This procedure was applied to paraffin sections of CNS tissue from CISD2 deficient and littermate control mice. Discrete nuclear and cytoplasmic staining features were detected in all mice. Although widely present in neurons, punctate cytoplasmic staining was particularly prominent in large neurons within the hindbrain. Evaluation of extended depth of focus images, from serial focal planes, revealed numerous stained cytoplasmic structures. Additionally, the simplified staining procedure was applied to paraffin sections from Alzheimer's disease and control cases. Despite suboptimal processing conditions compared to mouse tissue, discrete staining of cytoplasmic structures was revealed in some neurons, although many other neurons had nondescript staining features. In addition, initial findings revealed iron deposited within some vessels from patients with Alzheimer's disease. In summary, since paraffin sections are commonly used for histological preparations, this simplified histochemical procedure could facilitate the study of iron in various CNS conditions by revealing staining details often missed by other procedures.
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http://dx.doi.org/10.1177/1759091420982169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809306PMC
January 2021

Development of New International Antiphospholipid Syndrome Classification Criteria Phase I/II Report: Generation and Reduction of Candidate Criteria.

Arthritis Care Res (Hoboken) 2020 Nov 30. Epub 2020 Nov 30.

Barbara Volcker Center for Women and Rheumatic Diseases, Hospital for Special Surgery; Weill Cornell Medicine, New York, NY, USA.

Objectives: An international multi-disciplinary initiative, jointly supported by American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR), is underway to develop new rigorous classification criteria to identify patients with high likelihood of Antiphospholipid Syndrome (APS) for research purposes. We applied an evidence- and consensus- based approach to identify candidate criteria and develop a hierarchical organization of criteria within domains.

Methods: During Phase I, the APS classification criteria Steering Committee used systematic literature reviews and surveys of international APS physician scientists to generate a comprehensive list of items related to APS. In Phase II, we reviewed the literature, administered surveys, formed domain subcommittees, and used Delphi exercises and nominal group technique to reduce potential APS candidate criteria. Candidate criteria were hierarchically organized into clinical and laboratory domains.

Results: Phase I generated 152 candidate criteria, expanded to 261 items with the addition of subgroups and candidate criteria with potential negative weights. Using iterative item reduction techniques in Phase II, we initially reduced these items to 64 potential candidate criteria organized into ten clinical and laboratory domains. Subsequent item reduction methods resulted in 27 candidate criteria, hierarchically organized into six additive domains (laboratory, macrovascular, microvascular, obstetric, cardiac, and hematologic) for APS classification.

Conclusion: Using data- and consensus-driven methodology, we identified twenty-seven APS candidate criteria in six clinical or laboratory domains. In the next phase, the proposed candidate criteria will be used for real-world case collection and further refined, organized, and weighted to determine an aggregate score and threshold for APS classification.
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http://dx.doi.org/10.1002/acr.24520DOI Listing
November 2020

Olfactory gyrus intracerebral hemorrhage in a patient with COVID-19 infection.

J Clin Neurosci 2020 Sep 23;79:275-276. Epub 2020 Jul 23.

Departments of Neurology, SUNY Downstate Health Sciences University, Brooklyn, NY, United States; Emergency Medicine, SUNY Downstate Health Sciences University, Brooklyn, NY, United States; Department of Neurology, Kings County Hospital Center, Brooklyn, NY, United States. Electronic address:

Since the outbreak with novel corona virus in December 2019, a myriad of different neurological manifestations in patients with COVID-19 infection have been reported. We present a case of non-traumatic intracranial hemorrhage in the olfactory gyrus in a patient who tested positive for SARS-COV-2. The area of hemorrhage is not a common location for spontaneous hemorrhage. Given that loss of smell is considered a relatively common symptom of this pandemic, it is an intriguing association of COVID-19 and olfactory gyrus ICH for neurotropism of SARS-CoV2 for olfactory bulb and glia cells through nasal mucosa. Future studies will need to elucidate the exact mechanism of anosmia from COVID-19 and potential mechanisms leading to ICH.
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http://dx.doi.org/10.1016/j.jocn.2020.07.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377802PMC
September 2020

Managing Ischemic Stroke in Patients Already on Anticoagulation for Atrial Fibrillation: A Nationwide Practice Survey.

J Stroke Cerebrovasc Dis 2020 Dec 11;29(12):105291. Epub 2020 Sep 11.

Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University Medical College, New York, NY, United States.

Background And Purpose: We sought to understand practice patterns in management of patients who have ischemic stroke while adherent to oral anticoagulation for non-valvular atrial fibrillation (NVAF) in the United States (US).

Methods: We distributed an iteratively revised online survey to US neurologists in May-June 2019. Survey questions focused on clinicians' practices regarding diagnostic evaluation and secondary prevention after ischemic stroke in patients already on oral anticoagulation for NVAF. Standard descriptive statistics were used to summarize participants' characteristics and responses.

Results: Of the 120 participating clinicians, 79% were attending physicians. Most respondents (66%) were trained in vascular neurology, and 79% were employed in hospital-based, academic settings. For patients with ischemic stroke despite anticoagulation, most respondents indicated that they obtain extracranial and intracranial vessel imaging (72% and 82%, respectively). Most respondents (83%) routinely change therapy to a direct oral anticoagulant (DOAC) for patients experiencing ischemic stroke while on warfarin. In cases of ischemic stroke while on a DOAC, 38% of respondents routinely switch agents, 42% do not routinely switch agents, and 20% routinely add an antiplatelet agent. In this scenario, 83% of respondents who switch agents indicated that the reason was a possible better response to a drug that acts through a different mechanism. The most common reason for not switching while on a DOAC was the lack of randomized trial data.

Conclusions: There is a high degree of variability in practice patterns among US neurologists caring for patients with ischemic stroke while already on oral anticoagulation for NVAF.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105291DOI Listing
December 2020

Sequence-Activity Relationships for the Snf7 Insecticidal dsRNA in Chrysomelidae.

Front Plant Sci 2020 25;11:1303. Epub 2020 Aug 25.

Regulatory Science, Bayer Crop Science, Chesterfield, MO, United States.

The responsiveness of insects to oral delivery of insecticidal dsRNA has been shown to be dependent on dsRNA length and sequence match. Previous work with the western corn rootworm (WCR, ; Coleoptera: Chrysomelidae) demonstrated that at least one ≥21 nt match must be present in the DvSnf7 dsRNA of approximately ≥60 base-pairs (bp) for activity. Further data is needed on the activity of <21 nt matches along with characterization of relationship between activity and the number of ≥21 nt matches. To characterize the sequence-activity relationship for insecticidal dsRNA further, the activity of orthologous Snf7 dsRNAs with 19, 20, and 21 nt contiguous matches against WCR was compared. Neither 19 nor 20 nt sequence matches were active, supporting that a ≥21 nt sequence match is required for activity. The relationship between the number of 21 nt matches with activity of Snf7 dsRNA orthologs from several Chrysomelid species was characterized using WCR and Colorado potato beetle (CPB, Coleoptera Chrysomelidae). For WCR, there was a strong relationship between an increasing number of 21 nt matches and increased activity (, lower LC values). A similar relationship was observed for CPB with an exception for a single ortholog, which may be related to the exceptionally high rate of polymorphisms in CPB. Overall, these results demonstrate a general relationship between the number of 21 nt matches and activity, and this relationship could be used to inform a testing and assessment plan for an ecological risk assessment for an insecticidal dsRNA.
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http://dx.doi.org/10.3389/fpls.2020.01303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477086PMC
August 2020

Review and analysis of the potential for glyphosate to interact with the estrogen, androgen and thyroid pathways.

Pest Manag Sci 2020 Sep 17;76(9):2886-2906. Epub 2020 Jul 17.

Global Regulatory Science, Bayer Crop Science, Chesterfield, MO, USA.

Glyphosate was recently evaluated for its potential to interact with the estrogen, androgen and thyroid (EAT) hormone pathways, including steroidogenesis, under the United States Environmental Protection Agency's (USEPA) Endocrine Disruptor Screening Program (EDSP), then by Germany, the rapporteur Member State who led the European Annex 1 renewal for glyphosate, and then by the European Food Protection Agency (EFSA) also as part of the Annex 1 renewal for glyphosate. Under the EDSP, 11 Tier 1 assays were run following the USEPA's validated 890-series test guidelines and included five in vitro and six in vivo assays to evaluate the EAT pathways. Steroidogenesis was evaluated as part of the estrogen and androgen pathways. An up-to-date critical review has been conducted that considered results from the EDSP Tier 1 battery, guideline regulatory studies and an in-depth analysis of the literature studies that informed an endocrine assessment. A strength of this evaluation was that it included data across multiple levels of biological organization, and mammalian and nonmammalian test systems. There was strong agreement across the in vitro and in vivo Tier 1 battery, guideline studies and relevant literature studies, demonstrating that glyphosate does not interact with EAT pathways including steroidogenesis. Based on an analysis of the comprehensive toxicology database for glyphosate and the literature, this review has concluded that glyphosate does not have endocrine-disrupting properties through estrogen, androgen, thyroid and steroidogenic modes of action. © 2020 Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.5983DOI Listing
September 2020

Sublethal Endpoints in Non-target Organism Testing for Insect-Active GE Crops.

Front Bioeng Biotechnol 2020 9;8:556. Epub 2020 Jun 9.

USDA, Corn Insects and Crop Genetics Research Unit, Ames, IA, United States.

Historically, genetically engineered (GE) plants that have incorporated genes conferring insect protection have primarily used Cry proteins derived from () to achieve their insecticidal phenotype. As a result, regulators have developed a level of familiarity and confidence in reviewing plants incorporating these insecticidal proteins. However, new technologies have been developed that produce GE plants that incorporate pest protection by triggering an RNA interference (RNAi) response or proteins other than Cry proteins. These technologies have new modes of action. Although the overall assessment paradigm for GE plants is robust, there are ongoing discussions about the appropriate tests and measurement endpoints needed to inform non-target arthropod assessment for technologies that have a different mode of action than the Cry proteins. As a result, increasing attention is being paid to the use of sublethal endpoints and their value for environmental risk assessment (ERA). This review focuses on the current status and history of sublethal endpoint use in insect-active GE crops, and evaluates the future use of sublethal endpoints for new and emerging technologies. It builds upon presentations made at the Workshop on Sublethal Endpoints for Non-target Organism Testing for Non- GE Crops (Washington DC, USA, 4-5 March 2019), and the discussions of government, academic and industry scientists convened for the purpose of reviewing the progress and status of sublethal endpoint testing in non-target organisms.
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http://dx.doi.org/10.3389/fbioe.2020.00556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295912PMC
June 2020

Depression and Psychosocial Stress Are Associated With Subclinical Carotid Atherosclerosis Among Women Living With HIV.

J Am Heart Assoc 2020 07 22;9(13):e016425. Epub 2020 Jun 22.

Department of Medicine Georgetown University Medical Center Washington DC.

Background To identify reasons for increased atherosclerotic risk among women living with HIV (WLWH), we evaluated the associations between psychosocial risk factors (depressive symptoms, perceived stress, and posttraumatic stress disorder symptoms) and subclinical atherosclerosis among WLWH and HIV-negative women. Methods and Results Carotid artery focal plaque (localized intima-media thickness >1.5 mm) was measured using B-mode ultrasound imaging in 2004-2005 and 2010-2012 in the Women's Interagency HIV Study. We created psychosocial risk groups using latent class analysis and defined prevalent plaque at the final measurement. We also examined repeated semiannual depression measures with respect to focal plaque formation throughout follow-up. The associations between latent class and prevalent plaque, and between depressive symptom persistence and plaque formation, were assessed separately by HIV status using multivariable logistic regression. Among 700 women (median age 47 years), 2 latent classes were identified: high (n=163) and low (n=537) psychosocial risk, with corresponding prevalence of depression (65%/13%), high stress (96%/12%), and probable posttraumatic stress disorder (46%/2%). Among WLWH, plaque prevalence was 23% and 11% in high versus low psychosocial risk classes (adjusted odds ratio [aOR], 2.12; 95% CI, 1.11-4.05) compared with 9% and 9% among HIV-negative women (aOR, 1.07; 95% CI, 0.24-4.84), respectively. New plaque formation occurred among 17% and 9% of WLWH who reported high depressive symptoms at ≥45% versus <45% of visits (aOR, 1.96; 95% CI, 1.06-3.64), compared with 9% and 7% among HIV-negative women (aOR, 0.82; 95% CI, 0.16-4.16), respectively. Conclusions Psychosocial factors were independent atherosclerotic risk factors among WLWH. Research is needed to determine whether interventions for depression and psychosocial stress can mitigate the increased risk of atherosclerosis for WLWH.
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http://dx.doi.org/10.1161/JAHA.120.016425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670495PMC
July 2020

Recurrent thrombosis in patients with antiphospholipid antibodies and an initial venous or arterial thromboembolic event: A systematic review and meta-analysis.

J Thromb Haemost 2020 09 21;18(9):2274-2286. Epub 2020 Jul 21.

RTI International, Research Triangle Park, North Carolina, USA.

Background: Patients with antiphospholipid antibodies (aPL) and thromboembolism (TE) are at risk for recurrent TE. Few studies, however, distinguish patients based on the initial event.

Objectives: We performed a systematic review and meta-analysis to investigate patients with aPL and venous TE (VTE), provoked or unprovoked, and patients with arterial TE (ATE).

Patients/methods: We conducted searches in PubMed, CINAHL, Cochrane, and EMBASE. Inclusion criteria were prospective trials or cohort studies investigating patients with aPL and ATE or VTE. Excluded studies did not provide estimated recurrence rates, did not specify whether the incident event was ATE or VTE, included patients with multiple events, or included <10 patients. Two-year summary proportions were estimated using a random effects model.

Results: Ten studies described patients with VTE, 2 with ATE, and 5 with VTE or ATE. The 2-year proportion for recurrent TE in patients with VTE who were taking anticoagulant therapy was 0.054 (95% confidence interval [CI], 0.037-0.079); the 2-year proportion for patients not taking anticoagulant therapy was 0.178 (95% CI, 0.150-0.209). Most studies did not distinguish whether VTE were provoked or unprovoked. The 2-year proportion for recurrent TE in patients with ATE who were taking anticoagulant therapy was 0.220 (95% CI, 0.149-0.311); the 2-year proportion for patients taking antiplatelet therapy was 0.216 (95% CI, 0.177-0.261).

Conclusions: Patients with aPL and ATE may benefit from a different antithrombotic approach than patients with aPL and VTE. Prospective studies with well-defined cohorts with aPL and TE are necessary to determine optimal antithrombotic strategies.
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http://dx.doi.org/10.1111/jth.14936DOI Listing
September 2020

Reduced 25(OH) Vitamin D Association with Lower Alpha-1-Antitrypsin Blood Levels in Type 2 Diabetic Patients.

J Am Coll Nutr 2021 Feb 10;40(2):98-103. Epub 2020 Apr 10.

Departments of Pediatrics and Medicine, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.

Reduced circulating levels of 25(OH)VD are associated with an increased incidence of chronic lung diseases. Alpha-1-antitrypsin (AAT) is needed to maintain healthy lung function. This study examined the hypothesis that circulating levels of AAT are lower in adult type 2 diabetic patients and that a positive association exists between circulating AAT levels and 25(OH)VD levels in these patients. Fasting blood was obtained after written informed consent from type 2 diabetic patients (n = 80) and normal siblings or volunteers (n = 22) attending clinics at LSUHSC according to the protocol approved by the Institutional Review Board for Human studies. Plasma AAT and 25(OH)VD levels were determined using ELISA kits. HbA levels and chemistry profiles were analyzed at the clinical laboratory of LSUHSC hospital. ATT and 25(OH)VD levels were significantly lower in type 2 diabetic patients compared with those of age-matched healthy controls. There was a significant positive correlation between 25(OH)VD and ATT deficiency. AAT levels showed significant positive correlation with HDL cholesterol levels in type 2 diabetic patients. There was no correlation between AAT levels and those of HbA or with the duration of diabetes of T2D patients. These results suggest that 25(OH)VD deficiency may predispose type 2 diabetic patients to AAT deficiency. Whether reduced levels of circulating AAT indeed contribute to the increased risk for lung dysfunction in subjects with type 2 diabetes needs further investigation.
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http://dx.doi.org/10.1080/07315724.2020.1740629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554069PMC
February 2021

Seven-Year Experience From the National Institute of Neurological Disorders and Stroke-Supported Network for Excellence in Neuroscience Clinical Trials.

JAMA Neurol 2020 06;77(6):755-763

University of Rochester, Rochester, New York.

Importance: One major advantage of developing large, federally funded networks for clinical research in neurology is the ability to have a trial-ready network that can efficiently conduct scientifically rigorous projects to improve the health of people with neurologic disorders.

Observations: National Institute of Neurological Disorders and Stroke Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) was established in 2011 and renewed in 2018 with the goal of being an efficient network to test between 5 and 7 promising new agents in phase II clinical trials. A clinical coordinating center, data coordinating center, and 25 sites were competitively chosen. Common infrastructure was developed to accelerate timelines for clinical trials, including central institutional review board (a first for the National Institute of Neurological Disorders and Stroke), master clinical trial agreements, the use of common data elements, and experienced research sites and coordination centers. During the first 7 years, the network exceeded the goal of conducting 5 to 7 studies, with 9 funded. High interest was evident by receipt of 148 initial applications for potential studies in various neurologic disorders. Across the first 8 studies (the ninth study was funded at end of initial funding period), the central institutional review board approved the initial protocol in a mean (SD) of 59 (21) days, and additional sites were added a mean (SD) of 22 (18) days after submission. The median time from central institutional review board approval to first site activation was 47.5 days (mean, 102.1; range, 1-282) and from first site activation to first participant consent was 27 days (mean, 37.5; range, 0-96). The median time for database readiness was 3.5 months (mean, 4.0; range, 0-8) from funding receipt. In the 4 completed studies, enrollment met or exceeded expectations with 96% overall data accuracy across all sites. Nine peer-reviewed manuscripts were published, and 22 oral presentations or posters and 9 invited presentations were given at regional, national, and international meetings.

Conclusions And Relevance: NeuroNEXT initiated 8 studies, successfully enrolled participants at or ahead of schedule, collected high-quality data, published primary results in high-impact journals, and provided mentorship, expert statistical, and trial management support to several new investigators. Partnerships were successfully created between government, academia, industry, foundations, and patient advocacy groups. Clinical trial consortia can efficiently and successfully address a range of important neurologic research and therapeutic questions.
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http://dx.doi.org/10.1001/jamaneurol.2020.0367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483960PMC
June 2020

Parathyroidectomy in First Trimester of Pregnancy.

J Endocr Soc 2020 Mar 5;4(3):bvaa015. Epub 2020 Feb 5.

Department of Otolaryngology-Head and Neck Surgery, Louisiana State University Health Sciences Center, Shreveport, Louisiana.

Primary hyperparathyroidism is not commonly diagnosed during pregnancy. For pregnant women with mild, asymptomatic disease, surgery can be avoided unless the degree of hypercalcemia becomes more severe or they develop complications. However, there are no evidence-based guidelines to assist clinicians regarding the management of primary hyperparathyroidism during pregnancy. When surgery is deemed necessary during pregnancy, the second trimester is generally considered to be the optimal time. We report the case of a 31-year-old female G1P0 who presented at 6 weeks gestation with symptoms of nausea, vomiting, polyuria, and corrected calcium of 14.8 mg/dL. Due to the extreme degree of hypercalcemia and refractory to medical treatment, it was decided that surgery could not be delayed until the second trimester. At 7w3d gestational age the patient had resection of a 37 gram, 5 × 4 × 3 cm right inferior parathyroid adenoma.
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http://dx.doi.org/10.1210/jendso/bvaa015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049289PMC
March 2020

Managing Acute Pain and Opioid Risks Following Wisdom Teeth Extraction: An Illustrative Case.

MedEdPORTAL 2019 11 22;15:10855. Epub 2019 Nov 22.

Assistant Professor, Department of Dental Public Health, University of Pittsburgh School of Dental Medicine.

Introduction: The opioid epidemic has awakened educators to the insufficiency of training in the areas of pain management and substance use disorders within the curricula of health sciences schools. The University of Pittsburgh Center of Excellence in Pain Education created an online educational module focusing on factors contributing to the opioid epidemic and the role of robust interprofessional communication in avoiding common practitioner errors.

Methods: The 1-hour module created by an interprofessional team comprised a pretest, video presentation featuring case vignettes, posttest, and learner satisfaction survey. The content of the module focused on four core concepts: (1) managing acute perioperative pain, (2) maximizing opioid safety, and (3) identifying and (4) managing suspected opioid abuse and diversion.

Results: Data were obtained from 250 dental, pharmacy, and nursing students from the University of Pittsburgh who completed the module as part of their respective profession-specific curricula. Results collapsed across the three school-specific implementations indicated an average increase in knowledge test scores from pre- to posttest ( = -8.82, < .001). In addition, the learner satisfaction data revealed an overall positive response to the module, with students commenting that they enjoyed the module and felt it provided them with a valuable learning experience.

Discussion: Learner outcomes and feedback suggest that our interprofessional team was successful in creating an effective learning module applicable to several health care professions, namely, pharmacy, dentistry, and nursing. Future studies might address the application of the knowledge gained to actual patient care.
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http://dx.doi.org/10.15766/mep_2374-8265.10855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953741PMC
November 2019

Computerized cognitive performance assessments in the Brooklyn Cognitive Impairments in Health Disparities Pilot Study.

Alzheimers Dement 2019 11;15(11):1420-1426

Department of Neurology, State University of New York Downstate Health Sciences University, Brooklyn, NY, USA. Electronic address:

Introduction: Detecting cognitive impairment in diverse, health disparities communities is an urgent health care priority.

Methods: The Brooklyn Cognitive Impairments in Health Disparities Pilot Study investigated quantitative aspects and liking of a computerized cognitive performance assessment, Cognigram, among individuals ≥ 40 years in traditional and nontraditional primary care settings.

Results: Cognigram was piloted in the Emergency Department, Family Medicine, and Geriatric Psychiatry clinics: 58 adults (23 men, 35 women), 67.9 ± 9.8 years (range 43-91), completed the Cognigram and 5-item liking survey. The observed liking range was 2 to maximum score 5 (67% scored 4-5; no sex or age differences).

Discussion: The Cognigram was well liked in waiting rooms of primary care settings. Assistance from a trained adult and clinic endorsement were keys to success. How the Cognigram performs in a geographically compact, population-dense global setting, such as Brooklyn with high vascular disease risk and a plethora of health disparities, is being tested.
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http://dx.doi.org/10.1016/j.jalz.2019.07.004DOI Listing
November 2019

A New Transcranial Doppler Scoring System for Evaluating Middle Cerebral Artery Stenosis.

J Neuroimaging 2020 01 13;30(1):97-103. Epub 2019 Nov 13.

Department of Neurology and Emergency Medicine, State University of New York Downstate Health Sciences University, and Department of Neurology, Kings County Hospital Center, Brooklyn, NY.

Background And Purpose: Transcranial Doppler (TCD) criteria for cerebrovascular stenosis are only based on velocity with unsatisfactory positive predictive value (PPV) in previous studies. We refined a published scoring system that integrates several characteristics of TCD data in diagnosing middle cerebral artery (MCA) stenosis.

Methods: Using the TCD-digital subtraction angiography (DSA) database from Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) trial, velocity, spectrum pattern, diffuse ratio, and asymmetry ratio were assessed. The cutpoints were defined for each parameter and a point value was assigned to each category within that parameter. A summed score was calculated for each MCA. The accuracy was assessed for different cutpoints in predicting ≥50% MCA stenosis measured by DSA. Logistic regression and C-statistics were used for analysis.

Results: A total of 114 MCAs were included in vessel-based and 87 patients were included in patient-based analysis. Compared to the velocity-only cutpoints in SONIA, the score results in much improved PPV while negative predictive value (NPV) remains unchanged. The score based on mean velocity (score 0: <140 cm/s, score 3: ≥140 cm/s), spectrum pattern (score 0: no turbulence; score 1: mild turbulence; 2: significant turbulence), and asymmetry ratio (score 0: ratio <1.5, score 1: ratio 1.5-2; score 2: ratio ≥2.1) has the highest NPV while PPV remains favorable (PPV: 72% [95% CI 54-90%]; NPV: 84% [95% CI: 75-93%], area under curve [AUC]: .76 [95% CI: .66-.86]).

Conclusions: The multiparameter scoring system incorporating several characteristics of TCD measures yielded higher PPV while maintaining high NPV compared with the single-parameter velocity criteria in diagnosing MCA ≥50% stenosis.
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http://dx.doi.org/10.1111/jon.12678DOI Listing
January 2020

Lateral SMASectomy.

Clin Plast Surg 2019 Oct 30;46(4):523-532. Epub 2019 Jul 30.

Department of Plastic Surgery, Manhattan Eye, Ear, and Throat Hospital, Private Practice at Steven Levine MD, 210 East 64th Street, 3rd Floor, New York City, NY 10065, USA. Electronic address: https://twitter.com/StevenLevineMD.

The lateral superficial musculoaponeurotic system-ectomy (SMASectomy) is a safe, versatile, and easily reproducible technique in facelift surgery. The ability to resect a portion of the superficial musculoaponeurotic system (SMAS) over the junction of the mobile and fixed SMAS produces a powerful lift with similar aesthetic results to a traditional SMAS flap, but without the additional risks of nerve injury. The ability to alter the vector of motion of the underlying SMAS makes the technique adaptable to a variety of facial characteristics. The lateral SMASectomy is a viable and powerful method that has stood the test of time.
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http://dx.doi.org/10.1016/j.cps.2019.06.003DOI Listing
October 2019

Medical Mobile Applications for Stroke Survivors and Caregivers.

J Stroke Cerebrovasc Dis 2019 Nov 12;28(11):104318. Epub 2019 Aug 12.

The State University of New York (SUNY) Downstate Medical Center, New York, New York; Department of Neurology, Kings County Hospital Center, New York, New York.

Background: Recent studies estimate nearly half of the US population can access mobile medical applications (apps) on their smartphones. The are no systematic data available on apps focused on stroke survivors/caregivers.

Objective: To identify apps (a) designed for stroke survivors/caregivers, (b) dealing with a modifiable stroke risk factor (SRF), or (c) were developed for other purposes but could potentially be used by stroke survivors/caregivers.

Methods: A systematic review of the medical apps in the US Apple iTunes store was conducted between August 2013 and January 2016 using 18 predefined inclusion/exclusion criteria. SRFs considered were: diabetes, hypertension, smoking, obesity, atrial fibrillation, and dyslipidemia.

Results: Out of 30,132 medical apps available, 843 (2.7%) eligible apps were identified. Of these apps, (n = 74, 8.7%) apps were specifically designed for stroke survivors/caregivers use and provided the following services: language/speech therapy (n = 28, 37%), communication with aphasic patients (n = 19, 25%), stroke risk calculation (n = 11, 14%), assistance in spotting an acute stroke (n = 8, 10%), detection of atrial fibrillation (n = 3, 4%), direction to nearby emergency room (n = 3, 4%), physical rehabilitation (n = 3, 4%), direction to the nearest certified stroke center (n = 1, < 2%), and visual attention therapy (n = 1, <2%). 769 apps identified that were developed for purposes other than stroke. Of these, the majority (n = 526, 68%) addressed SRFs.

Conclusions: Over 70 medical apps exist to specifically support stroke survivors/caregivers and primarily targeted language and communication difficulties. Apps encompassing most stroke survivor/caregiver needs could be developed and tested to ensure the issues faced by these populations are being adequately addressed.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2019.104318DOI Listing
November 2019

Assessing the Potential for Interaction in Insecticidal Activity Between MON 87751 × MON 87701 Produced by Conventional Breeding.

Environ Entomol 2019 09;48(5):1241-1248

Regulatory Sciences, Bayer Crop Science, Chesterfield, MO.

Pyramiding (combining) of plant incorporated protectants (PIPs) with insecticidal activity in genetically engineered crops is a strategy used to improve efficacy as well as delay potential resistance for a specific group of targets. In some countries, a regulatory risk assessment is required for breeding "stacks" expressing multiple PIPs and these countries may require an assessment of potential interaction among the PIPs. This study evaluated whether combining soybean events MON 87551 and MON 87701 results in a toxicological interaction that effects a species that is controlled by each event. MON 87751 coexpresses the Cry1A.105 and Cry2Ab2 proteins and MON 87701 expresses the Cry1Ac protein. EC50 values for MON 87751 and MON 87701 were comparable in diet-incorporation bioassays using corn earworm (Lepidoptera: Noctuidae, Helicoverpa zea) and the observed combined activity of the stack was consistent with predictions of additivity (i.e., no interaction). Under the concentration and response addition models, predicted and observed median effect levels differed by <10%. These results demonstrate independent action at the median effect level between the insecticidal activity of MON 87751 and MON 87701. Taken together, no interaction between these PIPs and acceptable margins of safety for the individual proteins to nontarget organisms, it is appropriate to bridge back to the risk assessments for the individual products that demonstrated environmental safety of stack products containing both MON 87751 and MON 87701.
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http://dx.doi.org/10.1093/ee/nvz082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766477PMC
September 2019

An Engineered Galactosylceramidase Construct Improves AAV Gene Therapy for Krabbe Disease in Twitcher Mice.

Hum Gene Ther 2019 09 18;30(9):1039-1051. Epub 2019 Jul 18.

Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, Missouri.

Krabbe disease is an inherited neurodegenerative disease caused by mutations in the gene. In the infantile form, patients die before 3 years of age. Systemic adeno-associated virus serotype 9 (AAV9) gene therapy was recently shown to reverse the disease course in human patients in another lethal infantile neurodegenerative disease. To explore AAV9 therapy for Krabbe disease, we engineered a codon-optimized AAV9 galactosylceramidase vector. We further incorporated features to allow AAV9-derived galactosylceramidase to more efficiently cross the blood-brain barrier and be secreted from transduced cells. We tested the optimized vector by a single systemic injection in the twitcher mouse, an authentic Krabbe disease model. Untreated twitcher mice showed characteristic neuropathology and motion defects. They died prematurely with a median life span of 41 days. Intravenous injection in 2-day-old twitcher mice reduced central and peripheral neuropathology and significantly improved the gait pattern and body weight. Noticeably, the median life span was extended to 150 days. Intraperitoneal injection in 6- to 12-day-old twitcher mice also significantly improved the motor function, body weight, and median life span (to 104 days). Our results far exceed the ≤70 days median life span seen in all reported stand-alone systemic AAV therapies. Our study highlights the importance of vector engineering for Krabbe disease gene therapy. The engineered vector warrants further development.
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http://dx.doi.org/10.1089/hum.2019.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761594PMC
September 2019

Overcoming Challenges of Incorporating Higher Tier Data in Ecological Risk Assessments and Risk Management of Pesticides in the United States: Findings and Recommendations from the 2017 Workshop on Regulation and Innovation in Agriculture.

Integr Environ Assess Manag 2019 Sep 7;15(5):714-725. Epub 2019 Aug 7.

Bayer US, Crop Science, Environmental Chemistry, Research Triangle Park, North Carolina.

Pesticide regulation requires regulatory authorities to assess the potential ecological risk of pesticides submitted for registration, and most risk assessment schemes use a tiered testing and assessment approach. Standardized ecotoxicity tests, environmental fate studies, and exposure models are used at lower tiers and follow well-defined methods for assessing risk. If a lower tier assessment indicates that the pesticide may pose an ecological risk, higher tier studies using more environmentally realistic conditions or assumptions can be performed to refine the risk assessment and inform risk management options. However, there is limited guidance in the United States on options to refine an assessment and how the data will be incorporated into the risk assessment and risk management processes. To overcome challenges to incorporation of higher tier data into ecological risk assessments and risk management of pesticides, a workshop was held in Raleigh, North Carolina. Attendees included representatives from the United States Environmental Protection Agency, United States Department of Agriculture, National Oceanic and Atmospheric Administration, universities, commodity groups, consultants, nonprofit organizations, and the crop protection industry. Key recommendations emphasized the need for 1) more effective, timely, open communication among registrants, risk assessors, and risk managers earlier in the registration process to identify specific protection goals, address areas of potential concern where higher tier studies or assessments may be required, and if a higher tier study is necessary that there is agreement on study design; 2) minimizing the complexity of study designs while retaining high value to the risk assessment and risk management process; 3) greater transparency regarding critical factors utilized in risk management decisions with clearly defined protection goals that are operational; and 4) retrospective analyses of success-failure learnings on the acceptability of higher tier studies to help inform registrants on how to improve the application of such studies to risk assessments and the risk management process. Integr Environ Assess Manag 2019;15:714-725. © 2019 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).
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http://dx.doi.org/10.1002/ieam.4173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852661PMC
September 2019

Independent ischemic stroke risk factors in older Americans: a systematic review.

Aging (Albany NY) 2019 05;11(10):3392-3407

State University of New York Downstate Medical Center, Department of Neurology and Stroke Center, New York City Health + Hospitals/Kings County, Brooklyn, NY 11203, USA.

The Framingham Stroke Risk Profile (FSRP) is a validated model for predicting 10-year ischemic stroke risk in middle-aged adults, yet has not been demonstrated to consistently translate in older populations. This is a systematic review of independent risk factors measured among 65 year olds, with subsequent first ischemic stroke, using PRISMA guidelines. We appraised peer-reviewed publications that included participants 65 years old at risk assessment. Combined with other criteria, results were abstracted from 28 papers reporting six types of stroke risk factors: Serologic/Diagnostic, Conventional, Psychosocial, Genetic, Cognitive, and Antibiotic use. These studies demonstrated levels of serum androgens, C-reactive protein, and advanced glycation endproducts; thrombin generation; left ventricular mass; depressive symptoms; phosphodiesterase 4D single nucleotide polymorphisms; coagulation factor XII gene; peak thrombus generation; and lower cognitive functioning were independent risk factors for ischemic stroke in older adults. Plasma adipokines, free fatty acids and antibiotic use did not predict ischemic stroke. Purpose in life and APOEε2 allele were protective for ischemic stroke. This systematic review provides evidence of risk and protective factors for ischemic stroke in older cohorts that are not included in the FSRP. Further studies are needed to understand whether these factors are important enough to comprise a risk score.
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http://dx.doi.org/10.18632/aging.101987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555455PMC
May 2019

Antiphospholipid Antibodies: Cognitive and Motor Decline, Neuroimaging and Neuropathology.

Neuroepidemiology 2019 8;53(1-2):100-107. Epub 2019 May 8.

Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.

Background: Few data are available on associations of antiphospholipid (aPL) antibodies with cognitive and motor decline in aging, and cerebrovascular disease on in vivo neuroimaging and postmortem neuropathology.

Methods: This longitudinal, clinical-pathologic study (aPL antibodies, brain infarcts, and cognitive and motor decline in aging), was derived from 2 ongoing community-based cohort studies. A panel of 3 aPL antibodies was assayed in serum from 956 older individuals (mean age = 81.1 years; 72% women). Serum was also tested in a subset for markers of inflammation (C-reactive protein [CRP]) and blood-brain barrier breakdown (matrix metalloproteinases, MMPs). Annual clinical evaluations documented cognitive (17 neuropsychological tests) and motor function including parkinsonism. Cerebrovascular disease data were derived from in vivo neuroimaging and postmortem neuropathologic evaluations (699 individuals). We examined associations of aPL with cognitive and motor decline, other serum markers, neuroimaging, and neuropathology.

Results: Of 956 individuals, 197 (20.6%) had aPL positivity, defined as positivity on any of the assays, at the time of first measurement. During a mean follow-up of 6.6 years (SD 4), overall aPL positivity was not associated with change in global cognition (estimate = -0.005, SE 0.011; p = 0.622) or parkinsonian signs (estimate = -0.003, SE 0.017; p = 0.860). aPL were not associated with serum CRP or MMPs (both p > 0.268). aPL were not associated with in vivo brain magnetic resonance imaging white matter hyperintensities or infarcts (both p > 0.376). Among those autopsied, aPL were not associated with pathologically confirmed brain infarcts, or cerebral atherosclerosis or arteriolosclerosis (all p≥ 0.447).

Conclusions: In older individuals followed longitudinally, aPL do not relate to cognitive or motor decline, inflammation, or cerebrovascular disease on in vivo neuroimaging or postmortem neuropathology.
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http://dx.doi.org/10.1159/000500157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698409PMC
June 2020

Disparities in the Use of Intravenous t-PA among Ischemic Stroke Patients: Population-based Recent Temporal Trends.

J Stroke Cerebrovasc Dis 2019 May 8;28(5):1243-1251. Epub 2019 Feb 8.

The Stroke Center and Department of Neurology, SUNY Downstate College of Medicine and Medical Center, Brooklyn, New York; Department of Neurology and Emergency Medicine, Kings County Hospital Center, Brooklyn, New York.

Objective: To explore a 5-year comparison of disparities in intravenous t-PA (IV t-PA) use among acute ischemic stroke (AIS) patients based on race, gender, age, ethnic origin, hospital status, and geographic location.

Methods: We extracted patients' demographic information and hospital characteristics for 2010 and 2014 from the New York Statewide Planning and Research Cooperative System (SPARCS). We compared disparities in IV t-PA use among AIS patients in 2010 to that in 2014 to estimate temporal trends. Multiple logistic regression was performed to compare disparities based on demographic variables, hospital designation, and geographic location.

Results: Overall, there was approximately a 2% increase in IV t-PA from 2010 to 2014. Blacks were 15% less likely to receive IV t-PA compared to Whites in 2014, but in 2010, there was no difference. Patients aged 62-73 had lower odds of receiving IV t-PA than age group ≤61 in both 2010 and 2014. Designated stroke centers in the Lower New York State region were associated with reduced odds of IV t-PA use in 2010 while those located in the Upper New York State region were associated with increased odds of IV t-PA use in both 2010 and 2014, compared to their respective nondesignated counterparts. Gender, ethnic origin, and insurance status were not associated with IV t-PA utilization in both 2010 and 2014.

Conclusion: Overall IV t-PA utilization among AIS patients increased between 2010 and 2014. However, there are evident disparities in IV t-PA use based on patient's race, age, hospital geography, and stroke designation status.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2019.01.013DOI Listing
May 2019

Does the Magnitude of the Electrocardiogram QT Interval Dispersion Predict Stroke Outcome?

J Stroke Cerebrovasc Dis 2019 Jan 2;28(1):44-48. Epub 2018 Oct 2.

Department of Neurology, Stroke Center, State University of New York (SUNY) Downstate Medical Center, Brooklyn, New York; Department of Emergency Medicine, Kings County Hospital Center, Brooklyn, New York. Electronic address:

Background: QT dispersion, maximal interlead difference in QT interval on 12-lead electrocardiogram (ECG), measures cardiac repolarization abnormalities. Data are conflicting whether QT dispersion predicts adverse outcome in acute ischemic stroke (AIS) patients. Our objective is to determine if QT dispersion predicts: (1) short-term clinical outcome in AIS, and (2) stroke location (insular versus noninsular cortex).

Methods: Admission ECGs from 412 consecutive patients with acute stroke symptoms from 2 university-based stroke centers were reviewed. QT dispersion was measured. A neuroradiologist reviewed brain imaging for insular cortex involvement. Favorable clinical outcomes at discharge were modified Rankin Scale (mRS) score of 0-1, discharge National Institutes of Health Stroke Scale (NIHSS) score less than 2, and discharge to home. Multiple logistic regressions were performed for each outcome measure and to determine the association between insular infarct and QT dispersion.

Results: Of 145 subjects in the final analysis, median age was 65 years (interquartile range [IQR] 56-75), male patients were 38%, black patients were 68%, median QT dispersion was 78 milliseconds (IQR 59-98), and median admission NIHSS score was 4 (IQR 2-6). QT dispersion did not predict short-term clinical outcome for mRS score (odds ratio [OR] = 1.001, 95% confidence interval [CI] .99-1.01, P = .85), NIHSS at discharge (OR = .994, 95% CI .98-1.01, P = .30), or discharge disposition (OR = 1.001, 95% CI .99-1.01, P = .81). Insular cortex involvement did not correlate with QT dispersion magnitude (OR = 1.009, 95% CI .99-1.02, P = .45).

Conclusions: We could not demonstrate that QT dispersion is useful in predicting short-term clinical outcome at discharge in AIS. Further, the magnitude of QT dispersion did not predict insular cortical stroke location.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2018.09.006DOI Listing
January 2019

Distinguishing between endocrine disruption and non-specific effects on endocrine systems.

Regul Toxicol Pharmacol 2018 Nov 12;99:142-158. Epub 2018 Sep 12.

Bayer CropScience, 2 TW Alexander Dr, Research Triangle Park, NC, 27709, USA. Electronic address:

The endocrine system is responsible for growth, development, maintaining homeostasis and for the control of many physiological processes. Due to the integral nature of its signaling pathways, it can be difficult to distinguish endocrine-mediated adverse effects from transient fluctuations, adaptive/compensatory responses, or adverse effects on the endocrine system that are caused by mechanisms outside the endocrine system. This is particularly true in toxicological studies that require generation of effects through the use of Maximum Tolerated Doses (or Concentrations). Endocrine-mediated adverse effects are those that occur as a consequence of the interaction of a chemical with a specific molecular component of the endocrine system, for example, a hormone receptor. Non-endocrine-mediated adverse effects on the endocrine system are those that occur by other mechanisms. For example, systemic toxicity, which perturbs homeostasis and affects the general well-being of an organism, can affect endocrine signaling. Some organs/tissues can be affected by both endocrine and non-endocrine signals, which must be distinguished. This paper examines in vitro and in vivo endocrine endpoints that can be altered by non-endocrine processes. It recommends an evaluation of these issues in the assessment of effects for the determination of endocrine disrupting properties of chemicals. This underscores the importance of using a formal weight of evidence (WoE) process to evaluate potential endocrine activity.
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http://dx.doi.org/10.1016/j.yrtph.2018.09.002DOI Listing
November 2018