Publications by authors named "J Glenn Morris"

7,966 Publications

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Endovascular Treatment of Infective Endocarditis-Related Acute Large Vessel Occlusion Stroke.

J Stroke Cerebrovasc Dis 2021 Apr 8;30(6):105775. Epub 2021 Apr 8.

Department of Neurology, Boston University Medical Center, 72 East Concord Street, Boston, MA 02118, United States; Department of Neurosurgery, Boston University Medical Center, United States. Electronic address:

Objectives: Embolic stroke is a frequent complication of infective endocarditis yet lacks acute treatment as intravenous thrombolysis should be avoided due to high risk of intracerebral hemorrhage. Mechanical thrombectomy for large vessel occlusion may be a promising treatment but there is limited data on safety outcomes in infective endocarditis.

Materials And Methods: In this multi-center retrospective case series, we reviewed data from patients with infective endocarditis-related large vessel occlusion who underwent mechanical thrombectomy in 9 US hospitals.

Results: We identified 15 patients at 9 hospitals. A minority presented with signs suggesting infection (2 patients (14%) had fever, 7 (47%) were tachycardic, 2 (13%) were hypotensive, and 8 (53%) had leukocytosis). The median National Institute of Health Stroke Score decreased from 19 (range 9-25) at presentation to 7 post-thrombectomy (range 0-22, median best score post-thrombectomy), and the median modified Rankin Scale on or after discharge for survivors was 3 (range 0-6). Approximately 57% of patients had a modified Rankin Scale between 0 and 3 on or after discharge. Hemorrhagic transformation was observed in 7/15 (47%). The mechanical thrombectomy group had 2/9 petechial hemorrhagic transformation (22%), compared to 4/6 parenchymal hematomas (67%) in the tissue plasminogen activator + mechanical thrombectomy group.

Conclusions: Our findings suggest that patients with large vessel occlusion due to infective endocarditis may not present with overt signs of infection. Mechanical thrombectomy may be an effective treatment in this patient population for whom intravenous thrombolysis should be avoided.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105775DOI Listing
April 2021

A Simple Physical Therapy Algorithm Is Successful in Decreasing Skilled Nursing Facility Length of Stay and Increasing Cost Savings After Hip Fracture With No Increase in Adverse Events.

Geriatr Orthop Surg Rehabil 2021 24;12:2151459321998615. Epub 2021 Mar 24.

Department of Orthopaedics and Rehabilitation, Yale School of Medicine, New Haven, CT, USA.

Introduction: Shorter length of stays (LOS) at a Skilled Nursing Facility (SNF) after hip fracture surgery would be expected to lead to costs savings for the healthcare system. Evidence also suggests that shorter SNF stays also leads to improved 30-day outcomes, thus compounding this value proposition. Our Integrated Fragility Hip Fracture Program created a simple algorithm at discharge to provide each post-operative hip fracture patient with an expected SNF LOS. We studied whether this intervention produced a shorter SNF LOS and other observable short-term outcomes.

Methods: We retrospectively reviewed all original Medicare hip fracture patients treated with operative fixation who were admitted to our hospital in 2015, 2017 and 2018. We selected patients who were discharged to a single SNF following hospitalization, and excluded patients with incomplete records. The algorithm for the expected LOS recommendation was based on the degree of assistance the patient needed for ambulation: 7 days ("0-person assist"), 14 days ("1-person assist"), or 21 days ("2-person assist"). We compare the SNF LOS of our hip fracture patient population between those discharged to a program participant, those SNF that agreed to this algorithm, and those discharged to a non-program participant SNF.

Results: We identified 246 patients meeting our selection criteria. 69 were discharged to a program participant SNF. Patients discharged to a participant SNF had similar baseline demographics and ASA distributions to those discharged to a non-participant provider. There was a statistically significant difference in length of stay between the groups, with program participant patients spending an average of 23 days at the SNF while the control group spent an average of 31 days. (p < 0.001). Program participant discharges were also associated with additional cost savings. There was no significant difference in ED visits within 90 days of discharge.

Discussion: SNF LOS for geriatric hip fractures can be decreased with implementation of a simple physical therapy driven algorithm based on the patient's ambulatory independence at hospital discharge. : This is a simple, yet completely unique program that seems to have increased the value of healthcare provided.
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http://dx.doi.org/10.1177/2151459321998615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995299PMC
March 2021

F-aza-T-dCyd (NSC801845), a Novel Cytidine Analog, in Comparative Cell Culture and Xenograft Studies with the Clinical Candidates T-dCyd, F-T-dCyd, and Aza-T-dCyd.

Mol Cancer Ther 2021 Apr;20(4):625-631

Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, Maryland.

In this article, 5-aza-4'-thio-2'-β-fluoro-2'-deoxycytidine (F-aza-T-dCyd, NSC801845), a novel cytidine analog, is first disclosed and compared with T-dCyd, F-T-dCyd, and aza-T-dCyd in cell culture and mouse xenograft studies in HCT-116 human colon carcinoma, OVCAR3 human ovarian carcinoma, NCI-H23 human NSCLC carcinoma, HL-60 human leukemia, and the PDX BL0382 bladder carcinoma. In three of five xenograft lines (HCT-116, HL-60, and BL-0382), F-aza-T-dCyd was more efficacious than aza-T-dCyd. Comparable activity was observed for these two agents against the NCI-H23 and OVCAR3 xenografts. In the HCT-116 study, F-aza-T-dCyd [10 mg/kg intraperitoneal (i.p.), QDx5 for four cycles], produced complete regression of the tumors in all mice with a response that proved durable beyond postimplant day 150 (129 days after the last dose). Similarly, complete tumor regression was observed in the HL-60 leukemia xenograft when mice were dosed with F-aza-T-dCyd (10 mg/kg i.p., QDx5 for three cycles). In the PDX BL-0382 bladder study, both oral and i.p. dosing of F-aza-T-dCyd (8 mg/kg QDx5 for three cycles) produced regressions that showed tumor regrowth beginning 13 days after dosing. These findings indicate that further development of F-aza-T-dCyd (NSC801845) is warranted. GRAPHICAL ABSTRACT: http://mct.aacrjournals.org/content/molcanther/20/4/625/F1.large.jpg.
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http://dx.doi.org/10.1158/1535-7163.MCT-20-0738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8030693PMC
April 2021

Comparing the Visual Perception According to the Performance Using the Eye-Tracking Technology in High-Fidelity Simulation Settings.

Behav Sci (Basel) 2021 Mar 5;11(3). Epub 2021 Mar 5.

Department of Anesthesiology, Faculty of Medicine, Montreal, Centre d'Apprentissage des Attitudes et Habiletés Cliniques (CAAHC), Université de Montréal, Montréal, QC H1T 2M4, Canada.

Introduction: We used eye-tracking technology to explore the visual perception of clinicians during a high-fidelity simulation scenario. We hypothesized that physicians who were able to successfully manage a critical situation would have a different visual focus compared to those who failed.

Methods: A convenience sample of 18 first-year emergency medicine residents were enrolled voluntarily to participate in a high-fidelity scenario involving a patient in shock with a 3rd degree atrioventricular block. Their performance was rated as pass or fail and depended on the proper use of the pacing unit. Participants were wearing pre-calibrated eye-tracking glasses throughout the 9-min scenario and infrared (IR) markers installed in the simulator were used to define various Areas of Interest (AOI). Total View Duration (TVD) and Time to First Fixation (TFF) by the participants were recorded for each AOI and the results were used to produce heat maps.

Results: Twelve residents succeeded while six failed the scenario. The TVD for the AOI containing the pacing unit was significantly shorter (median [quartile]) for those who succeeded compared to the ones who failed (42 [31-52] sec vs. 70 [61-90] sec, = 0.0097). The TFF for the AOI containing the ECG and vital signs monitor was also shorter for the participants who succeeded than for those who failed (22 [6-28] sec vs. 30 [27-77] sec, = 0.0182).

Discussion: There seemed to be a connection between the gaze pattern of residents in a high-fidelity bradycardia simulation and their performance. The participants who succeeded looked at the monitor earlier (diagnosis). They also spent less time fixating the pacing unit, using it promptly to address the bradycardia. This study suggests that eye-tracking technology could be used to explore how visual perception, a key information-gathering element, is tied to decision-making and clinical performance.
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http://dx.doi.org/10.3390/bs11030031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998119PMC
March 2021

Plasma Amyloid-Beta Levels in a Pre-Symptomatic Dutch-Type Hereditary Cerebral Amyloid Angiopathy Pedigree: A Cross-Sectional and Longitudinal Investigation.

Int J Mol Sci 2021 Mar 13;22(6). Epub 2021 Mar 13.

Department of Biomedical Sciences, Macquarie University, North Ryde, NSW 2109, Australia.

Plasma amyloid-beta (Aβ) has long been investigated as a blood biomarker candidate for Cerebral Amyloid Angiopathy (CAA), however previous findings have been inconsistent which could be attributed to the use of less sensitive assays. This study investigates plasma Aβ alterations between pre-symptomatic Dutch-type hereditary CAA (D-CAA) mutation-carriers (MC) and non-carriers (NC) using two Aβ measurement platforms. Seventeen pre-symptomatic members of a D-CAA pedigree were assembled and followed up 3-4 years later (NC = 8; MC = 9). Plasma Aβ1-40 and Aβ1-42 were cross-sectionally and longitudinally analysed at baseline (T1) and follow-up (T2) and were found to be lower in MCs compared to NCs, cross-sectionally after adjusting for covariates, at both T1(Aβ1-40: = 0.001; Aβ1-42: = 0.0004) and T2 (Aβ1-40: = 0.001; Aβ1-42: = 0.016) employing the Single Molecule Array (Simoa) platform, however no significant differences were observed using the xMAP platform. Further, pairwise longitudinal analyses of plasma Aβ1-40 revealed decreased levels in MCs using data from the Simoa platform ( = 0.041) and pairwise longitudinal analyses of plasma Aβ1-42 revealed decreased levels in MCs using data from the xMAP platform ( = 0.041). Findings from the Simoa platform suggest that plasma Aβ may add value to a panel of biomarkers for the diagnosis of pre-symptomatic CAA, however, further validation studies in larger sample sets are required.
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http://dx.doi.org/10.3390/ijms22062931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000178PMC
March 2021

A Tale of Two Institutions: Analyzing the Impact of Gamified Student Response Systems on Student Anxiety in Two Different Introductory Biology Courses.

CBE Life Sci Educ 2021 Jun;20(2):ar19

Department of Biology, University of Alabama at Birmingham, Birmingham, AL 35294.

Anxiety can impact overall performance and persistence in college. Student response systems (SRSs), real-time active-learning technologies used to engage students and gauge their understanding, have been shown to elicit anxiety for some students. Kahoot! is an SRS technology that differs from others in that it involves gamification, the use of gamelike elements. Recent studies have explored the impact of active-learning strategies on student anxiety across different institutions, but there is little known about how Kahoot! impacts student perceived anxiety, especially in comparison with other active-learning strategies. In two complementary yet parallel studies of introductory biology courses at a western research-intensive institution ( = 694) and a southeastern research-intensive institution ( = 60), we measured students' perceived anxiety. We then explored how students were influenced by nongraded Kahoot! play and other elements of instruction. Using previously developed and course-specific pre- and post-course surveys, we found students at both universities agreed that nongraded Kahoot! play caused less anxiety compared with other pedagogical practices, such as working in small groups or reading the textbook. After playing Kahoot!, lower-performing students demonstrated greater engagement and lower levels of anxiety compared with their peers, suggesting that Kahoot! may be a particularly engaging active-learning strategy for these students.
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http://dx.doi.org/10.1187/cbe.20-08-0187DOI Listing
June 2021

Prospective Quantification of CSF Biomarkers in Antibody-Mediated Encephalitis.

Neurology 2021 Apr 1. Epub 2021 Apr 1.

Gregory S Day: Department of Neurology, Mayo Clinic, Jacksonville, Florida, United States of America Melanie Y Yarbrough: Department of Pathology and Immunology; Washington University School of Medicine, St. Louis, Missouri, United States of AmericaPeter Körtvelyessy: Department of Neurology; University of Magdeburg, Magdeburg, Germany; and Department of Neurology and Experimental Neurology; Charité, Universitätmedizin Berlin, Germany Harald Prüss: Department of Neurology and Experimental Neurology; Charité, Universitätmedizin Berlin, GermanyRobert C Bucelli: Department of Neurology; Washington University School of Medicine, Saint Louis, Missouri, United States of America Marvin J Fritzler: Department of Medicine; Cumming School of Medicine, University of Calgary, Calgary, Alberta, CanadaWarren Mason: Department of Medicine; Division of Neurology, University of Toronto, Toronto, Ontario David F Tang-Wai: Department of Medicine; Division of Neurology, University of Toronto, Toronto, OntarioClaude Steriade: NYU Langone Comprehensive Epilepsy Center; NYU Langone Health, New York City, New York, United States of America Julien Hébert: Department of Medicine; Division of Neurology, University of Toronto, Toronto, OntarioRachel L Henson: Department of Neurology; Washington University School of Medicine, Saint Louis, Missouri, United States of America; and The Charles F. and Joanne Knight Alzheimer Disease Research Center; Washington University School of Medicine, Saint Louis, Missouri, United States of America Elizabeth M Herries: Departments of Pathology and Immunology, and Neurology; Washington University School of Medicine, St. Louis, Missouri, United States of AmericaJack H Ladenson: Departments of Pathology and Immunology, and Neurology; Washington University School of Medicine, St. Louis, Missouri, United States of America A Sebastian Chiriboga-Lopez: Department of Neurology, Mayo Clinic, Jacksonville, Florida, United States of AmericaNeill R Graff-Radford: Department of Neurology, Mayo Clinic, Jacksonville, Florida, United States of America John C Morris: Department of Neurology; Washington University School of Medicine, Saint Louis, Missouri, United States of America; and The Charles F. and Joanne Knight Alzheimer Disease Research Center; Washington University School of Medicine, Saint Louis, Missouri, United States of AmericaAnne M Fagan: Department of Neurology; Washington University School of Medicine, Saint Louis, Missouri, United States of America; and The Charles F. and Joanne Knight Alzheimer Disease Research Center; Washington University School of Medicine, Saint Louis, Missouri, United States of America.

Objectives: To determine whether neuronal and neuroaxonal injury, neuroinflammation and synaptic dysfunction associate with clinical course and outcomes in antibody-mediated encephalitis (AME), we measured biomarkers of these processes in CSF from patients presenting with AME and cognitively normal individuals.

Methods: Biomarkers of neuronal (total-tau, VILIP-1) and neuroaxonal damage (neurofilament light chain [NfL]), inflammation (YKL-40) and synaptic function (neurogranin, SNAP-25) were measured in CSF obtained from 45 patients at the time of diagnosis of NMDA receptor (n=34) or LGI1/CASPR-2 (n=11) AME, and 39 age- and sex-similar cognitively normal individuals. The association between biomarkers and modified Rankin Scores were evaluated in a subset (n=20) of longitudinally followed patients.

Results: Biomarkers of neuroaxonal injury (NfL) and neuroinflammation (YKL-40) were elevated in AME cases at presentation, while markers of neuronal injury and synaptic function were stable (total-tau) or decreased (VILIP-1, SNAP-25, neurogranin). The log-transformed ratio of YKL-40/SNAP-25 optimally discriminated cases from cognitively normal individuals (AUC=0.99; 95%CI: 0.97, >0.99). Younger age (ρ=-0.56; p=0.01), lower VILIP-1 (ρ=-0.60; p<0.01) and SNAP-25 (ρ=-0.54; p=0.01), and higher log(YKL-40/SNAP-25) [(ρ=0.48; p=0.04] associated with greater disease severity (higher modified Rankin Score) in prospectively followed patients. Higher YKL-40 (ρ=0.60; p=0.02) and neurogranin (ρ=0.55; p=0.03) at presentation were associated with higher modified Rankin Scores 12-months following hospital discharge.

Conclusions: CSF biomarkers suggest that neuronal integrity is acutely maintained in AME patients, despite neuroaxonal compromise. Low-levels of biomarkers of synaptic function may reflect antibody-mediated internalization of cell-surface receptors, and may represent an acute correlate of antibody-mediated synaptic dysfunction, with the potential to inform disease severity and outcomes.
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http://dx.doi.org/10.1212/WNL.0000000000011937DOI Listing
April 2021

Association of Virtual Surgical Planning With External Incisions in Complex Maxillectomy Reconstruction.

JAMA Otolaryngol Head Neck Surg 2021 Apr 1. Epub 2021 Apr 1.

Department of Anatomic Modeling, Mayo Clinic, Rochester, Minnesota.

Importance: Maxillectomy can commonly be performed through a transoral approach, but maxillectomy defect reconstruction can be difficult to precisely design, contour, and inset through this approach.

Objective: To evaluate whether the use of virtual surgical planning (VSP) and 3-dimensional (3-D) modeling is associated with a decrease in the requirement of lateral rhinotomy (LR) for patients undergoing total and partial maxillectomy reconstruction.

Design, Setting, And Participants: This retrospective cohort study was conducted among patients undergoing subtotal or total maxillectomy with microvascular free flap reconstruction with or without VSP and 3-D modeling at a single tertiary care academic medical center between January 1, 2008, and October 3, 2019.

Interventions: Maxillectomy and free flap reconstruction with or without VSP.

Main Outcomes And Measures: Necessity of LR or other external incision for contouring, placement, and fixation of reconstruction as well as surgical complications.

Results: Fifteen patients (12 men [80%]; mean age, 64 years) underwent maxillectomy with free flap reconstruction without VSP. Eight patients (53%) in this group underwent total maxillectomy, and 4 patients in this group (27%) underwent partial maxillectomy. Twenty-three patients (18 men [78%]; mean age, 58 years) underwent maxillectomy with free flap reconstruction and VSP and 3-D modeling. Twelve of these patients (52%) underwent total maxillectomy, and 11 (48%) underwent partial maxillectomy. Lateral rhinotomy was necessary for 1 patient (4%) in the VSP group vs 12 patients (80%; 95% CI, 54%-98%) in the pre-VSP group. There were no LR complications in the VSP group vs 6 in the pre-VSP group. Among both groups, 14 patients underwent fibula free flap, 22 patients underwent subscapular system free flap, and 2 patients underwent cutaneous or osteocutaneous radial forearm free flap. There were no flap failures in the LR group and 1 flap failure in the group without LR.

Conclusions And Relevance: This cohort study suggests that the use of VSP and 3-D modeling for maxillectomy reconstruction is associated the a decrease in the need for external incisions without compromising reconstructive flap utility.
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http://dx.doi.org/10.1001/jamaoto.2021.0251DOI Listing
April 2021

Emergence of porcine delta-coronavirus pathogenic infections among children in Haiti through independent zoonoses and convergent evolution.

medRxiv 2021 Mar 25. Epub 2021 Mar 25.

Coronaviruses have caused three major epidemics since 2003, including the ongoing SARS-CoV-2 pandemic. In each case, coronavirus emergence in our species has been associated with zoonotic transmissions from animal reservoirs , underscoring how prone such pathogens are to spill over and adapt to new species. Among the four recognized genera of the family - , - human infections reported to date have been limited to alpha- and betacoronaviruses . We identify, for the first time, porcine deltacoronavirus (PDCoV) strains in plasma samples of three Haitian children with acute undifferentiated febrile illness. Genomic and evolutionary analyses reveal that human infections were the result of at least two independent zoonoses of distinct viral lineages that acquired the same mutational signature in the and the glycoprotein genes by convergent evolution. In particular, structural analysis predicts that one of the changes in the Spike S1 subunit, which contains the receptor-binding domain, may affect protein's flexibility and binding to the host cell receptor. Our findings not only underscore the ability of deltacoronaviruses to adapt and potentially lead to human-to-human transmission, but also raise questions about the role of such transmissions in development of pre-existing immunity to other coronaviruses, such as SARS-CoV-2.
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http://dx.doi.org/10.1101/2021.03.19.21253391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010738PMC
March 2021

Short- and long-term outcomes of three-dimensional printed surgical guides and virtual surgical planning versus conventional methods for fibula free flap reconstruction of the mandible: Decreased nonunion and complication rates.

Head Neck 2021 Mar 31. Epub 2021 Mar 31.

Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, Minnesota, USA.

Background: To determine whether virtual surgical planning and three-dimensional printed cutting guides (3D/VSP) improved radiographic bone union compared to conventional methods (CM) in fibula free flap (FFF) reconstruction of the mandibles.

Methods: Retrospective study from the years 2000-2018 at a tertiary hospital. Osseous union was evaluated by a radiologist blinded to each patient's treatment.

Results: Two hundred sixty patients who underwent FFF tissue transfer, 28 with VSP and 3D cutting guides. Bony union was not achieved in 46 (20%) patients who underwent CM compared to 1 (4%) of patients with VSP and guides (p = 0.036). FFF complication was significantly higher in CM with 87 patients (38%) compared to three patients (11%) in 3D/VSP (p = 0.005). Median time to bony union for patients who underwent CM was 1.4 years compared to 0.8 years in 3D/VSP.

Conclusions: 3D/VSP reduced the rate of radiographic nonunion and flap-related complications in FFF reconstruction for mandibular defects.
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http://dx.doi.org/10.1002/hed.26688DOI Listing
March 2021

A randomised, double-blind, sham-controlled trial of deep brain stimulation of the bed nucleus of the stria terminalis for treatment-resistant obsessive-compulsive disorder.

Transl Psychiatry 2021 Mar 29;11(1):190. Epub 2021 Mar 29.

Neurosciences Queensland, St Andrew's War Memorial Hospital, Spring Hill, QLD, Australia.

Deep brain stimulation (DBS) is a promising treatment for severe, treatment-resistant obsessive-compulsive disorder (OCD). Here, nine participants (four females, mean age 47.9 ± 10.7 years) were implanted with DBS electrodes bilaterally in the bed nucleus of the stria terminalis (BNST). Following a one-month postoperative recovery phase, participants entered a three-month randomised, double-blind, sham-controlled phase before a twelve-month period of open-label stimulation incorporating a course of cognitive behavioural therapy (CBT). The primary outcome measure was OCD symptoms as rated with the Yale-Brown Obsessive-Compulsive Scale (YBOCS). In the blinded phase, there was a significant benefit of active stimulation over sham (p = 0.025, mean difference 4.9 points). After the open phase, the mean reduction in YBOCS was 16.6 ± 1.9 points (χ (11) = 39.8, p = 3.8 × 10), with seven participants classified as responders. CBT resulted in an additive YBOCS reduction of 4.8 ± 3.9 points (p = 0.011). There were two serious adverse events related to the DBS device, the most severe of which was an infection during the open phase necessitating device explantation. There were no serious psychiatric adverse events related to stimulation. An analysis of the structural connectivity of each participant's individualised stimulation field isolated right-hemispheric fibres associated with YBOCS reduction. These included subcortical tracts incorporating the amygdala, hippocampus and stria terminalis, in addition to cortical regions in the ventrolateral and ventromedial prefrontal cortex, parahippocampal, parietal and extrastriate visual cortex. In conclusion, this study provides further evidence supporting the efficacy and tolerability of DBS in the region of the BNST for individuals with otherwise treatment-refractory OCD and identifies a connectivity fingerprint associated with clinical benefit.
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http://dx.doi.org/10.1038/s41398-021-01307-9DOI Listing
March 2021

Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic.

Authors:
Thanh N Nguyen Diogo C Haussen Muhammad M Qureshi Hiroshi Yamagami Toshiyuki Fujinaka Ossama Y Mansour Mohamad Abdalkader Michael Frankel Zhongming Qiu Allan Taylor Pedro Lylyk Omer F Eker Laura Mechtouff Michel Piotin Fabricio Oliveira Lima Francisco Mont'Alverne Wazim Izzath Nobuyuki Sakai Mahmoud Mohammaden Alhamza R Al-Bayati Leonardo Renieri Salvatore Mangiafico David Ozretic Vanessa Chalumeau Saima Ahmad Umair Rashid Syed Irteza Hussain Seby John Emma Griffin John Thornton Jose Antonio Fiorot Rodrigo Rivera Nadia Hammami Anna M Cervantes-Arslanian Hormuzdiyar H Dasenbrock Huynh Le Vu Viet Quy Nguyen Steven Hetts Romain Bourcier Romain Guile Melanie Walker Malveeka Sharma Don Frei Pascal Jabbour Nabeel Herial Fawaz Al-Mufti Atilla Ozcan Ozdemir Ozlem Aykac Dheeraj Gandhi Chandril Chugh Charles Matouk Pascale Lavoie Randall Edgell Andre Beer-Furlan Michael Chen Monika Killer-Oberpfalzer Vitor Mendes Pereira Patrick Nicholson Vikram Huded Nobuyuki Ohara Daisuke Watanabe Dong Hun Shin Pedro Sc Magalhaes Raghid Kikano Santiago Ortega-Gutierrez Mudassir Farooqui Amal Abou-Hamden Tatsuo Amano Ryoo Yamamoto Adrienne Weeks Elena A Cora Rotem Sivan-Hoffmann Roberto Crosa Markus Möhlenbruch Simon Nagel Hosam Al-Jehani Sunil A Sheth Victor S Lopez Rivera James E Siegler Achmad Fidaus Sani Ajit S Puri Anna Luisa Kuhn Gianmarco Bernava Paolo Machi Daniel G Abud Octavio M Pontes-Neto Ajay K Wakhloo Barbara Voetsch Eytan Raz Shadi Yaghi Brijesh P Mehta Naoto Kimura Mamoru Murakami Jin Soo Lee Ji Man Hong Robert Fahed Gregory Walker Eiji Hagashi Steve M Cordina Hong Gee Roh Ken Wong Juan F Arenillas Mario Martinez-Galdamez Jordi Blasco Alejandro Rodriguez Vasquez Luisa Fonseca M Luis Silva Teddy Y Wu Simon John Alex Brehm Marios Psychogios William J Mack Matthew Tenser Tatemi Todaka Miki Fujimura Roberta Novakovic Jun Deguchi Yuri Sugiura Hiroshi Tokimura Rakesh Khatri Michael Kelly Lissa Peeling Yuichi Murayama Hugh Stephen Winters Johnny Wong Mohamed Teleb Jeremy Payne Hiroki Fukuda Kosuke Miyake Junsuke Shimbo Yusuke Sugimura Masaaki Uno Yohei Takenobu Yuji Matsumaru Satoshi Yamada Ryuhei Kono Takuya Kanamaru Masafumi Morimoto Junichi Iida Vasu Saini Dileep Yavagal Saif Bushnaq Wenguo Huang Italo Linfante Jawad Kirmani David S Liebeskind Viktor Szeder Ruchir Shah Thomas G Devlin Lee Birnbaum Jun Luo Anchalee Churojana Hesham E Masoud Carlos Ynigo Lopez Brendan Steinfort Alice Ma Ameer E Hassan Amal Al Hashmi Mollie McDermott Maxim Mokin Alex Chebl Odysseas Kargiotis Georgios Tsivgoulis Jane G Morris Clifford J Eskey Jesse Thon Leticia Rebello Dorothea Altschul Oriana Cornett Varsha Singh Jeyaraj Pandian Anirudh Kulkarni Pablo M Lavados Veronica V Olavarria Kenichi Todo Yuki Yamamoto Gisele Sampaio Silva Serdar Geyik Jasmine Johann Sumeet Multani Artem Kaliaev Kazutaka Sonoda Hiroyuki Hashimoto Adel Alhazzani David Y Chung Stephan A Mayer Johanna T Fifi Michael D Hill Hao Zhang Zhengzhou Yuan Xianjin Shang Alicia C Castonguay Rishi Gupta Tudor G Jovin Jean Raymond Osama O Zaidat Raul G Nogueira

Stroke Vasc Neurol 2021 Mar 26. Epub 2021 Mar 26.

Neurology, Marcus Stroke & Neuroscience Center, Grady Memorial Hospital, Emory University School of Medicine, Atlanta, GA, USA

Background: During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study's objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines.

Methods: We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation.

Findings: There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p<0.0001). Embolisation of ruptured aneurysms declined with 1170-1035 procedures, respectively, representing an 11.5% (95%CI -13.5% to -9.8%, p=0.002) relative drop. Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations, a 24.9% relative decline (95% CI -28.0% to -22.1%, p<0.0001). A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1% (95% CI 32.3% to 50.6%, p=0.008) despite a decrease in SAH admissions in this tertile.

Interpretation: There was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction.
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http://dx.doi.org/10.1136/svn-2020-000695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006491PMC
March 2021

Global Impact of COVID-19 on Stroke Care and Intravenous Thrombolysis.

Authors:
Raul G Nogueira Muhammed M Qureshi Mohamad Abdalkader Sheila Ouriques Martins Hiroshi Yamagami Zhongming Qiu Ossama Yassin Mansour Anvitha Sathya Anna Czlonkowska Georgios Tsivgoulis Diana Aguiar de Sousa Jelle Demeestere Robert Mikulik Peter Vanacker James E Siegler Janika Kõrv Jose Biller Conrad W Liang Navdeep S Sangha Alicia M Zha Alexandra L Czap Christine Anne Holmstedt Tanya N Turan George Ntaios Konark Malhotra Ashis Tayal Aaron Loochtan Annamarei Ranta Eva A Mistry Anne W Alexandrov David Y Huang Shadi Yaghi Eytan Raz Sunil A Sheth Mahmoud H Mohammaden Michael Frankel Eric Guemekane Bila Lamou Hany M Aref Ahmed Elbassiouny Farouk Hassan Tarek Menecie Wessam Mustafa Hossam M Shokri Tamer Roushdy Fred S Sarfo Tolulope Oyetunde Alabi Babawale Arabambi Ernest O Nwazor Taofiki Ajao Sunmonu Kolawole Wahab Joseph Yaria Haytham Hussein Mohammed Philip B Adebayo Anis D Riahi Samia Ben Sassi Lenon Gwaunza Gift Wilson Ngwende David Sahakyan Aminur Rahman Zhibing Ai Fanghui Bai Zhenhui Duan Yonggang Hao Wenguo Huang Guangwen Li Wei Li Ganzhe Liu Jun Luo Xianjin Shang Yi Sui Ling Tian Hongbin Wen Bo Wu Yuying Yan Zhengzhou Yuan Hao Zhang Jun Zhang Wenlong Zhao Wenjie Zi Thomas W Leung Chandril Chugh Vikram Huded Bindu Menon Jeyaraj Durai Pandian P N Sylaja Fritz Sumantri Usman Mehdi Farhoudi Elyar Sadeghi Hokmabadi Anat Horev Anna Reznik Rotem Sivan Hoffmann Nobuyuki Ohara Nobuyuki Sakai Daisuke Watanabe Ryoo Yamamoto Ryosuke Doijiri Naoki Tokuda Takehiro Yamada Tadashi Terasaki Yukako Yazawa Takeshi Uwatoko Tomohisa Dembo Hisao Shimizu Yuri Sugiura Fumio Miyashita Hiroki Fukuda Kosuke Miyake Junsuke Shimbo Yusuke Sugimura Yoshiki Yagita Yohei Takenobu Yuji Matsumaru Satoshi Yamada Ryuhei Kono Takuya Kanamaru Hidekazu Yamazaki Manabu Sakaguchi Kenichi Todo Nobuaki Yamamoto Kazutaka Sonoda Tomoko Yoshida Hiroyuki Hashimoto Ichiro Nakahara Aida Kondybayeva Kamila Faizullina Saltanat Kamenova Murat Zhanuzakov Jang-Hyun Baek Yangha Hwang Jin Soo Lee Si Baek Lee Jusun Moon Hyungjong Park Jung Hwa Seo Kwon-Duk Seo Sung Il Sohn Chang Jun Young Rechdi Ahdab Wan Asyraf Wan Zaidi Zariah Abdul Aziz Hamidon Bin Basri Law Wan Chung Aznita Binti Ibrahim Khairul Azmi Ibrahim Irene Looi Wee Yong Tan Nafisah Wan Yahya Stanislav Groppa Pavel Leahu Amal M Al Hashmi Yahia Zakaria Imam Naveed Akhtar Maria Carissa Pineda-Franks Christian Oliver Co Dmitriy Kandyba Adel Alhazzani Hosam Al-Jehani Carol Huilian Tham Marlie Jane Mamauag Narayanaswamy Venketasubramanian Chih-Hao Chen Sung-Chun Tang Anchalee Churojana Esref Akil Ozlem Aykaç Atilla Ozcan Ozdemir Semih Giray Syed Irteza Hussain Seby John Huynh Le Vu Anh Duc Tran Huy Hoang Nguyen Thong Nhu Pham Thang Huy Nguyen Trung Quoc Nguyen Thomas Gattringer Christian Enzinger Monika Killer-Oberpfalzer Flavio Bellante Sofie De Blauwe Geert Vanhooren Sylvie De Raedt Anne Dusart Robin Lemmens Noemie Ligot Matthieu Pierre Rutgers Laetitia Yperzeele Filip Alexiev Teodora Sakelarova Marina Roje Bedeković Hrvoje Budincevic Igor Cindrić Zlatko Hucika David Ozretic Majda Seferovic Saric Frantiek Pfeifer Igor Karpowic David Cernik Martin Sramek Miroslav Skoda Helena Hlavacova Lukas Klecka Martin Koutny Daniel Vaclavik Ondrej Skoda Jan Fiksa Katerina Hanelova Miroslava Nevsimalova Robert Rezek Petr Prochazka Gabriela Krejstova Jiri Neumann Marta Vachova Henryk Brzezanski David Hlinovsky Dusan Tenora Rene Jura Lubomír Jurák Jan Novak Ales Novak Zdenek Topinka Petr Fibrich Helena Sobolova Ondrej Volny Hanne Krarup Christensen Nicolas Drenck Helle Klingenberg Iversen Claus Z Simonsen Thomas Clement Truelsen Troels Wienecke Riina Vibo Katrin Gross-Paju Toomas Toomsoo Katrin Antsov Francois Caparros Charlotte Cordonnier Maria Dan Jean-Marc Faucheux Laura Mechtouff Omer Eker Emilie Lesaine Basile Ondze Roxane Peres Fernando Pico Michel Piotin Raoul Pop Francois Rouanet Tatuli Gubeladze Mirza Khinikadze Nino Lobjanidze Alexander Tsikaridze Simon Nagel Peter Arthur Ringleb Michael Rosenkranz Holger Schmidt Annahita Sedghi Timo Siepmann Kristina Szabo Götz Thomalla Lina Palaiodimou Dimitrios Sagris Odysseas Kargiotis Peter Klivenyi Laszlo Szapary Gabor Tarkanyi Alessandro Adami Fabio Bandini Paolo Calabresi Giovanni Frisullo Leonardo Renieri Davide Sangalli Anne V Pirson Maarten Uyttenboogaart Ido van den Wijngaard Espen Saxhaug Kristoffersen Waldemar Brola Małgorzata Fudala Ewa Horoch-Lyszczarek Michal Karlinski Radoslaw Kazmierski Pawel Kram Marcin Rogoziewicz Rafal Kaczorowski Piotr Luchowski Halina Sienkiewicz-Jarosz Piotr Sobolewski Waldemar Fryze Anna Wisniewska Malgorzata Wiszniewska Patricia Ferreira Paulo Ferreira Luisa Fonseca João Pedro Marto Teresa Pinho E Melo Ana Paiva Nunes Miguel Rodrigues Vítor Tedim Cruz Cristian Falup-Pecurariu Georgi Krastev Miroslav Mako María Alonso de Leciñana Juan F Arenillas Oscar Ayo-Martin Antonio Cruz Culebras Exuperio Diez Tejedor Joan Montaner Soledad Pérez-Sánchez Miguel Angel Tola Arribas Alejandro Rodriguez Vasquez Michael Mazya Gianmarco Bernava Alex Brehm Paolo Machi Urs Fischer Jan Gralla Patrik L Michel Marios-Nikos Psychogios Davide Strambo Soma Banerjee Kailash Krishnan Joseph Kwan Asif Butt Luciana Catanese Andrew Demchuk Thalia Field Jennifer Haynes Michael D Hill Houman Khosravani Ariane Mackey Aleksandra Pikula Gustavo Saposnik Courtney Anne Scott Ashkan Shoamanesh Ashfaq Shuaib Samuel Yip Miguel A Barboza Jose Domingo Barrientos Ligia Ibeth Portillo Rivera Fernando Gongora-Rivera Nelson Novarro-Escudero Anmylene Blanco Michael Abraham Diana Alsbrook Dorothea Altschul Anthony J Alvarado-Ortiz Ivo Bach Aamir Badruddin Nobl Barazangi Charmaine Brereton Alicia Castonguay Seemant Chaturvedi Saqib A Chaudhry Hana Choe Jae H Choi Sushrut Dharmadhikari Kinjal Desai Thomas G Devlin Vinodh T Doss Randall Edgell Mark Etherton Mudassir Farooqui Don Frei Dheeraj Gandhi Mikayel Grigoryan Rishi Gupta Ameer E Hassan Johanna Helenius Artem Kaliaev Ritesh Kaushal Priyank Khandelwal Ayaz M Khawaja Naim N Khoury Benny S Kim Dawn O Kleindorfer Feliks Koyfman Vivien H Lee Lester Y Leung Guillermo Linares Italo Linfante Helmi L Lutsep Lisa Macdougall Shailesh Male Amer Malik Hesham Masoud Molly McDermott Brijesh P Mehta Jiangyong Min Manoj Mittal Jane G Morris Sumeet S Multani Fadi Nahab Krishna Nalleballe Claude B Nguyen Roberta Novakovic-White Santiago Ortega-Gutierrez Rahul H Rahangdale Pankajavalli Ramakrishnan Jose Rafael Romero Natalia Rost Aaron Rothstein Sean Ruland Ruchir Shah Malveeka Sharma Brian Silver Marc Simmons Abhishek Singh Amy K Starosciak Sheryl L Strasser Viktor Szeder Mohamed Teleb Jenny P Tsai Barbara Voetsch Oscar Balaguera Virginia A Pujol Lereis Adriana Luraschi Marcele Schettini Almeida Fabricio Buchdid Cardoso Adriana Conforto Leonardo De Deus Silva Luidia Varrone Giacomini Fabricio Oliveira Lima Alexandre L Longo Pedro Sc Magalhães Rodrigo Targa Martins Francisco Mont'alverne Daissy Liliana Mora Cuervo Leticia Costa Rebello Lenise Valler Viviane Flumignan Zetola Pablo M Lavados Victor Navia Verónica V Olavarría Juan Manuel Almeida Toro Pablo Felipe Ricardo Amaya Hernan Bayona Angel Basilio Corredor-Quintero Carlos Eduardo Rivera Ordonez Diana Katherine Mantilla Barbosa Osvaldo Lara Mauricio R Patiño Luis Fernando Diaz Escobar Donoband Edson Dejesus Melgarejo Farina Analia Cardozo Villamayor Adolfo Javier Zelaya Zarza Danny Moises Barrientos Iman Liliana Rodriguez Kadota Bruce Campbell Graeme J Hankey Casey Hair Timothy Kleinig Alice Ma Rodrigo Tomazini Martins Ramesh Sahathevan Vincent Thijs Daniel Salazar Teddy Yuan-Hao Wu Diogo C Haussen David Liebeskind Dileep Yavagal Tudor G Jovin Osama O Zaidat Thanh N Nguyen

Neurology 2021 Mar 25. Epub 2021 Mar 25.

Radiation Oncology, Boston Medical Center.

Objective: The objectives of this study were to measure the global impact of the pandemic on the volumes for intravenous thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with two control 4-month periods.

Methods: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases.

Results: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95%CI, -11.7 to - 11.3, p<0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95%CI, -13.8 to -12.7, p<0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95%CI, -13.7 to -10.3, p=0.001). Recovery of stroke hospitalization volume (9.5%, 95%CI 9.2-9.8, p<0.0001) was noted over the two later (May, June) versus the two earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.3% (1,722/52,026) of all stroke admissions.

Conclusions: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.
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http://dx.doi.org/10.1212/WNL.0000000000011885DOI Listing
March 2021

Cognitively normal APOE ε4 carriers have specific elevation of CSF SNAP-25.

Neurobiol Aging 2021 Feb 11;102:64-72. Epub 2021 Feb 11.

Department of Neurology, Washington University, Saint Louis, MO, USA; Knight Alzheimer Disease Research Center, Washington University, St. Louis, MO, USA. Electronic address:

Cerebrospinal fluid (CSF) synaptosomal-associated protein 25 (SNAP-25) and neurogranin (Ng) are recently described biomarkers for pre- and postsynaptic integrity known to be elevated in symptomatic Alzheimer disease (AD). Their relationship with Apolipoprotein E (APOE) ε4 carrier status, the major genetic risk factor for AD, remains unclear. In this study, CSF SNAP-25 and Ng were compared in cognitively normal APOE ε4 carriers and noncarriers (n = 274, mean age 65 ± 9.0 years, 39% APOE ε4 carriers, 58% female). CSF SNAP-25, not CSF Ng, was specifically elevated in APOE ε4 carriers versus noncarriers (5.95 ± 1.72 pg/mL, 4.44 ± 1.40 pg/mL, p < 0.0001), even after adjusting for age, sex, years of education, and amyloid status (p < 0.0001). CSF total tau (t-tau), phosphorylated-tau-181 (ptau181), and neurofilament light chain (NfL) also did not vary by APOE ε4 status. Our findings suggest APOE ε4 carriers have amyloid-related and amyloid-independent presynaptic disruption as reflected by elevated CSF SNAP-25 levels. In contrast, postsynaptic disruption as reflected by elevations in CSF neurogranin is related to amyloid status.
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http://dx.doi.org/10.1016/j.neurobiolaging.2021.02.008DOI Listing
February 2021

European trends in mortality in children with congenital anomalies: 2000-2015.

Birth Defects Res 2021 Mar 25. Epub 2021 Mar 25.

Population Health Research Institute, St George's, University of London, London, United Kingdom.

Objective: To investigate if the survival of children with congenital anomalies has improved from 2000 to 2015 and whether there is heterogeneity in the improvements across Europe.

Design: Population-based study of routine collected data from the WHO database on mortality and causes.

Setting: Data on 31 European countries from 2000 to 2015.

Main Outcome Measures: All-cause and congenital anomaly mortality rates for infants and children up to age 9 in countries and regions of Europe.

Results: The relative odds of all-cause mortality in 2015 compared with 2000 was 0.54 (95% CI: 0.50-0.59) for under 1, 0.48 (95% CI: 0.44-0.53) for ages 1-4, and 0.53 (95% CI: 0.49-0.56) for ages 5-9 with the relative odds of mortality from congenital anomalies being 0.49 (95% CI: 0.44-0.55), 0.51 (95% CI: 0.44-0.60), and 0.65 (95% CI: 0.53-0.80), respectively. The proportion of deaths from congenital anomalies remained relatively constant over time (26, 16, and 9% for under 1, ages 1-4, and ages 5-9, respectively) and was similar in all regions of Europe. For mortality from all causes and from congenital anomalies heterogeneity between countries and regions of Europe was high, with the countries in Eastern Europe having higher rates, but also experiencing greater relative reductions in mortality from 2000 to 2015.

Conclusion: There was a large geo-spatial disparity in all cause and congenital anomaly mortality for infants and children up to 9. However, all regions saw a significant decrease in all cause and congenital anomaly mortality rates, with the proportions of deaths from congenital anomalies remaining constant over this time.
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http://dx.doi.org/10.1002/bdr2.1892DOI Listing
March 2021

Naegleria fowleri: Protein structures to facilitate drug discovery for the deadly, pathogenic free-living amoeba.

PLoS One 2021 24;16(3):e0241738. Epub 2021 Mar 24.

Department of Medicine, Division Allergy and Infectious Disease, Center for Emerging and Re-emerging Infectious Disease (CERID) University of Washington, Seattle, Washington, United States of America.

Naegleria fowleri is a pathogenic, thermophilic, free-living amoeba which causes primary amebic meningoencephalitis (PAM). Penetrating the olfactory mucosa, the brain-eating amoeba travels along the olfactory nerves, burrowing through the cribriform plate to its destination: the brain's frontal lobes. The amoeba thrives in warm, freshwater environments, with peak infection rates in the summer months and has a mortality rate of approximately 97%. A major contributor to the pathogen's high mortality is the lack of sensitivity of N. fowleri to current drug therapies, even in the face of combination-drug therapy. To enable rational drug discovery and design efforts we have pursued protein production and crystallography-based structure determination efforts for likely drug targets from N. fowleri. The genes were selected if they had homology to drug targets listed in Drug Bank or were nominated by primary investigators engaged in N. fowleri research. In 2017, 178 N. fowleri protein targets were queued to the Seattle Structural Genomics Center of Infectious Disease (SSGCID) pipeline, and to date 89 soluble recombinant proteins and 19 unique target structures have been produced. Many of the new protein structures are potential drug targets and contain structural differences compared to their human homologs, which could allow for the development of pathogen-specific inhibitors. Five of the structures were analyzed in more detail, and four of five show promise that selective inhibitors of the active site could be found. The 19 solved crystal structures build a foundation for future work in combating this devastating disease by encouraging further investigation to stimulate drug discovery for this neglected pathogen.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241738PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990177PMC
March 2021

Intravascular lithotripsy-assisted balloon angioplasty to facilitate transfemoral transcatheter aortic valve implantation in a patient with coral reef aorta.

BMJ Case Rep 2021 Mar 23;14(3). Epub 2021 Mar 23.

Cardiology, Mater Misericordiae University Hospital, Dublin, Ireland.

This case describes the management of a woman in her 70s with severe symptomatic aortic stenosis and concomitant severe stenosis of the suprarenal abdominal aorta due to 'oral eef' calcification of the ortic wall and lumen (CRA). Due to her religious beliefs as a Jehovah's Witness regarding the use of blood products, she rejected the option of surgical aortic valve replacement. Transfemoral (TF) delivery of a transcatheter aortic valve was challenged by the presence of CRA. A successful TF transcatheter aortic valve implantation (TAVI) was achieved by the treatment of the CRA with intravascular lithotripsy-assisted angioplasty, followed by delivery and deployment of a self-expanding TAVI valve.
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http://dx.doi.org/10.1136/bcr-2020-240876DOI Listing
March 2021

Childhood obesity and multiple sclerosis: A Mendelian randomization study.

Mult Scler 2021 Mar 22:13524585211001781. Epub 2021 Mar 22.

Centre for Clinical Epidemiology, Department of Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada/Department of Human Genetics, McGill University, Montreal, QC, Canada/Department of Medicine, McGill University Montreal, QC, Canada/Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada/Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.

Background: Higher childhood body mass index (BMI) has been associated with an increased risk of multiple sclerosis (MS).

Objective: To evaluate whether childhood BMI has a causal influence on MS, and whether this putative effect is independent from early adult obesity and pubertal timing.

Methods: We performed Mendelian randomization (MR) using summary genetic data on 14,802 MS cases and 26,703 controls. Large-scale genome-wide association studies provided estimates for BMI in childhood ( = 47,541) and adulthood ( = 322,154). In multivariable MR, we examined the direct effects of each timepoint and further adjusted for age at puberty. Findings were replicated using the UK Biobank ( = 453,169).

Results: Higher genetically predicted childhood BMI was associated with increased odds of MS (odds ratio (OR) = 1.26/SD BMI increase, 95% confidence interval (CI): 1.07-1.50). However, there was little evidence of a direct effect after adjusting for adult BMI (OR = 1.03, 95% CI: 0.70-1.53). Conversely, the effect of adult BMI persisted independent of childhood BMI (OR = 1.43; 95% CI: 1.01-2.03). The addition of age at puberty did not alter the findings. UK Biobank analyses showed consistent results. Sensitivity analyses provided no evidence of pleiotropy.

Conclusion: Genetic evidence supports an association between childhood obesity and MS susceptibility, mediated by persistence of obesity into early adulthood but independent of pubertal timing.
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http://dx.doi.org/10.1177/13524585211001781DOI Listing
March 2021

Performance of a Point of Care Test for Detecting IgM and IgG Antibodies Against SARS-CoV-2 and Seroprevalence in Blood Donors and Health Care Workers in Panama.

Front Med (Lausanne) 2021 2;8:616106. Epub 2021 Mar 2.

Centro de Biología Celular y Molecular de las Enfermedades, City of Knowledge, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT-AIP), Panama City, Panama.

Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic, which has reached 28 million cases worldwide in 1 year. The serological detection of antibodies against the virus will play a pivotal role in complementing molecular tests to improve diagnostic accuracy, contact tracing, vaccine efficacy testing, and seroprevalence surveillance. Here, we aimed first to evaluate a lateral flow assay's ability to identify specific IgM and IgG antibodies against SARS-CoV-2 and second, to report the seroprevalence estimates of these antibodies among health care workers and healthy volunteer blood donors in Panama. We recruited study participants between April 30th and July 7th, 2020. For the test validation and performance evaluation, we analyzed serum samples from participants with clinical symptoms and confirmed positive RT-PCR for SARS-CoV-2, and a set of pre-pandemic serum samples. We used two by two table analysis to determine the test positive and negative percentage agreement as well as the Kappa agreement value with a 95% confidence interval. Then, we used the lateral flow assay to determine seroprevalence among serum samples from COVID-19 patients, potentially exposed health care workers, and healthy volunteer donors. Our results show this assay reached a positive percent agreement of 97.2% (95% CI 84.2-100.0%) for detecting both IgM and IgG. The assay showed a Kappa of 0.898 (95%CI 0.811-0.985) and 0.918 (95% CI 0.839-0.997) for IgM and IgG, respectively. The evaluation of serum samples from hospitalized COVID-19 patients indicates a correlation between test sensitivity and the number of days since symptom onset; the highest positive percent agreement [87% (95% CI 67.0-96.3%)] was observed at ≥15 days post-symptom onset (PSO). We found an overall antibody seroprevalence of 11.6% (95% CI 8.5-15.8%) among both health care workers and healthy blood donors. Our findings suggest this lateral flow assay could contribute significantly to implementing seroprevalence testing in locations with active community transmission of SARS-CoV-2.
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http://dx.doi.org/10.3389/fmed.2021.616106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968482PMC
March 2021

Draft Genome Sequence of a Burkholderia cepacia Complex Strain Isolated from a Human Intra-abdominal Abscess.

Microbiol Resour Announc 2021 Mar 18;10(11). Epub 2021 Mar 18.

Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA

complex (Bcc) bacteria are opportunistic pathogens with high transmissibility and mortality. Here, we report the draft genome sequence of a Bcc strain isolated from a deep abscess culture in an immunocompetent patient with no relevant prior medical history.
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http://dx.doi.org/10.1128/MRA.00091-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7975878PMC
March 2021

Apolipoprotein E4 Moderates the Association Between Vascular Risk Factors and Brain Pathology.

Alzheimer Dis Assoc Disord 2021 Mar 16. Epub 2021 Mar 16.

Departments of Molecular and Integrative Physiology Neurology Physical Therapy and Rehabilitation Science, University of Kansas Medical Center University of Kansas Alzheimer's Disease Center, Fairway, KS.

Background: The strongest genetic risk factor for late-onset Alzheimer disease (AD), Apolipoprotein E4 (APOE4), increases cardiovascular disease risk and may also act synergistically with vascular risk factors to contribute to AD pathogenesis. Here, we assess the interaction between APOE4 and vascular risk on cerebrovascular dysfunction and brain pathology.

Methods: This is an observational study of cognitively normal older adults, which included positron emission tomography imaging and vascular risk factors. We measured beat-to-beat blood pressure and middle cerebral artery velocity at rest and during moderate-intensity exercise. Cerebrovascular measures included cerebrovascular conductance index and the cerebrovascular response to exercise.

Results: There was a significant interaction between resting cerebrovascular conductance index and APOE4 carrier status on β-amyloid deposition (P=0.026), with poor conductance in the cerebrovasculature associated with elevated β-amyloid for the APOE4 carriers only. There was a significant interaction between non-high-density lipoprotein cholesterol and APOE4 carrier status (P=0.014), with elevated non-high-density lipoprotein cholesterol predicting a blunted cerebrovascular response to exercise in APOE4 carriers and the opposite relationship in noncarriers.

Conclusions: Both cerebral and peripheral vascular risk factors are preferentially associated with brain pathology in APOE4 carriers. These findings provide insight into pathogenic vascular risk mechanisms and target strategies to potentially delay AD onset.
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http://dx.doi.org/10.1097/WAD.0000000000000442DOI Listing
March 2021

Fruit-Induced Anaphylaxis: Clinical Presentation and Management.

J Allergy Clin Immunol Pract 2021 Mar 13. Epub 2021 Mar 13.

Division of Allergy and Clinical Immunology, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, QC, Canada.

Background: Data are sparse regarding the clinical characteristics and management of fruit-induced anaphylaxis.

Objective: To assess clinical characteristics and management of patients with fruit-induced anaphylaxis and determine factors associated with severe reactions and epinephrine use.

Methods: Over 9 years, children and adults presenting with anaphylaxis to seven emergency departments in four Canadian provinces and patients requiring emergency medical services in Outaouais, Quebec were recruited as part of the Cross-Canada Anaphylaxis Registry. A standardized form documenting symptoms, triggers, and management was collected. Multivariate logistic regression was used to identify factors associated with severe reactions and epinephrine treatment in the pre-hospital setting.

Results: We recruited 250 patients with fruit-induced anaphylaxis, median age 10.2 years (interquartile range, 3.6-23.4 years); 48.8% were male. The most common fruit triggers were kiwi (15.6%), banana (10.8%), and mango (9.2%). Twenty-three patients reported having eczema (9.3%). Epinephrine use was low in both the pre-hospital setting and the emergency department (28.4% and 40.8%, respectively). Severe reactions to fruit were more likely to occur in spring and among those with eczema (adjusted odds ratio [aOR] = 1.12, 95% confidence interval [CI], 1.03-1.23; and 1.17, 95% CI, 1.03-1.34, respectively). Patients with moderate and severe reactions (aOR = 1.23; 95% CI, 1.06-1.43) and those with a known food allergy (aOR = 1.38; 95% CI, 1.24-1.54) were more likely to be treated with epinephrine in the pre-hospital setting.

Conclusions: Severe anaphylaxis to fruit is more frequent in spring. Cross-reactivity to pollens is a potential explanation that should be evaluated further.
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http://dx.doi.org/10.1016/j.jaip.2021.02.055DOI Listing
March 2021

Segregation of functional networks is associated with cognitive resilience in Alzheimer's disease.

Brain 2021 Mar 16. Epub 2021 Mar 16.

Institute for Stroke and Dementia Research, University Hospital, Ludwig-Maximilian-University LMU, Munich, Germany.

Cognitive resilience is an important modulating factor of cognitive decline in Alzheimer's disease, but the functional brain mechanisms that support cognitive resilience remain elusive. Given previous findings in normal aging, we tested the hypothesis that higher segregation of the brain's connectome into distinct functional networks represents a functional mechanism underlying cognitive resilience in Alzheimer's disease. Using resting-state functional MRI, we assessed both resting-state-fMRI global system segregation, i.e. the balance of between-network to within-network connectivity, and the alternate index of modularity Q as predictors of cognitive resilience. We performed all analyses in two independent samples for validation: First, we included 108 individuals with autosomal dominantly inherited Alzheimer's disease and 71 non-carrier controls. Second, we included 156 amyloid-PET positive subjects across the spectrum of sporadic Alzheimer's disease as well as 184 amyloid-negative controls. In the autosomal dominant Alzheimer's disease sample, disease severity was assessed by estimated years from symptom onset. In the sporadic Alzheimer's sample, disease stage was assessed by temporal-lobe tau-PET (i.e. composite across Braak stage I & III regions). In both samples, we tested whether the effect of disease severity on cognition was attenuated at higher levels of functional network segregation. For autosomal dominant Alzheimer's disease, we found higher fMRI-assessed system segregation to be associated with an attenuated effect of estimated years from symptom onset on global cognition (p = 0.007). Similarly, for sporadic Alzheimer's disease patients, higher fMRI-assessed system segregation was associated with less decrement in global cognition (p = 0.001) and episodic memory (p = 0.004) per unit increase of temporal lobe tau-PET. Confirmatory analyses using the alternate index of modularity Q revealed consistent results. In conclusion, higher segregation of functional connections into distinct large-scale networks supports cognitive resilience in Alzheimer's disease.
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http://dx.doi.org/10.1093/brain/awab112DOI Listing
March 2021

Rapid Integrated Healthcare Response for the First US Evacuees from Wuhan, China, During the COVID-19 Pandemic.

Disaster Med Public Health Prep 2020 Dec 22:1-3. Epub 2020 Dec 22.

Riverside University Health System Medical Center, Moreno Valley, CA, USA.

On January 29, 2020, a total of 195 US citizens were evacuated from the coronavirus disease 2019 (COVID-19) epidemic in Wuhan, China, to March Air Reserve Base in Riverside, California, and entered the first federally mandated quarantine in over 50 years. With less than 1-d notice, a multi-disciplinary team from Riverside County and Riverside University Health System in conjunction with local and federal agencies established on-site 24-h medical care and behavioral health support. This report details the coordinated efforts by multiple teams that took place to provide care for the passengers and to support the surrounding community.
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http://dx.doi.org/10.1017/dmp.2020.497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985635PMC
December 2020

An Intergenerational Exploration of Breastfeeding Journeys Through the Lens of African American Mothers and Grandmothers.

J Hum Lact 2021 Mar 9:890334421999304. Epub 2021 Mar 9.

Editor in Chief, Journal of Human Lactation, Honeoye Falls, NY, USA.

Background: Many individuals comprise a nursing mother's social support network. Grandmothers within African American families, historically, have played a vital role in the transmission of culture. Understanding intergenerational perspectives within African American families related to infant feeding and scholarship about breastfeeding is critical, given the breastfeeding patterns among African American women.

Research Aim: To describe intergenerational perspectives within African American families, where the mother has successfully breastfed.

Methods: A prospective, cross-sectional, qualitative design using semi-structured interviews was used. African American nursing mothers and maternal grandmothers ( = 14) residing in the Metro-St. Louis area, who reflected economic and educational diversity, were recruited. Inductive and iterative data analysis, framed by Black Feminist Theory allowed for emerging patterns reflecting the participants' voices.

Results: Three of the six (50%) grandmother participants had breastfed. The majority of the mother participants were married ( 5; 62.5%) and had a college degree ( 4; 50.0%) or a high school diploma ( 1; 12.5%); and four (50.0%) had received the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). Three patterns emerged: (a) intergenerational connections; (b) changes in breastfeeding experiences over time; and (c) going with the flow (referring to the choice to work within the constraints of one's circumstances). Grandmothers supported mothers' breastfeeding decisions; grandmothers who had breastfed benefited from the updated information the mothers provided; and grandmothers who did not breastfeed acquired new breastfeeding knowledge, which informed the ways they supported the mothers.

Conclusion: The intergenerational perspectives surrounding breastfeeding within African American families participating in this study offer future research directions.
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http://dx.doi.org/10.1177/0890334421999304DOI Listing
March 2021

An Outbreak of COVID-19 Among H-2A Temporary Agricultural Workers.

Am J Public Health 2021 Apr;111(4):571-573

Michael Lauzardo and J. Glenn Morris Jr are with the Emerging Pathogens Institute, University of Florida, Gainesville. Nadia R. Kovacevich, Anthony D. Dennis, and Paul D. Myers are with the Alachua County Health Department, Gainesville, FL. Joan Flocks is the with the Center for Governmental Responsibility, Levin College of Law, University of Florida.

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http://dx.doi.org/10.2105/AJPH.2020.306082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958039PMC
April 2021

Combining structured and unstructured data in EMRs to create clinically-defined EMR-derived cohorts.

BMC Med Inform Decis Mak 2021 Mar 8;21(1):91. Epub 2021 Mar 8.

Department of Cardiology, Concord Hospital, Sydney, Australia.

Background: There have been few studies describing how production EMR systems can be systematically queried to identify clinically-defined populations and limited studies utilising free-text in this process. The aim of this study is to provide a generalisable methodology for constructing clinically-defined EMR-derived patient cohorts using structured and unstructured data in EMRs.

Methods: Patients with possible acute coronary syndrome (ACS) were used as an exemplar. Cardiologists defined clinical criteria for patients presenting with possible ACS. These were mapped to data tables within the production EMR system creating seven inclusion criteria comprised of structured data fields (orders and investigations, procedures, scanned electrocardiogram (ECG) images, and diagnostic codes) and unstructured clinical documentation. Data were extracted from two local health districts (LHD) in Sydney, Australia. Outcome measures included examination of the relative contribution of individual inclusion criteria to the identification of eligible encounters, comparisons between inclusion criterion and evaluation of consistency of data extracts across years and LHDs.

Results: Among 802,742 encounters in a 5 year dataset (1/1/13-30/12/17), the presence of an ECG image (54.8% of encounters) and symptoms and keywords in clinical documentation (41.4-64.0%) were used most often to identify presentations of possible ACS. Orders and investigations (27.3%) and procedures (1.4%), were less often present for identified presentations. Relevant ICD-10/SNOMED CT codes were present for 3.7% of identified encounters. Similar trends were seen when the two LHDs were examined separately, and across years.

Conclusions: Clinically-defined EMR-derived cohorts combining structured and unstructured data during cohort identification is a necessary prerequisite for critical validation work required for development of real-time clinical decision support and learning health systems.
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http://dx.doi.org/10.1186/s12911-021-01441-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938556PMC
March 2021

Association between Perceived Discrimination and Vaping among College Students.

Subst Use Misuse 2021 7;56(5):738-741. Epub 2021 Mar 7.

Psychology Department, The University of Memphis, Memphis, Tennessee, USA.

Background: Perceived discrimination has been associated with a higher prevalence of e-cigarette use among adult samples. However, little is understood about the relationship between discrimination and various vaping behaviors among college students. : College students completed an online survey about e-cigarette use ( = 488; 73.2% women; 52.7% White, 30.5% Black/African American, 6.1% Asian, 5.3% other races, 3.9% Multiracial). Participants completed the Everyday Discrimination Scale and identified which of their identities discrimination was most directed toward. Regressions, controlling for significant covariates of outcomes, examined discrimination in relation to e-cigarette ever use, current use, and frequency of use. : A higher discrimination score predicted greater odds of ever vaping compared with never use  = 1.21, =.03). Controlling for race (=.003), greater discrimination was related to increased likelihood of established vaping (100+ times) versus lighter levels of use ( = 1.22, =.04). Discrimination was not associated with likelihood of current vaping (>.05). Among e-cigarette users, greater perceived discrimination was related to an increased time spent vaping per day ( =1.69,  = 0.204, =.05). Greater perceived discrimination was associated with more frequent vaping among college students. Current results extend previous findings by suggesting that among college e-cigarette users, those who experience discrimination are more likely to use these products frequently rather than experimentally. Findings can inform the identification and development of resources for students experiencing discrimination to prevent the uptake of e-cigarette use.
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http://dx.doi.org/10.1080/10826084.2021.1887250DOI Listing
March 2021