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  1. Article ; Online: Retrospective Multicenter Cohort Study on Safety and Electroencephalographic Response to Lacosamide for Neonatal Seizures.

    Kaur, Moninder / Utidjian, Levon / Abend, Nicholas S / Dickinson, Kimberley / Roebling, Robert / McDonald, Jill / Maltenfort, Mitchell G / Foskett, Nadia / Elmoufti, Sami / Guerriero, Rejean M / Jain, Badal G / Pajor, Nathan M / Rao, Suchitra / Shellhaas, Renée A / Slaughter, Laurel / Forrest, Christopher B

    Pediatric neurology

    2024  Volume 155, Page(s) 18–25

    Abstract: Background: There is growing evidence supporting the safety and effectiveness of lacosamide in older children. However, minimal data are available for neonates. We aimed to determine the incidence of adverse events associated with lacosamide use and ... ...

    Abstract Background: There is growing evidence supporting the safety and effectiveness of lacosamide in older children. However, minimal data are available for neonates. We aimed to determine the incidence of adverse events associated with lacosamide use and explore the electroencephalographic seizure response to lacosamide in neonates.
    Methods: A retrospective cohort study was conducted using data from seven pediatric hospitals from January 2009 to February 2020. For safety outcomes, neonates were followed for ≤30 days from index date. Electroencephalographic response of lacosamide was evaluated based on electroencephalographic reports for ≤3 days.
    Results: Among 47 neonates, 98% received the first lacosamide dose in the intensive care units. During the median follow-up of 12 days, 19% of neonates died, and the crude incidence rate per 1000 patient-days (95% confidence interval) of the adverse events by diagnostic categories ranged from 2.8 (0.3, 10.2) for blood or lymphatic system disorders and nervous system disorders to 10.5 (4.2, 21.6) for cardiac disorders. Electroencephalographic seizures were observed in 31 of 34 patients with available electroencephalographic data on the index date. There was seizure improvement in 29% of neonates on day 1 and also in 29% of neonates on day 2. On day 3, there was no change in 50% of neonates and unknown change in 50% of neonates.
    Conclusions: The results are reassuring regarding the safety of lacosamide in neonates. Although some neonates had fewer seizures after lacosamide administration, the lack of a comparator arm and reliance on qualitative statements in electroencephalographic reports limit the preliminary efficacy results.
    Language English
    Publishing date 2024-03-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 639164-3
    ISSN 1873-5150 ; 0887-8994
    ISSN (online) 1873-5150
    ISSN 0887-8994
    DOI 10.1016/j.pediatrneurol.2024.03.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Efficacy and hazards of 425 nm oral cavity light dosing to inactivate SARS-CoV-2.

    Stockslager, Max A / Kocher, Jacob F / Arwood, Leslee / Stasko, Nathan / McDonald, Rebecca A / Tapsak, Mark A / Emerson, David

    Journal of dentistry

    2022  Volume 123, Page(s) 104203

    Abstract: Objective: Using a battery of preclinical tests to support development of a light-based treatment for COVID-19, establish a range of 425 nm light doses that are non-hazardous to the tissues of the oral cavity and assess whether a 425 nm light dose in ... ...

    Abstract Objective: Using a battery of preclinical tests to support development of a light-based treatment for COVID-19, establish a range of 425 nm light doses that are non-hazardous to the tissues of the oral cavity and assess whether a 425 nm light dose in this non-hazardous range can inactivate SARS-CoV-2 in artificial saliva.
    Methods: The potential hazards to oral tissues associated with a range of acute 425 nm light doses were assessed using a battery of four preclinical tests: (1) cytotoxicity, using well-differentiated human large airway and buccal epithelial models; (2) toxicity to commensal oral bacteria, using a panel of model organisms; (3) light-induced histopathological changes, using ex vivo porcine esophageal tissue, and (4) thermal damage, by dosing the oropharynx of intact porcine head specimens. Then, 425 nm light doses established as non-hazardous using these tests were evaluated for their potential to inactivate SARS-CoV-2 in artificial saliva.
    Results: A dose range was established at which 425 nm light is not cytotoxic in well-differentiated human large airway or buccal epithelial models, is not cytotoxic to a panel of commensal oral bacteria, does not induce histopathological damage in ex vivo porcine esophageal tissue, and does not induce thermal damage to the oropharynx of intact porcine head specimens. Using these tests, no hazards were observed for 425 nm light doses less than 63 J/cm
    Conclusion: Preclinical hazard assessments and SARS-CoV-2 inactivation efficacy testing were combined to guide the development of a 425 nm light-based treatment for COVID-19.
    Clinical significance: The process used here to evaluate the potential hazards associated with 425 nm acute light dosing of the oral cavity to treat COVID-19 can be extended to other wavelengths, anatomical targets, and therapeutic applications to accelerate the development of novel photomedicine treatments.
    MeSH term(s) Animals ; COVID-19 ; Humans ; Mouth ; Oropharynx ; SARS-CoV-2 ; Saliva ; Saliva, Artificial ; Swine
    Chemical Substances Saliva, Artificial
    Language English
    Publishing date 2022-06-17
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 186068-9
    ISSN 1879-176X ; 0300-5712
    ISSN (online) 1879-176X
    ISSN 0300-5712
    DOI 10.1016/j.jdent.2022.104203
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: SAD-1 kinase controls presynaptic phase separation by relieving SYD-2/Liprin-α autoinhibition.

    McDonald, Nathan A / Tao, Li / Dong, Meng-Qiu / Shen, Kang

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Neuronal development orchestrates the formation of an enormous number of synapses that connect the nervous system. In developing presynapses, the core active zone structure has been found to assemble through a liquid-liquid phase separation. Here, we ... ...

    Abstract Neuronal development orchestrates the formation of an enormous number of synapses that connect the nervous system. In developing presynapses, the core active zone structure has been found to assemble through a liquid-liquid phase separation. Here, we find that the phase separation of SYD-2/Liprin-α, a key active zone scaffold, is controlled by phosphorylation. Using phosphoproteomics, we identify the SAD-1 kinase to phosphorylate SYD-2 and a number of other substrates. Presynaptic assembly is impaired in
    Language English
    Publishing date 2023-06-12
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.06.12.544643
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: SAD-1 kinase controls presynaptic phase separation by relieving SYD-2/Liprin-α autoinhibition.

    McDonald, Nathan A / Tao, Li / Dong, Meng-Qiu / Shen, Kang

    PLoS biology

    2023  Volume 21, Issue 12, Page(s) e3002421

    Abstract: Neuronal development orchestrates the formation of an enormous number of synapses that connect the nervous system. In developing presynapses, the core active zone structure has been found to assemble through liquid-liquid phase separation. Here, we find ... ...

    Abstract Neuronal development orchestrates the formation of an enormous number of synapses that connect the nervous system. In developing presynapses, the core active zone structure has been found to assemble through liquid-liquid phase separation. Here, we find that the phase separation of Caenorhabditis elegans SYD-2/Liprin-α, a key active zone scaffold, is controlled by phosphorylation. We identify the SAD-1 kinase as a regulator of SYD-2 phase separation and determine presynaptic assembly is impaired in sad-1 mutants and increased by overactivation of SAD-1. Using phosphoproteomics, we find SAD-1 phosphorylates SYD-2 on 3 sites that are critical to activate phase separation. Mechanistically, SAD-1 phosphorylation relieves a binding interaction between 2 folded domains in SYD-2 that inhibits phase separation by an intrinsically disordered region (IDR). We find synaptic cell adhesion molecules localize SAD-1 to nascent synapses upstream of active zone formation. We conclude that SAD-1 phosphorylates SYD-2 at developing synapses, activating its phase separation and active zone assembly.
    MeSH term(s) Animals ; Presynaptic Terminals/metabolism ; Caenorhabditis elegans Proteins/metabolism ; Synapses/metabolism ; Caenorhabditis elegans/metabolism ; Intercellular Signaling Peptides and Proteins/metabolism
    Chemical Substances Caenorhabditis elegans Proteins ; SYD-2 protein, C elegans ; Intercellular Signaling Peptides and Proteins
    Language English
    Publishing date 2023-12-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2126776-5
    ISSN 1545-7885 ; 1544-9173
    ISSN (online) 1545-7885
    ISSN 1544-9173
    DOI 10.1371/journal.pbio.3002421
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Scurvy Presenting with Severe Skin Changes.

    McDonald, Nathan A / Martin, Victoria J / Daniel, Nicholas J

    The Journal of emergency medicine

    2022  Volume 63, Issue 1, Page(s) 111–114

    MeSH term(s) Ascorbic Acid/therapeutic use ; Humans ; Scurvy/complications ; Scurvy/diagnosis ; Skin
    Chemical Substances Ascorbic Acid (PQ6CK8PD0R)
    Language English
    Publishing date 2022-08-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 605559-x
    ISSN 0736-4679
    ISSN 0736-4679
    DOI 10.1016/j.jemermed.2022.05.022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Author Correction: Assembly of synaptic active zones requires phase separation of scaffold molecules.

    McDonald, Nathan A / Fetter, Richard D / Shen, Kang

    Nature

    2021  Volume 595, Issue 7866, Page(s) E35

    Language English
    Publishing date 2021-06-18
    Publishing country England
    Document type Published Erratum
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-021-03340-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Finding functions of phase separation in the presynapse.

    McDonald, Nathan A / Shen, Kang

    Current opinion in neurobiology

    2021  Volume 69, Page(s) 178–184

    Abstract: Synapses are the basic units of neuronal communication. Understanding how synapses assemble and function is therefore essential to understanding nervous systems. Decades of study have identified many molecular components and functional mechanisms of ... ...

    Abstract Synapses are the basic units of neuronal communication. Understanding how synapses assemble and function is therefore essential to understanding nervous systems. Decades of study have identified many molecular components and functional mechanisms of synapses. Recently, an additional level of synaptic protein organization has been identified: phase separation. In the presynapse, components of the central active zone and a synaptic vesicle-clustering factor have been shown to form liquid-liquid phase-separated condensates or hydrogels. New in vivo functional studies have directly tested how phase separation impacts both synapse formation and function. Here, we review this emerging evidence for in vivo functional roles of phase separation at the presynapse and discuss future functional studies necessary to understand its complexity.
    MeSH term(s) Neurogenesis ; Neurons ; Synapses ; Synaptic Vesicles
    Language English
    Publishing date 2021-05-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1078046-4
    ISSN 1873-6882 ; 0959-4388
    ISSN (online) 1873-6882
    ISSN 0959-4388
    DOI 10.1016/j.conb.2021.04.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Emergency physician resource utilization varies by years of experience.

    McDonald, Nathan / Antkowiak, Peter S / Burke, Ryan / Chiu, David T / Stenson, Bryan A / Sanchez, Leon D

    Journal of the American College of Emergency Physicians open

    2024  Volume 5, Issue 2, Page(s) e13162

    Abstract: Objectives: One of the most pivotal decisions an emergency physician (EP) makes is whether to admit or discharge a patient. The emergency department (ED) work-up leading to this decision involves several resource-intensive tests. Previous studies have ... ...

    Abstract Objectives: One of the most pivotal decisions an emergency physician (EP) makes is whether to admit or discharge a patient. The emergency department (ED) work-up leading to this decision involves several resource-intensive tests. Previous studies have demonstrated significant differences in EP resource utilization, measured by lab tests, advanced imaging (magnetic resonance imaging [MRI], computed tomography [CT], ultrasound), consultations, and propensity to admit a patient. However, how an EP's years of experience may impact their resource utilization and propensity to admit patients has not been well characterized. This study seeks to better understand how EPs' years of experience, post-residency, relates to their use of advanced imaging and patient disposition.
    Methods: Ten years of ED visits were analyzed for this study from a single, academic tertiary care center in the urban Northeast United States. The primary outcomes were utilization of advanced imaging during the visit (CT, MRI, or formal ultrasound) and whether the patient was admitted. EP years of experience was categorized into 0-2 years, 3-5 years, 6-8 years, 9-11 years, and 12 or more years. Patient age, sex, Emergency Severity Index (ESI), and the attending EP's years of experience were collected. The relationship between EP years of experience and each outcome was assessed with a linear mixed model with a random effect for provider and patient age, sex, and ESI as covariates.
    Results: A total of 460,937 visits seen by 65 EPs were included in the study. Over one-third (37.6%) of visits had an advanced imaging study ordered and nearly half (49.5%) resulted in admission. Compared to visits with EPs with 0-2 years of experience, visits with EPs with 3-5 or 6-8 years of experience had significantly lower odds of advanced imaging occurring. Visits seen by EPs with more than 2 years of experience had lower odds of admission than visits by EPs with 0-2 years of experience.
    Conclusion: More junior EPs tend to order more advanced imaging studies and have a higher propensity to admit patients. This may be due to less comfort in decision-making without advanced imaging or a lower risk tolerance. Conversely, the additional clinical experience of the most senior EPs, with greater than 9 years of experience, likely impacts their resource utilization patterns such that their use of advanced imaging does not significantly differ from the most junior EPs.
    Language English
    Publishing date 2024-04-23
    Publishing country United States
    Document type Journal Article
    ISSN 2688-1152
    ISSN (online) 2688-1152
    DOI 10.1002/emp2.13162
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Hybrid assemblies of microbiome

    Lind, Abigail L / McDonald, Nathan A / Gerrick, Elias R / Bhatt, Ami S / Pollard, Katherine S

    bioRxiv : the preprint server for biology

    2023  

    Abstract: The most prevalent microbial eukaryote in the human gut ... ...

    Abstract The most prevalent microbial eukaryote in the human gut is
    Language English
    Publishing date 2023-11-20
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.11.20.567959
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Inactivation of the Hippo tumor suppressor pathway promotes melanoma

    Marc A. Vittoria / Nathan Kingston / Kristyna Kotynkova / Eric Xia / Rui Hong / Lee Huang / Shayna McDonald / Andrew Tilston-Lunel / Revati Darp / Joshua D. Campbell / Deborah Lang / Xiaowei Xu / Craig J. Ceol / Xaralabos Varelas / Neil J. Ganem

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 17

    Abstract: Activating mutations of BRAF alone are inadequate to drive melanoma formation. Here the authors show that activation of Hippo signalling by oncogenic BRAF represents an additional safeguard to limit BRAF-dependent human melanocyte growth and melanoma ... ...

    Abstract Activating mutations of BRAF alone are inadequate to drive melanoma formation. Here the authors show that activation of Hippo signalling by oncogenic BRAF represents an additional safeguard to limit BRAF-dependent human melanocyte growth and melanoma formation.
    Keywords Science ; Q
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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