Scopus list of publications for November 26, 2023
Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations
(2023) Nature Communications, 14 (1), art. no. 7452, .
Zhao, S.a b , Mekbib, K.Y.b c , van der Ent, M.A.d , Allington, G.b e , Prendergast, A.f , Chau, J.E.g , Smith, H.b c , Shohfi, J.b c , Ocken, J.c , Duran, D.h , Furey, C.G.c i j , Hao, L.T.b , Duy, P.Q.k , Reeves, B.C.c , Zhang, J.l , Nelson-Williams, C.l , Chen, D.d , Li, B.m , Nottoli, T.n , Bai, S.n , Rolle, M.b , Zeng, X.g o , Dong, W.l o , Fu, P.-Y.a , Wang, Y.-C.a , Mane, S.l , Piwowarczyk, P.p , Fehnel, K.P.p , See, A.P.p , Iskandar, B.J.q , Aagaard-Kienitz, B.q r , Moyer, Q.J.b , Dennis, E.b , Kiziltug, E.b , Kundishora, A.J.c , DeSpenza, T., Jr.c , Greenberg, A.B.W.b , Kidanemariam, S.M.s , Hale, A.T.t , Johnston, J.M.t , Jackson, E.M.u , Storm, P.B.v w , Lang, S.-S.v w , Butler, W.E.b , Carter, B.S.b , Chapman, P.b , Stapleton, C.J.b , Patel, A.B.b , Rodesch, G.x y , Smajda, S.y , Berenstein, A.z , Barak, T.c , Erson-Omay, E.Z.c , Zhao, H.l m , Moreno-De-Luca, A.aa , Proctor, M.R.p , Smith, E.R.p , Orbach, D.B.p ab , Alper, S.L.ac , Nicoli, S.l ad ae , Boggon, T.J.g ad , Lifton, R.P.o , Gunel, M.c , King, P.D.d , Jin, S.C.a af , Kahle, K.T.b c ag ah
a Department of Genetics, Washington University School of Medicine, St. Louis, MO, United States
b Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
c Department of Neurosurgery, Yale School of Medicine, New Haven, CT, United States
d Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, United States
e Department of Pathology, Yale School of Medicine, New Haven, CT, United States
f Yale Zebrafish Research Core, Yale School of Medicine, New Haven, CT, United States
g Department of Molecular Biophysics and Biochemistry, Yale School of Medicine, New Haven, CT, United States
h Department of Neurosurgery, University of Mississippi Medical Center, Jackson, MS, United States
i Department of Neurosurgery, Barrow Neurological Institute, Phoenix, AZ, United States
j Ivy Brain Tumor Center, Department of Translational Neuroscience, Barrow Neurological Institute, Phoenix, AZ, United States
k Department of Neurosurgery, University of Virginia School of Medicine, Charlottesville, VA, United States
l Department of Genetics, Yale School of Medicine, New Haven, CT, United States
m Department of Biostatistics, Yale School of Public Health, New Haven, CT, United States
n Yale Genome Editing Center, Department of Comparative Medicine, Yale School of Medicine, New Haven, CT, United States
o Laboratory of Human Genetics and Genomics, The Rockefeller University, New York, NY, United States
p Department of Neurosurgery, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
q Department of Neurological Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
r Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
s Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada
t Department of Neurosurgery, University of Alabama School of Medicine, Birmingham, AL, United States
u Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States
v Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia, PA, United States
w Division of Neurosurgery, Children’s Hospital of Philadelphia, Philadelphia, PA, United States
x Service de Neuroradiologie Diagnostique et Thérapeutique, Hôpital Foch, Suresnes, France
y Department of Interventional Neuroradiology, Hôpital Fondation A. de Rothschild, Paris, France
z Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY, United States
aa Department of Radiology, Autism & Developmental Medicine Institute, Genomic Medicine Institute, Geisinger, Danville, PA, United States
ab Department of Neurointerventional Radiology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
ac Division of Nephrology and Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, and Department of Medicine, Harvard Medical School, Boston, MA, United States
ad Department of Pharmacology, Yale School of Medicine, New Haven, CT, United States
ae Yale Cardiovascular Research Center, Department of Internal Medicine, Section of Cardiology, Yale School of Medicine, New Haven, CT, United States
af Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
ag Division of Genetics and Genomics, Boston Children’s Hospital, Boston, MA, United States
ah Broad Institute of MIT and Harvard, Cambridge, MA, United States
Abstract
To elucidate the pathogenesis of vein of Galen malformations (VOGMs), the most common and most severe of congenital brain arteriovenous malformations, we performed an integrated analysis of 310 VOGM proband-family exomes and 336,326 human cerebrovasculature single-cell transcriptomes. We found the Ras suppressor p120 RasGAP (RASA1) harbored a genome-wide significant burden of loss-of-function de novo variants (2042.5-fold, p = 4.79 x 10−7). Rare, damaging transmitted variants were enriched in Ephrin receptor-B4 (EPHB4) (17.5-fold, p = 1.22 x 10−5), which cooperates with p120 RasGAP to regulate vascular development. Additional probands had damaging variants in ACVRL1, NOTCH1, ITGB1, and PTPN11. ACVRL1 variants were also identified in a multi-generational VOGM pedigree. Integrative genomic analysis defined developing endothelial cells as a likely spatio-temporal locus of VOGM pathophysiology. Mice expressing a VOGM-specific EPHB4 kinase-domain missense variant (Phe867Leu) exhibited disrupted developmental angiogenesis and impaired hierarchical development of arterial-capillary-venous networks, but only in the presence of a “second-hit” allele. These results illuminate human arterio-venous development and VOGM pathobiology and have implications for patients and their families. © 2023, The Author(s).
Funding details
CTSA1405
National Institutes of HealthNIH5U54HG006504, K12 228168, R01 NS109358, R01 NS111029-01A1
Howard Hughes Medical InstituteHHMI2R01 HL120888, R01 HL146352
National Institute of General Medical SciencesNIGMST32GM007205
March of Dimes FoundationMDF
National Center for Advancing Translational SciencesNCATSR00HL143036-02, TL1 TR001864
Children’s Discovery InstituteCDICDI-FR-2021-926
Rudi Schulte Research InstituteRSRIR01 117609
Document Type: Article
Publication Stage: Final
Source: Scopus
Contribution of macrophages to neural survival and intracochlear tissue remodeling responses following cochlear implantation
(2023) Journal of Neuroinflammation, 20 (1), art. no. 266, .
Rahman, M.T.a , Mostaert, B.J.a , Hunger, B.a , Saha, U.a , Claussen, A.D.a , Razu, I.a , Nasrin, F.a , Khan, N.A.a , Eckard, P.a , Coleman, S.b , Oleson, J.b , Kirk, J.R.c , Hirose, K.d , Hansen, M.R.a
a Department of Otolaryngology-Head and Neck Surgery, The University of Iowa, Iowa City, IA 52242, United States
b Department of Biostatistics, The University of Iowa, Iowa City, IA, United States
c Cochlear Limited, Sydney, Australia
d Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, United States
Abstract
Background: Cochlear implants (CIs) restore hearing to deafened patients. The foreign body response (FBR) following cochlear implantation (post-CI) comprises an infiltration of macrophages, other immune and non-immune cells, and fibrosis into the scala tympani, a space that is normally devoid of cells. This FBR is associated with negative effects on CI outcomes including increased electrode impedances and loss of residual acoustic hearing. This study investigates the extent to which macrophage depletion by an orally administered CSF-1R specific kinase (c-FMS) inhibitor, PLX-5622, modulates the tissue response to CI and neural health. Main text: 10- to 12-week-old CX3CR1 + /GFP Thy1 + /YFP mice on C57BL/6J/B6 background was fed chow containing 1200 mg/kg PLX5622 or control chow for the duration of the study. 7 days after starting the diet, 3-channel cochlear implants were implanted in the ear via the round window. Serial impedance and neural response telemetry (NRT) measurements were acquired throughout the study. Electric stimulation began 7 days post-CI until 28 days post-CI for 5 h/day, 5 days/week, with programming guided by NRT and behavioral responses. Cochleae harvested at 10, 28 or 56 days post-CI were cryosectioned and labeled with an antibody against α-smooth muscle actin (α-SMA) to identify myofibroblasts and quantify the fibrotic response. Using IMARIS image analysis software, the outlines of scala tympani, Rosenthal canal, modiolus, and lateral wall for each turn were traced manually to measure region volume. The density of nuclei, CX3CR1 + macrophages, Thy1 + spiral ganglion neuron (SGN) numbers, and the ratio of the α-SMA + volume/scala tympani volume were calculated. Cochlear implantation in control diet subjects caused infiltration of cells, including macrophages, into the cochlea. Fibrosis was evident in the scala tympani adjacent to the electrode array. Mice fed PLX5622 chow showed reduced macrophage infiltration throughout the implanted cochleae across all time points. However, scala tympani fibrosis was not reduced relative to control diet subjects. Further, mice treated with PLX5622 showed increased electrode impedances compared to controls. Finally, treatment with PLX5622 decreased SGN survival in implanted and contralateral cochleae. Conclusion: The data suggest that macrophages play an important role in modulating the intracochlear tissue response following CI and neural survival. © 2023, The Author(s).
Author Keywords
Biomaterials; Cochlear implant; Fibrosis; Foreign body response; Inflammation
Document Type: Article
Publication Stage: Final
Source: Scopus
Quantitative Analysis of S1PR1 Expression in the Postmortem Multiple Sclerosis Central Nervous System
(2023) ACS Chemical Neuroscience, 14 (22), pp. 4039-4050.
Jiang, H.a , Zhou, C.a , Qiu, L.a , Gropler, R.J.a , Brier, M.R.a b , Wu, G.F.b , Cross, A.H.b , Perlmutter, J.S.a b , Benzinger, T.L.S.a c , Tu, Z.a
a Department of Radiology, Washington University School of Medicine, St Louis, MO 63110, United States
b Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, United States
c Department of Neurological Surgery, Washington University School of Medicine, St Louis, MO 63110, United States
Abstract
Multiple sclerosis (MS) is an immune-mediated disease that is characterized by demyelination and inflammation in the central nervous system (CNS). Previous studies demonstrated that sphingosine-1-phosphate receptor (S1PR) modulators effectively inhibit S1PR1 in immune cell trafficking and reduce entry of pathogenic cells into the CNS. Studies have also implicated a nonimmune, inflammatory role of S1PR1 within the CNS in MS. In this study, we explored the expression of S1PR1 in the development and progression of demyelinating pathology of MS by quantitative assessment of S1PR1 expression using our S1PR1-specific radioligand, [3H]CS1P1, in the postmortem human CNS tissues including cortex, cerebellum, and spinal cord of MS cases and age- and sex-matched healthy cases. Immunohistochemistry with whole slide scanning for S1PR1 and various myelin proteins was also performed. Autoradiographic analysis using [3H]CS1P1 showed that the expression of S1PR1 was statistically significantly elevated in lesions compared to nonlesion regions in the MS cases, as well as normal healthy controls. The uptake of [3H]CS1P1 in the gray matter and nonlesion white matter did not significantly differ between healthy and MS CNS tissues. Saturation autoradiography analysis showed an increased binding affinity (Kd) of [3H]CS1P1 to S1PR1 in both gray matter and white matter of MS brains compared to healthy brains. Our blocking study using NIBR-0213, a S1PR1 antagonist, indicated [3H]CS1P1 is highly specific to S1PR1. Our findings demonstrated the activation of S1PR1 and an increased uptake of [3H]CS1P1 in the lesions of MS CNS. In summary, our quantitative autoradiography analysis using [3H]CS1P1 on human postmortem tissues shows the feasibility of novel imaging strategies for MS by targeting S1PR1.
Author Keywords
autoradiograph; central nervous system; lesion; multiple sclerosis; S1PR1; [3H]CS1P1
Document Type: Article
Publication Stage: Final
Source: Scopus
Enzymatic vitamin A2 production enables red-shifted optogenetics
(2023) Pflugers Archiv European Journal of Physiology, .
Gerhards, J.a , Volkov, L.I.b , Corbo, J.C.b , Malan, D.a , Sasse, P.a
a Institute of Physiology I, Medical Faculty, University of Bonn, Bonn, 53125, Germany
b Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, United States
Abstract
Optogenetics is a technology using light-sensitive proteins to control signaling pathways and physiological processes in cells and organs and has been applied in neuroscience, cardiovascular sciences, and many other research fields. Most commonly used optogenetic actuators are sensitive to blue and green light, but red-light activation would allow better tissue penetration and less phototoxicity. Cyp27c1 is a recently deorphanized cytochrome P450 enzyme that converts vitamin A1 to vitamin A2, thereby red-shifting the spectral sensitivity of visual pigments and enabling near-infrared vision in some aquatic species. Here, we investigated the ability of Cyp27c1-generated vitamin A2 to induce a shift in spectral sensitivity of the light-gated ion channel Channelrhodopsin-2 (ChR2) and its red-shifted homolog ReaChR. We used patch clamp to measure photocurrents at specific wavelengths in HEK 293 cells expressing ChR2 or ReaChR. Vitamin A2 incubation red-shifted the wavelength for half-maximal currents (λ50%) by 6.8 nm for ChR2 and 12.4 nm for ReaChR. Overexpression of Cyp27c1 in HEK 293 cells showed mitochondrial localization, and HPLC analysis showed conversion of vitamin A1 to vitamin A2. Notably, the λ50% of ChR2 photocurrents was red-shifted by 10.5 nm, and normalized photocurrents at 550 nm were about twofold larger with Cyp27c1 expression. Similarly, Cyp27c1 shifted the λ50% of ReaChR photocurrents by 14.3 nm and increased normalized photocurrents at 650 nm almost threefold. Since vitamin A2 incubation is not a realistic option for in vivo applications and expression of Cyp27c1 leads to a greater red-shift in spectral sensitivity, we propose co-expression of this enzyme as a novel strategy for red-shifted optogenetics. © 2023, The Author(s).
Author Keywords
ChR2; Cyp27c1; Optogenetics; ReaChR; Vitamin A2
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Sex-specific genetic architecture of late-life memory performance
(2023) Alzheimer’s and Dementia, .
Eissman, J.M.a b , Archer, D.B.a b , Mukherjee, S.c , Lee, M.L.c , Choi, S.-E.c , Scollard, P.c , Trittschuh, E.H.d e , Mez, J.B.f , Bush, W.S.g , Kunkle, B.W.h , Naj, A.C.i j , Gifford, K.A.a , Cuccaro, M.L.h , Cruchaga, C.k l , Pericak-Vance, M.A.h , Farrer, L.A.f m n , Wang, L.-S.j , Schellenberg, G.D.j , Mayeux, R.P.o p q , Haines, J.L.g , Jefferson, A.L.a , Kukull, W.A.r , Keene, C.D.s , Saykin, A.J.t u , Thompson, P.M.v , Martin, E.R.h , Bennett, D.A.w , Barnes, L.L.w , Schneider, J.A.w , Crane, P.K.c , Hohman, T.J.a b , Dumitrescu, L.a b
a Vanderbilt Memory & Alzheimer’s Center, Vanderbilt University Medical Center, Nashville, TN, United States
b Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, United States
c Department of Medicine, University of Washington, Seattle, WA, United States
d Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, United States
e VA Puget Sound Health Care System, GRECC, Seattle, WA, United States
f Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, United States
g Cleveland Institute for Computational Biology, Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, United States
h John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, United States
i Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States
j Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States
k Department of Psychiatry, Washington University School of Medicine, St Louis, MO, United States
l NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO, United States
m Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States
n Department of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA, United States
o Columbia University, New York, NY, United States
p The Taub Institute for Research on Alzheimer’s Disease and The Aging Brain, Columbia University, New York, NY, United States
q The Institute for Genomic Medicine, Columbia University Medical Center and The New York Presbyterian Hospital, New York, NY, United States
r Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, United States
s Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States
t Department of Radiology and Imaging Services, Indiana University School of Medicine, Indianapolis, IN, United States
u Department of Medical and Molecular Genetics, School of Medicine, Indiana University, Indianapolis, IN, United States
v Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
w Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL, United States
Abstract
BACKGROUND: Women demonstrate a memory advantage when cognitively healthy yet lose this advantage to men in Alzheimer’s disease. However, the genetic underpinnings of this sex difference in memory performance remain unclear. METHODS: We conducted the largest sex-aware genetic study on late-life memory to date (Nmales = 11,942; Nfemales = 15,641). Leveraging harmonized memory composite scores from four cohorts of cognitive aging and AD, we performed sex-stratified and sex-interaction genome-wide association studies in 24,216 non-Hispanic White and 3367 non-Hispanic Black participants. RESULTS: We identified three sex-specific loci (rs67099044—CBLN2, rs719070—SCHIP1/IQCJ-SCHIP), including an X-chromosome locus (rs5935633—EGL6/TCEANC/OFD1), that associated with memory. Additionally, we identified heparan sulfate signaling as a sex-specific pathway and found sex-specific genetic correlations between memory and cardiovascular, immune, and education traits. DISCUSSION: This study showed memory is highly and comparably heritable across sexes, as well as highlighted novel sex-specific genes, pathways, and genetic correlations that related to late-life memory. Highlights: Demonstrated the heritable component of late-life memory is similar across sexes. Identified two genetic loci with a sex-interaction with baseline memory. Identified an X-chromosome locus associated with memory decline in females. Highlighted sex-specific candidate genes and pathways associated with memory. Revealed sex-specific shared genetic architecture between memory and complex traits. © 2023 The Authors. Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association.
Author Keywords
aging; Alzheimer’s disease; cognition; endophenotypes; Genomics; GWAS; memory; sex differences; sex-specific
Funding details
R01AG36836, R01AG48015, RC2AG036547, RF1AG57473, U01AG32984, U01AG46152, U01AG46161, U01AG61356
P20 AG068024, P20 AG068053, P20 AG068077, P20 AG068082, P30 AG062421, P30 AG062422, P30 AG062429, P30 AG062677, P30 AG062715, P30 AG066444, P30 AG066462, P30 AG066468, P30 AG066506, P30 AG066507, P30 AG066508, P30 AG066509, P30 AG066511, P30 AG066512, P30 AG066514, P30 AG066515, P30 AG066518, P30 AG066519, P30 AG066530, P30 AG066546, P30 AG072931, P30 AG072946, P30 AG072947, P30 AG072958, P30 AG072959, P30 AG072972, P30 AG072973, P30 AG072975, P30 AG072976, P30 AG072977, P30 AG072978, P30 AG072979, P30 AG079280
R01 AG22018, R01 AG42210
U54AG052427
P30 AG010161, R01 AG01101, R01 AG019085, R01 AG030146, R01 AG17917, RC2 AG036650, U01 AG06781, U01 HG004610, U24 AG21886
U24AG041689
R01 AG017917
National Institutes of HealthNIHP01AG026276, P01AG03991, P30AG066444, P30AG066462, R01AG044546, R01AG064614, R01AG064877, RF1AG053303, RF1AG054080, RF1AG058501, U01AG052410, U01AG058922, U01‐AG024904, U24 AG072122
U.S. Department of DefenseDODW81XWH‐12‐2‐0012
National Institute on AgingNIAP30 AG10161, P30AG72975, R01 AG059716, R01 AG15819, R01AG17917, R01AG22018, R01AG30146, R01AG36042, RC2AG036528, U01 AG006781, U01 AG068057, U01AG032984, U19 AG066567, U24 AG056270, U24 AG074855
National Institute of Biomedical Imaging and BioengineeringNIBIB
Alzheimer’s AssociationAA
Alzheimer’s Drug Discovery FoundationADDF
Illinois Department of Public HealthIDPH
Biogen
AbbVie
University of Pennsylvania
Alzheimer’s Disease Neuroimaging InitiativeADNIU01 AG024904
BioClinica
Hope Center for Neurological Disorders
Translational Genomics Research InstituteTGEN
National Alzheimer’s Coordinating CenterNACCU01 AG016976
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
The Negative Effects of Travel on Student Athletes Through Sleep and Circadian Disruption
(2023) Journal of Biological Rhythms, .
Heller, H.C.a , Herzog, E.b , Brager, A.c , Poe, G.d , Allada, R.e , Scheer, F.f , Carskadon, M.g , de la Iglesia, H.O.h , Jang, R.d , Montero, A.i , Wright, K.j , Mouraine, P.k , Walker, M.P.l , Goel, N.m , Hogenesch, J.n , Van Gelder, R.N.o , Kriegsfeld, L.l , Mah, C.k , Colwell, C.p , Zeitzer, J.k , Grandner, M.q , Jackson, C.L.r s , Roxanne Prichard, J.t , Kay, S.A.u , Paul, K.v
a Department of Biology, Stanford University, StanfordCA, United States
b Department of Biology, Washington University, St. Louis, MO, United States
c U.S. Army John F. Kennedy Special Warfare Center and School, Fort Bragg, NC, United States
d UCLA Brain Research Institute, Los Angeles, CA, United States
e Department of Neurobiology, Northwestern University, Chicago, IL, United States
f Medical Chronobiology Program, Brigham and Women’s Hospital, Boston, MA, United States
g Department of Psychiatry and Human Behavior, Bradley Hospital, Brown University, Providence, RI, United States
h Department of Biology, University of Washington, Seattle, WA, United States
i Department of Psychology, Flinders University, Adelaide, SA, Australia
j Integrative Physiology, University of Colorado, Boulder, CO, United States
k Department of Psychiatry and Behavioral Sciences, Stanford University, StanfordCA, United States
l Department of Psychology, University of California, Berkeley, CA, United States
m Department of Psychiatry and Behavioral Sciences, Rush University, Chicago, IL, United States
n Department of Genetics, Cincinnati University, Cincinnati, OH, United States
o Department of Ophthalmology, University of Washington, Seattle, WA, United States
p Department of Psychiatry and Behavioral Sciences, University of California, Los Angeles, CA, United States
q University of Arizona College of Medicine, Tucson, AZ, United States
r Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle ParkNC, United States
s Division of Intramural Research, National Institute on Minority Health and Health Disparities, National Institutes of Health, BethesdaMD, United States
t Department of Psychology, University of St. Thomas, St Paul, MN, United States
u Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
v Integrative Biology and Physiology, University of California, Los Angeles, CA, United States
Abstract
Collegiate athletes must satisfy the academic obligations common to all undergraduates, but they have the additional structural and social stressors of extensive practice time, competition schedules, and frequent travel away from their home campus. Clearly such stressors can have negative impacts on both their academic and athletic performances as well as on their health. These concerns are made more acute by recent proposals and decisions to reorganize major collegiate athletic conferences. These rearrangements will require more multi-day travel that interferes with the academic work and personal schedules of athletes. Of particular concern is additional east-west travel that results in circadian rhythm disruptions commonly called jet lag that contribute to the loss of amount as well as quality of sleep. Circadian misalignment and sleep deprivation and/or sleep disturbances have profound effects on physical and mental health and performance. We, as concerned scientists and physicians with relevant expertise, developed this white paper to raise awareness of these challenges to the wellbeing of our student-athletes and their co-travelers. We also offer practical steps to mitigate the negative consequences of collegiate travel schedules. We discuss the importance of bedtime protocols, the availability of early afternoon naps, and adherence to scheduled lighting exposure protocols before, during, and after travel, with support from wearables and apps. We call upon departments of athletics to engage with sleep and circadian experts to advise and help design tailored implementation of these mitigating practices that could contribute to the current and long-term health and wellbeing of their students and their staff members. © 2023 The Author(s).
Author Keywords
academic and athletic performance; chronic jet lag; circadian misalignment; sleep and circadian health; student mental health
Funding details
National Institutes of HealthNIH
National Institute of Environmental Health SciencesNIEHSZ1AES103325
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Post-stroke Depressive Symptoms and Cognitive Performances: A Network Analysis
(2023) Archives of Physical Medicine and Rehabilitation, .
Shi, Y.a b , Lenze, E.J.c , Mohr, D.C.d e , Lee, J.-M.f , Hu, L.a b , Metts, C.L.g , Fong, M.W.M.h i , Wong, A.W.K.h j k
a Center for Healthful Behavior Change, Institute for Excellence in Health Equity, NYU Langone Health, New York, NY, United States
b Department of Population Health, New York University Grossman School of Medicine, New York, NY, United States
c Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
d Center for Behavioral Intervention Technologies, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
e Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
f Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
g Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, United States
h Department of Physical Medicine and Rehabilitation, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
i Michigan Avenue Neuropsychologists, Chicago, IL, United States
j Center for Rehabilitation Outcomes Research, Shirley Ryan AbilityLab, Chicago, IL, United States
k Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
Abstract
Objective: To examine the relationships between post-stroke depression and cognition using network analysis. In particular, we identified central depressive symptoms, central cognitive performances, and bridge components that connect these 2 constructs. Design: An observational study. We applied network analysis to analyze baseline data to visualize and quantify the relationships between depression and cognition. Setting: Home and Community. Participants: 202 participants with mild-to-moderate stroke (N=202; mean age: 59.7 years; 55% men; 55% Whites; 90% ischemic stroke). Intervention: Not applicable. Main Outcome Measures: Patient Health Questionnaire (PHQ-8) for depressive symptoms and the NIH Toolbox Cognitive Battery for cognitive performances. Results: Depressive symptoms were positively intercorrelated with the network, with symptoms from similar domains clustered together. Mood (expected influence=1.58), concentration (expected influence=0.67), and guilt (expected influence=0.63) were the top 3 central depressive symptoms. Cognitive performances also showed similar network patterns, with executive function (expected influence=0.89), expressive language (expected influence=0.68), and processing speed (expected influence=0.48) identified as the top 3 central cognitive performances. Psychomotor functioning (bridge expected influence=2.49) and attention (bridge expected influence=1.10) were the components connecting depression and cognition. Conclusions: The central and bridge components identified in this study might serve as targets for interventions against these deficits. Future trials are needed to compare the effectiveness of interventions targeting the central and bridge components vs general interventions treating depression and cognitive impairment as a homogenous clinical syndrome. © 2023 American Congress of Rehabilitation Medicine
Author Keywords
Cognition; Depression; Network analysis; Neuropsychiatry; Stroke
Funding details
P2CHD101899
National Institutes of HealthNIH
American Diabetes AssociationADA
National Institute of Neurological Disorders and StrokeNINDS
Craig H. Neilsen FoundationCHNF
Patient-Centered Outcomes Research InstitutePCORI
National Center for Medical Rehabilitation ResearchNCMRRK01HD095388
Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNICHD
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Diagnostic Utility of Cerebrospinal Fluid Biomarkers in Patients with Rapidly Progressive Dementia
(2023) Annals of Neurology, .
Kuchenbecker, L.A.a , Tipton, P.W.b , Martens, Y.a , Brier, M.R.c , Satyadev, N.b , Dunham, S.R.c , Lazar, E.B.b d , Dacquel, M.V.a , Henson, R.L.c , Bu, G.a , Geschwind, M.D.e , Morris, J.C.c , Schindler, S.E.c , Herries, E.c , Graff-Radford, N.R.b , Day, G.S.b
a Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, United States
b Department of Neurology, Mayo Clinic Florida, Jacksonville, FL, United States
c Department of Neurology, Washington University School of Medicine, Saint Louis, MO, United States
d Hackensack Meridian JFK University Medical Center, Edison, NJ, United States
e Department of Neurology, University of California, San Francisco, San Francisco, CA, United States
Abstract
Objective: This study was undertaken to apply established and emerging cerebrospinal fluid (CSF) biomarkers to improve diagnostic accuracy in patients with rapidly progressive dementia (RPD). Overlap in clinical presentation and results of diagnostic tests confounds etiologic diagnosis in patients with RPD. Objective measures are needed to improve diagnostic accuracy and to recognize patients with potentially treatment-responsive causes of RPD. Methods: Biomarkers of Alzheimer disease neuropathology (amyloid-β 42/40 ratio, phosphorylated tau [p-tau181, p-tau231]), neuroaxonal/neuronal injury (neurofilament light chain [NfL], visinin-like protein-1 [VILIP-1], total tau), neuroinflammation (chitinase-3-like protein [YKL-40], soluble triggering receptor expressed on myeloid cells 2 [sTREM2], glial fibrillary acidic protein [GFAP], monocyte chemoattractant protein-1 [MCP-1]), and synaptic dysfunction (synaptosomal-associated protein 25kDa, neurogranin) were measured in CSF obtained at presentation from 78 prospectively accrued patients with RPD due to neurodegenerative, vascular, and autoimmune/inflammatory diseases; 35 age- and sex-matched patients with typically progressive neurodegenerative disease; and 72 cognitively normal controls. Biomarker levels were compared across etiologic diagnoses, by potential treatment responsiveness, and between patients with typical and rapidly progressive presentations of neurodegenerative disease. Results: Alzheimer disease biomarkers were associated with neurodegenerative causes of RPD. High NfL, sTREM2, and YKL-40 and low VILIP-1 identified patients with autoimmune/inflammatory diseases. MCP-1 levels were highest in patients with vascular causes of RPD. A multivariate model including GFAP, MCP-1, p-tau181, and sTREM2 identified the 44 patients with treatment-responsive causes of RPD with 89% accuracy. Minimal differences were observed between typical and rapidly progressive presentations of neurodegenerative disease. Interpretation: Selected CSF biomarkers at presentation were associated with etiologic diagnoses and treatment responsiveness in patients with heterogeneous causes of RPD. The ability of cross-sectional biomarkers to inform upon mechanisms that drive rapidly progressive neurodegenerative disease is less clear. ANN NEUROL 2023. © 2023 American Neurological Association.
Funding details
National Institute on AgingNIAK23AG064029, P30AG062677, P30AG066444
Document Type: Article
Publication Stage: Article in Press
Source: Scopus