“Spectral hallmark of auditory-tactile interactions in the mouse somatosensory cortex” (2020) Communications Biology
Spectral hallmark of auditory-tactile interactions in the mouse somatosensory cortex
(2020) Communications Biology, 3 (1), art. no. 64, .
Zhang, M.a c , Kwon, S.E.b d , Ben-Johny, M.a e , O’Connor, D.H.b , Issa, J.B.a f
a Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
b Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Kavli Neuroscience Discovery Institute, and Brain Science Institute, Baltimore, MD 21205, United States
c Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130, United States
d Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, United States
e Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, United States
f Department of Neurobiology, Northwestern University, Evanston, IL 60201, United States
Abstract
To synthesize a coherent representation of the external world, the brain must integrate inputs across different types of stimuli. Yet the mechanistic basis of this computation at the level of neuronal populations remains obscure. Here, we investigate tactile-auditory integration using two-photon Ca2+ imaging in the mouse primary (S1) and secondary (S2) somatosensory cortices. Pairing sound with whisker stimulation modulates tactile responses in both S1 and S2, with the most prominent modulation being robust inhibition in S2. The degree of inhibition depends on tactile stimulation frequency, with lower frequency responses the most severely attenuated. Alongside these neurons, we identify sound-selective neurons in S2 whose responses are inhibited by high tactile frequencies. These results are consistent with a hypothesized local mutually-inhibitory S2 circuit that spectrally selects tactile versus auditory inputs. Our findings enrich mechanistic understanding of multisensory integration and suggest a key role for S2 in combining auditory and tactile information. © 2020, The Author(s).
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Infectious diseases occurring in the context of substance use disorders: A concise review” (2020) Journal of the Neurological Sciences
Infectious diseases occurring in the context of substance use disorders: A concise review
(2020) Journal of the Neurological Sciences, 411, art. no. 116719, .
Kolla, B.P.a , Oesterle, T.a , Gold, M.b , Southwick, F.c , Rummans, T.a
a Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN 55905, United States
b Washington University in St Louis, School of Medicine, St Louis, MO, United States
c Department of Medicine, University of Florida, Gainesville, FL, United States
Abstract
Prevalence of infectious diseases is substantially higher among patients with substance use disorders (SUD). Factors associated with drug use including sharing needles and injecting supplies, presence of contaminants in drugs and drug use related paraphernalia, risky behaviors associated with drug use, immune suppression secondary to chronic drug use, poverty and homelessness all increase the risk of infections. Persons with SUD have low rates of health care utilization and may miss opportunities for early diagnosis and care of infectious complications of substance use. When infectious diseases are comorbid with drug use, they are associated with substantial morbidity and mortality and result in significant healthcare costs. Patients with SUD may be rescued from an overdose, detoxified or treated for a SUD but facilities and clinicians are often reluctant to assume responsibility for evaluation and treatment of concurrent infectious or medical diseases. Increased screening for these disorders, utilizing vaccinations and other preventative strategies including clean supplies and safe injecting sites and providing comprehensive substance use and infectious disease treatment have the potential to significantly improve patient related outcomes and enhance public health. In this paper we review the prevalence of various common infectious diseases among persons who use drugs, their clinical presentation, mode of transmission, screening and diagnosis. We detail some of the common mechanisms by which persons who use drugs are at increased risk of contracting infections. We also discuss preventive and treatment strategies for infectious diseases occurring in the context of SUD. © 2020 Elsevier B.V.
Author Keywords
Drug use; HIV; Infections; Infectious diseases; Injecting drug use
Document Type: Review
Publication Stage: Final
Source: Scopus
“Social anxiety and age are associated with neural response to social evaluation during adolescence” (2020) Developmental Cognitive Neuroscience
Social anxiety and age are associated with neural response to social evaluation during adolescence
(2020) Developmental Cognitive Neuroscience, 42, art. no. 100768, .
Smith, A.R.a , Nelson, E.E.b , Kircanski, K.a , Rappaport, B.I.c , Do, Q.B.d , Leibenluft, E.a , Pine, D.S.a , Jarcho, J.M.e
a Emotion and Development Branch, National Institute of Mental Health, Bethesda, MD, United States
b Center for Biobehavioral Health, Research Institute at Nationwide Children’s Hospital, Department of Pediatrics, College of Medicine, Ohio State University, Columbus, OH, United States
c Department of Psychological & Brain Sciences, Washington University in St. Louis, St. Louis, MO, United States
d Department of Psychology, University of Pittsburgh, Pittsburgh, PA, United States
e Department of Psychology, Temple University, Philadelphia, PA, United States
Abstract
Adolescence is a sensitive period for the development of adaptive social behaviors and social anxiety, possibly due to aspects of brain development. However, research is needed to examine interactions among age, social anxiety, and social dynamics previously shown to influence neural responding. The current functional magnetic resonance imaging (fMRI) study examines brain function in 8–18 year-olds with varying levels of social anxiety. Interactions are examined among age, social anxiety, and two key task factors: valence and predictability of social interactions. Results demonstrate age, social anxiety severity, and each of the two key task-based factors interact to predict neural response in the caudate, middle and superior temporal gyri. In particular, among adolescents less-than 13 years of age, higher social anxiety predicted greater responding to unpredictable negative evaluations. However, in this same age group, the opposite pattern emerged during receipt of unpredictable positive evaluations, with less neural response in more anxious youth. Adolescents aged 13 and older overall showed less robust effects. We discuss these findings in terms of age- and anxiety-related differences in socioemotional processing. © 2020
Author Keywords
Adolescence; Neuroimaging; Social anxiety; Social evaluation
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“The development of event perception and memory” (2020) Cognitive Development
The development of event perception and memory
(2020) Cognitive Development, 54, art. no. 100848, .
Zheng, Y.a b , Zacks, J.M.b , Markson, L.b
a Northwestern University, United States
b Washington University in St. Louis, United States
Abstract
Adults segment continuous and dynamic environment into discrete units, and individual differences in segmentation predict individual differences in memory. Similar parsing mechanisms have been identified in infants, using different methods, but little is known about event segmentation in older children or about its relations to memory. We tested event segmentation and its relations to memory in 5- to 7-year-old children and adults. Participants performed two event comprehension tasks with short animated narrative movies: a unitization task, in which they pressed a key to mark boundaries between meaningful events, and a dwell time task, in which they viewed a self-paced slideshow, and completed two memory tasks. Adults outperformed children as expected. For both age groups, better event comprehension was associated with better memory, though which measures showed this relationship varied. Thus, by school age, children have developed event segmentation mechanisms that, like adults, contribute to episodic memory formation. © 2020 Elsevier Inc.
Author Keywords
Development of event comprehension; Event memory; Event segmentation
Document Type: Article
Publication Stage: Final
Source: Scopus
“Staged Laser Interstitial Thermal Therapy (LITT) Treatments to Left Insular Low-Grade Glioma” (2020) Neurosurgery
Staged Laser Interstitial Thermal Therapy (LITT) Treatments to Left Insular Low-Grade Glioma
(2020) Neurosurgery, 86 (3), pp. E337-E342.
Hafez, D.M.a , Liekweg, C.a , Leuthardt, E.C.b c d
a Department of Neurosurgery, Barnes-Jewish Hospital, Washington University School of Medicine, St. Louis, MO, United States
b Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, United States
c Center for Innovation in Neuroscience and Technology, Washington University School of Medicine, St. Louis, MO, United States
d Brain Laser Center, Washington University School of Medicine, St. Louis, MO, United States
Abstract
BACKGROUND AND IMPORTANCE: Low-grade insular gliomas remain challenging tumors for aggressive resection because of the numerous functional and vascular structures surrounding them. Because of the potential morbidities associated with open surgical resection, less invasive techniques may confer a more optimal balance between cytoreduction and surgical complications. For this reason, we evaluated the use of laser interstitial thermal therapy (LITT) for resection of a dominant hemisphere oligodendroglioma World Health Organization (WHO) grade II in a 68-yr-old patient by use of multiple staged surgeries for its resection. CLINICAL PRESENTATION: Patient KK was a 68-yr-old female who was found to have a large, left-sided insular mass that was shown to be an oligodendroglioma WHO grade II, positive for codeletion 1p/19q and IDH1 mutant on biopsy. Over the course of 3 mo, KK underwent 2 stages of LITT, targeting different areas of the 5-cm tumor. The 60-d magnetic resonance imaging (MRI) demonstrated a reduction in size of the tumor from 5.2 × 3.3 × 2.4 cm to 3.6 × 1.9 × 1.4 cm. She returned for a second stage targeting the anterior portion of the tumor. KK did well postoperatively and went on to postsurgical chemoradiation. At the 2-yr follow-up, the lesion showed near resolution on MRI. CONCLUSION: This case report demonstrates successful use of LITT for staged surgeries to treat a left hemisphere-dominant insular lesion. This establishes the use of LITT as a viable, minimally invasive option to treat tumors that are difficult to access or pose concerns for increased morbidity through an open surgery. © Congress of Neurological Surgeons 2019.
Author Keywords
Craniotomy; Insular tumor; Laser; LITT; Minimally invasive; Oligodendroglioma
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Encephalitic Alphaviruses Exploit Caveola-Mediated Transcytosis at the Blood-Brain Barrier for Central Nervous System Entry” (2020) mBio
Encephalitic Alphaviruses Exploit Caveola-Mediated Transcytosis at the Blood-Brain Barrier for Central Nervous System Entry
(2020) mBio, 11 (1), .
Salimi, H.a , Cain, M.D.a , Jiang, X.a , Roth, R.A.a , Beatty, W.L.a , Sun, C.b , Klimstra, W.B.b , Hou, J.a , Klein, R.S.a c d
a Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
b Department of Immunology and Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, United States
c Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, United States
d Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, United States
Abstract
Venezuelan and western equine encephalitis viruses (VEEV and WEEV, respectively) invade the central nervous system (CNS) early during infection, via neuronal and hematogenous routes. While viral replication mediates host shutoff, including expression of type I interferons (IFN), few studies have addressed how alphaviruses gain access to the CNS during established infection or the mechanisms of viral crossing at the blood-brain barrier (BBB). Here, we show that hematogenous dissemination of VEEV and WEEV into the CNS occurs via caveolin-1 (Cav-1)-mediated transcytosis (Cav-MT) across an intact BBB, which is impeded by IFN and inhibitors of RhoA GTPase. Use of reporter and nonreplicative strains also demonstrates that IFN signaling mediates viral restriction within cells comprising the neurovascular unit (NVU), differentially rendering brain endothelial cells, pericytes, and astrocytes permissive to viral replication. Transmission and immunoelectron microscopy revealed early events in virus internalization and Cav-1 association within brain endothelial cells. Cav-1-deficient mice exhibit diminished CNS VEEV and WEEV titers during early infection, whereas viral burdens in peripheral tissues remained unchanged. Our findings show that alphaviruses exploit Cav-MT to enter the CNS and that IFN differentially restricts this process at the BBB.IMPORTANCE VEEV, WEEV, and eastern equine encephalitis virus (EEEV) are emerging infectious diseases in the Americas, and they have caused several major outbreaks in the human and horse population during the past few decades. Shortly after infection, these viruses can infect the CNS, resulting in severe long-term neurological deficits or death. Neuroinvasion has been associated with virus entry into the CNS directly from the bloodstream; however, the underlying molecular mechanisms have remained largely unknown. Here, we demonstrate that following peripheral infection alphavirus augments vesicular formation/trafficking at the BBB and utilizes Cav-MT to cross an intact BBB, a process regulated by activators of Rho GTPases within brain endothelium. In vivo examination of early viral entry in Cav-1-deficient mice revealed significantly lower viral burdens in the brain than in similarly infected wild-type animals. These studies identify a potentially targetable pathway to limit neuroinvasion by alphaviruses. Copyright © 2020 Salimi et al.
Author Keywords
alphavirus; blood-brain barrier; caveola-mediated transcytosis; caveolin-1; IFNAR; in vivo animal model; transcytosis assay; type I interferon; Venezuelan encephalitis virus; western equine encephalitis virus
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Exercise training results in lower amyloid plaque load and greater cognitive function in an intensity dependent manner in the tg2576 mouse model of alzheimer’s disease” (2020) Brain Sciences
Exercise training results in lower amyloid plaque load and greater cognitive function in an intensity dependent manner in the tg2576 mouse model of alzheimer’s disease
(2020) Brain Sciences, 10 (2), art. no. 88, .
Thomas, R.a , Zimmerman, S.D.a , Yuede, K.M.b , Cirrito, J.R.b c d , Tai, L.M.e , Timson, B.F.a , Yuede, C.M.b c d
a Department of Biomedical Sciences, Missouri State University, Springfield, MO 65897, United States
b Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, United States
c Hope Center, Washington University School of Medicine, St. Louis, MO 63110, United States
d Alzheimer’s Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, United States
e Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL 60607, United States
Abstract
Three months of exercise training (ET) decreases soluble Aβ40 and Aβ42 levels in an intensity dependent manner early in life in Tg2576 mice (Moore et al., 2016). Here, we examined the effects of 12 months of low-and high-intensity exercise training on cognitive function and amyloid plaque load in the cortex and hippocampus of 15-month-old Tg2576 mice. Low-(LOW) and high-(HI) intensity ET animals ran at speeds of 15 m/min on a level treadmill and 32 m/min at a 10% grade, respectively, for 60 min/day, five days/week, from 3 to 15 months of age. Sedentary mice (SED) were placed on a level, non-moving, treadmill for the same duration. ET mice demonstrated a significantly lower amyloid plaque load in the cortex and hippocampus that was intensity dependent. Improvement in cognitive function, assessed by Morris Water Maze and Novel Object Recognition tests, was greater in the HI group compared to the LOW and SED groups. LOW mice performed better in the initial latency to the platform location during the probe trial of the Morris Water Maze (MWM) test than SED, but not in any other aspect of MWM or the Novel Object Recognition test. The results of this study indicate that exercise training decreases amyloid plaque load in an intensity dependent manner and that high-intensity exercise training improves cognitive function relative to SED mice, but the intensity of the LOW group was below the threshold to demonstrate robust improvement in cognitive function in Tg2576 mice. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Author Keywords
Alzheimer’s disease; Amyloid plaque; Cognitive function; Exercise training; Tg2576 mice
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Renal Excretion of Contrast on CT Myelography: A Specific Marker of CSF Leak” (2020) AJNR. American Journal of Neuroradiology
Renal Excretion of Contrast on CT Myelography: A Specific Marker of CSF Leak
(2020) AJNR. American Journal of Neuroradiology, 41 (2), pp. 351-356.
Behbahani, S., Raseman, J., Orlowski, H., Sharma, A., Eldaya, R.
From the Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States
Abstract
BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the sensitivity and specificity of renal/ureteric opacification on postmyelographic CT as a sign of CSF leak. MATERIALS AND METHODS: We performed a retrospective review of postmyelographic CT scans from 49 consecutive patients seen between January 2008 and August 2018 with imaging and/or clinical findings related to intracranial hypotension. Each scan was evaluated by both a neuroradiology fellow and a board-certified neuroradiologist for the presence of contrast in the renal excretory system. A similar assessment was also performed on 90 consecutive control subjects who underwent CT myelography for alternative indications. RESULTS: Among the 49 patients with suspected CSF leak, 21 (43%) had an overt CSF leak on postmyelographic CT (group 1) and 28 (57%) did not (group 2). Overall, renal contrast was identified in 7/49 patients (14.3%): 5 (24%) patients in group 1, and 2 (7%) patients in group 2. Renal contrast was not seen in any of the 90 controls on postmyelographic CT. CONCLUSIONS: Renal contrast was exclusively seen in patients with a clinically or radiographically suspected CSF leak. Given its 100% specificity, identification of this finding should prompt a second look for subtle myelographic contrast extravasation or an underlying CSF-venous fistula. Our results suggest that this sign may be considered an additional diagnostic criterion for CSF leak in the absence of an identifiable leak. © 2020 by American Journal of Neuroradiology.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Phosphorylation at Serine 21 in G protein-coupled receptor kinase 1 (GRK1) is required for normal kinetics of dark adaption in rod but not cone photoreceptors” (2020) FASEB Journal
Phosphorylation at Serine 21 in G protein-coupled receptor kinase 1 (GRK1) is required for normal kinetics of dark adaption in rod but not cone photoreceptors
(2020) FASEB Journal, 34 (2), pp. 2677-2690.
Kolesnikov, A.V.a , Chrispell, J.D.b , Osawa, S.b , Kefalov, V.J.a , Weiss, E.R.b
a Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint Louis, MO, United States
b Department of Cell Biology and Physiology, The University of North Carolina, Lineberger Comprehensive Cancer Center, Chapel Hill, NC, United States
Abstract
Timely recovery of the light response in photoreceptors requires efficient inactivation of photoactivated rhodopsin. This process is initiated by phosphorylation of its carboxyl terminus by G protein-coupled receptor kinase 1 (GRK1). Previously, we showed that GRK1 is phosphorylated in the dark at Ser21 in a cAMP-dependent manner and dephosphorylated in the light. Results in vitro indicate that dephosphorylation of Ser21 increases GRK1 activity, leading to increased phosphorylation of rhodopsin. This creates the possibility of light-dependent regulation of GRK1 activity and its efficiency in inactivating the visual pigment. To address the functional role of GRK1 phosphorylation in rods and cones in vivo, we generated mutant mice in which Ser21 is substituted with alanine (GRK1-S21A), preventing dark-dependent phosphorylation of GRK1. GRK1-S21A mice had normal retinal morphology, without evidence of degeneration. The function of dark-adapted GRK1-S21A rods and cones was also unaffected, as demonstrated by the normal amplitude and kinetics of their responses obtained by ex vivo and in vivo ERG recordings. In contrast, rod dark adaptation following exposure to bright bleaching light was significantly delayed in GRK1-S21A mice, suggesting that the higher activity of this kinase results in enhanced rhodopsin phosphorylation and therefore delays its regeneration. In contrast, dark adaptation of cones was unaffected by the S21A mutation. Taken together, these data suggest that rhodopsin phosphorylation/dephosphorylation modulates the recovery of rhodopsin to the ground state and rod dark adaptation. They also reveal a novel role for cAMP-dependent phosphorylation of GRK1 in regulating the dark adaptation of rod but not cone photoreceptors. © 2019 Federation of American Societies for Experimental Biology
Author Keywords
cAMP; photoreceptor; phototransduction; protein phosphorylation; vision
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Corrigendum: 2-Pyrrolidinone and Succinimide as Clinical Screening Biomarkers for GABA-Transaminase Deficiency: Anti-seizure Medications Impact Accurate Diagnosis (Frontiers in Neuroscience, (2019), 13, 10.3389-fnins.2019.00394)” (2020) Frontiers in Neuroscience
Corrigendum: 2-Pyrrolidinone and Succinimide as Clinical Screening Biomarkers for GABA-Transaminase Deficiency: Anti-seizure Medications Impact Accurate Diagnosis (Frontiers in Neuroscience, (2019), 13, 10.3389/fnins.2019.00394)
(2020) Frontiers in Neuroscience, 13, art. no. 1344, .
Kennedy, A.D.a g , Pappan, K.L.a , Donti, T.b , Delgado, M.R.c , Shinawi, M.d , Pearson, T.S.e , Lalani, S.R.b , Craigen, W.J.b , Sutton, V.R.b , Evans, A.M.a , Sun, Q.b , Emrick, L.T.b f , Elsea, S.H.b
a Metabolon, Inc, Morrisville, NC, United States
b Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States
c Department of Neurology and Neurotherapeutics, Texas Scottish Rite Hospital for Children, The University of Texas Southwestern Medical Center, Dallas, TX, United States
d Department of Pediatrics, Washington University School of Medicine St. Louis, St. Louis, MO, United States
e Department of Neurology, Washington University School of Medicine St. Louis, St. Louis, MO, United States
f Department of Neurology, Baylor College of Medicine, Houston, TX, United States
g †Adam D. Kennedy, Baebies, Inc, Morrisville, NC, United States
Abstract
In the original article, there was a mistake in Figure 1 and Figure 3A as published. “Succinamic acid” was omitted from the pathway in Figure 1 and Figure 3A. The corrected figures and figure legends appear below. Additionally, there was a mistake in Figure 4B as published. “Succinimide” wasmistakenly used as the primary biomarker in plasma for the original data analysis, but “succinamic acid” is the proper biomarker. The data have been reanalyzed with succinamic acid to reflect this error. The corrected figure and figure legend appears below. Table 1 and Table 2 have also been updated to reflect these changes: In line with the changes made above, a correction has also been made to the Abstract: “Broad-scale untargeted biochemical phenotyping is a technology that supplements widely accepted assays, such as organic acid, amino acid, and acylcarnitine analyses typically utilized for the diagnosis of inborn errors of metabolism. In this study, we investigate the analyte changes associated with 4-aminobutyrate aminotransferase (ABAT, GABA transaminase) deficiency and treatments that affect GABA metabolism. GABA-transaminase deficiency is a rare neurodevelopmental and neurometabolic disorder caused by mutations in ABAT and resulting in accumulation of GABA in the cerebrospinal fluid (CSF). For that reason, measurement of GABA in CSF is currently the primary approach to diagnosis. GABA-transaminase deficiency results in severe developmental delay with intellectual disability, seizures, and movement disorder, and is often associated with death in childhood. Using an untargeted metabolomics platform, we analyzed EDTA plasma, urine, and CSF specimens from four individuals with GABA-transaminase deficiency to identify biomarkers by comparing the biochemical profile of individual patient samples to a pediatric-centric population cohort. Metabolomic analyses of over 1,000 clinical plasma samples revealed a rich source of biochemical information. Three out of four patients showed significantly elevated levels of the molecule 2-pyrrolidinone (Zscore ≥ 2) in plasma, and whole exome sequencing revealed variants of uncertain significance in ABAT. Additionally, these same patients also had elevated levels of succinimide or its ring-opened form, succinamic acid, in plasma, urine, and CSF and/or homocarnosine in urine and CSF. In the analysis of clinical EDTA plasma samples, the levels of succinamic acid and 2-pyrrolidinone showed a high level of correlation (R = 0.72), indicating impairment in GABA metabolism and further supporting the association with GABA-transaminase deficiency and the pathogenicity of the ABAT variants. Further analysis of metabolomic data across our patient population revealed the association of elevated levels of 2-pyrrolidinone with administration of vigabatrin, a commonly used anti-seizure medication and a known inhibitor of GABA-transaminase. These data indicate that anti-seizure medications may alter the biochemical and metabolomic data, potentially impacting the interpretation and diagnosis for the patient. Further, these data demonstrate the power of combining broad scale genotyping and phenotyping technologies to diagnose inherited neurometabolic disorders and support the use of metabolic phenotyping of plasma to screen for GABA-transaminase deficiency.”. © Copyright © 2020 Kennedy, Pappan, Donti, Delgado, Shinawi, Pearson, Lalani, Craigen, Sutton, Evans, Sun, Emrick and Elsea.
Author Keywords
2-pyrrolidinone; 4-aminobutyrate aminotransferase deficiency; GABA; GABA-transaminase deficiency; inborn error of metabolism; neurometabolic; neurotransmitter; vigabatrin
Document Type: Erratum
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Individualization of attention-deficit/hyperactivity disorder treatment: pharmacotherapy considerations by age and co-occurring conditions” (2020) CNS Spectrums
Individualization of attention-deficit/hyperactivity disorder treatment: pharmacotherapy considerations by age and co-occurring conditions
(2020) CNS Spectrums, .
Mattingly, G.W.a b c , Wilson, J.a b c , Ugarte, L.b c , Glaser, P.a
a Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
b Midwest Research Group, St. Charles, MO, United States
c St. Charles Psychiatric Associates, St. Charles, MO, United States
Abstract
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that manifests in childhood and can persist into adolescence and adulthood. Impairments associated with ADHD can impact quality of life, social interactions, and increase the risk of morbidity and mortality; however, for many patients, effective treatment can lessen these effects. Pharmacotherapy with stimulants or nonstimulants is recommended in conjunction with psychosocial therapy for most patients. Determining the optimal pharmacotherapy can be complex, and the clinician needs to consider many factors such as the patient’s age, comorbidities, and lifestyle. Furthermore, the needs of the patient with ADHD will change over time, with specific challenges to consider at each stage of life. A variety of Food and Drug Administration (FDA)-approved stimulant and nonstimulant formulations are available with different modes of delivery and durations of effect. This armamentarium of ADHD medications can be used to individualize ADHD treatment for each patient’s needs. This article combines current information from the literature and the first-hand experience of the authors to provide guidance on ADHD treatment options for patients of different ages and for some of the more common comorbidities. © Cambridge University Press 2020.
Author Keywords
ADHD; autism; comorbidities; depression; pharmacotherapy; substance use disorder
Document Type: Review
Publication Stage: Article in Press
Source: Scopus
“Predicting sporadic Alzheimer’s disease progression via inherited Alzheimer’s disease-informed machine-learning” (2020) Alzheimer’s and Dementia
Predicting sporadic Alzheimer’s disease progression via inherited Alzheimer’s disease-informed machine-learning
(2020) Alzheimer’s and Dementia, .
Franzmeier, N.a , Koutsouleris, N.b , Benzinger, T.c d , Goate, A.e f , Karch, C.M.d g h , Fagan, A.M.d g i , McDade, E.d i , Duering, M.a , Dichgans, M.a j k , Levin, J.j k l , Gordon, B.A.d m n , Lim, Y.Y.o , Masters, C.L.o , Rossor, M.p , Fox, N.C.p , O’Connor, A.p , Chhatwal, J.q , Salloway, S.r , Danek, A.l , Hassenstab, J.d i n , Schofield, P.R.s t , Morris, J.C.d h i , Bateman, R.J.d i , Ewers, M.a , the Alzheimer’s disease neuroimaging initiative (ADNI)u , the Dominantly Inherited Alzheimer Network (DIAN)u
a Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMUMunich, Germany
b Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-Universität LMUMunich, Germany
c Department of Radiology, Washington University in St. Louis, St. Louis, MO, United States
d Knight Alzheimer’s Disease Research Center, Washington University in St. Louis, St. Louis, MO, United States
e Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States
f Ronald M. Loeb Center for Alzheimer’s Disease, Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, United States
g Hope Center for Neurological Disorders, Washington University in St. Louis, St. Louis, MO, United States
h Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, United States
i Department of Neurology, Washington University in St. Louis, St. Louis, MO, United States
j Munich Cluster for Systems NeurologyMunich, Germany
k German Center for Neurodegenerative Diseases (DZNE)Munich, Germany
l Department of Neurology, Ludwig-Maximilians-Universität MünchenMunich, Germany
m Mallinckrodt Institute of Radiology, Washington University, St. Louis, MO, United States
n Department of Psychological and Brain Sciences, Washington University, St. Louis, MO, United States
o The Florey Institute, The University of Melbourne, Parkville, VIC, Australia
p Dementia Research Centre, University College London, Queen Square, London, United Kingdom
q Massachusetts General Hospital, Department of Neurology, Harvard Medical School, Boston, MA, United States
r Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI, United States
s Neuroscience Research Australia, Randwick, NSW, Australia
t School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia
Abstract
Introduction: Developing cross-validated multi-biomarker models for the prediction of the rate of cognitive decline in Alzheimer’s disease (AD) is a critical yet unmet clinical challenge. Methods: We applied support vector regression to AD biomarkers derived from cerebrospinal fluid, structural magnetic resonance imaging (MRI), amyloid-PET and fluorodeoxyglucose positron-emission tomography (FDG-PET) to predict rates of cognitive decline. Prediction models were trained in autosomal-dominant Alzheimer’s disease (ADAD, n = 121) and subsequently cross-validated in sporadic prodromal AD (n = 216). The sample size needed to detect treatment effects when using model-based risk enrichment was estimated. Results: A model combining all biomarker modalities and established in ADAD predicted the 4-year rate of decline in global cognition (R2 = 24%) and memory (R2 = 25%) in sporadic AD. Model-based risk-enrichment reduced the sample size required for detecting simulated intervention effects by 50%–75%. Discussion: Our independently validated machine-learning model predicted cognitive decline in sporadic prodromal AD and may substantially reduce sample size needed in clinical trials in AD. © 2020 The Authors. Alzheimer’s & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer’s Association.
Author Keywords
Alzheimer’s disease; autosomal-dominant Alzheimer’s disease; biomarkers; machine learning; MRI; PET; progression prediction; risk enrichment
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access
“Spatial navigation ability predicts progression of dementia symptomatology” (2020) Alzheimer’s and Dementia
Spatial navigation ability predicts progression of dementia symptomatology
(2020) Alzheimer’s and Dementia, .
Levine, T.F.a , Allison, S.L.b c , Stojanovic, M.a , Fagan, A.M.d e f , Morris, J.C.d f , Head, D.a d g
a Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO, United States
b Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
c Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, Madison, WI, United States
d Knight Alzheimer Disease Research Center, Washington University in St. Louis, St. Louis, MO, United States
e Hope Center for Neurological Disorders, Washington University in St. Louis, St. Louis, MO, United States
f Neurology Department, Washington University in St. Louis, St. Louis, MO, United States
g Radiology Department, Washington University in St. Louis, St. Louis, MO, United States
Abstract
Introduction: Spatial navigation deficits are observed in Alzheimer’s disease cross-sectionally, but prediction of longitudinal clinical decline has been less examined. Methods: Cognitive mapping (CM) was assessed in 95 participants and route learning (RL) was assessed in 65 participants at baseline. Clinical progression over an average of 4 to 5 years was assessed using the clinical dementia rating (CDR) scale. Relative predictive ability was compared to episodic memory, hippocampus, and cerebrospinal fluid biomarkers (phosphorylated tau/amyloid β 42 (ptau181/Aβ42) ratio). Results: CM and RL were predictors of clinical progression (P’s < 0.032). All measures, except RL-Learning remained predictors with episodic memory in models (P’s < 0.048). Only RL-Retrieval remained a predictor when ptau181/Aβ42 was included (P < 0.001). CM interacted with hippocampus and ptau181/Aβ42 in prediction (P’s < 0.013). CM, RL, and episodic memory evidenced strong diagnostic accuracy (area under the curve (AUC) = 0.894, 0.794, and 0.735, respectively); CM tended to perform better than episodic memory (P = 0.056). Discussion: Baseline spatial navigation performance may be appropriate for assessing risk of clinical progression. © 2019 the Alzheimer’s Association
Author Keywords
Allocentric; amyloid; egocentric; place learning; preclinical Alzheimer’s disease; response learning
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Differential Behavioral and Neural Profiles in Youth With Conduct Problems During Risky Decision-Making” (2020) Journal of Research on Adolescence
Differential Behavioral and Neural Profiles in Youth With Conduct Problems During Risky Decision-Making
(2020) Journal of Research on Adolescence, .
van Hoorn, J.a , McCormick, E.M.a , Perino, M.T.b , Rogers, C.R.c , Telzer, E.H.a
a University of North Carolina at Chapel Hill, United States
b Washington University at Saint Louis, United States
c Texas Tech University, United States
Abstract
Neuroimaging work has examined neural processes underlying risk taking in adolescence, yet predominantly in low-risk youth. To determine whether we can extrapolate from current neurobiological models, this functional magnetic resonance imaging study investigated risk taking and peer effects in youth with conduct problems (CP; N = 19) and typically developing youth (TD; N = 25). Results revealed higher real-life risk taking, lower risky decisions, and no peer effects on a risk-taking task in CP youth. CP youth showed greater ventral striatum (VS) activity during safe than risky decisions, whereas TD youth showed greater VS activation during risky decisions. Differential VS activity explained higher real-life risk taking in CP youth. Findings provide preliminary evidence that risk-taking behavior in youth with CD problems is characterized by differential neural patterns. © 2020 Society for Research on Adolescence
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Targeting Refractory Sarcomas and Malignant Peripheral Nerve Sheath Tumors in a Phase I/II Study of Sirolimus in Combination with Ganetespib (SARC023)” (2020) Sarcoma
Targeting Refractory Sarcomas and Malignant Peripheral Nerve Sheath Tumors in a Phase I/II Study of Sirolimus in Combination with Ganetespib (SARC023)
(2020) Sarcoma, 2020, art. no. 5784876, .
Kim, A.a , Lu, Y.b , Okuno, S.H.c , Reinke, D.d , Maertens, O.e , Perentesis, J.f , Basu, M.f , Wolters, P.L.g , De Raedt, T.e , Chawla, S.h , Chugh, R.i , Van Tine, B.A.j , O’Sullivan, G.k , Chen, A.k , Cichowski, K.e , Widemann, B.C.g
a Children’s National Medical Center, 111 Michigan Ave., Washington, DC 20010, United States
b SARC Statistics, Weill Cornell Medicine Healthcare and Policy Research, 602 East 67th Street, New York, NY 10065, United States
c Mayo Clinic, 200 First St., Rochester, MN 55905, United States
d SARC, 24 Frank Lloyd Wright Drive, Ann Arbor, MI 48105, United States
e Children’s Hospital of Philadelphia, Univeristy of Pennsylvania, 3501 Civic Center Boulevard, Philadelphia, PA 19104, United States
f Cincinnati Children’s Hospital, Uinviersity of Cincinnati, 3333 Burnet Ave., Cincinnati, OH 45229, United States
g Pediatric Oncology Branch, National Cancer Institute, 10 Center Drive, Bethesda, MD 20892, United States
h Sarcoma Oncology Center, 2811 Wilshire Blvd, Santa Monica, CA 90403, United States
i University of Michigan, SPC 5912, 1500 E. Medical Center Dr., Ann Arbor, MI 48109, United States
j Washington University in St. Louis, 660 S Euclid Ave., St. Louis, MO 63110, United States
k National Cancer Institute, Developmental Therapeutics Clinic, Division of Cancer Treatment and Diagnosis, Bethesda, MD 20892, United States
Abstract
Purpose. Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas. Combining Hsp90 inhibitors to enhance endoplasmic reticulum stress with mTOR inhibition results in dramatic MPNST shrinkage in a genetically engineered MPNST mouse model. Ganetespib is an injectable potent small molecule inhibitor of Hsp90. Sirolimus is an oral mTOR inhibitor. We sought to determine the safety, tolerability, and recommended dose of ganetespib and sirolimus in patients with refractory sarcomas and assess clinical benefits in patients with unresectable/refractory MPNSTs. Patients and Methods. In this multi-institutional, open-label, phase 1/2 study of ganetespib and sirolimus, patients ≥16 years with histologically confirmed refractory sarcoma (phase 1) or MPNST (phase 2) were eligible. A conventional 3 + 3 dose escalation design was used for phase 1. Pharmacokinetic and pharmacodynamic measures were evaluated. Primary objectives of phase 2 were to determine the clinical benefit rate (CBR) of this combination in MPNSTs. Patient-reported outcomes assessed pain. Results. Twenty patients were enrolled (10 per phase). Toxicities were manageable; most frequent non-DLTs were diarrhea, elevated liver transaminases, and fatigue. The recommended dose of ganetespib was 200 mg/m2 intravenously on days 1, 8, and 15 with sirolimus 4 mg orally once daily with day 1 loading dose of 12 mg. In phase 1, one patient with leiomyosarcoma achieved a sustained partial response. In phase 2, no responses were observed. The median number of cycles treated was 2 (1-4). Patients did not meet the criteria for clinical benefit as defined per protocol. Pain ratings decreased or were stable. Conclusion. Despite promising preclinical rationale and tolerability of the combination therapy, no responses were observed, and the study did not meet parameters for further evaluation in MPNSTs. This trial was registered with (NCT02008877). © 2020 AeRang Kim et al.
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Alcohol sensitivity in women after undergoing bariatric surgery: a cross-sectional study” (2020) Surgery for Obesity and Related Diseases
Alcohol sensitivity in women after undergoing bariatric surgery: a cross-sectional study
(2020) Surgery for Obesity and Related Diseases, .
Acevedo, M.B.a , Teran-Garcia, M.b c , Bucholz, K.K.d , Eagon, J.C.e , Bartholow, B.D.f , Burd, N.A.b g , Khan, N.b g , Rowitz, B.b h i , Pepino, M.Y.a b
a Department of Food Science and Human Nutrition, College of Agricultural, Consumer and Environmental Sciences, University of Illinois Urbana-Champaign, Urbana, IL, United States
b Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL, United States
c Department of Human Development and Family Studies, University of Illinois Urbana-Champaign, Urbana, IL, United States
d Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
e Department of Surgery, Washington University School of Medicine, St. Louis, MO, United States
f Department of Psychological Sciences, University of Missouri, Columbia, MO, United States
g Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL, United States
h Carle Foundation Hospital, Urbana, IL, United States
i Carle Illinois College of Medicine, Urbana, IL, United States
Abstract
Background: Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), the most common bariatric surgeries performed worldwide, increase the risk to develop an alcohol use disorder. This might be due, in part, to surgery-related changes in alcohol pharmacokinetics. Another risk factor, unexplored within this population, is having a reduced subjective response to alcohol’s sedative effects. Objectives: To assess whether the alcohol sensitivity questionnaire (ASQ), a simple self-report measure, could pinpoint reduced alcohol sensitivity in the bariatric population. Setting: University medical centers in Missouri and Illinois. Methods: Women who had RYGB (n = 16), SG (n = 28), or laparoscopic adjustable gastric banding surgery (n = 11) within the last 5 years completed the ASQ for both pre- and postsurgical timeframes, and 45 of them participated in oral alcohol challenge testing postsurgery. Blood alcohol concentration (BAC) and subjective stimulation and sedation were measured before and for 3.5 hours after drinking. Results: In line with faster and higher peak BACs after RYGB and SG than laparoscopic adjustable gastric banding surgery (P <.001), postsurgery ASQ scores were more reduced from presurgery scores after RYGB/SG than after laparoscopic adjustable gastric banding surgery (−2.3 ±.3 versus −1.2 ±.2; P <.05). However, despite the dramatic changes in BAC observed when ingesting alcohol after RYGB/SG surgeries, which resulted in peak BAC that were approximately 50% above the legal driving limit, a third of these women felt almost no alcohol-related sedative effects. Conclusions: Although RYGB/SG dramatically increased sensitivity to alcohol in all participants, meaningful interindividual differences remained. The ASQ might help identify patients at increased risk to develop an alcohol use disorder after surgery. © 2020 American Society for Bariatric Surgery
Author Keywords
Alcohol; Bariatric surgery; Ethanol; Laparoscopic adjustable gastric banding surgery; Metabolic surgery; Pharmacokinetics; Roux-en-Y gastric bypass; Sleeve gastrectomy; Subjective response
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Attention Focus Does Not Influence Performance of Sit-to-Stand in Young and Older Adults” (2020) Journal of Motor Behavior
Attention Focus Does Not Influence Performance of Sit-to-Stand in Young and Older Adults
(2020) Journal of Motor Behavior, .
Pinto, V.A.a , Campolina, A.B.a , Mazoni, A.F.b , Mattos, D.J.S.c , Vaz, D.V.d
a Rehabilitation Sciences Graduate Program, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
b Physical Education Graduate Program, Universidade Estadual de Campinas, Campinas, Brazil
c Washington University School of Medicine in Saint Louis, Saint Louis, MO, United States
d Department of Physical Therapy, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
Abstract
An external focus of attention can improve performance, but there is little research on effects for the elderly in every day, well-learned mobility tasks. 57 older and 59 young adults performed the sit-to-stand and stand-to-sit while holding a cup, at three difficulty levels (cup empty or full, at normal or fast speed). Half were instructed to focus internally (on their movements) and half externally (on the cup). The effects of focus, age, and difficulty level were tested for movement time, mean inclination of the cup, inclination variability, and smoothness with 2 × 2 × 3 ANOVAs. Significant effects of difficulty were consistent across variables (p < 0.05). An effect of focus was present only for the inclination variability of the stand-to-sit (p < 0.03), favoring an internal focus (less variability). The age × focus interaction was significant for mean cup inclination, but post hoc tests failed to reveal any significant differences. The results of this study, together with the literature, suggest that an external focus may not benefit the performance of young or older adults in general mobility activities of daily living. The prevalent assumption that an external focus is always beneficial for performance needs further empirical testing. ©, © Taylor & Francis Group, LLC.
Author Keywords
Elderly; focus of attention; mobility
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“A ten-year retrospective evaluation of acute flaccid myelitis at 5 pediatric centers in the United States, 2005–2014” (2020) PLoS ONE
A ten-year retrospective evaluation of acute flaccid myelitis at 5 pediatric centers in the United States, 2005–2014
(2020) PLoS ONE, 15 (2), art. no. e0228671, .
Cortese, M.M.a , Kambhampati, A.K.b , Schuster, J.E.c , Alhinai, Z.d m , Nelson, G.R.e , Guzman Perez-Carrillo, G.J.f , Vossough, A.g , Smit, M.A.d n , McKinstry, R.C.f , Zinkus, T.h , Moore, K.R.i , Rogg, J.M.j , Candee, M.S.e , Sejvar, J.J.k , Hopkins, S.E.l
a Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, United States
b Contracting Agency to the Division of Viral Diseases, IHRC, Inc., Centers for Disease Control and Prevention, Atlanta, GA, United States
c Division of Infectious Diseases, Department of Pediatrics, Children’s Mercy Kansas City, Kansas City, MO, United States
d Division of Infectious Diseases, Department of Pediatrics, Alpert Medical School, Hasbro Children’s Hospital, Brown University, Providence, RI, United States
e Division of Child Neurology, Department of Pediatrics, Primary Children’s Hospital, University of Utah, Salt Lake City, UT, United States
f Neuroradiology Section, Mallinckrodt Institute of Radiology, St. Louis Children’s Hospital, Washington University School of Medicine, St. Louis, MO, United States
g Department of Radiology, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, United States
h Department of Radiology, Children’s Mercy Kansas City, Kansas City, MO, United States
i Department of Medical Imaging, Primary Children’s Hospital, University of Utah, Salt Lake City, UT, United States
j Department of Diagnostic Imaging, Alpert Medical School, Hasbro Children’s Hospital, Brown University, Providence, RI, United States
k Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, United States
l Division of Neurology, Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, United States
m Pediatric Infectious Diseases, Department of Child Health, Sultan Qaboos University, Muscat, Oman
n Division of Infectious Diseases, Department of Pediatrics, Children’s Hospital Los Angeles and Keck School of Medicine of University of Southern California, Los Angeles, CA, United States
Abstract
Background Acute flaccid myelitis (AFM) is a severe illness similar to paralytic poliomyelitis. It is unclear how frequently AFM occurred in U.S. children after poliovirus elimination. In 2014, an AFM cluster was identified in Colorado, prompting passive US surveillance that yielded 120 AFM cases of unconfirmed etiology. Subsequently, increased reports were received in 2016 and 2018. To help inform investigations on causality of the recent AFM outbreaks, our objective was to determine how frequently AFM had occurred before 2014, and if 2014 cases had different characteristics. Methods We conducted a retrospective study covering 2005–2014 at 5 pediatric centers in 3 U.S. regions. Possible AFM cases aged ≤18 years were identified by searching discharge ICD-9 codes and spinal cord MRI reports (>37,000). Neuroradiologists assessed MR images, and medical charts were reviewed; possible cases were classified as AFM, not AFM, or indeterminate. Results At 5 sites combined, 26 AFM cases were identified from 2005–2013 (average annual number, 3 [2.4 cases/100,000 pediatric hospitalizations]) and 18 from 2014 (12.6 cases/100,000 hospitalizations; Poisson exact p<0.0001). A cluster of 13 cases was identified in September–October 2014 (temporal scan p = 0.0001). No other temporal or seasonal trend was observed. Compared with cases from January 2005–July 2014 (n = 29), cases from August–December 2014 (n = 15) were younger (p = 0.002), more frequently had a preceding respiratory/febrile illness (p = 0.03), had only upper extremities involved (p = 0.008), and had upper extremity monoplegia (p = 0.03). The cases had higher WBC counts in cerebrospinal fluid (p = 0.013). Conclusion Our data support emergence of AFM in 2014 in the United States, and those cases demonstrated distinctive features compared with preceding sporadic cases. Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Document Type: Review
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Early Mechanical Hearing Devices” (2019) Hearing Journal
Early Mechanical Hearing Devices
(2019) Hearing Journal, 72 (8), pp. 8-9.
Sarli, C.C.a , Uchanski, R.M.b
a Becker Medical Library’s Translational Research Support Division, Washington University, School of Medicine in St. LouisMO, United States
b Otolaryngology Department, Program in Audiology and Communication Sciences, United States
Document Type: Short Survey
Publication Stage: Final
Source: Scopus