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WashU weekly Neuroscience publications

“CRISPR/Cas9 mediated generation of an ovine model for infantile neuronal ceroid lipofuscinosis (CLN1 disease)” (2019) Scientific Reports

CRISPR/Cas9 mediated generation of an ovine model for infantile neuronal ceroid lipofuscinosis (CLN1 disease)
(2019) Scientific Reports, 9 (1), art. no. 9891, . 

Eaton, S.L.a , Proudfoot, C.a , Lillico, S.G.a , Skehel, P.b c , Kline, R.A.a , Hamer, K.e , Rzechorzek, N.M.d e , Clutton, E.f , Gregson, R.f , King, T.a , O’Neill, C.A.g , Cooper, J.D.h i , Thompson, G.b , Whitelaw, C.B.a , Wishart, T.M.a c

a The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, United Kingdom
b Centre for Discovery Brain Science, University of Edinburgh, Hugh Robson Building, Edinburgh, United Kingdom
c Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh, United Kingdom
d Centre for Clinical Brain Sciences, University of Edinburgh, Chancellor’s Building, 49 Little France Crescent, Edinburgh, United Kingdom
e Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Edinburgh, United Kingdom
f Wellcome Trust Critical Care Laboratory for Large Animals, Roslin Institute, Easter Bush, Edinburgh, United Kingdom
g BioMarin Pharmaceutical Inc, San Rafael, CA, United States
h Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, David Geffen School of Medicine, UCLA, Torrance, CA, United States
i Department of Pediatrics, Washington University School of Medicine, St Louis, MO, United States

Abstract
The neuronal ceroid lipofuscinoses (NCLs) are a group of devastating monogenetic lysosomal disorders that affect children and young adults with no cure or effective treatment currently available. One of the more severe infantile forms of the disease (INCL or CLN1 disease) is due to mutations in the palmitoyl-protein thioesterase 1 (PPT1) gene and severely reduces the child’s lifespan to approximately 9 years of age. In order to better translate the human condition than is possible in mice, we sought to produce a large animal model employing CRISPR/Cas9 gene editing technology. Three PPT1 homozygote sheep were generated by insertion of a disease-causing PPT1 (R151X) human mutation into the orthologous sheep locus. This resulted in a morphological, anatomical and biochemical disease phenotype that closely resembles the human condition. The homozygous sheep were found to have significantly reduced PPT1 enzyme activity and accumulate autofluorescent storage material, as is observed in CLN1 patients. Clinical signs included pronounced behavioral deficits as well as motor deficits and complete loss of vision, with a reduced lifespan of 17 ± 1 months at a humanely defined terminal endpoint. Magnetic resonance imaging (MRI) confirmed a significant decrease in motor cortical volume as well as increased ventricular volume corresponding with observed brain atrophy and a profound reduction in brain mass of 30% at necropsy, similar to alterations observed in human patients. In summary, we have generated the first CRISPR/Cas9 gene edited NCL model. This novel sheep model of CLN1 disease develops biochemical, gross morphological and in vivo brain alterations confirming the efficacy of the targeted modification and potential relevance to the human condition. © 2019, The Author(s).

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“Myelinating Schwann cells ensheath multiple axons in the absence of E3 ligase component Fbxw7” (2019) Nature Communications

Myelinating Schwann cells ensheath multiple axons in the absence of E3 ligase component Fbxw7
(2019) Nature Communications, 10 (1), art. no. 2976, . 

Harty, B.L.a b c , Coelho, F.c , Pease-Raissi, S.E.d , Mogha, A.c , Ackerman, S.D.b g , Herbert, A.L.b h , Gereau, R.W., IVe , Golden, J.P.e , Lyons, D.A.f , Chan, J.R.d , Monk, K.R.b c

a Thaden School, 410 SE Staggerwing Lane, Bentonville, AR 72712, United States
b Department of Developmental Biology, Washington University School of Medicine, 660S. Euclid Ave., St. Louis, MO 63110, United States
c Vollum Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, United States
d Department of Neurology, Weill Institute for Neuroscience, University of California San Francisco, 675 Nelson Rising Lane, San Francisco, CA 94158, United States
e Department of Anesthesiology, Washington University Pain Center, 660S. Euclid Ave., St. Louis, MO 63110, United States
f Centre for Brain Discovery Sciences, MS Society Centre for Translational Research, Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, 49 Little France Crescent, Edinburgh, EH16 4SB, United Kingdom
g Institute of Neuroscience, University of Oregon, 1440 Franklin Blvd., Eugene, OR 97403, United States
h Department of Developmental Biology, Stanford University, 279W. Campus Dr., Stanford, CA 94305, United States

Abstract
In the central nervous system (CNS), oligodendrocytes myelinate multiple axons; in the peripheral nervous system (PNS), Schwann cells (SCs) myelinate a single axon. Why are the myelinating potentials of these glia so fundamentally different? Here, we find that loss of Fbxw7, an E3 ubiquitin ligase component, enhances the myelinating potential of SCs. Fbxw7 mutant SCs make thicker myelin sheaths and sometimes appear to myelinate multiple axons in a fashion reminiscent of oligodendrocytes. Several Fbxw7 mutant phenotypes are due to dysregulation of mTOR; however, the remarkable ability of mutant SCs to ensheathe multiple axons is independent of mTOR signaling. This indicates distinct roles for Fbxw7 in SC biology including modes of axon interactions previously thought to fundamentally distinguish myelinating SCs from oligodendrocytes. Our data reveal unexpected plasticity in the myelinating potential of SCs, which may have important implications for our understanding of both PNS and CNS myelination and myelin repair. © 2019, The Author(s).

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“Brain controllability: Not a slam dunk yet” (2019) NeuroImage

Brain controllability: Not a slam dunk yet
(2019) NeuroImage, 200, pp. 552-555. 

Suweis, S.a b , Tu, C.c d , Rocha, R.P.b e f , Zampieri, S.b g , Zorzi, M.h i , Corbetta, M.b j k

a Dipartimento di Fisica e Astronomia, ‘G. Galilei’ & INFN, Università di Padova, Padova, Italy
b Padova Neuroscience Center, Università di Padova, Padova, Italy
c Department of Environmental Science, Policy, and Management, University of California, Berkeley, United States
d School of Ecology and Environmental Science, Yunnan UniversityYunnan, China
e Department of Physics, School of Philosophy, Sciences and Letters of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil
f Departamento de Física, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil
g Dipartimento di Ingegneria dell’informazione, Università di Padova, Padova, Italy
h Dipartimento di Psicologia Generale, Università di Padova, Padova, Italy
i Fondazione Ospedale San Camillo IRCCS, Venezia, Italy
j Dipartimento di Neuroscienze, Universita’ di Padova, Padova, Italy
k Departments of Neurology, Radiology, Neuroscience and Bioengineering, Washington University, School of Medicine, St. Louis, United States

Abstract
In our recent article [1] published in this journal we provide quantitative evidence to show that there are warnings and caveats in the way Gu and collaborators [2] define controllability of brain networks and measure the contribution of each of its nodes. The comment by Pasqualetti et al. [3] confirms the need to go beyond the methodology and approach presented in Gu et al.’s original work. In fact, they recognize that “the source of confusion is due to the fact that assessing controllability via numerical analysis typically leads to ill-conditioned problems, and thus often generates results that are difficult to interpret”. This is indeed the first warning we discussed in [1]: our work was not meant to prove that brain networks are not controllable from one node, rather we wished to highlight that the one node controllability framework and all consequent results were not properly justified based on the methodology presented in Gu et al. [2]. We used in our work the same method of Gu et al. not because we believe it is the best methodology, but because we extensively investigated it with the aim of replicating, testing, and extending their results. The warning and caveats we have proposed are the results of this investigation. Indeed, on the basis of our controllability analyses of multiple human brain networks datasets, we concluded: “The λmin(WK) are statistically compatible with zero and thus the associated controllability Gramian cannot be inverted1. These results show that it is not possible to infer one node controllability of the brain numerically”. Hence both groups agree that one node controllability cannot be inferred numerically. © 2019

Document Type: Article
Publication Stage: Final
Source: Scopus

“Differences in early auditory exposure across neonatal environments” (2019) Early Human Development

Differences in early auditory exposure across neonatal environments
(2019) Early Human Development, 136, pp. 27-32. 

Liszka, L.a , Smith, J.b , Mathur, A.c , Schlaggar, B.L.d e , Colditz, G.f g , Pineda, R.a c

a Program in Occupational Therapy, Washington University Program in Occupational Therapy, St. Louis, MO, United States
b Division of Quality, Safety and Practice Excellence, Saint Louis Children’s Hospital, St. Louis, MO, United States
c Department of Pediatrics, Washington University School of Medicine in St. Louis, United States
d Kennedy Krieger Institute, Baltimore, MD, United States
e Departments of Neurology and Pediatrics, Johns Hopkins University School of Medicine, United States
f Public Health Sciences, Washington University School of Medicine in St. LouisMO, United States
g Institute for Public Health, Washington University in St. LouisMO, United States

Abstract
Background: To date, no study has compared preterm and full term auditory environments. Aim: To define differences in auditory exposure for preterm infants at term equivalent age in the neonatal intensive care unit (NICU) compared to auditory exposure in hospital rooms on a labor and delivery ward after full term birth. Study design: Ninety-eight infants (48 preterm infants born 28 weeks gestation in the NICU at term equivalent age and 50 full term infants in a hospital room on the labor and delivery ward within 4 days of birth) had auditory exposure measured over a single 16-hour period using the Language Environment Acquisition (LENA) device. Results: More language (p < 0.001) was observed on the labor and delivery ward than in the NICU, with an average of 3.3 h more language in a 16-hour period and an average of 14,110 more words spoken around infants in a 16-hour period on the labor and delivery ward (p < 0.001). More electronic sounds were observed in the NICU, with an average of 2.3 h more in the 16-hour period (p < 0.001). The average decibel level in the NICU was lower than in the hospital rooms on the labor and delivery ward (57.16 ± 2.30 dB, compared to 63.31 ± 2.22 dB; p < 0.001). Conclusion: The NICU auditory environment for preterm infants is different than the auditory environment for full term infants, with less language, more electronic sounds, and quieter stimuli. This understanding can aid in developing appropriate interventions that enhance positive forms of auditory exposures. © 2019 Elsevier B.V.

Author Keywords
Full term birth;  Language;  Neonatal intensive care unit;  Preterm birth;  Sound

Document Type: Article
Publication Stage: Final
Source: Scopus

“Leverage points to improve smoking cessation treatment in a large tertiary care hospital:A systems-based mixed methods study” (2019) BMJ Open

Leverage points to improve smoking cessation treatment in a large tertiary care hospital:A systems-based mixed methods study
(2019) BMJ Open, 9 (7), art. no. e030066, . 

Ramsey, A.T.a , Prentice, D.b , Ballard, E.c , Chen, L.-S.a , Bierut, L.J.a

a Department of Psychiatry, Washington University School of Medicine in Saint Louis, Saint Louis, MO, United States
b Department of Research for Patient Care Services, Barnes-Jewish Hospital, Saint Louis, MO, United States
c Brown School of Social Work and Public Health, Washington University in Saint Louis, Saint Louis, MO, United States

Abstract
Objectives To generate system insights on patient and provider levers and strategies that must be activated to improve hospital-based smoking cessation treatment. Design Mixed methods study including a series of in-depth group model building sessions, which informed the design of an online survey completed by healthcare providers and a structured interview protocol administered at the bedside to patients who smoke. Setting Large, tertiary care hospital in the Midwestern United States. Participants Group model building: 28 healthcare providers and 22 previously-hospitalised patients; Online survey: 308 healthcare providers; Bedside interviews: 205 hospitalised patients. Primary and secondary outcome measures Hypothesis-generating, participatory qualitative methods informed the examination of the following quantitative outcomes: Patient interest versus provider perception of patient interest in smoking cessation and treatment; patient-reported receipt versus provider-reported offering of inpatient smoking cessation interventions; and priority ratings of importance and feasibility of strategies to improve treatment. Results System insights included patients frequently leaving the floor to smoke, which created major workflow disruption. Leverage points included interventions to reduce withdrawal symptoms, and action ideas included nurse-driven protocols for timely administration of nicotine replacement therapy. Quantitative data corroborated system insights; for instance, 80% of providers reported that patients frequently leave the floor to smoke, leading to safety risks, missed assessments and inefficient use of staff time. Patients reported significantly lower rates of receiving any smoking cessation interventions, compared with provider reports (mean difference=17.4%-33.7%, p<0.001). Although 92% of providers cited patient interest as a key barrier, only 4% of patients indicated no interest in quitting or reducing smoking. Conclusions Engaging hospital providers and patients in participatory approaches to develop an implementation strategy revealed discrepant perceptions of patient interest and frequency of hospital-based treatment for smoking. These findings spurred adoption of standardised point-of-care treatment for cigarette smoking, which remains highly prevalent yet undertreated among hospitalised patients. © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Author Keywords
Internal medicine;  Preventive medicine;  Qualitative research;  Quality in health care

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“Symptom-level analysis of DSM-IV/DSM-5 personality pathology in later life: Hierarchical structure and predictive validity across self-and informant ratings” (2019) Journal of Abnormal Psychology

Symptom-level analysis of DSM-IV/DSM-5 personality pathology in later life: Hierarchical structure and predictive validity across self-and informant ratings
(2019) Journal of Abnormal Psychology, 128 (5), pp. 365-384. 

Boudreaux, M.J.a , South, S.C.b , Oltmanns, T.F.a

a Department of Psychological and Brain Sciences, Washington University in St. Louis, One Brookings Drive, St. Louis, MO 63130, United States
b Department of Psychological Sciences, Purdue University, United States

Abstract
Dissatisfaction with the categorical model of personality disorder led to several investigations on alternative, dimensional systems. The majority of these studies were conducted at the syndrome-level where each diagnostic criterion is summed or averaged within each disorder. Studies at the symptom-level have identified symptom dimensions that define and cut across categories, but the number and nature of dimensions varies across studies. The purpose of the present study was to examine the hierarchical structure and impact of personality pathology at the symptom-level across self-and informant ratings in a large community sample of older adults (N 1,630; ages 55 to 64). Results indicated that multiple structural patterns can be organized within a common hierarchical framework, with a general factor of maladjustment at the top, 2 broad dimensions of internalizing and externalizing pathology directly below, and progressively more specific symptom dimensions toward the bottom. Factors at each level of the hierarchy were similar across self-and informant ratings. The 4-factor model showed significant incremental validity in predicting a range of life outcomes over simpler models, while increasingly complex models incrementally but modestly improved predictive power. Several consistencies emerged between the current findings and prior factor analytic studies. The most unexpected result was the conspicuous absence of a disinhibition factor reflecting antisocial and impulsivity-related problems. This anomaly may involve the older age of our sample and the changing expression of personality pathology in later life. © 2019 American Psychological Association.

Author Keywords
Factor analysis;  Maladaptive personality;  Multisource assessment of personality pathology;  Personality disorder;  Predictive validity

Document Type: Article
Publication Stage: Final
Source: Scopus

“The role of afferent input in postamputation pain: a randomized, double-blind, placebo-controlled crossover study” (2019) Pain

The role of afferent input in postamputation pain: a randomized, double-blind, placebo-controlled crossover study
(2019) Pain, 160 (7), pp. 1622-1633. 

Buch, N.S.a b , Ahlburg, P.a , Haroutounian, S.c , Andersen, N.T.d , Finnerup, N.B.b e , Nikolajsen, L.a

a Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Aarhus, Denmark
b Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
c Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States
d Section for Biostatistics, Department of Public Health, Aarhus University, Aarhus, Denmark
e Department of Neurology, Aarhus University Hospital, Arhus, Denmark

Abstract
In this randomized, double-blind, placebo-controlled crossover study, we investigated whether a peripheral nerve block could temporarily eliminate phantom and stump pain after amputation. Amputees with constant postamputation pain were included and randomized to receive a nerve block with lidocaine 2% with adrenaline or saline in a crossover design. Spontaneous phantom and stump pain and evoked responses were assessed at baseline and at fixed time-points until 120 minutes after lidocaine or saline injection. The primary outcome was the difference in absolute change between worst pain intensity, either phantom or stump pain, at baseline and at 30 minutes after lidocaine or saline injection. Twelve amputees were randomized and 9 patients were included in the analysis. The absolute change in median worst pain intensity between lidocaine and saline injection was -2.0 (interquartile range, -4.0 to 0.0) (n = 9, P = 0.12). Nine of 9 patients reported at least some pain relief after lidocaine injection compared with only 2 of 9 patients after saline injection (P = 0.02). Phantom pain intensity was significantly reduced after lidocaine compared with saline injection (P = 0.04), whereas there was no significant change in stump pain intensity between the 2 interventions (P = 0.17). In all 9 amputees, evoked responses were eliminated after lidocaine injection. Thus, our findings suggest that afferent input from the peripheral nervous system plays an important role in postamputation pain.

Document Type: Article
Publication Stage: Final
Source: Scopus

“AQP1 Overexpression in the CSF of Obstructive Hydrocephalus and Inversion of Its Polarity in the Choroid Plexus of a Chiari Malformation Type II Case” (2019) Journal of Neuropathology and Experimental Neurology

AQP1 Overexpression in the CSF of Obstructive Hydrocephalus and Inversion of Its Polarity in the Choroid Plexus of a Chiari Malformation Type II Case
(2019) Journal of Neuropathology and Experimental Neurology, 78 (7), pp. 641-647. 

Castañeyra-Ruiz, L.a , Hernández-Abad, L.G.b , Carmona-Calero, E.M.c , Castañeyra-Perdomo, A.c , González-Marrero, I.c

a Department of Neurological Surgery, Washington University, School of Medicine and the St. Louis Children’s Hospital, St. Louis, MO, United States
b Instituto de Investigación y Ciencias, Puerto del Rosario, Fuerteventura
c Departamento de Anatomía, Anatomía, Patológica e Histología, Facultad de Medicina, Universidad de La Laguna, Tenerife, La Laguna, Spain

Abstract
The choroid plexus (ChP) is involved in the production of cerebrospinal fluid (CSF) and is intimately related to CSF physiopathology. Aquaporin-1 (AQP1) is the water channel directly implicated in CSF production and a potential therapeutic target in the management of CSF circulation disorders. Pathologies that present ventriculomegaly are associated with defective CSF turnover and AQPs are involved in both the production and reabsorption of CSF. This work examines the levels of AQP1 and its dynamics in ventriculomegaly conditions such as congenital hydrocephalus (communicating and obstructive) or type II lissencephaly versus control. We specifically address the expression of AQP1 in the CSF of 16 term-pregnancy infants where it was found to be significantly increased in obstructive cases when compared with communicating hydrocephalus or control patients. We also defined histologically the expression of AQP1 in the ChP from 6 nonsurvival preterm-pregnancy infants ranging ages between 20 and 25 gestational weeks in which AQP1 was mainly expressed at the apical pole of the ChP epithelium (ChPE) in control and lissencephalic patients. AQP1 expression from the Chiari malformation case showed an inverted polarity being expressed in the basal pole of the ChPE colocalizing with the glucose transporter 1 where this transporter is naturally located. © 2019 American Association of Neuropathologists, Inc. All rights reserved.

Author Keywords
Aquaporin-1;  Chiari malformation;  Choroid plexus;  Hydrocephalus;  Lissencephaly;  Ventriculomegaly

Document Type: Article
Publication Stage: Final
Source: Scopus

“Pituitary Adenoma in Pediatric and Adolescent Populations” (2019) Journal of Neuropathology and Experimental Neurology

Pituitary Adenoma in Pediatric and Adolescent Populations
(2019) Journal of Neuropathology and Experimental Neurology, 78 (7), pp. 626-632. 

Chen, J., Schmidt, R.E., Dahiya, S.

Division of Neuropathology, Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, United States

Abstract
Pituitary adenomas are rare in children and adolescents and although mostly benign, they can sometimes be challenging to manage due to their locally invasive nature. In this study, we examined the clinicopathologic features of 42 pituitary adenomas in patients ≤21 years of age. The youngest patient was 8 years old (median age: 18 years), and the female-to-male ratio was 1.8:1. Five patients had recurrence after resection. There was no obvious difference between the recurrent rates in the typical (11.7%) and atypical adenomas (12.5%) based on the 2004 WHO classification. However, the recurrence rate was much higher in adenomas with an elevated proliferation index of ≥3% (20.8%) or with evidence of local invasion (18.2%). Adenomas with combination of an elevated proliferation index of ≥3% and imaging evidence of local invasion had the highest recurrence rate of 25%. In summary, pituitary adenomas are more frequent in adolescents as compared with children and are more common in girls. An elevated proliferation index of ≥3% and evidence of local invasion on imaging seem to correlate with a high probability of recurrence. Furthermore, we observe rarity of α-thalassemia/mental retardation syndrome X-linked (ATRX) protein loss (surrogate to ATRX mutation) in these tumors without any connotation on prognosis. © 2019 American Association of Neuropathologists, Inc.

Author Keywords
ATRX;  atypical;  clinicopathologic features;  invasive;  pediatric;  pituitary neuroendocrine neoplasm;  prognosis;  WHO classification

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“Working Memory Impairment Across Psychotic disorders” (2019) Schizophrenia Bulletin

Working Memory Impairment Across Psychotic disorders
(2019) Schizophrenia Bulletin, 45 (4), pp. 804-812. Cited 2 times.

Gold, J.M.a , Barch, D.M.b , Feuerstahler, L.M.c , Carter, C.S.d , MacDonald, A.W.e , Ragland, J.D.d , Silverstein, S.M.f g , Strauss, M.E.h , Luck, S.J.i

a Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, United States
b Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO, United States
c Graduate School of Education, University of California at Berkeley, Berkeley, CA, United States
d Department of Psychiatry and Behavioral Sciences, University of California at Davis, Davis, CA, United States
e Department of Psychology, University of Minnesota, Minneapolis, MN, United States
f Rutgers University Behavioral Health Care, Piscataway, NJ, United States
g Rutgers University, Robert Wood Johnson Medical School Department of Psychiatry, Piscataway, NJ, United States
h Department of Psychology, University of New Mexico, Albuquerque, NM, United States
i Department of Psychology, Center for Mind and Brain, University of California at Davis, Davis, CA, United States

Abstract
BACKGROUND: Working memory (WM) has been a central focus of cognitive neuroscience research because WM is a resource that is involved in many different cognitive operations. The goal of this study was to evaluate the clinical utility of WM paradigms developed in the basic cognitive neuroscience literature, including methods designed to estimate storage capacity without contamination by lapses of attention. METHODS: A total of 61 people with schizophrenia, 49 with schizoaffective disorder, 47 with bipolar disorder with psychosis, and 59 healthy volunteers were recruited. Participants received multiple WM tasks, including two versions each of a multiple Change Detection paradigm, a visual Change Localization paradigm, and a Running Span task. RESULTS: Healthy volunteers performed better than the combined patient group on the visual Change Localization and running span measures. The multiple Change Detection tasks provided mixed evidence about WM capacity reduction in the patient groups, but a mathematical model of performance suggested that the patient groups differed from controls in their rate of attention lapsing. The 3 patient groups performed similarly on the WM tasks. Capacity estimates from the Change Detection and Localization tasks showed significant correlations with functional capacity and functional outcome. CONCLUSIONS: The patient groups generally performed in a similarly impaired fashion across tasks, suggesting that WM impairment and attention lapsing are general features of psychotic disorders. Capacity estimates from the Change Localization and Detection tasks were related to functional capacity and outcome, suggesting that these methods may be useful in a clinical context. © The Author(s) 2018. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Author Keywords
capacity limitations;  cognitive impairment;  psychosis;  schizophrenia;  working memory

Document Type: Article
Publication Stage: Final
Source: Scopus

“Difference in Speech Recognition between a Default and Programmed Telecoil Program” (2019) Journal of the American Academy of Audiology

Difference in Speech Recognition between a Default and Programmed Telecoil Program
(2019) Journal of the American Academy of Audiology, 30 (6), pp. 502-515. 

Ledda, K.T., Valente, M., Oeding, K., Kallogjeri, D.

Division of Adult Audiology, Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Washington University in St. Louis, St. Louis, MO, United States

Abstract
BACKGROUND: Hearing loss can lead to isolation and social withdrawal. The telephone oftentimes connects persons with hearing loss to society; however, telephone use is impeded by narrow bandwidth, loss of visual cues, electromagnetic interference, and inherent phone-line noise. In the past, research assessing telephone communication has consistently reported that switching from the microphone to a telecoil will typically result in the acoustic signal being discernibly softer. Properly used telecoils improve the signal-to-noise ratio (SNR), decrease the chance for acoustic feedback, and overcome the impact of distance and reverberation creating an opportunity for clearer telephone communication. Little research, however, has examined matching the telecoil frequency response to the prescribed target of the microphone frequency response (National Acoustics Laboratories, Non-Linear, version 1 [NAL-NL1]). PURPOSE: The primary goal of this study was to determine if differences exist in speech recognition for sentences (AZ-BIO) and consonant-vowel nucleus-consonant monosyllabic words (CNC) between two telecoil conditions (default and programmed). A secondary goal was to determine if differences exist in speech recognition for sentences between male and female talkers. RESEARCH DESIGN: A single-blinded randomized controlled trial. STUDY SAMPLE: Twenty experienced adult hearing aid users with bilateral symmetric slight to severe sensorineural hearing loss were recruited from Washington University in St. Louis School of Medicine. In addition, ten normal-hearing participants were recruited to determine the presentation level of the speech stimuli for the hearing aid participants. DATA COLLECTION AND ANALYSIS: Participants underwent real-ear measures to program the microphone frequency response of a receiver-in-the-canal hearing aid to NAL-NL1. Using the manufacturer software, one telecoil program remained as the manufacturer default and a second telecoil program was programmed so the sound pressure level for an inductive telephone simulator frequency response matching the microphone’s frequency response to obtain as close to a 0 dB relative simulated equivalent telephone sensitivity value as possible. Participants then completed speech recognition measures including AZ-BIO sentences (male and female talkers) and CNC monosyllabic words and phonemes, using both telecoil programs. A mixed model analysis was performed to examine if significant differences in speech recognition exist between the two conditions and speech stimuli. RESULTS: Results revealed significant improvement in overall speech recognition for the programmed telecoil performance compared with default telecoil performance (p < 0.001). Also, improved performance in the programmed telecoil was reported with a male talker (p < 0.001) and performance for sentences compared with monosyllabic words (p < 0.001) or phonemes (p < 0.001). CONCLUSIONS: The programmed telecoil condition revealed significant improvement in speech recognition for all speech stimuli conditions compared with the default telecoil (sentences, monosyllables, and phonemes). Additional improvement was observed in both telecoil conditions when the talker was male. American Academy of Audiology.

Document Type: Article
Publication Stage: Final
Source: Scopus

“Comparing Linear and Volumetric Vestibular Schwannoma Measurements Between T1 and T2 Magnetic Resonance Imaging Sequences” (2019) Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society and European Academy of Otology and Neurotology

Comparing Linear and Volumetric Vestibular Schwannoma Measurements Between T1 and T2 Magnetic Resonance Imaging Sequences
(2019) Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, (5S Suppl 1), pp. S67-S71. 

Tolisano, A.M.a , Wick, C.C.b , Hunter, J.B.a

a Department of Otolaryngology-Head and Neck Surgery, University of Texas Southwestern Medical Center, Dallas, TX, United States
b Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, United States

Abstract
OBJECTIVE: To compare linear and volumetric vestibular schwannoma (VS) measurements between different magnetic resonance imaging (MRI) sequences. STUDY DESIGN: Retrospective case series. SETTING: Tertiary care university hospital. PATIENTS: Those with VS that had at least two separate MRI studies containing both T1-weighted contrast (T1C) and high-resolution T2-weighted (HRT2) images. INTERVENTION: Two neurotologists measured the greatest linear axial dimension and segmentation volumes of VS. MAIN OUTCOME MEASURE: 1) Correlation between T1C and HRT2 VS linear and volumetric measurements. 2) Comparing the interpretation of VS growth between T1C and HRT2 sequences and reviewers, defined as an increase in tumor diameter of more than or equal to 2 mm or a volume increase of more than or equal to 20%. RESULTS: Twenty-three patients met inclusion criteria. Imaging studies encompassed a median of 25.2 months. At the initial imaging study, inter-observer measurements between reviewers, analyzed with intraclass correlation coefficients, for T1C diameters, T1C volumes, HRT2 diameters, and HRT2 volumes were 0.983 (95% confidence interval [CI] 0.972-0.989), 0.989 (95% CI 0.982-0.993), 0.992 (95% CI 0.988-0.995), and 0.998 (95% CI 0.995-0.999), respectively. The Cohen’s kappa for growth rates between T1C diameters, T1C volumes, HRT2 diameters, and HRT2 volumes was 0.564 (95% CI 0.284-0.844), 0.704 (95% CI 0.514-0.894), 0.605 (95% CI 0.319-0.891), and 0.475 (95% CI 0.242-0.708), respectively. CONCLUSIONS: There are significant differences in VS volume measurements when utilizing T1C versus HRT2 images. However, there is “excellent” interobserver agreement between T1C and HRT2 diameters and volumes. T1C VS volumes may be more reliable than HRT2 volumes to determine growth.

Document Type: Article
Publication Stage: Final
Source: Scopus

“Peer victimization and dysfunctional reward processing: ERP and behavioral responses to social and monetary rewards” (2019) Frontiers in Behavioral Neuroscience

Peer victimization and dysfunctional reward processing: ERP and behavioral responses to social and monetary rewards
(2019) Frontiers in Behavioral Neuroscience, 13, art. no. 120, . 

Rappaport, B.I.a , Hennefield, L.b , Kujawa, A.c , Arfer, K.B.d , Kelly, D.b , Kappenman, E.S.e , Luby, J.L.b , Barch, D.M.a b f

a Department of Psychological & Brain Sciences, Washington University in St. Louis, St. Louis, MO, United States
b Department of Psychiatry, School of Medicine, Washington University in St. Louis, St. Louis, MO, United States
c Department of Psychology & Human Development, Vanderbilt University, Nashville, TN, United States
d Center for HIV Identification, Prevention, and Treatment Services, University of California, Los Angeles, Los Angeles, CA, United States
e Department of Psychology, San Diego State University, San Diego, CA, United States
f Department of Radiology, School of Medicine, Washington University in St. Louis, St. Louis, MO, United States

Abstract
Peer victimization (or bullying) is a known risk factor for depression, especially among youth. However, the mechanisms connecting victimization experience to depression symptoms remains unknown. As depression is known to be associated with neural blunting to monetary rewards, aberrant responsiveness to social rewards may be a key deficit connecting socially stressful experiences with later depression. We, therefore, sought to determine whether adolescents’ experiences with social stress would be related to their current response to social rewards over less socially relevant monetary rewards. Neural responses to monetary and social rewards were measured using event-related potentials (ERPs) to peer acceptance and rejection feedback (Island Getaway task) and to monetary reward and loss feedback (Doors task) in a sample of 56 late adolescents/emerging young adults followed longitudinally since preschool. In the Island Getaway task, participants voted whether to “keep” or “kick out” each co-player, providing an index of prosocial behavior, and then received feedback about how each player voted for the participant. Analyses tested whether early and recent peer victimization was related to response to rewards (peer acceptance or monetary gains), residualized for response to losses (peer rejection or monetary losses) using the reward positivity (RewP) component. Findings indicated that both experiencing greater early and greater recent peer victimization were significantly associated with participants casting fewer votes to keep other adolescents (“Keep” votes) and that greater early peer victimization was associated with reduced neural response to peer acceptance. Early and recent peer victimization were significantly more associated with neural response to social than monetary rewards. Together, these findings suggest that socially injurious experiences such as peer victimization, especially those occurring early in childhood, relate to two distinct but important findings: that early victimization is associated with later reduced response to peer acceptance, and is associated with later tendency to reject peers. Findings also suggest that there is evidence of specificity to reward processing of different types; thus, future research should expand studies of reward processing beyond monetary rewards to account for the possibility that individual differences may be related to other, more relevant, reward types. © 2019 Rappaport, Hennefield, Kujawa, Arfer, Kelly, Kappenman, Luby and Barch.

Author Keywords
Adolescence;  Depression;  Event-related potentials (ERP);  Monetary reward;  Peer victimization;  Reward;  Social reward

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“A phase 1 and randomized, placebo-controlled phase 2 trial of bevacizumab plus dasatinib in patients with recurrent glioblastoma: Alliance/North Central Cancer Treatment Group N0872” (2019) Cancer

A phase 1 and randomized, placebo-controlled phase 2 trial of bevacizumab plus dasatinib in patients with recurrent glioblastoma: Alliance/North Central Cancer Treatment Group N0872
(2019) Cancer, . 

Galanis, E.a , Anderson, S.K.b , Twohy, E.L.b , Carrero, X.W.b , Dixon, J.G.b , Tran, D.D.c j , Jeyapalan, S.A.d , Anderson, D.M.e , Kaufmann, T.J.f , Feathers, R.W.g , Giannini, C.h , Buckner, J.C.a , Anastasiadis, P.Z.g , Schiff, D.i

a Department of Oncology, Mayo Clinic, Rochester, MN, United States
b Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN, United States
c Oncology Division, Washington University School of Medicine, St. Louis, MO, United States
d Department of Neurology, Tufts Medical Center, Boston, MA, United States
e Department of Hematology/Oncology, Regions Hospital, St Paul, MN, United States
f Department of Radiology, Mayo Clinic, Rochester, MN, United States
g Department of Cancer Biology, Mayo Clinic, Jacksonville, FL, United States
h Department of Pathology, Mayo Clinic, Rochester, MN, United States
i Department of Neurology, University of Virginia Medical Center, Charlottesville, VA, United States
j Lillian S. Wells Department of Neurosurgery, University of Florida College of Medicine, Gainesville, FL, United States

Abstract
Background: Src signaling is markedly upregulated in patients with invasive glioblastoma (GBM) after the administration of bevacizumab. The Src family kinase inhibitor dasatinib has been found to effectively block bevacizumab-induced glioma invasion in preclinical models, which led to the hypothesis that combining bevacizumab with dasatinib could increase bevacizumab efficacy in patients with recurrent GBM. Methods: After the completion of the phase 1 component, the phase 2 trial (ClinicalTrials.gov identifier NCT00892177) randomized patients with recurrent GBM 2:1 to receive 100 mg of oral dasatinib twice daily (arm A) or placebo (arm B) on days 1 to 14 of each 14-day cycle combined with 10 mg/kg of intravenous bevacizumab on day 1 of each 14-day cycle. The primary endpoint was 6-month progression-free survival (PFS6). Results: In the 121 evaluable patients, the PFS6 rate was numerically, but not statistically, higher in arm A versus arm B (28.9% [95% CI, 19.5%-40.0%] vs 18.4% [95% CI, 7.7%-34.4%]; P =.22). Similarly, there was no significant difference in the median overall survival noted between the treatment arms (7.3 months and 7.7 months, respectively; P =.93). The objective response rate was 15.7% in arm A and 26.3% in arm B (P =.52), but with a significantly longer duration in patients treated on arm A (16.3 months vs 2 months). The incidence of grade ≥3 toxicity was comparable between treatment arms, with hematologic toxicities occurring more frequently in arm A versus arm B (15.7% vs 7.9%) (adverse events were assessed as per the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). Correlative tissue analysis demonstrated an association between pSRC/LYN signaling in patient tumors and outcome. Conclusions: Despite upregulation of Src signaling in patients with GBM, the combination of bevacizumab with dasatinib did not appear to significantly improve the outcomes of patients with recurrent GBM compared with bevacizumab alone. © 2019 American Cancer Society

Author Keywords
bevacizumab;  dasatinib;  phase 2 trial;  recurrent glioblastoma;  Src family kinase inhibitors

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Screening eye exams in youth with type 1 diabetes under 18 years of age: Once may be enough?” (2019) Pediatric Diabetes

Screening eye exams in youth with type 1 diabetes under 18 years of age: Once may be enough?
(2019) Pediatric Diabetes, . 

Gubitosi-Klug, R.A.a , Bebu, I.b , White, N.H.c , Malone, J.d , Miller, R.e , Lorenzi, G.M.f , Hainsworth, D.P.g , Trapani, V.R.b , Lachin, J.M.b , Tamborlane, W.V.h , for The Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group*i

a Case-Western Reserve University, Cleveland, OH, United States
b George Washington University, Rockville, MD, United States
c Washington University, St. Louis, MO, United States
d University of South Florida, Tampa, FL, United States
e University of Maryland, Baltimore, MD, United States
f University of California, San Diego, CA, United States
g University of Missouri, Columbia, MO, United States
h Yale University, New Haven, CT, United States

Abstract
Case series and registry data suggest that diabetic retinopathy requiring treatment is rare in youth with type 1 diabetes (T1D) prior to 18 years of age. We evaluated this question in the standardized clinical trial setting by retrospectively reviewing diabetic retinopathy examinations from participants in the Diabetes Control and Complications Trial (DCCT) who were 13 to <18 years of age at randomization. Standardized stereoscopic 7-field fundus photographs were obtained every 6 months during DCCT (1983-1993). Photographs were graded centrally using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Transitions in diabetic retinopathy status over time were described. A total of 195 participants with median baseline glycated hemoglobin (HbA1c) of 9.3% (103 in the conventional and 92 in the intensive treatment groups) had an average of 5.3 diabetic retinopathy assessments during 2.3 years of follow-up (range 1-11) while under 18 years of age during the DCCT. No participant developed severe non-proliferative diabetic retinopathy or proliferative diabetic retinopathy and only one participant (in the intensive group) reached clinically significant macular edema (CSME) while less than 18 years of age. In this incident case, baseline characteristics included diabetes duration 9.3 years, HbA1c 10.3%, LDL 131 mg/dL, and mild non-proliferative diabetic retinopathy (35/35 ETDRS scale); CSME resolved without treatment. Similar analyses using age cut-offs of <19, 20, or 21 years showed a slight rise in diabetic retinopathy requiring treatment over late adolescence. Clinical trial evidence suggests that frequent eye exams may not be universally necessary in youth <18 years of age with T1D. © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Author Keywords
adolescents;  diabetic retinopathy;  screening;  type 1 diabetes

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Higher executive abilities following a blood transfusion in children and young adults with sickle cell disease” (2019) Pediatric Blood and Cancer

Higher executive abilities following a blood transfusion in children and young adults with sickle cell disease
(2019) Pediatric Blood and Cancer, art. no. e27899, . 

Hood, A.M.a , King, A.A.b , Fields, M.E.c , Ford, A.L.d , Guilliams, K.P.d e , Hulbert, M.L.c , Lee, J.-M.e f , White, D.A.a

a Department of Psychological & Brain Sciences, Washington University, St. Louis, MO, United States
b Program in Occupational Therapy and Pediatrics, Division of Hematology and Oncology, Washington University School of Medicine and St. Louis Children’s Hospital, St. Louis, MO, United States
c Division of Pediatric Hematology/Oncology, Washington University School of Medicine, St. Louis, MO, United States
d Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
e Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
f Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Individuals with sickle cell disease (SCD) experience cognitive deficits; however, it remains unclear whether medical treatments for SCD improve cognition. Given that executive abilities are typically impaired in individuals with SCD, they were the focus of the current study. Our primary hypothesis was that executive abilities would be higher acutely soon after a blood transfusion in children and young adults with SCD. We used tests from the NIH Toolbox to assess executive abilities in 27 participants with SCD receiving chronic transfusion in comparison to 34 participants with SCD receiving hydroxyurea (HU) and 41 non-SCD demographically matched controls, all of whom were tested at two time points. Participants in the transfusion group completed cognitive testing within 3 days after a transfusion (soon after transfusion) and then within 3 days before their next transfusion (long after transfusion) over an interval of 3-7 weeks. We found that executive abilities were significantly poorer for the transfusion and HU groups than for the control group. In support of our primary hypothesis, executive abilities for the transfusion group were significantly better soon after a transfusion compared to long after a transfusion, χ2(1) = 17.8, P &lt;.0001. Our results demonstrate that executive abilities were higher acutely following a blood transfusion. These findings have implications for daily functioning, medical decision making, and academic achievement in children and young adults with SCD. © 2019 Wiley Periodicals, Inc.

Author Keywords
cognition;  executive abilities;  hemoglobin;  hydroxyurea;  sickle cell disease;  transfusion

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Genome-wide association studies of the self-rating of effects of ethanol (SRE)” (2019) Addiction Biology

Genome-wide association studies of the self-rating of effects of ethanol (SRE)
(2019) Addiction Biology, art. no. e12800, . 

Lai, D.a , Wetherill, L.a , Kapoor, M.b , Johnson, E.C.c , Schwandt, M.d , Ramchandani, V.A.e , Goldman, D.d , Joslyn, G.f , Rao, X.a , Liu, Y.a , Farris, S.g , Mayfield, R.D.g , Dick, D.h , Hesselbrock, V.i , Kramer, J.j , McCutcheon, V.V.c , Nurnberger, J.a k , Tischfield, J.l , Goate, A.b , Edenberg, H.J.a m , Porjesz, B.n , Agrawal, A.c , Foroud, T.a , Schuckit, M.o

a Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United States
b Department of Neuroscience, Icahn School of Medicine at Mt. Sinai, New York, NY, United States
c Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
d Office of the Clinical Director, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, United States
e Section on Human Psychopharmacology, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, United States
f Ernest Gallo Clinic and Research Center, Emeryville, CA, United States
g Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, TX, United States
h Department of Psychology, Virginia Commonwealth University, Richmond, VA, United States
i Department of Psychiatry, University of Connecticut, Farmington, CT, United States
j Department of Psychiatry, Roy Carver College of Medicine, University of Iowa, Iowa City, IA, United States
k Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, United States
l Department of Genetics and the Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ, United States
m Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, United States
n Henri Begleiter Neurodynamics Lab, Department of Psychiatry, State University of New York, Downstate Medical Center, Brooklyn, NY, United States
o Department of Psychiatry, University of California, San Diego Medical School, San Diego, CA, United States

Abstract
The level of response (LR) to alcohol as measured with the Self-Report of the Effects of Alcohol Retrospective Questionnaire (SRE) evaluates the number of standard drinks usually required for up to four effects. The need for a higher number of drinks for effects is genetically influenced and predicts higher risks for heavy drinking and alcohol problems. We conducted genome-wide association study (GWAS) in the African-American (COGA-AA, N = 1527 from 309 families) and European-American (COGA-EA, N = 4723 from 956 families) subsamples of the Collaborative Studies on the Genetics of Alcoholism (COGA) for two SRE scores: SRE-T (average of first five times of drinking, the period of heaviest drinking, and the most recent 3 months of consumption) and SRE-5 (the first five times of drinking). We then meta-analyzed the two COGA subsamples (COGA-AA + EA). Both SRE-T and SRE-5 were modestly heritable (h2: 21%-31%) and genetically correlated with alcohol dependence (AD) and DSM-IV AD criterion count (rg: 0.35-0.76). Genome-wide significant associations were observed (SRE-T: chromosomes 6, rs140154945, COGA-EA P = 3.30E-08 and 11, rs10647170, COGA-AA+EA P = 3.53E-09; SRE-5: chromosome13, rs4770359, COGA-AA P = 2.92E-08). Chromosome 11 was replicated in an EA dataset from the National Institute on Alcohol Abuse and Alcoholism intramural program. In silico functional analyses and RNA expression analyses suggest that the chromosome 6 locus is an eQTL for KIF25. Polygenic risk scores derived using the COGA SRE-T and SRE-5 GWAS predicted 0.47% to 2.48% of variances in AD and DSM-IV AD criterion count in independent datasets. This study highlights the genetic contribution of alcohol response phenotypes to the etiology of alcohol use disorders. © 2019 Society for the Study of Addiction

Author Keywords
genetic correlation;  genome-wide association study (GWAS);  heritability;  polygenic risk score;  RNA expression;  self-rating of the effects of ethanol (SRE)

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Battery-free, fully implantable optofluidic cuff system for wireless optogenetic and pharmacological neuromodulation of peripheral nerves” (2019) Science Advances

Battery-free, fully implantable optofluidic cuff system for wireless optogenetic and pharmacological neuromodulation of peripheral nerves
(2019) Science Advances, 5 (7), art. no. eaaw5296, . 

Zhang, Y.a b , Mickle, A.D.c d , Gutruf, P.b e , McIlvried, L.A.c d , Guo, H.b , Wu, Y.b , Golden, J.P.c d , Xue, Y.f g , Grajales-Reyes, J.G.c d , Wang, X.h , Krishnan, S.b , Xie, Y.b , Peng, D.b i , Su, C.-J.b , Zhang, F.j , Reeder, J.T.b , Vogt, S.K.c d , Huang, Y.b f g , Rogers, J.A.b k l m n o , Gereau, R.W., IVc d p

a Department of Biomedical, Biological, and Chemical Engineering, University of Missouri, Columbia, MO 65211, United States
b Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208, United States
c Washington University Pain Center, Department of Anesthesiology, Washington University, St. Louis, MO 63110, United States
d Washington University School of Medicine, 660 S. Euclid Ave., Box 8054, St. Louis, MO 63110, United States
e Biomedical Engineering, College of Engineering, University of Arizona, Bioscience Research Laboratories, 1230 N. Cherry Ave., Tucson, AZ 85721, United States
f Department of Civil and Environmental Engineering, Northwestern University, Evanston, IL 60208, United States
g Department of Mechanical Engineering, Northwestern University, Evanston, IL 60208, United States
h Department of Mechanical and Aerospace Engineering, University of Missouri, Columbia, MO 65211, United States
i College of Optoelectronic Engineering, Shenzhen University, Shenzhen, 518060, China
j School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30318, United States
k Simpson Querrey Institute, Northwestern University, Chicago, IL 60611, United States
l Center for Bio-Integrated Electronics, Northwestern University, Evanston, IL 60208, United States
m Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, United States
n Department of Chemistry, Northwestern University, Evanston, IL 60208, United States
o Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States
p Departments of Neuroscience and Biomedical Engineering, Washington University, St. Louis, MO 63110, United States

Abstract
Studies of the peripheral nervous system rely on controlled manipulation of neuronal function with pharmacologic and/or optogenetic techniques. Traditional hardware for these purposes can cause notable damage to fragile nerve tissues, create irritation at the biotic/abiotic interface, and alter the natural behaviors of animals. Here, we present a wireless, battery-free device that integrates a microscale inorganic light-emitting diode and an ultralow-power microfluidic system with an electrochemical pumping mechanism in a soft platform that can be mounted onto target peripheral nerves for programmed delivery of light and/or pharmacological agents in freely moving animals. Biocompliant designs lead to minimal effects on overall nerve health and function, even with chronic use in vivo. The small size and light weight construction allow for deployment as fully implantable devices in mice. These features create opportunities for studies of the peripheral nervous system outside of the scope of those possible with existing technologies. Copyright © 2019 The Authors.

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“Magnetic Resonance Imaging Findings in Pediatric Pseudotumor Cerebri Syndrome” (2019) Pediatric Neurology

Magnetic Resonance Imaging Findings in Pediatric Pseudotumor Cerebri Syndrome
(2019) Pediatric Neurology, . 

Kohli, A.A.a , Vossough, A.b , Mallery, R.M.c , Woo, J.H.d , Sheldon, C.A.e , Paley, G.L.f , Digre, K.B.g , Friedman, D.I.h , Farrar, J.T.i , McCormack, S.E.j , Liu, G.T.k l m , Szperka, C.L.m n

a Department of Ophthalmology and Visual Science, Yale School of Medicine, New Haven, CT, United States
b Division of Radiology at the Children’s Hospital of Philadelphia, Philadelphia, PA, United States
c Department of Neurology, Brigham and Women’s Hospital, Boston, MA, United States
d Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA, United States
e Department of Ophthalmology & Visual Sciences, The University of British Columbia, Vancouver, British Columbia, Canada
f Department of Ophthalmology, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
g John A. Moran Eye Center, University of Utah, Salt Lake City, UT, United States
h Department of Neurology & Neurotherapeutics and Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX, United States
i Center for Clinical Epidemiology & Statistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States
j Division of Endocrinology & Diabetes, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA, United States
k Division of Ophthalmology, Neuro-Ophthalmology Service, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA, United States
l The Scheie Eye Institute, Hospital of the University of Pennsylvania, Philadelphia, PA, United States
m Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA, United States
n Division of Neurology, Children’s Hospital of Philadelphia, Philadelphia, PA, United States

Abstract
Background: Revised diagnostic criteria for pseudotumor cerebri syndrome require three of four neuroimaging findings in the absence of papilledema. We examined the sensitivity and specificity of three or more of four of these magnetic resonance imaging (MRI) findings for pseudotumor cerebri syndrome in children. Methods: As part of clinical care, patients in whom there was suspicion for pseudotumor cerebri syndrome underwent neurological and fundoscopic examinations, lumbar puncture, MRI, or magnetic resonance venogram. For this retrospective study, we used this information to classify 119 subjects into definite (n = 66) or probable pseudotumor cerebri syndrome (n = 12), elevated opening pressure without papilledema (n = 23), or controls who had normal opening pressure without papilledema (n = 24). A neuroradiologist, unaware of the clinical findings or original MRI report, reviewed MRIs for pituitary gland flattening, flattening of the posterior sclera, optic nerve sheath distention, and transverse venous sinus stenosis. Results: The presence of three or more MRI findings has a sensitivity of 62% (95% confidence interval: 47% to 75%) and a specificity of 95% (95% confidence interval: 77% to 100%), compared with controls. Two of three (transverse venous sinus stenosis, pituitary gland flattening, flattening of the posterior sclera) had a similar sensitivity and specificity. Transverse venous sinus stenosis alone had a slightly higher sensitivity (74%, 95% confidence interval: 60% to 85%) and specificity (100%, 95% confidence interval: 80% to 100%). Conclusions: In children, three of four of the proposed neuroimaging criteria and transverse venous sinus stenosis alone have a moderate sensitivity and robust specificity for pseudotumor cerebri syndrome. MRIs should be reviewed for these criteria, and their presence should raise suspicion for pseudotumor cerebri syndrome in children, particularly if the presence of papilledema is uncertain. © 2019 Elsevier Inc.

Author Keywords
Diagnostic criteria;  Imaging;  Pediatric;  Pseudotumor cerebri syndrome

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“White and gray matter brain development in children and young adults with phenylketonuria” (2019) NeuroImage: Clinical

White and gray matter brain development in children and young adults with phenylketonuria
(2019) NeuroImage: Clinical, 23, art. no. 101916, . 

Hawks, Z.a , Hood, A.M.a , Lerman-Sinkoff, D.B.a b , Shimony, J.S.c , Rutlin, J.c , Lagoni, D.a , Grange, D.K.d , White, D.A.a d

a Department of Psychological & Brain Sciences, Washington University, Campus Box 1125, St. Louis, MO, United States
b Department of Biomedical Engineering, Washington University, St. Louis, MO, United States
c Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States
d Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Phenylketonuria (PKU) is a recessive disorder characterized by disruption in the metabolism of the amino acid phenylalanine (Phe). Prior research indicates that individuals with PKU have substantial white matter (WM) compromise. Much less is known about gray matter (GM) in PKU, but a small body of research suggests volumetric differences compared to controls. To date, developmental trajectories of GM structure in individuals with PKU have not been examined, nor have trajectories of WM and GM been examined within a single study. To address this gap in the literature, we compared longitudinal brain development over a three-year period in individuals with PKU (n = 35; 18 male) and typically-developing controls (n = 71; 35 male) aged 7–21 years. Using diffusion tensor imaging (DTI) and structural magnetic resonance imaging (MRI), we observed whole-brain and regional WM differences between individuals with PKU and controls, which were often exacerbated with increasing age. In marked contrast with trajectories of WM development, trajectories of GM development did not differ between individuals with PKU and controls, indicating that neuropathology in PKU is more prominent in WM than GM. Within individuals with PKU, mediation analyses revealed that whole-brain mean diffusivity (MD) and regional MD in the corpus callosum and centrum semiovale mediated the relationship between dietary treatment compliance (i.e., Phe control) and executive abilities, suggesting a plausible neurobiological mechanism by which Phe control may influence cognitive outcomes. Our findings clarify the specificity, timing, and cognitive consequences of whole-brain and regional WM pathology, with implications for treatment and research in PKU. © 2019

Author Keywords
Brain;  Developmental trajectories;  Executive abilities;  Gray matter;  Phenylketonuria;  White matter

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“Screening and offering online programs for eating disorders: Reach, pathology, and differences across eating disorder status groups at 28 U.S. universities” (2019) International Journal of Eating Disorders

Screening and offering online programs for eating disorders: Reach, pathology, and differences across eating disorder status groups at 28 U.S. universities
(2019) International Journal of Eating Disorders, . 

Fitzsimmons-Craft, E.E.a , Balantekin, K.N.b , Eichen, D.M.c , Graham, A.K.d , Monterubio, G.E.a , Sadeh-Sharvit, S.e f g , Goel, N.J.h i , Flatt, R.E.e f , Saffran, K.e , Karam, A.M.a , Firebaugh, M.-L.a , Trockel, M.e , Taylor, C.B.e f , Wilfley, D.E.a

a Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
b Department of Exercise and Nutrition Sciences, University at Buffalo, Buffalo, NY, United States
c Department of Pediatrics, University of California, San Diego, San Diego, CA, United States
d Department of Medical Social Sciences, Northwestern University, Chicago, IL, United States
e Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, United States
f Center for m2Health, Palo Alto University, Palo Alto, CA, United States
g Baruch Ivcher School of Psychology, Interdisciplinary Center, Herzliya, Israel
h Department of Psychology, Virginia Commonwealth University, Richmond, VA, United States
i Institute for Inclusion, Inquiry and Innovation (iCubed), Virginia Commonwealth University, Richmond, VA, United States

Abstract
Objective: The Internet-based Healthy Body Image (HBI) Program, which uses online screening to identify individuals at low risk of, high risk of, or with an eating disorder (ED) and then directs users to tailored, evidence-based online or in-person interventions to address individuals’ risk or clinical status, was deployed at 28 U.S. universities as part of a randomized controlled trial. The purpose of this study is to report on: (a) reach of HBI, (b) screen results, and (c) differences across ED status groups. Method: All students on participating campuses ages 18 years or older were eligible, although recruitment primarily targeted undergraduate females. Results: The screen was completed 4,894 times, with an average of 1.9% of the undergraduate female student body on each campus taking the screen. ED risk in participating students was high—nearly 60% of students screened were identified as being at high risk for ED onset or having an ED. Key differences emerged across ED status groups on demographics, recruitment method, ED pathology, psychiatric comorbidity, and ED risk factors, highlighting increasing pathology and impairment in the high-risk group. Discussion: Findings suggest efforts are needed to increase reach of programs like HBI. Results also highlight the increasing pathology and impairment in the high-risk group and the importance of programs such as HBI, which provide access to timely screening and intervention to prevent onset of clinical EDs. © 2019 Wiley Periodicals, Inc.

Author Keywords
college students;  digital technologies;  eating disorders;  guided self-help;  prevention;  screening

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Tenascin C regulates multiple microglial functions involving TLR4 signaling and HDAC1” (2019) Brain, Behavior, and Immunity

Tenascin C regulates multiple microglial functions involving TLR4 signaling and HDAC1
(2019) Brain, Behavior, and Immunity, . 

Haage, V.a , Elmadany, N.a , Roll, L.b , Faissner, A.b , Gutmann, D.H.a c , Semtner, M.a , Kettenmann, H.a

a Cellular Neurosciences, Max-Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, 13125, Germany
b Zellmorphologie und Molekulare Neurobiologie, Fakultät für Biologie und Biotechnologie, Ruhr-Universität Bochum, Bochum, Nordrhein-Wastfalen 44801, Germany
c Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, United States

Abstract
Tenascin C (Tnc) is an extracellular matrix glycoprotein, expressed in the CNS during development, as well as in the setting of inflammation, fibrosis and cancer, which operates as an activator of Toll-like receptor 4 (TLR4). Although TLR4 is highly expressed in microglia, the effect of Tnc on microglia has not been elucidated to date. Herein, we demonstrate that Tnc regulates microglial phagocytic activity at an early postnatal age (P4), and that this process is partially dependent on microglial TLR4 expression. We further show that Tnc regulates proinflammatory cytokine/chemokine production, chemotaxis and phagocytosis in primary microglia in a TLR4-dependent fashion. Moreover, Tnc induces histone-deacetylase 1 (HDAC1) expression in microglia, such that HDAC1 inhibition by MS-275 decreases Tnc-induced microglial IL-6 and TNF-α production. Finally, Tnc− / − cortical microglia have reduced HDAC1 expression levels at P4. Taken together, these findings establish Tnc as a regulator of microglia function during early postnatal development. © 2019 The Authors

Author Keywords
Early postnatal development;  ECM protein Tenascin C;  HDAC1;  Microglia;  Phagocytosis;  TLR4

Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access

“Lack of fractalkine receptor on macrophages impairs spontaneous recovery of ribbon synapses after moderate noise trauma in c57bl/6 mice” (2019) Frontiers in Neuroscience

Lack of fractalkine receptor on macrophages impairs spontaneous recovery of ribbon synapses after moderate noise trauma in c57bl/6 mice
(2019) Frontiers in Neuroscience, 13 (JUN), art. no. 620, . 

Kaur, T.a , Clayman, A.C.b , Nash, A.J.b , Schrader, A.D.a , Warchol, M.E.a , Ohlemiller, K.K.a b

a Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO, United States
b Program in Audiology and Communication Sciences, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Noise trauma causes loss of synaptic connections between cochlear inner hair cells (IHCs) and the spiral ganglion neurons (SGNs). Such synaptic loss can trigger slow and progressive degeneration of SGNs. Macrophage fractalkine signaling is critical for neuron survival in the injured cochlea, but its role in cochlear synaptopathy is unknown. Fractalkine, a chemokine, is constitutively expressed by SGNs and signals via its receptor CX3CR1 that is expressed on macrophages. The present study characterized the immune response and examined the function of fractalkine signaling in degeneration and repair of cochlear synapses following noise trauma. Adult mice wild type, heterozygous and knockout for CX3CR1 on a C57BL/6 background were exposed for 2 h to an octave band noise at 90 dB SPL. Noise exposure caused temporary shifts in hearing thresholds without any evident loss of hair cells in CX3CR1 heterozygous mice that have intact fractalkine signaling. Enhanced macrophage migration toward the IHC-synaptic region was observed immediately after exposure in all genotypes. Synaptic immunolabeling revealed a rapid loss of ribbon synapses throughout the basal turn of the cochlea of all genotypes. The damaged synapses spontaneously recovered in mice with intact CX3CR1. However, CX3CR1 knockout (KO) animals displayed enhanced synaptic degeneration that correlated with attenuated suprathreshold neural responses at higher frequencies. Exposed CX3CR1 KO mice also exhibited increased loss of IHCs and SGN cell bodies compared to exposed heterozygous mice. These results indicate that macrophages can promote repair of damaged synapses after moderate noise trauma and that repair requires fractalkine signaling. © 2019 Kaur, Clayman, Nash, Schrader, Warchol and Ohlemiller.

Author Keywords
C57bl/6 mice;  Cochlea;  Fractalkine;  Macrophages;  Noise-induced hearing loss;  Ribbon synapses

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“Strategies for the Recruitment and Retention of Racial/Ethnic Minorities in Alzheimer Disease and Dementia Clinical Research” (2019) Current Alzheimer research

Strategies for the Recruitment and Retention of Racial/Ethnic Minorities in Alzheimer Disease and Dementia Clinical Research
(2019) Current Alzheimer research, 16 (5), pp. 458-471. 

Wong, R.a , Amano, T.a , Lin, S.-Y.b , Zhou, Y.c , Morrow-Howell, N.a d

a Brown School, Washington University in St. Louis, Saint Louis, MO, United States
b Rory Meyers College of Nursing, New York University, New York, NY, United States
c School of Social Work, University of Washington, Seattle, WA, United States
d Friedman Center for Aging, Washington University in St. Louis, Saint Louis, MO, United States

Abstract
BACKGROUND: Racial/ethnic minorities have among the highest risks for Alzheimer disease and dementia, but remain underrepresented in clinical research studies. OBJECTIVE: To synthesize the current evidence on strategies to recruit and retain racial/ethnic minorities in Alzheimer disease and dementia clinical research. METHODS: We conducted a systematic review by searching CINAHL, EMBASE, MEDLINE, PsycINFO, and Scopus. We included studies that met four criteria: (1) included a racial/ethnic minority group (African American, Latino, Asian, American Indian or Alaska Native, and Native Hawaiian or Other Pacific Islander); (2) implemented a recruitment or retention strategy for Alzheimer disease or dementia clinical research; (3) conducted within the U.S.; and (4) published in a peer-reviewed journal. RESULTS: Of the 19 included studies, 14 (73.7%) implemented recruitment strategies and 5 (26.3%) implemented both recruitment and retention strategies. Fifteen studies (78.9%) focused on African Americans, two (10.6%) on both African Americans and Latinos, and two (10.5%) on Asians. All the articles were rated weak in the study quality. Four major themes were identified for the recruitment strategies: community outreach (94.7%), advertisement (57.9%), collaboration with health care providers (42.1%), and referral (21.1%). Three major themes were identified for the retention strategies: follow-up communication (15.8%), maintain community relationship (15.8%), and convenience (10.5%). CONCLUSION: Our findings highlight several promising recruitment and retention strategies that investigators should prioritize when allocating limited resources, however, additional well-designed studies are needed. By recruiting and retaining more racial/ethnic minorities in Alzheimer disease and dementia research, investigators may better understand the heterogeneity of disease progression among marginalized groups. PROSPERO registration #CRD42018081979. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

Author Keywords
Alzheimer disease;  dementia;  ethnicity;  minority;  race;  recruitment;  retention;  systematic review.

Document Type: Article
Publication Stage: Final
Source: Scopus

“A Pilot Follow-Up Study of Older Alcohol-Dependent COGA Adults” (2019) Alcoholism: Clinical and Experimental Research

A Pilot Follow-Up Study of Older Alcohol-Dependent COGA Adults
(2019) Alcoholism: Clinical and Experimental Research, . 

Chan, G.a , Kramer, J.R.b , Schuckit, M.A.c , Hesselbrock, V.a , Bucholz, K.K.d , Edenberg, H.J.e , Acion, L.b , Langbehn, D.b , McCutcheon, V.d , Nurnberger, J.I., Jr.e , Hesselbrock, M.a , Porjesz, B.f , Bierut, L.d , Marenna, B.C.b , Cookman, A.b , Kuperman, S.b

a University of Connecticut, Farmington, CT, United States
b Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, United States
c University of California, San Diego, La Jolla, CA, United States
d Washington University, St. Louis, MO, United States
e Indiana University, Indianapolis, IN, United States
f State University of New York, Brooklyn, NY, United States

Abstract
Background: Alcohol consumption and problems are increasing among older adults, who are at elevated risk for alcohol-related accidents and medical problems. This paper describes a pilot follow-up of older adults with a history of alcohol dependence that was designed to determine the feasibility of conducting a more extensive investigation. Methods: The sample consisted of previously assessed subjects in the Collaborative Studies on the Genetics of Alcoholism who: (i) were age 50+; (ii) had lifetime DSM-IV AD; and (iii) had DNA available. Individuals were located through family contacts, Internet searches, and death registries. A brief telephone interview assessed demographics, health, and alcohol involvement. Results: Of the total sample (N = 2,174), 36% were contacted, 24% were deceased, and 40% were not yet located. Most (89%) contacted subjects were interviewed, and 99% of them agreed to future evaluation. Thirty percent of interviewed subjects reported abstinence for 10+ years, 56% reported drinking within the past year, and 14% last drank between >1 and 10 years ago. There were no age-related past-year differences in weekly consumption (overall sample mean: 16 drinks), number of drinking weeks (30.8), maximum number of drinks in 24 hours (8.1), or prevalence of weekly risky drinking (19%). Among those who drank within the past 5 years, the 3 most common alcohol-related problems were spending excessive time drinking or recovering (49%), drinking more/longer than intended (35%), and driving while intoxicated (35%); and about a third (32%) received some form of treatment. Conclusions: Over a 1-year period, we located 60% of individuals last seen an average of 23 years ago. The majority of contacted individuals were interviewed and willing to be evaluated again. Although the proportion of individuals currently drinking diminished with age, subjects exhibited troublesome levels of alcohol consumption and problems. Our findings suggest the importance and feasibility of a more comprehensive follow-up. © 2019 by the Research Society on Alcoholism

Author Keywords
Alcohol Dependence;  COGA;  Follow-Up;  Older Adults

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“De novo substitutions of TRPM3 cause intellectual disability and epilepsy” (2019) European Journal of Human Genetics

De novo substitutions of TRPM3 cause intellectual disability and epilepsy
(2019) European Journal of Human Genetics, . 

Dyment, D.A.a b , Terhal, P.A.c , Rustad, C.F.d , Tveten, K.e , Griffith, C.f , Jayakar, P.g , Shinawi, M.h , Ellingwood, S.i , Smith, R.i , van Gassen, K.c , McWalter, K.j , Innes, A.M.k , Lines, M.A.a b

a Children’s Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada
b Department of Pediatrics, University of Ottawa, Ottawa, ON, Canada
c Department of Genetics, University Medical Centre Utrecht, Utrecht, Netherlands
d Department of Medical Genetics, Oslo University Hospital, Oslo, Norway
e Department of Medical Genetics, Telemark Hospital Trust, Skien, Norway
f University of South Florida, Tampa, FL, United States
g Nicklaus Children’s Hospital, Miami, FL, United States
h Department of Pediatrics, Division of Genetics and Genomic Medicine, Washington University School of Medicine, St. Louis, MO, United States
i Department of Pediatrics, Division of Genetics, Maine Medical Center, Portland, ME, United States
j GeneDx, Gaithersburg, MD, United States
k Department of Medical Genetics and Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

Abstract
The developmental and epileptic encephalopathies (DEE) are a heterogeneous group of chronic encephalopathies frequently associated with rare de novo nonsynonymous coding variants in neuronally expressed genes. Here, we describe eight probands with a DEE phenotype comprising intellectual disability, epilepsy, and hypotonia. Exome trio analysis showed de novo variants in TRPM3, encoding a brain-expressed transient receptor potential channel, in each. Seven probands were identically heterozygous for a recurrent substitution, p.(Val837Met), in TRPM3’s S4–S5 linker region, a conserved domain proposed to undergo conformational change during gated channel opening. The eighth individual was heterozygous for a proline substitution, p.(Pro937Gln), at the boundary between TRPM3’s flexible pore-forming loop and an adjacent alpha-helix. General-population truncating variants and microdeletions occur throughout TRPM3, suggesting a pathomechanism other than simple haploinsufficiency. We conclude that de novo variants in TRPM3 are a cause of intellectual disability and epilepsy. © 2019, The Author(s).

Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access

“Optic Nerve Head Drusen: The Relationship Between Intraocular Pressure and Optic Nerve Structure and Function(2018) Journal of neuro-ophthalmology : the Official Journal of the North American Neuro-Ophthalmology Society

Optic Nerve Head Drusen: The Relationship Between Intraocular Pressure and Optic Nerve Structure and Function
(2018) Journal of neuro-ophthalmology : the Official Journal of the North American Neuro-Ophthalmology Society, 38 (2), pp. 147-150. Cited 2 times.

Nolan, K.W., Lee, M.S., Jalalizadeh, R.A., Firl, K.C., Van Stavern, G.P., McClelland, C.M.

Department of Ophthalmology and Visual Neurosciences (KWN, MSL, KCF, CMM), University of Minnesota School of Medicine, Minneapolis, Minnesota; and Department of Ophthalmology and Visual Sciences (RAJ, GPVS), Washington University School of Medicine, St. Louis, Missouri

Abstract
OBJECTIVE: To determine whether at the time of diagnosis, the intraocular pressure (IOP) in patients with optic nerve head drusen (ONHD) correlates with the perimetric mean deviation (PMD) and the mean retinal nerve fiber layer (RNFL) thickness on optical coherence tomography (OCT). METHODS: This retrospective chart review included adults with ONHD from 2 academic medical centers. Inclusion criteria were age older than 18 years, definitive diagnosis of ONHD, measurement of IOP, and an automated visual field (VF) within 3 months of diagnosis. Exclusion criteria were unreliable VFs, use of IOP-lowering therapy, and visually significant ocular comorbidities. Data were collected from the initial visit. Age, IOP, method of diagnosis of ONHD, mean RNFL thickness, and PMD were recorded. Multiple and logistic regression models were used to control for potential confounders in statistical analyses. RESULTS: Chart review identified 623 patients, of which 146 patients met inclusion criteria. Mean age was 44.2 years (range: 19-82 years). Average PMD of 236 eyes was -5.22 dB (range, -31.2 to +1.21 dB). Mean IOP was 15.7 mm Hg (range: 6-24 mm Hg). Forty eyes (16.9%) underwent RNFL measurement using OCT; mean RNFL thickness was 79.9 μm (range: 43-117 μm). There was no statistically significant association between IOP and PMD (P = 0.13) or RNFL thickness (P = 0.65). Eyes with ocular hypertension tended to have less depressed PMD than those without (P= 0.031). Stratified analyses of visible and buried subgroups yielded similar results. CONCLUSIONS: Lowering IOP in patients with ONHD has been proposed as a means to prevent progression of optic neuropathy. Our study demonstrated that among predominately normotensive eyes, higher IOP was not associated with greater VF loss or thinner RNFL at the time of presentation. This suggests that lowering IOP may not be beneficial in preventing visual loss in normotensive eyes with ONHD.

Document Type: Article
Publication Stage: Final
Source: Scopus

“Laughter-Induced Transient Vision Loss in a Patient With Silent Sinus Syndrome” (2018) Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society

Laughter-Induced Transient Vision Loss in a Patient With Silent Sinus Syndrome
(2018) Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society, 38 (1), pp. 30-31. 

Reggie, S.N., Kalyam, K., Holds, J.B., Chung, S.M.

Department of Ophthalmology (SNR, JBH, SMC), St. Louis University School of Medicine, St. Louis, Missouri; Department of Ophthalmology and Visual Sciences (KK), Washington University in St. Louis, St. Louis, Missouri; and Ophthalmic Plastic and Cosmetic Surgery Inc. (JBH), St. Louis, Missouri

Abstract
BACKGROUND: To report a patient with silent sinus syndrome (SSS) who experienced transient ipsilateral monocular vision loss during intense laughter. METHODS: Case report. RESULTS: Our patient’s transient vision loss completely resolved after maxillary sinus decompression and during 7 months of follow-up. CONCLUSIONS: Although the precise mechanism of our patient’s vision loss remains undetermined, we suspect that the vascular supply to the eye and/or the optic nerve was compromised as the result of the combination of laughter (causing Valsalva maneuver and increased intrathoracic pressure) and SSS.

Document Type: Article
Publication Stage: Final
Source: Scopus