WashU weekly Neuroscience publications

Incidence and predictors of post-traumatic stress symptoms in a cohort of patients with intracerebral hemorrhage
(2020) Clinical Neurology and Neurosurgery, 190, art. no. 105657, . 

Garton, A.L.^a , Gupta, V.P.^b , Pucci, J.U.^c , Couch, C.K.^d , Connolly, E.S., Jr^c

^a Department of Neurosurgery, NewYork-Presbyterian Hospital, Weill Cornell Medical Center, New York City, NY, United States
^b Department of Neurosurgery, Washington University in St. Louis School of Medicine, St. Louis, MS, United States
^c Department of Neurosurgery, Columbia University, College of Physicians and Surgeons, New York City, NY, United States
^d Department of Neurology, Columbia University, College of Physicians and Surgeons, New York City, NY, United States

Abstract
Objectives: Examine the incidence and predictors of PTSD symptoms in a cohort of patients with ICH. Patients and Methods: This study uses a prospective cohort of 108 patients with complete follow-up data including a questionnaire regarding stress symptoms (PCL-S: PTSD checklist specific for a stressor) at 3, 6, and 12 months. Results: The incidence of novel stress symptoms following ICH was approximately 6.5%. Age was negatively associated with PTSD symptoms with only trend-level significance (3 months: OR = 0.83, p = 0.087; 6 months: OR = 0.70, p = 0.015; 12 months: OR = 0.88, p = 0.087). Gender did not affect PTSD symptom development, (t = 1.34, p = 0.18). Pre-morbid functioning, initial stroke prognosis, total number of complications, and length of hospital/ICU stay were not associated with PTSD symptoms; however, each was significantly correlated with poorer functional outcomes. Yet, poorer functional outcomes were observed in those with higher reports of PTSD symptoms (r = 0.24, p = 0.01). Conclusion: Functional outcomes in ICH are correlated with PTSD symptoms, however the mechanism and relationship are difficult to elucidate. Further research is needed to determine possible mechanisms by which a stroke patient may develop PTSD. © 2019 Elsevier B.V.

Author Keywords
Functional outcomes;  Intracerebral hemorrhage (ICH);  Mental health outcomes;  Post-traumatic stress disorder (PTSD);  Stroke;  Stroke severity

Document Type: Article
Publication Stage: Final
Source: Scopus

Evidence for gene-smoking interactions for hearing loss and deafness in Japanese American families
(2020) Hearing Research, 387, art. no. 107875, . 

Wan, J.Y.^a , Cataby, C.^b , Liem, A.^a , Jeffrey, E.^a , Norden-Krichmar, T.M.^a , Goodman, D.^a , Santorico, S.A.^c , Edwards, K.L.^{a b} , Boerwinkle, E.^d , Buse, J.^e , DeFronzo, R.^d , Ehrmann, D.^f , Elbein, S.C.^g , Fujimoto, W.^h , Kahn, S.E.^h , Hanis, C.L.^d , Mulivor, R.A.ⁱ , Beck, J.C.ⁱ , Norris, J.^j , Permutt, M.A.^k , Behn, P.^k , Raffel, L.^l , Robbins, D.C.^m , American Diabetes Association GENNID Study Groupⁿ

^a Department of Epidemiology, University of California, Irvine, United States
^b Department of Population Health and Disease Prevention, University of California, Irvine, United States
^c Department of Mathematical and Statistical Sciences, University of Colorado, Denver, United States
^d University of Texas Health Science Center, United States
^e University of North Carolina, United States
^f University of Chicago, United States
^g University of Utah/University of Arkansas, United States
^h University of Washington, United States
ⁱ Coriell Cell Repositories, United States
^j University of Colorado School of Medicine, United States
^k Washington University School of Medicine, United States
^l Cedars-Sinai Medical Center, United States
^m Medlantic Research Institute, United States

Abstract
Background: This study investigated the relationship between smoking and hearing loss and deafness (HLD) and whether the relationship is modified by genetic variation. Data for these analyses was from the subset of Japanese American families collected as part of the American Diabetes Association Genetics of Non-insulin Dependent Diabetes Mellitus study. Logistic regression with generalized estimating equations assessed the relationship between HLD and smoking. Nonparametric linkage analysis identified genetic regions harboring HLD susceptibility genes and ordered subset analysis was used to identify regions showing evidence for gene-smoking interactions. Genetic variants within these candidate regions were then each tested for interaction with smoking using logistic regression models. Results: After adjusting for age, sex, diabetes status and smoking duration, for each pack of cigarettes smoked per day, risk of HLD increased 4.58 times (odds ratio (OR) = 4.58; 95% Confidence Interval (CI): (1.40,15.03)), and ever smokers were over 5 times more likely than nonsmokers to report HLD (OR = 5.22; 95% CI: (1.24, 22.03)). Suggestive evidence for linkage for HLD was observed in multiple genomic regions (Chromosomes 5p15, 8p23 and 17q21), and additional suggestive regions were identified when considering interactions with smoking status (Chromosomes 7p21, 11q23, 12q32, 15q26, and 20q13) and packs-per-day (Chromosome 8q21). Conclusions: To our knowledge this was the first report of possible gene-by-smoking interactions in HLD using family data. Additional work, including independent replication, is needed to understand the basis of these findings. HLD are important public health issues and understanding the contributions of genetic and environmental factors may inform public health messages and policies. © 2019

Author Keywords
Family;  Gene-environment interaction;  Genome-wide linkage;  Hearing loss;  Linkage;  Smoking

Document Type: Article
Publication Stage: Final
Source: Scopus

Greenspace exposure and sleep: A systematic review
(2020) Environmental Research, 182, art. no. 109081, . 

Shin, J.C.^a , Parab, K.V.^b , An, R.^c , Grigsby-Toussaint, D.S.^a

^a Department Behavioral and Social Sciences, Center for Health Equity Research, Department of Behavioral and Social Science, School of Public Health, Brown University, Providence, RI, United States
^b Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Champaign, IL, United States
^c Brown School, Washington University in St. Louis, St. Louis, MO, United States

Abstract
Green space is considered a critical environmental factor for sleep quality and quantity. However, no systematic review exploring this relationship exists. The purpose of this systematic review was to 1) explore research related to green space and sleep, and 2) examine the impact of green space exposure on sleep quality and quantity. Papers from eight electronic databases were eligible for inclusion if they met the following criteria: well-designed, any analysis exploring green space and sleep, provided sleep and green space measurement, published in peer-reviewed journals, and written in English. Thirteen eligible studies related to green space and sleep were selected after peer-review procedures. Cross-sectional studies (n = 7) used either a questionnaire or the combination of Geographic Information Systems and remote sensing images for green space measurement, while questionnaires were primarily used to measure both sleep quality and quantity. Intervention studies (n = 5) were categorized into three types: walking program, gardening, and working in a forest. Eleven out of thirteen studies concluded that green space exposure was associated with improvement in both sleep quality and quantity. The findings support the evidence of a positive association between green space exposures and sleep quality and quantity, and also suggest green exercise and therapeutic gardening as possible intervention methods to improve sleep outcomes. © 2019

Document Type: Article
Publication Stage: Final
Source: Scopus

Fluselenamyl: Evaluation of radiation dosimetry in mice and pharmacokinetics in brains of non-human primate
(2020) Nuclear Medicine and Biology, 82-83, pp. 33-40. 

Sundaram, G.S.M.^a , Jones, L.^a , Zhou, Y.^a , Laforest, R.^a , Sharma, V.^{a b c}

^a Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110, United States
^b Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, United States
^c Department of Biomedical Engineering, School of Engineering & Applied Science, Washington University, St. Louis, 63105, United States

Abstract
Introduction: To allow quantitative assessment of therapeutic efficacy for therapeutic interventions (either approved or undergoing FDA approvals) for either inhibiting or reducing development of Aβ pathophysiology in vivo, 18F-labelled tracers, such as Florbetapir, Florbetaben, and Flutemetamol have been approved. Previously, we have reported on development and preclinical validation of 18F-Fluselenamyl, comprising traits of translatable Aβ imaging agents. Herein, we report the dosimetry data for 18F-Fluselenamyl to provide radiation dose deposited within organs and determine effective dose (ED) for human studies, while also evaluating its pharmacokinetics in the nonhuman primate brains. Methods: To evaluate safety profiles of 18F-Fluselenamyl for enabling its deployment as a PET imaging agent for monitoring Aβ pathophysiology in vivo, we estimated the human radiation dosimetry extrapolated from rodent biodistribution data obtained by standard method of organ dissection. Animal biodistribution studies were performed in FVB/NCR mice (20 males, 20 females), following tail-vein injection of the tracer. Following euthanasia of mice, organs were harvested, counted, radiation dose to each organ and whole body was determined using the standard MIRD methodology. For evaluation of pharmacokinetics in non-human primates, following intravenous injection of the tracer, dynamic PET scan of rhesus monkey brains were performed, and co-registered with MR for anatomical reference. Parametric images of tracer transport rate constant and distribution volume relative to cerebellum were generated using a simplified reference tissue model and a spatially-constraint linear regression algorithm. Results: The critical organ in humans has been determined to be the gall bladder with a gender average radiation absorbed dose of 0.079 mGy/MBq with an effective dose of 0.017 mSv/MBq and 0.020 mSv/MBq, in males and females, respectively. Therefore, these data provide preliminary projections on human dosimetry derived from rodent estimates, thereby defining safe imaging conditions for further validations in human subjects. Additionally, the tracer penetrated the non-human primate brain and excreted to background levels at later-time points thus pointing to the potential for high signal/noise ratios during noninvasive imaging. Tissue time activity curves (TACs) also show fast initial uptake with maximum projection of activity at 2–6 min post administration followed by clearance of activity at later time-points from cortex, cerebellum, and white matter of nonhuman primate brain. Parametric images confirmed that the 18F-Fluselenamyl has relative high transport rate constant at striatum, thalamus, and cortex. Conclusions: The data obtained from radiation dosimetry studies in mice indicate that 18F-Fluselenamyl can be safely used for further evaluation in humans. Additionally, 18F-Fluselenamyl demonstrated ability to traverse the blood brain barrier (BBB) and indicated high initial influx, followed by clearance to background levels in non-human primate brains. Combined information indicates that 18F-Fluselenamyl would be a potential candidate for detecting amyloid plaques in the living human brain. © 2019 Elsevier Inc.

Document Type: Article
Publication Stage: Final
Source: Scopus

Greater delay discounting and cannabis coping motives are associated with more frequent cannabis use in a large sample of adult cannabis users
(2020) Drug and Alcohol Dependence, 207, art. no. 107820, . 

Sofis, M.J.^a , Budney, A.J.^a , Stanger, C.^a , Knapp, A.A.^b , Borodovsky, J.T.^c

^a Geisel School of Medicine, Dartmouth College, Center for Technology and Behavioral Health, 46 Centerra Parkway, Suite 315, Lebanon, NH, United States
^b Department of Preventive Medicine, Northwestern University Center for Behavioral Intervention Technologies (CBITs), 750 N. Lake Shore Drive ChicagoIL 60611, United States
^c Department of Psychiatry, Washington University School of Medicine in St. Louis, 660 South Euclid Avenue, Box 8134, St. Louis, MO 63110, United States

Abstract
Background: Self-regulation deficits expressed through a decreased ability to value future rewards (delay discounting (DD)) and impaired emotion regulation (negative urgency (NU), cannabis coping motives (CCM), and anxiety sensitivity (AS)) relate to more frequent or problematic cannabis use. However, there is a need to better understand how self-regulation and emotion regulation constructs reflect competition between deliberative and reactive systems that drive individual differences in cannabis use patterns. Further, few studies assess frequency of cannabis use within and across days of use, which may obscure differentiation of individual differences. Methods: In a large national sample of 2545 cannabis users, Latent Class Analysis was used to derive participant sub-classes based on two frequency indices, self-reported cannabis use days and times cannabis was used per day. Three classes emerged: Low (1–9 days/month, 1 time/day; 23 %), moderate (10–29 days/month, 2–3 times/day; 41 %), and high (30 days/month, ≥4 times/day; 36 %). Relationships among frequency classes and emotional regulation and impulsivity were assessed with a multinomial logistic regression. Results: Higher frequency use was associated with greater DD (χ2 = 6.0, p = .05), greater CCM (χ2 = 73.3, p < .001), and lower cognitive AS (χ2 = 12.1, p = .002), when controlling for demographics, tobacco use, and number of cannabis administration methods. Frequency class and NU were not significantly associated. Conclusions: Identifying meaningful patterns of cannabis use may improve our understanding of individual differences that increase risk of frequent or problematic cannabis use. Excessive delay discounting and using cannabis to cope with negative affect may be relevant targets for treatments designed to reduce cannabis use. © 2019 Elsevier B.V.

Author Keywords
Anxiety sensitivity;  Cannabis;  Cannabis coping motives;  Delay discounting;  Latent class analysis;  Marijuana

Document Type: Article
Publication Stage: Final
Source: Scopus

Loss-of-Function Variants in PPP1R12A: From Isolated Sex Reversal to Holoprosencephaly Spectrum and Urogenital Malformations
(2020) American Journal of Human Genetics, 106 (1), pp. 121-128. 

Hughes, J.J.^a , Alkhunaizi, E.^{b c} , Kruszka, P.^a , Pyle, L.C.^d , Grange, D.K.^e , Berger, S.I.^{a f g} , Payne, K.K.^h , Masser-Frye, D.ⁱ , Hu, T.^a , Christie, M.R.^j , Clegg, N.J.^j , Everson, J.L.^{k l} , Martinez, A.F.^a , Walsh, L.E.^h , Bedoukian, E.^d , Jones, M.C.ⁱ , Harris, C.J.^m , Riedhammer, K.M.^{n o} , Choukair, D.^p , Fechner, P.Y.^q , Rutter, M.M.^r , Hufnagel, S.B.^s , Roifman, M.^{b c} , Kletter, G.B.^t , Delot, E.^{f g} , Vilain, E.^{f g} , Lipinski, R.J.^{k l} , Vezina, C.M.^{k l} , Muenke, M.^a , Chitayat, D.^{b c}

^a Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, United States
^b The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, M5G 1X5, Canada
^c Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, M5G 1X8, Canada
^d Division of Human Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, United States
^e Department of Pediatrics, Division of Genetics and Genomic Medicine, Washington University School of Medicine, St. Louis, MO 63110, United States
^f Center for Genetic Medicine Research, Children’s National Hospital, Washington, DC 20010, United States
^g Department of Genomics and Precision Medicine, George Washington University, Washington, DC 20037, United States
^h Division of Child Neurology, Riley Hospital for Children, Indianapolis, IN 46202, United States
ⁱ Department of Pediatrics, Division of Genetics, University of California San Diego—Rady Children’s Hospital, San Diego, CA 92123, United States
^j Texas Scottish Rite Hospital for Children, Dallas, TX 75219, United States
^k Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin—Madison, Madison, WI 53706, United States
^l Molecular and Environmental Toxicology Center, University of Wisconsin—Madison, Madison, WI 53706, United States
^m Department of Pediatric Genetics, University of Missouri Medical Center, Columbia, MO 65212, United States
ⁿ Institute of Human Genetics, Klinikum rechts der Isar, Technical University of Munich, Munich, 4JQ2+9Q, Germany
^o Department of Nephrology, Klinikum rechts der Isar, Technical University of Munich, Munich, 4JQ2+9Q, Germany
^p Division of Paediatric Endocrinology and Diabetology, University Children’s Hospital, Heidelberg, 69120, Germany
^q Division of Pediatric Endocrinology, Seattle Children’s Hospital, University of Washington, Seattle, WA 98105, United States
^r Division of Endocrinology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, United States
^s Rare Disease Institute, Children’s National Hospital, Washington, DC 20010, United States
^t Pediatric Endocrinology, Mary Bridge Children’s Hospital, Tacoma, WA 98404, United States

Abstract
In two independent ongoing next-generation sequencing projects for individuals with holoprosencephaly and individuals with disorders of sex development, and through international research collaboration, we identified twelve individuals with de novo loss-of-function (LoF) variants in protein phosphatase 1, regulatory subunit 12a (PPP1R12A), an important developmental gene involved in cell migration, adhesion, and morphogenesis. This gene has not been previously reported in association with human disease, and it has intolerance to LoF as illustrated by a very low observed-to-expected ratio of LoF variants in gnomAD. Of the twelve individuals, midline brain malformations were found in five, urogenital anomalies in nine, and a combination of both phenotypes in two. Other congenital anomalies identified included omphalocele, jejunal, and ileal atresia with aberrant mesenteric blood supply, and syndactyly. Six individuals had stop gain variants, five had a deletion or duplication resulting in a frameshift, and one had a canonical splice acceptor site loss. Murine and human in situ hybridization and immunostaining revealed PPP1R12A expression in the prosencephalic neural folds and protein localization in the lower urinary tract at critical periods for forebrain division and urogenital development. Based on these clinical and molecular findings, we propose the association of PPP1R12A pathogenic variants with a congenital malformations syndrome affecting the embryogenesis of the brain and genitourinary systems and including disorders of sex development. © 2019

Author Keywords
disorders of sex development;  embryogenesis;  encephalocele;  facial dysmorphism;  forebrain;  holoprosencephaly;  hypospadias;  MYPT1;  omphalocele;  PPP1R12A

Document Type: Article
Publication Stage: Final
Source: Scopus

The metabotropic glutamate receptor 5 negative allosteric modulator fenobam: pharmacokinetics, side effects, and analgesic effects in healthy human subjects
(2020) Pain, 161 (1), pp. 135-146. 

Cavallone, L.F.^a , Montana, M.C.^a , Frey, K.^a , Kallogjeri, D.^b , Wages, J.M.^c , Rodebaugh, T.L.^d , Doshi, T.^e , Kharasch, E.D.^f , Gereau, R.W., 4th^{a g}

^a Department of Anesthesiology, Washington University in Saint Louis School of Medicine, St. Louis, MO, United States
^b Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
^c Pain Center, Precision Spine Care, TX, Texarkana, United States
^d Department of Psychological and Brain Sciences, Washington University in Saint Louis, St. Louis, MO, United States
^e Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, MD, Baltimore, United States
^f Department of Anesthesiology, Duke University School of Medicine, Durham, United States
^g Department of Anesthesiology, Washington University in Saint Louis, Washington University Pain Center, St. Louis, MO, United States

Abstract
Metabotropic glutamate receptor 5 (mGlu5) has been shown to modulate nociception in animals, but no mGlu5 antagonists have been developed commercially as analgesics. The mGlu5 antagonist fenobam [N-(3-chlorophenyl)-N’-(4,5-dihydro-1-methyl-4-oxo-1H-imidazole-2-yl)urea] was originally evaluated for development as a nonbenzodiazepine anxiolytic. Fenobam is analgesic in numerous mouse pain models, acting exclusively through mGlu5 blockade. Furthermore, fenobam showed no signs of analgesic tolerance with up to 2 weeks of daily dosing in mice. Analgesic effects of fenobam in humans have not been reported. The purpose of this investigation was to evaluate fenobam pharmacokinetics and analgesic effects in humans. We first evaluated single-dose oral fenobam disposition in a parallel-group dose-escalation study in healthy volunteers. A second investigation tested the analgesic effects of fenobam in an established experimental human pain model of cutaneous sensitization using capsaicin cream and heat, in a double-blind placebo-controlled study. The primary outcome measure was the area of hyperalgesia and allodynia around the area applied with heat/capsaicin. Secondary outcome measures included nociception, measured as pain rating on a visual analog scale, heat pain detection threshold, and effects on cognition and mood. Fenobam plasma exposures showed considerable interindividual variability and were not linear with dose. Fenobam reduced sensitization vs placebo at a single timepoint (peak plasma concentration); we found no other difference between fenobam and placebo. Our results suggest highly variable fenobam disposition and minimal analgesic effects at the dose tested. We suggest that future studies testing analgesic effects of mGlu5 blockade are warranted, but such studies should use molecules with improved pharmacokinetic profiles.

Document Type: Article
Publication Stage: Final
Source: Scopus

Cerebral cortical folding, parcellation, and connectivity in humans, nonhuman primates, and mice
(2019) Proceedings of the National Academy of Sciences of the United States of America, 116 (52), pp. 26173-26180. Cited 1 time.

Van Essen, D.C.^a , Donahue, C.J.^a , Coalson, T.S.^a , Kennedy, H.^{b c d} , Hayashi, T.^e , Glasser, M.F.^{a f}

^a Department of Neuroscience, Washington University, School of Medicine, St. Louis, MO 63110, United States
^b Univ Lyon, Université Claude Bernard Lyon 1, INSERM, Stem Cell and Brain Research Institute U1208, Bron, 69500, France
^c Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200031, China
^d Shanghai Center for Brain Science, Brain-Inspired Intelligence Technology, Shanghai, 200031, China
^e Laboratory for Brain Connectomics Imaging, RIKEN Center for Biosystems Dynamics Research, Kobe, 650-0047, Japan
^f Department of Radiology, Washington University, School of Medicine, St. Louis, MO 63110, United States

Abstract
Advances in neuroimaging and neuroanatomy have yielded major insights concerning fundamental principles of cortical organization and evolution, thus speaking to how well different species serve as models for human brain function in health and disease. Here, we focus on cortical folding, parcellation, and connectivity in mice, marmosets, macaques, and humans. Cortical folding patterns vary dramatically across species, and individual variability in cortical folding increases with cortical surface area. Such issues are best analyzed using surface-based approaches that respect the topology of the cortical sheet. Many aspects of cortical organization can be revealed using 1 type of information (modality) at a time, such as maps of cortical myelin content. However, accurate delineation of the entire mosaic of cortical areas requires a multimodal approach using information about function, architecture, connectivity, and topographic organization. Comparisons across the 4 aforementioned species reveal dramatic differences in the total number and arrangement of cortical areas, particularly between rodents and primates. Hemispheric variability and bilateral asymmetry are most pronounced in humans, which we evaluated using a high-quality multimodal parcellation of hundreds of individuals. Asymmetries include modest differences in areal size but not in areal identity. Analyses of cortical connectivity using anatomical tracers reveal highly distributed connectivity and a wide range of connection weights in monkeys and mice; indirect measures using functional MRI suggest a similar pattern in humans. Altogether, a multifaceted but integrated approach to exploring cortical organization in primate and nonprimate species provides complementary advantages and perspectives. © 2019 National Academy of Sciences. All rights reserved.

Author Keywords
Cerebral cortex;  Macaque;  Marmoset;  Neuroanatomy;  Neuroimaging

Document Type: Conference Paper
Publication Stage: Final
Source: Scopus
Access Type: Open Access

A qualitative study of older adults’ perspectives on initiating exercise and mindfulness practice
(2019) BMC Geriatrics, 19 (1), art. no. 354, . 

Parra, D.C.^a , Wetherell, J.L.^b , Van Zandt, A.^a , Brownson, R.C.^{c d e} , Abhishek, J.^f , Lenze, E.J.^g

^a Program in Physical Therapy, Washington University in St. Louis, School of Medicine, 4444 Forest Park Ave, Campus Box 8502, St. Louis, MO 63108, United States
^b VA San Diego Healthcare System and Department of Psychiatry, University of California, San Diego, 3350 La Jolla Village Drive San Diego, San Diego, CA 92161, United States
^c Prevention Research Center in St. Louis, Brown School at Washington University in St. Louis, 1 Brookings Drive, Campus Box 1196, St. Louis, MO 63130, United States
^d Department of Surgery (Division of Public Health Sciences), 660 S. Euclid Ave, Campus Box 8100, St. Louis, MO 63110, United States
^e Alvin J. Siteman Cancer Center, Washington University School of Medicine, Washington University in St. Louis, 4921 Parkview Place, Saint Louis, MO, United States
^f Department of Biology, Washington University School of Medicine, Washington University in St. Louis, 1 Brookings Drive, St. Louis, MO 63130, United States
^g Department of Psychiatry, Healthy Mind Lab., 600 S. Taylor Ave., St. Louis, MO 63110, United States

Abstract
Background: Mindfulness practice and exercise are ways by which older adults can improve and maintain their physical, emotional and cognitive health. Methods: This single-site qualitative study gathered insights of older adults’ perceptions about initiating and maintaining mindfulness and exercise practices. We carried out focus groups with 41 adults aged 65-85 who had recently initiated Mindfulness Based Stress Reduction (MBSR), structured exercise, or their combination as part of participation in a clinical trial. We used a semi-structured interview to ask them open-ended questions regarding the benefits, barriers and facilitators of participating in mindfulness and/or exercise interventions. The interview also included questions regarding translation of these practices into community settings as well as the long-Term maintenance potential of these practices. Results: Older adults indicated that the mindfulness training increased their awareness and self-reflection and fostered a more self-Accepting attitude. Furthermore, they improved their self-care habits and reported having better familial and social relationships. The main barrier for both the exercise and Mindfulness group was time management. The social benefits and sense of community were some of the primary motivators for older adults in the exercise and/or MBSR interventions. However, the research on how to motivate older adults to initiate healthy behavioral changes also needs to be answered. The benefits of exercise and MBSR are a motivation in and of themselves, as indicated by some of the participants. Conclusions: This study indicates that mindfulness training and exercise can serve as tools to cultivate important health lifestyle qualities among older adults, who are in the midst of mental, social, emotional and physical change. If it were not for the purpose of the research or the incentives provided by the research team, these older adults may have never started the healthy behavioral changes. From the responses, this may indicate that older adults may need more incentives to begin and maintain behavioral changes other than for their own health benefit. © 2019 The Author(s).

Author Keywords
Exercise;  Mindfulness;  Mindfulness-based stress reduction;  Older adults;  Qualitative study

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

Children Use Regions in the Visual Processing and Executive Function Networks during a Subsequent Memory Reading Task
(2019) Cerebral Cortex (New York, N.Y. : 1991), 29 (12), pp. 5180-5189. 

Farah, R.^{a b} , Coalson, R.S.^c , Petersen, S.E.^d , Schlaggar, B.L.^{e f} , Horowitz-Kraus, T.^{a b g}

^a Educational Neuroimaging Center, Faculty of Biomedical Engineering
^b Faculty of Education in Science and Technology, TechnionHaifa, Israel
^c Departments of Neurology and Radiology
^d Division of Neuropsychology, Department of Psychology, Washington University Medical School, St. Louis, MO, USA
^e Kennedy Krieger Institute, MD, Baltimore, United States
^f Departments of Neurology and Pediatrics, Johns Hopkins University School of Medicine, United States
^g Reading and Literacy Discovery Center, Division of General and Community Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

Abstract
Memory encoding is a critical process for memory function, which is foundational for cognitive functioning including reading, and has been extensively studied using subsequent memory tasks. Research in adults using such tasks indicates the participation of visual and cognitive-control systems in remembered versus forgotten words. However, given the known developmental trajectories of these systems, the functional neuroanatomy of memory encoding in children may be different than in adults. We examined brain activation for silent word reading and checkerboard viewing during an event-related reading task in 8-12 year-old children. Results indicate greater activation for checkerboard viewing than lexical processing in early visual regions, as well as for lexical processing versus checkerboard viewing in regions in left sensorimotor mouth, cingulo-opercular and dorsal-attention networks. Greater activation for remembered than forgotten words was observed in bilateral visual system and left lateralized regions within the ventral- and dorsal-attention, cingulo-opercular and fronto-parietal networks. These findings suggest a relatively mature reliance on the cognitive-control system, but greater reliance on the visual system in children when viewing words subsequently remembered. The location of regions with greater activity for remembered words reinforces the involvement of the attention and cognitive-control systems in subsequent memory in reading. © The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Author Keywords
children;  cognitive control;  functional MRI;  memory;  visual processing

Document Type: Article
Publication Stage: Final
Source: Scopus

An update on the progress of preclinical models for guiding therapeutic management of neuronal ceroid lipofuscinosis
(2019) Expert Opinion on Orphan Drugs, 7 (12), pp. 555-568. 

Nelvagal, H.R., Cooper, J.D.

Department of Pediatrics, Division of genetics and genomics, Washington University School of Medicine in St. Louis, St Louis, MO, United States

Abstract
Introduction: The neuronal ceroid lipofuscinoses (NCLs) are a group of pediatric inherited neurodegenerative disorders affecting children and young adults. All forms of NCL are fatal and with no curative therapies available there is a pressing need to model their pathology in biological model systems to enable the systematic and rigorous testing of preclinical therapies. Areas covered: This article discusses and provides an update on the recent advances in modelling NCL disease pathology in various different model systems and their relevance to testing preclinical therapies so as to ensure optimal translation into human patients. The research articles discussed here were curated from PubMed (Last accessed-12.4.19) and Google Scholar (Last access-12.4.19) databases. Expert opinion: Both in vitro and in vivo biological model systems have been established for various forms of NCL. These have informed us about pathophysiology, revealed novel therapeutic targets, and provided landmarks of disease progression against which to test potential therapies. Studying NCL pathology across different species has been very informative regarding where therapies need to be delivered with an increasing focus on disease outside the brain. Testing such therapies in animal models of increasing complexity has allowed the translation of more efficacious therapies for clinical trials. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.

Author Keywords
Batten disease;  CRISPR/Cas9;  enzyme replacement therapy;  gene therapy;  large animal models;  lysosomal storage disorders;  Neuronal ceroid lipofuscinoses

Document Type: Review
Publication Stage: Final
Source: Scopus

Reaching for a healthier lifestyle: A photovoice investigation of healthy living in people with serious mental illness
(2019) Progress in Community Health Partnerships: Research, Education, and Action, 13 (4), pp. 371-383. 

Weinstein, L.C.^a , Chilton, M.^b , Turchi, R.^c , Klassen, A.^c , Lanoue, M.^d , Lamar, S.^e , Yorgey, S.^e , Kramer, L.^e , Smith, I.^e , Cabassa, L.^f

^a Department of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, United States
^b Health Management and Policy, Dornsife School of Public Health, Drexel University, United States
^c Dornsife School of Public Health, Drexel University, United States
^d School of Population Health, Thomas Jefferson University, United States
^e Pathways to Housing PA, United States
^f Brown School of Social Work, Washington University in St. Louis, United States

Abstract
Background: People with mental illness in the United States are almost twice as likely to be obese compared with those without a mental illness. Lifestyle factors, such as poor dietary choices and physical inactivity, are often cited as causes of obesity in this population, which limits the response to the obesity epidemic primarily to behavioral change interventions. In response, this project is grounded in a human rights framework to assure that the people most affected by the problem are included in understanding and addressing the problem. We sought to investigate social and structural factors that affect weight loss in partnership with community co-researchers enrolled in a group lifestyle program for overweight/obese people with serious mental illness (SMI) living in supportive housing settings. Methods: Using Photovoice methodology, eight co-researchers identified barriers and facilitators to healthy living in their community over seven weekly sessions. Results: Co-researchers selected 33 photos reflecting two overarching themes: 1) structural barriers, such as poor-quality food, high transportation costs, limited SNAP benefits, limits of food pantries, easy availability of tobacco and alcohol products, and limited places for exercise and 2) strategies for overcoming structural barriers. Conclusions: Co-researchers highlighted structural barriers that were a cause or consequence of food insecurity and situations that threaten the right to healthy food and opportunities for a healthy life. Co-researchers reported examples of knowledge and skills they learned through participation in the project that were used to overcome structural barriers to healthy eating and physical activity, and likely contributed to weight loss. © 2019 Johns Hopkins University Press.

Author Keywords
Community-based participatory research;  Disabled persons;  Health disparities;  Mental disorders;  Mental health;  Obesity;  Poverty;  Schizophrenia and disorders with psychotic features;  Social conditions

Document Type: Article
Publication Stage: Final
Source: Scopus

Learning hierarchically organized science categories: simultaneous instruction at the high and subtype levels
(2019) Cognitive Research: Principles and Implications, 4 (1), art. no. 48, . 

Nosofsky, R.M.^a , Slaughter, C.^a , McDaniel, M.A.^b

^a Psychological and Brain Sciences, Indiana University, 1101 E. Tenth Street, Bloomington, IN 47405, United States
^b Washington University in St. Louis, St. Louis, MO, United States

Abstract
Background: Most science categories are hierarchically organized, with various high-level divisions comprising numerous subtypes. If we suppose that one’s goal is to teach students to classify at the high level, past research has provided mixed evidence about whether an effective strategy is to require simultaneous classification learning of the subtypes. This past research was limited, however, either because authentic science categories were not tested, or because the procedures did not allow participants to form strong associations between subtype-level and high-level category names. Here we investigate a two-stage response-training procedure in which participants provide both a high-level and subtype-level response on most trials, with feedback provided at both levels. The procedure is tested in experiments in which participants learn to classify large sets of rocks that are representative of those taught in geoscience classes. Results: The two-stage procedure yielded high-level classification performance that was as good as the performance of comparison groups who were trained solely at the high level. In addition, the two-stage group achieved far greater knowledge of the hierarchical structure of the categories than did the comparison controls. Conclusion: In settings in which students are tasked with learning high-level names for rock types that are commonly taught in geoscience classes, it is best for students to learn simultaneously at the high and subtype levels (using training techniques similar to the presently investigated one). Beyond providing insights into the nature of category learning and representation, these findings have practical significance for improving science education. © 2019, The Author(s).

Author Keywords
Category learning;  Education;  Instruction;  Memory

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

A Novel Joint Brain Network Analysis Using Longitudinal Alzheimer’s Disease Data
(2019) Scientific Reports, 9 (1), art. no. 19589, . 

Kundu, S.^a , Lukemire, J.^a , Wang, Y.^a , Guo, Y.^a , Weiner, M.W.^b , Schuff, N.^{b h} , Rosen, H.J.^b , Miller, B.L.^b , Neylan, T.^b , Hayes, J.^b , Finley, S.^b , Aisen, P.^c , Khachaturian, Z.^{c l} , Thomas, R.G.^c , Donohue, M.^c , Walter, S.^c , Gessert, D.^c , Sather, T.^c , Jiminez, G.^c , Thal, L.^c , Brewer, J.^c , Vanderswag, H.^c , Fleisher, A.^c , Davis, M.^c , Morrison, R.^c , Petersen, R.^d , Jack, C.R.^d , Bernstein, M.^d , Borowski, B.^d , Gunter, J.^d , Senjem, M.^d , Vemuri, P.^d , Jones, D.^d , Kantarci, K.^d , Ward, C.^d , Mason, S.S.^d , Albers, C.S.^d , Knopman, D.^d , Johnson, K.^d , Jagust, W.^e , Landau, S.^e , Trojanowki, J.Q.^f , Shaw, L.M.^f , Lee, V.^f , Korecka, M.^f , Figurski, M.^f , Arnold, S.E.^f , Karlawish, J.H.^f , Wolk, D.^f , Toga, A.W.^g , Crawford, K.^g , Neu, S.^g , Schneider, L.S.^g , Pawluczyk, S.^g , Beccera, M.^g , Teodoro, L.^g , Spann, B.M.^g , Beckett, L.^h , Harvey, D.^h , Fletcher, E.^h , Carmichael, O.^h , Olichney, J.^h , DeCarli, C.^h , Green, R.C.ⁱ , Sperling, R.A.ⁱ , Johnson, K.A.ⁱ , Marshall, G.ⁱ , Frey, M.ⁱ , Lane, B.ⁱ , Rosen, A.ⁱ , Tinklenberg, J.ⁱ , Saykin, A.J.^j , Foroud, T.M.^j , Shen, L.^j , Faber, K.^j , Kim, S.^j , Nho, K.^j , Farlow, M.R.^j , Hake, A.M.^j , Matthews, B.R.^j , Herring, S.^j , Hunt, C.^j , Morris, J.^k , Raichle, M.^k , Holtzman, D.^k , Cairns, N.J.^k , Householder, E.^k , Taylor-Reinwald, L.^k , Ances, B.^k , Carroll, M.^k , Leon, S.^k , Mintun, M.A.^k , Schneider, S.^k , Oliver, A.^k , Raudin, L.^l , Sorensen, G.^m , Kuller, L.ⁿ , Mathis, C.ⁿ , Lopez, O.L.ⁿ , Oakley, M.A.ⁿ , Paul, S.^o , Relkin, N.^o , Chaing, G.^o , Raudin, L.^o , Davies, P.^p , Fillit, H.^q , Hefti, F.^r , Mesulam, M.M.^s , Kerwin, D.^s , Mesulam, M.-M.^s , Lipowski, K.^s , Wu, C.-K.^s , Johnson, N.^s , Grafman, J.^s , Potter, W.^t , Snyder, P.^u , Schwartz, A.^v , Montine, T.^w , Peskind, E.R.^w , Fox, N.^x , Thompson, P.^y , Apostolova, L.^y , Tingus, K.^y , Woo, E.^y , Silverman, D.H.S.^y , Lu, P.H.^y , Bartzokis, G.^y , Koeppe, R.A.^z , Heidebrink, J.L.^z , Lord, J.L.^z , Potkin, S.G.^z , Preda, A.^z , Nguyenv, D.^z , Foster, N.^aa , Reiman, E.M.^ab , Chen, K.^ab , Fleisher, A.^ab , Tariot, P.^ab , Reeder, S.^ab , Potkin, S.^ac , Mulnard, R.A.^ac , Thai, G.^ac , Mc-Adams-Ortiz, C.^ac , Buckholtz, N.^ad , Hsiao, J.^ad , Albert, M.^ae , Albert, M.^ae , Onyike, C.^ae , D’Agostino, D.^ae , Kielb, S.^ae , Simpson, D.M.^ae , Frank, R.^af , Kaye, J.^ag , Quinn, J.^ag , Lind, B.^ag , Carter, R.^ag , Dolen, S.^ag , Doody, R.S.^ah , Villanueva-Meyer, J.^ah , Chowdhury, M.^ah , Rountree, S.^ah , Dang, M.^ah , Stern, Y.^ah , Honig, L.S.^ah , Bell, K.L.^ah , Marson, D.^ai , Griffith, R.^ai , Clark, D.^ai , Geldmacher, D.^ai , Brockington, J.^ai , Roberson, E.^ai , Grossman, H.^aj , Mitsis, E.^aj , de Toledo-Morrell, L.^ak , Shah, R.C.^ak , Fleischman, D.^ak , Arfanakis, K.^ak , Duara, R.^al , Varon, D.^al , Greig, M.T.^al , Roberts, P.^al , Galvin, J.E.^am , Cerbone, B.^am , Michel, C.A.^am , Rusinek, H.^am , de Leon, M.J.^am , Glodzik, L.^am , De Santi, S.^am , Doraiswamy, P.M.^an , Petrella, J.R.^an , Wong, T.Z.^an , James, O.^an , Smith, C.D.^ao , Jicha, G.^ao , Hardy, P.^ao , Sinha, P.^ao , Oates, E.^ao , Conrad, G.^ao , Porsteinsson, A.P.^ap , Goldstein, B.S.^ap , Martin, K.^ap , Makino, K.M.^ap , Ismail, M.S.^ap , Brand, C.^ap , Womack, K.^aq , Mathews, D.^aq , Quiceno, M.^aq , Diaz-Arrastia, R.^aq , King, R.^aq , Weiner, M.^aq , Martin-Cook, K.^aq , DeVous, M.^aq , Levey, A.I.^ar , Lah, J.J.^ar , Cellar, J.S.^ar , Burns, J.M.^as , Anderson, H.S.^as , Swerdlow, R.H.^as , Graff-Radford, N.R.^at , Parfitt, F.^at , Kendall, T.^at , Johnson, H.^at , van Dyck, C.H.^au , Carson, R.E.^au , MacAvoy, M.G.^au , Chertkow, H.^av , Bergman, H.^av , Hosein, C.^av , Black, S.^aw , Stefanovic, B.^aw , Caldwell, C.^aw , Hsiung, G.-Y.R.^ax , Feldman, H.^ax , Mudge, B.^ax , Assaly, M.^ax , Kertesz, A.^ay , Rogers, J.^ay , Bernick, C.^ay , Munic, D.^ay , Kertesz, A.^az , Kertesz, A.^ba , Rogers, J.^ba , Finger, E.^ba , Pasternak, S.^ba , Rachinsky, I.^ba , Drost, D.^ba , Sadowsky, C.^bb , Martinez, W.^bb , Villena, T.^bb , Turner, R.S.^bc , Johnson, K.^bc , Reynolds, B.^bc , Sabbagh, M.N.^bd , Belden, C.M.^bd , Jacobson, S.A.^bd , Sirrel, S.A.^bd , Kowall, N.^be , Killiany, R.^be , Budson, A.E.^be , Norbash, A.^be , Johnson, P.L.^be , Allard, J.^bf , Lerner, A.^bg , Ogrocki, P.^bg , Hudson, L.^bg , Kittur, S.^bh , Borrie, M.^bi , Lee, T.-Y.^bi , Bartha, R.^bi , Johnson, S.^bj , Asthana, S.^bj , Carlsson, C.M.^bj , Fruehling, J.J.^bj , Harding, S.^bj , Bates, V.^bk , Capote, H.^bk , Rainka, M.^bk , Scharre, D.W.^bl , Kataki, M.^bl , Adeli, A.^bl , Petrie, E.C.^bl , Li, G.^bl , Zimmerman, E.A.^bm , Celmins, D.^bm , Brown, A.D.^bm , Pearlson, G.D.^bn , Blank, K.^bn , Anderson, K.^bn , Santulli, R.B.^bo , Kitzmiller, T.J.^bo , Schwartz, E.S.^bo , Sink, K.M.^bp , Williamson, J.D.^bp , Garg, P.^bp , Watkins, F.^bp , Ott, B.R.^bq , Querfurth, H.^bq , Tremont, G.^bq , Salloway, S.^br , Malloy, P.^br , Correia, S.^br , Mintzer, J.^bs , Spicer, K.^bs , Bachman, D.^bs , Massoglia, D.^bs , Pomara, N.^bt , Hernando, R.^bt , Sarrael, A.^bt , Schultz, S.K.^bu , Ponto, L.L.B.^bu , Shim, H.^bu , Smith, K.E.^bu , Smith, A.^bv , Fargher, K.^bv , Raj, B.A.^bv , Friedl, K.^bw , Yesavage, J.A.^bx , Taylor, J.L.^bx , Furst, A.J.^bx , The Alzheimer’s Disease Neuroimaging Initiative^by

^a Department of Biostatistics and Bioinformatics, Emory University, Atlanta, Ga 30322, United States
^b UC San Francisco, California, United States
^c UC San Diego, California, United States
^d Mayo Clinic, Rochester, NY, United States
^e UC Berkeley, California, United States
^f UPenn, Philadelphia, PA, United States
^g USC, Los Angeles, California, United States
^h UC Davis, California, United States
ⁱ Brigham and Women’s Hospital/Harvard Medical School, Boston, MA, United States
^j Indiana University, Bloomington, IN, United States
^k Washington University St Louis, Missouri, United States
^l Prevent Alzheimer’s Disease, Rockville, MD 2020, United States
^m Siemens, Munich, Germany
ⁿ University of Pittsburg, Pennsylvania, United States
^o Cornell University, Ithaca, NY, United States
^p Albert Einstein College of Medicine of Yeshiva University, Bronx, NY, United States
^q AD Drug Discovery Foundation, New York City, New York, United States
^r Acumen Pharmaceuticals, Livermore, CA, United States
^s Northwestern University, Evanston and Chicago, Illinois, United States
^t National Institute of Mental Health, Rockville, MD, United States
^u Brown University, Providence, RI, United States
^v Eli Lilly, Indianapolis, Indiana, United States
^w University of Washington, Seattle, WA, United States
^x University of London, London, United Kingdom
^y UCLA, Los Angeles, California, United States
^z University of Michigan, Ann Arbor, MI, United States
^aa University of Utah, Salt Lake, UT, United States
^ab Banner Alzheimer’s Institute, Phoenix, AZ, United States
^ac UC Irvine, Irvine, CA, United States
^ad National Institute on Aging, Bethesda, MD, United States
^ae Johns Hopkins University, Baltimore, MD, United States
^af Richard Frank Consulting, Washington, DC, United States
^ag Oregon Health and Science University, Portland, OR, United States
^ah Baylor College of Medicine, Houston, TX, United States
^ai University of Alabama, Birmingham, AL, United States
^aj Mount Sinai School of Medicine, New York City, New York, United States
^ak Rush University Medical Center, Chicago, IL, United States
^al Wien Center, Miami, FL, United States
^am New York University, New York City, New York, United States
^an Duke University Medical Center, Durham, NC, United States
^ao University of Kentucky, Lexington, KY, United States
^ap University of Rochester Medical Center, Rochester, NY, United States
^aq University of Texas Southwestern Medical School, Dallas, TX, United States
^ar Emory University, Atlanta, GA, United States
^as University of Kansas, Medical Center, Kansas City, KS, United States
^at Mayo Clinic, Jacksonville, FL, United States
^au Yale University School of Medicine, New Haven, CT, United States
^av McGill University/Montreal-Jewish General Hospital, Montreal, QC, Canada
^aw Sunnybrook Health Sciences, Toronto, ON, Canada
^ax U.B.C. Clinic for AD & Related Disorders, Vancouver, BC, Canada
^ay Cognitive Neurology–St Joseph’s, London, Ontario, Canada
^az Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, United States
^ba St Joseph’s Health Care, London, Ontario, Canada
^bb Premiere Research Institute, Palm Beach Neurology, Miami, FL, United States
^bc Georgetown University Medical Center, Washington, DC, United States
^bd Banner Sun Health Research Institute, Sun City, AZ, United States
^be Boston University, Boston, Massachusetts, United States
^bf Howard University, Washington, DC, United States
^bg Case Western Reserve University, Cleveland, OH, United States
^bh Neurological Care of CNY, Liverpool, NY, United States
^bi Parkwood Hospital, LondonON, Canada
^bj University of Wisconsin, Madison, WI, United States
^bk Dent Neurologic Institute, Amherst, NY, United States
^bl Ohio State University, Columbus, OH, United States
^bm Albany Medical College, Albany, NY, United States
^bn Hartford Hospital, Olin Neuropsychiatry Research Center, Hartford, CT, United States
^bo Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, United States
^bp Wake Forest University Health Sciences, Winston-Salem, NC, United States
^bq Rhode Island Hospital, Providence, RI, United States
^br Butler Hospital, Providence, RI, United States
^bs Medical University South Carolina, Charleston, SC, United States
^bt Nathan Kline Institute, Orangeburg, NY, United States
^bu University of Iowa College of Medicine, Iowa City, IA, United States
^bv University of South Florida: USF Health Byrd Alzheimer’s Institute, Tampa, FL, United States
^bw Department of Defense, Arlington, VA, United States
^bx Stanford University, StanfordCA, United States

Abstract
There is well-documented evidence of brain network differences between individuals with Alzheimer’s disease (AD) and healthy controls (HC). To date, imaging studies investigating brain networks in these populations have typically been cross-sectional, and the reproducibility of such findings is somewhat unclear. In a novel study, we use the longitudinal ADNI data on the whole brain to jointly compute the brain network at baseline and one-year using a state of the art approach that pools information across both time points to yield distinct visit-specific networks for the AD and HC cohorts, resulting in more accurate inferences. We perform a multiscale comparison of the AD and HC networks in terms of global network metrics as well as at the more granular level of resting state networks defined under a whole brain parcellation. Our analysis illustrates a decrease in small-worldedness in the AD group at both the time points and also identifies more local network features and hub nodes that are disrupted due to the progression of AD. We also obtain high reproducibility of the HC network across visits. On the other hand, a separate estimation of the networks at each visit using standard graphical approaches reveals fewer meaningful differences and lower reproducibility. © 2019, The Author(s).

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

Leadership Roles in Opioid Stewardship and the Treatment of Patients with Opioid Use Disorder Among Medical Toxicologists
(2019) Journal of Medical Toxicology, . 

Carpenter, J.E.^a , Murray, B.P.^{a b} , Mazer-Amirshahi, M.^c , Laes, J.A.R.^d , Nacca, N.^e , Nelson, L.S.^f , Perrone, J.^g , Schwarz, E.S.^h , Wiegand, T.J.^e , Wax, P.M.ⁱ

^a Emory University School of Medicine, 50 Hurt Plaza SE, Suite 600, Atlanta, GA 30303, United States
^b Wright-Patterson Medical Center, Wright-Patterson AFB, OH, United States
^c MedStar Washington Hospital Center, Washington, DC, United States
^d Hennepin Healthcare, Minneapolis, MN, United States
^e University of Rochester Medical Center, Rochester, NY, United States
^f Rutgers New Jersey Medical School, Newark, NJ, United States
^g University of Pennsylvania, Philadelphia, PA, United States
^h Washington University School of Medicine in St. Louis, St. Louis, MO, United States
ⁱ University of Texas Southwestern Medical School, Dallas, TX, United States

Abstract
Background: Despite significant efforts, deaths due to drug overdose remain at near record levels. In efforts combat this crisis, the Joint Commission now requires that accredited hospitals implement safe opioid prescribing practices. Emergency department visits and hospitalizations related to opioid use disorder (OUD) provide an opportunity to initiate evidence-based treatment. However, both situations require the presence of qualified physician leaders and clinicians, which many facilities lack. Medical toxicologists have the expertise needed to fill these voids, but the scope and prevalence of their involvement are unknown. We sought to determine the engagement of medical toxicologists in leading opioid stewardship initiatives and the treatment of patients with OUD. Methods: Members of the American College of Medical Toxicology (ACMT) were surveyed about their leadership roles in opioid stewardship and clinical practices regarding OUD from March-June 2019. ACMT represents more than 80% of the nation’s board-certified medical toxicologists. The electronic survey utilized branching logic and results are presented descriptively; thus, responses are presented as a percentage of the number of respondents to individual questions rather than the total number of participants. Results: One hundred and thirty-one out of 382 eligible individuals from at least 76 institutions responded to the survey. A majority (60%) had a DATA 2000 X-waiver, 21% were board-certified in addiction medicine (AM), and an additional 22% were definitely or possibly planning to pursue board certification in AM. Sixteen percent of respondents reported having a formal leadership role to address opioid pain management and stewardship, and 17% had a formal leadership role that specifically addresses clinical treatment for OUD within their institution. Fifty-seven respondents prescribed buprenorphine in emergency medicine practice, 41 as inpatient consultants, and 23 in an outpatient clinic. Conclusions: Medical toxicologists can serve as leaders to promote safe opioid prescribing practices through both institutional and governmental opioid task forces and opioid stewardship programs. They also provide important addiction-related clinical care to patients with OUD. © 2019, American College of Medical Toxicology.

Author Keywords
Addiction medicine;  Buprenorphine;  Opioid use disorder;  Toxicology

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

Cognition, ADHD Symptoms, and Functional Impairment in Children and Adolescents With Neurofibromatosis Type 1
(2019) Journal of Attention Disorders, . 

Payne, J.M.^{a b} , Haebich, K.M.^a , MacKenzie, R.^c , Walsh, K.S.^d , Hearps, S.J.C.^a , Coghill, D.^{a b} , Barton, B.^{e f} , Pride, N.A.^{e f} , Ullrich, N.J.^g , Tonsgard, J.H.^h , Viskochil, D.ⁱ , Schorry, E.K.^j , Klesse, L.^k , Fisher, M.J.^l , Gutmann, D.H.^m , Rosser, T.ⁿ , Packer, R.J.^d , Korf, B.^o , Acosta, M.T.^d , Bellgrove, M.A.^p , North, K.N.^{a b}

^a Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, VIC, Australia
^b University of Melbourne, Parkville, VIC, Australia
^c La Trobe University, Bundoora, VIC, Australia
^d Children’s National Health System, Washington, DC, United States
^e The Children’s Hospital at WestmeadNSW, Australia
^f The University of SydneyNSW, Australia
^g Boston Children’s HospitalMA, United States
^h The University of Chicago Medicine Comer Children’s HospitalIL, United States
ⁱ The University of Utah, Salt Lake City, United States
^j Cincinnati Children’s Hospital Medical CenterOH, United States
^k University of Texas Southwestern Medical Center, Dallas, United States
^l Children’s Hospital of PhiladelphiaPA, United States
^m Washington University School of Medicine, St Louis, MO, United States
ⁿ Children’s Hospital Los AngelesCA, United States
^o The University of Alabama at Birmingham, United States
^p Monash University, Clayton, VIC, Australia

Abstract
Objective: We examined the contribution of attention and executive cognitive processes to ADHD symptomatology in NF1, as well as the relationships between cognition and ADHD symptoms with functional outcomes. Methods: The study sample consisted of 141 children and adolescents with NF1. Children were administered neuropsychological tests that assessed attention and executive function, from which latent cognitive variables were derived. ADHD symptomatology, adaptive skills, and quality of life (QoL) were assessed using parent-rated questionnaires. Path analyses were conducted to test relationships among cognitive functioning, ADHD symptomatology, and functional outcomes. Results: Significant deficits were observed on all outcome variables. Cognitive variables did not predict ADHD symptomatology. Neither did they predict functional outcomes. However, elevated ADHD symptomatology significantly predicted functional outcomes. Conclusion: Irrespective of cognitive deficits, elevated ADHD symptoms in children with NF1 negatively impact daily functioning and emphasize the importance of interventions aimed at minimizing ADHD symptoms in NF1. © The Author(s) 2019.

Author Keywords
ADHD;  cognition;  executive function;  functional impairment;  neurofibromatosis type 1

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