Arts & Sciences McKelvey School of Engineering School of Medicine Weekly Publications

WashU weekly Neuroscience publications

"Relationships between food-related behaviors, obesity, and medication use in individuals with Smith-Magenis syndrome" (2022) Research in Developmental Disabilities

Relationships between food-related behaviors, obesity, and medication use in individuals with Smith-Magenis syndrome(2022) Research in Developmental Disabilities, 127, art. no. 104257, . 

Gandhi, A.A.a , Wilson, T.A.a , Sisley, S.b c , Elsea, S.H.a , Foster, R.H.d e

a Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, United Statesb Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, United Statesc Children’s Nutrition Research Center, Houston, TX 77030, United Statesd Department of Psychology, St. Louis Children’s Hospital, St. Louis, MO 63110, United Statese Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, United States

AbstractBackground: Smith-Magenis syndrome (SMS) is a complex neurodevelopmental disorder that includes obesity and food-seeking/satiety-related behaviors. Aims: This study examined associations between food-related/hyperphagic behaviors, weight, and medication use in individuals with SMS. Methods/Procedures: Caregivers of individuals with SMS in the Parents and Researchers Interested in SMS (PRISMS) Patient Registry completed a demographic/medication questionnaire, the Hyperphagia Questionnaire for Clinical Trials, and the Food Related Problems Questionnaire. Outcomes/Results: Among 49 participants (Mage = 16.41 ± 12.73 years, range = 4–69 years, 55% girls/women), individuals with SMS with overweight/obesity (n = 22) had worse overall food-related problems including greater impaired satiety (p < 0.05), maladaptive eating behaviors (p < 0.05), inappropriate response (p < 0.01), and hyperphagia (p < 0.01) compared to individuals of normal/underweight (n = 27). Those taking anti-depressants/anxiolytics (n = 16) had greater maladaptive eating behaviors (p < 0.05), hyperphagic behaviors (p < 0.05), and hyperphagic severity (p < 0.05) than those not taking anti-depressants/anxiolytics (n = 33). Boys/men with SMS had greater maladaptive eating behaviors (p < 0.05), inappropriate response (p < 0.05), and hyperphagic drive (p < 0.01) than girls/women with SMS. Conclusions/Implications: Maladaptive food-related behaviors were higher in individuals with SMS with overweight/obesity, taking anti-depressants/anxiolytics, or who were male. Medications in this population should be chosen with weight-related side effects in mind. © 2022 Elsevier Ltd

Author KeywordsFood-seeking;  Hyperphagia;  Medications;  Obesity;  Satiety;  Smith-Magenis syndrome

Funding detailsScoliosis Research SocietySRS

Document Type: ArticlePublication Stage: FinalSource: Scopus

"Impact of Sleep Disturbance, Physical Function, Depression and Anxiety on Male Lower Urinary Tract Symptoms: Results from the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN)" (2022) The Journal of Urology

Impact of Sleep Disturbance, Physical Function, Depression and Anxiety on Male Lower Urinary Tract Symptoms: Results from the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN)(2022) The Journal of Urology, 208 (1), pp. 155-163. 

Glaser, A.P.a , Mansfield, S.b , Smith, A.R.b , Helfand, B.T.a , Lai, H.H.c , Sarma, A.d , Yang, C.C.e , Taddeo, M.f , Clemens, J.Q.d g , Cameron, A.P.d , Flynn, K.E.h , Andreev, V.b , Fraser, M.O.i , Erickson, B.A.j , Kirkali, Z.k , Griffith, J.W.f , and the LURN Study Groupl

a Department of Surgery, Division of Urology, NorthShore University HealthSystem, Evanston, IL, United Statesb Arbor Research Collaborative for Health, Ann Arbor, MI, United Statesc Division of Urologic Surgery, Departments of Surgery and Anesthesiology, Washington University School of Medicine, St. Louis, MO, United Statesd Department of Urology, University of Michigan Health System, Ann Arbor, MI, United Statese Department of Urology, University of Washington, Seattle, WA, United Statesf Department of Medical Social Sciences, Northwestern University-Feinberg School of Medicine, Chicago, IL, Mexicog Dow Division of Health Services Research, University of Michigan, Ann Arbor, MI, United Statesh Medical College of Wisconsin, Milwaukee, WI, United Statesi Department of Surgery, Division of Urology, Duke University, Durham, NCj Department of Urology, University of Iowa Carver College of Medicine, Iowa City, IA, United Statesk National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, United States

AbstractPURPOSE: The impact of nonurological factors on male lower urinary tract symptoms (LUTS) remains unclear. We investigated cross-sectional and longitudinal associations among anxiety, depression, physical function, sleep quality and urinary symptom subdomains. MATERIALS AND METHODS: Data from 518 men in the LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network) study were analyzed to identify associations between Patient-Reported Outcomes Measurement Information System® (PROMIS®) depression, anxiety, sleep disturbance and physical function measures and LUTS subdomains, as derived from the American Urological Association Symptom Index and LUTS Tool. Multivariable linear regression was used to assess the relationships between PROMIS measures and LUTS subdomains at baseline and at 3- and 12-month followup. RESULTS: Baseline depression and anxiety were associated with urinary incontinence (p <0.001), voiding symptoms (p <0.001) and quality of life (p=0.002), whereas baseline sleep disturbance was associated with voiding and storage symptoms and quality of life (p <0.001 for all). Urinary symptom severity improved in all subdomains at 3 and 12 months. Similar associations between PROMIS measures and LUTS subdomains were observed at all time points, but baseline depression, anxiety, sleep disturbance and physical function measures were not associated with longitudinal trajectories of LUTS. CONCLUSIONS: Urinary symptom subdomains are independently associated with modifiable clinical variables including sleep quality and depression at all time points, but these variables do not predict the degree of improvement in LUTS following urological evaluation and treatment over the medium term. Bidirectional assessment and randomized experiments may improve our understanding of these relationships.

Author Keywordsanxiety;  depression;  lower urinary tract symptoms;  patient reported outcome measures;  quality of life

Document Type: ArticlePublication Stage: FinalSource: Scopus

"Comorbidities Are Complex: The Dynorphin/Kappa Opioid Receptor System in a Preclinical Model of Stress and Alcohol (2022) Biological Psychiatry

Comorbidities Are Complex: The Dynorphin/Kappa Opioid Receptor System in a Preclinical Model of Stress and Alcohol(2022) Biological Psychiatry, 91 (12), pp. 1000-1002. 

Conway, S.M., Al-Hasani, R.

Department of Anesthesiology and the Washington University Pain Center, Washington University in St. Louis, St. Louis, Missouri; Center for Clinical Pharmacology, University of Health Sciences and Pharmacy and Washington University School of Medicine, St. Louis, Missouri

Document Type: ArticlePublication Stage: FinalSource: Scopus

"Randomized Phase 2 Study of ACE-083 in Patients With Charcot-Marie-Tooth Disease" (2022) Neurology

Randomized Phase 2 Study of ACE-083 in Patients With Charcot-Marie-Tooth Disease(2022) Neurology, 98 (23), pp. E2356-E2367. 

Thomas, F.P.a , Brannagan, T.H.b , Butterfield, R.J.c , Desai, U.d , Habib, A.A.e , Herrmann, D.N.f , Eichinger, K.J.f , Johnson, N.E.g , Karam, C.h , Pestronk, A.i , Quinn, C.j , Shy, M.E.k , Statland, J.M.l , Subramony, S.H.m , Walk, D.n , Stevens-Favorite, K.o , Miller, B.p , Leneus, A.p , Fowler, M.p , Van De Rijn, M.p , Attie, K.M.p

a Hackensack University Medical Center, Hackensack Meridian School of Medicine, Nutley, NJ, United Statesb Columbia University Medical Center, New York, NY, United Statesc University of Utah, Salt Lake City, United Statesd Carolinas Healthcare System Neurosciences Institute, Charlotte, NC, United Statese University of California Irvine, United Statesf University of Rochester Medical CenterNY, United Statesg Virginia Commonwealth University, Richmond, United Statesh Oregon Health and Science University, Portland, United Statesi Washington University School of Medicine, St. Louis, MO, United Statesj University of Pennsylvania, Philadelphia, United Statesk University of Iowa, Iowa City, United Statesl University of Kansas Medical Center, Kansas City, United Statesm University of Florida, Gainesville, United Statesn University of Minnesota, Minneapolis, United Stateso Cadent Medical Communications, Llc, A Syneos Health Group Company, New York, NY, United Statesp Acceleron Pharma, Cambridge, MA, United States

AbstractBackground and ObjectivesThe goal of this work was to determine whether locally acting ACE-083 is safe and well tolerated and increases muscle volume, motor function, and quality of life (QoL) in adults with Charcot-Marie-Tooth disease (CMT) type 1.MethodsThis phase 2 study enrolled adults with CMT1 or CMTX (N = 63). Part 1 was open label and evaluated the safety and tolerability of different dose levels of ACE-083 for use in part 2. Part 2 was a randomized, placebo-controlled, 6-month study of 240 mg/muscle ACE-083 injected bilaterally into the tibialis anterior muscle, followed by a 6-month, open-label extension in which all patients received ACE-083. Pharmacodynamic endpoints included total muscle volume (TMV; primary endpoint), contractile muscle volume (CMV), and fat fraction. Additional secondary endpoints included 6-minute walk test, 10-m walk/run, muscle strength, and QoL. Safety was assessed with treatment-emergent adverse events (TEAEs) and clinical laboratory tests.ResultsIn part 1 (n = 18), ACE-083 was generally safe and well tolerated at all dose levels, with no serious adverse events, TEAEs of grade 3 or greater, or death reported. In part 2 (n = 45 enrolled, n = 44 treated), there was significantly greater change in TMV with ACE-083 compared with placebo (least-squares mean difference 13.5%; p = 0.0096). There was significant difference between ACE-083 and placebo for CMV and change in ankle dorsiflexion strength. Fat fraction and all other functional outcomes were not significantly improved by ACE-083. Moderate to mild injection-site reactions were the most common TEAEs.DiscussionDespite significantly increased TMV and CMV, patients with CMT receiving ACE-083 in tibialis anterior muscles did not demonstrate greater functional improvement compared with those receiving placebo.Trial Registration InformationClinical Trials Registration: NCT03124459.Classification of EvidenceThis study provides Class II evidence that intramuscular ACE-083 is safe and well tolerated and increases total muscle volume after 6 months of treatment in adults with CMT1 or CMTX. © American Academy of Neurology.

Funding detailsNational Institutes of HealthNIHCenters for Disease Control and PreventionCDCDD19-002U.S. Food and Drug AdministrationFDA7R01FD006071-02National Institute of Neurological Disorders and StrokeNINDS4K23NS091511, R01NS104010Friedreich’s Ataxia Research AllianceFARAGenzymeMuscular Dystrophy AssociationMDACSL BehringFSH SocietyAcceleronAveXis

Document Type: ArticlePublication Stage: FinalSource: Scopus

"Serotonin type 3 receptor subunit gene polymorphisms associated with psychosomatic symptoms in irritable bowel syndrome: A multicenter retrospective study" (2022) World Journal of Gastroenterology

Serotonin type 3 receptor subunit gene polymorphisms associated with psychosomatic symptoms in irritable bowel syndrome: A multicenter retrospective study(2022) World Journal of Gastroenterology, 28 (21), pp. 2334-2349. 

Berens, S.a , Dong, Y.b c , Fritz, N.b , Wahl, V.b , Martinez, C.b i , Schmitteckert, S.b , Rappold, G.b y , Engel, F.c , Tesarz, J.c , Walstab, J.d , D’Amato, M.e f g , Zheng, T.g , Boekstegers, F.h , Bermejo, J.L.h , Clevers, E.j , Gauss, A.k , Herzog, W.l , Spiller, R.m , Goebel-Stengel, M.n , Mönnikes, H.o , Andresen, V.p , Thomas, F.q , Keller, J.r , Pehl, C.s , Stein-Thöringer, C.t , Clarke, G.u , Dinan, T.G.u , Quigley, E.M.v , Sayuk, G.w , Simrén, M.x , van Oudenhove, L.z aa , Schaefert, R.c ab , Niesler, B.y ac

a Department of General Internal Medicine and Psychosomatics, University Hospital Heidelberg, Heidelberg, 69120, Germanyb Department of Human Molecular Genetics, Institute of Human Genetics, University of Heidelberg, Heidelberg, 69120, Germanyc Department of General Internal Medicine and Psychosomatics, Internal Medicine II, University Hospital Heidelberg, Heidelberg, 69120, Germanyd Department of Human Molecular Genetics, University of Heidelberg, Heidelberg, 69120, Germanye Gastrointestinal Genetics Lab, CIC bioGUNE – BRTA, Derio, 48160, Spainf IKERBASQUE, Basque Foundation for Science, Bilbao, 48001, Spaing Unit of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, 17177, Swedenh Institute of Medical Biometry and Informatics, Heidelberg University, Heidelberg, 69120, Germanyi Lleida Institute for Biomedical Research Dr. Pifarré Foundation (IRBLleida), Av. Alcalde Rovira Roure, Lleida, 25198, Spainj Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders, KU Leuven, Leuven, 3000, Belgiumk Department of Gastroenterology Infectious Diseases and Intoxications, University of Heidelberg, Heidelberg, 69120, Germanyl Department of General Internal Medicine and Psychosomatics, Heidelberg University, Heidelberg, 69120, Germanym Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, NG7 2QL, United Kingdomn Helios Klinikum Rottweil, Rottweil, 78628, Germanyo Department of Medicine, Institute of Neurogastroenterology (H.M.), Martin-Luther-Hospital, Belin14193, Germanyp Israelitisches Krankenhaus in Hamburg, Hamburg, 22297, Germanyq Internal Medicine II, Helios Klinikum Krefeld, Krefeld, 47805, Germanyr Israelitisches Krankenhaus Hamburg, Hamburg22297, Ghanas Krankenhaus Vilsbiburg, Vilsbiburg, 84137, Germanyt Division of Microbiome and Cancer, German Cancer Research Center (DKFZ), Heidelberg, 69120, Germanyu Department of Psychiatry and Neurobehavioral Science, University College Cork, Cork, T23, Irelandv Medicine in Digestive Disorders, Department of Medicine, Lynda K. and David M. Underwood Center for Digestive Disorders, Houston Methodist, Houston, TX 77030, United Statesw Division of Gastroenterology, Washington University, Department of Psychiatry, School of Medicine, John Cochran Veteran Affairs Medical Center, St. Louis, MO 63110, United Statesx Department of Internal Medicine, Section of Gastroenterology and Hepatology, Sahlgrenska University Hospital, Gothenburg, SE-41685, Swedeny Interdisciplinary Center for Neurosciences (IZN), University of Heidelberg, Heidelberg, 69120, Germanyz Cognitive and Affective Neuroscience Lab, Department of Psychological and Brain Sciences, Dartmouth College, Hanover, NH 03748, United Statesaa Laboratory for Brain-Gut Axis Studies, Translational Research Center for Gastrointestinal Disorders, Department of Chronic Diseases Metabolism and Ageing, KU Leuven, Leuven, 3000, Belgiumab Department of Psychosomatic Medicine, Division of Internal Medicine, University Hospital Basel, Basel, CH-4031, Switzerlandac Department of Human Molecular Genetics, Heidelberg University, Heidelberg, 69120, Germany

AbstractBACKGROUND Single-nucleotide polymorphisms (SNPs) of the serotonin type 3 receptor subunit (HTR3) genes have been associated with psychosomatic symptoms, but it is not clear whether these associations exist in irritable bowel syndrome (IBS). AIM To assess the association of HTR3 polymorphisms with depressive, anxiety, and somatization symptoms in individuals with IBS. METHODS In this retrospective study, 623 participants with IBS were recruited from five specialty centers in Germany, Sweden, the United States, the United Kingdom, and Ireland. Depressive, anxiety, and somatization symptoms and sociodemographic characteristics were collected. Four functional SNPs – HTR3A c.-42C>T, HTR3B c.386A>C, HTR3C c.489C>A, and HTR3E c.*76G>A – were genotyped and analyzed using the dominant and recessive models. We also performed separate analyses for sex and IBS subtypes. SNP scores were calculated as the number of minor alleles of the SNPs above. The impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx assays. RESULTS Depressive and anxiety symptoms significantly worsened with increasing numbers of minor HTR3C c.489C>A alleles in the dominant model (Fdepressive = 7.475, Pdepressive = 0.006; Fanxiety = 6.535, Panxiety = 0.011). A higher SNP score (range 0-6) was linked to a worsened depressive symptoms score (F = 7.710, P-linear trend = 0.006) in IBS. The potential relevance of the HTR3C SNP was corroborated, showing changes in the expression level of 5-HT3AC variant receptors. CONCLUSION We have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with IBS. The SNP score indicated that an increasing number of minor alleles is linked to the worsening of depressive symptoms in IBS. © The Author(s) 2022.

Author Keywords5-HT3 receptor subunit gene polymorphisms;  Anxiety;  Depression;  Irritable bowel syndrome;  Single-nucleotide polymorphism score;  Somatization

Funding detailsAstraZenecaEuropean Cooperation in Science and TechnologyCOSTBM1106

Document Type: ArticlePublication Stage: FinalSource: Scopus

"Recapitulation of endogenous 4R tau expression and formation of insoluble tau in directly reprogrammed human neurons" (2022) Cell Stem Cell

Recapitulation of endogenous 4R tau expression and formation of insoluble tau in directly reprogrammed human neurons(2022) Cell Stem Cell, 29 (6), pp. 918-932.e8. 

Capano, L.S.a b c , Sato, C.d , Ficulle, E.g , Yu, A.h , Horie, K.d , Kwon, J.-S.a i , Burbach, K.F.a j , Barthélemy, N.R.d , Fox, S.G.h , Karch, C.M.e f k , Bateman, R.J.d e f , Houlden, H.g , Morimoto, R.I.h , Holtzman, D.M.d e f , Duff, K.E.g , Yoo, A.S.a b f

a Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, United Statesb Center for Regenerative Medicine, Washington University School of Medicine, St. Louis, MO 63110, United Statesc Program in Molecular and Cell Biology, Washington University School of Medicine, St. Louis, MO, United Statesd Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, United Statese Knight Alzheimer’s Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, United Statesf Hope Center for Neurological Disorders, Knight ADRC, St. Louis, MO 63110, United Statesg UK Dementia Research Institute at University College London, London, WC1E 6BT, United Kingdomh Department of Molecular Biosciences, Rice Institute for Biomedical Research, Northwestern University, Evanston, IL 60208, United Statesi Program in Computational and Systems Biology, Washington University School of Medicine, St. Louis, MO, United Statesj Program in Molecular Genetics and Genomics, Washington University School of Medicine, St. Louis, MO, United Statesk Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, United States

AbstractTau is a microtubule-binding protein expressed in neurons, and the equal ratios between 4-repeat (4R) and 3-repeat (3R) isoforms are maintained in normal adult brain function. Dysregulation of 3R:4R ratio causes tauopathy, and human neurons that recapitulate tau isoforms in health and disease will provide a platform for elucidating pathogenic processes involving tau pathology. We carried out extensive characterizations of tau isoforms expressed in human neurons derived by microRNA-induced neuronal reprogramming of adult fibroblasts. Transcript and protein analyses showed that miR neurons expressed all six isoforms with the 3R:4R isoform ratio equivalent to that detected in human adult brains. Also, miR neurons derived from familial tauopathy patients with a 3R:4R ratio altering mutation showed increased 4R tau and the formation of insoluble tau with seeding activity. Our results collectively demonstrate the utility of miRNA-induced neuronal reprogramming to recapitulate endogenous tau regulation comparable with the adult brain in health and disease. © 2022 Elsevier Inc.

Author Keywords4R tau;  adult human neurons;  insoluble tau;  microRNA-induced neurons;  neuronal reprogramming;  tau isoform ratio;  tau isoforms;  tau seeding;  tauopathy

Funding detailsP01 AG026276P01 AG03991JIT659HNational Institutes of HealthNIHNational Institute on AgingNIARF1AG056296National Institute of Neurological Disorders and StrokeNINDSAG063521, K01AG062796, R01 NS095773, R01NS107488Eli Lilly and CompanyRocheColumbia UniversityDesert Research InstituteDRICure Alzheimer’s FundCAFUniversity of WashingtonUWInstitute of Clinical and Translational SciencesICTST32 GM007067Wellcome TrustWTR56 NS110890Alzheimer’s Disease Research Center, University of WashingtonADRC, UWAlzheimer’s Disease Research Center, University of PittsburghADRCP30 AG066444, P50 AG05691Medical Research CouncilMRCAlzheimer’s SocietyAlzheimer’s Research UKARUKEisai

Document Type: ArticlePublication Stage: FinalSource: Scopus

"Interactions Between Weight Loss and Plasma Neurodegenerative Markers for Determining Cognitive Decline Among Community-Dwelling Older Adults" (2022) The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences

Interactions Between Weight Loss and Plasma Neurodegenerative Markers for Determining Cognitive Decline Among Community-Dwelling Older Adults(2022) The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 77 (6), pp. 1159-1168. 

Giudici, K.V.a , Guyonnet, S.a b , Morley, J.E.c , Nguyen, A.D.c , Aggarwal, G.c , Parini, A.d , Li, Y.e f , Bateman, R.J.e , Vellas, B.a b , de Souto Barreto, P.a b , MAPT/DSA Groupg

a Gerontopole of Toulouse, Institute of Ageing, Toulouse University Hospital (CHU Toulouse), Toulouse, Franceb University of Toulouse III, INSERM, UPS, Toulouse, Francec Division of Geriatric Medicine, School of Medicine, Saint Louis University, St. Louis, MO, United Statesd Institute of Metabolic and Cardiovascular Diseases (I2MC), INSERM UMR 1048, University of Toulouse III Paul Sabatier, Toulouse, Francee Department of Neurology, Washington University School of Medicine, St. Louis, MO, United Statesf Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, United States

AbstractThis study aimed to investigate the interaction between weight loss (WL) and plasma amyloid-β 42/40 (Aβ 42/40), neurofilament light chain (NfL), progranulin, and their association with cognitive decline over time among older adults. This 5-year observational approach included 470 participants from the Multidomain Alzheimer Preventive Trial, mean age 76.8 years (SD = 4.5), 59.4% women. WL was defined as ≥5% decrease over the first year. Biomarkers were measured at 12 months. Cognitive function was assessed yearly from 12 months onward by Mini-Mental State Examination (MMSE); Clinical Dementia Rating sum of boxes (CDR-SB); a composite score based on Category Naming Test; Digit Symbol Substitution Test; 10 MMSE orientation items (MMSEO) and free and total recall of the Free and Cued Selective Reminding test; and these tests individually. Twenty-seven participants (5.7%) presented WL. In adjusted analyses, combined WL + lower Aβ 42/40 (≤0.103, lowest quartile) was related with more pronounced 4-year cognitive decline according to CDR-SB (p < .0001) and MMSEO (p = .021), compared with non-WL + higher Aβ 42/40. WL + higher NfL (>94.55 pg/mL, highest quartile) or progranulin (>38.4 ng/mL, 3 higher quartiles) were related with higher cognitive decline according to CDR-SB, MMSE, MMSEO, and composite score (all p < .03), compared with non-WL + lower NfL or higher progranulin. Regrouping progranulin quartiles (Q1-Q3 vs Q4) revealed higher cognitive decline among the WL + lower progranulin group compared with non-WL + lower progranulin. In conclusion, 1-year WL was associated with subsequent higher 4-year cognitive decline among older adults presenting low Aβ 42/40 or high NfL. Future studies combining plasma biomarker assessments and body weight surveillance may be useful for identifying people at risk of cognitive impairment. Clinical trial number: NCT00672685. © The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Author KeywordsAmyloid-β;  Cognition;  Neurofilament light chain;  Progranulin

Document Type: ArticlePublication Stage: FinalSource: Scopus

"Racial Segregation and Cognitive Function Among Older Adults in the United States: Findings From the Reasons for Geographic and Racial Differences in Stroke Study" (2022) The Journals of Gerontology. Series B, Psychological Sciences and Social Sciences

Racial Segregation and Cognitive Function Among Older Adults in the United States: Findings From the Reasons for Geographic and Racial Differences in Stroke Study(2022) The Journals of Gerontology. Series B, Psychological Sciences and Social Sciences, 77 (6), pp. 1132-1143. 

Jang, J.B.a , Hicken, M.T.b , Mullins, M.c , Esposito, M.d , Sol, K.a , Manly, J.J.e , Judd, S.f , Wadley, V.g , Clarke, P.J.h

a Institute for Social Research, University of Michigan, Ann Arbor, United Statesb Institute for Social Research, Department of Internal Medicine, University of Michigan, Ann Arbor, United Statesc Rogel Cancer Center, Center for Improving Patient and Population Health, Institute for Social Research, University of Michigan, Ann Arbor, United Statesd Department of Sociology, Washington University in St. LouisMO, United Statese Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Department of Neurology, Columbia UniversityNY, United Statesf Department of Biostatistics, University of Alabama at Birmingham, United Statesg Department of Medicine, Division of Gerontology, Geriatrics, Palliative Care, University of Alabama at Birmingham, United Statesh Institute for Social Research, Department of Epidemiology, University of Michigan, Ann Arbor, United States

AbstractOBJECTIVES: Residential segregation is one of the fundamental features of health disparities in the United States. Yet little research has examined how living in segregated metropolitan areas is related to cognitive function and cognitive decline with age. We examined the association between segregation at the metropolitan statistical area (MSA) level and trajectories of age-related cognitive function. METHOD: Using data from Black and White older adults in the REasons for Geographic and Racial Differences in Stroke study (n = 18,913), we employed linear growth curve models to examine how living in racially segregated MSAs at baseline, measured by the degree of non-Hispanic Black (NHB) isolation and NHB dissimilarity, was associated with trajectories of age-related cognitive function and how the associations varied by race and education. RESULTS: Living in MSAs with greater levels of isolation was associated with lower cognitive function (b = -0.093, p < .05) but was not associated with rates of change in cognitive decline with age. No effects of living in isolated MSAs were found for those with at least a high school education, but older adults with less than a high school education had lower cognitive function in MSAs with greater isolation (b = -0.274, p < .05). The degree of dissimilarity was not associated with cognitive function. The association between segregation and cognitive function did not vary by race. DISCUSSION: Metropolitan segregation was associated with lower cognitive function among older adults, especially for those with lower education living in racially isolated MSAs. This suggests complex associations between individual socioeconomic status, place, and cognitive health. © The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Author KeywordsCognitive function;  Multilevel linear model;  Racial segregation;  REGARDS study

Document Type: ArticlePublication Stage: FinalSource: Scopus

"Improving Follow-Up for Adolescents With Depression in Primary Care" (2022) Pediatrics

Improving Follow-Up for Adolescents With Depression in Primary Care(2022) Pediatrics, 149 (6), . 

Garbutt, J., Dodd, S., Rook, S., Graham, S., Wang, R., Sterkel, R., Plax, K.

Department of Pediatrics, Washington University, St. Louis, MO, United States

AbstractBACKGROUND: Few adolescents with depression receive treatment in accordance with national guidelines. This quality improvement project took place in 11 primary care practices with the primary aim of increasing the percentage of teens with depression who received follow-up care within 6 weeks of diagnosis and within 3 months, once stable. METHODS: The primary strategy was external practice facilitation for 12 months. The change process used goal setting and plan-do-study-act cycles to identify and implement change ideas. A preanalysis and postanalysis was completed to evaluate process change, provider confidence, and patient improvement. RESULTS: Randomly selected samples of 199 and 217 charts of teens newly diagnosed with depression were reviewed before and after the intervention, respectively. Chart data for these measurements was provided by 10 and 9 practices, respectively. The percentage of patients with follow-up care within 6 weeks after diagnosis increased from 40% to 81% (P < .001), the percentage with a follow-up visit within 3 months once stable increased from 30% to 60% (P < .001), and the percentage in remission at 6 months increased from 7% to 21% (P < .001). Providers reported increased confidence to diagnose and manage depression, assess severity, provide pharmacotherapy, and educate families. CONCLUSIONS: Practices improved follow-up care for teens with depression. In addition, providers experienced an improvement in their confidence to diagnose and manage depression. Working with a facilitator, each practice implemented standardized systems to provide effective care in the medical home, increase providers’ confidence to address this common problem, and improve patient outcomes. Copyright © 2022 by the American Academy of Pediatrics.

Document Type: ArticlePublication Stage: FinalSource: Scopus

"Pain Relief with Combination Acetaminophen/Codeine or Ibuprofen following Third-Molar Extraction: A Systematic Review and Meta-Analysis" (2022) Pain Medicine (Malden, Mass.)

Pain Relief with Combination Acetaminophen/Codeine or Ibuprofen following Third-Molar Extraction: A Systematic Review and Meta-Analysis(2022) Pain Medicine (Malden, Mass.), 23 (6), pp. 1176-1185. 

Watson, H.a , Hildebolt, C.b , Rowland, K.c

a Department of Applied Dental Medicine, Southern Illinois University School of Dental Medicine, Alton, IL, United Statesb Department of Radiology, Washington University School of Medicine, St. Louis, MO, United Statesc Department of Biomedical Sciences, University of Houston College of Medicine, Houston, TX, United States

AbstractOBJECTIVE: The purpose of our study was to perform a systematic review and meta-analysis of randomized, blinded, placebo-controlled studies that, following third-molar extraction, utilized either a combination of acetaminophen (600 mg) with codeine (60 mg) or ibuprofen (400 mg) for pain management. DESIGN: We searched PubMed, and the trial registry ClinicalTrials.gov databases with the keywords “molar or molars,” “tooth or teeth,” “extraction,” and “pain.” Selected studies were: (1) randomized, blinded, placebo controlled, (2) utilized either a single-dose combination acetaminophen (600 mg) with codeine (60 mg) (A/C) or ibuprofen, and (3) recorded standardized pain relief (PR) at 6 hours, or summed total pain relief over 6 hours (TOTPAR6). Of the 2,949 articles that were identified, 79 were retrieved for full-text analysis, and 20 of these studies met our inclusion criteria. RESULTS: For A/C, the weighted, standardized mean difference (SMD) for TOTPAR6 was 0.796 (95% confidence interval [CI], 0.597-0.995), P < .001, and for PR at 6 hours, the SMD was 0.0186 (0.007 to 0.378; P = .059), whereas for ibuprofen the SMD for TOTPAR6 was 3.009 (1.283 to 4.735; P = .001), and for PR at 6 hours, the SMD was 0.854 (95% CI, 0.712-0.996; P < .001). A SMD of 0.8 or larger is indicative of a large effect. CONCLUSIONS: Our data indicate that single dose of ibuprofen (400 mg) is an effective pain reducer for post third molar extraction pain. © The Author(s) 2021. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Author KeywordsAcetaminophen;  Codeine;  Ibuprofen;  Orofacial Pain;  Third Molar

Document Type: ArticlePublication Stage: FinalSource: Scopus

"Synthetic gene circuits for preventing disruption of the circadian clock due to interleukin-1-induced inflammation" (2022) Science Advances

Synthetic gene circuits for preventing disruption of the circadian clock due to interleukin-1-induced inflammation(2022) Science Advances, 8 (21), p. eabj8892. 

Pferdehirt, L.a b c d , Damato, A.R.e , Dudek, M.f , Meng, Q.-J.f , Herzog, E.D.e , Guilak, F.a b c d

a Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USAb Shriners Hospitals for Children-St. Louis, St. Louis, MO 63110, USAc Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, MO 63110, USAd Department of Biomedical Engineering, Washington University, St. Louis, MO 63105, USAe Department of Biology, Washington University, St. Louis, MO 63130, USAf Wellcome Centre for Cell Matrix Research, Division of Cell Matrix Biology and Regenerative Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Oxford RoadManchester M13 9PT, United Kingdom

AbstractThe circadian clock regulates tissue homeostasis through temporal control of tissue-specific clock-controlled genes. In articular cartilage, disruptions in the circadian clock are linked to a procatabolic state. In the presence of inflammation, the cartilage circadian clock is disrupted, which further contributes to the pathogenesis of diseases such as osteoarthritis. Using synthetic biology and tissue engineering, we developed and tested genetically engineered cartilage from murine induced pluripotent stem cells (miPSCs) capable of preserving the circadian clock in the presence of inflammation. We found that circadian rhythms arise following chondrogenic differentiation of miPSCs. Exposure of tissue-engineered cartilage to the inflammatory cytokine interleukin-1 (IL-1) disrupted circadian rhythms and degraded the cartilage matrix. All three inflammation-resistant approaches showed protection against IL-1-induced degradation and loss of circadian rhythms. These synthetic gene circuits reveal a unique approach to support daily rhythms in cartilage and provide a strategy for creating cell-based therapies to preserve the circadian clock.

Document Type: ArticlePublication Stage: FinalSource: Scopus

"Occupational Therapy Practice Guidelines for People With Parkinson's Disease" (2022) The American Journal of Occupational Therapy: Official Publication of the American Occupational Therapy Association

Occupational Therapy Practice Guidelines for People With Parkinson’s Disease(2022) The American Journal of Occupational Therapy: Official Publication of the American Occupational Therapy Association, 76 (3), . 

Wood, J.a , Henderson, W.b , Foster, E.R.c

a Julia Wood, MOT, OTR/L, is Director of Professional and Community Education, Lewy Body Dementia Association, Lilburn, GA;b MOT, OTR/L, University of Missouri, is Associate Clinical Professor in Occupational Therapy, Columbia, United Statesc Erin R. Foster, PhD, OTD, OTR/L, is Associate Professor in Occupational Therapy, Neurology and Psychiatry, Washington University School of Medicine, St. Louis, MO

AbstractIMPORTANCE: Occupational therapy practitioners address the occupational performance and participation needs of people with Parkinson’s disease (PD) and their care partners. OBJECTIVE: This Practice Guideline is informed by systematic reviews on the use of occupational therapy interventions to promote participation in occupations for people with PD and to facilitate their caregivers’ participation in the caregiver role. This guideline is meant to support practitioners’ clinical decision making when working with people with PD and their care partners. METHOD: We examined and synthesized the results of four systematic reviews and integrated those results into clinical recommendations for practice. RESULTS: Thirty-three articles from the systematic reviews served as the basis for the clinical recommendations in this Practice Guideline. Clinical recommendations are provided for interventions that have strong or moderate supporting evidence. CONCLUSION AND RECOMMENDATIONS: Multidisciplinary, tailored, goal-oriented intervention is recommended for people with PD. Various forms of exercise can be used to improve activities of daily living and instrumental activities of daily living performance and social participation, and interventions should incorporate health behavior change techniques to support adequate physical activity levels in daily life. Mindfulness meditation and exercise can be used to support sleep, and task-oriented training can be used to improve performance of specific tasks. Occupational therapy practitioners should incorporate self-management, coaching, compensatory, cognitive-behavioral, and other approaches into multicomponent treatment plans depending on the client’s needs and goals. Additional potentially appropriate intervention approaches or areas to address are discussed on the basis of existing or emerging evidence and expert opinion. What This Article Adds: This Practice Guideline provides a summary and applications of the current evidence supporting occupational therapy intervention for people with PD. It includes case examples and suggested decision-making algorithms to support practitioners in addressing client goals. Copyright © 2022 by the American Occupational Therapy Association, Inc.

Document Type: ArticlePublication Stage: FinalSource: Scopus

"Development of a Comprehensive Battery to Collect Social and Structural Determinants of Health (SSDOH) in Cognitively Normal or Very Mildly Impaired Persons" (2022) Alzheimer Disease and Associated Disorders

Development of a Comprehensive Battery to Collect Social and Structural Determinants of Health (SSDOH) in Cognitively Normal or Very Mildly Impaired Persons(2022) Alzheimer Disease and Associated Disorders, 36 (2), pp. 97-102. 

Streitz, M.L.a , Denny, A.a , Xiong, C.b , McCue, L.b , Stites, S.D.c , Midgett, S.d , Mechanic-Hamilton, D.e , Moulder, K.L.a , Morris, J.C.a , Balls-Berry, J.a

a Department of Neurology, Knight Alzheimer Disease Research Center, Washington University School of Medicine, 4488 Forest Park Avenue, St. Louis, MO 63108, United Statesb Department of Biostatistics, Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, MI, United Statesc Departments of Psychiatry, Perelman School of Medicine, University of Pennsylvania Alzheimer Disease Research Center, Philadelphia, PA, United Statesd Department of Medicine, Perelman School of Medicine, University of Pennsylvania Alzheimer Disease Research Center, Philadelphia, PA, United Statese Department of Neurology, Perelman School of Medicine, University of Pennsylvania Alzheimer Disease Research Center, Philadelphia, PA, United States

AbstractIntroduction: Research addressing Alzheimer disease and related dementias must examine nonbiological factors influencing the risk for and expression of Alzheimer disease and related dementias. These factors address the interplay of cognition with lived experiences and social and structural determinants of health (SSDOH). However, coordinated measures of SSDOH are limited. Methods: The Knight Alzheimer Disease Research Center (ADRC) at Washington University in St. Louis developed and piloted a comprehensive battery to measure SSDOH. One hundred and twelve participants, very mildly cognitively impaired or unimpaired, enrolled in memory studies completed the electronic SSDOH battery. The Clinical Dementia Rating (CDR) determined the presence or absence of cognitive impairment. Results: Four domains demonstrated above acceptable intraclass correlation scores for test-retest reliability (≥0.70), including adverse childhood events, discrimination, social status, and early education. Twenty very mildly impaired participants completed the electronic pilot study. Conclusion: Our findings indicate that participants with early-stage symptomatic Alzheimer disease are able to participate in electronic SSDOH data collection. In collaboration with the University of Pennsylvania ADRC, we replaced/modified certain assessments to increase intraclass correlation. The resulting battery, Social and Structural Life-courses Influencing Aging and Dementia (SS-DIAD), can serve as a SSDOH collection tool and is currently utilized in cognitively impaired and unimpaired research participants at both ADRCs. © 2022 Lippincott Williams and Wilkins. All rights reserved.

Author KeywordsAlzheimer disease;  cognition;  older adults;  social and structural determinants of health

Funding detailsNational Institutes of HealthNIHK23 AG065499National Institute on AgingNIAP01 AG026276, P01 AG03991, P30 AG010124, P30 AG066444, R01 AG053550, R01 AG067505Alzheimer’s AssociationAAAACSF-19-617940, AARF-17-528934, K23 AG065442

Document Type: ArticlePublication Stage: FinalSource: Scopus

"Bilateral Painful Hand Seizures: An Atypical Somatotopic Syndrome" (2022) Neurohospitalist

Bilateral Painful Hand Seizures: An Atypical Somatotopic Syndrome(2022) Neurohospitalist, . 

Koleske, J.a , Amar, J.Y.b , Chou, C.A.c , Varadhachary, A.S.b

a Washington University School of Medicine, St. Louis, MO, United Statesb Department of Neurology, Washington University School of Medicine, St. Louis, MO, United Statesc Department of Neurology, Oregon Health and Science University, Portland, OR, United States

AbstractPainful Hand Seizures are a rarely reported form of secondary sensory seizures (SSS) characterized by painful, bilateral sensorimotor hand involvement and preserved consciousness. We report our case to aid neurologists in recognizing SSS as an atypical presentation of seizures. © The Author(s) 2022.

Author Keywordspainful hand seizures;  secondary sensory seizures;  SII;  somatosensory cortex

Document Type: ArticlePublication Stage: Article in PressSource: Scopus

"Alcohol Use Disorder, Psychiatric Comorbidities, Marriage and Divorce in a High-Risk Sample" (2022) Psychology of Addictive Behaviors

Alcohol Use Disorder, Psychiatric Comorbidities, Marriage and Divorce in a High-Risk Sample(2022) Psychology of Addictive Behaviors, . 

Thomas, N.S.a , Kuo, S.I.-C.b , Aliev, F.b , McCutcheon, V.V.c , Meyers, J.M.d , Chan, G.e , Hesselbrock, V.e , Kamarajan, C.d , Kinreich, S.d , Kramer, J.R.f , Kuperman, S.f , Lai, D.g , Plawecki, M.H.h , Porjesz, B.d , Schuckit, M.A.g i , Dick, D.M.b , Bucholz, K.K.a c , Salvatore, J.E.a b

a Department of Psychology, Virginia Commonwealth University, United Statesb Department of Psychiatry, Robert Wood Johnson Medical School, Rutgers University, United Statesc Department of Psychiatry, Washington University School of Medicine, United Statesd Department of Psychiatry and Behavioral Sciences, State University of New York Downstate Medical Center, United Statese Department of Psychiatry, University of Connecticut School of Medicine, United Statesf Department of Psychiatry, University of Iowa, United Statesg Department of Medical and Molecular Genetics, Indiana University, United Statesh Department of Psychiatry, Indiana University, United Statesi Department of Psychiatry, University of California San Diego Medical School, United States

AbstractObjective: To examine associations between alcohol use disorder (AUD), its psychiatric comorbidities, and their interactions, with marital outcomes in a diverse high-risk, genetically informative sample. Method: Participants included European ancestry (EA; n = 4,045) and African ancestry (AA; n = 1,550) individuals from the multigenerational Collaborative Study on the Genetics of Alcoholism (COGA) sample (56% female, Mage ~ 41 years). Outcomes were lifetime marriage and divorce. Predictors included lifetime AUD, an alcohol problems polygenic score (PRS), and AUD comorbidities, including conduct or antisocial personality disorder (ASP), cannabis dependence/abuse (CAN), frequent tobacco use (TOB), and major depressive disorder (MDD). Mixed effect Cox models and generalized linear mixed effects models were fit. Results: Among EA participants, those with AUD and CAN were less likely to marry (hazard ratios [HRs] 0.70–0.83, ps &lt; 0.01). Among AA participants, those with AUD and TOB were less likely to marry (HRs 0.66–0.82, ps &lt; 0.05) and those with MDD were more likely to marry (HR = 1.34, ps &lt; 0.01). Among EA participants, AUD, CAN, TOB, and MDD were associated with higher odds of divorce (odds ratios [ORs] 1.59–2.21, ps &lt; 0.01). Among AA participants, no predictors were significantly associated with divorce. Significant random effects indicated genetic and environmental influences on marriage, but only environmental factors on divorce. Conclusions: In a high-risk sample, AUD was associated with reduced likelihood of marriage in EA and AA individuals and increased risk of divorce in EA individuals. These associations were largely independent of comorbidities. Genetic and environmental background factors contributed to marriage, while only environmental background factors contributed to divorce. © 2022. American Psychological Association

Author KeywordsAlcohol use disorder;  Collaborative study on the genetics of alcoholism (coga);  Divorce;  Marriage;  Psychiatric comorbidities

Funding detailsNational Institute on Alcohol Abuse and AlcoholismNIAAAK01AA024152, R01AA028064, U10AA008401

Document Type: ArticlePublication Stage: Article in PressSource: Scopus

"Dystonia in individuals with spastic cerebral palsy and isolated periventricular leukomalacia" (2022) Developmental Medicine and Child Neurology

Dystonia in individuals with spastic cerebral palsy and isolated periventricular leukomalacia(2022) Developmental Medicine and Child Neurology, . 

Ueda, K., Aravamuthan, B.R., Pearson, T.S.

Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States

AbstractAIM: To determine the prevalence of dystonia in individuals with periventricular leukomalacia (PVL) and spastic cerebral palsy (CP), but without basal ganglia and thalamic injury (BGTI) on brain magnetic resonance imaging (MRI). METHOD: This was a retrospective study of individuals with spastic CP and PVL on MRI evaluated between 2005 and 2018 in a CP center. Individuals with non-PVL brain lesions on MRI, including BGTI, were excluded. Dystonia was assessed via blinded review of neurological exam videos by pediatric movement disorders specialists. RESULTS: Eighty-five participants (45 males, 40 females; mean age at videotaping 12 years [standard deviation 5 years 6 months], range 4–26 years) met inclusion and exclusion criteria. Of these participants, 50 (59%) displayed dystonia in their exam videos. The most common locations of dystonia were the fingers and hip adductors. The prevalence of dystonia was unaffected by the gestational age or severity of PVL, and was affected by Gross Motor Function Classification System level. INTERPRETATION: Dystonia is common in individuals with spastic CP and PVL, even without BGTI on MRI. Our findings suggest vigilance for dystonia in individuals with spastic CP should remain high, even without MRI evidence of BGTI. © 2022 Mac Keith Press.

Funding detailsNational Institute of Neurological Disorders and StrokeNINDS

Document Type: ArticlePublication Stage: Article in PressSource: Scopus

"Apolipoprotein E (APOE) genotype, dementia, and memory performance among Caribbean Hispanic versus US populations" (2022) Alzheimer's and Dementia

Apolipoprotein E (APOE) genotype, dementia, and memory performance among Caribbean Hispanic versus US populations(2022) Alzheimer’s and Dementia, . 

Llibre-Guerra, J.J.a , Li, J.b , Qian, Y.b , Llibre-Rodriguez, J.D.J.c , Jiménez-Velázquez, I.Z.d , Acosta, D.e , Salas, A.f , Llibre-Guerra, J.C.g , Valvuerdi, A.g , Harrati, A.h , Weiss, J.i , Liu, M.-M.j , Dow, W.H.i j

a Department of Neurology, Washington University in St. Louis, St. Louis, MO, United Statesb Department of Population Health Sciences, Weill Cornell Medical College, Cornell University, New York, NY, United Statesc Medical University of Havana, Havana, Cubad Department of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan, Puerto Ricoe Universidad Nacional Pedro Henriquez Ureña (UNPHU), Santo Domingo, Dominican Republicf Medicine Department, Caracas University Hospital, Faculty of Medicine, Universidad Central de Venezuela, Caracas, Venezuelag National Institute of Neurology and Neurosurgery, La Habana, Cubah Department of Medicine, Stanford University, Stanford, CA, United Statesi Department of Demography, University of California at Berkeley, Berkeley, CA, United Statesj School of Public Health, University of California at Berkeley, Berkeley, CA, United States

AbstractIntroduction: Apolipoprotein E (APOE) is considered the major susceptibility gene for developing Alzheimer’s disease. However, the strength of this risk factor is not well established across diverse Hispanic populations. Methods: We investigated the associations among APOE genotype, dementia prevalence, and memory performance (immediate and delayed recall scores) in Caribbean Hispanics (CH), African Americans (AA), Hispanic Americans (HA) and non-Hispanic White Americans (NHW). Multivariable logistic regressions and negative binomial regressions were used to examine these associations by subsample. Results: Our final dataset included 13,516 participants (5198 men, 8318 women) across all subsamples, with a mean age of 74.8 years. Prevalence of APOE ε4 allele was similar in CHs, HAs, and NHWs (21.8%–25.4%), but was substantially higher in AAs (33.6%; P < 0.001). APOE ε4 carriers had higher dementia prevalence across all groups. Discussion: APOE ε4 was similarly associated with increased relative risk of dementia and lower memory performance in all subsamples. © 2022 the Alzheimer’s Association.

Author Keywordsadmixture;  Alzheimer’s disease;  apolipoprotein E;  Blacks;  cognitive performance;  dementia;  Hispanics/Latinos;  Non-Hispanic Whites

Funding detailsGR066133, GR080002National Institutes of HealthNIHR01AG064778National Institute on AgingNIAK01AG066946Alzheimer’s AssociationAAAARFD21851415, SG20690363

Document Type: ArticlePublication Stage: Article in PressSource: Scopus

"Combinatorial panel with endophenotypes from multilevel information of diffusion tensor imaging and lipid profile as predictors for depression" (2022) Australian and New Zealand Journal of Psychiatry

Combinatorial panel with endophenotypes from multilevel information of diffusion tensor imaging and lipid profile as predictors for depression(2022) Australian and New Zealand Journal of Psychiatry, . 

Liu, J.a b c , Liu, Z.d , Wei, Y.b c , Zhang, Y.e , Womer, F.Y.f , Jia, D.b c , Wei, S.a , Wu, F.a , Kong, L.a , Jiang, X.a , Zhang, L.b c , Tang, Y.a , Zhang, X.b c g h , Wang, F.a b c g

a Department of Psychiatry, The First Affiliated Hospital of China Medical University, Liaoning, Shenyang, Chinab Early Intervention Unit, Department of Psychiatry, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Jiangsu, Nanjing, Chinac Functional Brain Imaging Institute, Nanjing Medical University, Jiangsu, Nanjing, Chinad School of Public health, China Medical University, Liaoning, Shenyang, Chinae Department of Psychiatry, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Canadaf Department of Psychiatry, Washington University School of Medicine, St. Louis, United Statesg Nanjing Brain Hospital, Medical School, Nanjing University, Jiangsu, Nanjing, Chinah School of Biomedical Engineering and Informatics, Nanjing Medical University, Jiangsu, Nanjing, China

AbstractObjective: Clinical heterogeneity in major depressive disorder likely reflects the range of etiology and contributing factors in the disorder, such as genetic risk. Identification of more refined subgroups based on biomarkers such as white matter integrity and lipid-related metabolites could facilitate precision medicine in major depressive disorder. Methods: A total of 148 participants (15 genetic high-risk participants, 57 patients with first-episode major depressive disorder and 76 healthy controls) underwent diffusion tensor imaging and plasma lipid profiling. Alterations in white matter integrity and lipid metabolites were identified in genetic high-risk participants and patients with first-episode major depressive disorder. Then, shared alterations between genetic high-risk and first-episode major depressive disorder were used to develop an imaging x metabolite diagnostic panel for genetically based major depressive disorder via factor analysis and logistic regression. A fivefold cross-validation test was performed to evaluate the diagnostic panel. Results: Alterations of white matter integrity in corona radiata, superior longitudinal fasciculus and the body of corpus callosum and dysregulated unsaturated fatty acid metabolism were identified in both genetic high-risk participants and patients with first-episode major depressive disorder. An imaging x metabolite diagnostic panel, consisting of measures for white matter integrity and unsaturated fatty acid metabolism, was identified that achieved an area under the receiver operating characteristic curve of 0.86 and had a significantly higher diagnostic performance than that using either measure alone. And cross-validation confirmed the adequate reliability and accuracy of the diagnostic panel. Conclusion: Combining white matter integrity in corpus callosum, superior longitudinal fasciculus and corona radiata, and unsaturated fatty acid profile may improve the identification of genetically based endophenotypes in major depressive disorder to advance precision medicine strategies. © The Royal Australian and New Zealand College of Psychiatrists 2022.

Author Keywordsbiomarker panel;  endophenotype;  Major depressive disorder;  unsaturated fatty acids;  white matter integrity

Funding detailsLT20170073110117059, 3110118055U20A60052015225018National Natural Science Foundation of ChinaNSFCU1808204Natural Science Foundation of Liaoning Province2019-MS-05National Key Research and Development Program of ChinaNKRDPC2016YFC1306900, 2018YFC1311600National Science Fund for Distinguished Young Scholars81725005Liaoning Revitalization Talents ProgramXLYC1808036

Document Type: ArticlePublication Stage: Article in PressSource: Scopus

"The Cutaneous Branches of the Median and Ulnar Nerves in the Palm" (2022) Journal of Hand Surgery

The Cutaneous Branches of the Median and Ulnar Nerves in the Palm(2022) Journal of Hand Surgery, . 

Bertelli, J.A.a , Seltser, A.b , Gasparelo, K.R.a , Hill, E.J.R.c d

a Department of Orthopedic Surgery, Governador Celso Ramos Hospital, Santa Catarina, Florianópolis, Brazilb Department of Hand Surgery, Sheba Medical Center, Affiliated with Sackler School of Medicine, Tel Aviv University, Ramat Gan, Israelc Department of Medicine and Surgery, Harris Manchester College, Oxford University, England, Oxford, United Kingdomd Division of Hand and Microsurgery, Department of Orthopedic Surgery, Washington University in St. LouisMissouri

AbstractPurpose: The dermatomal distributions of the ulnar and median nerves on the palmar skin of the hand have been studied thoroughly. However, the anatomic course of the median and ulnar cutaneous nerve branches and how they supply the skin of the palm is not well understood. Methods: The cutaneous branches of the median and ulnar nerves were dissected bilaterally in 9 fresh cadavers injected arterially with green latex. Results: We observed 3 groups of cutaneous nerve branches in the palm of the hand: a proximal row group consisting of long branches that originated proximal to the superficial palmar arch and reached the distal palm, first web space, or hypothenar region; a distal row group consisting of branches originating between the superficial palmar arch and the transverse fibers of the palmar aponeurosis (these nerves had a longitudinal trajectory and were shorter than the branches originating proximal to the palmar arch); and a metacarpophalangeal group, composed of short perpendicular branches originating on the palmar surface of the proper palmar digital nerves at the web space. The radial and ulnar borders of the hand distal to the palmar arch were innervated by short transverse branches arising from the proper digital nerves of the index and little finger. Nerve branches did not perforate the palmar aponeurosis in 16 of 18 cases. Conclusions: The palm of the hand was consistently innervated by 20–35 mm long cutaneous branches originating proximal to the palmar arch and shorter branches originating distal to the palmar arch. These distal branches were either perpendicular or parallel to the proper palmar digital nerves. Clinical relevance: Transfer of long proximal row branches may present an opportunity to restore sensibility in nerve injuries. © 2022 American Society for Surgery of the Hand

Author KeywordsBrachial plexus;  median nerve;  nerve transfer;  spinal cord injury;  ulnar nerve

Document Type: ArticlePublication Stage: Article in PressSource: Scopus

"Human inference reflects a normative balance of complexity and accuracy" (2022) Nature Human Behaviour

Human inference reflects a normative balance of complexity and accuracy(2022) Nature Human Behaviour, . 

Tavoni, G.a , Doi, T.b , Pizzica, C.c , Balasubramanian, V.c d , Gold, J.I.c

a Department of Neuroscience, Washington University in St. Louis, St. Louis, MO, United Statesb Department of Psychology, University of Pennsylvania, Philadelphia, PA, United Statesc Department of Neuroscience, University of Pennsylvania, Philadelphia, PA, United Statesd Department of Physics & Astronomy, University of Pennsylvania, Philadelphia, PA, United States

AbstractWe must often infer latent properties of the world from noisy and changing observations. Complex, probabilistic approaches to this challenge such as Bayesian inference are accurate but cognitively demanding, relying on extensive working memory and adaptive processing. Simple heuristics are easy to implement but may be less accurate. What is the appropriate balance between complexity and accuracy? Here we model a hierarchy of strategies of variable complexity and find a power law of diminishing returns: increasing complexity gives progressively smaller gains in accuracy. The rate of diminishing returns depends systematically on the statistical uncertainty in the world, such that complex strategies do not provide substantial benefits over simple ones when uncertainty is either too high or too low. In between, there is a complexity dividend. In two psychophysical experiments, we confirm specific model predictions about how working memory and adaptivity should be modulated by uncertainty. © 2022, The Author(s), under exclusive licence to Springer Nature Limited.

Funding details1533623575556National Institutes of HealthNIHR01 MH115557, R01EB026945University of PennsylvaniaWashington University in St. LouisWUSTL

Document Type: ArticlePublication Stage: Article in PressSource: Scopus