Digital Commons Network^™

Developments In Intervertebral Disc Disease Research: Pathophysiology, Mechanobiology, And Therapeutics, K. T. Weber, T. D. Jacobsen, R. Maidhof, J. Virojanapa, C. Overby, O. Bloom, S. Quraishi, M. Levine, N. O. Chahine

Journal Articles

Low back pain is a leading cause of disability worldwide and the second most common cause of physician visits. There are many causes of back pain, and among them, disc herniation and intervertebral disc degeneration are the most common diagnoses and targets for intervention. Currently, clinical treatment outcomes are not strongly correlated with diagnoses, emphasizing the importance for characterizing more completely the mechanisms of degeneration and their relationships with symptoms. This review covers recent studies elucidating cellular and molecular changes associated with disc mechanobiology, as it relates to degeneration and regeneration. Specifically, we review findings on the biochemical changes in …

Dynamic Reciprocity Between Cells And Their Microenvironment In Reproduction, J. T. Thorne, T. R. Segal, S. Chang, S. Jorge, J. H. Segars, P. C. Leppert

Journal Articles

Dynamic reciprocity (DR) refers to the ongoing, bidirectional interaction between cells and their microenvironment, specifically the extracellular matrix (ECM). The continuous remodeling of the ECM exerts mechanical force on cells and modifies biochemical mediators near the cell membrane, thereby initiating cell-signaling cascades that produce changes in gene expression and cell behavior. Cellular changes, in turn, affect the composition and organization of ECM components. These continuous interactions are the fundamental principle behind DR, and its critical role throughout development and adult tissue homeostasis has been extensively investigated. While DR in the mammary gland has been well described, we provide direct evidence …

Selective Impairment Of Spatial Cognition Caused By Autoantibodies To The N-Methyl-D-Aspartate Receptor, E. H. Chang, B. T. Volpe, M. Mackay, C. Aranow, C. Kowal, P. Mattis, R. Berlin, S. Mader, T. S. Huerta, P. T. Huerta, B. Diamond, +3 Additional Authors

Journal Articles

Patients with systemic lupus erythematosus (SLE) experience cognitive abnormalities in multiple domains including processing speed, executive function, and memory. Here we show that SLE patients carrying antibodies that bind DNA and the GluN2A and GluN2B subunits of the N-methyl-d-aspartate receptor (NMDAR), termed DNRAbs, displayed a selective impairment in spatial recall. Neural recordings in a mouse model of SLE, in which circulating DNRAbs penetrate the hippocampus, revealed that CA1 place cells exhibited a significant expansion in place field size. Structural analysis showed that hippocampal pyramidal cells had substantial reductions in their dendritic processes and spines. Strikingly, these abnormalities became evident at …

American Bar Association Commission On Youth At Risk, Commission On Homelessness And Poverty, Health Law Section Report To The House Of Delegates: Overuse Of Psychotropic Medication Among Children And Youth In State Custody, Allison Flood

Hofstra Law Student Works

Children in foster care and youth involved in the juvenile justice system are prescribed psychotropic medications at alarmingly high rates. Foster children are given psychotropic medications at a rate nine times higher than children not in foster care. And over fifty percent of the youth involved in the juvenile justice system are prescribed psychotropic medications within one month of intake.

While psychotropic medications can be a useful part of a child’s treatment plan, over-medication causes these children and youth to “act like zombies”, contemplate harming themselves, or worse, commit suicide. Additionally, the side effects of over-medication are endless. They can …

Lifetime Prevalence, Age Of Risk, And Genetic Relationships Of Comorbid Psychiatric Disorders In Tourette Syndrome, M. E. Hirschtritt, P. C. Lee, D. L. Pauls, Y. Dion, M. A. Grados, R. A. King, P. Sandor, W. M. Mcmahon, G. J. Lyon, C. A. Mathews, +4 Additional Authors

Journal Articles

IMPORTANCE: Tourette syndrome (TS) is characterized by high rates of psychiatric comorbidity; however, few studies have fully characterized these comorbidities. Furthermore, most studies have included relatively few participants (

Prenatal Exposure To Maternal Smoking And Symptom Severity Among Offspring With First-Episode Nonaffective Psychosis, F. Bernardini, C. R. Wan, A. Crisafio, S. H. Massey, M. T. Compton

Journal Articles

No abstract provided.

Evaluating The Relationship Between Cannabis Use And Iq In Youth And Young Adults At Clinical High Risk Of Psychosis, L. Buchy, L. J. Seidman, K. S. Cadenhead, T. D. Cannon, B. A. Cornblatt, E. F. Walker, S. W. Woods, C. E. Bearden, D. H. Mathalon, J. Addington, +4 Additional Authors

Journal Articles

Among people with psychosis, those with a history of cannabis use show better cognitive performance than those who are cannabis naive. It is unknown whether this pattern is present in youth at clinical high risk (CHR) of psychosis. We evaluated relationships between IQ and cannabis use while controlling for use of other substances known to impact cognition in 678 CHR and 263 healthy control (HC) participants. IQ was estimated using the Vocabulary and Block Design subtests of the Wechsler Abbreviated Scale of Intelligence. Drug and alcohol use severity and frequency were assessed with the Alcohol and Drug Use Scale, and …

Contributions Of Early Cortical Processing And Reading Ability To Functional Status In Individuals At Clinical High Risk For Psychosis, R. Carrion, B. A. Cornblatt, D. Mclaughlin, J. Chang, A. M. Auther, R. H. Olsen, D. C. Javitt

Journal Articles

Background: There is a growing recognition that individuals at clinical high risk need intervention for functional impairments, along with emerging psychosis, as the majority of clinical high risk (CHR) individuals show persistent deficits in social and role functioning regardless of transition to psychosis. Recent studies have demonstrated reduced reading ability as a potential cause of functional disability in schizophrenia, related to underlying deficits in generation of mismatch negativity (MMN). The present study extends these findings to subjects at CHR. Methods: The sample consisted of 34 CHR individuals and 33 healthy comparison subjects (CNTLs) from the Recognition and Prevention (RAP) Program …

The Impact Of Psychosis On The Course Of Cognition: A Prospective, Nested Case-Control Study In Individuals At Clinical High-Risk For Psychosis, R. Carrion, D. Mclaughlin, A. M. Auther, R. Olsen, Christoph Correll, B. A. Cornblatt

Journal Articles

BACKGROUND: Although cognitive deficits in patients with schizophrenia are rooted early in development, the impact of psychosis on the course of cognitive functioning remains unclear. In this study a nested case-control design was used to examine the relationship between emerging psychosis and the course of cognition in individuals ascertained as clinical high-risk (CHR) who developed psychosis during the study (CHR + T). METHOD: Fifteen CHR + T subjects were administered a neurocognitive battery at baseline and post-psychosis onset (8.04 months, s.d. = 10.26). CHR + T subjects were matched on a case-by-case basis on age, gender, and time to retest …

Postnatal Neurodevelopmental Expression And Glutamate-Dependent Regulation Of The Znf804a Rodent Homologue, E. H. Chang, A. Kirtley, T. S. Chandon, P. Borger, S. Husain-Krautter, V. Vingtdeux, A. Malhotra

Journal Articles

The zinc finger protein ZNF804A rs1344706 variant is a replicated genome-wide significant risk variant for schizophrenia and bipolar disorder. While its association with altered brain structure and cognition in patients and healthy risk allele carriers is well documented, the characteristics and function of the gene in the brain remains poorly understood. Here, we used in situ hybridization to determine mRNA expression levels of the ZNF804A rodent homologue, Zfp804a, across multiple postnatal neurodevelopmental time points in the rat brain. We found changes in Zfp804a expression in the rat hippocampus, frontal cortex, and thalamus across postnatal neurodevelopment. Zfp804a mRNA peaked at postnatal …

Responses To Tobacco Smoking-Related Health Messages In Young People With Recent-Onset Schizophrenia, D. J. Coletti, M. Brunette, M. John, J. M. Kane, A. Malhotra, D. G. Robinson

Journal Articles

Virtually no research has examined the responses of youth with recent-onset psychosis (ROP) to smoking-related health warnings. We examined predictors of response and tested hypotheses that participants with ROP would (a) assess warnings as less effective than a healthy comparison (HC) group, and (b) assess video warnings as more effective than pictures. ROP participants (n = 69) hadtreatment; the HC group (n = 79) had no major mental illness. Participants viewed 10 pictorial warnings, 8 videos depicting similar messages, and were interviewed regarding tobacco use, health literacy, and smoking knowledge. We assessed response at baseline and at 4-week follow-up. ROP …

Psychosis Prevention: A Modified Clinical High Risk Perspective From The Recognition And Prevention (Rap) Program, B. A. Cornblatt, R. Carrion, A. Auther, D. Mclaughlin, R. H. Olsen, M. John, C. U. Correll

Journal Articles

OBJECTIVE: Early intervention and prevention of psychosis remain a major challenge. Prediction would be greatly advanced with improved ability to identify individuals at true risk, which, at present, is moderate at best. The authors tested a modified strategy to improve prediction by selecting a more homogeneous high-risk sample (attenuated positive symptom criteria only, age range of mid-teens to early 20s) than is currently standard, combined with a systematic selection of neurodevelopmental deficits. METHOD: A sample of 101 treatment-seeking adolescents (mean age, 15.9 years) at clinical high risk for psychosis were followed clinically for up to 5 years (mean follow-up time, …

Examining The Psychosis Continuum, P. Derosse, K. H. Karlsgodt

Journal Articles

The notion that psychosis may exist on a continuum with normal experience has been proposed in multiple forms throughout the history of psychiatry. However, in recent years there has been an exponential increase in efforts aimed at elucidating what has been termed the 'psychosis continuum'. The present review seeks to summarize some of the more basic characteristics of this continuum and to present some of the recent findings that provide support for its validity. While there is still considerable work to be done, the emerging data holds considerable promise for advancing our understanding of both risk and resilience to psychiatric …

White Matter Microstructure In The Executive Network Associated With Aggression In Healthy Adolescents And Young Adults, K. H. Karlsgodt, A. A. Bato, M. A. Blair, P. Derosse, P. Szeszko, A. K. Malhotra

Journal Articles

Predicting which individuals may engage in aggressive behavior is of interest in today's society; however, there is little data on the neural basis of aggression in healthy individuals. Here, we tested whether regional differences in white matter (WM) microstructure were associated with later reports of aggressive tendencies. We recontacted healthy young adults an average of 3 years after they underwent research MRI scans. Via electronic survey, we administered the Buss Perry Aggression Questionnaire. We divided aggression into Aggressive Thoughts (Anger and Hostility subscales) and Aggressive Acts (Verbal and Physical subscales) and used Tract-Based Spatial Statistics to test the relationship of …

The Accumbofrontal Tract: Diffusion Tensor Imaging Characterization And Developmental Change From Childhood To Adulthood, K. H. Karlsgodt, M. John, T. Ikuta, P. Rigoard, B. D. Peters, P. Derosse, A. K. Malhotra, P. R. Szeszko

Journal Articles

The presence of an anatomical connection between the orbitofrontal cortex and ventral striatum, forming a so-called reward network, is well established across species. This connection has important implications for reward processing and is relevant to a number of neuropsychiatric disorders. Moreover, white matter (WM) is known to continue to mature across adolescence and into early adulthood, and developmental change in the reward network is an important component of models of decision making and risk taking. Despite the importance of this connection, the underlying WM has only recently been characterized in humans histologically, and not yet in-vivo using brain imaging. Here, …

Prescription Practices In The Treatment Of First-Episode Schizophrenia Spectrum Disorders: Data From The National Raise-Etp Study, D. G. Robinson, N. R. Schooler, M. John, C. U. Correll, P. Marcy, J. Severe, A. Goldstein, S. Azrin, R. Heinssen, J. M. Kane, +7 Additional Authors

Journal Articles

Objective: Treatment guidelines suggest distinctive medication strategies for first-episode and multiepisode patients with schizophrenia. To assess the extent to which community clinicians adjust their usual treatment regimens for first-episode patients, the authors examined prescription patterns and factors associated with prescription choice in a national cohort of early-phase patients. Method: Prescription data at study entry were obtained from 404 participants in the Recovery After an Initial Schizophrenia Episode Project's Early Treatment Program (RAISE-ETP), a nationwide multisite effectiveness study for patients with first-episode schizophrenia spectrum disorders. Treatment with antipsychotics did not exceed 6 months at study entry. Results: The authors identified 159 …

Independent Evidence For An Association Between General Cognitive Ability And A Genetic Locus For Educational Attainment, J. W. Trampush, T. Lencz, S. Guha, S. Mukherjee, P. Derosse, M. John, O. A. Andreassen, I. J. Deary, D. C. Glahn, A. K. Malhotra, +41 Additional Authors

Journal Articles

Cognitive deficits and reduced educational achievement are common in psychiatric illness; understanding the genetic basis of cognitive and educational deficits may be informative about the etiology of psychiatric disorders. A recent, large genome-wide association study (GWAS) reported a genome-wide significant locus for years of education, which subsequently demonstrated association to general cognitive ability (g) in overlapping cohorts. The current study was designed to test whether GWAS hits for educational attainment are involved in general cognitive ability in an independent, large-scale collection of cohorts. Using cohorts in the Cognitive Genomics Consortium (COGENT; up to 20,495 healthy individuals), we examined the relationship …

Evidence From Structural And Diffusion Tensor Imaging For Frontotemporal Deficits In Psychometric Schizotypy, P. Derosse, G. C. Nitzburg, T. Ikuta, B. D. Peters, A. K. Malhotra, P. Szeszko

Journal Articles

BACKGROUND: Previous studies of nonclinical samples exhibiting schizotypal traits have provided support for the existence of a continuous distribution of psychotic symptoms in the general population. Few studies, however, have examined the neural correlates of psychometric schizotypy using structural and diffusion tensor imaging (DTI). METHODS: Healthy volunteers between the ages of 18 and 68 were recruited from the community and assessed using the Schizotypal Personality Questionnaire and received structural and DTI exams. Participants with high (N = 67) and low (N = 71) psychometric schizotypy were compared on gray and white matter volume, and cortical thickness in frontal and temporal …

White Matter Development In The Early Stages Of Psychosis, B. D. Peters, K. H. Karlsgodt

Journal Articles

Schizophrenia has been conceptualized as a disorder of both neurodevelopment and a disorder of connectivity. One important aspect of the neurodevelopmental hypothesis is that schizophrenia is no longer thought to have discrete illness time points, but rather a long trajectory of brain changes, spanning many years, across a series of stages of the disease including the prodrome, first episode, and chronic period. As the disease progresses, there is a complex relationship between age related changes and disease related changes. Therefore, neural changes, and specifically white matter based connectivity changes, in schizophrenia may be best conceptualized based on a lifespan trajectory. …

Cross-Disorder Genome-Wide Analyses Suggest A Complex Genetic Relationship Between Tourette's Syndrome And Ocd, D. Yu, C. A. Mathews, R. D. Bruun, C. Budman, N. J. Cox, D. L. Pauls, +113 Additional Authors

Journal Articles

OBJECTIVE: Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD. METHOD: The authors conducted a GWAS in 2,723 cases (1,310 with OCD, 834 with Tourette's syndrome, 579 with OCD plus Tourette's syndrome/chronic tics), 5,667 ancestry-matched controls, and 290 OCD parent-child trios. GWAS summary statistics were examined for enrichment of functional variants associated with gene expression levels in brain regions. Polygenic score analyses …

The Macrophage Inhibitor Cni-1493 Blocks Metastasis In A Mouse Model Of Ewing Sarcoma Through Inhibition Of Extravasation, A. J. Hesketh, C. Maloney, C. A. Behr, M. C. Edelman, R. D. Glick, Y. Al-Abed, M. Symons, S. Z. Soffer, B. M. Steinberg

Journal Articles

Metastatic Ewing Sarcoma carries a poor prognosis, and novel therapeutics to prevent and treat metastatic disease are greatly needed. Recent evidence demonstrates that tumor-associated macrophages in Ewing Sarcoma are associated with more advanced disease. While some macrophage phenotypes (M1) exhibit anti-tumor activity, distinct phenotypes (M2) may contribute to malignant progression and metastasis. In this study, we show that M2 macrophages promote Ewing Sarcoma invasion and extravasation, pointing to a potential target of anti-metastatic therapy. CNI-1493 is a selective inhibitor of macrophage function and has shown to be safe in clinical trials as an anti-inflammatory agent. In a xenograft mouse model …

Immune Dysregulation In Patients Persistently Infected With Human Papillomaviruses 6 And 11, A. V. Lucs, J. A. Devoti, L. Hatam, A. Afzal, A. L. Abramson, B. M. Steinberg, V. R. Bonagura

Journal Articles

Human Papillomaviruses (HPVs) 6 and 11 are part of a large family of small DNA viruses, some of which are commensal. Although much of the population can contain or clear infection with these viruses, there is a subset of individuals who develop persistent infection that can cause significant morbidity and on occasion mortality. Depending on the site of infection, patients chronically infected with these viruses develop either recurrent, and on occasion, severe genital warts or recurrent respiratory papillomas that can obstruct the upper airway. The HPV-induced diseases described are likely the result of a complex and localized immune suppressive milieu …

N-Acetylcysteine Attenuates Tumor Necrosis Factor Alpha Levels In Autoimmune Inner Ear Disease Patients, S. Pathak, C. Stern, A. Vambutas

Journal Articles

Autoimmune inner ear disease (AIED) is a poorly understood disease marked by bilateral, rapidly progressive hearing loss triggered by unknown stimuli, which is corticosteroid responsive in 60 % of patients. Although the mechanism of the disease is not precisely understood, a complex interaction of cytokines is believed to contribute toward the inflammatory disease process and hearing loss. Previously, we showed the role of TNF-alpha in steroid-sensitive and IL-1beta in steroid-resistant immune-mediated hearing loss. N-Acetylcysteine (NAC), a broad spectrum antioxidant, has been effective in other autoimmune disorders. Other studies have shown NAC to have a protective adjunct role in human idiopathic …

Poly(I:C) Induces Controlled Release Of Il-36gamma From Keratinocytes In The Absence Of Cell Death, A. A. Rana, A. V. Lucs, J. Devoti, L. Blanc, J. Papoin, R. Wu, C. J. Papayannakos, A. Abramson, V. R. Bonagura, B. M. Steinberg

Journal Articles

The epithelium is part of an integrated immune system where cytokines, toll-like receptors and their ligands, and extracellular vesicles play a crucial role in initiating an innate immune response. IL-36gamma is a pro-inflammatory member of the IL-1 family that is mainly expressed by epithelial cells, but regulation of its expression and release are only beginning to be understood. Previous studies reported that IL-36gamma is abundant in recurrent respiratory papillomatosis, a rare but devastating disease caused by human papillomaviruses (HPV) types 6 and 11, in which papillomas recurrently grow in and block the airway. Despite the overexpression of IL-36gamma, papilloma tissues …

Giant Cell Tumor Of The Larynx Treated By Surgery And Adjuvant Denosumab: Case Report And Review Of The Literature, A. E. Yancoskie, D. K. Frank, J. E. Fantasia, S. Savona, N. Eiseler, I. Reder, L. B. Kahn

Journal Articles

Giant cell tumor of the larynx (GCTL) is a rare entity; only 34 cases have been reported in the literature. We report a case of GCTL in a 46 year-old male presenting clinical, radiographic, histological and therapeutic features. Previously reported cases are also reviewed.

Beta-Human Chorionic Gonadotropin Producing Osteosarcoma Of The Sacrum In A 26-Year-Old Woman: A Case Report And Review Of The Literature, R. Glass, J. R. Asirvatham, L. Kahn, M. Aziz

Journal Articles

Ectopic secretion of beta-human chorionic gonadotropin is considered a poor prognostic marker in epithelial tumors. However, very few cases have been reported in sarcomas. We present the case of a 26-year-old female who presented with a metastatic osteosarcoma. She underwent usual testing prior to starting treatment and was found to have elevated levels of beta-human chorionic gonadotropin. As the patient was not pregnant, another source of beta-human chorionic gonadotropin secretion had to be considered. The tumor cells demonstrated positive staining for beta-human chorionic gonadotropin by immunohistochemistry, and serum levels of beta-human chorionic gonadotropin were used to monitor tumor progression and …

Tbl1xr1 In Physiological And Pathological States, J. Y. Li, G. Daniels, J. Wang, X. Zhang

Journal Articles

Transducin (beta)-like 1X related protein 1 (TBL1XR1/TBLR1) is an integral subunit of the NCoR (nuclear receptor corepressor) and SMRT (silencing mediator of retinoic acid and thyroid hormone receptors) repressor complexes. It is an evolutionally conserved protein that shares high similarity across all species. TBL1XR1 is essential for transcriptional repression mediated by unliganded nuclear receptors (NRs) and othe regulated transcription factors (TFs). However, it can also act as a transcription activator through the recruitment of the ubiquitin-conjugating/19S proteasome complex that mediates the exchange of corepressors for coactivators. TBL1XR1 is required for the activation of multiple intracellular signaling pathways. TBL1XR1 germline mutations …

High Mobility Group Box Protein 1 (Hmgb1): The Prototypical Endogenous Danger Molecule, Huan Yang, H. Wang, Sangeeta S. Chavan, Ulf Andersson

Journal Articles

No abstract provided.

Milk Fat Globule Epidermal Growth Factor-Factor 8-Derived Peptide Attenuates Organ Injury And Improves Survival In Sepsis, W. L. Yang, A. Sharma, F. Zhang, S. Matsuo, Z. Wang, H. Wang, P. Wang

Journal Articles

INTRODUCTION: Sepsis involves overwhelming inflammatory responses with subsequent immune-suppression that can lead to multiple organ dysfunction and ultimately death. Milk fat globule epidermal growth factor-factor 8 (MFG-E8) is a secretory protein found to have multiple biological activities against autoimmune and inflammatory diseases. MFG-E8 contains an Arg-Gly-Asp (RGD) motif involved in cell-cell and cell-matrix interactions. In sepsis, excessive neutrophils migration through endothelial cells and matrix to sites of inflammation results in organ damage. We hypothesized that MFG-E8-derived short peptides (MSP) flanking its RGD motif could provide protection against organ injury in sepsis. METHODS: The differentiated human neutrophil-like HL-60 cells (dHL60) were …

Transmucosal Bleomycin For Tongue Lymphatic Malformations, E. W. Cerrati, T. M. O., D. Binetter, Y. Bernstein, M Waner

Journal Articles

No abstract provided.