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Articles 571 - 600 of 1127

Full-Text Articles in Neurosciences

Developmental Basis Of Shh Medulloblastoma Heterogeneity, Maxwell P Gold, Winnie Ong, Andrew M Masteller, David R Ghasemi, Julie Anne Galindo, Noel R Park, Nhan C Huynh, Aneesh Donde, Veronika Pister, Raul A Saurez, Maria C Vladoiu, Grace H Hwang, Tanja Eisemann, Laura K Donovan, Adam D Walker, Joseph Benetatos, Christelle Dufour, Livia Garzia, Rosalind A Segal, Robert J Wechsler-Reya, Jill P Mesirov, Andrey Korshunov, Kristian W Pajtler, Scott L Pomeroy, Olivier Ayrault, Shawn M Davidson, Jennifer A Cotter, Michael D Taylor, Ernest Fraenkel Jan 2024

Developmental Basis Of Shh Medulloblastoma Heterogeneity, Maxwell P Gold, Winnie Ong, Andrew M Masteller, David R Ghasemi, Julie Anne Galindo, Noel R Park, Nhan C Huynh, Aneesh Donde, Veronika Pister, Raul A Saurez, Maria C Vladoiu, Grace H Hwang, Tanja Eisemann, Laura K Donovan, Adam D Walker, Joseph Benetatos, Christelle Dufour, Livia Garzia, Rosalind A Segal, Robert J Wechsler-Reya, Jill P Mesirov, Andrey Korshunov, Kristian W Pajtler, Scott L Pomeroy, Olivier Ayrault, Shawn M Davidson, Jennifer A Cotter, Michael D Taylor, Ernest Fraenkel

Faculty, Staff and Students Publications

Many genes that drive normal cellular development also contribute to oncogenesis. Medulloblastoma (MB) tumors likely arise from neuronal progenitors in the cerebellum, and we hypothesized that the heterogeneity observed in MBs with sonic hedgehog (SHH) activation could be due to differences in developmental pathways. To investigate this question, here we perform single-nucleus RNA sequencing on highly differentiated SHH MBs with extensively nodular histology and observed malignant cells resembling each stage of canonical granule neuron development. Through innovative computational approaches, we connect these results to published datasets and find that some established molecular subtypes of SHH MB appear arrested at different …


Development Of A Rabbit Human Glioblastoma Model For Testing Of Endovascular Selective Intra-Arterial Infusion (Esia) Of Novel Stem Cell-Based Therapeutics, Peter Kan, Visish M Srinivasan, Joy Gumin, Roberto Garcia, Stephen R Chen, Jeremiah N Johnson, Dalis E Collins, Melissa M Chen, Daniel Ledbetter, Jason Huse, Zean Aaron Evan Luna, Ariadna Robledo, Viren Vasandani, Abhijit Rao, Sanjay K Singh, Elizabeth J Shpall, Juan Fueyo, Candelaria Gomez-Manzano, Frederick F Lang Jan 2024

Development Of A Rabbit Human Glioblastoma Model For Testing Of Endovascular Selective Intra-Arterial Infusion (Esia) Of Novel Stem Cell-Based Therapeutics, Peter Kan, Visish M Srinivasan, Joy Gumin, Roberto Garcia, Stephen R Chen, Jeremiah N Johnson, Dalis E Collins, Melissa M Chen, Daniel Ledbetter, Jason Huse, Zean Aaron Evan Luna, Ariadna Robledo, Viren Vasandani, Abhijit Rao, Sanjay K Singh, Elizabeth J Shpall, Juan Fueyo, Candelaria Gomez-Manzano, Frederick F Lang

Faculty, Staff and Student Publications

BACKGROUND: Endovascular selective intra-arterial (ESIA) infusion of cellular oncotherapeutics is a rapidly evolving strategy for treating glioblastoma. Evaluation of ESIA infusion requires a unique animal model. Our goal was to create a rabbit human GBM model to test IA infusions of cellular therapies and to test its usefulness by employing clinical-grade microcatheters and infusion methods to deliver mesenchymal stem cells loaded with an oncolytic adenovirus, Delta-24-RGD (MSC-D24).

METHODS: Rabbits were immunosuppressed with mycophenolate mofetil, dexamethasone, and tacrolimus. They underwent stereotactic xenoimplantation of human GBM cell lines (U87, MDA-GSC-17, and MDA-GSC-8-11) into the right frontal lobe. Tumor formation was confirmed on …


A Retrospective Genomic Landscape Of 661 Young Adult Glioblastomas Diagnosed Using 2016 Who Guidelines For Central Nervous System Tumors, James F Haberberger, Worthy Pegram, Nicholas Britt, Kelsie Schiavone, Eric Severson, Radwa Sharaf, Lee A Albacker, Erik Williams, Mirna Lechpammer, Amanda Hemmerich, Douglas Lin, Richard S P Huang, Matthew Hiemenz, Julia Elvin, Ryon Graf, Glenn Lesser, David Kram, Roy Strowd, Wenya Linda Bi, Lori A Ramkissoon, Michael B Cohen, Prasanth Reddy, James Creeden, Jeffrey S Ross, Brian M Alexander, Shakti H Ramkissoon Jan 2024

A Retrospective Genomic Landscape Of 661 Young Adult Glioblastomas Diagnosed Using 2016 Who Guidelines For Central Nervous System Tumors, James F Haberberger, Worthy Pegram, Nicholas Britt, Kelsie Schiavone, Eric Severson, Radwa Sharaf, Lee A Albacker, Erik Williams, Mirna Lechpammer, Amanda Hemmerich, Douglas Lin, Richard S P Huang, Matthew Hiemenz, Julia Elvin, Ryon Graf, Glenn Lesser, David Kram, Roy Strowd, Wenya Linda Bi, Lori A Ramkissoon, Michael B Cohen, Prasanth Reddy, James Creeden, Jeffrey S Ross, Brian M Alexander, Shakti H Ramkissoon

Faculty, Staff and Student Publications

The authors present a cohort of 661 young adult glioblastomas diagnosed using 2016 WHO World Health Organization Classification of Tumors of the Central Nervous System, utilizing comprehensive genomic profiling (CGP) to explore their genomic landscape and assess their relationship to currently defined disease entities. This analysis explored variants with evidence of pathogenic function, common copy number variants (CNVs), and several novel fusion events not described in literature. Tumor mutational burden (TMB) mutational signatures, anatomic location, and tumor recurrence are further explored. Using data collected from CGP, unsupervised machine-learning techniques were leveraged to identify 10 genomic classes in previously assigned young …


Doxycycline For Transgene Control Disrupts Gut Microbiome Diversity Without Compromising Acute Neuroinflammatory Response, Emily J Koller, Caleb A Wood, Zoe Lai, Ella Borgenheimer, Kristi L Hoffman, Joanna L Jankowsky Jan 2024

Doxycycline For Transgene Control Disrupts Gut Microbiome Diversity Without Compromising Acute Neuroinflammatory Response, Emily J Koller, Caleb A Wood, Zoe Lai, Ella Borgenheimer, Kristi L Hoffman, Joanna L Jankowsky

Faculty, Staff and Students Publications

The tetracycline transactivator (tTA) system provides controllable transgene expression through oral administration of the broad-spectrum antibiotic doxycycline. Antibiotic treatment for transgene control in mouse models of disease might have undesirable systemic effects resulting from changes in the gut microbiome. Here we assessed the impact of doxycycline on gut microbiome diversity in a tTA-controlled model of Alzheimer's disease and then examined neuroimmune effects of these microbiome alterations following acute LPS challenge. We show that doxycycline decreased microbiome diversity in both transgenic and wild-type mice and that these changes persisted long after drug withdrawal. Despite the change in microbiome composition, doxycycline treatment …


Heat Shock Factor 1 Directly Regulates Transsulfuration Pathway To Promote Prostate Cancer Proliferation And Survival, J Spencer Hauck, David Moon, Xue Jiang, Mu-En Wang, Yue Zhao, Lingfan Xu, Holly Quang, William Butler, Ming Chen, Everardo Macias, Xia Gao, Yiping He, Jiaoti Huang Jan 2024

Heat Shock Factor 1 Directly Regulates Transsulfuration Pathway To Promote Prostate Cancer Proliferation And Survival, J Spencer Hauck, David Moon, Xue Jiang, Mu-En Wang, Yue Zhao, Lingfan Xu, Holly Quang, William Butler, Ming Chen, Everardo Macias, Xia Gao, Yiping He, Jiaoti Huang

Faculty, Staff and Students Publications

There are limited therapeutic options for patients with advanced prostate cancer (PCa). We previously found that heat shock factor 1 (HSF1) expression is increased in PCa and is an actionable target. In this manuscript, we identify that HSF1 regulates the conversion of homocysteine to cystathionine in the transsulfuration pathway by altering levels of cystathionine-β-synthase (CBS). We find that HSF1 directly binds the CBS gene and upregulates CBS mRNA levels. Targeting CBS decreases PCa growth and induces tumor cell death while benign prostate cells are largely unaffected. Combined inhibition of HSF1 and CBS results in more pronounced inhibition of PCa cell …


Gene Regulation And Speciation In A Migratory Divide Between Songbirds, Matthew I M Louder, Hannah Justen, Abigail A Kimmitt, Koedi S Lawley, Leslie M Turner, J David Dickman, Kira E Delmore Jan 2024

Gene Regulation And Speciation In A Migratory Divide Between Songbirds, Matthew I M Louder, Hannah Justen, Abigail A Kimmitt, Koedi S Lawley, Leslie M Turner, J David Dickman, Kira E Delmore

Faculty, Staff and Students Publications

Behavioral variation abounds in nature. This variation is important for adaptation and speciation, but its molecular basis remains elusive. Here, we use a hybrid zone between two subspecies of songbirds that differ in migration - an ecologically important and taxonomically widespread behavior---to gain insight into this topic. We measure gene expression in five brain regions. Differential expression between migratory states was dominated by circadian genes in all brain regions. The remaining patterns were largely brain-region specific. For example, expression differences between the subspecies that interact with migratory state likely help maintain reproductive isolation in this system and were documented in …


Statins Are Rarely Prescribed For Incidentally Discovered Covert Cerebrovascular Disease: A Retrospective Cohort In A Large Electronic Health Record (Ehr) Identified Using Natural Language Processing, Lester Y Leung, Eric Puttock, David F Kallmes, Patrick Luetmer, Sunyang Fu, Chengyi X Zheng, Hongfang Liu, Wansu Chen, David M Kent Jan 2024

Statins Are Rarely Prescribed For Incidentally Discovered Covert Cerebrovascular Disease: A Retrospective Cohort In A Large Electronic Health Record (Ehr) Identified Using Natural Language Processing, Lester Y Leung, Eric Puttock, David F Kallmes, Patrick Luetmer, Sunyang Fu, Chengyi X Zheng, Hongfang Liu, Wansu Chen, David M Kent

Faculty, Staff and Student Publications

Introduction: While incidentally discovered covert cerebrovascular diseases (id-CCD) are associated with future stroke, it is not known if patients with id-CCD are prescribed statins.

Methods: Patients age ≥50 with id-CCD on neuroimaging from 2009 to 2019 with no prior ischaemic stroke, transient ischaemic attack or dementia were identified using natural language processing in a large real-world cohort. Robust Poisson multivariable regression was used to assess statin prescription among patients without prior statins.

Results: Among 2 41 050 patients, 74 975 patients (31.1%; 4.7% with covert brain infarcts (CBI); 29.0% with white matter disease (WMD)) had id-CCD. 53.5% (95% CI 53.2 …


Vagus Nerve Stimulation For The Therapy Of Dravet Syndrome: A Systematic Review And Meta-Analysis, Shuang Chen, Man Li, Ming Huang Jan 2024

Vagus Nerve Stimulation For The Therapy Of Dravet Syndrome: A Systematic Review And Meta-Analysis, Shuang Chen, Man Li, Ming Huang

Faculty, Staff and Student Publications

OBJECTIVE: Dravet syndrome (DS) is a refractory developmental and epileptic encephalopathy characterized by seizures, developmental delay and cognitive impairment with a variety of comorbidities, including autism-like behavior, speech dysfunction, and ataxia. Vagus nerve stimulation (VNS) is one of the common therapies for DS. Here, we aim to perform a meta-analysis and systematic review of the efficacy of VNS in DS patients.

METHODS: We systematically searched four databases (PubMed, Embase, Cochrane and CNKI) to identify potentially eligible studies from their inception to January 2024. These studies provided the effective rate of VNS in treating patients with DS. The proportions of DS …


A Novel Super-Resolution Microscopy Platform For Cutaneous Alpha-Synuclein Detection In Parkinson's Diseasea Novel Super-Resolution Microscopy Platform For Cutaneous Alpha-Synuclein Detection In Parkinson's Disease, Ofir Sade, Daphna Fischel, Noa Barak-Broner, Shir Halevi, Irit Gottfried, Dana Bar-On, Stefan Sachs, Anat Mirelman, Avner Thaler, Aviv Gour, Meir Kestenbaum, Mali Gana Weisz, Saar Anis, Claudio Soto, Melanie Shanie Roitman, Shimon Shahar, Kathrin Doppler, Markus Sauer, Nir Giladi, Nirit Lev, Roy N Alcalay, Sharon Hassin-Baer, Uri Ashery Jan 2024

A Novel Super-Resolution Microscopy Platform For Cutaneous Alpha-Synuclein Detection In Parkinson's Diseasea Novel Super-Resolution Microscopy Platform For Cutaneous Alpha-Synuclein Detection In Parkinson's Disease, Ofir Sade, Daphna Fischel, Noa Barak-Broner, Shir Halevi, Irit Gottfried, Dana Bar-On, Stefan Sachs, Anat Mirelman, Avner Thaler, Aviv Gour, Meir Kestenbaum, Mali Gana Weisz, Saar Anis, Claudio Soto, Melanie Shanie Roitman, Shimon Shahar, Kathrin Doppler, Markus Sauer, Nir Giladi, Nirit Lev, Roy N Alcalay, Sharon Hassin-Baer, Uri Ashery

Faculty, Staff and Student Publications

Alpha-synuclein (aSyn) aggregates in the central nervous system are the main pathological hallmark of Parkinson’s disease (PD). ASyn aggregates have also been detected in many peripheral tissues, including the skin, thus providing a novel and accessible target tissue for the detection of PD pathology. Still, a well-established validated quantitative biomarker for early diagnosis of PD that also allows for tracking of disease progression remains lacking. The main goal of this research was to characterize aSyn aggregates in skin biopsies as a comparative and quantitative measure for PD pathology. Using direct stochastic optical reconstruction microscopy (dSTORM) and computational tools, …


Management Of Anhedonia After Epilepsy Surgery, Gerardo Maria De Araujo Filho, Antonio L Teixeira Jan 2024

Management Of Anhedonia After Epilepsy Surgery, Gerardo Maria De Araujo Filho, Antonio L Teixeira

Faculty, Staff and Student Publications

Anhedonia is clinically defined as difficulty or inability to feel pleasure or to be motivated to perform activities that were previously pleasurable. Anhedonia is a core feature of depressive disorders but can be present in other conditions such as substance use and anxiety disorders. Herein we report the case of a 34-year-old female who developed marked anhedonia after left cortico-amygdalohippocampectomy. Despite optimal seizure control, the person struggled with anhedonia and other depressive symptoms. After ruling out medico-neurologic complications, she was prescribed with a selective serotonin reuptake inhibitor and cognitive-behavioral therapy. Anhedonia can be a challenging neuropsychiatric presentation that requires ruling …


Targeting The Renin-Angiotensin System (Ras) For Neuropsychiatric Disorders, Aline Silva De Miranda, Danielle S Macedo, Natalia P Rocha, Antonio L Teixeira Jan 2024

Targeting The Renin-Angiotensin System (Ras) For Neuropsychiatric Disorders, Aline Silva De Miranda, Danielle S Macedo, Natalia P Rocha, Antonio L Teixeira

Faculty, Staff and Student Publications

BACKGROUND: Neuropsychiatric disorders, such as mood disorders, schizophrenia, and Alzheimer's disease (AD) and related dementias, are associated to significant morbidity and mortality worldwide. The pathophysiological mechanisms of neuropsychiatric disorders remain to be fully elucidated, which has hampered the development of effective therapies. The Renin Angiotensin System (RAS) is classically viewed as a key regulator of cardiovascular and renal homeostasis. The discovery that RAS components are expressed in the brain pointed out a potential role for this system in central nervous system (CNS) pathologies. The understanding of RAS involvement in the pathogenesis of neuropsychiatric disorders may contribute to identifying novel therapeutic …


Multimodal Prediction Of Obsessive-Compulsive Disorder And Comorbid Depression Severity And Energy Delivered By Deep Brain Electrodes, Saurabh Hinduja, Ali Darzi, Itir Onal Ertugrul, Nicole Provenza, Ron Gadot, Eric A Storch, Sameer A Sheth, Wayne K Goodman, Jeffrey F Cohn Jan 2024

Multimodal Prediction Of Obsessive-Compulsive Disorder And Comorbid Depression Severity And Energy Delivered By Deep Brain Electrodes, Saurabh Hinduja, Ali Darzi, Itir Onal Ertugrul, Nicole Provenza, Ron Gadot, Eric A Storch, Sameer A Sheth, Wayne K Goodman, Jeffrey F Cohn

Faculty, Staff and Students Publications

To develop reliable, valid, and efficient measures of obsessive-compulsive disorder (OCD) severity, comorbid depression severity, and total electrical energy delivered (TEED) by deep brain stimulation (DBS), we trained and compared random forests regression models in a clinical trial of participants receiving DBS for refractory OCD. Six participants were recorded during open-ended interviews at pre- and post-surgery baselines and then at 3-month intervals following DBS activation. Ground-truth severity was assessed by clinical interview and self-report. Visual and auditory modalities included facial action units, head and facial landmarks, speech behavior and content, and voice acoustics. Mixed-effects random forest regression with Shapley feature …


Scan-Less Microscopy Based On Acousto-Optic Encoded Illumination, Andrea Marchese, Pietro Ricci, Peter Saggau, Martí Duocastella Jan 2024

Scan-Less Microscopy Based On Acousto-Optic Encoded Illumination, Andrea Marchese, Pietro Ricci, Peter Saggau, Martí Duocastella

Faculty, Staff and Students Publications

Several optical microscopy methods are now available for characterizing scientific and industrial processes at sub-micron resolution. However, they are often ill-suited for imaging rapid events. Limited by the trade-off between camera frame-rate and sensitivity, or the need for mechanical scanning, current microscopes are optimized for imaging at hundreds of frames-per-second (fps), well-below what is needed in processes such as neuronal signaling or moving parts in manufacturing lines. Here, we present a scan-less technology that allows sub-micrometric imaging at thousands of fps. It is based on combining a single-pixel camera with parallelized encoded illumination. We use two acousto-optic deflectors (AODs) placed …


Proceedings Of The 11th Annual Deep Brain Stimulation Think Tank: Pushing The Forefront Of Neuromodulation With Functional Network Mapping, Biomarkers For Adaptive Dbs, Bioethical Dilemmas, Ai-Guided Neuromodulation, And Translational Advancements, Kara A Johnson, Nico U F Dosenbach, Evan M Gordon, Cristin G Welle, Kevin B Wilkins, Helen M Bronte-Stewart, Valerie Voon, Takashi Morishita, Yuki Sakai, Amanda R Merner, Gabriel Lázaro-Muñoz, Theresa Williamson, Andreas Horn, Ro'ee Gilron, Jonathan O'Keeffe, Aryn H Gittis, Wolf-Julian Neumann, Simon Little, Nicole R Provenza, Sameer A Sheth, Alfonso Fasano, Abbey B Holt-Becker, Robert S Raike, Lisa Moore, Yagna J Pathak, David Greene, Sara Marceglia, Lothar Krinke, Huiling Tan, Hagai Bergman, Monika Pötter-Nerger, Bomin Sun, Laura Y Cabrera, Cameron C Mcintyre, Noam Harel, Helen S Mayberg, Andrew D Krystal, Nader Pouratian, Philip A Starr, Kelly D Foote, Michael S Okun, Joshua K Wong Jan 2024

Proceedings Of The 11th Annual Deep Brain Stimulation Think Tank: Pushing The Forefront Of Neuromodulation With Functional Network Mapping, Biomarkers For Adaptive Dbs, Bioethical Dilemmas, Ai-Guided Neuromodulation, And Translational Advancements, Kara A Johnson, Nico U F Dosenbach, Evan M Gordon, Cristin G Welle, Kevin B Wilkins, Helen M Bronte-Stewart, Valerie Voon, Takashi Morishita, Yuki Sakai, Amanda R Merner, Gabriel Lázaro-Muñoz, Theresa Williamson, Andreas Horn, Ro'ee Gilron, Jonathan O'Keeffe, Aryn H Gittis, Wolf-Julian Neumann, Simon Little, Nicole R Provenza, Sameer A Sheth, Alfonso Fasano, Abbey B Holt-Becker, Robert S Raike, Lisa Moore, Yagna J Pathak, David Greene, Sara Marceglia, Lothar Krinke, Huiling Tan, Hagai Bergman, Monika Pötter-Nerger, Bomin Sun, Laura Y Cabrera, Cameron C Mcintyre, Noam Harel, Helen S Mayberg, Andrew D Krystal, Nader Pouratian, Philip A Starr, Kelly D Foote, Michael S Okun, Joshua K Wong

Faculty, Staff and Students Publications

The Deep Brain Stimulation (DBS) Think Tank XI was held on August 9-11, 2023 in Gainesville, Florida with the theme of "Pushing the Forefront of Neuromodulation". The keynote speaker was Dr. Nico Dosenbach from Washington University in St. Louis, Missouri. He presented his research recently published in Nature inn a collaboration with Dr. Evan Gordon to identify and characterize the somato-cognitive action network (SCAN), which has redefined the motor homunculus and has led to new hypotheses about the integrative networks underpinning therapeutic DBS. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers, and …


Editorial: Symmetry As A Guiding Principle In Artificial And Brain Neural Networks, Volume Ii, Fabio Anselmi, Ankit B Patel Jan 2024

Editorial: Symmetry As A Guiding Principle In Artificial And Brain Neural Networks, Volume Ii, Fabio Anselmi, Ankit B Patel

Faculty, Staff and Students Publications

No abstract provided.


Dimensionality Reduction And Nearest Neighbors For Improving Out-Of-Distribution Detection In Medical Image Segmentation, Mckell Woodland, Nihil Patel, Austin Castelo, Mais Al Taie, Mohamed Eltaher, Joshua P Yung, Tucker J Netherton, Tiffany L Calderone, Jessica I Sanchez, Darrel W Cleere, Ahmed Elsaiey, Nakul Gupta, David Victor, Laura Beretta, Ankit B Patel, Kristy K Brock Jan 2024

Dimensionality Reduction And Nearest Neighbors For Improving Out-Of-Distribution Detection In Medical Image Segmentation, Mckell Woodland, Nihil Patel, Austin Castelo, Mais Al Taie, Mohamed Eltaher, Joshua P Yung, Tucker J Netherton, Tiffany L Calderone, Jessica I Sanchez, Darrel W Cleere, Ahmed Elsaiey, Nakul Gupta, David Victor, Laura Beretta, Ankit B Patel, Kristy K Brock

Faculty, Staff and Students Publications

Clinically deployed deep learning-based segmentation models are known to fail on data outside of their training distributions. While clinicians review the segmentations, these models tend to perform well in most instances, which could exacerbate automation bias. Therefore, detecting out-of-distribution images at inference is critical to warn the clinicians that the model likely failed. This work applied the Mahalanobis distance (MD) post hoc to the bottleneck features of four Swin UNETR and nnU-net models that segmented the liver on T1-weighted magnetic resonance imaging and computed tomography. By reducing the dimensions of the bottleneck features with either principal component analysis or uniform …


Functional Genomics And Small Molecules In Mitochondrial Neurodevelopmental Disorders, Daniel G Calame, Lisa T Emrick Jan 2024

Functional Genomics And Small Molecules In Mitochondrial Neurodevelopmental Disorders, Daniel G Calame, Lisa T Emrick

Faculty, Staff and Students Publications

Mitochondria are critical for brain development and homeostasis. Therefore, pathogenic variation in the mitochondrial or nuclear genome which disrupts mitochondrial function frequently results in developmental disorders and neurodegeneration at the organismal level. Large-scale application of genome-wide technologies to individuals with mitochondrial diseases has dramatically accelerated identification of mitochondrial disease-gene associations in humans. Multi-omic and high-throughput studies involving transcriptomics, proteomics, metabolomics, and saturation genome editing are providing deeper insights into the functional consequence of mitochondrial genomic variation. Integration of deep phenotypic and genomic data through allelic series continues to uncover novel mitochondrial functions and permit mitochondrial gene function dissection on an …


International Society For Pediatric And Adolescent Diabetes Clinical Practice Consensus Guidelines 2024: Diabetes Technologies - Insulin Delivery, Torben Biester, Cari Berget, Charlotte Boughton, Laura Cudizio, Laya Ekhlaspour, Marisa E Hilliard, Leenatha Reddy, Suzanne Sap Ngo Um, Melissa Schoelwer, Jennifer L Sherr, Klemen Dovc Jan 2024

International Society For Pediatric And Adolescent Diabetes Clinical Practice Consensus Guidelines 2024: Diabetes Technologies - Insulin Delivery, Torben Biester, Cari Berget, Charlotte Boughton, Laura Cudizio, Laya Ekhlaspour, Marisa E Hilliard, Leenatha Reddy, Suzanne Sap Ngo Um, Melissa Schoelwer, Jennifer L Sherr, Klemen Dovc

Faculty, Staff and Students Publications

The International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines represent a rich repository that serves as the only comprehensive set of clinical recommendations for children, adolescents, and young adults living with diabetes worldwide. This chapter builds on the 2022 ISPAD guidelines, and summarizes recent advances in the technology behind insulin administration, with special emphasis on insulin pump therapy, especially on glucose-responsive integrated technology that is feasible with the use of automated insulin delivery (AID) systems in children and adolescents. The International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines represent a rich repository that serves as the only comprehensive …


Mecp2-Related Disorders While Gene-Based Therapies Are On The Horizon, Katherine Allison, Mirjana Maletic-Savatic, Davut Pehlivan Jan 2024

Mecp2-Related Disorders While Gene-Based Therapies Are On The Horizon, Katherine Allison, Mirjana Maletic-Savatic, Davut Pehlivan

Faculty, Staff and Students Publications

The emergence of new genetic tools has led to the discovery of the genetic bases of many intellectual and developmental disabilities. This creates exciting opportunities for research and treatment development, and a few genetic disorders (e.g., spinal muscular atrophy) have recently been treated with gene-based therapies. MECP2 is found on the X chromosome and regulates the transcription of thousands of genes. Loss of MECP2 gene product leads to Rett Syndrome, a disease found primarily in females, and is characterized by developmental regression, motor dysfunction, midline hand stereotypies, autonomic nervous system dysfunction, epilepsy, scoliosis, and autistic-like behavior. Duplication of MECP2 causes …


Metabolic Bioactivation Of Antidepressants: Advance And Underlying Hepatotoxicity, Saleh M Khalil, Kevin R Mackenzie, Mirjana Maletic-Savatic, Feng Li Jan 2024

Metabolic Bioactivation Of Antidepressants: Advance And Underlying Hepatotoxicity, Saleh M Khalil, Kevin R Mackenzie, Mirjana Maletic-Savatic, Feng Li

Faculty, Staff and Students Publications

Many drugs that serve as first-line medications for the treatment of depression are associated with severe side effects, including liver injury. Of the 34 antidepressants discussed in this review, four have been withdrawn from the market due to severe hepatotoxicity, and others carry boxed warnings for idiosyncratic liver toxicity. The clinical and economic implications of antidepressant-induced liver injury are substantial, but the underlying mechanisms remain elusive. Drug-induced liver injury may involve the host immune system, the parent drug, or its metabolites, and reactive drug metabolites are one of the most commonly referenced risk factors. Although the precise mechanism by which …


Citrulline And Adi-Peg20 Reduce Inflammation In A Juvenile Porcine Model Of Acute Endotoxemia, Caitlin Vonderohe, Barbara Stoll, Inka Didelija, Trung Nguyen, Mahmoud Mohammad, Yava Jones-Hall, Miguel A Cruz, Juan Marini, Douglas Burrin Jan 2024

Citrulline And Adi-Peg20 Reduce Inflammation In A Juvenile Porcine Model Of Acute Endotoxemia, Caitlin Vonderohe, Barbara Stoll, Inka Didelija, Trung Nguyen, Mahmoud Mohammad, Yava Jones-Hall, Miguel A Cruz, Juan Marini, Douglas Burrin

Faculty, Staff and Students Publications

BACKGROUND: Arginine is a conditionally essential amino acid that is depleted in critically ill or surgical patients. In pediatric and adult patients, sepsis results in an arginine-deficient state, and the depletion of plasma arginine is associated with greater mortality. However, direct supplementation of arginine can result in the excessive production of nitric oxide (NO), which can contribute to the hypotension and macrovascular hypo-reactivity observed in septic shock. Pegylated arginine deiminase (ADI-PEG20, pegargiminase) reduces plasma arginine and generates citrulline that can be transported intracellularly to generate local arginine and NO, without resulting in hypotension, while maintaining microvascular patency. The objective of …


Precision Needle-Punch Tumor Enrichment From Paraffin Blocks Improves The Detection Of Clinically Actionable Genomic Alterations And Biomarkers, Douglas I Lin, Richard S P Huang, Ioannis Ladas, Rachel B Keller, Nimesh R Patel, Sotirios Lakis, Brennan Decker, Tyler Janovitz, Douglas A Mata, Jeffrey S Ross, Jo-Anne Vergilio, Julia A Elvin, Roy S Herbst, Philip C Mack, Jonathan K Killian Jan 2024

Precision Needle-Punch Tumor Enrichment From Paraffin Blocks Improves The Detection Of Clinically Actionable Genomic Alterations And Biomarkers, Douglas I Lin, Richard S P Huang, Ioannis Ladas, Rachel B Keller, Nimesh R Patel, Sotirios Lakis, Brennan Decker, Tyler Janovitz, Douglas A Mata, Jeffrey S Ross, Jo-Anne Vergilio, Julia A Elvin, Roy S Herbst, Philip C Mack, Jonathan K Killian

Faculty, Staff and Student Publications

BACKGROUND: While many molecular assays can detect mutations at low tumor purity and variant allele frequencies, complex biomarkers such as tumor mutational burden (TMB), microsatellite instability (MSI), and genomic loss of heterozygosity (gLOH) require higher tumor purity for accurate measurement. Scalable, quality-controlled, tissue-conserving methods to increase tumor nuclei percentage (TN%) from tumor specimens are needed for complex biomarkers and hence necessary to maximize patient matching to approved therapies or clinical trial enrollment. We evaluated the clinical utility and performance of precision needle-punch enrichment (NPE) compared with traditional razor blade macroenrichment of tumor specimens on molecular testing success.

METHODS: Pathologist-directed NPE …


High Doses Of Caffeine-Induced Cerebral Infarction Leading To Partial Locked-In Syndrome In A Young Adult: A Novel Association?, Vijay Sinha, Loc Lam, Michael V Nguyen Jan 2024

High Doses Of Caffeine-Induced Cerebral Infarction Leading To Partial Locked-In Syndrome In A Young Adult: A Novel Association?, Vijay Sinha, Loc Lam, Michael V Nguyen

Faculty, Staff and Student Publications

INTRODUCTION: This is a case of a 30-year-old male with no prior medical conditions presented to the emergency department for presumed seizures after ingesting 900 mg of caffeine via pre-workout drinks and pills.

CASE PRESENTATION: The patient was described as having nearly 15 min of generalized seizure activity observed by emergency medical service, requiring midazolam. A head computerized tomography (CT) demonstrated a possible thrombus, and further, CT angiography and CT perfusion confirmed a basilar artery occlusion. He was treated with tissue plasminogen activator and underwent thrombectomy achieving TICI grade 3 in the left posterior cerebral artery and TICI grade 2b …


Corrigendum: High-Definition Transcranial Direct Current Stimulation For Upper Extremity Rehabilitation In Moderate-To-Severe Ischemic Stroke: A Pilot Study, Jordan N Williamson, Shirley A James, Dorothy He, Sheng Li, Evgeny V Sidorov, Yuan Yang Jan 2024

Corrigendum: High-Definition Transcranial Direct Current Stimulation For Upper Extremity Rehabilitation In Moderate-To-Severe Ischemic Stroke: A Pilot Study, Jordan N Williamson, Shirley A James, Dorothy He, Sheng Li, Evgeny V Sidorov, Yuan Yang

Faculty, Staff and Student Publications

No abstract provided.


Novel Oppositional Defiant Disorder Or Conduct Disorder 24 Months After Traumatic Brain Injury In Children And Adolescents, Daniel S Lowet, Florin Vaida, John R Hesselink, Linda Ewing-Cobbs, Russell J Schachar, Sandra B Chapman, Erin D Bigler, Elisabeth A Wilde, Ann E Saunders, Tony T Yang, Olga Tymofiyeva, Mingxiong Huang, Jeffrey E Max Jan 2024

Novel Oppositional Defiant Disorder Or Conduct Disorder 24 Months After Traumatic Brain Injury In Children And Adolescents, Daniel S Lowet, Florin Vaida, John R Hesselink, Linda Ewing-Cobbs, Russell J Schachar, Sandra B Chapman, Erin D Bigler, Elisabeth A Wilde, Ann E Saunders, Tony T Yang, Olga Tymofiyeva, Mingxiong Huang, Jeffrey E Max

Faculty, Staff and Student Publications

Objective: The authors sought to identify predictive factors of new-onset or novel oppositional defiant disorder or conduct disorder assessed 24 months after traumatic brain injury (TBI).

Methods: Children ages 5 to 14 years who had experienced TBI were recruited from consecutive hospital admissions. Soon after injury, participants were assessed for preinjury characteristics, including psychiatric disorders, socioeconomic status (SES), psychosocial adversity, and family function, and the presence and location of lesions were documented by MRI. Psychiatric outcomes, including novel oppositional defiant disorder or conduct disorder, were assessed 24 months after injury.

Results: Of the children without preinjury oppositional defiant disorder, conduct …


Measurement Of 8-Hydroxy-2′-Deoxyguanosine In Serum And Cerebrospinal Fluid Of Horses With Neuroaxonal Degeneration And Other Causes Of Proprioceptive Ataxia, Megan Palmisano, Jeaneen Kulp, Susan Bender, Darko Stefanovski, Mary Robinson, Amy Johnson Jan 2024

Measurement Of 8-Hydroxy-2′-Deoxyguanosine In Serum And Cerebrospinal Fluid Of Horses With Neuroaxonal Degeneration And Other Causes Of Proprioceptive Ataxia, Megan Palmisano, Jeaneen Kulp, Susan Bender, Darko Stefanovski, Mary Robinson, Amy Johnson

Faculty, Staff and Student Publications

BACKGROUND: Eight-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative damage evaluated in human neurodegenerative disease, has potential to correlate with postmortem diagnosis of neuroaxonal dystrophy/degenerative myeloencephalopathy (NAD/DM) in horses.

HYPOTHESIS: We hypothesized that 8-OHdG will be higher in CSF and serum from NAD/DM horses compared with horses with other neurologic diseases (CVSM, EPM) and a control group of neurologically normal horses. We also hypothesized that 8-OHdG will be higher in CSF compared with serum from NAD/DM horses.

ANIMALS: Fifty client-owned horses with postmortem diagnoses: 20 NAD/DM, 10 CVSM, 10 EPM, and 10 control horses. Serum and CSF samples were obtained between November …


Proportional Sway-Based Electrotactile Feedback Improves Lateral Standing Balance, V S Raghav Hari Krishna, Jeonghee Kim, Shuo-Hsiu Chang, Yoonsuck Choe, Hangue Park Jan 2024

Proportional Sway-Based Electrotactile Feedback Improves Lateral Standing Balance, V S Raghav Hari Krishna, Jeonghee Kim, Shuo-Hsiu Chang, Yoonsuck Choe, Hangue Park

Faculty, Staff and Student Publications

INTRODUCTION: Plantar cutaneous augmentation is a promising approach in balance rehabilitation by enhancing motion-dependent sensory feedback. The effect of plantar cutaneous augmentation on balance has been mainly investigated in its passive form (e.g., textured insole) or on lower-limb amputees. In this study, we tested the effect of plantar cutaneous augmentation on balance in its active form (i.e., electrical stimulation) for individuals with intact limbs.

METHODS: Ten healthy subjects participated in the study and were instructed to maintain their balance as long as possible on the balance board, with or without electrotactile feedback evoked on the medial side of the heel, …


In Sickness And In Health-Type I Interferon And The Brain, Wei Cao Jan 2024

In Sickness And In Health-Type I Interferon And The Brain, Wei Cao

Faculty, Staff and Student Publications

Type I interferons (IFN-I) represent a group of pleiotropic cytokines renowned for their antiviral activity and immune regulatory functions. A multitude of studies have unveiled a critical role of IFN-I in the brain, influencing various neurological processes and diseases. In this mini-review, I highlight recent findings on IFN-I's effects on brain aging, Alzheimer's disease (AD) progression, and central nervous system (CNS) homeostasis. The multifaceted influence of IFN-I on brain health and disease sheds light on the complex interplay between immune responses and neurological processes. Of particular interest is the cGAS-STING-IFN-I axis, which extensively participates in brain aging and various forms …


20-Year Inflation-Adjusted Medicare Reimbursements (Years: 2000-2020) For Common Lumbar And Cervical Degenerative Disc Disease Procedures, Pedram Honarpisheh, Samantha L Parker, Christopher R Conner, Sami Anjum, Jessica R Stark, John C Quinn, John M Caridi Jan 2024

20-Year Inflation-Adjusted Medicare Reimbursements (Years: 2000-2020) For Common Lumbar And Cervical Degenerative Disc Disease Procedures, Pedram Honarpisheh, Samantha L Parker, Christopher R Conner, Sami Anjum, Jessica R Stark, John C Quinn, John M Caridi

Faculty, Staff and Student Publications

OBJECTIVE: Reimbursement trends for common procedures have persistently declined over the past 2 decades. Spinal instrumentational and fusion procedures are increasingly utilized and have increased in clinical complexity, yet longitudinal inflation-adjusted data for Medicare reimbursements of these procedures have not been evaluated.

METHODS: The Centers for Medicare and Medicaid Services (CMS) Physician Fee Schedule Look-Up Tool was used to extract Medicare reimbursements for the 5 most common spinal procedures and associated instrumentations from 2000-2020. Current Procedural Terminology (CPT) codes include 22551, 22600, 22633, 63030, and 63047 as well as instrumentation CPT codes 22840 and 22842-6. The nominal values were adjusted …


Critical Dialogue And Capacity-Building Projects Reduced Alcohol And Substance Use In A Randomized Clinical Trial Among Formerly Incarcerated Men, Liliane Cambraia Windsor, Ellen Benoit, Carol Lee, Alexis Jemal, Kari Kugler, Douglas C Smith, Rogério M Pinto, Salma Musaad Jan 2024

Critical Dialogue And Capacity-Building Projects Reduced Alcohol And Substance Use In A Randomized Clinical Trial Among Formerly Incarcerated Men, Liliane Cambraia Windsor, Ellen Benoit, Carol Lee, Alexis Jemal, Kari Kugler, Douglas C Smith, Rogério M Pinto, Salma Musaad

Faculty, Staff and Students Publications

Background:

Rates of alcohol and/or substance use (ASU) among residents of predominantly Black and marginalized communities are similar to ASU rates in White communities. Yet ASU has worse consequences in predominantly Black and marginalized communities (e.g., higher incarceration).

Objective:

We randomized participants to one of 16 intervention conditions using a 24 full factorial design to optimize a multilevel intervention reducing ASU among 602 formerly incarcerated men with substance-use-disorders (SUD). Candidate intervention components included (1) critical dialogue (CD; six weekly 2-hour-long group sessions vs. no CD sessions), (2) Quality of Life Wheel (QLW; six weekly 1-hour-long group sessions vs. no …