Neurosciences Commons^™

Mutations In The Transcriptional Regulator Mecp2 Severely Impact Key Cellular And Molecular Signatures Of Human Astrocytes During Maturation, Jialin Sun, Sivan Osenberg, Austin Irwin, Li-Hua Ma, Nigel Lee, Yangfei Xiang, Feng Li, Ying-Wooi Wan, In-Hyun Park, Mirjana Maletic-Savatic, Nurit Ballas

Faculty, Staff and Students Publications

Mutations in the MECP2 gene underlie a spectrum of neurodevelopmental disorders, most commonly Rett syndrome (RTT). We ask whether MECP2 mutations interfere with human astrocyte developmental maturation, thereby affecting their ability to support neurons. Using human-based models, we show that RTT-causing MECP2 mutations greatly impact the key role of astrocytes in regulating overall brain bioenergetics and that these metabolic aberrations are likely mediated by dysfunctional mitochondria. During post-natal maturation, astrocytes rely on neurons to induce their complex stellate morphology and transcriptional changes. While MECP2 mutations cause cell-intrinsic aberrations in the astrocyte transcriptional landscape, surprisingly, they do not affect the neuron-induced …

Cost-Effectiveness Analysis Of Overground Robotic Training Versus Conventional Locomotor Training In People With Spinal Cord Injury, Daniel Pinto, Allen W Heinemann, Shuo-Hsiu Chang, Susan Charlifue, Edelle C Field-Fote, Catherine L Furbish, Arun Jayaraman, Candace Tefertiller, Heather B Taylor, Dustin D French

Faculty, Staff and Student Publications

BACKGROUND: Few, if any estimates of cost-effectiveness for locomotor training strategies following spinal cord injury (SCI) are available. The purpose of this study was to estimate the cost-effectiveness of locomotor training strategies following spinal cord injury (overground robotic locomotor training versus conventional locomotor training) by injury status (complete versus incomplete) using a practice-based cohort.

METHODS: A probabilistic cost-effectiveness analysis was conducted using a prospective, practice-based cohort from four participating Spinal Cord Injury Model System sites. Conventional locomotor training strategies (conventional training) were compared to overground robotic locomotor training (overground robotic training). Conventional locomotor training included treadmill-based training with body weight …

Ultrasound Assessment Of Spastic Muscles In Ambulatory Chronic Stroke Survivors Reveals Function-Dependent Changes, Javier González-Buonomo, Alexander H Pham, Jaskiran Ghuman, Aila Malik, Nuray Yozbatiran, Gerard E Francisco, Walter R Frontera, Sheng Li

Faculty, Staff and Student Publications

OBJECTIVE: To correlate ultrasound characteristics of spastic muscles with clinical and functional measurements in chronic stroke survivors.

METHODS: Ultrasound assessment and clinical and functional assessments were performed in 28 ambulatory stroke survivors (12 females, mean age 57.8 ± 11.8 years, 76 ± 45 months after stroke).

RESULTS: Muscle thickness in the affected side was decreased compared with the contralateral side (p < 0.001). The decrease was more evident in the upper limb muscles. On the affected side, the modified Heckmatt scale score was lowest (closer to normal) in the rectus femoris (RF) muscle compared with other muscles (biceps brachii (BB), flexor carpi ulnaris (FCU) and medial gastrocnemius (MG)). Muscle thickness and echogenicity of spastic muscles did not correlate with spasticity, as measured with the modified Ashworth scale (MAS), Fugl-Meyer motor assessment scores, age, or time since stroke. There was a significant negative correlation between grip strength and percentage decrease in muscle thickness for the spastic FCU muscle (r = -0.49, p = 0.008). RF muscle thickness correlated with ambulatory function (Timed Up and Go test (r = 0.44, p = 0.021) and 6-metre walk test (r = 0.41, p = 0.032)). There was no significant correlation between echogenicity and functional assessments Conclusion: Ambulatory chronic stroke survivors had function-dependent changes in muscle thickness on the affected side. Muscle thickness and echogenicity of spastic muscles did not correlate with spasticity, Fugl-Meyer motor assessment scores, age, or time since stroke.

Circadian Rhythms As Modulators Of Brain Health During Development And Throughout Aging, Rachel Van Drunen, Kristin Eckel-Mahan

Faculty, Staff and Student Publications

The circadian clock plays a prominent role in neurons during development and throughout aging. This review covers topics pertinent to the role of 24-h rhythms in neuronal development and function, and their tendency to decline with aging. Pharmacological or behavioral modification that augment the function of our internal clock may be central to decline of cognitive disease and to future chronotherapy for aging-related diseases of the central nervous system.

The Role Of Pharmacotherapy In Treatment Of Meningioma: A Systematic Review, Ataollah Shahbandi, Darsh S Shah, Caroline C Hadley, Akash J Patel

Faculty, Staff and Students Publications

The safety and efficacy of various pharmacotherapeutic regimens on refractory meningiomas have been the focus of investigations. We present a comprehensive review of the previous efforts and the current state of ongoing clinical trials. A PRISMA-compliant review of the MEDLINE and ClinicalTrial.gov databases of the National Library of Medicine were performed. The primary outcomes of interest for included articles were radiographic response, overall survival, progression-free survival, six-month progression-free survival, and adverse events. Overall, 34 completed trials and 27 ongoing clinical trials were eligible. Six-month progression-free survival was reported in 6-100% of patients in the completed studies. Hematological disorders were the …

Antagonistic Effect Of Cyclin-Dependent Kinases And A Calcium-Dependent Phosphatase On Polyglutamine-Expanded Androgen Receptor Toxic Gain Of Function, Diana Piol, Laura Tosatto, Emanuela Zuccaro, Eric N Anderson, Antonella Falconieri, Maria J Polanco, Caterina Marchioretti, Federica Lia, Joseph White, Elisa Bregolin, Giovanni Minervini, Sara Parodi, Xavier Salvatella, Giorgio Arrigoni, Andrea Ballabio, Albert R La Spada, Silvio C E Tosatto, Fabio Sambataro, Diego L Medina, Udai B Pandey, Manuela Basso, Maria Pennuto

Duncan NRI Faculty and Staff Publications

Spinal and bulbar muscular atrophy is caused by polyglutamine (polyQ) expansions in androgen receptor (AR), generating gain-of-function toxicity that may involve phosphorylation. Using cellular and animal models, we investigated what kinases and phosphatases target polyQ-expanded AR, whether polyQ expansions modify AR phosphorylation, and how this contributes to neurodegeneration. Mass spectrometry showed that polyQ expansions preserve native phosphorylation and increase phosphorylation at conserved sites controlling AR stability and transactivation. In small-molecule screening, we identified that CDC25/CDK2 signaling could enhance AR phosphorylation, and the calcium-sensitive phosphatase calcineurin had opposite effects. Pharmacologic and genetic manipulation of these kinases and phosphatases modified polyQ-expanded AR …

The Lysosomal Ragulator Complex Activates Nlrp3 Inflammasome In Vivo Via Hdac6, Kohei Tsujimoto, Tatsunori Jo, Daiki Nagira, Hachiro Konaka, Jeong Hoon Park, Shin-Ichiro Yoshimura, Akinori Ninomiya, Fuminori Sugihara, Takehiro Hirayama, Eri Itotagawa, Yusei Matsuzaki, Yuki Takaichi, Wataru Aoki, Shotaro Saita, Shuhei Nakamura, Andrea Ballabio, Shigeyuki Nada, Masato Okada, Hyota Takamatsu, Atsushi Kumanogoh

Duncan NRI Faculty and Staff Publications

The cellular activation of the NLRP3 inflammasome is spatiotemporally orchestrated by various organelles, but whether lysosomes contribute to this process remains unclear. Here, we show the vital role of the lysosomal membrane-tethered Ragulator complex in NLRP3 inflammasome activation. Deficiency of Lamtor1, an essential component of the Ragulator complex, abrogated NLRP3 inflammasome activation in murine macrophages and human monocytic cells. Myeloid-specific Lamtor1-deficient mice showed marked attenuation of NLRP3-associated inflammatory disease severity, including LPS-induced sepsis, alum-induced peritonitis, and monosodium urate (MSU)-induced arthritis. Mechanistically, Lamtor1 interacted with both NLRP3 and histone deacetylase 6 (HDAC6). HDAC6 enhances the interaction between Lamtor1 and NLRP3, resulting …

Single-Cell Multi-Omics Integration For Unpaired Data By A Siamese Network With Graph-Based Contrastive Loss, Chaozhong Liu, Linhua Wang, Zhandong Liu

Faculty, Staff and Students Publications

BACKGROUND: Single-cell omics technology is rapidly developing to measure the epigenome, genome, and transcriptome across a range of cell types. However, it is still challenging to integrate omics data from different modalities. Here, we propose a variation of the Siamese neural network framework called MinNet, which is trained to integrate multi-omics data on the single-cell resolution by using graph-based contrastive loss.

RESULTS: By training the model and testing it on several benchmark datasets, we showed its accuracy and generalizability in integrating scRNA-seq with scATAC-seq, and scRNA-seq with epitope data. Further evaluation demonstrated our model's unique ability to remove the batch …

Ticagrelor Plus Aspirin Vs Clopidogrel Plus Aspirin In Mild Non-Cardioembolic Ischemic Stroke: A Protocol Of A Randomized, Controlled, Active Comparator Arm, Outcome Assessor Blind, Feasibility Study, Athena Sharifi-Razavi, Amir Moghadam Ahmadi, Nasim Tabrizi, Razieh Daz

Farber Institute for Neuroscience Staff Papers and Presentations

Background & Objectives: The risk of recurrence after a transient ischemic attack (TIA) or minor stroke is high especially within three months after first event. The aim of study is assessing the efficacy of ticagrelor plus aspirin in reduction of mild non-cardioembolic ischemic stroke or high risk TIA recurrence during first 3 months.

Methods: This is a randomized, controlled, active comparator arm, outcome assessor blind, parallel group, feasibility study design on 90 patients with diagnosis of non-cardioembolic minor ischemic stroke or high risk TIA admitted in Bou-Ali Sina Hospital, Sari, Iran. After meeting all inclusion and exclusion criteria, patients will …

Evaluating The Impact Of Using A Wound-Specific Oral Nutritional Supplement To Support Wound Healing In A Rehabilitation Setting, Rya K Clark, Argyrios Stampas, Kirk W Kerr, Jeffrey L Nelson, Suela Sulo, Luis Leon-Novelo, Esther Ngan, Dehuti Pandya

Faculty, Staff and Student Publications

Chronic wounds adversely affect patient quality of life, increase the risk of mortality, and impose high costs on healthcare systems. Since protein-energy malnutrition or specific nutrient deficiencies can delay wound healing, nutritionally focused care is a key strategy to help prevent or treat the occurrence of non-healing wounds. The objective of our study of inpatients in a rehabilitation hospital was to quantify the effect of daily wound-specific oral nutritional supplementation (WS-ONS) on healing chronic wounds. Using electronic medical records, we conducted a retrospective analysis of patients with chronic wounds. We identified records for (a) a treatment group who received standard …

Lipids And Lipoproteins May Play A Role In The Neuropathology Of Alzheimer’S Disease, Omer Akyol, Sumeyya Akyol, Mei-Chuan Chou, Shioulan Chen, Ching-Kuan Liu, Salih Selek, Jair C Soares, Chu-Huang Chen

Faculty, Staff and Student Publications

Alzheimer's disease (AD) and other classes of dementia are important public health problems with overwhelming social, physical, and financial effects for patients, society, and their families and caregivers. The pathophysiology of AD is poorly understood despite the extensive number of clinical and experimental studies. The brain's lipid-rich composition is linked to disturbances in lipid homeostasis, often associated with glucose and lipid abnormalities in various neurodegenerative diseases, including AD. Moreover, elevated low-density lipoprotein (LDL) cholesterol levels may be related to a higher probability of AD. Here, we hypothesize that lipids, and electronegative LDL (L5) in particular, may be involved in the …

A Story Of Hope: How A Community Project Is Transforming The Lives Of Filipino Children With Intellectual And Developmental Disabilities, Lance Vincent C. Sese, Ma Celina L. Guillermo

Ateneo School of Medicine and Public Health Publications

The issue of social inequality became more prevalent during the pandemic and with it, the call for preferential option toward the vulnerable. 1 Not only do we protect them from sickness and death, but we are also called to improve their quality of life. Thus, it is imperative that in this call for inclusivity, we address the gap, one group at a time—for example, children with special needs. The project discussed in this perspective article exemplifies the importance of collaboration in bridging the gap to create a more holistic environment for Filipino children with special needs. This article then serves …

Associations Of Snfl With Clinico-Radiological Measures In A Large Ms Population., Elias S Sotirchos, Kathryn C Fitzgerald, Carol M Singh, Matthew D Smith, Maria Reyes-Mantilla, Carrie M Hersh, Megan H Hyland, Ryan Canissario, Sarah B Simmons, Georgina Arrambide, Xavier Montalban, Manuel Comabella, Robert T Naismith, Min Qiao, Lauren B Krupp, Jacqueline A Nicholas, Katja Akgün, Tjalf Ziemssen, Richard Rudick, Elizabeth Fisher, Robert A Bermel, Ellen M Mowry, Peter A Calabresi

Neuroscience Articles

OBJECTIVE: Evaluation of serum neurofilament light chain (sNfL), measured using high-throughput assays on widely accessible platforms in large, real-world MS populations, is a critical step for sNfL to be utilized in clinical practice.

METHODS: Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) is a network of healthcare institutions in the United States and Europe collecting standardized clinical/imaging data and biospecimens during routine clinic visits. sNfL was measured in 6974 MS and 201 healthy control (HC) participants, using a high-throughput, scalable immunoassay.

RESULTS: Elevated sNfL levels for age (sNfL-E) were found in 1238 MS participants (17.8%). Factors associated with …

Stereo-Eeg-Guided Network Modulation For Psychiatric Disorders: Surgical Considerations, Sameer A Sheth, Ben Shofty, Anusha Allawala, Jiayang Xiao, Joshua A Adkinson, Raissa K Mathura, Victoria Pirtle, John Myers, Denise Oswalt, Nicole R Provenza, Nisha Giridharan, Angela M Noecker, Garrett P Banks, Ron Gadot, Ricardo A Najera, Adrish Anand, Ethan Devara, Huy Dang, Eleonora Bartoli, Andrew Watrous, Jeffrey Cohn, David Borton, Sanjay J Mathew, Cameron C Mcintyre, Wayne Goodman, Kelly Bijanki, Nader Pouratian

Faculty, Staff and Students Publications

BACKGROUND: Deep brain stimulation (DBS) and other neuromodulatory techniques are being increasingly utilized to treat refractory neurologic and psychiatric disorders.

OBJECTIVE: /Hypothesis: To better understand the circuit-level pathophysiology of treatment-resistant depression (TRD) and treat the network-level dysfunction inherent to this challenging disorder, we adopted an approach of inpatient intracranial monitoring borrowed from the epilepsy surgery field.

METHODS: We implanted 3 patients with 4 DBS leads (bilateral pair in both the ventral capsule/ventral striatum and subcallosal cingulate) and 10 stereo-electroencephalography (sEEG) electrodes targeting depression-relevant network regions. For surgical planning, we used an interactive, holographic visualization platform to appreciate the 3D anatomy …

The Tmem106b T186s Coding Variant Increases Neurite Arborization And Synaptic Density In Primary Hippocampal Neurons, Quynh Nguyen, Caleb A Wood, Peter J Kim, Joanna L Jankowsky

Faculty, Staff and Students Publications

The lysosomal protein TMEM106B was identified as a risk modifier of multiple dementias including frontotemporal dementia and Alzheimer’s disease. The gene comes in two major haplotypes, one associated with disease risk, and by comparison, the other with resilience. Only one coding polymorphism distinguishes the two alleles, a threonine-to-serine substitution at residue 185 (186 in mouse), that is inherited in disequilibrium with multiple non-coding variants. Transcriptional studies suggest synaptic, neuronal, and cognitive preservation in human subjects with the protective haplotype, while murine in vitro studies reveal dramatic effects of TMEM106B deletion on neuronal development. Despite this foundation, the field has not …

Δfosb Is Part Of A Homeostatic Mechanism That Protects The Epileptic Brain From Further Deterioration, Jerome Clasadonte, Tania Deprez, Gabriel S Stephens, Georges Mairet-Coello, Pierre-Yves Cortin, Maxime Boutier, Aurore Frey, Jeannie Chin, Marek Rajman

Faculty, Staff and Students Publications

Activity induced transcription factor ΔFosB plays a key role in different CNS disorders including epilepsy, Alzheimer's disease, and addiction. Recent findings suggest that ΔFosB drives cognitive deficits in epilepsy and together with the emergence of small molecule inhibitors of ΔFosB activity makes it an interesting therapeutic target. However, whether ΔFosB contributes to pathophysiology or provides protection in drug-resistant epilepsy is still unclear. In this study, ΔFosB was specifically downregulated by delivering AAV-shRNA into the hippocampus of chronically epileptic mice using the drug-resistant pilocarpine model of mesial temporal epilepsy (mTLE). Immunohistochemistry analyses showed that prolonged downregulation of ΔFosB led to exacerbation …

Stereo-Eeg-Guided Network Modulation For Psychiatric Disorders: Interactive Holographic Planning, Angela M Noecker, Jeffrey Mlakar, Kelly R Bijanki, Mark A Griswold, Nader Pouratian, Sameer A Sheth, Cameron C Mcintyre

Faculty, Staff and Students Publications

Background: Connectomic modeling studies are expanding understanding of the brain networks that are modulated by deep brain stimulation (DBS) therapies. However, explicit integration of these modeling results into prospective neurosurgical planning is only beginning to evolve. One challenge of employing connectomic models in patient-specific surgical planning is the inherent 3D nature of the results, which can make clinically useful data integration and visualization difficult.

Methods: We developed a holographic stereotactic neurosurgery research tool (HoloSNS) that integrates patient-specific brain models into a group-based visualization environment for interactive surgical planning using connectomic hypotheses. HoloSNS currently runs on the HoloLens 2 platform and …

Concurrent Idh1 And Idh2 Mutations In Glioblastoma: A Case Report, Ali S Haider, Chibawanye I Ene, Paolo Palmisciano, Maryam Haider, Ganesh Rao, Leomar Y Ballester, Gregory N Fuller

Faculty, Staff and Students Publications

Isocitrate dehydrogenase (IDH) mutations are cornerstone diagnostic features in glioma classification. IDH mutations are typically characterized by mutually exclusive amino acid substitutions in the genes encoding for the IDH1 and the IDH2 enzyme isoforms. We report our institutional case of a diffuse astrocytoma with progression to secondary glioblastoma and concurrent IDH1/IDH2 mutations. A 49-year-old male underwent a subtotal resection of a lobular lesion within the right insula in 2013, revealing a WHO grade 3 anaplastic oligoastrocytoma, IDH1 mutated, 1p19q intact. Symptomatic tumor progression was suspected in 2018, leading to a surgical tumor biopsy that demonstrated WHO grade 4 IDH1 and …

Editorial: Molecular Mechanisms In Ocular Development And Disease, Rajalekshmy Shyam, Daisy Y Shu, Elizabeth Zuniga-Sanchez, Deepika Vasudevan

Faculty, Staff and Students Publications

No abstract provided.

Mass Spectrometry Imaging As An Emerging Tool For Studying Metabolism In Human Brain Organoids, Gerarda Cappuccio, Saleh M Khalil, Sivan Osenberg, Feng Li, Mirjana Maletic-Savatic

Faculty, Staff and Students Publications

Human brain organoids are emerging models to study human brain development and pathology as they recapitulate the development and characteristics of major neural cell types, and enable manipulation through an in vitro system. Over the past decade, with the advent of spatial technologies, mass spectrometry imaging (MSI) has become a prominent tool for metabolic microscopy, providing label-free, non-targeted molecular and spatial distribution information of the metabolites within tissue, including lipids. This technology has never been used for studies of brain organoids and here, we set out to develop a standardized protocol for preparation and mass spectrometry imaging of human brain …

Forniceal Deep Brain Stimulation In A Mouse Model Of Rett Syndrome Increases Neurogenesis And Hippocampal Memory Beyond The Treatment Period, Qi Wang, Bin Tang, Shuang Hao, Zhenyu Wu, Tingting Yang, Jianrong Tang

Faculty, Staff and Students Publications

BACKGROUND: Rett syndrome (RTT), caused by mutations in the X-linked gene encoding methyl-CpG binding protein 2 (MeCP2), severely impairs learning and memory. We previously showed that forniceal deep brain stimulation (DBS) stimulates hippocampal neurogenesis with concomitant improvements in hippocampal-dependent learning and memory in a mouse model of RTT.

OBJECTIVES: To determine the duration of DBS benefits; characterize DBS effects on hippocampal neurogenesis; and determine whether DBS influences MECP2 genotype and survival of newborn dentate granular cells (DGCs) in RTT mice.

METHODS: Chronic DBS was delivered through an electrode implanted in the fimbria-fornix. We tested separate cohorts of mice in contextual …

Preexisting Depression And Ambulatory Status After Stroke: Florida-Puerto Rico Collaboration To Reduce Stroke Disparities, Amy K Starosciak, Kefeng Wang, Hao Ying, Kaushik Ravipati, Samantha Spring, Carolina M Gutierrez, Hannah Gardener, David Z Rose, Dianne Foster, Chuanhui Dong, Angus Jameson, Ayham Alkhachroum, Jose G Romano, Ralph L Sacco, Tatjana Rundek, Negar Asdaghi

Faculty, Staff and Student Publications

OBJECTIVE: Stroke is a global public health burden, and therefore it is critical to identify modifiable risk factors to reduce stroke incidence and improve outcomes. Depression is such a risk factor; however, the association between preexisting depression and stroke outcomes, such as independent ambulation, is not well studied, especially among racial-ethnic minority groups. To address this gap in the literature, effects of preexisting depression on ambulatory status at hospital discharge after stroke were evaluated among individuals participating in the racially and ethnically diverse Florida-Puerto Rico Collaboration to Reduce Stroke Disparities project.

METHODS: Data were analyzed from a total of 42,031 …

A Comparison Of One Year Outcomes Between Standardized Locomotor Training And Usual Care After Motor Incomplete Spinal Cord Injury: Community Participation, Quality Of Life And Re-Hospitalization, Candace Tefertiller, Meghan Rozwod, Sandra Wojciehowski, Mitch Sevigny, Susan Charlifue, Jessica M Ketchum, Jeffrey Berliner, Heather B Taylor, Andrea L Behrman, Susan Harkema, Gail Forrest, Mary Schmidt Read, Michelle Basso

Faculty, Staff and Student Publications

CONTEXT/OBJECTIVE: Spinal cord injury (SCI) often results in a significant loss of mobility and independence coinciding with reports of decreased quality of life (QOL), community participation, and medical complications often requiring re-hospitalization. Locomotor training (LT), the repetition of stepping-like patterning has shown beneficial effects for improving walking ability after motor incomplete SCI, but the potential impact of LT on psychosocial outcomes has not been well-established. The purpose of this study was to evaluate one year QOL, community participation and re-hospitalization outcomes between individuals who participated in a standardized LT program and those who received usual care (UC).

DESIGN/SETTING/PARTICIPANTS: A retrospective …

Interpersonal Violence Against Women With Spinal Cord Injury: Adding Insult To Injury, Susan Robinson-Whelen, Rosemary B Hughes, Kimberley Aguillard, Diana Gonzalez, Heather B Taylor

Faculty, Staff and Student Publications

BACKGROUND: Mounting empirical evidence suggests that, compared to women without disabilities, women with disabilities are more likely to experience interpersonal violence (IPV). However, there is extremely limited research attention on IPV against women with spinal cord injury (SCI), a particularly understudied and underserved population.

OBJECTIVES: To conduct the first known examination of lifetime IPV experience in women with SCI, to explore demographic and disability-related correlates of IPV, and to examine the health impacts of IPV.

METHODS: The sample included 175 women with traumatic SCI from across the United States who enrolled in a randomized controlled trial of an online psychological …

Bacterial Meningitis In Africa, Tatiana Barichello, Carlos Henrique Rocha Catalão, Ursula K Rohlwink, Martijn Van Der Kuip, Dan Zaharie, Regan S Solomons, Ronald Van Toorn, Marceline Tutu Van Furth, Rodrigo Hasbun, Federico Iovino, Vivian Ssonko Namale

Faculty, Staff and Student Publications

Bacterial meningitis differs globally, and the incidence and case fatality rates vary by region, country, pathogen, and age group; being a life-threatening disease with a high case fatality rate and long-term complications in low-income countries. Africa has the most significant prevalence of bacterial meningitis illness, and the outbreaks typically vary with the season and the geographic location, with a high incidence in the meningitis belt of the sub-Saharan area from Senegal to Ethiopia. Streptococcus pneumoniae (pneumococcus) and Neisseria meningitidis (meningococcus) are the main etiological agents of bacterial meningitis in adults and children above the age of one. Streptococcus agalactiae (group …

A Deep Learning Approach To Predict Collateral Flow In Stroke Patients Using Radiomic Features From Perfusion Images, Giles Tetteh, Fernando Navarro, Raphael Meier, Johannes Kaesmacher, Johannes C Paetzold, Jan S Kirschke, Claus Zimmer, Roland Wiest, Bjoern H Menze

Faculty, Staff and Student Publications

Collateral circulation results from specialized anastomotic channels which are capable of providing oxygenated blood to regions with compromised blood flow caused by arterial obstruction. The quality of collateral circulation has been established as a key factor in determining the likelihood of a favorable clinical outcome and goes a long way to determining the choice of a stroke care model. Though many imaging and grading methods exist for quantifying collateral blood flow, the actual grading is mostly done through manual inspection. This approach is associated with a number of challenges. First, it is time-consuming. Second, there is a high tendency for …

The Insulin And Igf Signaling Pathway Sustains Breast Cancer Stem Cells By Irs2/Pi3k-Mediated Regulation Of Myc, Manoj Sivan, Stefano Negrini, Carlotte Kiekens, Fary Khan, Gerard E Francisco, Francesca Gimigliano

Faculty, Staff and Student Publications

No abstract provided.

Sex-Biased Autophagy As A Potential Mechanism Mediating Sex Differences In Ischemic Stroke Outcome, Brian Noh, Louise D Mccullough, Jose F Moruno-Manchon

Faculty, Staff and Student Publications

Stroke is the second leading cause of death and a major cause of disability worldwide, and biological sex is an important determining factor in stroke incidence and pathology. From childhood through adulthood, men have a higher incidence of stroke compared with women. Abundant research has confirmed the beneficial effects of estrogen in experimental ischemic stroke but genetic factors such as the X-chromosome complement can also play an important role in determining sex differences in stroke. Autophagy is a self-degrading cellular process orchestrated by multiple core proteins, which leads to the engulfment of cytoplasmic material and degradation of cargo after autophagy …

Preoperative Tractography Algorithm For Safe Resection Of Tumors Located In The Descending Motor Pathways Zone, Edgar G Ordonez-Rubiano, Jason M Johnson, Nadin Abdalá-Vargas, Oscar F Zorro, Jorge H Marin-Munoz, Ricardo Álvarez-Tobián, Valeria Forlizzi, Carlos Castillo Rangel, Sabino Luzzi, Alvaro Campero, Javier G Patiño-Gómez, Matias Baldoncini

Faculty, Staff and Student Publications

BACKGROUND: Diffusion tensor imaging (DTI) tractography facilitates maximal safe resection and optimizes planning to avoid injury during subcortical dissection along descending motor pathways (DMPs). We provide an affordable, safe, and timely algorithm for preoperative DTI motor reconstruction for gliomas adjacent to DMPs.

METHODS: Preoperative DTI reconstructions were extracted from a prospectively acquired registry of glioma resections adjacent to DMPs. The surgeries were performed over a 7-year period. Demographic, clinical, and radiographic data were extracted from patients' electronic medical records.

RESULTS: Nineteen patients (12 male) underwent preoperative tractography between January 1, 2013, and May 31, 2020. The average age was 44.5 …

Retinal Alpha-Synuclein Accumulation Correlates With Retinal Dysfunction And Structural Thinning In The A53t Mouse Model Of Parkinson’S Disease, Katie K N Tran, Vickie H Y Wong, Anh Hoang, David I Finkelstein, Bang V Bui, Christine T O Nguyen

Faculty, Staff and Student Publications

Abnormal alpha-synuclein (α-SYN) protein deposition has long been recognized as one of the pathological hallmarks of Parkinson's disease's (PD). This study considers the potential utility of PD retinal biomarkers by investigating retinal changes in a well characterized PD model of α-SYN overexpression and how these correspond to the presence of retinal α-SYN. Transgenic A53T homozygous (HOM) mice overexpressing human α-SYN and wildtype (WT) control littermates were assessed at 4, 6, and 14  months of age (male and female,