Neurosurgery Commons^™

Dual Enhancement In The Radiosensitivity Of Prostate Cancer Through Nanoparticles And Chemotherapeutics, Nolan Jackson, Iona Hill, Abdulaziz Alhussan, Kyle Bromma, Jessica Morgan, Belal Abousaida, Yasmin Zahra, Yuri Mackeyev, Wayne Beckham, Steven Herchko, Sunil Krishnan, Devika Basnagge Chithrani

Faculty, Staff and Student Publications

BACKGROUND: Radiotherapy (RT) is an essential component in the treatment regimens for many cancer patients. However, the dose escalation required to improve curative results is hindered due to the normal tissue toxicity that is induced. The introduction of radiosensitizers to RT treatment is an avenue that is currently being explored to overcome this issue. By introducing radiosensitizers into tumor sites, it is possible to preferentially enhance the local dose deposited. Gold nanoparticles (GNPs) are a potential candidate that have shown great promise in increasing the radiosensitivity of cancer cells through an enhancement in DNA damage. Furthermore, docetaxel (DTX) is a …

Radiolabeled Nanomaterial For Cancer Diagnostics And Therapeutics: Principles And Concepts, Muskan Goel, Yuri Mackeyev, Sunil Krishnan

Faculty, Staff and Student Publications

In the last three decades, radiopharmaceuticals have proven their effectiveness for cancer diagnosis and therapy. In parallel, the advances in nanotechnology have fueled a plethora of applications in biology and medicine. A convergence of these disciplines has emerged more recently with the advent of nanotechnology-aided radiopharmaceuticals. Capitalizing on the unique physical and functional properties of nanoparticles, radiolabeled nanomaterials or nano-radiopharmaceuticals have the potential to enhance imaging and therapy of human diseases. This article provides an overview of various radionuclides used in diagnostic, therapeutic, and theranostic applications, radionuclide production through different techniques, conventional radionuclide delivery systems, and advancements in the delivery …

Proton Therapy With Concurrent Chemotherapy For Thoracic Esophageal Cancer: Toxicity, Disease Control, And Survival Outcomes, Michael S Rutenberg, Bradford S Hoppe, Jason S Starr, Ziad Awad, Mathew Thomas, Christopher G Morris, Perry Johnson, Randal H Henderson, Jeremy C Jones, Bharatsinh Gharia, Steven Bowers, Herbert C Wolfsen, Sunil Krishnan, Stephen J Ko, Hani M Babiker, Romaine C Nichols

Faculty, Staff and Student Publications

PURPOSE: When treating esophageal cancer with radiation therapy, it is critical to limit the dose to surrounding structures, such as the lung and/or heart, as much as possible. Proton radiation therapy allows a reduced radiation dose to both the heart and lungs, potentially reducing the risk of cardiopulmonary toxicity. Here, we report disease control, survival, and toxicity outcomes among patients with esophageal cancer treated with proton radiation therapy and concurrent chemotherapy (chemoradiation therapy; CRT) with or without surgery.

MATERIALS AND METHODS: We enrolled 17 patients with thoracic esophageal carcinoma on a prospective registry between 2010 and 2021. Patients received proton …

Editorial: Modulation Of Microglia Reactivity And Plasticity In Cns Injury, Zhenyan He, Hailiang Tang, Jiping Tang, Xuying He, Ningbo Xu, Devin W Mcbride

Faculty, Staff and Student Publications

No abstract provided.

Behavioral Improvements Following Lesion Resection For Pediatric Epilepsy: Pediatric Psychosurgery?, Huy Dang, Abdul Basit Khan, Nisha Gadgil, Himanshu Sharma, Cristina Trandafir, Fatema Malbari, Howard L Weiner

Faculty, Staff and Students Publications

Introduction: Resection of brain lesions associated with refractory epilepsy to achieve seizure control is well accepted. However, concurrent behavioral effects of these lesions such as changes in mood, personality, and cognition and the effects of surgery on behavior have not been well characterized. We describe 5 such children with epileptogenic lesions and significant behavioral abnormalities which improved after surgery.

Case descriptions: Five children (ages 3-14 years) with major behavioral abnormalities and lesional epilepsy were identified and treated at our center. Behavioral problems included academic impairment, impulsivity, self-injurious behavior, and decreased social interaction with diagnoses of ADHD, oppositional defiant disorder, and …

Future Directions In Psychiatric Neurosurgery: Proceedings Of The 2022 American Society For Stereotactic And Functional Neurosurgery Meeting On Surgical Neuromodulation For Psychiatric Disorders, Frederick L Hitti, Alik S Widge, Patricio Riva-Posse, Donald A Malone, Michael S Okun, Maryam M Shanechi, Kelly D Foote, Sarah H Lisanby, Elizabeth Ankudowich, Srinivas Chivukula, Edward F Chang, Aysegul Gunduz, Clement Hamani, Ashley Feinsinger, Cynthia S Kubu, Winston Chiong, Jennifer A Chandler, Rafael Carbunaru, Binith Cheeran, Robert S Raike, Rachel A Davis, Casey H Halpern, Nora Vanegas-Arroyave, Dejan Markovic, Sarah K Bick, Cameron C Mcintyre, R Mark Richardson, Darin D Dougherty, Brian H Kopell, Jennifer A Sweet, Wayne K Goodman, Sameer A Sheth, Nader Pouratian

Faculty, Staff and Students Publications

OBJECTIVE: Despite advances in the treatment of psychiatric diseases, currently available therapies do not provide sufficient and durable relief for as many as 30-40% of patients. Neuromodulation, including deep brain stimulation (DBS), has emerged as a potential therapy for persistent disabling disease, however it has not yet gained widespread adoption. In 2016, the American Society for Stereotactic and Functional Neurosurgery (ASSFN) convened a meeting with leaders in the field to discuss a roadmap for the path forward. A follow-up meeting in 2022 aimed to review the current state of the field and to identify critical barriers and milestones for progress. …

Postsurgical Morbidity And Mortality Favorably Informs Deep Brain Stimulation For New Indications Including Schizophrenia And Schizoaffective Disorder, Judith M Gault, Patrick Hosokawa, Daniel Kramer, Elyn R Saks, Paul S Appelbaum, John A Thompson, Ann Olincy, Nicola Cascella, Akira Sawa, Wayne Goodman, Nidal Moukaddam, Sameer A Sheth, William S Anderson, Rachel A Davis

Faculty, Staff and Students Publications

BACKGROUND: Deep brain stimulation (DBS) shows promise for new indications like treatment-refractory schizophrenia in early clinical trials. In the first DBS clinical trial for treatment refractory schizophrenia, despite promising results in treating psychosis, one of the eight subjects experienced both a symptomatic hemorrhage and an infection requiring device removal. Now, ethical concerns about higher surgical risk in schizophrenia/schizoaffective disorder (SZ/SAD) are impacting clinical trial progress. However, insufficient cases preclude conclusions regarding DBS risk in SZ/SAD. Therefore, we directly compare adverse surgical outcomes for all surgical procedures between SZ/SAD and Parkinson's disease (PD) cases to infer relative surgical risk relevant to …

Cerebellar High-Grade Glioma: A Translationally Oriented Review Of The Literature, Ashley L B Raghu, Jason A Chen, Pablo A Valdes, Walid Ibn Essayed, Elizabeth Claus, Omar Arnaout, Timothy R Smith, E Antonio Chiocca, Pier Paolo Peruzzi, Joshua D Bernstock

Faculty, Staff and Student Publications

World Health Organization (WHO) grade 4 gliomas of the cerebellum are rare entities whose understanding trails that of their supratentorial counterparts. Like supratentorial high-grade gliomas (sHGG), cerebellar high-grade gliomas (cHGG) preferentially affect males and prognosis is bleak; however, they are more common in a younger population. While current therapy for cerebellar and supratentorial HGG is the same, recent molecular analyses have identified features and subclasses of cerebellar tumors that may merit individualized targeting. One recent series of cHGG included the subclasses of (1) high-grade astrocytoma with piloid features (HGAP, ~31% of tumors); (2) H3K27M diffuse midline glioma (~8%); and (3) …

Lipid-Nanoparticle-Mediated Delivery Of Docetaxel Prodrug For Exploiting Full Potential Of Gold Nanoparticles In The Treatment Of Pancreatic Cancer, Abdulaziz Alhussan, Nolan Jackson, Sarah Eaton, Nancy Dos Santos, Ingrid Barta, Josh Zaifman, Sam Chen, Yuen Yi C Tam, Sunil Krishnan, Devika B Chithrani

Faculty, Staff and Student Publications

Current chemoradiation therapy suffers from normal tissue toxicity. Thus, we are proposing incorporating gold nanoparticles (GNPs) and docetaxel (DTX), as they have shown very promising synergetic radiosensitization effects. Here, we explored the effect of a DTX prodrug encapsulated in lipid nanoparticles (LNP_DTX-P) on GNP uptake in pancreatic cancer models in vitro and in vivo. For the in vitro experiment, a pancreatic cancer cell line, MIA PaCa-2, was cultured and dosed with 1 nM GNPs and 45 nM free DTX or an equivalent dose of LNP_DTX-P. For the in vivo experiment, MIA PaCa-2 cells were implanted subcutaneously …

A General Catalyst Controlled Route To Prostaglandin F2a, Laura Cunningham, Sourabh Mishra, Leon Matthews, Stephen P Fletcher

Faculty, Staff and Student Publications

We report a general, catalyst-controlled route to prostaglandin F2_α and its analogues. The approach uses a Rh-catalyzed dynamic kinetic asymmetric Suzuki–Miyaura coupling reaction between a racemic bicyclic allyl chloride and alkenyl boronic esters bearing chiral alcohols to give cyclopentyl intermediates bearing 3 contiguous stereocenters. The route provides advanced intermediates in 99% ee as a single diastereoisomer in all cases examined, with the absolute stereochemistry of the cyclopentane core controlled by the ligand. Intermediates that could be used to produce prostaglandin analogues such as bimatoprost, latanoprost, fluprostenol, and cloprostenol were synthesized. The final two stereocenters were installed via Pd-catalyzed Tsuji–Trost …

Sources Of Calcium At Connexin 36 Gap Junctions In The Retina, Pui Man Rosalind Lai, Jee-Yeon Ryu, Sang-Cheol Park, Bradley A Gross, Lawrence D Dickinson, Sarajune Dagen, Mohammad Ali Aziz-Sultan, Alan S Boulos, Daniel L Barrow, H Hunt Batjer, Spiros Blackburn, Edward F Chang, P Roc Chen, Geoffrey P Colby, Garth Rees Cosgrove, Carlos A David, Arthur L Day, Kai U Frerichs, Mika Niemela, Steven G Ojemann, Nirav J Patel, Xiangen Shi, Edison P Valle-Giler, Anthony C Wang, Babu G Welch, Edie E Zusman, Scott T Weiss, Rose Du

Faculty, Staff and Student Publications

Background and Objectives

While somatic mutations have been well-studied in cancer, their roles in other complex traits are much less understood. Our goal is to identify somatic variants that may contribute to the formation of saccular cerebral aneurysms.

Methods

We performed whole-exome sequencing on aneurysm tissues and paired peripheral blood. RNA sequencing and the CRISPR/Cas9 system were then used to perform functional validation of our results.

Results

Somatic variants involved in supervillin (SVIL) or its regulation were found in 17% of aneurysm tissues. In the presence of a mutation in the SVIL gene, the expression level of SVIL …

Intraoperative Localization And Preservation Of Reading In Ventral Occipitotemporal Cortex, Oscar Woolnough, Kathryn M Snyder, Cale W Morse, Meredith J Mccarty, Samden D Lhatoo, Nitin Tandon

Faculty, Staff and Student Publications

OBJECTIVE: Resective surgery in language-dominant ventral occipitotemporal cortex (vOTC) carries the risk of causing impairment to reading. Because it is not on the lateral surface, it is not easily accessible for intraoperative mapping, and extensive stimulation mapping can be time-consuming. Here the authors assess the feasibility of using task-based electrocorticography (ECoG) recordings intraoperatively to help guide stimulation mapping of reading in vOTC.

METHODS: In 11 patients undergoing extraoperative, intracranial seizure mapping, the authors recorded induced broadband gamma activation (70-150 Hz) during a visual category localizer. In 2 additional patients, whose pathologies necessitated resections in language-dominant vOTC, task-based functional mapping was …

Uncloaking Cell-Impermeant Gold Nanorods Via Tumor Microenvironmental Cathepsin B Facilitates Cancer Cell Penetration And Potent Radiosensitization, Subhiksha Raghuram, Yuri Mackeyev, Jessica Symons, Yasmin Zahra, Valeria Gonzalez, Krishnan K Mahadevan, Katherinne I Requejo, Anton Liopo, Paul Derry, Eugene Zubarev, Onur Sahin, Joseph Byung-Kyu Kim, Pankaj K Singh, Sang Hyun Cho, Sunil Krishnan

Faculty, Staff and Student Publications

Major impediments to conveyance of intravenously administered drugs to tumors are biofouling, opsonization, and rapid clearance from the circulation by macrophages and reticuloendothelial phagocytes. Cloaking nanoparticles with stealth epilayers partly overcomes these hurdles but it also foils interactions with tumor cells. Here, we describe the synthesis, characterization, and validation of smart gold nanorods (GNRs) that spontaneously transform from inert passengers in the blood stream to active cell-penetrating nanoparticles within tumors to potently sensitize tumors to radiation therapy. Intrinsically cationic and cell-penetrating GNRs were shielded from phagocytosis with a cloaking polyethylene glycol epilayer containing an intervening cleavable peptide. In the absence …

A Phase Ii Randomized Double Blinded Trial Evaluating The Efficacy Of Curcumin With Pre-Operative Chemoradiation For Rectal Cancer, Jillian R Gunther, Awalpreet S Chadha, Sushovan Guha, Gottumukkala S Raju, Dipen M Maru, Mark F Munsell, Yan Jiang, Peiying Yang, Edd Felix, Marilyn Clemons, Geena George Mathew, Pankaj K Singh, John M Skibber, Miguel A Rodriguez-Bigas, George J Chang, Cathy Eng, Marc E Delclos, Christopher H Crane, Prajnan Das, Sunil Krishnan

Faculty, Staff and Student Publications

Background

In vivo studies demonstrate that curcumin increases radioresponse of colorectal cancers. To demonstrate efficacy in humans, we performed a randomized double-blind study of locally advanced rectal cancer (LARC) patients receiving pre-operative chemoradiation therapy (CRT) ± curcumin. We used pathologic complete response (pCR) rate as a surrogate for clinical outcome.

Methods

From 2008–2010, LARC patients were randomized to placebo/curcumin in a 1:2 ratio. Patients received CRT [50.4 gray in 28 fractions; capecitabine (825 mg/m² twice daily)] followed by surgery. Curcumin (4 grams orally, twice daily) or placebo was given throughout CRT and 6 weeks afterward. Toxicity was monitored weekly. …

Endovascular Repair Of Intercostal Patch Aneurysms In A Patient With Loyes-Dietz Syndrome, Guilherme B Lima, Laura Ocasio, Marina Dias-Neto, Emanuel R Tenorio, Thanila A Macedo, Gustavo S Oderich

Faculty, Staff and Student Publications

No abstract provided.

Scale-Up Of A Rh-Catalyzed Asymmetric Sp3–Sp2 Suzuki–Miyaura-Type Reaction, Laura Cunningham, Mireia Sidera Portela, Stephen P Fletcher

Faculty, Staff and Student Publications

Csp²–Csp² Suzuki–Miyaura couplings (SMCs) are ubiquitous in the synthesis of small molecules, but analogous Csp²–Csp³ bond-forming SMCs are rare, especially asymmetric variants. Recently, we developed a series of Rh-catalyzed couplings between racemic sp³-hybridized allyl chlorides and heteroaryl boronic acids. Here, we demonstrate that these catalytic asymmetric reactions can be scaled-up to give over 100 g of a product. The reaction we chose to test couples a heteroaromatic boronic acid derivative and a racemic bicyclic electrophile to give a product with three contiguous stereogenic centers. The SMC product was obtained as a single …

Pancreatic Tumor Microenvironmental Acidosis And Hypoxia Transform Gold Nanorods Into Cell-Penetrant Particles For Potent Radiosensitization, Pradipta Ranjan Rauta, Yuri Mackeyev, Keith Sanders, Joseph B K Kim, Valeria V Gonzalez, Yasmin Zahra, Muhammad A Shohayeb, Belal Abousaida, Geraldine V Vijay, Okan Tezcan, Paul Derry, Anton V Liopo, Eugene R Zubarev, Rickey Carter, Pankaj Singh, Sunil Krishnan

Faculty, Staff and Student Publications

Coating nanoparticles with stealth epilayers increases circulation time by evading opsonization, macrophage phagocytosis, and reticuloendothelial sequestration. However, this also reduces internalization by cancer cells upon reaching the tumor. We designed gold nanorods (GNRs) with an epilayer that retains stealth properties in circulation but transforms spontaneously in the acidotic tumor microenvironment to a cell-penetrating particle. We used a customized stoichiometric ratio of l-glutamic acid and l-lysine within an amphiphilic polymer of poly(l-glutamic acid-co-l-lysine), or P(Glu-co-Lys), to effect this transformation in acidotic environments. P(Glu-co-Lys)-GNRs were internalized by cancer cells to facilitate potent in vitro radiosensitization. When administered intravenously in mice, they accumulate …

Antibody-Drug Conjugates For The Treatment Of Her2-Positive Breast Cancer, Mariana K Najjar, Sara G Manore, Angelina T Regua, Hui-Wen Lo

Faculty, Staff and Student Publications

Human epidermal growth factor receptor 2 (HER2) receptor tyrosine kinase is overexpressed in 20–30% of breast cancers and is associated with poor prognosis and worse overall patient survival. Most women with HER2-positive breast cancer receive neoadjuvant chemotherapy plus HER2-targeted therapies. The development of HER2-directed therapeutics is an important advancement in targeting invasive breast cancer. Despite the efficacy of anti-HER2 monoclonal antibodies, they are still being combined with adjuvant chemotherapy to improve overall patient outcomes. Recently, significant progress has been made towards the development of a class of therapeutics known as antibody-drug conjugates (ADCs), which leverage the high specificity of HER2-targeted …

Venous Sinus Stenting For Low Pressure Gradient Stenoses In Idiopathic Intracranial Hypertension, Mehmet Enes Inam, Juan Carlos Martinez-Gutierrez, Matthew J Kole, Francisco Sanchez, Elvira Lekka, Van Thi Thanh Truong, Victor Lopez-Rivera, Faheem G Sheriff, Laura A Zima, Claudia Pedroza, Rosa Tang, Ore-Ofe Adesina, Allison Engstrom, Sunil A Sheth, Peng Roc Chen

Faculty, Staff and Student Publications

BACKGROUND: Medically refractory idiopathic intracranial hypertension (IIH) is frequently treated with venous sinus stenosis stenting with high success rates. Patient selection has been driven almost exclusively by identification of supraphysiological venous pressure gradients across stenotic regions based on theoretical assessment of likelihood of response.

OBJECTIVE: To explore the possibility of benefit in low venous pressure gradient patients.

METHODS: Using a single-center, prospectively maintained registry of patients with IIH undergoing venous stenting, we defined treatment groups by gradient pressures of ≤4, 5 to 8, and >8 mmHg based on the most frequently previously published thresholds for stenting. Baseline demographics, clinical, and …

Ten-Year Review Of Antihypertensive Prescribing Practices After Stroke And The Associated Disparities From The Florida Stroke Registry, Amanda J Taylor, Jung Hwan Kim, David Ress

Faculty, Staff and Student Publications

The hemodynamic response function (HRF) measured with functional magnetic resonance imaging is generated by vascular and metabolic responses evoked by brief (<4 s) stimuli. It is known that the human HRF varies across cortex, between subjects, with stimulus paradigms, and even between different measurements in the same cortical location. However, our results demonstrate that strong HRFs are remarkably repeatable across sessions separated by time intervals up to 3 months. In this study, a multisensory stimulus was used to activate and measure the HRF across the majority of cortex (>70%, with lesser reliability observed in some areas of prefrontal cortex). HRFs were measured with high spatial resolution (2‐mm voxels) in central gray matter to minimize variations caused by partial‐volume effects. HRF amplitudes and temporal dynamics were highly repeatable across four sessions in 20 subjects. Positive and negative HRFs were consistently observed across sessions and subjects. Negative HRFs were generally weaker and, thus, more variable than positive HRFs. Statistical measurements showed that across‐session variability is highly correlated to …

Wide-Necked Middle Cerebral Artery Aneurysm Clipping Following Failed Occlusion After Woven Endobridge Placement: 2-Dimensional Operative Video, Stephen Capone, Anil Roy, Matthew Kole, Spiros L Blackburn

Faculty, Staff and Student Publications

No abstract provided.

Testing A Behavioral Activation Gaming App For Depression During Pregnancy: Multimethod Pilot Study, Philipp Karschnia, Jacob S Young, Antonio Dono, Levin Häni, Stephanie T Juenger, Tommaso Sciortino, Francesco Bruno, Nico Teske, Ramin A Morshed, Alexander F Haddad, Yalan Zhang, Sophia Stoecklein, Michael A Vogelbaum, Juergen Beck, Nitin Tandon, Shawn Hervey-Jumper, Annette M Molinaro, Roberta Rudà, Lorenzo Bello, Oliver Schnell, Yoshua Esquenazi, Maximilian I Ruge, Stefan J Grau, Martin Van Den Bent, Michael Weller, Mitchel S Berger, Susan M Chang, Joerg-Christian Tonn

Faculty, Staff and Student Publications

In IDH-wildtype glioblastomas which meet the histopathological or molecular diagnosis criteria, it remains unclear whether the presence of TERT promotor mutations provides additional prognostic information. Based on a multicenter cohort of 466 IDH-wildtype glioblastomas (including 396 with and 70 patients without TERT promotor mutations), we found that TERT promotor mutations were neither associated with progression-free survival nor overall survival. This held true in various treatment-based or molecular subgroups. This argues against standardized analysis for TERT promotor mutation status for the purpose of prognostic or therapeutic relevance in newly diagnosed IDH-wildtype glioblastoma that otherwise meets the histopathological and …

The Complex Relationship Between Integrins And Oncolytic Herpes Simplex Virus 1 In High-Grade Glioma Therapeutics, Kimberly Ann Rivera-Caraballo, Mitra Nair, Tae Jin Lee, Balveen Kaur, Ji Young Yoo

Faculty, Staff and Student Publications

High-grade gliomas (HGGs) are lethal central nervous system tumors that spread quickly through the brain, making treatment challenging. Integrins are transmembrane receptors that mediate cell-extracellular matrix (ECM) interactions, cellular adhesion, migration, growth, and survival. Their upregulation and inverse correlation in HGG malignancy make targeting integrins a viable therapeutic option. Integrins also play a role in herpes simplex virus 1 (HSV-1) entry. Oncolytic HSV-1 (oHSV) is the most clinically advanced oncolytic virotherapy, showing a superior safety and efficacy profile over standard cancer treatment of solid cancers, including HGG. With the FDA-approval of oHSV for melanoma and the recent conditional approval of …

Patterns Of Failure After Radiation Therapy In Primary Spinal High-Grade Gliomas: A Single Institutional Analysis, Rituraj Upadhyay, Swapnil Khose, Halyna Pokhylevych, Arnold C Paulino, Mary Frances Mcaleer, Amol Ghia, Jing Li, Debra Nana Yeboa, Monica Loghin, Rebecca Harrison, Barbara O'Brien, Carlos Kamiya-Matsuoka, John De Groot, Vinay K Puduvalli, Claudio Tatsui, Christopher Alvarez-Breckenridge, Sujit Prabhu, Larry Rhines, Wafik Zaky, Frank Lin, Jeffery S Weinberg, Gregory Fuller, David I Sandberg, Jason Michael Johnson, Susan L Mcgovern

Faculty, Staff and Student Publications

Background

Primary spinal high-grade gliomas (S-HGG) are rare aggressive tumors; radiation therapy (RT) often plays a dominant role in management. We conducted a single-institution retrospective review to study the clinicopathological features and management of S-HGGs.

Methods

Patients with biopsy-proven S-HGG who received RT from 2001 to 2020 were analyzed for patient, tumor, and treatment characteristics. Kaplan–Meier estimates were used for survival analyses.

Results

Twenty-nine patients were identified with a median age of 25.9 years (range 1–74 y). Four patients had GTR while 25 underwent subtotal resection or biopsy. All patients were IDH wildtype and MGMT-promoter unmethylated, where available. H3K27M mutation …

Asymmetric Synthesis Of Nortropanes Via Rh-Catalyzed Allylic Arylation, Yan Zhang, F Wieland Goetzke, Kirsten E Christensen, Stephen P Fletcher

Faculty, Staff and Student Publications

Tropane derivatives are extensively used in medicine, but catalytic asymmetric methods for their synthesis are underexplored. Here, we report Rh-catalyzed asymmetric Suzuki–Miyaura-type cross-coupling reactions between a racemic N-Boc-nortropane-derived allylic chloride and (hetero)aryl boronic esters. The reaction proceeds via an unexpected kinetic resolution, and the resolved enantiopure allyl chloride can undergo highly enantiospecific reactions with N-, O-, and S-containing nucleophiles. The method was applied in a highly stereoselective formal synthesis of YZJ-1139(1), a potential insomnia treatment that recently completed Phase II clinical trials. Our report represents an asymmetric catalytic method for the synthesis of YZJ-1139(1) and related compounds.

Tale Of Two Cities: Narrative Review Of Oxygen, Sung-Ho Ahn, Angela Burkett, Atzhiry Paz, Jude P Savarraj, Sarah Hinds, Georgene Hergenroeder, Aaron M Gusdon, Xuefeng Ren, Jeong-Ho Hong, Huimahn A Choi

Faculty, Staff and Student Publications

BACKGROUND: Cerebral edema (CE) at admission is a surrogate marker of 'early brain injury' (EBI) after subarachnoid hemorrhage (SAH). Only recently has the focus on the changes in CE after SAH such as delayed resolution or newly developed CE been examined. Among several factors, an early systemic inflammatory response has been shown to be associated with CE. We investigate inflammatory markers in subjects with early CE which does not resolve, i.e., persistent CE after SAH.

METHODS: Computed tomography scans of SAH patients were graded at admission and at 7 days after SAH for CE using the 0-4 'subarachnoid hemorrhage early …

Dual Leucine Zipper Kinase Regulates Dscam Expression Through A Noncanonical Function Of The Cytoplasmic Poly(A)-Binding Protein, Monika Singh, Bing Ye, Jung Hwan Kim

Faculty, Staff and Student Publications

Dual leucine zipper kinase (DLK) plays a pivotal role in the development, degeneration, and regeneration of neurons. DLK can regulate gene expression post-transcriptionally, but the underlying mechanism remains poorly understood. The Drosophila DLK, Wallenda (Wnd), regulates the expression of Down syndrome cell adhesion molecule (Dscam) to control presynaptic arbor growth. This regulation is mediated by the 3′ untranslated region (3′UTR) of Dscam mRNA, which suggests that RNA binding proteins (RBPs) mediate DLK function. We performed a genome-wide cell-based RNAi screen of RBPs and identified the cytoplasmic poly(A)-binding protein, pAbp, as an RBP that mediates Wnd-induced increase in Dscam expression. Genetic …

Event-Related Phase Synchronization Propagates Rapidly Across Human Ventral Visual Cortex, Oscar Woolnough, Kiefer J Forseth, Patrick S Rollo, Zachary J Roccaforte, Nitin Tandon

Faculty, Staff and Student Publications

Visual inputs to early visual cortex integrate with semantic, linguistic and memory inputs in higher visual cortex, in a manner that is rapid and accurate, and enables complex computations such as face recognition and word reading. This implies the existence of fundamental organizational principles that enable such efficiency. To elaborate on this, we performed intracranial recordings in 82 individuals while they performed tasks of varying visual and cognitive complexity. We discovered that visual inputs induce highly organized posterior-to-anterior propagating patterns of phase modulation across the ventral occipitotemporal cortex. At individual electrodes there was a stereotyped temporal pattern of phase progression …

Magnetically Recoverable Silica-Decorated Ferromagnetic-Nanoceria Nanocatalysts And Their Use With O- And N-Butyloxycarbonylation Reaction Via Solvent-Free Condition, Shripad M Patil, Runjhun Tandon, Nitin Tandon

Faculty, Staff and Student Publications

Silica-decorated ferrite nanoparticles, a new kind, coated with ceric ammonium nitrate (CAN), have been prepared successfully by simple coprecipitation techniques. Powder X-ray diffraction spectroscopy (PXRD), Fourier transform-infrared spectroscopy (FT-IR), field emission-scanning electron microscope (FE-SEM), wavelength-dispersive X-ray spectroscopy (WDX), energy-dispersive spectroscopy (EDS), inductive coupled plasma-optical emission spectroscopy (ICP-OES), and thermogravimetric analysis (TGA) techniques were used to characterize these nanoparticles. The catalysts are further studied for catalytic activity in solvent-free conditions. Importantly, these nanoparticles have been collected from the reaction mixture using an external magnet and recycled up to minimum of 15 cycles with no substantial loss of catalytic characteristics.

Glyoxal Fixation Is Optimal For Immunostaining Of Brain Vessels, Pericytes And Blood-Brain Barrier Proteins, Sithara Thomas, Jayanarayanan Sadanandan, Spiros L Blackburn, Devin W Mcbride, Ari Dienel, Sungha Hong, Hussein A Zeineddine, Peeyush Kumar Thankamani

Faculty, Staff and Student Publications

Brain vascular staining is very important for understanding cerebrovascular pathologies. 4% paraformaldehyde is considered the gold standard fixation technique for immunohistochemistry and it revolutionized the examination of proteins in fixed tissues. However, this fixation technique produces inconsistent immunohistochemical staining results due to antigen masking. Here, we test a new fixation protocol using 3% glyoxal and demonstrate that this method improves the staining of the brain vasculature, pericytes, and tight junction proteins compared to 4% paraformaldehyde. Use of this new fixation technique will provide more detailed information about vascular protein expressions, their distributions, and colocalizations with other proteins at the molecular …