Neurosurgery Commons^™

It's Not That We Care Less: Insights Into Health Care Utilization For Comorbid Diabetes And Depression Among Latinos, Sharon Borja, Miriam G Valdovinos, Kenia M Rivera, Natalia Giraldo-Santiago, Robin E Gearing, Luis R Torres

Faculty, Staff and Student Publications

Despite robust knowledge regarding the socio-economic and cultural factors affecting Latino* access to healthcare, limited research has explored service utilization in the context of comorbid conditions like diabetes and depression. This qualitative study, embedded in a larger mixed-methods project, aimed to investigate perceptions held by Latinos and their social support systems (i.e., family members) regarding comorbid diabetes and depression and to identify barriers and facilitators to their help-seeking behaviors and treatment engagement. Bilingual and bicultural researchers conducted eight focus groups with 94 participants in a large U.S. metropolitan area and were primarily conducted in Spanish. The participants either had a …

Important Features For Protein Foldings In Two Acyl Carrier Proteins From Enterococcus Faecalis, Seoyeong Yoo, Jiwon Yeon, Eunhee Kim, Yangmee Kim

Faculty, Staff and Student Publications

The emergence of multi-drug resistant Enterococcus faecalis raises a serious threat to global public health. E. faecalis is a gram-positive intestinal commensal bacterium found in humans. E. faecalis can endure extreme environments such as high temperature, pressure, and high salt, which facilitates them to cause infection in hospitals. E. faecalis has two acyl carrier proteins, AcpA (EfAcpA) in de novo fatty acid synthesis (FAS) and AcpB (EfAcpB) which utilizes exogenous fatty acids. Previously, we determined the tertiary structures of these two ACPs and investigated their structure-function relationships. Solution structures revealed that overall folding of these two ACPs is similar to …

Intratumoral Biosynthesis Of Gold Nanoclusters By Pancreatic Cancer To Overcome Delivery Barriers To Radiosensitization, Aaron S Schwartz-Duval, Yuri Mackeyev, Iqbal Mahmud, Philip L Lorenzi, Mihai Gagea, Sunil Krishnan, Konstantin V Sokolov

Faculty, Staff and Student Publications

Nanoparticle delivery to solid tumors is a prime challenge in nanomedicine. Here, we approach this challenge through the lens of biogeochemistry, the field that studies the flow of chemical elements within ecosystems as manipulated by living cellular organisms and their environments. We leverage biogeochemistry concepts related to gold cycling against pancreatic cancer, considering mammalian organisms as drivers for gold nanoparticle biosynthesis. Sequestration of gold nanoparticles within tumors has been demonstrated as an effective strategy to enhance radiotherapy; however, the desmoplasia of pancreatic cancer impedes nanoparticle delivery. Our strategy overcomes this barrier by applying an atomic-scale agent, ionic gold, for intratumoral …

The Geriatric Nutritional Risk Index As A Predictor Of Complications In Geriatric Trauma Patients, Daniel H Wang, Yoko Fujita, Antonio Dono, Ana G Rodriguez Armendariz, Mauli Shah, Nagireddy Putluri, Pavel S Pichardo-Rojas, Chirag B Patel, Jay-Jiguang Zhu, Jason T Huse, Brittany C Parker Kerrigan, Frederick F Lang, Yoshua Esquenazi, Leomar Y Ballester

Faculty, Staff and Student Publications

Cerebrospinal fluid (CSF) analysis is underutilized in patients with glioblastoma (GBM), partly due to a lack of studies demonstrating the clinical utility of CSF biomarkers. While some studies show the utility of CSF cell-free DNA analysis, studies analyzing CSF metabolites in patients with glioblastoma are limited. Diffuse gliomas have altered cellular metabolism. For example, mutations in isocitrate dehydrogenase enzymes (e.g., IDH1 and IDH2) are common in diffuse gliomas and lead to increased levels of D-2-hydroxyglutarate in CSF. However, there is a poor understanding of changes CSF metabolites in GBM patients. In this study, we performed targeted metabolomic analysis of CSF …

Surgical Management Of Choanal Atresia: Two Classic Cases And Review Of The Literature, Philipp Karschnia, Jorg Dietrich, Francesco Bruno, Antonio Dono, Stephanie T Juenger, Nico Teske, Jacob S Young, Tommaso Sciortino, Levin Häni, Martin Van Den Bent, Michael Weller, Michael A Vogelbaum, Ramin A Morshed, Alexander F Haddad, Annette M Molinaro, Nitin Tandon, Juergen Beck, Oliver Schnell, Lorenzo Bello, Shawn Hervey-Jumper, Niklas Thon, Stefan J Grau, Yoshua Esquenazi, Roberta Rudà, Susan M Chang, Mitchel S Berger, Daniel P Cahill, Joerg-Christian Tonn

Faculty, Staff and Student Publications

BACKGROUND: Resection of the contrast-enhancing (CE) tumor represents the standard of care in newly diagnosed glioblastoma. However, some tumors ultimately diagnosed as glioblastoma lack contrast enhancement and have a 'low-grade appearance' on imaging (non-CE glioblastoma). We aimed to (a) volumetrically define the value of non-CE tumor resection in the absence of contrast enhancement, and to (b) delineate outcome differences between glioblastoma patients with and without contrast enhancement.

METHODS: The RANO resect group retrospectively compiled a global, eight-center cohort of patients with newly diagnosed glioblastoma per WHO 2021 classification. The associations between postoperative tumor volumes and outcome were analyzed. Propensity score-matched …

Phase 1 Trial Of Tpi 287, A Microtubule Stabilizing Agent, In Combination With Bevacizumab In Adults With Recurrent Glioblastoma, Samuel A Goldlust, Louis B Nabors, Sigmund Hsu, Nimish Mohile, Paul J Duic, Tara Benkers, Samuel Singer, Mayank Rao, Lori Cappello, Sandra L Silberman, George Farmer

Faculty, Staff and Student Publications

BACKGROUND: Recurrent glioblastoma (rGBM) has limited treatment options. This phase 1 protocol was designed to study the safety and preliminary efficacy of TPI 287, a central nervous system penetrant microtubule stabilizer, in combination with bevacizumab (BEV) for the treatment of rGBM.

METHODS: GBM patients with up to 2 prior relapses without prior exposure to anti-angiogenic therapy were eligible. A standard 3 + 3 design was utilized to determine the maximum tolerated dose (MTD) of TPI 287. Cohorts received TPI 287 at 140-220 mg/m

RESULTS: Twenty-four patients were enrolled at 6 centers. Treatment was generally well tolerated. Fatigue, myelosuppression, and peripheral …

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 …

Updates Of The Role Of B-Cells In Ischemic Stroke, Silin Wu, Sidra Tabassum, Cole T Payne, Heng Hu, Aaron M Gusdon, Huimahn A Choi, Xuefang S Ren

Faculty, Staff and Student Publications

Ischemic stroke is a major disease causing death and disability in the elderly and is one of the major diseases that seriously threaten human health and cause a great economic burden. In the early stage of ischemic stroke, neuronal structure is destroyed, resulting in death or damage, and the release of a variety of damage-associated pattern molecules induces an increase in neuroglial activation, peripheral immune response, and secretion of inflammatory mediators, which further exacerbates the damage to the blood-brain barrier, exacerbates cerebral edema, and microcirculatory impairment, triggering secondary brain injuries. After the acute phase of stroke, various immune cells initiate …

Mir-29 And Mir-140 Regulate Trail-Induced Drug Tolerance In Lung Cancer, Suyeon Kim, Ki Wook Lee, Yongjin Yoo, Sang Hee Park, Ji Won Lee, Suhyun Jeon, Shaginyan Illia, Pooja Joshi, Hyun Woo Park, Han-En Lo, Jimin Seo, Yeonwoo Kim, Min Chang, Tae Jin Lee, Jong Bae Seo, Sung-Hak Kim, Carlo M Croce, Inki Kim, Sung-Suk Suh, Young-Jun Jeon

Faculty, Staff and Student Publications

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has chemotherapeutic potential as a regulator of an extrinsic apoptotic ligand, but its effect as a drug is limited by innate and acquired resistance. Recent findings suggest that an intermediate drug tolerance could mediate acquired resistance, which has made the main obstacle for limited utility of TRAIL as an anti-cancer therapeutics. We propose miRNA-dependent epigenetic modification drives the drug tolerant state in TRAIL-induced drug tolerant (TDT). Transcriptomic analysis revealed miR-29 target gene activation in TDT cells, showing oncogenic signature in lung cancer. Also, the restored TRAIL-sensitivity was associated with miR-29ac and 140-5p expressions, which …

Coronary Laser With Simultaneous Contrast Injection For The Treatment Of Stent Underexpansion, Mohsen Mohandes, Alberto Pernigotti, Cristina Moreno, Luis Mauricio Torres, Francisco Fernández, Diego Zambrano, Alfredo Bardají

Faculty, Staff and Student Publications

BACKGROUND: Stent underexpansion is a challenge in interventional cardiology. Some off-label treatments, such as rotational atherectomy, intravascular lithotripsy (IVL) and coronary lasing, have been used to overcome the problem. The purpose of this study is to evaluate the safety and efficacy of coronary laser atherectomy with simultaneous contrast injection and subsequent balloon dilation to optimize stent expansion.

METHODS: Coronary laser atherectomy with simultaneous contrast injection was used. After lasing, non-compliant balloon dilation at high pressure was performed to overcome the underexpanded point. The average increase in the minimum stent area (MSA) was measured by intravascular ultrasound (IVUS), and any complication …

Genetic Loss Of Mir-205 Causes Increased Mammary Gland Development, Alessandra Cataldo, Douglas G Cheung, John P Hagan, Matteo Fassan, Sukhinder Sandhu-Deol, Carlo M Croce, Gianpiero Di Leva, Marilena V Iorio

Faculty, Staff and Student Publications

MiRNAs play crucial roles in a broad spectrum of biological processes, both physiological and pathological. Different reports implicate miR-205 in the control of breast stem cell properties. Differential miR-205 expression has been observed in different stages of mammary gland development and maturation. However, a functional role in this process has not been clearly demonstrated. We generated an miR-205 knockout in the FVB/N mouse strain, which is viable and characterized by enhanced mammary gland development. Indeed, mammary glands of miR-205

Guidelines For Prehospital Management Of Traumatic Brain Injury 3rd Edition: Executive Summary, Gregory W J Hawryluk, Al Lulla, Randy Bell, Andy Jagoda, Halinder S Mangat, Bentley J Bobrow, Jamshid Ghajar

Faculty, Staff and Student Publications

Prehospital care markedly influences outcome from traumatic brain injury, yet it remains highly variable. The Brain Trauma Foundation's guidelines informing prehospital care, first published in 2002, have sought to identify and disseminate best practices. Many of its recommendations relate to the management of airway, breathing and circulation, and infrastructure for this care. Compliance with the second edition of these guidelines has been associated with significantly improved survival. A working group developed evidence-based recommendations informing assessment, treatment, and transport decision-making relevant to the prehospital care of brain injured patients. A literature search spanning May 2005 to January 2022 supplemented data contained …

Pharyngeal Oxygen Delivery Device Sustains Manikin Lung Oxygenation Longer Than High-Flow Nasal Cannula, Jeramie B Hanson, John R Williams, Emily H Garmon, Phillip M Morris, Russell K Mcallister, Courtney N Shaver, William C Culp

Faculty, Staff and Student Publications

PURPOSE: Hypoxemia during a failed airway scenario is life threatening. A dual-lumen pharyngeal oxygen delivery device (PODD) was developed to fit inside a traditional oropharyngeal airway for undisrupted supraglottic oxygenation and gas analysis during laryngoscopy and intubation. We hypothesized that the PODD would provide oxygen as effectively as high-flow nasal cannula (HFNC) while using lower oxygen flow rates.

METHODS: We compared oxygen delivery of the PODD to HFNC in a preoxygenated, apneic manikin lung that approximated an adult functional residual capacity. Four arms were studied: HFNC at 20 and 60 liters per minute (LPM) oxygen, PODD at 10 LPM oxygen, …

Correlations Between Mental Health, Physical Activity, And Body Composition In American College Students After The Covid-19 Pandemic Lockdown, Luis Torres, Manuela C Caciula, Alin S Tomoiaga, Carmen Gugu-Gramatopol

Faculty, Staff and Student Publications

Restrictions associated with the COVID-19 pandemic had forced American college students to significantly reduce their daily energy expenditure and increase their sedentary behaviors, thus presumably increasing mental health symptoms, decreasing physical activity levels, and enhancing the promotion of unhealthy eating habits. This study aimed to explore the correlations between mental health symptoms, physical activity levels, and body composition in college students in the years following the pandemic, focusing on the lingering effects of lockdown measures. American college students completed pre-existing, well-validated surveys for both mental health (Hospital Anxiety and Depression Scale) and physical activity (International Physical Activity Questionnaire—Long Form). Body …

Plasma Biomarkers For Brain Injury In Extracorporeal Membrane Oxygenation, Shrey Kapoor, Anna Kolchinski, Aaron M Gusdon, Lavienraj Premraj, Sung-Min Cho

Faculty, Staff and Student Publications

Extracorporeal membrane oxygenation (ECMO) is a life-saving intervention for patients with refractory cardiorespiratory failure. Despite its benefits, ECMO carries a significant risk of neurological complications, including acute brain injury (ABI). Although standardized neuromonitoring and neurological care have been shown to improve early detection of ABI, the inability to perform neuroimaging in a timely manner is a major limitation in the accurate diagnosis of neurological complications. Therefore, blood-based biomarkers capable of detecting ongoing brain injury at the bedside are of great clinical significance. This review aims to provide a concise review of the current literature on plasma biomarkers for ABI in …

Post-Zygotic Rescue Of Meiotic Errors Causes Brain Mosaicism And Focal Epilepsy, Katherine E Miller, Adithe C Rivaldi, Noriyuki Shinagawa, Sahib Sran, Jason B Navarro, Jesse J Westfall, Anthony R Miller, Ryan D Roberts, Yassmine Akkari, Rachel Supinger, Mark E Hester, Mohammad Marhabaie, Meethila Gade, Jinfeng Lu, Olga Rodziyevska, Meenakshi B Bhattacharjee, Gretchen K Von Allmen, Edward Yang, Hart G W Lidov, Chellamani Harini, Manish N Shah, Jeffrey Leonard, Jonathan Pindrik, Ammar Shaikhouni, James E Goldman, Christopher R Pierson, Diana L Thomas, Daniel R Boué, Adam P Ostendorf, Elaine R Mardis, Annapurna Poduri, Daniel C Koboldt, Erin L Heinzen, Tracy A Bedrosian

Faculty, Staff and Student Publications

Somatic mosaicism is a known cause of neurological disorders, including developmental brain malformations and epilepsy. Brain mosaicism is traditionally attributed to post-zygotic genetic alterations arising in fetal development. Here we describe post-zygotic rescue of meiotic errors as an alternate origin of brain mosaicism in patients with focal epilepsy who have mosaic chromosome 1q copy number gains. Genomic analysis showed evidence of an extra parentally derived chromosome 1q allele in the resected brain tissue from five of six patients. This copy number gain is observed only in patient brain tissue, but not in blood or buccal cells, and is strongly enriched …

The Tardigrade Damage Suppressor Protein Dsup Promotes Dna Damage In Neurons, Elliot Murphy, Kiefer J Forseth, Cristian Donos, Kathryn M Snyder, Patrick S Rollo, Nitin Tandon

Faculty, Staff and Student Publications

Language depends critically on the integration of lexical information across multiple words to derive semantic concepts. Limitations of spatiotemporal resolution have previously rendered it difficult to isolate processes involved in semantic integration. We utilized intracranial recordings in epilepsy patients (n = 58) who read written word definitions. Descriptions were either referential or non-referential to a common object. Semantically referential sentences enabled high frequency broadband gamma activation (70-150 Hz) of the inferior frontal sulcus (IFS), medial parietal cortex, orbitofrontal cortex (OFC) and medial temporal lobe in the left, language-dominant hemisphere. IFS, OFC and posterior middle temporal gyrus activity was modulated by …

A Genome-Wide Association Study Of Outcome After Aneurysmal Subarachnoid Haemorrhage: Discovery Analysis, Ben Gaastra, Sheila Alexander, Mark K Bakker, Hemant Bhagat, Philippe Bijlenga, Spiros L Blackburn, Malie K Collins, Sylvain Doré, Christoph J Griessenauer, Philipp Hendrix, Eun Pyo Hong, Isabel C Hostettler, Henry Houlden, Koji Iihara, Jin Pyeong Jeon, Bong Jun Kim, Jiang Li, Sandrine Morel, Paul Nyquist, Dianxu Ren, Ynte M Ruigrok, David Werring, Will Tapper, Ian Galea, Diederik Bulters

Faculty, Staff and Student Publications

Candidate gene studies have identified genetic variants associated with clinical outcomes following aneurysmal subarachnoid haemorrhage (aSAH), but no genome-wide association studies have been performed to date. Here we report the results of the discovery phase of a two-stage genome-wide meta-analysis of outcome after aSAH. We identified 157 independent loci harbouring 756 genetic variants associated with outcome after aSAH (p < 1 × 10⁻⁴), which require validation. A single variant (rs12949158), in SPNS2, achieved genome-wide significance (p = 4.29 × 10⁻⁸) implicating sphingosine-1-phosphate signalling in outcome after aSAH. A large multicentre international effort to recruit samples for validation …

Can Craniosynostosis Be Diagnosed On Physical Examination? A Retrospective Review, Carmen A Zavala, Laura A Zima, Matthew R Greives, Stephen A Fletcher, Manish N Shah, Brandon A Miller, David I Sandberg, Phuong D Nguyen

Faculty, Staff and Student Publications

Craniosynostosis is a developmental craniofacial defect in which one or more sutures of the skull fuse together prematurely. Uncorrected craniosynostosis may have serious complications including elevated intracranial pressure, developmental delay, and blindness. Proper diagnosis of craniosynostosis requires a physical examination of the head with assessment for symmetry and palpation of sutures for prominence. Often, if craniosynostosis is suspected, computed tomography (CT) imaging will be obtained. Recent literature has posited that this is unnecessary. This study aims to address whether physical examination alone is sufficient for the diagnosis and treatment planning of single suture craniosynostosis. Between 2015 and 2022, the Divisions …

Endogenous Fluctuations In Cortical State Selectively Enhance Different Modes Of Sensory Processing In Human Temporal Lobe, Arun Parajuli, Diego Gutnisky, Nitin Tandon, Valentin Dragoi

Faculty, Staff and Student Publications

The degree of synchronized fluctuations in neocortical network activity can vary widely during alertness. One influential idea that has emerged over the past few decades is that perceptual decisions are more accurate when the state of population activity is desynchronized. This suggests that optimal task performance may occur during a particular cortical state - the desynchronized state. Here we show that, contrary to this view, cortical state can both facilitate and suppress perceptual performance in a task-dependent manner. We performed electrical recordings from surface-implanted grid electrodes in the temporal lobe while human subjects completed two perceptual tasks. We found that …

Prognostic Evaluation Of Re-Resection For Recurrent Glioblastoma Using The Novel Rano Classification For Extent Of Resection: A Report Of The Rano Resect Group, Philipp Karschnia, Antonio Dono, Jacob S Young, Stephanie T Juenger, Nico Teske, Levin Häni, Tommaso Sciortino, Christine Y Mau, Francesco Bruno, Luis Nunez, Ramin A Morshed, Alexander F Haddad, Michael Weller, Martin Van Den Bent, Juergen Beck, Shawn Hervey-Jumper, Annette M Molinaro, Nitin Tandon, Roberta Rudà, Michael A Vogelbaum, Lorenzo Bello, Oliver Schnell, Stefan J Grau, Susan M Chang, Mitchel S Berger, Yoshua Esquenazi, Joerg-Christian Tonn

Faculty, Staff and Student Publications

BACKGROUND: The value of re-resection in recurrent glioblastoma remains controversial as a randomized trial that specifies intentional incomplete resection cannot be justified ethically. Here, we aimed to (1) explore the prognostic role of extent of re-resection using the previously proposed Response Assessment in Neuro-Oncology (RANO) classification (based upon residual contrast-enhancing (CE) and non-CE tumor), and to (2) define factors consolidating the surgical effects on outcome.

METHODS: The RANO resect group retrospectively compiled an 8-center cohort of patients with first recurrence from previously resected glioblastomas. The associations of re-resection and other clinical factors with outcome were analyzed. Propensity score-matched analyses were …

Abnormal Motion Capture In Acute Stroke (Bionics): A Low-Cost Tele-Evaluation Tool For Automated Assessment Of Upper Extremity Function In Stroke Patients, Syed A Zamin, Kaichen Tang, Emily A Stevens, Melissa Howard, Dorothea M Parker, Allyson Seals, Xiaoqian Jiang, Sean Savitz, Shayan Shams

Faculty, Staff and Student Publications

BACKGROUND: The incidence of stroke and stroke-related hemiparesis has been steadily increasing and is projected to become a serious social, financial, and physical burden on the aging population. Limited access to outpatient rehabilitation for these stroke survivors further deepens the healthcare issue and estranges the stroke patient demographic in rural areas. However, new advances in motion detection deep learning enable the use of handheld smartphone cameras for body tracking, offering unparalleled levels of accessibility.

METHODS: In this study we want to develop an automated method for evaluation of a shortened variant of the Fugl-Meyer assessment, the standard stroke rehabilitation scale …

Brain Imaging With Portable Low-Field Mri, W Taylor Kimberly, Annabel J Sorby-Adams, Andrew G Webb, Ed X Wu, Rachel Beekman, Ritvij Bowry, Steven J Schiff, Adam De Havenon, Francis X Shen, Gordon Sze, Pamela Schaefer, Juan Eugenio Iglesias, Matthew S Rosen, Kevin N Sheth

Faculty, Staff and Student Publications

The advent of portable, low-field MRI (LF-MRI) heralds new opportunities in neuroimaging. Low power requirements and transportability have enabled scanning outside the controlled environment of a conventional MRI suite, enhancing access to neuroimaging for indications that are not well suited to existing technologies. Maximizing the information extracted from the reduced signal-to-noise ratio of LF-MRI is crucial to developing clinically useful diagnostic images. Progress in electromagnetic noise cancellation and machine learning reconstruction algorithms from sparse k-space data as well as new approaches to image enhancement have now enabled these advancements. Coupling technological innovation with bedside imaging creates new prospects in …

False-Positive Early Indium-111 Leukocyte Scan, F Lomena, R Abello, A Garcia, C Piera, R Herranz, J Pavia, J Setoain

Faculty, Staff and Student Publications

Introduction

We aimed to evaluate IDH1 p.R132H mutation and 2-hydroxyglutarate (2HG) in cerebrospinal fluid (CSF) as biomarkers for patients with IDH-mutant gliomas.

Methods

CSF was collected from patients with infiltrating glioma, and 2HG levels were measured by liquid chromatographymass spectrometry. IDH1 p.R132H mutant allele frequency (MAF) in CSF-ctDNA was measured by digital droplet PCR (ddPCR). Tumor volume was measured from standard-of-care magnetic resonance images.

Results

The study included 48 patients, 6 with IDH-mutant and 42 with IDH-wildtype gliomas, and 57 samples, 9 from the patients with IDH-mutant and 48 from the patients with IDH-wildtype gliomas. …

Platelet-Derived Exerkine Cxcl4/Platelet Factor 4 Rejuvenates Hippocampal Neurogenesis And Restores Cognitive Function In Aged Mice, Odette Leiter, David Brici, Stephen J Fletcher, Xuan Ling Hilary Yong, Jocelyn Widagdo, Nicholas Matigian, Adam B Schroer, Gregor Bieri, Daniel G Blackmore, Perry F Bartlett, Victor Anggono, Saul A Villeda, Tara L Walker

Faculty, Staff and Student Publications

The beneficial effects of physical activity on brain ageing are well recognised, with exerkines, factors that are secreted into the circulation in response to exercise, emerging as likely mediators of this response. However, the source and identity of these exerkines remain unclear. Here we provide evidence that an anti-geronic exerkine is secreted by platelets. We show that platelets are activated by exercise and are required for the exercise-induced increase in hippocampal precursor cell proliferation in aged mice. We also demonstrate that increasing the systemic levels of the platelet-derived exerkine CXCL4/platelet factor 4 (PF4) ameliorates age-related regenerative and cognitive impairments in …

Primary Balloon Angioplasty Of Venous Sinus Stenosis In Idiopathic Intracranial Hypertension, Juan Carlos Martinez-Gutierrez, Matthew J Kole, Victor Lopez-Rivera, Mehmet Enes Inam, Rosa Tang, Nagham Al-Zubidi, Ore-Ofeoluwatomi Adesina, Elvira Lekka, Allison C Engstrom, Sunil Sheth, Claudia Pedroza, Arthur L Day, Peng Roc Chen

Faculty, Staff and Student Publications

Background: Venous sinus stenosis (VSS) stenting has emerged as an effective treatment for patients with Idiopathic Intracranial Hypertension (IIH). However, stenting carries risk of in-stent stenosis/thrombosis and cumulative bleeding risk from long-term dual antiplatelet (DAPT) use. Thus, we investigated the potential safety and efficacy of primary balloon angioplasty as an alternative to stenting in IIH.

Methods: A prospectively maintained single-center registry of IIH patients undergoing endovascular procedures was queried. Inclusion criteria included patients with confirmed IIH and angiographically demonstrable VSS who underwent interventions from 2012- 2021. Patients were dichotomized into primary balloon angioplasty (Group A) and primary stenting (Group S), …

Catalytic Enantioselective Synthesis Of 3-Piperidines From Arylboronic Acids And Pyridine, Sourabh Mishra, Sedef Karabiyikoglu, Stephen P Fletcher

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Piperidines are frequently found in natural products and are of importance to the pharmaceutical industry. A generally useful asymmetric route to enantiomerically enriched 3-substituted piperidines remains elusive. Here we report a cross-coupling approach to enantioenriched 3-piperidines from pyridine- and sp²-hybridized boronic acids. The key step involves a Rh-catalyzed asymmetric reductive Heck reaction of aryl, heteroaryl, or vinyl boronic acids and phenyl pyridine-1(2H)-carboxylate to provide 3-substituted tetrahydropyridines in high yield and excellent enantioselectivity with a wide functional group tolerance. A three-step process involving i) partial reduction of pyridine, ii) Rh-catalyzed asymmetric carbometalation, and then iii) another reduction …

The Genetics Of Primary Ciliary Dyskinesia In Puerto Rico, Paolo Zanoni, Katharina Steindl, Heinrich Sticht, Beatrice Oneda, Pascal Joset, Ivan Ivanovski, Anselm H C Horn, Elena M Cabello, Julia Laube, Markus Zweier, Alessandra Baumer, Anita Rauch, Nadia Khan

Faculty, Staff and Student Publications

Pediatric Moyamoya Angiopathy (MMA) is a progressive intracranial occlusive arteriopathy that represents a leading cause of transient ischemic attacks and strokes in childhood. Despite this, up to now no large, exclusively pediatric MMA cohort has been subjected to systematic genetic investigation. In this study, we performed molecular karyotyping, exome sequencing and automated structural assessment of missense variants on a series of 88 pediatric MMA patients and correlated genetic, angiographic and clinical (stroke burden) findings. The two largest subgroups in our cohort consisted of RNF213 and neurofibromatosis type 1 (NF1) patients. While deleterious RNF213 variants were associated with a severe MMA …

An Erk5-Nrf2 Axis Mediates Senescence-Associated Stemness And Atherosclerosis, Jun-Ichi Abe, Masaki Imanishi, Shengyu Li, Aijun Zhang, Kyung Ae Ko, Venkata S K Samanthapudi, Ling-Ling Lee, Angelica Paniagua Bojorges, Young Jin Gi, Brian P Hobbs, Anita Deswal, Joerg Herrmann, Steven H Lin, Eduardo N Chini, Ying H Shen, Keri L Schadler, Thi-Hong-Minh Nguyen, Anisha A Gupte, Cielito Reyes-Gibby, Sai-Ching J Yeung, Rei J Abe, Elizabeth A Olmsted-Davis, Sunil Krishnan, Robert Dantzer, Nicolas L Palaskas, John P Cooke, Henry J Pownall, Momoko Yoshimoto, Keigi Fujiwara, Dale J Hamilton, Jared K Burks, Guangyu Wang, Nhat-Tu Le, Sivareddy Kotla

Faculty, Staff and Student Publications

BACKGROUND: ERK5 (extracellular signal-regulated kinase 5) is a dual kinase transcription factor containing an N-terminal kinase domain and a C-terminal transcriptional activation domain. Many ERK5 kinase inhibitors have been developed and tested to treat cancer and inflammatory diseases. However, recent data have raised questions about the role of the catalytic activity of ERK5 in proliferation and inflammation. We aimed to investigate how ERK5 reprograms myeloid cells to the proinflammatory senescent phenotype, subsequently leading to atherosclerosis.

METHODS: A ERK5 S496A (dephosphorylation mimic) knock in (KI) mouse model was generated using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic …

Adapting And Testing The Care Partner Hospital Assessment Tool For Use In Dementia Care: Protocol For A 2 Sequential Phase Study, Beth Fields, Nicole Werner, Manish N Shah, Scott Hetzel, Blair P Golden, Andrea Gilmore-Bykovskyi, Dorothy Farrar Edwards

Faculty, Staff and Student Publications

Background

Research and policy demonstrate the value of and need for systematically identifying and preparing care partners for their caregiving responsibilities while their family member or friend living with dementia is hospitalized. The Care Partner Hospital Assessment Tool (CHAT) has undergone content and face validation and has been endorsed as appropriate by clinicians to facilitate the timely identification and preparation of care partners of older adult patients during their hospitalization. However, the CHAT has not yet been adapted or prospectively evaluated for use with care partners of hospitalized people living with dementia. Adapting and testing the CHAT via a pilot …