Digital Commons Network^™

Prefronto-Cerebellar Neuromodulation Affects Appetite In Obesity, Elena M. Marron, Raquel Viejo-Sobera, Guillem Cuatrecasas, Diego Redolar-Ripoll, Pilar García Lorda, Abhishek Datta, Marom Bikson, Greta Magerowksi, Miguel Alonso-Alonso

Publications and Research

Human neuroimaging studies have consistently reported changes in cerebellar function and integrity in association with obesity. To date, however, the nature of this link has not been studied directly. Emerging evidence suggests a role for the cerebellum in higher cognitive functions through reciprocal connections with the prefrontal cortex. The purpose of this exploratory study was to examine appetite changes associated with noninvasive prefronto-cerebellar neuromodulation in obesity. 12 subjects with class I obesity (mean BMI 32.9 kg/m2) underwent a randomized, single-blinded, sham-controlled, crossover study, during which they received transcranial direct current stimulation (tDCS; active/sham) aimed at simultaneously enhancing the activity of …

Agep Overlap Induced By Hydroxychloroquine: A Case Report And Literature Review., Christopher Mercogliano, Muhammad Khan, Catherine Lin, Elan Mohanty, Ryan Zimmerman

Reading Hospital Internal Medicine Residency

Acute Generalized Exanthematous Pustulosis (AGEP) is a rare drug reaction manifesting as pustular lesions with surrounding erythema following exposure. The disease is often self-limited and treatment is supportive. It may present in an atypical variant with vesicles that desquamate into erosions, which classifies the disease as an AGEP/SJS Overlap. This overlap syndrome can carry a substantial mortality rate and necessitate elevation in the level of care. Hydroxychloroquine has been implicated in cases of AGEP, and we present a case of AGEP/SJS overlap attributed to this common medication. Given the prevalence of drug eruptions, it is critical for the physicians to …

Genome-Wide Mega-Analysis Identifies 16 Loci And Highlights Diverse Biological Mechanisms In The Common Epilepsies., Bassel Abou-Khalil, Pauls Auce, Andreja Avbersek, Melanie Bahlo, David J. Balding, Thomas Bast, Larry Baum, Albert J. Becker, Felicitas Becker, Bianca Berghuis, Samuel F. Berkovic, Katja E. Boysen, Jonathan P. Bradfield, Lawrence C. Brody, Russell J. Buono, Ellen Campbell, Gregory D. Cascino, Claudia B. Catarino, Gianpiero L. Cavalleri, Stacey S. Cherny, Krishna Chinthapalli, Alison J. Coffey, Alastair Compston, Antonietta Coppola, Patrick Cossette, John J. Craig, Gerrit-Jan De Haan, Peter De Jonghe, Carolien G.F. De Kovel, Norman Delanty, Chantal Depondt, Orrin Devinsky, Dennis J. Dlugos, Colin P. Doherty, Christian E. Elger, Johan G. Eriksson, Thomas N. Ferraro, Martha Feuch, Ben Francis, Andre Franke, Jacqueline A. French, Saskia Freytag, Verena Gaus, Eric B. Geller, Christian Gieger, Tracy Glauser, Simon Glynn, David B. Goldstein, Hongsheng Gui, Youling Guo, Kevin F. Haas, Hakon Hakonarson, Kerstin Hallmann, Sheryl Haut, Erin L. Heinzen, Ingo Helbig, Christian Hengsbach, Helle Hjalgrim, Michele Iacomino, Andrés Ingason, Jennifer Jamnadas-Khoda, Michael R. Johnson, Reetta Kälviäinen, Anne-Mari Kantanen, Dalia Kasperavičiūte, Dorothee Kasteleijn-Nolst Trenite, Heidi E. Kirsch, Robert C. Knowlton, Bobby P.C. Koeleman, Roland Krause, Martin Krenn, Wolfram S. Kunz, Ruben Kuzniecky, Patrick Kwan, Dennis Lal, Yu-Lung Lau, Anna-Elina Lehesjoki, Holger Lerche, Costin Leu, Wolfgang Lieb, Dick Lindhout, Warren D. Lo, Iscia Lopes-Cendes, Daniel H. Lowenstein, Alberto Malovini, Anthony G. Marson, Thomas Mayer, Mark Mccormack, James L. Mills, Nasir Mirza, Martina Moerzinger, Rikke S. Møller, Anne M. Molloy, Hiltrud Muhle, Mark Newton, Ping-Wing Ng, Markus M. Nöthen, Peter Nürnberg, Terence J. O’Brien, Karen L. Oliver, Palotie Palotie, Faith Pangilinan, Sarah Peter, Slavé Petrovski, Annapurna Poduri, Michael Privitera, Rodney Radtke, Sarah Rau, Philipp S. Reif, Eva M. Reinthaler, Felix Rosenow, Josemir W. Sander, Thomas Sander, Theresa Scattergood, Steven C. Schachter, Christoph J. Schankin, Ingrid E. Scheffer, Bettina Schmitz, Susanne Schoch, Pak C. Sham, Jerry J. Shih, Graeme J. Sills, Sanjay M. Sisodiya, Lisa Slattery, Alexander Smith, David F. Smith, Michael C. Smith, Philip E. Smith, Anja C.M. Sonsma, Doug Speed, Michael R. Sperling, Bernhard J. Steinhoff, Ulrich Stephani, Remi Stevelink, Konstantin Strauch, Pasquale Striano, Hans Stroink, Rainer Surges, K. Meng Tan, Liu Lin Thio, G. Neil Thomas, Marian Todaro, Rossana Tozzi, Maria S. Vari, Ellen P.G. Vining, Frank Visscher, Sarah Von Spiczak, Nicole M. Walley, Yvonne G. Weber, Zhi Wei, Judith Weisenberg, Christopher D. Whelan, Peter Widdess-Walsh, Markus Wolff, Wolking Wolking, Wanling Yang, Federico Zara, Fritz Zimprich

Department of Neurology Faculty Papers

The epilepsies affect around 65 million people worldwide and have a substantial missing heritability component. We report a genome-wide mega-analysis involving 15,212 individuals with epilepsy and 29,677 controls, which reveals 16 genome-wide significant loci, of which 11 are novel. Using various prioritization criteria, we pinpoint the 21 most likely epilepsy genes at these loci, with the majority in genetic generalized epilepsies. These genes have diverse biological functions, including coding for ion-channel subunits, transcription factors and a vitamin-B6 metabolism enzyme. Converging evidence shows that the common variants associated with epilepsy play a role in epigenetic regulation of gene expression in the …

Targeting The Brd4/Foxo3a/Cdk6 Axis Sensitizes Akt Inhibition In Luminal Breast Cancer, Jingyi Liu, Weijie Guo, Zhibing Duan, Lei Zeng, Yadi Wu, Yule Chen, Fang Tai, Yifan Wang, Yiwei Lin, Qiang Zhang, Yanling He, Jiong Deng, Rachel L. Stewart, Chi Wang, Pengnian Charles Lin, Saghi Ghaffari, B. Mark Evers, Suling Liu, Ming-Ming Zhou, Binhua P. Zhou, Jian Shi

Molecular and Cellular Biochemistry Faculty Publications

BRD4 assembles transcriptional machinery at gene super-enhancer regions and governs the expression of genes that are critical for cancer progression. However, it remains unclear whether BRD4-mediated gene transcription is required for tumor cells to develop drug resistance. Our data show that prolonged treatment of luminal breast cancer cells with AKT inhibitors induces FOXO3a dephosphorylation, nuclear translocation, and disrupts its association with SirT6, eventually leading to FOXO3a acetylation as well as BRD4 recognition. Acetylated FOXO3a recognizes the BD2 domain of BRD4, recruits the BRD4/RNAPII complex to the CDK6 gene promoter, and induces its transcription. Pharmacological inhibition of either BRD4/FOXO3a association or …

Preservation Of Hearing And Facial Nerve Function With The Microsurgical Excision Of Large Vestibular Schwannomas: Experience With The Retrosigmoid Approach, Muhammad Shaheryar Ahmed Rajput, Ahmad Nawaz Ahmad, Asif Ali Arain, Muhammad Adeel, Syed Akram, Mohammad Sohail Awan, Muhammad Ehsan Bari

Section of Neurosurgery

Introduction: Vestibular schwannomas (VS) are the most common benign neoplasms of a cerebellopontine angle (CPA), which arise from the Schwann cells of the vestibulocochlear nerve. Eighty percent of CPA tumors are VS followed by meningioma as the second common mass lesion in this critical potential space. Treatment options range from watchful waiting with serial imaging studies to radiosurgery or a microsurgical excision or a combination of surgery and radiation therapy. The primary objective of the study was to assess hearing and facial nerve status before and after the surgery via the retrosigmoid approach.
Methods: The database of Aga Khan University …

Notch Signaling Regulates Mitochondrial Metabolism And Nf-Κb Activity In Triple-Negative Breast Cancer Cells Via Ikkα-Dependent Non-Canonical Pathways, Fokhrul Hossain, Claudia Sorrentino, Deniz A. Ucar, Yin Peng, Margarite Matossian, Dorota Wyczechowska, Judy Crabtree, Jovanny Zabaleta, Silvana Morello, Luis Del Valle, Matthew Burow, Bridgette Collins-Burow, Antonio Pannuti, Lisa M. Minter, Todd E. Golde, Barbara A. Osborne, Lucio Miele

School of Medicine Faculty Publications

Triple negative breast cancer (TNBC) patients have high risk of recurrence and metastasis, and current treatment options remain limited. Cancer stem-like cells (CSCs) have been linked to cancer initiation, progression and chemotherapy resistance. Notch signaling is a key pathway regulating TNBC CSC survival. Treatment of TNBC with PI3K or mTORC1/2 inhibitors results in drug-resistant, Notch-dependent CSC. However, downstream mechanisms and potentially druggable Notch effectors in TNBC CSCs are largely unknown. We studied the role of the AKT pathway and mitochondrial metabolism downstream of Notch signaling in TNBC CSC from cell lines representative of different TNBC molecular subtypes as well as …

Early Oral Feeding After Bowel Resection, Jennifer Strang

Theses & Dissertations

Research Focus: The primary purpose of this project was to determine if there was an association of factors with time to first solid meal in gastrointestinal (GI) surgery patients and the impact solid diet has on length of stay (LOS) in the hospital, GI symptoms, and incidence of post-operative ileus (POI). A secondary purpose was to observe and describe when an oral diet was started and the progression of diet after GI surgery.

Research Methods: This study was a cross-sectional, retrospective chart review of a convenience sample in a multi-centered hospital system conducted in 84 GI resection patients …

Clostridium Sporogenes Bacteremia In An Immunocompetent Patient, Waiel Abusnina, Mena Shehata, Emhemmid S. Karem, Zeynep C. Koc, Elie Khalil

Internal Medicine

Of the 200 Clostridium spp. known to exist, approximately 30 have been associated with human disease. Commonly found in soil, marine sediment and mammalian intestinal tracts, these gram-positive bacilli are known to cause infections ranging from cellulitis to septicemia. Isolates that are identified by clinical microbiology laboratories include Clostridium perfrigens species in 20–40% of cases. However, when Clostridium sporogenes is identified, is rarely considered to be pathogenic. We present a case of Clostridium sporogenes bacteremia secondary to lower limb cellulitis and osteomyelitis in an immunocompetent patient.

Characterizing The Gut Microbiota During Plasmodium Infection And Antimalarial Treatment., Joshua E. Denny

Electronic Theses and Dissertations

Plasmodium, the parasitic cause of malaria, is a global pathogen, annually causing 216 million infections and 445,000 deaths. As drug resistance continues develop and no effective vaccine is available, it is critical to understand the factors underlying the severity of this disease. Plasmodium is an extra-gastrointestinal tract infection where the parasite infects red blood cells causing clinical malaria. However, recent publications have pointed to interactions between the gut microbiota and malaria. With this in mind, the role of the gut microbiota in malaria infection was studied. C57BL/6 mice from different vendors displayed differential resistance and susceptibility to severe malaria, …

Effect Of Differences In Metabolic Activity Of Melanoma Models On Response To Lonidamine Plus Doxorubicin., Kavindra Nath, Jeffrey Roman, David S. Nelson, Lili Guo, Seung-Cheol Lee, Stepan Orlovskiy, Kevin Muriuki, Daniel F. Heitjan, Stephen Pickup, Dennis B. Leeper, Ian A. Blair, Mary E. Putt, Jerry D. Glickson

Department of Radiation Oncology Faculty Papers

Lonidamine (LND), a metabolic modulator, sensitizes DB-1 human melanoma to doxorubicin (DOX) chemotherapy by acidifying and de-energizing the tumor. This report compares the effects of LND on two human melanoma lines, DB-1 and WM983B, which exhibit different metabolic properties. Using liquid chromatography mass spectrometry and Seahorse analysis, we show that DB-1 was more glycolytic than WM983B in vitro. ³¹P magnetic resonance spectroscopy (MRS) indicates that LND (100 mg/kg, i.p.) induces similar selective acidification and de-energization of WM983B xenografts in immunosuppressed mice. Over three hours, intracellular pH (pHi) of WM983B decreased from 6.91 ± 0.03 to 6.59 ± 0.10 (p …

Utility And Accuracy Of Primary And Secondary Ultrasonographic Signs For Diagnosing Acute Appendicitis In Pediatric Patients, W. Akhtar, Mujtaba Z. Naveed, Kumail Khandwala

Department of Radiology

Introduction Making an accurate diagnosis of acute appendicitis (AA) is vital to prevent the morbid complications associated with untreated AA. This is challenging in up to 30% of pediatric patients which is a significantly high number. Ultrasound (US) has been generally used as the initial mode of imaging in pediatric patients due to the lack of ionizing radiation. Given its variable accuracy, adjuvants such as secondary signs can be used to aid the radiologist in making an accurate diagnosis. Materials and methods Patients between the ages of two and sixteen years with acute abdominal pain suspicious for AA, who underwent …

Il-12 Gene Electrotransfer Triggers A Change In Immune Response Within Mouse Tumors, Guilan Shi, Chelsea Edelblute, Sezgi Arpag, Cathryn Lundberg, Richard Heller

Bioelectrics Publications

Metastatic melanoma is an aggressive skin cancer with a relatively low survival rate. Immune-based therapies have shown promise in the treatment of melanoma, but overall complete response rates are still low. Previous studies have demonstrated the potential of plasmid IL-12 (pIL-12) delivered by gene electrotransfer (GET) to be an effective immunotherapy for melanoma. However, events occurring in the tumor microenvironment following delivery have not been delineated. Therefore, utilizing a B16F10 mouse melanoma model, we evaluated changes in the tumor microenvironment following delivery of pIL-12 using different GET parameters or injection of plasmid alone. The results revealed a unique immune cell …

Morphometric Characteristics And Time To Hatch As Efficacious Indicators For Potential Nanotoxicity Assay In Zebrafish, Seyed-Mohammadreza Samaee, Nafiseh Manteghi, Robert A. Yokel, Mohammad Reza Mohajeri-Tehrani

Pharmaceutical Sciences Faculty Publications

Although the effects of nano-sized titania (nTiO₂) on hatching events (change in hatching time and total hatching) in zebrafish have been reported, additional consequences of nTiO₂ exposure (i.e., the effects of nTiO₂-induced changes in hatching events and morphometric parameters on embryo-larvae development and survivability) have not been reported. To address this knowledge gap, embryos 4 h postfertilization were exposed to nTiO₂ (0, 0.01, 10, and 1000 μg/mL) for 220 h. Hatching rate (58, 82, and 106 h postexposure [hpe]), survival rate (8 times from 34 to 202 hpe), and 21 morphometric characteristics (8 times …

Trends And Costs Of External Electrical Bone Stimulators And Grafting Materials In Anterior Lumbar Interbody Fusion., Anthony D'Oro, Zorica Buser, Darrel Scott Brodke, Jong-Beom Park, Sangwook Tim Yoon, Jim Aimen Youssef, Hans-Joerg Meisel, Kristen Radcliff, Patrick Hsieh, Jeffrey Chun Wang

Rothman Institute Papers

STUDY DESIGN: Retrospective review.

PURPOSE: To identify the trends in stimulator use, pair those trends with various grafting materials, and determine the influence of stimulators on the risk of revision surgery.

OVERVIEW OF LITERATURE: A large number of studies has reported beneficial effects of electromagnetic energy in healing long bone fractures. However, there are few clinical studies regarding the use of electrical stimulators in spinal fusion.

METHODS: We used insurance billing codes to identify patients with lumbar disc degeneration who underwent anterior lumbar interbody fusion (ALIF). Comparisons between patients who did and did not receive electrical stimulators following surgery were …

Levels Of Par-1 Kinase Determine The Localization Of Bruchpilot At The Drosophila Neuromuscular Junction Synapses., Kara R. Barber, Martin Hruska, Keegan M. Bush, Jade A. Martinez, Hong Fei, Irwin B. Levitan, Matthew B. Dalva, Yogesh P. Wairkar

Farber Institute for Neuroscience Faculty Papers

Functional synaptic networks are compromised in many neurodevelopmental and neurodegenerative diseases. While the mechanisms of axonal transport and localization of synaptic vesicles and mitochondria are relatively well studied, little is known about the mechanisms that regulate the localization of proteins that localize to active zones. Recent finding suggests that mechanisms involved in transporting proteins destined to active zones are distinct from those that transport synaptic vesicles or mitochondria. Here we report that localization of BRP-an essential active zone scaffolding protein in Drosophila, depends on the precise balance of neuronal Par-1 kinase. Disruption of Par-1 levels leads to excess accumulation of …

Using The Engagedmd Multimedia Platform To Improve Informed Consent For Ovulation Induction, Intrauterine Insemination, And In Vitro Fertilization, Jody L. Madeira, Jennifer Rehbein, Mindy S. Christianson, Miryoung Lee, J. Preston Parry, Guido Pennings, Steven R. Lindheim Md

Articles by Maurer Faculty

Objective: To study patient and provider feedback on how a multimedia platform (EngagedMD) helps patients to understand the risks and consequences of in vitro fertilization (IVF), ovulation induction (OI), and intrauterine insemination (IUI) treatments and the impact of the informed consent process.

Design: Prospective survey study.

Setting: IVF units in the United States.

Patient(s): Six-thousand three-hundred and thirty-three patients who viewed the multimedia platform before IVF or OI-IUI treatment at 13 U.S. IVF centers and 128 providers.

Intervention(s): Quantitative survey with 17 questions.

Main Outcome Measure(s): Assessment of the impact of a multimedia platform on patient anxiety, comprehension, and satisfaction …

Non-Neutralizing Antibodies Elicited By Recombinant Lassa-Rabies Vaccine Are Critical For Protection Against Lassa Fever., Tiago Abreu-Mota, Katie R. Hagen, Kurt Cooper, Peter B. Jahrling, Gene Tan, Christoph Wirblich, Reed F. Johnson, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

Lassa fever (LF), caused by Lassa virus (LASV), is a viral hemorrhagic fever for which no approved vaccine or potent antiviral treatment is available. LF is a WHO priority disease and, together with rabies, a major health burden in West Africa. Here we present the development and characterization of an inactivated recombinant LASV and rabies vaccine candidate (LASSARAB) that expresses a codon-optimized LASV glycoprotein (coGPC) and is adjuvanted by a TLR-4 agonist (GLA-SE). LASSARAB elicits lasting humoral response against LASV and RABV in both mouse and guinea pig models, and it protects both guinea pigs and mice against LF. We …

Development Of Onchocerca Volvulus In Humanized Nsg Mice And Detection Of Parasite Biomarkers In Urine And Serum., John B. Patton, Sasisekhar Bennuru, Mark L. Eberhard, Jessica A. Hess Ligas, April R. Torigian, Sara Lustigman, Thomas B. Nutman, David Abraham

Department of Microbiology and Immunology Faculty Papers

BACKGROUND: The study of Onchocerca volvulus has been limited by its host range, with only humans and non-human primates shown to be susceptible to the full life cycle infection. Small animal models that support the development of adult parasites have not been identified.

METHODOLOGY/PRINCIPAL FINDINGS: We hypothesized that highly immunodeficient NSG mice would support the survival and maturation of O. volvulus and alteration of the host microenvironment through the addition of various human cells and tissues would further enhance the level of parasite maturation. NSG mice were humanized with: (1) umbilical cord derived CD34+ stem cells, (2) fetal derived liver, …

The Role Of Non-Neuronal Acetylcholine In Urogenital Chlamydial Infection, Jessica R. Lockhart

Electronic Theses and Dissertations

Chlamydia trachomatiscauses a bacterial sexually transmitted infection, Chlamydia, that is often chronic and casues reproductive complications in women. We hypothesized that Chlamydia infection increases local acetylcholine (ACh) production, which regulates the host’s inflammatory response to the infection. Female mice infected with C. muridarumwere sacrificed at days 3, 9, 15, and 21 post-infection, genital tract tissues harvested, and immunohistochemistry performed to enumerate ACh-producing cells. Infection increased the number of ACh-producing cells in cervical tissue at days 3,15, and 21 post-infection (pi), uterine tissue at day 3 and 9 pi, and ovarian tissue day 3, 15, and 21 pi. These …

The Tumor Microenvironment Regulates Retinoblastoma Cell Survival, Zachary K. Goldsmith

Theses and Dissertations (ETD)

Retinoblastoma (Rb) is the most common intraocular malignancy in children comprising 4% of all pediatric tumors. Early intervention increases survival rates up to 95% in developed countries; being survival rates associated to socio-economic status. Despite the high survival rates in developed countries, preservation of the eye and vision are continuing challenges in the management of Rb. Vitreous seeds constitute the greatest challenge in treatment of Rb. The unique location of these seeds within the vitreous makes them difficult to treat. Viable seeds showed reduced proliferative capacity and metabolism. making the majority refractory to current chemotherapeutics. This prompted the development of …

The Dietary Intake And Practices Of Adolescent Girls In Low- And Middle-Income Countries: A Systematic Review, Emily C. Keats, Aviva I. Rappaport, Shailja Shah, Christina Oh, Reena Jain, Zulfiqar Ahmed Bhutta

Department of Paediatrics and Child Health

In many low- and middle-income countries (LMICs) the double burden of malnutrition is high among adolescent girls, leading to poor health outcomes for the adolescent herself and sustained intergenerational effects. This underpins the importance of adequate dietary intake during this period of rapid biological development. The aim of this systematic review was to summarize the current dietary intake and practices among adolescent girls (10⁻19 years) in LMICs. We searched relevant databases and grey literature using MeSH terms and keywords. After applying specified inclusion and exclusion criteria, 227 articles were selected for data extraction, synthesis, and quality assessment. Of the included …

Genetic Predisposition To Necrotizing Enterocolitis In Premature Infants: Current Knowledge, Challenges, And Future Directions., Alain Cuna, Lovya George, Venkatesh Sampath

Manuscripts, Articles, Book Chapters and Other Papers

The role of genetics in the pathogenesis of necrotizing enterocolitis (NEC) was initially informed by epidemiological data indicating differences in prevalence among different ethnic groups as well as concordance in twins. These early observations, together with major advances in genomic research, paved the way for studies that begin to reveal the contribution of genetics to NEC. Using the candidate gene or pathway approach, several potential pathogenic variants for NEC in premature infants have already been identified. More recently, genome-wide association studies and exome-sequencing based studies for NEC have been reported. These advances, however, are tempered by the lack of adequately …

A Multicenter Study To Evaluate Pulmonary Function In Osteogenesis Imperfecta., Allison Tam, Shan Chen, Evan Schauer, Ingo Grafe, Venkata Bandi, Jay R. Shapiro, Robert D. Steiner, Peter A. Smith, Michael B. Bober, Tracy Hart, David Cuthbertson, Jeffrey Krischer, Mary Mullins, Peter H. Byers, Robert A. Sandhaus, Michaela Durigova, Francis H. Glorieux, Frank Rauch, Vernon Reid Sutton, Brendan Lee, Members Of The Brittle Bone Disorders Consortium, Eric T. Rush, Sandesh C S Nagamani

Manuscripts, Articles, Book Chapters and Other Papers

Pulmonary complications are a significant cause for morbidity and mortality in osteogenesis imperfecta (OI). However, to date, there have been few studies that have systematically evaluated pulmonary function in individuals with OI. We analyzed spirometry measurements, including forced vital capacity (FVC) and forced expiratory volume in the first second (FEV₁ ), in a large cohort of individuals with OI (n = 217) enrolled in a multicenter, observational study. We show that individuals with the more severe form of the disease, OI type III, have significantly reduced FVC and FEV₁ which do not follow the expected trends of the …

Immediate Neurophysiological Effects Of Transcranial Electrical Stimulation, Anli Liu, Mihály Vöröslakos, Gregory Kronberg, Simon Henin, Matthew R. Krause, Yu Huang, Alexander Opitz, Ashesh Mehta, Christopher C. Pack, Bart Krekelberg, Antal Berényi, Lucas C. Parra, Lucia Melloni, Orrin Devinsky, György Buzsáki

Publications and Research

Noninvasive brain stimulation techniques are used in experimental and clinical fields for their potential effects on brain network dynamics and behavior. Transcranial electrical stimulation (TES), including transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS), has gained popularity because of its convenience and potential as a chronic therapy. However, a mechanistic understanding of TES has lagged behind its widespread adoption. Here, we review data and modelling on the immediate neurophysiological effects of TES in vitro as well as in vivo in both humans and other animals. While it remains unclear how typical TES protocols affect neural activity, we …

Increased Excitability Induced In The Primary Motor Cortex By Transcranial Ultrasound Stimulation, Benjamin C. Gibson, Joseph L. Sanguinetti, Bashar W. Badran, Alfred B. Yu, Evan P. Klein, Christopher C. Abbott, Jeffrey T. Hansberger, Vincent P. Clark

Publications and Research

Background: Transcranial Ultrasound Stimulation (tUS) is an emerging technique that uses ultrasonic waves to noninvasively modulate brain activity. As with other forms of non-invasive brain stimulation (NIBS), tUS may be useful for altering cortical excitability and neuroplasticity for a variety of research and clinical applications. The effects of tUS on cortical excitability are still unclear, and further complications arise from the wide parameter space offered by various types of devices, transducer arrangements, and stimulation protocols. Diagnostic ultrasound imaging devices are safe, commonly available systems that may be useful for tUS. However, the feasibility of modifying brain activity with diagnostic tUS …

Rapid And Robust Restoration Of Breathing Long After Spinal Cord Injury, Philippa M. Warren, Stephanie C. Steiger, Thomas E. Dick, Peter M. Macfarlane, Warren J. Alilain, Jerry Silver

Spinal Cord and Brain Injury Research Center Faculty Publications

There exists an abundance of barriers that hinder functional recovery following spinal cord injury, especially at chronic stages. Here, we examine the rescue of breathing up to 1.5 years following cervical hemisection in the rat. In spite of complete hemidiaphragm paralysis, a single injection of chondroitinase ABC in the phrenic motor pool restored robust and persistent diaphragm function while improving neuromuscular junction anatomy. This treatment strategy was more effective when applied chronically than when assessed acutely after injury. The addition of intermittent hypoxia conditioning further strengthened the ventilatory response. However, in a sub-population of animals, this combination treatment caused excess …

Macrophage-Derived Netrin-1 Promotes Abdominal Aortic Aneurysm Formation By Activating Mmp3 In Vascular Smooth Muscle Cells, Tarik Hadi, Ludovic Boytard, Michele Silvestro, Dornazsadat Alebrahim, Samson Jacob, Jordyn Feinstein, Krista Barone, Wes Spiro, Susan Hutchison, Russell Simon, Debra L. Rateri, Florence Pinet, David Fenyo, Mark Adelman, Kathryn J. Moore, Holger K. Eltzschig, Alan Daugherty, Bhama Ramkhelawon

Physiology Faculty Publications

Abdominal aortic aneurysms (AAA) are characterized by extensive extracellular matrix (ECM) fragmentation and inflammation. However, the mechanisms by which these events are coupled thereby fueling focal vascular damage are undefined. Here we report through single-cell RNA-sequencing of diseased aorta that the neuronal guidance cue netrin-1 can act at the interface of macrophage-driven injury and ECM degradation. Netrin-1 expression peaks in human and murine aneurysmal macrophages. Targeted deletion of netrin-1 in macrophages protects mice from developing AAA. Through its receptor neogenin-1, netrin-1 induces a robust intracellular calcium flux necessary for the transcriptional regulation and persistent catalytic activation of matrix metalloproteinase-3 (MMP3) …

“His Mind Will Work Better With Both Of Us”: A Qualitative Study On Fathers’ Roles And Coparenting Of Young Children In Rural Pakistan, Joshua Jeong, Saima Siyal, Günther Fink, Dana Charles Mccoy, Aisha Khizar Yousafzai

Department of Paediatrics and Child Health

Background: Parents are the primary providers of nurturing care for young children’s healthy early development. However, the literature on parenting in early childhood, especially in low- and middle-income countries, has primarily focused on mothers. In this study, we investigate how parents make meaning of fathers’ parenting roles with regards to their young children’s early health and development in rural Pakistan.
Methods: Data were collected between January and March 2017 through in-depth interviews with fathers (N = 33) and their partners (N = 32); as well as separate focus group discussions with fathers (N = 7) and mothers (N = 7). …

His Mind Will Work Better With Both Of Us”: A Qualitative Study On Fathers’ Roles And Coparenting Of Young Children In Rural Pakistan, Joshua Jeong, Saima Siyal, Günther Fink, Dana Charles Mccoy, Aisha Khizar Yousafzai

Department of Paediatrics and Child Health

Background: Parents are the primary providers of nurturing care for young children’s healthy early development. However, the literature on parenting in early childhood, especially in low- and middle-income countries, has primarily focused on mothers. In this study, we investigate how parents make meaning of fathers’ parenting roles with regards to their young children’s early health and development in rural Pakistan.
Methods: Data were collected between January and March 2017 through in-depth interviews with fathers (N = 33) and their partners (N = 32); as well as separate focus group discussions with fathers (N = 7) and mothers (N = 7). …

Semaphorin 5a Drives Melanoma Progression: Role Of Bcl-2, Mir-204 And C-Myb., Simona D'Aguanno, Elisabetta Valentini, Maria Grazia Tupone, Marianna Desideri, Marta Di Martile, Manuela Spagnuolo, Simonetta Buglioni, Cristiana Ercolani, Italia Falcone, Marco De Dominici, Michele Milella, Maria Giulia Rizzo, Bruno Calabretta, Carlo Cota, Andrea Anichini, Daniela Trisciuoglio, Donatella Del Bufalo

Department of Cancer Biology Faculty Papers

BACKGROUND: Melanoma, the most aggressive form of skin cancer, is characterized by high rates of metastasis, drug resistance and mortality. Here we investigated the role of Semaphorin 5A (Sema5A) on the properties associated with melanoma progression and the factors involved in Sema5A regulation.

METHODS: Western blotting, qRT-PCR, Chromatin immunoprecipitation (ChIP) assay, immunohistochemistry of melanoma patient specimens and xenograft tissues, in vitro Transwell assay for cell migration and invasion evaluation, in vitro capillary-like structure formation analysis.

RESULTS: A significant correlation of Sema5A mRNA expression and melanoma progression was observed by analyzing GEO profile dataset. Endogenous Sema5A protein was detected in 95% …