Medicine and Health Sciences Commons^™

Examining The Evidence Base For Burnout, Renzo Bianchi, Irvin Schonfeld

Publications and Research

Burnout has elicited growing interest among occupational health specialists in recent decades. Since 2019, the World Health Organization has characterized burnout as a syndrome resulting from chronic, unmanageable workplace stress. Accordingly, three symptoms define the entity: (i) feelings of energy depletion or exhaustion; (ii) increased mental distance from one’s job or feelings of negativism or cynicism towards one’s job; and (iii) a sense of ineffectiveness and lack of accomplishment. We call into question the definition of burnout embodied in the Maslach Burnout Inventory and incorporated into the ICD-11. We draw stakeholders’ attention to the fact that burnout’s symptoms and etiology …

Novel Technologies To Characterize And Engineer The Microbiome In Inflammatory Bowel Disease, Alba Boix-Amorós, Hilarly Monaco, Elisa Sambataro, Jose C. Clemente

Publications and Research

We present an overview of recent experimental and computational advances in technology used to characterize the microbiome, with a focus on how these developments improve our understanding of inflammatory bowel disease (IBD). Specifically, we present studies that make use of flow cytometry and metabolomics assays to provide a functional characterization of microbial communities. We also describe computational methods for strain-level resolution, temporal series, myco - biome and virome data, co-occurrence networks, and compositional data analysis. In addition, we review novel techniques to therapeutically manipulate the microbiome in IBD. We discuss the benefits and drawbacks of these technologies to increase awareness …

Medical Norm Of Psychiatric Misdiagnoses In Rare Disease Patients, Rachel Han

Publications and Research

Spring 2022 ENG 120 Student Final Research Paper on the medical norm of psychiatric misdiagnosis throughout the diagnostic journeys of rare disease patients. The idea of a norm was taken from Chimamanda Ngozi Adichie's Tedx Talk "The Danger of a Single Story". Paper discusses prevalence, harmful effects, and origin of this medical norm. Includes discussion of statistical data quoted relating to prevalence of rare diseases as well as anecdotal evidence of the severe ramifications of this norm. Discussion of how medically unexplained symptoms such as mysterious chronic pain often lead to the phenomenon of the psychogenic inference. Origins of this …

Transcranial Direct Current Stimulation On Parkinson’S Disease: Systematic Review And Meta-Analysis, Paloma Cristina Alves De Oliveira, Thiago Anderson Brito De Araújo, Daniel Gomes Da Silva Machado, Abner Cardoso Rodrigues, Marom Bikson, Suellen Marinho Andrade, Alexandre Hideki Okano, Hougelle Simplicio, Rodrigo Pegado, Edgard Morya

Publications and Research

Background: Clinical impact of transcranial direct current stimulation (tDCS) alone for Parkinson’s disease (PD) is still a challenge. Thus, there is a need to synthesize available results, analyze methodologically and statistically, and provide evidence to guide tDCS in PD.

Objective: Investigate isolated tDCS effect in different brain areas and number of stimulated targets on PD motor symptoms.

Methods: A systematic review was carried out up to February 2021, in databases: Cochrane Library, EMBASE, PubMed/MEDLINE, Scopus, and Web of science. Full text articles evaluating effect of active tDCS (anodic or cathodic) vs. sham or control on motor symptoms of PD were …

Toward A Multimodal Computer-Aided Diagnostic Tool For Alzheimer’S Disease Conversion, Danilo Pena, Jessika Suescun, Mya Schiess, Timothy M. Ellmore, Luca Giancardo, Alzheimer’S Disease Neuroimaging Initiative

Publications and Research

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. It is one of the leading sources of morbidity and mortality in the aging population AD cardinal symptoms include memory and executive function impairment that profoundly alters a patient’s ability to perform activities of daily living. People with mild cognitive impairment (MCI) exhibit many of the early clinical symptoms of patients with AD and have a high chance of converting to AD in their lifetime. Diagnostic criteria rely on clinical assessment and brain magnetic resonance imaging (MRI). Many groups are working to help automate this process to improve the clinical workflow. Current …

Stimulating The Facial Nerve To Treat Ischemic Stroke: A Systematic Review, Turner S. Baker, Justin Robeny, Danna Cruz, Alexis Bruhat, Alfred-Marc Iloreta, Anthony Costa, Thomas James Oxley

Publications and Research

Acute ischemic stroke (AIS) is a common devastating disease that has increased yearly in absolute number of cases since 1990. While mechanical thrombectomy and tissue plasminogen activator (tPA) have proven to be effective treatments, their window-of-efficacy time is very short, leaving many patients with no viable treatment option. Over recent years there has been a growing interest in stimulating the facial nerves or ganglions to treat AIS. Pre-clinical studies have consistently demonstrated an increase in collateral blood flow (CBF) following ganglion stimulation, with positive indications in infarct size and neurological scores. Extensive human trials have focused on trans-oral electrical stimulation …

Leveraging High-Resolution 7-Tesla Mri To Derive Quantitative Metrics For The Trigeminal Nerve And Subnuclei Of Limbic Structures In Trigeminal Neuralgia, Judy Alper, Alan C. Seifert, Gaurav Verma, Kuang-Han Huang, Yael Jacob, Ameen Al Qadi, John W. Rutland, Sheetal Patel, Joshua Bederson, Raj K. Shrivastava, Bradley N. Delman, Priti Balchandani

Publications and Research

Background: Trigeminal Neuralgia (TN) is a chronic neurological disease that is strongly associated with neurovascular compression (NVC) of the trigeminal nerve near its root entry zone. The trigeminal nerve at the site of NVC has been extensively studied but limbic structures that are potentially involved in TN have not been adequately characterized. Specifically, the hippocampus is a stress-sensitive region which may be structurally impacted by chronic TN pain. As the center of the emotion-related network, the amygdala is closely related to stress regulation and may be associated with TN pain as well. The thalamus, which is involved in the trigeminal …

Bcr Affinity Influences T-B Interactions And B Cell Development In Secondary Lymphoid Organs, Alec J. Wishnie, Tzippora Chwat-Edelstein, Mary Attaway, Bao Q. Vuong

Publications and Research

B cells produce high-affinity immunoglobulins (Igs), or antibodies, to eliminate foreign pathogens. Mature, naïve B cells expressing an antigen-specific cell surface Ig, or B cell receptor (BCR), are directed toward either an extrafollicular (EF) or germinal center (GC) response upon antigen binding. B cell interactions with CD4+ pre-T follicular helper (pre- Tfh) cells at the T-B border and effector Tfh cells in the B cell follicle and GC control B cell development in response to antigen. Here, we review recent studies demonstrating the role of B cell receptor (BCR) affinity in modulating T-B interactions and the subsequent differentiation of B …

Decoding Clinical Biomarker Space Of Covid-19: Exploring Matrix Factorization-Based Feature Selection Methods, Farshad Saberi-Movahed, Mahyar Mohammadifard, Adel Mehrpooya, Mohammad Rezaei-Ravari, Kamal Berahmand, Mehrdad Rostami, Saeed Karami, Mohammad Najafzadeh, Davood Hajinezhad, Mina Jamshidi, Farshid Abedi, Mahtab Mohammadifard, Elnaz Farbod, Farinaz Safavi, Mohammadreza Dorvash, Shahrzad Vahedi, Mahdi Eftekhari, Farid Saberi-Movahed, Iman Tavassoly

Publications and Research

One of the most critical challenges in managing complex diseases like COVID-19 is to establish an intelligent triage system that can optimize the clinical decision-making at the time of a global pandemic. The clinical presentation and patients’ characteristics are usually utilized to identify those patients who need more critical care. However, the clinical evidence shows an unmet need to determine more accurate and optimal clinical biomarkers to triage patients under a condition like the COVID-19 crisis. Here we have presented a machine learning approach to find a group of clinical indicators from the blood tests of a set of COVID-19 …

Predicting Synchronized Gene Coexpression Patterns From Fibration Symmetries In Gene Regulatory Networks In Bacteria, Ian Leifer, Mishael Sánchez‑Pérez, Cecilia Ishida, Hernán A. Makse

Publications and Research

Background: Gene regulatory networks coordinate the expression of genes across physiological states and ensure a synchronized expression of genes in cellular subsystems, critical for the coherent functioning of cells. Here we address the question whether it is possible to predict gene synchronization from network structure alone. We have recently shown that synchronized gene expression can be predicted from symmetries in the gene regulatory networks described by the concept of symmetry fibrations. We showed that symmetry fibrations partition the genes into groups called fibers based on the symmetries of their ’input trees’, the set of paths in the network through which …

Interfacial Dynamics And Ionic Transport Of Radiologic Contrast Media In Carbohydrate Matrix: Utility And Limits Of X-Ray Imaging, Lin Mousa, Hayley Sanchez, Subhendra Sarkar, Zoya Vinokur

Publications and Research

Hello, our names are Lin Mousa and Hayley Sanchez, this semester we participated in a research project dedicated to analyzing the interactions of contrast media with the molecular components of fruits to compare how they would react with the human brain. This project involved the injection of fruits with varying contrasts and the imaging of the diffusion and interactions of the contrast within the fruits with X-rays. With setup technical parameters on the x-ray equipment images were taken with identical setups at an hourly rate for several days. The final results of this experiment indicated that contrasts such as Gadolinium …

A Systematic Review And Meta-Analysis On The Efficacy Of Repeated Transcranial Direct Current Stimulation For Migraine, Guoshuai Cai, Zhu Xia, Leigh Charvet, Feifei Xiao, Abhishek Datta, X Michelle Androulakis

Publications and Research

Purpose: Transcranial direct current stimulation (tDCS) may have therapeutic potential in the management of migraine. However, studies to date have yielded conflicting results. We reviewed studies using repeated tDCS for longer than 4 weeks in migraine treatment, and performed meta-analysis on the efficacy of tDCS in migraine.

Methods: In this meta-analysis, we included the common outcome measurements reported across randomized controlled trials (RCTs). Subgroup analysis was performed at different post-treatment endpoints, and with different stimulation intensities and polarities.

Results: Five RCTs were included in the quantitative meta-analysis with a total of 104 migraine patients. We found a significant reduction of …

Pirnas As Modulators Of Disease Pathogenesis, Kayla J. Rayford, Ayorinde Cooley, Jelonia T. Rumph, Ashutosh Arun, Girish Rachakonda, Fernando Villalta, Maria F. Lima, Siddharth Pratap, Smita Misra, Pius N. Nde

Publications and Research

Advances in understanding disease pathogenesis correlates to modifications in gene expression within different tissues and organ systems. In depth knowledge about the dysregulation of gene expression profiles is fundamental to fully uncover mechanisms in disease development and changes in host homeostasis. The body of knowledge surrounding mammalian regulatory elements, specifically regulators of chromatin structure, transcriptional and translational activation, has considerably surged within the past decade. A set of key regulators whose function still needs to be fully elucidated are small non-coding RNAs (sncRNAs). Due to their broad range of unfolding functions in the regulation of gene expression during transcription and …

When The Pandemic Opts For The Lockdown: Secretion System Evolution In The Cholera Bacterium, Francis J. Santoriello, Stefan Pukatzki

Publications and Research

Vibrio cholerae, the causative agent of the diarrheal disease cholera, is a microbe capable of inhabiting two different ecosystems: chitinous surfaces in brackish, estuarine waters and the epithelial lining of the human gastrointestinal tract. V. cholerae defends against competitive microorganisms with a contact-dependent, contractile killing machine called the type VI secretion system (T6SS) in each of these niches. The T6SS resembles an inverted T4 bacteriophage tail and is used to deliver toxic effector proteins into neighboring cells. Pandemic strains of V. cholerae encode a unique set of T6SS effector proteins, which may play a role in pathogenesis or pandemic …

A Bisphosphonate With A Low Hydroxyapatite Binding Affinity Prevents Bone Loss In Mice After Ovariectomy And Reverses Rapidly With Treatment Cessation, Abigail A. Coffman, Jelena Basta-Pljakic, Rosa M. Guerra, Frank H. Ebetino, Mark W. Lundy, Robert J. Majeska, Mitchell B. Schaffler

Publications and Research

Bisphosphonates (BPs) are a mainstay of osteoporosis treatment; however, concerns about bone health based on oversuppression of remodeling remain. Long-term bone remodeling suppression adversely affects bone material properties with microdamage accumulation and reduced fracture toughness in animals and increases in matrix mineralization and atypical femur fractures in patients. Although a “drug holiday” from BPs to restore remodeling and improve bone quality seems reasonable, clinical BPs have long functional half-lives because of their high hydroxyapatite (HAP) binding affinities. This places a practical limit on the reversibility and effectiveness of a drug holiday. BPs with low HAP affinity and strong osteoclast inhibition …

Age And Sex Differences In Load-Induced Tibial Cortical Bone Surface Strain Maps, Alessandra Carriero, Behzad Javaheri, Neda Bassir Kazeruni, Andrew A. Pitsillides, Sandra J. Shefelbine

Publications and Research

Bone adapts its architecture to the applied load; however, it is still unclear how bone mechano-adaptation is coordinated and why potential for adaptation adjusts during the life course. Previous animal models have suggested strain as the mechanical stimulus for bone adaptation, but yet it is unknown how mouse cortical bone load-related strains vary with age and sex. In this study, full-field strain maps (at 1 N increments up to 12 N) on the bone surface were measured in young, adult, and old (aged 10, 22 weeks, and 20 months, respectively), male and female C57BL/6J mice with load applied using a …

A Peek Inside The Machines Of Bacterial Nucleotide Excision Repair, Thanyalak Kraithong, Silas Hartley, David Jeruzalmi, Danaya Pakotiprapha

Publications and Research

Double stranded DNA (dsDNA), the repository of genetic information in bacteria, archaea and eukaryotes, exhibits a surprising instability in the intracellular environment; this fragility is exacerbated by exogenous agents, such as ultraviolet radiation. To protect themselves against the severe consequences of DNA damage, cells have evolved at least six distinct DNA repair pathways. Here, we review recent key findings of studies aimed at understanding one of these pathways: bacterial nucleotide excision repair (NER). This pathway operates in two modes: a global genome repair (GGR) pathway and a pathway that closely interfaces with transcription by RNA polymerase called transcription-coupled repair (TCR). …

Outcomes In Patients With Covid-19 Disease And High Oxygen Requirements, Geurys Rojas-Marte, Arsalan Talib Hashmi, Mazin Khalid, Nnamdi Chukwuka, Joshua Fogel, Alejandro Munoz-Martinez, Samantha Ehrlich, Maham Akbar Waheed, Dikshya Sharma, Shaurya Sharma, Awais Aslam, Sabah Siddiqui, Chirag Agarwal, Yuri Malyshev, Carlos Henriquez-Felipe, Jacob Shani

Publications and Research

Background: Approximately 19% of people infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) progress to severe or critical stages of the coronavirus disease 2019 (COVID-19) with a mortality rate exceeding 50%. We aimed to examine the char- acteristics, mortality rates, intubation rate, and length of stay (LOS) of patients hospitalized with COVID-19 disease with high oxygen re- quirements (critically ill).

Methods: We conducted a retrospective analysis in a single center in Brooklyn, New York. Adult hospitalized patients with confirmed COVID-19 disease and high oxygen requirements were included. We performed multivariate logistic regression analyses for statistically significant variables to …

Aphasia In Multilingual Patients, Mira Goral, Zahra Hejazi

Publications and Research

Purpose of Review

We summarize recent published work concerning assessment and treatment of aphasia in bilingual and multilingual people and review current related models of treatment outcomes. As well, we discuss studies that address the recently debated topic of cognitive processes in bilingual individuals with aphasia, with a focus on the effects of bilingualism on aphasia recovery and its potential protective effects.

Recent Findings

Providing assessment and treatment tools that best serve multilingual individuals with aphasia and unpacking the variables and mechanisms that underlie response to treatment have emerged as goals of several recent studies. Additionally, while findings are still …

Trypanosoma Cruzi Modulates Piwi-Interacting Rna Expression In Primary Human Cardiac Myocytes During The Early Phase Of Infection, Kayla J. Rayford, Ayorinde Cooley, Ashutosh Arun, Girish Rachakonda, Yulia Kleschenko, Fernando Villalta, Siddharth Pratap, Maria F. Lima, Pius N. Nde

Publications and Research

Trypanosoma cruzi dysregulates the gene expression profile of primary human cardiomyocytes (PHCM) during the early phase of infection through a mechanism which remains to be elucidated. The role that small non-coding RNAs (sncRNA) including PIWI-interacting RNA (piRNA) play in regulating gene expression during the early phase of infection is unknown. To understand how T. cruzi dysregulate gene expression in the heart, we challenged PHCM with T. cruzi trypomastigotes and analyzed sncRNA, especially piRNA, by RNA-sequencing. The parasite induced significant differential expression of host piRNAs, which can target and regulate the genes which are important during the early infection phase. An …

Pandemic Vibrio Cholerae Shuts Down Site-Specific Recombination To Retain An Interbacterial Defence Mechanism, Francis J. Santoriello, Lina Michel, Daniel Unterweger, Stefan Pukatzki

Publications and Research

Vibrio cholerae is an aquatic microbe that can be divided into three subtypes: harmless environmental strains, localised pathogenic strains, and pandemic strains causing global cholera outbreaks. Each type has a contact-dependent type VI secretion system (T6SS) that kills neighbouring competitors by translocating unique toxic effector proteins. Pandemic isolates possess identical effectors, indicating that T6SS effectors may affect pandemicity. Here, we show that one of the T6SS gene clusters (Aux3) exists in two states: a mobile, prophage-like element in a small subset of environmental strains, and a truncated Aux3 unique to and conserved in pandemic isolates. Environmental Aux3 can be readily …

Proteomic Analysis Of Platelet-Rich And Platelet-Poor Plasma, Olga Miroshnychenko, Robert J. Chalkley, Ryan D. Leib, Peter A. Everts, Jason L. Dragoo

Publications and Research

Background

Autologous blood products, such as platelet-rich plasma (PRP) are commercial products broadly used to accelerate healing of tissues after injuries. However, their content is not standardized and significantly varies in composition, which may lead to differences in clinical efficacy. Also, the underlying molecular mechanisms for therapeutic effects are not well understood.

Purpose

A proteomic study was performed to compare the composition of low leukocyte PRP, platelet poor plasma (PPP), and blood plasma. Pathway analysis of the proteomic data was performed to evaluate differences between plasma formulations at the molecular level. Low abundance regulatory proteins in plasma were identified and …

Applications Of Non-Invasive Neuromodulation For The Management Of Disorders Related To Covid-19, Abrahão Fontes Baptista, Adriana Baltar, Alexandre Hideki Okano, Alexandre Moreira, Ana Carolina Pinheiro Campos, Ana Mércia Fernandes, André Russowsky Brunoni, Bashar W. Badran, Clarice Tanaka, Daniel Ciampi De Andrade, Daniel Gomes Da Silva Machado, Edgard Morya, Eduardo Trujillo, Jaiti K. Swami, Joan A. Camprodon, Katia Monte-Silva, Katia Nunes Sá, Isadora Nunes, Juliana Barbosa Goulardins, Marom Bikson, Pedro Sudbrack-Oliveira, Priscila De Carvalho, Rafael Jardim Duarte-Moreira, Rosana Lima Pagano, Samuel Katsuyuki Shinjo, Yossi Zana

Publications and Research

Background: Novel coronavirus disease (COVID-19) morbidity is not restricted to the respiratory system, but also affects the nervous system. Non-invasive neuromodulation may be useful in the treatment of the disorders associated with COVID-19.

Objective: To describe the rationale and empirical basis of the use of non-invasive neuromodulation in the management of patients with COVID-10 and related disorders.

Methods: We summarize COVID-19 pathophysiology with emphasis of direct neuroinvasiveness, neuroimmune response and inflammation, autonomic balance and neurological, musculoskeletal and neuropsychiatric sequela. This supports the development of a framework for advancing applications of non-invasive neuromodulation in the management COVID-19 and related disorders.

Results: …

Update On The Use Of Transcranial Electrical Brain Stimulation To Manage Acute And Chronic Covid-19 Symptoms, Giuseppina Pilloni, Marom Bikson, Bashar W. Badran, Mark S. George, Steven A. Kautz, Alexandre Hideki Okano, Abrahão Fontes Baptista, Leigh E. Charvet

Publications and Research

The coronavirus disease 19 (COVID-19) pandemic has resulted in the urgent need to develop and deploy treatment approaches that can minimize mortality and morbidity. As infection, resulting illness, and the often prolonged recovery period continue to be characterized, therapeutic roles for transcranial electrical stimulation (tES) have emerged as promising non-pharmacological interventions. tES techniques have established therapeutic potential for managing a range of conditions relevant to COVID-19 illness and recovery, and may further be relevant for the general management of increased mental health problems during this time. Furthermore, these tES techniques can be inexpensive, portable, and allow for trained self-administration. Here, …

A Body Shape Index Significantly Predicts Mri-Defined Abdominal Adipose Tissue Depots In Non-Obese Asian Indians With Type 2 Diabetes Mellitus, Shajith Anoop, Jesse Krakauer, Nir Krakauer, Anoop Misra

Publications and Research

Introduction: We aimed to determine the correlations of volumes of subcutaneous abdominal adipose tissue (SCAT) (anterior, posterior, superficial and deep), total SCAT, intraperitoneal adipose tissue, retroperitoneal abdominal adipose tissue (RPAT), total intra-abdominal adipose tissue (IAAT), pancreatic volume, liver span, total body fat (TBF) and truncal fat mass (TFM) with anthropometric indices, viz., A Body Shape Index (ABSI), Hip Index, their Z scores and Anthropometric Risk Index in non-obese (body mass index (BMI) /m²) Asian Indians with type 2 diabetes mellitus (T2DM).

Research design and methods: Non-obese patients with T2DM (cases; n, 85) and BMI-matched, healthy subjects …

Visual Corticocortical Inputs To Ferret Area 18, Reem Khalil, Moody Roberne Jensy Saint Louis, Shaima Alsuwaidi, Jonathan B. Levitt

Publications and Research

Visual cortical areas in the adult mammalian brain are linked by a network of interareal feedforward and feedback circuits. We investigated the topography of feedback projections to ferret (Mustela putorius furo) area 18 from extrastriate areas 19, 21, and Ssy. Our objective was to characterize the anatomical organization of the extrastriate feedback pool to area 18. We also wished to determine if feedback projections to area 18 share similar features as feedback projections to area 17. We injected the tracer cholera toxin B subunit (CTb) into area 18 of adult ferrets to visualize the distribution and pattern of retrogradely labeled …

Cryo‑Electron Microscopy Structure Of The 70s Ribosome From Enterococcus Faecalis, Eileen L. Murphy, Kavindra V. Singh, Bryant Avila, Torsten Kleffmann, Steven T. Gregory, Barbara E. Murray, Kurt L. Krause, Reza Khayat, Gerwald Jogl

Publications and Research

Enterococcus faecalis is a gram-positive organism responsible for serious infections in humans, but as with many bacterial pathogens, resistance has rendered a number of commonly used antibiotics ineffective. Here, we report the cryo-EM structure of the E. faecalis 70S ribosome to a global resolution of 2.8 Å. Structural differences are clustered in peripheral and solvent exposed regions when compared with Escherichia coli, whereas functional centres, including antibiotic binding sites, are similar to other bacterial ribosomes. Comparison of intersubunit conformations among five classes obtained after three-dimensional classification identifies several rotated states. Large ribosomal subunit protein bL31, which forms intersubunit bridges to …

Ionophoric Polyphenols Are Permeable To The Blood Brain Barrier, Interact With Human Serum Albumin And Calf Thymus Dna, And Inhibit Ache Enzymatic Activity, Alberto Martinez, Mai Zahran, Miguel Gomez, Johnny Guevara, Rosemary Pichardo-Bueno, Junaid Asim, Gabriel Ortiz, Yaa Andoh, Sinji Shibutani, Baljit Kaur

Publications and Research

Alzheimer’s disease (AD) is the most common form of dementia that affects more than 40 million people around the world. The incidence is expected to rapidly increase due to the lack of any effective treatment. In previous work we synthesized a family of five ionophoric polyphenols (compounds 1–5) that targeted important aspects related to AD, such as the toxic aggregation of amyloid-β peptides, the production of reactive oxygen species, or the excessive presence of Cu²⁺ ions. Here, in order to gain insights into their potential therapeutic value, we have tested the ability of compounds 1– …

A Study Of The Relationship Between Uric Acid And Substantia Nigra Brain Connectivity In Patients With Rem Sleep Behavior Disorder And Parkinson’S Disease, Timothy M. Ellmore, Jessika Suescun, Richard J. Castriotta, Mya C. Schiess

Publications and Research

Low levels of the natural antioxidant uric acid (UA) and the presence of REM sleep behavior disorder (RBD) are both associated with an increased likelihood of developing Parkinson’s disease (PD). RBD and PD are also accompanied by basal ganglia dysfunction including decreased nigrostriatal and nigrocortical resting state functional connectivity. Despite these independent findings, the relationship between UA and substantia nigra (SN) functional connectivity remains unknown. In the present study, voxelwise analysis of covariance was used in a cross-sectional design to explore the relationship between UA and whole-brain SN functional connectivity using the eyes-open resting state fMRI method in controls without …

Epigenetic Targeting Of Mcl-1 Is Synthetically Lethal With Bcl-Xl/Bcl-2 Inhibition In Model Systems Of Glioblastoma, Enyuan Shang, Trang T. T. Nguyen, Chang Shu, Mike-Andrew Westhoff, Georg Karpel-Massler, Markus D. Siegelin

Publications and Research

Apoptotic resistance remains a hallmark of glioblastoma (GBM), the most common primary brain tumor in adults, and a better understanding of this process may result in more efficient treatments. By utilizing chromatin immunoprecipitation with next-generation sequencing (CHIP-seq), we discovered that GBMs harbor a super enhancer around the Mcl-1 locus, a gene that has been known to confer cell death resistance in GBM.We utilized THZ1, a known super-enhancer blocker, and BH3-mimetics, including ABT263, WEHI-539, and ABT199. Combined treatment with BH3-mimetics and THZ1 led to synergistic growth reduction in GBM models. Reduction in cellular viability was accompanied by significant cell death induction …