Medical Specialties Commons^™

Growth And Differentiation Factor 15 (Gdf15) Levels Predict Adverse Respiratory Outcomes In Premature Neonates, Faeq Almudares, Joseph Hagan, Xinpu Chen, Sridevi Devaraj, Bhagavatula Moorthy, Krithika Lingappan

Faculty, Staff and Students Publications

Growth and differentiation factor 15 (GDF15) is a stress-responsive cytokine, and its expression increases during inflammation, hyperoxia, and senescence. Significantly, GDF15 is secreted by the placenta, and maternal levels increase throughout pregnancy. Serum GDF15 level is a promising biomarker for many lung diseases like pulmonary hypertension and pulmonary fibrosis. However, circulating GDF15 levels in preterm infants and their role as a predictor of respiratory outcomes have not been studied. We hypothesized that GDF15 levels would increase with gestational age at birth, and that postnatal GDF15 will be correlated with adverse respiratory outcomes in preterm infants. Scavenged blood samples were retrieved …

Coping During The Covid-19 Pandemic Among Young Adults Experiencing Homelessness And Unstable Housing: A Qualitative Study, Karen Divalerio Gibbs, Jennifer Torres Jones, Whitney Lamark, Sarah Abdulmooti, Lauren Bretz, Kelly D Kearney, Sarah Carter Narendorf, Diane M Santa Maria

Faculty, Staff and Students Publications

BACKGROUND: Young adults experiencing homelessness (YAEH) experience more stressors compared to housed peers, yet little is known about the impact of the COVID-19 pandemic on these youth. The purpose of this qualitative study was to explore how YAEH perceived the pandemic's impact on their well-being and coping.

METHODS: YAEH were recruited from those participating in an HIV prevention study. Semi-structured interviews were conducted and analysis was guided by Lazarus and Folkman's transactional theory of stress and coping.

RESULTS: Four major themes were identified from interviews with 40 youth: (1) ongoing harms, (2) COVID-19 as a stressor, (3) mental health impacts, …

Physiologic Profile Associated With Severe Multisystem Inflammatory Syndrome In Children: A Retrospective Study, Fabio Savorgnan, Alvaro Moreira, Axel Moreira, Ananth Annapragada, S Kristen Sexson Tejtel, Saul Flores, Craig G Rusin, Lara Shekerdemian, Sebastian Acosta

Faculty, Staff and Students Publications

OBJECTIVE: The purpose of this study was to describe the clinical presentation and physiologic profile of individuals with varying degrees of severity of multisystem inflammatory syndrome in children (MIS-C).

METHODS: We performed a retrospective study of children diagnosed with MIS-C admitted to a single quaternary children's hospital from May 2020 to April 2021. We created an MIS-C severity score using the following parameters: hospital admission status (e.g., floor vs intensive care unit), need for inotropic or vasoactive medications, and need for mechanical ventilation. Univariate and multivariate analyses were performed to associate risk factors corresponding to the MIS-C severity score.

RESULTS: …

Versican Provides The Provisional Matrix For Uterine Spiral Artery Dilation And Fetal Growth, Yusuke Sagae, Akihito Horie, Akihiro Yanai, Tsutomu Ohara, Baku Nakakita, Yoshimi Kitawaki, Asuka Okunomiya, Hirohiko Tani, Ken Yamaguchi, Junzo Hamanishi, John P Lydon, Takiko Daikoku, Hideto Watanabe, Masaki Mandai

Faculty, Staff and Students Publications

The extracellular matrix (ECM) in the endometrium plays a crucial role in mammalian pregnancy. We have shown that versican secreted from the endometrial epithelium promotes embryo implantation. Versican is a proteoglycan, a major player in the provisional matrix, and versikine, its N-terminal fragment cleaved by ADAMTS proteinases, serves as a bioactive molecule. Here, since versican expression in the placenta was dynamically altered in humans and mice, we investigated the role of versican in pregnancy using uterine-specific Vcan deletion mice (uKO mice) and ADAMTS-resistant versican expressing mice (V1R mice). uKO mice exhibited insufficient spiral artery dilation, followed by fetal growth restriction …

Assessment Of The Cytolytic Potential Of A Multivirus-Targeted T Cell Therapy Using A Vital Dye-Based, Flow Cytometric Assay, Kiriakos Koukoulias, Penelope G Papayanni, Julia Jones, Manik Kuvalekar, Ayumi Watanabe, Yovana Velazquez, Sarah Gilmore, Anastasia Papadopoulou, Ann M Leen, Spyridoula Vasileiou

Faculty, Staff and Students Publications

Reliable and sensitive characterization assays are important determinants of the successful clinical translation of immunotherapies. For the assessment of cytolytic potential, the chromium 51 (51Cr) release assay has long been considered the gold standard for testing effector cells. However, attaining the approvals to access and use radioactive isotopes is becoming increasingly complex, while technical aspects [i.e. sensitivity, short (4-6 hours) assay duration] may lead to suboptimal performance. This has been the case with our ex vivo expanded, polyclonal (CD4+ and CD8+) multivirus-specific T cell (multiVST) lines, which recognize 5 difficult-to-treat viruses [Adenovirus (AdV), BK virus (BKV), cytomegalovirus (CMV), Epstein Barr …

Editorial: Health Effects And Pathophysiological Mechanisms Of One-Carbon Metabolism Nutrients Intake Throughout The Life Cycle, Jufen Liu, Yunping Lei, Lei Wang, Chao Guo

Faculty, Staff and Students Publications

No abstract provided.

Brain Monoamine Vesicular Transport Disease Caused By Homozygous Slc18a2 Variants: A Study In 42 Affected Individuals, Ken Saida, Reza Maroofian, Toru Sengoku, Tadahiro Mitani, Alistair T Pagnamenta, Dana Marafi, Maha S Zaki, Thomas J O'Brien, Ehsan Ghayoor Karimiani, Rauan Kaiyrzhanov, Marina Takizawa, Sachiko Ohori, Huey Yin Leong, Gulsen Akay, Hamid Galehdari, Mina Zamani, Ratna Romy, Christopher J Carroll, Mehran Beiraghi Toosi, Farah Ashrafzadeh, Shima Imannezhad, Hadis Malek, Najmeh Ahangari, Hoda Tomoum, Vykuntaraju K Gowda, Varunvenkat M Srinivasan, David Murphy, Natalia Dominik, Hasnaa M Elbendary, Karima Rafat, Sanem Yilmaz, Seda Kanmaz, Mine Serin, Deepa Krishnakumar, Alice Gardham, Anna Maw, Tekki Sreenivasa Rao, Sarah Alsubhi, Myriam Srour, Daniela Buhas, Tamison Jewett, Rachel E Goldberg, Hanan Shamseldin, Eirik Frengen, Doriana Misceo, Petter Strømme, José Ricardo Magliocco Ceroni, Chong Ae Kim, Gozde Yesil, Esma Sengenc, Serhat Guler, Mariam Hull, Mered Parnes, Dilek Aktas, Banu Anlar, Yavuz Bayram, Davut Pehlivan, Jennifer E Posey, Shahryar Alavi, Seyed Ali Madani Manshadi, Hamad Alzaidan, Mohammad Al-Owain, Lama Alabdi, Ferdous Abdulwahab, Futoshi Sekiguchi, Kohei Hamanaka, Atsushi Fujita, Yuri Uchiyama, Takeshi Mizuguchi, Satoko Miyatake, Noriko Miyake, Reem M Elshafie, Kamran Salayev, Ulviyya Guliyeva, Fowzan S Alkuraya, Joseph G Gleeson, Kristin G Monaghan, Katherine G Langley, Hui Yang, Mahsa Motavaf, Saeid Safari, Mozhgan Alipour, Kazuhiro Ogata, André E X Brown, James R Lupski, Henry Houlden, Naomichi Matsumoto

Faculty, Staff and Students Publications

Purpose: Brain monoamine vesicular transport disease is an infantile-onset movement disorder that mimics cerebral palsy. In 2013, the homozygous SLC18A2 variant, p.Pro387Leu, was first reported as a cause of this rare disorder, and dopamine agonists were efficient for treating affected individuals from a single large family. To date, only 6 variants have been reported. In this study, we evaluated genotype-phenotype correlations in individuals with biallelic SLC18A2 variants.

Methods: A total of 42 affected individuals with homozygous SLC18A2 variant alleles were identified. We evaluated genotype-phenotype correlations and the missense variants in the affected individuals based on the structural modeling of rat …

Genetics In Medicine Open To Us All, Bo Yuan

Faculty, Staff and Students Publications

No abstract provided.

The Role Of Neural And Genetic Processes In Learning To Read And Specific Reading Disabilities: Implications For Instruction, Jessica A Church, Elena L Grigorenko, Jack M Fletcher

Faculty, Staff and Students Publications

To learn to read, the brain must repurpose neural systems for oral language and visual processing to mediate written language. We begin with a description of computational models for how alphabetic written language is processed. Next, we explain the roles of a dorsal sublexical system in the brain that relates print and speech, a ventral lexical system that develops the visual expertise for rapid orthographic processing at the word level, and the role of cognitive control networks that regulate attentional processes as children read. We then use studies of children, adult illiterates learning to read, and studies of poor readers …

Primary Spinal Intramedullary Anaplastic Ganglioglioma In A Pediatric Patient, Huy Dang, Abdul Basit Khan, Nisha Gadgil, Marc Prablek, Frank Y Lin, Melissa M Blessing, Guillermo Aldave, David Bauer

Faculty, Staff and Students Publications

BACKGROUND: Gangliogliomas (GGs) are rare tumors of the central nervous system composed of neoplastic neural and glial cells and are typically low-grade. Intramedullary spinal anaplastic GGs (AGG) are rare, poorly understood, and often aggressive tumors that can result in widespread progression along the craniospinal axis. Due to the rarity of these tumors, data are lacking to guide clinical and pathologic diagnosis and standard of care treatment. Here, we present a case of pediatric spinal AGG to provide information on our institutional approach to work-up and to highlight unique molecular pathology.

CASE DESCRIPTION: A 13-year-old female presented with signs of spinal …

Linked-Read Based Analysis Of The Medulloblastoma Genome, Melissa Zwaig, Michael J Johnston, John J Y Lee, Hamza Farooq, Marco Gallo, Nada Jabado, Michael D Taylor, Jiannis Ragoussis

Faculty, Staff and Students Publications

INTRODUCTION: Medulloblastoma is the most common type of malignant pediatric brain tumor with group 4 medulloblastomas (G4 MBs) accounting for 40% of cases. However, the molecular mechanisms that underlie this subgroup are still poorly understood. Point mutations are detected in a large number of genes at low incidence per gene while the detection of complex structural variants in recurrently affected genes typically requires the application of long-read technologies.

METHODS: Here, we applied linked-read sequencing, which combines the long-range genome information of long-read sequencing with the high base pair accuracy of short read sequencing and very low sample input requirements.

RESULTS: …

Bridging Science And Spirituality: The Intersection Of Religion And Public Health In The Covid-19 Pandemic, Shahana Ayub, Gibson O Anugwom, Tajudeen Basiru, Vishi Sachdeva, Nazar Muhammad, Anil Bachu, Maxwell Trudeau, Gazal Gulati, Amanda Sullivan, Saeed Ahmed, Lakshit Jain

Faculty, Staff and Students Publications

BACKGROUND: The COVID-19 pandemic has had global impacts on social interactions and religious activities, leading to a complex relationship between religion and public health policies. This article reviews impact of the COVID-19 pandemic on religious activities and beliefs in relation to the spread of the virus, as well as the potential of religious leaders and faith communities in mitigating the impact of the pandemic through public health measures and community engagement.

METHODS: A literature review was conducted using PubMed and Google Scholar, with search terms including "religion," "COVID-19," "pandemic," "coronavirus," and "spirituality." We included English articles published between January 2020 …

Calcitonin Gene-Related Peptide Protects From Soluble Fms-Like Tyrosine Kinase-1-Induced Vascular Dysfunction In A Preeclampsia Mouse Model, Akansha Mishra, Ancizar Betancourt, Vipin Alukkal Vidyadharan, Chellakkan Selvanesan Blesson, Michael Belfort, Chandra Yallampalli, Madhu Chauhan

Faculty, Staff and Students Publications

Introduction: Preeclampsia (PE) is a hypertensive disorder during pregnancy associated with elevated levels of soluble FMS-like tyrosine kinase (sFLT-1) and increased vascular sensitivity to angiotensin II (ATII). Calcitonin gene-related peptide (CALCA) is a potent vasodilator that inhibits the ATII-induced increase in blood pressure and protects against ATII-induced increases in oxidative stress through a mitochondrial-dependent pathway in male mice. In rodent pregnancy, CALCA facilitates pregnancy-induced vascular adaptation. Most of the vascular effects of CALCA are mediated by vascular smooth muscle cells (VSMCs). We recently reported that CALCA treatment inhibits sFLT-1-induced decreases in cAMP synthesis in omental artery smooth muscle cells (OASMCs) …

Non-Invasive And Objective Tear Film Breakup Detection On Interference Color Images Using Convolutional Neural Networks, Yasushi Kikukawa, Shin Tanaka, Takuya Kosugi, Stephen C Pflugfelder

Faculty, Staff and Students Publications

PURPOSE: Dry eye disease affects hundreds of millions of people worldwide and is one of the most common causes for visits to eye care practitioners. The fluorescein tear breakup time test is currently widely used to diagnose dry eye disease, but it is an invasive and subjective method, thus resulting in variability in diagnostic results. This study aimed to develop an objective method to detect tear breakup using the convolutional neural networks on the tear film images taken by the non-invasive device KOWA DR-1α.

METHODS: The image classification models for detecting characteristics of tear film images were constructed using transfer …

Multimodal Imaging Of Choroidal Lesions In An Elderly Man With Uveal Lymphoid Hyperplasia, John R Chancellor, Christina Y Weng

Faculty, Staff and Students Publications

Purpose: To describe the case of an elderly man who was incidentally found to have multiple hypopigmented choroidal lesions in the left eye in the absence of intraocular inflammation. Methods: A case report was analyzed, including the laboratory workup and imaging results. Results: The workup for conditions, including birdshot chorioretinopathy, syphilis, and tuberculosis, were negative. Ancillary imaging confirmed a diagnosis of uveal lymphoid hyperplasia (ULH). The patient was stable under observation for more than 1 year. Conclusions: Careful examination and imaging findings can aid in differentiating between ULH and other diagnoses.

Dry Eye Disease In Astronauts: A Narrative Review, Timon Ax, Bergita Ganse, Fabian N Fries, Nóra Szentmáry, Cintia S De Paiva, Francesc March De Ribot, Slade O Jensen, Berthold Seitz, Thomas J Millar

Faculty, Staff and Students Publications

Long-duration spaceflight can have adverse effects on human health. One of the most common ocular conditions experienced by astronauts is dry eye disease (DED). Symptoms of DED include feelings of eye irritation, eye strain, foreign body sensation and blurred vision. Over 30% of International Space Station expedition crew members reported irritation and foreign body sensation. We reviewed the current literature on the prevalence and mechanisms of DED in astronauts and its potential implications for long-duration spaceflight, including the influence of environmental factors, such as microgravity and fluid shift on tear film physiology in space. DED has negative effects on astronaut …

Factor V Leiden-Independent Activated Protein C Resistance: Communication From The Plasma Coagulation Inhibitors Subcommittee Of The International Society On Thrombosis And Haemostasis Scientific And Standardisation Committee, Gary W Moore, Elisabetta Castoldi, Jun Teruya, Eriko Morishita, Dorothy M Adcock

Faculty, Staff and Students Publications

Activated protein C resistance (APC-R) due to the single-nucleotide polymorphism factor V Leiden (FVL) is the most common cause of hereditary thrombophilia. It is found predominantly in Caucasians and is uncommon or absent in other populations. Although FVL is responsible for >90% of cases of hereditary APC-R, a number of other F5 variants that also confer various degrees of APC-R and thrombotic risk have been described. Acquired APC-R due to increased levels of coagulation factors, reduced levels of inhibitors, or the presence of autoantibodies occurs in a variety of conditions and is an independent risk factor for thrombosis. It is …

The Use Of Reframing: Increasing The Importance Of Lifestyle Medicine, Molly R Vega, Saad Nadeem, Elizabeth M Vaughan, Craig A Johnston

Faculty, Staff and Students Publications

Lifestyle behavior modification is an essential component to prevention and treatment of non-communicable diseases worldwide. For the last 40 years, studies have recognized that there is suboptimal training of physicians in lifestyle medicine and its implementation in clinical settings. The lack of nutrition and exercise counseling occurring in the medical office does not reflect the high level of evidence supporting its use. Lifestyle behavior counseling is complex; as are the individualized needs of patients. Therefore, we suspect that the lack of knowledge in nutrition and exercise prescriptions are not the only barriers to providing optimal care. Reframing lifestyle medicine interventions …

Cardiovascular Disease Risk Stratification In The Pakistani Population With And Without Metabolic Syndrome: A Single Centre Cross-Sectional Study, Amber Hanif Palla, Asad Saulat Fatimi, Salim S Virani, Syeda Sadia Fatima

Faculty, Staff and Students Publications

Existing atherosclerotic cardiovascular disease (ASCVD) risk stratification algorithms are predominantly validated only for Western populations, and do not include parameters of metabolic syndrome (MetS) which may increase the relative risk for cardiovascular disease in South Asians. This study aimed to compare the differences between 10-year ASCVD risk by the Framingham Risk Score (FRS), Pooled Cohort Risk Equations (PCE), and QRISK3 calculators in a cohort of apparently healthy Pakistani adults and stratify the ASCVD risk by MetS status.A cross-sectional study recruited 179 subjects between the ages of 40 to 74 years from the outpatient department of the Aga Khan University Hospital …

Malignant Insulinoma Arising From Nonfunctioning Pancreatic Neuroendocrine Tumor, Ritodhi Chatterjee, Basim Ali, Son H Nguyen, Rui Chen, Yvonne H Sada

Faculty, Staff and Students Publications

Pancreatic neuroendocrine tumors are rare neoplasms characterized into nonfunctioning (NF-PNET) and functioning (F-PNET) subtypes. F-PNETs typically involve overt symptoms related to excessive hormone secretion but may rarely present first as NF-PNETs with delayed transformation. We present a patient with known NF-PNET with liver metastases who developed hypoglycemia 2 years after initial diagnosis due to malignant insulinoma. Hypoglycemia was refractory to continuous dextrose but improved temporarily after diazoxide and hepatic artery embolization. Malignant insulinomas are usually metastatic at presentation and portend poor prognosis. Hypoglycemia may be medically managed with steroids, somatostatin analogues, and diazoxide, along with therapies to reduce tumor burden.

Editorial: Tumor Metabolism: From Molecular Mechanisms To Clinical Application, Chunming Cheng, Si Zhang, Dongyin Guan, Yi Wang, Nidhi Jyotsana

Faculty, Staff and Students Publications

No abstract provided.

Heart Failure Drug Treatment-Inertia, Titration, And Discontinuation: A Multinational Observational Study (Evolution Hf), Gianluigi Savarese, Takuya Kishi, Orly Vardeny, Samuel Adamsson Eryd, Johan Bodegård, Lars H Lund, Marcus Thuresson, Biykem Bozkurt

Faculty, Staff and Students Publications

Background: Guidelines recommend early initiation of multiple guideline-directed medical therapies (GDMTs) to reduce mortality/rehospitalization in patients with heart failure and reduced ejection fraction. Understanding GDMT use is critical to improving clinical practice.

Objectives: This study sought to describe GDMT use in Japan, Sweden, and the United States in contemporary real-world settings.

Methods: EVOLUTION HF (Utilization of Dapagliflozin and Other Guideline Directed Medical Therapies in Heart Failure Patients: A Multinational Observational Study Based on Secondary Data) is an observational cohort study using routine-care databases. Patients initiating any GDMT within 12 months of a hospitalization for heart failure (hHF) discharge were included. …

Ultrahigh Resolution Lipid Mass Spectrometry Imaging Of High-Grade Serous Ovarian Cancer Mouse Models, Xin Ma, Andro Botros, Sylvia R Yun, Eun Young Park, Olga Kim, Soojin Park, Thu-Huyen Pham, Ruihong Chen, Murugesan Palaniappan, Martin M Matzuk, Jaeyeon Kim, Facundo M Fernández

Faculty, Staff and Students Publications

No effective screening tools for ovarian cancer (OC) exist, making it one of the deadliest cancers among women. Considering that little is known about the detailed progression and metastasis mechanism of OC at a molecular level, it is crucial to gain more insights into how metabolic and signaling alterations accompany its development. Herein, we present a comprehensive study using ultra-high-resolution Fourier transform ion cyclotron resonance matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to investigate the spatial distribution and alterations of lipids in ovarian tissues collected from double knockout (n = 4) and triple mutant mouse models (n …

Oocyte-Specific Wee1-Like Protein Kinase 2 Is Dispensable For Fertility In Mice, Kaori Nozawa, Zian Liao, Yuhkoh Satouh, Ting Geng, Masahito Ikawa, Diana Monsivais, Martin M Matzuk

Faculty, Staff and Students Publications

Wee1-like protein kinase 2 (WEE2) is an oocyte-specific protein tyrosine kinase involved in the regulation of oocyte meiotic arrest in humans. As such, it has been proposed as a candidate for non-hormonal female contraception although pre-clinical models have not been reported. Therefore, we developed two novel knockout mouse models using CRISPR/Cas9 to test loss-of-function of Wee2 on female fertility. A frameshift mutation at the Wee2 translation start codon in exon 2 had no effect on litter size, litter production, or the ability of oocytes to maintain prophase I arrest. Because of the lack of a reproductive phenotype, we additionally generated …

Peripherally-Induced Movement Disorders: An Update, Abhishek Lenka, Joseph Jankovic

Faculty, Staff and Students Publications

BACKGROUND: Peripherally-induced movement disorders (PIMD) should be considered when involuntary or abnormal movements emerge shortly after an injury to a body part. A close topographic and temporal association between peripheral injury and onset of the movement disorders is crucial to diagnosing PIMD. PIMD is under-recognized and often misdiagnosed as functional movement disorder, although both may co-exist. Given the considerable diagnostic, therapeutic, and psychosocial-legal challenges associated with PIMD, it is crucial to update the clinical and scientific information about this important movement disorder.

METHODS: A comprehensive PubMed search through a broad range of keywords and combinations was performed in February 2023 …

Editorial: Peripheral Stimulation: Neuromodulation Of The Central Nervous System Through Existing Pathways, Musa Ozturk, Julio Cesar Hernandez-Pavon, Alexander Kent, Jose L Pons, Ilknur Telkes, Arjun Tarakad

Faculty, Staff and Students Publications

No abstract provided.

Editorial: Surgical Techniques For The Management Of Pain, Anthony K Allam, Ashwin Viswanathan, Jason M Schwalb, Parag G Patil, M Benjamin Larkin

Faculty, Staff and Students Publications

No abstract provided.

Automated Artifact Injection Into Sensing-Capable Brain Modulation Devices For Neural-Behavioral Synchronization And The Influence Of Device State, Michaela E Alarie, Nicole R Provenza, Jeffrey A Herron, Wael F Asaad

Faculty, Staff and Students Publications

No abstract provided.

Attenuating Side Effects Of Deep Brain Stimulation In The Bed Nucleus Of The Stria Terminalis For Obsessive Compulsive Disorder Using Current-Steering Strategies, Huy Q Dang, Nicole R Provenza, Garrett P Banks, Nisha Giridharan, Michelle Avendano-Ortega, Sarah A Mckay, Ethan Devara, Ben Shofty, Eric A Storch, Sameer A Sheth, Wayne K Goodman

Faculty, Staff and Students Publications

No abstract provided.

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

Faculty, Staff and Students Publications

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

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