Medical Specialties Commons^™

Up To 8-Year Follow-Up From Resonate-2: First-Line Ibrutinib Treatment For Patients With Chronic Lymphocytic Leukemia, Paul M Barr, Carolyn Owen, Tadeusz Robak, Alessandra Tedeschi, Osnat Bairey, Jan A Burger, Peter Hillmen, Steve E Coutre, Claire Dearden, Sebastian Grosicki, Helen Mccarthy, Jian-Yong Li, Fritz Offner, Carol Moreno, Cathy Zhou, Emily Hsu, Anita Szoke, Thomas J Kipps, Paolo Ghia

Faculty, Staff and Student Publications

We report long-term follow-up from the RESONATE-2 phase 3 study of the once-daily Bruton's tyrosine kinase inhibitor ibrutinib, which is the only targeted therapy with significant progression-free survival (PFS) and overall survival (OS) benefit in multiple randomized chronic lymphocytic leukemia (CLL) studies. Patients (≥65 years) with previously untreated CLL, without del(17p), were randomly assigned 1:1 to once-daily ibrutinib 420 mg until disease progression/unacceptable toxicity (n = 136) or chlorambucil 0.5-0.8 mg/kg ≤12 cycles (n = 133). With up to 8 years of follow-up (range, 0.1-96.6 months; median, 82.7 months), significant PFS benefit was sustained for ibrutinib vs chlorambucil (hazard ratio …

Nox4 Expression In Osteo-Progenitors Controls Bone Development In Mice During Early Life, Jin Ran Chen, Oxana P. Lazarenko, Michael L. Blackburn, Jennifer F. Chen, Christopher E. Randolph, Jovanny Zabaleta, Katrin Schroder, Kim B. Pedersen, Martin J.J. Ronis

School of Medicine Faculty Publications

Tightly regulated and cell-specific NADPH-oxidases (Nox) represent one of the major sources of reactive oxygen species (ROS) signaling molecules that are involved in tissue development and stem cell self-renewal. We have characterized the role of Nox4 in osteo-progenitors during postnatal bone development. Nox4 expression in bone and ROS generation were increased during early osteoblast differentiation and bone development. Stromal osteoblastic cell self-renewal, proliferation and ROS production were significantly lower in samples from whole-body Nox4 knockout mice (Nox4-/-) and conditional knockout (CKO) mice with depletion of Nox4 in the limb bud mesenchyme compared with those from control mice (Nox4fl/fl), but they …

Descriptive Analysis Of Acute Ischemic Stroke In Covid-19 Patients Through The Course Of The Covid-19 Pandemic, Amman Bhasin, Jay Liuhong Liu, Keval Shah, Amin Marji, Ricky Sareini, Shishir Rao, Wazim Mohamed, Kumar Rajamani, Parthasarathi Chamiraju, Ayaz Khawaja

Medical Student Research Symposium

Coronavirus disease 2019 (COVID-19) has been associated with Acute Ischemic Stroke (AIS). Here, we characterize our institutional experience with management of COVID-19 and AIS. Baseline demographics, clinical, imaging, and outcomes data were determined in patients with COVID-19 and AIS presenting within March 2020 thru October 2020, and November 2020 thru August 2021, based on institutional COVID-19 hospitalization volume. Of 2512 COVID-19 patients, 35 (1.39%, mean age 63.3 years, 54% women) had AIS. AIS recognition was frequently delayed after COVID-19 symptoms (median 19.5 days). Four patients (31%) were on therapeutic anticoagulation at AIS recognition. AIS mechanism was undetermined or due to …

Mortality From Aspiration Pneumonia: Incidence, Trends, And Risk Factors, Trisha Gupte, John D. Cramer M.D., Arthur Knack Phd, Ccc-Slp

Medical Student Research Symposium

Aspiration pneumonia is a potentially preventable, aggressive type of pneumonia. Little is understood on the burden in mortality from aspiration pneumonia. Our objectives were to first examine the burden of mortality from aspiration pneumonia in the United States and second investigate comorbidities associated with aspiration pneumonia to understand risk factors. We conducted a case-control study of individuals who died of aspiration pneumonia matched to those who died of other causes. We analyzed all deaths in the United States using the Multiple Cause of Death Dataset from 1999-2017. Cases were matched with controls based on age, sex, and race. We calculated …

Acetyl Isogambogic Acid Activates Unfolded Protein Response And Apoptosis In Head And Neck Cancer, Mehrnoosh Ghafouri, Chester Gauss, Yue Xi Phd, Thomas Jetmore Md, Jordyn Lucas Md, Michael U. Callaghan Md, Andrew M. Fribley Phd

Medical Student Research Symposium

Head and neck squamous cell carcinoma (HNSCC) develops in the mucous membranes of the mouth, nose, and throat. HNSCC is the sixth most common malignancy in the world with 650,000 new diagnosis and 350,000 death every year. Current treatments are chemotherapy and radiation however, the 5-year survival rate for patients at stage 3 or 4 is less than 50%. There is an urgent unmet clinical need to investigate novel treatments for these patients. HNSCC is characterized by dysregulated cell growth rate and aberrant protein synthesis which leads to increased protein folding demand and the need for chaperones. This high protein …

Meta-Analysis Of 175 Patients With Covid-19 And Seizures, Status Epilepticus, Or Cortical Myoclonus: An Individual Patient Data Analysis, Aditi Kappagantu Bs, Helena A. Brantz Ms, Amman Bhasin Ba, Cristina Jageka Bs, Rooqash Ali Md, Izzy Saef Md, Brittany M. Stopa Mph, Ayaz Khawaja Md

Medical Student Research Symposium

Objective

To characterize management and outcomes of seizures, status epilepticus, and cortical myoclonus in COVID-19, with individual patient data analysis of published literature.

Methods

Systematic literature review was conducted in accordance with PRISMA guidelines. Criteria included new-onset seizures, status epilepticus, and/or cortical myoclonus with concomitant COVID-19. COVID-19 severity was dichotomized into mild and severe cases. Good outcome was defined as discharge without severe deficits, and/or return to baseline.

Results

A total of 105 studies reporting 176 patients (male 56.3%;mean age 47.8,SD 25.6) were included. Status epilepticus occurred in 47 patients (26.7%) and myoclonus in 41 (23.3%). Severe COVID-19 occurred in …

Impact Of Delayed Dermatology Consultation On Inpatient Care, Andrew S. Kao, Andrew D. King, Redina Bardhi, Meghan Mansour, Steven Daveluy

Medical Student Research Symposium

Introduction: Dermatology consultation for inpatient skin disorders enhances care by changing diagnoses, management plans, and reducing length of stay. Our goal is to quantify the time delay from primary team to dermatology consult, and its impact on hospital course as well as overall patient care.

Methods: Retrospective chart review of all inpatient dermatology consults from October 1, 2013 to December 31, 2016 at five hospitals within the Detroit Medical Center. Data included demographics, diagnosis, management plans from primary and consulting teams, and timing of initial recognition of skin problem to dermatology and other specialties consultations.

Results: 873 consultations met criteria …

Improving Satisfaction Of Patients Living With Hidradenitis Suppurativa Through Administration Of An Intake Form, Emilia M. Clementi, Steven Daveluy

Medical Student Research Symposium

Background

Hidradenitis suppurativa (HS) is an incurable, chronic inflammatory skin that is caused by follicular occlusion and affects around 1% of people in the United States ¹. Because of its chronic, grave nature, patients may be dissatisfied with their care. Improving the fecundity of HS patients’ interaction with their physicians may be an important step towards improving patient outcomes. Currently, there is no standardized patient intake form for HS patients at Wayne Health. The intake form describes key patient details, such as their current treatments, pain level, and associated symptoms. This project measures the efficacy of this tool after …

Predictive Factors For Length Of Hospital Stay In Pediatric Dog Bite Patients, Dominic Alessio-Bilowus, Nishant Kumar, Elika Ridelman Ph.D, Christina Shanti Md

Medical Student Research Symposium

Title: Predictive Factors for Length of Hospital Stay in Pediatric Dog Bite Patients

Authors: Alessio-Bilowus D¹, Kumar N², Ridelman E¹, Shanti C^2
1Wayne State University, Detroit, MI; ²Children’s Hospital of Michigan, Detroit, MI

Introduction: Dog bite injuries are a source of significant morbidity in the United States, with children being at increased risk compared to adults, yet there is a lack of published data on factors affecting hospital length of stay (LOS) in pediatric patients.

Methods: A full-text retrospective chart review was conducted of all patients presenting to our urban, academic …

Functional Attenuation Coefficient Imaging Of Rod Inner Segment: The Shape Of Things To Come, Cole Goodman

Medical Student Research Symposium

Purpose: Dysfunction of mitochondria and their linked processes within the rod cell (i.e., the rod energy-landscape) are leading hypotheses for rod atrophy in retinitis pigmentosa (RP). It remains unclear how to translate the detailed information available from isolated cell / mitochondria studies into how mitochondria are functioning and responding to treatment in vivo. Here we present a new rod energy-landscape biomarker that can help address this problem using a common clinical tool.

Methods: In mice, OCT data was converted into attenuation coefficients (AC) to map the light-scattering of mitochondria within the inner segment (IS), which fills ~75% of its volume …

Identifying Predictors For Inflammation-Induced Preterm Birth: A Murine Study, Tzu Ning Liu Bs, Jose Galaz Md, Nardhy Gomez-Lopez Phd

Medical Student Research Symposium

Introduction: Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. A large proportion of preterm deliveries is affected by intra-amniotic inflammation, which can occur in the presence (intra-amniotic infection) or absence (sterile intra-amniotic inflammation) of microbes. Studies have shown an association between intra-amniotic inflammation, cervical shortening, and changes in the cervicovaginal microbiome. However, their causal relationships are unknown. This study aims to determine the causality of intra-amniotic inflammation, cervical shortening, and cervicovaginal microbiome alterations.

Methods: Pregnant C57BL/6 dams received an ultrasound-guided intra-amniotic injection of an endotoxin lipopolysaccharide (LPS) or the alarmin interleukin-1 alpha (IL-1 alpha) on 16.5 …

Recovery Time Following Operative Versus Nonoperative Humeral Shaft Fracture Treatment, Susan Wager, Trevor D. Wolterink, Jager Haan, Yash Hedge, Chrystina James, Stephanie J. Muh

Medical Student Research Symposium

INTRODUCTION: Humeral shaft fractures represent approximately 5% of fractures in the United States. Treatment modalities include nonoperative, and operative with open reduction internal fixation (ORIF) or intramedullary nail (IMN). There is no consensus on which option is best. The purpose of this study was to compare the length of time from fracture care to radiographic union between nonoperative, ORIF, and IMN treatments for humeral shaft fractures.

METHODS: This retrospective study analyzed trends in the management of midshaft humerus fracture between July of 2013 and December of 2020. Fracture characteristics and treatment outcomes were recorded from patients with humeral shaft fractures …

A Prospective Study Investigating The Relationship Between Diagnostic Lumbar Medial Branch Blocks And The Use Of Sedation, Hannah C. Milad, Nimesh Patel Md, Ashwin Vaidyanathan Md, Katherine A. Nowak Phd, Rohit C. Aiyer Md

Medical Student Research Symposium

INTRODUCTION: Diagnostic medial branch blocks (MBB) confirm whether the origin of lower back pain is the facet joint, but are prone to false positive results. This study investigates the effects of midazolam sedation on perceived intensity of pain relief following lumbar MBB and determines the frequency of positive results in sedated patients for the corresponding treatment, radiofrequency thermocoagulation (RFTC).

METHODS: This prospective observational study compares pain scores between patients who undergo the MBB procedure with midazolam sedation (treatment) and without (control). Participants reported baseline and post-injection NRS pain scores, and 4, 8 weeks post-RFTC. If >80% pain relief was achieved …

Complications Of Pediatric Cochlear Implant Surgery, Andrew Stefan, Sabrina Bernardo, William Azkoul Ii, Bianca Siegel

Medical Student Research Symposium

Background:

Cochlear implantation (CI) surgery is the standard of care treatment for pediatric patients diagnosed with severe to profound sensorineural hearing loss. While considered a relatively safe operation, any invasive procedure involving the cranium has risks. However, there are few recent studies in the United States that have analyzed complication rates among children who have received CI. Furthermore, existing studies fail to discuss specific risk factors that led to post-operative complications, nor offer solutions to reduce their incidence. This study aims to 1) determine the incidence of specific complications in pediatric CI patients and 2) identify evidence-based risk factors for …

Tumor Vasculature Changes Before Or During Treatment To Predict Response To Systemic Therapy, Avinash Ramkissoon, Faria Ali, Thomas Vander Woude, Stephen Brown, James Ewing, Lisa Rogers

Medical Student Research Symposium

A diagnosis of non-small cell lung cancer (NSCLC) carries a grim prognosis, with 5-year survival rates of 25%. 25-30% of NSCLC patients have brain metastases at initial presentation, which carries an even worse prognosis. New systemic therapies such as targeted-therapies and immuno-therapies have potential to provide better outcomes, but are not without challenges. First, efficacy is limited to a subset of patients. Second, the blood-brain barrier limits penetration, which varies among patients. Third, toxicities can be considerable. Current practice involves waiting 3-6 months to follow-up and assess tumor response; however, by then, it is later than ideal to try other …

Endoscopic Cricoid Split As A Treatment For Subglottic Stenosis: A Systematic Review, Silvia Aluia, Katherine Akers, Michael Chung Md

Medical Student Research Symposium

Introduction: Subglottic stenosis, a fibrotic narrowing of the airway below the vocal cords extending to the lower border of the cricoid cartilage, can be classified as congenital, idiopathic, or acquired in neonates from prolonged intubation. Treatment has more recently expanded from open surgical intervention to include endoscopic procedures. This systematic review aims to evaluate existing literature on anterior and posterior endoscopic cricoid split procedures as a treatment for congenital and acquired subglottic stenosis in order to explore the efficacy of these techniques.

Methods: Literature searches were conducted in PubMed/MEDLINE, EMBASE, Web of Science, Cochrane Library, and Google scholar, which produced …

Time-To-Surgery And Short-Term Outcomes Of Trimalleolar Ankle Fracture During The Covid-19 Pandemic, Gabriel Burdick Bs, Rami Beydoun Bs, Alexander Pietroski Ms, Jonathan Warren Bs, Bushra Fathima Bs, Trevor Wolterink Bs, Michael Mcintosh Bs, Neethi Sriranga Bs, Stephanie Muh Md

Medical Student Research Symposium

PURPOSE: The purpose of this study was to evaluate the impact of the Coronavirus Disease 2019 (COVID-19) pandemic on time-to-surgery, complication rates, and functional outcomes of open reduction and internal fixation (ORIF) for trimalleolar ankle fracture.

METHODS: This retrospective cohort study compared patients who underwent ORIF for trimalleolar ankle fracture between April and July of 2020 of the COVID-19 pandemic (COVID group) to a pre-pandemic cohort treated in 2018 (2018 group). Demographic information, fracture characteristics, and surgical outcomes were collected from patients’ medical charts.

RESULTS: The COVID and 2018 groups consisted of 32 and 100 patients, respectively. The two groups …

Discharged Against Medical Advice In The Postpartum Period: Why Should We Care?, Gurbani Bedi Bs, Mariam Ayyash Md, Mscr, Monique Swain Md

Medical Student Research Symposium

Objective: To understand reasons and events surrounding postpartum discharges against medical advice (AMA) in an urban population in Detroit, Michigan.

Methods: A retrospective chart review was conducted looking at women who left AMA in the postpartum period from Henry Ford Hospital in Detroit, Michigan between 2013 and 2021.

Results: 111 women (0.18%) left AMA in the postpartum period between 2013 and 2021. 35.1% of women were Black, 53% were White, 11.7% were of other races. 4.5% of women had home births and were brought in by EMS shortly after delivery. 44.1% of women had preterm births. 35.1% delivered via cesarean …

Cardio-Net: A Matlab-Based Software For The Display And Diagnostic Utilization Of Vectorcardiograms, Ali H. Mannaa, Domenico Gatti

Medical Student Research Symposium

Background: The 12-lead technique is the standard in ECG, however alternate cardiography modalities such as vectorcardiography (VCG) exist . While the VCG modality offers unique clinical metrics and certain advantages over ECG, it is hardly utilized due to it being more difficult to obtain than ECG. Here we introduce Cardio-Net, a MATLAB-based software that uses standard 12-lead ECG data to generate and visualize VCGs. Furthermore, we demonstrate the diagnostic potential of VCG by utilizing a recurrent neural network (RNN) to accurately classify vectorcardiograms.

Methods: MATLAB version 2019b and the following toolboxes were used for data processing: Deep learning, …

Validation Of The Termination Of Resuscitation Rules In Detroit, Arqam Husain, Adam D. Chalek, Robert Dunne

Medical Student Research Symposium

Introduction: 326,000 patients suffer from an out of hospital cardiac arrest (OHCA) each year. The Termination of Resuscitation (TOR) criteria guides physicians in determining the futility of continuing CPR and transporting patients to the hospital. We examined compliance with current BLS TOR rules and assessed an alternate set of rules to derive improved TOR guidelines for OHCAs in Detroit.

Methods: A retrospective study was conducted utilizing non-traumatic OHCA cases in Detroit from January 1, 2017 to December 31, 2019, which includes time before and after BLS TOR guidelines were implemented. Patients younger than 18 and arrests of traumatic origin or …

Language Preference Impact On The Outcomes Of Those Lost To Follow-Up After A Diagnosis Of Pregnancy Of Unknown Location, Erin A. Leestma, Mayra A. Shafique, Megan Mcnitt, Annmarie Vilkins

Medical Student Research Symposium

Pregnancy of unknown location (PUL) is a temporary diagnosis when there is a positive pregnancy test but an intrauterine gestational sac and/or fetal pole are not visualized with ultrasonography. The three potential outcomes for such a pregnancy are failed pregnancy, an early intrauterine pregnancy or an ectopic/abnormal pregnancy. Given the serious associated morbidity of ectopic pregnancy, these PUL require strict follow up of bHCG levels to help the clinician determine the likely outcome of the PUL (failed vs early vs ectopic) and choose the best intervention (expectant management, surgical management or medical management). One potential barrier to follow-up identified in …

Corticosteroid Injection Exhibits Symptomatic Improvement In Cts Patients With Negative Emgs, Brooke G. Garnica, Aaron R. Prater, Elizabeth A. Washnock-Schmid, Alaa Hazime, Dr. Charles S. Day

Medical Student Research Symposium

Introduction

While corticosteroid injections for carpal tunnel syndrome (CTS) are effective in patients with mild EMGs, no literature has examined the effectiveness of injections in patients with negative EMGs. We hypothesized that patients with negative EMGs will have minimal symptomatic and functional improvement.

Methods

The Boston Carpal Tunnel Questionnaire (BCTQ) was administered to patients clinically diagnosed with CTS and a negative or mild EMG prior to corticosteroid injection. The BCTQ comprises functional (FSS) and symptom status (SSS) questions. The patient was re-evaluated at 2-weeks, 1-, 3-, and 6-months post-injection. Data were analyzed via one-way ANOVA tests. A post-hoc Benjamini-Hochberg FDR …

The Short-Term Effects Of Fine Airborne Particulate Matter And Climate On Covid-19 Disease Dynamics, El Hussain Shamsa, Kezhong Zhang

Medical Student Research Symposium

Background: Despite more than 60% of the United States population being fully vaccinated, COVID-19 cases continue to spike in a temporal pattern. These patterns in COVID-19 incidence and mortality may be linked to short-term changes in environmental factors.

Methods: Nationwide, county-wise measurements for COVID-19 cases and deaths, fine-airborne particulate matter (PM_2.5), and maximum temperature were obtained from March 20, 2020 to March 20, 2021. Multivariate Linear Regression was used to analyze the association between environmental factors and COVID-19 incidence and mortality rates in each season. Negative Binomial Regression was used to analyze daily fluctuations of COVID-19 cases …

How Do Anesthesiologists Prefer To Reduce Preoperative Anxiety In Pediatric Patients?, Arif Musa, Jahan Tajran, Rana Movahedi, Jeffrey C. Wang, David Safani, Christopher Cooke, Guillaume Farah, Syed F. Hussain, Brendan Lynch, Gligor Gucev

Medical Student Research Symposium

250 or less

Ets-Related Gene (Erg) Is Differentially Expressed In Dermatofibroma (Fibrous Histiocytoma) As Compared With Dermatofibromasarcoma Protuberans And Hypertrophic Scars: A Pilot Immunohistochemical Study, Meredith Hengy, Jesse Veenstra, Kyle Perry, David M. Ozog, Ben Friedman

Medical Student Research Symposium

Immunohistochemical staining can be of great utility in differentiating various cutaneous spindle cell neoplasms, particularly when the histomorphological appearance of the lesions is inconclusive. Nuclear staining for ETS-related gene (ERG), a highly sensitive endothelial cell marker, has seldom been studied in the context of cutaneous spindle cell neoplasms. Little is known about its specificity for vascular differentiation. In this pilot study, immunohistochemical analysis for ERG was performed on fifteen dermatofibromas (DF), ten keloids, and nine dermatofibrosarcoma protuberans tumors (DFSP). Consistent nuclear expression of ERG was found in DF [100% (15/15) of the lesions demonstrated >50% labeling of tumor cells with …

False-Positive Serum Igm/Igg To Sars-Cov-2 In A Rare Pulmonary Neuroendocrine Carcinoma With Ocular Metastasis: A Case Report, Irandi P. Pratomo, Gatut Priyonugroho, Aris Ramdhani, Dian Zamroni, Thariqah Salamah, Yayi D.B Susanto, Ramdinal A. Zairinal, Annisa N. Witjaksono, Dita Aditianingsih, Jamal Zaini

The New Ropanasuri Journal of Surgery

The Coronavirus disease 2019 (COVID-19) pandemic impacts pulmonary cancer management since it shares similar clinical features and creates fear among patients to visit hospitals due to possible in-hospital disease transmission. We report a patient who presented with a rare case of a pulmonary neuroendocrine tumor with an ocular involvement, which, unfortunately, experienced a delay in diagnostics. The first hospitalization was due to superior vena cava syndrome, pleural and pericardial effusions, and swollen left eye. The patient was diagnosed with pulmonary cancer, released after the symptoms were relieved, and expected to visit a referral hospital for further diagnostics and treatments. The …

Pivotal Trial Of Mri-Guided Transurethral Ultrasound Ablation In Men With Localized Prostate Cancer: Three-Year Follow-Up, Steven S. Raman, Sandeep Arora, Katarzyna J. Macura, Aytekin Oto, Jurgen Fütterer, Robert Staruch, Temel Tirkes, David Bonekamp, Masoom Haider, Derek W. Cool, Kiran Nandalur

Conference Presentation Abstracts

Purpose: MRI-guided transurethral ultrasound ablation (TULSA) of prostate tissue is a novel directional ultrasound heating under real-time MRI thermometry feedback control. We report 3-year outcomes from the pivotal TULSA-PRO Ablation Clinical Trial. Materials and Methods: With IRB approval and HIPAA compliance, 115 men with organ-confined prostate cancer (≤T2b, PSA ≤15 ng/ml, Grade Group [GG] 1-2) across 13 centers underwent whole-gland ablation sparing the urethra, bladder neck, and urinary sphincter. Primary endpoints were safety and PSA reduction at 1 year. Secondary endpoints: prostate volume reduction, mpMRI, and 10 core biopsy at 1 year; quality of life, PSA, and salvage to 3 …

The Cgas-Sting Pathway Affects Vertebral Bone But Does Not Promote Intervertebral Disc Cell Senescence Or Degeneration, Olivia K. Ottone, C. James Kim, John A. Collins, Makarand V. Risbud

Department of Orthopaedic Surgery Faculty Papers

The DNA-sensing cGAS-STING pathway promotes the senescence-associated secretory phenotype (SASP) and mediates type-I interferon inflammatory responses to foreign viral and bacterial DNA as well as self-DNA. Studies of the intervertebral disc in humans and mice demonstrate associations between aging, increased cell senescence, and disc degeneration. Herein we assessed the role of STING in SASP promotion in STING gain- (N153S) and loss-of-function mouse models. N153S mice evidenced elevated circulating levels of proinflammatory markers including IL-1β, IL-6, and TNF-α, showed elevated monocyte and macrophage abundance in the vertebral marrow, and exhibited a mild trabecular and cortical bone phenotype in caudal vertebrae. Interestingly, …

Variants In Asph Cause Exertional Heat Illness And Are Associated With Malignant Hyperthermia Susceptibility, Yukari Endo, Linda Groom, Alper Celik, Natalia Kraeva, Chang Seok Lee, Sung Yun Jung, Lois Gardner, Marie-Anne Shaw, Susan L Hamilton, Philip M Hopkins, Robert T Dirksen, Sheila Riazi, James J Dowling

Faculty, Staff and Students Publications

Exertional heat illness (EHI) and malignant hyperthermia (MH) are life threatening conditions associated with muscle breakdown in the setting of triggering factors including volatile anesthetics, exercise, and high environmental temperature. To identify new genetic variants that predispose to EHI and/or MH, we performed genomic sequencing on a cohort with EHI/MH and/or abnormal caffeine-halothane contracture test. In five individuals, we identified rare, pathogenic heterozygous variants in ASPH, a gene encoding junctin, a regulator of excitation-contraction coupling. We validated the pathogenicity of these variants using orthogonal pre-clinical models, CRISPR-edited C2C12 myotubes and transgenic zebrafish. In total, we demonstrate that ASPH variants represent …

Estimating Circadian Phase In Elementary School Children: Leveraging Advances In Physiologically Informed Models Of Circadian Entrainment And Wearable Devices, Jennette P Moreno, Kevin M Hannay, Olivia Walch, Hafza Dadabhoy, Jessica Christian, Maurice Puyau, Abeer El-Mubasher, Fida Bacha, Sarah R Grant, Rebekah Julie Park, Philip Cheng

Faculty, Staff and Students Publications

STUDY OBJECTIVES: Examine the ability of a physiologically based mathematical model of human circadian rhythms to predict circadian phase, as measured by salivary dim light melatonin onset (DLMO), in children compared to other proxy measurements of circadian phase (bedtime, sleep midpoint, and wake time).

METHODS: As part of an ongoing clinical trial, a sample of 29 elementary school children (mean age: 7.4 ± .97 years) completed 7 days of wrist actigraphy before a lab visit to assess DLMO. Hourly salivary melatonin samples were collected under dim light conditions (<5 >lx). Data from actigraphy were used to generate predictions of circadian …