Medical Specialties Commons^™

Improving Radiotherapy Workflow: Evaluation And Implementation Of Deep Learning Auto-Segmentation In A Multi-User Environment, And Development Of Automatic Contour Quality Assurance System, Jingwei Duan

Theses and Dissertations--Radiation Medicine

Radiotherapy is a frequently used therapeutic modality for cancer patients. Accurately contouring of tumors and organs at risk (OARs) is critical for developing optimal treatment plans in radiotherapy, especially after the implementation of Intensity-modulated radiation therapy (IMRT) and Stereotactic Body Radiation Therapy (SBRT). The manual contouring process is time-consuming and suffers from inter-observer variations. However, manual contouring is often hindered by laborious clinical duties, leading to reduced effectiveness, and increased segmentation errors due to fatigue. Additionally, online adaptive radiation therapy(ART), which has been shown to benefit patient outcomes, places higher demands on contouring and quality assurance (QA) speed.

Recently, deep …

Development Of A Community-Based Plan For An Effective Behavioral Intervention To Reduce Childhood Obesity In A Rural Appalachian Community, Jennifer Stacy Wells

Theses and Dissertations--Nutrition and Food Systems

Rural children experience increased rates of obesity and reduced access to specialized weight management facilities, which makes receiving the recommended frequency of care difficult. Clinical-community partnerships, recommended by the American Academy of Pediatrics (AAP) to expand access, have been shown to be a feasible strategy of care delivery. Examination of literature and stakeholder interviews were used to inform the development of a collaborative pediatric weight management program in a rural, Appalachian community. Screening articles as well as intervention articles were reviewed. Outcomes of screening articles reviewed included BMI measures (3), screening practices (7), and referral practices (4). Common outcomes of …

Alternative Pharmacology: Exploring Ketamine Use For Treatment Resistant Mental Health Disorders, Kiersten L. Ash

Soaring: A Journal of Undergraduate Research

No abstract provided.

Social Determinants Of Mental Health Considerations For Counseling Children And Adolescents, Kaprea F. Johnson, Patrick D. Cunningham, Camila Tirado, Oswaldo Moreno, Nancy N. Gillespie, Bisola Duyile, Dequindre C. Hughes, Emily Goodman Scott, Dana Brookover

Counseling & Human Services Faculty Publications

Childhood is a crucial period for developing a strong social and emotional foundation critical for mental well-being. Given that the childhood developmental period is vital for mental health, it is essential to address social determinants that can disrupt development and have lasting adverse effects on psychological and physical health. Therefore, professional counselors specializing in children and adolescent mental health care can benefit from understanding and utilizing the social determinants of mental health (SDOMH) framework in practice. This article details the SDOMH framework and considerations for SDOMH-informed treatments for professional counselors working in settings with children and adolescents.

Soft X-Ray And Susceptibility Based Magnetic Resonance Imaging To Map Iron Distribution In Apples: Initial Results To Model Iron Storage In Water-Deficient Or Dehydrated Biological Tissue, Subhendra N. Sarkar, Eric Lobel, Evans Lespinasse, Zoya Vinokur, Analia Basilicata, Sonia Orellana, Maria Orellana, Aaliyah Salmon, Joanna Syska, Aravis Mcbroom, Jian Wang, Anam Riaz, Jodi-Ann Douglas

Publications and Research

Radiology departments have contributed significantly to greenhouse gases including release of toxic imaging contrast media to environment. We feel Radiology also has several spectroscopy and imaging tools that may apply to monitor and support cleaner environmental goals. The current manuscript is one of the firsts to prompt Radiology to move in that direction by non invasive imaging of bio metals that are less abundant in biological tissues but play key roles as co-factors in tissue structure and function. Conventional analytical tools are mostly invasive and cannot characterize the native oxidation states of bio metals. We chose carbohydrate matrix of metal-rich …

Investigating Relationships Found In The Kidney Microenvironment To Aid In Understanding Malfunctions Of Proteins In Chronic Kidney Disease, Ademide Ogunsina

Holster Scholar Projects

The kidneys are the filtration organ that helps filter out waste from our body. Kidney disease is an ailment that causes damage to the kidney so that it cannot filter our blood and other bodily fluids properly. It is also one of the least researched illnesses in the medical field. And with about 10-15 percent of the American population suffering from kidney disease, there is an urgency in finding more ways to help find a solution.

I examined the damaged kidney environment at the cellular level to find out what protein processes cause the malfunction of the kidneys. Methodologies employed …

Implementation Of A Multipronged Approach To Improve Pre-Operative Efficiency And First Case On Time Start Performance, Melyssa A. Stokes

Master's Theses and Capstones

Background: Surgical services are an important source of revenue and important economic driver of hospital systems. Surgical services account for approximately 42% of a hospital’s annual revenue, however, it also constitutes 40% of facility operating costs (Gupta, et al., 2022 & Morel & Gomez, 2021). Despite the high costs associated with surgical services delays remain a significant issue across the nation. On-time starts for the first surgical cases of the day is a key performance metric tracked by surgical facilities to determine efficiency. Currently, 50 – 90% of first surgical cases are delayed throughout the United States and the most …

Implementation Of Point-Of-Care Tick-Borne Disease Powerplan™ And Algorithm For Early Detection And Treatment Of Tick-Borne Diseases, Ashley Pinkham

DNP Scholarly Projects

Abstract

Local Problem: The Concord Hospital system, serving 30+ communities, is situated in the heart of New Hampshire surrounded by densely wooded forests, lakes, and mountains and is a mecca for camping, vacationing, and sightseeing, doubling its population of 1.6 million residents during spring, summer, and fall months. Despite the serenity, there is a predator that lingers among the hiking trails and lake shorelines. From January 2021 through August 2022 there were a total of 41 hospitalizations from tick-borne diseases, some with life threatening symptoms. Unfortunately, nearly half (43%) of patients presented to their primary care provider first where the …

Intervention To Improve Screening Mammograms In Clinical Practice., Saida Khamooshi

DNP Scholarly Projects

Abstract

Breast cancer remains a challenging health issue in the United States, representing the second leading cause of cancer deaths for women. The key approach to tackle this issue is the early detection of breast cancer through annual mammography screening in asymptomatic women. This quality improvement project sought to improve the proportion of breast cancer screening documentation in a private obstetrics and gynecology practice that serves primarily Black women. In addition, the project is thought to improve the current utilization of office mammogram services and its mammogram completion rate. Comprehensive interventions implemented included establishing clear guidelines, staff education, using paper …

The Write Stuff - Winter 2023 (Vol. 20, No. 1), Research Medical Library

Write Stuff 2023

• Protected health information
• Literature reviews: Which type should I write?
• Finding examples of funded NIH applications
• New NIH policy for data management and sharing now in effect
• Unusual terms used in scientific writing and publishing: Person-first language

The Kynurenine Pathway In Alzheimer’S Disease: A Meta-Analysis Of Central And Peripheral Levels, Brisa S Fernandes, Mehmet Enes Inam, Nitesh Enduru, Joao Quevedo, Zhongming Zhao

Faculty, Staff and Student Publications

OBJECTIVE: Changes in the kynurenine pathway are recognized in psychiatric disorders, but their role in Alzheimer's disease (AD) is less clear. We aimed to conduct a systematic review and meta-analysis to determine whether tryptophan and kynurenine pathway metabolites are altered in AD.

METHODS: We performed a systematic review and random-effects meta-analyses. Inclusion criteria were studies that compared AD and cognitively normal (CN) groups and assessed tryptophan or kynurenine pathway metabolites in cerebrospinal fluid or peripheral blood.

RESULTS: Twenty-two studies with a total of 1,356 participants (664 with AD and 692 CN individuals) were included. Tryptophan was decreased only in peripheral …

An Online Intervention To Improve The Health And Well-Being Of Informal Caregivers Of Individuals With Alzheimer's Disease: A Pilot Study, Yujun Liu, M. Courtney Hughes, Abby Baumbach, Lily Derain

Faculty Articles, Papers, and Other Scholarship

Objective: Describe an intervention to improve the health and well-being of informal caregivers of individuals with Alzheimer's disease (AD) and present pilot program findings.

Methods: Participants (N = 31, mean age = 45.7) were randomly assigned to one of two conditions: an online synchronous didactic lesson and peer support session series or an asynchronous didactic only session series. Outcome variables included physical health, nutrition intake, and stress. One-way ANOVA was conducted to examine the effects of the intervention. The least significant difference (LSD) post hoc test was used to analyze the difference pattern between means.

Results: Participants in both conditions …

The Burden And Characteristics Of Hiv Infected Covid-19 Patients At A Tertiary Care Hospital In Sub-Saharan Africa, Alok Iyer

Master of Medicine in Internal Medicine

Background: Since the first case of COVID-19, which was caused by the novel SARS-CoV-2 virus, was identified in Wuhan, China in December 2019, the infection has rapidly spread throughout the world. By March 2020, the World Health Organization declared COVID-19 to be a pandemic. On March 12, 2020, Kenya announced its first COVID-19 infection case. Since then, the number of cases has risen steadily, reaching 5190 cases and 144 fatalities (as of June 30, 2020), endangering the nation's healthcare system. In Kenya, where the prevalence of HIV is 4.9%, 1.38 million adults and 105,000 children are estimated to be HIV …

Factors Associated With Non-Uptake Of Implantable Cardioverter-Defibrillator (Icd) Among Eligible Patients At A Tertiary Hospital In Kenya, Emmanuel Benge Aluoch

Master of Medicine in Internal Medicine

Background: Sudden Cardiac Death (SCD) is a major cause of mortality among patients with cardiovascular disease accounting for about 50% of deaths. Several studies have demonstrated the safety and efficacy of Implantable Cardioverter-Defibrillator (ICD) implantation in both primary and secondary prevention of SCD in at-risk populations. Despite well-publicized guidelines, ICD implantation rates remain low particularly in Africa with a paucity of data regarding factors associated with non-uptake and reasons for implant refusal. The study aimed to characterize these factors and identify reasons for ICD refusal. Understanding these factors and reasons for non-implantation will provide an opportunity to optimize ICD uptake …

Obstructive Sleep Apnea Syndrome Among Hypertensive Patients At A Tertiary Hospital In Kenya, Salim Abdallah Salim

Master of Medicine in Internal Medicine

Introduction: Obstructive sleep apnea (OSA) is a type of breathing problem during sleep caused by the blockage of the upper airway, which can cause a reduction or complete cessation of airflow. Warning signs of OSA include snoring, night sweats, and high blood pressure. However, there is limited research on the prevalence of OSA in hypertensive patients in sub-Saharan Africa (SSA). This study purposed to elucidate the likelihood and clinical characteristics of OSA among hypertensive patients at a tertiary hospital in Nairobi, Kenya. Methods: This prospective cross-sectional study occurred at the Aga Khan University Hospital in Nairobi, Kenya. A total of …

Prediction Of Mortality And Major Adverse Kidney Events In Critically Ill Patients With Acute Kidney Injury, Javier A. Neyra, Victor M. Ortiz-Soriano, Lucas J. Liu, Taylor D. Smith, Xilong Li, Donglu Xie, Beverly Adams-Huet, Orson W. Moe, Robert D. Toto, Jin Chen

Markey Cancer Center Faculty Publications

Rationale & Objective: Risk prediction tools for assisting acute kidney injury (AKI) management have focused on AKI onset but have infrequently addressed kidney recovery. We developed clinical models for risk stratification of mortality and major adverse kidney events (MAKE) in critically ill patients with incident AKI.

Study Design: Multicenter cohort study.

Setting & Participants: 9,587 adult patients admitted to heterogeneous intensive care units (ICUs; March 2009 to February 2017) who experienced AKI within the first 3 days of their ICU stays.

Predictors: Multimodal clinical data consisting of 71 features collected in the first 3 days of ICU stay.

Outcomes: (1) …

An International Real-World Analysis Of Relapsed/Refractory Lymphoma Occurring During Pregnancy, Faheem Farooq, Justin S. Brandt, Elyce Cardonick, Evgeniya Polushkina, Julie M. Vose, Sairah Ahmed, Praveen Ramakrishnan Geethakumari, Adam J. Olszewski, Hesham Yasin, Umar Farooq, Nada Hamad, Yong Lin, Charlotte Maggen, Robert Fruscio, Mina Mhallem Gziri, Karina Dahl Steffensen, Frédéric Amant, Andrew M. Evens

Journal Articles: Oncology and Hematology

No abstract provided.

High-Grade B-Cell Lymphoma, Not Otherwise Specified: A Multi-Institutional Retrospective Study, Adam S. Zayac, Daniel J. Landsburg, Mitchell E. Hughes, Allison M. Bock, Grzegorz S. Nowakowski, Emily C. Ayers, Mark Girton, Marie Hu, Amy K. Beckman, Shaoying Li, L Jeffrey Medeiros, Julie E. Chang, Adam Stepanovic, Habibe Kurt, Jose Sandoval-Sus, M Ali Ansari-Lari, Shalin K. Kothari, Anna Kress, Mina L. Xu, Pallawi Torka, Suchitra Sundaram, Stephen D. Smith, Kikkeri N. Naresh, Yasmin H. Karimi, Narendranath Epperla, David A. Bond, Umar Farooq, Mahak Saad, Andrew M. Evens, Karan Pandya, Seema G. Naik, Manali Kamdar, Bradley Haverkos, Reem Karmali, Timothy S. Oh, Julie M. Vose, Heather Nutsch, Paul G. Rubinstein, Amina Chaudhry, Adam J. Olszewski

Journal Articles: Oncology and Hematology

In this multi-institutional retrospective study, we examined the characteristics and outcomes of 160 patients with high-grade B-cell lymphoma, not otherwise specified (HGBL-NOS)-a rare category defined by high-grade morphologic features and lack of MYC rearrangements with BCL2 and/or BCL6 rearrangements ("double hit"). Our results show that HGBL-NOS tumors are heterogeneous: 83% of patients had a germinal center B-cell immunophenotype, 37% a dual-expressor immunophenotype (MYC and BCL2 expression), 28% MYC rearrangement, 13% BCL2 rearrangement, and 11% BCL6 rearrangement. Most patients presented with stage IV disease, a high serum lactate dehydrogenase, and other high-risk clinical factors. Most frequent first-line regimens included dose-adjusted cyclophosphamide, …

Integrative Analysis Of Clinicopathological Features Defines Novel Prognostic Models For Mantle Cell Lymphoma In The Immunochemotherapy Era: A Report From The North American Mantle Cell Lymphoma Consortium, Julie M. Vose, Kai Fu, Lu Wang, Adnan Mansoor, Douglas Stewart, Hongxia Cheng, Lynette M. Smith, Ji Yuan, Hina Naushad Qureishi, Brian K. Link, Melissa H. Cessna, Paul M. Barr, Brad S. Kahl, Matthew S. Mckinney, Nadia Khan, Ranjana H. Advani, Peter Martin, Andre H. Goy, Tycel J. Phillips, Amitkumar Mehta, Manali Kamdar, Michael Crump, Barbara Pro, Christopher R. Flowers, Caron A. Jacobson, Sonali M. Smith, Deborah M. Stephens, Veronika Bachanova, Zhaohui Jin, Shishou Wu, Francisco Hernandez-Ilizaliturri, Pallawi Torka, Andrea Anampa-Guzmán, Farshid Kashef, Xing Li, Sunandini Sharma, Timothy Greiner, James O. Armitage, Matthew A. Lunning, Dennis D. Weisenburger, Gregory Bociek, Javeed Iqbal, Guohua Yu, Chengfeng Bi, North American Mantle Cell Lymphoma Consortium

Journal Articles: Oncology and Hematology

BACKGROUND: Patients with mantle cell lymphoma (MCL) exhibit a wide variation in clinical presentation and outcome. However, the commonly used prognostic models are outdated and inadequate to address the needs of the current multidisciplinary management of this disease. This study aims to investigate the clinical and pathological features of MCL in the immunochemotherapy era and improve the prognostic models for a more accurate prediction of patient outcomes.

METHODS: The North American Mantle Cell Lymphoma Project is a multi-institutional collaboration of 23 institutions across North America to evaluate and refine prognosticators for front-line therapy. A total of 586 MCL cases diagnosed …

Quality Of Life And Sexual Function Of Women With Endometriosis At The Aga Khan University Hospital Nairobi, Edna Mohere Chacha

Master of Medicine in Obstetrics and Gynecology

Introduction: Endometriosis is a benign, chronic condition that affects up to ten percent of women of childbearing age. It’s marked by the presence of endometrial tissue outside the uterine cavity (Giudice, 2010). It is a health condition with wide-ranging and pervasive sequelae making it a significant health concern requiring appropriate action (Rush & Misajon, 2018). We observed that there was a paucity of data relating to how endometriosis impacted on female sexual function and quality of life in sub-Saharan Africa, Kenya included. Objectives: The primary goal of this empirical investigation was to determine the quality of life of women who …

Africa Guidelines For Hepatocellular Carcinoma Buildup Process, Ghassan Abou-Alfa, Mary Afihene, Marinela Capanu, Joanne Chou, Akwi Asombang, Olusegun Alatise, Adda Bounedjar, Lina Cunha, Hailemichael Mekonnen, Papa Diop, Reda Elwakil, Mahamat Ali, Ntokozo Ndlovu, Jerry Ndumbalo, Precious Makondi, Christian Tzeuton, Tiago Castria, Adwoa Afrakoma Agyei-Nkansah, Fiyinfolu Balogun, Alain Bougouma, Blaise Ibara, Eduard Jonas, Stephen Kimani, Peter Kingham, Reshad Kurrimbukus, Nazik Hammad, Mona Fouad, Noha S. El Baghdady, Eloumou Fiacre, Vikash Sewram, C. Wendy Spearman, Ju Yang, Lewis Roberts, Ashraf Abdelaziz

Pharmacy

Abstract

Purpose

Hepatocellular carcinoma (HCC), the fourth most common cancer in Africa, has a dismal overall survival of only 3 months like in sub-Saharan Africa. This is affected by the low gross domestic product and human development index, absence of coherent guidelines, and other factors.

Methods

An open forum for HCC-experienced health care workers from Africa and the rest of the world was held in October 2021. Participants completed a survey to help assess the real-life access to screening, diagnoses, and treatment in the North and Southern Africa (NS), East and West Africa (EW), Central Africa (C), and the rest …

Standard Deviations Of Mr Signal Intensities Show A Consistent Trend During Imaging Follow-Ups For Glioblastoma Patients When Corrected For Non-Biological Heterogeneity Due To Hardware And Software Variation, Subhendra N. Sarkar, Rafael Rojas, Evans Lespinasse, Xiangfu Zhang, Ruth Zeron

Publications and Research

Introduction

Glioblastoma multiforme (GBM) has a poor prognosis in spite of advanced MRI guided treatments today. Routine MRI using conventional T₁ or advanced permeability based MRI of GBM often does not adequately represent changing tumor phases or overall survival. In this work, region of interest (ROI) based tissue MR standard deviation (SD) is demonstrated as an important MRI variable that could be a potential biomarker of GBM heterogeneity and radioresistance.

Materials and methods

MRI characterization is often qualitative and lacks reproducibility. Using standardized MRI phantoms we have normalized retrospective records of 12 radioresistant GBM patients that underwent radiation therapy …

Does The Cdc Covid-19 Exposure Assessment Criteria For Healthcare Personnel Work In A Healthcare Setting In Pakistan?, Imran Hassan, Unab Khan, Shehreen Ali, Asif Hakim, Asad Ali

Department of Family Medicine

Objective: To evaluate the real-world performance of the CDC's "Interim US guidance for risk assessment and work restriction for healthcare personnel with exposure to COVID-19" at a private healthcare system in Pakistan.
Study design: Retrospective observational study.
Place and duration of study: The Aga khan University Hospital, Karachi, and its associated healthcare facilities in all four provinces of Pakistan, from February to September 2020.
Methodology: Healthcare personnel (HCPs) assessed and tested for exposures to COVID-19 were included in the study. An exposure category was assigned to each HCP presenting with exposure to COVID-19 based on the CDC criteria. Percentage positivity …

Lifetime Interpersonal Violence Or Abuse And Diabetes Rates By Sex And Race, Maureen Sanderson, Mekeila Cook, L. Lauren Brown, Veronica Mallett, Ann L. Coker

Obstetrics and Gynecology Faculty Publications

Introduction: Lifetime exposure to interpersonal violence or abuse has been associated with several chronic diseases, including adult-onset diabetes, yet this pattern has not been confirmed by sex and race within a large cohort.\Methods: Data from the Southern Community Cohort Study collected between 2002−2009 and 2012−2015 were used to explore the relationship between lifetime interpersonal violence or abuse and diabetes (N=25,251). Prospective analyses of lower-income people living in the southeastern U.S. were conducted in 2022 to examine the risk of adult-onset diabetes associated with lifetime interpersonal violence or abuse by sex and race. Lifetime interpersonal violence or abuse was defined as …

Cd47 Antisense Oligonucleotide Treatment Attenuates Obesity And Its-Associated Metabolic Dysfunction, Taesik Gwag, Dong Li, Eric Ma, Zhenheng Guo, Ying Liang, Shuxia Wang

Saha Cardiovascular Research Center Faculty Publications

Previous study from our lab has revealed a new role of CD47 in regulating adipose tissue function, energy homeostasis and the development of obesity and metabolic disease in CD47 deficient mice. In this study, the therapeutic potential of an antisense oligonucleotide (ASO) targeting to CD47 in obesity and its‑associated complications was determined in two obese mouse models (diet induced and genetic models). In diet induced obesity, male C57BL6 mice were fed with high fat (HF) diet to induce obesity and then treated with CD47ASO or control ASO for 8 weeks. In genetic obese mouse model, male six‑week old ob/ob mice …

Platelet Glycogenolysis Is Important For Energy Production And Function, Kanakanagavalli Shravani Prakhya, Hemendra J. Vekaria, Daniёlle M. Coenen, Linda Omali, Joshua Lykins, Smita Joshi, Hammodah Rawhi Hammodah Alfar, Qing Jun Wang, Patrick G. Sullivan, Sidney W. Whiteheart

Saha Cardiovascular Research Center Faculty Publications

Although the presence of glycogen in platelets was established in the 1960s, its importance to specific functions (i.e., activation, secretion, aggregation, and clot contraction) remains unclear. Patients with glycogen storage disease often present with increased bleeding and glycogen phosphorylase (GP) inhibitors, when used as treatments for diabetes, induce bleeding in preclinical studies suggesting some role for this form of glucose in hemostasis. In the present work, we examined how glycogen mobilization affects platelet function using GP inhibitors (CP316819 and CP91149) and a battery of ex vivo assays. Blocking GP activity increased glycogen levels in resting and thrombin-activated platelets and inhibited …

The Complementary Roles Of Vamp-2, -3, And -7 In Platelet Secretion And Function, Smita Joshi, Kanakanagavalli Shravani Prakhya, Alexis N. Smith, Harry Chanzu, Ming Zhang, Sidney W. Whiteheart

Saha Cardiovascular Research Center Faculty Publications

Platelet secretion requires Soluble N-ethylmaleimide Sensitive Attachment Protein Receptors (SNAREs). Vesicle SNAREs/Vesicle-Associated Membrane Proteins (v-SNAREs/ VAMPs) on granules and t-SNAREs in plasma membranes mediate granule release. Platelet VAMP heterogeneity has complicated the assessment of how/if each is used and affects hemostasis. To address the importance of VAMP-7 (V7), we analyzed mice with global deletions of V3 and V7 together or platelet-specific deletions of V2, V3, and global deletion of V7. We measured the kinetics of cargo release, and its effects on three injury models to define the context-specific roles of these VAMPs. Loss of V7 minimally affected dense and α …

Best3-Mediated Mekk2/3 Activation: A Novel Therapeutic Target In Aortopathies, Tatiana Zyrianova, Benjamin Lopez, Kathlyn Zou, Charles Gu, Dayna Pham, Sriharsha Talapaneni, Christopher M. Waters, Riccardo Olcese, Andreas Schwingshackl

Saha Cardiovascular Research Center Faculty Publications

Influenza-A virus (IAV) infects yearly an estimated one billion people worldwide, resulting in 300,000–650,000 deaths. Preventive vaccination programs and antiviral medications represent the mainstay of therapy, but with unacceptably high morbidity and mortality rates, new targeted therapeutic approaches are urgently needed. Since inflammatory processes are commonly associated with measurable changes in the cell membrane potential (Em), we investigated whether Em hyperpolarization via TREK-1 (K2P 2.1) K þ channel activation can protect against influenza-A virus (IAV)-induced pneumonia. We infected mice with IAV, which after 5 days caused 10–15% weight loss and a decrease in spontaneous activity, representing a clinically relevant infection. …

Deep Learning, 3d Ultrastructural Analysis Reveals Quantitative Differences In Platelet And Organelle Packing In Covid-19/Sarscov2 Patient-Derived Platelets, Sagar S. Matharu, Cassidy S. Nordmann, Kurtis R. Ottman, Rahul Akkem, Douglas Palumbo, Denzel R. D. Cruz, Kenneth Campbell, Gail Sievert, Jamie L. Sturgill, James Zachary Porterfield, Smita Joshi, Hammodah Rawhi Hammodah Alfar, Chi Peng, Irina D. Pokrovskaya, Jeffrey A. Kamykowski, Jeremy P. Wood, Beth A. Garvy, Maria A. Aronova, Sidney W. Whiteheart, Richard D. Leapman, Brian Storrie

Saha Cardiovascular Research Center Faculty Publications

Platelets contribute to COVID-19 clinical manifestations, of which microclotting in the pulmonary vasculature has been a prominent symptom. To investigate the potential diagnostic contributions of overall platelet morphology and their α-granules and mitochondria to the understanding of platelet hyperactivation and micro-clotting, we undertook a 3D ultrastructural approach. Because differences might be small, we used the high-contrast, high-resolution technique of focused ion beam scanning EM (FIB-SEM) and employed deep learning computational methods to evaluate nearly 600 individual platelets and 30 000 included organelles within three healthy controls and three severely ill COVID-19 patients. Statistical analysis reveals that the α-granule/ mitochondrion-to-plateletvolume ratio …

Lrp1 Protects Against Excessive Superior Mesenteric Artery Remodeling By Modulating Angiotensin Ii–Mediated Signaling, Jackie M. Zhang, Dianaly T. Au, Hisashi Sawada, Michael K. Franklin, Jessica J. Moorleghen, Deborah A. Howatt, Pengjun Wang, Brittany O. Aicher, Brian Hampton, Mary Migliorini, Fenge Ni, Adam E. Mullick, Mashhood M. Wani, Areck A. Ucuzian, Hong S. Lu, Selen C. Muratoglu, Alan Daugherty, Dudley K. Strickland

Saha Cardiovascular Research Center Faculty Publications

Vascular smooth muscle cells (vSMCs) exert a critical role in sensing and maintaining vascular integrity. These cells abundantly express the low-density lipoprotein receptor–related protein 1 (LRP1), a large endocytic signaling receptor that recognizes numerous ligands, including apolipoprotein E–rich lipoproteins, proteases, and protease-inhibitor complexes. We observed the spontaneous formation of aneurysms in the superior mesenteric artery (SMA) of both male and female mice in which LRP1 was genetically deleted in vSMCs (smLRP1–/– mice). Quantitative proteomics revealed elevated abundance of several proteins in smLRP1–/– mice that are known to be induced by angiotensin II–mediated (AngII-mediated) signaling, suggesting that this pathway was dysregulated. …