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Full-Text Articles in Medical Specialties

Bivalirudin Stability In Citrated Plasma And Citrated Whole Blood, Karen Bruzdoski, Vadim Kostousov, Jun Teruya Jan 2024

Bivalirudin Stability In Citrated Plasma And Citrated Whole Blood, Karen Bruzdoski, Vadim Kostousov, Jun Teruya

Faculty, Staff and Students Publications

No abstract provided.


High-Fat Diets Promote Peritoneal Inflammation And Augment Endometriosis-Associated Abdominal Hyperalgesia, Tristin Herup-Wheeler, Mingxin Shi, Madeleine E Harvey, Chandni Talwar, Ramakrishna Kommagani, James A Maclean, Kanako Hayashi Jan 2024

High-Fat Diets Promote Peritoneal Inflammation And Augment Endometriosis-Associated Abdominal Hyperalgesia, Tristin Herup-Wheeler, Mingxin Shi, Madeleine E Harvey, Chandni Talwar, Ramakrishna Kommagani, James A Maclean, Kanako Hayashi

Faculty, Staff and Students Publications

Immune dysfunction is one of the central components in the development and progression of endometriosis by establishing a chronic inflammatory environment. Western-style high-fat diets (HFD) have been linked to greater systemic inflammation to cause metabolic and chronic inflammatory diseases, and are also considered an environmental risk factor for gynecologic diseases. Here, we aimed to examine how HFD cause an inflammatory environment in endometriosis and discern their contribution to endometriotic-associated hyperalgesia. Our results showed that HFD-induced obesity enhanced abdominal hyperalgesia that was induced by endometriotic lesions. Peritoneal inflammatory macrophages and cytokine levels increased by lesion induction were elevated by chronic exposure …


Pseudoviruses, A Safer Toolbox For Vaccine Development Against Enveloped Viruses, Syamala R Thimmiraju, Jason T Kimata, Jeroen Pollet Jan 2024

Pseudoviruses, A Safer Toolbox For Vaccine Development Against Enveloped Viruses, Syamala R Thimmiraju, Jason T Kimata, Jeroen Pollet

Faculty, Staff and Students Publications

Introduction: Pseudoviruses are recombinant, replication-incompetent, viral particles designed to mimic the surface characteristics of native enveloped viruses. They are a safer, and cost-effective research alternative to live viruses. With the potential emergence of the next major infectious disease, more vaccine scientists must become familiar with the pseudovirus platform as a vaccine development tool to mitigate future outbreaks.

Areas covered: This review aims at vaccine developers to provide a basic understanding of pseudoviruses, list their production methods, and discuss their utility to assess vaccine efficacy against enveloped viral pathogens. We further illustrate their usefulness as wet-lab simulators for emerging mutant variants, …


Diagnostic Accuracy Of Urinary N Terminal Pro-B Type Natriuretic Peptides For Hemodynamically Significant-Patent Ductus Arteriosus In Preterm Infants, Srirupa Hari Gopal, Ganga Gokulakrishnan, Madhulika Kulkarni, Caraciolo J Fernandes, Mohan Pammi Jan 2024

Diagnostic Accuracy Of Urinary N Terminal Pro-B Type Natriuretic Peptides For Hemodynamically Significant-Patent Ductus Arteriosus In Preterm Infants, Srirupa Hari Gopal, Ganga Gokulakrishnan, Madhulika Kulkarni, Caraciolo J Fernandes, Mohan Pammi

Faculty, Staff and Students Publications

Background: Echocardiography is the gold standard for the diagnosis hemodynamically significant-patent ductus arteriosus (hs-PDA). It requires trained personnel and is not readily available. Urinary biomarkers can be used as an adjunct.

Objective: The objective of this study was to systematically review the diagnostic accuracy of urinary N terminal pro-B type natriuretic peptides (NT-proBNP) for hs-PDA in preterm neonates.

Methods: We included studies that evaluated urinary NT-proBNP and urinary NT-proBNP/creatinine ratio (index tests) in preterm neonates with hs-PDA (participants) in comparison with echocardiogram (reference standard). Methodological quality and certainty of evidence were assessed using Quality Assessment of Diagnostic-Accuracy Studies (QUADAS-2) and …


Emulating A Randomized Clinical Trial With Real-World Data To Evaluate The Effect Of Antidepressant Use In Ptsd Patients With High Suicide Risk, Oshin Miranda, Xiguang Qi, M Daniel Brannock, Ryan Whitworth, Thomas Kosten, Neal David Ryan, Gretchen L Haas, Levent Kirisci, Lirong Wang Jan 2024

Emulating A Randomized Clinical Trial With Real-World Data To Evaluate The Effect Of Antidepressant Use In Ptsd Patients With High Suicide Risk, Oshin Miranda, Xiguang Qi, M Daniel Brannock, Ryan Whitworth, Thomas Kosten, Neal David Ryan, Gretchen L Haas, Levent Kirisci, Lirong Wang

Faculty, Staff and Students Publications

INTRODUCTION: Post-Traumatic Stress Disorder (PTSD) entails behavioral changes with increased risk of suicide, and there is no consensus on the preferred antidepressants for treatment of those PTSD patients who are at elevated risk for suicide.

METHODS: We conducted a clinical trial emulation study comparing suicide-related events (SREs) among those patients' initiating antidepressants within 60 days after a qualifying SRE. Patients were followed from initiation of antidepressant until any of the following: treatment cessation, switching, death, or loss to follow-up. The outcome is a new onset of an SRE.

RESULTS: Citalopram exhibited a significantly fewer case with new SREs compared to …


A Novel System To Culture Human Intestinal Organoids Under Physiological Oxygen Content To Study Microbial-Host Interaction, Tatiana Y Fofanova, Umesh C Karandikar, Jennifer M Auchtung, Reid L Wilson, Antonio J Valentin, Robert A Britton, K Jane Grande-Allen, Mary K Estes, Kristi Hoffman, Sashirekha Ramani, Christopher J Stewart, Joseph F Petrosino Jan 2024

A Novel System To Culture Human Intestinal Organoids Under Physiological Oxygen Content To Study Microbial-Host Interaction, Tatiana Y Fofanova, Umesh C Karandikar, Jennifer M Auchtung, Reid L Wilson, Antonio J Valentin, Robert A Britton, K Jane Grande-Allen, Mary K Estes, Kristi Hoffman, Sashirekha Ramani, Christopher J Stewart, Joseph F Petrosino

Faculty, Staff and Students Publications

Mechanistic investigation of host-microbe interactions in the human gut are hindered by difficulty of co-culturing microbes with intestinal epithelial cells. On one hand the gut bacteria are a mix of facultative, aerotolerant or obligate anaerobes, while the intestinal epithelium requires oxygen for growth and function. Thus, a coculture system that can recreate these contrasting oxygen requirements is critical step towards our understanding microbial-host interactions in the human gut. Here, we demonstrate Intestinal Organoid Physoxic Coculture (IOPC) system, a simple and cost-effective method for coculturing anaerobic intestinal bacteria with human intestinal organoids (HIOs). Using commensal anaerobes with varying degrees of oxygen …


Dialysis Modality, Transplant Characteristics, And Incident Atrial Fibrillation After Kidney Transplant: An Observational Study Using Usrds Data, Leonardo Pozo Garcia, Sai Liu, Colin R Lenihan, Maria E Montez-Rath, Tara I Chang, Wolfgang C Winkelmayer, Pascale Khairallah Jan 2024

Dialysis Modality, Transplant Characteristics, And Incident Atrial Fibrillation After Kidney Transplant: An Observational Study Using Usrds Data, Leonardo Pozo Garcia, Sai Liu, Colin R Lenihan, Maria E Montez-Rath, Tara I Chang, Wolfgang C Winkelmayer, Pascale Khairallah

Faculty, Staff and Students Publications

RATIONALE & OBJECTIVE: Atrial fibrillation is the most common arrhythmia and is increasing in prevalence. The prevalence of atrial fibrillation is high among patients receiving dialysis, affecting ∼21.3% of the patients receiving hemodialysis and 15.5% of those receiving peritoneal dialysis. The association of previous dialysis modality with incident atrial fibrillation in patients after receiving their first kidney transplant has not been studied.

STUDY DESIGN: We used the United States Renal Data System to retrospectively identify adult, Medicare-insured patients who received their first kidney transplant between January 1, 2005, and September 30, 2012 and who had not previously been diagnosed with …


Treatment Guidelines For Hyponatremia: Stay The Course, Richard H Sterns, Helbert Rondon-Berrios, Horacio J Adrogué, Tomas Berl, Volker Burst, David M Cohen, Mirjam Christ-Crain, Martin Cuesta, Guy Decaux, Michael Emmett, Aoife Garrahy, Fabrice Gankam-Kengne, John K Hix, Ewout J Hoorn, Kamel S Kamel, Nicolaos E Madias, Alessandro Peri, Julie Refardt, Mitchell H Rosner, Mark Sherlock, Stephen M Silver, Alain Soupart, Chris J Thompson, Joseph G Verbalis Jan 2024

Treatment Guidelines For Hyponatremia: Stay The Course, Richard H Sterns, Helbert Rondon-Berrios, Horacio J Adrogué, Tomas Berl, Volker Burst, David M Cohen, Mirjam Christ-Crain, Martin Cuesta, Guy Decaux, Michael Emmett, Aoife Garrahy, Fabrice Gankam-Kengne, John K Hix, Ewout J Hoorn, Kamel S Kamel, Nicolaos E Madias, Alessandro Peri, Julie Refardt, Mitchell H Rosner, Mark Sherlock, Stephen M Silver, Alain Soupart, Chris J Thompson, Joseph G Verbalis

Faculty, Staff and Students Publications

International guidelines designed to minimize the risk of complications that can occur when correcting severe hyponatremia have been widely accepted for a decade. On the basis of the results of a recent large retrospective study of patients hospitalized with hyponatremia, it has been suggested that hyponatremia guidelines have gone too far in limiting the rate of rise of the serum sodium concentration; the need for therapeutic caution and frequent monitoring of the serum sodium concentration has been questioned. These assertions are reminiscent of a controversy that began many years ago. After reviewing the history of that controversy, the evidence supporting …


Spatial Transcriptomics Resolve An Emphysema-Specific Lymphoid Follicle B Cell Signature In Chronic Obstructive Pulmonary Disease, Joselyn Rojas-Quintero, Scott A Ochsner, Felicia New, Prajan Divakar, Chen Xi Yang, Tianshi David Wu, Jerid Robinson, Darshan Shimoga Chandrashekar, Nicholas E Banovich, Ivan O Rosas, Maor Sauler, Farrah Kheradmand, Amit Gaggar, Camilla Margaroli, Raul San Jose Estepar, Neil J Mckenna, Francesca Polverino Jan 2024

Spatial Transcriptomics Resolve An Emphysema-Specific Lymphoid Follicle B Cell Signature In Chronic Obstructive Pulmonary Disease, Joselyn Rojas-Quintero, Scott A Ochsner, Felicia New, Prajan Divakar, Chen Xi Yang, Tianshi David Wu, Jerid Robinson, Darshan Shimoga Chandrashekar, Nicholas E Banovich, Ivan O Rosas, Maor Sauler, Farrah Kheradmand, Amit Gaggar, Camilla Margaroli, Raul San Jose Estepar, Neil J Mckenna, Francesca Polverino

Faculty, Staff and Students Publications

Rationale

Within chronic obstructive pulmonary disease (COPD), emphysema is characterized by a significant yet partially understood B cell immune component.

Objectives

To characterize the transcriptomic signatures from lymphoid follicles (LFs) in ever-smokers without COPD and patients with COPD with varying degrees of emphysema.

Methods

Lung sections from 40 patients with COPD and ever-smokers were used for LF proteomic and transcriptomic spatial profiling. Formalin- and O.C.T.-fixed lung samples obtained from biopsies or lung explants were assessed for LF presence. Emphysema measurements were obtained from clinical chest computed tomographic scans. High-confidence transcriptional target intersection analyses were conducted to resolve emphysema-induced transcriptional networks. …


Pik-Iii Exerts Anti-Fibrotic Effects In Activated Fibroblasts By Regulating P38 Activation, Santiago Sanchez, Aaron K Mcdowell-Sanchez, Sharaz B Al-Meerani, Juan D Cala-Garcia, Alan R Waich Cohen, Scott A Ochsner, Neil J Mckenna, Lindsay J Celada, Minghua Wu, Shervin Assassi, Ivan O Rosas, Konstantin Tsoyi Jan 2024

Pik-Iii Exerts Anti-Fibrotic Effects In Activated Fibroblasts By Regulating P38 Activation, Santiago Sanchez, Aaron K Mcdowell-Sanchez, Sharaz B Al-Meerani, Juan D Cala-Garcia, Alan R Waich Cohen, Scott A Ochsner, Neil J Mckenna, Lindsay J Celada, Minghua Wu, Shervin Assassi, Ivan O Rosas, Konstantin Tsoyi

Faculty, Staff and Students Publications

Systemic sclerosis (SSc), also known as scleroderma, is an autoimmune-driven connective tissue disorder that results in fibrosis of the skin and internal organs such as the lung. Fibroblasts are known as the main effector cells involved in the progression of SSc through the induction of extracellular matrix (ECM) proteins and myofibroblast differentiation. Here, we demonstrate that 4'-(cyclopropylmethyl)-N2-4-pyridinyl-[4,5'-bipyrimidine]-2,2'-diamine (PIK-III), known as class III phosphatidylinositol 3-kinase (PIK3C3/VPS34) inhibitor, exerts potent antifibrotic effects in human dermal fibroblasts (HDFs) by attenuating transforming growth factor-beta 1 (TGF-β1)-induced ECM expression, cell contraction and myofibroblast differentiation. Unexpectedly, neither genetic silencing of PIK3C3 nor other PIK3C3 inhibitors (e.g., …


Achieving Surgical, Obstetric, Trauma, And Anesthesia (Sota) Care For All In South Asia, Siddhesh Zadey, Shirish Rao, Isha Gondi, Natalie Sheneman, Chaitrali Patil, Anveshi Nayan, Himanshu Iyer, Arti Raj Kumar, Arun Prasad, G Allen Finley, Chellapuram Raja Krishna Prasad, Chintamani, Dhananjaya Sharma, Dhruva Ghosh, Gnanaraj Jesudian, Irum Fatima, Jogi Pattisapu, Justin Sangwook Ko, Lovenish Bains, Mashal Shah, Mohammed Shadrul Alam, Narmada Hadigal, Naveen Malhotra, Nilmini Wijesuriya, Prateek Shukla, Sadaf Khan, Sunil Pandya, Tariq Khan, Tashi Tenzin, Venkat Raja Hadiga, Daniel Peterson Jan 2024

Achieving Surgical, Obstetric, Trauma, And Anesthesia (Sota) Care For All In South Asia, Siddhesh Zadey, Shirish Rao, Isha Gondi, Natalie Sheneman, Chaitrali Patil, Anveshi Nayan, Himanshu Iyer, Arti Raj Kumar, Arun Prasad, G Allen Finley, Chellapuram Raja Krishna Prasad, Chintamani, Dhananjaya Sharma, Dhruva Ghosh, Gnanaraj Jesudian, Irum Fatima, Jogi Pattisapu, Justin Sangwook Ko, Lovenish Bains, Mashal Shah, Mohammed Shadrul Alam, Narmada Hadigal, Naveen Malhotra, Nilmini Wijesuriya, Prateek Shukla, Sadaf Khan, Sunil Pandya, Tariq Khan, Tashi Tenzin, Venkat Raja Hadiga, Daniel Peterson

Faculty, Staff and Students Publications

South Asia is a demographically crucial, economically aspiring, and socio-culturally diverse region in the world. The region contributes to a large burden of surgically-treatable disease conditions. A large number of people in South Asia cannot access safe and affordable surgical, obstetric, trauma, and anesthesia (SOTA) care when in need. Yet, attention to the region in Global Surgery and Global Health is limited. Here, we assess the status of SOTA care in South Asia. We summarize the evidence on SOTA care indicators and planning. Region-wide, as well as country-specific challenges are highlighted. We also discuss potential directions-initiatives and innovations-toward addressing these …


Effects Of Covid-19 On Sleep Services Use And Its Recovery, Amin Ramezani, Amir Sharafkhaneh, Ahmed S Bahammam, Samuel T Kuna, Javad Razjouyan Jan 2024

Effects Of Covid-19 On Sleep Services Use And Its Recovery, Amin Ramezani, Amir Sharafkhaneh, Ahmed S Bahammam, Samuel T Kuna, Javad Razjouyan

Faculty, Staff and Students Publications

PURPOSE: The COVID-19 pandemic affected the utilization of various healthcare services differentially. Sleep testing services utilization (STU), including Home Sleep Apnea Testing (HSAT) and Polysomnography (PSG), were uniquely affected. We assessed the effects of the pandemic on STU and its recovery using the Veterans Health Administration (VHA) data.

PATIENTS AND METHODS: A retrospective cohort study from the VHA between 01/2019 and 10/2023 of veterans with age ≥ 50. We extracted STU data using Current Procedural Terminology codes for five periods based on STU and vaccination status: pre-pandemic (Pre-Pan), pandemic sleep test moratorium (Pan-Mor), and pandemic pre-vaccination (Pan-Pre-Vax), vaccination (Pan-Vax), and …


Age-Associated Temporal Decline In Butyrate-Producing Bacteria Plays A Key Pathogenic Role In The Onset And Progression Of Neuropathology And Memory Deficits In 3×Tg-Ad Mice, Paula M Chilton, Smita S Ghare, Benjamin T Charpentier, Scott A Myers, Aakarsha V Rao, Joseph F Petrosino, Kristi L Hoffman, John C Greenwell, Neetu Tyagi, Jyotirmaya Behera, Yali Wang, Lucy J Sloan, Jingwen Zhang, Christopher B Shields, Gregory E Cooper, Leila Gobejishvili, Scott R Whittemore, Craig J Mcclain, Shirish S Barve Jan 2024

Age-Associated Temporal Decline In Butyrate-Producing Bacteria Plays A Key Pathogenic Role In The Onset And Progression Of Neuropathology And Memory Deficits In 3×Tg-Ad Mice, Paula M Chilton, Smita S Ghare, Benjamin T Charpentier, Scott A Myers, Aakarsha V Rao, Joseph F Petrosino, Kristi L Hoffman, John C Greenwell, Neetu Tyagi, Jyotirmaya Behera, Yali Wang, Lucy J Sloan, Jingwen Zhang, Christopher B Shields, Gregory E Cooper, Leila Gobejishvili, Scott R Whittemore, Craig J Mcclain, Shirish S Barve

Faculty, Staff and Students Publications

Alterations in the gut-microbiome-brain axis are increasingly being recognized to be involved in Alzheimer's disease (AD) pathogenesis. However, the functional consequences of enteric dysbiosis linking gut microbiota and brain pathology in AD progression remain largely undetermined. The present work investigated the causal role of age-associated temporal decline in butyrate-producing bacteria and butyrate in the etiopathogenesis of AD. Longitudinal metagenomics, neuropathological, and memory analyses were performed in the 3×Tg-AD mouse model. Metataxonomic analyses showed a significant temporal decline in the alpha diversity marked by a decrease in butyrate-producing bacterial communities and a concurrent reduction in cecal butyrate production. Inferred metagenomics analysis …


Vaccines Against Extraintestinal Pathogenic Escherichia Coli (Expec): Progress And Challenges, Ling Qiu, Dylan Chirman, Justin R Clark, Yikun Xing, Haroldo Hernandez Santos, Ellen E Vaughan, Anthony W Maresso Jan 2024

Vaccines Against Extraintestinal Pathogenic Escherichia Coli (Expec): Progress And Challenges, Ling Qiu, Dylan Chirman, Justin R Clark, Yikun Xing, Haroldo Hernandez Santos, Ellen E Vaughan, Anthony W Maresso

Faculty, Staff and Students Publications

The emergence of antimicrobial resistance (AMR) is a principal global health crisis projected to cause 10 million deaths annually worldwide by 2050. While the Gram-negative bacteria Escherichia coli is commonly found as a commensal microbe in the human gut, some strains are dangerously pathogenic, contributing to the highest AMR-associated mortality. Strains of E. coli that can translocate from the gastrointestinal tract to distal sites, called extraintestinal E. coli (ExPEC), are particularly problematic and predominantly afflict women, the elderly, and immunocompromised populations. Despite nearly 40 years of clinical trials, there is still no vaccine against ExPEC. One reason for this is …


Mitochondrial-Related Hub Genes In Dermatomyositis: Muscle And Skin Datasets-Based Identification And In Vivo Validation, Shuo Wang, Yiping Tang, Xixi Chen, Siyuan Song, Xi Chen, Qiao Zhou, Li Zeng Jan 2024

Mitochondrial-Related Hub Genes In Dermatomyositis: Muscle And Skin Datasets-Based Identification And In Vivo Validation, Shuo Wang, Yiping Tang, Xixi Chen, Siyuan Song, Xi Chen, Qiao Zhou, Li Zeng

Faculty, Staff and Students Publications

Background: Mitochondrial dysfunction has been implicated in the pathogenesis of dermatomyositis (DM), a rare autoimmune disease affecting the skin and muscles. However, the genetic basis underlying dysfunctional mitochondria and the development of DM remains incomplete.

Methods: The datasets of DM muscle and skin tissues were retrieved from the Gene Expression Omnibus database. The mitochondrial related genes (MRGs) were retrieved from MitoCarta. DM-related modules in muscle and skin tissues were identified with the analysis of weighted gene co-expression network (WGCNA), and then compared with the MRGs to obtain the overlapping mitochondrial related module genes (mito-MGs). Subsequently, differential expression genes (DEGs) obtained …


Prospective Associations Of Psychedelic Treatment For Co-Occurring Alcohol Misuse And Posttraumatic Stress Symptoms Among United States Special Operations Forces Veterans, Stacey B Armstrong, Yitong Xin, Nathan D Sepeda, Martín Polanco, Lynnette A Averill, Alan K Davis Jan 2024

Prospective Associations Of Psychedelic Treatment For Co-Occurring Alcohol Misuse And Posttraumatic Stress Symptoms Among United States Special Operations Forces Veterans, Stacey B Armstrong, Yitong Xin, Nathan D Sepeda, Martín Polanco, Lynnette A Averill, Alan K Davis

Faculty, Staff and Students Publications

This study evaluated prospective associations of ibogaine and 5-MeO-DMT treatment for risky alcohol use and post-traumatic stress disorder (PTSD) symptoms among United States (US) Special Operations Forces Veterans (SOFV). Data were collected during standard clinical operations at pre-treatment and 1-month (1 m), 3-months (3 m), and 6-months (6 m) post-treatment in an ibogaine and 5-MeO-DMT treatment program in Mexico. Of the 86 SOFV that completed treatment, 45 met criteria for risky alcohol use at pre-treatment (mean age = 44; male = 100%; White = 91%). There was a significant reduction in alcohol use from pre-treatment (M = 7.2, SD = …


Folate Regulation Of Planar Cell Polarity Pathway And F-Actin Through Folate Receptor Alpha, Xiao Han, Xuanye Cao, Robert M Cabrera, Paula Andrea Pimienta Ramirez, Ying Linda Lin, Bogdan J Wlodarczyk, Cuilian Zhang, Richard H Finnell, Yunping Lei Jan 2024

Folate Regulation Of Planar Cell Polarity Pathway And F-Actin Through Folate Receptor Alpha, Xiao Han, Xuanye Cao, Robert M Cabrera, Paula Andrea Pimienta Ramirez, Ying Linda Lin, Bogdan J Wlodarczyk, Cuilian Zhang, Richard H Finnell, Yunping Lei

Faculty, Staff and Students Publications

Folate deficiency contribute to neural tube defects (NTDs) which could be rescued by folate supplementation. However, the underlying mechanisms are still not fully understood. Besides, there is considerable controversy concerning the forms of folate used for supplementation. To address this controversy, we prepared culture medium with different forms of folate, Folic acid (FA) and 5-methyltetrahydrofolate(5mTHF), at concentration of 5uM, 500nM, 50nM and folate free, respectively. Mouse embryonic fibroblasts (MEFs) were treated with different folates continuously for three passages and cell proliferation and F-actin was monitored. We determined that compared to 5mTHF, FA showed stronger effects on promoting cell proliferation and …


Integrative Computational Analyses Implicate Regulatory Genomic Elements Contributing To Spina Bifida, Paul Wolujewicz, Vanessa Aguiar-Pulido, Gaurav Thareja, Karsten Suhre, Olivier Elemento, Richard H Finnell, M Elizabeth Ross Jan 2024

Integrative Computational Analyses Implicate Regulatory Genomic Elements Contributing To Spina Bifida, Paul Wolujewicz, Vanessa Aguiar-Pulido, Gaurav Thareja, Karsten Suhre, Olivier Elemento, Richard H Finnell, M Elizabeth Ross

Faculty, Staff and Students Publications

PURPOSE: Spina bifida (SB) arises from complex genetic interactions that converge to interfere with neural tube closure. Understanding the precise patterns conferring SB risk requires a deep exploration of the genomic networks and molecular pathways that govern neurulation. This study aims to delineate genome-wide regulatory signatures underlying SB pathophysiology.

METHODS: An untargeted, genome-wide approach was used to interrogate regulatory regions for rare single-nucleotide and copy-number variants (rSNVs and rCNVs, respectively) predicted to affect gene expression, comparing results from SB patients with healthy controls. Qualifying variants were subjected to a deep learning prioritization framework to identify the most functionally relevant variants, …


Regulatory Elements In Sem1-Dlx5-Dlx6 (7q213) Locus Contribute To Genetic Control Of Coronal Nonsyndromic Craniosynostosis And Bone Density-Related Traits, Paola Nicoletti, Samreen Zafer, Lital Matok, Inbar Irron, Meidva Patrick, Rotem Haklai, John Erol Evangelista, Giacomo B Marino, Avi Ma'ayan, Anshuman Sewda, Greg Holmes, Sierra R Britton, Won Jun Lee, Meng Wu, Ying Ru, Eric Arnaud, Lorenzo Botto, Lawrence C Brody, Jo C Byren, Michele Caggana, Suzan L Carmichael, Deirdre Cilliers, Kristin Conway, Karen Crawford, Araceli Cuellar, Federico Di Rocco, Michael Engel, Jeffrey Fearon, Marcia L Feldkamp, Richard Finnell, Sarah Fisher, Christian Freudlsperger, Gemma Garcia-Fructuoso, Rhinda Hagge, Yann Heuzé, Raymond J Harshbarger, Charlotte Hobbs, Meredith Howley, Mary M Jenkins, David Johnson, Cristina M Justice, Alex Kane, Denise Kay, Arun Kumar Gosain, Peter Langlois, Laurence Legal-Mallet, Angela E Lin, James L Mills, Jenny E V Morton, Peter Noons, Andrew Olshan, John Persing, Julie M Phipps, Richard Redett, Jennita Reefhuis, Elias Rizk, Thomas D Samson, Gary M Shaw, Robert Sicko, Nataliya Smith, David Staffenberg, Joan Stoler, Elizabeth Sweeney, Peter J Taub, Andrew T Timberlake, Jolanta Topczewska, Steven A Wall, Alexander F Wilson, Louise C Wilson, Simeon A Boyadjiev, Andrew O M Wilkie, Joan T Richtsmeier, Ethylin Wang Jabs, Paul A Romitti, David Karasik, Ramon Y Birnbaum, Inga Peter Jan 2024

Regulatory Elements In Sem1-Dlx5-Dlx6 (7q213) Locus Contribute To Genetic Control Of Coronal Nonsyndromic Craniosynostosis And Bone Density-Related Traits, Paola Nicoletti, Samreen Zafer, Lital Matok, Inbar Irron, Meidva Patrick, Rotem Haklai, John Erol Evangelista, Giacomo B Marino, Avi Ma'ayan, Anshuman Sewda, Greg Holmes, Sierra R Britton, Won Jun Lee, Meng Wu, Ying Ru, Eric Arnaud, Lorenzo Botto, Lawrence C Brody, Jo C Byren, Michele Caggana, Suzan L Carmichael, Deirdre Cilliers, Kristin Conway, Karen Crawford, Araceli Cuellar, Federico Di Rocco, Michael Engel, Jeffrey Fearon, Marcia L Feldkamp, Richard Finnell, Sarah Fisher, Christian Freudlsperger, Gemma Garcia-Fructuoso, Rhinda Hagge, Yann Heuzé, Raymond J Harshbarger, Charlotte Hobbs, Meredith Howley, Mary M Jenkins, David Johnson, Cristina M Justice, Alex Kane, Denise Kay, Arun Kumar Gosain, Peter Langlois, Laurence Legal-Mallet, Angela E Lin, James L Mills, Jenny E V Morton, Peter Noons, Andrew Olshan, John Persing, Julie M Phipps, Richard Redett, Jennita Reefhuis, Elias Rizk, Thomas D Samson, Gary M Shaw, Robert Sicko, Nataliya Smith, David Staffenberg, Joan Stoler, Elizabeth Sweeney, Peter J Taub, Andrew T Timberlake, Jolanta Topczewska, Steven A Wall, Alexander F Wilson, Louise C Wilson, Simeon A Boyadjiev, Andrew O M Wilkie, Joan T Richtsmeier, Ethylin Wang Jabs, Paul A Romitti, David Karasik, Ramon Y Birnbaum, Inga Peter

Faculty, Staff and Students Publications

PURPOSE: The etiopathogenesis of coronal nonsyndromic craniosynostosis (cNCS), a congenital condition defined by premature fusion of 1 or both coronal sutures, remains largely unknown.

METHODS: We conducted the largest genome-wide association study of cNCS followed by replication, fine mapping, and functional validation of the most significant region using zebrafish animal model.

RESULTS: Genome-wide association study identified 6 independent genome-wide-significant risk alleles, 4 on chromosome 7q21.3 SEM1-DLX5-DLX6 locus, and their combination conferred over 7-fold increased risk of cNCS. The top variants were replicated in an independent cohort and showed pleiotropic effects on brain and facial morphology and bone mineral density. Fine …


Pretreatment Characteristics Associated With Symptom Reduction During Group Cognitive Processing Therapy Versus Exposure Therapy For Ptsd: An Exploratory Study Of Veterans, Christopher Hunt, Brooks Casas, Pearl H Chiu, Lia J Smith, Laura Priorello, Kelly Lee, Matthew Estey, Mary R Newsome, M Wright Williams Jan 2024

Pretreatment Characteristics Associated With Symptom Reduction During Group Cognitive Processing Therapy Versus Exposure Therapy For Ptsd: An Exploratory Study Of Veterans, Christopher Hunt, Brooks Casas, Pearl H Chiu, Lia J Smith, Laura Priorello, Kelly Lee, Matthew Estey, Mary R Newsome, M Wright Williams

Faculty, Staff and Students Publications

Exposure and cognitive-based therapies are both effective for PTSD, but knowledge of which intervention is best for which patient is lacking. This lack of knowledge is particularly noticeable for group treatments, as no study has examined whether responses to different group therapies are associated with different pretreatment characteristics. Here, we explored whether pretreatment levels of three types of psychological characteristics-PTSD symptom clusters, posttraumatic cognitions, and emotion regulation difficulties-were associated with symptom reduction during group-delivered cognitive versus exposure-based PTSD treatment. Participants were Veterans with PTSD drawn from two previous clinical trials: one of group CPT (GCPT;


Research Considerations For Prospective Studies Of Patients With Coma And Disorders Of Consciousness, Lorenzo Tinti, Thomas Lawson, Erika Molteni, Daniel Kondziella, Verena Rass, Tarek Sharshar, Yelena G Bodien, Joseph T Giacino, Stephan A Mayer, Moshgan Amiri, Susanne Muehlschlegel, Chethan P Venkatasubba Rao, Paul M Vespa, David K Menon, Giuseppe Citerio, Raimund Helbok, Molly Mcnett Jan 2024

Research Considerations For Prospective Studies Of Patients With Coma And Disorders Of Consciousness, Lorenzo Tinti, Thomas Lawson, Erika Molteni, Daniel Kondziella, Verena Rass, Tarek Sharshar, Yelena G Bodien, Joseph T Giacino, Stephan A Mayer, Moshgan Amiri, Susanne Muehlschlegel, Chethan P Venkatasubba Rao, Paul M Vespa, David K Menon, Giuseppe Citerio, Raimund Helbok, Molly Mcnett

Faculty, Staff and Students Publications

Disorders of consciousness are neurological conditions characterized by impaired arousal and awareness of self and environment. Behavioural responses are absent or are present but fluctuate. Disorders of consciousness are commonly encountered as a consequence of both acute and chronic brain injuries, yet reliable epidemiological estimates would require inclusive, operational definitions of the concept, as well as wider knowledge dissemination among involved professionals. Whereas several manifestations have been described, including coma, vegetative state/unresponsive wakefulness syndrome and minimally conscious state, a comprehensive neurobiological definition for disorders of consciousness is still lacking. The scientific literature is primarily observational, and studies-specific aetiologies lead to …


Editorial: Epilepsy And Alzheimer’S Disease: Shared Pathology, Clinical Presentations, And Targets For Treatment, Beth Leeman-Markowski, Jeannie Chin, Dominique Leitner, Keith Vossel Jan 2024

Editorial: Epilepsy And Alzheimer’S Disease: Shared Pathology, Clinical Presentations, And Targets For Treatment, Beth Leeman-Markowski, Jeannie Chin, Dominique Leitner, Keith Vossel

Faculty, Staff and Students Publications

No abstract provided.


Editorial: Symmetry As A Guiding Principle In Artificial And Brain Neural Networks, Volume Ii, Fabio Anselmi, Ankit B Patel Jan 2024

Editorial: Symmetry As A Guiding Principle In Artificial And Brain Neural Networks, Volume Ii, Fabio Anselmi, Ankit B Patel

Faculty, Staff and Students Publications

No abstract provided.


Comparison Of Four Protocols For In Vitro Differentiation Of Human Embryonic Stem Cells Into Trophoblast Lineages By Bmp4 And Dual Inhibition Of Activin/Nodal And Fgf2 Signaling, Zahra Anvar, Imen Chakchouk, Momal Sharif, Sangeetha Mahadevan, Li Su, Swathi Anikar, Fatemeh Alavi Naini, Alloysius Budi Utama, Ignatia B Van Den Veyver Jan 2024

Comparison Of Four Protocols For In Vitro Differentiation Of Human Embryonic Stem Cells Into Trophoblast Lineages By Bmp4 And Dual Inhibition Of Activin/Nodal And Fgf2 Signaling, Zahra Anvar, Imen Chakchouk, Momal Sharif, Sangeetha Mahadevan, Li Su, Swathi Anikar, Fatemeh Alavi Naini, Alloysius Budi Utama, Ignatia B Van Den Veyver

Faculty, Staff and Students Publications

Human embryonic stem cells (hESCs) cultured in media containing bone morphogenic protein 4 (BMP4; B) differentiate into trophoblast-like cells. Supplementing media with inhibitors of activin/nodal signaling (A83-01) and of fibroblast growth factor 2 (PD173074) suppresses mesoderm and endoderm formation and improves specification of trophoblast-like lineages, but with variable effectiveness. We compared differentiation in four BMP4-containing media: mTeSR1-BMP4 only, mTeSR1-BAP, basal medium with BAP (basal-BAP), and a newly defined medium, E7-BAP. These media variably drive early differentiation towards trophoblast-like lineages with upregulation of early trophoblast markers CDX2 and KRT7 and downregulation of pluripotency markers (OCT4 and NANOG). As expected, based on …


The Uterine Secretome Initiates Growth Of Gynecologic Tissues In Ectopic Locations, Jan Sunde, Morgan Wasickanin, Tiffany A Katz, Laurel Gillette, Sanam Bidadi, Derek O'Neil, Ramya Masand, Richard O Burney, Kathleen A Pennington Jan 2024

The Uterine Secretome Initiates Growth Of Gynecologic Tissues In Ectopic Locations, Jan Sunde, Morgan Wasickanin, Tiffany A Katz, Laurel Gillette, Sanam Bidadi, Derek O'Neil, Ramya Masand, Richard O Burney, Kathleen A Pennington

Faculty, Staff and Students Publications

Endosalpingiosis (ES) and endometriosis (EM) refer to the growth of tubal and endometrial epithelium respectively, outside of their site of origin. We hypothesize that uterine secretome factors drive ectopic growth. To test this, we developed a mouse model of ES and EM using tdTomato (tdT) transgenic fluorescent mice as donors. To block implantation factors, progesterone knockout (PKO) tdT mice were created. Fluorescent lesions were present after oviduct implantation with and without WT endometrium. Implantation was increased (p<0.05) when tdt oviductal tissue was implanted with endometrium compared to oviductal tissue alone. Implantation was reduced (p<0.0005) in animals implanted with minced tdT oviductal tissue with PKO tdT endometrium compared to WT endometrium. Finally, oviductal tissues was incubated with and without a known implantation factor, leukemia inhibitory factor (LIF) prior to and during implantation. LIF promoted lesion implantation. In conclusion, endometrial derived implantation factors, such as LIF, are necessary to initiate ectopic tissue growth. We have developed an animal model of ectopic growth of gynecologic tissues in a WT mouse which will potentially allow for development of new prevention and treatment modalities.


Atypical Haemorrhagic Presentation Of Neuro-Retinitis And Serous Retinal Detachment Secondary To Cat-Scratch Disease, Henry C Skrehot, Amer F Alsoudi, Ryan P Nolan, Adam J Cantor, Asad Loya, Rod Foroozan Jan 2024

Atypical Haemorrhagic Presentation Of Neuro-Retinitis And Serous Retinal Detachment Secondary To Cat-Scratch Disease, Henry C Skrehot, Amer F Alsoudi, Ryan P Nolan, Adam J Cantor, Asad Loya, Rod Foroozan

Faculty, Staff and Students Publications

Cat-scratch disease (CSD) is a self-limited disease caused by Bartonella henselae, a fastidious gram-negative intracellular bacillus bacterium. Neuroretinitis, a form of optic neuropathy characterised clinically by optic disc swelling and a macular star, is an uncommon manifestation of CSD occurring in approximately 1-2% of cases. We report a case of a 14-year-old female who presented to the emergency department with a chief complaint of acute painless vision loss described as a large black spot in the centre of her right eye vision 2 weeks after being scratched by cats. Fundus examination revealed Frisen grade 5 disc oedema with an …


Single Cell Analysis Of Short-Term Dry Eye Induced Changes In Cornea Immune Cell Populations, Jehan Alam, Ebru Yaman, Gerda Cristal Villalba Silva, Rui Chen, Cinita S De Paiva, Mary Ann Stepp, Stephen C Pflugfelder Jan 2024

Single Cell Analysis Of Short-Term Dry Eye Induced Changes In Cornea Immune Cell Populations, Jehan Alam, Ebru Yaman, Gerda Cristal Villalba Silva, Rui Chen, Cinita S De Paiva, Mary Ann Stepp, Stephen C Pflugfelder

Faculty, Staff and Students Publications

BACKGROUND: Dry eye causes corneal inflammation, epitheliopathy and sensorineural changes. This study evaluates the hypothesis that dry eye alters the percentages and transcriptional profiles of immune cell populations in the cornea.

METHODS: Desiccating stress (DS) induced dry eye was created by pharmacologic suppression of tear secretion and exposure to drafty low humidity environment. Expression profiling of corneal immune cells was performed by single-cell RNA sequencing (scRNA-seq). Cell differentiation trajectories and cell fate were modeled through RNA velocity analysis. Confocal microscopy was used to immunodetect corneal immune cells. Irritation response to topical neurostimulants was assessed.

RESULTS: Twelve corneal immune cell populations …


Optical Coherence Elastography Measures The Biomechanical Properties Of The Ex Vivo Porcine Cornea After Lasik, Achuth Nair, Fernando Zvietcovich, Manmohan Singh, Mitchell P Weikert, Salavat R Aglyamov, Kirill V Larin Jan 2024

Optical Coherence Elastography Measures The Biomechanical Properties Of The Ex Vivo Porcine Cornea After Lasik, Achuth Nair, Fernando Zvietcovich, Manmohan Singh, Mitchell P Weikert, Salavat R Aglyamov, Kirill V Larin

Faculty, Staff and Students Publications

SIGNIFICANCE: The biomechanical impact of refractive surgery has long been an area of investigation. Changes to the cornea structure cause alterations to its mechanical integrity, but few studies have examined its specific mechanical impact.

AIM To quantify how the biomechanical properties of the cornea are altered by laser assisted in situ keratomileusis (LASIK) using optical coherence elastography (OCE) in ex vivo porcine corneas.

APPROACH: Three OCE techniques, wave-based air-coupled ultrasound (ACUS) OCE, heartbeat (Hb) OCE, and compression OCE were used to measure the mechanical properties of paired porcine corneas, where one eye of the pair was left untreated, and the …


The Co-Expression Of The Depolarizing And Hyperpolarizing Mechanosensitive Ion Channels In Mammalian Retinal Neurons, Vivian Y Pang, Zhuo Yang, Samuel M Wu, Ji-Jie Pang Jan 2024

The Co-Expression Of The Depolarizing And Hyperpolarizing Mechanosensitive Ion Channels In Mammalian Retinal Neurons, Vivian Y Pang, Zhuo Yang, Samuel M Wu, Ji-Jie Pang

Faculty, Staff and Students Publications

Introduction

The elevation of the intraocular and extraocular pressures is associated with various visual conditions, including glaucoma and traumatic retinal injury. The retina expresses mechanosensitive channels (MSCs), but the role of MSCs in retinal physiology and pathologies has been unclear.

Methods

Using immunocytochemistry, confocal microscopy, and patch-clamp recording techniques, we studied the co-expression of K+-permeable (K-MSCs) TRAAK and big potassium channel BK with the epithelial sodium channel ENaC and transient receptor potential channel vanilloid TPRV4 and TRPV2 favorably permeable to Ca2+ than Na+ (together named N-MSCs), and TRPV4 activity in the mouse retina.

Results

TRAAK immunoreactivity …


Evaluating One-Week Post-Casting Alignment Checks And Surgical Intervention Rates In Pediatric Type Iia Supracondylar Humeral Fractures, Jason Z Amaral, Rebecca J Schultz, Benjamin M Martin, Jacob P Scioscia, Basel Touban, Barkha N Chhabra, Kelly Cline, Scott D Mckay Jan 2024

Evaluating One-Week Post-Casting Alignment Checks And Surgical Intervention Rates In Pediatric Type Iia Supracondylar Humeral Fractures, Jason Z Amaral, Rebecca J Schultz, Benjamin M Martin, Jacob P Scioscia, Basel Touban, Barkha N Chhabra, Kelly Cline, Scott D Mckay

Faculty, Staff and Students Publications

BACKGROUND: This study aims to determine the rate of surgical intervention in children with type IIA supracondylar humerus fractures (SCHF) following routine post-casting radiographic assessment. We hypothesized that no cases would convert to operative management following one-week post-casting alignment assessments.

METHODS: This single-center retrospective study focused on pediatric patients diagnosed with type IIA SCHF from 2019 to 2022. Patients were treated with initial long arm cast immobilization, followed by a one-week post-casting radiographic alignment check in cast. Fractures were graded in consensus using the Wilkins-Modified Gartland classification system by three fellowship-trained pediatric orthopaedic surgeons. Demographics, casting details, follow-up dates, and …