Diseases Commons^™

Gm1 Ganglioside As A Disease-Modifying Therapeutic For Parkinson’S Disease: A Multi-Functional Glycosphingolipid That Targets Multiple Parkinson’S Disease-Relevant Pathogenic Mechanisms, Jay S. Schneider

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Parkinson’s disease (PD) is a progressive neurodegenerative disorder affecting millions of patients worldwide. Many therapeutics are available for treating PD symptoms but there is no disease-modifying therapeutic that has been unequivocally shown to slow or stop the progression of the disease. There are several factors contributing to the failure of many putative disease-modifying agents in clinical trials and these include the choice of patients and clinical trial designs for disease modification trials. Perhaps more important, however, is the choice of therapeutic, which for the most part, has not taken into account the multiple and complex pathogenic mechanisms and processes involved …

Cellular And Molecular Mechanisms Of Liver Fibrosis In Patients With Nafld, Jessica I Sanchez, Edwin R Parra, Jingjing Jiao, Luisa M Solis Soto, Debora A Ledesma, Omar A Saldarriaga, Heather L Stevenson, Laura Beretta

Faculty, Staff and Student Publications

The expression of immune- and cancer-related genes was measured in liver biopsies from 107 NAFLD patients. The strongest difference in overall gene expression was between liver fibrosis stages F3 and F4, with 162 cirrhosis-associated genes identified. Strong correlations with fibrosis progression from F1 to F4 were observed for 91 genes, including CCL21, CCL2, CXCL6, and CCL19. In addition, the expression of 21 genes was associated with fast progression to F3/F4 in an independent group of eight NAFLD patients. These included the four chemokines, SPP1, HAMP, CXCL2, and IL-8. A six-gene signature including SOX9, THY-1, and CD3D had the highest performance …

Balloon Dilatation In The Management Of Congenital Obstructive Lesions Of The Heart: Review Of Author's Experiences And Observations-Part I, P Syamasundar Rao

Faculty, Staff and Student Publications

Balloon dilatation techniques became available to treat congenital obstructive lesions of the heart in the early/mid-1980s. The purpose of this review is to present the author's experiences and observations on the techniques and outcomes of balloon dilatation of pulmonary stenosis (PS), aortic stenosis (AS) and aortic coarctation (AC), both native and postsurgical re-coarctations. Balloon dilatation resulted in a reduction of peak pressure gradient across the obstructive lesion at the time of the procedure as well as at short-term and long-term follow-ups. Complications such as recurrence of stenosis, valvar insufficiency (for PS and AS cases) and aneurysm formation (for AC cases) …

A Phase 2 Study Of Nivolumab Combined With Ibrutinib In Patients With Diffuse Large B-Cell Richter Transformation Of Cll, Nitin Jain, Jayastu Senapati, Beenu Thakral, Alessandra Ferrajoli, Philip Thompson, Jan Burger, Sreyashi Basu, Tapan Kadia, Naval Daver, Gautam Borthakur, Marina Konopleva, Naveen Pemmaraju, Erin Parry, Catherine J Wu, Joseph Khoury, Carlos Bueso-Ramos, Naveen Garg, Xuemei Wang, Wanda Lopez, Ana Ayala, Susan O'Brien, Hagop Kantarjian, Michael Keating, James Allison, Padmanee Sharma, William Wierda

Faculty, Staff and Student Publications

Richter transformation (RT) is a rare complication of chronic lymphocytic leukemia (CLL) that has dismal outcomes. Upregulation of PD-1/PD-L1 drives immunological evasion in patients with RT. We hypothesized that combining nivolumab, a PD-1 blocking antibody, with the BTK inhibitor (BTKi) ibrutinib could potentiate tumor-cell killing. We conducted an investigator-initiated phase 2 clinical trial to assess the efficacy of combined nivolumab and ibrutinib in patients with diffuse large B-cell lymphoma (DLBCL) RT and CLL. Patients included were ≥18 years of age with adequate hepatic and renal function. Patients received nivolumab every 2 weeks of a 4-week cycle for a maximum of …

An Ocular Th1 Immune Response Promotes Corneal Nerve Damage Independently Of The Development Of Corneal Epitheliopathy, Alexia Vereertbrugghen, Manuela Pizzano, Florencia Sabbione, Irene Angelica Keitelman, Carolina Maiumi Shiromizu, Douglas Vera Aguilar, Federico Fuentes, Cintia S De Paiva, Mirta Giordano, Analía Trevani, Jeremías G Galletti

Faculty, Staff and Students Publications

Proper sight is not possible without a smooth, transparent cornea, which is highly exposed to environmental threats. The abundant corneal nerves are interspersed with epithelial cells in the anterior corneal surface and are instrumental to corneal integrity and immunoregulation. Conversely, corneal neuropathy is commonly observed in some immune-mediated corneal disorders but not in others, and its pathogenesis is poorly understood. Here we hypothesized that the type of adaptive immune response may influence the development of corneal neuropathy. To test this, we first immunized OT-II mice with different adjuvants that favor T helper (Th)1 or Th2 responses. Both Th1-skewed mice (measured …

Exploring The Hinterland: The Development Of A Person-Centered Music Therapy Method For A Hospice Patient With Lewy Body Dementia, Paige Chaplin

Expressive Therapies Capstone Theses

This thesis explores the development and implementation of a music therapy method with an individual diagnosed with dementia with Lewy Bodies (DLB) receiving home hospice services. There is very little known about the effect of music therapy on patients diagnosed with DLB. Informed by Tom Kitwood’s Person-Centered Care (PCC) philosophy for dementia care, Yumiko Sato’s Musical Life Review (MLR) model, and Lisa Kelly and Bill Ahessy’s Reminiscence-Focused Music Therapy (RFMT) model, a clinical method was developed to explore the effects of person-centered music therapy on reminiscence, caregiver connection, and identity. I drew inspiration from music therapy concepts by Tony Wigram …

Epidemiology Of Island And Mainland Populations: How Does Culture Influence Health Risk Factors Of Non-Communicable, Chronic, And Metabolic Diseases?, Jake Thomas D. Palisoc

Honors Projects

Non-communicable diseases (NCDs), including chronic and metabolic diseases, are responsible for 74% of global mortality and are strongly influenced by health risk factors. Geographical differences in NCDs have been identified in several countries but have not been completely explained through cultural factors, specifically island and mainland cultures. This study aimed to develop an epidemiological framework for determining diseases with the highest mortality for further investigation regarding different health risk factors rooted in a specific population’s cultural foundations. Preliminary findings indicated diabetes type II (D2) and CKD caused by hypertension and D2 to have the highest risk factor and mortality percentage …

Parent Perspectives Of School/Daycare Experiences In Young Children Newly Diagnosed With Diabetes, Alexa Stern, Brenda Duran, Randi Streisand, Christine H Wang, Carrie Tully, Lauren Clary, Katherine Gallagher, Fran Cogen, Lefkothea Karaviti, Maureen Monaghan, Marisa E Hilliard

Faculty, Staff and Students Publications

OBJECTIVE: A central part of family adjustment to a new diagnosis of type 1 diabetes (T1D) is integrating T1D management into the child's school/daycare. This may be particularly challenging for young children who rely on adults for their diabetes management. This study aimed to describe parent experiences with school/daycare during the first 1.5 years following a young child's T1D diagnosis.

METHODS: As part of a randomized controlled trial of a behavioral intervention, 157 parents of young children with new-onset (<2 >months) T1D reported on their child's school/daycare experience at baseline and at 9- and 15-month post-randomization. We used a mixed-methods …

Toll-Like Receptors 2, 4, And 9 Modulate Promoting Effect Of Copd-Like Airway Inflammation On K-Ras-Driven Lung Cancer Through Activation Of The Myd88/Nf-ĸb Pathway In The Airway Epithelium, Walter V Velasco, Nasim Khosravi, Susana Castro-Pando, Nelly Torres-Garza, Maria T Grimaldo, Avantika Krishna, Michael J Clowers, Misha Umer, Sabah Tariq Amir, Diana Del Bosque, Soudabeh Daliri, Maria Miguelina De La Garza, Marco Ramos-Castaneda, Scott E Evans, Seyed Javad Moghaddam

Faculty, Staff and Student Publications

INTRODUCTION: Toll-like receptors (TLRs) are an extensive group of proteins involved in host defense processes that express themselves upon the increased production of endogenous damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) due to the constant contact that airway epithelium may have with pathogenic foreign antigens. We have previously shown that COPD-like airway inflammation induced by exposure to an aerosolized lysate of nontypeable

METHODS: In the present study, we have dissected the role of TLRs in this process by knocking out TLR2, 4, and 9 and analyzing how these deletions affect the promoting effect of COPD-like airway inflammation on …

Mass Spectrometry Imaging Reveals Abnormalities In Cardiolipin Composition And Distribution In Astrocytoma Tumor Tissues, Anna C Krieger, Luis A Macias, J Clay Goodman, Jennifer S Brodbelt, Livia S Eberlin

Faculty, Staff and Students Publications

Cardiolipin (CL) is a mitochondrial lipid with diverse roles in cellular respiration, signaling, and organelle membrane structure. CL content and composition are essential for proper mitochondrial function. Deranged mitochondrial energy production and signaling are key components of glial cell cancers and altered CL molecular species have been observed in mouse brain glial cell xenograft tumors. The objective of this study was to describe CL structural diversity trends in human astrocytoma tumors of varying grades and correlate these trends with histological regions within the heterogeneous astrocytoma microenvironment. To this aim, we applied desorption electrospray ionization coupled with high field asymmetric ion …

Joint Effect Of Human Papillomavirus Exposure, Smoking And Alcohol On Risk Of Oral Squamous Cell Carcinoma, Zheng Yang, Peng Sun, Kristina R Dahlstrom, Neil Gross, Guojun Li

Faculty, Staff and Students Publications

BACKGROUND: Smoking, alcohol consumption, and human papillomavirus (HPV) infection are known risk factors for oral squamous cell carcinoma (OSCC) including SCC of oropharynx (SCCOP) and SCC of oral cavity (SCCOC). Researchers have examined each of these risk factors independently, but few have observed the potential risk of their interaction. This study investigated the interactions among these risk factors and risk of OSCC.

METHODS: Totally 377 patients with newly diagnosed SCCOP and SCCOC and 433 frequency-matched cancer-free controls by age and sex were included. Multivariable logistic regression was performed to calculate ORs and 95% CIs.

RESULTS: We found that overall OSCC …

Pou4f1-Tbr1 Transcriptional Cascade Controls The Formation Of Jam2-Expressing Retinal Ganglion Cells, Takae Kiyama, Halit Y Altay, Tudor C Badea, Chai-An Mao

Faculty, Staff and Student Publications

More than 40 retinal ganglion cell (RGC) subtypes have been categorized in mouse based on their morphologies, functions, and molecular features. Among these diverse subtypes, orientation-selective Jam2-expressing RGCs (J-RGCs) has two unique morphologic characteristics: the ventral-facing dendritic arbor and the OFF-sublaminae stratified terminal dendrites in the inner plexiform layer. Previously, we have discovered that T-box transcription factor T-brain 1 (Tbr1) is expressed in J-RGCs. We further found that Tbr1 is essential for the expression of Jam2, and Tbr1 regulates the formation and the dendritic morphogenesis of J-RGCs. However, Tbr1 begins to express in terminally differentiated RGCs around …

Association Of Type 2 Diabetes Subgroups With Cognitive Status Without Modification From Lifestyle Intervention, Michael P Bancks, James Lovato, Ashok Balasubramanyam, Mace Coday, Karen C Johnson, Medha Munshi, Candida Rebello, Lynne E Wagenknecht, Mark A Espeland

Faculty, Staff and Students Publications

CONTEXT: Type 2 diabetes is a risk factor for incident dementia but whether risk and treatment/prevention strategies differ by diabetes subgroup is unknown.

OBJECTIVE: We assessed (1) whether specific type 2 diabetes (T2D) subgroups are associated with mild cognitive impairment (MCI) or probable dementia (PD), and (2) whether T2D subgroups modified the association of the Action for Health in Diabetes (Look AHEAD) multidomain intensive lifestyle intervention (ILI) with MCI/PD.

METHODS: We included 3760 Look AHEAD participants with T2D and overweight or obesity randomly assigned to 10 years of ILI or diabetes support and education. We used k-means clustering techniques with …

Review Of Gynaecological Cancer Among Aboriginal And/Or Torres Strait Islander People In Australia, Aime Powell, Ami Morseu-Diop, Maya Morton Ninomiya, Uday Narayan Yadav, Emily Phillips, Devendra Raj Singh, Tamara Butler, Emma Allanson, Lisa J. Whop

Journal of the Australian Indigenous HealthInfoNet

Gynaecological cancers bear a significant burden on the health of Australians. Whilst Australia has made great strides in reducing the overall gynaecological cancer burden nationally, Aboriginal and/or Torres Strait Islander women continue to experience disproportionately high rates of gynaecological cancers.

This review focuses on the social, cultural, and historical contexts that contribute to inequitable gynaecological cancer rates among Aboriginal and/or Torres Strait Islander women. An in-depth discussion on cervical cancer, ovarian cancer, and uterine cancer are described; including the incidence, mortality, survival, and management of these diseases for Aboriginal and/or Torres Strait Islander women.

It highlights both the persistent barriers …

Sarcopenia And Cardiovascular Diseases, Abdulla A Damluji, Maha Alfaraidhy, Noora Alhajri, Namit N Rohant, Manish Kumar, Christina Al Malouf, Samira Bahrainy, Min Ji Kwak, Wayne B Batchelor, Daniel E Forman, Michael W Rich, James Kirkpatrick, Ashok Krishnaswami, Karen P Alexander, Gary Gerstenblith, Peggy Cawthon, Christopher R Defilippi, Parag Goyal

Faculty, Staff and Student Publications

Sarcopenia is the loss of muscle strength, mass, and function, which is often exacerbated by chronic comorbidities including cardiovascular diseases, chronic kidney disease, and cancer. Sarcopenia is associated with faster progression of cardiovascular diseases and higher risk of mortality, falls, and reduced quality of life, particularly among older adults. Although the pathophysiologic mechanisms are complex, the broad underlying cause of sarcopenia includes an imbalance between anabolic and catabolic muscle homeostasis with or without neuronal degeneration. The intrinsic molecular mechanisms of aging, chronic illness, malnutrition, and immobility are associated with the development of sarcopenia. Screening and testing for sarcopenia may be …

Low Educational Attainment Is Associated With Higher All-Cause And Cardiovascular Mortality In The United States Adult Population, Najah Khan, Zulqarnain Javed, Isaac Acquah, Kobina Hagan, Madiha Khan, Javier Valero-Elizondo, Ryan Chang, Umair Javed, Mohamad B. Taha, Salim S. Virani

Office of the Provost

Introduction: Educational attainment is an important social determinant of health (SDOH) for cardiovascular disease (CVD). However, the association between educational attainment and all-cause and CVD mortality has not been longitudinally evaluated on a population-level in the US, especially in individuals with atherosclerotic cardiovascular disease (ASCVD). In this nationally representative study, we assessed the association between educational attainment and the risk of all-cause and cardiovascular (CVD) mortality in the general adult population and in adults with ASCVD in the US.
Methods: We used data from the 2006-2014 National Death Index-linked National Health Interview Survey for adults ≥ 18 years. We generated …

Traf4-Mediated Nonproteolytic Ubiquitination Of Androgen Receptor Promotes Castration-Resistant Prostate Cancer, Ramesh Singh, Huan Meng, Tao Shen, Lance Edward V Lumahan, Steven Nguyen, Hong Shen, Subhamoy Dasgupta, Li Qin, Dileep Karri, Bokai Zhu, Feng Yang, Cristian Coarfa, Bert W O'Malley, Ping Yi

Faculty, Staff and Students Publications

Castration-resistant prostate cancer (CRPC) poses a major clinical challenge with the androgen receptor (AR) remaining to be a critical oncogenic player. Several lines of evidence indicate that AR induces a distinct transcriptional program after androgen deprivation in CRPCs. However, the mechanism triggering AR binding to a distinct set of genomic loci in CRPC and how it promotes CRPC development remain unclear. We demonstrate here that atypical ubiquitination of AR mediated by an E3 ubiquitin ligase TRAF4 plays an important role in this process. TRAF4 is highly expressed in CRPCs and promotes CRPC development. It mediates K27-linked ubiquitination at the C-terminal …

Expanding Endoscopic Boundaries: Endoscopic Resection Of Large Appendiceal Orifice Polyps With Endoscopic Mucosal Resection And Endoscopic Submucosal Dissection, Ankur P Patel, Mai A Khalaf, Margarita Riojas-Barrett, Tara Keihanian, Mohamed O Othman

Faculty, Staff and Students Publications

BACKGROUND: Large appendiceal orifice polyps are traditionally treated surgically. Recently, endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have been utilized as alternative resection techniques.

AIM: To evaluate the efficacy and safety of endoscopic resection techniques for the management of large appendiceal orifice polyps.

METHODS: This was a retrospective observational study conducted to assess the feasibility and safety of EMR and ESD for large appendiceal orifice polyps. This project was approved by the Baylor College of Medicine Institutional Review Board. Patients who underwent endoscopic resection of appendiceal orifice polyps ≥ 1 cm from 2015 to 2022 at a tertiary …

A Pilot Study Of Hand Autografts Treated With Autologous Skin Cell Suspension, Paige Deville, Jeffrey E. Carter, Madeline Lechtenberg, Herbert A. Phelan

School of Medicine Faculty Publications

55th Annual Meeting of the American Burn Association, ABA 2023, May 16 - 19, 2023, Dallas, TX

Burn Injury Assessment Study (Bias): Is There Room To Improve?, Jeffrey Carter, Herbert Phelan, John Friedstat, William Hickerson, James Holmes, James Hwang, Steven Kahn, Alisa Savetamal, Jeffrey Shupp

School of Medicine Faculty Publications

55th Annual Meeting of the American Burn Association, ABA 2023, May 16 - 19, 2023, Dallas, TX

Autologous Skin Cell Suspensions For Reconstruction Of Nonthermal Soft Tissue Wounds: A Case Series, Paige Deville, Elle Lovick, Jeffrey Carter, Herbert Phelan

School of Medicine Faculty Publications

55th Annual Meeting of the American Burn Association, ABA 2023, May 16 - 19, 2023, Dallas, TX

Injury To Intervention: Is There Another Opportunity To Improve Burn Care?, William L. Hickerson, Jeffrey E. Carter, John Friedstat, James H. Holmes, James Hwang, Steven A. Kahn, Herbert A. Phelan, Alisa Savetamal

School of Medicine Faculty Publications

55th Annual Meeting of the American Burn Association, ABA 2023, May 16 - 19, 2023, Dallas, TX

Access To Burn Care: A 10 Year Perspective Of Burn Centers In The U.S, Elle Lovick, Jeffrey Carter, Herbert Phelan, Randy Kearns, Bart Phillips, William Hickerson

School of Medicine Faculty Publications

55th Annual Meeting of the American Burn Association, ABA 2023, May 16 - 19, 2023, Dallas, TX

Select Survey Of Human Cadaver Skin Allograft Utilization By 21 Senior Academic Burn Surgeons, William Hickerson, Franco Aveau, Narayan Iyer, James Jeng, Victor Joe

School of Medicine Faculty Publications

55th Annual Meeting of the American Burn Association, ABA 2023, May 16-19,2023, Dallas, TX

Correction Of T-Cell Repertoire And Autoimmune Diabetes In Nod Mice By Non-Myeloablative T-Cell Depleted Allogeneic Hsct, Rakefet Sidlik Muskatel, Bar Nathansohn-Levi, Shlomit Reich-Zeliger, Michal Mark, Liat Stoler-Barak, Chava Rosen, Irit Milman-Krentsis, Esther Bachar Lustig, Robert Pete Gale, Nir Friedman, Yair Reisner

Faculty, Staff and Student Publications

The induction of partial tolerance toward pancreatic autoantigens in the treatment of type 1 diabetes mellitus (T1DM) can be attained by autologous hematopoietic stem cell transplantation (HSCT). However, most patients treated by autologous HSCT eventually relapse. Furthermore, allogeneic HSCT which could potentially provide a durable non-autoimmune T-cell receptor (TCR) repertoire is associated with a substantial risk for transplant-related mortality. We have previously demonstrated an effective approach for attaining engraftment without graft versus host disease (GVHD) of allogeneic T-cell depleted HSCT, following non-myeloablative conditioning, using donor-derived anti-3rd party central memory CD8 veto T cells (Tcm). In the present study, we investigated …

Secondary Immunohistochemical Analysis Of Viable Cells As Determined By Hematoxylin And Eosin Staining, Bonnie Carney, Cameron D'Orio, Jeffrey Shupp, Jeffrey Carter, William Hickerson, James Holmes, Herbert Phelan

School of Medicine Faculty Publications

55th Annual Meeting of the American Burn Association, ABA 2023, May 16 - 19, 2023, Dallas, TX

Open-Label, Expanded-Access Study Of A Bioengineered Allogeneic Cellularized Construct In Adults With Deep Partial- Thickness Burns, Angela Gibson, Victor Joe, Joshua Carson, Jeff Litt, Jeffrey Carter, James Holmes

School of Medicine Faculty Publications

55th Annual Meeting of the American Burn Association, ABA 2023, May 16 - 19, 2023, Dallas, TX

Adipose Derived Stem Cell Paracrine Factor Release In Smokers Vs Non Smokers With Burn Injuries, Paige Deville, Alison Smith, Herbert Phelan, Jeffrey Carter, Olivia Warren, Cameron Fontenot

School of Medicine Faculty Publications

55th Annual Meeting of the American Burn Association, ABA 2023, May 16 - 19, 2023, Dallas, TX

The Rising Use Of Fire As A Weapon, Jason Woods, Jeffrey Carter, Kathe Conlon, Carl Flores, Randy Kearns

School of Medicine Faculty Publications

55th Annual Meeting of the American Burn Association, ABA 2023, May 16 - 19, 2023, Dallas, TX

Characteristics Of Verified And Designated Burn Centers, Jeffrey Carter, Randy Kearns, Elle Lovick, Erica Murata, Bart Phillips

School of Medicine Faculty Publications

55th Annual Meeting of the American Burn Association, ABA 2023, May 16 - 19, 2023, Dallas, TX