Digital Commons Network^™

Effect Of Access Cavity Preparation And Cement On The Fracture Load Of Translucent Zirconia Crowns, Andrea Fenton, Amir H. Nejat, Edwin Kee, Xiaoming Xu, Albert F. Mcmullen Iii

School of Dentistry Faculty Publications

Purpose: To evaluate the effect of endodontic access hole preparation and choice of luting cement on the fracture resistance of translucent zirconia (5Y) crowns. Materials and Methods: Polymethylmethacrylate (PMMA) dies, representing a prepared maxillary molar tooth, were milled. Translucent zirconia crowns were milled from 5Y (Cercon XTML) zirconia discs and sintered. Forty crowns were divided into four groups (n = 10 per group) based on access hole preparation (accessed, non-accessed) and type of luting cement (resin cement, resin modified glass ionomer (RMGI) cement). Crowns were cemented on the PMMA dies with either resin cement (Panavia SA Cement Universal, Kuraray Noritake …

Organizational Factors That Impact Emergency Room Sepsis Bundle Compliance In U.S. Hospitals, Jason Lee Kimbrell

All ETDs from UAB

ORGANIZATIONAL FACTORS THAT IMPACT EMERGENCY ROOM SEPSIS BUNDLE COMPLIANCE IN U.S. HOSPITALS JASON L. KIMBRELL HEALTH SERVICES ADMINISTRATION ABSTRACT This in-depth study examines the organizational factors within U.S. hospital emergency rooms (ERs) that impact care teams’ adherence to established, time-sensitive sepsis protocols. The regression analysis revealed a concerning trend: for each 1% increase in annual patient walk-out rates, compliance with sepsis protocols declines by 2.10%. Additionally, the impact on poor ER throughput where the ESI level 3 length of stay increases by 1 minute, a hospital's compliance with the 3hr POA sepsis bundle decreases by .08%. These findings underscore the …

Experiences Of Discrimination And Neighborhood Cohesion In Risk Of Poor Mental Health Outcomes Among Older, Community-Dwelling Participants In The Regards Study, Marquita S. Brooks

All ETDs from UAB

Mental health disorders impact approximately 14% of persons aged 65 and older and often are undertreated or underrecognized. Assessment of factors that link environmental, sociocultural, behavioral, and biological factors to overall health and disease is integral to guiding research on health disparities in older populations. Although research suggests associations between environmental factors (i.e., discrimination and neighborhood cohesion) and mental health outcomes, there is limited research on these factors within the U.S. Therefore, our study assessed the relationship between discrimination, neighborhood cohesion, and mental health outcomes in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, a national, prospective …

The Role Of B Cells In A Mouse Model Of Multiple System Atrophy, Gabrielle Childers

All ETDs from UAB

Multiple system atrophy (MSA) is a rare, fast progressing, debilitating and ultimately fatal movement disorder. The pathological hallmark of MSA disease is the aggregation and misfolding of alpha-synuclein (α-syn) protein in the cytoplasm of oligodendrocytes, termed glial cytoplasmic inclusions (GCIs). Accumulation of these GCIs result in progressive demyelination and neurodegeneration of the striatonigral and olivopontocerebellar regions of the brain. Currently, no therapeutics have been approved that slow or halt the progression of this devastating disease. Neuroinflammation, has been increasingly appreciated as a key neuropathological feature of disease, especially activation of tissue resident innate immune cells. Recently, evidence of adaptive immune …

Stroke Survivors: Predicting Cognitive Outcomes By Stroke Severity, Caregiver Factors, & Social Determinants Of Health, Jason Alexander Blake

All ETDs from UAB

Physical and cognitive disabilities are common following a stroke, often leading to significant changes in survivors' daily lives and increasing dependency on caregivers. These changes can include involuntary retirement, loss of independence, and decreased social engagement, which may necessitate adjustments in living arrangements and long-term care. This dissertation investigates the predictors of cognitive outcomes in stroke survivors, with a particular focus on the roles of stroke severity and caregiver factors. Utilizing data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) project, this research captures the different predictors of post-stroke cognition through biennial assessments. Through longitudinal studies, this …

Core Grade 7: Principles For Moving From Evidence To Recommendations And Decisions, Gordon Guyatt, Per Olav Vandvik, Alfonso Iorio, Arnav Agarwal, Liang Yao, Prashanti Eachempati, Linan Zeng, Derek K. Chu, Rohan D'Souza, Thomas Agoritsas, M. Hassan Murad, Stefan Schandelmaier, Jamie Rylance, Benjamin Djulbegovic, Victor M. Montori, Monica Hultcrantz, Romina Brignardello-Petersen

Peninsula Dental School

This seventh article in a seven part series presents the Core GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach for moving from evidence to recommendations or policy decisions. Core GRADE users make strong recommendations for an intervention versus a comparator when the desirable consequences clearly outweigh the undesirable consequences, and a conditional (weak) recommendation when the balance is less clear. Primary considerations in deciding on recommendations considering an individual patient perspective include balance of benefits, harms, and burdens; the certainty of evidence; and values and preferences. Secondary considerations, most important from a population perspective, include costs, feasibility, acceptability, and …

Moderating Role Of Locus Of Control On The Relationship Between Self-Efficacy And Trust In Ai, Amelia Gillies

Walden Dissertations and Doctoral Studies

The rapid integration of artificial intelligence (AI) into essential sectors, including healthcare, customer services, and defense, has underscored the importance of user trust in AI systems. Psychological traits such as locus of control (the extent to which individuals attribute outcomes to internal or external factors) and self-efficacy (individuals’ confidence in their ability) have been identified as significant factors influencing trust in these automated systems. Previous studies have independently linked these psychological traits to trust in technology; however, there has been limited exploration of potential moderating effects of locus of control on the relationship between digital technology self-efficacy and trust in …

Correlations Within And Between Highly Multiplexed Proteomic Assays Of Human Plasma, Mary R Rooney, Jingsha Chen, Christie M Ballantyne, Ron C Hoogeveen, Eric Boerwinkle, Bing Yu, Keenan A Walker, Pascal Schlosser, Elizabeth Selvin, Nilanjan Chatterjee, David Couper, Morgan E Grams, Josef Coresh

Faculty, Staff and Students Publications

Introduction: The number of assays on proteomic platforms has grown rapidly. The leading platforms, SomaScan and Olink, have strengths and limitations. Comparisons of precision on the latest platforms-SomaScan 11k and Olink Explore HT-have not yet been established.

Methods: Among 102 participants in the Atherosclerosis Risk in Communities Study (mean age 74 years, 53% women, 47% Black), we used split plasma samples to measure platform precision. CV and Spearman correlations were calculated for each assay. Cross-platform agreement was assessed for overlapping proteins.

Results: SomaScan 11k demonstrated a median correlation of 0.85 for the 10 778 assays and a median CV of …

An Antibody Biomarker Associated With Onchocerca Volvulus Microfilariae Identified By Proteomic Analysis Of Parasite Tissues Isolated From Paraffin Embedded O. Volvulus Nodules By Laser Capture Microdissection, Sarah E Greene, Kerstin Fischer, Lucia S Di Maggio, Bruce A Rosa, Yuefang Huang, Irina Diekmann, Byoung-Kyu Cho, Jessica Lukowski, Young A Goo, Makedonka Mitreva, Nicholas Opoku, Gary J Weil, Peter U Fischer

2020-Current year OA Pubs

Onchocerciasis (river blindness), a neglected tropical disease caused by the filarial nematode Onchocerca volvulus, impacts millions of people in sub-Saharan Africa. The WHO coordinates global efforts to eliminate onchocerciasis and has prioritized development of improved diagnostic tests to aid these efforts. To find new microfilarial-associated diagnostic targets to help identify active infections, we used laser capture microdissection to isolate embryonic stages from histologic sections of O. volvulus worms in subcutaneous nodules excised from onchocerciasis patients. Proteomic analysis identified 2,512 O. volvulus proteins in those tissues, including 264 found only in the microfilariae (Mf). From this pool of diagnostic candidates, we …

Pyruvate Dehydrogenase Kinase 4 Mediates Sex Specific Outcomes In Sepsis Induced Cardiomyopathy, John Yap

Dissertations

During sepsis, males often experience worse cardiac outcomes than females. Here, we identified pyruvate dehydrogenase kinase 4 (PDK4) as a key contributor to this disparity. PDK4 is a mitochondrial protein that regulates glucose utilization by inhibiting pyruvate dehydrogenase (PDH). Using a mouse model of endotoxemia, we induced acute inflammation with a sublethal dose of lipopolysaccharide (LPS), which caused cardiac dysfunction and significantly increased myocardial PDK4 expression in males but not females. Cardiac-specific PDK4 overexpression promoted LPS-induced cardiac dysfunction in both sexes, whereas cardiac-specific PDK4 knockout provided protection. In wild-type males, LPS disrupted cardiac metabolism by decreasing PDH activity and fatty …

Targeting Eya1 Phosphatase Activity In Mll-Rearranged Leukemia, Lola Badmus

Dissertations

MLL-rearranged (MLL-r) leukemia is an aggressive subset of acute leukemia, accounting for up to 10% of adult and 70% of infant AML and ALL cases. These leukemias are driven by MLL fusion proteins, which recruit epigenetic cofactors to dysregulate gene expression, leading to poor prognosis and resistance to conventional chemotherapy. Previous lab work identified EYA1’s role in leukemogenesis, establishing it as a therapeutic target in MLL-r leukemia. EYA1, is a transcriptional coactivator and protein tyrosine phosphatase (PTP). Originally a gout medication, benzbromarone (BBR), was identified in an NCI Diversity Set screen as an EYA1-specific PTP inhibitor. BBR provides a tool …

Benefits And Challenges Of Collaborative Networks Addressing Food System Disruptions During The Covid-19 Pandemic, Dikshya Dahal, Tania Schusler

School of Environmental Sustainability: Faculty Publications and Other Works

The COVID-19 pandemic disrupted food systems with disproportionate impacts on marginalized social groups, which in the USA included racial and ethnic minorities, working class families, immigrants, seniors, and people with disabilities, among others. The pandemic also greatly affected the operations of nonprofit organizations, which play important roles in disaster response. We explored how social networks supported non-profit organizations’ efforts to address increased food insecurity and food-related business disruptions during the pandemic in the Chicago region, IL, USA. We used mixed methods including a Social Network Analysis (SNA) of 48 organizations and their reported partners plus focus group discussions with representatives …

Plasma Insulin-Like Growth Factor-Binding Protein-7 Is Positively Associated With Age, Obesity, Mortality, And Cancer In Postmenopausal Women, Melissa C Orenduff, Carl F Pieper, Emma H Allott, Michael F Coleman, Su Yon Jung, Mara Z Vitolins, Jenifer I Fenton, Chu Chen, Candyce H Kroenke, Fred K Tabung, Ana Barac, Electra D Paskett, Michael N Pollak, Jennifer Hays-Grudo, Shine Chang, Stephen D Hursting

Faculty, Staff and Student Publications

Background: Predictors of premature death and cancer development are needed to more precisely identify individuals who may warrant preventive intervention. Circulating insulin-like growth factor (IGF)-binding protein-7 (IGFBP7) and, to a lesser extent, the IGFBP7/IGF-1 ratio are emerging biomarkers of renal and cardiovascular morbidity. However, their relationships with aging, obesity, mortality, and cancer risk remain unclear.

Methods: This hypothesis-generating study investigated plasma IGFBP7, IGF-1, and their ratio as predictors of all-cause mortality and the incidence of any cancer (excluding nonmelanoma skin cancer), obesity-related cancer (composite of 13 cancer types), and breast cancer in a large longitudinal cohort of postmenopausal women. We …

Restoration Of The Tumor Suppressor Function Of Y220c-Mutant P53 By Rezatapopt, A Small-Molecule Reactivator, Anna M Puzio-Kuter, Lizhong Xu, Mary Kate Mcbrayer, Romyr Dominique, Hongju H Li, Bruce J Fahr, Alyssa M Brown, Amy E Wiebesiek, Brandon M Russo, Chris L Mulligan, Hong Yang, Josh Battaglia, Kimberly A Robell, Dafydd H Thomas, Kuo-Sen Huang, Alexander Solovyov, Benjamin D Greenbaum, Jonathan D Oliner, Thomas W Davis, Melissa L Dumble, Melissa L Johnson, Shunbin Xiong, Peirong Yang, Guillermina Lozano, Marc M Fellous, Binh T Vu, Alison M Schram, Arnold J Levine, Masha V Poyurovsky

Faculty, Staff and Student Publications

Restoration of the tumor suppressor function of tumor-associated p53 mutants, including the Y220C substitution, has posed a significant challenge for therapeutic discovery. In this study, we describe rezatapopt (PC14586), part of a series of compounds designed to reactivate the p53 Y220C mutant. These compounds restore p53 tumor suppressor function by correcting its conformation and enabling it to bind DNA and activate downstream target genes, thus inducing antiproliferative changes in tumor cells. Our findings are supported by biochemical and structural analysis, in vitro and in vivo transcriptomics, and functional data, revealing the recovery of multiple aspects of the wild-type p53 program. …

Audiological Characteristics And Associations With Psychological Inflexibility, Karen Muñoz, Bailey Sorensen, Aryn Kamerer, Michael P. Twohig

Psychology Faculty Publications

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Exploring South Asian Parent Perceptions Of Involvement In Their Child’S Schooling, Qazi Mohammed Faaizuddin Biabani

Theses and Dissertations from DePaul University

No abstract provided.

Posterior Predictive Design For Phase I Clinical Trials, Chenqi Fu, Shouhao Zhou, J Jack Lee

Faculty, Staff and Student Publications

Interval-based designs represent cutting-edge adaptive methodologies for phase I clinical trials to identify the maximum tolerated dose (MTD). These designs exhibit robust performance comparable to more intricate, model-based designs, and their pretabulated decision rule enables them to be implemented as simply as the conventional algorithm-based designs. In this paper, we introduce the posterior predictive (PoP) design, a novel interval-based design that leverages advanced Bayesian predictive hypothesis testing techniques for dose escalation and de-escalation. Our work moves beyond the existing model-assisted interval-based designs by achieving global optimality in dose transition. Theoretically, the global optimality ensures that the proposed design can consistently …

Lipoprotein(A) And Heart Failure Among Black And White Participants In Atherosclerosis Risk In Communities Study, Framingham Offspring Study, And Multi-Ethnic Study Of Atherosclerosis: The Pooling Project, Sarah Nomura, Weihua Guan, Yixin Zhang, Geoffrey H Tison, Hiroaki Ikezaki, Margaret R Diffenderfer, Ching-Ti Liu, Ron C Hoogeveen, Christie M Ballantyne, Ernst J Schaefer, Michael Y Tsai

Faculty, Staff and Students Publications

Background: This study investigated Lp(a) (lipoprotein(a)) levels with heart failure (HF) incidence overall and ejection fraction (EF) subtypes among Black and White participants in a pooled analysis of MESA (Multi-Ethnic Study of Atherosclerosis), FOS (Framingham Offspring Study), and ARIC (Atherosclerosis Risk in Communities Study).

Methods: This study was conducted among 16 771 White and Black participants in ARIC (N=10 347), MESA (N=4150), and FOS (N=2274). Baseline was time of Lp(a) measurement (ARIC Visit 4: 1996-1998; MESA Visit 1: 2000-2002; FOS Cycle 6: 1995-1998). HF with reduced EF (HFrEF) was defined as EF < 50% and ≥50% as HF with preserved EF (HFpEF). Cox proportional hazards regression was used to evaluate associations between Lp(a) (log-transformed continuous, dichotomized at ≥30 mg/dL and ≥50 mg/dL, and quartiles) and HF (overall, HFpEF, HFrEF) in the overall population and stratified by race. Analyses were replicated excluding prior history of myocardial infarction.

Results: There were 2759 HF cases (HFpEF N=859; …

Oral Pcsk9 Inhibitors: Can Novel Therapies Overcome Barriers To Effective Ldl-Cholesterol Management?, Christie M Ballantyne, Alberico L Catapano, Khurram Nasir

Faculty, Staff and Students Publications

No abstract provided.

Time-Driven Activity-Based Costing For Cervical Myelopathy Surgery: A Step Towards Total Episode Costs, Kavantissa M. Keppetipola, Adam Leibold, Jay Trivedi, Ashmal Sami, Advith Sarikonda, D. Mitchell Self, Emily L. Isch, Steven R. Glener, Srinivas Prasad, Jack Jallo, Joshua E. Pelta-Heller, James Harrop, Alex R. Vaccaro, Ahilan Sivaganesan

Department of Neurosurgery Faculty Papers

INTRODUCTION: Time-driven activity-based costing (TDABC) is a highly accurate method for determining the true cost of delivering a healthcare service. However, TDABC is most often applied to a singular phase of care such as an outpatient visit or a surgical event. Here we broaden the scope by using TDABC to estimate the costs of surgically treating cervical myelopathy - from the moment of surgical scheduling until post-operative hospital discharge.

METHODS: In a single-center retrospective study at a large tertiary academic institution, TDABC was employed to measure pre-operative, intra-operative, and post-operative (inpatient) costs for 63 patients undergoing elective surgery for cervical …

A Meta-Analysis And Systematic Review Of Cardiac Troponin I Vs T In Community Dwelling Adults: Is Specificity At Risk?, Yashika Parashar, Aya Awwad, Soahum Bagchi, Brian Claggett, Saman Asad Siddiqui, Ajari Winifred Ogheneochuko, Christie M Ballantyne, Christopher Defilippi

Faculty, Staff and Students Publications

Background: Cardiac troponin I and T measured by high-sensitivity assays (hs-cTn) are detectable in most ambulatory adults. Hs-cTnI and T may perform differently for prediction of cardiovascular (CV) events. In adults with myopathies and advanced age, hs-cTnT can lose CV specificity. We undertook a meta-analysis of ambulatory studies measuring hs-cTn to determine whether hs-cTnI is a superior predictor of CV outcomes.

Methods: Articles evaluating hs-cTnI or T for incident heart failure (HF), myocardial infarction (MI), CV, and all-cause death in ambulatory adults were screened. Adjusted HRs were extracted standardized as hs-cTn tertile 3 vs 1. Pooled effects were calculated, and …

Three Dimensional Multiscalar Neurovascular Nephron Connectivity Map Of The Human Kidney Across The Lifespan, Liam Mclaughlin, Bo Zhang, Siddharth Sharma, Amanda L Knoten, Madhurima Kaushal, Jeffrey M Purkerson, Heidie L Huyck, Gloria S Pryhuber, Joseph P Gaut, Sanjay Jain

2020-Current year OA Pubs

The human kidney maintains homeostasis through a complex network of up to a million nephrons, its fundamental tissue units. Using innovative tissue processing and light sheet fluorescence microscopy, we mapped the 3D neurovascular connectivity of nephrons to understand how their structural organization enables coordinated functions like filtration, absorption, and blood pressure regulation. Our analysis revealed developmental changes in glomerular orientation, density, volume, and innervation from birth through aging. We discovered an extensive nerve network connecting different nephron segments and organizing glomeruli into distinct communities. These communities are linked through "mother glomeruli" that serve as control centers, creating a repeating pattern …

Perceptions Of Spirituality And Of God: A Psychological Qualitative Study, Christopher E. Peck, Timothy B. Smith, Jamila Mastny

Faculty Publications

The majority of people living in the U.S. report that spirituality is an important part of their life that is influential to their well-being. However, individuals vary widely in how they conceptualize spirituality, which often stems from and overlaps with their conceptualizations of God or so-called “God image”. Examination of people’s experiences of spirituality and conceptualization of God can enable psychologists to improve their understanding of individuals’ core personal experiences. This study evaluates both spirituality and God image, as well as the relationship between these two constructs, using qualitative hermeneutic analysis of interviews with 63 adults (51% women, 49% men, …

Dynamics Of Urban Heat And Green Infrastructure, Yunjae Ock

Dissertations and Theses

This dissertation provides a comprehensive analysis of the interaction between urban heat and green infrastructure (GI) in terms of dynamic aspects, spatiotemporal variation across various spatial scales, temporal phases, and socioeconomic contexts. By integrating a national-scale longitudinal analysis, street-level structural assessments, and neighborhood-specific resilience frameworks, this study enhances our understanding of how cities can utilize existing ecological assets to mitigate increasing heat risks while addressing systemic inequities.

Urban areas face unprecedented thermal challenges due to climate change and the urban heat island effect, with marginalized communities disproportionately affected. Although cities are increasingly adopting GI expansion for heat mitigation, significant knowledge …

In Situ Structure And Assembly Of The Abc-Type Tripartite Pump Macab-Tolc, Tong Huo, Wenfang Zhang, Zhili Yu, Wei Zheng, Yaoming Wu, Qiuyu Ren, Zekai Wan, Junli Cao, Zhao Wang, Xiaodong Shi

Faculty, Staff and Students Publications

The MacAB-TolC tripartite efflux pump is widely distributed in Gram-negative bacteria, extruding antibiotics and virulence factors that lead to multidrug resistance and pathogenicity. However, the in situ structure and assembly mechanism of MacAB-TolC remain unclear. Here, we resolve the in situ structures of the MacAB-TolC efflux pump in Escherichia coli by electron cryo-tomography and subtomogram averaging. In the cells without antibiotic treatment, we observe a fully assembled MacAB-TolC pump. When Escherichia coli cells are treated with erythromycin, in addition to the tripartite pumps, we also discover the emergence of MacA-TolC subcomplexes without MacB, indicating flexible binding of MacB in the …

Mitral Valve Surgery After Failed Transcatheter Intervention For Mitral Regurgitation: Surgical Techniques, Challenges And Outcomes, Mateo Marin-Cuartas, Syed Zaid, Jörg Kempfert, Michael A Borger, Serdar Akansel, Thilo Noack, David Holzhey, Tsuyoshi Kaneko, Isaac George, Gorav Ailawadi, Robert L Smith, Arnar Geirrson, Ahmed El-Eshmawi, Dimosthenis Pandis, Suzanne De Waha, Nikolaos Bonaros, Fabien Praz, Maurizio Taramasso, Michele De Bonis, Lenard Conradi, Christian Hagl, Nicolas Doll, Mahmoud Wehbe, Alexey Dashkevich, Manuela De La Cuesta, Jagdip Kang, Zara Dietze, Philipp Kiefer, Gilbert H L Tang

Faculty, Staff and Students Publications

Objectives: This review article aims to examine the surgical approach to patients with failed mitral transcatheter edge-to-edge repair (M-TEER), focusing on operative challenges, decision-making and contemporary outcome data. Technical considerations, including device removal and the management of complex mitral valve (MV) anatomy, are discussed.

Methods: We performed a comprehensive literature review and gathered the experience from high-volume centres in the surgical management of failed M-TEER.

Results: MV surgery after failed M-TEER is a complex but increasingly necessary procedure as the use of M-TEER grows. It occurs in up to 6% of patients, with a median age of 70-76 years at …

Beyond The Surface: Mapping Dde's Metabolic Footprint On Adolescent Obesity, Zhenjiang Li, Shudi Pan, Brittney O Baumert, Jiawen Carmen Chen, Jesse A Goodrich, Hongxu Wang, Sarah Rock, Justin Ryder, Damaskini Valvi, Todd Jenkins, Stephanie Sisley, Xiangping Lin, Scott M Bartell, Thomas H Inge, Stavra Xanthakos, Brooklynn Mcneil, Anna R Robuck, Catherine E Mullins, Sandrah P Eckel, Rob S Mcconnell, Michele A La Merrill, Douglas I Walker, David V Conti, Lida Chatzi

Faculty, Staff and Students Publications

Background: Bariatric surgery is an intervention for severe obesity, leading to significant weight loss and metabolic improvements. However, the release of lipophilic chemicals accumulated in adipose tissue during weight loss presents a unique clinical challenge and research opportunity. Dichlorodiphenyldichloroethylene (DDE) is a persistent organic pollutant increasingly recognized as obesogen, while the biological mechanisms through which DDE influences body mass index (BMI) and waist circumference remain underexplored.

Objectives: We aimed to identify metabolic signatures mediating the association between DDE exposure and weight loss by plasma and adipose tissue metabolomics.

Methods: We conducted a longitudinal study involving 60 adolescents with severe obesity …

Phage-Induced Protection Against Lethal Bacterial Reinfection, Yikun Xing, Haroldo J Hernandez Santos, Ling Qiu, Samantha R Ritter, Jacob J Zulk, Rachel Lahowetz, Kathryn A Patras, Austen L Terwilliger, Anthony W Maresso

Faculty, Staff and Students Publications

Bacteriophages, or phages, are viruses that target and infect bacteria. Due to a worldwide rise in antimicrobial resistance (AMR), phages have been proposed as a promising alternative to antibiotics for the treatment of resistant bacterial infections. Up to this point in history, phage use in preclinical animal studies, clinical trials, and emergency-use compassionate care cases has centered around the original observation from 1915 showing phage as lytic agent, and thus a treatment that kills bacteria. Here, we describe an activity associated with phage therapy that extends beyond lytic activity that results in long-term protection against reinfection. This activity is potent, …

Mutant P53 Gain Of Function: Why Many See It, Why Some Do Not, Guillermina Lozano, Carol Prives, Kanaga Sabapathy

Faculty, Staff and Student Publications

Mutations in the TP53 tumor-suppressor gene in human cancer are unique in that 60% to 70% are of the missense variety, resulting in a full-length protein that is often highly expressed in patients' tumors. These missense mutant proteins often exhibit pro-oncogenic activities (referred to as gain of function) in mouse models and human cell lines and correlate with poor cancer prognosis in some cases.

Xbp1s-Edem2 Prevents The Onset And Development Of Hfpef By Ameliorating Cardiac Lipotoxicity, Oveena Fonseka, Rida Raja, Claire Ross, Sanskruti R Gare, Jiayan Zhang, Susanne S Hille, Katharine King, Andrea Ruiz-Velasco, Namrita Kaur, Xinyi Chen, Jessica M Miller, Riham R E Abouleisa, Qinghui Ou, Zhiyong Zou, Xiangjun Zhao, Cristian Sotomayor-Flores, Derk Frank, Eileithyia Swanton, Martin R Pool, Sara Missaglia, Daniela Tavian, Gabriele G Schiattarella, Tao Wang, Luigi Venetucci, Christian Pinali, Martin K Rutter, Bernard D Keavney, Elizabeth J Cartwright, Tamer M A Mohamed, Oliver J Müller, Wei Liu

Center for Medical Ethics and Health Policy Staff Publications

Background: Morbidity and mortality of heart failure with preserved ejection fraction (HFpEF) is increased in metabolic disorders. However, options for preventing and treating these prevalent outcomes are limited. Intramyocardial lipotoxicity contributes to cardiac dysfunction. Here, we investigate the mechanisms underlying EDEM2 (endoplasmic reticulum degradation-enhancing alpha-mannosidase-like protein 2) regulation of cardiac lipid homeostasis and assess strategies that inhibit the incidence and progression of HFpEF.

Methods: Metabolic stress was induced in C57BL/6 male mice using a high-fat diet and Nω-nitro-L-arginine methyl ester. The recombinant adeno-associated virus 9 delivery system was used for loss- and gain-of-function studies. Palmitic acid and oleic acid …