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Full-Text Articles in Diseases

Integrated Inflammatory Signaling Landscape Response After Delivering Elovanoid Free-Fatty-Acid Precursors Leading To Experimental Stroke Neuroprotection, Madigan M. Reid, Ludmila Belayev, Larissa Khoutorova, Pranab K. Mukherjee, Andre Obenaus, Kierany Shelvin, Stacey Knowles, Sung Ha Hong, Nicolas G. Bazan Sep 2023

Integrated Inflammatory Signaling Landscape Response After Delivering Elovanoid Free-Fatty-Acid Precursors Leading To Experimental Stroke Neuroprotection, Madigan M. Reid, Ludmila Belayev, Larissa Khoutorova, Pranab K. Mukherjee, Andre Obenaus, Kierany Shelvin, Stacey Knowles, Sung Ha Hong, Nicolas G. Bazan

School of Graduate Studies Faculty Publications

Despite efforts to identify modulatory neuroprotective mechanisms of damaging ischemic stroke cascade signaling, a void remains on an effective potential therapeutic. The present study defines neuroprotection by very long-chain polyunsaturated fatty acid (VLC-PUFA) Elovanoid (ELV) precursors C-32:6 and C-34:6 delivered intranasally following experimental ischemic stroke. We demonstrate that these precursors improved neurological deficit, decreased T2WI lesion volume, and increased SMI-71 positive blood vessels and NeuN positive neurons, indicating blood–brain barrier (BBB) protection and neurogenesis modulated by the free fatty acids (FFAs) C-32:6 and C-34:6. Gene expression revealed increased anti-inflammatory and pro-homeostatic genes and decreases in expression of pro-inflammatory genes in …


Her3 Functions As An Effective Therapeutic Target In Triple Negative Breast Cancer To Potentiate The Antitumor Activity Of Gefitinib And Paclitaxel, Hui Lyu, Fei Shen, Sanbao Ruan, Congcong Tan, Jundong Zhou, Ann D. Thor, Bolin Liu Sep 2023

Her3 Functions As An Effective Therapeutic Target In Triple Negative Breast Cancer To Potentiate The Antitumor Activity Of Gefitinib And Paclitaxel, Hui Lyu, Fei Shen, Sanbao Ruan, Congcong Tan, Jundong Zhou, Ann D. Thor, Bolin Liu

School of Medicine Faculty Publications

Background: Triple negative breast cancer (TNBC) represents a significant clinical challenge. Chemotherapy remains the mainstay for a large part of TNBC patients, whereas drug resistance and tumor recurrence frequently occur. It is in urgent need to identify novel molecular targets for TNBC and develop effective therapy against the aggressive disease. Methods: Immunohistochemistry was performed to examine the expression of HER3 in TNBC samples. Western blots were used to assess protein expression and activation. Cell proliferation and viability were determined by cell growth (MTS) assays. TCGA databases were analyzed to correlate HER3 mRNA expression with the clinical outcomes of TNBC patients. …


Sugar-Sweetened Beverages And Artificially Sweetened Beverages Consumption And The Risk Of Nonalcoholic Fatty Liver (Nafld) And Nonalcoholic Steatohepatitis (Nash), Tung Sung Tseng, Wei Ting Lin, Peng Sheng Ting, Chiung Kuei Huang, Po Hung Chen, Gabrielle V. Gonzalez, Hui Yi Lin Sep 2023

Sugar-Sweetened Beverages And Artificially Sweetened Beverages Consumption And The Risk Of Nonalcoholic Fatty Liver (Nafld) And Nonalcoholic Steatohepatitis (Nash), Tung Sung Tseng, Wei Ting Lin, Peng Sheng Ting, Chiung Kuei Huang, Po Hung Chen, Gabrielle V. Gonzalez, Hui Yi Lin

School of Public Health Faculty Publications

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are fast becoming the most common chronic liver disease and are often preventable with healthy dietary habits and weight management. Sugar-sweetened beverage (SSB) consumption is associated with obesity and NAFLD. However, the impact of different types of SSBs, including artificially sweetened beverages (ASBs), is not clear after controlling for total sugar intake and total caloric intake. The aim of this study was to examine the association between the consumption of different SSBs and the risk of NAFLD and NASH in US adults. The representativeness of 3739 US adults aged ≥20 years …


Human Alcohol-Microbiota Mice Have Increased Susceptibility To Bacterial Pneumonia, Kelly C. Cunningham, Deandra R. Smith, Daniel N. Villageliú, Christi M. Ellis, Amanda E. Ramer-Tait, Jeffrey D. Price, Todd A. Wyatt, Daren L. Knoell, Mystera M. Samuelson, Patricia E. Molina, David A. Welsh, Derrick R. Samuelson Sep 2023

Human Alcohol-Microbiota Mice Have Increased Susceptibility To Bacterial Pneumonia, Kelly C. Cunningham, Deandra R. Smith, Daniel N. Villageliú, Christi M. Ellis, Amanda E. Ramer-Tait, Jeffrey D. Price, Todd A. Wyatt, Daren L. Knoell, Mystera M. Samuelson, Patricia E. Molina, David A. Welsh, Derrick R. Samuelson

School of Medicine Faculty Publications

Preclinical studies have shown that chronic alcohol abuse leads to alterations in the gastrointestinal microbiota that are associated with behavior changes, physiological alterations, and immunological effects. However, such studies have been limited in their ability to evaluate the direct effects of alcohol-associated dysbiosis. To address this, we developed a humanized alcohol-microbiota mouse model to systematically evaluate the immunological effects of chronic alcohol abuse mediated by intestinal dysbiosis. Germ-free mice were colonized with human fecal microbiota from individuals with high and low Alcohol Use Disorders Identification Test (AUDIT) scores and bred to produce human alcohol-associated microbiota or human control-microbiota F1 progenies. …


Peripheral Arterial Disease And Complications Of Total Knee Arthroplasty: Indications For Advanced Vascular Imaging And Minimally Invasive Soft Tissue Coverage Procedures, Kristopher Katira, Antony Martin, Anna Garbuzov, James Ferrer, Brian Chuong, Ross Parkerson, George Chimento Sep 2023

Peripheral Arterial Disease And Complications Of Total Knee Arthroplasty: Indications For Advanced Vascular Imaging And Minimally Invasive Soft Tissue Coverage Procedures, Kristopher Katira, Antony Martin, Anna Garbuzov, James Ferrer, Brian Chuong, Ross Parkerson, George Chimento

School of Medicine Faculty Publications

Soft tissue coverage of knee wounds can be challenging, in particular in the setting of peripheral arterial disease and knee arthroplasty complications. Options for soft-tissue coverage range from conservative wound care to invasive pedicled and free flaps. Unlike traditional wound coverage problems in plastic surgery patients, arthroplasty coverage decisions oblige surgeons to take into account the possibility of secondary orthopedic procedures. The two cases presented in this manuscript demonstrate the importance of vascular imaging, in particular angiography. In both cases, the workhorse medial gastrocnemius flap harvest could have resulted in critical limb ischemia. When secondary orthopedic revision is required at …


Candida-Induced Granulocytic Myeloid-Derived Suppressor Cells Are Protective Against Polymicrobial Sepsis, Shannon Esher Righi, Amanda J. Harriett, Elizabeth A. Lilly, Paul L. Fidel Jr., Mairi C. Noverr Sep 2023

Candida-Induced Granulocytic Myeloid-Derived Suppressor Cells Are Protective Against Polymicrobial Sepsis, Shannon Esher Righi, Amanda J. Harriett, Elizabeth A. Lilly, Paul L. Fidel Jr., Mairi C. Noverr

School of Dentistry Faculty Publications

Polymicrobial intra-abdominal infections (IAI) can lead to life-threatening sepsis with significant morbidity and mortality, especially when pathogenic fungi are involved. We have employed an established clinically relevant mouse model of fungal/bacterial IAI and shown that immunization with low-virulence Candida species, that is, Candida dubliniensis, can induce responses that protect against sepsis via the suppression of lethal inflammation. This protection is dependent on long-lived Gr-1(+) polymorphonuclear leukocytes that display characteristics consistent with myeloid-derived suppressor cells (MDSCs) and trained innate immunity. Here we aimed to functionally and phenotypically characterize these protective Gr-1(+) leukocytes. Compared to nonimmunized control mice, we observed increased levels …


Design, Analysis, And Interpretation Of Treatment Response Heterogeneity In Personalized Nutrition And Obesity Treatment Research, Roger S. Zoh, Bridget H. Esteves, Xiaoxin Yu, Amanda J. Fairchild, Ana I. Vazquez, Andrew G. Chapple, Andrew W. Brown, Brandon George, Derek Gordon, Douglas Landsittel, Gary L. Gadbury, Greg Pavela, Gustavo De Los Campos, Luis M. Mestre, David B. Allison Sep 2023

Design, Analysis, And Interpretation Of Treatment Response Heterogeneity In Personalized Nutrition And Obesity Treatment Research, Roger S. Zoh, Bridget H. Esteves, Xiaoxin Yu, Amanda J. Fairchild, Ana I. Vazquez, Andrew G. Chapple, Andrew W. Brown, Brandon George, Derek Gordon, Douglas Landsittel, Gary L. Gadbury, Greg Pavela, Gustavo De Los Campos, Luis M. Mestre, David B. Allison

School of Public Health Faculty Publications

It is increasingly assumed that there is no one-size-fits-all approach to dietary recommendations for the management and treatment of chronic diseases such as obesity. This phenomenon that not all individuals respond uniformly to a given treatment has become an area of research interest given the rise of personalized and precision medicine. To conduct, interpret, and disseminate this research rigorously and with scientific accuracy, however, requires an understanding of treatment response heterogeneity. Here, we define treatment response heterogeneity as it relates to clinical trials, provide statistical guidance for measuring treatment response heterogeneity, and highlight study designs that can quantify treatment response …


Rod-Specific Downregulation Of Omega-3 Very-Long-Chain Polyunsaturated Fatty Acid Pathway In Age-Related Macular Degeneration, William C. Gordon, Marie Audrey I. Kautzmann, Bokkyoo Jun, Megan L. Cothern, Zhide Fang, Nicolas G. Bazan Sep 2023

Rod-Specific Downregulation Of Omega-3 Very-Long-Chain Polyunsaturated Fatty Acid Pathway In Age-Related Macular Degeneration, William C. Gordon, Marie Audrey I. Kautzmann, Bokkyoo Jun, Megan L. Cothern, Zhide Fang, Nicolas G. Bazan

School of Medicine Faculty Publications

Docosahexaenoic acid (DHA; 22:6) plays a key role in vision and is the precursor for very-long-chain polyunsaturated fatty acids (VLC-PUFAs). The release of 32- and 34-carbon VLC-PUFAs and DHA from sn-1 and sn-2 of phosphatidylcholine (PC) leads to the synthesis of cell-survival mediators, the elovanoids (ELVs) and neuroprotectin D1 (NPD1), respectively. Macula and periphery from age-related macular degeneration (AMD) donor retinas were assessed for the availability of DHA-related lipids by LC-MS/MS-based lipidomic analysis and MALDI-molecular imaging. We found reduced retina DHA and VLC-PUFA pathways to synthesize omega-3 ELVs from precursors that likely resulted in altered disks and photoreceptor loss. Additionally, …


An Examination Of The Relationships Between The Neighborhood Social Environment, Adiposity, And Cardiometabolic Disease Risk In Adolescence: A Cross-Sectional Study, Kara D. Denstel, Robbie A. Beyl, Denise M. Danos, Maura M. Kepper, Amanda E. Staiano, Katherine T. Theall, Tung Sung Tseng, Stephanie T. Broyles Sep 2023

An Examination Of The Relationships Between The Neighborhood Social Environment, Adiposity, And Cardiometabolic Disease Risk In Adolescence: A Cross-Sectional Study, Kara D. Denstel, Robbie A. Beyl, Denise M. Danos, Maura M. Kepper, Amanda E. Staiano, Katherine T. Theall, Tung Sung Tseng, Stephanie T. Broyles

School of Public Health Faculty Publications

Background: Disadvantaged neighborhood environments are a source of chronic stress which undermines optimal adolescent health. This study investigated relationships between the neighborhood social environment, specifically, chronic stress exposures, adiposity, and cardiometabolic disease risk factors among 288 Louisiana adolescents aged 10 to 16 years. Methods: This cross-sectional study utilized baseline data from the Translational Investigation of Growth and Everyday Routines in Kids (TIGER Kids) study. Adolescent data were obtained using self-reported questionnaires (demographics and perceived neighborhood disorder), anthropometry, body imaging, and a blood draw while objective neighborhood data for the concentrated disadvantage index were acquired from the 2016 American Community Survey …


Topiramate (Topamax): Evolving Role In Weight Reduction Management: A Narrative Review, Irza Wajid, Alexis Vega, Katherine Thornhill, Jack Jenkins, Chandler Merriman, Debbie Chandler, Sahar Shekoohi, Elyse M. Cornett, Alan D. Kaye Aug 2023

Topiramate (Topamax): Evolving Role In Weight Reduction Management: A Narrative Review, Irza Wajid, Alexis Vega, Katherine Thornhill, Jack Jenkins, Chandler Merriman, Debbie Chandler, Sahar Shekoohi, Elyse M. Cornett, Alan D. Kaye

School of Medicine Faculty Publications

Obesity has emerged as a widespread disease with epidemic proportions, necessitating effective management to enhance the overall health outcomes of patients. Medical intervention for weight loss becomes necessary when diet and exercise prove ineffective, and topiramate emerges as a potential treatment option for this global problem. Currently approved as an anti-epileptic and migraine prophylaxis medication, topiramate is frequently utilized as adjunctive therapy for patients with mood and eating disorders, as well as for alcohol use disorders. Its multifaceted mechanisms of action contribute to reducing neuronal excitation and enhancing neuronal inhibition. Given its variety of mechanisms, topiramate shows several off-label outcomes, …


Comparative Polar And Lipid Plasma Metabolomics Differentiate Kshv Infection And Disease States, Sara R. Privatt, Camila Pereira Braga, Alicia Johnson, Salum J. Lidenge, Luke Berry, John R. Ngowi, Owen Ngalamika, Andrew G. Chapple, Julius Mwaiselage, Charles Wood, John T. West, Jiri Adamec Aug 2023

Comparative Polar And Lipid Plasma Metabolomics Differentiate Kshv Infection And Disease States, Sara R. Privatt, Camila Pereira Braga, Alicia Johnson, Salum J. Lidenge, Luke Berry, John R. Ngowi, Owen Ngalamika, Andrew G. Chapple, Julius Mwaiselage, Charles Wood, John T. West, Jiri Adamec

School of Medicine Faculty Publications

Background: Kaposi sarcoma (KS) is a neoplastic disease etiologically associated with infection by the Kaposi sarcoma-associated herpesvirus (KSHV). KS manifests primarily as cutaneous lesions in individuals due to either age (classical KS), HIV infection (epidemic KS), or tissue rejection preventatives in transplantation (iatrogenic KS) but can also occur in individuals, predominantly in sub-Saharan Africa (SSA), lacking any obvious immune suppression (endemic KS). The high endemicity of KSHV and human immunodeficiency virus-1 (HIV) co-infection in Africa results in KS being one of the top 5 cancers there. As with most viral cancers, infection with KSHV alone is insufficient to induce tumorigenesis. …


Minoxidil Weakens Newly Synthesized Collagen In Fibrotic Synoviocytes From Osteoarthritis Patients, Stefan Sarkovich, Peter P. Issa, Andrew Longanecker, Davis Martin, Kaitlyn Redondo, Patrick Mcternan, Jennifer Simkin, Luis Marrero Aug 2023

Minoxidil Weakens Newly Synthesized Collagen In Fibrotic Synoviocytes From Osteoarthritis Patients, Stefan Sarkovich, Peter P. Issa, Andrew Longanecker, Davis Martin, Kaitlyn Redondo, Patrick Mcternan, Jennifer Simkin, Luis Marrero

School of Medicine Faculty Publications

Purpose: Synovial fibrosis (SFb) formation and turnover attributable to knee osteoarthritis (KOA) can impart painful stiffness and persist following arthroplasty. To supplement joint conditioning aimed at maximizing peri-operative function, we evaluated the antifibrotic effect of Minoxidil (MXD) on formation of pyridinoline (Pyd) cross-links catalyzed by Plod2-encoded lysyl hydroxylase (LH)2b that strengthen newly synthesized type-I collagen (COL1) in fibroblastic synovial cells (FSCs) from KOA patients. MXD was predicted to decrease Pyd without significant alterations to Col1a1 transcription by FSCs stimulated with transforming growth factor (TGF)β1. Methods: Synovium from 10 KOA patients grouped by SFb severity was preserved for picrosirius and LH2b …


Small Molecules Targeting Insm1 For The Treatment Of High-Risk Neuroblastoma, Michael S. Lan, Chiachen Chen Aug 2023

Small Molecules Targeting Insm1 For The Treatment Of High-Risk Neuroblastoma, Michael S. Lan, Chiachen Chen

School of Medicine Faculty Publications

Human neuroblastoma (NB) is the most common childhood extracranial tumor arising from the sympathetic nervous system. It is also a clinically heterogeneous disease that ranges from spontaneous regression to high-risk stage 4 disease. The cause of this disease remains elusive. However, the amplification of NMYC oncogene occurred in roughly 30% of NB patients, which strongly correlated with the advanced stage of disease subtype and the worse prognosis status. We discovered that N-Myc oncoprotein binds and activates INSM1, a zinc-finger transcription factor of neuroendocrine tumors. We also found that INSM1 modulates N-Myc stability mediated through PI3K/AKT/GSK3β signaling pathway. Therefore, INSM1 emerges …


Unlocking The Potential Of Kinase Targets In Cancer: Insights From Canceromicsnet, An Ai-Driven Approach To Drug Response Prediction In Cancer, Manali Singha, Limeng Pu, Gopal Srivastava, Xialong Ni, Brent A. Stanfield, Ifeanyi K. Uche, Paul J.F. Rider, Konstantin G. Kousoulas, J. Ramanujam, Michal Brylinski Aug 2023

Unlocking The Potential Of Kinase Targets In Cancer: Insights From Canceromicsnet, An Ai-Driven Approach To Drug Response Prediction In Cancer, Manali Singha, Limeng Pu, Gopal Srivastava, Xialong Ni, Brent A. Stanfield, Ifeanyi K. Uche, Paul J.F. Rider, Konstantin G. Kousoulas, J. Ramanujam, Michal Brylinski

School of Medicine Faculty Publications

Deregulated protein kinases are crucial in promoting cancer cell proliferation and driving malignant cell signaling. Although these kinases are essential targets for cancer therapy due to their involvement in cell development and proliferation, only a small part of the human kinome has been targeted by drugs. A comprehensive scoring system is needed to evaluate and prioritize clinically relevant kinases. We recently developed CancerOmicsNet, an artificial intelligence model employing graph-based algorithms to predict the cancer cell response to treatment with kinase inhibitors. The performance of this approach has been evaluated in large-scale benchmarking calculations, followed by the experimental validation of selected …


A Cryptic Microdeletion Del(12)(P11.21p11.23) Within An Unbalanced Translocation T(7;12)(Q21.13;Q23.1) Implicates New Candidate Loci For Intellectual Disability And Kallmann Syndrome, Afif Ben-Mahmoud, Shotaro Kishikawa, Vijay Gupta, Natalia T. Leach, Yiping Shen, Oana Moldovan, Himanshu Goel, Bruce Hopper, Kara Ranguin, Nicolas Gruchy, Saskia M. Maas, Yves Lacassie, Soo Hyun Kim, Woo Yang Kim, Bradley J. Quade, Cynthia C. Morton, Cheol Hee Kim, Lawrence C. Layman, Hyung Goo Kim Aug 2023

A Cryptic Microdeletion Del(12)(P11.21p11.23) Within An Unbalanced Translocation T(7;12)(Q21.13;Q23.1) Implicates New Candidate Loci For Intellectual Disability And Kallmann Syndrome, Afif Ben-Mahmoud, Shotaro Kishikawa, Vijay Gupta, Natalia T. Leach, Yiping Shen, Oana Moldovan, Himanshu Goel, Bruce Hopper, Kara Ranguin, Nicolas Gruchy, Saskia M. Maas, Yves Lacassie, Soo Hyun Kim, Woo Yang Kim, Bradley J. Quade, Cynthia C. Morton, Cheol Hee Kim, Lawrence C. Layman, Hyung Goo Kim

School of Medicine Faculty Publications

In a patient diagnosed with both Kallmann syndrome (KS) and intellectual disability (ID), who carried an apparently balanced translocation t(7;12)(q22;q24)dn, array comparative genomic hybridization (aCGH) disclosed a cryptic heterozygous 4.7 Mb deletion del(12)(p11.21p11.23), unrelated to the translocation breakpoint. This novel discovery prompted us to consider the possibility that the combination of KS and neurological disorder in this patient could be attributed to gene(s) within this specific deletion at 12p11.21-12p11.23, rather than disrupted or dysregulated genes at the translocation breakpoints. To further support this hypothesis, we expanded our study by screening five candidate genes at both breakpoints of the chromosomal translocation …


Sars-Cov-2 Infection In Unvaccinated High-Risk Pregnant Women In The Bronx, Ny, Usa Is Associated With Decreased Apgar Scores And Placental Villous Infarcts, Sandra E. Reznik, Patricia M. Vuguin, Alexa Cohen, Rasha Khoury, Olivier Loudig, Ridin Balakrishnan, Susan A. Fineberg, Francine Hughes, Malini Harigopal, Maureen J. Charron Aug 2023

Sars-Cov-2 Infection In Unvaccinated High-Risk Pregnant Women In The Bronx, Ny, Usa Is Associated With Decreased Apgar Scores And Placental Villous Infarcts, Sandra E. Reznik, Patricia M. Vuguin, Alexa Cohen, Rasha Khoury, Olivier Loudig, Ridin Balakrishnan, Susan A. Fineberg, Francine Hughes, Malini Harigopal, Maureen J. Charron

School of Medicine Faculty Publications

Babies born to severe acute respiratory syndrome corona virus-2 (SARS-CoV-2)-infected mothers are at greater risk for perinatal morbidity and more likely to receive a neurodevelopmental diagnosis in the first year of life. However, the effect of maternal infection on placental function and neonatal outcomes varies depending upon the patient population. We set out to test our hypothesis that maternal SARS-CoV-2 infection in our underserved, socioeconomically disadvantaged, mostly unvaccinated, predominantly African American and Latina population in the Bronx, NY would have effects evident at birth. Under IRB approval, 56 SARS-CoV-2-positive patients infected during the “first wave” of the pandemic with alpha …


Her3 Targeting Augments The Efficacy Of Panobinostat In Claudin-Low Triple-Negative Breast Cancer Cells, Hui Lyu, Defu Hou, Hao Liu, Sanbao Ruan, Congcong Tan, Jiande Wu, Chindo Hicks, Bolin Liu Aug 2023

Her3 Targeting Augments The Efficacy Of Panobinostat In Claudin-Low Triple-Negative Breast Cancer Cells, Hui Lyu, Defu Hou, Hao Liu, Sanbao Ruan, Congcong Tan, Jiande Wu, Chindo Hicks, Bolin Liu

School of Medicine Faculty Publications

Patients with triple-negative breast cancer (TNBC) have a poor prognosis and high relapse rate due to limited therapeutic options. This study was conducted to determine the mechanisms of action of panobinostat, a pan-inhibitor of histone deacetylase (HDAC) and FDA-approved medication for multiple myeloma, in TNBC and to provide a rationale for effective drug combinations against this aggressive disease. RNA sequencing analyses of the claudin-low (CL) TNBC (MDA-MB-231) cells untreated or treated with panobinostat were performed to identify the differentially expressed genes. Adaptive alterations in gene expression were analyzed and validated in additional CL TNBC cells. Tumor xenograft models were used …


Dietary Intake During A Pragmatic Cluster-Randomized Weight Loss Trial In An Underserved Population In Primary Care, John W. Apolzan, Corby K. Martin, Robert L. Newton, Candice A. Myers, Connie L. Arnold, Terry C. Davis, William D. Johnson, Dachuan Zhang, Christoph Höchsmann, Vivian A. Fonseca, Kara D. Denstel, Emily F. Mire, Benjamin F. Springgate, Carl J. Lavie, Peter T. Katzmarzyk, Phillip Brantley, Ronald Horswell, Tina K. Thethi, Jonathan Gugel, Eboni Price-Haywood, Kathleen B. Kennedy, Daniel F. Sarpong Aug 2023

Dietary Intake During A Pragmatic Cluster-Randomized Weight Loss Trial In An Underserved Population In Primary Care, John W. Apolzan, Corby K. Martin, Robert L. Newton, Candice A. Myers, Connie L. Arnold, Terry C. Davis, William D. Johnson, Dachuan Zhang, Christoph Höchsmann, Vivian A. Fonseca, Kara D. Denstel, Emily F. Mire, Benjamin F. Springgate, Carl J. Lavie, Peter T. Katzmarzyk, Phillip Brantley, Ronald Horswell, Tina K. Thethi, Jonathan Gugel, Eboni Price-Haywood, Kathleen B. Kennedy, Daniel F. Sarpong

School of Medicine Faculty Publications

Background: Currently there are limited data as to whether dietary intake can be improved during pragmatic weight loss interventions in primary care in underserved individuals. Methods: Patients with obesity were recruited into the PROPEL trial, which randomized 18 clinics to either an intensive lifestyle intervention (ILI) or usual care (UC). At baseline and months 6, 12, and 24, fruit and vegetable (F/V) intake and fat intake was determined. Outcomes were analyzed by repeated-measures linear mixed-effects multilevel models and regression models, which included random cluster (clinic) effects. Secondary analyses examined the effects of race, sex, age, and food security status. Results: …


Use Of The Decipher Genomic Classifier Among Men With Prostate Cancer In The United States, Nicholas G. Zaorsky, James A. Proudfoot, Angela Y. Jia, Raed Zuhour, Randy Vince Jr., Yang Liu, Xin Zhao, Jim Hu, Nicola Schussler, Jennifer L. Stevens, Suzanne Bentler, Rosemary D. Cress, Jennifer A. Doherty, Eric B. Durbin, Susan Gershman, Iona Cheng, Lou Gonsalves, Brenda Y. Hernandez, Lihua Liu, Bozena M. Morawski, Maria Schymura, Stephen M. Schwartz, Kevin C. Ward, Charles Wiggins, Xiao-Cheng Wu, Jonathan Shoag, Lee Ponsky, Alan Dal Pra, Edward M. Schaeffer, Et Al Aug 2023

Use Of The Decipher Genomic Classifier Among Men With Prostate Cancer In The United States, Nicholas G. Zaorsky, James A. Proudfoot, Angela Y. Jia, Raed Zuhour, Randy Vince Jr., Yang Liu, Xin Zhao, Jim Hu, Nicola Schussler, Jennifer L. Stevens, Suzanne Bentler, Rosemary D. Cress, Jennifer A. Doherty, Eric B. Durbin, Susan Gershman, Iona Cheng, Lou Gonsalves, Brenda Y. Hernandez, Lihua Liu, Bozena M. Morawski, Maria Schymura, Stephen M. Schwartz, Kevin C. Ward, Charles Wiggins, Xiao-Cheng Wu, Jonathan Shoag, Lee Ponsky, Alan Dal Pra, Edward M. Schaeffer, Et Al

School of Medicine Faculty Publications

Background: Management of localized or recurrent prostate cancer since the 1990s has been based on risk stratification using clinicopathological variables, including Gleason score, T stage (based on digital rectal exam), and prostate-specific antigen (PSA). In this study a novel prognostic test, the Decipher Prostate Genomic Classifier (GC), was used to stratify risk of prostate cancer progression in a US national database of men with prostate cancer. Methods: Records of prostate cancer cases from participating SEER (Surveillance, Epidemiology, and End Results) program registries, diagnosed during the period from 2010 through 2018, were linked to records of testing with the GC prognostic …


Computational Modeling And Synthesis Of Pyridine Variants Of Benzoyl-Phenoxy-Acetamide With High Glioblastoma Cytotoxicity And Brain Tumor Penetration, Charles H. Ingraham, Joanna Stalinska, Sean C. Carson, Susan B. Colley, Monika Rak, Adam Lassak, Francesca Peruzzi, Krzysztof Reiss, Branko S. Jursic Jul 2023

Computational Modeling And Synthesis Of Pyridine Variants Of Benzoyl-Phenoxy-Acetamide With High Glioblastoma Cytotoxicity And Brain Tumor Penetration, Charles H. Ingraham, Joanna Stalinska, Sean C. Carson, Susan B. Colley, Monika Rak, Adam Lassak, Francesca Peruzzi, Krzysztof Reiss, Branko S. Jursic

School of Graduate Studies Faculty Publications

Glioblastomas are highly aggressive brain tumors for which therapeutic options are very limited. In a quest for new anti-glioblastoma drugs, we focused on specific structural modifications to the benzoyl-phenoxy-acetamide (BPA) structure present in a common lipid-lowering drug, fenofibrate, and in our first prototype glioblastoma drug, PP1. Here, we propose extensive computational analyses to improve the selection of the most effective glioblastoma drug candidates. Initially, over 100 structural BPA variations were analyzed and their physicochemical properties, such as water solubility (− logS), calculated partition coefficient (ClogP), probability for BBB crossing (BBB_SCORE), probability for CNS penetration (CNS-MPO) and calculated cardiotoxicity (hERG), were …


Targeted Muscle Reinnervation To Reduce Postoperative Pain In Patients Undergoing Hindquarter Resections, Mikaela H. Sullivan, Gavin L. Mills, Hiba Saifuddin, Elyse J. Brinkman, Brian T. Carlsen, Steven L. Moran, Matthew T. Houdek Jul 2023

Targeted Muscle Reinnervation To Reduce Postoperative Pain In Patients Undergoing Hindquarter Resections, Mikaela H. Sullivan, Gavin L. Mills, Hiba Saifuddin, Elyse J. Brinkman, Brian T. Carlsen, Steven L. Moran, Matthew T. Houdek

School of Medicine Faculty Publications

Background/Aim: Pre-emptive targeted muscle reinnervation (TMR) at the time of amputation results in less phantom limb pain (PLP) compared with untreated amputee controls. There is limited literature describing the technique in patients undergoing hindquarter amputation despite up to 90% of these patients reporting PLP and 50% presenting with painful neuroma. The purpose of the current study was to describe the motor nerves accessible through a primary hind-quarter amputation to be used for TMR and review pain outcomes in clinical case correlates of patients with TMR. Patients and Methods: Six limbs were obtained from three fresh adult cadavers and proximal sensory …


Effect Of Biological Variation In Hba1c And Blood Glucose On The Diagnosis Of Prediabetes, James M. Hempe, Shengping Yang, Daniel S. Hsia Jul 2023

Effect Of Biological Variation In Hba1c And Blood Glucose On The Diagnosis Of Prediabetes, James M. Hempe, Shengping Yang, Daniel S. Hsia

School of Medicine Faculty Publications

Introduction: People with a low or high haemoglobin glycation index (HGI) have lower or higher HbA1c than other people with the same FPG. This study compared the prevalence of prediabetes based on FPG, 2hOGTT and HbA1c in people with low, moderate or high HGI. Methods: Prediabetes was diagnosed based on ADA cutpoints in 10,488 NHANES participants without self-reported diabetes. HGI was calculated as the difference between a participant's observed HbA1c and a predicted HbA1c where predicted HbA1c = 0.024 FPG + 3.1. Participants were divided into low (HGI < −0.15%), moderate (HGI −0.15% to +0.15%) and high (HGI > +0.15%) HGI subgroups. Results: The prevalence of prediabetes was 42.4% based on …


Mediation Of Bmi On 25-Hydroxyvitamin D Levels In U.S. Adults With Sugar-Sweetened Beverages Consumption, Wei Ting Lin, Gabrielle V. Gonzalez, Yu Hsiang Kao, Hui Yi Lin, Mirandy S. Li, David W. Seal, Chien Hung Lee, Chih Yang Hu, Lei Shih Chen, Tung Sung Tseng Jul 2023

Mediation Of Bmi On 25-Hydroxyvitamin D Levels In U.S. Adults With Sugar-Sweetened Beverages Consumption, Wei Ting Lin, Gabrielle V. Gonzalez, Yu Hsiang Kao, Hui Yi Lin, Mirandy S. Li, David W. Seal, Chien Hung Lee, Chih Yang Hu, Lei Shih Chen, Tung Sung Tseng

School of Public Health Faculty Publications

Body mass index (BMI) as well as sugar-sweetened beverages (SSB) has been suggested to independently decrease 25-hydroxyvitamin D (25(OH)D). However, the relationship between SSB, BMI, and 25(OH)D is uncertain. This study aimed to investigate the potential mediating role of BMI in the association between SSB intake and 25(OH)D. A total of 4505 representative U.S. adults aged above 20 years and without liver conditions were selected from the 2013–2014 NHANES. All analyses were performed under survey modules with appropriate sampling weights. The prevalence of 25(OH)D insufficiency and deficiency was 37.8% and 24.1% in U.S. adults, respectively. Compared with non-SSB consumers, an …


Nanoparticle-Based Treatment Approaches For Skin Cancer: A Systematic Review., Michael Joseph Diaz, Nicole Natarelli, Shaliz Aflatooni, Sarah J. Aleman Jul 2023

Nanoparticle-Based Treatment Approaches For Skin Cancer: A Systematic Review., Michael Joseph Diaz, Nicole Natarelli, Shaliz Aflatooni, Sarah J. Aleman

School of Medicine Faculty Publications

Nanoparticles have shown marked promise as both antineoplastic agents and drug carriers. Despite strides made in immunomodulation, low success rates and toxicity remain limitations within the clinical oncology setting. In the present review, we assess advances in drug delivery nanoparticles, for systemic and topical use, in skin cancer treatment. A systematic review of controlled trials, meta-analyses, and Cochrane review articles was conducted. Eligibility criteria included: (1) a primary focus on nanoparticle utility for skin cancer; (2) available metrics on prevention and treatment outcomes; (3) detailed subject population; (4) English language; (5) archived as full-text journal articles. A total of 43 …


Targeting Mcl-1 By A Small Molecule Nsc260594 For Triple-Negative Breast Cancer Therapy, Shengli Dong, Margarite D. Matossian, Hassan Yousefi, Maninder Khosla, Bridgette M. Collins-Burow, Matthew E. Burow, Suresh K. Alahari Jul 2023

Targeting Mcl-1 By A Small Molecule Nsc260594 For Triple-Negative Breast Cancer Therapy, Shengli Dong, Margarite D. Matossian, Hassan Yousefi, Maninder Khosla, Bridgette M. Collins-Burow, Matthew E. Burow, Suresh K. Alahari

School of Graduate Studies Faculty Publications

Triple-negative breast cancers (TNBCs) are aggressive forms of breast cancer and tend to grow and spread more quickly than most other types of breast cancer. TNBCs can neither be targeted by hormonal therapies nor the antibody trastuzumab that targets the HER2 protein. There are urgent unmet medical needs to develop targeted drugs for TNBCs. We identified a small molecule NSC260594 from the NCI diversity set IV compound library. NSC260594 exhibited dramatic cytotoxicity in multiple TNBCs in a dose-and time-dependent manner. NSC260594 inhibited the Myeloid cell leukemia-1 (Mcl-1) expression through downregulation of Wnt signaling proteins. Consistent with this, NSC260594 treatment increased …


The Role Of Gut Dysbiosis In The Loss Of Intestinal Immune Cell Functions And Viral Pathogenesis, Farzaneh Fakharian, Siva Thirugnanam, David A. Welsh, Woong Ki Kim, Jay Rappaport, Kyle Bittinger, Namita Rout Jul 2023

The Role Of Gut Dysbiosis In The Loss Of Intestinal Immune Cell Functions And Viral Pathogenesis, Farzaneh Fakharian, Siva Thirugnanam, David A. Welsh, Woong Ki Kim, Jay Rappaport, Kyle Bittinger, Namita Rout

School of Medicine Faculty Publications

The gut microbiome plays a critical role in maintaining overall health and immune function. However, dysbiosis, an imbalance in microbiome composition, can have profound effects on various aspects of human health, including susceptibility to viral infections. Despite numerous studies investigating the influence of viral infections on gut microbiome, the impact of gut dysbiosis on viral infection and pathogenesis remains relatively understudied. The clinical variability observed in SARS-CoV-2 and seasonal influenza infections, and the presence of natural HIV suppressors, suggests that host-intrinsic factors, including the gut microbiome, may contribute to viral pathogenesis. The gut microbiome has been shown to influence the …


Two Pediatric Cases Within A Familial Cluster And Hereditary Diffuse Gastric Carcinoma: A Tale Of 2 Sisters, Lacey Falgout, Lawrence L. Gensler Jul 2023

Two Pediatric Cases Within A Familial Cluster And Hereditary Diffuse Gastric Carcinoma: A Tale Of 2 Sisters, Lacey Falgout, Lawrence L. Gensler

School of Medicine Faculty Publications

Hereditary diffuse gastric cancer is a familial form of poorly differentiated signet ring cell carcinoma (SRCC) caused by a mutation in the CDH1/E-cadherin gene-mediating cell adhesion. CDH1 mutations are inherited in an autosomal dominant fashion and exhibit a high level of penetrance. SRCC diagnosis is exceedingly rare in the pediatric population. We report a case of SRCC in 2 sisters (10 and 15 years) and their father (41 years).


Lower Urinary Tract Symptoms In Depression: A Review, Danyon J. Anderson, Alise Aucoin, Colton R. Toups, Devin Cormier, Matthew Mcdonald, Jamal Hasoon, Omar Viswanath, Alan D. Kaye, Ivan Urits Jul 2023

Lower Urinary Tract Symptoms In Depression: A Review, Danyon J. Anderson, Alise Aucoin, Colton R. Toups, Devin Cormier, Matthew Mcdonald, Jamal Hasoon, Omar Viswanath, Alan D. Kaye, Ivan Urits

School of Medicine Faculty Publications

Lower Urinary Tract Symptoms (LUTS) are frequently present in the general population as patients age with approximately a third of individuals experiencing LUTS during their lifetime. LUTS can be further defined as having any of the following symptoms: urinary hesitancy, straining, nocturia, increased urination frequency, and dysuria. LUTS has the potential for patients to contribute their symptoms to what can normally occur as we age. This can lead to a decrease in patients seeking care and could negatively impact patients’ health-related quality of life (HRQL). In conjunction with LUTS, we obtained from our analysis that LUTS and depression are closely …


Outpatient Sexually Transmitted Infection Testing And Treatment Patterns In The United States: A Real-World Database Study, Rebecca Lillis, Louis Kuritzky, Zune Huynh, Rodney Arcenas, Avneet Hansra, Roma Shah, Baiyu Yang, Stephanie N. Taylor Jul 2023

Outpatient Sexually Transmitted Infection Testing And Treatment Patterns In The United States: A Real-World Database Study, Rebecca Lillis, Louis Kuritzky, Zune Huynh, Rodney Arcenas, Avneet Hansra, Roma Shah, Baiyu Yang, Stephanie N. Taylor

School of Medicine Faculty Publications

Background: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the most common notifiable sexually transmitted infections (STIs) in the United States. Because symptoms of these infections often overlap with other urogenital infections, misdiagnosis and incorrect treatment can occur unless appropriate STI diagnostic testing is performed in clinical settings. The objective of this study was to describe STI diagnostic testing and antimicrobial treatment patterns and trends among adolescent and adult men and women with lower genitourinary tract symptoms (LGUTS). Methods: We analyzed insurance claims data from the IBM® MarketScan® Research Databases. Patients included were between 14 and 64 years old with …


High Glucose-Upregulated Pd-L1 Expression Through Ras Signaling-Driven Downregulation Of Ptrh1 Leads To Suppression Of T Cell Cytotoxic Function In Tumor Environment, Chenggang Gao, Jiaoshun Chen, Jianwei Bai, Haoxiang Zhang, Yanyi Tao, Shihong Wu, Hehe Li, Heshui Wu, Qiang Shen, Tao Yin Jul 2023

High Glucose-Upregulated Pd-L1 Expression Through Ras Signaling-Driven Downregulation Of Ptrh1 Leads To Suppression Of T Cell Cytotoxic Function In Tumor Environment, Chenggang Gao, Jiaoshun Chen, Jianwei Bai, Haoxiang Zhang, Yanyi Tao, Shihong Wu, Hehe Li, Heshui Wu, Qiang Shen, Tao Yin

School of Graduate Studies Faculty Publications

Background: Nearly 80% of patients with pancreatic cancer suffer from glucose intolerance or diabetes. Pancreatic cancer complicated by diabetes has a more immunosuppressive tumor microenvironment (TME) and is associated with a worse prognosis. The relationship between glucose metabolism and programmed cell death-Ligand 1 (PD-L1) is close and complex. It is important to explore the regulation of high glucose on PD-L1 expression in pancreatic cancer and its effect on infiltrating immune effectors in the tumor microenvironment. Methods: Diabetic murine models (C57BL/6) were used to reveal different immune landscape in euglycemic and hyperglycemic pancreatic tumor microenvironment. Bioinformatics, WB, iRIP [Improved RNA Binding …