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Using Rna-Based Therapies To Target The Kidney In Cardiovascular Disease, Trecia C Palmer, Robert W Hunter Jan 2023

Using Rna-Based Therapies To Target The Kidney In Cardiovascular Disease, Trecia C Palmer, Robert W Hunter

Faculty, Staff and Student Publications

RNA-based therapies are currently used for immunisation against infections and to treat metabolic diseases. They can modulate gene expression in immune cells and hepatocytes, but their use in other cell types has been limited by an inability to selectively target specific tissues. Potential solutions to this targeting problem involve packaging therapeutic RNA molecules into delivery vehicles that are preferentially delivered to cells of interest. In this review, we consider why the kidney is a desirable target for RNA-based therapies in cardiovascular disease and discuss how such therapy could be delivered. Because the kidney plays a central role in maintaining cardiovascular …


Heterogeneity Of Memory T Cells In Aging, Abhinav Jain, Ines Sturmlechner, Cornelia M Weyand, Jörg J Goronzy Jan 2023

Heterogeneity Of Memory T Cells In Aging, Abhinav Jain, Ines Sturmlechner, Cornelia M Weyand, Jörg J Goronzy

Faculty, Staff and Student Publications

Immune memory is a requisite and remarkable property of the immune system and is the biological foundation of the success of vaccinations in reducing morbidity from infectious diseases. Some vaccines and infections induce long-lasting protection, but immunity to other vaccines and particularly in older adults rarely persists over long time periods. Failed induction of an immune response and accelerated waning of immune memory both contribute to the immuno-compromised state of the older population. Here we review how T cell memory is influenced by age. T cell memory is maintained by a dynamic population of T cells that are heterogeneous in …


Association Of Immune-Related Adverse Events With The Outcomes Of Immune Checkpoint Inhibitors In Patients With Dmmr/Msi-H Metastatic Colorectal Cancer, Vincenzo Nasca, Francesco Barretta, Francesca Corti, Sara Lonardi, Monica Niger, Maria Elena Elez, Marwan Fakih, Priya Jayachandran, Aakash Tushar Shah, Massimiliano Salati, Elisabetta Fenocchio, Lisa Salvatore, Chiara Cremolini, Javier Ros, Margherita Ambrosini, Giacomo Mazzoli, Rossana Intini, Michael J Overman, Rosalba Miceli, Filippo Pietrantonio Jan 2023

Association Of Immune-Related Adverse Events With The Outcomes Of Immune Checkpoint Inhibitors In Patients With Dmmr/Msi-H Metastatic Colorectal Cancer, Vincenzo Nasca, Francesco Barretta, Francesca Corti, Sara Lonardi, Monica Niger, Maria Elena Elez, Marwan Fakih, Priya Jayachandran, Aakash Tushar Shah, Massimiliano Salati, Elisabetta Fenocchio, Lisa Salvatore, Chiara Cremolini, Javier Ros, Margherita Ambrosini, Giacomo Mazzoli, Rossana Intini, Michael J Overman, Rosalba Miceli, Filippo Pietrantonio

Faculty, Staff and Student Publications

BACKGROUND: Immune checkpoint inhibitors (ICIs) show a tremendous activity in microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC), but a consistent fraction of patients does not respond. Prognostic/predictive markers are needed. Despite previous investigations in other tumor types, immune-related adverse events (irAEs) have not been well evaluated in patients with MSI-H cancers treated with ICIs.

METHODS: We conducted an international cohort study at tertiary cancer centers collecting clinic-pathological features from 331 patients with MSI-H mCRC treated with ICIs. Of note, the irAEs were summarized using a 'burden score' constructed in a way that the same score value could be obtained by …


Evaluation Of Scrub Typhus Surveillance, Alwar District, Rajasthan, India, July-August 2020, Surendra M Prajapati, Kanica Kaushal, Simmi Tiwari, Ajit Shewale, Tushar Nale, Tanzin Dikid Jan 2023

Evaluation Of Scrub Typhus Surveillance, Alwar District, Rajasthan, India, July-August 2020, Surendra M Prajapati, Kanica Kaushal, Simmi Tiwari, Ajit Shewale, Tushar Nale, Tanzin Dikid

Faculty, Staff and Student Publications

INTRODUCTION: Scrub typhus is one of the most underreported and fatal illnesses accounting for 23% of all febrile illness. Rajasthan reported cases during 2018-2019 in state reporting system but did not report any case to central Integrated Disease Surveillance Programme (IDSP) unit. We evaluated the Scrub typhus surveillance system in Alwar district, Rajasthan, with the objective of describing and evaluating the system and providing evidence-based recommendations to identify gaps.

MATERIAL AND METHODS: In cross-sectional study, we reviewed records and conducted key informant interviews at district- and block-level health facilities. Using US Centers for Disease Control guidelines, we evaluated the system …


Determinants Of Human Papillomavirus Vaccine Hesitancy Among Lebanese Parents, Ramia Zakhour, Hani Tamim, Farah Faytrouni, Maha Makki, Rayan Hojeij, Lama Charafeddine Jan 2023

Determinants Of Human Papillomavirus Vaccine Hesitancy Among Lebanese Parents, Ramia Zakhour, Hani Tamim, Farah Faytrouni, Maha Makki, Rayan Hojeij, Lama Charafeddine

Faculty, Staff and Student Publications

Introduction: Human papillomavirus (HPV) is the most common sexually transmitted infection. HPV is responsible for cancer of cervix uteri. Despite its safety and immunogenicity, HPV vaccine hesitancy is one of the most challenging topics that pediatricians face.

Methods: We aimed to describe the impact of knowledge, attitude, and practice towards vaccines in general, on practice related to HPV vaccination in Lebanon. A questionnaire addressed to parents of students (3-18 years of age) was distributed in 2 public and 2 private schools randomly selected from the greater Beirut area during the school year 2017-2018. Questionnaires covered knowledge, attitude, and practices of …


Iga-Biome Profiles Correlate With Clinical Parkinson's Disease Subtypes, Eric L Brown, Heather T Essigmann, Kristi L Hoffman, Ashley S Alexander, Michael Newmark, Zhi-Dong Jiang, Jessika Suescun, Mya C Schiess, Craig L Hanis, Herbert L Dupont Jan 2023

Iga-Biome Profiles Correlate With Clinical Parkinson's Disease Subtypes, Eric L Brown, Heather T Essigmann, Kristi L Hoffman, Ashley S Alexander, Michael Newmark, Zhi-Dong Jiang, Jessika Suescun, Mya C Schiess, Craig L Hanis, Herbert L Dupont

Faculty, Staff and Student Publications

BACKGROUND: Parkinson's disease is a heterogeneous neurodegenerative disorder with distinctive gut microbiome patterns suggesting that interventions targeting the gut microbiota may prevent, slow, or reverse disease progression and severity.

OBJECTIVE: Because secretory IgA (SIgA) plays a key role in shaping the gut microbiota, characterization of the IgA-Biome of individuals classified into either the akinetic rigid (AR) or tremor dominant (TD) Parkinson's disease clinical subtypes was used to further define taxa unique to these distinct clinical phenotypes.

METHODS: Flow cytometry was used to separate IgA-coated and -uncoated bacteria from stool samples obtained from AR and TD patients followed by amplification and …


Regional Outbreak Of Multidrug-Resistant Klebsiella Pneumoniae Carbapenemase-Producing Pseudomonas Aeruginosa, Bekana K Tadese, Anna Nutt, Ifrah Chaudhary, Charlene Offiong, Charles Darkoh Jan 2023

Regional Outbreak Of Multidrug-Resistant Klebsiella Pneumoniae Carbapenemase-Producing Pseudomonas Aeruginosa, Bekana K Tadese, Anna Nutt, Ifrah Chaudhary, Charlene Offiong, Charles Darkoh

Faculty, Staff and Student Publications

Klebsiella pneumoniae carbapenemase-producing P. aeruginosa (KPC-CRPA) are rare in the United States. An outbreak of KPC-CRPA was investigated in Texas using molecular and epidemiologic methods and 17 cases of KPC-CRPA were identified. The isolates were genetically related and harbored the emerging P. aeruginosa multilocus sequence type 235, the first in the United States.


Understanding The Implications Of Under-Reporting, Vaccine Efficiency And Social Behavior On The Post-Pandemic Spread Using Physics Informed Neural Networks: A Case Study Of China, Samiran Ghosh, Alonso Ogueda-Oliva, Aditi Ghosh, Malay Banerjee, Padmanabhan Seshaiyer Jan 2023

Understanding The Implications Of Under-Reporting, Vaccine Efficiency And Social Behavior On The Post-Pandemic Spread Using Physics Informed Neural Networks: A Case Study Of China, Samiran Ghosh, Alonso Ogueda-Oliva, Aditi Ghosh, Malay Banerjee, Padmanabhan Seshaiyer

Faculty, Staff and Student Publications

In late 2019, the emergence of COVID-19 in Wuhan, China, led to the implementation of stringent measures forming the zero-COVID policy aimed at eliminating transmission. Zero-COVID policy basically aimed at completely eliminating the transmission of COVID-19. However, the relaxation of this policy in late 2022 reportedly resulted in a rapid surge of COVID-19 cases. The aim of this work is to investigate the factors contributing to this outbreak using a new SEIR-type epidemic model with time-dependent level of immunity. Our model incorporates a time-dependent level of immunity considering vaccine doses administered and time-post-vaccination dependent vaccine efficacy. We find that vaccine …


Age-Induced Changes In Anti-Tumor Immunity Alter The Tumor Immune Infiltrate And Impact Response To Immuno-Oncology Treatments, Suzanne I Sitnikova, Jennifer A Walker, Laura B Prickett, Michelle Morrow, Viia E Valge-Archer, Matthew J Robinson, Robert W Wilkinson, Simon J Dovedi Jan 2023

Age-Induced Changes In Anti-Tumor Immunity Alter The Tumor Immune Infiltrate And Impact Response To Immuno-Oncology Treatments, Suzanne I Sitnikova, Jennifer A Walker, Laura B Prickett, Michelle Morrow, Viia E Valge-Archer, Matthew J Robinson, Robert W Wilkinson, Simon J Dovedi

Faculty, Staff and Student Publications

INTRODUCTION: Immuno-oncology (IO) research relies heavily on murine syngeneic tumor models. However, whilst the average age for a cancer diagnosis is 60 years or older, for practical purposes the majority of preclinical studies are conducted in young mice, despite the fact that ageing has been shown to have a significant impact on the immune response.

METHODS: Using aged (60-72 weeks old) mice bearing CT26 tumors, we investigated the impact of ageing on tumor growth as well as the immune composition of the tumor and peripheral lymphoid organs.

RESULTS: We found many differences in the immune cell composition of both the …


Hpv-Related Oropharyngeal Cancer Early Detection In Gay And Bisexual Men Is An “Orphan” Practice: A Qualitative Analysis Among Healthcare Providers, I Niles Zoschke, Sarah L Bennis, J Michael Wilkerson, Cynthia L Stull, Alan G Nyitray, Samir S Khariwala, C Mark Nichols, B R Simon Rosser, Charlene Flash, Michael W Ross Jan 2023

Hpv-Related Oropharyngeal Cancer Early Detection In Gay And Bisexual Men Is An “Orphan” Practice: A Qualitative Analysis Among Healthcare Providers, I Niles Zoschke, Sarah L Bennis, J Michael Wilkerson, Cynthia L Stull, Alan G Nyitray, Samir S Khariwala, C Mark Nichols, B R Simon Rosser, Charlene Flash, Michael W Ross

Faculty, Staff and Student Publications

Introduction: Among US men, oropharyngeal cancer (cancer of the back of the mouth and throat) is the 8th most common cancer. If detected early, human papillomavirus (HPV)-16-associated oropharyngeal cancer has a high 5-year survival rate. Risk factors such as high numbers of oral sex partners, disparities in smoking and drinking, and low rates of HPV vaccination may put gay and bisexual men at even higher risk for oropharyngeal cancer.

Methods: We recruited 21 healthcare providers in Minneapolis-St. Paul, Minnesota and Houston, Texas to participate in semi-structured interviews. Nurses, physician assistants, dental hygienists, and dentists were asked about their clinical experiences …


Identification Of Microbiological Factors Associated With Periodontal Health Disparities, Bing-Yan Wang, Aize Cao, Meng-Hsuan Ho, Derek Wilus, Sally Sheng, Hsiu-Wan Meng, Elissa Guerra, Jianming Hong, Hua Xie Jan 2023

Identification Of Microbiological Factors Associated With Periodontal Health Disparities, Bing-Yan Wang, Aize Cao, Meng-Hsuan Ho, Derek Wilus, Sally Sheng, Hsiu-Wan Meng, Elissa Guerra, Jianming Hong, Hua Xie

Faculty, Staff and Student Publications

The present study aimed at identifying risk factors associated with periodontitis development and periodontal health disparities with emphasis on differential oral microbiota. The prevalence of periodontitis is recently rising dentate adults in the US, which presents a challenge to oral health and overall health. The risk of developing periodontitis is higher in African Americans (AAs), and Hispanic Americans (HAs) than in Caucasian Americans (CAs). To identify potentially microbiological determinations of periodontal health disparities, we examined the distribution of several potentially beneficial and pathogenic bacteria in the oral cavities of AA, CA, and HA study participants. Dental plaque samples from 340 …


Assessing Pandemic Preparedness, Response, And Lessons Learned From The Covid-19 Pandemic In Four South American Countries: Agenda For The Future, Andrea Ramírez Varela, Michael Touchton, J Jaime Miranda, Juliana Mejía Grueso, Rachid Laajaj, Gabriel Carrasquilla, Martha Vives Florez, Ana María Vesga Gaviria, Ana María Ortiz Hoyos, Esteban Orlando Vanegas Duarte, Alejandra Velásquez Morales, Nubia Velasco, Silvia Restrepo Restrepo Jan 2023

Assessing Pandemic Preparedness, Response, And Lessons Learned From The Covid-19 Pandemic In Four South American Countries: Agenda For The Future, Andrea Ramírez Varela, Michael Touchton, J Jaime Miranda, Juliana Mejía Grueso, Rachid Laajaj, Gabriel Carrasquilla, Martha Vives Florez, Ana María Vesga Gaviria, Ana María Ortiz Hoyos, Esteban Orlando Vanegas Duarte, Alejandra Velásquez Morales, Nubia Velasco, Silvia Restrepo Restrepo

Faculty, Staff and Student Publications

INTRODUCTION: The COVID-19 pandemic emerged in a context that lacked adequate prevention, preparedness, and response (PPR) activities, and global, regional, and national leadership. South American countries were among world's hardest hit by the pandemic, accounting for 10.1% of total cases and 20.1% of global deaths.

METHODS: This study explores how pandemic PPR were affected by political, socioeconomic, and health system contexts as well as how PPR may have shaped pandemic outcomes in Argentina, Brazil, Colombia, and Peru. We then identify lessons learned and advance an agenda for improving PPR capacity at regional and national levels. We do this through a …


A Novel Bayesian Spatial-Temporal Approach To Quantify Sars-Cov-2 Testing Disparities For Small Area Estimation, Cici Bauer, Xiaona Li, Kehe Zhang, Miryoung Lee, Esmeralda Guajardo, Susan Fisher-Hoch, Joseph Mccormick, Maria E Fernandez, Belinda Reininger Jan 2023

A Novel Bayesian Spatial-Temporal Approach To Quantify Sars-Cov-2 Testing Disparities For Small Area Estimation, Cici Bauer, Xiaona Li, Kehe Zhang, Miryoung Lee, Esmeralda Guajardo, Susan Fisher-Hoch, Joseph Mccormick, Maria E Fernandez, Belinda Reininger

Faculty, Staff and Student Publications

Objectives. To propose a novel Bayesian spatial–temporal approach to identify and quantify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing disparities for small area estimation.

Methods. In step 1, we used a Bayesian inseparable space–time model framework to estimate the testing positivity rate (TPR) at geographically granular areas of the census block groups (CBGs). In step 2, we adopted a rank-based approach to compare the estimated TPR and the testing rate to identify areas with testing deficiency and quantify the number of needed tests. We used weekly SARS-CoV-2 infection and testing surveillance data from Cameron County, Texas, between March 2020 …


From The National To The Local: Issues Of Trust And A Model For Community-Academic-Engagement, Olufunmilayo Chinekezi, Lauri Andress, Etsemaye P Agonafer, Susan Massick, Sarah Piepenbrink, Karey M Sutton, Philip M Alberti, Desiree De La Torre, Shannon Guillot-Wright, Marshala Lee Jan 2023

From The National To The Local: Issues Of Trust And A Model For Community-Academic-Engagement, Olufunmilayo Chinekezi, Lauri Andress, Etsemaye P Agonafer, Susan Massick, Sarah Piepenbrink, Karey M Sutton, Philip M Alberti, Desiree De La Torre, Shannon Guillot-Wright, Marshala Lee

Faculty, Staff and Student Publications

Inequities in health and health care in the United States have persisted for decades, and the impacts on equity from the COVID-19 pandemic were no exception. In addition to the disproportionate burden of the disease across various populations, the pandemic posed several challenges, which exacerbated these existing inequities. This has undoubtedly contributed to deeply rooted public mistrust in medical research and healthcare delivery, particularly among historically and structurally oppressed populations. In the summer of 2020, given the series of social injustices posed by the pandemic and highly publicized incidents of police brutality, notably the murder of George Floyd, the Association …


A Case Of Successful Treatment Of Recurrent Urinary Tract Infection By Extended-Spectrum Β-Lactamase Producing, Naomi Bier, Blake Hanson, Zhi-Dong Jiang, Herbert L Dupont, Cesar A Arias, William R Miller Jan 2023

A Case Of Successful Treatment Of Recurrent Urinary Tract Infection By Extended-Spectrum Β-Lactamase Producing, Naomi Bier, Blake Hanson, Zhi-Dong Jiang, Herbert L Dupont, Cesar A Arias, William R Miller

Faculty, Staff and Student Publications

Recurrent urinary tract infections (UTIs) are a challenging clinical entity that can be frustrating for patient and physician alike. Repeated rounds of antibiotics can select for multidrug-resistant organisms, further complicating care. We describe the successful use of fecal microbiota transplantation (FMT) for the treatment of recurrent extended-spectrum β-lactamase (ESBL)-producing


Fostering A High-Functioning Team In Cancer Care Using The 4r Oncology Model: Assessment In A Large Health System And A Blueprint For Other Institutions, Raymond Liu, Christine B Weldon, Elizabeth Linehan, Nancy Gordon, Thea Abbe, Marti Hennings, Henie James, Jed Katzel, Chun Ng, Megumi Tomita, Jeffrey B Velotta, Stephanie Ossowski, Lori C Sakoda, Sharon Likely Sprague, Anna Dowling, Kimberly Beringer, Arliene Ravelo, Elaine Yu, Julia R Trosman Jan 2023

Fostering A High-Functioning Team In Cancer Care Using The 4r Oncology Model: Assessment In A Large Health System And A Blueprint For Other Institutions, Raymond Liu, Christine B Weldon, Elizabeth Linehan, Nancy Gordon, Thea Abbe, Marti Hennings, Henie James, Jed Katzel, Chun Ng, Megumi Tomita, Jeffrey B Velotta, Stephanie Ossowski, Lori C Sakoda, Sharon Likely Sprague, Anna Dowling, Kimberly Beringer, Arliene Ravelo, Elaine Yu, Julia R Trosman

Faculty, Staff and Student Publications

PURPOSE: Delivering cancer care by high-functioning multidisciplinary teams promises to address care fragmentation, which threatens care quality, affects patient outcomes, and strains the oncology workforce. We assessed whether the 4R Oncology model for team-based interdependent care delivery and patient self-management affected team functioning in a large community-based health system.

METHODS: 4R was deployed at four locations in breast and lung cancers and assessed along four characteristics of high-functioning teams: recognition as a team internally and externally; commitment to an explicit shared goal; enablement of interdependent work to achieve the goal; and engagement in regular reflection to adapt objectives and processes. …


A Case Of Successful Treatment Of Recurrent Urinary Tract Infection By Extended-Spectrum Β-Lactamase Producing Klebsiella Pneumoniae Using Oral Lyophilized Fecal Microbiota Transplant, Naomi Bier, Blake Hanson, Zhi-Dong Jiang, Herbert L Dupont, Cesar A Arias, William R Miller Jan 2023

A Case Of Successful Treatment Of Recurrent Urinary Tract Infection By Extended-Spectrum Β-Lactamase Producing Klebsiella Pneumoniae Using Oral Lyophilized Fecal Microbiota Transplant, Naomi Bier, Blake Hanson, Zhi-Dong Jiang, Herbert L Dupont, Cesar A Arias, William R Miller

Faculty, Staff and Student Publications

Recurrent urinary tract infections (UTIs) are a challenging clinical entity that can be frustrating for patient and physician alike. Repeated rounds of antibiotics can select for multidrug-resistant organisms, further complicating care. We describe the successful use of fecal microbiota transplantation (FMT) for the treatment of recurrent extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae UTIs in a patient with an ileal conduit and urostomy. In the 18 months after FMT, the patient had not experienced new infections with ESBL-producing organisms. The urine and stool microbiomes of the patient were tracked before and post-FMT using 16s RNA sequencing with measurement of α-diversity. Sequencing of …


Development And Validation Of Early Death Risk Score Model For Emergency Status Prediction In Very Severe Aplastic Anemia, Xu Liu, Wenrui Yang, Li Zhang, Liping Jing, Lei Ye, Kang Zhou, Yuan Li, Jianping Li, Huihui Fan, Yang Yang, Youzhen Xiong, Xin Zhao, Fengkui Zhang Jan 2023

Development And Validation Of Early Death Risk Score Model For Emergency Status Prediction In Very Severe Aplastic Anemia, Xu Liu, Wenrui Yang, Li Zhang, Liping Jing, Lei Ye, Kang Zhou, Yuan Li, Jianping Li, Huihui Fan, Yang Yang, Youzhen Xiong, Xin Zhao, Fengkui Zhang

Faculty, Staff and Student Publications

This study developed and validated the Early Death Risk Score Model for early identification of emergency patients with very severe aplastic anemia (VSAA). All 377 patients with VSAA receiving first-line immunosuppressive therapy (IST) were categorized into training (n=252) and validation (n=125) cohorts. In the training cohort, age >24 years, absolute neutrophil count ≤0.015×109/L, serum ferritin >900ng/mL and times of fever before IST >1 time were significantly associated with early death. Covariates were assigned scores and categorized as: low (score 0-4), medium (score 5-7) and high (score ≥8) risk. Early death rate was significantly different between risk groups and the validation …


Super-Resolution And Segmentation Deep Learning For Breast Cancer Histopathology Image Analysis, Aniwat Juhong, Bo Li, Cheng-You Yao, Chia-Wei Yang, Dalen W Agnew, Yu Leo Lei, Xuefei Huang, Wibool Piyawattanametha, Zhen Qiu Jan 2023

Super-Resolution And Segmentation Deep Learning For Breast Cancer Histopathology Image Analysis, Aniwat Juhong, Bo Li, Cheng-You Yao, Chia-Wei Yang, Dalen W Agnew, Yu Leo Lei, Xuefei Huang, Wibool Piyawattanametha, Zhen Qiu

Faculty, Staff and Student Publications

Traditionally, a high-performance microscope with a large numerical aperture is required to acquire high-resolution images. However, the images' size is typically tremendous. Therefore, they are not conveniently managed and transferred across a computer network or stored in a limited computer storage system. As a result, image compression is commonly used to reduce image size resulting in poor image resolution. Here, we demonstrate custom convolution neural networks (CNNs) for both super-resolution image enhancement from low-resolution images and characterization of both cells and nuclei from hematoxylin and eosin (H&E) stained breast cancer histopathological images by using a combination of generator and discriminator …


Risk Factors Associated With Severe Clostridioides Difficile Infection In Patients With Cancer, Denise Marie A Francisco, Liangliang Zhang, Ying Jiang, Adilene Olvera, Javier Adachi, Eduardo Yepez Guevara, Samuel L Aitken, Kevin W Garey, Christine B Peterson, Kim-Anh Do, Ryan Dillon, Engels N Obi, Robert Jenq, Pablo C Okhuysen Jan 2023

Risk Factors Associated With Severe Clostridioides Difficile Infection In Patients With Cancer, Denise Marie A Francisco, Liangliang Zhang, Ying Jiang, Adilene Olvera, Javier Adachi, Eduardo Yepez Guevara, Samuel L Aitken, Kevin W Garey, Christine B Peterson, Kim-Anh Do, Ryan Dillon, Engels N Obi, Robert Jenq, Pablo C Okhuysen

Faculty, Staff and Student Publications

INTRODUCTION: Antibiotic use is a risk factor for Clostridioides difficile infection (CDI). Few studies have correlated use of prior antibiotic classes with CDI, microbiome composition, and disease severity in patients with cancer. We hypothesized that previous antibiotic exposure and fecal microbiome composition at time of presentation are risk factors for severe CDI in patients with cancer.

METHODS: This non-interventional, prospective, cohort study examined 200 patients with cancer who had their first episode or first recurrence of CDI. C. difficile was identified using nucleic acid amplification testing. Univariate analysis was used to determine significant risk factors for severe CDI. Fecal microbiome …


The Interplay Between Neoantigens And Immune Cells In Sarcomas Treated With Checkpoint Inhibition, Irantzu Anzar, Brandon Malone, Pubudu Samarakoon, Ioannis Vardaxis, Boris Simovski, Hugues Fontenelle, Leonardo A Meza-Zepeda, Richard Stratford, Emily Z Keung, Melissa Burgess, Hussein A Tawbi, Ola Myklebost, Trevor Clancy Jan 2023

The Interplay Between Neoantigens And Immune Cells In Sarcomas Treated With Checkpoint Inhibition, Irantzu Anzar, Brandon Malone, Pubudu Samarakoon, Ioannis Vardaxis, Boris Simovski, Hugues Fontenelle, Leonardo A Meza-Zepeda, Richard Stratford, Emily Z Keung, Melissa Burgess, Hussein A Tawbi, Ola Myklebost, Trevor Clancy

Faculty, Staff and Student Publications

INTRODUCTION: Sarcomas are comprised of diverse bone and connective tissue tumors with few effective therapeutic options for locally advanced unresectable and/or metastatic disease. Recent advances in immunotherapy, in particular immune checkpoint inhibition (ICI), have shown promising outcomes in several cancer indications. Unfortunately, ICI therapy has provided only modest clinical responses and seems moderately effective in a subset of the diverse subtypes.

METHODS: To explore the immune parameters governing ICI therapy resistance or immune escape, we performed whole exome sequencing (WES) on tumors and their matched normal blood, in addition to RNA-seq from tumors of 31 sarcoma patients treated with pembrolizumab. …


Small Molecule Inhibitor Of Tau Self-Association In A Mouse Model Of Tauopathy: A Preventive Study In P301l Tau Jnpl3 Mice, Eliot J Davidowitz, Patricia Lopez, Heidy Jimenez, Leslie Adrien, Peter Davies, James G Moe Jan 2023

Small Molecule Inhibitor Of Tau Self-Association In A Mouse Model Of Tauopathy: A Preventive Study In P301l Tau Jnpl3 Mice, Eliot J Davidowitz, Patricia Lopez, Heidy Jimenez, Leslie Adrien, Peter Davies, James G Moe

Faculty, Staff and Student Publications

Advances in tau biology and the difficulties of amyloid-directed immunotherapeutics have heightened interest in tau as a target for small molecule drug discovery for neurodegenerative diseases. Here, we evaluated OLX-07010, a small molecule inhibitor of tau self-association, for the prevention of tau aggregation. The primary endpoint of the study was statistically significant reduction of insoluble tau aggregates in treated JNPL3 mice compared with Vehicle-control mice. Secondary endpoints were dose-dependent reduction of insoluble tau aggregates, reduction of phosphorylated tau, and reduction of soluble tau. This study was performed in JNPL3 mice, which are representative of inherited forms of 4-repeat tauopathies with …


Pediatric Diarrhea Patients Living In Urban Areas Have A Higher Incidence Of Clostridioides Difficile Infection, Ayodele T Adesoji, Osaro Mgbere, Charles Darkoh Jan 2023

Pediatric Diarrhea Patients Living In Urban Areas Have A Higher Incidence Of Clostridioides Difficile Infection, Ayodele T Adesoji, Osaro Mgbere, Charles Darkoh

Faculty, Staff and Student Publications

Clostridioides difficile infection (CDI) is a major cause of antibiotic-associated diarrhea and an unappreciated contributor to child mortality in low- and middle-income countries where the diagnosis may be difficult. There is little information about the prevalence of CDI among infants, children, and adolescents in Africa. Using a cross-sectional design, seventy-six samples were collected from pediatric patients presenting with diarrhea, including infants (≤ 2 years old), children (2-12 years), and adolescents (13 ≤17 years) from three hospitals between January and December 2019. Demographic data, medical history, and prior antibiotic use were recorded. Toxigenic culture and PCR were used to detect and …


Population-Based Assessment Of The Burden Of Covid-19 Infection In African Countries: A First-Year Report Card And Public Health Implications, Osaro Mgbere, Ogbonna Collins Nwabuko, Olajumoke A Olateju, Omolola E Adepoju, Winston Liaw, Charles Darkoh, Ekere James Essien Jan 2023

Population-Based Assessment Of The Burden Of Covid-19 Infection In African Countries: A First-Year Report Card And Public Health Implications, Osaro Mgbere, Ogbonna Collins Nwabuko, Olajumoke A Olateju, Omolola E Adepoju, Winston Liaw, Charles Darkoh, Ekere James Essien

Faculty, Staff and Student Publications

BACKGROUND: The COVID-19 pandemic constitutes a global health threat and poses a major burden on the African continent. We assessed the real-world burden of COVID-19 infection in African Union (AU) member states to determine the distributional patterns of epidemiological measures during the first 1 year of the pandemic.

METHODS: This retrospective cross-sectional study utilized COVID-19 data from publicly available data repositories of the African Center for Disease Control and Prevention and

RESULTS: A total of 3.21 million cases were reported during the 1-year period, with 2.6 million recoveries, 536,784 cases remaining active, and 77,486 deaths. Most countries (49.1%,

CONCLUSION: Understanding …


Evolutionary Aspects Of Infections: Inflammation And Sickness Behaviors, Robert Dantzer Jan 2023

Evolutionary Aspects Of Infections: Inflammation And Sickness Behaviors, Robert Dantzer

Faculty, Staff and Student Publications

Sickness behavior was conceptualized initially as the behavioral counterpart of the fever response to infectious pathogens. It helps to raise body temperature to its higher setpoint and to maintain it at this new level and it has the additional benefit of enabling a weakened organism to protect itself from other dangers. The discovery of the behavioral effects of proinflammatory cytokines produced by activated immune cells provided a cellular and molecular basis to this phenomenon. The administration of cytokines or cytokine inducers like lipopolysaccharide to healthy rodents allowed to reveal the similarities and differences between inflammation-induced sickness behavior and the fever …


Examining The Role Of Autonomy Support, Goal Setting, And Care Coordination Quality On Hiv Prep Adherence In Black Men Who Have Sex With Men: Hptn 073, Donte T Boyd, Laron E Nelson, Mandy J Hill, Darren Whitfield, S Raquel Ramos, Samuel Akyirem, Lynda Emel, Leo Wilton, Lisa Hightow-Weidman, Steve Shoptaw, Manya Magnus, Kenneth H Mayer, Estelle Piwowar-Manning, Stephaun E Wallace, Sheldon D Fields, Darrell P Wheeler Jan 2023

Examining The Role Of Autonomy Support, Goal Setting, And Care Coordination Quality On Hiv Prep Adherence In Black Men Who Have Sex With Men: Hptn 073, Donte T Boyd, Laron E Nelson, Mandy J Hill, Darren Whitfield, S Raquel Ramos, Samuel Akyirem, Lynda Emel, Leo Wilton, Lisa Hightow-Weidman, Steve Shoptaw, Manya Magnus, Kenneth H Mayer, Estelle Piwowar-Manning, Stephaun E Wallace, Sheldon D Fields, Darrell P Wheeler

Faculty, Staff and Student Publications

Autonomy support is a concept that is derived from self-determination theory. Autonomy refers to the freedom to act as one chooses. The current study aimed to examine if autonomy support was associated with dried blood spot validated pre-exposure prophylaxis (PrEP) adherence, and whether the association was mediated by PrEP adherence goal setting and progress toward PrEP adherence goals. Our sample was drawn from Black men who have sex with men (MSM) from across three cities (Chapel Hill, NC; Los Angeles, CA; and Washington, DC) in the United States between February 2013 and September 2014. We used logistic regression to evaluate …


Are Trauma Surgeons Prepared? A Survey Of Trauma Surgeons’ Disaster Preparedness Before And During The Covid-19 Pandemic, Jay Doucet, David V Shatz, Lewis J Kaplan, Eileen M Bulger, Jeannette Capella, Deborah A Kuhls, Mary Fallat, Kyle N Remick, Christopher Newton, Adam Fox, Randeep Jawa, John A Harvin, David P Blake, Marko Bukur, Jonathan Gates, James Ficke, Mark L Gestring, The American Association For Surgery Of Trauma Disaster Committee Jan 2023

Are Trauma Surgeons Prepared? A Survey Of Trauma Surgeons’ Disaster Preparedness Before And During The Covid-19 Pandemic, Jay Doucet, David V Shatz, Lewis J Kaplan, Eileen M Bulger, Jeannette Capella, Deborah A Kuhls, Mary Fallat, Kyle N Remick, Christopher Newton, Adam Fox, Randeep Jawa, John A Harvin, David P Blake, Marko Bukur, Jonathan Gates, James Ficke, Mark L Gestring, The American Association For Surgery Of Trauma Disaster Committee

Faculty, Staff and Student Publications

OBJECTIVE: US trauma centers (TCs) must remain prepared for mass casualty incidents (MCIs). However, trauma surgeons may lack formal MCI training. The recent COVID-19 pandemic drove multiple patient surges, overloaded Emergency Medical Services (EMS) agencies, and stressed TCs. This survey assessed trauma surgeons' MCI training, experience, and system and personal preparedness before the pandemic compared with the pandemic's third year.

METHODS: Survey invitations were emailed to all 1544 members of the American Association for the Surgery of Trauma in 2019, and then resent in 2022 to 1575 members with additional questions regarding the pandemic. Questions assessed practice type, TC characteristics, …


Bacterial Meningitis In Africa, Tatiana Barichello, Carlos Henrique Rocha Catalão, Ursula K Rohlwink, Martijn Van Der Kuip, Dan Zaharie, Regan S Solomons, Ronald Van Toorn, Marceline Tutu Van Furth, Rodrigo Hasbun, Federico Iovino, Vivian Ssonko Namale Jan 2023

Bacterial Meningitis In Africa, Tatiana Barichello, Carlos Henrique Rocha Catalão, Ursula K Rohlwink, Martijn Van Der Kuip, Dan Zaharie, Regan S Solomons, Ronald Van Toorn, Marceline Tutu Van Furth, Rodrigo Hasbun, Federico Iovino, Vivian Ssonko Namale

Faculty, Staff and Student Publications

Bacterial meningitis differs globally, and the incidence and case fatality rates vary by region, country, pathogen, and age group; being a life-threatening disease with a high case fatality rate and long-term complications in low-income countries. Africa has the most significant prevalence of bacterial meningitis illness, and the outbreaks typically vary with the season and the geographic location, with a high incidence in the meningitis belt of the sub-Saharan area from Senegal to Ethiopia. Streptococcus pneumoniae (pneumococcus) and Neisseria meningitidis (meningococcus) are the main etiological agents of bacterial meningitis in adults and children above the age of one. Streptococcus agalactiae (group …


Within Subject Cross-Tissue Analyzes Of Epigenetic Clocks In Substance Use Disorder Postmortem Brain And Blood, Brenda Cabrera-Mendoza, Laura Stertz, Katherine Najera, Sudhakar Selvaraj, Antonio L Teixeira, Thomas D Meyer, Gabriel R Fries, Consuelo Walss-Bass Jan 2023

Within Subject Cross-Tissue Analyzes Of Epigenetic Clocks In Substance Use Disorder Postmortem Brain And Blood, Brenda Cabrera-Mendoza, Laura Stertz, Katherine Najera, Sudhakar Selvaraj, Antonio L Teixeira, Thomas D Meyer, Gabriel R Fries, Consuelo Walss-Bass

Faculty, Staff and Student Publications

There is a possible accelerated biological aging in patients with substance use disorders (SUD). The evaluation of epigenetic clocks, which are accurate estimators of biological aging based on DNA methylation changes, has been limited to blood tissue in patients with SUD. Consequently, the impact of biological aging in the brain of individuals with SUD remains unknown. In this study, we evaluated multiple epigenetic clocks (DNAmAge, DNAmAgeHannum, DNAmAgeSkinBlood, DNAmPhenoAge, DNAmGrimAge, and DNAmTL) in individuals with SUD (n = 42), including alcohol (n = 10), opioid (n = 19), and stimulant use disorder (n = 13), and controls (n = 10) in …


Imaging Peripheral Lymphatic Dysfunction In Chronic Conditions, Eva M Sevick-Muraca, Caroline E Fife, John C Rasmussen Jan 2023

Imaging Peripheral Lymphatic Dysfunction In Chronic Conditions, Eva M Sevick-Muraca, Caroline E Fife, John C Rasmussen

Faculty, Staff and Student Publications

The lymphatics play important roles in chronic diseases/conditions that comprise the bulk of healthcare worldwide. Yet the ability to routinely image and diagnose lymphatic dysfunction, using commonly available clinical imaging modalities, has been lacking and as a result, the development of effective treatment strategies suffers. Nearly two decades ago, investigational near-infrared fluorescence lymphatic imaging and ICG lymphography were developed as routine diagnostic for clinically evaluating, quantifying, and treating lymphatic dysfunction in cancer-related and primary lymphedema, chronic venous disease, and more recently, autoimmune and neurodegenerative disorders. In this review, we provide an overview of what these non-invasive technologies have taught us …