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Management Of Gunshot Wounds Near The Elbow: Experiences At A High-Volume Level I Trauma Center, Umar Ghilzai, Abdullah Ghali, Aaron Singh, Thomas Wesley Mitchell, Scott A Mitchell Mar 2024

Management Of Gunshot Wounds Near The Elbow: Experiences At A High-Volume Level I Trauma Center, Umar Ghilzai, Abdullah Ghali, Aaron Singh, Thomas Wesley Mitchell, Scott A Mitchell

Faculty, Staff and Students Publications

BACKGROUND: Gunshot-related fractures near the elbow are challenging, and available data to guide the practitioner are lacking. This report analyzes injury patterns and treatment strategies in a case series from a high-volume urban trauma center.

METHODS: All periarticular gunshot fractures near the elbow treated at a level 1 trauma center from 2014 to 2018 were retrospectively reviewed. Fracture location, patient demographics, concomitant injuries, treatment modalities, and complications were analyzed.

RESULTS: Twenty-four patients were identified. All patients received prophylactic antibiotics upon admission and underwent urgent surgical debridement. Open reduction and internal fixation (ORIF) was performed with initial debridement in 22 of …


Crises In Antimicrobial Stewardship: Misuse Of Clarithromycin For Helicobacter Pylori Therapy, David Y Graham Mar 2024

Crises In Antimicrobial Stewardship: Misuse Of Clarithromycin For Helicobacter Pylori Therapy, David Y Graham

Faculty, Staff and Students Publications

Helicobacter pylori is a class I carcinogen that infects more than 100 million individuals in the United States. Antimicrobial therapy for H. pylori has typically been prescribed empirically rather than based on susceptibility testing. Until recently, therapeutic recommendations have generally ignored the principles of antibiotic stewardship. A combination of a proton pump inhibitor (PPI), amoxicillin, and clarithromycin (triple therapy) remains popular despite increasing clarithromycin resistance and poor cure rates. Concomitant therapy (a PPI, amoxicillin, clarithromycin, and metronidazole) is recommended and widely used despite all patients receiving at least one unneeded antibiotic. In 2020, the Food and Drug Administration approved vonoprazan, …


Tuberculosis In People Of Ukrainian Origin In The European Union And The European Economic Area, 2019 To 2022, Krista Stoycheva, Veronica Cristea, Csaba Ködmön, Senia Rosales-Klintz, Dominik Zenner, Anca Vasiliu, Marieke Van Der Werf, Christoph Lange Mar 2024

Tuberculosis In People Of Ukrainian Origin In The European Union And The European Economic Area, 2019 To 2022, Krista Stoycheva, Veronica Cristea, Csaba Ködmön, Senia Rosales-Klintz, Dominik Zenner, Anca Vasiliu, Marieke Van Der Werf, Christoph Lange

Faculty, Staff and Students Publications

Approximately five million Ukrainians were displaced to the EU/EEA following the Russian invasion of Ukraine. While tuberculosis (TB) notification rates per 100,000 Ukrainians in the EU/EEA remained stable, the number of notified TB cases in Ukrainians increased almost fourfold (mean 2019-2021: 201; 2022: 780). In 2022, 71% cases were notified in three countries, and almost 20% of drug-resistant TB cases were of Ukrainian origin. Targeted healthcare services for Ukrainians are vital for early diagnosis and treatment, and preventing transmission.


Tex46 Knockout Male Mice Are Sterile Secondary To Sperm Head Malformations And Failure To Penetrate Through The Zona Pellucida, Yoshitaka Fujihara, Haruhiko Miyata, Ferheen Abbasi, Tamara Larasati, Kaori Nozawa, Zhifeng Yu, Masahito Ikawa, Martin M Matzuk Mar 2024

Tex46 Knockout Male Mice Are Sterile Secondary To Sperm Head Malformations And Failure To Penetrate Through The Zona Pellucida, Yoshitaka Fujihara, Haruhiko Miyata, Ferheen Abbasi, Tamara Larasati, Kaori Nozawa, Zhifeng Yu, Masahito Ikawa, Martin M Matzuk

Faculty, Staff and Students Publications

Each year, infertility affects 15% of couples worldwide, with 50% of cases attributed to men. It is assumed that sperm head shape is important for sperm-zona pellucida (ZP) penetration but research has yet to elucidate why. We generated testis expressed 46 (Tex46) knockout mice to investigate the essential roles of TEX46 in mammalian reproduction. We used RT-PCR to demonstrate that Tex46 was expressed exclusively in the male reproductive tract in mice and humans. We created Tex46−/− mice using the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system and analyzed their fertility. Tex46 null spermatozoa …


Genomic Data In The All Of Us Research Program, All Of Us Research Program Genomics Investigators Mar 2024

Genomic Data In The All Of Us Research Program, All Of Us Research Program Genomics Investigators

Faculty, Staff and Students Publications

Comprehensively mapping the genetic basis of human disease across diverse individuals is a long-standing goal for the field of human genetics1–4. The All of Us Research Program is a longitudinal cohort study aiming to enrol a diverse group of at least one million individuals across the USA to accelerate biomedical research and improve human health5,6. Here we describe the programme’s genomics data release of 245,388 clinical-grade genome sequences. This resource is unique in its diversity as 77% of participants are from communities that are historically under-represented in biomedical research and 46% are …


Determining A Urinary-Specific Antibiogram And Risk Factors Of Trimethoprim/Sulfamethoxazole, Ciprofloxacin And Multidrug Resistance Among Enterobacterales In Primary Care, Marissa Valentine-King, Michael A Hansen, Roger Zoorob, Matthew Schlueter, Jennifer L Matas, Samuel E Willis, Lisa C K Danek, Kenneth Muldrew, Mohammad Zare, Forrest Hudson, Robert L Atmar, Andrew Chou, Barbara W Trautner, Larissa Grigoryan Mar 2024

Determining A Urinary-Specific Antibiogram And Risk Factors Of Trimethoprim/Sulfamethoxazole, Ciprofloxacin And Multidrug Resistance Among Enterobacterales In Primary Care, Marissa Valentine-King, Michael A Hansen, Roger Zoorob, Matthew Schlueter, Jennifer L Matas, Samuel E Willis, Lisa C K Danek, Kenneth Muldrew, Mohammad Zare, Forrest Hudson, Robert L Atmar, Andrew Chou, Barbara W Trautner, Larissa Grigoryan

Faculty, Staff and Student Publications

Background: Risk factors for ciprofloxacin or MDR in primary care urine specimens are not well defined.

Objectives: We created a primary care-specific antibiogram for Escherichia coli isolates from cases with complicated and uncomplicated urinary tract infection (UTI) and evaluated risk factors for ciprofloxacin, trimethoprim/sulfamethoxazole and MDR among Enterobacterales.

Methods: We conducted a cross-sectional study to determine resistance and risk factors by collecting urine cultures from all patients (≥18 years) presenting with provider-suspected UTI at two primary care, safety-net clinics in Houston, TX, USA between November 2018 and March 2020.

Results: Among 1262 cultures, 308 cultures grew 339 uropathogens. Patients with …


Tuberculosis In People Of Ukrainian Origin In The European Union And The European Economic Area, 2019 To 2022, Krista Stoycheva, Veronica Cristea, Csaba Ködmön, Senia Rosales-Klintz, Dominik Zenner, Anca Vasiliu, Marieke Van Der Werf, Christoph Lange Mar 2024

Tuberculosis In People Of Ukrainian Origin In The European Union And The European Economic Area, 2019 To 2022, Krista Stoycheva, Veronica Cristea, Csaba Ködmön, Senia Rosales-Klintz, Dominik Zenner, Anca Vasiliu, Marieke Van Der Werf, Christoph Lange

Faculty, Staff and Students Publications

Approximately five million Ukrainians were displaced to the EU/EEA following the Russian invasion of Ukraine. While tuberculosis (TB) notification rates per 100,000 Ukrainians in the EU/EEA remained stable, the number of notified TB cases in Ukrainians increased almost fourfold (mean 2019-2021: 201; 2022: 780). In 2022, 71% cases were notified in three countries, and almost 20% of drug-resistant TB cases were of Ukrainian origin. Targeted healthcare services for Ukrainians are vital for early diagnosis and treatment, and preventing transmission.


Best Practices For Helicobacter Pylori Management, David Y Graham Mar 2024

Best Practices For Helicobacter Pylori Management, David Y Graham

Faculty, Staff and Students Publications

For decades, antimicrobial therapy for Helicobacter pylori infection has been given empirically, and the results of therapy (success or failure) have either not been confirmed or when confirmed have not been used to modify prescribing behavior. These practices coupled with increasing antibiotic resistance have resulted in low cure rates overall. Susceptibility testing for H pylori has increasingly become available, especially in the United States. Availability of susceptibility-based therapy has encouraged adoption of the principles of antimicrobial stewardship for H pylori infection (eg, limiting antibiotic choice to antibiotics for which the infection is susceptible given at optimal doses, formulations, frequency of …


Discontinuation Of Contact Precautions In Patients With Hospital-Acquired Mrsa And Vre Infections During The Covid-19 Pandemic: A Multi-Center Experience, Gillean Kelly, Marisa Hudson, Bridget Apple, Debora Bundage, Bradley Lembcke, Todd Lasco, Mayar Al Mohajer Mar 2024

Discontinuation Of Contact Precautions In Patients With Hospital-Acquired Mrsa And Vre Infections During The Covid-19 Pandemic: A Multi-Center Experience, Gillean Kelly, Marisa Hudson, Bridget Apple, Debora Bundage, Bradley Lembcke, Todd Lasco, Mayar Al Mohajer

Faculty, Staff and Students Publications

Variations in the literature support the benefit of contact precautions for methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) infections in the hospital setting. During personal protective equipment shortages throughout the COVID-19 pandemic, contact precautions were discontinued for MRSA and VRE-infected patients. Rates of hospital-acquired MRSA and VRE infections were compared before and after this intervention, along with hand hygiene proportions. Contact precaution discontinuation did not lead to an increase in hospital-acquired MRSA or VRE infections.


Interim Estimates Of 2023-24 Seasonal Influenza Vaccine Effectiveness - United States, Aaron M Frutos, Ashley M Price, Elizabeth Harker, Emily L Reeves, Haris M Ahmad, Vel Murugan, Emily T Martin, Stacey House, Elie A Saade, Richard K Zimmerman, Manjusha Gaglani, Karen J Wernli, Emmanuel B Walter, Marian G Michaels, Mary A Staat, Geoffrey A Weinberg, Rangaraj Selvarangan, Julie A Boom, Eileen J Klein, Natasha B Halasa, Adit A Ginde, Kevin W Gibbs, Yuwei Zhu, Wesley H Self, Sara Y Tartof, Nicola P Klein, Kristin Dascomb, Malini B Desilva, Zachary A Weber, Duck-Hye Yang, Sarah W Ball, Diya Surie, Jennifer Decuir, Fatimah S Dawood, Heidi L Moline, Ariana P Toepfer, Benjamin R Clopper, Ruth Link-Gelles, Amanda B Payne, Jessie R Chung, Brendan Flannery, Nathaniel M Lewis, Samantha M Olson, Katherine Adams, Mark W Tenforde, Shikha Garg, Lisa A Grohskopf, Carrie Reed, Sascha Ellington, Cdc Influenza Vaccine Effectiveness Collaborators Feb 2024

Interim Estimates Of 2023-24 Seasonal Influenza Vaccine Effectiveness - United States, Aaron M Frutos, Ashley M Price, Elizabeth Harker, Emily L Reeves, Haris M Ahmad, Vel Murugan, Emily T Martin, Stacey House, Elie A Saade, Richard K Zimmerman, Manjusha Gaglani, Karen J Wernli, Emmanuel B Walter, Marian G Michaels, Mary A Staat, Geoffrey A Weinberg, Rangaraj Selvarangan, Julie A Boom, Eileen J Klein, Natasha B Halasa, Adit A Ginde, Kevin W Gibbs, Yuwei Zhu, Wesley H Self, Sara Y Tartof, Nicola P Klein, Kristin Dascomb, Malini B Desilva, Zachary A Weber, Duck-Hye Yang, Sarah W Ball, Diya Surie, Jennifer Decuir, Fatimah S Dawood, Heidi L Moline, Ariana P Toepfer, Benjamin R Clopper, Ruth Link-Gelles, Amanda B Payne, Jessie R Chung, Brendan Flannery, Nathaniel M Lewis, Samantha M Olson, Katherine Adams, Mark W Tenforde, Shikha Garg, Lisa A Grohskopf, Carrie Reed, Sascha Ellington, Cdc Influenza Vaccine Effectiveness Collaborators

Faculty, Staff and Students Publications

In the United States, annual influenza vaccination is recommended for all persons aged ≥6 months. Using data from four vaccine effectiveness (VE) networks during the 2023-24 influenza season, interim influenza VE was estimated among patients aged ≥6 months with acute respiratory illness-associated medical encounters using a test-negative case-control study design. Among children and adolescents aged 6 months-17 years, VE against influenza-associated outpatient visits ranged from 59% to 67% and against influenza-associated hospitalization ranged from 52% to 61%. Among adults aged ≥18 years, VE against influenza-associated outpatient visits ranged from 33% to 49% and against hospitalization from 41% to 44%. VE …


The Card8 Inflammasome Dictates Hiv/Siv Pathogenesis And Disease Progression, Qiankun Wang, Kolin M Clark, Ritudhwaj Tiwari, Nagarajan Raju, Gregory K Tharp, Jeffrey Rogers, R Alan Harris, Muthuswamy Raveendran, Steven E Bosinger, Tricia H Burdo, Guido Silvestri, Liang Shan Feb 2024

The Card8 Inflammasome Dictates Hiv/Siv Pathogenesis And Disease Progression, Qiankun Wang, Kolin M Clark, Ritudhwaj Tiwari, Nagarajan Raju, Gregory K Tharp, Jeffrey Rogers, R Alan Harris, Muthuswamy Raveendran, Steven E Bosinger, Tricia H Burdo, Guido Silvestri, Liang Shan

Faculty, Staff and Students Publications

While CD4+ T-cell depletion is key to disease progression in people living with HIV and SIV-infected macaques, the mechanisms underlying this depletion remain incompletely understood, with most cell death involving uninfected cells. In contrast, SIV infection of “natural” hosts such as sooty mangabeys do not cause CD4+ depletion and AIDS despite high-level viremia. Here, we report that the CARD8 inflammasome is activated immediately after HIV entry by the viral protease encapsulated in incoming virions. Sensing of HIV protease activity by CARD8 leads to rapid pyroptosis of quiescent cells without productive infection, while T-cell activation abolishes CARD8 function and increases permissiveness …


Impact And Prevalence Of Comorbidities And Complications On The Severity Of Covid-19 In Association With Age, Gender, Obesity, And Pre-Existing Smoking: A Meta-Analysis, Soulandi Djorwé, Amale Bousfiha, Néhémie Nzoyikorera, Joseph Nyandwi, Bellamine Kawthar, Abderrahim Malki Feb 2024

Impact And Prevalence Of Comorbidities And Complications On The Severity Of Covid-19 In Association With Age, Gender, Obesity, And Pre-Existing Smoking: A Meta-Analysis, Soulandi Djorwé, Amale Bousfiha, Néhémie Nzoyikorera, Joseph Nyandwi, Bellamine Kawthar, Abderrahim Malki

BioMedicine

Background: COVID-19 patients usually present multiple comorbidities and complications associated with severe forms of SARS-CoV-2 infection. This study aimed to assess the risk factors and prevalence of comorbidities and complications contributing to the severity of COVID-19.

Methods: This meta-analysis was performed according to PRISMA guidelines. We searched various databases, including PubMed, Google Scholar, and Scopus (between 2020 and 2023), for eligible studies for this meta-analysis.

Results: Thirty-three studies were eligible, including 85812 patients, of which 36% (30634/85812) had severe disease, whereas 64% (55178/85812) had non-severe disease. Severe cases were potentially correlated with the following factors: gender (male) (odd ratio (OR) …


Paired Single-B-Cell Transcriptomics And Receptor Sequencing Reveal Activation States And Clonal Signatures That Characterize B Cells In Acute Myeloid Leukemia, Shengnan Guo, Gopi S Mohan, Bofei Wang, Tianhao Li, Naval Daver, Yuting Zhao, Patrick K Reville, Dapeng Hao, Hussein A Abbas Feb 2024

Paired Single-B-Cell Transcriptomics And Receptor Sequencing Reveal Activation States And Clonal Signatures That Characterize B Cells In Acute Myeloid Leukemia, Shengnan Guo, Gopi S Mohan, Bofei Wang, Tianhao Li, Naval Daver, Yuting Zhao, Patrick K Reville, Dapeng Hao, Hussein A Abbas

Faculty, Staff and Student Publications

BACKGROUND: Acute myeloid leukemia (AML) is associated with a dismal prognosis. Immune checkpoint blockade (ICB) to induce antitumor activity in AML patients has yielded mixed results. Despite the pivotal role of B cells in antitumor immunity, a comprehensive assessment of B lymphocytes within AML's immunological microenvironment along with their interaction with ICB remains rather constrained.

METHODS: We performed an extensive analysis that involved paired single-cell RNA and B-cell receptor (BCR) sequencing on 52 bone marrow aspirate samples. These samples included 6 from healthy bone marrow donors (normal), 24 from newly diagnosed AML patients (NewlyDx), and 22 from 8 relapsed or …


Bactericidal Efficacy Of The Combination Of Maresin-Like Proresolving Mediators And Carbenicillin Action On Biofilm-Forming Burn Trauma Infection-Related Bacteria, Anbu Mozhi Thamizhchelvan, Abdul Razak Masoud, Shanchun Su, Yan Lu, Hongying Peng, Yuichi Kobayashi, Yu Wang, Nathan K. Archer, Song Hong Feb 2024

Bactericidal Efficacy Of The Combination Of Maresin-Like Proresolving Mediators And Carbenicillin Action On Biofilm-Forming Burn Trauma Infection-Related Bacteria, Anbu Mozhi Thamizhchelvan, Abdul Razak Masoud, Shanchun Su, Yan Lu, Hongying Peng, Yuichi Kobayashi, Yu Wang, Nathan K. Archer, Song Hong

School of Medicine Faculty Publications

Biofilm-associated bacterial infections are the major reason for treatment failure in many diseases including burn trauma infections. Uncontrolled inflammation induced by bacteria leads to materiality, tissue damage, and chronic diseases. Specialized proresolving mediators (SPMs), including maresin-like lipid mediators (MarLs), are enzymatically biosynthesized from omega-3 essential long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), by macrophages and other leukocytes. SPMs exhibit strong inflammation-resolving activities, especially inflammation provoked by bacterial infection. In this study, we explored the potential direct inhibitory activities of three MarLs on Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacteria in their biofilms that are leading …


Current And Emerging Antiviral Agents In The Prevention And Treatment Of Cytomegalovirus In Pediatric Transplant Recipients, Kristen G Valencia Deray, Lara A Danziger-Isakov, Kevin J Downes Feb 2024

Current And Emerging Antiviral Agents In The Prevention And Treatment Of Cytomegalovirus In Pediatric Transplant Recipients, Kristen G Valencia Deray, Lara A Danziger-Isakov, Kevin J Downes

Faculty, Staff and Students Publications

Despite current prophylaxis regimens, cytomegalovirus (CMV) is common in hematopoietic cell transplantation (HCT) and solid organ transplantation (SOT) and remains a significant cause of morbidity and mortality. Newer antiviral medications are reshaping the landscape for prevention and treatment of CMV DNAemia, infection, and disease. Letermovir is approved for CMV prevention in adult HCT patients and is attractive due to the absence of marrow suppression seen with ganciclovir/valganciclovir. Letermovir should not be routinely used for CMV treatment due to its low threshold for resistance. Maribavir is approved for the treatment of refractory or resistant CMV disease in HCT and SOT recipients …


Gamma Delta T Cells In Acute Myeloid Leukemia: Biology And Emerging Therapeutic Strategies, Adishwar Rao, Akriti Agrawal, Gautam Borthakur, Venkata Lokesh Battula, Abhishek Maiti Feb 2024

Gamma Delta T Cells In Acute Myeloid Leukemia: Biology And Emerging Therapeutic Strategies, Adishwar Rao, Akriti Agrawal, Gautam Borthakur, Venkata Lokesh Battula, Abhishek Maiti

Faculty, Staff and Student Publications

γδ T cells play an important role in disease control in acute myeloid leukemia (AML) and have become an emerging area of therapeutic interest. These cells represent a minor population of T lymphocytes with intrinsic abilities to recognize antigens in a major histocompatibility complex-independent manner and functionally straddle the innate and adaptive immunity interface. AML shows high expression of phosphoantigens and UL-16 binding proteins that activate the Vδ2 and Vδ1 subtypes of γδ T cells, respectively, leading to γδ T cell-mediated cytotoxicity. Insights from murine models and clinical data in humans show improved overall survival, leukemia-free survival, reduced risk of …


The Future Of Targeted Therapy For Leiomyosarcoma, Ryan A Denu, Amanda M Dann, Emily Z Keung, Michael S Nakazawa, Elise F Nassif Haddad Feb 2024

The Future Of Targeted Therapy For Leiomyosarcoma, Ryan A Denu, Amanda M Dann, Emily Z Keung, Michael S Nakazawa, Elise F Nassif Haddad

Faculty, Staff and Student Publications

Leiomyosarcoma (LMS) is an aggressive subtype of soft tissue sarcoma that arises from smooth muscle cells, most commonly in the uterus and retroperitoneum. LMS is a heterogeneous disease with diverse clinical and molecular characteristics that have yet to be fully understood. Molecular profiling has uncovered possible targets amenable to treatment, though this has yet to translate into approved targeted therapies in LMS. This review will explore historic and recent findings from molecular profiling, highlight promising avenues of current investigation, and suggest possible future strategies to move toward the goal of molecularly matched treatment of LMS. We focus on targeting the …


Evidence Review And Considerations For Use Of First Line Genome Sequencing To Diagnose Rare Genetic Disorders, Kristen M Wigby, Deanna Brockman, Gregory Costain, Caitlin Hale, Stacie L Taylor, John Belmont, David Bick, David Dimmock, Susan Fernbach, John Greally, Vaidehi Jobanputra, Shashikant Kulkarni, Elizabeth Spiteri, Ryan J Taft Feb 2024

Evidence Review And Considerations For Use Of First Line Genome Sequencing To Diagnose Rare Genetic Disorders, Kristen M Wigby, Deanna Brockman, Gregory Costain, Caitlin Hale, Stacie L Taylor, John Belmont, David Bick, David Dimmock, Susan Fernbach, John Greally, Vaidehi Jobanputra, Shashikant Kulkarni, Elizabeth Spiteri, Ryan J Taft

Center for Medical Ethics and Health Policy Staff Publications

Early use of genome sequencing (GS) in the diagnostic odyssey can reduce suffering and improve care, but questions remain about which patient populations are most amenable to GS as a first-line diagnostic test. To address this, the Medical Genome Initiative conducted a literature review to identify appropriate clinical indications for GS. Studies published from January 2011 to August 2022 that reported on the diagnostic yield (DY) or clinical utility of GS were included. An exploratory meta-analysis using a random effects model evaluated DY based on cohort size and diagnosed cases per cohort. Seventy-one studies met inclusion criteria, comprising over 13,000 …


Isothiocyanates Potentiate Tazemetostat-Induced Apoptosis By Modulating The Expression Of Apoptotic Genes, Members Of Polycomb Repressive Complex 2, And Levels Of Tri-Methylating Lysine 27 At Histone 3 In Human Malignant Melanoma Cells, Ioannis Anestopoulos, Ioannis Paraskevaidis, Sotiris Kyriakou, Lambrini E. Giova, Dimitrios T. Trafalis, Sotiris Botaitis, Rodrigo Franco, Aglaia Pappa, Mihalis L. Panayiotidis Feb 2024

Isothiocyanates Potentiate Tazemetostat-Induced Apoptosis By Modulating The Expression Of Apoptotic Genes, Members Of Polycomb Repressive Complex 2, And Levels Of Tri-Methylating Lysine 27 At Histone 3 In Human Malignant Melanoma Cells, Ioannis Anestopoulos, Ioannis Paraskevaidis, Sotiris Kyriakou, Lambrini E. Giova, Dimitrios T. Trafalis, Sotiris Botaitis, Rodrigo Franco, Aglaia Pappa, Mihalis L. Panayiotidis

School of Veterinary and Biomedical Sciences: Faculty Publications

In this study, we utilized an in vitro model consisting of human malignant melanoma as well as non-tumorigenic immortalized keratinocyte cells with the aim of characterizing the therapeutic effectiveness of the clinical epigenetic drug Tazemetostat alone or in combination with various isothiocyanates. In doing so, we assessed markers of cell viability, apoptotic induction, and expression levels of key proteins capable of mediating the therapeutic response. Our data indicated, for the first time, that Tazemetostat caused a significant decrease in viability levels of malignant melanoma cells in a dose- and time-dependent manner via the induction of apoptosis, while non-malignant keratinocytes were …


Tailoring T Fh Profiles Enhances Antibody Persistence To A Clade C Hiv-1 Vaccine In Rhesus Macaques, Anil Verma, Chase E. Hawes, Sonny R. Elizaldi, Justin C. Smith, Dhivyaa Rajasundaram, Gabriel Kristian Pedersen, Xiaoying Shen, La Tonya D. Williams, Georgia D. Tomaras, Pamela A. Kozlowski, Rama R. Amara, Smita S. Iyer Feb 2024

Tailoring T Fh Profiles Enhances Antibody Persistence To A Clade C Hiv-1 Vaccine In Rhesus Macaques, Anil Verma, Chase E. Hawes, Sonny R. Elizaldi, Justin C. Smith, Dhivyaa Rajasundaram, Gabriel Kristian Pedersen, Xiaoying Shen, La Tonya D. Williams, Georgia D. Tomaras, Pamela A. Kozlowski, Rama R. Amara, Smita S. Iyer

School of Medicine Faculty Publications

CD4 T follicular helper cells (Tfh) are essential for establishing serological memory and have distinct helper attributes that impact both the quantity and quality of the antibody response. Insights into Tfh subsets that promote antibody persistence and functional capacity can critically inform vaccine design. Based on the Tfh profiles evoked by the live attenuated measles virus vaccine, renowned for its ability to establish durable humoral immunity, we investigated the potential of a Tfh1/17 recall response during the boost phase to enhance persistence of HIV-1 Envelope (Env) antibodies in rhesus macaques. Using a DNA-prime encoding gp160 antigen and Tfh polarizing cytokines …


Exploring The Antibacterial Potential And Underlying Mechanisms Of Prunella Vulgaris L On Methicillin-Resistant Staphylococcus Aureus, Ziyin Li, Qiqi He, Feifei Xu, Xinxin Yin, Zhuofan Guan, Jia Song, Zhini He, Xingfen Yang, Chen Situ Feb 2024

Exploring The Antibacterial Potential And Underlying Mechanisms Of Prunella Vulgaris L On Methicillin-Resistant Staphylococcus Aureus, Ziyin Li, Qiqi He, Feifei Xu, Xinxin Yin, Zhuofan Guan, Jia Song, Zhini He, Xingfen Yang, Chen Situ

Faculty, Staff and Student Publications

Prunella vulgaris L. (PV) is a widely distributed plant species, known for its versatile applications in both traditional and contemporary medicine, as well as in functional food development. Despite its broad-spectrum antimicrobial utility, the specific mechanism of antibacterial action remains elusive. To fill this knowledge gap, the present study investigated the antibacterial properties of PV extracts against methicillin-resistant Staphylococcus aureus (MRSA) and assessed their mechanistic impact on bacterial cells and cellular functions. The aqueous extract of PV demonstrated greater anti-MRSA activity compared to the ethanolic and methanolic extracts. UPLC-ESI-MS/MS tentatively identified 28 phytochemical components in the aqueous extract of PV. …


A Stool Based Qpcr For The Diagnosis Of Tb In Children And People Living With Hiv In Uganda, Eswatini And Mozambique (Stool4tb): A Protocol For A Multicenter Diagnostic Evaluation, Lucia Carratala-Castro, Willy Ssengooba, Alex Kay, Sozinho Acácio, Joanna Ehrlich, Andrew R Dinardo, Nosisa Shiba, Joachim K Nsubuga, Shilzia Munguambe, Belén Saavedra-Cervera, Patricia Manjate, Durbbin Mulengwa, Busizwe Sibandze, Mangaliso Ziyane, George Kasule, Edson Mambuque, Moorine Penninah Sekadde, Eric Wobudeya, Moses L Joloba, Jan Heyckendorf, Christoph Lange, Sabine Hermans, Anna Mandalakas, Alberto L García-Basteiro, Elisa Lopez-Varela, Stool4tb Global Partnership Feb 2024

A Stool Based Qpcr For The Diagnosis Of Tb In Children And People Living With Hiv In Uganda, Eswatini And Mozambique (Stool4tb): A Protocol For A Multicenter Diagnostic Evaluation, Lucia Carratala-Castro, Willy Ssengooba, Alex Kay, Sozinho Acácio, Joanna Ehrlich, Andrew R Dinardo, Nosisa Shiba, Joachim K Nsubuga, Shilzia Munguambe, Belén Saavedra-Cervera, Patricia Manjate, Durbbin Mulengwa, Busizwe Sibandze, Mangaliso Ziyane, George Kasule, Edson Mambuque, Moorine Penninah Sekadde, Eric Wobudeya, Moses L Joloba, Jan Heyckendorf, Christoph Lange, Sabine Hermans, Anna Mandalakas, Alberto L García-Basteiro, Elisa Lopez-Varela, Stool4tb Global Partnership

Faculty, Staff and Students Publications

BACKGROUND: Tuberculosis (TB) is a major cause of mortality worldwide. Children and people living with HIV (PLHIV) have an increased risk of mortality, particularly in the absence of rapid diagnosis. The main challenges of diagnosing TB in these populations are due to the unspecific and paucibacillary disease presentation and the difficulty of obtaining respiratory samples. Thus, novel diagnostic strategies, based on non-respiratory specimens could improve clinical decision making and TB outcomes in high burden TB settings. We propose a multi-country, prospective diagnostic evaluation study with a nested longitudinal cohort evaluation to assess the performance of a new stool-based qPCR, developed …


New Onset Positive Autoantibodies Following Covid-19 Infection, David Hernandez, Adnaan Sheikh, Shakira Laing, Mariana Adieb, Omar Siddiqui, Rohail Baig, Annabel Antonini, James Vienneau, Camden Burns Feb 2024

New Onset Positive Autoantibodies Following Covid-19 Infection, David Hernandez, Adnaan Sheikh, Shakira Laing, Mariana Adieb, Omar Siddiqui, Rohail Baig, Annabel Antonini, James Vienneau, Camden Burns

Advances in Clinical Medical Research and Healthcare Delivery

The World Health Organization (WHO) declared the novel coronavirus (COVID-19) outbreak a global pandemic on March 11, 2020. Since the original outbreak in December 2019, over 100 million people have been confirmed to have been infected by COVID-19 and over two million people have died. The presentation seen in patients may vary widely based on multiple factors. Fever has been reported in up to 99% of patients, while other common symptoms seen are dyspnea, fatigue, anosmia, and myalgia. Around 80% of COVID-19 patients present with a mild respiratory illness that can be managed at home, while around 15% need basic …


Covid-19-Associated Myocarditis: Screening For Early Diagnosis, Yousuf Khan, Salmman Ahmed, Samuel John Wlasowicz, Ronald G. Lott Iii, Xavier C. Zonna Feb 2024

Covid-19-Associated Myocarditis: Screening For Early Diagnosis, Yousuf Khan, Salmman Ahmed, Samuel John Wlasowicz, Ronald G. Lott Iii, Xavier C. Zonna

Advances in Clinical Medical Research and Healthcare Delivery

The SARS-CoV-2 virus (causing COVID-19), has infected about 770 million people, and caused the death of about 6.9 million people worldwide in the span of three years (John Hopkins Resource Center). Common symptoms of a patient infected with the virus include shortness of breath, fever, chills, fatigue, loss of taste or smell, and muscle aches. However, recent studies have also shown a prevalence of patients presenting with cardiac inflammation (endocarditis, myocarditis or pericarditis) as a potential comorbidity, both during the infectious stage as well as after the infection has subsided. A pattern of specific clinical markers may be indicative of …


The Pathogenicity Of Vancomycin-Resistant Enterococcus Faecalis To Colon Cancer Cells, Li Zhang, Mingxia Deng, Jing Liu, Jiajie Zhang, Fangyu Wang, Wei Yu Feb 2024

The Pathogenicity Of Vancomycin-Resistant Enterococcus Faecalis To Colon Cancer Cells, Li Zhang, Mingxia Deng, Jing Liu, Jiajie Zhang, Fangyu Wang, Wei Yu

Faculty, Staff and Student Publications

BACKGROUND: The aim of this study was to investigate the pathogenicity of vancomycin-resistant Enterococcus faecalis (VREs) to human colon cells in vitro.

METHODS: Three E. faecalis isolates (2 VREs and E. faecalis ATCC 29212) were cocultured with NCM460, HT-29 and HCT116 cells. Changes in cell morphology and bacterial adhesion were assessed at different time points. Interleukin-8 (IL-8) and vascular endothelial growth factor A (VEGFA) expression were measured via RT-qPCR and enzyme-linked immunosorbent assay (ELISA), respectively. Cell migration and human umbilical vein endothelial cells (HUVECs) tube formation assays were used for angiogenesis studies. The activity of PI3K/AKT/mTOR signaling pathway was measured …


Intouch Week Of February 19, 2024, New York Medical College Feb 2024

Adaptation Of Chagas Disease Screening Recommendations For A Community Of At-Risk Hiv In The United States, Jesica Hayon, Sofia Lupo, Cristina Poveda, Kathryn M Jones, Qian Qian, Hulin Wu, Thomas P Giordano, Charles J Fleischmann, Caryn Bern, Jeffrey D Whitman, Eva H Clark Feb 2024

Adaptation Of Chagas Disease Screening Recommendations For A Community Of At-Risk Hiv In The United States, Jesica Hayon, Sofia Lupo, Cristina Poveda, Kathryn M Jones, Qian Qian, Hulin Wu, Thomas P Giordano, Charles J Fleischmann, Caryn Bern, Jeffrey D Whitman, Eva H Clark

Faculty, Staff and Students Publications

Chagas disease (CD), caused by Trypanosoma cruzi, is underdiagnosed in the United States. Improved screening strategies are needed, particularly for people at risk for life-threatening sequelae of CD, including people with human immunodeficiency virus (HIV, PWH). Here we report results of a CD screening strategy applied at a large HIV clinic serving an at-risk population.


Deciphering Early-Stage Molecular Mechanisms Of Negative Pressure Wound Therapy In A Murine Model, Yu-Chiau Shyu, Ting-Shuo Huang, Hua-Sheng Chiu, Pavel Sumazin, Xin-Yu Lin, Po-Cheng Liao, Cai-Cin Liou, Fang-Chia Hsu, Jyuan-Siou Lin, Chih-Chin Hsu, Pang-Hung Hsu, Chi-Chin Sun, Chien-Tzung Chen Feb 2024

Deciphering Early-Stage Molecular Mechanisms Of Negative Pressure Wound Therapy In A Murine Model, Yu-Chiau Shyu, Ting-Shuo Huang, Hua-Sheng Chiu, Pavel Sumazin, Xin-Yu Lin, Po-Cheng Liao, Cai-Cin Liou, Fang-Chia Hsu, Jyuan-Siou Lin, Chih-Chin Hsu, Pang-Hung Hsu, Chi-Chin Sun, Chien-Tzung Chen

Faculty, Staff and Students Publications

Negative Pressure Wound Therapy (NPWT) is a commonly employed clinical strategy for wound healing, yet its early-stage mechanisms remain poorly understood. To address this knowledge gap and overcome the limitations of human trials, we establish an NPWT C57BL/6JNarl mouse model to investigate the molecular mechanisms involved in NPWT. In this study, we investigate the intricate molecular mechanisms through which NPWT expedites wound healing. Our focus is on NPWT's modulation of inflammatory immune responses and the concurrent orchestration of multiple signal transduction pathways, resulting in shortened coagulation time and reduced inflammation. Notably, we observe a significant rise in dickkopf-related protein 1 …


Long Trimer-Immunization Interval And Appropriate Adjuvant Reduce Immune Responses To The Soluble Hiv-1-Envelope Trimer Base, Hongying Duan, Angela R Corrigan, Cheng Cheng, Andrea Biju, Christopher A Gonelli, Adam S Olia, I-Ting Teng, Kai Xu, Sijy O'Dell, Sandeep Narpala, Mike Castro, Leonid Serebryannyy, Jennifer Wang, Danealle K Parchment, Edward K Sarfo, Jelle Van Schooten, John-Paul Todd, Shuishu Wang, Darcy R Harris, Hui Geng, Alexander J Jafari, Vrc Production Program, Ruth A Woodward, Nicole A Doria-Rose, Kathryn E Foulds, Adrian B Mcdermott, Marit J Van Gils, Richard A Koup, Theodore C Pierson, Peter D Kwong, John R Mascola Feb 2024

Long Trimer-Immunization Interval And Appropriate Adjuvant Reduce Immune Responses To The Soluble Hiv-1-Envelope Trimer Base, Hongying Duan, Angela R Corrigan, Cheng Cheng, Andrea Biju, Christopher A Gonelli, Adam S Olia, I-Ting Teng, Kai Xu, Sijy O'Dell, Sandeep Narpala, Mike Castro, Leonid Serebryannyy, Jennifer Wang, Danealle K Parchment, Edward K Sarfo, Jelle Van Schooten, John-Paul Todd, Shuishu Wang, Darcy R Harris, Hui Geng, Alexander J Jafari, Vrc Production Program, Ruth A Woodward, Nicole A Doria-Rose, Kathryn E Foulds, Adrian B Mcdermott, Marit J Van Gils, Richard A Koup, Theodore C Pierson, Peter D Kwong, John R Mascola

Faculty, Staff and Student Publications

Soluble 'SOSIP'-stabilized HIV-1 envelope glycoprotein (Env) trimers elicit dominant antibody responses targeting their glycan-free base regions, potentially diminishing neutralizing responses. Previously, using a nonhuman primate model, we demonstrated that priming with fusion peptide (FP)-carrier conjugate immunogens followed by boosting with Env trimers reduced the anti-base response. Further, we demonstrated that longer immunization intervals further reduced anti-base responses and increased neutralization breadth. Here, we demonstrate that long trimer-boosting intervals, but not long FP immunization intervals, reduce the anti-base response. Additionally, we identify that FP priming before trimer immunization enhances antibody avidity to the Env trimer. We also establish that adjuvants Matrix …


Targeting Cyp51 In The Treatment Of Acanthamoeba Keratitis, Ashkan Hassani, Vineet Sadarangani, Brad Haubrich Feb 2024

Targeting Cyp51 In The Treatment Of Acanthamoeba Keratitis, Ashkan Hassani, Vineet Sadarangani, Brad Haubrich

Annual Research Symposium

Acanthamoeba castellanii causes a rare but serious ocular infection called Acanthamoeba keratitis. Risk factors for infection include contact with contaminated water and poor hygiene of contact lenses. The first-line treatment is comprised of a months-long schedule of antibiotics. However, in cases where pharmacological interventions fail to address the infection, surgery may be necessary, with the continued risk of potential vision loss. Consequently, new treatments are needed, whether new pharmacological agents or new combination therapies with current agents. As an aerobic parasite, Acanthamoeba synthesizes ergosterol as a cell membrane insert, and ergosterol biosynthesis inhibitors (EBIs), common in antifungal pharmaceuticals, could potentially …