Translational Medical Research Commons^™

Nitric Oxide Does Not Improve Liver Mitochondrial Function 48 Hours After Cecal Ligation And Perforation In Experimental Sepsis, Pierre Eyenga, Shey-Shing Sheu

Center for Translational Medicine Faculty Papers

Nitric oxide (NO) has a dual effect on mitochondria. Incubating liver mitochondria with NO improves oxidative phosphorylation (OXPHOS) efficiency by decreasing state 4 respiration more than ATP synthesis and preventing mitochondrial permeability transition pore (mPTP) opening. We evaluated the effect of L-arginine (L-arg), an NO donor, on isolated liver mitochondrial respiration and mPTP in sepsis. Male mice were subjected to cecal ligation and perforation (CLP) with saline resuscitation or sham. After 8, 24, and 48 h, with and without L-arg, we measured isolated liver mitochondrial respiration and cytochrome c oxidase (COX) activity using polarographic methods and calcium retention capacity (CRC) …

Pilot Survey Of Attitudes Toward Xenotransplantation Among Nursing Students In London, Uk., Daniel Rodger, Luz A. Padilla, Daniel J. Hurst, David K C Cooper, Gilberto Buzzi, Antonio Ríos

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Solid organ xenotransplantation has been approved for clinical trials in the United States. Because of the role of nurses in patient decision-making, it is important to understand the attitudes of the future nursing workforce toward xenotransplantation. This pilot study aimed to investigate the attitudes of adult nursing students toward xenotransplantation.

METHODS: A cross-sectional survey design was used. The online pilot survey was completed by 33 undergraduate adult nursing students at one university in London, England. A minority of the hospitals that students may have had a clinical placement in had a transplant unit. The protocol for this study was …

Profile Of Trna-Derived Short Non-Coding Rnas During Monocyte Differentiation And Their Role In Macrophage Survival, Anahita Jayaram, Sanjeev Galande, Soroush Sharbati, Deepak A. Deshpande, Phd, Kamlesh Pawar

Center for Translational Medicine Faculty Papers

Monocytes, a type of leukocytes, are key players in immune responses, transitioning to macrophages at infection sites. Differentiation, which is crucial for macrophage survival and resistance to apoptosis, is a tightly regulated process. Based on our earlier findings implicating the 5'-fragment of tRNAHisGUG (5'-HisGUG) in macrophage biology, we specifically focused on these fragments to investigate its regulation during monocyte-to-macrophage differentiation and its role in macrophage survival. We performed small RNA sequencing during monocyte-to-macrophage differentiation using THP-1 cells and identified 5'-HisGUG as a prominently regulated tDR. Notably, transfection of 5'-HisGUG in macrophages decreased survival under apoptotic stress. We propose that 5'-HisGUG …

Muscle Rev-Erb Controls Time-Dependent Adaptations To Chronic Exercise In Mice, Jidong Liu, Fang Xiao, Abhinav Choubey, Udhaya Kumar S, Yanxiang Wang, Sungguan Hong, Tingting Yang, Husniye Gul Otlu, Ege Sanem Oturmaz, Emanuele Loro, Yuxiang Sun, Pradip Saha, Tejvir S Khurana, Li Chen, Xinguo Hou, Zheng Sun

Center on Aging Staff Publications

The best time of the day for chronic exercise training and the mechanism underlying the timing effects is unclear. Here, we show that low-intensity, low-volume treadmill training in mice before sleep yields greater benefits than after waking for muscle contractile performance and systemic glucose tolerance. Baseline muscle performance also exhibits diurnal variations, with higher strength but lower endurance before sleep than after waking. Muscle-specific knockout of circadian clock genes Rev-erbα/β (Rev-MKO) in male mice eradicates the diurnal variations in both training and baseline conditions without affecting muscle mass, mitochondrial content, food intake, or spontaneous activities. Multi-omics and metabolic measurements reveal …

A Collective Case Study Of How Researchers Describe Their Experiences, Challenges, And Perceived Impact Of Patient Engagement, Lorna M. Richards

Doctor of Philosophy in Translational Health Sciences Dissertations

Background: Patient engagement (PE) in clinical research has become “extensively and internationally recognized as important and gained growing policy attention, supported by scientific evidence” (Al-Tannir et al., 2017, Background section). The proliferation of PE directives has driven the paradigm shift in drug development from a paternalistic approach to a more patient-centric approach influenced by regulatory agencies, funders, and academic initiatives (Bombak & Hanson, 2017). However, too often, PE activities are not well considered for discovering actionable insights but are merely an empty formality. For PE to be meaningful, patient involvement must be planned, supported, and valued by clinical researchers.

Objectives: …

Increasing Community Members' Engagement In Cancer Research: The Making Research Clear Program, Rebecca J. Melillo, Christiane J. El Khoury, Joshua Blanding-Godbolt, Q. Greene, Karen M. Bussard, Amy Leader

Kimmel Cancer Center Faculty Papers

BACKGROUND: Despite the importance of engaging community members in research, multiple barriers from the perspective of the investigator and community member exist. The Making Research CLEAR (Community Learning and Experience about Research) Program aims to bridge the gap between research conducted at an NCI-designated cancer center and the community.

METHODS: Community members and a cancer center investigator were paired for a 6-month immersive research experience. Community members had at least one research experience per month with their investigator, while also attending cancer center activities such as Institutional Review Board (IRB) meetings, research lectures, protocol review meetings, and community outreach events. …

Advancing Novel Contrast Agents For Applications In Fluorescence-Guided Neurosurgery Using Fluorescence Cryotomography, Augustino Vittorio Scorzo

Dartmouth College Ph.D Dissertations

Fluorescence guided surgery (FGS) is an emerging surgical technique that aims to help surgeons identify tissue types to assist in surgical decision making - ideally providing “cut-by-color” guidance. A primary application for this approach is the identification of tumor tissue to achieve more accurate and complete tumor removal while simultaneously minimizing damage to surrounding normal tissue. The cornerstone of tumor visualization for FGS is the administration of fluorescent contrast agents, or in some cases metabolic precursors, designed to accumulate specifically in tumor tissue, and a wide range of agents that use different targeting mechanisms are currently under investigation. Although these …

Mechanistic Insights Into The Flash Effect: The Role Of Oxygen And Radiation Chemistry In Ultra-High Dose Rate Radiation Therapy, Jacob Pierce Sunnerberg

Dartmouth College Ph.D Dissertations

The development of new cancer therapies focuses on widening the therapeutic ratio between tumor control and normal tissue toxicity. Over the last decade, ultra-high dose rate (UHDR) radiation therapy, commonly known as FLASH radiotherapy (FLASH-RT), has shown promising potential to reduce normal tissue toxicity while maintaining tumor control. However, the underlying mechanisms of the FLASH effect remain poorly understood. This thesis explores the radiation-chemical basis of FLASH-RT, focusing on the role of oxygen and reactive oxygen species in modulating biological outcomes.

A comprehensive set of in vitro studies demonstrated that UHDR delivery significantly alters radiation chemistry compared to conventional dose …

Measuring What Matters To Patients: A Multiple Methods Sequential Study Of Disease Burden, Quality Of Life, And The Alignment Of Patient-Reported Outcome Measurements For High-Risk Myelodysplastic Syndrome And Acute Myelogenous Leukemia Patients, Anthony J. Messina

Doctor of Philosophy in Translational Health Sciences Dissertations

Background

High-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are aggressive hematologic malignancies with poor prognoses, where extending survival often comes at the cost of substantial morbidity. This study was grounded in the quality of survival (QoS) framework, which emphasizes that treatment outcomes should balance longevity with the health-related quality of life (HRQoL) experienced during the period of survival. In this context, patient-reported outcomes are crucial to capturing what truly matters to patients. However, existing patient-reported outcome measures (PROMs) used in MDS/AML clinical trials may not fully reflect patient priorities. A complementary Wilson–Cleary model perspective, linking biological factors to …

Summary Of: Evaluating Community Engagement Efforts In A Clinical And Translational Research Initiative, Kelly Finck Waters, Brenda Joly, Carolyn E. Gray, Jan K. Carney, Kathleen Fairfield

Northern New England Clinical & Translational Research

Community engagement is a core element of translational science, yet tools to assess its quality and reach remain limited. This study evaluated the Northern New England Clinical and Translational Research Network’s efforts to strengthen community academic partnerships through its Community Engagement and Outreach Core using the PARTNER CPRM platform, which combines network analysis with survey-based trust and value metrics.

Study found @ "Evaluating community engagement efforts in a clinical and translationa" by Kelly Finck Waters, Brenda Joly et al.

Computerized Diagnostic Decision Support Systems-Isabel Pro Versus Chatgpt-4 Part Ii, Joe M Bridges, Xiaoqian Jiang, Michael Ige, Oluwatoniloba Toyobo

Faculty, Staff and Student Publications

Objective: Does a Tree-of-Thought prompt and reconsideration of Isabel Pro's differential improve ChatGPT-4's accuracy; does increasing expert panel size improve ChatGPT-4's accuracy; does ChatGPT-4 produce consistent outputs in sequential requests; what is the frequency of fabricated references?

Materials and methods: Isabel Pro, a computerized diagnostic decision support system, and ChatGPT-4, a large language model. Using 201 cases from the New England Journal of Medicine, each system produced a differential diagnosis ranked by likelihood. Statistics were Mean Reciprocal Rank, Recall at Rank, Average Rank, Number of Correct Diagnoses, and Rank Improvement. For reproducibility, the study compared the initial expert panel run …

Development And Mechanistic Investigation Of Recombinant Type Iii Humanized Collagen Gel For Mid-Facial Soft Tissue Repair, Qian Wang, Qifei An, Yuanzhou Wang, Jingbo Yang, Xiujuan Zhang, Shibo Jiang, Min Chen, Lu Lu, Yun Zhu

Center for Translational Medicine Faculty Papers

Mid-facial depression is a key sign of facial aging, primarily caused by the loss of collagen leading to depletion of the extracellular matrix (ECM). However, the existing fillers for soft tissue augmentation have shown certain limitations in repairing mid-facial depression. Therefore, we herein report the development of a novel recombinant humanized type III collagen gel (C3Gel) through rational design and modification of a commercially available recombinant type III humanized collagen lyophilized fiber product. Both biological activity and tissue repair mechanisms of C3Gel were systematically evaluated in vitro and in vivo. C3Gel formed a dense fibrous structure around cells, significantly improving …

Spatiotemporal Calcium Signaling Patterns Underlying Opposing Effects Of Histamine And Tas2r Agonists In Airway Smooth Muscle, Stanley Conaway, Joshua Richard, Deepak A. Deshpande

Center for Translational Medicine Faculty Papers

Intracellular calcium (Ca²⁺) release via phospholipase C (PLC) following G-protein-coupled receptor (GPCR) activation is typically linked to membrane depolarization and airway smooth muscle (ASM) contraction. However, recent findings show that bitter taste receptor agonists, such as chloroquine (CQ), induce a paradoxical and potent relaxation response despite activating the Ca²⁺ signaling pathway. This relaxation has been hypothesized to be driven by a distinct compartmentalization of calcium ions toward the cellular periphery, subsequently leading to membrane hyperpolarization, in contrast to the contractile effects of histamine. In this study, we further investigate the spatiotemporal dynamics of Ca²⁺ signaling in …

The Effect Of Celecoxib And Mumab911 On Strain Adaptive Bone Remodeling And Fracture Repair In Female Mice: Implications For Rapidly Progressive Osteoarthritis, Nicholas Ruggiero, Alexandra Ciuciu, Ashkan Sedigh, Ibtesam Rajpar, David Shelton, Patrice Belanger, Kathryn Gropp, John A. Collins, Theresa A. Freeman, Ryan E. Tomlinson

Department of Orthopaedic Surgery Faculty Papers

Debilitating pain is the primary clinical feature of osteoarthritis (OA) that drives the enormous healthcare costs. Osteoarthritis-related pain is often treated with non-steroidal anti-inflammatory drugs (NSAIDs), which effectively relieve pain and inflammation by inhibition of prostaglandin synthesis. Antibodies directed against nerve growth factor (NGF) were tested some time ago as an alternative potential analgesic for musculoskeletal pain, including osteoarthritis-related pain. Unfortunately, clinical development of these drugs was put on hold due to adverse outcomes - primarily rapidly progressive osteoarthritis. Both prostaglandin synthesis and NGF have been implicated as critical mediators of strain adaptive bone remodeling, which may play a role …

Engagement In Responsible Conduct Of Research: A Descriptive Case Study Of The Factors Of Organizational Culture And Implementation Drivers That Influence Research Integrity Practice, Cortni Beth Romaine

Doctor of Philosophy in Translational Health Sciences Dissertations

This qualitative descriptive case study investigates the relationship between organizational culture and the Responsible Conduct of Research (RCR) across multiple research institutions. Utilizing elements of the Cultural Dynamics Model and the Implementation Drivers Framework, the study examines how institutional structures and cultural norms shape research integrity practices. Data collection involved in-depth interviews with faculty, postdoctoral researchers, and graduate students, as well as an artifact review of institutional policies, training resources, and guidance for research best practices.

Findings revealed three key themes: (1) Microculture Experiences, where RCR engagement is largely dictated by localized lab cultures, with principal investigators (PIs) playing a …

Implementation Of A Clinical Pathway For Complicated Appendicitis In Children, Kristin E. Lemarbe, Andrew Glaza, Alexander L. Chen, Diane Studzinski, Amanda Henderson, Anthony Stallion, Nathan Novotny, Begum Akay, Pavan Brahmamdam

Conference Presentation Abstracts

No abstract provided.

Postoperative Calcium Supplementation Adherence In Total Thyroidectomy And Parathyroidectomy Patients - Risk Factors And Outcomes, Katelyn Ward, Cydney Mcchesney, John Nida, Negin Mohtashemian, Jacob Mesiti, Emmanuel Nageeb, Diane Studzinski, Rose Callahan, Peter Czako, Sapna Nagar

Conference Presentation Abstracts

No abstract provided.

Surgical Site Infection Bundle For Babies - Preliminary Data, Cullen Woodley, Katelyn Ward, John Nida, Alexis Lonjin, Diane Studzinski, Nathan Novotny, Pavan Brahmamdam, Begum Akay

Conference Presentation Abstracts

No abstract provided.

A Retrospective Study Of Pulmonary Function Tests In Bronchiectasis: An Infectious Disease Of The Respiratory System, Vinod Mutkule, Mahesh Shinde, Vidya Bapmare, Sangramsingh Dixit, Atharva Sharma, Kshitij Sarwey, Yogeshwari Patil, Sanket Jethlia, Aayushi Dwivedi, Disha Pardeshi, Anmol Rai, Kunal Shah, Vidhi Kalwar

The University of Louisville Journal of Respiratory Infections

Introduction: Bronchiectasis, currently being recognized worldwide, is an abnormal dilatation of the bronchi and bronchioles brought on by recurrent cycles of inflammation and airway infection. Impaired pulmonary function has a predictive significance in bronchiectasis. When treating patients with suspected or confirmed respiratory diseases, pulmonary function tests (PFT) are useful examinations. Very few studies have been done on PFTs in bronchiectasis. The main aim of this study is to study PFTs in bronchiectasis.

Method: This is a retrospective observational study done on 50 patients over two years at the tertiary care center. The previous records of patients were collected from the …

High Ligation Versus Floor Repair For Adolescent Inguinal Hernias: A Matched Comparison Of Recurrence And Complications, Katelyn Ward, Melanie Ermler, Elizabeth Theirl, Ryan Davis, Huong Tran, Begum Akay, Anthony Stallion, Nathan Novotny, Pavan Brahmamdam

Conference Presentation Abstracts

Background: The optimal surgical approach for inguinal hernias in adolescent patients remains an area of debate. While high ligation (HL) for indirect hernias is standard in younger children, floor repair (FR), usually with mesh, is preferred in adults due to the higher incidence of direct hernias and weakness of the abdominal wall. This study compares recurrence rates and perioperative complications between HL and FR in adolescent patients.

Methods: A retrospective study was performed on 10-17 year old patients who underwent inguinal hernia repair within a single hospital system between 7/2013 and 6/2023. Operations were performed by pediatric surgeons, pediatric urologists, …