Translational Medical Research Commons^™

Investigate The Delivery Efficiency Improvement For Sparc Compared To Impt, Peilin Liu, B A. De Jong, S Chang, Lili Zhao, G Liu, Craig Stevens, Rohan Deraniyagala, E W. Korevaar, J A. Langendijk, Xiaoqiang Li, Xuanfeng Ding

Conference Presentation Abstracts

Purpose: To assess the efficiency improvement of SPArc compared to IMPT in proton clinical operation.Methods: A random clinical operation day at a proton therapy center with a two room system. Aa total of 10 Head & Neck cancer cases treated on Jan 6th, 2021were selected and SPArc plans were generated for all the cases with similar target coverage and dose constraints of organ at risk (OARs). 3% range uncertainties and 3mm setup uncertainties were applied for robust optimization. The log files of clinical IMPT were exported to calculate true treatment delivery time. The machine-specific delivery sequence model was utilized to …

Test-Retest Reliability Of Virtual Reality Devices In Quantifying For Relative Afferent Pupillary Defect, Prithul Sarker, Nasif Zaman, Joshua Ong, Phani Paladugu, Molly Aldred, Ethan Waisberg, Andrew G. Lee, Alireza Tavakkoli

Student Papers, Posters & Projects

Background: The swinging flashlight test (SFT) is one of the most prominent clinical tests for detecting the relative afferent pupillary defect (RAPD). A positive RAPD localizes the lesion to the affected afferent pupil pathway and is a critical part of any ophthalmic exam. Testing for an RAPD, however, can be challenging (especially when small), and there is significant intrarater and interrater variability.

Methods: Prior studies have shown that the pupillometer can improve the detection and measurement of RAPD. In our previous research, we have demonstrated an automatic SFT by utilizing virtual reality (VR), named VR-SFT. We applied our methods to …

A Comprehensive Investigation Of Linear Energy Transfer Optimization Effectiveness In Intensity-Modulated Proton Therapy Via Alternating Direction Method Of Multipliers (Impt Let-Admm), Q Fan, G Liu, Lili Zhao, Xiaoqiang Li, Xuanfeng Ding, S Dai

Conference Presentation Abstracts

Linear energy transfer (LET)-guided optimization in intensity-modulated proton therapy (IMPT) via alternating direction method of multipliers (ADMM) has the potential to improve its biological effectiveness (IMPTLET- ADMM), in which the LET distribution in target can be escalated, while the LET distribution in the organs at risk can be mitigated. This study aims to quantitatively investigate the effectiveness of LET optimization in IMPT via ADMM with different solvers in its iteration loop. Methods: The clinical dose-volume-histogram (DVH) constraint noted dose sub-problem and clinical LET -volume-histogram (LVH) constraint noted LET sub-problem are combined to generate a composite objective function, which is available …

Urinary Cytokines As Potential Biomarkers Of Mild Cognitive Impairment And Alzheimer’S Disease: A Pilot Study, Nadia Ashrafi, Sumeyya Akyol, Sangeetha Vishweswaraiah, Abhishek Maiti, Ilyas Ustun, Sarah Bartolone, Travonia Brown-Hughes, Roland Thorpe Jr, Tammy Osentoski, Stacey Ruff, Amita Pai, Michael E. Maddens, Zaid Imam, Stewart Graham

Conference Presentation Abstracts

No abstract provided.

The Effects Of Dual Iqos And Cigarette Smoke Exposure On Airway Epithelial Cells: Implications For Lung Health And Respiratory Disease Pathogenesis, Pritam Saha, Siddhi Jain, Ipsita Mukherjee, Samir R. Panda, Amir A. Zeki, V.G.M. Naidu, Pawan Sharma

Center for Translational Medicine Faculty Papers

Background Cigarette smoking remains a primary cause of chronic lung diseases. After a steady decline, smoking rates have recently increased especially with the introduction of newer electronic nicotine delivery devices, and it is also emerging that dual- or poly-product usage is on the rise. Additionally, with the introduction of IQOS (a heated tobacco product) globally, its impact on human health needs to be investigated. In this study we tested if dual exposure (cigarette smoke (CS)+IQOS) is detrimental to lung epithelial cells when compared with CS or IQOS exposure alone.

Methods Human airway epithelial cells (BEAS-2B) were exposed to either CS, …

Comparing Performance Of Spectral Image Analysis Approaches For Detection Of Cellular Signals In Time-Lapse Hyperspectral Imaging Fluorescence Excitation-Scanning Microscopy, Marina Parker, Naga S. Annamdevula, Donald Pleshinger, Zara Ijaz, Josephine Jalkh, Raymond Penn, Deepak Deshpande, Thomas C. Rich, Silas J. Leavesley

Center for Translational Medicine Faculty Papers

Hyperspectral imaging (HSI) technology has been applied in a range of fields for target detection and mixture analysis. While HSI was originally developed for remote sensing applications, modern uses include agriculture, historical document authentication, and medicine. HSI has also shown great utility in fluorescence microscopy. However, traditional fluorescence microscopy HSI systems have suffered from limited signal strength due to the need to filter or disperse the emitted light across many spectral bands. We have previously demonstrated that sampling the fluorescence excitation spectrum may provide an alternative approach with improved signal strength. Here, we report on the use of excitation-scanning HSI …

Gp38 As A Vaccine Target For Crimean-Congo Hemorrhagic Fever Virus, Gabrielle Scher, Dennis A. Bente, Megan C. Mears, Maria N.B. Cajimat, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

Crimean-Congo Hemorrhagic Fever Virus (CCHFV) is a tick-borne virus that causes severe hemorrhagic disease in humans. There is a great need for effective vaccines and therapeutics against CCHFV for humans, as none are currently internationally approved. Recently, a monoclonal antibody against the GP38 glycoprotein protected mice against lethal CCHFV challenge. To show that GP38 is required and sufficient for protection against CCHFV, we used three inactivated rhabdoviral-based CCHFV-M vaccines, with or without GP38 in the presence or absence of the other CCHFV glycoproteins. All three vaccines elicited strong antibody responses against the respective CCHFV glycoproteins. However, only vaccines containing GP38 …

Protocol Of A Multicentre Randomised Controlled Trial Assessing Transperineal Prostate Biopsy To Reduce Infectiouscomplications, Jim Hu, Alec Zhu, Andrew Vickers, Mohamad Ezzeddine Allaf, Behfar Ehdaie, Anthony Schaeffer, Christian Pavlovich, Ashley E. Ross, David A. Green, Gerald Wang, Serge Ginzburg, Jeffrey S. Montgomery, Arvin George, John N. Graham, Benjamin T. Ristau, Andres Correa, Jonathan E. Shoag, Keith J. Kowalczyk, Tenny R. Zhang, E.M. Schaeffer

Einstein Health Papers

Introduction Approximately one million prostate biopsies are performed annually in the USA, and most are performed using a transrectal approach under local anaesthesia. The risk of postbiopsy infection is increasing due to increasing antibiotic resistance of rectal flora. Single-centre studies suggest that a clean, percutaneous transperineal approach to prostate biopsy may have a lower risk of infection. To date, there is no high-level evidence comparing transperineal versus transrectal prostate biopsy. We hypothesise that transperineal versus transrectal prostate biopsy under local anaesthesia has a significantly lower risk of infection, similar pain/discomfort levels and comparable detection of non-low-grade prostate cancer.

Methods and …

Persistently Elevated Hbv Viral-Host Junction Dna In Urine As A Biomarker For Hepatocellular Carcinoma Minimum Residual Disease And Recurrence: A Pilot Study, Selena Y Lin, Dina Halegoua-De Marzio, Peter Block, Yu-Lan Kao, Jesse M. Civan, Fwu-Shan Shieh, Wei Song, Hie-Won Hann, Ying-Hsiu Su

Department of Medicine Faculty Papers

Hepatitis B virus (HBV)-host junction sequences (HBV-JSs) has been detected in the urine of patients with HBV infection. This study evaluated HBV-JSs as a marker of minimum residual disease (MRD) and tumor recurrence after treatment in HBV-hepatocellular carcinoma (HCC) patients. Archived serial urine DNA from two HBV–HCC with recurrence as confirmed by MRI and four HBV-related cirrhosis (LC) patients were used. Urinary HBV-JSs were identified by an HBV-targeted NGS assay. Quantitative junction-specific PCR assays were developed to investigate dynamic changes of the most abundant urinary HBV-JS. Abundant urinary HBV-JSs were identified in two cases of tumor recurrence. In case 1, …

Pimt Is A Novel And Potent Suppressor Of Endothelial Activation, Chen Zhang, Zhifu Guo, Wennan Liu, Kyosuke Kazama, Louis Hu, Xiaobo Sun, Lu Wang, Hyoungjoo Lee, Lin Lu, Xiao-Feng Yang, Ross Summer, Jianxin Sun

Division of Pulmonary and Critical Care Medicine Faculty Papers

Proinflammatory agonists provoke the expression of cell surface adhesion molecules on endothelium in order to facilitate leukocyte infiltration into tissues. Rigorous control over this process is important to prevent unwanted inflammation and organ damage. Protein L-isoaspartyl O-methyltransferase (PIMT) converts isoaspartyl residues to conventional methylated forms in cells undergoing stress-induced protein damage. The purpose of this study was to determine the role of PIMT in vascular homeostasis. PIMT is abundantly expressed in mouse lung endothelium and PIMT deficiency in mice exacerbated pulmonary inflammation and vascular leakage to LPS(lipopolysaccharide). Furthermore, we found that PIMT inhibited LPS-induced toll-like receptor signaling through its interaction …

Job Satisfaction And Burnout In Nursing, Tasha M. Tovar

MSN Capstone Projects

Job satisfaction, or lack thereof, can directly lead to burnout. Nursing is known globally as a high-stress career, thus leading to an increased level of burnout. Job burnout is among the most important occupational disorders and phenomena which have received great attention in the recent century (Nabizadeh et al., 2020). Multiple studies have proven that subtle, low-cost interventions can decrease the burnout experienced by nurses, leading to reduced turnover rates and an increase in the quality of patient care. Higher quality of care leads to improvement in patient satisfaction scores and also to increased reimbursement rates (Jun et al., 2021). …

Understanding Coordinated Specialty Care Best Practice Through Fidelity Practices: A Qualitative Exploration, Halley Read

Doctor of Philosophy in Translational Health Sciences Dissertations

Background: Coordinated Specialty Care (CSC) is a multidisciplinary care model for providing care to youth and young adults having their first episode of psychosis. While outcomes of CSC effectiveness are overwhelmingly positive, and widespread implementation has occurred in all US states and territories, what is CSC best practice regarding components and fidelity to the model is not clear. CSC implementation is well documented from a fidelity to the model standpoint, but the highly variable fidelity practices and versions of the model are not well understood. Nor are the experiences of those who deliver or receive care. Adding to the complexity …

Thymic Stromal Lymphopoietin Participates In The Host Response To Intra-Amniotic Inflammation Leading To Preterm Labor And Birth, Tomi Kanninen, Li Tao, Roberto Romero, Yi Xu, Marcia Arenas-Hernandez, Jose Galaz, Zhenjie Liu, Derek Miller, Dustyn Levenson, Jonathan M. Greenberg, Jonathan Panzer, Justin Padron, Kevin Theis, Nardhy Gomez-Lopez Phd

Medical Student Research Symposium

Objective: To determine if bacteria (Ureaplasma parvum and Sneathia spp.) associated with intra-amniotic infection can trigger the induction of cytokine Thymic stromal lymphopoietin (TSLP) in human amnion epithelial cells (hAECs) in vitro.

Material or subjects: Amniotic fluid and chorioamniotic membrane (CAM) were collected from women with sPTL who delivered at term (n=30) or preterm without intra-amniotic inflammation (n=34), with sterile intra-amniotic inflammation (SIAI, n=27), or with intra-amniotic infection (IAI, n=17). Amnion epithelial cells (AECs), Ureaplasma parvum, and Sneathia spp. were also utilized.

Methods: The expression of TSLP, TSLPR, and IL-7Rα was evaluated in amniotic fluid or CAM by …

Glut1 Is Redundant In Hypoxic And Glycolytic Nucleus Pulposus Cells Of The Intervertebral Disc, Shira N. Johnston, Elizabeth S. Silagi, Vedavathi Madhu, Duc H. Nguyen, Irving M. Shapiro, Makarand V. Risbud

Department of Orthopaedic Surgery Faculty Papers

Glycolysis is central to homeostasis of nucleus pulposus (NP) cells in the avascular intervertebral disc. Since the glucose transporter, GLUT1, is a highly enriched phenotypic marker of NP cells, we hypothesized that it is vital for the development and postnatal maintenance of the disc. Surprisingly, primary NP cells treated with 2 well-characterized GLUT1 inhibitors maintained normal rates of glycolysis and ATP production, indicating intrinsic compensatory mechanisms. We showed in vitro that NP cells mitigated GLUT1 loss by rewiring glucose import through GLUT3. Of note, we demonstrated that substrates, such as glutamine and palmitate, did not compensate for glucose restriction resulting …

Mst1-Mediated Phosphorylation Of Nur77 Improves The Endometrial Receptivity In Human And Mice, Xinyu Cai, Yue Jiang, Zhiwen Cao, Mei Zhang, Na Kong, Lina Yu, Yedong Tang, Shuangbo Kong, Wenbo Deng, Haibin Wang, Jianxin Sun, Lijun Ding, Ruiwei Jiang, Haixiang Sun, Guijun Yan

Center for Translational Medicine Faculty Papers

Background: Successful embryo implantation requires the attachment of a blastocyst to the receptive endometrial epithelium, which was disturbed in the women with recurrent implantation failure (RIF). Endometrial β3-integrin was the most important adhesion molecule contributing to endometrial receptivity in both humans and mice. Nur77 has been proven indispensable for fertility in mice, here we explore the role of Nur77 on embryo-epithelial adhesion and potential treatment to embryo implantation failure.

Methods: The expression and location of Mst1 and Nur77 in endometrium from fertile women and RIF patients were examined by IHC, qRT-PCR and Western blotting. In vitro kinase assay following with …

The Neuroadvocacy Toolkit: A Knowledge Translation Strategy To Strengthen Food Fortification Policies To Prevent Neural Tube Defects In Latin American Countries. A Mixed-Method Study, Kemel A. Ghotme

Doctor of Philosophy in Translational Health Sciences Dissertations

Background. Neural tube defects are one of the leading congenital malformations that affect children in Latin America and worldwide, leading to pregnancy terminations, morbidity, mortality, and long-term disability. The most cost-effective and equitable way to prevent them is by implementing public health policies for food fortification with folic acid. However, a lack of knowledge translation strategies partly accounts for the incomplete enactment, enforcement, and scaling-up of mandatory fortification. There is no evidence in the scientific literature of studies attempting to identify the factors contributing to the development and implementation of knowledge translation strategies aiming to influence policymakers’ decisions regarding mandatory …

An Entosis-Like Process Induces Mitotic Disruption In Pals1 Microcephaly Pathogenesis, Noelle A Sterling, Jun Young Park, Raehee Park, Seo-Hee Cho, Seonhee Kim

Center for Translational Medicine Faculty Papers

Entosis is cell cannibalism utilized by tumor cells to engulf live neighboring cells for pro- or anti-tumorigenic purposes. It is unknown whether this extraordinary cellular event can be pathogenic in other diseases such as microcephaly, a condition characterized by a smaller than normal brain at birth. We find that mice mutant for the human microcephaly-causing gene Pals1, which exhibit diminished cortices due to massive cell death, also exhibit nuclei enveloped by plasma membranes inside of dividing cells. These cell-in-cell (CIC) structures represent a dynamic process accompanied by lengthened mitosis and cytokinesis abnormalities. As shown in tumor cells, ROCK inhibition completely …

Cocaine Sensitizes The Cd4+ T Cells For Hiv Infection By Co-Stimulating Nfat And Ap-1, Adhikarimayum Lakhikumar Sharma, Dylan Shafer, Daniel Netting, Mudit Tyagi

Center for Translational Medicine Faculty Papers

The productive infection of HIV, which generates new viral progeny, depends on the activation status of the cell. In this study, we found cocaine exposure sensitizes partially active CD4+ T cells and makes them poised for productive HIV infection. We discovered that cocaine treatment enhances the metabolic state of the cells by co-stimulating several transcription factors, mainly NFAT and AP-1, the two transcription factors, which specifically play a crucial role in enhancing both HIV and the overall cellular gene expression in T cells. We found that cocaine-induced AP-1 works in tandem with NFAT to boost HIV transcription. The enhanced HIV …

Expansion Of The Detrusor Muscular Ring Surrounding The Bladder Neck On Mri: Moving Beyond The Prostate As An Etiology Of Lower Urinary Tract Symptoms Due To Benign Prostatic Hyperplasia, Kiran Nandalur, David Walker, Hong Ye, Sayf A. Al-Katib, Brian Seifman, David Gangwish, Abhay Dhaliwal, Connor Ervin, Kayla Dobies, Channing Sesoko, Sirisha Nandalur, Bernadette Zwaans, Jennifer Nguyen, Jason Hafron

Conference Presentation Abstracts

Purpose: The etiology of lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH) remains uncertain. The purpose of our study was to quantitatively analyze pelvic anatomic characteristics on magnetic resonance imaging (MRI) to assess for independent factors for symptoms.
*Methods and Materials: This retrospective single-institution study evaluated treatment-naïve men who underwent prostate MRI within 3 months of International Prostate Symptom Score (IPSS) from June 2021 to February 2022. Factors measured on MRI included: detrusor muscular ring surrounding the bladder neck measured as area and alternatively diameter, central gland (CG) mean apparent diffusion coefficient (ADC), levator hiatus (LH) volume, intrapelvic …

Piperine Attenuates Cigarette Smoke-Induced Oxidative Stress, Lung Inflammation, And Epithelial-Mesenchymal Transition By Modulating The Sirt1/Nrf2 Axis, Pritam Saha, Sneha Durugkar, Siddhi Jain, P A Shantanu, Samir R Panda, Aishwarya Jala, Sharad Gokhale, Pawan Sharma, V G M Naidu

Center for Translational Medicine Faculty Papers

Piperine (PIP) is a major phytoconstituent in black pepper which is responsible for various pharmacological actions such as anti-inflammatory, antioxidant, and antitumor activity. To investigate the effects and mechanisms of PIP on cigarette smoke (CS)-induced lung pathology using both in-vitro and in-vivo models. BEAS-2B and A549 cells were exposed to CS extract (CSE) for 48 h; BALB/c mice were exposed to CS (9 cigarettes/day, 4 days) to induce features of airway disease. PIP at doses of (0.25, 1.25, and 6.25 µM, in vitro; 1 and 10 mg/kg, in vivo, i.n) and DEX (1 µM, in vitro; 1 mg/kg, in vivo, …

Regulation Of Airway Smooth Muscle Cell Proliferation By Diacylglycerol Kinase: Relevance To Airway Remodeling In Asthma, Miguel Angel Hernandez-Lara, Santosh K Yadav, Sushrut D. Shah, Mariko Okumura, Yuichi Yokoyama, Raymond B. Penn,, Taku Kambayashi, Deepak A. Deshpande

Center for Translational Medicine Faculty Papers

Airway remodeling in asthma involves the hyperproliferation of airway smooth muscle (ASM) cells. However, the molecular signals that regulate ASM growth are not completely understood. Gq-coupled G protein-coupled receptor and receptor tyrosine kinase signaling regulate ASM cell proliferation via activation of phospholipase C, generation of inositol triphosphate (IP3) and diacylglycerol (DAG). Diacylglycerol kinase (DGK) converts DAG into phosphatidic acid (PA) and terminates DAG signaling while promoting PA-mediated signaling and function. Herein, we hypothesized that PA is a pro-mitogenic second messenger in ASM, and DGK inhibition reduces the conversion of DAG into PA resulting in inhibition of ASM cell proliferation. We …

Addressing The Underdiagnosis Of Familial Hypercholesterolemia: A Mixed Methods Study Exploring The Knowledge And Practice Behaviors Of Cardiology Healthcare Providers, Isha Kalia Ms, Mph, Cgc

Doctor of Philosophy in Translational Health Sciences Dissertations

Background: Familial Hypercholesterolemia (FH) is a common genetic disorder that is vastly underdiagnosed and undertreated. FH causes lifelong elevated low-density lipoprotein cholesterol, resulting in an increased risk for coronary heart disease, myocardial infarctions, and sudden cardiac death. Cardiology healthcare providers (CHCPs) are in an ideal position to not only screen cardiology patients for FH but also to diagnose and manage FH patients.

Objectives: Describe the practice behaviors of CHCPs in the screening, diagnosis, and management of FH, as well as gain a deeper understanding of the perspectives of CHCPs regarding FH screening and diagnostic interventions that can be implemented in …

Anxiolytics For Bronchodilation: Refinements To Gaba, Ajay P Nayak, Steven S An

Department of Medicine Faculty Papers

No abstract provided.

Grk2 Regulates Adp Signaling In Platelets Via P2y1 And P2y12., Xuefei Zhao, Matthew Cooper, James V Michael, Yanki Yarman, Aiden Baltz, J Kurt Chuprun, Walter J Koch, Steven E. Mckenzie, Maurizio Tomaiuolo, Timothy J Stalker, Li Zhu, Peisong Ma

Department of Medicine Faculty Papers

The critical role of G protein-coupled receptor kinase 2 (GRK2) in regulating cardiac function has been well documented for >3 decades. Targeting GRK2 has therefore been extensively studied as a novel approach to treating cardiovascular disease. However, little is known about its role in hemostasis and thrombosis. We provide here the first evidence that GRK2 limits platelet activation and regulates the hemostatic response to injury. Deletion of GRK2 in mouse platelets causes increased platelet accumulation after laser-induced injury in the cremaster muscle arterioles, shortens tail bleeding time, and enhances thrombosis in adenosine 5'-diphosphate (ADP)-induced pulmonary thromboembolism and in FeCl3-induced carotid …

Development Of A Decellularized Hydrogel Composite And Its Application In A Novel Model Of Disc-Associated Low Back Pain In Female Sprague Dawley Rats, David Lillyman

Department of Agricultural and Biological Systems Engineering: Dissertations, Theses, and Student Research

Chronic low back pain is a global socioeconomic crisis compounded by an absence of reliable, curative treatments. The predominant pathology associated with chronic low back pain is degeneration of intervertebral discs in the lumbar spine. During degeneration, nerves can sprout into the intervertebral disc tissue and be chronically subjected to inflammatory and mechanical stimuli, resulting in pain. Pain arising from the intervertebral disc, or disc-associated pain, is a complex, multi-faceted disorder which necessitates valid animal models to screen therapeutics and study pathomechanisms of pain.

While many research teams have created animal models of disc degeneration, the translation of these platforms …

Lost In Translation? Communicating Nutrition Science, Lindsay Yarabek Datlow

Doctor of Philosophy in Translational Health Sciences Dissertations

Diet is directly correlated with overall health; therefore, nutrition is a critical piece of the obesity-epidemic puzzle. The news media has become a primary source for nutrition information yet results from International Food Information Council surveys indicate that the majority of Americans view the nutrition news they read as inconsistent and confusing. Very recent inquiry provides empirical evidence that nutrition confusion could be fueled by media. Nutrition confusion has been causally linked to “nutrition backlash,” which is complete disregard for even the most strongly supported nutrition advice. Understanding how nutrition research is translated in the news media and the mechanisms …

Characterization And Assessment Of Barriers And Facilitators To The Decision-Making Process For Blood And Blood Donor Safety In The United States: A Collective Case Study, Lauren A. Crowder

Doctor of Philosophy in Translational Health Sciences Dissertations

Background: Over 16 million blood components are transfused to patients in need every year in the United States (Jones et al., 2021). Because of the reliance on human blood donors, the donation and transfusion of blood will always be associated with some level of risk for both donors and recipients; the tolerability of these risks may vary from stakeholder to stakeholder. While the U.S. Food and Drug Administration (FDA) concedes that attaining a blood supply with zero risk for transmission of infectious diseases may be unattainable (U.S. Food and Drug Administration, 2019), they continue to strive for the lowest …

Regulation Of Oxidative Phosphorylation Of Liver Mitochondria In Sepsis, Pierre Eyenga, Benjamin Rey, Lilia Eyenga, Shey-Shing Sheu

Center for Translational Medicine Faculty Papers

The link between liver dysfunction and decreased mitochondrial oxidative phosphorylation in sepsis has been clearly established in experimental models. Energy transduction is plastic: the efficiency of mitochondrial coupling collapses in the early stage of sepsis but is expected to increase during the recovery phases of sepsis. Among the mechanisms regulating the coupling efficiency of hepatic mitochondria, the slipping reactions at the cytochrome oxidase and ATP synthase seem to be a determining element, whereas other regulatory mechanisms such as those involving proton leakage across the mitochondrial membrane have not yet been formally proven in the context of sepsis. If the dysfunction …

Akt Inhibition In The Central Nervous System Induces Signaling Defects Resulting In Psychiatric Symptomatology, Apostolia-Maria Tsimberidou, Antonis Skliris, Alan Valentine, Jamie Shaw, Ursula Hering, Henry Hiep Vo, Tung On Chan, Roger S Armen, Jeffrey R Cottrell, Jen Q Pan, Philip N Tsichlis

Center for Translational Medicine Faculty Papers

Background: Changes in the expression and activity of the AKT oncogene play an important role in psychiatric disease. We present translational data assessing the role of AKT in psychiatric symptoms.

Methods: (1) We assessed the protein activity of an AKT3 mutant harboring a PH domain mutation (Q60H) detected in a patient with schizophrenia, the corresponding AKT1 mutant (Q61H), and wild-type AKT1 and AKT3 transduced in AKT-null mouse fibroblasts and modeled the Q61H mutation onto the crystal structure of the Akt1 PH domain. (2) We analyzed the results of earlier genome-wide association studies to determine the distribution of schizophrenia-associated single-nucleotide polymorphisms …

Potential Benefits Of Combined Statin And Metformin Therapy On Resistance Training Response In Older Individuals, Douglas E. Long, Kate Kosmac, Cory M. Dungan, Marcas M. Bamman, Charlotte A. Peterson, Phillip A. Kern

Clinical and Translational Science Faculty Publications

Metformin and statins are currently the focus of large clinical trials testing their ability to counter age-associated declines in health, but recent reports suggest that both may negatively affect skeletal muscle response to exercise. However, it has also been suggested that metformin may act as a possible protectant of statin-related muscle symptoms. The potential impact of combined drug use on the hypertrophic response to resistance exercise in healthy older adults has not been described. We present secondary statin analyses of data from the MASTERS trial where metformin blunted the hypertrophy response in healthy participants (>65 years) following 14 weeks …